Mastering Nutrition

The last lesson covered how insulin, glucagon, and allosteric regulators from within the liver ensure that the liver only engages in gluconeogenesis when it can and when it needs to. This lesson focuses on an additional layer of regulation: cortisol. Cortisol is the principal glucocorticoid in humans. Glucocorticoids are steroid hormones produced by the adrenal cortex that increase blood glucose. Cortisol has multiple actions on the liver, muscle, adipose, and pancreas that all converge on making glucose more available to the brain. Among them, it increases movement of fatty acids from adipose to the liver, which provide the energy for gluconeogenesis, and the movement of amino acids from skeletal muscle to the liver, which provide the building blocks for gluconeogenesis. Cortisol serves both to antagonize insulin, thereby acutely increasing gluconeogenesis, and to increase the synthesis of gluconeogenic enzymes, which amplifies all other pro-gluconeogenic signaling and increases the total capacity for gluconeogenesis. In fact, even the day-to-day regulation of gluconeogenesis by glucagon is strongly dependent on normal healthy levels of cortisol in the background. Since gluconeogenesis is an extremely expensive investment with a negative return, it makes sense that the body would regulate it as a stress response, and thus place it under control by cortisol. This raises the question of whether carbohydrate restriction increases cortisol. Several studies are reviewed in this lesson that indicate that 1) there may be an extreme level of carbohydrate restriction that always increases cortisol, and 2) carbohydrate restriction definitely increases cortisol in some people. It may be the case that other stressors in a person's "stress bucket" determine whether and how strongly the person reacts to carbohydrate restriction with elevated cortisol. For the full episode, go to chrismasterjohnphd.com/mwm/2/31 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Since gluconeogenesis is extremely expensive, it has to be tightly regulated so that it only occurs when both of two conditions are met: 1) the liver has enough energy to invest a portion into synthesizing glucose, and 2) the rest of the body is in need of that glucose. Since the liver is the metabolic hub of the body that also plays a major role in anabolic synthesis and nitrogen disposal, it also regulates glycolysis and gluconeogenesis according to whether amino acids are available to supply energy in place of glucose and whether there is sufficient citrate and associated energy for biosynthesis. This lesson covers how insulin, glucagon, alanine, citrate, fructose 2-6-bisphosphate, ATP, ADP, and AMP regulate the flux between glycolysis and gluconeogenesis. For the full episode, go to chrismasterjohnphd.com/mwm/2/30 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Gluconeogenesis is extremely expensive. Three steps of glycolysis are so energetically favorable that they are irreversible. Getting around them requires four gluconeogenesis-specific enzymes and the investment of a much larger amount of energy. Overall, six ATP worth of energy are invested to yield glucose, a molecule that only yields 2 ATP when broken down in glycolysis. This lesson covers the details of the reactions as well as the rationale for investing so much energy. One of the most pervasive themes in biology is the drive to conserve energy. That we will spend this much energy synthesizing glucose is a testament to how essential it is to our life and well being. For the full episode, go to chrismasterjohnphd.com/mwm/2/29 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Insulin is commonly seen as a response to blood glucose whose primary role is to keep blood glucose within a narrow range. This view of insulin fails to account for its many roles outside of energy metabolism that govern long-term investments in health. The biochemistry and physiology of insulin secretion suggest, rather, that insulin is a gauge of short-term energy status and energetic versatility. Since glucose can only be stored in small amounts and since it is the most versatile of the macronutrients in its ability to support specialized pathways of energy metabolism, it makes sense that it would be wired to the pancreas as the primary signal of short-term energy status and energetic versatility. In this lesson, we review the unique uses of glucose and the mechanisms of insulin signaling to synthesize them into a more nuanced view of the role of insulin than is typically presented. For the full episode, go to chrismasterjohnphd.com/mwm/2/28 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The pentose phosphate pathway provides a deep look into a stunning array of essential roles for glucose. In it, glucose becomes the source of NADPH, used for antioxidant defense, detoxification, recycling of nutrients like vitamin K and folate, and the anabolic synthesis of fatty acids, cholesterol, neurotransmitters, and nucleotides. At the same time, glucose also becomes the source of 5-carbon sugars, used structurally in DNA, RNA, and energy carriers like ATP, coenzyme A, NADH, NADPH, and FADH2. DNA is needed for growth, reproduction, and cellular repair; RNA is needed to translate genetic information from DNA into all of the structures in our bodies; the energy carriers constitute the very infrastructure of the entire system of energy metabolism. This lesson covers the details of the pentose phosphate pathway, how it operates in multiple modes according to the relative needs of the cell for ATP, NADPH, and 5-carbon sugars, the role of glucose 6-phosphate dehydrogenase deficiency and thiamin deficiency in its dysfunction, and what it means for the importance of glucose to human health. For the full episode, go to chrismasterjohnphd.com/mwm/2/27 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In August of this year, 25-year-old bodybuilding mom Meegan Hefford was found unconscious in her apartment, brought to the hospital where she was declared brain-dead, and died soon after. The cause? "Too much protein before competition," according to the New York Post. She had recently doubled her gym routine, started dieting, and begun slamming protein shakes in preparation for an upcoming bodybuilding competition. No one knew she had a rare genetic disorder that would make the breakdown of protein acutely toxic for her until after her death. Does this tragic case carry lessons for the rest of us without rare genetic disorders? In this episode, I make the answer a definitive YES. Protein is essential to life and health, but its metabolic byproduct, ammonia, is toxic. Humans dispose of excess nitrogen largely as urea, a nontoxic metabolite of ammonia that can be safely excreted in the urine. Rare genetic defects like Hefford's interfere directly with the production of urea. Other genetic defects that interfere with the use of certain fuels, especially fatty acids and branched-chain amino acids, can indirectly impair the synthesis of urea during metabolic crisis. Impairments of urea synthesis lead to the accumulation of ammonia, with devastating neurological consequences. Null genes manifest in infancy and are best studied. Partial genetic deficiencies, like Hefford's are often asymptomatic through adulthood until dietary changes (protein supplementation, carbohydrate restriction, fasting) or metabolic demands (intense exercise, illness) force a greater rate of protein catabolism. There is at least one genetic polymorphism in a urea cycle gene that is COMMON and associated with disease: the A allele of