new research about vitamin d

Featured Topics

Featured series.

A series of random questions answered by Harvard experts.

Explore the Gazette

Read the latest.

How old is too old to run?

America’s graying. We need to change the way we think about age.

Can we talk?

“This is the first direct evidence we have that daily supplementation may reduce AD incidence, and what looks like more pronounced effect after two years of supplementation for vitamin D,” said Karen Costenbader, senior author of the study.

Michele Blackwell/Unsplash

Vitamin D supplements lower risk of autoimmune disease, researchers say

Haley Bridger

BWH Communications

Study of older adults is ‘first direct evidence’ of protection against rheumatoid arthritis, psoriasis, other conditions

In a new study, investigators from Brigham and Women’s Hospital found the people who took vitamin D, or vitamin D and omega-3 fatty acids, had a significantly lower rate of autoimmune diseases — such as rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, and psoriasis — than people who took a placebo.

With their findings published Wednesday in BMJ , the team had tested this in the large-scale vitamin D and omega-3 trial (VITAL), a randomized study which followed participants for approximately five years. Investigators found the people who took vitamin D, or vitamin D and omega-3 fatty acids had a significantly lower rate of AD than people who took a placebo.

“It is exciting to have these new and positive results for nontoxic vitamins and supplements preventing potentially highly morbid diseases,” said senior author Karen Costenbader of the  Brigham’s Division of Rheumatology, Inflammation and Immunity.  “This is the first direct evidence we have that daily supplementation may reduce AD incidence, and what looks like more pronounced effect after two years of supplementation for vitamin D. We look forward to honing and expanding our findings and encourage professional societies to consider these results and emerging data when developing future guidelines for the prevention of autoimmune diseases in midlife and older adults.”

“Now, when my patients, colleagues, or friends ask me which vitamins or supplements I’d recommend they take to reduce risk of autoimmune disease, I have new evidence-based recommendations for women age 55 years and older and men 50 years and older,” said Costenbader. “I suggest vitamin D 2000 IU a day and marine omega-3 fatty acids (fish oil), 1000 mg a day — the doses used in VITAL.”

VITAL is a randomized, double-blind, placebo-controlled research study of 25,871 men (age 50 and older) and women (age 55 and older) across the U.S., conducted to investigate whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor fish oil, 1 gram) could reduce the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. Participants were randomized to receive either vitamin D with an omega-3 fatty acid supplement; vitamin D with a placebo; omega-3 fatty acid with a placebo; or placebo only. Prior to the launch of VITAL, investigators determined that they would also look at rates of AD among participants, as part of an ancillary study.

“Given the benefits of vitamin D and omega-3s for reducing inflammation, we were particularly interested in whether they could protect against autoimmune diseases,” said JoAnn Manson, co-author and director of the parent VITAL trial at the Brigham.

Participants answered questionnaires about new diagnoses of diseases, including rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and inflammatory bowel disease, with space to write in all other new onset ADs. Trained physicians reviewed patients’ medical records to confirm reported diagnoses.

“Autoimmune diseases are common in older adults and negatively affect health and life expectancy. Until now, we have had no proven way of preventing them, and now, for the first time, we do,” said first author, Jill Hahn, a postdoctoral fellow at the Brigham. “It would be exciting if we could go on to verify the same preventive effects in younger individuals.”

Among patients who were randomized to receive vitamin D, 123 participants in the treatment group and 155 in the placebo group were diagnosed with confirmed AD (22 percent reduction). Among those in the fatty acid arm, confirmed AD occurred in 130 participants in the treatment group and 148 in the placebo group. Supplementation with omega-3 fatty acids alone did not significantly lower incidence of AD, but the study did find evidence of an increased effect after longer duration of supplementation.

The VITAL study included a large and diverse sample of participants, but all participants were older and results may not be generalizable to younger individuals who experience AD earlier in life. The trial also only tested one dose and one formulation of each supplement. The researchers note that longer follow-up may be more informative to assess whether the effects are long-lasting.

This study was funded by the National Institutes of Health grants R01 AR059086, U01 CA138962, R01 CA138962.

Share this article

You might like.

No such thing, specialist says — but when your body is trying to tell you something, listen

Experts say instead of disability, focus needs to shift to ability, health, with greater participation, economically and socially

Study finds that conversation – even online – could be an effective strategy to help prevent cognitive decline and dementia

When math is the dream

Dora Woodruff was drawn to beauty of numbers as child. Next up: Ph.D. at MIT.

Seem like Lyme disease risk is getting worse? It is.

The risk of Lyme disease has increased due to climate change and warmer temperature. A rheumatologist offers advice on how to best avoid ticks while going outdoors.

Three will receive 2024 Harvard Medal

In recognition of their extraordinary service

Long COVID treatment: Does your vitamin D level play a role?

BY Kenny Cheng April 29, 2024

We’ve long known that soaking up more sunlight can boost serotonin levels and improve mental health by ramping up vitamin D production. Now, a group of researchers who analyzed dozens of studies, dating from January 2022 to August 2023, have found that having low levels of vitamin D may increase risk of severe COVID-19—and may raise risk for and possibly delay recovery from Long COVID. The research team also identified a possible interplay between vitamin D and metformin, a medication that may help prevent Long COVID.

The clinical review , conducted by researchers at Assiut University in Egypt and published in Inflammopharmacology , analyzed 58 clinical studies that investigated the therapeutic effects of vitamin D in more than 14 million patients with COVID-19. The authors found that 49 studies (86%) demonstrated that having a higher vitamin D level was associated with less severe COVID-19 symptoms . The researchers concluded that vitamin D likely acts against COVID-19 by protecting the respiratory system and regulating the innate and adaptive immune system .

It looks possible that vitamin D also plays a role in Long COVID . In the review, the researchers stated: “There are promising reasons to enhance research on the effects of vitamin D supplements in Long COVID patients.” They found four observational studies that supported the role of vitamin D deficiency (hypovitaminosis D) as a possible risk factor for Long COVID. This builds upon previous evidence that found Long COVID patients had lower vitamin D levels compared to their counterparts without Long COVID, underlining the potential for vitamin D to help prevent the condition.

The finding also provides an opening for the use of metformin, a drug investigated in a recent Long COVID phase 3 clinical trial . In this trial, early treatment of COVID-19 with metformin , a drug used since the 1950s to treat type 2 diabetes , reduced the need for health care services for severe COVID-19 by 42.3% after 14 days and the risk of Long COVID by 41.3% during a 10-month follow-up.

In their conclusion, the authors explain that their study suggests a new potential treatment for both COVID-19 and Long COVID: vitamin D supplementation combined with early use of metformin, which has been observed to target “multiple pathological pathways of COVID-19 in a diabetes-independent manner.” The researchers argued that randomized controlled trials using a vitamin D/metformin cocktail could provide an important and much-needed new approach to the treatment of Long COVID.

Kenny Cheng is an undergraduate majoring in molecular, cellular, and developmental biology at Yale University .

The last word from Lisa Sanders, MD:

This study was a survey of investigations into the role that vitamin D plays in the severity of COVID-19 and the risk of Long COVID. Many studies have shown that low vitamin D levels put individuals at risk of having more severe infections with the SARS-CoV-2 virus. Some suggest that treatment with vitamin D may speed recovery and reduce the risk of developing Long COVID.

This is bolstered by research into the use of metformin during acute COVID infections to reduce the likelihood of developing Long COVID. The physiology of this protection is thought to be due to metformin’s effect on the vitamin D receptor, suggesting that increased vitamin D levels may reduce the risk of developing Long COVID. Randomized controlled trials will tell us if it really helps once you have Long COVID.

Much of the world’s population, especially northern Europeans, Americans, and residents of the Middle East, are deficient in vitamin D. And studies of vitamin D in the treatment of COVID-19 show that those with deficiencies are most likely to benefit from vitamin D supplementation. So, should we all be taking vitamin D—just in case we get COVID? Maybe.

There are lots of benefits from having the right amount of vitamin D. It’s good for your bones and muscles. It has many other important benefits, and there’s good research that having enough is important for overall health. Luckily, there is a free source of vitamin D—the sun. Most people can get all the vitamin D they need with five to 30 minutes of sunshine, most days a week. If you are concerned about skin aging, as I am, then put sunscreen on your face but leave your arms and legs exposed while you get your regular dose. After your sun bath, you can apply sunscreen everywhere else. As with everything in life, too much of a good thing can be bad. Taking 1,000 IU of vitamin D3 daily is sufficient for most adults who don’t get the sunshine.

If you’d like to share your experience with Long COVID for possible use in a future post (under a pseudonym), write to us at: LongCovid [email protected]

Information provided in Yale Medicine content is for general informational purposes only. It should never be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider for any questions you have regarding a medical condition.

More news from Yale Medicine

Vitamin D regulates microbiome-dependent cancer immunity

Affiliations.

• 1 Immunobiology Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
• 2 Cancer Immunosurveillance Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
• 3 Inflammatory Cell Dynamics Section, Laboratory of Integrative Cancer Immunology (LICI), Center for Cancer Research (CCR), National Cancer Institute (NCI), Bethesda, MD 20892, USA.
• 4 Department of Immunology and Inflammation, Imperial College London, London SW7 2AZ, UK.
• 5 Bioinformatics and Biostatistics STP, The Francis Crick Institute, London NW1 1AT, UK.
• 6 MRC Toxicology Unit, University of Cambridge, Cambridge CB2 1QR, UK.
• 7 Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
• 8 Microbiome and Genetics Core, LICI, CCR, NCI, Bethesda, MD 20892, USA.
• 9 National Center of Excellence for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Faculty of Medicine, Aalborg University, Department of Gastroenterology and Hepatology, Aalborg University Hospital, A DK-2450 Copenhagen, Denmark.
• 10 Metabolomics STP, The Francis Crick Institute, London NW1 1AT, UK.
• 11 Cancer Inflammation and Immunity Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
• 12 Tumor Immunogenomics and Immunosurveillance (TIGI) Lab, UCL Cancer Institute, London WC1E 6DD, UK.
• 13 AhRimmunity Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
• 14 Experimental Histopathology, The Francis Crick Institute, London NW1 1AT, UK.
• 15 Department of Pathobiology and Population Sciences, The Royal Veterinary College, North Mimms, Hatfield, Hertfordshire AL9 7TA, UK.
• 16 Genetic Mechanisms of Disease Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
• 17 Institute of Liver and Digestive Health, Division of Medicine, Royal Free Hospital, University College London, London NW3 2QG, UK.
• PMID: 38662827
• DOI: 10.1126/science.adh7954

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Publication types

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't
• Bacteroides fragilis*
• Gastrointestinal Microbiome* / drug effects
• Immune Checkpoint Inhibitors / pharmacology
• Immune Checkpoint Inhibitors / therapeutic use
• Immunotherapy
• Intestinal Mucosa / immunology
• Intestinal Mucosa / metabolism
• Intestinal Mucosa / microbiology
• Mice, Inbred C57BL
• Neoplasms / immunology
• Neoplasms / microbiology
• Vitamin D* / pharmacology
• Immune Checkpoint Inhibitors

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

April 25, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

Study finds vitamin D alters mouse gut bacteria to give better cancer immunity

by The Francis Crick Institute

Researchers at the Francis Crick Institute, the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH) and Aalborg University in Denmark, have found that vitamin D encourages the growth of a type of gut bacteria in mice which improves immunity to cancer.

Reported in Science , the researchers found that mice given a diet rich in vitamin D had better immune resistance to experimentally transplanted cancers and improved responses to immunotherapy treatment. This effect was also seen when gene editing was used to remove a protein that binds to vitamin D in the blood and keeps it away from tissues.

Surprisingly, the team found that vitamin D acts on epithelial cells in the intestine, which in turn increase the amount of a bacteria called Bacteroides fragilis. This microbe gave mice better immunity to cancer as the transplanted tumors didn't grow as much, but the researchers are not yet sure how.

To test if the bacteria alone could give better cancer immunity, mice on a normal diet were given Bacteroides fragilis. These mice were also better able to resist tumor growth but not when the mice were placed on a vitamin D-deficient diet.

Previous studies have proposed a link between vitamin D deficiency and cancer risk in humans, although the evidence hasn't been conclusive .

To investigate this, the researchers analyzed a dataset from 1.5 million people in Denmark, which highlighted a link between lower vitamin D levels and a higher risk of cancer. A separate analysis of a cancer patient population also suggested that people with higher vitamin D levels were more likely to respond well to immune-based cancer treatments.

Although Bacteroides fragilis is also found in the microbiome in humans, more research is needed to understand whether vitamin D helps provide some immune resistance to cancer through the same mechanism.

Caetano Reis e Sousa, head of the Immunobiology Laboratory at the Crick, and senior author, said, "What we've shown here came as a surprise—vitamin D can regulate the gut microbiome to favor a type of bacteria which gives mice better immunity to cancer.

"This could one day be important for cancer treatment in humans, but we don't know how and why vitamin D has this effect via the microbiome. More work is needed before we can conclusively say that correcting a vitamin D deficiency has benefits for cancer prevention or treatment."

Evangelos Giampazolias, former postdoctoral researcher at the Crick, and now Group Leader of the Cancer Immunosurveillance Group at the Cancer Research UK Manchester Institute, said, "Pinpointing the factors that distinguish a 'good' from a 'bad' microbiome is a major challenge. We found that vitamin D helps gut bacteria to elicit cancer immunity improving the response to immunotherapy in mice.

"A key question we are currently trying to answer is how exactly vitamin D supports a 'good' microbiome. If we can answer this, we might uncover new ways in which the microbiome influences the immune system, potentially offering exciting possibilities in preventing or treating cancer."

Romina Goldszmid, Stadtman Investigator in NCI's Center For Cancer Research, said, "These findings contribute to the growing body of knowledge on the role of microbiota in cancer immunity and the potential of dietary interventions to fine-tune this relationship for improved patient outcomes. However, further research is warranted to fully understand the underlying mechanisms and how they can be harnessed to develop personalized treatment strategies."

Research Information Manager at Cancer Research UK, Dr. Nisharnthi Duggan said, "We know that vitamin D deficiency can cause health problems, however, there isn't enough evidence to link vitamin D levels to cancer risk. This early-stage research in mice , coupled with an analysis of Danish population data, seeks to address the evidence gap. While the findings suggest a possible link between vitamin D and immune responses to cancer, further research is needed to confirm this.

"A bit of sunlight can help our bodies make vitamin D but you don't need to sunbathe to boost this process. Most people in the UK can make enough vitamin D by spending short periods of time in the summer sun. We can also get vitamin D from our diet and supplements. We know that staying safe in the sun can reduce the risk of cancer, so make sure to seek shade, cover up and apply sunscreen when the sun is strong."

Explore further

Feedback to editors

New study finds genetic markers that explain up to 12% of the differences between two people's blood pressure

Microbiome researchers challenge the state of the art in colon cancer biomarker discovery

X-chromosome inactivation may reduce autism risk, study in mice suggests

2 hours ago

Microarray patches safe and effective for vaccinating children, trial shows

12 hours ago

Healthy lifestyle may offset effects of life-shortening genes by more than 60%

Fentanyl inhalation may cause potentially irreversible brain damage, warn doctors

Frequent teen vaping might boost risk of toxic lead and uranium exposure

Study in Haiti suggests early-onset heart failure is prevalent form of heart disease in low-income countries

14 hours ago

AI algorithms can determine how well newborns nurse, study shows

15 hours ago

Kaposi sarcoma discovery and mouse model could facilitate drug development

Related stories.

Researcher makes promising discoveries on role of vitamin B6 in pancreatic cancer

Feb 23, 2024

Study suggests that maintaining normal vitamin D levels may benefit patients with advanced skin cancer

Apr 24, 2023

Study suggests Black, Hispanic women with low vitamin D more likely to develop breast cancer

Apr 25, 2022

Reducing vitamin B5 slows breast cancer growth in mice

Nov 9, 2023

Is too much vitamin C harmful?

Jun 16, 2020

Obesity and vitamin D deficiency may indicate greater risk for breast cancer

Sep 19, 2018

Recommended for you

Cancer cell–immune cell interactions can predict immunotherapy response

18 hours ago

Researchers discover enzymes that open new path to universal donor blood

Scientists discover key bacterium that maintains protective intestinal mucus barrier under low-fiber diet

20 hours ago

Let us know if there is a problem with our content

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

An official website of the United States government

Here’s how you know

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( A locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

• Heart-Healthy Living
• High Blood Pressure
• Sickle Cell Disease
• Sleep Apnea
• Information & Resources on COVID-19
• The Heart Truth®
• Learn More Breathe Better®
• Blood Diseases and Disorders Education Program
• Publications and Resources
• Blood Disorders and Blood Safety
• Sleep Science and Sleep Disorders
• Lung Diseases
• Health Disparities and Inequities
• Heart and Vascular Diseases
• Precision Medicine Activities
• Obesity, Nutrition, and Physical Activity
• Population and Epidemiology Studies
• Women’s Health
• Research Topics
• Clinical Trials
• All Science A-Z
• Grants and Training Home
• Policies and Guidelines
• Funding Opportunities and Contacts
• Training and Career Development
• Email Alerts
• NHLBI in the Press
• Research Features
• Past Events
• Upcoming Events
• Mission and Strategic Vision
• Divisions, Offices and Centers
• Advisory Committees
• Budget and Legislative Information
• Jobs and Working at the NHLBI
• Contact and FAQs
• NIH Sleep Research Plan
• News and Events
• < Back To All News

Vitamin D for heart health: where the benefits begin and end

High-dose supplements don’t help the hearts of most adults any more than modest doses do, but researchers say there’s still more to learn about the value of this essential vitamin   

It’s a workhorse nutrient that strengthens bones, supports immune function, helps the heart , and powers the body in many other ways. But recent findings about vitamin D are clear: High doses do not improve heart and circulatory health for most adults any more than modest doses do.      “It takes only small-to-moderate amounts of vitamin D to have optimal cardiovascular function,” said JoAnn E. Manson M.D., Dr.P.H., a study author and chief of the division of preventive medicine at Brigham and Women’s Hospital and Harvard Medical School. “More is not better,” she explained.      Through ongoing research, Manson has found that adults who take either moderate or high-dose daily vitamin D supplements of at least 1,000 IU haven’t had a reduced risk for having a heart attack, stroke, or cardiovascular-related death compared to adults taking a placebo without vitamin D.      This research, which has been supported by the NIH-funded Vitamin D and Omega-3 Trial (VITAL), aligns with recommendations released in June by the U.S. Preventive Services Task Force , which cited insufficient evidence to recommend adults take vitamin D or any other supplement to prevent cardiovascular disease.      These findings also add to mounting evidence that vitamin D supplements are not the panacea many thought they were for a host of health problems. VITAL and other randomized trials have found, for example, that higher intakes haven’t prevented cancer, bone fractures, or falls, nor have they alleviated knee pain, cognitive decline, or atrial fibrillation – among other conditions.    It is why researchers have begun shifting their focus to other more nuanced questions about the vitamin. For example, why do some people benefit from it more than others? Could supplements benefit specific populations, such as those with increased risks for heart disease? And given that VITAL showed high-dose vitamin D supplements reduced risks for autoimmune conditions, could they also help reduce the severity of COVID-19 ?  

Vitamin D: Get enough, but not too much   

While researchers sort through these questions, the guidelines that have been in place for years still apply.      The National Academy of Medicine recommends a daily intake of 600 IU of vitamin D (mostly from foods) for people ages 1-70 and 800 IU for adults ages 71 and older. However, Manson notes it is reasonable for adults concerned about not getting enough vitamin D to take a daily supplement of 1,000-2,000 IU during the pandemic. She cautions against taking more. Consuming more than 4,000 IU daily, the upper daily limit, is considered mega-dosing and could lead to adverse effects, including high calcium levels in the blood or kidney stones.   

So, what’s the best way to get vitamin D?  

Getting incidental sun exposure, such as by being physically active outdoors, and eating vitamin D-rich foods , including fatty fish, fortified dairy products and cereals, and certain mushrooms, such as those exposed to ultraviolet light, are good places to start, Manson explained. Reading nutrition labels can also help people assess how much vitamin D they consume through food.      After that, supplements can provide a boost for people concerned about getting too little. Or directly exposing the skin to sunlight for 15 minutes a few times each week will get you there, too, Manson said.     But when it comes to vitamin D and the prevention of heart disease, Manson said “all you need is to get into that middle range where you’re not deficient.”  

Understanding vitamin D and heart health  

The idea that higher vitamin D intake could improve heart health emerged years ago when observational studies found people with higher blood levels of vitamin D had lower rates of cardiovascular disease.      To see if vitamin D drove this effect or was just a marker of risk, researchers conducted randomized, controlled trials , including VITAL. In 2011-2013, more than 25,000 adults enrolled in VITAL, which found that high-dose vitamin D supplements did not prevent cardiovascular events. And Manson, a study director for VITAL, also conducted a meta-analysis about this topic. After reviewing 21 randomized trials related to vitamin D and cardiovascular disease, she found that “not a single one showed clear benefits of vitamin D supplements in preventing heart disease or stroke.”     “In observational research, correlation does not prove causation,” she explained, underscoring the need for randomized, controlled trials.      Multiple factors could explain why adults with higher vitamin D levels have been less likely to have cardiovascular disease in observational studies, Manson said. Exercise is one. People who spend more time outdoors engaged in physical activity, which supports heart and vascular health, may have higher vitamin D levels from incidental sun exposure. Diet is another. Fish and other nutrient-dense meals support heart health and tend to be higher in vitamin D.        Inflammation is a third, she said. Levels of inflammation can serve as signals of disease. And since vitamin D can bind to a protein that’s more likely to be depleted from inflammation, lower levels may be a marker, as opposed to a causal factor, for chronic conditions like heart disease.   However, once adults have sufficient vitamin D levels, the benefits plateau, Manson explained. “You don’t have further cardiovascular disease risk reductions with higher intake or blood levels of vitamin D.”  

