Role of antioxidants and a nutrient rich diet in Alzheimer's disease.

The joint attack on the body by metabolic acidosis and oxidative stress suggests that treatment in degenerative diseases, including Alzheimer's disease (AD), may require a normalizing of extracellular and intracellular pH with simultaneous supplementation of an antioxidant combination cocktail at a sufficiently high dose. Evidence is also accumulating that combinations of antioxidants may be more effective, taking advantage of synergistic effects of appropriate antioxidants as well as a nutrient-rich diet to prevent and reverse AD. This review focuses on nutritional, nutraceutical and antioxidant treatments of AD, although they can also be used in other chronic degenerative and neurodegenerative diseases.

Reduction of inclusion body pathology in ApoE-deficient mice fed a combination of antioxidants.

Clinical studies have shown that the antioxidant vitamin E can slow the progression of Alzheimer's disease (AD). Other antioxidants reported to affect cognitive function include ginkgo biloba, vitamin C, and lipoic acid. To examine the effects of combination antioxidant therapy (CAT) on longevity and neuropathology in mice, we supplemented the diet of ApoE-deficient mice with vitamin E, ginkgo biloba, pycnogenol, and ascorbyl palmitate. ApoE-deficient mice normally exhibit increased numbers of PAS-positive inclusion bodies with aging. However, supplementation with CAT resulted in a significant increase in life span and a marked reduction of inclusion body histopathology in the hippocampus. In addition, while untreated apoE-deficient mice exhibited increased levels of TUNEL staining, a marker of DNA fragmentation, supplementation with CAT resulted in a significant reduction in the levels of TUNEL staining. These findings suggest that oxidative mechanisms, perhaps related to neuronal apoptosis, are integral to inclusion body formation in aging mice. The association between the reduced number of apoptotic cells and the reduction in inclusion bodies may explain in part the increased longevity of mice fed CAT, and supports the contention that the combined actions of selected antioxidants may be therapeutically effective against neurodegenerative diseases.