Ketogenic Mechanism of Action

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While the obvious, measurable change from the Ketogenic Diet is the increase in Ketone Levels, there are many different changes that occur and the benefits of the Ketogenic Diet could be dependent on any of these changes.

  • Increased Ketone Levels. The increase in Ketones is likely to be responsible for a number of the benefits.
    • AcAc. This is a fuel for the brain, and it's preferentially used over glucose. It also tends to acidify the blood.
    • BOHB. Unclear if there are direct benefits from BOHB. (BOHB could be thought of as a way of temporarily storing AcAc without acidifying the blood. AcAc is converted to BOHB, then back to AcAc for use.)
    • Acetone. Originally thought to be an inactive waste product, this has shown to be biologically active in a number of ways. Some suggest that this might be the mechanism for action for Epilepsy treatment[1], but the rapidness of "breakthrough seizures" after breaking the ketogenic diet tends to undermine that argument as acetone levels will decay more slowly than other ketones[2].
  • Reduced Blood Glucose. The Ketogenic Diet tends to reduce and stabilize blood glucose levels, and this is likely to be responsible for some of the benefits.
    • Cancer cells require glucose and can't use Ketones.
    • There is a strong (90%) correlation between reduced blood glucose and seizure reduction for Epilepsy.
  • Reduced Insulin Levels. The lower carbohydrate availability reduces insulin levels and prevents insulin spikes. This may have a number of health impacts, including a reduction in the risk for diabetes and metabolic syndrome.
  • Food Avoidance. Some of the benefits of the Ketogenic Diet may come from the removal of specific foods that cause problems.
    • Gluten. There are a number of health problems linked to gluten, which is a protein found in many grains. There is wheat allergy, celiac disease and irritable bowel syndrome (IBS), but there are also a number of other subclinical issues linked to gluten including neuropathies. This might be the mechanism behind the treatment of Schizophrenia with the ketogenic diet.
    • Fructose. Because Fructose has some potential health impacts, its removal from the diet may have some health benefits.
  • Modified Fiber Intake. Typically the Ketogenic Diet results in reduced Fiber intake, which tends to lead to constipation, a common Health Risk of the Ketogenic Diet. It's unlikely, but possible, but this reduction in fiber might help some health condition. On the other hand, the constipation suffered with the Ketogenic Diet may require much higher levels of fiber than the comparable Standard American Diet, which may have some health benefits.
  • Changes to digestive flora. The Ketogenic Diet produces changes in the intestinal bacteria, and reduces the availability of Short Chain Fatty acids, especially butyrate[3]. (This is more likely to have negative than positive effects, and contribute to the constipation problems that are common on the Ketogenic Diet.)
  • Blood pH Levels. The Ketogenic Diet tends to acidify the blood slightly, and this may have some health impacts.
  • Increased Fat Intake. The Ketogenic Diet obviously involves a dramatic increase in the dietary fat intake, which may have some direct benefits, especially around ensuring an adequate supply of essential fats.
  • Thyroid Changes. Studies have shown a reduction in thyroid hormone production, particularly T3. This may contribute to the conservation of Glycogen during exercise.
  • Supplementation. The Ketogenic Diet requires nutrient supplements, and there maybe health benefits if an underlying deficiency has been overcome. (Note that it is not clear if the Ketogenic Diet changes the Recommended Daily Allowance of nutrients.)
  • Nutrient Deficiency. While nutrient deficiency is typically a Health Risk of the Ketogenic Diet, it is possible that a deficiency could improve a health condition if patients have been getting an excess of a particular nutrient.

1 See Also

2 References

  1. MP. Kalapos, Possible mechanism for the effect of ketogenic diet in cases of uncontrolled seizures. The reconsideration of acetone theory., Med Hypotheses, volume 68, issue 6, pages 1382-8, 2007, doi 10.1016/j.mehy.2006.10.041, PMID 17166670
  2. G. Yellen, Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet., Epilepsia, volume 49 Suppl 8, pages 80-2, Nov 2008, doi 10.1111/j.1528-1167.2008.01843.x, PMID 19049596
  3. SH. Duncan, A. Belenguer, G. Holtrop, AM. Johnstone, HJ. Flint, GE. Lobley, Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces., Appl Environ Microbiol, volume 73, issue 4, pages 1073-8, Feb 2007, doi 10.1128/AEM.02340-06, PMID 17189447