The future of vitamin D research  

Researchers, including those leading VITAL, are now turning their attention to how vitamin D supplements may help people in other ways.      Some are looking at how high-dose vitamin D supplements may support immune function in people with autoimmune conditions, including rheumatoid arthritis, lupus, and psoriasis. In this case, the results appear promising. Adults who took a high-dose vitamin D supplement for five years had a 22% reduced risk for having an autoimmune condition. Other researchers, including Manson, are studying if vitamin D can reduce the severity of COVID-19 infections, shorten recovery, and lower the risk of long COVID.      Looking at how vitamin D may help people living with type 2 diabetes and cancer are the anchors of other studies. While vitamin D supplementation hasn’t prevented cancer , Manson and other VITAL researchers are studying if higher intake may slow its progression and reduce cancer-related deaths.     Alvin A. Chandra, M.D., a VITAL researcher and assistant professor in the division of cardiology at the University of Texas Southwestern Medical Center, is also curious if a parallel relationship exists with vitamin D and heart disease.     “There may be subgroups of patients who are at higher risk for adverse cardiovascular outcomes who may benefit from vitamin D supplementation,” he said. This could include people who have had a heart attack, stroke, or heart failure. And if there are benefits, either for vitamin D and/or omega-3 supplements, Chandra said he wants to know what levels would provide a protective effect.     VITAL researchers are also studying mechanisms that may influence or indicate how easily vitamin D can be absorbed and used by the body. These variables may help explain why about one in every four to five Americans is at risk for having inadequate levels of vitamin D.      Darker skin color can affect skin synthesis of vitamin D from sun exposure, for instance. According to the 2011-2014 National Health and Nutrition Examination Survey , about one in six Black children or adults was at risk for having a vitamin D deficiency compared to one in 13 Asian Americans, one in 17 Hispanics, and one in 40 whites. Aging, allergies, and underlying conditions, including Crohn’s disease and celiac disease, can also impair absorption and have other effects, as can limited sun exposure, dietary restrictions, and extended breastfeeding.       How vitamin D interacts with other nutrients, such as magnesium and vitamin K, and impacts its absorption and biological actions are topics of other studies, Manson added. Researchers are also studying genetic links that may explain differences in how the vitamin is metabolized and binds to receptors.     The result, she explained, could lead to personalized vitamin D requirements. Particular groups that benefit most from supplementation could also be identified and helped.       “This is all part of precision prevention,” she explained. 

Resources          

• To learn about vitamin D,  https://ods.od.nih.gov/factsheets/VitaminD-Consumer .          
• To learn about heart health, visit https://www.nhlbi.nih.gov/health/heart-healthy-living .        
• To learn about VITAL research, visit https://www.vitalstudy.org/index.html .   

Related Health Topics

Related news & features.

Premium Content

• MIND, BODY, WONDER

Can vitamin D help fight cancer?

An intriguing new study in mice suggests that it might. Here’s what that could mean for humans.

Our own immune system is one of our greatest allies in suppressing the development of cancer in our bodies, but it often needs a little push. One way of doing this is by using a class of medications called ‘ checkpoint inhibitors .' These medicines release the brakes on certain immune cells—called killer T cells—that then try and kill cancer cells. These can be very effective treatments for certain kinds of skin, lung, and kidney cancers, but unfortunately, they don’t work for every patient.

A flurry of studies published in 2018 demonstrated that the patients’ microbiome may have something to do with this. People who did or didn’t respond to checkpoint inhibitor therapy were found to have consistent differences in the bacteria commonly found in their gut. And in 2021, two studies found that transferring microbes from the fecal matter of people who did respond to the therapy to the gut of those who didn’t , could improve therapeutic benefits in the latter patients.

Now an unexpected discovery in mice, published in the April 25 issue of the journal Science , hints at one factor that might explain why people respond differently to cancer therapy: the level of vitamin D in their gut tissue might promote the presence and growth of certain bacteria that stimulates killer T cells to attack the cancer.

Vitamin D, which we can get from our diet—by eating things like fatty fish or egg yolks—or produce in our skin when exposed to sunlight, plays a crucial role in our metabolism and the health of our bones, muscles, nerves, and immune system. There had been evidence that it might play a protective role in cancer as well, but the new findings in mice were still a surprise.

( Want to strengthen your bones? Look beyond vitamin D )

Testing whether the same mechanisms operate in humans will require careful further study, says Caetano Reis e Sousa, an immunologist at the Francis Crick Institute in London, England, and the senior author of the study,   but it’s worth investigating.

“Vitamin D impacts the activity of hundreds of genes, so it’s complicated,” says Reis e Sousa. But in several datasets he and his colleagues have analyzed, patients with higher vitamin D activity had a higher chance of surviving various cancers, and responded better to immunotherapy.

The researchers also found evidence that in Denmark, where the sunshine that helps humans produce vitamin D in their skin is relatively rare, detailed health records reveal that people who had a lack of vitamin D had an elevated risk of developing cancer in the following decade. “This is probably an underestimate,” says Reis e Sousa, “because at least some of these people probably decided to take vitamin D supplements after learning about the deficiency.”

This study provides yet another reason to make sure you produce or consume enough vitamin D, says Carsten Carlberg, a biochemist at the Polish Academy of Sciences in Olsztyn who has studied the impacts of the vitamin for decades, and was not involved in the Science study. He warns, however, that it would be unwise to rush to conclusions about ourselves based on findings in mice. “There are 75 million years of evolution separating mice and humans.”

An intriguing observation

Reis e Sousa has long been interested in genes that affect the immune system’s ability to attack cancer cells. To identify these genes, researchers in his lab work with mice in which a gene that they suspect is involved in either promoting or suppressing cancer, has been switched off. By transplanting cancer cells into these modified mice, they can track how long it takes for the cells to grow into a tumor.  

When his colleague Evangelos Giampazolias, now at the Cancer Research UK Manchester Institute, discovered that switching off the gene which provides instructions to make the aptly named vitamin D-binding protein reduces the growth of skin cancer cells in mice, Reis e Sousa was intrigued.

But it was the next experiment, he says, “that really did my head in.”

Just to make sure their discoveries weren’t due to some quirk in the lab environment, Reis e Sousa’s team raised mice with the disabled gene in the same cage as mice that carried a fully functional version.

To their surprise, it turned out that the cage mates’ tumors were also growing more slowly. But why would proximity to a more cancer-resistant animal slow down tumor growth in normal mice as well?

The power of poop

One explanation for this, Giampazolias and Reis e Sousa soon realized, was that mice eat each other's poop; and that something in that poop must have been transferred from the mice with the deactivated gene to the normal mice they were caged with.

You May Also Like

Probiotics, prebiotics, postbiotics. What’s the difference?

Why is stomach cancer rising in young women?

The holidays can take a toll on your gut health. Here’s how to deal.

To test whether the effect had something to do with the gut microbes living in the genetically modified mice, Reis e Sousa’s team gave some of the mice with the deactivated gene a course of antibiotics. When that made the cancer resistance and their ability to pass it on to their cage mates disappear, it became clear the gut bacteria in mouse poop were somehow slowing the tumor growth.

Vitamin D-binding protein keeps most of the vitamin D in the blood, Reis e Sousa explains. “This reduces the amount of vitamin D that reaches the body’s tissues, including those lining the gut.”

The higher levels of vitamin D that resulted when Reis e Sousa’s team disabled the gene encoding vitamin D-binding protein promoted the growth and presence of a particular bacterium— Bacteroides fragilis— which is common in the human colon as well. And those bacteria, Reis e Sousa explains, may stimulate the immune system.

Switching off the gene, increasing the amount of vitamin D in the food of genetically normal mice, or adding more Bacteroides fragilis   to the mouse gut all had the same effect: more killer T cells attacking the tumor, and slowing down its growth.

As a result of these higher vitamin D levels, the mice also had a better response to immunotherapy.

“We don’t know yet how the bacteria do this,” says Reis e Sousa. “But the effect is unmistakably there.”

New therapies

Reis e Sousa, who is of Portuguese descent and whose darker complexion means that he produces less vitamin D in sun-starved London, found out he was lacked enough of the vitamin about a decade ago, and has taken supplements ever since. “As a general rule,” he says, “if you’re diagnosed as deficient in vitamin D, it seems sensible to try and correct it. But that doesn’t depend on this study, of course.”

He adds that people should always consult their primary care physician before taking vitamin supplements—even if one learns they have a vitamin D deficiency—until more is known about the impact of vitamin D supplements on cancer risk and other aspects of human health. “There might be negative effects that we haven’t found out about, such as increased risk of autoimmune disease.”

( Some vitamins and minerals simply work better when eaten together )

He also warns against spending too much time in the spring sun to dose up on vitamin D.

“We do not advocate to increase sun exposure, which can also increase the risk of skin cancer, negating any benefit. You don’t need to go sunbathing for vitamin D, just going for a walk is probably enough.”

More importantly, says Reis e Sousa, the study will hopefully inspire new research to find out if supplements of either vitamin D or Bacteroides fragilis might improve the outlook for cancer patients undergoing immunotherapy or other treatments.

Walter Willett, a physician and nutrition researcher at the Harvard T.H. Chan School of Public Health who was not involved in the current study, agrees the data in Reis e Sousa’s new study suggest likely benefits of vitamin D for human cancer patients. “This is consistent with some of our own findings. We have found lower risks of colorectal cancer in women with high blood levels of vitamin D. I have also been involved in a trial showing lower cancer mortality in people receiving vitamin D supplements.”

Willett thinks vitamin D supplements are probably a good idea. “It makes sense for most people living in northern climates to take supplemental vitamin D and not bother with the expense of testing for vitamin D levels. The best way to do this is as a standard multi-vitamin/multi-mineral supplement containing 800 or 1000 International Units of vitamin D, which costs less than 10 cents per day.”

Whether the benefits of vitamin D in humans are mediated by the microbiome needs confirmation, Willett adds. "This will require new, large studies running over multiple years.”  

There are many clinicians currently exploring whether it is beneficial to manipulate the microbiome to improve cancer therapy, Reis e Sousa says. “They can be remarkably successful in improving therapy outcomes, but they can also be dangerous, especially when people are immunosuppressed. We hope our discoveries may lead to more refined therapeutic applications.”

Related Topics

• DIGESTIVE SYSTEM
• MICROBIOLOGY
• VITAMINS AND SUPPLEMENTS

These microbes found in tumors promote cancer. What if we just kill them?

Don't trash the peels! The skins of fruits and veggies pack a nutritional punch

Revving Up Resistance to Cancer With Novel Immunotherapies

What your fitness level says about your risk of cancer

4 herbal traditions used every day, all over the world

• Environment
• Perpetual Planet

History & Culture

• History & Culture
• Mind, Body, Wonder
• Paid Content
• Terms of Use
• Privacy Policy
• Your US State Privacy Rights
• Children's Online Privacy Policy
• Interest-Based Ads
• About Nielsen Measurement
• Do Not Sell or Share My Personal Information
• Nat Geo Home
• Attend a Live Event
• Book a Trip
• Inspire Your Kids
• Shop Nat Geo
• Visit the D.C. Museum
• Learn About Our Impact
• Support Our Mission
• Advertise With Us
• Customer Service
• Renew Subscription
• Manage Your Subscription
• Work at Nat Geo
• Sign Up for Our Newsletters
• Contribute to Protect the Planet

Copyright © 1996-2015 National Geographic Society Copyright © 2015-2024 National Geographic Partners, LLC. All rights reserved

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland

Paweł płudowski.

1 Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland

Beata Kos-Kudła

2 Department of Endocrinology and Neuroendocrine Tumors, and the Department of Pathophysiology and Endocrinology in Zabrze, Medical University of Silesia, 40-952 Katowice, Poland

Mieczysław Walczak

3 Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland

Andrzej Fal

4 Department of Allergy, Lung Diseases and Internal Medicine of the Central Clinical Hospital, Ministry of Interior, 02-507 Warsaw, Poland

Dorota Zozulińska-Ziółkiewicz

5 Department and Clinic of Internal Diseases and Diabetology, Medical University of Poznan, 60-834 Poznan, Poland

Piotr Sieroszewski

6 Department of Fetal Medicine and Gynecology, Medical University of Łodz, 90-419 Łodz, Poland

Jarosław Peregud-Pogorzelski

7 Department of Pediatrics, Oncology and Pediatric Immunology, Pomeranian Medical University, 70-204 Szczecin, Poland

Ryszard Lauterbach

8 Department of Neonatology, Jagiellonian University Hospital, 31-501 Krakow, Poland

Tomasz Targowski

9 Department of Geriatrics, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland

Andrzej Lewiński

10 Department of Endocrinology and Metabolic Diseases, Medical University of Łodz, 93-338 Łodz, Poland

Robert Spaczyński

11 Center for Gynecology, Obstetrics and Infertility Pastelova, 60-198 Poznan, Poland

Mirosław Wielgoś

12 Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015 Warsaw, Poland

Jarosław Pinkas

13 School of Public Health, The Center of Postgraduate Medical Education, 01-826 Warsaw, Poland

Teresa Jackowska

14 Department of Pediatrics, Centre for Postgraduate Medical Education, 01-813 Warsaw, Poland

Ewa Helwich

15 Department of Neonatology and Neonatal Intensive Care, Institute of Mother and Child, 01-211 Warsaw, Poland

Artur Mazur

16 Institute of Medical Sciences, Medical College of Rzeszow University, 35-310 Rzeszow, Poland

Marek Ruchała

17 Department of Endocrinology, Metabolism and Internal Medicine, Medical University of Poznan, 60-355 Poznan, Poland

Arkadiusz Zygmunt

Mieczysław szalecki.

18 Department of Endocrinology and Diabetology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland, and the Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland

Artur Bossowski

19 Department of Pediatrics, Endocrinology, Diabetology with Cardiology Unit, Medical University of Bialystok, 15-274 Bialystok, Poland

Justyna Czech-Kowalska

20 Department of Neonatology and Neonatal Intensive Care, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland

Marek Wójcik

Beata pyrżak.

21 Department of Pediatrics and Endocrinology, Medical University of Warsaw, 02-091 Warsaw, Poland

Michał A. Żmijewski

22 Department of Histology, Medical University of Gdansk, 80-211 Gdansk, Poland

Paweł Abramowicz

23 Department of Pediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, 15-274 Bialystok, Poland

Jerzy Konstantynowicz

Ewa marcinowska-suchowierska.

24 Department of Internal Medicine and Geriatric Cardiology, and the Department of Geriatrics and Gerontology, School of Public Health, The Center of Postgraduate Medical Education, 02-673 Warsaw, Poland

Andrius Bleizgys

25 Clinic of Internal Diseases, Family Medicine and Oncology, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania

Spirydon N. Karras

26 Laboratory of Biological Chemistry, Medical School, Aristotle University, 55535 Thessaloniki, Greece

William B. Grant

27 Sunlight, Nutrition and Health Research Center, San Francisco, CA 94164, USA

Carsten Carlberg

28 Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland

Stefan Pilz

29 Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria

Michael F. Holick

30 Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA

Waldemar Misiorowski

31 Department of Endocrinology, Centre of Postgraduate Medical Education, Bielanski Hospital, 01-809 Warsaw, Poland

Associated Data

Not applicable.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists’ voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20–30 ng/mL (50–75 nmol/L)], and optimal concentration [30–50 ng/mL (75–125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D 3 ) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

1. Introduction

Vitamin D metabolism and its role in human health and disease have been studied, showing a broad spectrum of pleiotropic effects. Vitamin D from the diet or through the cutaneous synthesis as well as from supplements, over the counter drugs (OTC), or prescription drugs, is subsequently hydroxylated in the liver to 25-hydroxyvitamin D, i.e., 25(OH)D, and then in the kidneys, forming biologically active metabolite 1,25-dihydroxyvitamin D. Of note, vitamin D 2 coming from sun dried mushrooms and UV irradiated yeast, and vitamin D 3 originating from sun exposure and the dietary intake of oily fish, cod liver oil and supplemented foods are both metabolized in the liver to 25-hydroxyvitamin D. In fact, 25(OH)D represents either or both 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 and should be treated as the major circulating metabolite form, with a longer mean half-life of about 13–15 days, in comparison to other chemical forms. The two main pathways of degradation of both 25(OH)D and 1,25(OH) 2 D are the C23 lactone pathway and the C24 oxidation pathway. The abovementioned vitamin D metabolites are degraded by the actions of CYP24A1 (24-hydroxylase). After several steps, calcitroic acid, one of the end products of the C24 oxidation pathway, is excreted, mainly in the bile and thus in the feces.

The currently available epidemiological data support the view that vitamin D deficiency is common worldwide, including Poland [ 1 , 2 , 3 , 4 , 5 ]. However, associations between vitamin D status and global and public health have not been fully explored yet. Furthermore, most but not all published studies, reporting health risks and morbidity due to vitamin D deficiency, demonstrate good and well-balanced evidence [ 6 , 7 , 8 , 9 , 10 ]. A number of negative studies regarding vitamin D effects should also be acknowledged in the literature from the last decade [ 11 , 12 , 13 , 14 , 15 ]. Some recent data based on RCTs with vitamin D have shown contradictory results. However, conclusions from the majority of those reports, particularly using extension studies, prolonged observation time, and specific endpoints, demonstrate the beneficial effects of vitamin D in cancer prevention and the all-cause mortality rate [ 6 , 7 ].

In Poland, the history of vitamin D started in 1822 when Dr. Śniadecki found the relation between nutritional rickets and sun exposure in children living in big cities compared to rural areas in Poland. The first vitamin D recommendations were prepared and published in Poland in 2009, followed by the second and third in 2013 and 2018 [ 16 , 17 , 18 ]. Table 1 provides insights into those guidelines. The rationale of the present consensus paper and the updated recommendations was based on the compelling evidence and increasing amount of information on the effects of vitamin D on health in all age groups. The objective was to provide a concise and organized practice guidance for preventive supplementation and the management of the deficiency.

Summary of previous vitamin D supplementation guidelines for Poland and Central Europe.

† 1 ng/mL = 2.5 nmol/L; ‡ 40 IU = 1 μg.

This document provides the consensus agreement of a joint expert panel and a working group with contributors, expert clinicians representing national medical societies, and national consultants involved due to their expertise as well as recognized researchers having a consequential and significant track record in the field of vitamin D, particularly regarding associations with major health problems, global health, epidemiology of the deficiency, and relations to human morbidity.

Agreement on established recommendations was finally achieved after extensive, balanced, and comprehensive discussions and revisions of the document, leading to a consensus on all items. On this occasion, the panel members decided to refrain from grading the strength of the recommendations, thus, no quantitative rating of the evidence was used.

An executive writing group (P.P.; W.B.G.; E.M-S.; P.A.; J.K.; M.A.Ż.; W.M.) was appointed to prepare the first draft of the manuscript, and this draft manuscript was then sent to an expert group for critical revision. The most recent evidence published following the expert group discussions was considered and included in the draft by the executive writing group. The first author was responsible for the preparation of the final version of the manuscript and for sending it to the entire expert group for final approval of the content and of the final recommendations. Following the unanimous final endorsement of the recommendations and content by all expert group members, the document was submitted for publication.

3. Recommendations on Vitamin D: A 2023 Update

Outline of the general recommendations.

• (1) Prevention and treatment schedules of vitamin D deficiency in Poland are based on the use of cholecalciferol or, under specific medical conditions, on the use of calcifediol. Cholecalciferol should be considered as the first choice for both prophylactic and treatment options. Calcifediol should be used as the second choice, when cholecalciferol use does not improve serum 25(OH)D concentration or an immediate increase in serum 25(OH)D is required.
• (2) Prevention of vitamin D deficiency in the general population with the use of cholecalciferol should be individualized depending on age, body weight, the sun exposure of an individual, dietary habits and lifestyle.
• (3) If disease-specific practice guidelines are not available, preventive treatment of vitamin D deficiency in the risk groups should be implemented according to arrangements for the general population; the maximal admissible daily doses of cholecalciferol ( Table 2 ) for a given age group in the general population are recommended for use in the risk groups of vitamin D deficiency.
• (4) In the general population with documented vitamin D deficiency, the dosing of cholecalciferol (or calcifediol) should be based on serum 25(OH)D concentration and chronological (calendar) age, and in case of cholecalciferol, additionally on body weight.
• (5) In the risk groups, in case of vitamin D deficiency documented by laboratory assays, the cholecalciferol (or calcifediol) treatment and dosage adjustment should be based on 25(OH)D concentration as well as age, the nature of the underlying disease, medical therapy, and in case of cholecalciferol, additionally on body weight.
• (6) Adjusting the dosing regimen to the patient’s preference and supplementing on a weekly or monthly basis may positively impact adherence.
• (7) In the general population, the specific indications for 25(OH)D assay testing were not established and the screening of serum 25(OH)D in the entire population is not recommended.
• (8) In the risk groups, the evaluation of vitamin D status, based on serum 25(OH)D assay, is strongly recommended.
• (9) If supplementation with use of calcifediol in daily doses of 10 µg in oral solution is required for medical reasons, the first control of serum 25(OH)D is recommended within 6–8 days.

