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Huberman Lab

Essentials: Breathing for Mental & Physical Health & Performance | Dr. Jack Feldman

with Dr. Jack Feldman

Published November 13, 2025
View Show Notes

About This Episode

Andrew Huberman and respiratory neuroscientist Dr. Jack Feldman discuss how breathing is generated and controlled by the brain, with emphasis on the pre-Bötzinger complex, the diaphragm, and the evolution of mammalian respiration. They explore physiological sighs, how breathing patterns influence emotional and cognitive states, rodent studies of slow breathing and fear, and potential mechanisms involving the vagus nerve, olfaction, and carbon dioxide regulation. In the latter part, they discuss magnesium threonate's effects on synaptic plasticity and cognitive aging, including animal and human data on learning, memory, and mild cognitive decline.

Topics Covered

Breathwork Autonomic nervous system Anxiety Mental health Brain health Aging Respiration Magnesium threonate Fear conditioning Neuroplasticity

Disclaimer: We provide independent summaries of podcasts and are not affiliated with or endorsed in any way by any podcast or creator. All podcast names and content are the property of their respective owners. The views and opinions expressed within the podcasts belong solely to the original hosts and guests and do not reflect the views or positions of Summapod.

Quick Takeaways

  • Breathing is rhythmically controlled by a small brainstem region called the pre-Bötzinger complex, which drives the diaphragm and intercostal muscles to generate inspiration.
  • Mammals uniquely possess a diaphragm, which provides a powerful mechanical advantage that allows a huge gas-exchange surface area in the lungs to be expanded with minimal effort, supporting large, oxygen-demanding brains.
  • Physiological sighs-spontaneous deep breaths occurring roughly every five minutes-are essential for reopening collapsed alveoli and maintaining healthy lung function.
  • Rodent experiments in which awake mice breathe ten times more slowly for 30 minutes per day over four weeks show a strong reduction in conditioned fear responses, comparable to major manipulations in the amygdala.
  • Breathing can influence brain and emotional states through multiple pathways, including nasal airflow signals to the olfactory bulb, vagal afferents from the lungs and viscera, and changes in carbon dioxide and pH.
  • Chronic hyperventilation can lower CO2 and contribute to anxiety, while training anxious patients to slow their breathing and restore CO2 levels toward normal can reduce their symptoms.
  • Breathing-related rhythms modulate many body and brain functions, including heart rate, pupil size, and possibly circuits involved in depression and other mood states.
  • Simple practices like box breathing (equal-length inhale, hold, exhale, hold) for 5-20 minutes can subjectively improve alertness and emotional state and are easy entry points for breath practice.
  • Magnesium threonate appears to increase synaptic plasticity by raising brain magnesium, enhancing long-term potentiation in neurons, improving cognition and lifespan in rodents, and reversing several years of cognitive aging in humans with mild cognitive decline.
  • Mechanistic, circuit-level understanding from animal studies helps identify minimum effective doses and protocols for breathing and supplementation practices that can later be tested in humans.

Podcast Notes

Introduction and framing of the conversation

Host and guest introduction

Andrew Huberman introduces Huberman Lab Essentials[0:00]
• He explains that Huberman Lab Essentials revisits past episodes to extract potent and actionable science-based tools for mental health, physical health, and performance.
Andrew states his professional background[0:09]
• He is a professor of neurobiology and ophthalmology at Stanford School of Medicine.
Introduction of Dr. Jack Feldman[0:16]
• Andrew welcomes Dr. Jack Feldman and calls him his go-to source for all things respiration and brain-breathing interactions.
• Jack expresses pleasure at being there.

Basic mechanics and neural control of breathing

Why we need to breathe: oxygen, CO2, and pH

Fundamental reason for airflow in and out[0:46]
• We inhale and exhale to supply oxygen for body metabolism and to remove carbon dioxide produced by aerobic metabolism.
Carbon dioxide and blood pH regulation[1:00]
• Carbon dioxide strongly affects the acid-base balance of the blood (pH), and all living cells are very sensitive to pH.
• The body is highly invested in tightly regulating blood pH, making CO2 removal critical.

