HoldsUp

Mark Hyman, MD · 2025-08-27 · Mark Hyman (host), Ben Greenfield

Why I Stopped 'Biohacking' and Started Living | Ben Greenfield

36 research-tied claims examined: 4 contradicted 5 overstated 5 context 18 supported 4 unverified

18

Supported by research

0:00:40Ben Greenfieldsupportedhigh

The US Surgeon General in 2023 identified loneliness as having the mortality equivalent of smoking approximately 15 cigarettes a day.

"I think it was Surgeon General in 2023 identified loneliness as the equivalent of smoking like 15 cigarettes a day." (said at 0:00:40)

The claim is accurate. In May 2023, the U.S. Surgeon General issued an advisory on loneliness and social connection ('Our Epidemic of Loneliness and Isolation'), which prominently highlighted that lacking social connection carries a mortality risk equivalent to smoking approximately 15 cigarettes a day. This equivalence calculation is based on meta-analytic evidence by Holt-Lunstad and colleagues analyzing 148 studies (308,849 participants), which demonstrated that strong social relationships confer a 50% increased likelihood of survival (OR = 1.50, 95% CI: 1.42–1.59), establishing social isolation as a risk factor for premature mortality comparable to major clinical risk factors like smoking.

0:07:47Ben Greenfieldsupportedmoderate

A published study demonstrated that performing 'soleus push-ups' (seated calf raises) improves glycemic variability.

"There was actually a study that came out on glycemic variability and doing this. They called them soleus push-ups, which is basically what you and I probably call a seated calf raise." (said at 0:07:47)

A landmark 2022 laboratory study by Hamilton et al. in iScience introduced the "soleus pushup" (SPU), a specialized seated calf contraction targeting the soleus muscle. The study demonstrated that performing this seated movement significantly improves systemic glucose regulation, showing a 52% reduction in postprandial glucose excursion and a 60% reduction in hyperinsulinemia.

0:08:27Ben Greenfieldsupportedhigh

Ventilatory threshold 1 (VT1) corresponds to the aerobic threshold where conversation becomes difficult, while ventilatory threshold 2 (VT2) corresponds to the anaerobic threshold where lactic acid accumulates faster than it can be cleared.

"VT1 is ventilatory threshold 1. That's when it starts to get hard to carry on a conversation and that's when you've reached what's called aerobic threshold... and you eventually reach VT2, which is when lactic acid starts to accumulate more quickly than it can be removed. Some people will also call that like the anaerobic threshold." (said at 0:08:27)

The speaker's description matches established exercise physiology principles. In incremental exercise testing, ventilatory threshold 1 (VT1) marks the aerobic threshold, corresponding to the initial increase in blood lactate accumulation and hyperventilation relative to oxygen uptake (where speaking comfortably becomes difficult). Ventilatory threshold 2 (VT2), also known as the respiratory compensation point or anaerobic threshold, occurs when exercise intensity reaches a level where lactate production exceeds the rate of clearance, leading to metabolic acidosis and rapid blood lactate accumulation.

0:15:35Ben Greenfieldsupportedmoderate

Blood flow restriction bands trick muscles into perceiving a heavier load by preventing lactic acid from exiting the muscle.

"Or I use blood flow restriction bands, which you can put around the arms and the legs to trick your muscles into thinking they're under a heavier load than they actually are because the lactic acid isn't able to exit the muscle." (said at 0:15:35)

The claim is supported by physiological evidence on blood flow restriction (BFR) training. BFR involves partial vascular occlusion (restricting venous outflow while preserving arterial inflow), which prevents metabolic byproducts—most notably lactic acid/lactate—from escaping the active skeletal muscle. This localized metabolite accumulation and reduced oxygen availability create high metabolic stress, accelerating fatigue in low-threshold slow-twitch muscle fibers. To maintain force production, the nervous system prematurely recruits high-threshold fast-twitch motor units that are typically reserved for heavy resistance loads. Thus, low-load exercise with BFR mimics the hypertrophic and neuromuscular environment of heavy-load exercise.

