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Alzheimer's disease (a form of dementia) is characterized by the build-up in the brain of a protein known as 'amyloid-beta'. Not surprisingly, amyloid-beta has been 'targeted' by drug companies, including Eli Lilli who produced the drug Semagacestat which did a nice job of retarding amyloid-beta synthesis. However, in trials, Semagacestat accelerated decline in brain function in those who took it.

I learned this fact today reading a review from the European Journal of Internal Medicine entitled "Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet" [1]. The review is dense with information, and I might extract its information over more than one blog. But for starters, I thought I would pull out at least some of the interest insights this paper contains.

One of the major points made in the paper is this: cholesterol and fat is really important to the brain. It points out that although the brain is only about 2 per cent of body weight, it contains about a quarter of the total cholesterol in the body. The authors point out several roles for cholesterol in the brain, including the synapse - the 'gap' where one cell can communicate with another. Communication here is via what are known as 'neurotransmitters', which are released by one nerve cell and float across the synaptic gap to exert the effect on the nerve adjacent to it. The authors summarise the importance of cholesterol in the brain like this:

Cholesterol is required everywhere in the brain as an antioxidant, an electrical insulator (in order to prevent ion leakage), as a structural scaffold for the neural network, and a functional component of all membranes. Cholesterol is also utilized in the wrapping and synaptic delivery of the neurotransmitters. It also plays an important role in the formation and functioning of synapses in the brain.

It's also true that the brain actively takes up cholesterol (in the form of LDL cholesterol). This in itself suggests that cholesterol is desired in the brain and does something useful. Interestingly, a gene defect which leads to impaired cholesterol uptake by the brain is also associated with an enhanced risk of Alzheimer's disease.

The authors of this review also point out that the fluid that circulates in and around the brain and spinal column (the cerebrospinal fluid) in individuals with Alzheimer's disease is low in cholesterol and other fats compared to individuals without this disease. Also, those who run low cholesterol levels are found to be at increased risk of dementia.

What this got to do with carbohydrate, though? As the reviewers point out, carbohydrates raised blood sugar levels, and sugar (either in the form of glucose or fructose) can damage tissues through the formation of 'advanced glycation end-products' (AGEs). AGE damage can affect LDL cholesterol, and impair its uptake into the brain.

The authors of the review note also that individuals with type 2 diabetes (who tend to run raised blood sugar levels) have a 2- to 5-fold enhanced risk of Alzheimer's disease. It's been suggested that the fundamental problem here is impaired cholesterol availability by the brain.

What we've learned from this is:

-our brains need cholesterol
-a high-carbohydrate diet is likely to stop our braining getting enough cholesterol

Now, do we have any takers for a low-fat, low-cholesterol, high-carbohydrate diet?

References:

1. Seneff A, et al. Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet Eur J Int Med 2011;22:134-140