Dietary Supplements for Longevity Round-table Notes

Participants & Context

• Panelists: Nick (Physionic), Siim (Siimland), Greg Potter (host)
• Theme: Dietary supplements & drugs for lifespan and healthspan extension
• Format: Lightning-round questions ➜ deep-dive discussion on evidence, mechanisms, safety, timing, personal practice

Hypothetical “Give-Everyone-Two” Exercise

Rules

• Adults ≥30 y, unlimited budget, body-weight–adjusted dosing allowed
• Panelists pick up to 2 nutraceuticals/drugs for population-wide distribution

Picks

Underrated / Under-Recognised Agents

Supplements / Nutraceuticals

• Taurine : BP ↓, metabolic & exercise benefits, cheap & safe
• Curcumin : ↓ blood sugar, anti-arthritic, anti-inflammatory
• Lutein + Zeaxanthin : ocular & brain health; carotenoids accumulate in retina
• Astaxanthin : senolytic, UV-skin protection, ↓ inflammation, lifespan ↑ (12 % in ITP mice)
• Glucosamine (sulfate) : joint & potential longevity signal (epidemiology)

Single Underrated Drug (forced choice)

• Nick → GLP-1 RAs (potency > pill-fear stigma)
• Siim → Acute BP meds (short-term safety > hypertension risk) ± Metformin/Acarbose
• Greg → PDE-5 inhibitors (Sildenafil/Tadalafil) for vascular, brain & QoL benefits

Evaluation Framework for Geroprotectors

1. Evidence bar
   • Lifespan/healthspan data in ≥2 model species
   • Human mechanistic markers and functional outcomes (grip, VO2, bloods)
2. Hallmarks tackled (e.g., mitochondrial dysfunction, senescence, nutrient sensing)
3. Effect size & population (bigger effect in sicker/older groups)
4. Safety / cost / sourcing
   • Third-party testing (ConsumerLab, Informed-Sport)
   • Beware proprietary blends & under-dosing (e.g., NMN on Amazon: only ~15 % meet label)
   • Contaminants (drug analogues, plastics in fibre powders)
5. Form & bioavailability
   • Curcumin (BioCurc > turmeric); Rhodiola rosavins:salidroside ratio; Mg citrate ≠ Mg oxide
6. Timing variables
   • Circadian phase (sleep aids p.m.; stimulants a.m.)
   • Training days vs. rest (metformin, rapamycin, senolytics best on rest days)
   • Life-stage (creatine for elders, berberine for 60 + dysglycaemia, senolytics late-life)
7. Interactions
   • Exercise: High-dose Vit C/E, NAC, metformin may blunt hypertrophy / VO2 gains
   • Diet: tannins inhibit Fe absorption; calorie restriction mimetics redundant in CR dieters
   • Genetics: MTNR1B variant → exaggerated glucose rise on melatonin
   • Drugs: Piperine inhibits CYP3A4 etc.

Classic Essential-Nutrient Supplements (Quick Takes)

Omega-3 (EPA + DHA)

• 1 g/d in algae oil RCT ↓ epigenetic “Pace of Aging” (Horvath study, 70-y cohort)
• Brain, CV & anti-inflam; higher dosed for triglyceride lowering (≥2–4 g EPA-only)

Vitamin D3 ± K2

• Sun << supplements in high-melanin + high-latitude populations
• Hyper-dosing (≥50,000 IU) risks hypercalcaemia; aim to maintain 50–100\,\text{nmol·L}^{-1}

Multivitamins

• COSMOS trial: small cognitive retention after 3 y
• Benefits scale inversely with diet quality; men vs. pre-menopausal women need different Fe, etc.

Deep-Dive on Specific Geroprotectors

1. NAD Boosters

2. Resveratrol

• Early hype (Sinclair, SIRT1) ➜ French paradox claim
• Lifespan only in obese, coconut-oil-fed mice
• ↓ BP, glucose in diabetics; possible ↓ VO2 and androgens; cost vs. benefit modest

3. Lithium (micro-dose \approx0.3–1\,\text{mg/d})

• Ecological data: higher water Li → ↓ suicide, homicide, ↑ longevity
• Human micro-RCTs: slowed cognitive decline in MCI; neuroprotective; safety good at trace doses

4. Alpha-Ketoglutarate (AKG)

• Calcium-AKG (Rejuvant) 2 g time-release: retrospective 6-mo ↓ epigenetic age ~7 y
• Animal: +12–16 % median lifespan (f > m)
• Ongoing AEL RCT (grip, BP, inflamm.)
• Mechanisms: Krebs intermediate, stem-cell niche, collagen synthesis

5. Glycine & GLYC (Glycine + N-Acetyl-Cysteine)

• ITP: +4–6 % lifespan both sexes (methionine-glycine balance)
• Human: 3\,\text{g} pre-bed → ↑ sleep quality; 100\,\text{mg·kg}^{-1} GLYC in 70-y adults → ↑ glutathione, ↓ CRP, ↓ HOMA-IR, ↑ gait & grip
• Safe, sweet-tasting, inexpensive

