| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 1 | Creatine Monohydrate | S | 3–5 g/day; optional 20g/day loading ×5d | Replenishes phosphocreatine for faster ATP regeneration. Cell volumization may stimulate mTOR. Meta-analyses: +5–10% strength on top of training. Upper-body +4.4 kg, lower-body +11.4 kg vs. placebo. 2024 cognition MA (Desai et al., Front Nutr 11:1424972): memory SMD 0.31, processing speed SMD −0.51 (EFSA 2024 flagged pooling — treat as suggestive). [1] | Water retention (1–3 kg first week). Minor GI at high doses. No kidney damage in healthy individuals. Hair-loss concern directly tested: Antonio et al., JISSN 2025 (PMID 40265319), 12-wk double-blind RCT n=38 — no change in DHT, total/free T, or hair density vs. placebo. [2] | Most studied sport supplement in history. ISSN: "most effective ergogenic nutritional supplement." 2024 MA (23 RCTs, <50yo): significant strength gains. [1] Burke et al., Nutrients 17:2748, 2025 confirms across ages. Monohydrate is gold standard; alternatives offer no proven advantage. |
| 2 | Whey Protein | S | 20–40 g/serving; 1.6–2.2 g/kg/day total | Complete protein, highest leucine (~10–12%). Rapid digestion triggers robust MPS via mTOR/p70S6K. Meta-analyses: whey + RT significantly increases lean mass and strength. [3] | GI discomfort (lactose — use isolate). Acne exacerbation in susceptible. Quality varies. | 2018 meta-analysis (49 RCTs, 1,863 participants): protein supps augmented lean mass +0.30 kg and strength. [3] Total daily protein > timing or source. |
| 3 | Caffeine | S | 3–6 mg/kg, 30–60 min pre | CNS stimulant; blocks adenosine, ↑catecholamines. ↑1RM +2–3%, endurance, power, training volume. ↑Fat oxidation. [4] | Insomnia (half-life 5–6h). Anxiety, tachycardia, GI at high doses. Tolerance develops. Withdrawal headaches. | ISSN: "effective ergogenic aid." CYP1A2 genotype affects response. [4] |
| 4 | Beta-Alanine | A | 3.2–6.4 g/day split; 4+ wks | Precursor to carnosine (muscle buffer). Delays fatigue in 1–4 min efforts. Systematic review of 19 RCTs: improved performance. [5] | Paresthesia (tingling — harmless). No body comp effect. Minimal benefit <60s or >10min efforts. [5] | ISSN (2015): effective for exercise >60s. 4 weeks loading required. Best for hypertrophy/higher-rep work. [5] |
| 5 | L-Citrulline / Citrulline Malate | B | L-cit 3–6g or CM 6–8g, 40–60 min pre | Converted to arginine → ↑NO → vasodilation → ↑blood flow. One study: 8g CM ↑reps ~53%, ↓DOMS 40%. May ↑ATP +34%, ↑PCr recovery +20%. [6] | GI discomfort. Inconsistent results in 2021 review. Standardization issues (2:1 vs 1:1 ratio). Null in trained men: McKinlay et al., JISSN 22:2513944, 2025 — 6-wk RCT n=33: no strength difference vs. placebo. [6] | Less consistent than creatine/caffeine. Acute pump/RPE benefit holds; chronic strength benefit not established (McKinlay 2025). Best for pump/volume training. [6] |
| 6 | HMB (β-Hydroxy β-Methylbutyrate) | B | 3 g/day (1g × 3) | Leucine metabolite; ↓protein breakdown via ubiquitin-proteasome. 2025 umbrella review (Bideshki et al., 11 MAs): ↑muscle mass ES 0.21, ↑strength ES 0.27, ↑FFM ES 0.22 — small effects, weakest in young trained men. [7] | Expensive. Unpleasant taste. Benefit in young trained well-fed athletes small and inconsistent. [7] | ISSN 2024 Position Stand (Wilson et al., JISSN 21:2434734): recommends HMB primarily for older / sedentary / sarcopenic / disuse-atrophy populations; safety up to 1 yr. For young trained lifters, creatine is far better. [7] |
| 7 | Betaine (TMG) | B | 2.5 g/day | Methyl donor; involved in homocysteine metabolism and creatine synthesis. Some RCTs: ↑power, volume, body composition. May ↑GH/IGF-1 acutely. [8] | GI discomfort. Fishy body odor possible. Mixed results. [8] | Two positive RCTs (Cholewa et al.) but not all replicate. Inexpensive addition. [8] |
| 8 | Beetroot / Nitrate | B | 8.3–16.4 mmol nitrate (acute) or ≥3 days chronic | Nitrate→nitrite→NO pathway. ↑Exercise efficiency, ↓O₂ cost, ↑blood flow. Benefits for endurance and high-rep work. [11] Domínguez et al., Sports Med 2025 (PMC12106159): umbrella review of 20 SR/MAs supports dose; benefits attenuate in elite. | Beeturia (harmless). GI. Less effective in elite athletes. Interacts with PDE-5 inhibitors. [11] | Multiple days loading > single dose. More pronounced in recreational athletes. Eur J Appl Physiol, 2025: modest acute resistance-exercise effect. Stack with citrulline for dual NO coverage. [11] |