rs5963409 in the OTC gene is present in up to 25-30% of some populations. It impairs ammonia disposal and arginine synthesis and it increases the risk of hypertension and Alzheimer's disease. Does it impair protein tolerance? It hasn't been directly studied, but it is reasonable to believe that people with this polymorphism may not tolerate protein as well as others, and that arginine supplementation could help. We need to stop dismissing inborn errors of metabolism as too rare to be relevant and we need to start connecting the dots and learning the lessons they carry for everyone. This episode is brought to you by Paleovalley. I use their beef sticks as a convenient yet nutritious snack. They are made from 100% grass-fed beef and preserved through traditional fermentation. The fermentation makes them more digestible and gives them a fresher mouthfeel and texture compared to most other meat snacks I've tried, which tend to be too dry for me to fully enjoy. They also have a grass-fed organ complex that contains a blend of liver, heart, kidney, and brain, all stuffed into gel caps for those who can't bring themselves to eat these incredibly nutritious meats with a fork. Head to paleovalley.com and enter the promo code masterjohn at checkout for 30% off your order. This is a huge savings available for only a limited time. You can get 30% off everything on the site, ordering as much as you want, but only for the duration of the next three podcast episodes. Check it out now to make sure you get your discount! This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/047-are-we-all-evolved-to-eat-high Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Although insulin promotes storage of fat in adipose tissue, this occurs in the context of multiple layers of regulation where energy balance is the final determinant of how much fat we store. In a caloric deficit, the low energy status of muscle and heart will lead them to take up fat rather than adipose tissue, even in the presence of insulin. Insulin combined with low energy status will promote the uptake of glucose in skeletal muscle over adipose tissue and will promote the oxidation of glucose rather than its incorporation into fat. Some advocates of the carbohydrate hypothesis of obesity have argued that glucose is needed to form the glycerol backbone of triglycerides within adipose tissue. Although glucose can serve this role, it isn't necessary because adipose glyceroneogenesis and hepatic gluconeogenesis can both provide the needed glycerol phosphate. Further, low energy status promotes the use of glycerol as fuel and high energy status is needed to promote the formation of glycerol from glucose. Finally, fatty acids are needed to store fat in adipose tissue and they overwhelmingly come from dietary fat in almost any circumstance. Insulin can only promote de novo lipogenesis, the synthesis of fatty acids from other precursors such as carbohydrate, in the context of excess energy, and this pathway is minor in conditions of caloric deficit, caloric balance, or moderate caloric excess. Thus, although insulin does promote storage of fat in adipose tissue, it doesn't directly affect energy balance, and energy balance is the determinant of how much fat you store overall. For the full episode, go to chrismasterjohnphd.com/mwm/2/26 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Insulin prevents fat-burning in part by locking fat in adipose tissue and in part by shutting down transport of fatty acids into the mitochondrion inside cells. By downregulating lipoprotein lipase (LPL) at heart and skeletal muscle and upregulating it at adipose tissue, insulin shifts dietary fat away from heart and muscle and toward adipose tissue. By downregulating hormone-sensitive lipase in adipose tissue, it prevents the release of free fatty acids from adipose tissue into the blood. At the cellular level, insulin leads to the phosphorylation and deactivation of AMPK. Since AMPK inhibits acetyl CoA carboxylase, insulin-mediated deactivation of AMPK leads to activation of acetyl CoA carboxylase and the conversion of acetyl CoA to malonyl CoA. Malonyl CoA inhibits carnitine palmitoyl transferase-1 (CPT-1) and thus blocks the transport of fatty acids into the mitochondrion. Nevertheless, all of these steps are also regulated at the most fundamental level by energy status, as covered in lesson 22. Further, insulin stimulates the burning of carbohydrate for energy, as covered in lesson 24. So, is insulin's blockade of fat-burning sufficient to cause net fat storage, or does this critically depend on energy balance? This question will be answered in the next lesson. For the full episode, go to chrismasterjohnphd.com/mwm/2/25 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Most people interested in health and nutrition know that insulin clears glucose from the blood into cells, but it is much less widely appreciated that insulin also makes you burn that glucose for energy. Insulin stimulates the translocation of GLUT4 to the membrane of skeletal muscle, heart, and adipose cells, and activates hexokinase 2. GLUT 4 increases the rate of glucose transport across the cell membrane and hexokinase 2 locks the glucose into the cell, making sure that glucose travels inward rather than outward. Insulin stimulates glycogen synthase, causing you to store glucose as glycogen, but it also stimulates pyruvate dehydrogenase, causing you to burn pyruvate for energy. The key determinant of which one of these you do is the energy status of the cell. Glucose 6-phosphate is needed to activate glycogen synthase, and it only accumulates if high energy status is inhibiting phosphofructokinase. If low energy status is stimulating phosphofructokinase, the net effect of insulin is to irreversibly commit glucose to glycolysis, and then to stimulate the conversion of pyruvate to acetyl CoA, which then enters the citric acid cycle to allow the full combustion of the carbons and maximal synthesis of ATP. Thus, if you need the energy, the net effect of insulin is to make you burn glucose to get that energy. For the full episode, go to chrismasterjohnphd.com/mwm/2/24 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Insulin secretion. Remarkably, we know from dietary studies that we get the most insulin from eating carbohydrate, yet we know from molecular and cellular studies that insulin secretion is primarily triggered by the ratio of ATP to ADP inside the pancreatic beta-cell. The former implies that insulin is a response to glucose, while the latter implies that insulin is a response to total energy availability. What can explain this discrepancy? In this lesson, we explore the possibility that it is the anatomy and physiology that drive the dietary effect of carbohydrate rather than the biochemistry. Carbs are wired to get soaked up by the pancreas when blood sugar rises above the normal fasting level once the liver has taken its share to replete hepatic glycogen, whereas fats are wired to go primarily to the heart and muscle when those organs need energy and to go primarily to adipose tissue otherwise. The combination of circulatory routes and the relative expression of glucose transporters and lipoprotein lipase by different tissues likely directs fat to the pancreatic beta-cell as a source of ATP only during extreme hyperglycemia or when it exceeds adipose storage capacity due to obesity, insulin resistance, or very high-fat meals. The pancreatic beta-cell does have a diversity of complicated and often controversial secondary biochemical mechanisms that "amplify" the insulin-triggering effect of