6. Taurine

• Blood taurine ↓ 80 % from youth → 60 y
• Science 2023 multi-species paper: taurine repletion ↔ ↓ DNA damage, ↑ stem cell function, ↑ lifespan; supportive macaque data
• Human RCTs (6 g/d) ↓ BP, ↑ insulin sensitivity; exercise ergogenic

7. Ergothioneine

• Concentrated in oyster/king oyster mushrooms; transporter OCTN-1 allows tissue accumulation
• Pre-clinical: anti-oxidant, mito-protective, ↑ NAD, neuro- & cardio-protective; lifespan extension in C. elegans, mice (high dose)
• Early human trials: 5–25 mg/d underway; safety promising

8. Astaxanthin

• ITP: +12 % (mice)
• Human: UV-skin defence, ↓ triglycerides, ↑ endurance, potential fertility boost
• Typical dose 4–12\,\text{mg/d}; from Haematococcus pluvialis micro-algae; fat-soluble (take with meal)

9. Rapamycin & Exercise Interactions

• Inhibits mTORC1; lifespan ↑ in multiple species
• Concerns: may blunt muscle hypertrophy & immunity; pragmatic approach = weekly dose on non-training days

10. Metformin & Berberine

• ↓ VO2-max & mitochondrial adaptation to endurance training; beneficial for pre-diabetes/metabolic syndrome; rotate with training schedule

11. Urolithin A

• Mitophagy activator (pomegranate ellagitannin metabolite)
• Timeline Nutrition RCTs: only hamstring torque ↑; grip & endurance NS after 6 mo
• Cost >8\,\$\,\text{/day} at efficacious 1 g dose

12. Nobiletin

• Citrus peel polymethoxy-flavone; clocks re-alignment agent
• Takahashi lab: restores circadian amplitude; improves obesity & metabolic health in aged mice; human data awaited

Exercise–Supplement Interaction Cheat-Sheet

Timing & Life-Stage Guidelines

• Morning: majority of pills for adherence; stimulants; fat-solubles with breakfast lipids
• Evening/Pre-sleep: Glycine, Taurine, Melatonin, Magnesium bisglycinate
• Mid-life (40-60 y): Begin omega-3 focus, BP control, glucose moderators if biomarkers drifting
• Late-life (60 +): Creatine 5\,\text{g}, GLYC \approx15\,\text{g} combo, Senolytics pulses, low-dose Rapamycin

Practical Purchasing Checklist

1. Verify COA (certificate of analysis)
2. Dose math: match RCT dose (e.g., Taurine 6\,\text{g} > typical 500 mg capsules)
3. Form: e.g.
   • Astaxanthin esterified oil softgel
   • Calcium-AKG sustained-release tablets
4. Avoid: Proprietary blends without per-ingredient weight; “fairy-dust” actives
5. Batch test if athlete (WADA list)

Anecdotes & Miscellany

• Nick’s 3-h bodybuilding workouts & 90 lb weight gain ➜ “stupidest health phase”
• Siim crushed wardrobe doing lockdown pull-ups; confiscated caffeine powder at school
• Fun polls: AG1 vs. IM-08 vs. lose 30 → Nick would rather lose 30 than fund ads; Siim picks IM-08 (transparent labelling)
• “Is Brian Johnson healthiest man alive?” → Blood marker cherry-picking; impossible claim

Emerging “Watch List” Compounds

• C15:0 fatty acid (pentadecanoic) – low evidence, high marketing
• MPST-targeted ergothioneine derivatives – pending human work
• Senomorphic molecules (e.g., 17α-estradiol, sildenafil in ITP pipeline)
• Clock-modulators (REV-ERB agonists, nobiletin)

Key Numerical & Formula References

• GLYC effective dose \approx100\,\text{mg·kg}^{-1}\,(\text{glycine}+\text{NAC})
• Creatine maintenance 3–5\,\text{g/d}; loading 20\,\text{g/d} × 5 d
• Rapamycin trial pulses 5–10\,\text{mg weekly} (human off-label practice)
• Taurine lifespan mouse → human equivalent \sim3–6\,\text{g/d} (70 kg)
• Omega-3 CV dose \ge4\,\text{g EPA\/d}; general 1\,\text{g EPA+DHA}

Take-Home Heuristics

1. Fix diet, sleep, exercise first; supps = 5–10 % gain
2. Start cheap, proven, safe: Creatine, Omega-3, Magnesium, Glycine/Taurine
3. Escalate with age & biomarkers: Metformin, AKG, Rapamycin pulses, GLYC
4. Continuously reassess: new RCTs, personal labs, side-effects
5. Personalisation matters: genotype, sex, baseline status, medication stack, circadian pattern

“The people most likely to take a multivitamin are the least likely to need it.” – Greg Potter