DavidPerlmutterMD · 2018-05-26 · David Perlmutter (host), Rangan Chatterjee

How to Make Disease Disappear- with Dr. Rangan Chatterjee | The Empowering Neurologist EP. 73

17 research-tied claims examined: 2 contradicted 1 overstated 3 context 10 supported 1 unverified

Contradicted by research

0:33:34 David Perlmutter (host)contradictedhigh

LPS in the human body originates exclusively from the gut.

"And it can come from nowhere else; it comes from the gut exclusively." (said at 0:33:34)

The host claimed that lipopolysaccharide (LPS / endotoxin) in the human body originates exclusively from the gut. This claim is contradicted by extensive biomedical evidence establishing that systemic and circulating LPS also originates from non-gut sites harboring Gram-negative bacteria, most prominently the oral cavity (e.g., periodontal infections/pockets) as well as respiratory and urinary tract infections. Studies measuring subgingival and serum LPS activity demonstrate that oral dysbiosis and periodontitis directly contribute to circulating serum LPS levels independently of the gastrointestinal tract.

contradicts: Oral Microbial Determinants of Saliva and Serum Lipopolysaccharide Activity. (Journal of dental research 2026) · cited 5x in the literature
"Our study indicates that dysbiosis of the oral microbiome is a source of increased salivary and serum LPS activity." (abstract, conclusions, passage verified)
pubmed full study (doi)
contradicts: Periodontitis and Endotoxemia: Clinical and Microbiological Insights. (Journal of clinical periodontology 2026) · cited 2x in the literature
"These findings provide novel evidence that elevated serum LPS activities are closely linked with periodontitis diagnosis, associated with subgingival dysbiosis, and highlight the periodontal niche as a source of systemic endotoxemia." (abstract, conclusions, passage verified)
pubmed full study (doi)

0:41:28 David Perlmutter (host)contradictedmoderate

A study of 10,000 individuals who felt unconnected demonstrated that their risk of illness was triple the risk associated with smoking.

"That study that you just were alluding to of the 10,000 individuals who felt unconnected demonstrated that the risk of illness was in fact triple the risk of smoking." (said at 0:41:28)

No study of 10,000 individuals demonstrating that feeling unconnected carries triple the risk of smoking was located. Landmark meta-analyses evaluating social connection, morbidity, and mortality (such as Holt-Lunstad et al., 2010) benchmark the health risks of social isolation and low social connection as roughly comparable in magnitude to well-established risk factors like smoking (often popularized as equivalent to smoking up to 15 cigarettes a day), rather than threefold higher.

contradicts: Social relationships and mortality risk: a meta-analytic review. (PLoS medicine 2010) · cited 7313x in the literature
"Across 148 studies (308,849 participants), the random effects weighted average effect size was OR = 1.50 (95% CI 1.42 to 1.59), indicating a 50% increased likelihood of survival for participants with stronger social relationships... The influence of social relationships on risk for mortality is comparable with well-established risk factors for mortality." (abstract, conclusions, passage verified)
pubmed full study (doi)
contradicts: Benchmarking Social Isolation, Loneliness, and Smoking: Challenges and Opportunities for P… (American journal of epidemiology 2023) · cited 28x in the literature
"Over the past decade, the health implications of social isolation and loneliness garnered global attention due in part to a widely cited meta-analysis that benchmarked associations between cigarette smoking and mortality with associations between several social-relationship measures and mortality. Leaders in health systems, research, government, and popular media have since claimed that the harms of social isolation and loneliness are comparable to that of cigarette smoking." (abstract, passage verified)
pubmed full study (doi)

Overstated

0:40:22 Rangan Chatterjeeoverstatedmoderate

Social isolation presents a health risk that exceeds the health consequences of smoking.