ATP, and carbs are more versatile at supporting these mechanism than fat. These likely make a contribution to the dietary effect, but they strike me as unlikely to be the primary driver of the dietary effect. Thus, insulin is a response mainly to carbohydrate availability but also to total energy availability, and this driven mainly by the anatomy and physiology but also by the biochemistry. Seeing insulin as a response to cellular energy status will eventually help us broaden our view of insulin as a key governor of what to do with that energy that goes far, far beyond regulating blood glucose levels. For the full episode, go to chrismasterjohnphd.com/mwm/2/23 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson covers the regulation of beta-oxidation. The primary regulation of beta-oxidation occurs at the mitochondrial membrane, where fatty acids are transported into the mitochondrion. Acetyl CoA carboxylase governs both the formation of fatty acids from non-carbohydrate precursors and the transport of fatty acids into the mitochondrion. Its product, malonyl CoA, is a substrate for fatty acid synthesis in the cytosol but a regulator of fatty acid transport in the mitochondrion. Thus, there are two isoforms of acetyl CoA carboxylase that are regulated similarly. The cytosolic isoform plays a direct role in fatty acid synthesis and the mitochondrial isoform regulates beta-oxidation. This ensures that the two processes are regulated reciprocally, so that one is shut down to the extent the other is activated, thereby preventing wasteful futile cycling. The primary regulator of acetyl CoA carboxylase activity is, as you might expect by this point, energy status. When a cell needs more energy, it lets fatty acids into the mitochondrion. When it has too much, it shuts down fat-burning. For the full episode, go to chrismasterjohnphd.com/mwm/2/22 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson covers the regulation of glycolysis. The principle regulation occurs at phosphofructokinase, which guards the gate to the first irreversible, committed step to burn glucose for energy. What governs it? Energy. If you need more ATP, you burn more glucose; if you don't, you don't. If the cell has glucose beyond its needs for energy, it uses it for the pentose phosphate pathway, which allows the production of 5-carbon sugars and antioxidant defense if needed, or stores it as glycogen if there is room. If not, glucose-6-phosphate accumulates and shuts down hexokinase. This, together with low AMPK levels, causes glucose to get left in the blood. The other key regulated step of glycolysis is pyruvate kinase, where the primary purpose of regulation is to prevent futile cycling between steps of glycolysis and gluconeogenesis. On the whole, glycolysis and glucose uptake are regulated primarily by energy status and secondarily by glucose-specific decisions about the need for glycogen or for the pentose phosphate pathway. Since we mostly use glucose for energy under most circumstances, the key regulation of the pathway is the regulation of phosphofructokinase by energy status. This means glucose uptake is largely driven by energy status, and our decisions about preventing hyperglycemia should center on total energy balance. For the full episode, go to chrismasterjohnphd.com/mwm/2/21 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In this lesson, we examine the beta-oxidation in its simplest form: the breakdown of a long-chain, saturated fatty acid. We see once again the principle that the oxygen content of a molecule determines how much water its metabolism consumes and how much carbon dioxide its metabolism releases. In beta-oxidation, we consume one water per round and release no carbon dioxide. This reflects the fact that fatty acids are not hydrates of carbons like sugars are, which is where the name carbohydrate comes from. For the full episode, go to chrismasterjohnphd.com/mwm/2/20 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In this lesson, we examine the entire glycolytic pathway. We use as our theme the transfer of oxygen from phosphate to newly generated water. This explains why the standard stoichiometry of glycolysis found in textbooks show it generating two water molecules, and ties the information together with the analogous principles from substrate-level phosphorylation in the citric acid cycle and the relative differences in water consumption and carbon dioxide generation between fat and carbohydrate. As with our discussion of the citric acid cycle, we also reveal why the standard stoichiometry of glycolysis is misleading and why, when we account for atoms rather than molecules, we find glycolysis to be net water-neutral. For the full episode, go to chrismasterjohnphd.com/mwm/2/19 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Can fat fuel intensity in a competitive athlete? This lesson takes a critical look at the commonly cited evidence in favor of a neutral or beneficial effect of low-carbohydrate or ketogenic diets on sports performance, as well as key pieces of conflicting evidence. Bottom line? Fat can fuel duration, but probably can never fuel your peak intensity, just as the physiology would predict. For the full episode, go to chrismasterjohnphd.com/mwm/2/18 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Can athletes fat-adapt their workouts? This lesson lays down the principles of exercise biochemistry and physiology needed to understand the importance of the three energy systems supporting energy metabolism in skeletal muscle: the phosphagen system (ATP and creatine), anaerobic glycolysis (dependent on carbs), and oxidative phosphorylation (dependent on carbs, fat, or protein). We discuss why maximal intensity always depends on carbs if the intensity and duration are sufficient to deplete phosphocreatine concentrations, and clarify the window of time and intensity that can be fat-adapted. This sets the foundation for the next lesson, which looks at the evidence of how carbohydrate restriction and ketogenic diets impact sports performance. For the full episode, go to chrismasterjohnphd.com/mwm/2/17 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

"Anaplerosis" means "to fill up" and refers to substrates and reactions that fill up a metabolic pathway as its own substrates leak out for other purposes. The citric acid cycle is a central example of this because its intermediates are often used to synthesize other components the cell needs. On a mixed diet where carbohydrate provides much of the energy, pyruvate serves as the main anaplerotic substrate. During carbohydrate restriction, protein takes over. Fat is the least anaplerotic of the macronutrients because the main product of fatty acid metabolism, acetyl CoA, is not directly anaplerotic. There are several very minor pathways that allow some anaplerosis from fat, but they are unlikely to eclipse the need for protein to support this purpose during carbohydrate restriction. Thus, carbs and protein are the two primary sources of anaplerosis. This means carbs can spare the need for protein, and that protein requirements rise on a carb-restricted diet. For the full lesson, go to chrismasterjohnphd.com/mwm/2/16 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