Mechanical generation of airflow: lungs, diaphragm, and ribcage

How lung expansion draws air in[1:20]
• Expanding the lungs is likened to pulling apart a balloon: internal pressure drops, and air flows in.
• Expansion lowers pressure in the alveoli, and because outside pressure is higher, air flows into the lungs during inhalation.
Role of the diaphragm[1:53]
• The diaphragm sits just below the lungs and is the principal muscle of inspiration.
• When the diaphragm contracts, it pulls downward, exerting force on the lungs and causing them to expand.
Role of the ribcage and thoracic cavity[2:09]
• During inhalation, the ribcage rotates up and out, expanding the thoracic cavity and aiding lung expansion.
Passive exhalation at rest[2:13]
• At the end of inspiration, under resting conditions, one simply relaxes the inspiratory muscles.
• Exhalation is compared to releasing a pulled spring: the lung and ribcage recoil passively.

Pre-Bötzinger complex: brainstem rhythm generator for breathing

Location and size of the pre-Bötzinger complex[2:36]
• The pre-Bötzinger complex is a small region in the brainstem, just above the spinal cord.
• In humans it contains a few thousand neurons and exists on both sides of the brainstem, working in tandem.
Function in generating each breath[3:32]
• Every breath begins with neurons in the pre-Bötzinger complex becoming active.
• These neurons ultimately drive motor neurons that innervate the diaphragm and external intercostal muscles.
• When pre-Bötzinger neurons finish their burst of activity, inspiration stops and passive exhalation begins.

Nasal versus mouth breathing and muscle activation

Differences in airflow pathways[3:39]
• At rest, the tendency is to breathe through the nose, as normal airflow needs are easily handled via nasal passages.
• During exercise or high ventilation demand, people shift to mouth breathing because larger airways allow more airflow.
Effect on diaphragm and intercostal muscles[4:10]
• Jack states that the diaphragm and intercostal muscles are almost agnostic to whether nasal or oral pathways are open.

Multiple respiratory oscillators and active expiration

Discovery of a second respiratory oscillator

Original view of pre-Bötzinger as sole source[5:33]
• Initially, Feldman's group thought the pre-Bötzinger complex generated all rhythmic respiratory movements, both inspiration and expiration.
Identification of an active expiration oscillator[5:58]
• They later discovered a second oscillator that generates active expiration, such as forcefully exhaling during speech-like sounds or exercise.
• Jack gives examples like making a "shh" sound or forceful exhalation during exercise as active expiration.
Location and properties of the active expiration group[5:58]
• This group of cells is silent at rest but becomes active when expiratory muscles need to be driven.
• It appears to be an independent oscillator located in a region around the facial nucleus.

Central chemoreception and retrotrapezoid nucleus

Sensing CO2 and brain pH[6:57]
• Control of breathing is closely tied to sensing CO2 because large shifts in CO2 cause large shifts in brain pH.
• The brain is extremely sensitive to pH changes, so regulating CO2 within narrow limits is crucial.
Ventral surface of the brainstem as chemoreceptive area[7:05]
• Other researchers identified the ventral surface of the brainstem as critical for sensing CO2 (central chemoreception).
Discovery and naming of the retrotrapezoid nucleus[7:23]
• Feldman and colleagues identified a structure near the trapezoid nucleus that was not named in neuroanatomical atlases.
• They named it the retrotrapezoid nucleus, which is involved in CO2 sensing and is in the region associated with active expiration.

Evolutionary perspective on facial nuclei and respiratory control

Evolution of facial control centers and breathing

Face-related nuclei and early vertebrates[7:52]
• In more primitive creatures, facial muscles and control systems evolved around nuclei for eyes and mouth, as these animals needed to take things into their mouth for eating.
• Many sub-nuclei around the facial region developed various roles over evolutionary time.
Facial muscles in fluid and air movement[8:13]
• At some point in evolution, facial muscles were likely important for moving fluid and air in and out of the mouth.
• In mammals, some of these sub-nuclei now appear to control expiratory muscles.

