Thursday, July 22, 2010

Vitamin D: Latest Research Updates & Perspectives

D-HeroVitamin D is no longer considered a vitamin, but rather a hormone that may have remarkably beneficial functions well beyond those of regulating calcium absorption and bone health, including the relief of pain for many patients. This long blogpost provides an UPDATE on recently published research as well as some contrary perspectives and rather perplexing new guidelines on vitamin D.

We have previously written extensively on the role of vitamin D in pain conditions of various sorts [reports here / blogpost series here open in new window]. Additionally, the association with and possible causal effect of insufficient vitamin D in many chronic diseases is becoming more widely appreciated. Recent observational studies have reported inverse associations between levels of serum 25-hydroxyvitamin-D, or 25[OH]D, the metabolite that best reflects overall vitamin D status, and the risk of cancer, vascular disease, infectious conditions, autoimmune diseases, osteoporosis, type 2 diabetes mellitus, and obesity [Pearce and Cheetham 2010]. Still, what constitutes an optimal blood concentration of 25(OH)D for humans remains unknown and the subject of debate. Following, are some recently reported items of interest.

Vitamin D and Headache, Parkinson’s Disease, Dementia
There has been relatively little research on the association of vitamin D insufficiency with migraines and headaches, although there does seem to be a connection in case reports. A team of practitioners at a Dallas, Texas, headache and pain clinic observed insufficient average 25(OH)D levels of 25.9 ± 5.5 ng/mL in a cohort of 35 patients with headache and migraine, which was comparable to 24.7 ± 6.1 ng/mL in 35 patients with other pain conditions [Krusz et al. 2010]. In contrast, a control group of 12 “normal” patients without those disorders had significantly higher average levels of 36.4 ± 8.2 ng/mL (p<0.05). Unfortunately, the clinicians did not report whether supplementation with vitamin D to raise 25(OH)D levels in the patients with pain or headache/migraine had beneficial effects.

Writing in the July 2010 edition of Archives of Neurology researchers from Finland report the first longitudinal analysis of vitamin D status as a risk for Parkinson’s disease in a cohort of more than 3,000 participants aged 50 to 79 years [Knekt et al. 2010]. During a 29-year follow-up period, 50 incident Parkinson’s disease cases occurred in the group, with individuals having higher serum vitamin D concentrations showing a significantly 33% reduced risk of developing the disease. Adjustments in the analysis were made for sex, age, marital status, education, alcohol consumption, leisure-time physical activity, smoking, body mass index, and month of blood draw. The authors believe their results are consistent with the suggestion that high vitamin D status provides protection against Parkinson’s disease; however, large, prospective, controlled trials would be needed to confirm this.

In the July 12, 2010 issue of the Archives of Internal Medicine, Llewellyn and colleagues [2010] report that, in a prospective cohort study of 858 adults aged 65 years and older, baseline levels of serum 25(OH)D were inversely related to the rate of cognitive decline during a median follow-up of 6 years. This effect was most apparent in participants with the lowest levels of 25(OH)D (<10 ng/mL or 25 nmol/L) and persisted after adjusting for several potential confounding variables. Thus, accelerated cognitive decline is now added to the list of conditions that have been associated with deficient levels of vitamin D.

Contrarian Perspectives on Vitamin D Impact
In fair balance, researchers from New Zealand — editorializing in the Archives of Internal Medicine — note that the results of observational studies have prompted calls for widespread treatment of individuals with low levels of vitamin D and the establishment of public health programs aimed at raising levels of vitamin D to "healthy" values throughout the population [Grey and Bolland 2010]. Commonly, they note, 25(OH)D levels regarded as “sufficient” are higher than 30 ng/mL (75 nmol/L) and by some accounts >40 ng/mL (100 nmol/L). They concede that most individuals in the general population have at least insufficient vitamin D levels; however, they question whether the costs and difficulties of universally raising 25(OH)D levels is justified by available evidence.

Rather, Grey and Bolland [2010] believe it is “intuitively unlikely that a single hormone could play a substantial role in preventing or ameliorating the diverse range of diseases that have been linked to low levels of vitamin D.” A more plausible explanation for the findings of the observational vitamin D studies, they suggest, is that “less healthy individuals, who are more likely to subsequently experience morbid events, will be heavier, less active, and more sunlight-deprived than healthier ones and therefore have lower levels of 25(OH)D.” Hence, “low vitamin D levels may simply be a marker for lower health status rather than a cause of it” [emphasis added].

Unfortunately, sufficient numbers of prospective, randomized, and rigorously controlled trials of vitamin D have been lacking. Grey and Bollard [2010] note that this is especially the case regarding research investigations of non-musculoskeletal endpoints, such as vitamin D supplementation effects on body weight, glycemic control in type 2 diabetes mellitus, and the incidence of respiratory infections. They conclude that, “Put simply, a rigorous evidence base for recommending vitamin D supplementation for improving health outcomes, either skeletal or non-skeletal, in community-dwelling individuals does not currently exist, beyond the avoidance of vitamin D levels that can produce osteomalacia.”

They further suggest that merely repeating and updating meta-analyses of existing data sets, which has the potential to confuse rather than clarify, is inappropriate. And, of some importance, new and properly designed trials should also systematically assess potential harms of long-term vitamin D supplementation, which has been largely overlooked or dismissed. “We should invest in trials that provide the best possible evidence on the benefits and risks of vitamin D before we invest in costly, difficult, and potentially unrewarding interventional strategies,” they stress. However, they fail to recommend where funding might come from for such research trials, considering that vitamin D is a generic, low cost, nutritional product without potential “blockbuster drug” value to interest sponsors. And, government agencies worldwide have been reticent when it comes to broadly supporting such research.