| 9 | EAAs / BCAAs | C | EAAs: 6–12g; BCAAs: 5–10g | EAAs provide all MPS building blocks. BCAAs trigger MPS but need all 9 EAAs. May ↓soreness during fasted training. | Unnecessary if protein ≥1.6g/kg. BCAAs alone may suppress MPS by depleting other EAAs. Expensive. [9] | ISSN: "BCAAs alone do not optimally stimulate MPS." If protein is adequate, minimal benefit. Niche: fasted training only. [9] |
| 10 | Turkesterone / Ecdysteroids | F | 500–1,000 mg/day (marketed) | Insect molting hormones marketed as "natural anabolics." One small study (Isenmann 2019) had methodological issues. First direct turkesterone RCT (Res Directs Health Sci 4(1), 2024, 500 mg/day × 4 wk): no effect on body composition, strength, mood, or sleep. | Most products contain little to no active compound. Expensive. No proven benefit. [10] | Not replicated. JISSN 2025 (PMC12379694) ecdysteroid RCT confirms null. Widespread label fraud per independent labs. Save your money. [10] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 11 | Vitamin D3 | A | 2,000–5,000 IU/day; test levels | Deficiency (<20 ng/mL) strongly linked to low T. Correcting deficiency raised T ~25% in one RCT. Essential for bone, immune, muscle, mood. [15] | Toxicity at >10,000 IU/day long-term. Kidney stones. No T benefit if already replete (>40 ng/mL). [15] | Foundational. 40–50% deficient. T benefit = correcting deficiency, not superphysiological boosting. Test annually. [15] |
| 12 | Zinc | A | 15–30 mg/day if deficient | Essential cofactor for T synthesis. Deficiency rapidly ↓T. Lost in sweat — athletes at higher risk. Critical for immune, wound healing. [16] | Nausea on empty stomach. Chronic >40mg/day depletes copper. ZMA marketing overblown for non-deficient. [16] | Benefit = preventing/correcting deficiency. Monitor if heavy sweating, caloric restriction, or low-meat diet. [16] |
| 13 | Magnesium | A | 200–400 mg/day (glycinate/citrate/threonate) | 300+ enzymatic reactions. May support T (one study positive). ↑Sleep, ↓cramps, ↑recovery. ~50% of Americans deficient. [17] | Loose stools (especially citrate/oxide). Drug interactions. [17] | Foundational "insurance." Glycinate for sleep; threonate for cognition; citrate general. Take PM. [17] |
| 14 | Ashwagandha (KSM-66) | A | 300–600 mg/day standardized root | Adaptogen; ↓cortisol 14–28%. Multiple RCTs: 10–17% T increase. Also ↑VO2 max, improved recovery, ↓anxiety, ↑sleep. [12] Lopresti et al., BJPsych Open, 2024 MA (7 RCTs, n=488): cortisol −1.16 µg/dL significant, but no significant effect on perceived stress — biomarker/subjective disconnect. | Hepatotoxicity is rare but real: Hendrickson et al., Front Nutr 12:1658265, 2025 — ~23 published cholestatic-pattern case reports, latency 2–12 wk, mostly self-limiting but fatal/transplant cases reported. Avoid in preexisting liver disease; stop at first sign of jaundice/dark urine/pruritus. Thyroid stimulation, sedating, drug interactions. [12] | Strongest-evidenced adaptogen for lifters. KSM-66 best studied. T increase modest but meaningful. Cycle 8 on / 2–4 off. [12] |
| 15 | Tongkat Ali | B | 200–400 mg/day standardized | Eurycomanones may inhibit aromatase, ↓SHBG → ↑free T up to 15%. May improve sperm and stress hormones. [13] | GI, insomnia. Quality varies enormously. Limited long-term data. [13] | Lazarev et al. (2021): one of three with strongest T evidence. Look for Physta or LJ100. [13] |
| 16 | Fenugreek (Testofen) | B | 500–600 mg/day standardized | Furostanolic saponins may inhibit 5α-reductase/aromatase. 4/6 RCTs: significant T increase. May improve libido, body comp, insulin sensitivity. [14] | Maple syrup body odor. GI. May ↓blood sugar. Possible estrogenic effects. [14] | Testofen (50% fenusides) best studied. Effects modest (~5–15%). Inexpensive. [14] |
| 17 | D-Aspartic Acid (DAA) | F | 2–3 g/day | Involved in neuroendocrine T regulation. One RCT (Topo 2009): 42% T increase (untrained). Multiple subsequent RCTs in trained men: no effect or T DECREASE (Willoughby 2013; Melville 2015 6g/d → T decrease; Melville 2017 12-wk null). [18] | GI. Headaches. Higher 6 g/day dose reduced T. [18] | Tier downgrade C → F: single 2009 positive in untrained men never replicated; trained-men evidence null-to-negative. Pattern closer to Tribulus (F). Not recommended. [18] |