The diaphragm and the evolution of mammalian breathing

Mammals versus amphibians and reptiles in breathing strategies

Mammals as unique diaphragm users[9:06]
• Mammals are the only class of vertebrates that have a diaphragm.
• Amphibians and reptiles lack a diaphragm and thus have very different breathing mechanics.
Active versus passive inspiration and expiration across species[8:51]
• Amphibians and reptiles breathe by actively expiring and passively inspiring, due to lacking a powerful inspiratory muscle.
• Mammals, by contrast, actively inspire (via diaphragm) and typically passively expire at rest.

Mechanical efficiency and lung surface area

Alveolar-capillary membrane and oxygen transfer[9:24]
• Oxygen must cross the alveolar-capillary membrane, where air-filled alveoli interface with blood-filled capillaries.
• The key factor is surface area: larger surface area allows more oxygen to pass, and the process is entirely passive.
Branching architecture of the lungs[10:11]
• The airway starts as a single trachea that branches into two, then four, and so on, ending in tiny alveolar spheres.
• The number of branches and size of alveoli determine total gas-exchange surface area.
Mechanical challenge of expanding large surface area[9:59]
• An elastic membrane is easy to stretch when small, but if its area increases dramatically, much more force is needed to stretch it.
• Amphibians, lacking a powerful inspiratory muscle, could not generate enough force, so their lungs have fewer branches and modest surface area relative to body size.
Mammalian lungs: enormous surface area plus diaphragm[10:57]
• Mammals have roughly 400-500 million alveoli, creating an internal membrane about one-third the size of a tennis court.
• This vast membrane must be expanded with each breath, yet most people do not feel it as effortful because of the diaphragm's mechanical advantage.
• By moving down only about two-thirds of an inch, the diaphragm can expand this large membrane enough to pull air into the lungs.

Lung volumes, oxygen levels, and diaphragm's role in brain evolution

Typical resting and tidal lung volumes[12:08]
• At rest, lung volume is about 2.5 liters.
• A normal breath (tidal volume) adds roughly 500 milliliters, about the size of a fist, increasing lung volume by about 20%.
• This relatively small volume change, acting on a 70 square meter membrane, is enough to raise blood oxygen partial pressure from about 40 to 100 mmHg.
Diaphragm as enabler of large brains[12:34]
• Huberman asks whether humans' larger brains could be partly due to enhanced oxygen delivery made possible by the diaphragm.
• Feldman replies that a key step in evolving a large brain with continuous high oxygen demand was the development of the diaphragm.

Diaphragmatic versus non-diaphragmatic breathing and emotional effects

Question about belly breathing and health claims

Common advice about breathing with the diaphragm[13:04]
• Huberman notes widespread advice that diaphragmatic or "belly" breathing-belly expansion rather than chest lifting-is supposedly healthier.
• He is not aware of definitive studies directly comparing health benefits of diaphragmatic versus non-diaphragmatic breathing.

Feldman's stance on specific breathing styles

Agnosticism about specific muscle patterns[13:44]
• Feldman describes himself as somewhat agnostic regarding different breath patterns in practices like yoga and breathwork.
• He believes different patterns can act through different mechanisms, but he does not see the primary influence as which exact muscles are used (e.g., diaphragm versus abdomen movement).
Breathing and changes in emotion and cognition[14:05]
• He thinks breathing-induced changes in emotion and cognition are important but may not hinge mainly on muscle choice; he acknowledges this could reflect his own prejudice.

Physiological sighs: function and clinical relevance

Definition and frequency of physiological sighs

Automatic deep breaths every few minutes[14:33]
• Physiological sighs are spontaneous deep breaths that humans take approximately every five minutes.
• Feldman suggests lying quietly and observing one's breathing to notice that such deep breaths occur periodically and cannot be voluntarily stopped.

