💊 Supplements Facts

Chamomile extract (360mg apigenin) improved sleep quality in clinical trials (Hieu 2019, PMID 31299742). Chamomile tea provides only 5-10mg apigenin per cup versus 50-500mg in supplements.

500mg magnesium oxide × 8 weeks improved insomnia index scores, sleep time, and sleep efficiency vs placebo in elderly subjects (Abbasi 2012, PMID 23853635).

0.3mg melatonin is as effective as 3mg for sleep onset improvement (Zhdanova 2001, PMID 11679050). Most supplements contain 5-10mg — 10-30× the physiologically effective dose.

KSM-66 ashwagandha at 300mg twice daily reduced serum cortisol by 27.9% vs placebo over 60 days (Chandrasekhar 2012, PMID 23439798). Resistance-trained men showed +15% testosterone after 8 weeks (Wankhede 2015, PMID 26609282).

Shevtsov 2003 (PMID 12725561) found significant anti-fatigue and cognitive effects from a single dose of rhodiola extract. Active compounds rosavins and salidroside should be standardized to 3% and 1% respectively on product labels.

Wankhede et al. (2015, PMID 26609282): 57 trained men, KSM-66 300mg twice daily for 8 weeks, showed +15.4% serum testosterone vs +2.6% placebo. Subjects were recreational trainees, not elite athletes, with no screening for baseline stress levels.

All Fadogia agrestis testosterone evidence is from rodent studies. Zero human RCTs exist as of 2025. Rodent toxicity studies show testicular histological changes at high doses. Human effective dose is entirely unknown.

Chromiak & Antonio (2002, PMID 12173939): oral arginine at 5–9g blunts rather than enhances the exercise-induced GH pulse. The exercise stimulus itself produces a larger GH response than any studied oral supplement.

Rogerson et al. (2007, PMID 17530942): 5 weeks of Tribulus terrestris supplementation produced no significant changes in testosterone, body composition, or strength in elite rugby players vs placebo. Multiple independent RCTs replicate this null result.

Talbott et al. (2013, PMID 23754792): 200mg LJ100 daily × 4 weeks in 63 moderately stressed adults produced +37% serum testosterone vs baseline. Study was industry-funded; independent replication is limited.

Wilborn et al. (2004, PMID 15182367): ZMA supplementation in resistance-trained athletes produced no significant changes in testosterone, IGF-1, strength, or body composition vs placebo in an independent 8-week RCT.

Wolfe (2017, PMID 28852372): BCAAs alone cannot maximally stimulate MPS because all essential amino acids are required. Consuming BCAAs without other EAAs forces the body to catabolize its own muscle to supply missing substrates.

Antonio & Street (1999, PMID 10574520): 6 weeks of 0.9g/kg/day glutamine in resistance-trained athletes produced no significant effect on strength, lean mass, or muscle glycogen compared to placebo.

Beta-alanine at 3.2–6.4g/day elevates muscle carnosine ~40–60% over 4 weeks. Meta-analysis (Hobson 2012, PMID 22270875) showed a 2.85% improvement in exercise capacity for efforts of 60–240s duration. No benefit for efforts under 60s or over 25 minutes.

Caffeine at 3–6mg/kg taken 60 min pre-exercise improves aerobic performance by ~2–3% and reduces perceived exertion. CYP1A2 fast metabolizers show larger performance effects than slow metabolizers. Tolerance fully reverses after 1–4 days caffeine-free.

6g citrulline malate (2:1) produced a 52.92% increase in reps to fatigue and 40% reduction in DOMS vs placebo (Pérez-Guisado & Jakeman 2010, PMID 20386132). Most pre-workouts contain 2–3g — half the effective dose.

Creatine monohydrate at 3–5g/day increases muscle phosphocreatine ~20%. At $0.03–0.05/g it is the lowest cost-per-evidence supplement available. Cognitive meta-analysis (Avgerinos 2018, PMID 29704637) showed improved memory in older adults; McMorris 2007 (PMID 17828627) reversed cognitive decline after 24h sleep deprivation with 20g creatine.