"about how social isolation is, you know, it's a health risk superior to smoking, you know, in fact in terms of its health consequence." (said at 0:40:22)

The claim overstates the scientific evidence. Landmark meta-analyses by Holt-Lunstad and colleagues demonstrated that social relationships and social isolation carry mortality risks comparable to established risk factors such as smoking (often benchmarked as comparable to smoking up to 15 cigarettes a day) and exceeding factors like physical inactivity and obesity. However, the literature does not establish that social isolation's health risk exceeds or is superior to the overall health consequences of cigarette smoking.

partial: Social relationships and mortality risk: a meta-analytic review. (PLoS medicine 2010) · cited 7313x in the literature
"The influence of social relationships on risk for mortality is comparable with well-established risk factors for mortality." (abstract, conclusions, passage verified)
pubmed full study (doi)
partial: Loneliness and social isolation as risk factors for mortality: a meta-analytic review. (Perspectives on psychological science : a journal of the Association for Psychological Science 2015) · cited 5945x in the literature
"Across studies in which several possible confounds were statistically controlled for, the weighted average effect sizes were as follows: social isolation odds ratio (OR) = 1.29, loneliness OR = 1.26, and living alone OR = 1.32, corresponding to an average of 29%, 26%, and 32% increased likelihood of mortality, respectively." (abstract, results, passage verified)
pubmed full study (doi)
context: Benchmarking Social Isolation, Loneliness, and Smoking: Challenges and Opportunities for P… (American journal of epidemiology 2023) · cited 28x in the literature
"Leaders in health systems, research, government, and popular media have since claimed that the harms of social isolation and loneliness are comparable to that of cigarette smoking. Our commentary examines the basis of this comparison. We suggest that comparisons between social isolation, loneliness, and smoking have been helpful for raising awareness of robust evidence linking social relationships and health. However, the analogy often oversimplifies the evidence" (abstract, passage verified)
pubmed full study (doi)

Needs context

0:10:55 Rangan Chatterjeeneeds contextmoderate

Type 2 diabetes can be reversed or put into remission within 30 days using lifestyle interventions.

"I managed to showcase to five million people in the UK each week that, you know, a condition like type 2 diabetes, for example—this is back in 2015—could be reversed, and I showed in 30 days that that reversal, or, you know, the technical term now here is to put it in remission, we could talk about that later." (said at 0:10:55)

Intensive dietary interventions (such as very-low-calorie diets or total diet replacement) can rapidly normalize fasting plasma glucose, liver fat, and beta-cell function within 1 to 4 weeks (30 days), allowing discontinuation of glucose-lowering medications in many individuals with early type 2 diabetes. However, according to international consensus definitions (including from the American Diabetes Association and Diabetes UK), formal clinical 'remission' requires maintaining non-diabetic glycemic levels (HbA1c < 6.5% / 48 mmol/mol) for at least 3 months in the absence of glucose-lowering medications. Thus, while acute glycemic normalization and reversal of underlying pathophysiologic defects occur within 30 days, establishing true clinical remission requires demonstration of sustained glycemic control over time.

supports: Immediate and long-term effects of a very-low-calorie diet on diabetes remission and glyce… (Food science & nutrition 2019) · cited 43x in the literature
"Among 19 patients (age 48 ± 2 years, BMI 27.7 kg/m 2 ) who completed the study, rapid improvement in glycemic control was observed in the first 2 weeks of VLCD. At both 8 and 12 weeks, diabetes remission was achieved in 79%. Significant weight loss was accompanied by a significant reduction in IR and an increase in beta cell function, starting at 4 weeks of VLCD." (abstract, results, passage verified)
pubmed full study (doi)
supports: Very low calorie diets and total diet replacement in type 2 diabetes: where are we now? (Drug and therapeutics bulletin 2024) · cited 4x in the literature
"Management of type 2 diabetes has now been simplified by the understanding that the condition is caused by excess fat in the liver together with suppression of beta cell function by the associated excess liver export of fat. These factors can be reversed by substantial weight loss leading to remission in the early years after diagnosis, or at least major decrease in cardiovascular risks and improvement in glucose control for all. Weight loss by any means is successful, but it is most easily achieved by rapid action using a low or very low calorie diet of around 800 kcal/day followed by sustained modest restraint of dietary habits. Oral hypoglycaemic agents and one antihypertensive drug can be withdrawn on day 1 of the weight loss diet, raising the importance of appropriate deprescribing." (abstract, results, passage verified)
pubmed full study (doi)

0:19:19 Rangan Chatterjeeneeds contextmoderate

Chronic psychological stress causes increased intestinal permeability (leaky gut) and alters the gut microbiome composition.

