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Muscle gain

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Medication5 Hormone therapy8 Peptides and SARMs6 Supplements25 Practices3 Daily life1 Food and drink1 Diets1 Lab markers4

Medication

AcetaminophenLimited

Muscle growth with resistance training

One small trial found 4 g a day raised muscle and strength gains from 12 weeks of resistance training in older adults.

The numbers and sources

Effect: Over 12 weeks of knee extensor training, quadriceps volume rose 12.5% on acetaminophen 4 g a day and 8.6% on placebo, and strength rose 19 kg against 15 kg. Muscle protein content, water content and fiber type distribution did not differ between groups [18].
Population: 36 adults aged about 64 to 67, 11 on acetaminophen, 13 on ibuprofen and 12 on placebo [18].
Sources: [18]
Caveats: One small trial in older adults. The dose, 4 g a day, is above the 6 caplets (3,000 mg) in 24 hours given in the over-the-counter directions [19].

StatinsLimited

Lean mass gain with resistance training

Limited evidence: one 12-week study linked statin use to greater lean mass gains with resistance training in adults aged 60 to 69, without randomizing statin use.

The numbers and sources

Effect: In a 12-week resistance training study, statin use was associated with greater gains in lean mass [4].
Population: 49 community-dwelling adults aged 60 to 69 [4].
Sources: [4]
Caveats: Statin use was not randomized, and the abstract gives no effect size. It reports an association, not a cause.

AlbuterolModerate

Strength and sprint performance in people without asthma

Mixed results: beta-agonists improved strength and sprint performance by about 5% overall in people without asthma, mostly with oral, weeks-long or prohibited use. Inhaled approved doses barely differed.

Compared with placebo [11]

The numbers and sources

Effect: Overall, beta-agonists improved anaerobic performance by about 5% (SDM 0.29, 95% CI 0.16 to 0.42). The effect was 0.14 (95% CI 0.00 to 0.28) for drugs and doses approved in sport and 0.46 for prohibited ones, 0.16 for inhaled and 0.51 for oral use, and 0.20 for a single dose against 0.50 over weeks. Strength (0.35) and sprint (0.17) both improved [11].
Population: 34 randomized placebo-controlled studies with 472 participants without asthma [11].
Sources: [11]
Caveats: The authors state it is uncertain whether doses approved in sport improve performance. Results are pooled across beta-agonists [11].

NSAIDsLimited

Muscle growth and strength with resistance training

Small trials found mixed results: ibuprofen raised muscle gains in older adults, lowered them in young adults against aspirin, and made no difference in another.

The numbers and sources

Effect: Results differ by trial. In older adults training for 12 weeks, ibuprofen 1.2 g a day increased quadriceps volume 10.9% against 8.6% on placebo, and strength 19 kg against 15 kg [6]. In young adults training for 8 weeks, ibuprofen 1,200 mg a day increased quadriceps volume 3.7% against 7.5% on low-dose aspirin, and strength gains on the maximal-effort leg were smaller [7]. In young adults training for 6 weeks, ibuprofen 400 mg after each session did not change biceps thickness or strength against placebo [8]. A systematic review of 7 athlete trials found NSAIDs did not raise collagen synthesis or satellite cell activity after exercise [9].
Population: 36 adults aged about 64 to 67 [6]; 31 adults aged 18 to 35 [7]; 18 adults aged about 24, each arm its own control [8]; 346 athletes in 7 RCTs [9].
Sources: [6], [7], [8], [9]
Caveats: Small trials with different doses, ages and comparators. [7] compared ibuprofen with 75 mg aspirin, not placebo. No meta-analysis of training adaptations was sourced.

InsulinUntested

Muscle gain in people without diabetes

Not studied in people. Bodybuilders report injecting insulin to build muscle, and a review found little evidence-based human data for the practice.

No study in people. This rests on what users report, how it acts in the body.

The numbers and sources

Effect: A review of hormones used for anabolic purposes describes insulin as commonly abused by professional and recreational athletes, and states that the belief in added muscle mass is widespread among users despite a paucity of evidence-based data in humans [17]. In a questionnaire study of 92 male recreational bodybuilders, 43% reported regular hormone use, and 38% of those reported using insulin [18].
Population: 92 male recreational bodybuilders answering anonymous questionnaires [18]. No controlled trial in people without diabetes was located [17].
Sources: [17], [18]
Caveats: Not an approved use. What users report is not a measured effect. See the risk block on low blood sugar in people without diabetes.

