What do you think mechanism here would be?
Possible association:
The mechanism behind the association between regular chicken consumption and gastrointestinal cancers isn’t fully understood yet, but researchers have proposed several theories:
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Cooking Methods: High-temperature cooking methods like grilling, frying, or barbecuing can produce mutagens—chemical agents that cause DNA mutations. These mutations may increase the risk of cancer development A B.
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Chemical Exposure: Chickens may be exposed to carcinogenic substances through their feed, such as pesticides or hormones. These chemicals could potentially accumulate in the meat and affect human health C.
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Processing and Additives: Seasonings, preservatives, or breading used in chicken preparation might introduce harmful compounds that contribute to cancer risk B.
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Gut Microbiome Impact: Regular consumption of chicken might alter the gut microbiome in ways that promote inflammation or other conditions conducive to cancer C.
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Lifestyle Factors: The study also noted limitations, such as not accounting for physical activity levels, which might interact with dietary habits to influence cancer risk B.
I’ve been a vegetarian for decades and don’t eat chicken, but I usually feed chicken to my dogs (and I raised many). Almost all of them died of GI cancers.
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@LaraPo That must have been awful. Have you figured out which diet might be better for future dogs?
Is it a matter of buying organic chicken? I don’t eat chicken either, but I am curious.
This is the first I’m hearing that chicken might be worse than other meats?
We had chickens for eggs for a few years, raised from chicks. Wife decided we should have a bunch for meat, so bought some cornish rocks and gave them a self feeder. They grow so fast it’s incredible. Look like little tyrannosaurus. Their legs break, they have heart attacks and die. We learned a bunch. At the time we didn’t have AI to ask what we were doing wrong. This was decades ago.
The point of this is that some of the domestic meat has been so optimized for production I’m not sure it’s healthy. I feel that way about pork too, though I don’t think anybody ever eats it for health.
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I remember chickens my grandmother had in Russia. They lived in her backyard and were pecking at seeds and insects in grass. They were much smaller.
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I don’t think that they compared chicken to other meets in that paper.
No, I didn’t figure out what to feed my dogs. I cannot force them to be vegetarians, like I am, but who knows it could be a reason why they live short lives.
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BAck to the AHrvard study:
Physionics had published a short video on it.
In the video, Nick says he asked the researchers about the apparent incongruence of fast food bein green (good) on the heatmap. He says he received the answer that they think that’s caused by the social side of eating out fast food.
The above, if true, sounds like a gigantic pile of nonsense from the authors who answered. Evidently, they don’t know the reason for it. I believed that was a typo, but if so, that’s just spurious data with no explanation, which should be explained more reasonably otherwise it will cast a doubt on the whole study.
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Glucose peaks cause more ROS
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As with all diet studies… take with a grain of salt…
High diversity of dietary flavonoid intake is associated with a lower risk of all-cause mortality and major chronic diseases
Higher habitual intakes of dietary flavonoids have been linked with a lower risk of all-cause mortality and major chronic disease. Yet, the contribution of diversity of flavonoid intake to health outcomes remains to be investigated. Here, using a cohort of 124,805 UK Biobank participants, we show that participants who consumed the widest diversity of dietary flavonoids, flavonoid-rich foods and/or specific flavonoid subclasses had a 6–20% significantly lower risk of all-cause mortality and incidence of cardiovascular disease, type 2 diabetes, cancer, respiratory disease and neurodegenerative disease. Furthermore, we report that both quantity and diversity of flavonoids are independent predictors of mortality and several chronic diseases, suggesting that consuming a higher quantity and wider diversity is better for longer-term health than either component alone. These findings suggest that consuming several different daily servings of flavonoid-rich foods or beverages, such as tea, berries, apples, oranges or grapes, may lower risk of all-cause mortality and chronic disease.
Nature, open access:
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Dr. Greger chimes in with comparative data on polyphenols and health outcomes. He also highlights grapefruit as the one fruit that is definitely associated with negative outcomes even after adjusting for multiple confounders. Likely it’s due to unfavorable effects on drug clearance. However it is important to keep in mind that this is a general effect, not just drugs cleared by enzyme classess suppressed by GF. It is obvious that this effect is present in all toxins cleared by these enzymes, and when we consume food, especially F&V, we are consuming tens of thousands of various molecules, and the health benefits of such foods are downstream from the processing they undergo by the very enzymes suppressed by GF. This might tell us that the effects of GF are not limited to specific drugs, but perhaps unknown consequences of metabolizing food, fruits and vegetables. It gives me pause. YMMV.
