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Lactate

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Posted on October 4th 2023 (over 1 year)

In this clip, Dr. Martin Gibala examines the cognitive benefits of HIIT and the emerging insights on lactate's role in brain health.

Posted on October 4th 2023 (over 1 year)

In this clip, Dr. Martin Gibala explores HIIT's effects on VO2 max, highlighting the importance of personalized exercise routines.

Posted on September 27th 2023 (over 1 year)

In this clip, Dr. Martin Gibala describes the benefits and public health potentials of Reduced Exertion High-Intensity Training.

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News & Publications

  • If you’re struggling to remember things, a robust workout might help. Scientists have discovered that exercise can increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports learning and memory. A recent study in rats found that low-speed uphill exercise raises blood lactate levels, increasing lactate and BDNF in key brain regions involved in cognition.

    Researchers divided rats into three groups: One remained inactive, another walked on a flat treadmill, and a third walked uphill at a 40% incline. The exercise sessions lasted either 30 or 90 minutes. To see if lactate from the blood contributed to brain changes, some rats also received a direct lactate injection.

    Uphill exercise increased lactate levels in the animals' blood and brains, while flat treadmill walking did not. After 90 minutes, uphill exercise also raised BDNF levels in brain regions linked to memory and learning. The lactate injection showed that blood lactate passed into the brain, reinforcing that exercise-induced increases in blood lactate can influence brain chemistry.

    These findings suggest that walking uphill—even slowly—provides cognitive benefits by raising brain lactate and stimulating BDNF production. This type of exercise could be a practical and safe way to support brain health, especially for older adults or those looking to enhance memory and learning. To learn more strategies to boost brain health, check out the Cognitive Enhancement Blueprint, a member-only perk.

  • Lactate boosts cognitive function in mice, according to a new study. Mice had better spatial working and long-term memory after exercising and receiving supplemental lactate.

    Researchers studied the effects of exercise – with or without supplemental lactate – on cognitive function in mice. The mice engaged in moderate-intensity exercise (about 55 to 60 percent of their VO2 max) five days a week for five weeks. This level of intensity is just below the “lactate threshold” – the point at which lactate builds up in the bloodstream and compromises performance. At the end of the five-week period, they tested the animals' memory skills.

    They found that exercise plus supplemental lactate improved the animals' spatial working and long-term memory. In addition, the expression of various proteins produced in the hippocampus, including FNDC5 (also called irisin) and brain-derived neurotrophic factor (BDNF), increased, suggesting that supplemental lactate augments the beneficial effects of exercise on the hippocampus and subsequent cognitive function.

    Lactate is a compound produced in muscles during exercise via the breakdown of glucose. It is thought to participate in a sort of “lactate shuttle” in which it is transported from the muscles into tissues like the heart and brain, where it is used for energy. Evidence suggests that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal BDNF expression. Learn more about the lactate shuttle and its effects on the brain in this episode featuring Dr. George Brooks.

  • From the article:

    Current research has shown that (i) increased peripheral lactate levels (following high intensity exercise) are associated with increased peripheral BDNF levels, (ii) lactate infusion at rest can increase peripheral and central BDNF levels and (iii) lactate plays a very complex role in the brain’s metabolism. In this review, we summarize the role and relationship of lactate and BDNF in exercise induced neuroplasticity.

    […]

    Several trials have used blood lactate for the monitoring of exercise intensity. These studies indicate that higher lactate concentrations are associated with increased BDNF plasma and/or serum levels. Furthermore, current evidence indicates that high intensity interval training evokes larger BDNF levels compared to moderate and/or intensive continuous exercise […] Current research indicates that lactate transport from astrocytes to neurons plays a crucial role for memory formation and could be a link between exercise and neuroplasticity. Pharmacological inhibition of MCT 2 irreversibly impairs long-term memory. Van de Hall et al. have shown that lactate uptake in the brain increases from 8% at rest up to 20% during exercise.

  • Experiencing multiple concussions increases a person’s risk of poor brain function later in life, a new study shows. People who experienced three or more concussions exhibited cognitive deficits that worsened with each subsequent concussion.

    Researchers collected self-reported concussion histories from more than 5,700 adults between 50 and 70 years old. They administered cognitive tests to gauge changes in the participants' brain function every year for up to four years.

    They found that participants who experienced three mild concussions in their lifetime had difficulty with attention and performing complex tasks later in life. Participants who experienced four mild concussions had difficulty with processing speed and working memory – an aspect of cognitive function that allows a person to remember information for relevant tasks. However, experiencing even one moderate-to-severe concussion impaired the participants' attention and the ability to perform complex tasks and process information.

