DavidPerlmutterMD · 2021-05-03 · David Perlmutter (host), Robert H. Lustig
Take Back Your Health - with Dr. Robert H. Lustig | The Empowering Neurologist EP. 122
49 research-tied claims examined: 7 contradicted 7 overstated 7 context 20 supported 8 unverified
7 Contradicted by research
There are more metabolically unhealthy normal-weight individuals in the United States than metabolically unhealthy obese individuals.
"And actually it turns out there are more thin, sick people in America than there are fat, sick people" (said at 0:19:22)
Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) contradict the claim that there are more metabolically unhealthy normal-weight individuals ("thin, sick") in the United States than metabolically unhealthy obese individuals ("fat, sick"). An analysis of NHANES data from 1999 to 2018 (PMID: 35691704) found that the prevalence of metabolically unhealthy normal weight was 2.10% (declining from 3.77% in 1999), compared to a prevalence of 26.4% for metabolically unhealthy obesity (increasing from 19.0% in 1999). Even when looking at broader definitions or proportions within BMI categories (PMID: 26841729), approximately 30% of normal-weight US adults are cardiometabolically unhealthy compared to about 71% of obese adults (and 84% of class II/III obese adults), resulting in a substantially larger absolute and relative population of metabolically unhealthy individuals in the overweight and obese categories compared to the normal-weight category.
- contradicts: Misclassification of cardiometabolic health when using body mass index categories in NHANE… (International journal of obesity (2005) 2016) · cited 346x in the literature
"Nearly half of overweight individuals, 29% of obese individuals and even 16% of obesity type 2/3 individuals were metabolically healthy. Moreover, over 30% of normal weight individuals were cardiometabolically unhealthy." (abstract, results, passage verified)
pubmedfull study (doi) - contradicts: Trends in Metabolic Phenotypes According to Body Mass Index Among US Adults, 1999-2018. (Mayo Clinic proceedings 2022) · cited 22x in the literature
"The prevalence declined from 3.77% (72 of 1646) to 2.10% (68 of 2058) (difference, -1.67%; 95% CI, -3.22% to -0.12%; P=.006 for trend) for metabolically unhealthy normal weight, whereas it increased from 19.0% (343 of 1646) to 26.4% (574 of 2058) (difference, 7.41%; 95% CI, 2.67% to 12.2%; P<.001 for trend) for MU-OB." (abstract, results, passage verified)
pubmedfull study (doi)
Exercise does not reduce glycation and actually makes glycation worse.
"So it does not affect glycation; it actually makes glycation worse." (said at 0:35:54)
The claim that exercise does not reduce glycation and actually worsens it is directly contradicted by clinical trial and epidemiological evidence. Large meta-analyses of hundreds of randomized controlled trials show that exercise training consistently lowers glycated hemoglobin (HbA1c), a primary biomarker of protein glycation. Furthermore, a systematic review investigating the accumulation of advanced glycation end products (AGEs, measured via skin autofluorescence) found that higher physical activity and exercise levels are inversely associated with tissue glycation, with no studies finding that physical activity increases or worsens glycation accumulation.
- contradicts: The effect of exercise characteristics on HbA1c and other cardiovascular risk factors in a… (Cardiovascular diabetology 2025) · cited 12x in the literature
"All exercise types significantly improved HbA1c, with the largest reductions observed for combined training (− 0.74%, 95% CI [− 0.91; − 0.57], n = 38) and high-intensity interval training (HIIT) (− 0.71%, 95% CI [− 1.07; − 0.35], n = 13), followed by continuous aerobic training (CAT) (− .62%, 95% CI [− 0.84; − 0.41], n = 57) and resistance training (− 0.36%, 95% CI [− 0.51; − 0.20], n = 38)." (abstract, results, passage verified)
pubmedfull study (doi) - contradicts: Analysis of the potential association between physical activity and skin autofluorescence:… (Journal of epidemiology and community health 2026) · cited 1x in the literature
"Specifically, 58.8% of the studies reported a statistically significant inverse association, indicating that higher levels of PA or exercise frequency are correlated with lower SAF levels. The remaining studies (41.2%) reported non-significant results, though several showed favourable trends. No studies reported a positive association between PA and SAF." (abstract, results, passage verified)
pubmedfull study (doi)
Exercise does not reduce oxidative stress and actually makes oxidative stress worse.
