HoldsUp

Mark Hyman, MD · 2025-06-18 · Andy Galpin, Mark Hyman (host)

The Real Reason You're Always Tired Has Nothing to Do With Sleep

32 claims checked against research: 2 contradicted 1 contradicted online 8 overstated 3 needing context 12 supported 6 unverified

12

Supported by research

0:08:27Andy Galpinsupportedmoderate

Between 70% and 80% of sleep disorders go undiagnosed.

"Somewhere, depending on the data source you look at, 70 to 80% of sleep disorders will go undiagnosed." (said at 0:08:27)

Epidemiological studies and clinical reviews consistently estimate that approximately 80% (often reported as 70% to 90%, depending on the specific condition and demographic dataset) of sleep disorders, particularly obstructive sleep apnea (OSA), remain undiagnosed in the general population.

0:05:31Andy Galpinsupportedhigh

High altitude significantly exacerbates sleep apnea and sleep-disordered breathing.

"And then when he went to his house in Vail, he went from moderate to extreme sleep apnea. He had no idea... That will exacerbate sleep disorders massively." (said at 0:05:31)

Exposure to moderate-to-high altitude markedly exacerbates sleep-disordered breathing and sleep apnea severity. In a randomized crossover trial evaluating patients with obstructive sleep apnea traveling from low altitude (490 m) to mountain elevations (1,860 m and 2,590 m, comparable to mountain towns like Vail at ~2,500 m), median apnea-hypopnea index (AHI) nearly doubled, rising from 47.5 events/h at baseline to 90.0-90.9 events/h at 2,590 m. This exacerbation is largely driven by hypoxia-induced respiratory instability leading to frequent central apneas and periodic breathing layered over pre-existing obstructive events.

0:18:20Andy Galpinsupportedmoderate

CPAP therapy in patients with sleep apnea lowers elevated hematocrit and hemoglobin levels.

"There's a lot of data on this. If you take somebody that has apnea and put them on CPAP, hematocrit and hemoglobin will come down." (said at 0:18:20)

Published clinical evidence supports the claim that continuous positive airway pressure (CPAP) therapy reduces hemoglobin and hematocrit levels in patients with obstructive sleep apnea (OSA). A 2022 systematic review and meta-analysis of ten trials found that CPAP therapy led to statistically significant reductions in both hemoglobin (mean reduction of 3.76 g/L) and hematocrit (mean reduction of 1.1%). Although the magnitude of reduction is modest and the underlying trials were predominantly single-arm before-and-after studies rather than large randomized placebo-controlled trials, the direction and presence of the effect are consistent across the literature.

0:18:55Andy Galpinsupportedmoderate

Low iron or ferritin levels occur in more than 30% of physically active individuals.

"And low iron does lead to sleep disruption... And that's going to happen in over probably 30% of physically active people, which people don't realize and doctors usually don't check." (said at 0:18:55)

Published literature confirms that low iron or ferritin levels affect a large proportion of physically active individuals and athletes. A systematic review and meta-analysis of 17,519 athletes across 122 studies found that 53.9% exhibited hypoferritinemia (ferritin <50 mcg/L), and 23.0% had absolute iron deficiency (ferritin <20 mcg/L). When using athletic thresholds for low iron stores (ferritin <30–50 mcg/L) or examining female athletic cohorts specifically, the prevalence routinely exceeds 30%.

0:20:15Andy Galpinsupportedmoderate

Typical sleep onset latency is between 5 and 20 minutes, and falling asleep in under 2 minutes is an indicator of sleep deprivation.

"if you look at something like sleep onset latency, how long it takes you to fall asleep at night, right? The general numbers there are going to be 5 to 20 minutes, right? Okay. So if you're falling asleep within like two minutes, that's probably a good sign that you're sleep-deprived." (said at 0:20:15)

Sleep medicine literature generally considers a sleep onset latency of 10 to 20 minutes (or roughly 5 to 20 minutes) to be typical in healthy, non-sleep-deprived individuals. In objective testing (such as polysomnography or the Multiple Sleep Latency Test), healthy controls typically demonstrate average sleep onset latencies around 10 to 15 minutes, whereas latencies under 5 minutes—and particularly under 2 minutes—reflect severe daytime sleepiness characteristic of significant sleep deprivation (such as behaviourally induced insufficient sleep syndrome) or central disorders of hypersomnolence.

0:18:57Andy Galpinsupportedmoderate

Low iron or ferritin levels cause sleep disruption.

"And low iron does lead to sleep disruption." (said at 0:18:57)

The statement is supported by clinical and observational evidence. Iron deficiency and depleted iron stores (low serum ferritin) are established drivers of sleep disruption, primarily through central nervous system dopamine dysregulation, restless legs syndrome (RLS), periodic limb movement disorder, and restless sleep disorder. Studies and reviews show that low ferritin and iron deficiency anemia correlate with prolonged sleep-onset latency, lower sleep efficiency, reduced slow-wave sleep, and greater sleep fragmentation in both children and adults, and iron supplementation frequently improves these sleep disturbances.