Hormone therapy

Testosterone therapyStrongStudied in men

Fat-free mass and body fat in middle-aged and older men

Shown to add about 1.6 kg of fat-free mass and cut about 1.6 kg of body fat in middle-aged and older men, with no change in weight.

The numbers and sources

Effect: Testosterone raised fat-free mass by 1.6 kg (95% CI 0.6 to 2.6), a 2.7% rise over baseline, and cut total body fat by 1.6 kg (95% CI 0.6 to 2.5), a 6.2% drop. Body weight did not change [2]. A 2026 systematic review of 8 double-blind placebo-controlled trials in men with obesity and type 2 diabetes or metabolic syndrome found the most consistent effect was more lean mass and less fat mass [3].
Population: 1,083 men in 29 RCTs, weighted mean age 64.5, mean baseline testosterone 10.9 nmol/L [2]; men with functional secondary hypogonadism, obesity and type 2 diabetes or metabolic syndrome in 8 RCTs [3].
Sources: [2], [3]
Caveats: The meta-analysis is from 2005, and dose and preparation explained some of the heterogeneity between trials [2]. The 2026 review was not pooled and rated certainty for lean and fat mass as low [3]. Fat-free mass counts water and organs as well as muscle.

DHEAModerate

Lean mass and fat mass

Shown to raise lean mass by about 0.45 kg in adults, though a 2-year trial in older adults found no change in body composition.

The numbers and sources

Effect: Pooled RCTs found DHEA raised lean body mass by 0.45 kg (95% CI 0.15 to 0.75) and lowered fat mass by 0.85% (95% CI 0.51 to 1.18). Body weight did not change [1]. In elderly men, fat mass fell by an SMD of -0.35 (95% CI -0.65 to -0.05), but the effect disappeared after adjusting for rises in testosterone and estradiol [2]. A 2-year RCT found no significant effect on body composition in men or women [3].
Population: Adults in randomized trials [1]; 1,353 elderly men in 25 placebo-controlled RCTs, mean follow-up 36 weeks [2]; 87 elderly men and 57 elderly women with low DHEA-S over 2 years [3].
Sources: [1], [2], [3]
Caveats: The pooled lean mass gain is small, and the one long trial did not find it.

Growth hormoneModerate

Body composition in healthy older adults

Shown to lower fat mass about 2.1 kg and raise lean body mass about 2.1 kg in healthy older adults, with no change in weight.

The numbers and sources

Effect: Against no growth hormone, fat mass fell 2.1 kg (95% CI 1.35 to 2.8) and lean body mass rose 2.1 kg (95% CI 1.3 to 2.9). Weight did not change (0.1 kg, 95% CI -0.7 to 0.8). Total cholesterol fell 0.29 mmol/L, not significantly after adjusting for body composition. Bone density and other lipids did not change [1].
Population: 18 study populations with 220 treated participants, mean age 69, mean BMI 28, mean treatment 27 weeks [1].
Sources: [1]
Caveats: Most trials were small, and some outcomes were measured too rarely to pool [1]. The review was funded by AHRQ and the NIA. Lean body mass includes water, not only muscle.

Growth hormoneModerate

Visceral fat and thigh muscle in adults with obesity

Shown to lower visceral fat modestly and raise thigh muscle area with low-dose growth hormone in adults with obesity and no deficiency.

The numbers and sources

Effect: In adults with obesity and no growth hormone deficiency, low-dose growth hormone lowered visceral fat by an SMD of -0.34 (95% CI -0.57 to -0.12) and raised thigh muscle area by 6.33 cm² (95% CI 1.72 to 10.95) against placebo [4].
Population: 420 adults aged 18 to 65 in 10 RCTs lasting 4 to 72 weeks [4].
Sources: [4]
Caveats: Small trials with wide differences in length. Fasting glucose rose (see Risks) [4].

Growth hormoneModerate

Lean mass and leg strength in orthopedic patients

Shown to raise lean body mass about 3.6% and leg strength about 3.2% in orthopedic and sports medicine patients.