"I explained to her how stress can alter the gut, it can, you know, having too much stress can absolutely cause holes to appear in our gut wall, you know, what we call leaky gut. We know that too much stress can alter the balance of gut bugs in our intestine, in our large intestine." (said at 0:19:19)

Preclinical and human experimental studies demonstrate that psychological stress activates the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, prompting mast cell degranulation, modulation of epithelial tight junction proteins (such as claudins and occludin), and alterations in gut microbiota composition. However, stress does not cause physical or macroscopic "holes" in the intestinal wall; rather, it induces a microscopic increase in paracellular permeability across the epithelial barrier (often colloquially termed "leaky gut"). While animal models robustly show stress-induced intestinal hyperpermeability and dysbiosis, human evidence demonstrates more nuanced, modest, and transient increases in paracellular permeability.

supports: Acute psychological stress increases paracellular permeability and modulates immune activi… (United European gastroenterology journal 2023) · cited 12x in the literature
"Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability." (abstract, results, passage verified)
pubmed full study (doi)
context: Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidenc… (Neurobiology of stress 2023) · cited 43x in the literature
"In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans." (abstract, results, passage verified)
pubmed full study (doi)
supports: Psychological stress and immune dysregulation: Insights from neuroimmunology and the gut-b… (Behavioural brain research 2026) · cited 2x in the literature
"Emerging research highlights the gut-brain-immune axis as a critical mediator of these effects, where alterations in gut microbiota composition, microbial metabolites, and intestinal barrier integrity modulate systemic inflammation, immune cell function, and neural activity." (abstract, results, passage verified)
pubmed full study (doi)

0:32:24 David Perlmutter (host)needs contextmoderate

Research demonstrates significantly higher circulating levels of LPS (lipopolysaccharide) in individuals with major depressive disorder compared to those without the condition.

"Well, that study was actually founded on previous research, supportive research, that demonstrated much higher levels of LPS—I'll explain in a moment—in major depressive disorder in comparison to those who do not." (said at 0:32:24)

While research linking bacterial translocation and gut permeability to depression demonstrates elevated immune responses to lipopolysaccharides (LPS)—specifically significantly higher levels of anti-endotoxin antibodies and soluble CD14 (sCD14) in depressed individuals compared to non-depressed controls—direct measurement of circulating LPS levels yields a more nuanced picture. Meta-analytic evidence shows clear elevations in immune markers triggered by bacterial endotoxins rather than consistent simple elevations of free LPS alone. Furthermore, clinical evaluations within major depressive disorder (MDD) cohorts have found that circulating LPS levels inversely correlate with depression severity and anhedonia, with severely depressed patients exhibiting lower circulating LPS concentrations than those with mild-to-moderate depression.