Upper limits for daily cholecalciferol intake for vitamin D deficiency prophylaxis in the general population by age.

4. Prevention of Vitamin D Deficiency and Insufficiency: Recommendations for the General Population

4.1. neonates born at term and infants.

• (1) Age 0–6 months: 400 IU/day (10 µg/day) of cholecalciferol from first days of life, regardless of the feeding method.
• (2) Age 6–12 months: 400–600 IU/day (10–15 µg/day) of cholecalciferol, depending on the daily amount of vitamin D consumed with meals.
• (3) In term-born neonates and healthy infants calcifediol is not recommended.

4.2. Children (1–10 Years)

• (1) In healthy children aged 1–3 years, supplementation should be based on cholecalciferol administration provided in a daily dose of 600 IU (15 µg/day) and, due to age-related restrictions of sunbathing, is recommended throughout the year.
• (2) In healthy children aged 4–10 years sunbathing with uncovered forearms and legs for 15–30 minutes between 10 a.m. and 3 p.m. without sunscreen, starting from May until the end of September, cholecalciferol supplementation is not necessary, although still recommended and safe.
• (3) If these guidelines are not fulfilled in healthy children aged 4–10 years, supplementation of cholecalciferol in dose 600–1000 IU/day (15–25 µg/day) is recommended throughout the year, based on body weight and the dietary vitamin D intake.
• (4) In healthy children aged 1–10 years, calcifediol is not recommended.

4.3. Adolescents (11–18 Years)

• (1) In healthy adolescents, cholecalciferol as the first choice of supplementation and calcifediol as the second choice should both be used for the prevention of vitamin D deficiency.
• (2) In healthy adolescents, sunbathing with uncovered forearms and legs for 30–45 minutes between 10 a.m. and 3 p.m. without sunscreen, starting from May until the end of September, cholecalciferol supplementation is not necessary, although still recommended and safe.
• (3) If these guidelines are not fulfilled, supplementation based on cholecalciferol in a dose of 1000–2000 IU/day (25–50 µg/day) is recommended throughout the year, based on body weight and the dietary vitamin D intake.
• (4) If the above guidelines are not fulfilled, alternative prevention based on calcifediol in a daily dose of 10 µg (oral solution) is recommended throughout the year and the control assay of serum 25(OH)D should be performed 6–8 days after starting supplementation.

4.4. Adults (19–65 Years)

• (1) In healthy adults, cholecalciferol as the first choice of supplementation and calcifediol as the second choice should be both used for the prevention of vitamin D deficiency.
• (2) In healthy adults sunbathing with uncovered forearms and legs for 30–45 minutes between 10 a.m. and 3 p.m., without sunscreens starting from May until the end of September, cholecalciferol supplementation is not necessary, although still recommended and safe.

4.5. Younger Seniors (>65 Years), Older Seniors (>75 Years), Oldest Old Seniors (90 Years and Older)

4.5.1. younger seniors (>65–75 years).

• (1) In younger seniors’ cholecalciferol as the first choice of supplementation and calcifediol as the second choice should be both used for the prevention of vitamin D deficiency.
• (2) Due to decreased efficacy of the skin synthesis, supplementation based on cholecalciferol in a dose of 1000–2000 IU/day (25–50 µg/day), based on body weight and the dietary vitamin D intake, is recommended throughout the year.
• (3) If the above guidelines are not fulfilled, calcifediol in a daily dose of 10 µg (oral solution) as an alternative prevention is recommended throughout the year and the control assay of serum 25(OH)D should be performed 6–8 days after starting supplementation.

4.5.2. Older Seniors (>75–89 Years) and the Oldest Old Seniors (90 Years and Older)

• (1) In older seniors and in the oldest old seniors, cholecalciferol as the first choice of supplementation and calcifediol as the second choice should both be used for the prevention of vitamin D deficiency.
• (2) Due to decreased efficacy of the skin synthesis, potential malabsorption and altered metabolism of vitamin D, cholecalciferol supplementation of 2000–4000 IU/day (50–100 µg/day), based on body weight and the dietary vitamin D intake, is recommended throughout the year;
• (3) Calcifediol in a daily dose of 10 µg (oral solution) as the alternative prevention is recommended throughout the year if the above guidelines are not fulfilled and the control assay of serum 25(OH)D should be performed 6–8 days after starting supplementation.

4.6. Pregnancy and Lactation

• (1) Women planning pregnancy should receive adequate cholecalciferol supplementation (or—if reasonable—alternatively calcifediol), the same as in the general adult population, if possible, under the control of serum 25(OH)D concentration.
• (2) When pregnancy is confirmed until the end of breastfeeding, cholecalciferol supplementation should be carried out under the control of 25(OH)D concentration to achieve and maintain optimal concentrations within the ranges of >30–50 ng/mL.
• (3) If the assessment of serum 25(OH)D concentration is not accessible, it is recommended to use cholecalciferol at a dose of 2000 IU/day (50 µg/day), throughout pregnancy and lactation.
• (4) In some very specific medical conditions, calcifediol in a daily dose of 10 µg (oral solution) as an alternative prevention could be considered throughout a pregnancy and lactation with special medical supervision. Warning: this recommendation is out of the label of the registration indications of the drug.

4.7. Preterm Neonates

4.7.1. neonates born at <32 weeks of gestation.

• (1) If enteral nutrition is possible, a dose of 800 IU/day (20 µg/day) of cholecalciferol is recommended from the first days of life, regardless of the feeding method, during the first month of life. The intake from a diet should be calculated from the second month of life. Calcifediol is not recommended.
• (2) Supplementation should be monitored by serum 25(OH)D concentration assays, both during hospitalization (the first check-up after 4 weeks of supplementation) and/or followed up in the outpatient care.
• (3) Total daily cholecalciferol dose of 1000 IU (25 µg/day) and higher may confer a risk of vitamin D overdose, especially in neonates with birth weight <1000 g.

4.7.2. Neonates Born at 33–36 Weeks of Gestation

• (1) A total of 400 IU/day (10 µg/day) of cholecalciferol from the first days of life, regardless of the feeding method, is recommended; calcifediol is not recommended.
• (2) There is no need to control serum 25(OH)D concentrations routinely.
• (3) Supplementation under the control of serum 25(OH)D concentration should be considered in neonates at a higher risk of vitamin D deficiency (parenteral nutrition lasting >2 weeks, ketoconazole therapy >2 weeks, anticonvulsant treatment, cholestasis, birth weight <1500 g).

5. Supplementation in Groups at Risk of Vitamin D Deficiency

• (1) In patients at risk of vitamin D deficiency ( Table 3 ), cholecalciferol or calcifediol supplementation should be implemented and followed up under the control of serum 25(OH)D concentrations, in order to achieve and maintain the optimal concentration of >30–50 ng/mL.
• (2) If the assessment of serum 25(OH)D concentration is not possible in the risk groups, cholecalciferol dosing should be carried out according to the guidelines for the general population at the maximal doses for a given age group. Alternatively, calcifediol in a daily dose of 10 µg (oral solution) may be considered for preventive management.
• (3) Overweight and obesity need a special attention as this condition usually requires a double dose of cholecalciferol in relation to the doses recommended for age-matched peers with normal body weight. In obese individuals, calcifediol in a daily dose of 10 µg (oral solution) may be considered as an alternative second choice of prevention scheme. Obesity in children and adolescents is defined as BMI >90th percentile for age and sex reference; obesity in adults and the elderly is defined as BMI >30 kg/m 2 .

Risk groups for vitamin D deficiency or insufficiency according to a large body of published evidence and to Bleizgys [ 19 ].

6. Supplementation in Specific Groups at Risk of Vitamin D Hypersensitivity

• (1) Before starting supplementation, the risk of vitamin D hypersensitivity should be assessed if feasible ( SLC34A1 gene mutation, CYP24A1 gene mutation, hypercalciuria, hypercalcemia, nephrolithiasis, nephrocalcinosis, or history of other types of vitamin D hypersensitivity in an individual or family members). Patients with chronic kidney disease, especially dialysis patients, kidney transplant recipients, are at the risk of inadequate activation of vitamin D by hydroxylation in position 1α by CYP27B1 and deactivation by CYP24A1, because both enzymes are mostly active in proximal tubules of the kidneys.
• (2) In patients at risk of vitamin D hypersensitivity, supplementation should be supervised and carried out carefully, in an individual manner, always monitored with serum Ca, serum parathyroid hormone (PTH), serum 25(OH)D, serum 1,25(OH) 2 D and 24 hours calciuria (preferred over urinary Ca/creatinine ratio).
• (3) Patients who suffer from chronic granuloma-forming disorders including sarcoidosis, tuberculosis, and chronic fungal infections and some patients with lymphoma have activated macrophages that produce 1,25(OH) 2 D in an unregulated fashion. These patients may require vitamin D treatment to raise their serum 25(OH)D to approximately 25 ng/mL [ 17 , 20 ]. The 25(OH)D concentrations need to be carefully monitored, because hypercalciuria and hypercalcemia are usually observed when the 25(OH)D is above 30 ng/mL [ 17 , 20 ].
• (4) Patients with primary hyperparathyroidism and hypercalcemia are often vitamin D deficient. It is important to correct their vitamin D deficiency and maintain sufficiency. Most patients will not increase their serum calcium level, and serum PTH may even decrease. In patients with primary hyperparathyroidism serum 25(OH)D should be maintained >30 ng/mL. Supplementation with cholecalciferol should be cautious to prevent further increases in the serum or urinary calcium concentration [ 21 ].

7. Prophylactic and Treatment Recommendations Based on 25(OH)D Concentration Values

7.1. assessment of vitamin d status and diagnostic criteria.

It is recommended to measure both 25(OH)D 2 and 25(OH)D 3 , giving a total 25(OH)D serum concentration as a measure of vitamin D status. The 25(OH)D TOTAL, with intraassay variation <5% and interassay variation <10%, should be subject to quality assurance by the certifying system DEQAS. The best assays provide total 25(OH)D concentration, excluding 3-epi-25(OH)D. The diagnostics thresholds defining concentrations of serum 25(OH)D in Poland are as follows:

• (1) Concentrations ≤20 ng/ml (50 nmol/L) indicate vitamin D deficiency, a state that should be immediately treated medically with the use of therapeutic dosing.
• (2) Concentrations of >20 ng/ml (50 nmol/L) <30 ng/ml (75 nmol/L) reflect a suboptimal vitamin D status that calls for a moderate increase of dosing.
• (3) Concentrations of ≥30 ng/ml (75 nmol/L) up to 50 ng/ml (125 nmol/L) reflect adequate to optimal vitamin D status.
• (4) Concentrations of >50 ng/ml (125 nmol/L) up to 100 ng/ml (250 nmol/L) indicate a high vitamin D supply.
• (5) Concentrations higher than 100 ng/ml (250 nmol/L) reflect an increased risk for intoxication and need for a reduction/cessation of supplementation or treatment until obtaining target 25(OH)D concentration.

7.2. Principles of Supplementation and Treatment with Cholecalciferol and Calcifediol Based on Serum 25(OH)D Concentrations ≤20 ng/mL

• (1) A 25(OH)D value of ≤20 ng/mL reflects an urgent need to start the medical intervention regimen.
• (2) A single loading therapy with the use of a cholecalciferol dose of 100,000 IU and higher is not recommended in Poland.
• (3) Cholecalciferol and calcifediol dosing for therapy of vitamin D deficiency should be based on serum 25(OH)D concentrations and previous prophylactic schemes.
• (4) A daily and cumulative (weekly, biweekly, monthly) dosing regimen of therapy with the use of cholecalciferol in regards to obtaining and maintaining optimal 25(OH)D concentrations are complementary (1000 IU/d is equal to both 7000 IU/week and 30,000 IU/month, respectively), effective, and safe. Adjustment of the dosing of cholecalciferol regimen to the patient’s preferences and the therapy taken weekly or monthly can positively influence adherence. Caution is advised when using cholecalciferol inconsistently with the summary of product characteristics (SPCs).
• (5) Daily (oral solution), weekly (soft capsules), biweekly (soft capsules), and monthly (soft capsules) dosing schemes of therapy with the use of calcifediol are safe but not equal in regards to an increase of 25(OH)D concentrations, therefore caution is advised when using calcifediol inconsistently with the summary of product characteristics (SPCs).

7.3. The Serum 25(OH)D Concentration >100 ng/mL—Increased Risk of Toxicity

• (1) Vitamin D intoxication is defined as the condition in which serum 25(OH)D concentration >100 ng/mL is accompanied by hypercalcemia, hyperphosphatemia, hypercalciuria, and apparent PTH suppression.
• (2) Therapy of vitamin D deficiency has to be stopped forthwith; calcemia and calciuria should be assessed, and serum 25(OH)D concentration should be monitored at 1-month intervals until a 25(OH)D concentration of ≤50 ng/mL is reached.
• (3) In patients with clinical signs of vitamin D intoxication, appropriate evidence-based treatment should be immediately initiated.
• (4) Verify if the previous therapy regimen was appropriate, and correct the management accordingly (intake, dosing, compliance, type of preparation).
• (5) After reaching normocalcemia, normocalciuria, and 25(OH)D concentrations ≤50 ng/mL, prophylactic management or therapeutic intervention can be resumed after the exclusion of vitamin D hypersensitivity.

7.4. Serum 25(OH)D Concentrations >50–100 ng/mL—High Values

• (1) Verify if the previous therapy regimen was appropriate, and correct the management accordingly (intake, dosing, compliance, type of preparation).

7.5. Serum 25(OH)D Concentrations >75–100 ng/mL

• (1) Cholecalciferol or calcifediol therapy should be withheld for 1–2 months.
• (2) In neonates, infants and toddlers, calcemia and calciuria should be assessed, vitamin D hypersensitivity should be excluded, and reevaluation of serum 25(OH)D concentration should be carried out.
• (3) After 1–2 months or, in case of neonates, infants and toddlers, after reaching serum 25(OH)D concentration ≤50 ng/mL, a preventive dosing regimen may be restored.

7.6. Serum 25(OH)D Concentrations >50–75 ng/mL

• (1) If cholecalciferol or calcifediol intake regimens were appropriate, it is recommended to reduce the current dosing or to suspend dosing for 1 month, and to consider assessment of 25(OH)D concentration within the consecutive 3-month period.

7.7. The Serum 25(OH)D Concentration ≥30–50 ng/mL—Optimal Values

• (1) Continue previous management.

7.8. Suboptimal Serum 25(OH)D Concentration >20–30 ng/mL

• (2) If the intake regimen was appropriate and the patient adhered to therapy correctly, it is recommended to increase the dosing of cholecalciferol, and to consider reassessment of serum 25(OH)D concentration in 6 months.
• (3) In patients previously untreated, it is recommended to initiate the vitamin D supplementation using cholecalciferol at doses recommended for the general population.
• (4) In case of inadequate response to supplementation, when previous use of cholecalciferol was ineffective and expected increase in serum 25(OH)D was not achieved, calcifediol in a daily (oral solution), biweekly (soft capsules), or monthly dosing (soft capsules) is recommended.

7.9. Serum 25(OH)D ≤20 ng/mL—Vitamin D Deficiency

• (2) Therapeutic dose of cholecalciferol should be implemented immediately, based on age and body weight.
• (3) Treatment of vitamin D deficiency should be continued for 1–3 months or until the serum 25(OH)D concentration of ≥30–50 ng/mL is achieved, then it is recommended to use consecutive maintenance dose i.e., a preventive dose recommended for the general population, in relation to age and body weight.
• (4) In patients with skeletal symptoms, metabolic bone disease, and bone mineral disorders (bone deformations, bone pain, nonspecific musculoskeletal symptoms, fatigue syndrome, and history of fragility fractures), it is necessary to assess and monitor parameters of calcium-phosphate metabolism (Ca, PO 4 , ALP, PTH, urine Ca/creatinine ratio), and—if available—bone mineral density with the use of DXA.
• (5) For some patients with chronic diseases (obesity, malabsorption syndromes, liver diseases, chronic inflammatory diseases) or that are taking medications that interfere with hepatic cytochrome P450 (i.e., glucocorticoids, anticonvulsants, anticancer or antiretroviral drugs) a quick restoration of vitamin D deficiency is needed. For those patients, the optional use of calcifediol in therapeutic biweekly or monthly doses of 266 μg (soft capsules) is reasonable, safe, and justified.
• (6) After 1 to 3 months of cholecalciferol therapy, the reevaluation of serum 25(OH)D concentration should be performed.
• (7) In patients receiving calcifediol in a daily dose of 10 μg (oral solution), or biweekly and a monthly dose of 266 μg (soft capsules) reevaluation of 25(OH)D concentration should be performed within 6–8 days, or 6–8 weeks, respectively.

7.10. Cholecalciferol Therapy

• (1) From birth to 12 months of age: 2000 IU/day (50 µg/day); serum 25(OH)D concentration control assay no later than 4–6 weeks after.
• (2) Age 1–10 years: 4000 IU/day (100 µg/day); serum 25(OH)D concentration control assay no later than 6–8 weeks after.
• (3) Age 11–18 years: 4000 IU/day (100 µg/day) or 7000 IU/week (175 µg/week) or 10,000 IU/week (250 µg/week) or 20,000 IU taken biweekly (500 µg/biweekly) or 30,000 IU taken biweekly (750 µg/biweekly) or 30,000 IU/month (750 µg/month); serum 25(OH)D concentration control assay considered 8–12 weeks after, but not later, than up to 3 months after, depending on a dose of therapy.
• (4) Age 19–64 years: 4000 IU/day (100 µg/day) or 7000 IU/week (175 µg/week) or 10,000 IU/week (250 µg/week) or 20,000 IU taken biweekly (500 µg/biweekly) or 30,000 IU taken biweekly (750 µg/biweekly) or 30,000 IU/month (750 µg/month); serum 25(OH)D concentration control assay considered 8–12 weeks after, but not later, than up to 3 months after, depending on a dose of therapy.
• (5) Age 65–74 years: 4000 IU/day (100 µg/day) or 7000 IU/week (175 µg/week) or 10,000 IU/week (250 µg/week) or 20,000 IU taken biweekly (500 µg/biweekly) or 30,000 IU taken biweekly (750 µg/biweekly) or 30,000 IU/month (750 µg/month); serum 25(OH)D concentration control assay considered 8–12 weeks after, but not later, than up to 3 months after, depending on a dose of therapy.
• (6) Age 75–89 years: 4000 IU/day (100 µg/day) or 7000 IU/week (175 µg/week) or 10,000 IU/week (250 µg/week) or 20,000 IU taken biweekly (500 µg/biweekly) or 30,000 IU taken biweekly (750 µg/biweekly) or 30,000 IU/month (750 µg/month); serum 25(OH)D concentration control assay considered 8–12 weeks after, but not later, than up to 3 months after, depending on a dose of therapy.
• (7) Age 90 years and older: 4000 IU/day (100 µg/day) or 7000 IU/week (175 µg/week) or 10,000 IU/week (250 µg/week) or 20,000 IU taken biweekly (500 µg/biweekly) or 30,000 IU taken biweekly (750 µg/biweekly) or 30,000 IU/month (750 µg/month); serum 25(OH)D concentration control assay considered 8–12 weeks after, but not later, than up to 3 months after, depending on a dose of therapy.

7.11. Calcifediol Therapy

• (1) From birth to 12 months of age: calcifediol is not recommended for this age group, unless other special considerations occur;
• (2) 1–10 years: calcifediol is not recommended for this age group, unless other special considerations occur;
• (3) 11–18 years: calcifediol in a dose of 10 µg daily (oral solution; for prevention) or 266 µg (soft capsules; for therapy) taken biweekly or monthly; the first serum 25(OH)D concentration control assay no later than 6–8 days after prevention with the use of 10 µg and 4–6 weeks after therapy with the use of 266 µg;
• (4) 19–64 years: calcifediol in a dose of 10 µg daily (oral solution; for prevention) or 266 µg (soft capsules; for therapy) taken biweekly or monthly; the first serum 25(OH)D concentration control assay no later than 6–8 days after prevention with the use of 10 µg and 4–6 weeks after therapy with the use of 266 µg;
• (5) 65–74 years: calcifediol in a dose of 10 µg daily (oral solution; for prevention) or 266 µg (soft capsules; for therapy) taken biweekly or monthly; the first serum 25(OH)D concentration control assay no later than 6–8 days after prevention with the use of 10 µg and 4–6 weeks after therapy with the use of 266 µg;
• (6) 75–89 years: calcifediol in a dose of 10 µg daily (oral solution; for prevention) or 266 µg (soft capsules; for therapy) taken biweekly or monthly; the first serum 25(OH)D concentration control assay no later than 6–8 days after prevention with the use of 10 µg and 6–8 weeks after therapy with the use of 266 µg;
• (7) 90 years and older: calcifediol in a dose of 10 µg daily (oral solution; for prevention) or 266 µg (soft capsules; for therapy) taken biweekly or monthly; the first serum 25(OH)D concentration control assay no later than 6–8 days after prevention with the use of 10 µg and 6–8 weeks after therapy with the use of 266 µg;

8. Basic Principles of Calcium Intake during Supplementation and Treatment with Vitamin D

• (1) During the prevention and treatment of vitamin D deficiency, an appropriate dietary calcium intake should be assured, keeping in mind adequate hydration/rehydration.
• (2) If adequate dietary calcium intake is not possible, calcium salts supplements are recommended, preferably in divided doses, which should be taken with meals, keeping in mind appropriate hydration.

