HoldsUp

Mark Mattson

Johns Hopkins University School of Medicine

Mark Mattson is a neuroscientist, an adjunct professor of neuroscience at the Johns Hopkins University School of Medicine, and the former chief of the Neuroscience Research Laboratory at the National Institute on Aging. His research focuses on the cellular and molecular effects of dietary restriction, intermittent fasting, and metabolic switching on aging, longevity, and metabolic traits. He also studies mechanisms of neuroprotection, synaptic plasticity, neurogenesis, and the principle of hormesis in brain health.

82 claims checked on air: 4 context 2 contradicted 68 supported 8 unverified

What they said on air - citing their own research

7 citing their own research

0:09:08supportedvery lowtheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

Running wheel exercise and environmental enrichment in animals increase the number of mitochondria in nerve cells and synapses in certain brain regions.

"And we find that running wheel exercise, what we call environmental enrichment, where we have the animals in cages where they have essentially like a playground-type environment where they can maintain their mind more active, and under those conditions, exercise, mental exercise, there's an increase in the number of mitochondria in nerve cells, and associated with that, in some—at least in some brain regions—there can even be an increase in the number of synapses between nerve cells" (said at 0:09:08)

Animal and preclinical studies show that aerobic exercise (such as running) and cognitive/environmental enrichment stimulate mitochondrial biogenesis (increasing mitochondrial DNA copy number and key regulatory markers like PGC-1α) and promote synaptic plasticity and synaptogenesis in regions such as the hippocampus and cortex. Because the supporting evidence consists of animal models and narrative neurobiology reviews, the GRADE certainty is rated very low.

0:13:13supportedmoderatetheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

It typically takes at least 10 hours of fasting to deplete liver glycogen stores and initiate the metabolic switch to fat and ketone utilization.

"It typically takes at least 10 hours to deplete the glucose in the liver. So if a person eats breakfast, lunch, and dinner, and then has a snack around 8:00 or 9:00, they may get up and eat breakfast and have not depleted the energy in their liver and have not switched to using fats." (said at 0:13:13)

Established physiological literature confirms that following cessation of food intake, liver glycogen stores are progressively broken down to maintain circulating blood glucose levels. Depletion of hepatic glycogen stores and the subsequent 'metabolic switch'—characterized by increased adipose tissue lipolysis, fatty acid mobilization, hepatic fat oxidation, and ketone production—typically occurs after roughly 10 to 14 hours (or beyond 12 hours) of fasting. Consequently, eating late-evening snacks followed by breakfast without an extended overnight fasting window prevents the full transition to ketone and fat utilization.

0:24:25needs contextvery lowtheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

In animal studies, it takes approximately two weeks of intermittent fasting before measurable changes occur in antioxidant enzyme levels, mitochondrial numbers, synapse counts, and learning and memory.

"one thing we found in pretty much all of our animal studies where we look at the brains, it takes a couple weeks before we see measurable changes in whatever: upregulation of antioxidant enzyme levels, increased number of mitochondria in neurons, increased number of synapses, improvements in learning and memory." (said at 0:24:25)

Preclinical animal research and narrative reviews by Mark Mattson and colleagues demonstrate that bioenergetic challenges such as intermittent fasting trigger neuroplastic adaptations in rodent brains, including upregulation of antioxidant defenses, mitochondrial biogenesis, increased synaptic density, and improved learning and memory. However, the specific time course of approximately two weeks reflects experimental observation periods in rodent fasting protocols (such as alternate-day fasting) rather than an established physiological timeline validated in humans. Because these neurobiological findings derive primarily from animal and mechanistic studies, the certainty of evidence for this specific time-dependent adaptation is very low.

0:30:36supportedmoderatetheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

Intermittent fasting increases activity in certain neural networks during the fasting period.

"with intermittent fasting, there is evidence that during the fasting, there's actually some increase, at least in some neural networks, in activity, neural networks." (said at 0:30:36)

Preclinical and human neuroimaging studies demonstrate that intermittent fasting and the resulting metabolic switch to ketone utilization alter brain function, showing enhanced synaptic adaptations and activity across specific neural circuits, including hippocampal networks, hypothalamic pathways, and motor regions.

0:48:18supportedvery lowtheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

Mice undergoing treadmill training combined with alternate-day fasting for two months demonstrated statistically significantly superior running endurance compared to mice undergoing treadmill training on a normal diet.

"there was a statistically significantly better endurance in the mice that were on intermittent fasting during the two months of treadmill training." (said at 0:48:18)

A 2018 study led by researchers at the National Institute on Aging (Marosi et al., PMID 29485903) evaluated male mice randomized to either ad libitum feeding or alternate-day food deprivation (ADF) combined with daily treadmill training. After the training period, a run-to-exhaustion test confirmed that mice maintained on alternate-day fasting during treadmill training exhibited significantly superior running endurance compared to mice fed ad libitum during training. Because the available evidence derives exclusively from an animal model, the certainty of evidence is very low.

0:49:18supportedvery lowtheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

Treadmill exercise in alternate-day fasted mice increased blood ketone levels nearly twice as much as fasting alone.

"And they measured ketones, which were elevated with intermittent fasting, and the exercise increased the ketone levels much more, almost twice as much, by the—you know, when you take their blood after the end of the treadmill training." (said at 0:49:18)

A 2018 animal study by Marosi et al. evaluated male mice on alternate-day food deprivation (ADF) combined with daily treadmill endurance training for one month. Metabolomic and physiological analyses showed that alternate-day fasting triggered ketosis, and post-exercise measurements showed that treadmill running further potentiated this metabolic switch and circulating ketone metabolite levels compared to fasting alone.

0:49:18supportedvery lowtheir own paperDr. Mark Mattson on the Benefits of Stress, Metabolic Switch

Combining alternate-day fasting with treadmill exercise produces a greater increase in soleus muscle mitochondria count in mice than either intervention alone.

"they took out muscle cells from the soleus muscle, which is an endurance muscle in the leg of the mice, and they did some measurements that suggested that intermittent fasting and the exercise increased the number of mitochondria in the muscle cells, and that the increase was the most when you have the combination of the intermittent fasting and the exercise." (said at 0:49:18)

A preclinical study in male mice by Marosi et al. (2018) examined the effects of alternate-day food deprivation (ADF), daily treadmill exercise, or their combination. Analysis of soleus muscle and liver gene expression showed that intermittent fasting combined with treadmill training potentiated molecular pathways involved in mitochondrial biogenesis and metabolism more than diet or exercise alone. Because this evidence comes entirely from an animal experiment, the certainty of evidence for human outcomes is very low.

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