context: Leaky Gut Biomarkers as Predictors of Depression and Suicidal Risk: A Systematic Review an… (Diagnostics (Basel, Switzerland) 2025) · cited 17x in the literature
"For depressive symptoms, when compared to the controls, patients showed significantly increased levels of intestinal fatty acid-binding protein (I-FABP) (ES = 0.36; 95% CI = 0.11 to 0.61; p = 0.004; I 2 = 71.61%), zonulin (ES = 0.69; 95% CI = 0.02 to 1.36; p = 0.044; I 2 = 92.12%), antibodies against bacterial endotoxins (ES = 0.75; 95% CI = 0.54 to 0.98; p < 0.001; I 2 = 0.00%), and sCD14 (ES = 0.11; 95% CI = 0.01 to 0.21; p = 0.038; I 2 = 10.28%). No significant differences were found between the patients and controls in levels of LPS-binding protein (LBP) and alpha-1 antitrypsin (A-1-AT)." (abstract, results, passage verified)
pubmed full study (doi)
context: Higher Lipopolysaccharide Levels Are Linked to Less Anhedonia and Lower Severity of Major … (Brain sciences 2026)
"Patients with severe depression exhibited significantly lower circulating LPS levels than those with mild-to-moderate depression (95.6 vs. 165.2 pg/mL, p = 0.007), despite no significant differences in cytokine concentrations." (abstract, results, passage verified)
pubmed full study (doi)

Supported by research

0:05:52 Rangan Chatterjeesupportedhigh

Severe vitamin D deficiency in infants can cause profound hypocalcemia resulting in afebrile convulsions.

"his serum calcium was 0.97. The normal range is 2.2 to 2.6 in that hospital, so alarmingly low. And then a few hours further to that, they came back and said, "And we now know the reason why: he was extremely deficient in vitamin D."" (said at 0:05:52)

Severe vitamin D deficiency is a well-established cause of profound symptomatic hypocalcemia in neonates and infants, commonly presenting as afebrile or metabolic seizures. In pediatric surveillance cohorts and clinical studies, infants with severe hypovitaminosis D frequently present with severe hypocalcemia and associated neuromuscular irritability, tetany, or seizures, which resolve upon treatment with calcium and vitamin D supplementation.

supports: Nutritional rickets under 16 years: UK surveillance results. (Archives of disease in childhood 2020) · cited 56x in the literature
"Complications included delayed gross motor development (26.4%), fractures (9.6%), hypocalcaemic seizures (8%) and dilated cardiomyopathy (3%)." (abstract, results, passage verified)
pubmed full study (doi)
supports: Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study. (Journal of clinical research in pediatric endocrinology 2021) · cited 2x in the literature
"Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures." (abstract, introduction, passage verified)
pubmed full study (doi)
supports: Severe Vitamin D Deficiency as a Trigger for Metabolic Seizures in Infancy: A Case Series … (Nutrients 2026)
"Hypocalcemia represents a major cause of seizures in children in the absence of fever or infections. Hypovitaminosis D, usually associated with a lack of proper prophylactic regimens, can trigger those events." (abstract, introduction, passage verified)
pubmed full study (doi)

0:24:05 Rangan Chatterjeesupportedmoderate

Gut bacteria ferment dietary fiber to produce short-chain fatty acids, which signal to the brain through the vagus nerve and the bloodstream.

"the fiber that we eat, those gut bugs will eat, they'll make short-chain fatty acids. And those short-chain fatty acids can almost switch a light on in your brain by sort of connecting with the vagus nerve, or they can go around in the bloodstream and get to the brain." (said at 0:24:05)

Gut bacteria ferment non-digestible dietary fiber into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate. These metabolites communicate with the central nervous system through multiple established pathways, including direct activation of receptors (such as FFAR3) on vagal sensory neurons innervating the gastrointestinal tract, as well as entering the systemic circulation and crossing the blood-brain barrier to modulate neurophysiology and behavior.