    These findings underscore the risks associated with even mild brain injury. Some evidence suggests that lactate and ketones may be beneficial in treating brain injury. Learn more in this clip featuring Dr. Dominic D'Agostino.

  • Children performed better on tests after they exercised, a new study has found. The children also exhibited better cognitive control – the ability to focus on a task and act based on choice rather than impulse.

    Researchers asked 20 preadolescent boys and girls to walk on a treadmill for 20 minutes at a brisk pace sufficient to raise their heart rate to 60 percent of their estimated maximum. After their heart rate returned to nearly pre-exercise levels, the children completed cognitive control assessments and standardized tests in reading, spelling, and math. They completed similar assessments and tests on a different day but without having exercised beforehand. The researchers measured aspects of the children’s brain activity while taking the tests.

    They found that the children performed better on tests of reading comprehension and demonstrated better cognitive control after having exercised. The children’s brains reflected greater neural activity related to attention and working memory processes.

    Research has identified robust links between regular exercise and brain function. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons. In addition, exercise induces the production of lactate, which stimulates the production of neurotransmitters in the brain that promote focus and attention. Learn more about the brain benefits of lactate in this episode featuring Dr. George Brooks.

    The findings from this small study suggest that exercise helps kids perform better in school and underscores the importance of incorporating physical activity into education plans.

  • From the article:

    To investigate whether testosterone supplementation improves measures of aerobic function ― the peak oxygen uptake and the gas exchange lactate threshold ― Dr. Storer and his colleagues analayzed data from subjects in a larger randomized controlled study of men over age 65 who had low testosterone levels and difficulty performing the usual physical activities of daily living. For 6 months, 28 men in one group received 10 milligrams of testosterone gel and 36 men in a second group received a placebo gel. All subjects completed a cycle exercise test to measure their peak aerobic fitness before and after the 6 month study.

    The men taking testosterone displayed a slight improvement in aerobic fitness while those taking placebo showed a slight decline. This small increase in aerobic capacity in the testosterone group eliminated the expected decrease that men generally experience with natural aging.

    Among the men taking testosterone, the age-related decline in the peak oxygen uptake was 3.4 times less than expected, while the rate of decline among the men taking placebo accelerated to nearly twice the expected rate. The decrease in gas exchange lactate threshold was significantly smaller in the testosterone group than in the placebo group. Longer term studies are needed to evaluate safety and durability of effect.

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  • Aerobic exercise reduces symptoms of anxiety. bmchealthservres.biomedcentral.com

    Aerobic exercise – especially high-intensity exercise – reduces symptoms of anxiety, an analysis of 15 studies shows. These anti-anxiety effects endured for several months after cessation of the exercise.

    Reviewers analyzed data from 15 studies that investigated the effects of low- or high-intensity exercise on anxiety symptoms. All the participants in the studies had some degree of anxiety, with their conditions falling on a spectrum that included anxiety disorders, raised anxiety levels, and raised anxiety sensitivity – a condition in which a person feels anxious about the physical symptoms that often accompany anxiety. People on waiting lists for anxiety treatment who did not exercise served as comparisons.

    They found that participants who engaged in both low- and high-intensity aerobic exercise experienced greater improvements in their anxiety than non-exercising people on treatment waiting lists. High-intensity exercise reduced anxiety symptoms more effectively than low-intensity exercise. The various interventions lasted between 10 weeks and six months, with participants exercising three times a week, on average.

    Multiple mechanisms may be responsible for the anti-anxiety effects of exercise. For example, high-intensity exercise promotes the production of lactate, a byproduct of glucose metabolism that participates in the production of neurotransmitters, such as norepinephrine and serotonin. Low norepinephrine and serotonin levels can drive anxiety and the inability to handle stressful situations. Learn more about lactate and its effects on the brain in this episode featuring Dr. George Brooks.

  • From the article:

    Dr. Resnick, Scott Moffat, Ph.D., and their colleagues evaluated the testosterone levels of 574 men, ages 32 to 87, who participated in the Baltimore Longitudinal Study of Aging (BLSA). The investigators examined free and total testosterone levels-measured over an average of 19 years-in relationship to subsequent diagnosis of AD. Based on physical, neurological and neuropsychological exams, 54 of the 574 men were diagnosed with AD.

    The research team found that for every 50 percent increase in the free testosterone index in the bloodstream, there was about a 26 percent decrease in the risk of developing AD. Although overall free testosterone levels fell over time, these levels dropped more precipitously in those men who later developed AD. In fact, at the end of the study, men who were diagnosed with AD, on average, had about half the levels of circulating free testosterone as men who didn’t develop the disease. In some cases, the drop-offs in free testosterone levels associated with AD were detected up to a decade before diagnosis.

