Resveratrol: the $720M mistake 🧬

LONGEVITY LATEST

The Evidence-Based Edge on Living Longer and Better

Issue 05

👋 Welcome to Issue 05

This week, we’re talking about the slow fire — the quiet, chronic inflammation that simmers for decades behind cardiovascular disease, neurodegeneration, and most of what we call “ageing.” Three popular plant compounds claim to fight it. We graded them, and the results were uneven.

In this issue:

🔬 Top 3: Curcumin, resveratrol, and sulforaphane — graded

🎯 Spotlight: Fisetin — a natural senolytic worth watching

🚨 Hype Check: That “3.23 years younger” study

🥗 Superfood: Turmeric root

🔍 Deep Dive: Inflammageing

⚡ Biohacking Corner: Red light therapy

🔬 Top 3 Interventions Under the Microscope

1. Curcumin (Turmeric Polyphenol) — Evidence Grade: B

What it is. The main bioactive in turmeric. Curcumin inhibits NF-κB (the cell’s inflammation master switch) and activates Nrf2 (its antioxidant defence system). It also touches mTOR, AMPK, and sirtuin pathways — which is partly why it’s attracted so much research attention. The problem is getting it into your body: native curcumin has roughly 1% oral bioavailability. You need an enhanced formulation (Meriva, Theracurmin, or similar) for meaningful systemic levels.

Human evidence. There’s a lot of it — and it’s messy. A 2024 systematic review (Jafari et al., 103 RCTs, n=7,216) rated evidence as high for effects on CRP and fasting blood sugar, moderate for body composition. A 2025 umbrella review (Frontiers in Pharmacology, 25 meta-analyses) confirmed reductions in CRP (seven of ten analyses), IL-6 (five of eight), and TNF-α (six of nine). Dose-response data from 66 RCTs suggests ≤800 mg/day for up to ten weeks hits the sweet spot. The anti-inflammatory signal is real — but no trial has measured whether curcumin actually extends healthspan or reduces mortality.

Cautions. Generally well-tolerated. Can interact with blood thinners (warfarin, aspirin). Standard turmeric powder won’t cut it — you need a bioavailability-enhanced form.

Personal note: I’ve been taking 500 mg/day of a phospholipid-complexed curcumin for six months. My hs-CRP went from 1.8 to 0.6 mg/L. I can’t prove curcumin caused that — I changed several things simultaneously — but the trajectory is encouraging.

Takeaway. A useful anti-inflammatory with more RCT data than most supplements — but nobody’s shown it moves the needle on lifespan. Evidence Grade B.

2. Resveratrol (Stilbene Polyphenol) — Evidence Grade: C

What it is. The compound that launched a thousand supplements. Found in grape skins and red wine, resveratrol was catapulted to fame by David Sinclair’s 2006 mouse work showing it could activate SIRT1 and mimic caloric restriction. What happened next is a cautionary tale for the entire longevity field.

Human evidence. More than 200 clinical trials later, the picture is sobering. A 2024 systematic review (Brown et al., International Journal of Molecular Sciences) found “no conclusive clinical evidence to advocate its recommendation in any healthcare setting.” That said, resveratrol isn’t inert — it reliably reduces CRP and IL-6 and improves some metabolic markers across multiple trials. But the longevity thesis has collapsed: a 2020 CRISPR study showed it causes cellular stress without activating SIRT1 in normal human cells. GlaxoSmithKline spent $720 million developing SIRT1-targeted drugs, then walked away. The NIH Interventions Testing Program found it didn’t extend mouse lifespan either.

Cautions. Safe under 1 g/day. Poor bioavailability. Interacts with CYP3A4 substrates.

Takeaway. If you’re taking resveratrol for sirtuins and caloric restriction mimicry, the evidence says otherwise. Modest anti-inflammatory effects, but at £30–60/month you’re paying for a collapsed thesis. Evidence Grade C.

3. Sulforaphane (Isothiocyanate) — Evidence Grade: B

What it is. Here’s where things get interesting. Sulforaphane comes from glucoraphanin in cruciferous vegetables — broccoli sprouts are the richest source (we featured them in Issue 03’s Superfood). It’s the most potent natural activator of the Nrf2/Keap1 pathway, which controls over 200 cytoprotective genes. And unlike curcumin and resveratrol, it actually gets absorbed: roughly 80% oral bioavailability.

