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4. High carbohydrate diets and Alzheimer's disease.
This study was first published in Med Hypotheses.
2004;62(5):689-700.
"Alzheimer's disease (AD) is a common, progressive, neurodegenerative
disease that primarily afflicts the elderly. A well-defined risk
factor for late onset AD is possession of one or more alleles of the
epsilon-4 variant (E4) of the apolipoprotein E gene. Meta-analysis of
allele frequencies has found that E4 is rare in populations with long
historical exposure to agriculture, suggesting that consumption of a
high carbohydrate (HC) diet may have selected against E4 carriers. The
apoE4 protein alters lipid metabolism in a manner similar to a HC
diet, suggesting a common mechanism for the etiology of AD.
Evolutionarily discordant HC diets are proposed to be the primary
cause of AD by two general mechanisms. (1) Disturbances in lipid
metabolism within the central nervous system inhibits the function of
membrane proteins such as glucose transporters and the amyloid
precursor protein. (2) Prolonged excessive insulin/IGF signaling
accelerates cellular damage in cerebral neurons. These two factors
ultimately lead to the clinical and pathological course of AD. This
hypothesis also suggests several preventative and treatment
strategies. A change in diet emphasizing decreasing dietary
carbohydrates and increasing essential fatty acids (EFA) may
effectively prevent AD. Interventions that restore lipid homeostasis
may treat the disease, including drugs that increase fatty acid
metabolism, EFA repletion therapy, and ketone body treatment."(9).
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