Why Apply Drug Standards to Vitamin D Supplementation Studies?
What is a reasonable risk reduction goal to use in evaluating randomized, controlled trials (RCTs)? MedPage Today is negating benefits of vitamin D supplementation based on a meta-analysis which applied a 15% risk reduction target. Isn’t any nutritionally-attributable reduction in risk of fracture, cardiovascular disease (CVD) and cancer beneficial? If pharmaceutical treatments fail to achieve a 15% risk reduction, are they dismissed?
CVD, including coronary heart disease, stroke and peripheral vascular disease, is a leading cause of morbidity and death. For decades, aspirin has been a recommended therapy even though risk of hemorrhagic stroke increases. Treatment with aspirin does not reduce the risk of total cardiovascular events by 15%, has no effect on cardiovascular death or cancer mortality, and increases risk of nontrivial bleeding results by 31%. Yet recommendations for aspirin use persist.
Reducing high blood cholesterol, a risk factor for CVD, is an important goal of pharmacotherapy. A Cochrane Review of RCTs of statins (vs placebo or usual care) with a minimum of 1 year treatment and 6 months follow-up failed to find a 15% risk reduction. Yet, the conclusion reads: “Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life.” Indeed, new 2014 guidelines expanded statin use in the United States.
Drugs are routinely prescribed in the treatment of adults (primary prevention) with mild hypertension (systolic BP of 140-159 mmHG and/or diastolic BP 90-99 mmHg). A systematic review of 11 RCTs with 8,912 patients treated with antihypertensive drugs (compared to placebo) for 4 to 5 years did not reduce total mortality, coronary heart disease or total CVD events by 15%. Adverse events caused 9% of patients to discontinue treatment yet antihypertensive drugs are still recommended.
Why are Bolland and colleagues applying a 15% risk reduction to the benefits of vitamin D supplements? Is there no benefit to a 5 or 10% weight loss? Of course there is a benefit to weight loss when people are overweight. Is there no benefit to a 8% reduction in a disease endpoint with multivitamin supplementation? Nutrients are not drugs. The benefits (and risks) of nutrient RCTs are not the same as pharmaceutical doses of drugs. I have given 3 examples of drug interventions which do not yield a 15% risk reduction. Why apply this value to vitamin D supplementation?
Don’t be misinformed by headlines. Many people have low serum 25(OH)D3 concentrations and will benefit from using a vitamin D supplement. Be informed. Get your vitamin D status measured.
For an earlier review of the Bolland paper, see previous TalkingNutrition blog post.
Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. The Lancet Diabetes & Endocrinology - 24 April 2014. DOI: 10.1016/S2213-8587(14)70068-3
Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. 2012 Sao Paulo Med J doi:
Taylor F, Huffman MD, Macedo AF, Moore THM, Burke M, Smith GD, Ward K, Ebrahim S. Statins for primary prevention of cardiovascular disease. 2013 Cochrane Library doi: 10.1002/14651858.CD004816.pub5
Seshasai SRK, Wijesuriya S, Sivakumaran R, Nethercott S, Erquo S, Sattar N, Ray KK. Effect of aspirin on vascular and nonvascular outcomes: Meta-analysis of randomized controlled trials. 2012 Arch Intern Med doi: 10.1001/archinternmed.2011.628
Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Sesso HD, Buring JE. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2009 Jan 7;301(1):52-62. doi: 10.1001/jama.2008.862