Alveolar collapse and need for sighs

Microstructure of the lung and surfactant[15:06]
• There are about 500 million alveoli in the lungs, each roughly 200 microns across and lined with fluid containing surfactant.
• The fluid lining helps mechanics by making it somewhat easier to stretch the alveoli.
Slow, ongoing alveolar collapse[15:42]
• Alveoli have a tendency to collapse at a slow but nontrivial rate.
• Collapsed alveoli no longer participate in gas exchange, gradually reducing effective lung surface area if not reopened.
Why normal breaths are insufficient to reopen alveoli[16:02]
• A standard tidal breath is not large enough to re-expand collapsed alveoli.
• A deeper breath-such as a sigh-is needed to increase lung volume and generate enough pressure to pop them open.
• Nature solves this by generating involuntary physiological sighs about every five minutes, without requiring conscious effort.

Historical lessons from mechanical ventilation and sighs

Early polio treatment with negative-pressure ventilators[16:48]
• Early mechanical ventilation for polio victims used large steel tubes in which external pressure was periodically lowered.
• Dropping external pressure expanded the ribcage, which in turn expanded the lungs; returning pressure to normal allowed passive recoil.
High mortality and the role of larger breaths[17:02]
• Initially, there was a relatively high mortality rate among patients on these ventilators, which was puzzling.
• One solution was to provide larger breaths; when larger breaths were delivered, mortality rates dropped.
Discovery that periodic big breaths were sufficient[17:27]
• By the 1950s, it was recognized that not every breath had to be large; instead, a normal series of breaths interspersed with an occasional big breath was adequate.
• This mimicked physiological sighs and significantly reduced mortality in ventilated patients.
• Modern ventilators commonly include periodic "super breaths" to replicate sigh-like reopening of alveoli.

Breathing, overdose, gasping, and auto-resuscitation

Overdose deaths and breathing suppression

Drug combinations that stop breathing[19:53]
• Huberman notes that combining substances like alcohol and barbiturates can suppress breathing and cause death by asphyxiation.
Possible role of sigh suppression in overdose[20:23]
• He wonders whether suppression of physiological sighs during deep sedation or drug overdose might contribute to fatal respiratory failure.

Dying gasp and attempts at auto-resuscitation

Typical breathing pattern near natural death[20:47]
• Feldman describes that in mammals dying of natural causes, breathing slows, stops, and then gasps occur.
• These gasps are large breaths often called the "dying gasp."
Gasping as auto-resuscitation attempt[21:00]
• Gasping is often described as an attempt to auto-resuscitate-taking a super-deep breath that might restart breathing.
Relation between gasps and sighs in overdoses[20:29]
• It is unknown whether gasps are simply very large sighs or mechanistically distinct.
• Feldman suggests that if an overdose suppresses the ability to gasp in someone who might otherwise auto-resuscitate, that could prevent re-arousal of breathing and contribute to death.

Breathing, brain state, and emotional regulation

Bidirectional relationship between breathing and emotion

State-dependent breathing patterns[21:55]
• Huberman notes that stress, happiness, and relaxation are all associated with changes in breathing patterns.
Intentional breathing to alter internal state[21:55]
• He points out that changing our breathing can, in turn, influence internal emotional and cognitive states.

Feldman's transition from rhythm generation to state interactions

Initial focus on basic rhythm generation[22:09]
• For many years, Feldman focused narrowly on how the breathing rhythm is generated, staying in that "silo."
New interest in breathing and brain state[21:58]
• About a decade ago, he became intrigued by how breathing interacts with other brain functions, including emotion and cognition.
• He conceived of studying this in rodents, joking about teaching rodents to meditate.

