HoldsUp

DavidPerlmutterMD · 2025-02-24 · David Perlmutter (host), Jeff Krasno

Yes, Stress Can Be Good: The Health Benefits of Doing Hard Things | Jeff Krasno

30 research-tied claims examined: 1 contradicted 2 overstated 5 context 19 supported 2 corroborated online 1 unverified

1

Contradicted by research

0:37:29Jeff Krasnocontradictedhigh

Carotid body chemoreceptors sensing hypoxia and hypercapnia signal the body to produce erythropoietin (EPO) to stimulate red blood cell production.

"there's these little chemoreceptors, I think they're somewhere around the carotid artery, and they will sense that phenomenon and give your body a signal to create this protein called EPO, erythropoietin, to essentially activate the production of red blood cells." (said at 0:37:29)

The speaker misattributes the physiological sensor for erythropoietin (EPO) production to the carotid body chemoreceptors. While peripheral chemoreceptors located at the carotid bifurcation (the carotid bodies) sense hypoxia, hypercapnia, and acidosis, their primary function is to signal the brainstem to regulate ventilation and cardiovascular reflexes, not to stimulate EPO production. EPO synthesis is predominantly regulated directly within the kidneys (by interstitial peritubular cells) and liver via cell-autonomous oxygen-sensing pathways mediated by prolyl hydroxylase domain proteins and hypoxia-inducible factors (HIF-1/HIF-2).

2

Overstated

0:26:26David Perlmutter (host)overstatedhigh

Between 83% and 86% of American adults are either prediabetic or diabetic.

"When we see that, you know, some 83 to 86% of American adults now is either pre-diabetic or diabetic, it's hard to imagine that we should therefore consider that to be pretty much normal." (said at 0:26:26)

The speaker appears to have conflated overall cardiometabolic unhealthiness (frequently cited as ~88% of American adults not meeting optimal criteria across blood glucose, blood pressure, lipids, and adiposity) with the specific prevalence of prediabetes and diabetes. Based on National Health and Nutrition Examination Survey (NHANES) data, approximately 14% to 16% of US adults have diabetes (diagnosed or undiagnosed) and approximately 30% to 38% have prediabetes, combining for roughly 45% to 50% of US adults, not 83% to 86%.

0:44:29Jeff Krasnooverstatedlow

Heat exposure and sauna bathing stimulate the production of brain-derived neurotrophic factor (BDNF), promoting neurogenesis and neuroplasticity.

"So there's it appears that there's the production of all these different kinds of proteins, like BDNF is one that I think has been fairly celebrated as brain-derived neurotrophic factor that seems to maintain neurofunction and, you know, as I understand it, even contribute to neurobiogenesis, so neuroplasticity even later in life." (said at 0:44:29)

The claim is overstated. While acute or controlled passive heating interventions (such as repeated warm-water immersion) have been shown in small human trials to modestly increase circulating peripheral BDNF concentrations, evidence demonstrating that sauna bathing or heat therapy directly stimulates human adult neurogenesis or broad neuroplasticity in the brain is preliminary, indirect, or based on mechanistic extrapolations. Furthermore, excessive or prolonged heat stress has been shown in narrative and preclinical models to activate the hypothalamic-pituitary-adrenal axis and suppress BDNF signaling.

5

Needs context

0:48:27David Perlmutter (host)needs contextlow

Studies demonstrate that frequent sauna use significantly reduces the risk of both cardiovascular disease and cognitive decline.

"much of the work did start with the Swedish research demonstrating pretty significant reduction in risk of both cognitive decline as well as cardiovascular disease in individuals who use the sauna quite frequently living in a cold environment." (said at 0:48:27)

Prospective cohort data demonstrate strong inverse associations between frequent sauna bathing and the risk of both cardiovascular mortality and neurocognitive disorders. In the landmark Kuopio Ischaemic Heart Disease (KIHD) study of middle-aged Finnish men (often misattributed as Swedish), bathing 4–7 times per week was associated with a 66% lower risk of dementia (HR 0.34, 95% CI 0.16–0.71) and a 63% lower risk of sudden cardiac death (HR 0.37, 95% CI 0.18–0.75) compared with 1 session per week. However, these data are observational cohort findings establishing statistical associations rather than randomized trials demonstrating causality, and they originate primarily from Finnish rather than Swedish populations.

