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Vitamin D – What's the Latest Research?

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

Vitamin D is a fat-soluble vitamin produced by the body when skin is exposed to sunlight. It can be found in some foods, including oily fish, liver and mushrooms, and is available as a supplement.

The National Institutes of Health (NIH) recommend a daily intake of vitamin D of 15 µg (400IU) for most adults, with people over 70 recommended an increased intake of 20 µg. These guidelines assume that a person gets minimal sun exposure.

Vitamin D plays numerous roles in the body, including promoting calcium absorption in the gut to enable normal bone calcification and growth, reducing inflammation and modulating cell growth.

The form of vitamin D found in food, supplements and produced in the skin must be metabolized before it can be used by the body. The first step occurs in the liver, where vitamin D is converted to a hydroxylated form called 25-hydroxyvitamin D (25(OH)D). 25(OH)D is then further hydroxylated in the kidneys to the physiologically active form, 1,25-dihydroxyvitamin D.

Deficiency or insufficiency?

Clinicians use the amount of 25(OH)D present in the blood as a marker of insufficiency or deficiency. The NIH guidelines define deficiency as a serum concentration of 25(OH) D as less than 12 ng/mL, and insufficiency as less than 20 ng/mL, although other health organizations my use different values.

“Vitamin D is a crucial player in bone health, immune function and the regulation of diverse metabolic processes. Recent studies reveal an alarming statistic up to 42% of the population suffers from this deficiency,” said Dr. Kevin Huffman, a primary care physician and Medical Director of Florida Injury Centers.

Symptoms of vitamin D deficiency include muscle weakness, bone pain, muscle pain and tingling sensations in the hands and feet.

Studies have suggested vitamin D deficiency is linked to a loss of brain plasticity, worsened polycystic ovarian syndrome symptoms and, for expectant mothers, an increased risk of diabetes in their children.

Vitamin D deficiency linked to increased cancer mortality

“The connection between Vitamin D and carcinogenesis is intricate; it encompasses its pivotal role in regulating cell growth, apoptosis – programmed cellular death – as well as immune function,” said Huffman.


A recent study published in the European Journal of Cancer reviewed the impact of vitamin D deficiency on mortality in 18 different cancer types, as well as overall cancer mortality. The researchers analyzed data from 411,436 people in the UK Biobank using a cause-specific Cox regression model to adjust for other lifestyle or environmental factors that may influence the results.

Over a third (34.4%) of participants were vitamin D insufficient and 21.1% had vitamin D deficiency.

The paper reported that vitamin D deficiency was associated with increased mortality for total cancers and four specific cancers: stomach, colorectal, lung and prostate. Vitamin D insufficiency was also linked to increased lung and prostate cancer mortality.

The authors also investigated whether vitamin D or multivitamin supplementation influenced mortality outcomes and found that, compared to participants who didn’t take supplements, vitamin D supplementation was associated with lower lung cancer mortality as well as lower overall cancer mortality. Taking a multivitamin was associated with lower mortality from melanoma.

This research underscores the importance of adequate vitamin D intake, although further research is needed to identify the exact mechanisms by which vitamin D lowers the risk of cancer mortality.

Vitamin D can influence the gut microbiome to improve cancer immunotherapy responses

Another study, published in Science, has shown how vitamin D could improve responses to cancer immunotherapy.

Researchers observed a stronger antitumor immune response, reduced tumor growth and better responses to immunotherapy treatment in mice that were fed a vitamin D-rich diet.

They identified that the activity of vitamin D on intestinal epithelial cells altered the composition of the gut microbiome, favoring the growth of the species Bacteriodes fragilis, which stimulates antitumor immunity.

When mice on a normal diet were given B. fragilis, tumor growth decreased. However, the same tumor resistance was not seen in mice fed a diet lacking in vitamin D, indicating that sufficient vitamin D is key to promoting antitumor immunity through modulating the gut microbiome.

Caetano Reis e Sousa, senior author of the paper said, “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.”

Does vitamin D deficiency affect cardiovascular disease risk?

Studies have identified that vitamin D plays a role in cardiovascular health by acting on endothelial and smooth muscle tissues to regulate blood pressure and further research has outlined the association between vitamin D deficiency and cardiovascular disease in people with pre-existing risk factors, like type 2 diabetes or high blood pressure.

However, a 2021 review argued that there is “no strong evidence for beneficial vitamin D effects on CVD [cardiovascular disease] risk”, pointing out conflicting evidence from observational studies and randomized controlled trials.

A recent study aimed to assess the link between vitamin D levels and cardiovascular disease as well as cardiovascular events (such as heart attack and stroke) by analyzing 5,684 participants from Lausanne, Switzerland. The average follow-up time for this study was 14.4 years.

Vitamin D status was split into three categories based on serum 25(OH)D; normal, insufficiency (21 29 ng 25(OH)D/mL) or deficiency (less than 20 ng/mL). The researchers found that vitamin D deficiency was associated with an increased likelihood of cardiovascular events, but not cardiovascular disease or overall mortality.

The authors outlined that the number of cardiovascular events over the studied period was relatively small and suggested that analyzing a larger study cohort might clarify the effect of vitamin D on cardiovascular health.

Vitamin D deficiency and increased sepsis mortality in the elderly

Another recent study, published in Nutrients, revealed the impact of severe vitamin D deficiency on mortality outcomes in the elderly with sepsis. Of the 129 patients recruited to the study, 96 had vitamin D deficiency and of those, 62 patients had severe deficiency (serum 25(OH)D of less than 12ng/mL.) The researchers used the Sepsis-3 definition to categorize patients with a sequential organ failure assessment score of 2 or more as having sepsis.


The researchers identified that severe vitamin D deficiency was associated with an increase in 14-day, 28-day and overall in-hospital mortality from sepsis. In their paper, the authors highlight the role of vitamin D in immunity as a potential mechanism for this link, although they outline that: “The pathophysiology whereby vitamin D deficiency affects the mortality rate from sepsis is not yet clear.”

Vitamin D deficiency identified as a risk factor for young onset dementia

Young onset dementia – when dementia symptoms occur before age 65 – was previously thought to have a genetic cause, but a new study published in JAMA Neurology has challenged this.


By assessing over 350,000 under 65s in the UK, researchers have pinpointed 15 risk factors for young onset dementia, which included vitamin D deficiency.

Although there is still further research needed, the study illustrates how vitamin D status and other modifiable risk factors could be incorporated into dementia prevention strategies.

Huffman concludes that “It is crucial – indeed there can be no compromise that we encourage patients to fulfill their vitamin D requirements; this may require them to integrate sunlight exposure with dietary intake and supplements when necessary.”

Dr. Kevin Huffman was speaking to Katie Brighton, Scientific Copywriter for Technology Networks. 

About the interviewee: Dr. Kevin Huffman is a primary care physician and Medical Director of Florida Injury Centers. He has 35 years of experience as a primary care physician with an extensive background in diagnosing, treating and managing nutritional deficiencies and their comorbidities.