The numbers and sources

Effect: Across orthopedic studies, lean body mass rose in 15 of 23 studies, a mean difference of 3.63% against placebo, and leg extension strength rose by a mean difference of 3.17%. IGF-1 rose by a mean of 133.2%, in a dose-dependent way [5].
Population: 1,157 patients, mean age 54.3, in 22 studies of orthopedic surgery and sports medicine settings, mean dose 1.49 mg per day [5].
Sources: [5]
Caveats: The review rated its studies as moderate quality and pooled only where it could [5]. These were patients, not healthy athletes.

Growth hormoneModerate

Body composition and quality of life in growth hormone deficiency

Shown to lower body fat about 2.6 kg and raise lean mass about 1.4 kg in adults with growth hormone deficiency. Quality of life improved in most trials.

The numbers and sources

Effect: In adults with confirmed deficiency, growth hormone lowered weight by 2.31 kg (95% CI 1.96 to 2.66) and body fat by 2.56 kg (95% CI 2.16 to 2.97), and raised lean body mass by 1.38 kg (95% CI 1.10 to 1.65). BMI and bone density did not change. Quality of life improved in 11 of 16 trials, though the data could not be pooled [6].
Population: 54 RCTs with more than 3,400 adults with growth hormone deficiency [6].
Sources: [6]
Caveats: Trial quality was rated fair [6]. These results describe people with a diagnosed deficiency, not healthy adults.

Testosterone therapyLimitedStudied in men

Muscle size and strength at high doses in young men

One small 1996 trial at high doses found more muscle size and strength in young men with normal testosterone, most with training.

The numbers and sources

Effect: Over 10 weeks without exercise, men on testosterone gained more triceps area (424 vs -81 mm²), quadriceps area (607 vs -131 mm²), bench press (9 vs -1 kg) and squat (16 vs 3 kg) than men on placebo. With training, the testosterone group gained 6.1 kg of fat-free mass, 22 kg on bench press and 38 kg on squat, more than either non-exercise group. Mood and behavior did not change in any group [5].
Population: 43 healthy men with normal testosterone, in 4 groups, for 10 weeks [5].
Sources: [5]
Caveats: One small trial from 1996 at a dose the authors describe as supraphysiologic. It does not address men with low testosterone or use over years.

Menopausal hormone therapyModerateStudied in women

Muscle mass

Not shown to preserve lean mass in postmenopausal women, with no consistent benefit across trials.

The numbers and sources

Effect: Women on hormone therapy lost 0.06 kg less lean body mass than controls (95% CI -0.05 to 0.18), not a significant difference. Results were unchanged by treatment type, dose, duration or time since menopause [8]. A 2025 systematic review counted 7 of 12 RCTs suggesting more muscle on scans with hormone therapy, and found no consistent evidence of benefit overall [9].
Population: 12 RCTs with 4,474 women, mean age 59, median follow-up 2 years [8]; 15 RCTs and 28 observational studies of community-dwelling women [9].
Sources: [8], [9]
Caveats: GRADE quality of evidence was low [8]. The systematic review rated risk of bias high to severe, and most data were over 20 years old [9].

Peptides and SARMs

TesamorelinStrong

Lean body mass

Shown to add about 1.4 kg of lean mass over placebo in people with HIV. Lean mass is a scan measure, not strength.

The numbers and sources

Effect: Two meta-analyses found lean body mass rose by 1.42 kg against placebo (95% CI 1.13 to 1.71) [4][5].
Population: 909 people with HIV-associated lipodystrophy in 4 RCTs [4]; 5 RCTs against placebo [5].
Sources: [4], [5]
Caveats: Both reviews pooled largely the same trials in people with HIV. Lean mass is a scan measure, not strength.

MK-677Grey marketModerate

Fat-free mass

Shown to add about 1.1 kg of fat-free mass over a year in older adults, against a 0.5 kg loss on placebo. Body weight also rose.