0:53:37David Perlmutter (host)needs contexthigh

Skeletal muscle acts as an endocrine organ that produces and secretes myokines and signaling molecules, including irisin, cathepsin D, BDNF, and interleukin-6.

"there's a move to begin to consider muscles as an endocrine gland in that, you know, here they are creating these chemicals that uh go elsewhere in the body and do good things. You mentioned BDNF earlier, uh others like irisin, cathepsin D, even lactate, even acting as a neurotransmitter, nurturing mitochondria, uh and um, you know, certainly interleukin-6" (said at 0:53:37)

Skeletal muscle is widely recognized as an endocrine organ that synthesizes and secretes hundreds of signaling peptides, termed myokines, into circulation to communicate with other tissues such as the brain, liver, and adipose tissue. Interleukin-6 (IL-6), irisin, and brain-derived neurotrophic factor (BDNF) are thoroughly documented contraction-induced myokines. However, regarding cathepsin, the literature establishes cathepsin B (CTSB)—rather than cathepsin D—as the key exercise-induced myokine that crosses or communicates across the muscle-brain axis to influence neurogenesis and cognitive function.

1:05:35David Perlmutter (host)needs contexthigh

In the progression of insulin resistance, the pancreas produces increasingly high levels of insulin to compensate, and blood sugar only rises once the insulin stops working effectively.

"as we go down the path of insulin resistance, our pancreas works overtime, creates higher and higher levels of insulin, and ultimately, it's not a question of having not enough insulin, it's just not working anymore. And that's when the the blood sugar then goes up" (said at 1:05:35)

The speaker accurately describes the initial compensatory phase of insulin resistance, where the pancreas hypersecretes insulin to maintain normoglycemia despite reduced peripheral insulin sensitivity. However, the assertion that blood sugar rises purely because insulin 'is not working anymore' rather than from 'not enough insulin' misstates the pathophysiology. As established in extensive metabolic literature, blood glucose levels rise and overt type 2 diabetes manifests specifically when pancreatic beta-cells fail to produce enough insulin to meet the increased demand—representing a state of relative insulin deficiency combined with insulin resistance.

1:08:56Jeff Krasnoneeds contexthigh

Blue light around 480 nanometers stimulates intrinsically photosensitive retinal ganglion cells, which signal the suprachiasmatic nucleus and the pineal gland to release melatonin roughly 12 to 14 hours later.

"especially when the light is within that very um blue light range of around 480 nanometers, which is kind of just a little sliver of the electromagnetic wave spectrum. And, you know, we can receive that light from the superior field, kind of up here into the inferior part uh of our retina. There's these specialized neurons there called I think intrinsically photosensitive retinal ganglion cells, and they send a signal kind of down to the suprachiasmatic nucleus, which is sort of this timekeeper of the body, sends another signal to the pineal gland, which produces melatonin right around 12 or 14 hours later" (said at 1:08:56)

The core physiological pathways described are accurate, but the mechanics of melatonin release require clarification. Blue light around 480 nm activates intrinsically photosensitive retinal ganglion cells (ipRGCs), which express melanopsin (peak sensitivity ~481–483 nm) and project to the suprachiasmatic nucleus (SCN). The SCN controls the pineal gland, which synthesizes melatonin. However, light exposure does not send a signal that directly triggers melatonin release 12 to 14 hours later. Rather, acute light suppresses melatonin synthesis, while morning light entrains the SCN master circadian clock, setting the phase so that melatonin is produced and released at night in darkness, typically about 12 to 14 hours after morning wakefulness and light exposure.

1:16:04Jeff Krasnoneeds contexthigh

In the early 1900s, raw milk was a vector for transmitting tuberculosis.

"in kind of earlier times, in the early 1900s, that raw milk can actually, um, transmit tuberculosis in very, very rare cases" (said at 1:16:04)

Historical and epidemiological evidence confirms that unpasteurized (raw) milk from infected cattle was a major vector for transmitting zoonotic tuberculosis (Mycobacterium bovis) to humans in the early 1900s. However, describing this transmission as occurring in 'very, very rare cases' understates its historical public health impact. In the late 19th and early 20th centuries, consumption of raw milk contaminated with M. bovis caused substantial morbidity and a significant number of deaths, particularly from extrapulmonary tuberculosis in young children, until bovine tuberculin testing and widespread milk pasteurization effectively mitigated the risk.

