New Meta-Analysis Helps Demonstrate Importance of Vitamin D

The meta-analysis also serves as a sensible reminder to consumers not to make health-related decisions based on findings from the latest “study du jour,” as individual study or meta-analysis findings are often in conflict with one another for a variety of reasons, often relating to study design.

6 Jul 2012 --- A new meta-analysis1 published in the latest issue of the New England Journal of Medicine concludes that vitamin D supplementation at >800 IU daily for adults 65 and older helps prevent hip fracture and nonvertebral fracture. The findings of this meta-analysis, which pooled data from 11 double-blind, randomized, controlled trials and included over 30,000 participants, reinforce the importance of vitamin D for maintaining strong bones and protecting against osteoporosis in the aging population. Importantly, this meta-analysis incorporated data on the amount of vitamin D actually taken by the people in each study, not simply the amount they were assigned to take.

The meta-analysis also serves as a sensible reminder to consumers not to make health-related decisions based on findings from the latest “study du jour,” as individual study or meta-analysis findings are often in conflict with one another for a variety of reasons, often relating to study design.

“Scientific research establishes the fact that vitamin D is absolutely essential for building and maintaining strong, healthy bones. The elderly, especially post-menopausal women, are at elevated risk for osteoporosis,” said Annette Dickinson, Ph.D., consultant to the Council for Responsible Nutrition (CRN) and author of CRN’s recently published book The Benefits of Nutritional Supplements, 4th Edition. “We are particularly aware that consumer fatigue brought on by the onslaught of conflicting science creates confusion when it comes to knowing what is right for each individual, and we urge doctors and other health advisors to provide guidance based on the totality of evidence.”

The inconsistency in research is addressed in an editorial2 accompanying the meta-analysis by noted vitamin D expert Robert Heaney, M.D. Dr. Heaney, from the Osteoporosis Research Center at Creighton University Medical Center, emphasizes the need for research on vitamin D (and other nutrients) to take two important factors into account: 1) a subject’s baseline status, to indicate whether a nutrient inadequacy is present in the first place; and 2) adequacy of dose ensuring that a high enough dose is administered to reap a potential benefit. Dr. Heaney suggests that these two considerations are essential in the design of a vitamin D trial and existing variations from study to study undoubtedly contribute to the mixed findings from randomized controlled trials on vitamin D.

Says Dr. Heaney in his editorial, “Despite the consensus that more is not better, we have continued to conduct trials (and include them in meta-analyses) without regard to ensuring the presence of two key features: baseline status and dose adequacy.” He continues, “The question of how much vitamin D is enough is likely to remain muddled as long as meta-analyses focus on trial methodology rather than on biology.”

The meta-analysis, “A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention,” included participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every four months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Over 90 percent of the study subjects were women.

Reduction in the risk of fracture was shown in the groups taking 800 IU or more (up to 2000 IU), with a 30 percent reduction in the risk of hip fracture and a 14 percent reduction in the risk of any nonvertebral fracture. These significant benefits were observed in people who were assigned to take vitamin D and who actually took 800 IU or more of vitamin D.

The analysis shows that persons who are most vulnerable to vitamin D deficiency especially women 65 years of age or older with low baseline levels of 25-hydroxyvitamin D benefit from vitamin D supplementation at levels of 800 IU and above.

1 A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention. Bischoff-Ferrari A., et al. N Engl J Med 2012; 367:40-49.
2 Vitamin D — Baseline Status and Effective Dose. Heaney R., N Engl J Med 2012; 367:77-78.