One of the advantages of carbohydrate over fat is the ability to support the production of lactate. This is so important that carbohydrate is physiologically essential to red blood cells and certain brain cells known as astrocytes. For the same reason, it plays an important role in supporting the energy requirements of the lens and cornea, kidney medulla, and testes, and supports the quick boosts of peak energy needed during stressful situations that include high-intensity exercise. The biochemical role of lactate is to rescue NAD+ during times when NAD+ becomes limiting for glycolysis and glycolysis becomes a meaningful source of ATP. Through the Cori cycle, lactate can extract energy from the liver's supply of ATP and deliver it to other tissues such as skeletal muscle in the form of glucose. This lesson fleshes out the physiological and biochemical roles of lactate and serves as a foundation for the next lesson, which explores the role of carbohydrate in supporting sports performance. Watch the full lesson at chrismasterjohnphd.com/mwm/2/17 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Did you realize that thiamin deficiency can be caused by your environment? In the old days, beriberi was associated with the consumption of white rice. Nowadays, refined foods are an unlikely cause of thiamin deficiency because they are fortified. We associate deficiency syndromes such as Wernicke's encephalopathy and Korsakoff's psychosis primarily with chronic alcoholism. Yet there are regional outbreaks of thiamin deficiency among wildlife attributed to poorly characterized thiamin antagonists in the environment. Thiamin-destroying amoebas can pollute water, thiamin-destroying bacteria have been isolated from human feces, and thiamin-destroying fungi have also been identified. Could toxic indoor molds and systemic infections play a role as well? Thiamin deficiency is overwhelmingly neurological in nature and hurts the metabolism of carbohydrate much more than fat. Indeed, preliminary evidence suggests thiamin supplementation can help mitigate glucose intolerance. Ketogenic diets are the diets that maximally spare thiamin and are best characterized as treatments for neurological disorders. Anecdotally, ketogenic diet-responsive neurological problems sometimes arise as a result of infection. Could ketogenic diets be treating problems with thiamin or thiamin-dependent enzymes? One must exercise caution here: fat contains little thiamin, and ketogenic diets can actually cause thiamin deficiency if they don't contain added B vitamins. The relationships between thiamin, glucose metabolism, and neurological health are remarkable and desperately need our attention. For the full lesson, go to chrismasterjohnphd.com/mwm/2/14 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The pyruvate dehydrogenase complex catalyzes the one decarboxylation step that carbohydrate undergoes to generate acetyl CoA, which accounts for the one carbon dioxide molecule produced in carbohydrate metabolism that is not produced during the metabolism of fat. It also accounts for why burning carbs requires twice as much thiamin as fat. In fact, the pyruvate dehydrogenase complex is remarkably analogous to the alpha-ketoglutarate dehydrogenase complex, sharing all the same cofactors and catalyzing virtually the same reactions. In this lesson, we look at why this has to be true and how it works. This provides the foundation for our deeply practical look at thiamin in the next lesson. chrismasterjohnphd.com/mwm/2/13 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Since carbs are richer in oxygen than fat, they consume less water in their metabolism and release more carbon dioxide. Carbon dioxide puts stress on the lungs and its generation should be restricted in the case of lung injury to allow healing. This calls for a low-carbohydrate, high-fat diet. On the other hand, carbon dioxide is needed to support the action of vitamin K and biotin, and to promote delivery of oxygen to tissues during exercise. In our first glimpse into glycolysis and beta-oxidation, we find that understanding the basic chemical makeup of these molecules is deeply relevant to how we would manipulate the diet in many contexts of health and disease. For the full lesson, go to chrismasterjohnphd.com/mwm/2/12 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Now we take it clinical: how do we use what we've learned so far to interpret the section of a urinary organic acids test that reports the citric acid cycle metabolites? We begin by looking at the underlying chemistry to explain the curious absence of oxaloacetate on these tests. We conclude by mastering the ability to spot three unique patterns: energy overload, oxidative stress, and thiamin deficiency. For the full lesson go to chrismasterjohnphd.com/mwm/2/11 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson looks at the fundamental principle that atomic oxygen is the limiting factor for the release of carbon dioxide in metabolism, and when we don't have enough we take it from water. This will become very relevant when we cover fats versus carbohydrates, because they consume different amounts of water and release different amounts of carbon dioxide for this very reason. That, in turn, relates to a number of health endpoints such as the functions of vitamin K and biotin, delivery of oxygen to tissues, and the stress placed on the lungs during breathing. Here, we look at the principle in the citric acid cycle. In doing so, we see that, while textbooks only point to two water molecules consumed, a third water molecule is irreversibly consumed to donate oxygen to the cycle via phosphate. For the full lesson, go to chrismasterjohnphd.com/mwm/2/7 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson addresses the curious case of why CoA makes a brief cameo in the citric acid cycle during the formation of succinyl CoA only to leave again in the next step. We dig into the chemistry underlying the high-energy thioester bond that CoA forms with acyl groups, which explains more broadly one of the key roles of sulfur in energy metabolism. We conclude by looking at how the appearance of CoA allows us to harness energy released during the decarboxylation of alpha-ketoglutarate to form ATP directly during "substrate-level phosphorylation," or, alternatively, to use energy from ATP to invest in the synthesis of heme. chrismasterjohnphd.com/mwm/2/9 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This complex is so rich in biochemical concepts and relevance to health and disease. Having done the dirty work of looking at its organic chemistry mechanisms in the last lesson, here we explore broadly applicable biochemistry principles like energetic coupling and substrate channeling. We look at how thiamin deficiency, oxidative stress, arsenic, and heavy metal poisoning can affect metabolism, and how to recognize markers of these processes in blood or urine. We make the subtle yet critical distinction between oxidative stress and oxidative damage. We look at the role of this complex in Alzheimer's disease. We then turn to the product of this complex, succinyl CoA, to examine how it provides an entry into the cycle for odd-chain fatty acids and certain amino acids and an exit out of the cycle for the synthesis of heme. In doing so, we look at the roles of vitamins B12 and B6 in these processes, the use of methylmalonic acid to diagnose B12 deficiency, and the ability of B6 deficiency to cause sideroblastic anemia. For the full video, go to chrismasterjohnphd.com/mwm/2/8 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The alpha-ketoglutarate dehydrogenase complex is marvelously complex and incredibly rich in details that are relevant to the big picture of metabolism and to many issues of health and disease. Today, we break down what actually happens so that we can spend all of Wednesday's lesson discussing the rich array of relevant principles it brings to light. For