19

Supported by research

0:00:07Jeff Krasnosupportedmoderate

Crying is an adaptive response to emotional dysregulation that helps restore psychological and parasympathetic homeostasis.

"Crying is an adaptive response to emotional dysregulation. It's actually pulling us back to homeostasis, to psychological and parasympathetic homeostasis." (said at 0:00:07)

Psychophysiological studies support the hypothesis that crying serves a homeostatic, self-regulatory function mediated by parasympathetic activation. While the active phase of crying involves autonomic and sympathetic arousal, the resolution of tearful crying in healthy individuals is accompanied by significant increases in respiratory sinus arrhythmia (RSA)—a validated index of vagal/parasympathetic cardiac control—facilitating autonomic recovery and emotional regulation.

0:00:42David Perlmutter (host)supportedmoderate

Low-level, hormetic stress provides positive physiological benefits, including improved regulation of blood sugar and blood pressure.

"Well, as it turns out, a low level of stress of many different types turns out to have some positive physiological benefits. We call this hormesis, when a low-grade stressful activity has good effects on our physiology. So we can employ this notion of engaging good stress in our bodies to actually help us with our health, to regain, for example, better control over our blood sugar and our blood pressure." (said at 0:00:42)

The concept of hormesis—in which low-grade, mild physiological stressors stimulate adaptive cellular pathways that confer health benefits—is well-supported in the physiological literature. Mild metabolic and physical stressors such as exercise, intermittent fasting, and caloric restriction trigger nutrient- and stress-sensing pathways (including AMPK, sirtuins, and insulin signaling) that improve glycemic control, metabolic flexibility, and cardiovascular homeostasis.

0:19:17Jeff Krasnosupportedmoderate

Brown skin tags in areas such as armpits and the neck are early signs of insulin resistance.

"And I started growing these kind of strange brown skin tags in kind of my armpits, and I know some people get them on the back of their neck. And I subsequently began to understand that those were kind of early signs of insulin resistance." (said at 0:19:17)

Published observational studies and dermatological reviews consistently show that acrochordons (skin tags), particularly those located in intertriginous areas such as the neck and axillae (armpits), are significantly associated with hyperinsulinemia, elevated HOMA-IR scores, and insulin resistance. They are widely recognized as useful clinical cutaneous markers for underlying metabolic disturbances and impaired glucose metabolism.

0:37:49Jeff Krasnosupportedhigh

An excess of carbon dioxide increases body acidity, which decreases the binding affinity between hemoglobin and oxygen.

"So an excess of carbon dioxide, if you do like a long breath hold, for example, will make your body a tiny bit more acidic, and that acidity will lessen the affinity between hemoglobin and oxygen." (said at 0:37:49)

The speaker's statement accurately describes the classic Bohr effect, a foundational principle of respiratory and blood gas physiology. Accumulation of carbon dioxide (such as during breath-holding) increases carbonic acid and hydrogen ion concentration (lowering pH/increasing acidity). Protons binding to specific residues on hemoglobin stabilize the low-affinity T-state (deoxygenated conformation), shifting the oxygen-hemoglobin dissociation curve to the right and reducing hemoglobin's affinity for oxygen to facilitate oxygen release to tissues.

0:40:09David Perlmutter (host)supportedhigh

Changes in blood oxygenation trigger hypoxia-inducible factor 1-alpha (HIF-1a), which enhances transcription of vascular endothelial growth factor (VEGF) to promote blood vessel growth.

"it's the change in oxygenation that we experience that is what really triggers something called hypoxia-inducible factor 1-alpha, which in addition to what you mentioned earlier, also enhances our transcription of something called vascular endothelial growth factor, growing more blood vessels to give that blood to the areas of the body where those mitochondria live in the cells and need more oxygen to do the job of creating energy." (said at 0:40:09)

The speaker accurately describes the canonical oxygen-sensing and angiogenic signaling pathway. Reductions in cellular oxygen tension prevent prolyl hydroxylase-mediated degradation of hypoxia-inducible factor 1-alpha (HIF-1α), leading to its stabilization and translocation to the nucleus. There, HIF-1 acts as a transcription factor that upregulates vascular endothelial growth factor (VEGF) along with other angiogenic factors to stimulate new blood vessel growth (angiogenesis) and restore tissue oxygen delivery.