supports: Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid rec… (Molecular metabolism 2021) · cited 105x in the literature
"Short-chain fatty acids (SCFAs) produced via gut microbiota fermentation of dietary fiber have been proposed to regulate host metabolism and feeding behavior via the vagus nerve, but the molecular mechanisms have not yet been elucidated... SCFA, particularly propionate, signaling occurs via free fatty acid receptor 3 (FFAR3), that we found expressed in vagal sensory neurons innervating throughout the gut." (abstract, background and results, passage verified)
pubmed full study (doi)
supports: Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. (Molecular and cellular endocrinology 2022) · cited 684x in the literature
"A key focus in this regard have been the short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fibre, which include butyrate, acetate, and propionate. Ongoing research is focused on the entry of SCFAs into systemic circulation from the gut lumen, their migration to cerebral circulation and across the blood brain barrier, and their potential to exert acute and chronic effects on brain structure and function." (abstract, passage verified)
pubmed full study (doi)
supports: Short-chain fatty acids in mood and schizophrenia spectrum disorders: Evidence in the fiel… (Progress in neuro-psychopharmacology & biological psychiatry 2025) · cited 1x in the literature
"The communication within MGBA involves various pathways leading through the vagus nerve and the bloodstream mediators. The latter are represented by short-chain fatty acids (SCFAs), produced by gut microbiota from dietary fiber." (abstract, passage verified)
pubmed full study (doi)

0:25:28 Rangan Chatterjeesupportedhigh

According to US diagnostic thresholds, an HbA1c between 5.7% and 6.4% indicates prediabetes, and an HbA1c above 6.5% indicates type 2 diabetes.

"in the US, 5.7, I think to 6.4, is pre-diabetic, and above 6.5 is type 2 diabetes." (said at 0:25:28)

According to established US clinical diagnostic guidelines from the American Diabetes Association (ADA), an HbA1c level between 5.7% and 6.4% is classified as prediabetes (increased risk for diabetes), and an HbA1c of 6.5% or higher (≥6.5%) meets the diagnostic criterion for diabetes.

supports: Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. (Diabetes care 2010) · cited 241x in the literature
"We compared pre-diabetes, dysglycemia (diabetes or pre-diabetes), and diabetes identified by the proposed criteria (A1C ≥ 6.5% for diabetes and 6.0-6.4% [IEC] or 5.7-6.4% [ADA] for high risk/pre-diabetes) with standard OGTT diagnoses in three datasets." (abstract, methods, passage verified)
pubmed full study (doi)
supports: Definitions (and Current Controversies) of Diabetes and Prediabetes. (Current diabetes reviews 2016) · cited 74x in the literature
"Diagnosis of diabetes is established on (at least) one of the following criteria: a fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l), a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2-h plasma glucose during the 75-g oral glucose tolerance test (OGTT) ≥ 200 mg/dl (11.1 mmol/l) and/or an HbA1c ≥ 6.5%. Prediabetes is defined by the Position Statement of the American Diabetes Association as a fasting plasma glucose between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0 mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%" (abstract, passage verified)
pubmed full study (doi)

0:27:47 David Perlmutter (host)supportedlow

In a clinical trial by Dr. Sarah Hallberg testing a ketogenic diet for type 2 diabetes, 96% of participants reduced or discontinued insulin, 100% discontinued sulfonylureas, and average weight loss was 14% of body weight.

"Dr. Sarah Hallberg, who instituted a ketogenic diet in individuals with type 2 diabetes. And just to recap, 96% of these individuals were able to discontinue or reduce their insulin, and 100% were able to stop their sulfonylurea-class drugs. Average weight loss was 14% of body weight." (said at 0:27:47)

The speaker accurately recounts the findings of the 1-year clinical trial led by Dr. Sarah Hallberg evaluating a continuous remote care intervention utilizing nutritional ketosis (a ketogenic diet) for type 2 diabetes (PMID: 29417495). In that open-label, non-randomized controlled study of 262 intervention participants, sulfonylurea use was 100% eliminated, insulin was reduced or eliminated in 94% of users (very close to the spoken 96%), and mean weight loss was 13.8 kg (approximately 12% in the intention-to-treat cohort and up to ~14% among completers). Because the trial was non-randomized and open-label, the GRADE certainty of the evidence is low.

supports: Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 … (Diabetes therapy : research, treatment and education of diabetes and related disorders 2018) · cited 421x in the literature
"weight declined 13.8 ± 0.71 kg (P < 1.0 × 10 -16 ), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10 -16 )." (abstract, results, passage verified)
pubmed full study (doi)

0:16:28 Rangan Chatterjeesupportedhigh

The acute stress response raises cortisol and adrenaline levels, which suppresses digestion and increases blood glucose levels.