the full video, go to chrismasterjohnphd.com/mwm/2/7 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Are you interested in working with me one-on-one so I can help you better meet your health goals? Good news! I'm now accepting new clients for both hourly consultations and health and wellness packages. Here are the core things I'm best at that I would love to do for you: Help you develop actionable priorities and an overall strategy for improving your health. Discuss your experiences with you and suggest useful tests that you could ask your doctor about. Analyze the results of genetic tests, digital food logs, and blood and urine measurements for markers of health and nutritional status. I can then use these analyses to suggest practical strategies that you could implement with proper supervision of a health care professional. If you want to want to read more about what I have to offer, head over to the main consultations page: Health and Wellness Consultations With Chris Masterjohn, PhD Although I have no plans to expire the offer, I suggest you act rather swiftly if you want to book sessions between now and February because the spots available from September through January are limited and will fill up fast. After February, my availability is much more open. Once again, here are the links you may need: learn more about what I have to offer. Book an hourly session. Book a health and wellness package. Whether sooner or later, I look forward to working with you and helping you fulfill your health goals. If you have any questions about how this works, please do not hesitate to email me at chris [at] chrismasterjohnphd {dot} com. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

If you develop dry skin on a low-fat diet, especially if you're eating egg whites and throwing out the yolks, it could be a biotin deficiency. Or, it could be an essential fatty acid deficiency. Either way, egg yolks and liver come to the rescue. To get these episodes free of ads, with transcripts, and weeks or sometimes even months before they are released to the public, along with access to monthly live Q&A sessions, sign up for the CMJ Masterpass at https://chrismasterjohnphd.com/masterpass. Use the code LITE10 to get 10% off. To make it easier to get the discount, use this link, which has the coupon already activated: https://masterpass.chrismasterjohnphd.com/cmj-masterpass/2200/buy?coupon=LITE10 Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson looks at the third step of the citric acid cycle in much more detail, digging into the organic chemistry concepts involved in the conversion of isocitrate to α-ketoglutarate. We dive deep into this because it's the only way to explain why this step parts ways with most other decarboxylation reactions in that it does not require thiamin (vitamin B1). This, in turn, provides a basis for understanding why burning carbohydrate for fuel requires twice as much thiamin than burning fat, and why high-fat, low-carbohydrate, ketogenic diets can be used to overcome problems with thiamin deficiency or defects in thiamin-dependent enzymes. We conclude by looking at how this step allows the interconversion of amino acids and citric acid cycle intermediates, the role of vitamin B6 in this process, and the use of enzymes known as transaminases to diagnose B6 deficiency and liver dysfunction. For the full episode, go to chrismasterjohnphd.com/mwm/2/6 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Do you get dry skin when you put on muscle mass? It could be a zinc deficiency. Here's how to take care of it. To get these episodes free of ads, with transcripts, and weeks or sometimes even months before they are released to the public, along with access to monthly live Q&A sessions, sign up for the CMJ Masterpass at https://chrismasterjohnphd.com/masterpass. Use the code LITE10 to get 10% off. To make it easier to get the discount, use this link, which has the coupon already activated: https://masterpass.chrismasterjohnphd.com/cmj-masterpass/2200/buy?coupon=LITE10 Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The fifth MWM Energy Metabolism lesson explores the third and fourth steps of the citric acid cycle and explains how the rate of ATP production is regulated according to the cell's need for ATP. Together with lesson four, it explains how cells regulate their ATP production according to their needs and abilities. In the course of exploring this theme, we look at the role of AMP kinase (AMPK) in promoting energy uptake when ATP levels are low. Watch the full lesson at chrismasterjohnphd.com/mwm/2/5 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson explores the first two steps of the citric acid cycle and explains how the rate of ATP production is regulated according to the abilities of the electron transport chain. Together with lesson five, it explains how cells regulate their ATP production according to their needs and abilities. In the course of exploring this theme, we examine the role of reactive oxygen species in diabetes. Watch the full lesson at chrismasterjohnphd.com/mwm/2/4 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This lesson provides an overview of the basic objectives of using the citric acid cycle and the electron transport chain to make ATP. We start here because, no matter whether we burn protein, carbs, or fat, these two interrelated systems are what is shared in common. Watch the full lesson at chrismasterjohnphd.com/mwm/2/3 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The second MWM energy metabolism looks at how we use enzymes to exert exquisite control over what happens inside our bodies. If the second law of thermodynamics holds that entropy is always increasing, why don't we reach maximum entropy right away? Why do we observe any order at all? The activation energy represents the resistance to change that can be found in any substance. We exploit the concept biologically by maintaining a body temperature that provides insufficient energy for most relevant reactions to go forward without catalysis, and imposing upon this backdrop an expansive repertoire of enzymes that can, in a regulated fashion, lower the energy barriers sufficiently for reactions to go forward. This lesson looks at how they do that, and how we regulate their activity. Watch the full lesson at chrismasterjohnphd.com/mwm/2/2 Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The first MWM Energy Metabolism lesson answers the question, why do we have to eat such an enormous amount of food? The answer is to comply with the second law of thermodynamics. If you have a chemistry background, you should recognize this as a light review of the thermodynamics unit from a general chemistry class, with its most essential concepts teased out and packed into a half hour lesson. If you don't, you can use this as a basic foundation for understanding the biochemistry to follow. The lesson relates the 2nd law to food coloring dispersing in water, how a hydropower plant operates, ATP production, and why we need to eat our bodyweight in food more than once a month. In the process, we have a little fun. Watch the full lesson at chrismasterjohnphd.com/mwm/2/1. Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Masterclass With Masterjohn Energy Metabolism is a structured course that begins with foundational principles and progresses to advanced topics to give you everything you need to know about the biochemistry of how we break down food for energy, use the energy, and store the excess. It broadcasts FREE on YouTube and Facebook twice a week and is now in its 31st lesson. As a subscriber to the Mastering Nutrition podcast, you will now get the cliff notes of these lessons in audio format. This gives you three ways to engage with the course: If you just want the cliff notes, sit back and relax. As long as you're subscribed to the Mastering Nutrition podcast, they'll pop up in your feed one by one, every day that there's no other content released in the feed. That begins with lesson one later today. If you want to watch the full lessons, you can do so using the YouTube playlist, by going to the videos section of my Facebook page and playing the playlist, or by going to chrismasterjohnphd.com, hovering over "Masterclass" in the main menu on desktop and clicking the dropdown arrow to the right of "Masterclass" on mobile, and choosing "The Free Version." Sign up for MWM Pro for early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions, and a community with a forum for each lesson. However you choose to engage, enjoy! Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