0:41:45David Perlmutter (host)supportedhigh

The primary physiological drive that creates the urge to breathe during a breath hold is hypercapnia (elevated CO2) rather than hypoxia.

"what really triggers us to have the sense that we have to breathe is not the hypoxia, it's the hypercapnia. It's the elevated CO2" (said at 0:41:45)

Human respiratory physiology demonstrates that the primary stimulus driving the initial urge to breathe (and the onset of involuntary breathing movements) during breath-holding is hypercapnia (rising arterial carbon dioxide partial pressure, PaCO2) sensed by central and peripheral chemoreceptors, rather than hypoxia (falling PaO2). While severe hypoxia can synergistically amplify ventilatory drive, normal breath-hold breakpoints and the conscious sensation of air hunger are predominantly triggered by the rise in CO2 reaching a critical threshold.

0:49:59Jeff Krasnosupportedmoderate

Eighty percent of Americans have desk jobs, and Americans spend 94 percent of their time indoors or in a car.

"I think 80% of Americans now have a desk job and we spend 94% of our time inside or in a car." (said at 0:49:59)

The speaker's figures align closely with published observational and exposure-assessment data for the United States. In the landmark National Human Activity Pattern Survey (NHAPS), investigators found that Americans spend approximately 87% of their time indoors (in enclosed buildings) and about 6% in enclosed vehicles, totaling roughly 93% to 94% of time inside or in transit. Furthermore, analyses of occupational trends and workplace physical activity in the US indicate that over 80% of modern jobs are sedentary or predominantly low-activity desk/office roles.

0:55:05David Perlmutter (host)supportedmoderate

The surge of interleukin-6 released during exercise acts as a signal that activates AMP-activated protein kinase (AMPK) to stimulate fat mobilization and lower blood sugar.

"It is that surge of interleukin-6, by the way, that is the transmitter that activates AMP kinase to do all the cool things with respect to fat mobilization and and helping us lower our blood sugar." (said at 0:55:05)

Exercise stimulates the rapid release of muscle-derived interleukin-6 (IL-6, acting as a myokine) into the systemic circulation. In human and experimental models, elevated IL-6 activates AMP-activated protein kinase (AMPK) in skeletal muscle and adipose tissue, which in turn promotes lipolysis, fatty acid oxidation, GLUT4 translocation, and insulin-independent glucose uptake to aid in blood glucose disposal.

0:56:30Jeff Krasnosupportedhigh

Contracting skeletal muscle uptakes glucose directly without requiring insulin secretion from the pancreas.

"doesn't really require you to stress the pancreas to create insulin when you're actually contracting muscle, that it will uptake glucose without taxing um the pancreas." (said at 0:56:30)

Extensive physiological and biochemical research confirms that contracting skeletal muscle stimulates glucose uptake via an insulin-independent pathway. While resting glucose uptake depends largely on insulin-stimulated GLUT4 translocation, muscle contraction independently triggers GLUT4 vesicle translocation to the sarcolemma and T-tubules through distinct signaling mechanisms (such as AMPK activation, intracellular calcium flux, and mechanical stress). Consequently, contracting skeletal muscle can clear glucose directly from circulation without requiring pancreatic insulin secretion.

0:57:45David Perlmutter (host)supportedmoderate

An HbA1c level of 6.0% is associated with an increased risk of dementia and brain shrinkage.

"At an A1C of 6, you're already starting to have increased risk of dementia and brain shrinkage." (said at 0:57:45)

Large prospective cohort and neuroimaging studies confirm that HbA1c levels in the prediabetes range (5.7% to 6.4%, which includes 6.0%) and elevated non-diabetic glucose levels are associated with increased risks of dementia (particularly vascular dementia) as well as accelerated brain atrophy (reduced gray matter, white matter, and hippocampal volumes).

0:49:40Jeff Krasnosupportedmoderate

Hunter-gatherer populations typically walked approximately 7 to 10 miles (about 14,000 steps) per day.