The numbers and sources

Effect: At 12 months, fat-free mass changed by +1.1 kg (95% CI 0.7 to 1.5) on MK-677 and -0.5 kg (95% CI -1.1 to 0.2) on placebo. Intracellular water, a marker of body cell mass, changed by +0.8 kg against -1.0 kg [1]. In obese men over 8 weeks, fat-free mass rose on MK-677 compared with placebo by DEXA and by a four-compartment model [2].
Population: 65 healthy adults aged 60 to 81, over 2 years [1]; 24 obese men aged 18 to 50, BMI over 30 [2].
Sources: [1], [2]
Caveats: Fat-free mass includes water, organs and bone, not only muscle. Body weight also rose 2.7 kg against 0.8 kg on placebo [1].

SARMsGrey marketModerate

Lean body mass

Shown to add lean mass, about 1 to 1.5 kg across short trials, in healthy adults and people with cancer weight loss. Lean mass is not the same as strength.

The numbers and sources

Effect: LGD-4033 raised lean body mass in a dose-dependent way over 21 days [1]. Enobosarm raised total lean body mass in a dose-dependent way over 12 weeks, significant against placebo at the higher dose [2]. In people with cancer-related weight loss, lean mass rose by a median 1.5 kg and 1.0 kg in the two enobosarm groups by day 113, against 0.02 kg on placebo [3]. A 2026 review reports lean mass rising by roughly 1 to 1.5 kg across randomized trials [4].
Population: 76 healthy men aged 21 to 50 [1]; 120 healthy men over 60 and postmenopausal women [2]; 159 men over 45 and postmenopausal women with cancer and at least 2% weight loss, 100 in the efficacy analysis [3].
Sources: [1], [2], [3], [4]
Caveats: The trials were short. In the cancer trial, the gains were changes from baseline within each group, and the trial was funded by GTx, the developer [3]. Lean mass by DEXA is not the same as muscle strength.

BPC-157Grey marketUntested

Muscle injury

Not studied in people. Animal studies found faster recovery of cut and crushed leg muscles in rats.

No study in people. This rests on animal studies.

The numbers and sources

Effect: In rats whose quadriceps muscle was cut through, BPC-157 given by injection improved load to failure, walking recovery, muscle fiber regeneration and the muscle's appearance over 72 days [20]. In rats with a crushed calf muscle, BPC-157 given by injection or as a cream over 14 days reduced bruising and swelling and improved function, microscopic healing and muscle enzyme levels [21]. A 2019 review found that skeletal muscle injury models suggested a benefit after direct trauma [15].
Population: Rats [15][20][21].
Sources: [20], [21], [15]
Caveats: The two injury studies come from the same research group [20][21]. Cut and crushed muscles in rats do not show what happens after a muscle strain in people. The human studies located concerned knee pain, interstitial cystitis and intravenous safety [9].

CJC-1295 and ipamorelinGrey marketNo research yet

Muscle and strength

We haven't sourced research on this yet.

TB-500Grey marketNo research yet

Muscle healing

We haven't sourced research on this yet.

Supplements

CreatineStrong

Lean mass during resistance training

Shown to add about 1 kg of lean mass over placebo alongside resistance training, and almost none without exercise.

The numbers and sources

Effect: Across 35 RCTs (1,192 participants), creatine raised lean body mass by 0.68 kg over placebo overall, and by 1.10 kg (95% CI 0.56 to 1.65) when combined with resistance training. With no exercise the difference was 0.03 kg (95% CI -0.65 to 0.70) [1]. In older adults training 2 to 3 days a week, the gain was 1.37 kg (95% CI 0.97 to 1.76) [2]. In postmenopausal women it was 0.37 kg (95% CI 0.05 to 0.69) [3].
Population: Healthy adults of all ages [1]; 721 adults with mean ages of 57 to 70 across 22 trials lasting 7 to 52 weeks [2]; 608 postmenopausal women in 7 trials lasting 12 to 104 weeks [3].
Sources: [1], [2], [3]
Caveats: Men gained 1.46 kg (95% CI 0.47 to 2.46) and women 0.29 kg (95% CI -0.43 to 1.01), a difference that did not reach significance for women [1]. Lean mass by DXA counts water, and creatine raises muscle water, so lean mass is not the same measure as contractile tissue. Several authors of [3] also authored the ISSN position stand [4]. In a 2026 analysis of 11 RCTs in adults aged 60 and over, the added muscle mass was not significant (g 0.35, 95% CI -0.09 to 0.78, low certainty) [5].