| 18 | Shilajit (Purified) | C | 250–500 mg/day purified | Mineral-rich; fulvic acid. One RCT (PrimaVie): ~20% ↑total T, ~19% ↑free T in 45–55yo men. [20] | Unprocessed may contain heavy metals. Use only PrimaVie. GI. Limited data. [20] | Single-study evidence. Interesting but needs replication. [20] |
| 19 | Boron | C | 3–10 mg/day | May ↓SHBG (↑free T), support bone, ↓inflammation. One small study: significant free T increase at 10mg/day. [21] | Safe at rec. doses. Toxicity >20mg/day. Limited evidence. [21] | Inexpensive. Most useful for low dietary intake. Found in raisins, prunes, avocados, nuts. [21] |
| 20 | Tribulus Terrestris | F | 250–750 mg/day (marketed) | Marketed as T booster. Some studies: modest libido improvement, but NOT through testosterone elevation. | GI. No T effect in any well-controlled study. [19] | Multiple reviews confirm: does NOT ↑T. One of bodybuilding's most overhyped supplements. [19] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 21 | Collagen Peptides (Type I/III) | A | 10–15g/day + 50mg vit C, 30–60 min pre-exercise | Provides hydroxyproline + glycine for collagen synthesis. Shaw et al. (2017): 15g collagen + vit C doubled collagen synthesis. Bischof et al., Sports Med 54:2559, 2024 MA (19 trials, n=768): long-term collagen + RT significantly increased tendon CSA, FFM, max strength, recovery from EIMD. [22] | Not complete protein. Quality varies. Heavy metal risk (marine). Skin benefits mixed (see Longevity Playbook). | The vit C timing protocol is key. Centner et al., MSSE, 2025 (PMID 40623147): 16-wk RCT in young males — collagen increased muscle/tendon stiffness and explosive strength. 3–6 months for joint pain. [22] |
| 22 | UC-II (Undenatured Type II Collagen) | A | 40 mg/day on EMPTY stomach | Oral tolerance: trains immune system to stop attacking joint cartilage. Different mechanism than hydrolyzed collagen. 2016 RCT: UC-II > glucosamine + chondroitin for knee OA. [23] | Mild GI. Must be empty stomach. Slow onset: 60–120 days. [23] | Lugo et al. (2016): UC-II 40mg > G+CS for OA. 2025 SR (Crit Public Health 35:2588891, 17 trials): significant WOMAC pain/stiffness/function reduction at 40 mg/d. Henrotin et al., Ann Med 2025 reinforces mechanism. Sci Rep 15:17505, 2025: UC-II + hydrolyzed combo additive. [23] |
| 23 | Boswellia Serrata (AKBA) | A | 300–500 mg/day (≥30% AKBA) | 5-LOX inhibitor — blocks leukotrienes (different from NSAIDs). Multiple RCTs: ↓OA pain, sometimes = celecoxib. Fast onset (1–2 wks). Synergy with curcumin. [26] | GI (nausea, reflux). Interacts with anticoagulants. Rare liver enzyme elevation. [26] | Sethi et al. (2022): additive/synergistic with curcumin. Aflapin, 5-Loxin well studied. Best-evidenced herbal anti-inflammatory. [26] |
| 24 | Curcumin (Turmeric Extract) | A | 500–1,000 mg/day bioavailable form | Inhibits NF-κB, COX-2, LOX-5, TNF-α, IL-6. Meta-analyses: significant OA pain ↓ = ibuprofen in some trials. ↓DOMS. Antioxidant, neuroprotective. [27] 2025 NMA (Front Pharmacol 16:1664319): bioavailability-enhanced curcuminoids >250 mg/day reach clinically meaningful WOMAC reductions. | Poor bioavailability unless enhanced (<1% standard). May thin blood. May ↑oxalate. ↓Iron absorption. 2025 PK reappraisal (iScience S2589004225008363): piperine addition did NOT increase unconjugated curcumin AUC — see piperine row. | Use lipid/phytosome enhanced forms (Meriva, Theracurmin, BCM-95). ⚠️ May blunt acute post-workout inflammation needed for adaptation. [27] |
| 25 | Calcium + Vitamin K2 (MK-7) | A | Ca: 500–1,000mg; K2 MK-7: 100–200 mcg/day | Ca = primary bone mineral. K2 activates osteocalcin (Ca→bone) + Matrix GLA Protein (prevents arterial calcification). D3+K2+Ca = bone triad. [29] | Ca without K2 may ↑CVD risk. GI. Kidney stones. K2 interacts with warfarin. [29] | Especially important for females, >40, and during cutting phases. [29] |
| 26 | Glucosamine Sulfate | B | 1,500 mg/day | Building block for GAGs. May slow joint space narrowing. SR (146 studies): >90% positive. MOVES trial: as effective as celecoxib. [24] | Mixed evidence — ACR/AF against; AAOS "may help." GI. May ↑glucose. Shellfish allergy. [24] | Sulfate > hydrochloride. Best in combination. Lin et al., J Clin Med 13:7444, 2024 NMA (30 RCTs, n=5,265): G + omega-3 ranked top combination; G+CS+MSM also effective. 4–12 weeks onset. [24] |
