Unifying biology (3) Ketogenesis and hypoxia

One of the questions I’ve been trying to develop an intellectually satisfying answer to for the past decade is: Why did Kwasniewski and Lutz seem to advise against ketosis, was it empirical or esoteric?

I find the hypoxic in utero environment of the fetus and subsequent metabolic transition of the neonate to a normoxic environment and eventual metabolic transformation fascinating. After gestation interesting things are occurring metabolically, increases in lactate, increases in ketogenesis and gluconeogenesis. The scant number of tracer studies looking at infant metabolism seem to indicate that exogenous lactose from breast milk and endogenous glucose as a result of gluconeogenesis is being shunted towards biosynthetic pathways and glucose is metabolically spared. In breast fed infants, glucose concentrations increase cyclically maintaining normoglycaemia. In contrast, infants administered oral solutions of glucose develop cyclical hypoglycemia.

I suspect there are morphological and functional differences between infant and adult mitochondria. There are reasons for this suspicion. Infants administered glucose less than 1 month after gestation present with glucose intolerance and glucose tolerance subsequently increases over the following months of development; additionally, the metabolic substrate profile points in that direction.

Infants have generous amounts of adipose tissue and as the infant transitions to a toddler and child, adipose tissue declines. I would suggest this is a result of maturing mitochondrial morphology and function; and that elevated lactate and ketones reflects fatty acid oxidation (FAO) capacity. This physiological metabolic transition is a result of adapting to an externally normoxic environment. Interestingly, for every 1000 meter increase in elevation there is a reduction in neonate mass and an increase in the incidence of fetal death.

One of the central tenets of my hypothesis is that ketone formation indicates hypoxia be it a histophysiological adaptation to external environmental conditions and physiological stimuli or; a pathophysiological disorder resulting from chronic exposure to compounds and energy substrates that interfere with or block normal histophysiological adaptations. In other words, anything that chronically interferes or blocks normal homeostatic processes produces a maladapted and eventually, unadaptive state, leading to entropy i.e. degeneration and death.  

There is a beautiful cyclical metabolic signature from conception to death reflecting our ability to deal with oxygen and lack thereof; the energy substrates that build and prepare us for an oxygenated environment are eventually the same energy substrates that kill us. We develop in a hypoxic in utero environment and adapt to an oxygen rich environment. After birth and in the presence of oxygen our physiology matures and develops reflecting the external environmental conditions. As our mitochondria learn how to breathe, we slowly loose the ketogenic capacity present during early stages of life and transition to a reliance on fatty acids and develop the capacity to rely on glucose, fructose, and ketones when intermittent hypoxia is present. When intermittent hypoxia is present our mitochondria temporarily uncouple and become physiologically insulin sensitive and glucose is used to facilitate adaptation via biosynthetic pathways.  

As we age our ketogenic capacity continues to decline along with a diminishing fatty acid oxidation capacity. In the context of this decline, not only do we lose the ability to produce adequate ketones to continually adapt to intermittent hypoxia, our mitochondria degenerate losing the ability to metabolize fatty acids and our physiology becomes more and more reliant on glucose as a metabolic substrate and as a result we lose the ability to maintain physiological insulin resistance. Slowly the adaptive state of intermittent physiological insulin sensitivity becomes pathophysiological and we lose the physiological insulin resistance of our youth.

As I have reflected on in the past, glucose is a primitive energy substrate, a glucose driven metabolism, contrasted with glucose used as a biosynthetic substrate in the context of a fatty acid driven metabolism, will drive primitive histophysiology and the subsequent degeneration of the orchestra. Every day the orchestra slowly goes out of tune and eventually the musicians slowly start disappearing, eventually the conductor has no musicians and he will turn to the audience, take a bow, and you will take your last breath.

In the end you will suffocate to death.

Why did Kwasniewski and Lutz seem to advise against ketosis?

  1. Whether they knew better or not, chronic ketosis indicates hypoxia.
  2. The conservative amount of glucose needed to stay out of deep chronic ketosis facilitates physiological insulin resistance and supports adaptive physiological insulin sensitivity during intermittent hypoxia.
  3. Ketosis reflects fatty acid oxidation capacity.  

5 Comments Unifying biology (3) Ketogenesis and hypoxia

  1. JM

    To my understanding, it is a misinterpretation that Kwasniewski advised against ketosis. What he advised against was cycling in and out of it.

  2. Edward

    Hi JM, thanks for the comment! It very well could be a misinterpretation, regardless, for me it was a point of inspiration to investigate the various conditions, pathological and physiological under which ketogenesis is elevated in fasted and fed states and under various levels of hypoxia.

  3. Joanna

    I have read all of Kwasniewski’s books and a lot of other publications (in Polish), and my interpretation is that he is against ketonuria – he only mentions checking ketones in urine, never blood. The glucose provided from consumption of carbohydrates should spare the body the effort of gluconeogenesis – he repeatedly talks about providing the body with everything it needs in the smallest amount possible so it doesn’t have to work too much, which leads to quicker aging.

  4. Edward

    Hi Joanna, hope you are well.

    Of Kwasniewski, I’ve only read what I’ve been able to find translated and using Google translate for parts of his website which I can not tell if it is still active or not. Some things can get lost in translation so I have been open to the idea that my interpretation of his work could be misguided. It is for that reason I’ve always chose to work on my own and I generally see others work as inspiration to ask deeper questions instead of debating semantics in which those conversations tend to be shadowed in dogma. Thank you for the clarification.

    Your comment has inspired a post regarding GNG!

  5. Joanna

    Hi Edward,
    I’m fine, thank you.
    Dr K himself is retired, and the website is run by his son. I have not noticed any added content for years, but some biochemical issues are discussed on the forum at times. It is always stressed that what matters is the proportion of protein-fat-carbs, which also depends on other factors such as age, physical activity, diseases, altitude, etc.
    Also, I was wondering if you have ever come across the idea of allowing only one type of protein per day. It is advocated by one of Polish doctors, but I could not find any evidence or any other diet plans advocating such restriction eg. if you eat eggs in the morning, you should have them for lunch/dinner as well and no other source of protein. The doctor claims it delays the aging process as the body can better adjust the amount of protein it needs in a day so you do not overeat. Sounds outrageous?
    Looking forward to post on GNG! Take care!

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