1:00:14Andy Galpinsupportedhigh

At 10,000 feet of elevation, there is a notable physiological effect on the body.

"Okay, that's enough to get a physiological effect, though." (said at 1:00:14)

Exposure to elevations of approximately 10,000 feet (~3,000 meters) triggers well-documented acute and chronic physiological effects caused by hypobaric hypoxia. These include decreased arterial oxygen saturation (SpO2), hyperventilation (hypoxic ventilatory response), increased resting and submaximal heart rates, reduced maximal oxygen uptake (VO2max, typically by 15% to 20%), increased pulmonary artery systolic pressure, and, over sustained exposure, erythropoietic acclimatization.

1:09:25Andy Galpinsupportedmoderate

Lifting weights through a full range of motion provides sufficient stimulus to maintain flexibility and mobility without dedicated stretching routines.

"If you're lifting weights in a full range of motion, then flexibility is in large part taken care of." (said at 1:09:25)

Multiple systematic reviews and meta-analyses of randomized and controlled trials demonstrate that resistance training (particularly through a full range of motion with external loads) produces improvements in flexibility and joint range of motion comparable to dedicated stretch-training protocols. A 2023 meta-analysis of 55 studies found no significant difference in range-of-motion gains between resistance training and stretching alone, or between resistance training combined with stretching versus stretching alone. While specialized athletic flexibility demands (e.g., gymnastics, dance) may still require dedicated stretching, general flexibility and mobility are effectively developed and maintained through loaded full-range resistance training.

1:09:35Andy Galpinsupportedmoderate

Physical activity and exercise significantly reduce the risk and assist in the prevention of dementia and Alzheimer's disease.

"And there's ample research now on the brain. So you're talking about dementia and Alzheimer's prevention heavily positively benefited by these things." (said at 1:09:35)

Extensive observational research and large meta-analyses demonstrate that regular physical activity and exercise are associated with a significant reduction in the risk of incident all-cause dementia and Alzheimer's disease (typically a 20% to 25% relative risk reduction). Evidence from systematic reviews of prospective cohorts indicates that higher overall and leisure-time physical activity levels consistently correlate with lower risks of cognitive decline and neurodegenerative disorders.

1:14:34Mark Hyman (host)supportedlow

People with type 2 diabetes have mitochondria that function roughly half as effectively as those in people without type 2 diabetes.

"When you look at type 2 diabetics, their mitochondria are functioning half as effectively as people who don't have type 2 diabetes, and that is related to exercise." (said at 1:14:34)

Cross-sectional skeletal muscle biopsy studies show that individuals with type 2 diabetes have approximately a 40% to 50% reduction in mitochondrial respiratory chain enzyme activity (such as NADH:O2 oxidoreductase and subsarcolemmal electron transport chain activity) compared to non-diabetic controls. This functional deficit is closely linked to lower mitochondrial density and physical inactivity, and exercise training interventions have been shown to substantially restore mitochondrial volume and oxidative capacity. Because the primary human data rely on small cross-sectional biopsy cohorts (n = 10–12 per group), certainty is low.

1:06:06Andy Galpinsupportedmoderate

Serum magnesium is a poor indicator of total body magnesium status because the majority of magnesium in the human body is stored in bone.

"So not just serum magnesium—that's a really bad way to understand magnesium in the system, right, because it's almost all in bone—but something like magnesium RBC" (said at 1:06:06)

Published reviews confirm that serum magnesium is a poor indicator of total body magnesium status. Less than 1% to 2% of total body magnesium is located in blood and extracellular fluid, with the vast majority sequestered in bone and intracellular tissues. Because serum magnesium levels are homeostatically defended through bone exchange and renal conservation, normal serum levels can persist despite significant tissue depletion. Erythrocyte (RBC) magnesium measures intracellular concentration and provides a better indicator of cellular magnesium exposure over time.

1:36:00Mark Hyman (host)supportedhigh

The cost of sequencing a whole human genome has decreased from approximately one billion dollars to around $300.

"And so what was a billion-dollar test to get your genome sequenced is now $300." (said at 1:36:00)

The cost of sequencing a human genome has dropped dramatically over the past two decades. The initial sequencing of the first human genome via the international Human Genome Project took over a decade and cost roughly $2.7 to $3 billion (with Celera's parallel shotgun sequencing effort costing approximately $100 million). Following the advent and scaling of next-generation sequencing (NGS) and high-throughput platforms, the cost per human whole genome dropped to approximately $1,000 in the mid-2010s and has further declined to around $200–$300 on high-throughput modern platforms.

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.