9. Calcitriol and Active Analogues of Vitamin D

• (1) Calcitriol and active analogues of vitamin D (e.g., alfacalcidol) should not be used to prevent vitamin D deficiency.
• (2) Indications for treatment with these substances include conditions of impaired intrinsic vitamin D metabolism, such as renal failure or hypoparathyroidism.
• (3) Significantly higher risks of overdose and intoxication necessitate monitoring of serum Ca, phosphate and alkaline phosphatase, and daily urinary calcium excretion.
• (4) Attempts to assess 25(OH)D to monitor therapy with analogues is completely useless.

10. Discussion

10.1. natural vitamin d sources in brief.

The incidence and mortality rates for cardiovascular and respiratory diseases are much higher in winter than in summer. As a result, all-cause mortality rates in winter are 25% higher than in summer in the U.S. [ 22 , 23 ]. Since the risk for cardiovascular disease and infectious diseases is inversely correlated with serum 25(OH)D concentrations, it would be very useful to understand why the concentrations change with season and how to maintain summertime concentrations in winter. The primary driver of seasonal changes is solar ultraviolet-B (UVB) exposure. Solar UVB comprises 3–5% of midday solar UV radiation in mid-latitudes near solar noon in summer. However, solar UVB drops to near zero in winter for about six months a year in Poland [ 24 ]. One can make vitamin D from solar UVB exposure only when one’s shadow is shorter than one’s height, whether by season or by time of day. Serum 25(OH)D concentrations in winter in the absence of solar UVB radiation are approximately 50–70% of summertime peak values [ 25 , 26 , 27 ]. The primary reason is that 25(OH)D is stored in muscles related to serum 25(OH)D concentrations as well as the amount of exercise, and is recirculated in the serum through the influence of PTH as needed, such as in winter when serum 25(OH)D concentrations fall [ 28 , 29 , 30 ]. Dietary sources of vitamin D such as meat and fish [ 26 ] also help maintain serum 25(OH)D concentrations in winter, but do not supply enough vitamin D to maintain summertime values in winter. Thus, raising vitamin D supplementation doses in winter must be encouraged. However, in practical terms, exposing 18% of the body to the sun without sunscreen in Poland for approximately 15–30 minutes and 30–45 minutes a day between 10 a.m. and 3 p.m. is likely to be adequate for fair-skinned children aged 4–10 years and adolescents, adults, and seniors, respectively. However, care should be taken in summer not to expose the skin to the point of erythema (reddening). Direct exposure to the sun is not recommended for infants and toddlers aged up to 4 years.

10.2. Role of Vitamin D for Human Health According to Selected RCTs

The classical role of vitamin D is regulation of absorption and metabolism of calcium and phosphorus. Most of these effects are controlled by modifying gene expression, however, non-genomic targets of a fast response to vitamin D were also described [ 31 ]. Nearly all cells in the body contain vitamin D receptor (VDR), which belongs to the family of nuclear receptors acting as transcription factor. When the hormonal metabolite of vitamin D, calcitriol, binds to the VDR, it can affect gene expression, either upregulating or downregulating them. A vitamin D supplementation study reported that for 400, 4000, or 10,000 IU/day vitamin D 3 for 6 months, 162, 320, and 1289 genes were up- or down-regulated in their white blood cells, respectively [ 32 ]. This finding suggests that the increased risk of cardiovascular disease and mortality rates in winter is largely due to lower 25(OH)D concentrations in winter [ 23 ].

Serum 25(OH)D concentrations are inversely correlated with the risk of incidence and mortality rates for most diseases. The evidence regarding vitamin D and health outcomes comes from several types of studies. The medical system considers RCTs to provide the strongest evidence for the efficacy and adverse effects of pharmaceutical drugs. Unfortunately, RCTs with vitamin D supplementation designed and conducted in most of the 21st century have been based on the pharmaceutical drug model. Two assumptions of this model are that the trial is the only source of the studied agent and there is a linear dose-response relationship for the outcomes. In addition, growing knowledge about the health-promoting properties of vitamin D and widespread supplementation resulted in a general increase in 25(OH)D concentrations in the studied populations. This change is of course positive, but it is definitely harder to select control groups with low 25(OH)D concentration for RCTs or population-based studies. Examples of vitamin D RCTs that did not find the beneficial effects of vitamin D supplement include the Vitamin D and Omega-3 Trial (VITAL) regarding risk of cancer and cardiovascular disease [ 14 ] or the older reviews of RCTs [ 33 ] and a recent study on adult patients with thyroid disorders [ 34 ]. In VITAL, the mean 25(OH)D concentration for those in the treatment group was near 30 ng/mL, while in the thyroid study, the non-supplementing group had a mean 25(OH)D concentration of 26 ng/mL [ 14 ]. However, some studies in countries with very low mean 25(OH)D concentrations due to covering much of the skin and not getting enough vitamin D from diet or supplements can easily include many vitamin D-deficient participants. A good example is a study involving pregnant women in Iran [ 35 ]. The mean 25(OH)D concentration at baseline was 11 ng/mL and those treated with vitamin D supplementation to increase concentrations to above 20 ng/mL had a significantly reduced risk of gestational diabetes, preeclampsia, and preterm birth. Robert Heaney outlined the guidelines for nutrient trials, which would be appropriate for vitamin D [ 36 ]. The guidelines suggest that serum 25(OH)D concentrations be measured for all prospective participants, that those with low concentrations be included in the trial, that vitamin D doses be large enough to raise 25(OH)D concentrations high enough to significantly affect the health outcomes of interest, that achieved 25(OH)D concentrations be measured, and that the results should be based on serum 25(OH)D concentrations, not the presence or absence of vitamin D treatment. Since vitamin D RCTs have mostly not been properly designed, conducted, or analyzed, the effect of vitamin D has to be found from other types of studies [ 7 ].

10.3. Role of Vitamin D for Human Health According to Observational and Mendelian Randomization Studies in Brief

The most common other type of study is the observational study, generally based on serum 25(OH)D concentrations [ 7 ]. Observational studies are of three main types: prospective cohort studies, case-control studies, and cross-sectional studies. In the prospective cohort studies, participants are enrolled, blood samples taken, and the participants followed for times up to 10–20 years. Those who develop a health outcome of interest are paired with carefully selected controls who did not, and the risk ratios are calculated and adjusted for confounding factors.

Mendelian randomization studies examine the relationship between genetically determined serum 25(OH)D concentration and health outcomes in large databases. There are several steps involved in producing vitamin D in the skin and converting vitamin D to 25(OH)D concentration. Each step involves genes and the genes can have slightly different forms (alleles). The assumption is that, since individuals are randomized into study groups by the genetic variants they carry, bias due to confounding and reverse causation is avoided. It has recently been shown that analyzing the results for a large number of genetically determined 25(OH)D concentrations, thereby increasing the effect of very low 25(OH)D concentration, greatly improves the results as dose including data from ~300 000 participants, such as from the UK Biobank [ 6 ]. This methodology has already demonstrated causality for several health outcomes by that group including cardiovascular disease, dementia, and all-cause mortality rates, using data from the UK, Biobank as well as for hypertension, multiple sclerosis and type 2 diabetes mellitus by others that they cite.

To summarize, ecological studies have been used to find effects related to solar UVB doses, generally related to vitamin D production as done for cancer [ 37 , 38 ]. They have led to many other types of studies. Observational studies based on serum 25(OH)D concentrations of individuals and adjusted with respect to confounding risk-modifying factors have provided strong evidence that higher serum 25(OH)D concentrations are associated with reduced risk of many types of disease. Mendelian randomization studies are now able to demonstrate causality of vitamin D for many diseases [ 39 ], thereby replacing that role for RCTs, which generally have failed to do so [ 37 ]. Studies of mechanisms whereby vitamin D affects risk of disease also help confirm causality. Hill’s criteria for causality can be used with observational studies and mechanism to evaluate the evidence [ 40 ]. Hill’s criteria have been used in support of vitamin D in reducing risk of several types of disease including cancer [ 41 ] and cardiovascular disease [ 42 ].

10.4. Findings Regarding the Benefits of Higher 25(OH)D Concentrations

10.4.1. cardiometabolic diseases.

Since cardiometabolic diseases (diabetes, ischemic heart disease, and stroke) are the most important cause of death, they are the ones most important to understand the role of vitamin D. The first indication that vitamin D affected risk of cardiovascular disease (CVD) was likely the temporal ecological study by Robert Scragg in 1981, suggesting that the increased risk in winter was due to lower solar UVB doses and serum 25(OH)D concentrations [ 43 ]. It is now known that CVD mortality rates are about 25% higher in winter than in summer in mid-latitude countries and that lower serum 25(OH)D concentrations are the primary determinant. Observational studies of CVD incidence and mortality rates supported that hypothesis starting in 2008 [ 44 ]. A meta-analysis of prospective cohort studies regarding serum 25(OH)D and incidence and mortality from CVD was published in 2021 [ 45 ]. For the meta-analysis involving 28 studies, the relative risk for fatal CVD incidence declined from 1.0 at 8 ng/mL to 0.70 (96% CI, 0.65–0.75) at 25 ng/mL, i.e., a 30% reduction. Based on 10 studies, the risk of non-fatal CVD events was reduced by 20%, going from 8 ng/mL to 40 ng/mL (hazard ratio = 0.80 (95% CI, 0.70–0.95)).

A recently published article reported the risk of myocardial infarction as a function of serum 25(OH)D concentration for participants who had concentrations below 20 ng/mL at the start of the study [ 46 ]. The study ran for 20 years. For those who achieved 25(OH)D concentration from 21 and 29 ng/mL vs. <20 ng/mL, the hazard ratio was 1.14 (95% confidence interval (CI), 0.91–1.42), while for those who achieved >30 ng/mL vs. <20 ng/mL, the hazard ratio was 0.73 (95% CI, 0.55–0.96). It is noted that in the Vitamin D and Omega-3 Trial (VITAL), which enrolled over 25,000 participants and gave those in the vitamin D treatment arm 2000 IU/day vitamin D 3 , no effect of vitamin D supplementation was found for cardiovascular disease incidence or mortality [ 14 ]. However, the mean 25(OH)D concentration for those in the vitamin D treatment arm who supplied values, was 30 ng/mL. Thus, it could not be expected to find a beneficial effect when the whole data was analyzed. On the other hand, a stratified genetic-serum 25(OH)D concentration MR study did find a significant reduction in cardiovascular disease incidence [ 47 ].

10.4.2. Diabetes Mellitus

Vitamin D also reduces the risk of both type 1 and type 2 diabetes mellitus. The mechanisms include influence on beta-cell function, insulin sensitivity, and systematic inflammation [ 48 ]. A meta-analysis of 8 RCTs with a total of 4896 prediabetic patients treated with vitamin D or placebo was reported in 2020 [ 49 ]. The pooled risk ratio for vitamin D treatment vs. placebo was 0.89 (95% CI, 0.80–0.99) while the pooled hazard ratio was 0.88 (95% CI, 0.78–0.99). For 1126 patients with BMI <25 kg/m 2 , the relative risk was 0.73 (95% CI, 0.57–0.92) while for 2514 patients with BMI >30 kg/m 2 , the relative risk was 0.95 (95% CI, 0.84–1.08). There are at least two reasons why patients with high BMI did not benefit as well as those with low BMI. One reason is that the vitamin D dose did not raise the serum 25(OH)D concentration as much as for those with low BMI. The second reason is that systemic inflammation increases with BMI [ 50 ]. Vitamin D supplementation has been found to reduce inflammation in non-obese patients [ 51 ] but not in obese patients [ 52 ].

Results from the secondary analysis of a vitamin D RCT involving prediabetic patients supplemented with 4000 IU/day vitamin D 3 provides additional evidence of a beneficial effect of vitamin D. When the results were analyzed in terms of intention to treat, there was no significant difference in progression to type 2 diabetes mellitus. However, analysis of progression based on achieved 25(OH)D concentration for those supplemented with vitamin D, the hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D concentrations of 40–50 ng/ml (100–124 nmol/L) and ≥50 ng/mL (≥125 nmol/L) were 0.48 (0.29–0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a 25(OH)D concentration of 20–30 ng/mL (50–74 nmol/L) [ 53 ].

10.4.3. Cancer

The role of vitamin D in reducing risk of cancer was proposed in 1980 by the brothers Cedric and Frank Garland in a geographical ecological study of colon cancer mortality rates in the United States [ 54 ]. Colon cancer mortality rates were highest in the northeastern states, where annual solar radiation doses were lowest, and were lowest in the southwestern states, where doses were highest. Since then, numerous ecological studies have found inverse correlations between solar UVB doses, while many observational studies have found inverse correlations between serum 25(OH)D concentrations and cancer incidence, with reductions for high vs. low 25(OH)D concentrations of around 30% [ 38 ]. RCTs have only confirmed the role of vitamin D supplementation in reducing the risk of cancer mortality rates [ 55 ]. An RCT with 25,000 participants did show a reduced risk of all-cancer incidence rates for participants with BMI < 25 kg/m 2 (HR =0.76 [95% CI, 0.63–0.90]) [ 14 ]. The shortcomings of that RCT included that the mean 25(OH)D concentration for participants in the vitamin D treatment arm was near 31 ng/mL, that they were given 2000 IU/d of cholecalciferol, that all participants were permitted to take an additional 600–800 IU/day of vitamin D depending on age, and that the results were not analyzed with respect to baseline and achieved 25(OH)D concentrations [ 14 ]. Another more recently published RCT conducted in the United States involved patients with metastatic colorectal cancer (CRC) in order to investigate if cholecalciferol in high doses added to standard chemotherapy improves the outcomes in patients with CRC [ 56 ]. The patients’ baseline 25(OH)D concentrations were close to 18 ng/mL and the study group was given 8000 IU/day of cholecalciferol for 2 weeks followed by 4000 IU/day for the rest of the study vs. 400 IU/day in controls [ 56 ]. The multivariable HR for progression-free survival or death was 0.64 (95% CI, 0–0.90) [ 56 ].

The mechanisms whereby vitamin D reduces the risk of cancer incidence include regulation of cellular differentiation, proliferation, and apoptosis (suicide), while those that reduce mortality also include reduced formation of blood vessels to supply tumors with nutrients and reduced metastasis into surrounding tissues [ 38 ].

10.4.4. Infectious Diseases

Vitamin D has several mechanisms that help reduce the risk of viral and bacterial infections and progression to disease. One mechanism is that it induces the release of human cathelicidin, LL-37, a polypeptide with antimicrobial properties, making it an important component of the innate immune system [ 57 , 58 , 59 ]. It was proposed in 2020 that vitamin D could reduce the incidence and severity of COVID-19 [ 59 , 60 ]. Observational studies have found that higher 25(OH)D concentrations are associated with a reduced risk of COVID-19 [ 59 , 60 , 61 ]. A recent systematic review reported that vitamin D supplementation could significantly reduce the severity of COVID-19 in terms of reduced risk for intensive care, mechanical ventilation, and mortality [ 62 ].

A meta-analysis for double-blind RCTs for acute respiratory tract infection identified 1528 articles, of which 46 RCTs (75,541 participants) were eligible [ 8 ]. Data for the primary outcome were obtained for 48,488 participants (aged 0–95 years) in 43 studies. Protective effects were observed in a daily dosing regimen (OR = 0.78 [95% CI 0.65–0.94]; 19 studies), using 400–1000 IU/day (0.70 [0.55–0.89]; 10 studies), for 12 months or less (0.82 [0.72–0.93]; 29 studies), in young participants aged 1–16 years at enrolment (0.71 [0.57–0.90]; 15 studies) [ 8 ].

Respiratory syncytial virus (RSV)-associated acute respiratory infection causes substantial morbidity, leading to the hospitalization of 1 in every 56 healthy term–born infants in high-income settings [ 63 ]. An observational study conducted in the Netherlands on 256 neonates reported that those born with 25(OH)D concentrations <20 ng/mL compared with those with >30 ng/mL had an increased risk of developing severe lower respiratory tract infection RSV in the first year of life of 6.0 (95% CI, 1.6–24.9) [ 64 ].

Low vitamin D status also appeared as an important risk factor for sepsis incidence and mortality. In a meta-analysis involving 42 studies with 7434 children, 55% (95% CI, 49–61%) were vitamin D deficient [ 65 ]. Of the 889 children with sepsis from 18 studies, 64% (95% CI, 52–74%) were vitamin D deficient. The meta-analysis for mortality indicated that vitamin D deficiency increased the risk of death (OR = 1.81 [95% CI, 1.24–2.64]) [ 65 ].

10.4.5. Autoimmune Diseases

Vitamin D also reduces risk of autoimmune diseases. The VITAL trial found that supplementing with 2000 IU/d vitamin D 3 for 5.3 years significantly reduced the risk of autoimmune diseases [ 66 ]. The hazard ratio for vitamin D treatment compared to placebo was 0.78 (95% CI, 0.61–0.99). While results for individual autoimmune diseases were not significant due to low numbers of cases, the ones with reduced incidence were psoriasis, polymyalgia rheumatic disease, and rheumatoid arthritis. A recent review discussed the mechanisms whereby vitamin D reduces risk of autoimmune diseases [ 67 ]. The review also emphasized the preventive role of proper nutrition and maintaining sufficient vitamin D concentration in maternal blood during pregnancy, as well as in the early years of life.

10.4.6. Pregnancy Outcomes

Vitamin D is very important during pregnancy and lactation. Higher 25(OH)D concentrations are associated with a reduced risk of Cesarean delivery, gestational diabetes, pre-eclampsia, and preterm delivery [ 68 , 69 , 70 ]. Optimal 25(OH)D concentrations during pregnancy are over 30 ng/mL (75 nmol/L).

A trial conducted in Iran with pregnant women shows how vitamin D RCTs should be conducted [ 35 ]. A total of 900 pregnant women were included at each of the 2 hospitals. The women at one hospital were not treated, while those at the other hospital, if vitamin D deficient, were treated with vitamin D. The mean values for many factors were well-matched at the time of enrollment including the 25(OH)D concentration, which was 11 ng/mL. A total of 800 of the women with vitamin D deficiency (<20 ng/mL) were divided into 2 groups; 10–20 ng/mL or <10 ng/mL. These groups were each further divided into 4 groups of 100 participants and supplemented with 50,000 IU/week for 12 weeks up to 300 000 IU each week for 6 weeks, followed by 50 000 IU/week until delivery. At delivery, serum 25(OH)D concentrations were 21 ng/mL (95% CI, 18–25 ng/mL) in the screened group vs. 11 ng/mL (7–16 ng/mL) in the unscreened group. All maternal outcomes were significantly reduced in the screened group, including pre-eclampsia, gestational diabetes, preterm delivery, and composite adverse pregnancy outcomes. The features that made this an excellent study include enrolling participants with vitamin D deficiency, giving sufficient vitamin D to raise serum 25(OH)D to where it reduced risk of adverse outcomes, measuring achieved 25(OH)D concentration, and not giving even small doses of vitamin D to the control group.

In a recent editorial, Hollis and Wagner discuss the importance of starting supplementation for women thinking of becoming pregnant with 4000 IU/day vitamin D 3 [ 71 ]. They also point out that vitamin D RCTs should be based on serum 25(OH)D concentrations, not vitamin D dose, since RCTs based on dose are not appropriate since vitamin D per se is not the active agent, while serum 25(OH)D concentration is the best measure of the effect of vitamin D. They also point out that the reason why vitamin D is not getting more support for improving health is that it cannot be patented, and, thus, is not supported by health systems geared to use pharmaceutical drugs.

11. Calcifediol—Introduction and Implementation into Clinical Practice

In the recent practice guidelines it was decided to include calcifediol as an alternative, second choice drug for both the prevention and treatment of vitamin D deficiency in special groups of patients. Calcifediol is 25(OH)D, the primary circulating vitamin D metabolite. It can be taken in Poland using an oral solution or soft capsules. There are some advantages to using calcifediol compared to cholecalciferol [ 72 ]. Oral calcifediol results in a faster increase in serum 25(OH)D than oral cholecalciferol, in hours instead of days. In addition, oral calcifediol has a higher rate of intestinal absorption, which may have important advantages in case of decreased intestinal absorption capacity due to a variety of diseases. In addition, oral calcifediol has a linear dose-response curve, irrespective of the baseline serum 25(OH)D concentration, whereas the rise in serum 25(OH)D is lower after oral cholecalciferol when the baseline serum 25(OH)D concentration is higher. Finally, an intermittent intake of calcifediol results in fairly stable serum 25(OH)D. The faster increase in serum 25(OH)D concentration can be an advantage when it is important to treat a vitamin D-responsive disease quickly, such as for COVID-19. A pilot RCT study in Spain reported significant reductions in COVID-19 severity with calcifediol treatment in 2020 [ 73 ]. A review published prior to the COVID-19 pandemic pointed out cholecalciferol, with calcifediol reserved for patients with liver failure or severe intestinal malabsorption syndromes [ 74 ]. In addition, calcifediol may be a good option for treating patients with inflammatory respiratory diseases, such as asthma, COPD, or COVID-19 since it can rapidly increase serum 25(OH)D concentrations to more quickly reduce the viability and proliferation of viruses and bacteria as well as reduce the production of pro-inflammatory cytokines that damage the surfaces of organs [ 75 ]. While accumulating evidence suggests that calcifediol may be an attractive alternative to “native” vitamin D, RCT data are still missing, but more data on this topic may be available in the future. At this stage however, we continue to recommend vitamin D 3 (cholecalciferol) as a first-line substance to prevent and treat vitamin D deficiency and calcifediol as the second choice [ 76 , 77 ].