Human evidence. A 2025 review catalogued 84 registered clinical trials, 39 published (Saito et al., Journal of Nutritional Science). In healthy subjects, broccoli sprout consumption reduced leukocyte ROS and p38 MAP kinase signalling. Sulforaphane upregulates NQO1 and HO-1, key Phase II detoxification enzymes. A head-to-head comparison (Houghton, 2016) confirmed it activates Nrf2 more potently than curcumin, silymarin, or resveratrol. A 2024 clinical trial in HIV patients (Giron et al., Frontiers in Nutrition) showed CRP reductions with excellent tolerability.

Cautions. Mild GI effects (gas, bloating). If supplementing, look for glucoraphanin with added myrosinase — without the enzyme, conversion to sulforaphane is poor.

Personal note: I eat broccoli sprouts three to four times a week with a pinch of mustard seed powder to boost the myrosinase conversion. It’s one of the few cases where I think the whole food genuinely outperforms the supplement.

Takeaway. The clear winner of this trio. Superior bioavailability, the most potent Nrf2 activation of any natural compound, and a clinical evidence base that’s growing fast. Evidence Grade B — and if the current trial pipeline delivers, this one could move to an A.

🎯 Spotlight Treatment: Fisetin

A senolytic with remarkable mouse data — and a human evidence gap that matters.

Fisetin is a flavonol found in strawberries, apples, and onions. In 2018, a team led by James Kirkland at the Mayo Clinic screened ten flavonoids for senolytic activity — the ability to selectively kill senescent cells, those damaged “zombie” cells that accumulate with age and spew inflammatory signals into surrounding tissue. Fisetin came out on top.

Pros. Intermittent fisetin in aged wild-type mice extended both median and maximum lifespan (Yousefzadeh et al., 2018, EBioMedicine). A 2025 study (Murray et al.) found it reduced frailty and increased grip strength in old mice to a degree comparable to genetic clearance of senescent cells and the pharmaceutical senolytic ABT-263 — a striking result for a strawberry compound. In humans, a 2024 Mayo Clinic study in long-COVID patients (n=536) found those receiving fisetin (n=44) reported meaningful symptom relief with lower senescent cell markers.

Cons. No published human RCT has confirmed senolytic activity in healthy adults. A 2024 epigenetic clock study (Lee et al., Aging) found that six months of senolytic treatment actually accelerated some clock measures — a confusing result. Mouse doses translate to roughly 1,400 mg for a 70 kg human, far beyond the 40–100 mg in typical supplements. The “hit-and-run” intermittent dosing protocol that works in mice hasn’t been validated in people.

Bottom line: ⏳ Watch this space. We wouldn’t buy high-dose fisetin supplements yet — but we’re watching the clinical trial pipeline closely. If the human data matches even half the mouse results, this could be significant.

🚨 Hype Check: The Viral “3.23 Years Younger” Study

The Hype: A study claiming a diet and lifestyle programme reversed biological age by 3.23 years in eight weeks has gone viral — shared breathlessly across Instagram, longevity podcasts, and supplement brand marketing.

The Evidence: The study (Fitzgerald et al., 2021, Aging) is actually better designed than most that go viral — it’s a genuine randomised controlled trial, not an observational study or a press release. But look at the numbers. Total sample: 43 men aged 50–72. Treatment group: 18 people. The programme bundled diet changes, exercise, sleep guidance, relaxation practices, probiotics, and phytonutrients into a single eight-week package. The headline 3.23-year reduction was measured against controls using the first-generation Horvath clock (2013) — a tool that tracks chronological age patterns, not mortality risk. The within-group change (1.96 years) didn’t even reach statistical significance (p=0.066).

Why It’s Misleading: The entire treatment group would fit in a minibus. Six bundled interventions make it impossible to identify what drove the result. First-generation clocks are now considered less meaningful than mortality-trained tools like GrimAge or DunedinPACE. This is a hypothesis-generating pilot — not a conclusion.