    Previously, Dr. Resnick and her colleagues found that older men with high levels of circulating free testosterone have better visual and verbal memory and perform spatial tasks more adeptly than their peers.

    “It is quite possible that circulating free testosterone has a broad range of influences on the aging brain,” Dr. Resnick said.

    View full publication

  • Lactate is a compound that is produced primarily in the muscles via the breakdown of glucose during exercise. It can be “shuttled” from the muscles to various tissues, including the heart, and brain, where it can be used as an energy source. Evidence from a recent study suggests that lactate rejuvenates immune cells that target cancer.

    Specialized immune cells called CD8+ T cells are the primary drivers of anti-tumor immunity. During cancer progression, CD8+ T cells can experience “exhaustion,” a dysfunctional state caused by immune-related tolerance and immunosuppression in the environment surrounding the tumor.

    Researchers injected either lactate or glucose into mice that had cancer. The lactate markedly reduced cancer growth, but the glucose had little effect. They determined that the anti-tumor response was mediated by the CD8+ T cells. Depleting the CD8+ T cells negated lactate’s effect, confirming that lactate promotes anti-tumor immunity through CD8+ T cells.

    They also measured metabolites produced by CD8+ T cells (in culture) that had been treated with lactate. They found that the cells' uptake and subsequent metabolism of lactate increased. In addition, lactate inhibited the activity of histone deacetylases, and in turn, promoted the cells' stemness – the strictly controlled molecular processes that drive stem cell self-renewal and replication.

    These findings suggest that lactate rejuvenates the immune cell populations that target cancer, providing a possible mechanism by which exercise – which increases lactate production – reduces the risk of cancer. Learn more about lactate and the lactate shuttle in this episode featuring Dr. George Brooks.

  • Fast food during pregnancy harms both mother and offspring and interferes with milk production.

    Fast foods – burgers, fries, pizzas, sugar-sweetened drinks, and many others – are often high in calories, saturated fat, added sugars, and salt. Regular consumption of fast foods is associated with an increased risk for many chronic diseases. Findings from a recent study suggest that eating fast food during pregnancy negatively influences maternal health during pregnancy and undermines the nutritional quality of a mother’s breast milk.

    Breast milk is a complex and highly dynamic fluid that changes in composition in response to the growing infant’s needs. It contains both nutritional and non-nutritional components and is profoundly influenced by maternal health and dietary intake.

    The investigators fed one group of mice a high-fat, high-sugar diet that mimicked the nutritional content of fast food before, during, and after pregnancy. They fed another group a normal diet. They assessed the mothers' metabolic health, milk output, and milk composition, and assessed the offspring’s health.

    They found that the mice that ate the high-fat, high-sugar diet were heavier and had higher blood glucose and insulin levels during pregnancy than the mice that ate the normal diet. They also had fatty livers and showed signs of changes in their pancreatic tissues. More of the offspring born to the mice that ate the high-fat, high-sugar diet died during the lactation period due to poor maternal mammary gland development and diminished milk protein production.

    These findings suggest that eating foods that are high in fat and sugar (such as fast foods) during pregnancy negatively influences maternal health and undermines the nutritional quality of a mother’s breast milk. Learn more about breast milk and breastfeeding in our overview article.

  • Peripheral nerves have the ability to regenerate following trauma, surgery, and exposure to medications and toxins; however, the rate of regeneration is often very slow. The molecular signals that encourage regeneration dissipate over time so that regeneration ends too soon to effectively heal long nerves. Authors of a new report elucidate the role of monocarboxylate transporters and macrophage metabolism is promoting nerve regeneration.

    Macrophages (Greek for “large eaters”) are white blood cells that remove pathogens and cellular debris by engulfing and digesting them, making macrophages essential for cellular repair and immunity. Macrophages coordinate tissue regeneration efforts among multiple cell types by secreting a variety of cytokines to recruit additional support cells. In the case of nerve regeneration, macrophages promote the migration of Schwann cells, which produce myelin, to the site of damaged axons.

    Monocarboxylate transporters (MCTs) facilitate the movement of small energy molecules such as lactate and pyruvate into cells. When oxygen levels are low or metabolic demand is high, monocarboxylate compounds can be used instead of glucose for cellular energy. Emerging research demonstrates the role of MCTs in the progression of central nervous system disorders and neurodegenerative diseases; however, the role of MCTs on peripheral nerve injury is unknown.