12. Conclusions

The vitamin D status of toddlers, children, adolescents, adults and seniors again needs to be paid special attention to. The present paper provides the clinical consensus on the prevention and treatment of vitamin D deficiency in Poland. Prophylaxis of vitamin D deficiency should be re-introduced for medical societies, medical professionals, and healthcare policymakers. It is strongly postulated to include practical guidelines on the prevention and treatment of vitamin D deficiency into every day practice.

Acknowledgments

The authors of this manuscript would like to thank the President of the Polish Society of Endocrinology (B.K.-K.), the President of the Polish Society of Pediatric Endocrinology and Diabetes and the National Consultant in Pediatric Endocrinology and Diabetology (M.W.; Mieczysław Walczak), the President of the Polish Society of Public Health (A.F.), the President of the Polish Society of Diabetology (D.Z.-Z.), the President of the Polish Society of Gynecologists and Obstetricians (P.S.), the President of the Polish Pediatric Society (J.P.-P.), the President of the Polish Neonatology Society (R.L.), the National Consultant of the Polish Geriatric Society (T.T.), the National Consultant of Endocrinology (A.L.), the National Consultant of Gynecological Endocrinology and Reproduction and Vice President of the Polish Society of Reproductive Medicine and Embryology (R.S.), the National Consultant of Perinatology (M.W.; Mirosław Wielgoś), the National Consultant in the field of Public Health (J.P.), the National Consultant of Pediatrics and Vice President of the Polish Pediatric Society (T.J.), the National Consultant of Neonatology (E.H.), the Vice President of the Polish Pediatric Society (A.M.) and the President of the European Vitamin D Association (EVIDAS) (P.P.) for the efforts done to disseminate our recommendations.

Funding Statement

This research received no external funding.

Author Contributions

Writing—original draft preparation, P.P.; E.M.-S.; J.K., and W.M. (Waldemar Misiorowski). Writing the final review and final editing, P.P.; W.B.G.; P.A.; J.K.; M.A.Ż., and W.M. (Waldemar Misiorowski). All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

W.B.G. receives funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR, USA). The other authors have no conflicts of interest to declare.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Vitamin D is both a nutrient we eat and a hormone our bodies make. It is a fat-soluble vitamin that has long been known to help the body absorb and retain calcium and phosphorus ; both are critical for building bone. Also, laboratory studies show that vitamin D can reduce cancer cell growth, help control infections and reduce inflammation. Many of the body’s organs and tissues have receptors for vitamin D, which suggest important roles beyond bone health, and scientists are actively investigating other possible functions.

Few foods naturally contain vitamin D, though some foods are fortified with the vitamin. For most people, the best way to get enough vitamin D is taking a supplement because it is hard to eat enough through food. Vitamin D supplements are available in two forms: vitamin D2 (“ergocalciferol” or pre-vitamin D) and vitamin D3 (“cholecalciferol”). Both are also naturally occurring forms that are  produced in the presence of the sun’s ultraviolet-B (UVB) rays, hence its nickname, “the sunshine vitamin,” but D2 is produced in plants and fungi and D3 in animals, including humans. Vitamin D production in the skin is the primary natural source of vitamin D, but many people have insufficient levels because they live in places where sunlight is limited in winter, or because they have limited sun exposure due to being inside much of the time. Also, people with darker skin tend to have lower blood levels of vitamin D because the pigment (melanin) acts like a shade, reducing production of vitamin D (and also reducing damaging effects of sunlight on skin, including skin cancer).

Recommended Amounts

The Recommended Dietary Allowance for vitamin D provides the daily amount needed to maintain healthy bones and normal calcium metabolism in healthy people. It assumes minimal sun exposure.

RDA: The Recommended Dietary Allowance for adults 19 years and older is 600 IU (15 mcg) daily for men and women, and for adults >70 years it is 800 IU (20 mcg) daily.

UL: The Tolerable Upper Intake Level is the maximum daily intake unlikely to cause harmful effects on health. The UL for vitamin D for adults and children ages 9+ is 4,000 IU (100 mcg).

Many people may not be meeting the minimum requirement for the vitamin. NHANES data found that the median intake of vitamin D from food and supplements in women ages 51 to 71 years was 308 IU daily, but only 140 IU from food alone (including fortified products). [1] Worldwide, an estimated 1 billion people have inadequate levels of vitamin D in their blood, and deficiencies can be found in all ethnicities and age groups. [2-4] In the U.S., about 20% of White adults and 75% of Black adults have blood levels of vitamin D below 50 nmol/L. [83] In industrialized countries, doctors are seeing the resurgence of rickets, the bone-weakening disease that had been largely eradicated through vitamin D fortification. [5-7] There is scientific debate about how much vitamin D people need each day and what the optimal serum levels should be to prevent disease. The Institute of Medicine (IOM) released in November 2010 recommendations increasing the daily vitamin D intake for children and adults in the U.S. and Canada, to 600 IU per day. [1] The report also increased the upper limit from 2,000 to 4,000 IU per day. Although some groups such as The Endocrine Society recommend 1,500 to 2,000 IU daily to reach adequate serum levels of vitamin D, the IOM felt there was not enough evidence to establish a cause and effect link with vitamin D and health benefits other than for bone health.  Since that time, new evidence has supported other benefits of consuming an adequate amount of vitamin D, although there is still not consensus on the amount considered to be adequate.

Vitamin D and Health

The role of vitamin D in disease prevention is a popular area of research, but clear answers about the benefit of taking amounts beyond the RDA are not conclusive. Although observational studies see a strong connection with lower rates of certain diseases in populations that live in sunnier climates or have higher serum levels of vitamin D, clinical trials that give people vitamin D supplements to affect a particular disease are still inconclusive. This may be due to different study designs, differences in the absorption rates of vitamin D in different populations, and different dosages given to participants. Learn more about the research on vitamin D and specific health conditions and diseases:  

Several studies link low vitamin D blood levels with an increased risk of fractures in older adults. Some studies suggest that vitamin D supplementation in certain amounts may prevent such fractures, while others do not. [8-11]

• A meta-analysis of 12 randomized controlled trials that included more than 42,000 people 65+ years of age, most of them women, looked at vitamin D supplementation with or without calcium, and with calcium or a placebo. Researchers found that higher intakes of vitamin D supplements—about 500-800 IU per day—reduced hip and non-spine fractures by about 20%, while lower intakes (400 IU or less) failed to offer any fracture prevention benefit. [12]
• A systematic review looked at the effect of vitamin D supplements taken with or without calcium on the prevention of hip fractures (primary outcome) and fractures of any type (secondary outcome) in older men and postmenopausal women 65+ years of age. It included 53 clinical trials with 91,791 participants who lived independently or in a nursing home or hospital. It did not find a strong association between vitamin D supplements alone and prevention of fractures of any type. However, it did find a small protective effect from all types of fractures when vitamin D was taken with calcium. All of the trials used vitamin D supplements containing 800 IU or less. [13]
• The VITamin D and OmegA-3 TriaL (VITAL) double-blind placebo-controlled randomized trial of 25,871 women and men, 55+ years and 50+ years of age, respectively, did not find a protective effect from vitamin D supplements on bone fractures. [81] The participants were healthy at the start of the study—representative of the general population and not selected based on low bone mass, osteoporosis, or vitamin D deficiency—and were given either 2,000 IU of vitamin D or a placebo taken daily for about five years. Vitamin D did not lower the incidence of total bone fractures or fractures of the hip or spine.

Vitamin D may help increase muscle strength by preserving muscle fibers, which in turn helps to prevent falls, a common problem that leads to substantial disability and death in older people. [14–16] A combined analysis of multiple studies found that taking 700 to 1,000 IU of vitamin D per day lowered the risk of falls by 19%, but taking 200 to 600 IU per day did not offer any such protection. [17] However, the VITAL trial following healthy middle-aged men and women did not find that taking 2,000 IU of vitamin D daily compared with a placebo pill reduced the risk of falls. [82]

Though taking up to 800 IU of vitamin D daily may benefit bone health in some older adults, it is important to be cautious of very high dosage supplements. A clinical trial that gave women 70+ years of age a once-yearly dosage of vitamin D at 500,000 IU for five years caused a 15% increased risk of falls and a 26% higher fracture risk than women who received a placebo. [18] It was speculated that super-saturating the body with a very high dose given infrequently may have actually promoted lower blood levels of the active form of vitamin D that might not have occurred with smaller, more frequent doses. [13]

JoAnn Manson, MD, DrPH , leader of the main VITAL trial and coauthor of the report on fracture, commented:

“We conclude that, in the generally healthy U.S. population of midlife and older adults, vitamin D supplementation doesn’t reduce the risk of fractures or falls. This suggests that only small-to-moderate amounts of vitamin D are needed for bone health and fall prevention, achieved by most community-dwelling adults. Of course, vitamin D deficiency should always be treated and some high-risk patients with malabsorption syndromes, osteoporosis, or taking medications that interfere with vitamin D metabolism will benefit from supplementation.”

Nearly 30 years ago, researchers noticed an intriguing relationship between colon cancer deaths and geographic location: People who lived at higher latitudes, such as in the northern U.S., had higher rates of death from colon cancer than people who lived closer to the equator. [19] Many scientific hypotheses about vitamin D and disease stem from studies that have compared solar radiation and disease rates in different countries. These studies can be a good starting point for other research but don’t provide the most definitive information. The sun’s UVB rays are weaker at higher latitudes, and in turn, people’s vitamin D blood levels in these locales tend to be lower. This led to the hypothesis that low vitamin D levels might somehow increase colon cancer risk. [3]

Animal and laboratory studies have found that vitamin D can inhibit the development of tumors and slow the growth of existing tumors including those from the breast, ovary, colon, prostate, and brain. In humans, epidemiological studies show that higher serum levels of vitamin D are associated with substantially lower rates of colon, pancreatic, prostate, and other cancers , with the evidence strongest for colorectal cancer. [20-32]

However, clinical trials have not found a consistent association:

The Women’s Health Initiative trial, which followed roughly 36,000 women for an average of seven years, failed to find any reduction in colon or breast cancer risk in women who received daily supplements of 400 IU of vitamin D and 1,000 mg of calcium, compared with those who received a placebo. [33,34] Limitations of the study were suggested: 1) the relatively low dose of vitamin D given, 2) some people in the placebo group decided on their own to take extra calcium and vitamin D supplements, minimizing the differences between the placebo group and the supplement group, and 3) about one-third of the women assigned to vitamin D did not take their supplements. 4) seven years may be too short to expect a reduction in cancer risk. [35,36]

A large clinical trial called the VITamin D and OmegA-3 TriaL (VITAL) followed 25,871 men and women 50+ years of age free of any cancers at the start of the study who took either a 2,000 IU vitamin D supplement or placebo daily for a median of five years. [37] The findings did not show significantly different rates of breast, prostate, and colorectal cancer between the vitamin D and placebo groups. The authors noted that a longer follow-up period would be necessary to better assess potential effects of supplementation, as many cancers take at least 5-10 years to develop.

Although vitamin D does not seem to be a major factor in reducing cancer incidence, evidence including that from randomized trials suggests that having higher vitamin D status may improve survival if one develops cancer.  In the VITAL trial, a lower death rate from cancer was observed in those assigned to take vitamin D, and this benefit seemed to increase over time since starting on vitamin D. A meta-analysis of randomized trials of vitamin D, which included the VITAL study, found a 13% statistically significant lower risk of cancer mortality in those assigned to vitamin D compared to placebo. [38] These findings are consistent with observational data, which suggest that vitamin D may have a stronger effect on cancer progression than for incidence.  

The heart is basically a large muscle, and like skeletal muscle, it has receptors for vitamin D. [39] Immune and inflammatory cells that play a role in cardiovascular disease conditions like atherosclerosis are regulated by vitamin D. [40] The vitamin also helps to keep arteries flexible and relaxed, which in turn helps to control high blood pressure. [41]

In the Health Professionals Follow-up Study nearly 50,000 healthy men were followed for 10 years. [42] Those who had the lowest levels of vitamin D were twice as likely to have a heart attack as men who had the highest levels. Meta-analyses of epidemiological studies have found that people with the lowest serum levels of vitamin D had a significantly increased risk of strokes and any heart disease event compared with those with the highest levels. [40;43-46]

However, taking vitamin D supplements has not been found to reduce cardiovascular risk. A meta-analysis of 51 clinical trials did not demonstrate that vitamin D supplementation lowered the risk of heart attack, stroke, or deaths from cardiovascular disease. [47] The VITamin D and OmegA-3 TriaL (VITAL) came to the same conclusion; it followed 25,871 men and women free of cardiovascular disease who took either a 2,000 IU vitamin D supplement or placebo daily for a median of five years. No association was found between taking the supplements and a lower risk of major cardiovascular events (heart attack, stroke, or death from cardiovascular causes) compared with the placebo. [37]  

Vitamin D deficiency may negatively affect the biochemical pathways that lead to the development of Type 2 diabetes (T2DM), including impairment of beta cell function in the pancreas, insulin resistance, and inflammation. Prospective observational studies have shown that higher vitamin D blood levels are associated with lower rates of T2DM. [48]

More than 83,000 women without diabetes at baseline were followed in the Nurses’ Health Study for the development of T2DM. Vitamin D and calcium intakes from diet and supplements were assessed throughout the 20-year study. [49] The authors found that when comparing the women with the highest intakes of vitamin D from supplements with women with the lowest intakes, there was a 13% lower risk of developing T2DM. The effect was even stronger when vitamin D was combined with calcium: there was a 33% lower risk of T2DM in women when comparing the highest intakes of calcium and vitamin D from supplements (>1,200 mg, >800 IU daily) with the lowest intakes (<600 mg, 400 IU).

A randomized clinical trial gave 2,423 adults who had prediabetes either 4000 IU of vitamin D or a placebo daily for two years. The majority of participants did not have vitamin D deficiency at the start of the study. At two years, vitamin D blood levels in the supplement versus placebo group was 54.3 ng/mL versus 28.2 ng/mL, respectively, but no significant differences were observed in rates of T2DM at the 2.5 year follow-up. [50] The authors noted that a lack of effect of vitamin D may have been due to the majority of participants having vitamin D blood levels in a normal range of greater than 20 ng/mL, which is considered an acceptable level to reduce health risks.  Notably, among the participants who had the lowest blood levels of vitamin D at the beginning of the study, vitamin D supplementation did reduce risk of diabetes. This is consistent with the important concept that taking additional vitamin D may not benefit those who already have adequate blood levels, but those with initially low blood levels may benefit.

Vitamin D’s role in regulating the immune system has led scientists to explore two parallel research paths: Does vitamin D deficiency contribute to the development of multiple sclerosis, type 1 diabetes, and other so-called “autoimmune” diseases, where the body’s immune system attacks its own organs and tissues? And could vitamin D supplements help boost our body’s defenses to fight infectious disease, such as tuberculosis and seasonal flu?

Multiple Sclerosis The rate of multiple sclerosis (MS) is increasing in both developed and developing countries, with an unclear cause. However, a person’s genetic background plus environmental factors including inadequate vitamin D and UVB exposure have been identified to increase risk. [51] Vitamin D was first proposed over 40 years ago as having a role in MS given observations at the time including that rates of MS were much higher far north (or far south) of the equator than in sunnier climates, and that geographic regions with diets high in fish had lower rates of MS. [52] A prospective study of dietary intake of vitamin D found women with daily intake above 400 IU had a 40% lower risk of MS. [53] In a study among healthy young adults in the US, White men and women with the highest vitamin D serum levels had a 62% lower risk of developing MS than those with the lowest vitamin D levels. [54] The study didn’t find this effect among Black men and women, possibly because there were fewer Black study participants and most of them had low vitamin D levels, making it harder to find any link between vitamin D and MS if one exists. Another prospective study in young adults from Sweden also found a 61% lower risk of MS with higher serum vitamin D levels; [55] and a prospective study among young Finnish women found that low serum vitamin D levels were associated with a 43% increased risk of MS. [56] In prospective studies of persons with MS, higher vitamin D levels have been associated with reduced disease activity and progression. [57,58] While several clinical trials are underway to examine vitamin D as a treatment in persons with MS, there are no clinical trials aimed at prevention of MS, likely because MS is a rare disease and the trial would need to be large and of long duration. Collectively, the current evidence suggests that low vitamin D may have a causal role in MS and if so, approximately 40% of cases may be prevented by correcting vitamin D insufficiency. [59] This conclusion has been strengthened substantially by recent evidence that genetically determined low levels of vitamin D predict higher risk of multiple sclerosis.

Type 1 Diabetes Type 1 diabetes (T1D) is another disease that varies with geography—a child in Finland is about 400 times more likely to develop T1D than a child in Venezuela. [60] While this may largely be due to genetic differences, some studies suggest that T1D rates are lower in sunnier areas. Early evidence suggesting that vitamin D may play a role in T1D comes from a 30-year study that followed more than 10,000 Finnish children from birth: Children who regularly received vitamin D supplements during infancy had a nearly 90% lower risk of developing type 1 diabetes than those who did not receive supplements. [61] However, multiple studies examining the association between dietary vitamin D or trials supplementing children at high risk for T1D with vitamin D have produced mixed and inconclusive results [62] Approximately 40% of T1D cases begin in adulthood. A prospective study among healthy young adults in the US found that White individuals with the highest levels of serum vitamin D had a 44% lower risk of developing T1D in adulthood than those with the lowest levels. [63] No randomized controlled trials on vitamin D and adult onset T1D have been conducted, and it is not clear that they would be possible to conduct. More research is needed in this area.

Flu and the Common Cold The flu virus wreaks the most havoc in the winter, abating in the summer months. This seasonality led a British doctor to hypothesize that a sunlight-related “seasonal stimulus” triggered influenza outbreaks. [64] More than 20 years after this initial hypothesis, several scientists published a paper suggesting that vitamin D may be the seasonal stimulus. [65] Among the evidence they cite:

• Vitamin D levels are lowest in the winter months. [65]
• The active form of vitamin D tempers the damaging inflammatory response of some white blood cells, while it also boosts immune cells’ production of microbe-fighting proteins. [65]
• Children who have vitamin D-deficiency rickets are more likely to get respiratory infections, while children exposed to sunlight seem to have fewer respiratory infections. [65]
• Adults who have low vitamin D levels are more likely to report having had a recent cough, cold, or upper respiratory tract infection. [66]

A randomized controlled trial in Japanese school children tested whether taking daily vitamin D supplements would prevent seasonal flu. [67] The trial followed nearly 340 children for four months during the height of the winter flu season. Half of the study participants received pills that contained 1,200 IU of vitamin D; the other half received placebo pills. Researchers found that type A influenza rates in the vitamin D group were about 40% lower than in the placebo group; there was no significant difference in type B influenza rates.

Although randomized controlled trials exploring the potential of vitamin D to prevent other acute respiratory infections have yielded mixed results, a large meta-analysis of individual participant data indicated that daily or weekly vitamin D supplementation lowers risk of acute respiratory infections. [68] This effect was particularly prominent for very deficient individuals.

The findings from this large meta-analysis have raised the possibility that low vitamin D levels may also increase risk of or severity of novel coronavirus 2019 (COVID-19) infection. Although there is no direct evidence on this issue because this such a new disease, avoiding low levels of vitamin D makes sense for this and other reasons. Thus, if there is reason to believe that levels might be low, such as having darker skin or limited sun exposure, taking a supplement of 1000 or 2000 IU per day is reasonable. This amount is now part of many standard multiple vitamin supplements and inexpensive.

More research is needed before we can definitively say that vitamin D protects against the flu and other acute respiratory infections. Even if vitamin D has some benefit, don’t skip your flu shot. And when it comes to limiting risk of COVID-19, it is important to practice careful social distancing and hand washing.

Tuberculosis Before the advent of antibiotics, sunlight and sun lamps were part of the standard treatment for tuberculosis (TB). [69] More recent research suggests that the “sunshine vitamin” may be linked to TB risk. Several case-control studies, when analyzed together, suggest that people diagnosed with tuberculosis have lower vitamin D levels than healthy people of similar age and other characteristics. [70] Such studies do not follow individuals over time, so they cannot tell us whether vitamin D deficiency led to the increased TB risk or whether taking vitamin D supplements would prevent TB. There are also genetic differences in the receptor that binds vitamin D, and these differences may influence TB risk. [71] Again, more research is needed.

Other A utoimmune Conditions The Vitamin D and Omega 3 trial (VITAL), a randomized double-blind placebo-controlled trial following more than 25,000 men and women ages 50 and older, found that taking vitamin D supplements (2,000 IU/day) for five years, or vitamin D supplements with marine omega-3 fatty acids (1,000 mg/day), reduced the incidence of autoimmune diseases by about 22%, compared with a placebo. Autoimmune conditions observed included rheumatoid arthritis, psoriasis, polymyalgia rheumatica, and autoimmune thyroid diseases (Hashimoto’s thyroiditis, Graves’ disease). [80]   The doses in these supplements are widely available and generally well-tolerated. The authors recommended additional trials to test the effectiveness of these supplements in younger populations and those at high risk of developing autoimmune diseases.

