Review questions vitamin D for reducing chronic disease risk

Review questions vitamin D for reducing chronic disease risk

Low vitamin D levels may be a consequence of ill health and not the cause of chronic disease, says a new review, but industry groups have responded that supplementation is vital for bone health and should not be dismissed.

French researchers analyzed data from 290 prospective observational studies, and found that high blood levels of the sunshine vitamin might be protective. Indeed, the observational data indicated that high vitamin D levels were associated with a reduction in the risk of cardiovascular events of up to 58%, a reduction in the risk of diabetes of up to 38%, a reduction in the risk of colorectal cancer of up to 33%, and a reduction in the risk of so-called ‘all-cause mortality’ of up to 29%.

High vitamin D levels were also associated with improvements in cholesterol levels, markers of inflammation, glucose metabolism disorders, infectious diseases, weight gain, and cognitive function.

On the other hand, the overall data from 172 randomized clinical trials of vitamin D and non-bone health outcomes indicated no reduction in risk, leading the researchers to conclude that that low vitamin D is not a cause but a consequence of ill health

Professor Philippe Autier from the International Prevention Research Institute in Lyon, France and lead author on the review, said: “What this discrepancy suggests is that decreases in vitamin D levels are a marker of deteriorating health. Aging and inflammatory processes involved in disease occurrence and clinical course reduce vitamin D concentrations, which would explain why vitamin D deficiency is reported in a wide range of disorders.

“If the health benefits of high vitamin D concentrations shown by data from observational studies are not reproduced in randomized trials (the gold standard method for assessing a causal relation between an exposure and an outcome) then the relation between vitamin D status and disorders are probably the result of confounding or physiological events involved in these disorders.”


Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol.

Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.

Vitamin D deficiency (less than 20 ng/mL) can cause a number of health issues, including rickets and other musculoskeletal diseases. 

Cara Welch, PhD, Sr Vice President, Scientific & Regulatory Affairs for the Natural Products Association (NPA), told us that: "We’re looking at a mother of all meta-analyses, but just on non-skeletal disorders because, as the authors state, they are looking outside vitamin D’s proven “importance in bone health and calcium homeostasis.”  So on the non-skeletal disorders, this study seems to confirm what the industry already acknowledges – vitamin D is not the magic pill for all diseases. 

"However, I think it also corroborates what we’ve been saying about proper supplementation.  There are populations that would benefit from supplementation, people who are prone to vitamin D deficiency and aren’t getting it from their diet.  Additionally, it’s important for those who are suffering from chronic health disorders that results in lowered vitamin D concentrations to consider supplementing their diet."

Duffy MacKay, ND, vice president, scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), said: “Vitamin D is an essential nutrient for good health, and if you’re one of the many people who have low levels of vitamin D, supplementation is a safe and beneficial way to achieve healthy levels. The current Dietary Guidelines for Americans identify vitamin D as one of four nutrients of public health concern because consumers are falling short. Both doctors and consumers should take this into consideration and ensure vitamin D levels are checked during medical check-ups.

"This systematic review is important because it addresses the fact that when people get seriously ill, they often experience nutrient depletions, including low vitamin D levels. When this happens, dietary supplementation should be discussed by the patient and a team of healthcare practitioners because vitamin D is not easily obtained through food, and getting it through sunlight can pose risks—making supplementation a viable option. The authors of the review acknowledge this, specifically the importance of vitamin D supplementation in elderly women who are at risk for falls or fractures. Besides, people who are getting the nutrients they need are likely to respond better to the treatment of their condition—and generally feel better.

“Scientific research demonstrates that vitamin D, in combination with calcium, is critical for the prevention of skeletal diseases, such as osteoporosis. It may be unrealistic to expect vitamin D in isolation from other healthy habits to prevent a disease such as cancer or cardiovascular disease. But we know that one component of disease prevention involves a healthy diet, of which vitamin D is a vital part.”