Beetroot juice at 400–600mg nitrate (70ml concentrate) reduces O2 cost at submaximal exercise by 1–3% and improves time trial performance by ~1–2%. Peak plasma nitrate occurs 2–3 hours post-ingestion. Elite athletes show consistently smaller responses than recreational athletes.

Whey protein absorption rate is ~8–10g/hr vs casein's ~6g/hr; soy ~3.9g/hr. Leucine threshold for maximal muscle protein synthesis is ~3g per serving. Food vs powder is bioequivalent when leucine-matched — powder is a delivery convenience, not a superior anabolic signal.

At 0.2–0.3 g/kg body weight, sodium bicarbonate improves performance by ~1–3% in events lasting 1–10 minutes, with peak blood alkalosis at ~90 minutes post-ingestion. GI intolerance affects ~50% at the upper dose.

Magnesium oxide bioavailability is approximately 4% vs 80% for glycinate chelate forms. Fat-soluble vitamins (A, D, E, K) absorb 50–80% better when taken with a meal containing dietary fat vs fasted.

Systematic reviews consistently show that fewer than 20% of widely-marketed supplements have Tier 1 evidence. Industry-funded trials are 4× more likely to report positive outcomes than independent trials.

DSHEA (1994) shifted burden of proof to FDA to demonstrate harm after market entry. Roughly 75,000 supplement SKUs are sold in the US with no pre-market efficacy review. GMP certification requires manufacturing controls but not product testing.

~45% of athletes have suboptimal magnesium intake (Volpe 2015, PMID 25858281). Magnesium oxide: only ~4% absorbed despite 58–60% elemental Mg content. Magnesium glycinate: ~80% absorbed. Form selection is the critical decision.

Global supplement market: ~$177B in 2023, projected $272B by 2028 (CAGR ~9%). Typical manufacturer COGS is 10–20% of retail price. The highest-margin categories (exotic botanicals, proprietary blends) have the weakest evidence base.

NSF Certified for Sport and Informed Sport screen for 200+ WADA-prohibited substances. A 2020 study found 15% of 57 tested protein supplements contained measurable anabolic steroids or prohormones not listed on the label.

10mg boron daily for 7 days raised free testosterone 28.3%, lowered estradiol 39%, and reduced SHBG 9% in men (Naghii et al. 2011, PMID 21129941).

Only 6 supplements are Tier 1 across all goals. Protein and creatine appear in 4 of 6 goal categories. Most goal-specific additions (adaptogens, sleep aids) are Tier 2 at best — get fundamentals right before adding category-specific supplements.

Beginners gain more from training consistency than from any supplement. Untrained individuals show larger absolute strength gains from creatine than advanced athletes — 8–10kg lean mass in first year of training dwarfs any supplement effect. Evidence-based stacking adds 3–7% on top of an optimized training and nutrition base.

Creatine monohydrate costs $0.03–0.05/serving (5g) in bulk. A commercial pre-workout providing equivalent actives (creatine 3g, caffeine 200mg, citrulline 6g, beta-alanine 3.2g) costs $1.50–3.00/serving — 10–15× the DIY equivalent of $0.25–0.35/serving from raw ingredients.

Tiers are assigned by evidence quality: Tier 1 (multiple independent meta-analyses, replicated RCTs), Tier 2 (positive RCTs, limited meta-analyses), Tier 3 (mixed/weak RCT data), Tier 4 (no credible human RCT evidence). Only 6 supplements reach Tier 1 across all categories.

Vandenberghe 1996 (n=9) suggested caffeine impaired creatine's torque gains, but Hespel et al. 2002 found no interaction, and multiple subsequent studies confirm no meaningful interference at typical doses.

Shaw et al. (2017, PMID 27852613): 15g hydrolyzed collagen + 50mg vitamin C taken 60 min pre-exercise significantly increased collagen synthesis markers vs placebo in a crossover RCT with 8 subjects.

Geyer 2004 (PMID 15254749): 14.8% of 634 non-hormonal supplements contained undeclared anabolic steroids. USADA estimates ~25% of positive doping tests in sport involve contaminated supplements.