    The authors utilized multiple mouse models for their study. First, they compared sciatic nerve regeneration following injury among mice that did not express the MCT-1 protein in one of four cell types: macrophages, perineurial cells, Schwann cells, or dorsal root ganglia neurons. Second, they observed sciatic nerve regeneration in mice that over-expressed the MCT-1 protein in macrophages. Finally, they tested the ability of macrophage adoptive cell transfer, in which macrophages that are isolated from bone marrow, cultured in vitro, and reinfused, to improve nerve regeneration in mice lacking the MCT-1 protein.

    Removal of the MCT-1 protein from macrophages significantly reduced nerve regeneration as demonstrated by poor recovery of electrical activity over six weeks following nerve injury; however, removal of MCT-1 from perineurial cells, Schwann cells, or dorsal root ganglia neurons did not impair nerve regeneration. Removal of MCT-1 from macrophages also increased pro-inflammatory cytokines and decreased pro-regenerative cytokine concentrations in the damaged tissue. Not all of these altered cytokines are produced by macrophages, indicating that MCT-1 removal in macrophages modulates the activity of the broader immune system. MCT-1 removal from macrophages impaired mitochondrial function and reduced ATP production, worsening the ability of macrophages to adapt to stressful stimuli and/or high metabolic demands. These macrophages were also less able to clear cellular debris.

    Mice that over-expressed the MCT-1 protein in macrophages had significantly faster never regeneration compared to normal mice. MCT-1 expression did not affect motor, sensory, or behavioral recovery following nerve injury. Finally, in mice that did not express MCT-1 protein in macrophages, adoptive transfer of cells led to a complete recovery from nerve injury.

    The authors concluded that the MCT-1 protein in macrophages is essential for coordinating nerve regeneration and that adoptive macrophage transfer may be an important therapy in treating nerve injury. It is important to note that the MCT-1 protein transports ketones in addition to lactate and pyruvate. This invites speculation that certain forms of intense exercise, which promotes lactate uptake and utilization throughout the body, or nutritional ketosis may improve nerve regeneration; however, this theory has yet to be tested experimentally.

  • Metabolic dysfunction escalates with age and increases the risk of frailty and chronic disease. Many investigational antiaging drugs target enzymes involved in energy metabolism, such as mammalian target of rapamycin (mTOR) and insulin-like growth factor (IGF)-1. Findings of a new study in mice detail the role of sirtuins in energy metabolism and healthy aging.

    Sirtuins are enzymes that play key roles in healthspan and longevity in multiple organisms. They are linked to the regulation of a variety of metabolic processes, including the release of insulin, mobilization of lipids, response to stress, and modulation of lifespan. Sirtuins respond to physiological changes in energy levels, thereby regulating energy homeostasis and health.

    When fasting or exercising, the liver helps maintain blood sugar levels using the alternating processes of glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the creation of new glucose). In glycogenolysis, single glucose molecules are released from larger glucose chains, called glycogen, for use as energy. Because the body stores a limited amount of glycogen, the liver uses gluconeogenesis to create glucose from non-carbohydrate precursors, such as lactate and glycerol. The role of gluconeogenesis in aging is unclear, with one study reporting an increase in gluconeogenesis with age in rats and other studies in rats reporting decreased gluconeogenic ability.

    Using breeding techniques, the investigators produced a line of mice with livers that over-express the sirtuin enzyme SIRT6, which increases during fasting and regulates glucose metabolism. The researchers bred these mice with normal mice to produce litters with a mix of genotypes. Using this technique, the researchers were able to compare aging processes among littermates, which reduced confounding factors in their analyses.

    Compared to their normal siblings, male SIRT6 mice exhibited a 27 percent increase in average lifespan and an 11 percent increase in maximal lifespan. Female SIRT6 mice showed a 15 percent increase in both average and maximal lifespan. Normal mice experienced greater metabolic dysfunction, performed less physical activity, and developed more inflammatory and degenerative diseases with age compared to SIRT6 mice. A series of metabolic tests revealed that SIRT6 mice had increased gluconeogenic gene expression in the liver and enhanced glycerol release from adipose tissue, which provided extra fuel for gluconeogenesis.

    The authors concluded that SIRT6 controls healthspan and lifespan through regulating energy metabolism. This mechanistically complicated study will provide the groundwork for future aging research in humans.

  • Exercise is a critical component of public health recommendations to prevent cancer. A growing body of scientific research demonstrates that engaging in exercise after a cancer diagnosis can improve outcomes, but the mechanisms that mediate these effects are not fully characterized. Findings from a new study demonstrate that exercise alters the metabolism of cytotoxic T cells to improve their ability to attack cancer cells.

    Cytotoxic T cells play key roles in the body’s immune response. They destroy malignant cells by triggering apoptosis – a type of cellular self-destruct mechanism that rids the body of damaged or aged cells.