"our hunter-gatherer ancestors would walk somewhere between 7 and 10—I'm sorry... miles a day... So you can say, you know, 7 miles is about 14,000 steps if you're really keeping track." (said at 0:49:40)

Field studies tracking modern hunter-gatherer populations (such as the Tanzanian Hadza) with GPS and accelerometry confirm that adults maintain high levels of daily physical activity, averaging roughly 135 minutes of daily moderate-to-vigorous physical activity. Measured daily walking distances in these foraging populations generally range from approximately 4 to 6 miles (6–9 km) per day for women and 7 to 10 miles (11–15 km) per day for men, corresponding to roughly 12,000 to 16,000 steps per day across the population.

1:00:46Jeff Krasnosupportedmoderate

An excess of insulin in the human body eventually creates a resistance to itself.

"an excess of insulin in the human body will eventually create a resistance to itself." (said at 1:00:46)

Published scientific evidence supports the claim that an excess of insulin directly induces insulin resistance. While hyperinsulinemia was historically regarded primarily as a compensatory response to pre-existing insulin resistance, research demonstrates that sustained exposure to elevated insulin levels downregulates insulin receptor (INSR) gene expression and decreases cell-surface insulin receptor density, directly impairing downstream insulin signaling.

1:01:22Jeff Krasnosupportedhigh

Adipose accumulation is inflammatory, creating a bidirectional vicious cycle that exacerbates insulin resistance.

"the more fat that I accumulated, the more inflammatory that would be, and then the hard the more insulin resistant I would become. So it's a sort of vicious cycle." (said at 1:01:22)

Adipose tissue accumulation promotes chronic, low-grade inflammation (often termed meta-inflammation) through immune cell infiltration (particularly macrophages) and the secretion of pro-inflammatory cytokines and adipokines. This inflammatory cascade directly interferes with insulin signaling pathways (such as PI3K/Akt signaling via JNK and NF-κB activation), worsening insulin resistance. In turn, impaired insulin action exacerbates lipolysis, lipid accumulation, and adipose dysfunction, establishing a well-documented self-reinforcing vicious cycle.

1:03:38Jeff Krasnosupportedhigh

Under fasted conditions, cold-induced thermogenesis relies on breaking down triglycerides and oxidizing free fatty acids in the mitochondria to produce heat.

"my body would need to make heat, so it would look around for a substrate for the process of thermogenesis. But because I was eating very little carbs and I was 15 and 1/2 hours fasted, there wasn't a lot of glucose around, so what option did it have? It essentially had to break triglycerides down, it had to break oxidized fat for the use of those free fatty acids at the mitochondrial level for the production of heat" (said at 1:03:38)

The speaker accurately describes the physiological mechanism of cold-induced non-shivering thermogenesis, particularly under fasting conditions. Brown adipose tissue and thermogenic tissues primarily rely on intracellular lipolysis—the breakdown of stored triglycerides into free fatty acids—which are oxidized in the mitochondria to fuel uncoupled respiration and generate heat.

1:11:39Jeff Krasnosupportedhigh

Seasonal affective disorder (SAD) lamps provide approximately 10,000 lux of light.

"If you get these SAD lamps, they're like about 10,000 lux, right?" (said at 1:11:39)

Standard bright light therapy devices (SAD lamps/light boxes) used in clinical practice and trials are typically designed to provide 10,000 lux of white light at a specified viewing distance (usually for 30 minutes daily).

1:13:03David Perlmutter (host)supportedlow

Data indicates that children who consume whole or raw milk have a significant reduction in allergies and atopy.

"We see the the uh the data indicating a significant reduction in uh allergies, for example, in children, atopy, uh and um in in kids who are consuming whole milk, not just because of the the fact that it may contain bacteria, but other things, immunoglobulins, etc." (said at 1:13:03)

Epidemiological studies have reported an inverse association between the consumption of raw/unprocessed farm milk and childhood atopic diseases. In the GABRIELA multicenter study of school-aged children, reported raw cow's milk consumption was associated with statistically significant reductions in asthma (aOR 0.59), atopic sensitization (aOR 0.74), and hay fever (aOR 0.51). The association was independent of other farming exposures and was not observed with boiled farm milk, with researchers identifying heat-sensitive whey protein fractions as potential contributors. Because evidence is primarily derived from observational and cross-sectional designs, the certainty of evidence is low.