Rodent slow-breathing protocol and fear conditioning

Grant support and context[22:37]
• He obtained an R21 grant from NCCIH (National Center for Complementary and Integrative Health) to study such questions.
• He praises this institute for funding research on meditation, breathwork, supplements, herbs, and acupuncture, noting that many scientists had previously viewed such topics as too "woo woo."
Developing a slow-breathing protocol in mice[23:50]
• His lab recently achieved a "major breakthrough": a protocol that causes awake mice to breathe about ten times more slowly than normal.
• Mice tolerate this slow breathing well; the protocol is applied 30 minutes per day for four weeks, akin to a breath practice.
• Control animals experience the same procedures except that their breathing is not slowed.
Fear conditioning and freezing behavior[24:32]
• They collaborated with Michael Fanselow, described as a "guru" of fear, to run standard fear conditioning tests.
• In these tests, mice associate a context with shocks, and their fear is measured by how long they freeze when placed back into the context.
Effects of slow-breathing training on fear[23:50]
• Control mice showed typical freezing times consistent with standard mice.
• Mice that underwent the slow-breathing protocol froze much less, indicating a substantially reduced fear response.
• The magnitude of reduction in freezing was comparable to that produced by major manipulations of the amygdala, a key fear-processing region.

Human relevance and need for mechanistic studies

Why do animal mechanisms matter when humans already use meditation?[25:27]
• Huberman acknowledges that many people already accept meditation's benefits but emphasizes that most people neither meditate nor do breathwork.
• He stresses that understanding mechanisms and minimum effective dose is crucial for motivating broader adoption and designing effective, time-efficient protocols.
Placebo effects in humans versus rodents[26:28]
• Feldman highlights that human responses often include significant placebo effects, making mechanistic interpretation difficult.
• Mice do not have placebo beliefs, so demonstrating a legitimate effect of breathing manipulations in mice provides strong evidence of a real underlying mechanism.
• He argues that rodent evidence can be more convincing in some respects than many human studies for ruling out placebo contributions.
Clarifying that mice are doing breath practice, not meditation[26:52]
• Huberman notes that while we colloquially talk about rodents "meditating," in reality they are undergoing guided changes in breathing, not following human-like meditative instructions.
• The protocol is a breath practice: 30 minutes daily where respiration is slowed compared to normal breathing patterns.

Multiple pathways linking breathing to brain and body

Olfactory pathway and respiratory modulation of the brain

Nasal airflow and olfactory bulb signaling[27:55]
• Normal inhalation and exhalation through the nose create rhythmic signals from the nasal mucosa to the olfactory bulb.
• These olfactory bulb signals are modulated by respiration and project widely throughout the brain.
• Thus, nasal breathing inherently imposes a respiratory rhythm onto brain circuits via olfactory pathways.

Vagus nerve as a conduit of respiratory information

Afferent and efferent fibers in the vagus[28:30]
• The vagus nerve carries afferent signals from many viscera (lung, gut, etc.) to the brainstem, as well as efferent signals from brainstem to organs.
Lung stretch receptors and respiratory modulation[28:16]
• There are powerful receptors in the lung that respond to lung expansion and relaxation.
• Recordings from the vagus nerve show a strong respiratory modulation arising from these mechanical lung changes.
Vagus nerve stimulation and depression[28:57]
• Electrical stimulation of the vagus nerve can provide substantial relief in some forms of refractory depression.
• While mechanisms remain unclear, this shows that vagal afferent signaling can significantly influence mood and emotional states.
• Feldman suggests it is reasonable to think that naturally occurring respiratory rhythms in vagal input normally contribute to brain processing.

Carbon dioxide, pH, and anxiety

CO2 sensitivity and ventilation control[30:17]
• Under normal conditions, oxygen levels remain fairly constant (except at altitude), but CO2 levels can vary significantly with changes in breathing.
• Small shifts in CO2 produce pH changes, and breathing is regulated very sensitively to CO2 levels: even small CO2 changes alter ventilation.
Hyperventilation and low CO2 in anxiety[30:34]
• Feldman mentions colleague Alicia Moret, who works with anxious patients, many of whom hyperventilate.
• Hyperventilation lowers their CO2 levels below normal.
Breathing-based therapy to normalize CO2[30:58]
• Moret developed a therapeutic intervention in which patients are trained to breathe more slowly to restore CO2 levels toward normal.
• This CO2-normalizing approach yields reductions in anxiety symptoms in her patients.
• Feldman notes that very high CO2 levels can trigger panic attacks, showing CO2's strong influence on emotional state.

