Approximately 40% of people do not see a measurable increase in VO2 max after engaging in 2.5 hours per week of guideline-based moderate-intensity exercise for several months.
"In fact, research has shown that approximately 40% of people do not see a measurable increase in their VO2 max even after engaging in guideline-based moderate-intensity exercise, which is about 2.5 hours of this type of exercise per week for several months." (said at 0:09:45)
Several exercise training trials evaluating standard or guideline-based exercise protocols have reported apparent non-response rates of roughly 20% to 40% when assessing changes in VO2 max. However, critical reviews of the literature show that categorizing individuals as 'non-responders' often conflates true physiological non-responsiveness with normal within-subject test-retest measurement error and lack of control comparator arms. Furthermore, physiological studies demonstrate that increasing training volume or intensity eliminates apparent VO2 max non-response, and individuals who do not show a VO2 max increase often still achieve measurable improvements in submaximal fitness, insulin sensitivity, and other cardiometabolic parameters.
Astrocytes in the brain are predominantly glycolytic and produce lactate that is taken up by neurons via MCT transporters for energy.
"In fact, neurons are used to using lactate because astrocytes in the brain, which are a supporting cell for neurons, they're mostly glycolytic. That means they're mostly using glucose as energy; they're not using mitochondria, and they're producing lactate as a byproduct. So astrocytes are churning out tons of lactate in the brain, and that lactate is being taken up by neurons through the MCT transporters and used as energy." (said at 0:36:53)
The speaker accurately describes the core tenets of the Astrocyte-Neuron Lactate Shuttle (ANLS) model: astrocytes possess a predominantly glycolytic metabolic profile compared to neurons, producing and exporting lactate via monocarboxylate transporters (MCTs, predominantly MCT1 and MCT4), which neurons take up (primarily via MCT2) to fuel oxidative metabolism. However, the claim that astrocytes 'are not using mitochondria' is an oversimplification. While astrocytes favor glycolysis to meet high-energy demands during processes like glutamate uptake, they possess functional mitochondria that actively engage in oxidative phosphorylation, the tricarboxylic acid cycle, and metabolic maintenance.
- supports: Bioenergetics and redox adaptations of astrocytes to neuronal activity. (Journal of neurochemistry 2016) · cited 254x in the literature
"To enable this, astrocytes are constitutively glycolytic, robustly expressing 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3)... Astrocyte-derived glycolytic lactate thus sustains the energy needs of neurons, which in contrast to astrocytes mainly rely on oxidative phosphorylation." (abstract, results)
pubmedfull study (doi) - supports: Astrocytes and neurons communicate via a monocarboxylic acid shuttle. (AIMS neuroscience 2020) · cited 42x in the literature
"The repertoire of MCTs in astrocytes and neurons allows them to communicate via monocarboxylic acids." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions … (Biosensors 2020) · cited 35x in the literature
"In the last few decades, the concept of lactate shuttling between glial elements and neural elements has emerged in which the glial cells glycolytically metabolise glucose/glycogen to lactate, which is shuttled to the neural elements via the extracellular fluid." (abstract, results, passage verified)
pubmedfull study (doi)
Increased lactate utilization by neurons stimulates the release of norepinephrine in the brain.
"And when neurons in the brain are using more lactate, they're releasing a variety of neurotransmitters; they release more norepinephrine, for example, to help the brain working better, to have more focus and attention." (said at 0:40:27)
Preclinical animal research indicates that L-lactate can excite locus coeruleus neurons and trigger the release of norepinephrine in the brain, evoking physiological arousal. However, experimental findings demonstrate that this effect acts through a receptor-mediated signaling pathway independent of neuronal lactate uptake or metabolic utilization (caloric use). Furthermore, this mechanism has been demonstrated in rodent and in vitro models rather than direct human trials.
- context: Lactate-mediated glia-neuronal signalling in the mammalian brain. (Nature communications 2014) · cited 337x in the literature
"Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step." (abstract, results, passage verified)
pubmedfull study (doi)