1:15:43Jeff Krasnosupportedmoderate

Hospitalizations resulting from bacterial contamination of raw milk in the United States since the mid-1990s are in the hundreds.

"the hospitalizations due to, um, to, you know, kind of bacterial contamination of raw milk is like since the mid-'90s is like in the hundreds, you know." (said at 1:15:43)

CDC outbreak surveillance data and systematic reviews confirm that hospitalizations resulting from bacterial contamination of unpasteurized (raw) dairy products in the United States since the mid-1990s total in the hundreds. Epidemiological modeling of U.S. outbreak data from 2009–2014 estimated an average of 22 hospitalizations per year associated with unpasteurized dairy, driven primarily by bacterial pathogens such as Campylobacter spp., Salmonella spp., Shiga toxin-producing E. coli, and Listeria monocytogenes. A systematic review covering outbreaks from 2007 through 2020 identified 124 hospitalizations from 20 laboratory-confirmed outbreaks linked to unpasteurized dairy products alone.

1:01:22Jeff Krasnosupportedhigh

Glycated proteins are highly inflammatory in the human body.

"glycated proteins, etc., which can be highly inflammatory." (said at 1:01:22)

The speaker's statement that glycated proteins can be highly inflammatory is supported by well-established mechanistic and clinical literature. Advanced glycation end products (AGEs)—proteins or lipids that become non-enzymatically glycated—bind to cell-surface pattern recognition receptors, notably the receptor for advanced glycation end products (RAGE). This interaction activates downstream proinflammatory signaling cascades, such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), which stimulate the sustained production of inflammatory cytokines, reactive oxygen species, and downstream tissue injury in metabolic and vascular disorders.

1:12:09Jeff Krasnosupportedmoderate

The glymphatic system clears metabolic waste and cleans the brain during sleep.

"the glymphatic system um that helps to sort of clean up um your brain while you're sleeping." (said at 1:12:09)

The speaker's statement accurately reflects established neuroscience literature. The glymphatic system is a glia-mediated perivascular fluid transport network that facilitates the convective exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF), driving the clearance of metabolic byproducts (such as amyloid-β and other neurotoxic solutes) from the brain parenchyma. Experimental and neuroimaging studies show that interstitial space expands substantially during natural sleep, markedly accelerating glymphatic waste clearance compared to wakefulness.

2

Corroborated by web sources

0:14:54Jeff Krasnocorroborated (web)

Approximately 20% of United States GDP (around $4.5 trillion) is spent on healthcare.

"I think we're somewhere in the neighborhood of 20% of GDP essentially spent on sick care, I think $4.5 trillion more or less." (said at 0:14:54)

No published record matching the claim that approximately 20% of United States GDP (around $4.5 trillion) is spent on healthcare was located; this does not prove the claim false.

corroborated by web sources

According to official data from the Centers for Medicare & Medicaid Services (CMS), U.S. healthcare spending reached $4.5 trillion in 2022, representing approximately 17.3% to nearly 20% of GDP in recent years.

cms.govpgpf.org

0:15:07Jeff Krasnocorroborated (web)

United States healthcare spending is projected to reach approximately $11 trillion by 2040.

"I think if we continue on this trajectory, we'll be somewhere in the $11 trillion range by the year 2040" (said at 0:15:07)

No published record matching the projection that United States healthcare spending will reach approximately $11 trillion by 2040 was located; this does not prove the claim false.

corroborated by web sources

Projections extrapolating historical growth trends from the Centers for Medicare & Medicaid Services, including analyses by Deloitte, estimate that U.S. healthcare spending could reach approximately $11.8 trillion by 2040 if current spending trajectories continue unabated.

deloitte.comhealthcapital.com

1

No source found (not proven false)

0:24:35Jeff Krasnounverifiedvery low

Human emotional tears contain adrenocorticotropic hormone (ACTH), a stress hormone.

"But then humans have these unique emotional tears, and if you actually examine the chemistry of these tears, what you will find is ACTH, adrenocorticotropic hormone. That's a stress hormone." (said at 0:24:35)

No published record matching the claim that human emotional tears contain adrenocorticotropic hormone (ACTH) was located; this does not prove the claim false.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.