I recently listened to this podcast between Robb Wolf, author of The Paleo Solution and one of my favorite nutrition researchers, and Dr. Rhonda Patrick, founder of Found My Fitness and yet another one of my favorite researchers. It was a great discussion about a wide variety of topics mostly revolving around cell metabolism. I’ve included a summary of the key points discussed below.

Summary & Key Points:

  • For healthy cellular function and healthy aging in general, you need metabolic flexibility
  • Once a cell acquires so much damage to the genome, it becomes glycolytic
  • The act of becoming glycolytic does not cause a cell to become cancerous – immune cells, fast twitch muscle fibers, and astrocytes are all glycolytic but not cancerous
  • In cancer, the mitochondria are still working, they are just dysfunctional
  • Cells are primed to die. In normal oxidative respiration (breathing in oxygen and using it for energy), we release reactive oxygen species (ROS), which participate in healthy signaling involved in cell death. Cancer cells, since their mitochondria are dysfunctional, have the potential to produce more ROS, but since cancer cells want to stay alive, they switch to become glycolytic to reduce ROS and avoid the free radicals so it can stay alive.
  • It is energetically favorable, and thus preferential, for your cells to use lactate and ketones as energy sources since they can be transported into mitochondria and utilized without consuming energy (normal glucose oxidation requires energy in order to produce more energy).
  • Lactate and ketones are transported into mitochondria via monocarboxylate transporters which are present on cell membrane and on mitochondrial membrane.
  • If astrocytes in the brain are prevented from using lactate, it is possible to have long-term memory issues.
  • Lactate, when produced from muscle during exercise, is preferentially taken up into the brain
  • Patients with Parkinson’s Disease, when forced to undergo an intense workout, have their symptoms improved due to lactate production and utilization of lactate by the brain.
  • When cells utilize lactate and ketones, they can “spare” glucose (i.e. save it) for use in the pentose phosphate pathway, which is important for making compounds necessary for antioxidant (glutathione) synthesis. This is probably why utilization of lactate by the brain during traumatic brain injury is beneficial.
  • During traumatic brain injury, the brain/astrocytes become insulin resistant. This means they can’t utilize glucose to make lactate. If this is the case, then this implies that ketone body supplementation might be beneficial for traumatic brain injury patients because ketone bodies are the other source of energy that are preferentially taken up into the mitochondria similar to lactate.
  • Lactate also induces BDNF in the brain
  • You need healthy functional mitochondria in order to process lactate and ketones
  • Lactate from probiotics or from lactate producing bacteria is important because it helps maintain acidic environment in the stomach to prevent pathogenic bacteria from growing. The lactate, however, is also used by the gut goblet cells to produce energy in order to make mucin, which is the compound necessary for maintaining the gut barrier.
  • A potential downside to ketogenic diets are the fact that they are low in fermentable carbohydrate and thus it poses the risk of not providing the gut goblet cells with enough energy to produce mucin. The result: a breakdown of the gut barrier, and increase in intestinal permeability.
  • Both your cells AND your gut bacteria are on a circadian rhythm. So disruption in this cycle via loss of sleep can disrupt gut biome.
  • Insulin resistance can occur in upper intestine – most likely due to consumption of refined carbohydrates over time. This insulin resistance thus causes a loss of glucose utilization and thus lactate production and utilization by goblet cells, and a resulting breakdown of gut barrier.
  • The gut has the highest concentration of immune cells in the body (not the spleen). The gut barrier provides the separation between the immune cells and the gut bacteria. If there is breakdown of the gut barrier, then there is interaction of the immune cells with the gut bacteria and all sorts of pro-inflammatory signaling molecules can be released.
  • Potatoes and non-refined carbohydrates tend not to be processed in the upper portion of the small intestine. This is beneficial, as refined carbohydrates and sugar consumption over time can lead to insulin resistance in the upper portion of the intestine.
  • Sepsis is indistinguishable from poorly controlled type II diabetes
  • Inflammation can cause insulin receptor dysfunction
  • Inflammation increases VLDL synthesis and thus LDL synthesis
  • LDL, the small and dense particles that carry cholesterol and triglycerides, binds endotoxin (endotoxin is a part of the bacterial cell membrane that is released when bacteria die)
  • Endotoxin binds to the LDL receptor on the LDL particle surface and prevents the LDL particle from being recycled in the liver
  • Small LDL particles are the LDL particles that preferentially bind endotoxin
  • Dietary fat does not cause inflammation/heart disease, it is the consumption of refined sugars and refined carbohydrates that eventually lead to the breakdown of the gut barrier which subjects the bloodstream to endotoxin from gut microbiome
  • You should always have blood cholesterol and lipids checked twice in the event that the first time you had it checked, you were in a state of inflammation: as mentioned above endotoxin binds LDL and keeps LDL around in the bloodstream and causes inflammatory reactions
  • Metformin: improves insulin sensitivity, improves intestinal permeability, and mitigates the liver toxicity associated with LPS.
  • The benefits of caloric restriction observed from animal models probably doesn’t apply to humans because of the genetic reaction norms, i.e. the energetic inputs for offspring: for organisms with a very high energetic input for offspring production (such as fruit flies etc.), caloric restriction will have a large impact on longevity. The reasoning for this is that the organism is trying to get to a point to where nutrients are more available so they can have more offspring
  • Caloric restriction activates FOXO3, which is a transcription factor involved with longevity and inducing autophagy
  • IGF-1 is good for muscle recovery and the brain, but if you have a lot of inflammation and a poor diet and lifestyle then IGF-1 is not so good because it is a growth signal and doesn’t differentiate between healthy cells and damaged cells. And even though cells get death signals from their environment if they are damaged or on their way to becoming damaged, IGF-1 will cause these cells to ignore those signals.
  • Both energy and protein activate IGF-1, and IGF-1 activates mTOR.
  • IGF-1 binding proteins are regulated by sugar
  • High protein diets are good if you are exercising (i.e. not sedentary), and if you don’t have a lot of inflammation.

Questions:

  • Are tumors/cancer cells high in glutathione?
  • Is the act of utilizing energy for glucose oxidation (as opposed to energetically favorable ketosis etc.) beneficial? Perhaps the slight consumption of energy to make more energy (as occurs with glucose oxidation) is good because it involves enzymes and genetic expression that would otherwise not operate? Leading to other cell signaling?

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