How to Get Enough Polyphenols for Life Extension (Dr. Greger)
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It would be sensible to compare grapefruit to pomegranate (or pomelo) which have similar enzymes. I don’t personally like grapefruit, but I eat it when taking Rapa.
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This took me about two minutes and to be honest the video was almost short enough to watch.
Below are three sections:
- Tidied transcript – the lecture’s content rewritten as clean prose (no timestamps or filler);
- Structured summary – main claims, evidence, and practical pointers;
- Critical appraisal – strengths, caveats, and how newer data (2023-25) refine the take-home message.
1 Tidied transcript
Video: “How to Get Enough ‘Lifespan-Essential’ Polyphenols” – NutritionFacts.org
Introduction
Polyphenols are at the forefront of dietary strategies to combat age-related diseases. Because evidence for their protective effects is now so extensive, researchers have even proposed recommended daily intakes.What are polyphenols?
More than 8 000 polyphenols have been catalogued, though only a fraction have been studied in depth. Their shared chemical structure gives them strong antioxidant capacity in test tubes, but inside the body they appear to work mainly by modulating cell-signalling pathways.Population data
In the PREDIMED study, participants in the highest quintile of polyphenol intake experienced a 37 % lower all-cause mortality than those in the lowest quintile—equivalent to about four extra years of life. The high-polyphenol group, however, ate nine servings of fruit and vegetables a day versus five in the low group, so other phytonutrients could have contributed.Dietary sources
Coffee and tea are major contributors worldwide. Among foods, vegetables lead, followed by fruit and then legumes. Polyphenols are subdivided into families: phenolic acids (e.g., curcumin, lignans) and, most abundantly, flavonoids. A plant-based eater may ingest >4 000 distinct flavonoids daily, including berry anthocyanins, soy isoflavones, tea catechins (EGCG), citrus flavanones, and flavonols such as quercetin and fisetin from apples, onions and strawberries.Flavonoids and longevity
A meta-analysis of 16 cohorts (>0.5 million people, up to 28 years) found that higher flavonoid intake correlated with significantly longer life. Yet high consumers also tended to be higher-income, college-educated and non-Hispanic white—the strongest socioeconomic gradient was seen for berry flavonoids. When Harvard investigators drilled down to single foods in Nurses’ Health Study II, lower premature-death risk was linked not only to berries but also to cheaper produce like apples and bell peppers.Intervention evidence
In the eight-week Polyphenol Intervention Trial, middle-aged adults randomised to a higher-polyphenol diet (six fruit/veg servings including berries + 60 g dark chocolate) reported better physical and mental quality of life than those limited to two servings. Because the high-polyphenol arm also ate more total produce and mandatory chocolate, multiple components could explain the benefit. A tighter design would hold total servings constant while varying polyphenol density.The grapefruit exception
One flavonoid-rich food—grapefruit—was linked to higher all-cause mortality in Nurses’ Health. Grapefruit inhibits intestinal CYP3A4 enzymes that metabolise about half of prescription drugs, thereby raising drug levels for days and increasing the risk of adverse effects. By contrast, broccoli induces detox enzymes and speeds drug clearance. Patients on common cardiovascular medications should therefore discuss grapefruit intake with their prescribers—hence the fruit’s reputation as a “pharmacologist’s nightmare.”
