HoldsUp

FoundMyFitness · 2016-04-09 · Rhonda Patrick (host), Dominic D'Agostino

Dominic D'Agostino, Ph.D. on Modified Atkins Diet, Keto-Adaptation, Ketosis & More

56 claims checked against research: 2 contradicted 3 overstated 5 needing context 39 supported 7 unverified

5

Needs context

0:16:51Rhonda Patrick (host)needs contextvery low

Bile acids such as deoxycholic acid released during fat digestion cause endotoxin release.

"fat itself, in order to be digested, you have to make these bile acids like deoxycholic acid, which causes endotoxin release." (said at 0:16:51)

The statement conflates normal human bile synthesis with bacterial bile metabolism and the mechanism of endotoxin translocation. Primary bile acids (such as cholic acid and chenodeoxycholic acid) are synthesized by the liver to aid lipid digestion. Deoxycholic acid (DCA) is not produced directly by the human host for digestion; rather, it is a secondary bile acid formed in the intestine through the modification of primary bile acids by colonic bacteria. In vitro models demonstrate that secondary bile acids such as DCA can impair intestinal epithelial barrier integrity and increase paracellular permeability, which is a recognized pathway facilitating the translocation of bacterial endotoxin (lipopolysaccharide) across the gut barrier. However, bile acids do not directly generate or release endotoxins.

0:30:40Dominic D'Agostinoneeds contextlow

Using ketones as a metabolic fuel increases mitochondrial efficiency, requiring less oxygen to generate the same amount of ATP and producing fewer reactive oxygen species.

"From an acute point of view, as simply as a metabolic fuel, the mitochondrial efficiency is greater, so you'll have a greater mitochondrial membrane potential, a greater driving force for ATP synthase to make ATP. So it energizes the mitochondria in a way that would be expected from a metabolic fuel that's sort of superior from a bioenergetic point of view. So you have a greater capacity to generate ATP for a given amount of oxygen that's available. So with that occurring, the metabolic efficiency of the cell would be sort of preserved. You're using less oxygen to make the same amount of ATP, less reactive oxygen species." (said at 0:30:40)

The claim that ketone bodies increase ATP production and lower reactive oxygen species (ROS) levels is supported under certain stress conditions in cellular and animal models (PMID 25649993, PMID 12975474). For example, D-beta-hydroxybutyrate stimulates ATP production and reduces ROS levels in glucose-deprived cortical cultures (PMID 25649993). However, the generalization that ketone utilization inherently increases mitochondrial efficiency, uses less oxygen for a given ATP yield, and always reduces ROS is contradicted by other metabolic evidence. In healthy cortical neurons, ketone metabolism increases oxygen consumption and stimulates gene expression through the deliberate generation of ROS (PMID 27739595). Additionally, in vivo animal models of whole-body ketosis demonstrate a moderate uncoupling state resulting in lower oxidative efficiency compared to glucose oxidation (PMID 23852511).

0:33:36Rhonda Patrick (host)needs contextmoderate

Under normal physiology, astrocytes metabolize glucose and shuttle lactate to neurons, which convert lactate into pyruvate as an energy source.

"So neurons themselves actually use lactate generated from astrocytes. So they're using—I mean, neurons are actually using lactate, it's an energetically favorable source of energy, much like ketones... the astrocytes are using glucose, and that's why the brain uses glucose, and they're producing the lactate. The neurons are using the lactate because it's, you know, getting shunted and converted into pyruvate." (said at 0:33:36)

The speaker is describing the Astrocyte-Neuron Lactate Shuttle (ANLS) hypothesis, first proposed by Pellerin and Magistretti in 1994. Under this model, astrocytes take up glucose, perform glycolysis, and export lactate via monocarboxylate transporters, which neurons import and convert back to pyruvate via lactate dehydrogenase (LDH) for oxidative metabolism. While substantial mechanistic, animal, and in vitro evidence demonstrates that neurons can oxidize astrocyte-derived lactate—particularly during periods of synaptic plasticity or metabolic stress—the ANLS remains a debated model rather than an absolute rule of baseline brain metabolism. Neurons possess their own glucose transporters and glycolytic machinery, and direct neuronal glucose utilization is well-established as essential for sustaining synaptic transmission.

1:24:30Dominic D'Agostinoneeds contextvery low

Metformin causes mitochondrial stress by inhibiting complex I or complex II of the electron transport chain.

"And interestingly, metformin causes uh mitochondrial stress and actually mitochondrial uh damage, some researchers coined the term, you know, that it's it's it's stimulating reactive oxygen species production uh and causing mitochondrial dysfunction, metformin is, and this is kind of well known in the field... a lot of people are studying it from the perspective of, you know, impaired complex I or complex II activity in the mitochondria" (said at 1:24:30)

Metformin is well established in biochemical and cellular studies to inhibit respiratory chain complex I (NADH:ubiquinone oxidoreductase), leading to mild mitochondrial respiratory suppression, altered cellular energy balance, and AMPK activation. However, metformin selectively targets complex I and does not inhibit complex II; succinate-driven respiration through complex II remains functional and is frequently used experimentally to bypass metformin-induced complex I inhibition.

1:41:40Dominic D'Agostinoneeds contextlow

Exogenous ketone ester supplementation was originally investigated and developed for preventing central nervous system oxygen toxicity.

"And for oxygen toxicity, obviously, that was the original application." (said at 1:41:40)

Exogenous ketone esters, specifically 1,3-butanediol acetoacetate diester (BD-AcAc2) and (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, have been investigated for delaying central nervous system oxygen toxicity (CNS-OT) seizures in hyperbaric oxygen environments, with preclinical studies demonstrating significant delays in seizure latency. However, while CNS oxygen toxicity prevention (for military divers and hyperbaric oxygen applications) has been a primary target of research funding and preclinical evaluation (e.g., ONR-funded work by D'Agostino et al.), exogenous ketone esters were originally conceptualized and synthesized by Richard Veech, Kieran Clarke, and colleagues primarily as a metabolic tool to improve physical and cognitive performance, cardiac efficiency, and physical endurance under physiological stress. Thus, while preventing CNS oxygen toxicity was a early and prominent application investigated in preclinical models, framing it as the single original application requires qualification.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.