"We need our cortisol levels to go up. We need our adrenaline levels to go up. And in that moment, we can run faster, you know, our brain thinks sharper, we switch off digestion, we pour sugar into our bloodstream to help us do all these things." (said at 0:16:28)

Published human physiological studies confirm that acute stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis, leading to rapid surges in adrenaline (epinephrine) and cortisol. These hormonal elevations stimulate hepatic glucose production (via glycogenolysis and gluconeogenesis) and decrease peripheral glucose disposal, resulting in acute hyperglycemia to mobilize energy.

supports: Stress-induced hyperglycemia in healthy bungee jumpers without diabetes due to decreased p… (Diabetes technology & therapeutics 2012) · cited 21x in the literature
"Glucose levels and stress hormones were increased, right before and after the jump, whereas the immune response was decreased. Pancreatic β-cell function was decreased right before the jump, and insulin resistance was increased right after the jump. Higher levels of cortisol correlated with increased insulin resistance after the jump. Furthermore, larger increments of cortisol before and of epinephrine after the jump were associated with decreased pancreatic β-cell function." (abstract, results, passage verified)
pubmed full study (doi)
supports: Effect of epinephrine on glucose metabolism in humans: contribution of the liver. (The American journal of physiology 1984) · cited 122x in the literature
"Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues." (abstract, results, passage verified)
pubmed full study (doi)

0:22:54 Rangan Chatterjeesupportedhigh

Localized intestinal inflammation triggers the release of systemic cytokines that transmit inflammatory signals to other organ systems throughout the body.

"when there's inflammation in the gut, lots of immune messengers that we call cytokines get triggered off and they take that message of inflammation and they send it to different organ systems." (said at 0:22:54)

The claim is supported by extensive biomedical research on inflammatory bowel disease (IBD) and intestinal barrier dysfunction. Intestinal inflammation leads to mucosal barrier disruption, microbial translocation, and local immune cell activation, which triggers the systemic release of inflammatory cytokines (such as IL-6, TNF-alpha, and IL-1beta) into the bloodstream. These circulating cytokines act as immune messengers to propagate inflammatory signals to extraintestinal organ systems, including the lungs, liver, kidneys, joints, skin, eyes, and central nervous system.

supports: IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murin… (The American journal of pathology 2018) · cited 65x in the literature
"We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD." (abstract, results, passage verified)
pubmed full study (doi)
supports: Genetic Deletion of LRP5 and LRP6 in Macrophages Exacerbates Colitis-Associated Systemic I… (Journal of immunology (Baltimore, Md. : 1950) 2022) · cited 9x in the literature
"Extraintestinal manifestations are common in inflammatory bowel disease and involve several organs, including the kidney... Furthermore, our studies show that aggravated colitis-associated systemic inflammation and AKI observed in LRP5/6 LysM mice are due to increased bacterial translocation to extraintestinal sites and microbiota-dependent increased proinflammatory cytokine levels in the kidney." (abstract, results)
pubmed full study (doi)
supports: Deciphering the TLR4 and NLRP3 Inflammasome Crosstalk for Therapeutic Restoration of Intes… (Digestive diseases and sciences 2026) · cited 5x in the literature
"Dysregulation disrupts these protective mechanisms and initiates feed-forward cycle of epithelial damage, metabolic endotoxemia, dysbiosis, and heightened cytokine-driven inflammation. Such aberrant activity contributes to major intestinal diseases-including inflammatory bowel disease, necrotizing enterocolitis, and colorectal cancer-as well as extraintestinal conditions such as obesity, type 2 diabetes, and neuroinflammation through gut-brain axis pathways." (abstract, results, passage verified)
pubmed full study (doi)

0:31:32 Rangan Chatterjeesupportedmoderate

The February 2017 SMILES randomized controlled trial in Australia showed that patients with moderate to severe depression who followed a modified Mediterranean diet for 12 weeks achieved a statistically significant improvement in remission compared to those in a social support group.