    The authors of the study placed mice with cancer into one of two groups. Half of the mice exercised on a treadmill, but the other half remained inactive. They transferred cytotoxic T cells from the mice that exercised into the inactive mice. Then they isolated T cells, blood, and tissues from the exercising mice. Finally, the authors injected both groups of mice with antibodies that would destroy the animals' cytotoxic T cells.

    The mice that exercise exhibited slower cancer growth and reduced death rates than those that remained inactive. The inactive mice that received the cytotoxic T cells from exercised mice showed marked improvements in their disease status. The exercising mice had high blood levels of lactate, which altered the T cells' metabolism and increased the cells' activity. Destroying the animals' cytotoxic T cells negated the beneficial effects that the exercise had in terms of cancer growth and survival.

    Taken together, these findings suggest that exercise alters cytotoxic T cells to mediate exercise-induced cancer suppression. Treatment protocols that incorporate exercise might improve outcomes by activating the immune system.

  • Maternal consumption of omega-6 and omega-3 fatty acids is essential for fetal brain development. Maintaining the proper balance of these two fatty acids is critical, but the typical Western diet is high in omega-6s and low in omega-3s. Findings from a new study in mice suggest that a high omega-6 to omega-3 fatty acid ratio of intake during pregnancy alters dopamine signaling, contributing to overeating in offspring.

    Dopamine is a neurotransmitter best known for its role in motor activity, motivation, and pleasure control. When exposed to a rewarding stimulus, the brain responds by increasing dopamine release to motivate behavior. Neurons that release dopamine are activated when a reward is expected.

    The authors of the study fed female mice either regular mouse chow or chow that was high in omega-6 fatty acids and low in omega-3s. The mice began eating their respective diets before mating and then throughout pregnancy and lactation. After the offspring were weaned, they ate the same diets as their mothers.

    The authors measured how much of a sucrose-containing solution (three solutions containing 3, 10, or 30 percent sucrose) the mice consumed after being water-deprived or when allowed to consume freely. Then they examined whether the mice preferred only sucrose-containing solutions or a high-fat diet after being food deprived. Finally, they administered a dopamine-inhibiting drug to the mice to determine if dopamine signaling influenced the mice’s eating behaviors.

    The mice that had been fed the high omega-6/low omega-3 diet consumed far more sucrose solution whether they were water-deprived or allowed to consume freely, compared to the mice fed the regular diet. The high omega-6/low omega-3 mice also consumed higher quantities of sucrose solution or high-fat foods after being food-deprived. Administration of the dopamine inhibitor reduced the animals' intake, however.

    These findings suggest that mice that are fed a diet with a high omega-6 to omega-3 ratio from conception through early life develop a stronger preference for highly palatable foods, many of which can contribute to obesity and other chronic health conditions. Foods high in omega-3 fatty acids include salmon and their roe, shellfish, walnuts, and flaxseed. For a fun, tasty way to eat salmon roe, check out this episode in which Dr. Rhonda Patrick shares her recipe for salmon roe stacks.

  • From the article:

    Results of study, published in the journal Experimental Biology and Medicine, show that the BDNF response to acute high-intensity interval exercise was greater than continuous moderate-intensity exercise in obese subjects when compared to normal-weight subjects. Similarly, although acute high-intensity interval exercise induced greater blood lactate and plasma cortisol levels than continuous moderate-intensity exercise, obese subjects produced less blood lactate, but showed no difference in cortisol than normal-weight subjects.

    These findings suggest that acute high-intensity interval exercise may be a more effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels.

  • An abundance of scientific data demonstrates that regular exercise improves overall physical health. Findings from a new study demonstrate how different exercise intensities influence brain function.

    The study involved 22 young men (average age, 27 years) who exercised regularly. Each of the men completed questionnaires and underwent tests to assess their mood, mental health, and cognitive function. Then the men engaged in either low or high intensity exercise (relative to each individual’s fitness level) on a treadmill for 30 minutes, with the two exercise periods separated by several days. The low-intensity exercise was performed at 35 percent under the lactate threshold (the point at which an increase in blood lactate concentration of 0.4 mmol/l above the baseline is observed). The high-intensity exercise was performed at 20 percent above the lactate threshold.

    Although both forms of exercise improved the men’s reported moods, resting state functional magnetic resonance imaging provided insights into how the different exercise intensities influenced brain function. Whereas low-intensity exercise activated brain networks involved in cognition control and attention processing, high-intensity exercise activated networks involved in mood.

    These findings support other data indicating that exercise benefits brain health and suggest that exercise may be a promising modality for use in improving cognitive function and in treating mood disorders.