Vitamin D: Why a Conservative Policy Stance Does More Harm than Good
Chronic disease is the leading cause of death and disability worldwide, with four out of five Canadians over the age of 20 at risk. There is evidence suggesting that vitamin D insufficiency could be contributing to the huge economic burden associated with chronic disease. A causal link has been established between vitamin D insufficiency and some chronic diseases such as cancer, cardiovascular disease, diabetes, Multiple Sclerosis and other autoimmune disorders, suggesting that vitamin D could be both preventative and potentially a therapy for some of these diseases. These benefits are typically associated with vitamin D levels much higher than the current Canadian average. A study estimating the economic burden and premature death rate in Canada attributable to low vitamin D status found that increasing the mean serum level (roughly speaking, the amount of vitamin D in the blood stream from the average of 67 nmol/L to 105 nmol/L) could reduce annual death rates by 16.1 per cent (37 000 deaths/year) and ultimately reduce the chronic disease burden in Canada by $14.4 billion (6.9 per cent) less the cost of the program. Raising vitamin D levels could be done in Canada with supplements costing as little as $10 per person per year. So why aren’t we doing this to prevent chronic disease?
Experts who set guidelines for intake claim there is no evidence of benefit and there is risk of harm leading to conservative recommendations. The conservative policy position of the Institute of Medicine’s (IOM) comprehensive risk assessment of calcium and vitamin D, which was adopted by Health Canada, is that the role of vitamin D supplementation in the prevention and treatment of chronic non-skeletal diseases remains to be determined and there is a need for large randomized controlled trials (RCT) and dose-response data to test the effects of vitamin D on chronic disease outcomes including: autoimmunity, cancer, obesity, diabetes, hypertension and heart disease. This report stated that adults need only 600 International Units (IU) per day of vitamin D in the absence of solar UVB irradiance and that a mean serum of 20 ng/ml (50 nmol/l) is adequate. Additionally, those who are skeptics of the need for supplementation of vitamin D at higher doses point to previous recommendations for vitamin A and E that showed promising findings in observational studies, but resulted in serious health concerns in RCTs. Public health officials are clearly concerned about the need to not get “burned again”.
The major argument is that there isn’t adequate evidence for the safety of high dose vitamin D supplementation. This stance is buoyed by studies suggesting a lack of benefit in vitamin D supplementation. The trouble with these studies, such as one recently highlighted by Margret Wente in the Globe and Mail, is that they are not looking at supplementation at levels over 1000IU and are typically characterizing people who are likely becoming only slightly less vitamin D deficient. The debate certainly shouldn’t be deconstructed simply as whether you are a vitamin ‘believer’.
The issue isn’t as simple as being dismissed with inadequate evidence. Using the concept of “evidence-based medicine”, the IOM rates only evidence from randomized control trials as being of high enough quality to influence policy. Typically the term “evidence” is used with the intent to treat, generally in the context of testing pharmaceutical drugs at levels not seen endogenously in the body. This is different from the proposed vitamin D supplementation targeting physiological levels, where the vitamin D levels suggested as optimum can be obtained with exposure to UVB radiation.
There is no doubt that there is a need to show safety and effectiveness with vitamin D, and the past issues with micronutrients are a major reason for caution with vitamin D supplementation. However, vitamin D is fundamentally different than vitamin A and E. Vitamins A and E are anti-oxidants, which are important for trapping free radicals and protecting cells from damaging oxidation. As past RCTs have shown, these vitamins shouldn’t be consumed beyond the daily dietary recommended doses, as there is evidence of harm in RCTs that was not shown in observational studies. In contrast, vitamin D is a hormone and most tissues and cells in the body have a vitamin D receptor (VDR), which seems to be involved in a host of physiological activities. The vitamin D supplementation levels suggested are targets to reach physiological levels of vitamin D thought to be important for maintaining optimal health and preventing chronic disease.
This is important for Canadians because vitamin D deficiency in Canada is largely due to other factors, such as geographical relocation, changes in diet, ethnic and cultural differences, darker skin pigmentation and increased awareness of the phototoxicity of UV radiation. Quite simply, all Canadians can’t synthesize vitamin D for six months of the year during the “vitamin D winter” from October to March. In this context, ecological and observational evidence is well situated to address these factors. There is a large body of experimental findings, as well as ecological, case-control, retro- and prospective, observational and interventional studies, that suggest vitamin D deficiency has a role in a diverse range of physiological functions and chronic disease implications. The observational studies and some RCTs that were not accepted by the IOM committee as adequate evidence, indicate that the optimal serum 25(OH)D concentration is above 30ng/ml (75 nmol/l).
The conservative policy stance taken by the IOM suggests that we don’t place a high value on life. The value of statistical life year, assuming that 37 000 fewer deaths (0.001135 reduction in mortality rate) means that the value we place on life foregone with the current policy, is worth less than $88 000. The value of statistical life year is just the cost per person for the intervention divided by the mortality rate reduction due to the intervention. This, of course, depends on the cost of supplementing 4000 IU – 10000 IU per day (depending on the deficiency of the individual). If the benchmark $5 million for policy valuation is taken, then with an intervention cost of $100 per person per year, only 650 deaths would need to be prevented to justify supplementation to achieve these higher vitamin D levels.
So what should we do? The recommendation by the IOM and Health Canada is to wait for randomized control trials to come out. The greatest need is for long term RCT looking at the effect of high dose vitamin D supplementation, which will take over 10 years to obtain. However, RCTs don’t get it right all of the time, and by nature, are designed to address a different type of evidence requirement. In the meantime, the conservative stance taken on vitamin D supplementation could be putting millions of people at risk of increased disease rates and premature disability and death.
We do know that there is no evidence of harm associated with supplementation of 2000 to 4000 IU vitamin D per day, and potentially great benefits can be obtained. The Endocrine Society has released clinical practice guidelines that recommend 25(OH)D levels of 75nmol/L which requires at least 1000IU/day. The Alberta Medical Association estimates that between 70% and 97% of Canadians have Vitamin D insufficiency and to address this Toward Optimized Practice (TOP) has released new clinical practice guidelines (CPG) recommending Vitamin D supplementation of 800-2000 IU daily for the general adult population in Alberta. Given that vitamin D is a relatively inexpensive intervention, the promise of health benefits in terms of the potentially very large reduced burdens of chronic diseases holds great appeal for decision makers. With the increasing prevalence of chronic diseases in Canada, primary prevention is increasingly considered to be the most cost effective strategy for improving the health of Canadians, while reducing the service demands on the health-care system. Public health strategies are critical for primary prevention, and Health Canada should revisit what the appropriate range of normal 25(OH)D serum levels is for optimum health. Ultimately, changing policy to match supplementation guidelines targeted at reaching serum 25(OH)D levels of 75nmol/L should be reconsidered.