Protein powderStrong

Muscle mass and strength during resistance training

Shown to add about 2.5 kg of strength and 0.3 kg of fat-free mass during resistance training, with no extra gain above 1.62 g per kg of total protein.

The numbers and sources

Effect: Across 49 RCTs (1,863 participants), protein supplements increased 1RM strength by 2.49 kg (95% CI 0.64 to 4.33) and fat-free mass by 0.30 kg (95% CI 0.09 to 0.52) over control. Gains in fat-free mass did not rise further once total protein intake passed 1.62 g per kg a day. The effect fell with age and was larger in trained lifters (0.75 kg, 95% CI 0.09 to 1.40) [1]. An earlier meta-analysis of 22 RCTs (680 people) found 0.69 kg more fat-free mass (95% CI 0.47 to 0.91) and 13.5 kg more leg press 1RM (95% CI 6.4 to 20.7) [2]. In 12 studies of adults aged 18 to 30 (261 participants), whey raised bench press by 8.87 kg (95% CI 5.95 to 11.79) and squat by 9.60 kg (95% CI 5.61 to 13.60), and neither whey nor soy significantly changed lean body mass [3].
Population: Healthy adults in resistance training programs of 6 weeks or longer [1][2]. Young adults [3].
Sources: [1], [2], [3]
Caveats: The supplement effect depends on how much protein the diet already provides; the 1.62 g per kg breakpoint is total intake from food plus powder [1]. Trials mix whey, casein, soy and blends. The smaller 2025 review of young adults did not find the lean mass gain the two larger reviews report [3].

BCAAs and EAAsModerate

Muscle protein synthesis

Shown to raise muscle protein synthesis for hours, by 22% in one trial of trained men, but less than complete protein. Lean mass did not change in older adults.

The numbers and sources

Effect: In 10 resistance-trained young men, 5.6 g of BCAAs after training raised myofibrillar protein synthesis to 0.110%/h against 0.090%/h on placebo, 22% higher [1]. A review of human studies found BCAAs transiently stimulate protein synthesis, but less than a complete protein source with all essential amino acids [2]. In older adults, leucine supplements raised the fractional synthetic rate (SMD 1.08, 95% CI 0.50 to 1.67) in 9 RCTs, with no change in lean body mass (SMD 0.18, 95% CI -0.18 to 0.54) or leg lean mass [3].
Population: Young trained men [1]; older adults [3].
Sources: [1], [2], [3]
Caveats: Synthesis rates over hours do not predict muscle gained over months, as the leucine meta-analysis shows [3]. The 2017 trial was funded in part by GlaxoSmithKline [1]. Reference [2] is a narrative review.

BCAAs and EAAsModerate

Muscle mass and strength in older adults

Shown to improve strength and muscle mass modestly in older adults, for supplements rich in BCAAs, including EAA and whey products.

The numbers and sources

Effect: Across 35 RCTs in older people, BCAA-rich supplements, a category that included EAA and whey protein products, improved strength (SMD 0.35, 95% CI 0.15 to 0.55), muscle mass (SMD 0.25, 95% CI 0.10 to 0.40) and physical performance (SMD 0.29, 95% CI 0.00 to 0.57). EAA supplements improved handgrip strength more than whey protein in subgroup analysis [7]. In 52 patients having knee replacement, 9 g a day of EAAs from 1 week before to 2 weeks after surgery left rectus femoris area at 134% of baseline at 2 years against 114% on placebo, and quadriceps strength at 159% against 125%. Clinical outcomes did not differ [8]. In 10 RCTs and one prospective study of people with sarcopenia, leucine groups differed from placebo in handgrip strength (p = 0.03), appendicular muscle mass and gait speed (p = 0.008) [9].
Population: Older adults [7]; knee replacement patients [8]; 1,133 people over 65 with sarcopenia [9].
Sources: [7], [8], [9]
Caveats: High heterogeneity, and 14 of 35 trials had potential bias [7]. The pooled supplements are not pure BCAA products. The leucine review rated its evidence low quality and found leucine alone of limited benefit without other therapy [9].

CLAModerate

Lean mass

Shown to raise fat-free mass by about 0.3 kg in adults, under 1% of fat-free mass.