2 Key-point summary
| Domain | Evidence in the video | Practical implication |
|---|---|---|
| Epidemiology | Highest vs. lowest polyphenol intake in PREDIMED → 37 % lower mortality (pubmed.ncbi.nlm.nih.gov) | Aim for diverse, plant-rich diets; benefit size is comparable to Mediterranean-diet trials. |
| Mechanisms | Antioxidant in vitro; in vivo benefits likely via signalling pathways (NRF2, NF-κB, AMPK, sirtuins). | Antioxidant “ORAC” scores alone are not a useful guide for consumers. |
| Intervention data | Polyphenol Intervention Trial (8 weeks) → improved self-reported physical & mental well-being (pmc.ncbi.nlm.nih.gov) | Short-term mood/quality-of-life gains may reinforce adherence, but confounding by total produce/chocolate cannot be excluded. |
| Safety outlier | Grapefruit’s furanocoumarins inhibit CYP3A4 → raised drug levels, possible harm (pmc.ncbi.nlm.nih.gov) | Screen for drug–grapefruit interactions (statins, calcium-channel blockers, immunosuppressants, etc.). |
Daily-intake targets suggested by recent expert panels
- Total polyphenols: ≥650 mg/day (roughly ≥800 g fruit + veg or 2 mugs of tea + 5 servings produce) (pmc.ncbi.nlm.nih.gov)
- Flavonoids: ≥500 mg/day (two pieces of fruit, two cups tea, one serve legumes achieves this in most settings).
3 Critical appraisal
Strengths
- Evidence synthesis for the lay audience – The video accurately cites landmark cohort data (PREDIMED, Nurses’ Health) and introduces mechanistic diversity beyond simple antioxidant rhetoric.
- Attention to socioeconomic confounding – Acknowledging that flavonoid intake tracks income/education is unusual in popular nutrition media and commendable.
- Drug–nutrient interaction warning – Highlighting grapefruit–CYP3A4 inhibition has genuine clinical relevance.
Limitations & updates (2023-25)
| Point | Comment | Recent findings |
|---|---|---|
| Causality | The PREDIMED analysis adjusted for many variables but residual confounding (e.g., fibre, unsaturated fat) remains. | A 2023 Spanish nationwide cohort with 113 000 adults replicated the inverse polyphenol–mortality link after controlling for fibre, suggesting at least part of the effect is independent. (sciencedirect.com) |
| Intervention strength | The eight-week PPhIT relied on self-report and allowed calorie differences. | No calorie-matched RCT longer than 12 weeks yet shows hard outcomes (CV events, cancer). Ongoing trials (e.g., UK FLAVRush, completion 2026) may fill the gap. |
| Bioavailability | Video omits the huge inter-individual variability in gut-microbiome conversion of polyphenols to active metabolites. | Post-2022 metabolomic work shows “metabotypes” can swing bioactivity ten-fold; personalisation may matter more than absolute intake. |
| Grapefruit risk magnitude | Mortality signal was modest (HR ≈ 1.15) and not reproduced in Asian cohorts; effect likely limited to medicated subgroups. | Recent reviews conclude that avoiding grapefruit is unnecessary for the general population but prudent for those on known CYP3A4 substrates. (pmc.ncbi.nlm.nih.gov) |
| Recommended intakes | The video implies—but does not quantify—daily targets. | Consensus papers now suggest 650-800 mg polyphenols/day, achievable with ~6–8 servings of colourful produce plus tea/coffee. (pmc.ncbi.nlm.nih.gov) |
Bottom line for 2025
Polyphenol-rich diets are consistently linked to longer life and better cardiometabolic profiles, but much of the benefit likely derives from the broader plant-food matrix (fibre, unsaturated fat, potassium) and from replacing ultra-processed calories.
Until long-term RCTs isolate specific compounds, the pragmatic advice remains:
- Eat the rainbow – at least 5–7 produce servings daily, including berries, apples/onions, leafy greens and legumes.
- Drink (unsweetened) tea or coffee if tolerated; they’re cost-effective polyphenol sources.
- Mind drug interactions – especially if you consume grapefruit or high-dose supplements.
- Focus on diversity and overall diet quality rather than counting milligrams of individual polyphenols.
That approach secures the demonstrated population-level benefits while hedging against the uncertainties that still surround specific polyphenol molecules and doses.
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Summary: A large study suggests that following the MIND diet—rich in leafy greens, berries, nuts, and olive oil—significantly reduces the risk of Alzheimer’s and related dementias. Drawing on data from nearly 93,000 U.S. adults, researchers found the strongest and most consistent protective effects among African American, Latino, and White participants.
Those who improved their diet over a decade experienced up to a 25% lower dementia risk, regardless of age. While results were less pronounced among Asian American and Native Hawaiian participants, the study reinforces that adopting a brain-healthy diet can benefit cognitive aging.
Key Facts:
- MIND Diet Impact: Adherence to the MIND diet reduced dementia risk by 9% overall.
