# Additional Supplements for Anabolism (beyond protein, leucine, creatine)

Scope: supplements other than protein/EAA/leucine (covered in c012) and creatine / mass gainers (covered in c013). Goal is to honestly separate **modest helpers with real evidence** from **hype / marginal effect** for someone already doing resistance training with adequate protein and calories.

TL;DR tiers for a trained, well-fed bulker:
- **Modest helpers with real evidence (stack on top of protein + creatine):** beta-alanine (for volume/work capacity), vitamin D if deficient, omega-3 EPA+DHA (especially in older adults and during disuse/immobilization), citrulline malate (acute performance → cumulative volume).
- **Population-specific:** HMB in untrained / older / cachexia / during deficit — not in trained bulkers; probiotics (Lactobacillus) as an adjunct to protein absorption.
- **Mostly hype / marginal / mostly corrects deficiency:** ZMA, turkesterone / ecdysteroids, tongkat ali, fenugreek, L-carnitine for bulking.
- **Modest but real:** ashwagandha for strength/LBM in resistance trainees (small ES, consistent signal).

---

**Claim:** The ISSN position stand on HMB (Wilson et al. 2013) concludes HMB supplementation can enhance recovery, reduce muscle damage, and increase lean mass and strength — but the largest effects are concentrated in untrained individuals, older adults, and during periods of increased catabolic stress, not in trained, well-fed lifters already hitting protein targets.
- **Confidence:** C1
- **Sources:** https://jissn.biomedcentral.com/articles/10.1186/1550-2783-10-6 ; https://pubmed.ncbi.nlm.nih.gov/23374455/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Typical dose is 3 g/day of Ca-HMB (or HMB-FA). Position-stand language is deliberately hedged re: trained populations; the big effect sizes come from untrained/older/cachexia trials.

**Claim:** The Jakubowski/Rowlands and Phillips-camp critiques argue that several "HMB in trained athletes" trials (notably the Wilson 2014 12-week study in trained lifters reporting 7.4 kg LBM gain) show implausibly large effects that are not reproducible, and that methodologically sounder trials show HMB is no better than whey at matched leucine intake in trained individuals.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/27335614/ ; https://pubmed.ncbi.nlm.nih.gov/27335623/ ; https://pubmed.ncbi.nlm.nih.gov/24599749/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Rowlands 2016 letter to JSSM and the broader Phillips-lab line of argument (e.g. Stokes/Phillips reviews) consistently hold that adequate daily protein (~1.6 g/kg) plus creatine obviates HMB in trained lifters. Leucine itself (~2.5-3 g/meal) produces similar anti-catabolic signaling; HMB is a leucine metabolite.

**Claim:** The Durkalec-Michalski 2017 RCT (42 trained combat-sport athletes, 12 weeks) reported that 3 g/day HMB-FA improved fat-free mass gain (+0.2 kg) and reduced fat mass (−0.8 kg) vs. placebo, with improved anaerobic capacity — effect sizes are modest and the population is trained but in a sport with weight-cutting pressure, not classical hypertrophy bulking.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/28475500/ ; https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0170-2
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Best modern trial in "trained" populations but small n and combat-sport context. Effect size is small enough that for a straight bulker, HMB is a low-priority purchase. HMB-FA (free acid) has faster kinetics and higher peak plasma HMB than Ca-HMB; whether that translates into bigger clinical effect is contested.

**Claim:** Beta-alanine is an evidence-based performance supplement: the ISSN position stand (Trexler et al. 2015) and the Saunders 2017 meta-analysis (40 studies, ~1461 participants) show 3.2-6.4 g/day for 4+ weeks raises muscle carnosine and produces a small but reliable performance benefit (~2.85% improvement) on exercise lasting 30 s to 10 min — translating indirectly into slightly higher training volume and therefore a plausible indirect hypertrophy benefit.
- **Confidence:** C1
- **Sources:** https://jissn.biomedcentral.com/articles/10.1186/s12970-015-0090-y ; https://pubmed.ncbi.nlm.nih.gov/26175657/ ; https://pubmed.ncbi.nlm.nih.gov/27797728/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC5466204/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Direct effect on LBM is essentially nil; benefit for bulking is entirely via supporting higher-volume resistance training. Paresthesia ("beta-alanine tingles") is benign; split doses ≤1.6 g or use sustained-release to minimize. No meaningful anti-hypertrophy safety issues at position-stand doses.