MTHFR is an enzyme that allows folate (vitamin B9) to support the cellular process of methylation, which is important for the synthesis of creatine and phosphatidylcholine, the regulation of gene expression, neurotransmitter metabolism, and dozens of other processes. There are two common polymorphisms that decrease its activity, A1298C and C677T, with C677T having the stronger effect. Genetic decreases in MTHFR activity are associated with cardiovascular disease, neurologic and psychiatric disorders, pregnancy complications and birth defects, and cancer. While discussions of these polymorphism tend to focus on repleting methyl-folate, this should only be a small piece of the puzzle. The bigger pieces of the puzzle are restoring choline, creatine, and glycine. In this episode, I describe how the methylation system works, how it's regulated, and how it's altered with MTHFR variations. I then use this to develop a detailed dietary strategy and an evaluative strategy to make sure the dietary strategy is working. Show notes coming soon! This episode is brought to you by Ample Meal. Ample is a meal-in-a-bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbohydrate, plus all the vitamins and minerals you need in a single meal, all from a blend of natural ingredients. The protein is from whey and collagen. The fat is from coconut oil and macadamia nut oil. The carbohydrates, vitamins, and minerals come exclusively from food sources like sweet potatoes, bananas, cocoa powder, wheat and barley grass, and chlorella. I use Ample on Mondays when I have 12 hours of appointments with breaks no longer than 15 minutes. It keeps my brain going while I power through the long day, never letting food prep make me late for an appointment. Head to amplemeal.com and enter the promo code "CHRIS15" at checkout for a 15% discount off your first order. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/046-living-with-mthfr Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Insulin is almost universally considered a hormone whose primary purpose is to regulate blood glucose levels. Indeed, it does this. But is that the whole picture? When we look at what governs pancreatic insulin secretion inside the beta-cell, it's about total energy and the versatility of the short-term energy supply, not about glucose. When we look at what insulin does to energy metabolism, it does far more than regulate blood glucose: it governs how we use energy and what we do with it. What is insulin really doing? Find out in this episode. I can't promise the episode is practical, but I promise it's incredibly thought-provoking. You can find the show notes at chrismasterjohnphd.com/45. This episode is brought to you by Ample Meal. Ample is a meal-in-a-bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbohydrate, plus all the vitamins and minerals you need in a single meal, all from a blend of natural ingredients. The protein is from whey and collagen. The fat is from coconut oil and macadamia nut oil. The carbohydrates, vitamins, and minerals come exclusively from food sources like sweet potatoes, bananas, cocoa powder, wheat and barley grass, and chlorella. I use Ample on Mondays when I have 12 hours of appointments with breaks no longer than 15 minutes. It keeps my brain going while I power through the long day, never letting food prep make me late for an appointment. Head to amplemeal.com and enter the promo code "CHRIS15" at checkout for a 15% discount off your first order. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Here's what you'll find in this episode, and more: 00:55 Cliff Notes 12:45 Insulin is widely perceived as a response to blood glucose, yet there are a variety of reasons to see it as a response to short-term energy status and the versatility of that short-term energy. 14:48 Defining "insulin signaling." 18:00 Dietary effects on insulin and glucagon: fat, protein, and carbohydrate. 21:45 Effects of insulin outside of energy metabolism: for example, glutathione synthesis, production and activation of thyroid hormone, protection against glycation. 28:10 Insulin signaling is directly triggered by the level of ATP in the pancreatic beta-cell. 35:10 Amplification signals in beta-cell: anaplerosis, cataplerosis, lipogenesis, and the pentose phosphate pathway. 45:30 The anatomy and physiology of macronutrient transport mean that fat and carbohydrate are delivered to the pancreatic beta-cell in very different ways, resulting from circulatory routes and the relative expression of glucose transporters and lipoprotein lipase. 01:07:15 Unique roles of glucose in specialized energetic pathways. 01:07:50 Cytosolic ATP generation depends on glucose and is important to red blood cells, astrocytes, the lens and cornea of the eye, the kidney medulla, the testes, and under conditions of high-intensity exercise, stress, hypoxia, or suffocation. 01:11:10 Only glucose can allow a tissue to borrow energy from the liver in the Cori cycle. 01:14:30 Glucose is the primary anaplerotic substrate; protein is secondary; fat has little anaplerotic pathway. 01:15:50 Only glucose can support the pentose phosphate pathway, which provides NAPDH and 5-carbon sugars for DNA; RNA, all of the energy carriers in energy metabolism (NADPH, NADH, FADH2, Coenzyme A, ATP); synthesis of nucleotides, neurotransmitters, fatty acids, and cholesterol; recycling of vitamin K and folate. 01:21:40 Insulin as a response to total energy and energetic versatility. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/045-is-insulin-really-a-response Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Do carbs and insulin make you fat? The argument centers on the ability of insulin to promote the conversion of carbohydrate to fat and lock fat in adipose tissue, as well as the necessity of glucose to provide the backbone to fat molecules within adipose tissue. But the argument ignores that all of these pathways are fundamentally regulated at a biochemical level by how much energy you need and how much you have. In episode 44 of Mastering Nutrition, we take a deep dive into the details of the biochemistry and see how insulin serves as a gauge of whole-body energy and glucose availability but simply can't be the thing that makes you fat. This episode is brought to you by Ample Meal. Ample is a meal-in-a-bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbohydrate, plus all the vitamins and minerals you need in a single meal, all from a blend of natural ingredients. The protein is from whey and collagen. The fat is from coconut oil and macadamia nut oil. The carbohydrates, vitamins, and minerals come exclusively from food sources like sweet potatoes, bananas, cocoa powder, wheat and barley grass, and chlorella. I use Ample on Mondays when I have 12 hours of appointments with breaks no longer than 15 minutes. It keeps my brain going while I power through the long day, never letting food prep make me late for an appointment. Head to amplemeal.com and enter the promo code "CHRIS15" at checkout for a 15% discount off your first order. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Show notes for this episode are found at chrismasterjohnphd.com/44. In this episode, you'll find all of the following and more: 00:45 Cliff Notes 10:15 The biochemistry and physiology of the carbohydrate/insulin hypothesis of obesity: insulin stimulates de novo lipogenesis (fatty acid synthesis), promoting the conversion of carbohydrate to fat; insulin stimulates lipoprotein lipase (LPL) and inhibits hormone-sensitive lipase (HSL) at adipose tissue, locking fat into fat cells; since adipose tissue lacks glycerol kinase, it cannot reuse the glycerol backbone of fats digested by lipoprotein lipase, and dietary carbohydrate is needed to provide the glycerol 3-phosphate that forms the backbone of newly resynthesized triglycerides. 16:30 All biochemical pathways are regulated by cellular energy status. Key players are ATP, ADP, AMP, AMP kinase (AMPK), NADH/NAD+, FADH2/FAD, Ca2+, CoA and acyl CoAs, and citrate. 30:42 Although insulin promote storage of fat in fat tissue, this can be overridden by low energy status. 40:10 Although insulin promotes fat storage, it causes a proportionate increase glucose oxidation, so no net change in caloric balance. 46:10 Glucose oxidation in muscle is driven by energy status and that determines the availability of glucose to adipose tissue. 01:00:45 Glucose can act as the source of glycerol 3-P for adipose tissue triglyceride synthesis, but it isn't necessary because of gluconeogenesis and glyceroneogenesis. Furthermore, while it can serve this role, the degree to which it does so is driven by energy status. 01:05:50 Glucose can act as a source of glycerol 3-P for adipose, but it needs a source of fatty acids, which come mainly from fat as long as energy status is high enough. 01:06:50 Insulin can drive de novo lipogenesis, but only when energy status is high enough. 01:20:05 What happens when we eat carbs alone, fat alone, or both in the context of low and high energy status. 01:32:20 The path to weight loss is the path to a sustainable caloric deficit. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/044-the-biochemistry-of-why-insulin Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Our consciousness is like a net. We want the net to be fluid enough to let thoughts that bother us pass through without grabbing our attention, but strong enough to grab on to the ideas and motivations that will drive us to achieve what we value in life. Nutrition has a big impact on this net. In this episode, learn how foods like liver, egg yolks, meat, leafy greens, legumes, collagen, bone broth, spinach, wheat, and beets can impact how fluid or stable your mind is by impacting the methylation of dopamine, and how to achieve the proper balance. This episode is brought to you by Ample Meal. Ample is a meal-in-a-bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbohydrate, plus all the vitamins and minerals you need in a single meal, all from a blend of natural ingredients. The protein is from whey and collagen. The fat is from coconut oil and macadamia nut oil. The carbohydrates, vitamins, and minerals come exclusively from food sources like sweet potatoes, bananas, cocoa powder, wheat and barley grass, and chlorella. I use Ample on Mondays when I have 12 hours of appointments with breaks no longer than 15 minutes. It keeps my brain going while I power through the long day, never letting food prep make me late for an appointment. Head to amplemeal.com and enter "CHRIS15" at checkout for a 15% discount off your first order. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! In this episode, you'll find all the following and more: 00:38 Cliff Notes 12:15 Three stories illustrating how foods impact mental stability and fluidity. 13:00 How veganism profoundly worsened my OCD and panic attacks and going Weston A. Price made them disappear. 18:55 Jeffrey is an entrepreneur who uses intermittent fasting and low-protein lunches to remain hyper-focused through the workday, but at the risk of an occasional panic attack. 22:05 Jordan uses methylation supplements to optimize his energy and mental focus, but can experience a spectrum of methylation states that range from bodily tiredness on one end to intense focus suitable for creative and analytic work in the middle, to flighty productivity suitable for errands on the high end, to a severe crash characterized by apathy. 26:50 The methylation system and the roles of sulfur amino acids (methionine and cysteine), magnesium, ATP, B6, serine and glycine, folate, B12, niacin, riboflavin, thiamin, choline, betaine, and creatine. 34:18 The two principle fates of homocysteine. 40:10 Glycine as the endogenous buffer of extra methyl groups. 42:40 Obtaining betaine and choline from foods. 45:40 Creatine as a methyl group sparer. 48:20 Niacin and nicotinamide riboside as a tax on the methylation system. 50:25 Tonic and phasic dopamine, and how methylation mediated by catechol O-methyltransferase (COMT) regulates the balance. 57:20 How the balance of tonic and phasic dopamine determines the ease of switching mental states. 1:03:50 Worrier vs. warrior phenotype. 1:09:10 Histamine in the brain as an alertness signal and a potential contributor to panic attacks. 1:11:55 Explaining the three stories. 1:22:00 Practical conclusions. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/043-methylate-your-way-to-mental Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In this episode, we look at whether fat can fuel the athlete. We begin with the physiological principles involved, then take a look at the evidence from studies swapping fat for carbs to see how it impacts athletic performance. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/042-can-fat-fuel-the-athlete Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In this episode, I weigh in on the American Heart Association's new Presidential Advisory and Dietary Fats and Cardiovascular Disease, and all the headlines that have been spinning on the supposed risks of coconut oil. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! The show notes for this episode can be found at chrismasterjohnphd.com/41. In this episode, you will find all of the following and more: 03:55 The recent headlines on coconut oil 04:52 The American Heart Association's new Presidential Advisory, "Dietary Fats and Cardiovascular Disease" is not centrally about coconut oil, but it laments its the popularity of coconut oil. 07:10 This is a position paper reinforcing the conventional view about saturated fat as the stance against it within the scientific community has begun to soften around the edges. The 2015 dietary guidelines and the 2016 Ramsden paper reflect that softening. 14:39 The inclusion and exclusion criteria of the "4 core trials" of the AHA meta-analysis 16:38 The 4 core trials 17:00 The Finnish Mental Hospitals Study makes the largest contribution to the AHA conclusion but was not a randomized controlled trial and doesn't belong in this list. 23:44 The Oslo Diet-Heart Study was included and made a contribution, yet other trials were excluded on the basis of confounding that were far less confounded than Oslo. 27:38 The LA Veterans Administration Hospital Study showed that a vitamin E-deficient diet makes you vulnerable to the heart disease-promoting effects of smoking, and that vegetable oils cause more cancer than cigarettes. 