Breathing rhythms, networks, and mood disorders

Respiratory modulation of autonomic and other functions

Respiratory sinus arrhythmia and autonomic coupling[33:52]
• During expiration, the heart rate slows; this phenomenon is called respiratory sinus arrhythmia.
Other functions synchronized with breathing[33:43]
• Pupil diameter oscillates in sync with the respiratory cycle.
• Feldman states that "almost everything" in the body shows some degree of respiratory-linked modulation.

Circuit-level view of depression and circuit disruption

Depression as a self-reinforcing circuit[34:56]
• Feldman suggests conceptualizing depression as activity circulating within a neural circuit.
• As reverberating signals loop in this circuit, they can strengthen, eventually becoming so strong that breaking the pattern is difficult.
• Most people experience transient depression that eventually lifts because the circuit does not remain continuously active.
Electroconvulsive therapy and other disruptive interventions[34:45]
• Electroconvulsive shock (ECS) applies a one-second whole-brain shock, disrupting neural activity and weakening connections in circuits involved in depression.
• Focal deep brain stimulation and transcranial stimulation can similarly disrupt networks more locally.
• After disruption, as circuits reassemble, some connections in the depression-related network may be weakened, providing symptom relief.

Breathing practice as prolonged network perturbation

Extended disruption via slow breathing[35:31]
• If breathing rhythms contribute to a depressive circuit's operation, sustained change in breathing might disrupt that circuit.
• Feldman notes that whereas ECS disrupts circuits for about a second, breathing practice can provide 30 minutes of altered rhythmic input.
• Repeated disruptions from breathing practices could gradually weaken maladaptive circuits before they fully re-form.
Analogy of ruts in a dirt path[35:53]
• He likens entrenched depressive circuits to deep ruts in a dirt path formed by repeated walking.
• Breathing practices are compared to gradually filling in the rut, making it shallower so the person can step out of it.
• He speculates that for evolutionary or contingent reasons, disrupting circuits via breathing seems to improve emotional and cognitive function.

Practical breathing practices and personal use

Feldman's personal breathing practice

Preference for box breathing[36:55]
• Feldman reports obtaining significant benefit from relatively short (5-20 minute) sessions of box breathing.
• Box breathing is described as equal-length phases of inhale, hold, exhale, and hold.
Exploring different styles such as "tummo"[37:25]
• He is experimenting with a practice he calls "two mole" (phonetic reference to tummo-style breathing) out of curiosity, as it may operate through different mechanisms.
Views on various branded breathing methods[38:23]
• Feldman mentions colleagues who practice named methods such as Wim Hof breathing and thinks such approaches are useful if they attract people to breathing work.
• He wants more people to explore breathing practices but notes some branded methods and long sessions can be intimidating for beginners.

Simple advice for newcomers

Low-barrier starting point[37:29]
• He suggests telling friends to try a simple 5-10 minute breathing practice for a few days and see if they feel better.
• If they do not like it, they can simply stop; it is low-cost and low-risk.
• He says that invariably, his friends find such practices helpful.

Using breath practice to manage daily energy

Counteracting post-lunch performance dips[38:09]
• Feldman mentions evidence that performance declines after lunch.
• He often interrupts his day after lunch to do 5-10 minutes of breath practice to counteract this dip.
Specific box breathing pattern used[40:05]
• He typically uses a pattern of 5-second inhale, 5-second hold, 5-second exhale, and 5-second hold.
• Sometimes he doubles the durations to 10 seconds each, partly to reduce boredom, and finds the practice very helpful.