• A promising report in the Archives of Internal Medicine suggests that taking vitamin D supplements may reduce overall mortality rates: A combined analysis of multiple studies found that taking modest levels of vitamin D supplements was associated with a statistically significant 7% reduction in mortality from any cause. [72] The analysis looked at the findings from 18 randomized controlled trials that enrolled a total of nearly 60,000 study participants; most of the study participants took between 400 and 800 IU of vitamin D per day for an average of five years. Keep in mind that this analysis has several limitations, chief among them the fact that the studies it included were not designed to explore mortality in general, or explore specific causes of death.  A recent meta-analysis suggests that this reduction in mortality is driven mostly by a reduction in cancer mortality. [38] More research is needed before any broad claims can be made about vitamin D and mortality. [73]
• A large cohort study of more than 307,000 White European participants found a 25% increased risk of premature deaths from any cause in those who had vitamin D blood levels of 25 nmol/L (10 ng/ml), compared with those who had 50 nmol/L (20 ng/ml) (the National Academy of Medicine cites a vitamin D blood level of 50 nmol/L as adequate for most people). [74] Similar increases in risks were seen for deaths due to cardiovascular disease, cancer, and respiratory disease, and risks increased sharply among those with even lower levels of vitamin D. Although the numbers of non-White participants were small, the findings were similar in this group. The study used Mendelian randomization, which measured genetic variations to confirm these findings. This confirmation is important because it documents that the adverse health outcomes among people with low levels of vitamin D represent a causal relationship between vitamin D deficiency and premature death. Specifically, this method removed potential confounding by factors such as obesity, smoking, and alcohol intake.

In an analysis of more than 427,000 White European participants using Mendelian randomization, a 54% higher risk of dementia was seen among participants with low vitamin D blood levels of <25 nmol/L compared with those having adequate levels of 50 nmol/L. [75]

Food Sources

Few foods are naturally rich in vitamin D3. The best sources are the flesh of fatty fish and fish liver oils. Smaller amounts are found in egg yolks, cheese, and beef liver. Certain mushrooms contain some vitamin D2; in addition some commercially sold mushrooms contain higher amounts of D2 due to intentionally being exposed to high amounts of ultraviolet light. Many foods and supplements are fortified with vitamin D like dairy products and cereals.

• Cod liver oil
• Orange juice fortified with vitamin D
• Dairy and plant milks fortified with vitamin D
• Fortified cereals

Is There a Difference Between Vitamin D3 and Vitamin D2 Supplements?

Ultraviolet light.

Vitamin D3 can be formed when a chemical reaction occurs in human skin, when a steroid called 7-dehydrocholesterol is broken down by the sun’s UVB light or so-called “tanning” rays. The amount of the vitamin absorbed can vary widely. The following are conditions that decrease exposure to UVB light and therefore lessen vitamin D absorption:

• Use of sunscreen; correctly applied sunscreen can reduce vitamin D absorption by more than 90%. [78]
• Wearing full clothing that covers the skin.
• Spending limited time outdoors.
• Darker skin tones due to having higher amounts of the pigment melanin, which acts as a type of natural sunscreen. [79]
• Older ages when there is a decrease in 7-dehydrocholesterol levels and changes in skin, and a population that is likely to spend more time indoors.
• Certain seasons and living in northern latitudes above the equator where UVB light is weaker. [78] In the northern hemisphere, people who live in Boston (U.S.), Edmonton (Canada), and Bergen (Norway) can’t make enough vitamin D from the sun for 4, 5, and 6 months out of the year, respectively. [78] In the southern hemisphere, residents of Buenos Aires (Argentina) and Cape Town (South Africa) make far less vitamin D from the sun during their winter months (June through August) than they can during their spring and summer months. [78] The body stores vitamin D from summer sun exposure, but it must last for many months. By late winter, many people in these higher-latitude locales are deficient. [79]

Note that because ultraviolet rays can cause skin cancer, it is important to avoid excessive sun exposure and in general, tanning beds should not be used.

Signs of Deficiency and Toxicity

Vitamin D deficiency may occur from a lack in the diet, poor absorption, or having a metabolic need for higher amounts. If one is not eating enough vitamin D and does not receive enough ultraviolet sun exposure over an extended period (see section above), a deficiency may arise. People who cannot tolerate or do not eat milk, eggs, and fish, such as those with a lactose intolerance or who follow a vegan diet, are at higher risk for a deficiency. Other people at high risk of vitamin D deficiency include:

• People with inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or other conditions that disrupt the normal digestion of fat. Vitamin D is a fat-soluble vitamin that depends on the gut’s ability to absorb dietary fat.
• People who are obese tend to have lower blood vitamin D levels. Vitamin D accumulates in excess fat tissues but is not easily available for use by the body when needed. Higher doses of vitamin D supplementation may be needed to achieve a desirable blood level. Conversely, blood levels of vitamin D rise when obese people lose weight.
• People who have undergone gastric bypass surgery, which typically removes the upper part of the small intestine where vitamin D is absorbed.

Conditions resulting from prolonged vitamin D deficiency:

• Rickets: A condition in infants and children of soft bones and skeletal deformities caused by failure of bone tissue to harden.
• Osteomalacia: A condition in adults of weak and softened bones that can be reversed with supplementation. This is different than osteoporosis, in which the bones are porous and brittle and the condition is irreversible.

Vitamin D toxicity most often occurs from taking supplements. The low amounts of the vitamin found in food are unlikely to reach a toxic level, and a high amount of sun exposure does not lead to toxicity because excess heat on the skin prevents D3 from forming. It is advised to not take daily vitamin D supplements containing more than 4,000 IU unless monitored under the supervision of your doctor.

Symptoms of toxicity:

• Weight loss
• Irregular heart beat
• Hardening of blood vessels and tissues due to increased blood levels of calcium, potentially leading to damage of the heart and kidneys

Did You Know?

Catching the sun’s rays in a sunny office or driving in a car unfortunately won’t help to obtain vitamin D as window glass completely blocks UVB ultraviolet light.

Vitamins and Minerals

• Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press, 2010. https://www.ncbi.nlm.nih.gov/books/NBK56070/
• Holick MF. Vitamin D deficiency. New England Journal of Medicine . 2007 Jul 19;357(3):266-81.
• Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Archives of pediatrics & adolescent medicine . 2004 Jun 1;158(6):531-7.
• Lips PT. Worldwide status of vitamin D nutrition. The Journal of steroid biochemistry and molecular biology . 2010 Jul 1;121(1-2):297-300.
• Robinson PD, Högler W, Craig ME, Verge CF, Walker JL, Piper AC, Woodhead HJ, Cowell CT, Ambler GR. The re-emerging burden of rickets: a decade of experience from Sydney. Archives of Disease in Childhood . 2006 Jul 1;91(7):564-8.
• Kreiter SR, Schwartz RP, Kirkman Jr HN, Charlton PA, Calikoglu AS, Davenport ML. Nutritional rickets in African American breast-fed infants. The Journal of pediatrics . 2000 Aug 1;137(2):153-7.
• Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics . 2008 Aug 1;122(2):398-417.
• Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative metaanalysis of randomized controlled trials. The Journal of Clinical Endocrinology & Metabolism . 2007 Apr 1;92(4):1415-23.
• Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Jama . 2005 May 11;293(18):2257-64.
• Cauley JA, LaCroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Annals of internal medicine . 2008 Aug 19;149(4):242-50.
• Cauley JA, Parimi N, Ensrud KE, Bauer DC, Cawthon PM, Cummings SR, Hoffman AR, Shikany JM, Barrett-Connor E, Orwoll E. Serum 25-hydroxyvitamin D and the risk of hip and nonspine fractures in older men. Journal of Bone and Mineral Research . 2010 Mar;25(3):545-53.
• Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Archives of internal medicine . 2009 Mar 23;169(6):551-61.
• Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database of Systematic Reviews . 2014(4).
• Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. Effect of vitamin D on falls: a meta-analysis. Jama . 2004 Apr 28;291(16):1999-2006.
• Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Journal of the American Geriatrics Society . 2007 Feb;55(2):234-9.
• Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Archives of internal medicine . 2006 Feb 27;166(4):424-30.
• Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ . 2009 Oct 1;339:b3692.
• Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Jama . 2010 May 12;303(18):1815-22.
• Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer?. International journal of epidemiology . 1980 Sep 1;9(3):227-31.
• Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Annals of epidemiology . 2009 Jul 1;19(7):468-83.
• McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR, Eliassen AH, Zeleniuch-Jacquotte A, Agnoli C, Albanes D, Barnett MJ. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. JNCI: Journal of the National Cancer Institute . 2019 Feb 1;111(2):158-69.
• Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Alimentary pharmacology & therapeutics . 2009 Jul;30(2):113-25.
• Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case–control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. Journal of the National Cancer Institute . 2007 Jul 18;99(14):1120-9.
• Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. American journal of preventive medicine . 2007 Mar 1;32(3):210-6.
• Giovannucci E. Epidemiological evidence for vitamin D and colorectal cancer. Journal of Bone and Mineral Research . 2007 Dec;22(S2):V81-5.
• Lin J, Zhang SM, Cook NR, Manson JE, Lee IM, Buring JE. Intakes of calcium and vitamin D and risk of colorectal cancer in women. American journal of epidemiology . 2005 Apr 15;161(8):755-64.
• Huncharek M, Muscat J, Kupelnick B. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutrition and cancer . 2008 Dec 31;61(1):47-69.
• Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, Hankinson SE. Plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiology and Prevention Biomarkers . 2005 Aug 1;14(8):1991-7.
• Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC. Vitamin D and prevention of breast cancer: pooled analysis. The Journal of steroid biochemistry and molecular biology . 2007 Mar 1;103(3-5):708-11.
• Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Archives of Internal Medicine . 2007 May 28;167(10):1050-9.
• Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer causes & control . 2007 Sep 1;18(7):775-82.
• Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA, Hollis BW, Graubard BI, Berg CD, Ziegler RG. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiology and Prevention Biomarkers . 2008 Apr 1;17(4):889-94.
• Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine . 2006 Feb 16;354(7):684-96.
• Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O’Sullivan MJ, Yasmeen S, Hiatt RA. Calcium plus vitamin D supplementation and the risk of breast cancer. JNCI: Journal of the National Cancer Institute . 2008 Nov 19;100(22):1581-91.
• Holick MF. Calcium plus vitamin D and the risk of colorectal cancer. N Engl J Med . 2006; 354:2287-8; author reply 2287-8.
• Giovannucci E. Calcium plus vitamin D and the risk of colorectal cancer. N Engl J Med . 2006; 354:2287-8; author reply 2287-8.
• Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D’Agostino D, Friedenberg G. Vitamin D supplements and prevention of cancer and cardiovascular disease. New England Journal of Medicine . 2019 Jan 3;380(1):33-44.
• Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Annals of Oncology . 2019 May 1;30(5):733-43.
• Giovannucci E. Expanding roles of vitamin D. J Clin Endocrinol Metab . 2009; 94:418-20.
• Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circulation research . 2014 Jan 17;114(2):379-93.
• Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Molecular aspects of medicine . 2008 Dec 1;29(6):361-8.
• Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Archives of internal medicine . 2008 Jun 9;168(11):1174-80.
• Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. The Journal of Clinical Endocrinology & Metabolism . 2008 Oct 1;93(10):3927-35.
• Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, März W. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke . 2008 Sep 1;39(9):2611-3.
• Booth TW, Lanier PJ. Vitamin D deficiency and risk of cardiovascular disease. Circulation Res117. 2008;503:511.
• Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Archives of internal medicine . 2008 Jun 23;168(12):1340-9.
• Elamin MB, Abu Elnour NO, Elamin KB, Fatourechi MM, Alkatib AA, Almandoz JP, Liu H, Lane MA, Mullan RJ, Hazem A, Erwin PJ. Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism . 2011 Jul 1;96(7):1931-42.
• Mitri J, Pittas AG. Vitamin D and diabetes. Endocrinol Metab Clin North Am . 2014 Mar;43(1):205-32.
• Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes care . 2006 Mar 1;29(3):650-6.
• Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O’Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M; D2d Research Group. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med . 2019 Aug 8;381(6):520-530
• Dobson R, Giovannoni G. Multiple sclerosis–a review. European journal of neurology . 2019 Jan;26(1):27-40.
• Goldberg P. Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence: (A viewpoint) part 1: sunlight, dietary factors and epidemiology. International Journal of Environmental Studies . 1974 Jan 1;6(1):19-27.
• Munger KL, Zhang SM, O’reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology . 2004 Jan 13;62(1):60-5.
• Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Jama . 2006 Dec 20;296(23):2832-8.
• Salzer J, Hallmans G, Nyström M, Stenlund H, Wadell G, Sundström P. Vitamin D as a protective factor in multiple sclerosis. Neurology . 2012 Nov 20;79(21):2140-5.
• Munger KL, Hongell K, Åivo J, Soilu-Hänninen M, Surcel HM, Ascherio A. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology . 2017 Oct 10;89(15):1578-83.
• Ascherio A, Munger KL, White R, Köchert K, Simon KC, Polman CH, Freedman MS, Hartung HP, Miller DH, Montalbán X, Edan G. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA neurology . 2014 Mar 1;71(3):306-14.
• Fitzgerald KC, Munger KL, Köchert K, Arnason BG, Comi G, Cook S, Goodin DS, Filippi M, Hartung HP, Jeffery DR, O’Connor P. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA neurology . 2015 Dec 1;72(12):1458-65.
• Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention—an update. InSeminars in neurology 2016 Apr (Vol. 36, No. 02, pp. 103-114). Thieme Medical Publishers.
• Gillespie KM. Type 1 diabetes: pathogenesis and prevention. Cmaj . 2006 Jul 18;175(2):165-70.
• Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. The Lancet . 2001 Nov 3;358(9292):1500-3.
• Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. The Lancet . 2016 Jun 4;387(10035):2340-8.
• Munger KL, Levin LI, Massa J, Horst R, Orban T, Ascherio A. Preclinical serum 25-hydroxyvitamin D levels and risk of type 1 diabetes in a cohort of US military personnel. American journal of epidemiology . 2013 Mar 1;177(5):411-9.
• Hope-Simpson RE. The role of season in the epidemiology of influenza. Epidemiology & Infection . 1981 Feb;86(1):35-47.
• Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiology & Infection . 2006 Dec;134(6):1129-40.
• Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of internal medicine . 2009 Feb 23;169(4):384-90.
• Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. The American journal of clinical nutrition . 2010 May 1;91(5):1255-60.
• Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ . 2017 Feb 15;356:i6583.
• Zasloff M. Fighting infections with vitamin D. Nature medicine . 2006 Apr;12(4):388-90.
• Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. International journal of epidemiology . 2008 Feb 1;37(1):113-9.
• Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutrition reviews . 2009 May 1;67(5):289-93.
• Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Archives of internal medicine . 2007 Sep 10;167(16):1730-7.
• Giovannucci E. Can vitamin D reduce total mortality?. Archives of Internal Medicine . 2007 Sep 10;167(16):1709-10.
• Sutherland JP, Zhou A, Hyppönen E. Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Nonlinear Mendelian Randomization Study. Annals of Internal Medicine . 2022 Oct 25.
• Navale SS, Mulugeta A, Zhou A, Llewellyn DJ, Hyppönen E. Vitamin D and brain health: an observational and Mendelian randomization study. The American Journal of Clinical Nutrition . 2022 Apr 22.
• Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hyppönen E, Berry J, Vieth R, Lanham-New S. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. The American journal of clinical nutrition . 2012 Jun 1;95(6):1357-64.
• Wilson LR, Tripkovic L, Hart KH, Lanham-New SA. Vitamin D deficiency as a public health issue: using vitamin D 2 or vitamin D 3 in future fortification strategies. Proceedings of the Nutrition Society . 2017 Aug;76(3):392-9.
• Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis.  Am J Clin Nutr . 2004; 79:362-71
• Holick MF. Vitamin D deficiency.  N Engl J Med . 2007; 357:266-81.
• Hahn J, Cook NR, Alexander EK, Friedman S, Walter J, Bubes V, Kotler G, Lee IM, Manson JE, Costenbader KH. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ . 2022 Jan 26;376:e066452.
• LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med . 2022 Jul 28;387:299-309.
• LeBoff MS, Murata EM, Cook NR, Cawthon P, Chou SH, Kotler G, Bubes V, Buring JE, Manson JE. VITamin D and OmegA-3 TriaL (VITAL): effects of vitamin D supplements on risk of falls in the US population. The Journal of Clinical Endocrinology & Metabolism . 2020 Sep;105(9):2929-38.
• Ames BN, Grant WB, Willett WC. Does the high prevalence of vitamin D deficiency in African Americans contribute to health disparities?. Nutrients . 2021 Feb 3;13(2):499. *W.B.G. receives funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR). The other authors have no conflicts of interest to declare.

Last reviewed March 2023

Terms of Use

The contents of this website are for educational purposes and are not intended to offer personal medical advice. You should seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The Nutrition Source does not recommend or endorse any products.

Should you take vitamin D? Here’s the science

Some people take too much, and too many get too little. Experts explain who needs D supplements, and why.

By Katarina Zimmer / Knowable Magazine | Published Apr 21, 2024 12:00 PM EDT

This article was originally featured on  Knowable Magazine .

Nutritional science is supposed to chart a course to our healthier selves. But contradictory scientific results and interpretations can muddy the waters—and few nutrients have recently demonstrated that more clearly than vitamin D.

At one point, it seemed that everyone should be taking vitamin D supplements, and that doing so would protect against a whole host of maladies, from bone problems to heart disease and cancer. More recently, new studies appear to have debunked many of those claims.

But a closer look at the research reveals a more nuanced message around vitamin D supplements: They can be key to correcting deficiencies, though people who already have enough—which is most of the American public—are generally unlikely to see benefits from taking large doses. Experts have come to worry about supplement enthusiasts overdosing in the belief that more is better or, at the other extreme, some nutrient-deprived people shunning them altogether.

Ultimately, says  Roger Bouillon , an endocrinologist at KU Leuven in Belgium, “it’s like for most things. You need an optimal amount: not too little, not too much.”

Yet working out who needs vitamin D supplements, how much, and what the specific health benefits are, remains tricky, with questions remaining. Here’s some of what we know.

What does vitamin D do, and where does it come from?

The importance of vitamin D  came to light at the start of the Industrial Revolution  in the late 1700s, when people in northern climes crowded in dark, polluted cities and spent more time working indoors. The majority of children in cities like Boston developed rickets, wherein bones soften, weaken and often deform.

Scientists eventually discovered that exposure to sunlight would cure and prevent the disease. Later, researchers learned that UV light from  the Sun  kick-starts a reaction that generates vitamin D. The vitamin gets converted into its active form in the kidneys and then is shuttled to the intestine, where it stimulates cells to move calcium, a key building block of  bones , into the bloodstream. “The most important thing vitamin D does is intestinal calcium absorption,” says  Sylvia Christakos , a biochemist at Rutgers New Jersey Medical School.

Though the effects are most severe in children, vitamin D deficiencies can also cause a  softening of adult bones called osteomalacia , and increase the risk of osteoporosis, where bones become weak, brittle and  more prone to fractures . Though experts debate what exactly constitutes a vitamin D deficiency—and know that healthy levels may vary from person to person—everyone agrees that blood levels should not go below 12 nanograms per milliliter to avoid severe deficiency.

Such severe deficiencies—and the bone ailments they cause—are still rampant across the world. Surprisingly,  more than 30 percent of people in some sunny Middle Eastern countries  are severely deficient, which may be partly attributed to skin-covering traditional clothing. By contrast, in  Finland , a sun-deprived country with dark winters, severe deficiencies are relatively rare, thanks to government policies to fortify dairy products with extra vitamin D.

In contrast, around  20 percent of the United Kingdom’s population is severely deficient  by some estimates, due to its northern, cloudy weather and a lack of fortified foods. The United States, where many dairy products, and some juices and breakfast cereals, are fortified, falls somewhere in the middle:  Around 6 percent of people are severely deficient . “For the most part in the US, we don’t see frank nutrient deficiencies,” says  Regan Bailey , a nutrition expert at Texas A&M University who recently coauthored a  review on supplement use among the public  in the  Annual Review of Nutrition.  (Some research groups have produced much larger deficiency estimates by using blood level thresholds that many experts say are too high to qualify as nutrient deficiencies.)

Since 2010, the National Academy of Medicine has recommended  relatively modest daily doses : 400 international units (IUs) for babies, 600 IUs for everyone up to age 70 and 800 IUs for older people. These doses are designed to achieve levels of 20 nanograms per milliliter—more than enough to avoid severe deficiencies—for otherwise healthy people in the United States.

Most people should be able to get these doses through brief sun exposure, says John Christopher Gallagher, an endocrinologist at Creighton University in Omaha, Nebraska. Measuring vitamin D production in the skin is not an exact science, but five to 10 minutes’ daily exposure without sunblock of just the face, neck, hands and arms should do the trick in the sunnier months, even in temperate places like Boston. While it’s entirely possible to get enough vitamin D this way, the official stance of the American Academy of Dermatology is to not get vitamin D from sun exposure.

Fortified dairy products and other foods will also provide enough. Foods that naturally contain vitamin D, such as fatty fish, egg yolks, red meat, liver and irradiated or sun-dried mushrooms, which are especially rich in vitamin D due to their increased exposure to UV light, can also help. “If you’re out and about and you have sun exposure during some months of the year,” Gallagher says, “you probably get plenty of vitamin D.” That’s especially true if you have enough dairy in your diet.

Does anyone need supplements?

