In response to mounting physician interest in vitamins and dietary supplements, Monique Yohanan, MD, MPH, a physician editor at Epocrates, Inc, reviewed her picks for articles about vitamin D, calcium, and glucosamine(Drug information on glucosamine) that she considers “most likely to influence clinical practice” at the recent APA meeting in Honolulu.
Dr Yohanan also reviewed her choice of other top medical articles of 2010 at the APA meeting. What follows here and in future e-newsletters is a recap of the highlights of her comprehensive and practical review of those articles. Dr Yohanan is boarded in internal medicine, geriatrics, and hospice and palliative care.
Vitamin D and cognition
While there is “huge enthusiasm for vitamin D,” some of the outcomes of studies reported in 2010 are “equivocal,” Yohanan said. She urged her audience to pay attention to the differences between association and causation. As an example, she cited the study of Llewellyn and colleagues1 that sought to determine whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline.
The researchers looked prospectively at the relationship between vitamin D and cognitive decline in the InCHIANTI study, a population-based study conducted in Italy between 1998 and 2006, with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE). Substantial decline was defined as 3 or more points.
Those persons who were severely deficient in vitamin D (< 25 nmol/L) had a higher risk for substantial decline on the MMSE than those with sufficient levels (≥ 75 nmol/L). Those who were severely deficient also declined by an additional 0.3 MMSE points per year more than those with sufficient levels.
In her review, Yohanan said “that what the researchers ended up seeing is that there is a greater decline in mental function with people who have low levels. The researchers concluded that it’s the vitamin D. And they really sort of jump to that conclusion.”
In an editorial accompanying the Llewellyn’s article in the Archives of Internal Medicine, Grey and Bolland questioned whether low vitamin D might just be a marker for overall poor health.2
“It is now time to test the various hypotheses generated by observational studies of vitamin D, including that of Llewellyn and associates, in adequately designed and conducted randomized controlled trials,” Grey and Bolland concluded.” Very importantly, such trials will also provide an opportunity to systematically assess potential harms of vitamin D supplementation, an issue that has been largely overlooked or dismissed.”
Yohanan also cited a study by Sanders and coworkers3 that examined whether a single annual dose of 500,000 IU of cholecalciferol(Drug information on cholecalciferol) (vitamin D) administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. The researchers found that among older community-dwelling women, annual oral administration of high-dose cholecalciferol actually resulted in an increased risk of falls and fractures.
“There is this huge enthusiasm for vitamin D, but at this point, the evidence from randomized control trials for the prevention. . . just isn’t there yet,” said Yohanan.
Calcium and the heart
Oftentimes, when patients get a prescription for vitamin D, they also get a prescription for calcium, Yohanan pointed out. “We are just starting to see some of the literature on this, but it gives me pause,” she said.
In 2010, the British Medical Journal4 published a study about the effect of calcium supplements on the risk of myocardial infarction (MI) and cardiovascular events.
The researchers looked at 15 databases and randomized control trials from the databases. They had patient-level data from more than 8,000 (77% women; median follow-up, 3.6 years).
“They found 143 MIs infarctions in patients who were taking calcium and 111 in patients taking placebo,” Yohanan said. “The authors concluded that if you put 1,000 people on calcium for 5 years, you will prevent 26 fractures (a benefit, but small) but you would end up causing an additional 14 MIs.”
Glucosamine and joints
Randomized trials of glucosamine and chondroitin for osteoarthritis (OA) show mixed results, said Yohanan. A meta-analysis of 10 randomized controlled trials involving 3,803 patients that compared glucosamine and/or chondroitin with placebo or head to head were analyzed by Wandel and coworkers.5
The researchers found that compared with placebo, glucosamine, chondroitin, or their combination do not reduce joint pain or have an impact on narrowing of joint space. Looking at adverse events, the authors said the odds ratios of adverse events compared with placebo were 0.94 (0.59 to 1.47) for glucosamine and 0.99 (0.49 to 2.00) for chondroitin. No data were available on adverse events overall for the combination.
“We are confident that neither of the preparations is dangerous. Therefore, we see no harm in having patients continue these preparations as long as they perceive a benefit and cover the costs of treatment themselves,” they said.
Offering a personal anecdote, Yohanan said that despite the mixed evidence in human studies, she did feed glucosamine biscuits to her dog and saw a difference in the dog’s ability to jump on the couch again.