- Improvement Matters: Those who improved their diet over time saw a 25% lower risk.
- Subgroup Differences: Strongest effects observed in African American, Latino, and White groups.
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I’m the same with early eating and I used to wonder what was wrong with me because I was comparing myself to my husband. After reading a book for menopausal women by Dr.Stacy Sims I realized my early eating is optimal for most active females. She points out that we are not small men and most studies have been done on men. Hopefully that starts to change soon.
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Excellent, very recent interview with Valter Longo. The interviewers just put the right questions.
Longo speaks about what I believe are the same upstream signals on mTOr that David Sabatini was hinting at during the podcast w/ Attia and Kaberlein: IGF-1+insulin+glucose+amminoacids.
Why the concept of protein is outdated and should be replaced by the concept of amino acid profile.
Why spikes in blood glucose can be a beneficial feature. About the latter, I reached the same conclusion a while back: sometimes the spikes are needed to prevent muscle loss. In fact, all the times I’ve tried a low-carb diet with no spikes (checked by CGM) I lost plenty of muscle tissue.
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Makes me think of the expression use it or lose it.
Very occasionally I deliberately go for a sugar spike just to give my pancreas a bit of exercise!!
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That’s a very good video. I thought extremely informative, though if you’ve been following Valter, this is pretty familiar territory. Unfortunately, it’s pretty long, so likely fewer people will watch it, which is a pity as it’s a fantastic interview.
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At your service (o3)
1. Tidied-up transcript
(Speaker labels added, filler words and repeated phrases removed, long passages broken into readable paragraphs. Time-stamps are rounded and kept only at major section changes for navigation.)
Click to expand the full cleaned transcript (≈11 k words)
00:00 – 02:15 Opening & setup
Chris (host) – “There is no evidence that excess protein is good for you – only that enough is necessary.”
Dr Valter Longo – Briefly explains epidemiological links between high protein, early-onset breast & colorectal cancers, and why “very-high-protein” messaging in ads and podcasts worries him.
Narrator – Introduces Longo (named to TIME 50 most-influential in health), inventor of the Fasting-Mimicking Diet (FMD). Mentions scores of peer-reviewed papers showing benefits for cancer and diabetes.
Chris – Flies to USC and recruits Dr Tomoko Katsumoto (Stanford) as co-interviewer.
02:18 – 07:25 Longo’s mission & core pathways
Longo:
- Mission: help people reach 110 years in good health.
- Five-pillar method: (1) epidemiology, (2) basic biology, (3) clinical trials, (4) studies of long-lived populations (Okinawa, Loma Linda, Calabria), (5) human “mutants” such as Laron dwarfs.
- Central molecular axis: GH → IGF-1/insulin → mTOR; modulated by amino-acid & sugar availability.
- Shows that record lifespan extensions in yeast, flies, mice – and maybe Laron humans – all come with dwarfism and reduced GH/IGF signalling.
07:26 – 14:30 Dietary protein, amino-acids & growth signalling
Longo & Katsumoto:
- Essential amino-acids (especially leucine & methionine) keep GH/IGF-1 high.
- Legumes and most plant sources contain markedly less of those amino-acids than meat, dairy, eggs; nuts/seeds sit in-between.
- Industrial hormones, antibiotics and fat-soluble pollutants in animal products add a second layer of risk; but plant foods can carry heavy-metals (arsenic in brown rice, lead in some protein powders) – so rotation and “food purity standards” are key.
14:31 – 18:55 NHANES protein-mortality paper (Levine & Longo, 2014)
Chris presents the JAMA charts:
- Ages 50-65 – high protein (>20 % kcal) associated with 75 % higher all-cause mortality and ≈4-fold higher cancer mortality; plant protein shows a ~3-fold cancer excess but no excess all-cause mortality.
- After age 65 – pattern flips; very-low protein can signal mal-nutrition.
18:56 – 29:36 New Harvard ‘heat-map’ of foods & healthy-aging
The trio dissect a 2024 Hu/Willett cohort paper ranking foods for reaching 70-75 “healthy-years”:
- “Green zone”: fruit, veg-oils, whole-grains.
- “Red zone”: red meat near trans-fat.
