Ketogenic Diet

Ketogenic diets are diets in which, due to low carbohydrate intake, promote alternative metabolic pathways in which the cells of the body rely on ketones circulating in the blood, rather than depending on glucose. Please see the Theory section below for a biochemical description of the relevant metabolic pathways.

It is important to note that ketosis is not the same as diabetic keto-acidosis which is a life-threatening condition.

[Bosworth2018] gives a good tutorial on how to implement a ketogenic diet. She recommends a macronutrient mix of 20 grams carbohydrates (maximum), 80% of calories from fat, and the remainder from protein.

The Atkins diet is another ketogenic diet, which recommends 20 grams carbohydrates (maximum) , 60-70% fat, and 20-30% protein during the initial ("induction") phase, although subsequent phases increase carbohydrates and may not maintain ketosis.

Benefits attributed to Ketogenic diets include:

• Weight loss [Bosworth2018]
• Anti-inflammatory [Bosworth2018]
• Anti-cancer. [Bosworth2018] presents a case study of a patient having Chronic Lymphocytic Leukemia (CLL) who benefits from a ketogenic diet. [AlHilli2023  🕮 ] notes that a ketogenic diet benefits some kinds of cancer, but is counter-productive in a mouse model of ovarian cancer. While many forms of cancer fit the hypothesis proposed by Otto Warburg that cancer cells are not capable of mitochondrial respiration and therefore rely on anaerobic fermentation, and therefore are susceptible to a ketogenic diet that inhibits anaerobic fermentation, some cancers, including epithelial ovarian cancer, are exceptions to this rule and are capable of oxidative phosphorylation [Matassa2016  🕮 ]
• Treatment of intractable seizure activity
• Improved brain function [Bosworth2018]

The following information can be found in most any biochemistry text; for convenience, links are provided to Wikipedia articles, but as always, Ronald Reagan's maxim should be applied: "Trust but Verify."

Mamalian cells have multiple enzyme pathways for dealing with differing diets containing high or low levels of carbohydrates, fats, and proteins (which are made from amino acids). In particular, our bodies have genes that can convert:

• Fats into any needed carbohydrate and most needed amino acids (proteins).
• Carbohydrates into most needed fats and some needed amino acids (proteins).
• Most amino acids (proteins) into any needed carbohydrates.

Depending on our diet, some of these genes may be turned on or off due to epigenetic repression or induction, but given the appropriate diet and adequate time to adapt, any of these pathways can be turned on. That means that our body can adapt to:

• Diets with little or no carbohydrates;
• Diets with little or no fats, except the essential omega-3 and omega-6 fats;
• Diets with little or no proteins (amino acids), except the essential amino acids (Leucine, Lysine, Valine, Phenylalanine, Tryptophan, Threonine, and Methionine) and conditionlly essential amino acids (Arginine, Cysteine, Glutamine, Glycine, Proline, Tyrosine).

In addition, mamalian cells have enzyme pathways for generating energy (in the form of ATP) under conditions of high oxygen availablity (which is called respiration) or low oxygen availability (which is called fermentation).

Miscellaneous references pertaining to the ketogenic diet include: [Phinney2011] [Westman2015] [Zinn2017  🕮 ]

•       [AlHilli2023]   Mariam M AlHilli, Emily E Rhoades, Danielle Chau, Surabhi Tewari, et al. Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo.. Nutrients. 2023 Jun 13;15(12):2730. PMID: 37375634 DOI: 10.3390/nu15122730 PCMID: PMC10301007
•       [Bosworth2018]   Annette Bosworth. Anyway You Can: Doctor Bosworth Shares Her Mom's Cancer Journey: A BEGINNER'S GUIDE TO KETONES FOR LIFE. MeTone Life, LLC; Illustrated edition (February 15, 2018). Amazon
•       [Matassa2016]   D S Matassa 1, M R Amoroso, H Lu, R Avolio, et al. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer. Cell Death Differ. 2016 Sep 1;23(9):1542-54. PMID: 27206315 DOI: 10.1038/cdd.2016.39 PCMID: PMC5072430