| 27 | Chondroitin Sulfate | B | 800–1,200 mg/day | GAG component; resists compression, attracts water into cartilage. Meta-analyses: ↓pain, ↑function in knee OA. [24] | GI. Blood thinning potential. Slow onset (4–12 weeks). [24] | Prescribed for OA in many European countries. Best with glucosamine. GAIT: helped moderate-to-severe OA. [24] |
| 28 | MSM (Methylsulfonylmethane) | B | 1,000–3,000 mg/day | Organic sulfur for connective tissue. Anti-inflammatory/antioxidant. RCTs: ↓joint pain, ↑function in OA. May ↓DOMS. [25] | Very safe. Mild GI at higher doses. Some headache/insomnia initially. [25] | Best in combination (G+CS+MSM). 2024 NMA: ranked top 3 OA combos. Inexpensive, often overlooked. [25] |
| 29 | Cissus Quadrangularis | C | 300–600 mg/day standardized | Traditionally for fracture healing. Some RCTs: faster healing, ↓joint pain, ↑bone markers. | GI. May be adulterated (banned substance risk). Limited quality control. [28] | Popular in bodybuilding for tendon repair but human evidence sparse. Use reputable sources. [28] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 30 | Omega-3 (EPA/DHA Fish Oil) | S | 2–3g EPA+DHA daily | Anti-inflammatory via resolvins, protectins, maresins. ↓IL-6, TNF-α, CRP. ↓DOMS. May ↑MPS with RT. CVD, brain, eye, joint, longevity benefits. [31] | Fishy burps. Blood thinning >3g/day. May ↑LDL. Quality varies — use IFOS-tested. Rancid oil harmful. [31] | ISSN 2025 Position Stand (Jäger et al., JISSN 22:2441775, PMID 39810703): athletes at higher insufficiency risk; EPA+DHA enhance endurance + CV function; muscle hypertrophy benefit in young trained adults is inconsistent; with RT may improve strength dose/duration-dependently; reduces soreness; possible neuroprotection from repeated head impacts. Higher EPA = anti-inflammatory; higher DHA = brain/eyes. Min 8 weeks for full effect. [31] |
| 31 | Tart Cherry Extract / Juice | A | 480–960mg extract or 30mL 2×/day; 4–5 days pre-event | Rich in anthocyanins + natural melatonin. RCTs: ↓DOMS, faster strength recovery, ↓CRP/IL-6. Also ↑sleep quality. [30] | High sugar in juice form. Calories. May interact with blood thinners. [30] | One of best-evidenced recovery supplements. Two 2025 SR/MAs converge: PMC11918606 (EIMD in athletes — MVIC +9.13%, ↓IL-6/IL-8) and PMC13057130 (Nutrients 2025, 19 trials — MVC recovery ES 0.63 post → 2.14 at 72h). Howatson 2010 validated. Montmorency variety. [30] |
| 32 | Vitamin C | A | 500–1,000 mg/day; 50mg pre-exercise with collagen | Essential cofactor for collagen synthesis. Potent antioxidant. Supports immune function. Critical for tendon/ligament repair. [32] | ⚠️ Mega-dosing (>2g/day) may impair training adaptations (blunts ROS signaling). GI. Kidney stone risk (oxalate). [32] | Moderate doses (250–500mg) support recovery. High doses (>1g) post-exercise may interfere with adaptation. 500mg/day + 50mg with collagen pre-exercise. [32] |
| 33 | Astaxanthin | B | 4–12 mg/day | Carotenoid "king of antioxidants." Spans cell membrane bilayer. RCTs: ↓CK, ↑endurance, ↓DOMS. Protects skin from UV, supports eyes. [33] | Expensive. May interact with BP meds, anticoagulants. Orange skin at high doses. [33] | Does NOT blunt training adaptations (unlike high-dose C/E). Best for endurance athletes and high oxidative stress. [33] |
| 34 | Bromelain | C | 500–1,000 mg/day between meals | Proteolytic enzyme: anti-inflammatory, analgesic, anti-edema. ↓Swelling post-surgery. Some evidence for ↓DOMS. [34] | GI. Pineapple allergy. May ↑antibiotic absorption. Interacts with anticoagulants. Must be between meals. [34] | Best evidence post-surgical. Reasonable addition but not priority. [34] |
| 35 | Glutamine | C | 5–10 g/day | Most abundant AA. Depleted during intense exercise. Supports gut barrier, immune function. May ↓infection in overtraining. [35] | No consistent evidence for muscle/strength/recovery in well-fed athletes. Body produces ample normally. [35] | Real value: gut health (IBS, leaky gut) and immune support during extreme training. [35] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 36 | L-Theanine | A | 100–200 mg (often with caffeine) | Amino acid from green tea; ↑alpha brain waves. Synergizes with caffeine: focus + ↓jitteriness. ↑Sleep at bedtime dose. [36] Two 2025 SR/MAs (Mátyus et al., J Clin Med PMC12609247 + Nutr Rev 83:1873): small-to-moderate cognitive benefit at 1–2h post-dose for attention-switching. | Mildly sedating for some. May ↓BP slightly. Very safe through 50–500 mg matches placebo. [36] | 1:1 or 1:2 caffeine:theanine = "smart pre-workout." Calm focused energy. PMC12491391 (2025): improves selective attention in sleep-deprived young adults. Valuable for PM lifters. [36] |
