Study suggests vitamin D benefits and metabolism may depend on body weight

People with higher body mass index had a blunted response to vitamin D supplementation, explaining observed differences in outcomes such as cancer, diabetes, and autoimmune disease


Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have found new evidence that vitamin D may be metabolized differently in people with an elevated body mass index (BMI). The study, appearing in JAMA Network Open, is a new analysis of data from the VITAL trial, a large nationwide clinical trial led by Brigham researchers that investigated whether taking vitamin D or marine omega-3 supplements could reduce the risk of developing cancer, heart disease, or stroke.

“The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25,” said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham’s Division of Preventive Medicine. “There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI.”

Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.

The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.

The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.

“Most studies like this focus on the total vitamin D blood level,” said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. “The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others.”

The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.

“We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI,” Tobias said. “This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status.”

“This study sheds light on why we’re seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D,” said Manson. “These nuances make it clear that there’s more to the vitamin D story.”

The authors conclude that the VITAL findings are a call to action for the research community to continue exploring the potential benefits of vitamin D supplementation for preventing cancer and other diseases and to take BMI into account when evaluating the supplement’s health impacts.

Down on Vitamin D? It could be the cause of chronic inflammation

Sunset


There’s a direct link between low levels of vitamin D and high levels of inflammation. CREDIT Rebecca Wood

Inflammation is an essential part of the body’s healing process. But when it persists, it can contribute to a wide range of complex diseases including type 2 diabetes, heart disease, and autoimmune diseases.

Now, world-first genetic research from the University of South Australia shows a direct link between low levels of vitamin D and high levels of inflammation, providing an important biomarker to identify people at higher risk of or severity of chronic illnesses with an inflammatory component.

The study examined the genetic data of 294 ,970 participants in the UK Biobank, using Mendelian randomization to show the association between vitamin D and C-reactive protein levels, an indicator of inflammation.

Lead researcher, UniSA’s Dr Ang Zhou, says the findings suggest that boosting vitamin D in people with a deficiency may reduce chronic inflammation.

“Inflammation is your body’s way of protecting your tissues if you’ve been injured or have an infection,” Dr Zhou says.

“High levels of C-reactive protein are generated by the liver in response to inflammation, so when your body is experiencing chronic inflammation, it also shows higher levels of C-reactive protein.

“This study examined vitamin D and C-reactive proteins and found a one-way relationship between low levels of vitamin D and high levels of C-reactive protein, expressed as inflammation.

“Boosting vitamin D in people with deficiencies may reduce chronic inflammation, helping them avoid a number of related diseases.”

Supported by the National Health and Medical Research Council and published in the International Journal of Epidemiology the study also raises the possibility that having adequate vitamin D concentrations may mitigate complications arising from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as CVDs, diabetes, and autoimmune diseases.

Senior investigator and Director of UniSA’s Australian Centre for Precision HealthProfessor Elina Hyppönen, says these results are important and provide an explanation for some of the controversies in reported associations with vitamin D.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit.” Prof Hyppönen says. 

“These findings highlight the importance of avoiding clinical vitamin D deficiency, and provide further evidence for the wide-ranging effects of hormonal vitamin D.”

Vitamin D supplement ‘overdosing’ is possible and harmful, warn doctors


Vitamin D supplement ‘overdosing’ is possible and harmful, warn doctors


‘Overdosing’ on vitamin D supplements is both possible and harmful, warn doctors in the journal BMJ Case Reports after they treated a man who needed hospital admission for his excessive vitamin D intake.

‘Hypervitaminosis D’, as the condition is formerly known, is on the rise and linked to a wide range of potentially serious health issues, they highlight.

The case concerns a middle-aged man who was referred to hospital by his family doctor  after complaining of recurrent vomiting, nausea, abdominal pain, leg cramps, tinnitus (ringing in the ear), dry mouth, increased thirst, diarrhoea, and weight loss (28 lbs or 12.7 kg). 

These symptoms had been going on for nearly 3 months, and had started around 1 month after he began an intensive vitamin supplement regimen on the advice of a nutritional therapist.

The man had had various health issues, including tuberculosis, an inner ear tumour (left vestibular schwannoma), which had resulted in deafness in that ear, a build-up of fluid in the brain (hydrocephalus), bacterial meningitis, and chronic sinusitis.  

He had been taking high doses of more than 20 over the counter supplements every day containing: vitamin D 50000 mg—the daily requirement is 600 mg or 400 IU; vitamin K2 100 mg (daily requirement 100–300 μg); vitamin C, vitamin B9 (folate) 1000 mg (daily requirement 400 μg); vitamin B2 (riboflavin), vitamin B6, omega-3 2000 mg twice daily (daily requirement 200–500 mg), plus several other vitamin, mineral, nutrient, and probiotic supplements.

Once symptoms developed, he stopped taking his daily supplement cocktail, but his symptoms didn’t go away.

The results of blood tests ordered by his family doctor revealed that he had very high levels of calcium and slightly raised levels of magnesium. And his vitamin D level was 7 times over the level required for sufficiency.

The tests also indicated that his kidneys weren’t working properly (acute kidney injury). The results of various x-rays and scans to check for cancer were normal. 

The man stayed in hospital for 8 days, during which time he was given intravenous fluids to flush out his system and treated with bisphosphonates—drugs that are normally used to strengthen bones or lower excessive levels of calcium in the blood.

Two months after discharge from hospital, his calcium level had returned to normal, but his vitamin D level was still abnormally high.

“Globally, there is a growing trend of hypervitaminosis D, a clinical condition characterised by elevated serum vitamin D3 levels,” with women, children and surgical patients most likely to be affected, write the authors. 