"It does not affect oxidative stress; exercise actually makes oxidative stress worse." (said at 0:35:59)
The claim that exercise does not reduce oxidative stress and only worsens it is contradicted by systematic reviews and meta-analyses of randomized controlled trials. While a single, acute bout of strenuous exercise causes a transient increase in reactive oxygen species and oxidative stress biomarkers (such as protein carbonyls and F2-isoprostanes), regular exercise training induces adaptative increases in endogenous antioxidant enzymes (such as superoxide dismutase) and causes a net reduction in basal pro-oxidants and lipid peroxidation markers (such as malondialdehyde).
- contradicts: Effect of exercise intensity on redox biomarkers in healthy adults: A systematic review an… (PloS one 2025) · cited 3x in the literature
"Individual evaluations demonstrated an increase in antioxidant capacity (I2=0%, Z=4.56, p<0.00001) and superoxide dismutase (I2=52%, Z=1.94, p=0.05), an antioxidant enzyme, and decrease in pro-oxidant (I2=0%, Z=5.91, p<0.0001); there was no significant difference in glutathione peroxidase (I2=81%, Z=0.50, p=0.62). The effect of vigorous interventions showed an increase in antioxidants (Z=2.44, I2=67%, p=0.01) and a decrease in oxidants (Z=5.44, I2=0%, p<0.00001)" (abstract, results, passage verified)
pubmedfull study (doi) - contradicts: The effects of exercise on oxidative stress MDA and SOD in patients with type 2 diabetes: … (PeerJ 2025) · cited 5x in the literature
"The results of the meta-analysis showed that exercise can improve malondialdehyde (MDA), standardized mean difference (SMD) = -1.29, 95% CI [-1.87 to -0.71], P < 0.0001 in patients with T2DM; and improve superoxide dismutase (SOD), SMD = 0.59, 95% CI [0.17-1.01], P = 0.006 in patients with T2DM." (abstract, results, passage verified)
pubmedfull study (doi) - context: Optimal timing to assess exercise-induced oxidative stress: A systematic review and meta-a… (Experimental physiology 2025) · cited 2x in the literature
"Glutathione levels decreased immediately (g = -0.70; 95% CI: -0.96, -0.44; P < 0.001), at 30 min to 2 h (g = -0.81; 95% CI: -1.19, -0.43; P < 0.001), and 48 h post-exercise (g = -0.98; 95% CI: -1.50, -0.46; P < 0.01). F 2 -isoprostanes increased immediately post-exercise (g = 1.01; 95% CI: 0.70, 1.33; P < 0.001) and at 30 min to 2 h (g = 0.46; 95% CI: 0.23, 0.69; P < 0.001)." (abstract, results, passage verified)
pubmedfull study (doi)
African Americans accumulate less hepatic fat on average due to a mutation in the APOC3 gene.
"In African Americans, it should be 20 for that matter because they actually don't even make as much fat in the liver. They have a mutation in their APOC3 gene, so they actually don't accumulate as much fat." (said at 0:53:12)
The claim that African Americans accumulate less hepatic fat due to a mutation in the APOC3 gene is contradicted by population-based genetics studies examining APOC3 variants, hepatic triglyceride content (HTGC), and ethnicity. In a large multiethnic cohort study (the Dallas Heart Study, n=1,228 African Americans), candidate APOC3 gene variants (rs2854117 and rs2854116) showed no significant difference in hepatic fat content between carriers and noncarriers, refuting the proposed role of APOC3 variants in driving lower hepatic fat accumulation in African Americans (PMID: 21274868). Similarly, in obese pediatric cohorts evaluated across racial groups, APOC3 gene variants were not associated with hepatic fat fraction, whereas variants in genes such as PNPLA3 and GCKR were associated with liver fat accumulation across ethnicities (PMID: 22105854).
- contradicts: Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. (Hepatology (Baltimore, Md.) 2011) · cited 114x in the literature
"Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR)... No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study... Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women." (abstract, results and conclusions, passage verified)
pubmedfull study (doi) - contradicts: Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver i… (Hepatology (Baltimore, Md.) 2012) · cited 267x in the literature
"The PNPLA3, but not the APOC3 rs2854116 SNP, was associated with fatty liver but not with triglyceride levels." (abstract, results, passage verified)
pubmedfull study (doi)
Homocysteine is normally metabolized through the urea cycle to succinate by the enzyme methylenetetrahydrofolate reductase (MTHFR).