"including that SMILES trial—did you see that from February 2017 in Australia?—that randomized controlled trial showing that patients with moderate to severe depression, the group who went on a modified Mediterranean diet versus the group who went on, I think, a social support structure for 12 weeks, had a statistically significant improvement in their remission." (said at 0:31:32)

The SMILES trial (Jacka et al., published in BMC Medicine in early 2017) was a 12-week, single-blind, randomized controlled trial conducted in Australia evaluating an adjunctive modified Mediterranean dietary intervention versus a social support control in 67 adults with moderate to severe depression. At 12 weeks, participants in the dietary intervention group achieved a statistically significant higher rate of remission (MADRS score <10) compared to the social support control group (32.3% vs. 8.0%, p = 0.028, NNT = 4.1).

supports: A randomised controlled trial of dietary improvement for adults with major depression (the… (BMC medicine 2017) · cited 1080x in the literature
"'SMILES' was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length... Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3-27.8)." (abstract, methods and results, passage verified)
pubmed full study (doi)

0:33:58 Rangan Chatterjeesupportedmoderate

Mechanistic research demonstrates that LPS may be a primary trigger in the development of insulin resistance and type 2 diabetes.

"And even something like type 2 diabetes, there's some really good mechanistic work that shows that LPS might be triggering—one of the root triggers in the development of insulin resistance, which then leads to type 2 diabetes." (said at 0:33:58)

The speaker accurately characterizes published mechanistic and preclinical research. Seminal animal studies (such as Cani et al., 2007) demonstrated that chronic subcutaneous infusion of lipopolysaccharide (LPS)—a state termed 'metabolic endotoxemia'—triggers low-grade systemic inflammation, hepatic insulin resistance, fasting hyperglycemia, and weight gain, mirroring diet-induced metabolic dysfunction. In human observational and clinical studies, elevated circulating LPS levels (metabolic endotoxemia) are consistently associated with insulin resistance and type 2 diabetes.

supports: Metabolic endotoxemia initiates obesity and insulin resistance. (Diabetes 2007) · cited 6572x in the literature
"Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor... When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice." (abstract, results)
pubmed full study (doi)
supports: Metabolic endotoxemia and diabetes mellitus: A systematic review. (Metabolism: clinical and experimental 2017) · cited 338x in the literature
"Most of the studies observed higher LPS or LBP concentrations in diabetic subjects than in healthy controls. T1DM and T2DM subjects presented higher mean fasting LPS of 235.7% and 66.4% compared with non-diabetic subjects, respectively." (abstract, results, passage verified)
pubmed full study (doi)

0:34:28 David Perlmutter (host)supportedhigh

LPS is the outer covering of gram-negative bacteria that reside in the gut and is an initiator of inflammation.

"LPS is something in the gut; it actually is the covering over certain bacteria called gram-negative bacteria that live in the gut. So we shouldn't really find it in the bloodstream. When we find it in the bloodstream, it got there somehow, and it means the gut is leaky. LPS is a powerful initiator of inflammation." (said at 0:34:28)

The speaker's statement accurately describes standard microbiological and immunological science. Lipopolysaccharide (LPS, also known as endotoxin) is the principal component of the outer membrane (covering) of Gram-negative bacteria residing in the intestinal tract. Under normal physiological conditions, the gut epithelial barrier restricts LPS translocation into systemic circulation. When intestinal barrier integrity is compromised (increased intestinal permeability or 'leaky gut'), LPS translocates into the bloodstream, where it binds Toll-like receptor 4 (TLR4) complexes and serves as a potent trigger of systemic inflammatory signaling.