Generally, people need supplements only when they’re not likely to get enough from natural or dietary sources, health experts say. Deficiency-prone populations include breastfed infants who don’t get fortified formula, elderly people (whose skin makes vitamin D less efficiently) and pregnant women. People with dark skin tones should also take care to get sufficient vitamin D, because melanin pigmentation in the skin blocks UV light. People in northern latitudes like England “should all take a supplement during the winter,” adds nutritional scientist  Susan Lanham-New  of the University of Surrey in the UK, although that’s less important in places like the United States that have food fortification.

Experts worry that it’s often the people already getting enough vitamin D through diet and lifestyle who are the most likely to take supplements, Christakos notes. Meanwhile, communities who need vitamin D supplements the most might not realize their need and may have read news reports suggesting that the supplements aren’t necessary.

That’s an especially dangerous message in countries where deficiencies are common—for instance in the UK, where physicians still see children with deficiency-related ailments, says  Martin Hewison , a molecular endocrinologist at the University of Birmingham in that country. One of his UK colleagues is struggling to persuade some of her vitamin D-deficient patients to take supplements because they believe it is a waste of time.

For anyone concerned that they’re not getting enough vitamin D, experts say that up to 1,000 IUs a day would more than suffice. If possible, Lanham-New adds, make sure it’s vitamin D3, a version typically extracted from sheep wool that  appears to be better at raising vitamin D blood levels than D2 , which is often vegan and mushroom-based.

But avoid the high doses—of 5,000, 10,000 or 20,000 IUs, or even higher—that can be found in drugstores or online, stresses  JoAnn Manson , an endocrinologist and epidemiologist at Brigham and Women’s Hospital and Harvard Medical School. Too much vitamin D, even when taken occasionally, can sometimes cause bone health to deteriorate and lead to an overdose of calcium in the blood and urine, resulting in nausea and even kidney failure. There are reports of people in the UK and US  ending up in the hospital after taking excessive doses .

Some experts have advised that Black Americans, in particular, take higher doses of supplements—for instance, 2,500 IUs—as they’re especially prone to low levels. But here’s a mystery: Even though 17.5 percent of African Americans have deficient levels of vitamin D, those vitamin-deficient Blacks tend to have better bone health than comparably deficient white Americans, notes biomedical scientist  LaVerne Brown  of the National Institutes of Health. It’s possible, she says, that African Americans need less vitamin D than other populations, perhaps because they’re better at metabolizing vitamin D to its final active form. If that’s true, then high doses may have a greater risk of causing harm in African Americans.

“We just don’t have the studies that are focusing on these populations in order to come up with definitive answers,” Brown says. In the meantime, an  expert panel meeting in 2017  concluded that the current recommended intake should be enough for African Americans, the same as everyone else. “Anything above 800 IU, it’s not clear that there’s a real need for that,” Brown says.

Could higher doses have benefits?

More than two decades ago, scientists began to make observations suggesting that vitamin D at higher doses could have benefits beyond bone health. Dozens of studies described strong correlations between people’s vitamin D levels and a range of diseases like cardiovascular disease, type 2 diabetes and certain cancers. The lower someone’s vitamin D levels were, the likelier they were to have these diseases, while higher levels were associated with being healthier.

Other research showed that  many cell types—in the lungs, heart and immune system—have receptors for the vitamin to dock onto , hinting at far-reaching effects across the body. Giving vitamin D to lab mice with conditions mimicking human diseases could often improve their ailments. Vitamin D, it seemed, might help to tackle the major diseases of our time.

From New Zealand to Europe to North America, scientists launched large clinical trials, enrolling thousands of people over multiple years, to test whether vitamin D supplements would decrease their risk of disease. Importantly, the studies focused on members of the general public, who were largely healthy and had adequate levels of vitamin D. These people then received relatively large doses, of 2,000 or 4,000 IUs or even higher. The studies asked whether there were benefits from getting more than the recommended dietary allowance and ending up with blood levels even higher than 20 or 30 nanograms per milliliter, Manson explains.

To the disappointment of many scientists, giving these generous doses to healthy people  didn’t change their risk of developing cancer, heart disease  or asthma, nor did it significantly prevent the  progression to type 2 diabetes . Extra vitamin D beyond the recommended levels didn’t even do anything to  improve bone health  or  reduce the risk of fractures .

There may be a simple biological reason why more vitamin D isn’t necessarily better: The version of vitamin D found in supplements needs to be converted in the liver and kidneys to reach its final, active form—and that process is probably tightly controlled, says Bouillon. “The body regulates that so you have the exact amount, and not more than what you need.”

The takeaway, many experts agree, is that most healthy people aren’t going to benefit from high doses of vitamin D if they already have enough. The tantalizing associations that led researchers to suspect additional powers of vitamin D could have been an illusion: People with illnesses may end up with lower vitamin D levels because of the diseases themselves, or the unhealthy lifestyles that caused them, says Bouillon.

Are larger doses ever helpful?

A few of the recent trials hinted that some groups of people may benefit from higher doses, but these possible benefits need to be confirmed in further studies, says Manson, who ran one of the trials, called VITAL, which studied nearly 26,000 US adults over five years and looked at supplements of 2,000 IUs of vitamin D as well as omega-3 fatty acids. In that study, participants  didn’t have a lower risk of developing cancer  but they did have a 25 percent lower chance of it metastasizing or becoming fatal. Perhaps, says Manson, vitamin D makes tumors less likely to metastasize and kill. VITAL also reported that high doses of vitamin D made people less likely to develop certain autoimmune conditions like rheumatoid arthritis, psoriasis and lupus.

Manson notes that these benefits appeared to be most visible among people with a healthy weight, compared to overweight or obese participants. But she cautions that more research is needed to understand these observations and confirm the observed benefits of larger doses.

Physicians in clinical practice, of course, have leeway in prescribing higher doses to certain people as they see fit, such as for osteoporosis patients, or people with conditions that hamper the absorption of vitamin D through the diet, like Crohn’s disease and ulcerative colitis.

What don’t we know yet?

As they probe potential effects of higher doses in non-deficient people, researchers still don’t know how many roles vitamin D might have. The trouble is that recent trials don’t tell us whether having  enough  vitamin D is important for maintaining healthy heart function or avoiding cancer, for instance—only that having more than that won’t help in most cases.

To prove that adequate vitamin D has health benefits beyond keeping bones strong, scientists need more research in which some deficient people receive supplements and the rest receive a placebo. But such studies are hard to conduct in places like the US, where severe deficiencies are relatively rare. It’s also not ethically justifiable to seek out people who are deficient and then deprive half of them of much-needed supplements, because of the risk of poor bone health in vitamin D-deficient people.

Some scientists believe that having enough vitamin D could be key to maintaining heart and immune system health and preventing diabetes and cancer—and perhaps even be important for brain function, athletic performance and other claims. The evidence is particularly strong in the immune system, says Hewison, whose research points to key roles of vitamin D in immune cells; and indeed, human trials that by chance included some deficient people show benefits of supplementation in warding off infections.

But there just aren’t enough data yet, Hewison says. “I think this is the issue facing the field as a whole.”

This article originally appeared in  Knowable Magazine , an independent journalistic endeavor from Annual Reviews. Sign up for the  newsletter .

Editor’s note: This story was updated on April 23, 2024, to correct editorial style for identifying racial groups.

Like science, tech, and DIY projects?

Sign up to receive Popular Science's emails and get the highlights.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 22 January 2024

A view on vitamin D: a pleiotropic factor?

• Andrea Giustina 1 , 2 ,
• Marise Lazaretti-Castro 3 ,
• Adrian R. Martineau 4 ,
• Rebecca S. Mason   ORCID: orcid.org/0000-0003-1534-9697 5 ,
• Clifford J. Rosen   ORCID: orcid.org/0000-0003-3436-8199 6 &
• Inez Schoenmakers 7  

Nature Reviews Endocrinology volume  20 ,  pages 202–208 ( 2024 ) Cite this article

1106 Accesses

2 Citations

17 Altmetric

Metrics details

• Endocrine system and metabolic diseases
• Public health

Vitamin D is precursor of the steroid hormone calcitriol and has important functions throughout the body, including increasing intestinal absorption of calcium, magnesium and phosphate. Vitamin D deficiency has been linked with a range of disorders, including several bone diseases. However, large trials of vitamin D supplementation have produced mixed results. Here, experts from around the world discuss several key questions in the vitamin D research and clinical fields.

This is a preview of subscription content, access via your institution

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 12 print issues and online access

195,33 € per year

only 16,28 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Moreira, C. A. et al. Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC). Arch. Endocrinol. Metab. 64 , 462–478 (2020).

PubMed   PubMed Central   Google Scholar  

Bouillon, R. et al. Vitamin D and human health: lessons from the VDR receptor null mice. Endocr. Rev. 29 , 726–776 (2008).

Article   CAS   PubMed   PubMed Central   Google Scholar  

De Silva, W. G. M. et al. Evidence for involvement of nonclassical pathways in the protection from UV-induced DNA damage by vitamin D-related compounds. JBMR Plus 5 , e10555 (2021).

Article   PubMed   PubMed Central   Google Scholar  

Maretzke, F. et al. Role of vitamin D in preventing and treating selected extraskeletal diseases – an umbrella review. Nutrients 12 , 969 (2020).

Bilezikian, J. P. et al. Vitamin D: dosing, levels, form, and route of administration: does one approach fit all? Rev. Endocr. Metab. Disord. 22 , 1201–1218 (2021).

di Filippo, L. et al. Low vitamin D levels predict outcomes of COVID-19 in patients with both severe and non-severe disease at hospitalization. Endocrine 80 , 669–683 (2023).

di Filippo, L. et al. Low vitamin D levels are associated with long COVID syndrome in COVID-19 survivors. J. Clin. Endocrinol. Metab. 108 , e1106–e1116 (2023).

di Filippo, L. et al. Lack of vitamin D predicts impaired long-term immune response to COVID-19 vaccination. Endocrine 82 , 536–541 (2023).

Jolliffe, D. A. et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 9 , 276–292 (2021).

Article   CAS   PubMed   Google Scholar  

Jolliffe, D. A. et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax 74 , 337–345 (2019).

Article   PubMed   Google Scholar  

Middelkoop, K. et al. Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicentre phase 3 double-blind randomised placebo-controlled trial (ViDiKids). Int. J. Infect. Dis. 134 , 63–70 (2023).

Jolliffe, D. A. et al. Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data. Eur. Respir. J. 53 , 1802003 (2019).

Chakhtoura, M. et al. Vitamin D supplementation and fractures in adults: a systematic umbrella review of meta-analyses of controlled trials. J. Clin. Endocrinol. Metab. 107 , 882–898 (2022).

Hahn, J. et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 376 , e066452 (2022).

Keum, N., Chen, Q. Y., Lee, D. H., Manson, J. E. & Giovannucci, E. Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials. Br. J. Cancer 127 , 872–878 (2022).

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D (National Academies Press, 2011).

LeBoff, M. S. et al. Supplemental vitamin D and incident fractures in midlife and older adults. N. Engl. J. Med 387 , 299–309 (2022).

Schoenmakers, I. & Jones, K.S. in Feldman and Pike’s Vitamin D (eds Hewison, M., Bouillon, R. & Walsh, J.) 633–668 (Elsvier, 2024).

Borba, V. Z. C., Lazaretti-Castro, M., Moreira, S. D. S., de Almeida, M. C. C. & Moreira, E. D. Jr. Epidemiology of vitamin D (EpiVida) – a study of vitamin D status among healthy adults in Brazil. J. Endocr. Soc. 7 , bvac171 (2022).

Foroni, M. Z. et al. Serum 25 hydroxyvitamin D concentrations in individuals over 80 years old and their correlations with musculoskeletal and health parameters. Endocrine 79 , 559–570 (2023).

Luxwolda, M. F., Kuipers, R. S., Kema, I. P., Dijck-Brouwer, D. A. & Muskiet, F. A. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br. J. Nutr. 108 , 1557–1561 (2012).

Chapuy, M. C. et al. Calcium and vitamin D to prevent hip fractures in elderly women. N. Engl. J. Med 327 , 1637–1642 (1992).

Bouillon, R. Comparative analysis of nutritional guidelines for vitamin D. Nat. Rev. Endocrinol. 13 , 466–479 (2017).

Turck, D. et al. Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate. EFSA J. 21 , e08145 (2023).

Download references

Author information

Authors and affiliations.

Institute of Endocrine and Metabolic Sciences, San Raffaele Vita Salute University, Milano, Italy

• Andrea Giustina

IRCCS San Raffaele Hospital, Milano, Italy

Bone and Mineral Metabolism Research Unit, at Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Marise Lazaretti-Castro

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Adrian R. Martineau

School of Life and Environmental Sciences and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia

Rebecca S. Mason

Maine Health Institute for Research, Scarborough, ME, USA

Clifford J. Rosen

University of East Anglia, Medical school, Norwich, UK

Inez Schoenmakers

You can also search for this author in PubMed   Google Scholar

Contributions

Andrea Giustina. A.G. is Professor of Endocrinology and Metabolism at San Raffaele Vita-Salute University and Head of Endocrinology at IRCCS San Raffaele Hospital in Milano, Italy, where he is the Director of the Postgraduate Program in Endocrinology and of the Bone Center. He is past president of the European Society of Endocrinology and of the Pituitary Society.

Marise Lazaretti-Castro. M.L.-C. is Associate Professor of Endocrinology at Federal University of Sao Paulo (UNIFESP), Brazil, where she heads the Bone and Mineral Research Unit. In her career as a graduate adviser, she has trained more than 20 doctors and 30 Masters students, and has co-authored >200 journal articles and book chapters and lectured extensively in her area of expertise. M.L.-C. is a former President of the Brazilian Society for Bone Assessment, Osteoporosis and Osteometabolism, and is a member of Ex-Officio RAC Board of the International Osteoporosis Foundation.

Adrian R. Martineau. A.R.M. is Clinical Professor of Respiratory Infection and Immunity at Queen Mary University of London, UK. He leads a programme of laboratory research, clinical trials and meta-analysis characterizing effects of vitamin D on immune function and human health, with a focus on prevention and treatment of respiratory infections.

Rebecca S. Mason. R.S.M. is a medical doctor and scientist at the University of Sydney, Australia, with career awards for vitamin D and bone and mineral research. She contributed to Australasian position statements on vitamin D and to national guidelines on vitamin D testing and on the risks and benefits of sunlight exposure.

Clifford J. Rosen. C.J.R. is a board-certified endocrinologist and bone biologist. He received his MD at SUNY Syracuse, NY, USA, residency at UMass Medical Center Affiliated Hospitals, MA, USA, and fellowship at Dartmouth Medical Center, NH, USA. He has authored nearly 400 peer-reviewed papers and oversees a translational laboratory at Maine Medical Center Research Institute, ME, USA, that is continuously supported by four NIH grants. He is past president of the American Society of Bone and Mineral Research and is an associate editor of New England Journal of Medicine .

Inez Schoenmakers. I.S. is an Associate Professor at the Medical School, University of East Anglia, UK. Her research is focused on the investigation of calcium, phosphate and vitamin D metabolism, particularly in relation to bone health and how this is influenced by ageing, kidney function, nutrition and ethnicity. Her work contributed to recommendations on vitamin D requirements and safety for population health and patient management. These included guidelines formulated by the UK Scientific Advisory Committee on Nutrition, the European Food Safety Authority, the Royal Osteoporosis Society and the WHO review of evidence for recommendations for the prevention of nutritional rickets.

Corresponding authors

Correspondence to Andrea Giustina , Marise Lazaretti-Castro , Adrian R. Martineau , Rebecca S. Mason , Clifford J. Rosen or Inez Schoenmakers .

Ethics declarations

Competing interests.

A.G. is a consultant for Abiogen, Ipsen, Pfizer, Recordati and Takeda, and is a recipient of research grants (to his institution) from Pfizer and Takeda. A.R.M. declares receipt of funding in the last 36 months to support vitamin D research from the following companies which manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. A.R.M. also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; and receipt of a speaker fee from the Linus Pauling Institute. A.R.M. declares participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to Reduce Musculoskeletal Morbidity and Immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. R.S.M. has received speaker fees from Sanofi Australia. M.L.-C., C.J.R. and I.S. declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Giustina, A., Lazaretti-Castro, M., Martineau, A.R. et al. A view on vitamin D: a pleiotropic factor?. Nat Rev Endocrinol 20 , 202–208 (2024). https://doi.org/10.1038/s41574-023-00942-0

Download citation

Accepted : 12 December 2023

Published : 22 January 2024

Issue Date : April 2024

DOI : https://doi.org/10.1038/s41574-023-00942-0

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

New insights into the vitamin d/pth axis in endocrine-driven metabolic bone diseases.

• Luigi di Filippo
• John P. Bilezikian

Endocrine (2024)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Taking high-dose vitamin D supplements for five years did not affect the incidence of cardiovascular disease or cancer

A trial by the University of Eastern Finland found that taking a much higher dose of vitamin D than recommended for five years did not affect total mortality or the incidence of cardiovascular disease or cancer in older men and women.

In population studies, low levels of vitamin D in the body have been linked to an increased risk of many chronic diseases as well as premature death. However, it cannot be directly deduced from such observational studies whether the use of vitamin D supplementation can reduce the risk of disease or death. The early 2010s saw the commencement of large-scale vitamin D trials in several countries examining the effects of higher than recommended doses of vitamin D on the risk of developing diseases. One of these was the Finnish Vitamin D Trial (FIND) conducted at the University of Eastern Finland in 2012-2018.

In the FIND trial, 2,495 participants (men 60 years or older and women 65 years or older) were randomised for five years to either the placebo group or the groups that received either 40 or 80 micrograms (1600 or 3200 IU) of vitamin D 3 per day. All participants were free of cardiovascular disease and cancer at the start of the trial and were allowed to use their own vitamin D supplement of up to 20 micrograms (800 IU) per day (the recommended intake for this age group at the time when the trial was started). At the beginning and during the trial, research forms were used to collect comprehensive information from the subjects on lifestyle, nutrition, risk factors for and the incidence of diseases. Information on the incidence of diseases and on deaths was also obtained from national health registers. Approximately one fifth of the randomly selected subjects underwent more detailed examinations and provided blood samples.

Majority were not deficient in vitamin D at the start of the trial

During the five years of the trial, 119 participants developed cardiovascular disease, 129 subjects were diagnosed with cancer and 19 died. There was no statistically significant difference in the number of events between the groups. The vitamin D doses proved to be safe as no differences in side effects were observed between the groups. In the sub-sample examined in more detail, the mean blood vitamin D (calcidiol) concentration, was 75 nmol/L (30 ng/mL) at baseline. After one year, the mean calcidiol concentration was 100 nmol/L (40 ng/mL) in the group taking 40 micrograms of vitamin D per day and 120 nmol/L (48 ng/mL) in the group taking 80 micrograms of vitamin D per day. There was no significant change in the calcidiol concentrations in the placebo group. Only 9% of subjects had low vitamin D levels at baseline, i.e., they had a blood calcidiol concentration of less than 50 nmol/L (20 ng/mL).

The findings of the FIND trial are well in line with other similar studies that have shown that taking higher doses of vitamin D than recommended for many years does not have a significant effect on the risk of developing cardiovascular disease or cancer if the body's vitamin D status is already adequate. In Finland, the average vitamin D intake of the population has increased since the early 2000s due to, among other things, the vitamin D supplementation of vegetable oil spreads and liquid dairy products as well as the increased use of vitamin D supplements. Securing one's vitamin D intake with vitamin D supplements is still recommended, especially during the winter, if the diet is low in sources of vitamin D, such as fish or vitamin D-fortified foods. In Finland, vitamin D supplementation of 10 micrograms per day (400 IU) is recommended for the adult population; the recommendation is 20 micrograms per day (800 IU) for those aged 75 and over. However, the study does not support the use of large vitamin D doses for prevention of cardiovascular diseases or cancer.

In addition to these main findings, the FIND trial will provide comprehensive reports on the effects of vitamin D supplementation on, among other things, type 2 diabetes, fractures and falls, mood changes, infections, pain conditions, and other outcomes.

• Dietary Supplements and Minerals
• Mammography
• Breast cancer
• Cervical cancer

Story Source:

Materials provided by University of Eastern Finland . Note: Content may be edited for style and length.

Journal Reference :

• Jyrki K Virtanen, Tarja Nurmi, Antti Aro, Elizabeth R Bertone-Johnson, Elina Hyppönen, Heikki Kröger, Christel Lamberg-Allardt, JoAnn E Manson, Jaakko Mursu, Pekka Mäntyselkä, Sakari Suominen, Matti Uusitupa, Ari Voutilainen, Tomi-Pekka Tuomainen, Sari Hantunen. Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial—a randomized controlled trial . The American Journal of Clinical Nutrition , 2022; DOI: 10.1093/ajcn/nqab419

Cite This Page :

Explore More

• Mice Given Mouse-Rat Brains Can Smell Again
• New Circuit Boards Can Be Repeatedly Recycled
• Collisions of Neutron Stars and Black Holes
• Advance in Heart Regenerative Therapy
• Bioluminescence in Animals 540 Million Years Ago
• Profound Link Between Diet and Brain Health
• Loneliness Runs Deep Among Parents
• Food in Sight? The Liver Is Ready!
• Acid Reflux Drugs and Risk of Migraine
• Do Cells Have a Hidden Communication System?

Trending Topics

Strange & offbeat.

• Share full article

Advertisement

Supported by

Study Finds Another Condition That Vitamin D Pills Do Not Help

The vitamin pills do not prevent bone fractures in most people or protect against many other diseases, adding to questions about medical guidance many now take for granted.