0:21:51Ben Greenfieldsupportedmoderate

Salmon sperm DNA isolates are used topically in facial rejuvenation treatments with aesthetic benefits.

"The newer thing that I just discovered is salmon sperm... apparently it's some kind of like a DNA isolate from literal salmon... salmon sperm is the newer thing that they're putting on people's faces apparently with very good results." (said at 0:21:51)

DNA biopolymers extracted and purified from salmon sperm (testis tissue), commonly formulated as polydeoxyribonucleotides (PDRN) or polynucleotides (PN), are widely utilized in aesthetic dermatology and cosmetology for facial rejuvenation. Systematic reviews of randomized trials and observational studies show that topical formulations (e.g., creams, serums, gels) and intradermal micro-injections of salmon-derived PDRN/PN provide aesthetic improvements in skin elasticity, hydration, texture, and periorbital fine lines/wrinkles, largely mediated through adenosine A2A receptor activation and tissue repair pathways.

0:23:23Ben Greenfieldsupportedmoderate

Multilineage-differentiating stress-enduring (Muse) cells have low immunogenicity and low tumorigenicity compared to other stem cells.

"Muse stands for multilineage-differentiating stress-enduring cells, something like that. But apparently they have a really good effect with very good or less chance of like an immune system reaction in the body and less—I believe it's called—you would know this word better than me, tumorigenicity, something like that, so less cancer-causing potential." (said at 0:23:23)

Multilineage-differentiating stress-enduring (Muse) cells are an endogenous subpopulation of non-tumorigenic pluripotent stem cells (typically identified by SSEA-3 positivity) found within adult tissues and mesenchymal stem cell populations. Preclinical models and early clinical trials consistently demonstrate that Muse cells have low immunogenicity (permitting HLA-mismatched allogeneic transplantation without immunosuppressive therapy) and low tumorigenicity (they do not form teratomas or tumors in vivo, unlike embryonic stem cells or induced pluripotent stem cells).

0:20:15Ben Greenfieldsupportedmoderate

Red light therapy enhances collagen and elastin production in facial skin tissue.

"A lot of times you'll combine it with something like a red light mask, you know, to drive it deeper into the tissue or to enhance the collagen attraction to the face or the elastin production." (said at 0:20:15)

Photobiomodulation using red light (typically in the 630-660 nm range, often combined with near-infrared wavelengths) has been shown in human skin explants, dermal fibroblasts, and clinical studies to stimulate fibroblast activity and significantly upregulate the expression and synthesis of collagen (such as type I and type III collagen) and elastin fibers.

0:36:50Mark Hyman (host)supportedmoderate

A study published from Israel demonstrated that hyperbaric oxygen therapy improved brain health, rejuvenation, and longevity markers.

"And Israel published a study where they used this technology for brain health and rejuvenation longevity and they had pretty compelling data about—" (said at 0:36:50)

Researchers from the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center and Tel Aviv University in Israel published prominent clinical studies evaluating hyperbaric oxygen therapy (HBOT) for aging-related outcomes. A 2020 randomized controlled trial in 63 healthy older adults reported significant enhancements in global cognitive function, processing speed, attention, and regional cerebral blood flow following 60 daily HBOT sessions. A companion prospective trial in 35 older adults found that the same HBOT protocol was associated with a >20% increase in immune cell telomere length and a reduction in senescent cell percentages. While these findings represent promising proof-of-concept data, they derive from small, single-center cohorts and require replication in larger, multi-center trials.

0:38:05Ben Greenfieldsupportedmoderate

The US Surgeon General in 2023 reported that loneliness carries a mortality risk equivalent to smoking 15 cigarettes a day.

"And and you know, I think it was uh the Surgeon General in 2023 who identified loneliness as the equivalent of smoking like 15 cigarettes a day, you know? And so you're you're seeing increased blood pressure, increased cortisol, uh what else, increased inflammation." (said at 0:38:05)

The statement accurately reflects the 2023 U.S. Surgeon General's Advisory, 'Our Epidemic of Loneliness and Isolation,' which highlighted that social disconnection increases the risk of premature death to an extent comparable to smoking up to 15 cigarettes a day. This widely cited statistic originates from a landmark 2010 meta-analysis of 148 prospective studies (308,849 participants) by Holt-Lunstad and colleagues, which demonstrated that stronger social relationships confer a 50% increased likelihood of survival (OR = 1.50, 95% CI 1.42–1.59), an effect magnitude on all-cause mortality comparable to well-established risk factors such as cigarette smoking.

