Ketogenic Diet Review: Part 1 – Introduction

I have been intrigued by the idea of the ketogenic diet, but I haven’t yet thoroughly investigated the biochemical details of adopting it. I have an interest in adopting it for myself, but before I do so, I want to thoroughly research its potential positive and negative effects, largely because it is such a strange diet from an evolutionary perspective. Then again, maybe not. I’m no anthropologist, but it seems unlikely to me (however admittedly ignorant I am on this topic – if I am, please correct me, dear reader) that a large population of humans would have been exposed to long periods (i.e. generations) of near-complete absence of carbohydrates. However, there may have been at least one situation in which humans may have adapted to over the millennia: famine. So perhaps the ketogenic diet might facilitate superior health compared to a relatively carbohydrate-rich diet.

I understand some people offer differing definitions of a ketogenic diet (slightly different macronutrient ratios). In this series of posts, I am referring to this definition of the ketogenic diet: 5% carbohydrate, 20% protein, 75% fat.

In this series of posts, I intend to investigate this question, among others. Here are some questions I explicitly intend to answer:

  1. What effect does the ketogenic diet have on mitochondrial metabolism, and in particular, mitochondrial DNA? Mitochondrial DNA is known to degrade in aging, mitochondria are a primary site of fatty acid oxidation, and I suspect adopting a very-low carbohydrate diet would facilitate enhancements in mitochondrial number and function. These effects may prolong healthspan and help prevent development of diseases of aging
  2. Are there any significant, negative side-effects of maintaining a ketogenic diet in the long-term? Another way of stating this question is: is it optimal to mix a ketogenic diet with occasional carbohydrate intake (and if so, how often?)
  3. What are the long-term effects of the ketogenic diet? I intend to look into people who adopt this diet in the long-term for the purpose of reducing the incidence of seizures (as a treatment for epilepsy), assuming this population size is somewhat large, compliance is fairly high, and their health outcomes are tracked fairly-well in the long-term
  4. Does adoption of the ketogenic diet have any effect on the NAD+/NADH ratio? I am interested in this because of recent research showing that this ratio changes in old age, and some aspects of poor health in old age can be reversed by normalizing this ratio. And with such a dramatic changes in mitochondrial metabolism induced by the ketogenic diet, I suspect this ratio may also change; for better or worse, I’m not sure yet. So I may be digging into energy metabolism, oxidative phosphorylation, the citric acid cycle, and other aspects of energy metabolism
  5. Assuming the ketogenic diet “passes” with regard to my evaluation of its effects on health, one next question I will seek an answer to is: “what fats should I eat, and in what proportion?” There are quite a few different types of fatty acids. These have different effects on the body. Some are “essential”, while others are not. I am partial to medium chain triglycerides (“MCT”), the 8-, 10-, and 12-carbon saturated fatty acids, as well as oleic acid (18:1). I understand that stearic acid is not so bad either. But I will be looking into this question more closely, if I decide to  make 75% of my calories come from fat
  6. If I am going to adopt a ketogenic diet, what should I expect? How long will it take? How miserable will I be? I have tried this a few times, and only lasted a few days, after which I felt terribly fatigued and gave up.
  7. How should I induce ketogenesis? I understand there are methods of accelerating the adaptation to the ketogenic diet, such as prolonged fasted exercise (I looked for a reference for this for 30 minutes – can’t find it!). And the abstract of one paper on the ketogenic diet in dogs suggests that MCT can enhance ketone generation. Perhaps adopting these will make it easier for me to adopt (by shortening the relatively miserable adaptation phase)?
  8. Finally, assuming I am satisfied with what I find for all of the above, I will keep a daily journal of my ketosis induction, to document my experiences for myself (for later) and for others

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Maximus Peto is a longevity scientist focused on the biology of aging, health, nutrition, exercise, lifestyle, and longevity. In his scientific research, he has scanned 160,000+ scientific articles, read 8,000+ scientific abstracts, and studied 1,500+ full-text scientific publications. Maximus has worked with several leading organizations in aging and longevity, including the SENS Research Foundation, the Methuselah Foundation, and the Life Extension Foundation. He shares his knowledge of keeping people alive and healthy at Long Life Labs.