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Show notes:

Richard’s website is http://2ketodudes.com/ and Twitter is @2ketodudes

Richard gives his professional background; after half a maths degree he changed direction to a successful career on Wall Street and as a computer coder, working long hours with little sleep during which he became diabetic and packed on the fat.

Richard mentions a few examples of doctors with an engineering background, like Dr.Bernstein and Dr.Naiman, as well as engineers with excellent medical insight such as Ivor Cummins and Dave Feldman .

Raphael asks Richard to explain how he deals with the deluge of requests to sell exogenous ketones.

Richard explains how the chirality of a molecule, meaning whether it is the left and right-hand version, can affect how our metabolism handles it.

Richard gives the notorious thalidomide example, a drug that when initially released was of the wrong chirality and led to serious birth defects. Richard worries that the unresolved question about the appropriate chirality of exogenous ketones may harm the ketogenic diet’s hard won reputation.

Richard raises the concern that ‘artificially’ tipping the acetoacetate to beta-hydroxybutyrate ratio by taking exogenous beta-hydroxybutyrate may then lead to unwanted effects on our cellular redox states (the NAD+/NADH ratio).

Gabor is not a fan of supplements, in general.

However, Gabor does supplement with vitamin D3 during the winter time in Hungary.

Raphael explains that he supplements 300mg of Magnesium, 300mg of Potassium and 21mg of Zn daily because he estimates the risk-reward ratio might be favorable given I was chronically inflamed growing up due to my asthma and allergies. People with pulmonary issues are more likely to be Magnesium deficient .

Richard emphasizes that our body evolved to handle beta-hydroxybutyrate within a certain context (low insulin, low blood sugar…) and that it is not only a substrate contributing to ATP but also a signaling molecule.

Raphael and Richard mention how the FDA approved Precision Xtra ® blood glucose and ketone meter only reads the D-beta-hydroxybutyrate (right-handed) isoform of the molecule, yet many lab made ketones are the left-handed L-beta-hydroxybutyrate molecules – asking, can it measure ketone levels accurately when taking left-handed exogenous ketones?

Raphael points out that not all exogenous ketones are the same. There are salts, esters and come with other products to make it palatable (amongst other desirable characteristics).

Raphael says that Dr.D’Agostino has a very favorable view of (certain) exogenous ketones.

Raphael suggests applying the precautionary principle to exogenous ketones.

Raphael asks what the contexts are for ‘keto-ish’ being good enough vs a particular blood level of beta-hydroxybutyrate being necessary?

Raphael asks what level of blood beta-hydroxybutyrate determines ketosis?

Richard and Gabor mentions factors affecting how quickly one gets back into ketosis (sleep, nature of carbs, what carbs are eaten with, metabolic flexibility…)

Gabor raises the possibility that carbs + fat may kick you out of ketosis quicker than carbs alone.

Raphael brings up Marty Kendall’s questions posed to Dr.Ken Ford after the fantastic STEM-talk podcast episode with Nina Teicholz , regarding exogenous ketones, NAD+/NADH and at what blood level of beta-hydroxybutyrate is one in ketosis.

Richard mentions Virta Health’s great results visible in their recently published year-long randomized controlled pilot trial.

Raphael mentions ( @ascarbs ) Andrew Scarborough ’s case where exogenous ketones seemingly help with various aspects of his (now past!) brain tumor.

Richard mentions that aspects of ketone metabolism are being considered for future astronauts traveling to Mars. Who but Dr.D’Agostino would be involved in such a cool thing!

Raphael mentions how radiation can deplete NAD+ and ketone metabolism may help replenish NAD+.

Raphael brings up The Protein Question (discussed in episode #30 )

Richard notes that (the rare instance) of protein poisoning can happen – unlike fat or carbohydrate poisoning – due to ammonia buildup. *This is known to happen in hypocaloric scenarios called ‘rabbit starvation’ where only lean meats like rabbit are available. In fed, isocaloric, scenarios it’s difficult to know what the upper limits are protein intake are.

Richard mentions how unfortunate it is that some people pushing ‘high-protein’ diets not only want to feel vindicated eating that way but want others to eat that way too.

The point is made that in an isocaloric scenario it’s not generally feasible to consume much about 35% of calories from protein, which in grams is approximately 200-300g/day on a 2,000-2,700kcal/day diet .

Riched posits crossover trials looking at high levels of protein consumption may be confounded by the fact that the washout period between crossovers enables to properly buffer the buildup of ammonia, possibly giving a false sense of security about the very high end of protein intake in weight stable scenarios.

Raphael asks Gabor what he think about the effect to ‘up the protein’ to achieve caloric restriction when people are stalling in their fat-loss efforts.

Gabor considers this a plausible approach given the thermic effect of protein and more of a ‘biohack’ than a long-term solution.

Gabor lists other such possible hacks, such as using MCTs that have a high energy cost when being processed by the liver, or acute bouts of cold thermogenesis.

Gabor consider the notion of a ‘fat as a lever’ to simply be a restatement of the CICO (calories in calories out) truism.

Raphael questions the validity of defaulting to ‘upping protein’ as the go to advice for fat-loss stalls rather than, say, optimizing sleep or circadian entrainment.

Gabor proposes we focus on ‘sleeping to satiety’