| 37 | Creatine (Cognitive) | A | 3–5 g/day (same as muscle) | Brain uses significant ATP; creatine ↑brain PCr. Meta-analyses: improved short-term memory, reasoning — especially under stress/sleep deprivation, in vegetarians. [40] | Same as muscle dosing. [40] | Avgerinos 2018: improves memory and reasoning. Vegetarians show largest benefit. Free bonus if already supplementing. [40] |
| 38 | Alpha-GPC | B | 300–600 mg, 30–60 min pre | Choline donor → ↑acetylcholine. One study: 600mg ↑power output 14%. May enhance mind-muscle connection. [37] | Mixed safety signal: 2021 Korean cohort (PMID 34817582) stroke HR 1.46 over 10 yr; 2025 South Korean nationwide cohort (PMC12184023) found α-GPC use associated with LOWER risk of subsequent AD/VaD. Long-term use in healthy lifters still cautioned. Headache. GI. [37] | Power study (Bellar 2015) small (n=13). More consistent for aging cognition. J Food Sci 2025 review. Stack with caffeine. [37] |
| 39 | Lion's Mane Mushroom | B | 500–3,000 mg/day fruiting body | Hericenones/erinacines stimulate NGF synthesis. Human studies: ↑cognition, ↓anxiety. May support neuroplasticity. [38] | GI. Mushroom allergy. May interact with diabetes meds. Quality: fruiting body > mycelium on grain. [38] | Most promising nootropic mushroom. Not acute enhancer — 2–4 weeks for effects. Long-term brain investment. [38] |
| 40 | Rhodiola Rosea | B | 200–1,500 mg/day (3% rosavins, 1% salidroside) | Adaptogen; modulates cortisol, ↑fatigue resistance, ↑stress tolerance. RCTs: ↑endurance, ↓perceived exertion. [39] 2025 crossover RCT in resistance-trained athletes (Nutrients PMC12693935, 7 days): dose-dependent anaerobic + cognitive improvements at 200–1,500 mg/day. | Insomnia if late. Dry mouth. May interact with antidepressants (MAOI). [39] | Best for fatigue/stress resilience vs. raw performance. Ideal during demanding blocks. Nutrients 17:940, 2025: bench-press/bench-pull under mental fatigue. SHR-5 extract. [39] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 41 | Spirulina | B | 1–3 g/day (up to 10g); ≥8 wk for BP/lipid effects | 60–70% complete protein, all EAAs, iron, B-vitamins, phycocyanobilin. Studies: ↓triglycerides ~10–15%, ↓BP, ↑NK cells, ↑power (one study 20–30%, needs replication). [41] 2025 GRADE-assessed BP MA (Maleki et al., Phytother Res 39:e8377): SBP −4.41 mmHg, DBP −2.84 mmHg (moderate-quality). 2025 CV MA (Complement Ther Med): TG −14.75, TC −11.5, LDL −7.69, HDL +1.9 mg/dL. | Metallic taste. Microcystin contamination risk. GI. Avoid in autoimmune. [41] | Cardiometabolic indication is now better supported than ergogenic. Hawaiian/organic safer. [41] |
| 42 | Beetroot Powder | B | 5–10g/day (standardized nitrate) | Concentrated nitrate source. Also betaine, folate, K, betalains. See Section 1 #8. [11] | Beeturia. GI. Nitrate varies. Stains. [11] | Convenient alternative to juice. Stack with citrulline for dual NO coverage. [11] |
| 43 | Chlorella | C | 2–5 g/day | Green microalgae; chlorophyll, protein, B-vitamins, iron, CGF. May support heavy metal detox, immune, ↓cholesterol. [42] 2025 GRADE-assessed CV-risk SR/MA (Complement Ther Med): significant reductions in TC, LDL, BP markers. | GI (gas, nausea). Green stool. May interact with immunosuppressants/warfarin. "Broken cell wall" required. Null on BP (J Hum Nutr Diet 2025): chlorella subgroup did NOT reduce SBP (in contrast to spirulina). [42] | Less evidence than spirulina. Main value: nutritional supplement and detox support. [42] |
| 44 | Greens Powders (AG1, etc.) | C | 1 scoop/day per label | Blends of dehydrated vegetables, fruits, algae, probiotics. May improve energy and micronutrient status if poor veggie intake. First AG1 RCTs (industry-funded): JISSN 21:2409682, 2024 (12-wk gut microbiome): compositional shifts; PMC12481523, 2025 safety RCT: no renal/hepatic harm at 12 wk. | Expensive ($2–4/day). Proprietary blends. Not a substitute for vegetables. Industry-sponsored — interpret with skepticism. [43] | For lifters eating well: minimal additional benefit over a quality multi + targeted supplements at much lower cost. [43] |
See The Longevity Playbook v3.1 for comprehensive references. [LP-##] = Longevity Playbook reference number.
