HoldsUp

George Brooks

George A. Brooks, Ph.D., is a researcher in physiology and metabolism known for developing the lactate shuttle hypothesis. His published research focuses on carbohydrate and lactate kinetics, muscle fuel utilization, and mitochondrial bioenergetics in the context of exercise and aging. He also investigates the potential therapeutic applications of lactate in neurological conditions and metabolic regulation.

36 claims checked on air: 1 context 1 contradicted 1 overstated 31 supported 2 unverified 2 flagged

What they said on air - citing their own research

9 citing their own research

0:03:05supportedhightheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Glycolysis and lactate production occur continuously in all cells, where lactate acts as a fuel, a precursor for blood glucose, and a signaling molecule.

"glycolysis—the breakdown of sugar and glycogen—happens all the time in all cells, and we use it. We use it as a fuel. We use it to support our blood sugar level. We use it as a signaling molecule to activate certain metabolic processes. It's made in some cells, and it's used in other cells." (said at 0:03:05)

Extensive metabolic physiology research confirms the speaker's statement. Rather than being merely an anaerobic waste product, lactate is continuously produced under fully aerobic conditions and shuttles between producer (source) and consumer (sink) cells. Across human and mammalian studies, lactate is established as fulfilling three major metabolic roles: serving as a major oxidative fuel for tissues such as the heart, brain, and skeletal muscle; acting as the primary gluconeogenic precursor in the liver and kidneys to maintain blood glucose levels; and functioning as an autocrine, paracrine, and endocrine signaling molecule.

0:06:37supportedmoderatetheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Lactate transporters are located in plasma membranes and within the mitochondrial reticulum as lactate/pyruvate transporters.

"our unique contribution was to find that not only are they in the plasma membranes of muscles and heart and other tissues, but they're also in the mitochondria. They are the lactate/pyruvate transporter." (said at 0:06:37)

Published cell biology and biochemical studies confirm that monocarboxylate/lactate transporters (such as MCT1) are located both in plasma/sarcolemmal membranes and within the mitochondrial reticulum/inner mitochondrial membrane of cardiac muscle, skeletal muscle, and other tissues, where they transport monocarboxylates like lactate and pyruvate into mitochondria for oxidation.

0:08:41supportedmoderatetheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Trained athletes produce more lactate than untrained individuals, but clear and remove it more rapidly.

"And athletes actually produce more than people who are less capable or less highly trained, but they remove it; they use it." (said at 0:08:41)

Tracer kinetic studies in humans demonstrate that trained endurance athletes have higher capacities for both lactate production (rate of appearance) and lactate clearance/oxidation (rate of disposal and metabolic clearance rate) compared to untrained individuals. While lactate production is lower in trained individuals at the same absolute submaximal workload due to enhanced mitochondrial oxidative efficiency, at maximal workloads and at the lactate threshold, athletes achieve higher absolute rates of lactate production and simultaneously clear and utilize lactate much more rapidly.

0:11:46supportedvery lowtheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Incubating muscle cells with lactate upregulates over 600 genes associated with muscle adaptation and mitochondrial biogenesis.

"But we know from our studies that we've done with incubated muscle cells that if we just take muscle cells and we incubate them with lactate, we'll upregulate over 600 genes, all the genes basically of muscle adaptation." (said at 0:11:46)

In vitro experimental work demonstrates that incubating muscle cells with lactate stimulates cell signaling cascades and activates a broad transcriptional network, inducing the expression of monocarboxylate transporters (such as MCT1), mitochondrial components, and genes regulating mitochondrial biogenesis and metabolic adaptation. Because this evidence is derived entirely from isolated cell culture models rather than in vivo human physiological trials, the overall certainty is graded as very low.

0:30:11supportedlowtheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Infusing lactate in patients with traumatic brain injury increases total cerebral carbohydrate uptake (glucose plus lactate).