The numbers and sources

Effect: In the same 18 trials pooled for fat loss, fat-free mass rose 0.3 kg during CLA treatment, with no effect of dose or duration [4]. In 70 RCTs, fat-free mass rose 0.27 kg (95% CI 0.09 to 0.45) [3].
Population: Adults in RCTs [3][4].
Sources: [3], [4]
Caveats: The change was under 1% of fat-free mass [4].

Protein powderModerate

Muscle and strength in older adults

Shown to raise lower-body strength slightly in older adults, with lean mass gains only when combined with resistance training.

The numbers and sources

Effect: In 25 trials (1,454 adults aged 64 to 84), whey raised lower-body strength (SMD 0.16, 95% CI 0.04 to 0.28, 19 trials) and did not change upper-body strength or body composition overall. Combined with resistance training, whey raised lean body mass [4].
Population: Older adults, with or without resistance training [4].
Sources: [4]
Caveats: One meta-analysis. The lean mass finding comes from a subgroup [4].

FenugreekLimited

Muscle strength with training

Limited evidence: 4 of 6 small trials reported gains in strength, lean mass or lower body fat with fenugreek extracts alongside exercise.

The numbers and sources

Effect: A systematic review of 6 RCTs found 4 reported gains in muscle strength, repetitions to failure, lean mass or lower body fat with fenugreek extracts. Of two small glycogen trials, one found faster resynthesis and one did not [7].
Population: Participants in 6 RCTs of exercise or sport [7].
Sources: [7]
Caveats: Narrative synthesis without pooled effect sizes. Two of the trials had fewer than 10 participants [7].

Fish oilLimited

Muscle mass and function in older adults

Limited evidence: omega-3 added about 0.33 kg of muscle mass and slightly improved timed up and go in older adults.

The numbers and sources

Effect: Across 10 trials in older adults, omega-3 added 0.33 kg of muscle mass (95% CI 0.05 to 0.62) and shortened timed up and go by 0.30 seconds (95% CI -0.43 to -0.17). Above 2 g a day the muscle mass gain was 0.67 kg (95% CI 0.16 to 1.18) [34]. In 94 healthy older adults, 4 g a day of krill oil for 6 months increased muscle strength and size against a control oil, with similar responses by age, sex and BMI [35].
Population: Older adults in 10 RCTs [34]; adults 65 and older doing less than 1 hour of structured exercise a week [35].
Sources: [34], [35]
Caveats: Few trials, and the dose subgroup is post hoc. The search ended in July 2018 [34]. The krill oil report is a secondary analysis of one trial [35].

Protein powderLimited

Pre-sleep casein

Limited evidence: pre-sleep casein raised overnight muscle protein synthesis, with gains in size and strength in young men but not older men.

The numbers and sources

Effect: 20 to 40 g of casein about 30 minutes before sleep raised overnight protein synthesis rates in young and older men. Over 10 to 12 weeks of training, pre-sleep protein increased fiber size, strength and muscle mass in young men but not in older men [8]. In 24 trained soccer players, 30 g of casein before sleep and the same dose right after training both improved next-day anaerobic performance against no casein, and the two timings did not differ [9]. After sleeve gastrectomy, casein-enriched milk before sleep or during the day did not change body composition, strength or physical performance over 12 weeks compared with no supplement [10]. In 9 trained adults, 40 g of casein before sleep did not change sleep measures against a carbohydrate control, while the same dose of whey shortened sleep onset and lengthened sleep [11].
Population: Nine studies, mostly men [8]. 24 male soccer players [9]. 45 adults after bariatric surgery [10]. 9 young adults, crossover [11].
Sources: [8], [9], [10], [11]
Caveats: Reference [8] is a systematic review without pooling. Its authors note uneven total protein intake between groups, so the timing effect cannot be separated from extra protein [8]. The three newer trials are small [9][10][11].

HMBModerate

Muscle mass and strength in older adults and patients

Mixed results: HMB raised muscle mass and strength slightly in older adults and patients, but not when added to resistance training.