By Gina Kolata

The idea made so much sense it was almost unquestioningly accepted: Vitamin D pills can protect bones from fractures. After all, the body needs the vitamin for the gut to absorb calcium, which bones need to grow and stay healthy.

But now, in the first large randomized controlled study in the United States, funded by the federal government, researchers report that vitamin D pills taken with or without calcium have no effect on bone fracture rates. The results, published Thursday in The New England Journal of Medicine , hold for people with osteoporosis and even those whose blood tests deemed them vitamin D deficient.

These results followed other conclusions from the same study that found no support for a long list of purported benefits of vitamin D supplements.

So, for the millions of Americans who take vitamin D supplements and the labs that do more than 10 million vitamin D tests each year, an editorial published along with the paper has some advice: Stop.

“Providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements and people should stop taking vitamin D supplements in order to prevent major diseases or extend life,” wrote Dr. Steven R. Cummings, a research scientist at the California Pacific Medical Center Research Institute, and Dr. Clifford Rosen, a senior scientist at the the MaineHealth Institute for Research. Dr. Rosen is an editor at The New England Journal of Medicine.

There are exceptions, they say: People with conditions like celiac or Crohn’s disease need vitamin D supplements, as do those who live in conditions where they are deprived of sunshine and may not eat enough foods that are routinely supplemented with vitamin D, such as cereals and dairy products to help them absorb calcium.

Getting into such a severe vitamin D-deprived state is “very hard to do in the general population,” Dr. Cummings said.

The two scientists know that in making such strong statements they are taking on vitamin sellers, testing labs and advocates who have claimed that taking vitamin D, often in huge amounts, can cure or prevent a wide variety of ailments and even help people live longer.

Doctors often check for vitamin D levels as part of routine blood tests.

The study involved 25,871 participants — men aged 50 and older and women 55 and older — who were assigned to take 2,000 international units of vitamin D each day or a placebo.

The research was part of a comprehensive vitamin D study called VITAL. It was funded by the National Institutes of Health and began after an expert group convened by what is now the National Academy of Medicine, a nonprofit organization, examined the health effects of vitamin D supplements and found little evidence. The expert group’s members were supposed to come up with a minimum daily requirement for the vitamin but found that most clinical trials that had studied the subject were inadequate, making them ask if there was any truth to the claims that vitamin D improved health.

The prevailing opinion at the time was that vitamin D was likely to prevent bone fractures. Researchers thought that as vitamin D levels fell, parathyroid hormone levels would increase at a detriment to bones.

Dr. Rosen said those concerns led him and the other members of the National Academy of Medicine’s expert group to set what he called an “arbitrary value” of 20 nanograms per milliliter of blood as the goal for vitamin D levels and to advise people to get 600 to 800 international units of vitamin D supplements to achieve that goal.

Labs in the United States then arbitrarily set 30 nanograms per milliliter as the cutoff point for normal vitamin D levels, a reading so high that almost everyone in the population would be considered vitamin D deficient.

The presumed relationship between vitamin D and parathyroid levels has not held up in subsequent research, Dr. Rosen said. But uncertainty continued, so the National Institutes of Health funded the VITAL trial to get some solid answers about vitamin D’s relationship to health.

The first part of VITAL, previously published, found that vitamin D did not prevent cancer or cardiovascular disease in trial participants. Nor did it prevent falls , improve cognitive functioning , reduce atrial fibrillation , change body compositio n, reduce migraine frequency , improve stroke outcomes , protect against macular degeneration or reduce knee pain .

Another large study, in Australia, found that people taking the vitamin did not live longer .

Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital in Harvard Medical School and the leader of the main VITAL trial, said the study was so large it included thousands of people with osteoporosis or with vitamin D levels in a range considered low or “insufficient.” That allowed the investigators to determine that they also received no benefit for fracture reduction from the supplement.

“That will surprise many,” Dr. Manson said. “But we seem to need only small-to-moderate amounts of the vitamin for bone health. Larger amounts do not confer greater benefits.”

The bone study’s first author and principal investigator, Dr. Meryl S. LeBoff, an osteoporosis expert at Brigham and Women’s Hospital, said she was surprised. She had expected a benefit.

But she cautioned that the study did not address the question of whether people with osteoporosis or low bone mass just short of the condition should be taking vitamin D and calcium, along with osteoporosis medications. Professional guidelines say they should take vitamin D and calcium, and she will continue to adhere to them in her own practice.

Dr. Dolores Shoback, an osteoporosis expert at the University of California, San Francisco, also will continue to advise patients with osteoporosis and low bone mass to take vitamin D and calcium.

It is “a simple intervention and I will continue to prescribe it,” she said.

Others go a bit further.

Dr. Sundeep Khosla, a professor of medicine and physiology at the Mayo Clinic, said that since vitamin D “will do little or no harm and may have benefits,” he would continue to advise his patients with osteoporosis to take it, recommending the 600 to 800 units a day in the National Academy of Medicine report.

“I will still tell my family and friends who don’t have osteoporosis to take a multivitamin a day to make sure they don’t get vitamin D deficient,” he said.

Dr. Khosla follows that advice himself. Many multivitamin tablets now contain 1,000 units of vitamin D, he added.

But Dr. Cummings and Dr. Rosen remain firm, even questioning the very idea of a vitamin D deficiency for healthy people.

“If vitamin D doesn’t help, what is a vitamin D deficiency?” Dr. Cummings asked. “That implies you should take vitamin D.”

And Dr. Rosen, who signed off on the National Academy of Medicine report, has become a vitamin D therapeutic nihilist.

“I don’t believe any more in 600 units,” he said. “I don’t believe you should do anything.”

Gina Kolata writes about science and medicine. She has twice been a Pulitzer Prize finalist and is the author of six books, including “Mercies in Disguise: A Story of Hope, a Family's Genetic Destiny, and The Science That Saved Them.” More about Gina Kolata

A Guide to Supplements

Surveys suggest that more than half of americans use some kind of supplement. but how effective are all those pills, powders and tinctures.

Several companies are now selling bovine colostrum as a supplement for humans, claiming several health benefits. Here’s what experts say .

Research suggests that a daily multivitamin can improve cognition. But that doesn’t mean everyone should take one .

Proponents of castor oil claim it can improve vision, reduce wrinkles, boost hair growth and more. Can it really do all that ?

Some manufacturers claim that certain supplements can help you focus. Here is what the experts say .

Melatonin tricks your body into feeling like it’s time for bed, but it isn’t a sleeping pill. Here’s how to use it  and why it might be tricky for regular users to fall asleep without it .

Can you distinguish the good supplements from the harmful or useless ones? Take our quiz .

Scientists Reveal New Findings About Older Adults Who Take Vitamin D

Research suggests that supplementing with vitamin D may reduce the risk of heart attacks and other cardiovascular events.

We've been independently researching and testing products for over 120 years. If you buy through our links, we may earn a commission. Learn more about our review process.

• Vitamin D is widely known for its role in supporting immunity and bone health.
• New research suggests that supplementing with vitamin D may reduce the risk of heart attacks and other cardiovascular events.

Vitamin D is a unique nutrient in that it comes from the food we eat and is a hormone that our bodies make. The fat soluble vitamin has a slew of important functions and vitamin D health benefits , from supporting immunity and healthy bones to improving mood. But new research shows that it may have other protective benefits for older adults.

A recent study published in the British Medical Journal , looked at a large sample of older adults ages 60 to 84. Participants were divided into two groups – one was given a placebo, while the other was given a vitamin D supplement of 60,000 IU a month (which averages out to about 2,000 IU a day) for up to five years. At the end of the study, data was analyzed from over 16,800 participants who were still taking the tablets.

During the trial, there were about 1,336 major cardiovascular events (i.e. heart attack, stroke and procedures to treat coronary artery disease). But compared with the placebo group, the rate of major heart problems was slightly lower in the vitamin D group, especially for those who were already taking heart medicines like statins at the beginning of the study.

Although the results are compelling, the findings were not statistically significant and prior research has shown no association with vitamin D supplementation and major heart problems. Ultimately, the best strategies to support heart health and reduce risk of heart disease include eating a healthy balanced diet , staying physically active , quitting smoking, reducing alcohol consumption, keeping blood pressure under control and checking your cholesterol levels. It's also important to take your medicines as directed and attend regular check-ups with your health care team.

GHI Top Vitamin D Picks

MegaFood Vitamin D3

Vitafusion Vitamin D3

NOW Vitamin D-3

But that doesn't mean that vitamin D isn't important for heart health. In fact, vitamin D is needed to support blood vessels and normal blood pressure. What's more, a vitamin D deficiency has been associated with elevated levels of lipids (a.k.a fats) in your blood, as well as vascular dysfunction and arterial stiffening. Research has also linked a lower vitamin D status to an increased risk of ischemic stroke , heart attack and heart disease .

How much vitamin D do I need?

Older adults need about 600 – 800 IU of vitamin D daily, depending on their age. You can get this through a combination of sun exposure and vitamin-D rich foods , which include salmon, eggs, sardines, liver, white mushrooms and fortified foods.

But supplementing with more isn't always better. Since vitamin D is a fat-soluble vitamin, too much can put you at serious risk for toxicity including adverse side effects like kidney stones and high calcium levels in the blood. Our experts say that it is best not to consume more than 4,000 IU daily, which is the tolerable upper intake level.

Signs of vitamin D deficiency

We recommend speaking with your healthcare provider if you suspect a vitamin D deficiency, as they can take bloodwork and then recommend the appropriate supplementation dosage based on your current levels. Some common signs of vitamin D deficiency include:

• Mood changes
• Muscle pain and weakness
• Reduced immune function
• Increased inflammation
• Frequent infections
• Rickets (in children)
• Bone disorders

What should I look for in a vitamin D supplement?

Since the U.S. Food and Drug Administration (FDA) does not approve dietary supplements for safety and effectiveness prior to going to market, it's incredibly important to thoroughly research each supplement you add to your regimen and speak with your healthcare provider before doing so. Look for options that have been tested for purity, potency and safety by a credible third-party organization.

Our team of registered dietitians spent months analyzing dozens of vitamin D supplements to bring you our top-tested recommendations for the best vitamin D supplements on the market.

The bottom line: New research suggests that supplementing with vitamin D may reduce the risk of heart attacks, but the results were not statistically significant and more research is needed. That being said, vitamin D does play a role in supporting a healthy heart, blood vessels and normal blood pressure. If you suspect a deficiency, speak with your healthcare provider who can take bloodwork and determine the appropriate supplement dose for you. The best strategies to support heart health include eating a healthy balanced diet, staying physically active, quitting smoking, reducing alcohol consumption and keeping blood pressure under control.

Stefani (she/her) is a registered dietitian, a NASM-certified personal trainer and the director of the Good Housekeeping Institute Nutrition Lab, where she handles all nutrition-related content, testing and evaluation. She holds a bachelor’s degree in nutritional sciences from Pennsylvania State University and a master’s degree in clinical nutrition from NYU. She is also Good Housekeeping’s on-staff fitness and exercise expert. Stefani is dedicated to providing readers with evidence-based content to encourage informed food choices and healthy living. She is an avid CrossFitter and a passionate home cook who loves spending time with her big fit Greek family.

@media(max-width: 64rem){.css-o9j0dn:before{margin-bottom:0.5rem;margin-right:0.625rem;color:#ffffff;width:1.25rem;bottom:-0.2rem;height:1.25rem;content:'_';display:inline-block;position:relative;line-height:1;background-repeat:no-repeat;}.loaded .css-o9j0dn:before{background-image:url(/_assets/design-tokens/goodhousekeeping/static/images/Clover.5c7a1a0.svg);}}@media(min-width: 48rem){.loaded .css-o9j0dn:before{background-image:url(/_assets/design-tokens/goodhousekeeping/static/images/Clover.5c7a1a0.svg);}} Diet & Nutrition

Our 2024 Best Snack Awards Are Here!

The 101 on High-Protein Vegetables

If You Have High Cholesterol, Try This Supplement

Our Guide to the Healthiest Starbucks Drinks

Is Oat Milk Really a Scam? Not Exactly

13 Foods That'll Help You Sleep Through the Night

4 Health-Focused Smoothies To Brighten Your Day

What to Eat for Healthy Hair

The Best Multivitamins for Women

Good Housekeeping Dietary Supplements Methodology

Top Health Benefits of Coconut Water

Donna Kelce shared her Mother’s Day wish list – and we want everything

• TODAY Plaza
• Share this —

• Watch Full Episodes
• Read With Jenna
• Inspirational
• Relationships
• TODAY Table
• Newsletters
• Start TODAY
• Shop TODAY Awards
• Citi Concert Series
• Listen All Day

Follow today

More Brands

• On The Show

Do you need vitamin D supplements? New study casts doubt on benefits

A new study casts doubt on the widespread use of high-dose vitamin D supplements, suggesting that the pills do not actually prevent bone fractures in healthy adults without vitamin D deficiencies.

The debate about the effectiveness of vitamin pills and supplements for the general population is not new. Despite the $150 billion-dollar industry 's best efforts, research continues to show that the vitamin pills many of us think are doing our bodies good aren't actually doing much to make us healthier, TODAY previously reported .

“Vitamin D is really important for bone health, and (together) with calcium, it's incredibly important in terms of preventing osteoporosis,” NBC News medical contributor Dr. Natalie Azar said on TODAY Thursday. However, people without a vitamin D deficiency may not get added bone health benefits from high-dose daily supplement pills, according to a new study led by scientists at Harvard Medical School .

New study looks at benefits of vitamin D supplements for healthy people

In the large randomized controlled trial, researchers tested whether 2000 IU (international units) per day of vitamin D3 supplements by itself would result in a lower risk of bone fractures compared to a placebo.

The study included over 25,800 participants, all over the age of 50, who were generally healthy. Participants were not selected for vitamin D deficiency, low bone mass, or osteoporosis, the authors wrote.

After following these participants for over five years, researchers found that vitamin D3 supplements "did not result in a significantly lower risk of fractures than (the) placebo among generally healthy midlife and older adults," the study authors wrote.

“This was a study done in people who weren’t selected for vitamin D deficiency, so it’s not unusual that you wouldn’t find an effect of vitamin D supplements,” said Azar.

Most people in the U.S. have adequate blood levels of vitamin D, but nearly one out of four people have levels that are inadequate or too low for bone and overall health, according to the NIH .

Easy sources of vitamin D

Vitamin D not only keeps bones strong and healthy — it’s also important for immune function, muscle function and brain health, Azar said. We get vitamin D from four main sources, she added.

• Sunlight: Vitamin D is produced in the body when ultraviolet rays from sunlight strike the skin, which triggers vitamin D synthesis, according to the National Institutes of Health's Office of Dietary Supplements.
• Foods: Vitamin D-rich foods include salmon, tuna, mackerel, fish oil and cod liver oil, said Azar.
• Vitamin D-fortified foods: Fortified foods provide most of the vitamin D in American diets, according to NIH. These include milk, orange juice and fortified cereals, Azar said.
• Dietary supplements: Pills either contain vitamin D2 (plant-derived) or D3 (often derived from animals but can be from lichen), according to NIH.

"The NIH does recommend that folks do take vitamin D or at least ingest vitamin D every day," said Azar.

If someone does not get enough vitamin D from their diet or sunlight, or has a medical condition that affects vitamin D levels or bone density, they will need to take supplements. That's because not getting enough vitamin D can cause muscle weakness, bone pain, and lead to osteoporosis , which causes bones to become fragile and break more easily, according to the NIH.

Risk factors for a vitamin D deficiency include gastric bypass surgery, liver or kidney disease, malabsorption, Crohn’s disease, obesity, having darker skin and not getting enough sun exposure, said Azar.

“If you have risk factors for vitamin D deficiency or osteoporosis, you definitely should be continuing your vitamin D and calcium,” said Azar.

How much vitamin D is needed daily?

For everyone else, more vitamin D isn’t necessarily better. So how much vitamin D do healthy people need? "The dose that was used in this study (2000s IU daily) is a little bit higher than what is normally recommended for most Americans," Azar said.

These are the recommended dietary allowances for vitamin D, according to the NIH:

0–12 months: 10 mcg (400 IU)

1–13 years: 15 mcg (600 IU)

14–18 years: 15 mcg (600 IU) 

19–50 years: 15 mcg (600 IU)

51–70 years: 15 mcg (600 IU) 

> 70 years: 20 mcg (800 IU)

"It’s really important also to point out again (that) this study was done in normal healthy people," said Azar. So the takeaway from this study "doesn't necessarily apply to people who have risks for osteoporosis or who have low bone mass," she added.

So if you have a vitamin D deficiency, you can and should absolutely keep taking your vitamin D, said Azar. But healthy individuals may not reap as much benefit from these supplements.

Caroline Kee is a health reporter at TODAY based in New York City.

• April 24, 2024 | Shedding Pounds, Dodging Cancer: The Life-Saving Promise of Bariatric Surgery
• April 24, 2024 | Quantum Computing Meets Genomics: The Dawn of Hyper-Fast DNA Analysis
• April 24, 2024 | Scientists Turn to Venus in the Search for Alien Life
• April 24, 2024 | NASA Astronauts Enter Quarantine As Boeing Starliner Test Flight Approaches
• April 23, 2024 | Peeking Inside Protons: Supercomputers Reveal Quark Secrets

New Research Shows Vitamin D Deficiency Leads to Dementia

By University of South Australia June 15, 2022

New genetic study finds a direct link between dementia and a lack of vitamin D.

Dementia is diminished cognitive functioning with a loss of ability to remember, think, solve problems, or make decisions — if it has progressed to the point that it interferes with doing everyday activities. It is a broad term, rather than a specific disease. Alzheimer’s disease is a specific type of dementia and the most common, with 6 million Americans afflicted according to the Alzheimer’s Association.

It is not a normal sign of aging, even though it primarily affects older adults at least 65 years of age. According to the CDC, nearly 14 million Americans will be suffering from dementia by 2060.

Dementia is one of the major causes of disability and dependency among older people worldwide, affecting thinking and behaviors as you age. But what if you could stop this degenerative disease in its tracks?

A world-first study from the University of South Australia could make this a reality as new genetic research shows a direct link between dementia and a lack of vitamin D.

Investigating the association between vitamin D, neuroimaging features, and the risk of dementia and stroke, the study found:

• low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke.
• genetic analyses supported a causal effect of vitamin D deficiency and dementia.
• in some populations, as much as 17 percent of dementia cases might be prevented by increasing everyone to normal levels of vitamin D (50 nmol/L).

Dementia is a chronic or progressive syndrome that leads to deterioration in cognitive function. About 487,500 Australians live with dementia and it is the country’s second leading cause of death . Globally, more than 55 million people have dementia with 10 million new cases diagnosed every year.

Supported by the National Health and Medical Research Council, the genetic study analyzed data from 294,514 participants from the UK Biobank, examining the impact of low levels of vitamin D (25 nmol/L) and the risk of dementia and stroke. Nonlinear Mendelian randomization (MR) – a method of using measured variation in genes to examine the causal effect of a modifiable exposure on disease — were used to test for underlying causality for neuroimaging outcomes, dementia, and stroke.

Mendelian randomization is a epidemiological method of using measured variation in genes of known function to analyze the causal effect of a modifiable disease exposure on an outcome in observational studies.

Senior investigator and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen, says the findings are important for the prevention of dementia and appreciating the need to abolish vitamin D deficiency.

“Vitamin D is a hormone precursor that is increasingly recognized for widespread effects, including on brain health, but until now it has been very difficult to examine what would happen if we were able to prevent vitamin D deficiency,” Prof Hyppönen says.

“Our study is the first to examine the effect of very low levels of vitamin D on the risks of dementia and stroke, using robust genetic analyses among a large population.

“In some contexts, where vitamin D deficiency is relatively common, our findings have important implications for dementia risks. Indeed, in this UK population we observed that up to 17 percent of dementia cases might have been avoided by boosting vitamin D levels to be within a normal range.”

The findings are incredibly significant given the high prevalence of dementia around the world.

“Dementia is a progressive and debilitating disease that can devastate individuals and families alike,” Prof Hyppönen says.

“If we’re able to change this reality through ensuring that none of us is severely vitamin D deficient, it would also have further benefits and we could change the health and wellbeing for thousands.”

“Most of us are likely to be ok, but for anyone who for whatever reason may not receive enough vitamin D from the sun, modifications to diet may not be enough, and supplementation may well be needed.”

Reference: “Vitamin D and brain health: an observational and Mendelian randomization study” by Shreeya S Navale, Anwar Mulugeta, Ang Zhou, David J Llewellyn and Elina Hyppönen, 22 April 2022, The American Journal of Clinical Nutrition . DOI: 10.1093/ajcn/nqac107

More on SciTechDaily

How to Boost Your Immune System With 5 Common Vitamins

5 Vitamins to Add to Your Diet for Healthy, Glowing Skin

The Sunshine Vitamin That ’D’elivers on Cardiovascular Health

You need more vitamin d in the winter – here’s why.

Vitamin D Deficiency Can Impair Muscle Function

7 Signs You May Need More Vitamin C

Scientists Debunk Common Vitamin D Myths

New Research Shows High Vitamin D Levels May Protect Against COVID-19, Especially for Black People

Be the first to comment on "new research shows vitamin d deficiency leads to dementia", leave a comment cancel reply.

Email address is optional. If provided, your email will not be published or shared.

Save my name, email, and website in this browser for the next time I comment.