**Claim:** Vitamin D deficiency (25(OH)D <50 nmol/L or <20 ng/mL) is associated with reduced muscle strength and function, and correcting deficiency with supplementation improves strength; Beaudart 2014 meta-analysis (30 RCTs, older adults) reports a small positive effect on global muscle strength (SMD ~0.17) with the largest effects in baseline-deficient individuals.
- **Confidence:** C1
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/24748017/ ; https://academic.oup.com/jcem/article/99/11/4336/2836628
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Effect is strongest in older / deficient / sarcopenic populations. For already-replete young lifters, supplementing vitamin D does not reliably add strength or LBM — it is a deficiency-correction lever, not an ergogenic one.

**Claim:** In younger athletes, the Zhang 2019 meta-analysis of vitamin D supplementation (8 RCTs, athletes) reports a significant improvement in lower-limb muscle strength (SMD ~0.42) with supplementation, with larger benefits when baseline status is insufficient; typical effective dosing is 1,000-4,000 IU/day to reach and maintain 25(OH)D ≥75 nmol/L.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/31125416/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC6566799/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** A practical rule: test 25(OH)D; if <75 nmol/L, supplement 2,000-4,000 IU/day and retest. No meaningful benefit above repletion; chronic doses >10,000 IU/day carry hypercalcemia risk.

**Claim:** Omega-3 fatty acids (EPA+DHA) at ~3-5 g/day augment muscle protein synthesis in older adults (Smith 2011 reported ~0.3 g/kg insulin-amino-acid MPS rate improvement with 4 g/day fish oil × 8 weeks) and show mixed but generally favorable effects in younger adults (Smith 2015).
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/21159787/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC3499967/ ; https://pubmed.ncbi.nlm.nih.gov/25790328/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Smith 2011 (older adults) and Smith 2015 (healthy young/middle-aged) are the foundational MPS-stimulation studies. In trained young adults on adequate protein, omega-3s are probably a small plus for recovery/inflammation rather than a direct hypertrophy driver.

**Claim:** Omega-3 supplementation has a meaningful anti-catabolic effect during muscle disuse/immobilization: McGlory 2019 showed 5 g/day EPA+DHA attenuated the loss of quadriceps volume during 2 weeks of limb immobilization in young women, with the benefit persisting into the 2-week recovery phase.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/30620747/ ; https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.201802017R
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Strongest practical case for omega-3s in a bulking context is during injury, illness, or travel layoffs. Cochrane-style reviews in older adults (e.g. 2020 systematic reviews of omega-3 + resistance training) consistently show small additive LBM/strength effects on top of training, not a big standalone lever.

**Claim:** Citrulline malate acutely improves resistance-exercise performance: the Trexler 2019 meta-analysis (8 studies, 137 participants) reports a small but statistically significant increase in reps-to-failure (~+3 reps across multiple sets), typically from 8 g citrulline malate ~60 min pre-workout; the Perez-Guisado 2010 original bench-press trial showed 52.9% more total reps vs. placebo.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/30299361/ ; https://pubmed.ncbi.nlm.nih.gov/20386132/ ; https://journals.lww.com/nsca-jscr/Fulltext/2010/05000/Citrulline_Malate_Enhances_Athletic_Anaerobic.14.aspx
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Citrulline bypasses first-pass hepatic metabolism that limits oral arginine, so it raises plasma arginine and NO more reliably than arginine itself (relevant contrast to c012's "arginine is mostly hype" finding). Mechanism for bulking is the same as beta-alanine: indirect via more quality training volume. Effect size is small but the side-effect profile is clean.