"And the thing is that homocysteine is normally metabolized down the urea cycle to succinate by the enzyme MTHFR, methylenetetrahydrofolate reductase." (said at 1:01:26)
The speaker fundamentally misstates the biochemistry of homocysteine metabolism. Homocysteine is not metabolized through the urea cycle to succinate by methylenetetrahydrofolate reductase (MTHFR). In human biochemistry, homocysteine has two major pathways: remethylation back to methionine and transsulfuration to cysteine. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which provides the methyl group used by methionine synthase to remethylate homocysteine into methionine. The urea cycle is a distinct pathway responsible for ammonia detoxification, and succinate is an intermediate of the citric acid (TCA) cycle.
- contradicts: Metabolism of homocysteine and its relationship with cardiovascular disease. (Journal of thrombosis and thrombolysis 2004) · cited 59x in the literature
"Methionine regenerates by retrieving the methyl radical from 5-methyltetrahydrofolate (5-MTHF) creating tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine-beta-syntetase (CBS), it irreversibly converted into cystationine, a precursor of cysteine, glutathione, and other substances that are finally excreted in the urine." (abstract, passage verified)
pubmedfull study (doi) - contradicts: Genetics of homocysteine metabolism and associated disorders. (Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 2010) · cited 208x in the literature
"Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of two pathways: remethylation or transsulfuration." (abstract, passage verified)
pubmedfull study (doi)
ACE2 is normally a water channel in cells, especially in the lungs.
"ACE2, angiotensin-converting enzyme 2. Now, that is normally a water channel in cells, especially lung, but it drives the production of ACE2." (said at 1:07:40)
ACE2 (angiotensin-converting enzyme 2) is not a water channel; it is a membrane-bound zinc carboxypeptidase within the renin-angiotensin system that cleaves angiotensin II into angiotensin-(1-7) and serves as the cellular entry receptor for SARS-CoV and SARS-CoV-2. The cellular proteins that function as water channels are aquaporins (e.g., AQP1 through AQP5), which the speaker may have confused with ACE2 due to the similar abbreviation of Aquaporin-2 (AQP2).
- contradicts: Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partn… (Pharmacology & therapeutics 2010) · cited 504x in the literature
"Angiotensin-converting enzyme (ACE) 2 is a homolog to the carboxypeptidase ACE, which generates angiotensin II, the main active peptide of renin-angiotensin system (RAS). After the cloning of ACE2 in 2000, three major ACE2 functions have been described so far. First ACE2 has emerged as a potent negative regulator of the RAS counterbalancing the multiple functions of ACE." (abstract, background/results, passage verified)
pubmedfull study (doi) - contradicts: Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19. (Frontiers in immunology 2021) · cited 68x in the literature
"ACE2 is a carboxypeptidase which degrades angiotensin II, B1-bradykinin, or apelin, and thereby is a critical regulator of cardiovascular physiology and pathology." (abstract, results, passage verified)
pubmedfull study (doi) - context: Aquaporins in Respiratory System. (Advances in experimental medicine and biology 2023) · cited 5x in the literature
"Aquaporins (AQPs) are water channel proteins facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland secretion. In this chapter, we mainly focus on the expression of four AQPs in the lungs, which include AQP1, AQP2, AQP4, and AQP5 in normal and disease status" (abstract, introduction, passage verified)
pubmedfull study (doi)
High blood glucose crystallizes around ACE2 molecules to keep them open, increasing susceptibility to COVID-19 infection.
"High blood glucose basically crystallizes around the edges of those ACE2 molecules and keeps them open so that the virus has an even easier chance of infecting you." (said at 1:08:40)
The claim mischaracterizes the biochemistry of hyperglycemia and SARS-CoV-2 receptor interaction. Glucose does not physically "crystallize" on cell-surface receptors in aqueous biological fluids. In patients with elevated blood glucose, the actual molecular mechanism involves non-enzymatic glycation (the covalent attachment of glucose molecules to lysine residues) and increased cellular expression of ACE2. Furthermore, in silico structural modeling indicates that glycation of ACE2 residues reduces polar and van der Waals interactions with the viral Spike protein rather than mechanically holding the receptor open.
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.