The numbers and sources

Effect: In 9 RCTs (448 older adults), HMB raised fat-free mass (ES 0.37, 95% CI 0.16 to 0.58), with no change in fat mass. HMB alone raised fat-free mass (ES 0.59); HMB added to exercise did not (ES 0.06, 95% CI -0.26 to 0.38) [5]. In 21 RCTs (1,935 people over 50), HMB raised appendicular muscle mass by 1.56 kg (95% CI 0.03 to 3.09), lean mass by 0.28 kg, handgrip strength by 0.54 kg and gait speed by 0.06 m/s [6]. In 5 RCTs in sarcopenia, muscle mass index (SMD 0.32, 95% CI 0.00 to 0.64) and handgrip strength (SMD 0.65) rose, and gait speed did not change [7]. In 15 RCTs (2,137 patients with muscle-wasting conditions), HMB or HMB-containing supplements raised muscle mass (SMD 0.25, 95% CI -0.00 to 0.50) and strength (SMD 0.31, 95% CI 0.12 to 0.50) [8].
Population: Older adults [5][6]; people with sarcopenia [7]; hospital and clinical patients [8].
Sources: [5], [6], [7], [8], [9], [10]
Caveats: Many trials gave HMB in multi-ingredient nutrition drinks, so the effect of HMB alone is unclear [8]. No trial in [8] had low risk of bias in every category. Review [6] searched Chinese databases. Added to resistance training, HMB did not change muscle mass (SMD 0.05, 95% CI -0.10 to 0.20, 13 RCTs, 561 adults over 50) or strength [9], and a second review of 10 trials (596 older adults) found no change in lean mass, a borderline handgrip gain (SMD 0.24, 95% CI 0.00 to 0.48) and better physical performance scores (SMD 0.54), with half the trials at high risk of bias [10].

NMNModerate

Muscle and physical function

Mixed results: one review found no change in muscle mass, strength or gait speed in older adults, while others found better endurance or gait speed.

The numbers and sources

Effect: In adults with a mean age over 60, NMN did not change skeletal muscle index (MD -0.42, 95% CI -0.99 to 0.14), grip strength, gait speed (MD -0.01 m/s, 95% CI -0.08 to 0.06) or chair-stand time. Knee extension strength, SPPB scores and thigh muscle mass did not improve [4]. A network meta-analysis of NAD precursors reported higher endurance with NMN at medium dose (SMD 0.66, 95% CI 0.09 to 1.23) and high dose (SMD 1.02, 95% CI 0.43 to 1.60), with no change in strength [5]. One trial reported a longer six-minute walk on 300 to 900 mg a day than placebo [1]. A 2025 meta-analysis of 9 RCTs (412 middle-aged and older adults) found faster gait speed on NMN (SMD 0.34, 95% CI 0.03 to 0.66) and lower ALT (SMD -0.29, 95% CI -0.55 to -0.03) [6].
Population: Randomized trials in adults with mean ages of 60.9 to 83 years [4]; 27 studies with 1,599 adults across NR, NMN, NADH and nicotinamide [5]; 80 middle-aged adults [1]; 412 middle-aged and older adults [6].
Sources: [4], [5], [1], [6]
Caveats: The reviews disagree on endurance and on gait speed [4][5][6]. The pooled muscle analysis included 2 to 5 studies per measure [4]. The network analysis mixes precursors and populations [5].

Vitamin DModerate

Muscle strength

Shown to raise muscle strength slightly in older adults and those with low vitamin D, with no change in younger people. A newer review found no change.

The numbers and sources

Effect: Across 30 RCTs (5,615 people, mean age 61.1), vitamin D raised global muscle strength by an SMD of 0.17. Muscle mass (SMD 0.058) and power (SMD 0.057) did not change. The effect was larger with baseline 25-hydroxyvitamin D below 30 nmol/L and at 65 or older (SMD 0.25, 95% CI 0.01 to 0.48) than in younger people (SMD 0.03, 95% CI -0.08 to 0.14) [23]. Across 7 RCTs in adults 60 and older, vitamin D did not raise skeletal muscle mass index, lean mass or handgrip strength [24]. In 152 postmenopausal women with 25-hydroxyvitamin D below 30 ng/mL, 20 µg calcifediol or 3,200 IU vitamin D3 a day for 6 months did not differ from placebo on gait speed, knee strength and sit-to-stand tests (success in 53.6%, 55.5% and 61.4%) [25].
Population: Adults in 30 RCTs, with or without calcium [23]; adults with mean age 60 to 74 in 7 RCTs of 3 to 36 months [24]; women aged 50 to 70 with osteopenia or osteoporosis [25].
Sources: [23], [24], [25]
Caveats: An SMD of 0.17 is small, and the search for that review ended in January 2014 [23]. The newer review did not find a change in handgrip strength [24].

