Vitamin D- Under Fire

posted by on October 26th, 2015

No specific constituent of the diet is solely responsible for the emergence of Chronic Disease, but the overall quality of the diet, including supplementation, is paramount to prevention.

Periodically a story will hit the mainstream media about vitamins, supplementation or preventive health opposing a view the majority of the population hold, health experts included. A study out the New Zealand, published in Lancet Diabetes & Endocrinology (online January 24, 2014) did just that.  The study declared no measurable benefits of Vitamin D for chronic health complaints, in the face of volumes of investigations citing the benefits of vitamin D and improvement in health and quality of life (1,2).  The study was a meta-analysis, of 40 randomized-controlled studies.  The analysis was done by Mark Bolland of the University of Auckland in New Zealand.

Study Facts:

The 40 studies analyzed had a primary goal to evaluate the benefits of Vitamin D alone or with Calcium on the reduction of Osteoporosis and fracture rates. Secondary endpoints were prevention of chronic disease factors such as vascular disease and cancer.

Why is this important?

A common concern when using meta-analysis to make wide reaching claims is the failure to eliminate comparisons between studies that do not share strong similarities like: study size, elimination and inclusion criteria, and control for age, gender and measure of ingredient(s) being studied for example. What we learned may be a concern in taking the report in the Lancet at face value.

  • Study group size varied greatly with data from small groups, as small as 80 individuals, being weighed as heavily as large cohort studies. One study included 36,000 individuals
  • Administration amounts of Vitamin D varied from 200 iu/day to 9000 iu/day compared to some studies administering supra-physiologic doses either 1 time during the study period or one time per quarter.
  • Method of administration varied from per oral to Intramuscular injection.The Press reported: “Existing evidence does not lend support to the commonly held belief that vitamin D supplementation in general prevents osteoporosis, fractures and non-skeletal diseases”- Karl Michaelsson, Professor of Orthopedics Uppsala Univ., Sweden (in a comment accompanying the article)67.5 % of participants at the end of the study(s) conclusion had failed to reach accepted minimum requirements for vitamin D sufficiency (3), yet the conclusion was reached that vitamin D had no benefit rather than stating there may be room to support further research into outcomes in populations with sufficient vitamin D levels.
  • Why is this a problem?
  • Additionally there was a large variance between the lengths of studies. 48% of the studies included were less than a year in duration with 1 in 5 being less than 6 months in total duration. The benefits of any intervention in chronic disease may take years to truly appreciate its effects on health outcomes. A longer duration is essential when making claims about prevention.
  • One reason supplementation in the meta-analysis did not prove beneficial in reaching sufficiency was the treatment of Vitamin D2-ergocalciferol as equivalent to Vitamin D3, Cholecalciferol. The relative potencies of vitamins D2 and D3 are not equivocal.

Vitamin D2- ergoclaciferol is the inactive form of the Vitamin and requires conversion by the body into its active form D3 Cholecalciferol. Many patients will not make the conversion via liver, intestine and kidney due to already present disease, genetic factors, lifestyle and age.  While evaluating the validity of the analysis, understand both D2 and D3 will initially raise serum values of 25OHD, but vitamin D2 is limited in its capacity to keep 25OH-D in sufficient levels greater than 14 days after arresting administration due to its short half-life in the body. Evidence available today indicates that vitamin D3 is substantially more efficacious than vitamin D2.  Epidemiological studies report ergocalciferol D2 as being, at best 1/3 of the benefit of D3 (4,5).  This is of particular concern in the immuno-compromised, elderly, malnourished and those with liver, kidney or intestinal decline or anyone above the age of 40 due to natural decline in conversion from the skin.

What did the mainstream media and commentaries fail to mention.

The analysis found a small increase (5%) in the benefit of Vitamin D and Calcium in the reduction of mortality, but considered this percentage to be within a futility boundary.

  • This 5% reduction in mortality was compared to no increase in risk of mortality when compared to placebo.
  • Vitamin D in combination with Calcium did improve bone mineral density, and reduction in fracture, but not greater than by 15% when compared to placebo. The reports could not to make mention of the benefits of this increase over time because of the short duration of the studies included.
  • No data on nutritional status or Rx drug intake was included in the findings as contributing to fracture, heart disease or relative risk for cancer.
  • Risk factors associated with advanced years were not considered as a contributory factor to disease or infirmity when claiming no preventive benefits from Vitamin D alone or in combination with Calcium.
  • Average age of study participant 77
  • 86% of participants were females with 94% of the female population being post-menopausal by no less than 15 years, a primary risk factor for Osteoporosis and risk for fracture.According to Dr. Nancy Miller, ask:Was the stud designed to look at a primary outcome, but then reported on another? I.e.: was the study designed to answer the specific question about heart disease and cancer?At the end of the day, these points are true.2-You can’t start with an already unhealthy population and evaluate the preventive benefits of a supplement.4-If you torture the data long enough; you can get it to confess.

The numerous health benefits of Vitamin D are very well documented.  My recommendation when a study defies what historically is accepted and supported in the literature:

  • Understand Meta analysis can provide a lot of data but you only want to combine data that is similar.
  • Did the study take into consideration confounding factors like age, co-morbid disease or illness?
  • Was the study designed to evaluate the efficacy of supplementation or intervention in an appropriate population? In this case was it appropriate to make prevention claims in an elderly population?
  1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71.
  2. Liu S, Sonh Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older US women. Diabetes Care. 2005 Dec;28(12):2926-32.
  4. Lehmann B. The vitamin D3 pathway in human skin and its role for regulation of biological processes. Photochem Photobiol. 2005 Feb 1.
  5. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56.