"And we actually have done six patients, in collaboration with our colleagues at UCLA. We show that we can increase the carbohydrate uptake, that is the total of glucose plus lactate, in people with brain injury by infusing lactate." (said at 0:30:11)

Collaborative metabolic tracer and infusion studies conducted in human traumatic brain injury (TBI) patients by researchers at UCLA and UC Berkeley demonstrate that exogenous sodium L-lactate infusion increases net cerebral carbohydrate uptake. In these studies, infusing L-lactate changed cerebral metabolism from net lactate release to net lactate uptake (as measured by arteriovenous differences and isotopic tracers) while systemic glucose availability was maintained, resulting in increased total brain carbohydrate uptake (glucose plus lactate). The GRADE certainty is low due to the small sample sizes typical of intensive metabolic catheterization and tracer studies.

0:45:16supportedmoderatetheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

During exercise in men, infused or elevated blood lactate is metabolized preferentially over glucose by muscle, heart, and brain.

"because we've given lactate to men during exercise and it is preferred over glucose, and— In muscle, heart... Now, and also in brain." (said at 0:45:16)

Physiological tracer and infusion studies in humans demonstrate that when blood lactate concentrations are elevated (such as during exercise or via exogenous infusion), lactate is readily cleared and oxidized as a preferred fuel source relative to glucose by oxidative skeletal muscle fibers, the myocardium (heart), and the brain, down-regulating alternative substrate utilization.

0:45:47supportedhightheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Lactate is more reduced and contains more chemical energy than pyruvate.

"It's more reduced, so it actually has more energy than pyruvate." (said at 0:45:47)

Lactate is the reduced form of pyruvate, formed when lactate dehydrogenase catalyzes the transfer of two electrons and a proton from NADH to pyruvate (Pyruvate + NADH + H⁺ ⇌ Lactate + NAD⁺). Because lactate contains two additional electrons (reducing equivalents) compared to pyruvate's oxidized ketone group, it is in a more reduced state and has a higher chemical energy content (enthalpy of combustion). When lactate is oxidized back to pyruvate in oxidative tissues, the transferred reducing equivalent generates NADH, which yields additional ATP through the mitochondrial electron transport chain.

0:46:18supportedlowtheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

Neurons possess all the intact molecular apparatus necessary to take up glucose and produce lactate.

"But Rasha Hussien, who just poked her head in here, she has a paper where she showed that all the apparatus for neurons to take glucose and make lactate are intact always." (said at 0:46:18)

Preclinical biochemical and immunohistochemical studies by Hussien and Brooks demonstrated that neurons express key molecular components required for monocarboxylate transport and lactate metabolism, including monocarboxylate transporter isoforms (MCT1, MCT2) and lactate dehydrogenase (LDH) localized with neuronal mitochondria. These findings demonstrate that neurons possess the intact molecular machinery to participate in intracellular and cell-to-cell lactate transport and oxidation alongside standard glucose metabolism.

0:48:52overstatedlowtheir own paperGeorge Brooks, Ph.D. on Lactate Shuttle Theory, Relevance fo

When pyruvate is infused intravenously, red blood cells and the lungs convert it to lactate within seconds to a minute in one circulatory passage.

"when you infuse it in one circulatory passage, it's all lactate. So the lungs do that, and red blood cells do that. The red blood cells and the lungs are loaded with enzymes to convert pyruvate to lactate. So even if you want to try to give pyruvate, within seconds or a minute, it's going to be lactate anyway" (said at 0:48:52)

Evidence supports that red blood cells and pulmonary tissue rapidly take up and convert circulating pyruvate to lactate due to high lactate dehydrogenase (LDH) activity and monocarboxylate transporter (MCT) expression. However, claiming that pyruvate is completely converted ("it's all lactate") in a single circulatory passage overstates the magnitude of first-pass pulmonary extraction. In vivo tracer studies in animal models demonstrate a transpulmonary pyruvate fractional extraction of approximately 43% per circulatory transit, rather than complete conversion, though rapid equilibration toward lactate continues across subsequent passages and within erythrocytes.

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