ISIS News no.9/10 - Dietary Interventions for Alzheimer’s & Parkinson’s
The team’s work goes back to the 1990s, when they started using ‘metabolic control analysis’ (see Box) to study glucose metabolism in working rat hearts perfused with glucose, to which ketones or insulin or both have been added [2]. Insulin is a hormone that reduces glucose concentration in the blood, and deficiency of insulin is associated with type I diabetes.
Radioactive glucose was used to keep track of the rate at which glucose disappears and becomes transformed into different metabolites including glycogen (a storage product which is a large polymer of glucose). The results show that no single enzyme controls glucose metabolism. Instead, different enzymes are in control, depending on the prevailing conditions. For example, the heart works better in the presence of either ketones or insulin, but the combination of both ketones and insulin is no better than either alone. In the presence of glucose only, glycogen is broken down. With the addition of ketones, insulin or both, glycogen is synthesised. The concentrations of practically all the metabolites downstream of glucose are changed, many significantly, by the addition of ketones or insulin or both; as are the concentrations of the major energy intermediates, ATP and creatine phosphate.
At the same time, the effciency of the working heart increases by 25% in the presence of either insulin or ketones, and by 36% in the presence of both. The increase in efficiency is accompanied by dramatic changes in key metabolites in energy metabolism (those reactions leading directly to generating ATP in the mitochondria). The most interesting finding is that ketones appear to change the profile of energy metabolism in ways similar to insulin, which the researchers conclude, may have important clinical consequences. It has been shown
previously that increase in blood ketones to levels observed after a 48h fast almost completely reversed the mitochondrial abnormalities associated with insulin deficiency. Moderate increases in circulating ketones, the authors suggest, "should be viewed as a beneficial compensation for insulin deficiency and perhaps also for geriatric patients or others with peroxidative damage to the processes of mitochondrial energy transduction" [4]. Could it be that ketones may also help type I diabetes?
The next obvious step is phase I clinical trial in Alzheimer’s and Parkinson’s patients. The problem is that ketones can’t be taken directly because they are too acidic. A trimer (a molecule that consists of three ketones joined end to end) is neutral, and would be suitable as a food supplement. The bad news for Veech is: no drug company will make the stuff for him, while the institution Veech works for, the NIH, does not even consider his research worth funding in the mad dash for genetic causes of diseases and gene-based drug and interventions.
The good news is that the Navy will be funding the project, so the clinical trial will go ahead after all. Watch this space.
The team’s work goes back to the 1990s, when they started using ‘metabolic control analysis’ (see Box) to study glucose metabolism in working rat hearts perfused with glucose, to which ketones or insulin or both have been added [2]. Insulin is a hormone that reduces glucose concentration in the blood, and deficiency of insulin is associated with type I diabetes.
Radioactive glucose was used to keep track of the rate at which glucose disappears and becomes transformed into different metabolites including glycogen (a storage product which is a large polymer of glucose). The results show that no single enzyme controls glucose metabolism. Instead, different enzymes are in control, depending on the prevailing conditions. For example, the heart works better in the presence of either ketones or insulin, but the combination of both ketones and insulin is no better than either alone. In the presence of glucose only, glycogen is broken down. With the addition of ketones, insulin or both, glycogen is synthesised. The concentrations of practically all the metabolites downstream of glucose are changed, many significantly, by the addition of ketones or insulin or both; as are the concentrations of the major energy intermediates, ATP and creatine phosphate.
At the same time, the effciency of the working heart increases by 25% in the presence of either insulin or ketones, and by 36% in the presence of both. The increase in efficiency is accompanied by dramatic changes in key metabolites in energy metabolism (those reactions leading directly to generating ATP in the mitochondria). The most interesting finding is that ketones appear to change the profile of energy metabolism in ways similar to insulin, which the researchers conclude, may have important clinical consequences. It has been shown
previously that increase in blood ketones to levels observed after a 48h fast almost completely reversed the mitochondrial abnormalities associated with insulin deficiency. Moderate increases in circulating ketones, the authors suggest, "should be viewed as a beneficial compensation for insulin deficiency and perhaps also for geriatric patients or others with peroxidative damage to the processes of mitochondrial energy transduction" [4]. Could it be that ketones may also help type I diabetes?
The next obvious step is phase I clinical trial in Alzheimer’s and Parkinson’s patients. The problem is that ketones can’t be taken directly because they are too acidic. A trimer (a molecule that consists of three ketones joined end to end) is neutral, and would be suitable as a food supplement. The bad news for Veech is: no drug company will make the stuff for him, while the institution Veech works for, the NIH, does not even consider his research worth funding in the mad dash for genetic causes of diseases and gene-based drug and interventions.
The good news is that the Navy will be funding the project, so the clinical trial will go ahead after all. Watch this space.
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