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 45 | CoQ10 (Ubiquinol) | A | 100–200 mg/day ubiquinol | Essential for mitochondrial ATP. Levels ↓~40% with age and statins. Q-SYMBIO: 42% ↓mortality in heart failure. 2024 HF SR/MA (16 RCTs, n=2,136, PMID 39462324): ~40% HF mortality reduction, improved exercise capacity. ↑Cellular energy, ↓oxidative stress. [LP-33] | Expensive. GI. May ↓BP. Warfarin interaction. Take with fat. [LP-33] | Near-essential for lifters >35 or on statins. 2024 ubiquinol vs. ubiquinone SR/MA (Future Cardiol PMID 39049769): similar EF improvement (5.3% vs. 5.9%) — bioavailability advantage smaller than marketing implies. [LP-33] |
| 46 | NMN / NR (NAD+ Precursors) | B | NMN: 250–500mg; NR: 300–1,000mg | ↑NAD+ ~50–60%; mitochondria, DNA repair, sirtuins. NMN: ↑insulin sensitivity ~25% (Yoshino 2021). NR: ↓BP (Martens 2018). [LP-30][31] | ⚠️ Cancer caveat expanded to NMN: 2025 preclinical work — NMN shielded pancreatic cancer cells from three chemotherapeutics by boosting energy and dampening oxidative stress (adds to prior NR/metastasis concern [LP-32]). 64% of NMN products <1% labeled. Expensive. Active-cancer patients consult oncology. [LP-30] | Not proven performance enhancer for young lifters. Most valuable >40. Third-party tested only. [LP-30][31][32] |
| 47 | Quercetin | C | 500–1,000 mg/day | Senolytic (clears senescent cells + dasatinib). Anti-inflammatory, antihistamine. May ↑mitochondrial biogenesis. [LP-36] STAMINA pilot RCT (eBioMedicine 2025, PIIS2352-3964(25)00056-8): D+Q in older adults with MCI safe and feasible; functional-benefit signal preliminary. | GI. Poor bioavailability. Senolytic use needs medical supervision. [LP-36] | Modest endurance benefit. More relevant anti-aging/anti-allergy. Creatine/beta-alanine far better for performance. [LP-36] |
| 48 | Urolithin A | C | 500–1,000 mg/day | Activates mitophagy. Only ~40% produce naturally. JAMA Network Open 2022 RCT (Liu et al., n=66, 4 mo): primary ATP endpoint null; secondary endurance/mitochondrial markers improved. [LP-37] 2024 RCT in resistance-trained males (Bashir et al., JISSN 21:2419388): muscle endurance and protein metabolism. Front Nutr 12:1674446, 2025 academy soccer pilot. | Expensive. Limited data. GI. Mitopure is studied form. [LP-37] | Promising for mitochondrial health. Signal in already-trained athletes emerging but smaller than in middle-aged/sedentary cohorts. Maintain C-tier. [LP-37] |
| 49 | Resveratrol | C | 250–500 mg trans-resveratrol | Activates SIRT1 in theory. Some evidence for ↑blood flow, ↓inflammation. [LP-39] | Poor bioavailability (<1%). May impair adaptations at high doses. Estrogenic. [LP-39] | Overhyped. Weak/inconsistent human evidence. Pterostilbene may be superior. Not a priority. [LP-39] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 50 | Electrolytes (Na, K, Mg) | S | ~1,000–2,000mg Na + 3,500mg K + 300mg Mg (food+supps) | Critical for muscle contraction, nerve signaling, hydration, BP. Sweat depletes. Adequate Na ↑pump and performance. [48] | Excess Na ↑BP in salt-sensitive. Excess K dangerous with kidney disease. [48] | Overlooked by lifters drinking plain water. During cutting + heavy training, supplemental electrolytes essential. [48] |
| 51 | Fiber (Psyllium, Inulin) | A | 25–40g/day total (food+supps) | Gut microbiome, ↓cholesterol, ↑blood sugar control, ↑satiety during cutting. Psyllium ↓LDL ~7%. Inulin feeds Bifidobacteria. [47] | GI if ramped fast. Must ↑water. Can ↓medication/mineral absorption (separate 2h). [47] | Most lifters on high protein are severely fiber-deficient. Sabotages gut, hormones, immune function. Build to 30+g/day. [47] |
| 52 | Melatonin | A | 0.5–1 mg for circadian/grogginess; higher for clinical sleep-onset | Circadian rhythm regulator. Potent antioxidant. [44] Cruz-Sanabria et al., J Pineal Res 76:e12985, 2024 dose-response MA (26 RCTs): pooled peak effect on sleep-onset/total-sleep-time at ≈4 mg/day. 2024–2025 N-of-1/crossover work supports lower doses (0.5–1 mg) for circadian phase-shift + less morning grogginess. | Grogginess if dose too high. Vivid dreams. May suppress natural production at chronic high doses (debated). [44] | Use lowest effective dose. For circadian/sleep-onset hygiene: 0.5–1 mg. For more severe sleep-onset insomnia: higher (up to ~4 mg) may be more effective per MA, at cost of grogginess. Pairs with Mg glycinate. [44] |