Magnesium threonate, neuroplasticity, and cognitive aging

Context and disclosure around magnesium threonate

Huberman's interest in magnesium and supplementation[39:29]
• Huberman notes his long-term interest in supplements, including both prescription and non-prescription compounds, used non-haphazardly.
• He and Feldman share an interest in magnesium, though Huberman has mostly discussed it in the context of sleep, whereas Feldman is interested in cognition and durability of cognitive function.
Feldman's advisory role and company background[39:51]
• Feldman discloses that he is a scientific advisor to a company called Neuroscentria, whose CEO is his former graduate student Guo-Sung Liu.

Discovery of magnesium's effect on synaptic plasticity

From breathing research to learning and memory[40:11]
• Guo-Sung initially worked on breathing in Feldman's lab but had a deep interest in learning and memory.
• He later trained with Richard (Dick) Glenn at Stanford, and then with Susumu Tonegawa at MIT, both prominent memory researchers.
Question of signal versus noise in LTP[41:15]
• Guo-Sung became interested in how long-term potentiation (LTP)-a synaptic strengthening process-is affected by baseline neural noise.
• He asked whether stronger LTP could result from larger signals or from lower noise in the background activity.
In vitro experiments with hippocampal neurons[41:21]
• In cultured hippocampal neurons, he lowered background activity across neurons and observed that LTP became stronger.
• He achieved this by increasing magnesium levels in the bathing solution; elevated magnesium reduced background noise and enhanced LTP.
• Huberman notes that greater LTP essentially reflects increased neuroplasticity, i.e., a greater ability to rewire connections.

Animal studies: magnesium enrichment and cognition

Dietary magnesium and cognitive function in rodents[42:21]
• Guo-Sung tested the effect in rats by comparing a normal diet to one enriched with magnesium.
• Rats receiving magnesium-enriched diets displayed higher cognitive function and longer lifespans, described as "everything you'd want in some magic pill."
Challenge of getting magnesium into the brain[43:46]
• Most magnesium salts do not cross from the gut to the bloodstream and into the brain efficiently; they rely on membrane transporters.
• If one takes enough common magnesium supplements to raise blood levels significantly, gastrointestinal side effects such as diarrhea occur.

Magnesium threonate as a brain-penetrant form

Role of threonate and transporters[44:14]
• Working with chemist Fei Mao, they screened various magnesium compounds and found that magnesium threonate more effectively crossed the gut-blood barrier.
• Threonate is a metabolite of vitamin C and is abundant in the body, suggesting safety.
• They believe threonate may "supercharge" magnesium transporters, improving movement of magnesium across gut, blood-brain barrier, and into cells.

Human trial in mild cognitive decline

Study design and participants[44:26]
• They commissioned an independent company that commonly runs big-pharma trials to test magnesium threonate in humans with mild cognitive decline.
• Participants had cognitive performance that was age-inappropriate (worse than expected) based on a measure called Spearman's g-factor.
• Average biological age was about 51, but their cognitive age, per Spearman's g-factor norms, was about 61.
Spearman's g-factor and aging[44:58]
• Feldman explains that Spearman's g-factor, a general intelligence metric, starts at a certain population level at age 20 and declines by roughly 1% per year.
• This allows mapping a person's score to an approximate cognitive age.
Placebo-controlled, double-blind results[45:54]
• In the three-month, placebo-controlled, double-blind trial, those in the placebo group improved by about two years of cognitive age, a common magnitude due to placebo and practice effects.
• Those who received magnesium threonate improved by about eight years on average, with some individuals improving even more.
• Their cognition moved closer to their biological age, reversing a substantial portion of the age-related gap.

Dosing, blood levels, and subjective effects

Feldman's personal use and blood magnesium[47:06]
• Feldman had his blood magnesium checked and found it to be low-normal for his age.
• He began taking half of the studied dose of magnesium threonate, which raised his blood magnesium to high-normal, and he chose to remain within that range.
• He states that at his age he is primarily interested in slowing cognitive decline rather than increasing intelligence.
Reports from colleagues and sleep effects[48:00]
• Many academic colleagues he persuaded to try magnesium threonate did not report dramatic cognitive changes, although some felt a bit more alert or physically coordinated.
• However, many reported improved sleep, consistent with evidence that magnesium threonate can aid sleep onset and sleep depth.
• Huberman notes that the mechanistic story behind magnesium threonate and cognitive enhancement makes sense and appreciates Feldman's emphasis on mechanism.