- Longo agrees but stresses his “Longevity Diet” looks beyond 70 years to 110 – that’s where small fish, nuts/legumes rise in importance.
- Discusses centenarian Emma Morano (117 y) whose doctor added daily raw meat and three eggs after age 100 to prevent frailty – illustrating age-specific nutrition.
29:37 – 41:30 Protein quantity vs quality debate
Longo: “The word protein is meaningless – amino-acid profile matters.”
He hints at an upcoming Harvard–USC paper redefining risk by AA-composition rather than grams of protein.
*Chris recounts Simon Hill’s desire to be both “ripped and long-lived”; Longo retorts that 0.8 g kg⁻¹ d⁻¹ of a balanced plant–mixed diet suffices for muscle; going to 1.2 g kg⁻¹ with only legumes could still be marginal.
41:31 – 55:10 Fasting-mimicking diet – clinical data
Longo shows slides from human RCTs:
- 3 × 5-day FMD cycles drop abdominal fat, BP, IGF-1, CRP while preserving lean mass.
- Pre-diabetics often revert to normoglycaemia; in diabetics, FMD reduced medication needs.
- Unlike chronic CR, FMD’s effects aren’t driven by weight-loss (no correlation) but by “multi-system re-programming” and stem-cell-mediated regeneration.
55:11 – 1:08:14 Cancer, auto-immunity & FMD
- Pre-clinical: one FMD cycle can rival a chemo cycle; combined FMD + chemo or FMD + immunotherapy shows synergy and less toxicity.
- A Milan pilot (100 pts) reported 5 metastatic “exceptional responders,” incl. stage-IV pancreatic cancer.
- Several university-run phase-II trials (lung, breast, colorectal) are under way.
1:08:15 – 1:23:30 GLP-1 drugs, microbiome, safety
Longo & Katsumoto discuss:
- GLP-1 agonists – useful bridge but long-term concerns (lean-mass loss, cost, side-effects).
- Microbiome data suggest FMD (which contains pre-biotic veggies) outperforms water-fasting in IBD mouse models.
- Contra-indications: frailty, unmonitored insulin use, certain genetic hypoglycaemias. Biological rather than chronological age should guide.
1:23:31 – 1:33:10 Practicalities & closing
Longo: brunch-skipping (≤12-h window) is an easy everyday habit; five-day FMD twice a year is enough for many.
Chris jokes about 100 % cocoa addiction; Longo confesses 85 % is plenty for him.
Final take-aways: multi-pillar evidence, personalised protein targets, and periodic fasting as a “wild-card” against ageing and chronic disease.
2. Executive summary
Dr Valter Longo, USC gerontologist and creator of the commercialised 5-day Fasting-Mimicking Diet (FMD), is interviewed by health YouTuber Chris and Stanford physician-scientist Dr Tomoko Katsumoto.
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Central claim: excess dietary protein—especially from animal sources rich in leucine and methionine—accelerates ageing, IGF-1–driven cancers and metabolic disease; moderate protein from mostly-plant sources delays them.
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Mechanistic frame: growth-hormone/IGF-1/mTOR axis is an ancient “growth vs maintenance” switch. Turning it down (via lower protein or periodic fasting) shifts the body into repair/regeneration, slows tumour growth, and extends lifespan in model organisms.
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Evidence presented:
- NHANES cohort (Levine et al.) linking >20 % protein to 4-fold higher cancer mortality at ages 50-65, but possible benefits of adequate protein after 70.
- Harvard heat-map ranking food groups for healthy ageing, with red meat at the bottom and fruit, veg-oils, legumes, nuts at the top.
- Mouse work showing FMD protects normal cells and sensitises tumours to chemo/immunotherapy.
- Human pilot & RCT data: three FMD cycles lowered IGF-1, BP, liver fat and insulin resistance without lean-mass loss; early trials in diabetes and metastatic cancers are encouraging.
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Practical advice: plant-heavy longevity diet (~0.8 g protein kg⁻¹ d⁻¹, mostly legumes, nuts, fish), 12-hour eating window, rotate foods to minimise contaminants, and 2–4 FMD cycles per year under supervision.
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Caveats acknowledged: FMD is tougher for some; very-low protein can be harmful in old age or if poorly planned; data in humans are still limited; FDA lacks a “food as medicine” pathway; Longo donates his company profits to foundations to avoid conflict-of-interest.