**Claim:** Specific probiotic strains modestly enhance protein utilization and adaptation to resistance training: Jäger et al. (Lactobacillus paracasei / Bacillus coagulans / Bacillus subtilis DE111 trials, summarized in the 2019 ISSN probiotics position stand) show improved amino-acid appearance from plant protein and faster recovery; Toohey 2020 showed B. subtilis DE111 supplementation over 10 weeks of training improved body-composition markers in female athletes.
- **Confidence:** C2
- **Sources:** https://jissn.biomedcentral.com/articles/10.1186/s12970-019-0329-0 ; https://pubmed.ncbi.nlm.nih.gov/31864419/ ; https://pubmed.ncbi.nlm.nih.gov/31361552/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Effect sizes are modest and strain-specific — generic yogurt is not a substitute. Broader gut-microbiome → weight-gain literature (e.g., infant-GI-infection weight-gain signals, Akkermansia muciniphila in anti-obesity trials) is about fat/adiposity modulation, not muscle accretion. Intentionally manipulating the microbiome for LBM gain is scientifically underdeveloped — be honest that this is an adjunctive lever, not a primary tool.

**Claim:** L-carnitine and acetyl-L-carnitine do not drive weight gain; the evidence places carnitine supplementation in a weight-neutral to modest-weight-loss bracket (Pooyandjoo 2016 meta-analysis, ~1.3 kg weight reduction vs. placebo across 9 trials in overweight adults), making it inappropriate as a bulking supplement, though it has separate evidence for recovery and ischemia-related endpoints.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/27335245/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC6963458/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Cross-reference to any future "selective fat redistribution" claim file. Mentioned here for completeness because it recurrently appears in bodybuilding stacks — it is not a weight-gain aid.

**Claim:** ZMA (zinc + magnesium aspartate + B6) and its individual components have weak evidence for enhancing strength or LBM in non-deficient adults; the Wilborn 2004 ZMA RCT and subsequent trials show no significant effect on testosterone, IGF-1, strength, or body composition in resistance-trained men who are not zinc- or magnesium-deficient, though supplementing corrects deficiency-driven symptoms (sleep, recovery, performance).
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/18500945/ ; https://www.tandfonline.com/doi/abs/10.1080/15438620490280609 ; https://jissn.biomedcentral.com/articles/10.1186/1550-2783-1-2-12
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** ISSN-adjacent consensus: treat ZMA as a deficiency-correction / sleep-aid tool, not an anabolic. High-dose zinc chronically (>40 mg/day) risks copper deficiency.

**Claim:** Turkesterone and other ecdysteroids (beta-ecdysone, 20-hydroxyecdysone) show in-vitro and rodent anabolic signals and one small human trial (Isenmann 2019, 46 resistance-trained men, 10 weeks, ~200-800 mg/day ecdysterone) reported large strength and LBM gains — but the trial had a small n, inconsistencies in dosing/purity of commercial products have been repeatedly documented, and WADA added ecdysterone to its Monitoring Program in 2020.
- **Confidence:** C3
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/31123801/ ; https://link.springer.com/article/10.1007/s00204-019-02490-x ; https://www.wada-ama.org/en/resources/science-medicine/2020-monitoring-program
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** A single German trial, not replicated; label-content audits of commercial turkesterone products regularly find <10% of claimed dose or adulteration. Default tier for bulkers is C4-hype pending replication. Most marketing claims go far beyond what Isenmann 2019 supports.

**Claim:** Ashwagandha (Withania somnifera, typically KSM-66 or Sensoril extract, ~600 mg/day × 8-12 weeks) shows a consistent but modest signal for strength and lean-mass gains in resistance-training trials: Wankhede 2015 reported ~1.4-1.5 kg greater LBM gain and ~46 kg greater bench-press 1RM gain vs. placebo in 57 untrained men; Ziegenfuss 2018 confirmed modest strength and recovery benefits in recreationally active men.
- **Confidence:** C2
- **Sources:** https://pubmed.ncbi.nlm.nih.gov/26609282/ ; https://jissn.biomedcentral.com/articles/10.1186/s12970-015-0104-9 ; https://pubmed.ncbi.nlm.nih.gov/30181987/ ; https://pmc.ncbi.nlm.nih.gov/articles/PMC6266766/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Effect sizes from Wankhede 2015 are suspiciously large; most subsequent meta-analyses (e.g. Bonilla 2021) collapse the signal to a more modest small-to-moderate SMD. Mechanism probably involves a mild reduction in cortisol / perceived stress rather than a direct anabolic action. Rare hepatotoxicity signals reported; current position is "modest helper" but not a major lever.