Closing remarks and appreciation

Recognition of Feldman's contributions

Huberman's appreciation of rigor and pioneering work[49:24]
• Huberman highlights Feldman's background in physics and his focus on mechanistic detail and quantitative rigor.
• He calls Feldman a pioneer in modern respiration research, particularly in elucidating mechanisms underlying respiration with modern tools over many decades.
Invitation for future conversations[49:04]
• Huberman insists on a future part two conversation, noting that there is much more they could discuss.
• Feldman expresses appreciation for the opportunity and says he would be delighted to return.

Lessons Learned

Actionable insights and wisdom you can apply to your business, career, and personal life.

1

Seemingly small, automatic physiological processes like periodic sighs or gasps play critical maintenance roles in complex systems, and understanding them allows us to support or mimic them when they fail.

Reflection Questions:

  • • What automatic processes in your own life or work (habits, routines, system checks) quietly keep things functioning that you rarely think about?
  • • How could you deliberately support or back up these maintenance mechanisms so that if they falter (e.g., under stress), your system doesn't fail catastrophically?
  • • Where this week could you run a quick "health check"-physiological, emotional, or organizational-to ensure key maintenance processes are still operating well?
2

Deliberate, repeated changes in breathing patterns can measurably reshape fear and anxiety circuits, offering a low-cost, side-effect-light tool to complement or, in some cases, reduce reliance on more invasive interventions.

Reflection Questions:

  • • In which situations do you typically feel your anxiety or fear responses spike, and what does your breathing look like in those moments?
  • • How might integrating a simple daily practice (for example, 5-10 minutes of slow or box breathing) change your baseline reactivity over the next month?
  • • What specific scenario coming up in your life could you experiment with by intentionally adjusting your breathing before and during the event to see how it alters your state?
3

Mechanistic understanding-like how CO2, vagal input, and olfactory rhythms modulate the brain-enables you to design precise interventions instead of relying on vague advice such as "just relax" or "take a deep breath."

Reflection Questions:

  • • Where in your life are you currently using vague strategies (e.g., "try harder," "calm down") that could benefit from a clearer understanding of the underlying mechanism?
  • • How could you break down one recurring problem (stress, poor sleep, low focus) into specific levers you can manipulate, analogous to CO2, vagus, or airflow in this conversation?
  • • What is one concrete experiment you could run this week-changing something measurable and mechanism-based-to see if it improves an issue you care about?
4

Disrupting self-reinforcing neural or behavioral loops repeatedly but gently (as with extended breathing practice) can gradually weaken entrenched patterns like depressive ruminations, much like filling in a deep rut in a path.

Reflection Questions:

  • • What thought patterns or behaviors in your life feel like ruts you keep falling into, even when you intellectually know they're unhelpful?
  • • How could you introduce a brief, regular "disruption" ritual-such as a breathing exercise, movement break, or mental reset-at the times you typically slip into those ruts?
  • • Over the next month, how will you track whether these repeated, gentle disruptions are actually weakening the old pattern (e.g., through journaling, mood logs, or feedback from others)?
5

Improving the brain's underlying capacity for plasticity-such as by optimizing factors like magnesium levels-can enhance learning and slow cognitive decline more effectively than focusing only on task-specific drills.

Reflection Questions:

  • • What are you currently doing, if anything, to support your brain's general capacity to change (sleep quality, nutrition, mental challenge), not just to practice specific skills?
  • • How might your approach to learning or aging shift if you prioritized foundational brain health levers alongside practice and repetition?
  • • What is one concrete change you could implement this month (e.g., a sleep habit, nutritional adjustment, or new cognitive routine) aimed at supporting long-term brain plasticity rather than just short-term performance?

Episode Summary - Notes by Jordan

Essentials: Breathing for Mental & Physical Health & Performance | Dr. Jack Feldman
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