Our Verdict: The lifestyle habits in this study — better sleep, more vegetables, regular exercise — are worth doing regardless. You don’t need an underpowered pilot to justify them. Skip the hype, keep the habits.

🥗 Superfood Spotlight: Turmeric Root

Supplemental curcumin gets the headlines, but whole turmeric root deserves its own moment. Beyond curcumin, turmeric contains over 200 bioactive compounds, including turmerone — a sesquiterpene with neuroprotective properties in preclinical models. The epidemiological signal is worth noting: India, where daily turmeric consumption averages 2–4 g, has roughly one-quarter the age-adjusted Alzheimer’s prevalence of the United States. Diet, genetics, and lifestyle all confound that comparison, but the pattern holds across multiple population studies. For practical use: cook with fresh or ground turmeric (golden milk, curries, dressings), always with black pepper — piperine boosts curcumin absorption by roughly 2,000% — and a fat source for uptake.

🔍 Deep Dive: Inflammageing — The Fire That Ages You

Your immune system has a dimmer switch, and with age it gets stuck on low burn. This chronic, low-grade inflammation — termed “inflammageing” by immunologist Claudio Franceschi — now sits alongside genomic instability and mitochondrial dysfunction as one of the central hallmarks of ageing. It’s persistent, systemic, and largely invisible until the damage shows up as disease.

All three compounds we graded this week target this process. In the full Deep Dive, we unpack why inflammation becomes chronic with age, which biomarkers are worth tracking, and what the evidence actually supports for cooling the fire.

🔍 Read the full Deep Dive: Inflammageing and Chronic Inflammation → [link]

⚡ Biohacking Corner: Red Light Therapy

A 2025 umbrella review of RCT meta-analyses (Systematic Reviews) evaluated photobiomodulation across 35 health outcomes and found moderate-certainty evidence for musculoskeletal pain and cognitive impairment. A controlled trial (Wunsch & Matuschka, n=136) showed significant collagen density and wrinkle improvements after 30 sessions. The mechanism: red and near-infrared light (630–850 nm) is absorbed by cytochrome c oxidase in mitochondria, boosting ATP production.

If you’re curious about trying it:

Get the wavelengths right. 630–660 nm (red) and 810–850 nm (near-infrared). Both are well-supported. Devices outside this range are unlikely to deliver the same benefits.

Be consistent. Three to five sessions per week, 10–15 minutes each. Most studies show benefits emerging after four to eight weeks.

Respect the dose curve. More isn’t better — PBM follows a biphasic dose-response. Follow manufacturer distance guidelines (typically 15–30 cm).

Know what it’s good for. Strong evidence for skin health, wound healing, and pain. Weaker evidence for cognitive enhancement and weight loss. Expect modest, genuine improvement — not transformation.

A note on devices: the market is largely unregulated. Many consumer panels don’t deliver research-grade irradiance. Check power density specs before investing.

📊 Reader Pulse

Results from Issue 04: We asked about your CoQ10 and omega-3 usage. 51% of you take omega-3 only, 8% CoQ10 only, 29% both, 12% neither. Omega-3s dominate — and our Grade A rating supports that instinct.

This week’s question: Which anti-inflammatory approach do you lean on most? Reply with: (A) Curcumin/turmeric, (B) Anti-inflammatory diet, (C) Exercise, (D) Nothing specific. Results next issue.

👋 See You Next Week

Next week: The gut microbiome and longevity — probiotics, fermented foods, and fibre graded. Berberine returns under the Spotlight with new trial data (a reader favourite from Issue 02). And the Hype Check examines a £300 “gut age” testing kit.

(Sharp-eyed readers may notice we’d teased an NAD+ IV drip Hype Check last issue — it’s coming in Issue 07. The gut age kit was too timely to pass up.)

Know someone who’d benefit from this? Forward it — word of mouth is how we grow.

Stay curious and stay healthy!

— Christian Thomsen, Editor

See you in Issue 06!

Disclaimer: Longevity Latest provides educational content based on published scientific evidence. It does not constitute medical advice. Always consult a qualified healthcare professional before starting any new supplement or intervention.

© 2025 Longevity Latest Newsletter