St. John's Wort is a strong CYP3A4 inducer — reduces blood levels of oral contraceptives by ~40%, cyclosporine by ~50%. Omega-3 adds anticoagulant effect to warfarin; monitor INR closely above 3 g/day fish oil.

Tolerable Upper Intake Levels (ULs) from NIH/IOM represent the highest daily intake unlikely to cause adverse effects for most healthy adults. Caffeine UL: 400mg/day (Health Canada, EFSA). Vitamin D UL: 4000 IU/day; toxicity range begins ~10000 IU/day sustained. Zinc UL: 40mg/day. Iron UL: 45mg/day.

Commercial pre-workouts charge $1.50-3.00 per serving. The identical five-ingredient clinical stack from bulk suppliers costs $0.35-0.45 per serving — roughly 3-5× cheaper with transparent, full clinical doses.

Citrulline requires 6-8g to meaningfully increase blood arginine and reduce fatigue. Most pre-workouts contain 1-3g. Beta-alanine needs 3.2g/day; caffeine 3-6mg/kg bodyweight for performance effects.

Caffeine plasma concentration peaks 60-90 minutes after ingestion (McLellan 2016, PMID 26920240). Sodium bicarbonate blood alkalosis peaks ~90 minutes post-ingestion. Dietary nitrates (beetroot) need 2-3 hours.

Caffeine receptor sensitivity is largely restored after 1-4 days of abstinence (James 1997, PMID 9261522). Adenosine receptor upregulation is fully reversible; no permanent adrenal dysfunction occurs in healthy individuals.

Caffeine is the only pre-workout ingredient rated Tier 1 for both strength and endurance. Non-stimulant ingredients citrulline (Tier 2), beta-alanine (Tier 1), and creatine (Tier 1) provide meaningful performance support without adenosine pathway effects.

HMB at 3g/day showed significant lean mass gains in untrained subjects (Wilson 2014, PMID 25324020), but effect size in trained athletes is minimal. Free acid form (HMB-FA) has ~25% higher plasma AUC vs calcium salt (Fuller 2011, PMID 21664973).

Hydrolysate absorbs at ~8–10g/hr vs ~6–8g/hr for intact whey, but Tang 2009 found no meaningful difference in muscle protein synthesis post-workout compared to isolate. Leucine per 30g: concentrate ~2.5g, isolate ~2.7g, hydrolysate ~3.0g.

3g combined EPA+DHA daily significantly augmented the MPS response to amino acid infusion vs placebo (Smith 2011, PMID 21501832). Dose must be EPA+DHA content specifically — not total fish oil volume, which is often 3–5× higher.

Tart cherry concentrate reduced post-marathon strength loss by ~20% (Howatson 2010, PMID 19883392) and muscle soreness at 24–48h post-exercise (Connolly 2006, PMID 16790484). Dose: 480mg anthocyanins starting 4–5 days pre-event.

Tart cherry concentrate (30mL twice daily) reduced inflammation and strength loss in marathon runners (Howatson 2010, PMID 19883392). 480mg anthocyanin extract improved 5-min cycling time trial performance (Bell 2014, PMID 24383513).

Pilz 2011 (PMID 21154195): 3,332 IU/day vitamin D3 for 1 year raised testosterone ~25% in deficient men. Forrest 2011: 42% of US adults deficient (<20 ng/mL).

Beta-alanine (intracellular carnosine buffer) + sodium bicarbonate (extracellular buffer) provide additive performance effects in events 60–300 seconds. Caffeine + creatine: both Tier 1 with no meaningful antagonism.

Dulloo et al. (1989, PMID 2562898): caffeine increased 24-hour energy expenditure by 4.7% and thermogenesis by 10–29% depending on dose, in a controlled metabolic chamber study. Effect was dose-dependent and attenuated with tolerance.

Hemilä 2011 (PMID 21787551): zinc lozenges reduced cold duration by 1.65 days. Athletes lose 2–4 mg zinc/hour through sweat; RDA is 11 mg/day; UL is 40 mg/day.