Diet and Alzheimer's Disease: What the Evidence Shows

Martha Clare Morris, ScD

Disclosures
In This Article

Introduction

Our understanding of dietary influences on Alzheimer's disease is in its infancy, and the number of epidemiologic studies examining promising associations is limited. Thus, at this time, we cannot say with certainty that any particular nutritional component causes or prevents Alzheimer's disease. With that caveat, much of the evidence from early studies in many ways reflects a pattern of dietary associations very similar to more established dietary risk factors for cardiovascular diseases, such as heart disease. Thus, patients who adopt these dietary practices will reduce their risk for heart disease and may also curtail their risk of developing Alzheimer's disease.

Perhaps the best evidence of disease prevention involves the antioxidant nutrients, vitamins E and C. The neuropathologic features of Alzheimer's disease include amyloid beta (A-beta) plaques, an abnormal accumulation of A-beta protein outside neuronal cells, and neurofibrillary tangles within the cells. Numerous animal and laboratory studies have shown that Alzheimer's disease involves oxidative and inflammatory processes, although it is not known whether these processes are a cause or effect of the disease or both. The ultimate result, however, is disruption of neuronal cell functioning and signaling, leading to neuronal cell death.

The brain is a site of high metabolic activity that generates free radical molecules, oxygen molecules with unpaired electrons that are highly reactive and thus toxic to cell tissue. Infection, cell injury, and environmental toxins, such as smoking and pollution, also generate free radical molecules. The body possesses natural defense mechanisms to combat oxidative stress, including antioxidant proteins and nutrients. Vitamin E is a potent chain-breaking antioxidant that resides within cell membranes, where it can neutralize free radicals as they are generated. Vitamin E also has anti-inflammatory properties. Vitamin C, a less potent antioxidant than vitamin E, circulates within the plasma and retains the additional function of restoring vitamin E to its antioxidant capacity.

Animal and laboratory studies demonstrate that the antioxidant nutrients, and vitamin E in particular, protect the brain from damage due to oxidative and inflammatory mechanisms.[1,2] Rodents fed antioxidant-supplemented diets had superior learning acquisition and memory retention compared with rodents on control diets. At death, the brains of the antioxidant-fed rodents exhibited less neuronal cell loss and less evidence of oxidative damage and inflammation.[3,4]

The available evidence from human studies is limited and not altogether consistent. Two prospective studies, 1 of Chicago, Illinois, residents[5] and 1 in Rotterdam, The Netherlands,[6] found a lower risk of Alzheimer's disease with a higher food intake of vitamin E. However, another prospective study conducted in New York found no association.[7] Vitamin E intake in the New York study may have been too low to provide a neuroprotective benefit; the median of 7 IU/d for persons in the top third of intake was comparable to the lowest intake levels in the Chicago and Rotterdam studies.

Of the 3 trials, only the Rotterdam study found a reduced risk of Alzheimer's disease with high food intake of vitamin C. However, the Chicago study found that participants with the highest food intake of vitamin C were more than twice as likely to have a history of stroke or hypertension, and these persons may have increased their fruit consumption as a recent preventive measure, thus obscuring a potential protective association with Alzheimer's disease.

In none of the 3 prospective studies was vitamin E and vitamin C supplement use associated with less risk of Alzheimer's disease. Two other prospective studies[8,9] examined vitamin supplement use in relation to Alzheimer's disease, and only 1 of these[8] found evidence of reduced risk. There are several plausible explanations for the absence of association with vitamin E supplements. Vitamin E supplements have traditionally contained only alpha-tocopherol, the most biologically active form of vitamin E; however, gamma-tocopherol is the more abundant form in the US diet. Whereas alpha-tocopherol is the more potent antioxidant, gamma-tocopherol also has anti-inflammatory properties.[10] Recent studies indicate that the combined intake of the 8 different tocopherol forms reduces oxidative stress and inflammation to a greater degree than alpha-tocopherol alone.[11]

Another explanation for the absence of association with vitamin E supplements is that food intake may be a better indicator of long-term exposure to vitamin E. In addition, the study findings could be biased if many study participants initiated vitamin supplement use because of developing problems in cognition.

In summary, the strongest evidence for antioxidant protection against Alzheimer's disease rests with high food intake of vitamin E. The richest food sources of vitamin E include vegetable oils, margarine, nuts (especially almonds), and seeds (especially sunflower seeds). Moderate amounts of vitamin E are found in whole grains, egg yolk, and a limited number of vegetables (eg, collard greens) and fruits (eg, avocados, apples, melon).

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