0:38:27Ben Greenfieldsupportedmoderate

Loneliness increases the expression of genes related to inflammatory cytokines and decreases the regulation of genes responsible for antiviral activity.

"You see even increased expression of genes related to inflammatory cytokines and a decreased regulation of genes responsible for antiviral activity." (said at 0:38:27)

Perceived social isolation (loneliness) is associated with a molecular profile known as the conserved transcriptional response to adversity (CTRA). Transcriptomic profiling in humans and animal models shows that chronic loneliness is characterized by the upregulation of proinflammatory cytokine genes and the downregulation of genes involved in type I interferon responses and antiviral/antibody defenses.

0:35:24Ben Greenfieldsupportedlow

Hypoxic exposure induces mitophagy, clearing out old or dysfunctional mitochondria.

"probably the mitophagy would be induced by the hypoxic state, right? You're essentially creating a stressor that kills off old mitochondria and then flooding the cells with oxygen afterwards." (said at 0:35:24)

Hypoxic stress is a well-established biological trigger for selective mitochondrial autophagy (mitophagy). Under hypoxia, cells stabilize hypoxia-inducible factor 1-alpha (HIF-1α), which upregulates outer mitochondrial membrane receptor proteins such as BNIP3 and NIX (BNIP3L). These receptors target damaged, fragmented, or dysfunctional mitochondria for degradation in the autophagolysosome to limit reactive oxygen species production and maintain cellular homeostasis. Evidence is derived primarily from preclinical in vitro and animal mechanistic studies.

0:43:43Ben Greenfieldsupportedhigh

In ancient Greece, ostracism was a procedure where citizens wrote the name of a person on pottery shards called ostraca to vote to banish them for 10 years.

"It would have been ostracism, you know. It's uh that literally comes from a Greek uh term for the pottery shard called the ostraca that they used to actually write the name of the person who they wish to banish for 10 years" (said at 0:43:43)

Historical research confirms that in ancient Athens, ostracism was a democratic procedure in which citizens voted to banish a individual for a period of ten years by scratching or writing the person's name on broken pieces of pottery known as ostraca (singular: ostrakon).

1:00:40Ben Greenfieldsupportedvery low

Hypoxia stimulates mitophagy, cellular autophagy, and cellular resilience.

"even down to the hypoxia that we were talking about for mitophagy, just for cellular autophagy in general and cellular resilience" (said at 1:00:40)

Basic cellular and molecular biology research well establishes that hypoxia triggers adaptive cellular autophagy and selective mitochondrial autophagy (mitophagy) via hypoxia-inducible factors (such as HIF-1) and downstream effectors including BNIP3 and NIX/BNIP3L. This serves as an adaptive cellular survival mechanism to reduce reactive oxygen species generation and maintain cellular homeostasis. Because evidence for this cellular process is based on preclinical and in vitro mechanistic models, certainty is rated very low under clinical GRADE criteria.

1:03:45Ben Greenfieldsupportedmoderate

Botox injections into sexual organs relax muscle tissue and improve vascularity.

"they do Botox injections into your your sexual organs, which apparently relaxes the muscle tissue and allows for for better better uh vascularity." (said at 1:03:45)

Intracavernosal injection of botulinum neurotoxin type A (BoNT-A) into the corpus cavernosum has been investigated as a treatment for erectile dysfunction. Published randomized controlled trials and meta-analyses demonstrate that botulinum toxin relaxes corporal smooth muscle tissue and significantly improves penile vascularity, as measured by peak systolic velocity on cavernosal Doppler ultrasound, compared to placebo.

1:16:31Mark Hyman (host)supportedmoderate

Stephan van Vliet's metabolomic studies showed that the meat of fully regeneratively pasture-fed bison contains different metabolites, phytochemicals, and fatty acids compared to grain-finished bison.