Confusing New Guidance on Vitamin D Intake
In June 2010 the U.S. Department of Agriculture released its newly updated Dietary Guidelines for Americans, which was the first revision in many years [USDA 2010]. They note that merely 31% of Americans have adequate intake of vitamin D from foods, consequently a significant portion of the population has deficient or inadequate blood levels of 25(OH)D. From diet alone, less than 10% of men and women older than age 50 and fewer than 2% of those older than 70 years of have adequate vitamin D intake of 400 to 600 IU/day (10-15 mcg/d). Supplements are consumed by 37% of the population; however, even when adding this to dietary intake, fewer than 45% of adults older than 50 years of age and less than 25% of those older than age 70 meet the daily adequate intake.

At that, many believe the recommended daily adequate intake for vitamin D is set way too low, and the USDA Guidelines offer no new direction in that regard. They defer to the Institute of Medicine (IOM), which is currently reviewing the dietary reference intake (DRI) for vitamin D that had been established more than a decade ago in 1997. At that time, 25(OH)D levels of 11 to 12 ng/mL were considered as the lower limits of ‘normal,’ based on associations with healthy bone growth in children and normal parathyroid concentrations in adults. More recent research contradicts those assumptions, believing that much higher 25(OH)D levels are necessary for health. The IOM report with new recommendations is expected in the fall of 2010.

Meanwhile, in a separate report [Ubelacker 2010], Osteoporosis Canada released updated recommendations on how much vitamin D adults should be taking to keep their bones strong. New guidelines, appearing in the Canadian Medical Association Journal [Hanley et al. 2010], recommend daily supplements of 400 to 1,000 IU of vitamin D for adults under age 50 without osteoporosis or conditions affecting vitamin D absorption. Older adults, over age 50 with or without the bone-thinning disease, should take between 800 and 2,000 IU/day. The guidelines' authors say that some persons may find it more convenient to take their vitamin D weekly in a dose of 10,000 units [however, we should note, there is no research evidence to support the effectiveness or adequacy of such a once-weekly dosing regimen].

In contrast, Health Canada, the federal agency, has claimed for many years that adequate daily vitamin D intake for anyone aged 2 to 50 would be merely 200 IUs, which could be obtained through fortified dietary products. It further advises that all adults over age 50 should supplement their diet with 400 IU/day of vitamin D, which is a throwback to the 1997 DRIs established by the IOM. Adding further confusion, several years ago the Canadian Cancer Society, based on research suggesting that vitamin D may boost the immune system and reduce the risk of some cancers, recommended taking 1,000 IU/day during the fall and winter. Those at higher risk of insufficiency, among them older people and those with dark skin, should consider taking that amount all year round, the organization advised.

The major commonality in all of the recommendations is a recognition that all persons are at risk for vitamin D insufficiency or deficiency and that dietary intake of the vitamin is generally inadequate. Interestingly, there is little discussion about boosting vitamin D levels via regular exposure to sunshine; probably because, as we have noted, the Sun is a very unreliable source of vitamin D on a consistent basis. Therefore, the benefits of supplementation are becoming more widely accepted but the recommended daily amounts of vitamin D for health vary widely, are broadly inadequate, and confusing.

A Skeptic’s Acceptance of Vitamin D
Finally, we would like to thank Paul D. Maher, MD, MPH, for the clear and concise 3-part series he did discussing our prior work on vitamin D for pain at his blog, “The (Skeptic's) Health Journal Club.” Part III of the series, with back-links to the earlier 2 installments, can be accessed [here]. The blog itself, in which Dr. Maher discusses the scientific evidence for, and often debunks the myths behind, many “medical marvels” can be accessed [here].

CONFLICT OF INTEREST / DISCLAIMER: Pain Treatment Topics and the author (SBL) do not have any financial relationships with any manufacturers or promoters of nutritional supplements containing vitamin D. The information in these UPDATES reflects the evidence from the cited sources and is not intended to provide medical advice pertaining to any health conditions — readers should consult their healthcare providers if there are questions or concerns regarding the appropriateness of vitamin D supplementation for their individual needs.

> Grey A, Bolland M. Vitamin D. A Place in the Sun? Arch Intern Med. 2010;170(13):1099-1100 [
> Hanley DA, Cranney A, Jones G, et al. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. Can Med Assoc J. 2010(Jul); online ahead of print [
citation, no abstract].
> Knekt P, Kilkkinen A, Rissanen H, et al. Serum Vitamin D and the Risk of Parkinson Disease. Arch Neurol. 2010;67(7):808-811 [
> Krusz JC, Cagle JA, Albright JP, Scott-Krusz V. Vitamin D Levels in Pain and Headache Patients. Practical Pain Management. 2010(Jun);10(5):68-70 [see,].
> Llewellyn DJ, Lang IA, Langa KM; et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170(13):1135-1141. [
> Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. British Med J. 2010;340:b5664 [
article here].
> Ubelacker S. Osteoporosis Canada Issues Updated Vitamin D Guidelines for Bone Health. Health Reporter (Canadian Press). 2010(Jul 12) [article here].
> USDA (US Department of Agriculture). Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2010 (Advisory Report). 2010(Jun);Part D, Section 2: Nutrient Adequacy [full report here].