**Claim:** Tongkat ali (Eurycoma longifolia), fenugreek, and most other "test booster" herbs produce small, inconsistent, and frequently placebo-level effects on testosterone, strength, and LBM in trained men; meta-analyses and narrative reviews (e.g., 2021-2024 reviews of "natural testosterone boosters") repeatedly conclude that the only herbs with even borderline signal are ashwagandha and (in specific populations) fenugreek, and that effect sizes fall far short of what marketing claims.
- **Confidence:** C2
- **Sources:** https://pmc.ncbi.nlm.nih.gov/articles/PMC7360813/ ; https://pubmed.ncbi.nlm.nih.gov/32297682/ ; https://www.mdpi.com/2072-6643/13/10/3374 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC8303470/
- **Date checked:** 2026-04-14
- **Cross-verified:** yes
- **Notes:** Tier C4 for any specific "this herb gives you X kg LBM" claim. Fenugreek has some evidence for libido and free testosterone in sedentary/older men; translation to muscle gain in trained bulkers is unreliable. Tribulus terrestris has essentially no anabolic evidence. D-aspartic acid — initial Topo 2009 trial not replicated; recent work shows no effect in trained men. Safety: the main risk of this category is adulteration with undeclared androgens or SARMs, especially in proprietary-blend "test booster" stacks.

---

## Summary table: modest helper vs. hype

| Supplement | Tier | Typical dose | Effect size in trained bulker | Notes |
|---|---|---|---|---|
| Beta-alanine | Modest helper | 3.2-6.4 g/d, 4+ wk | Small (~3% perf), indirect via volume | Clean safety; tingles benign |
| Vitamin D | Modest helper (if deficient) | 1-4k IU/d to repletion | Small; meaningful only if baseline low | Deficiency lever only |
| Omega-3 EPA+DHA | Modest helper | 3-5 g/d EPA+DHA | Small on LBM; bigger during disuse/older | Best during injury/layoff |
| Citrulline malate | Modest helper | 6-8 g, 60 min pre | Small on reps; indirect via volume | Distinct from arginine (c012 hype) |
| Probiotics (specific strains) | Adjunct | Strain-specific | Small, strain-dependent | ISSN position 2019 |
| HMB | Population-specific | 3 g/d | Clear in untrained/older/cachexia; marginal in trained | ISSN 2013; contested trained-lifter effect |
| Ashwagandha | Modest helper | 600 mg/d KSM-66 | Small-to-moderate on strength/LBM | Likely partly via stress reduction |
| L-carnitine | Not for bulking | — | Weight-neutral to slight loss | Cross-ref; not a gainer |
| ZMA | Deficiency-correction only | Per label | Null in non-deficient | ISSN weak evidence |
| Turkesterone / ecdysteroids | Hype pending replication | — | Unreliable; single positive trial; purity issues | WADA monitoring list |
| Tongkat ali / fenugreek / other "test boosters" | Mostly hype | — | Placebo-level in trained | Adulteration risk |

## Practical ranking for a trained bulker already on protein + creatine

Tier S (add by default): nothing — you're already on the biggest tools.

Tier A (add if performance/volume is the bottleneck): beta-alanine, citrulline malate.

Tier B (add for specific situations): vitamin D if deficient; omega-3 during injury, travel, or for older lifters; HMB for a detraining phase or in older/cachectic populations; ashwagandha if stress/sleep is a limiter.

Tier C (skip unless correcting a known deficiency): ZMA, probiotics (unless a specific strain for a specific reason).

Tier D (do not buy): turkesterone/ecdysteroid products, tongkat ali, fenugreek, proprietary "test booster" blends, carnitine-as-a-bulker.