Recommended vitamin D levels can be obtained from the diet (eg wild mushrooms, oily fish), from exposure to sunlight, and supplements.

“Given its slow turnover (half-life of approximately 2 months), during which vitamin D toxicity develops, symptoms can last for several weeks,” warn the authors.

The symptoms of hypervitaminosis D are many and varied, they point out, and are mostly caused by excess calcium in the blood. They include drowsiness, confusion, apathy, psychosis, depression, stupor, coma, anorexia, abdominal pain, vomiting, constipation, peptic ulcers, pancreatitis, high blood pressure, abnormal heart rhythm, and kidney abnormalities, including renal failure. 

Other associated features, such as keratopathy (inflammatory eye disease), joint stiffness (arthralgia), and hearing loss or deafness, have also been reported, they add.

This is just one case, and while hypervitaminosis D is on the rise, it is still relatively uncommon, caution the authors.

Nevertheless, complementary therapy, including the use of dietary supplements, is popular, and people may not realise that it’s possible to overdose on vitamin D, or the potential consequences of doing so, they say.

“This case report further highlights the potential toxicity of supplements that are largely considered safe until taken in unsafe amounts or in unsafe combinations,” they conclude.

Vitamin D does not prevent type 2 diabetes in high-risk adults, trial finds

Shiitake mushrooms - a sources of vitamin D
Shiitake mushrooms – a sources of vitamin D

Daily vitamin D supplements do not seem to prevent the development of type 2 diabetes in people already at high risk of the condition, finds a trial from Japan published by The BMJ today.

The results show that supplements had no clinically meaningful effect in high risk adults, but suggest there may be a benefit for people with insufficient insulin secretion, although this finding remains unclear. 

Type 2 diabetes affects around 480 million people worldwide, and is predicted to increase to 700 million by 2045. Another half a billion people have impaired glucose tolerance or pre-diabetes (higher than normal blood sugar levels that, if left untreated, can develop into type 2 diabetes).

Weight loss and exercise can lower the risk of progression to type 2 diabetes, but are difficult to sustain, so new strategies are needed to tackle the problem.

Some studies have shown that vitamin D deficiency is associated with an increased risk of future diabetes, but trials of vitamin D supplements for preventing type 2 diabetes show inconsistent results.

To address this knowledge gap, researchers therefore set out to assess whether eldecalcitol (an active form of vitamin D used to treat osteoporosis in Japan) could reduce the risk of developing type 2 diabetes among people with impaired glucose tolerance.

Their findings are based on 1,256 Japanese adults with impaired glucose tolerance recruited from three hospitals in Japan between June 2013 and August 2019. Their average age was 61 (range 30-78) years, 46% were women, and 59% had a family history of type 2 diabetes.

Participants were randomly assigned to receive either a standard daily dose of eldecalcitol (630 participants) or placebo (626 participants) and were assessed for diabetes every three months over a three-year follow-up period.

During this period, the researchers found no meaningful differences between groups in those who developed diabetes (12.5% in the eldecalcitol group and 14% in the placebo group) or whose blood sugar levels returned to normal (23% in the eldecalcitol group and 20% in the placebo group).

However, after adjusting for 11 potentially influential factors, including age, sex, blood pressure, body mass index, and family history of diabetes, the results suggested that eldecalcitol might prevent type 2 diabetes in pre-diabetic patients with insufficient insulin secretion. But this finding remains unclear and the researchers say further work is needed before any firm conclusions can be made.

They did, however, find a significant increase in both lower back and hip bone mineral densities among those taking eldecalcitol compared with placebo. 

No significant difference in serious adverse events was seen between the two groups.

The researchers acknowledge some uncertainties, such as whether the dose of eldecalcitol used was appropriate for preventing diabetes, and whether the results apply to all ethnicities. Nevertheless, this was a large trial with regular follow-up and high adherence to treatment, suggesting that the findings are robust.

As such, they say: “Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with pre-diabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion.” And they call for further research to determine whether vitamin D is beneficial to people with pre-diabetes.

This new trial was well conducted and results are consistent with two other recent trials, says Tatiana Christides at Queen Mary University of London in a linked editorial. 

However, several questions remain, she writes, including whether vitamin D supplementation may be more effective for particular populations, and whether longer duration of treatment or younger age at initiation might be more beneficial.

Until further data are available from high quality randomised trials, she suggests healthcare professionals “should continue to discuss with patients the musculoskeletal health benefits of vitamin D and support them to achieve and maintain lifestyle changes that, although challenging to sustain, are known to decrease development of type 2 diabetes.”

The Vitamin D Dilemma: This Will Fundamentally Change the Way You Look at Low Vitamin D

The Vitamin D Dilemma: This Will Fundamentally Change the Way You Look at Low  Vitamin D - YouTube


The topic of vitamin D supplementation has been so controversial. Even before the pandemic scientists couldn’t seem to agree on what dose is best or when supplementation is a good idea. There is a tonne of research now on vitamin D as it pertains to COVID-19 and auto-immune diseases, but none of this has really been conclusive as to whether it actually reduces the severity of the disease.

This video discusses why low levels of Vitamin D may be an underlying indicator of metabolic disease and increased inflammation in the body more than anything else. In the video we discuss:

What factors influence the production of Vitamin D in the body.

The impact of inflammation and metabolic stress on Vitamin D levels.

How natural light is an important contributor to the production of Vitamin D, Melatonin, and reduced levels of inflammation?

The negative impact of high dose Vitamin D & Vitamin C over time.

Tips for getting the most benefit from Vitamin D supplementation