THE EVIDENCE,
IN THE OPEN.

Evidence review

COMPOUND BY COMPOUND.

Each compound in this library is listed with its current evidence level, the interpretation applied to that evidence, its limitations and the primary references behind it.

1. 01

   Nicotinamide Riboside

   Evidence level 02

   Oral nicotinamide riboside raises blood NAD⁺ metabolites in humans in controlled trials. Functional outcomes across those trials remain inconsistent and population-dependent.

   LimitationsIncreased NAD⁺ availability is a biomarker, not a demonstrated clinical benefit.

   References

   • Trammell SAJ et al. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.Nature Communications 7:12948
   • Martens CR et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD⁺ in healthy middle-aged and older adults.Nature Communications 9:1286
   • Elhassan YS et al. (2019). Nicotinamide riboside augments the aged human skeletal muscle NAD⁺ metabolome.Cell Reports 28(7):1717–1728
2. 02

   Calcium Alpha-Ketoglutarate

   Evidence level 01

   Alpha-ketoglutarate sits at the junction of energy and amino-acid metabolism. The longevity-relevant data are pre-clinical.

   LimitationsNo controlled human trial supports an ageing-related outcome. Model-organism lifespan data do not transfer to people.

   References

   • Chin RM et al. (2014). The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR.Nature 510:397–401
   • Asadi Shahmirzadi A et al. (2020). Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice.Cell Metabolism 32(3):447–456
3. 03

   Ubiquinol (CoQ10)

   Evidence level 02

   Coenzyme Q10 is an established component of mitochondrial electron transfer. Human trials exist, largely in defined clinical populations rather than healthy adults.

   LimitationsFindings in patient cohorts cannot be presented as benefits for healthy users.

   References

   • Mortensen SA et al. (Q-SYMBIO) (2014). The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure.JACC: Heart Failure 2(6):641–649
   • Hernández-Camacho JD et al. (2018). Coenzyme Q10 supplementation in aging and disease.Frontiers in Physiology 9:44
4. 04

   Glycine + N-Acetyl-L-Cysteine

   Evidence level 02

   Supplying both rate-limiting glutathione precursors has been studied in small human trials reporting restored intracellular glutathione and improved oxidative-stress markers in older adults.

   LimitationsTrials are small, open-label or short in duration. Biomarker change is not a clinical endpoint.

   References

   • Kumar P et al. (2021). Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress and mitochondrial dysfunction.Clinical and Translational Medicine 11(3):e372
   • Sekhar RV et al. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation.American Journal of Clinical Nutrition 94(3):847–853
5. 05

   Reduced L-Glutathione · L-Ergothioneine

   Evidence level 02

   Oral glutathione has been shown to raise body stores in a controlled trial. Ergothioneine is a diet-derived compound with a dedicated transporter; human data are largely observational and mechanistic.

   LimitationsAssociations between blood ergothioneine and health outcomes are observational and cannot establish causation.

   References

   • Richie JP et al. (2015). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.European Journal of Nutrition 54:251–263
   • Cheah IK, Halliwell B (2021). Ergothioneine, recent developments.Redox Biology 42:101868
   • Smith E et al. (2020). Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease.Heart 106(9):691–697
6. 06

   Standardised Pomegranate Extract

   Evidence level 02

   Pomegranate ellagitannins are converted by the gut microbiome into urolithins. Human trials of urolithin A report effects on muscle mitochondrial biomarkers; conversion capacity varies between individuals.

   LimitationsExtract and isolated-urolithin data are not interchangeable. Microbiome-dependent conversion limits generalisation.

   References

   • Andreux PA et al. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.Nature Metabolism 1:595–603
   • Liu S et al. (2022). Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults.JAMA Network Open 5(1):e2144279
   • Tomás-Barberán FA et al. (2017). Urolithins, the rescue of 'old' metabolites to understand a 'new' concept.Molecular Nutrition & Food Research 61(1)
7. 07

   Micronutrient cofactors · Taurine

   Evidence level 02

   Magnesium, vitamins D3, K2, B6, B12 and folate (5-MTHF) carry established physiological functions with authorised nutrient claims in the EU. Taurine's ageing-related data are pre-clinical.

   LimitationsAuthorised nutrient-function claims describe normal physiology. They are not anti-ageing claims, and taurine's animal data are not transferable to humans.

   References

   • European Commission (2012). Regulation (EU) No 432/2012 — list of permitted health claims made on foods.Official Journal of the European Union
   • EFSA NDA Panel (2017). Dietary reference values for nutrients — summary report.EFSA Supporting Publications 14(12):e15121
   • Singh P et al. (2023). Taurine deficiency as a driver of aging.Science 380(6649):eabn9257

Formulation philosophy

HOW EVIDENCE BECOMES FORMULATION.

Food supplements should not be used as a substitute for a varied, balanced diet and a healthy lifestyle.