Vitamins, Herbs, Supplements, and Antiinflammatories

Vitamin D

A study published in September 2014 of over 1500 healthy older adults found that those who had vitamin D deficiency were between 1.7 (mild deficiency) and 2.2 (severe deficiency) times more likely to develop all-cause dementia and Alzheimer’s disease ( Fig. 21.1 ) ( ). Since then, other studies have also found correlations between insufficient levels of vitamin D poor cognitive performance ( ). However, a prior study found that vitamin D supplementation on healthy older women had no effect on cognition or the development of mild cognitive impairment (MCI) or dementia ( ). How do we reconcile these studies? The simple answer is most likely that supplementation of vitamin D is helpful if an individual’s levels are low. Vitamin D levels are, in fact, low in many older adults. Moreover, there are other proven benefits of vitamin D in the older adult, such as improving bone health (when combined with calcium), and there are few reported side effects of vitamin D when taken in recommended dosages. We therefore recommend that our older adults with memory problems (whether because of normal aging or disease) either have their vitamin D levels checked or simply take vitamin D supplementation. Because there have been no positive trials in improving cognition or reducing dementia, the exact dose and form of vitamin D to recommend (D2, ergocalciferol vs. D3, cholecalciferol) is unclear at this time. The FDA recommends 400 IU (10 mcg) daily. Many guidelines recommend between 400 and 1000 IU daily, and most experts recommend the D3 (cholecalciferol) form. In our clinic we generally recommend 2000 IU of vitamin D3, or whatever dose is needed to achieve levels between 30 and 50 ng/mL. Note that there are some important and common drug interactions with vitamin D, including with digoxin, diltiazem, verapamil, thiazide diuretics, and others, so interactions should be checked before recommending vitamin D to your patient.

Vitamin E

A paper published in the New England Journal of Medicine in 1997 reported the results of a 2-year, double-blind, placebo-controlled, randomized trial in 341 patients with mild to moderate Alzheimer’s disease receiving either high doses (2000 IU/day) of vitamin E (alpha-tocopherol), selegiline 10 mg/day, both, or placebo. The results showed no statistically significant difference in the outcomes among the four groups. However, after adjustment for unequal baseline Mini-Mental State Examination (MMSE) scores by including MMSE as a covariate, all treatment groups—vitamin E, selegiline, and combined—showed better outcomes than the placebo ( ). In 2014 the Journal of the American Medical Association (JAMA) reported the results of a double-blind, placebo-controlled, randomized trial evaluating 613 patients with mild to moderate Alzheimer’s disease treated with vitamin E 2000 IU/day, memantine (Namenda) 20 mg/day, both, or placebo. The authors found that, compared with placebo, there was a slower rate of decline in the vitamin E group, but not in the memantine-alone group nor in the group treated with both vitamin E and memantine ( ). A randomized, double-blind, placebo-controlled study that evaluated vitamin E 2000 IU/day versus donepezil (Aricept) 10 mg versus placebo in over 750 patients with mild cognitive impairment over 3 years showed no benefit for vitamin E ( ). Another study examined 7540 patients with vitamin E 400 IU/day for 6 years and found no effects on the prevention of Alzheimer’s disease ( ).

How are we to best understand these somewhat conflicting data? How do we interpret a study in which there were no effects of treatment until a covariate analysis was performed to correct for unequal baseline, and then all treatments showed effects? What does it mean that another study found benefit for vitamin E alone but not when combined with memantine; does that mean that vitamin E is beneficial but memantine counteracts its beneficial effect? In our view, the data show that vitamin E provides no benefit in patients with mild cognitive impairment, and the data for the use of vitamin E in patients with mild to moderate Alzheimer’s disease remain unclear. Vitamin E may increase the risk of cardiac events in individuals with vascular disease or diabetes ( ), and vitamin E may cause problems with bleeding and/or easy bruising in some individuals ( ), including hemorrhagic stroke ( ).

Based upon the available data, regardless of whether they are cognitively healthy or they have been diagnosed with mild cognitive impairment or Alzheimer’s disease, we do not recommend vitamin E supplementation for our patients, and if they are already taking vitamin E solely to prevent or retard Alzheimer’s disease, we recommend that they discontinue it.