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Study questions role of vitamin D in disease


“Doubt cast on vitamin D’s role against disease,” reports BBC News. The news come from a study summarising a large body of evidence from the best kind of trials – randomised controlled trials (RCTs).

The results of these trials showed that vitamin D supplements didn’t appear to help prevent many diseases, including cancer and cardiovascular disease. Importantly, these trials did not cover – so do not apply to – diseases affecting the bones.

The review also highlighted that observational research has consistently found a link between low vitamin D levels and an increased risk of disease, including cardiovascular diseases, inflammatory and infectious diseases.

Because the RCTs did not show that vitamin D supplements helped these diseases, the researchers concluded that vitamin D deficiency might be a symptom related to these conditions, rather than the cause.

However, the reasons why the trials may have found no link between vitamin D supplementation and disease prevention include:

  • because no link exists and the RCT findings are true
  • the people in the RCTs did not have low enough vitamin D levels to start with to benefit from supplementation
  • they were not given a high enough dose of vitamin D to be effective, or
  • they were not taking supplements for long enough for them to impact on disease

It is not clear which explanation is the correct one at this stage, but the study authors highlight that research scheduled to report in 2017 may clarify whether vitamin D supplements protect against non-bone diseases. 

Where did the story come from?

The study was carried out by researchers from French and Belgian research institutions and was funded by the International Prevention Research Institute.

It was published in the peer-reviewed medical journal, The Lancet Diabetes and Endocrinology.

The media reporting was generally balanced and included both the study’s conclusions and comments on some of its limitations.

What kind of research was this?

This was a systematic review of evidence from prospective and intervention studies (randomised controlled trials) looking at whether low vitamin D levels caused various diseases, or whether disease caused low vitamin D levels. The effect of vitamin D supplementation on preventing disease was also looked into.

The researchers say low vitamin D levels have been associated with many diseases. However, the researchers pointed out that it is not clear whether low vitamin D is the cause of disease, or whether ill health causes vitamin D levels in the body to fall.

Vitamin D is vital for good bone health, so supplementation may be expected to have an effect on conditions that affect the bones and bone density. However, this research looked at a variety of diseases that do not affect bones – so-called non-skeletal diseases.

What did the research involve?

The research involved searching electronic databases to identify all published scientific research investigating vitamin D and disease up to 2012. The researchers focused on two specific style types: prospective studies and randomised control trials.

Prospective studies can’t prove cause and effect, but well-designed randomised control trials can, so the two study design types were included to ensure all the best available evidence was considered and to see if the findings were similar.

All the studies included measures of blood vitamin D levels before the development of any disease. Where possible, the main analysis synthesised all the published results into a single summary measure.

What were the basic results?

The systematic review included 290 prospective cohort studies (279 on disease occurrence and 11 on cancer characteristics or survival) and 172 randomised trials on major health outcomes and physiological parameters related to disease risk, death or inflammatory status.

Results from observational prospective studies

Investigators of most prospective studies reported moderate to strong links between low vitamin D concentrations in the blood and higher risks of illness or disease, including:

  • cardiovascular diseases
  • blood lipid (fat) concentration (such as cholesterol)
  • inflammation 
  • glucose metabolism disorders (such as impaired glucose tolerance and diabetes)
  • weight gain
  • infectious diseases
  • multiple sclerosis
  • mood disorders
  • declining cognitive function
  • impaired physical functioning
  • all-cause mortality (death from any cause)

High vitamin D concentrations were not associated with a lower risk of cancer, except colorectal (bowel) cancer. This indicated there was a link between low vitamin D levels and a host of different diseases, but cause and effect was not clear, so the pooled results from the RCTs aimed to find out what was causing what.

Results from RCTs

Results from intervention studies did not show a link between vitamin D supplementation and disease occurrence across the range of diseases tested, including colorectal cancer.

The 34 intervention studies included 2,805 individuals with an average (mean) vitamin D concentration lower than 50nmol/l at baseline. The trials found that supplementation with 50 micrograms per day or more of vitamin D did not have a significant effect on the risk of developing the various diseases examined. Supplementation in elderly people (mainly women) with 20 micrograms of vitamin D per day was reported to slightly reduce all-cause mortality.

How did the researchers interpret the results?

The researchers concluded that, “The discrepancy between observational and intervention studies suggests that low 25(OH)D [vitamin D] is a marker of ill health.

“Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D [vitamin D], which would explain why low vitamin D status is reported in a wide range of disorders.

“In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.”


This large systematic review suggests that low vitamin D levels in the blood may be the result of disease and illness, rather than the cause of it.

The review also found that vitamin D supplementation did not appear to help reduce the risk of developing non-skeletal diseases (diseases not affecting the bones) in people with low vitamin D levels in a range of diseases. Consequently, this review has cast doubt on the usefulness of people taking vitamin D to reduce their risk of any other diseases not affecting the bones.

This research is useful in drawing attention to the evidence gaps around the role of vitamin D in non-skeletal diseases. However, one of the main points to note is that the research did not cover bone diseases.

Vitamin D is essential for good bone health, particularly during times of skeletal growth (such as during infancy and childhood). The main reason that vitamin D supplementation is recommended is to increase bone health in people who may not be getting adequate vitamin D through natural sources.

The effect of vitamin D on bone health was not addressed, so readers shouldn’t conclude that this research casts doubt on the usefulness of taking vitamin D supplements for good bone health – this study only relates to the effects on diseases not affecting the bones.

However, this review still doesn’t prove that vitamin D definitely has no effect on non-skeletal diseases. A consistent link was found in observational studies, which was not seen in RCTs. There are a number of possible explanations that could explain this finding in the RCTs:

  • vitamin D isn’t effective at preventing disease and the result is true
  • the RCTs didn’t look at people with sufficiently low vitamin D levels for the supplements to have any meaningful biological effect
  • the RCTs did not give sufficiently high vitamin D supplementation for an effect to be detected
  • the supplements weren’t given for long enough to have an impact on disease

These issues were discussed by the study authors, who suggested that the vitamin D dose in the RCTs was probably not an issue. However, it is not clear which of these explanations, or alternatives, is correct.

The study highlights that further research needs to look into the effect of vitamin D on diseases not affecting the bones. It also shows that when studies look at non-skeletal diseases, researchers need to pay special attention to specific issues, such as the level of vitamin D deficiency and the dose and duration of supplementation, to eliminate alternative explanations for results like these. The researchers report that such research is underway and may be ready in 2017.

Who should have daily vitamin D supplements?

The Department of Health currently recommends a daily vitamin D supplement for those who may be at risk of deficiency. This includes:

  • pregnant and breastfeeding women
  • babies and children aged from 6 months to 5 years (unless receiving fortified infant formula)
  • people over the age of 65 exposed to little sunlight

These people should have 10 micrograms for adults, including pregnant women, and 7 to 8.5 micrograms for babies and children.



Readers' comments (2)

  • The review by Autier and colleagues had many problems. One was that it ignored ecological studies based on solar UVB doses, which show strong benefits for many types of cancer. Dr. Autier thinks people should stay out of the sun to avoid getting melanoma. The study also omitted case control studies (vitamin D levels measured at time of diagnosis) which uniformly show high levels associated with reduced risk of breast cancer. However, the most important problem was assuming that the randomized controlled trial (RCT) is the gold standard for compounds made naturally or obtained through diet. The partners of Dr. Autier's organization, International Prevention Research Institute, include many pharmaceutical companies. Most vitamin D RCTs to date have been poorly designed and conducted. Good ones should start with an understanding of the vitamin D-health outcome relation, enroll people at the low end, give them enough vitamin D to raise their levels to the high end, and measure the vitamin D level. See this open access paper
    Lappe JM, Heaney RP. Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrin. 2012;4(2):95-100.
    For the latest review of the health benefits of vitamin D, see this open access paper:
    Hossein-Nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo Clin Proc. 2013 July;88(7):720-55.
    For optimal health, vitamin D levels should be above 30-40 ng/ml (75-100 nmol/l).
    Oh, and also try to get vitamin D from the sun.

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  • I would like to give a rather cynical comment: As Bill Grant already mentioned funding to the International Prevention Research Institute who Autier and colleagues work for, are drug companies. If vitamin D really could prevent diseases, then drug companies have indeed something to worry. It could potentially mean less income to drug companies, because less medication will be used and sold. They will therefore have a particular interest to support researchers with ideas of reverse causality in the vitamin D case.
    Notably was also the enormously wide reporting of this paper, judging by the days and days of google alerts full of it. Although controversial, publicising this review, means discouraging people from taking vitamin D supplements, which could be in the interest of drug companies.

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