| 53 | Magnesium Glycinate (for sleep) | A | 200–400 mg Mg, 30–60 min pre-bed | Glycinate crosses BBB; calming GABAergic effects. ↑Sleep quality, ↓cramps, ↑recovery. Deficiency impairs sleep architecture. [17] 2025 Mg-bisglycinate RCT (PMC12412596, n=155): between-group sleep-quality difference trend-level (p=0.069), not significant alone. 2024 Mg-L-threonate RCT (S2590142724000193): 3 wk improved slow-wave sleep, mood, energy — stronger evidence for threonate on objective architecture. | Best-tolerated Mg form. [17] | Mg glycinate + low-dose melatonin + ashwagandha = popular natural sleep stack. For objective sleep architecture, threonate has stronger 2024–25 evidence. [17] |
| 54 | Probiotics | B | 10–50 billion CFU/day; strain-specific | Strain-specific: gut barrier, immune, nutrient absorption. May ↓URTI during hard training and ↓GI distress. [45] | Temporary bloating. Not all strains equal. May worsen SIBO. [45] | L. rhamnosus GG (immune); B. lactis (gut); S. boulardii (antibiotics). Most relevant during restriction/travel/heavy blocks. [45] |
| 55 | Digestive Enzymes | C | Per label, with high-protein meals | Protease, lipase, amylase may improve protein digestion on very high-protein diets. May ↓bloating from large meals. [46] | Dependency concern. GI. May interact with blood thinners. Usually unnecessary. [46] | Useful for documented low stomach acid or pancreatic insufficiency. Try HCl + pepsin first. [46] |
| # | Substance | Tier | Dose | How It Works / Benefits | Negatives / Side Effects | Key Evidence & Notes |
|---|---|---|---|---|---|---|
| 56 | Iron | A (if deficient) | 18–27 mg/day or as directed | Essential for hemoglobin, myoglobin, mitochondrial enzymes. Deficiency → fatigue, ↓performance, poor recovery. Athletes (especially females) at higher risk. [52] Šmid et al., Sports Med 54:1851, 2024 SR/MA/meta-regression: ferritin SMD 1.27 significant — but only meaningful when baseline ≤12 µg/L; Hb/transferrin saturation unchanged. Female-athlete SR 2024: performance improves 2–20% in ID females. | ⚠️ Do NOT supplement without blood test. Excess is toxic. GI. Inhibits zinc/calcium. [52] | Test: ferritin, serum iron, TIBC. Target ferritin >30 (sports docs prefer >50). Take with vit C on empty stomach. [52] |
| 57 | Vitamin K2 (MK-7) | A | 100–200 mcg/day | Activates Matrix GLA Protein (prevents arterial calcification) + osteocalcin (Ca→bones). Synergizes with D3+Ca. ↓Fracture risk. [29] | Interacts with warfarin. Generally safe. MK-7 > MK-4 (longer half-life). [29] | Completes "bone triad" (D3+K2+Ca). Important during cutting. Natto is richest food source. [29] |
| 58 | Glycine | B | 3–5g pre-bed; 5–15g/day for collagen | Critical for collagen (~33% glycine). RCTs: 3g pre-bed ↑sleep quality. Supports glutathione synthesis. ↑Insulin sensitivity. Inhibitory neurotransmitter. [49] | Very safe. Mild sweet taste. Nausea at very high doses. [49] | Underrated: sleep + connective tissue dual duty. Extremely inexpensive. One of best value supplements. [49] |
| 59 | Taurine | B | 1–3 g/day | Conditionally essential AA. Osmolyte, antioxidant, Ca²⁺ modulator. May improve exercise capacity in some athlete trials. [50] | Very safe (up to 6g studied). Minor GI. [50] | 2025 counterevidence retires the human-aging framing: Marcangeli et al., Aging Cell 24:e70191, 2025 (n=137 men 20–93) — no association of circulating taurine with age, muscle, strength, or mitochondrial function. Fernandez/de Cabo et al., Science, June 2025 (PMID 40472098) — across humans, monkeys, mice, taurine typically rose or stayed constant with age; unlikely a reliable aging biomarker. The 2023 Singh Science mouse-lifespan result has not translated. Niche value may remain in chronic disease / low-baseline contexts; longevity sales pitch should be retired. [50] |