36:41 The Medical Research Council study showed a trend toward a benefit of soybean oil that was not statistically significant. Lack of heat damage to the fats in the diet, coenzyme Q10, and omega-6/omega-3 balance could have played a role in the trend. 41:12 Exclusion of Rose 1965 and Minnesota Coronary Survey from the "4 core trials" was fair. 42:33 Controversy over the possible contribution of trans fats to the results of the Sydney Diet Heart Study. But this as a basis for exclcusion could have excluded the LA Veterans Administration Hospital Study as well. 47:59 The impact of including or excluding MRC and Sydney shows how the conclusions are driven not by the cumulative data but on the qualitative decisions about which studies to include. 52:02 The observational studies are hopelessly confounded by popular campaigns about the heart-healthiness of replacing saturated fat with polyunsaturated fat. 56:08 The experiments in monkeys using lard, palm oil, and dietary cholesterol to bring their plasma cholesterol to 300-400 mg/dL. 58:33 The oxidation of lipoproteins drives atherosclerosis and polyunsaturated fats drive the oxidation. This is embraced by the leading conventional thinkers. 1:06:00 The AHA position on coconut oil is based on its effect on LDL-C, explicitly arguing in favor of ignoring its effects on HDL-C, and explicitly acknowledging the complete absence of clinical evidence. 1:13:12 Coconut oil has benefits unrelated to heart disease, such as the antimicrobial (antifungal and antibacterial) effects of lauric, capric, and caprylic acids, and the increased energy expenditure and decreased appetite caused by capric and caprylic acids. 1:17:00 Coconut oil could protect against heart disease due to its low polyunsaturated fat content. 1:19:32 Traditional Pacific island diets were far higher in saturated fat than the standard American diet, yet heart disease was absent. 1:22:09 The Tokelau Migrant Study showed that the freedom from heart disease on Tokelau, where coconut consumption pushed saturated fat over 50% of calories, was not due to genetics or age. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/041-is-coconut-oil-killing-us Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Analia Camarasa asked this question on Facebook: Ever since you've mentioned PTH on your podcast we've been measuring it in the office. It's nice to see that when patients come in on high doses of D supplementation their PTH is maximally suppressed, as it should be. I wish you could talk about the outliers briefly, normal D at 31 ng/mL and PTH outside of the range eating a healthy WAP diet, for example. Watch the video for my response. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Vitamin D deficiency and calcium deficiency look very similar, and poorly interpreted blood tests can easily mislead us into taking the wrong supplements. Here's how to tell them apart. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Glutamate is the most abundant amino acid in the diet, but is usually bound up in proteins. In its free form, it contributes to the umami taste, which is the savory flavor associated with meat and mushrooms. Long, slow cooking and fermenting can both bring out this flavor.⠀ Unfortunately, some people don't tolerate glutamate well. Glutamate sensitivity is controversial, but some of the symptoms people say they experience are headaches, sweating, flushing, or sets of symptoms that mimic allergies. If you don't tolerate slowly cooked protein foods or fermented foods, you may have glutamate sensitivity. If you do, an oxaloacetate supplement may help. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

If you've got high cholesterol then this video is for you. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

In episode 31, I explain why glutathione survives digestion and can be absorbed intact, and why supplementing with it or eating it in foods helps support your health. My recommended supplements: Jarrow Reduced Glutathione and Core Med Science Optimized Liposomal Glutathione. In most cases, save money by trying Jarrow first. Use the discount code from this episode to sign up for Masterclass With Masterjohn Pro with a $20/year lifetime discount, offer ending May 13. This episode is a companion to Consuming Glutathione in Foods and Supplements, which has a searchable database of glutathione in 285 foods. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! In this episode, you will find all of the following and more: 0:00:38 Cliff Notes 0:08:22 What is glutathione and why is it important? 0:13:33 Special Masterclass With Masterjohn Pro discount for Mastering Nutrition listeners 0:20:10 Why does glutathione survive digestion? 0:20:50 How is glutathione absorbed intact? 0:35:48 Evidence for intact absorption of glutathione 0:36:00 Oral glutathione increases tissue glutathione in animals when glutathione synthesis is blocked with BSO. 0:38:12 Glutathione crosses CACO-2 monolayers, a model of human intestinal absorption, even when glutathione breakdown is inhibited with acivicin and glutathione synthesis is inhibited with BSO. 0:39:25 Isotopically labeled glutathione fed to mice enriches labeled glutathione in liver and red blood cell with no signs of the label in glutathione digestion products. 0:40:30 Glutathione supplements increase glutathione status in humans. 0:41:10 Caveats and contrary evidence. 0:48:15 What form of supplement (sublingual, liposomal, regular) is best? 0:56:10 What are the best specific supplements? 0:58:10 What dose should you use, and how should you know if you should use it? 0:58:43 Anecdote: 1 gram of glutathione relieves laughing-induced wheezing. 1:02:50 Glutathione in foods: reduced glutathione, total glutathione, glutathione-reactive substances, net glutathione 1:08:25 Glutathione content foods is not the be-all end-all of whether a food boosts glutathione status or whether it's healthy, but it's notable and important. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/040-why-you-should-eat-glutathione Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

Tracking calories can be really hard, but here's how to make it easy. Like, easy easy? Easy easy easy easy? Well, no, not easier than not tracking calories. But far easier than you would expect if you haven't tried it. And thousands of times easier than some other methods of tracking calories. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

This is how I recommend losing weight if you want a method that is reliable and easy to optimize over time. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.

The effect of sprouting on the folate concentration of legumes is incredible. It peaks on the fourth day of sprouting, though, according to a recent study. But is it always the fourth day in every legume under any condition sprouted in a home kitchen? Are the sprouted legumes on the store shelf four-day sprouts? Right now there are more questions than answers, but I believe that opting for sprouted legumes is a good way to supercharge your folate status as long as you still make an effort to get 2-3 servings of folate-rich foods per day. I cover this and another way to supercharge your folate status — eating egg yolks from pasture-raised chickens — in today's Chris Masterjohn Lite video. Access the show notes, transcript, and comments here. Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.