"there's Stephan van Vliet does some interesting studies looking at bison and bison that are purely fed on regenerative methods using kind of multiple wild plants that they eat versus a bison that's, you know, mostly grass-fed but then is, you know, feedlot-fed at the end with corn and grains. And they did very detailed metabolomic studies where they looked at not just, you know, things that were bad... that the metabolites in the meat of the fully regenerative bison were really quite different and had all sorts of phytochemicals that weren't in the other meat, that all sorts of, you know, fatty acids that weren't in there" (said at 1:16:31)

A comparative metabolomic study by Stephan van Vliet and colleagues (2023) profiled over 1,500 metabolites in striploins from pasture-finished versus pen-finished (grain/concentrates) bison (n = 20 per group). They found that 43% (671) of the profiled compounds differed significantly between finishing systems. Meat from pasture-finished bison contained significantly higher levels of phenolics (~2.3-fold), alpha-tocopherol (~5.8-fold), carotene (~2.0-fold), and very long-chain fatty acids (~1.3-fold), confirming that pasture-finishing alters the metabolite, phytochemical, and fatty acid composition of bison meat.

1:18:28Ben Greenfieldsupportedvery low

Excessive intake of methionine from meat can overstimulate mTOR, theoretically impairing longevity unless balanced with glycine.

"You also tend to see folks in the longevity camp who raise concerns about excess stimulation of mTOR, which could theoretically result in impaired longevity from excessive methionine intake, right? The amino acid that you find in a lot of meat, especially if you're not eating nose-to-tail source and balancing out methionine with glycine." (said at 1:18:28)

The speaker accurately describes a well-established theoretical hypothesis in longevity research. In preclinical literature and animal models (such as rodents and C. elegans), dietary methionine restriction extends lifespan, whereas excessive methionine activates nutrient-sensing pathways such as mTOR and increases metabolic strain. Furthermore, glycine supplementation has been shown to clear excess methionine via the methionine cycle and extend lifespan in animal studies (such as the NIA Interventions Testing Program). However, evidence is currently limited to animal models and mechanistic hypotheses, with no clinical trial data demonstrating that balancing dietary methionine with glycine alters human longevity.

  • supports: Glycine supplementation extends lifespan of male and female mice. (Aging cell 2019) · cited 98x in the literature
    "Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%-6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001)." (abstract, results, passage verified)
    pubmedfull study (doi)
  • supports: The regulation of healthspan and lifespan by dietary amino acids. (Translational medicine of aging 2021) · cited 43x in the literature
    "Here, we discuss how dietary protein and specific amino acids including methionine, the branched chain amino acids (leucine, isoleucine, and valine), tryptophan and glycine regulate metabolic health, healthspan, and aging, with attention to the specific molecular mechanisms that may participate in these effects." (abstract, passage verified)
    pubmedfull study (doi)
1:14:59Mark Hyman (host)supportedhigh

The Recommended Dietary Allowance (RDA) for daily protein intake is less than half of 1 gram per pound of body weight.

"which is twice as much or more than than the RDA, which is the government sort of minimum amount." (said at 1:14:59)

The Recommended Dietary Allowance (RDA) established for daily protein intake in healthy adults is 0.8 grams per kilogram of body weight per day (g/kg/d). Converted to imperial units (1 kg ≈ 2.205 lbs), 0.8 g/kg corresponds to approximately 0.36 grams per pound of body weight per day. This is well below half of 1 gram per pound (0.5 g/lb), meaning an intake of 1 gram per pound is roughly 2.75 times the standard RDA.

1:08:52Ben Greenfieldsupportedhigh

Sleep research guidelines recommend that adults get 7 to 9 hours of sleep per night.

"I'm supposed to be getting, you know, depending on the research you look at, seven to nine hours." (said at 1:08:52)

Major sleep research consensus guidelines, including those from the National Sleep Foundation and the American Academy of Sleep Medicine/Sleep Research Society, recommend that healthy adults obtain 7 to 9 hours of sleep per night for optimal health and well-being.

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.