Extracts from:
Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet
Stephanie Seneff, Glyn Wainwright, Luca Mascitelli
Department of Electrical Engineering and Computer Science, MIT Cambridge, MA, USA.
Summary:
Alzheimer’s disease (AD) may be caused by a deficiency in the supply of cholesterol, fats, and antioxidants to the brain, alongside an excess of dietary high-glycaemic index carbohydrates, particularly fructose.
Simple dietary modification, towards fewer highly processed carbohydrates and relatively more fats and cholesterol, is likely a protective measure against Alzheimer’s disease.
A first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport. This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function. Over time, a cascade response leads to impaired glutamate signalling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis.
Amyloid-β synthesis may represent a protective mechanism that redirects metabolism away from glucose and away from the mitochondria, in order to decrease the rate of further decline due to glycation and oxidative damage.
Increased production of glutamate is necessary to maintain signal transport in the face of cholesterol deficiency, yet glutamate causes further oxidative damage. Eventually, further maintenance of the cell is counterproductive, and it undergoes apoptosis. Once a sufficient number of cells are destroyed in this way, major cognitive decline is manifested.
Key points:
- The amyloid-β present in Alzheimer’s plaque may not be causal, since drug-induced suppression of its synthesis led to further cognitive decline in the controlled studies performed so far.
- Researchers have identified mitochondrial dysfunction and brain insulin resistance as early indicators of Alzheimer’s disease.
- ApoE-4 is a risk factor for Alzheimer’s disease, and ApoE is involved in the transport of cholesterol and fats, which are essential for signal transduction and protection from oxidative damage.
- The cerebrospinal fluid of Alzheimer’s brains is deficient in fats and cholesterol.
- Advanced glycation end-products (AGEs) are present in significant amounts in Alzheimer’s brains.
- Fructose, an increasingly pervasive sweetening agent, is ten times as reactive as glucose in inducing AGEs.
- Astrocytes play an important role in providing fat and cholesterol to neurons.
- Glycation damage interferes with the LDL-mediated delivery of fats and cholesterol to astrocytes, and therefore, indirectly, to neurons.
- ApoE induces synthesis of Aβ when lipid supply is deficient.
- Aβ redirects neuron metabolism towards other substrates besides glucose, by interfering with glucose and oxygen supply and increasing bioavailability of lactate and ketone bodies.
- Synthesis of the neurotransmitter, glutamate, is increased when cholesterol is deficient, and glutamate is a potent oxidizing agent.
- Over time, neurons become severely damaged due to chronic exposure to glucose and oxidizing agents, and are programmed for apoptosis due to highly impaired function.
- Once sufficiently many neurons are destroyed, cognitive decline is manifested.
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