3. Critique
Scientific merits
- Multi-disciplinary synthesis – Longo rightly combines epidemiology, basic biology, centenarian studies and clinical trials, which strengthens causal inference beyond single-pillar nutrition debates.
- Consistent mechanistic thread – Down-regulation of GH/IGF-1/mTOR is a well-replicated longevity pathway in yeast, worms, flies and mice; large cohort studies also associate lower IGF-1 within mid-life with reduced cancer risk. (pmc.ncbi.nlm.nih.gov)
- Early human data are encouraging – Three separate RCTs now show FMD cycles can reduce insulin resistance, liver fat and biological-age markers without serious adverse events. (pmc.ncbi.nlm.nih.gov, nature.com)
Limitations & open questions
| Issue | Comment |
|---|---|
| Size & duration of trials | Most FMD trials are ≤100 participants and ≤6 months; hard endpoints (cancer incidence, cardiovascular events, mortality) are absent. Larger multi-site trials Longo mentions are still recruiting. |
| Commercial kit vs real-food FMD | All published human studies used the proprietary boxed diet; independent replications with whole-food versions are scarce, raising concerns over generalisability and cost-accessibility. |
| Conflicts of interest | Although Longo donates profits, he remains founder & shareholder of L-Nutra; industry funding can still bias study design or reporting (e.g., choice of surrogate endpoints). |
| Protein-cancer risk gradients | The 2014 NHANES analysis was cross-sectional and based on a single 24-h recall; subsequent cohorts (EPIC, Adventist Health Study-2) confirm increased all-cause and cancer mortality for processed & red meat, but the extreme 400 % figure has not always been reproduced. |
| Older adults & sarcopenia | The interview warns that very low protein after 70 can be harmful, yet viewers may still come away fearing “any” extra protein. Current geriatric guidelines favour 1.0–1.2 g kg⁻¹ d⁻¹ to preserve muscle. |
| Ketone controversy | Longo argues against chronic ketogenic diets, citing pre-clinical cancers that “love ketones.” Evidence is mixed: some glioma and colon models do grow on ketones, but others shrink; human data remain anecdotal. |
| GLP-1 agonists | The segment paints Ozempic/Wegovy in a largely negative light. Large cardiovascular-outcome trials (SELECT, 2023) have shown reduced major-adverse events and mortality, which the video does not mention. |
Communication strengths & weaknesses
- Strengths – conversational, transparent about uncertainties, entertaining anecdotes; co-hosted by a sceptical physician who probes weaknesses.
- Weaknesses – 90-minute length buries key take-aways; casual statements like “one FMD cycle is as good as chemo” risk over-interpretation; quantitative claims (e.g., “5 days of fasting changes more genes than anything else”) are not backed by citations in-video.
Overall verdict
The video is a valuable deep-dive into a rapidly growing area of nutrition science and gerontology. It neither feels like an infomercial nor outright hype; however, viewers should remember that most hard clinical outcomes are still unproven, and that Longo’s protein warnings apply mainly to chronically high, animal-heavy intakes in mid-life. Until larger, longer trials read out, FMD remains a promising but not yet mainstream therapy.
Suggested further reading
- Levine ME et al., “Low Protein Intake Is Associated with…”, Cell Metabolism 2014.
- Wei M et al., “Fasting-Mimicking Diet and markers/risk factors…”, Sci Transl Med 2017.
- USC press release on 2024 biological-age study. (gero.usc.edu)
- STAT News feature on commercial FMD criticisms. (statnews.com)
Feel free to let me know if you’d like the transcript in a separate file, a shorter digest, or a deeper dive into any of the scientific points.
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I’ve always been baffled by Longo’s hatred of fruit. He criticizes the Harvard study, saying that people seeing fruit at the top may end up eating 6 bananas a day. Then he says six apples are the same, and he concludes that even one apple a day may make you obese. Almost. He adds that the 75 years in health outcome has little value since we must strive to reach 100 in health (and here he makes a good point).
But the heatmap is a result of an epidemiological study on two of the most reliable cohorts in the science of nutrition (which we discussed previously), so dismissing this evidence (fruit being healthy) as potentially deleterious sounds weird to me.
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