| 60 | Berberine | B | 500mg 2–3×/day with meals | AMPK activator (= metformin pathway). ↓Glucose, HbA1c, LDL, triglycerides. ↑Insulin sensitivity. [51] 2025 SR/MA (Front Pharmacol 16:1572197, PMID 40740996): LDL WMD −0.495 mmol/L (~19 mg/dL), significant TG, FPG, waist-circumference reductions. | GI (common). CYP inhibitor (drug interactions). May ↓blood sugar excessively. Bitter. [51] | "Nature's metformin." Relevant during bulking for metabolic health. NOT muscle-building. Dihydroberberine may be better tolerated. [51] |
| 61 | Vitamin B Complex | B | 1× RDA or targeted B12/folate | Cofactors in energy metabolism, ATP, amino acid metabolism, RBC formation. B12 deficiency common in plant-based diets. [53] | B6 >100mg/day → neuropathy. Niacin flush. Biotin interferes with labs. [53] | "Insurance" for restricted diets. Methylated forms for MTHFR variants. Deficiency sabotages everything. [53] |
| 62 | Black Pepper Extract (BioPerine) | C | 5–20 mg with other supps | Inhibits glucuronidation/CYP3A4. Mildly thermogenic. [56] 2025 PK reappraisal (iScience S2589004225008363): piperine addition did NOT increase unconjugated curcumin AUC — the widely-cited "2000%" figure (Shoba 1998) reflected conjugated curcumin which is less biologically active. 2025 GRADE-assessed MA still supports combined-form liver-enzyme/inflammation effects. | Same CYP inhibition can ↑drug levels unpredictably. May ↑stomach acid. [56] | Tier downgrade B → C: bioavailability rationale weaker than long claimed. Modern lipid/phytosome curcumin (Meriva, Theracurmin, BCM-95) are more practical bioavailability strategies. Cheap to add but don't expect the 20× multiplier marketing implies. [56] |
| 63 | Colostrum (Bovine) | C | 10–20 g/day | First milk; rich in IgG, lactoferrin, IGF-1. Some studies: ↓URTI, ↑gut barrier, modest lean mass gains. [54b] | Expensive. Dairy allergen. Quality varies. IGF-1 cancer concern (unproven). [54b] | Best evidence: immune support during heavy training + gut barrier. Not primary muscle-builder. [54b] |
| 64 | Maca Root | C | 1,500–3,000 mg/day | Peruvian root; ↑subjective energy, libido. Does NOT affect T. May improve sperm parameters. [55] | GI. Possible thyroid effects (goitrogens). [55] | NOT a T booster despite marketing. Benefits are T-independent. Gelatinized form better tolerated. [55] |
| 65 | Vitamin E (Mixed Tocopherols) | C | 15mg/day FROM FOOD; avoid supplements | Fat-soluble antioxidant protecting cell membranes. Important for immune function. In nuts, seeds, vegetable oils. | ⚠️ High-dose supplements (≥400 IU/day) INCREASE mortality +4% (Cochrane, 78 RCTs). May ↑prostate cancer (SELECT). [LP-54] | Get from food, NOT supplements. Clearest "more is worse" example. Nuts, seeds, olive oil provide adequate amounts. [LP-54] |
| 66 | Bergamot (Citrus bergamia BPF) | B | 500–1,500 mg/day BPF, 12 wk minimum | Citrus polyphenols inhibit HMG-CoA reductase and modulate AMPK. 2024 RCT in 64 hypercholesterolemic subjects (Foods 13(23):3883): significant LDL reduction at 150 mg/day × 12 wk. 14-trial MA: LDL WMD −55.43 mg/dL. | GI upset. May ↓blood glucose. Statin interactions possible at higher doses. 2025 combination-formulation RCT (S0021915025000759) showed null in mixed nutraceutical stacks — single extract preferable. | International Lipid Expert Panel: Class IIa, Level B for LDL reduction (15–35%). Cardiometabolic/longevity adjunct — not muscle-building. New v2.1 entry per 2024–2026 evidence threshold. |
| 67 | Plant Sterols / Stanols | A | 2 g/day with main meal | Compete with dietary cholesterol for intestinal absorption. 2024 SR/MA (Medicine (Baltimore) 103(42):e39827, 28 RCTs, n=1,777): significant TC, LDL, ApoB reductions; HDL increase. Stanols ~16.4% vs. sterols ~8.3% max LDL reduction. 2 g/day reduces LDL 7–12%. | Generally very safe. Rare GI. May modestly ↓β-carotene absorption (eat carotenoid-rich vegetables). | One of the most thoroughly RCT-validated nutraceutical LDL interventions; previously absent from this guide. Decades of replicated evidence — A-tier addition in v2.1. |