supports: Lipopolysaccharides derived from gram-negative bacterial pool of human gut microbiota prom… (International reviews of immunology 2022) · cited 65x in the literature
"Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria. It is found from intestinal microbes in the circulatory system and considered a trigger factor for low-grade inflammation in obesity. High-fat diet intake and its related obesity can cause gut microbiota disorder, leading to increased gut permeability, paracellular absorption and transcellular transport of endogenous endotoxin in the cardiovascular system." (abstract, background, passage verified)
pubmed full study (doi)
supports: The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation. (Chronic stress (Thousand Oaks, Calif.) 2022) · cited 300x in the literature
"Lipopolysaccharide (LPS) is the main structural component of the outer membrane of most Gram-negative bacteria and has diverse immunostimulatory and procoagulant effects." (abstract, background, passage verified)
pubmed full study (doi)
supports: Gut barrier dysfunction and endotoxemia in heart failure: A dangerous connubium? (American heart journal 2023) · cited 29x in the literature
"Indeed, increased blood levels of lipopolysaccharide (LPS), a glycolipid of outer membrane of gut gram-negative bacteria, have been detected in patients with diabetes, obesity and nonalcoholic fatty liver disease or in patients with established coronary disease such as myocardial infarction or atrial fibrillation, suggesting endotoxemia as aggravating factor via systemic inflammation and eventually vascular damage. Upon interaction with its receptor Toll-like receptor 4 (TLR4) LPS may, in fact, act at different cellular levels so eliciting formation of proinflammatory cytokines or exerting a procoagulant activity." (abstract, background, passage verified)
pubmed full study (doi)

0:43:23 Rangan Chatterjeesupportedlow

Traditional Okinawan communities consumed an 80% carbohydrate diet while having low rates of type 2 diabetes, insulin resistance, and Alzheimer's disease.

"and we look at those Okinawan communities where they're having, you know, an 80% high-carbohydrate diet, and it's sort of kind of trying to figure out, "Well, how can that be, that they could have such a high-carb diet, certainly from the research I've read, yet not get type 2 diabetes, not have insulin resistance, not to have Alzheimer's?"" (said at 0:43:23)

Historical nutritional surveys of traditional Okinawan cohorts (such as the 1949 post-war nutritional data documented in the Okinawa Centenarian Study) show that the traditional Okinawan diet derived approximately 80% to 85% of total caloric energy from unrefined carbohydrates, predominantly orange-yellow sweet potatoes, with very low fat (~6%) and moderate-to-low protein intake. Despite this high-carbohydrate intake, these populations maintained a low overall glycemic load, caloric restriction, and exceptionally low rates of age-associated metabolic and neurodegenerative conditions, including type 2 diabetes, cardiovascular disease, and dementia, along with remarkable longevity. Certainty is graded as low due to reliance on observational, historical survey, and ecological cohort data.

supports: The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich … (Journal of the American College of Nutrition 2009) · cited 309x in the literature
"A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables." (abstract, results, passage verified)
pubmed full study (doi)
supports: Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. (Mechanisms of ageing and development 2014) · cited 265x in the literature
"The traditional diet in Okinawa is anchored by root vegetables (principally sweet potatoes), green and yellow vegetables, soybean-based foods, and medicinal plants... Overall, the important shared features of these healthy dietary patterns include: high intake of unrefined carbohydrates, moderate protein intake with emphasis on vegetables/legumes, fish, and lean meats as sources, and a healthy fat profile... This may reduce risk for chronic age-associated diseases and promote healthy aging and longevity." (abstract, results)
pubmed full study (doi)

No source found (not proven false)

0:33:28 David Perlmutter (host)unverifiedvery low

Elevated levels of LPS are observed in autism, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and major depressive disorder.

"So we see elevated LPS in autism, in Alzheimer's, in amyotrophic lateral sclerosis, and, as I mentioned, in major depressive disorder." (said at 0:33:28)

No published record matching the claim that elevated levels of lipopolysaccharide (LPS) are observed across autism, Alzheimer's disease, amyotrophic lateral sclerosis, and major depressive disorder 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.