Ongoing trials

An accompanying editorial in The Lancet Diabetes & Endocrinology said that the odds are stacked against vitamin D being of use in preventing non-skeletal disorders.

“[However] large [ongoing] clinical trials to assess the effects of vitamin D on non-skeletal health outcomes are therefore justified. It would be a real boon to patients if the results are positive, but unless effect sizes for clinically important outcomes are large, the results will only confirm the neutral effect reported by most clinical trials thus far.”

Currently, five big clinical trials are underway testing vitamin D3 for a variety of outcomes in participants over 50 years of age. The table below outlines the trials, the interventions, outcomes and expected completion date.

Trial name





Expected completion




2,000 IU D3/day

CVD & Cancer





60,000 IU D3 once per month





New Zealand

100,000 IU D3 once per month

CVD, fractures, & respiratory disease




8 EU cities

2,000 IU D3/day

Fractures, BP, cognitive function, infection





1,600 or 3,200 IU D3/day

CVD, cancer, & diabetes


(Source: K. Kuppferschmidt, Science, 2012, Vol. 337, pp. 1476–7)

Prof Autier and his co-authors concluded: “These studies have the potential to test our hypotheses”.

Source: The Lancet Diabetes & Endocrinology
Published online ahead of print, doi: 10.1016/S2213-8587(13)70165-7
“Vitamin D status and ill health: a systematic review”
Authors: P. Autier, M. Boniol, C. Pizot, P. Mullie

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Comments (3)

Jorma Marttinen - 10 Dec 2013 | 10:36

Personal experience with MS

The daily dosage should be at least 100 mcg. I have personally taken 125 mcg/ day since 2003 and my MS(mild relapsing/remitting) symptons have stayed away. And no flus in ten years!

10-Dec-2013 at 10:36 GMT

Jerry Segers - 10 Dec 2013 | 08:00

Invalid Research Results Promotes Invalid Results

The authors of this Lancet study published, but took no note of, two glaring problems with the intervention studies they reviewed. First, the average base Vitamin D3 level of the participants was 50 nmol/L which is equivalent to 20 ng/mL. The normal range for vitamin D3 according to LabCor is 30-100 ng/mL so the participants started with a severe Vitamin D deficiency. It was further noted that the intervention was less than 50 mcg of vitamin D per day. The authors did not indicate vitamin D2 or D3 so I will assume D3 which is the more active form. Vitamin D2 has about 1/2 the activity as Vitamin D3. According to the dose of 50 mcg per day is expected to raise the vitamin D3 blood levels by 20 ng/ml to a total of 40 ng/mL after several months assuming full compliance with the protocol. Thus depending on the length of the intervention, there was no to minimal actual change in the vitamin D status of the participants. It remained low. This rightfully yielded little or no change in their condition. This is the equivalent of giving a person with a head ache a 1/4 of a single ibuprofen tablet and declaring that ibuprofen does not improve head ache status. For this reason, I disagree with Dr. Autier and his colleagues, the interventions above that are now in progress will not shed any new light on this subject. Every intervention listed is still much too small. In every case I have worked it took over 4000 IU(100 mcg) per day for many months to cause the measured Vitamin D3 levels to reach 50-80 ng/mL which the observational studies indicate is required for successful intervention. In one case it required 50,000 IU (1250 mcg) per day for over 3 months to raise the Vitamin D3 status of an overweight individual from 11 ng/mL to a respectable but still too low 40 ng/mL. I personally need 14,000 IU (350 mcg) per day of VItamin D3 to maintain 80 ng/mL Vitamin D3 status. What this review should have concluded was that low doses of vitamin D do not improve disease status. A result that would get my complete agreement. NOTE: The daily amount of Vitamin D3 supplement needed to increase blood levels to the 50-80 ng/mL range are above the upper limit for daily intake as recommended by the Institute of Medicine. Many researchers including this one believe the IOM recommendations are much too low. With specific reference to overweight individuals which require as much as three times the Vitamin D for the same blood results as a normal weight individual.

10-Dec-2013 at 20:00 GMT

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