CollagenLimited

Muscle mass and strength with training

Limited evidence: one review found gains in fat-free mass and strength with training, while 8 training trials found collagen added no strength gain.

The numbers and sources

Effect: Across 19 RCTs (768 healthy adults) training for 8 weeks or more, collagen peptides improved fat-free mass (SMD 0.48), muscle architecture (SMD 0.39), maximal strength (SMD 0.19) and 48-hour reactive strength recovery (SMD 0.43) [1]. A 2025 meta-analysis found muscle performance improved (SMD 0.60, 95% CI 0.05 to 1.15) [10]. In 8 training RCTs, strength rose with training in every trial, and collagen added no further gain [2].
Population: Healthy adults over 17 in exercise programs [1]; people in RCTs of collagen with or without calcium and vitamin D [10]; trained adults aged 18 to 52 [2].
Sources: [1], [10], [2]
Caveats: Sources disagree on strength. GRADE certainty was moderate for body composition and low for the other outcomes [1]. A systematic review found collagen did not raise muscle protein synthesis compared with isonitrogenous higher-quality proteins [3].

GABALimited

Growth hormone and lean mass

Small trials found 3 g raised growth hormone in trained men, but 200 mg a day did not change body fat or lean mass in women with obesity.

The numbers and sources

Effect: In 11 resistance-trained men, 3 g of GABA raised peak resting growth hormone about 400% and area under the curve about 375% compared with placebo, and growth hormone was also higher after exercise [7]. In 21 men training twice a week for 12 weeks, 10 g of whey plus 100 mg of GABA increased fat-free mass more than whey alone [8]. In 26 women with obesity training 3 days a week for 90 days, 200 mg of GABA a day did not change body fat, fat mass, fat-free mass or growth hormone compared with placebo. Within the GABA group, BMI and waist circumference fell and sit-up performance rose [9].
Population: 11 men aged 18 to 30, crossover [7]. 21 men aged 26 to 48 [8]. 26 women with obesity [9].
Sources: [7], [8], [9]
Caveats: All three trials were small. The within-group changes in the women's trial were not differences from placebo [9]. The lean mass trial was funded by Pharma Foods International, which supplied the GABA and employed four authors [8]. A rise in growth hormone was not shown to change muscle in [7].

L-arginineLimitedStudied in men

Growth hormone and muscle growth

Mixed results: small trials found oral arginine raised resting growth hormone but blunted its rise after lifting, and lean mass did not change in athletes over 45 days.

The numbers and sources

Effect: In 8 healthy men, 5 g and 9 g of oral arginine raised the growth hormone area under the curve over placebo at rest, while 13 g did not and caused stomach upset in most [16]. In 8 men, 7 g of arginine before resistance exercise gave a smaller growth hormone response than exercise alone [17]. In 14 strength-trained men, arginine before lifting blunted growth hormone (area under the curve 288.4 against 487.9 on placebo, p < 0.05), with no difference in IGF-1 [18]. In 56 male soccer players, 2 g a day for 45 days did not change lean body mass, fat mass or BMI against placebo [19].
Population: Healthy young men [16][17]. Strength-trained men [18]. Male soccer players aged 16 to 35 [19].
Sources: [16], [17], [18], [19]
Caveats: Small, short trials in men. Growth hormone was measured for hours after a single dose, and no trial measured muscle growth over a training program [16][17][18].

HMBStrong

Strength and fat-free mass in trained athletes and young lifters

Not shown to change strength, fat-free mass or fat mass in trained athletes or young adults in resistance training.

The numbers and sources

Effect: In 6 RCTs of trained and competitive athletes (193 participants), effect sizes were trivial and not significant for bench press (0.00), leg press (0.09), fat-free mass (0.16) and fat mass (-0.20) [1]. In 11 studies of adults aged 18 to 45 in resistance training, HMB raised total body mass slightly but did not change fat-free mass, fat mass or strength [2]. In 5 studies of athletes, fat-free mass trended up (0.30, 95% CI -0.07 to 0.68, p = 0.08), apparently only when protein intake was under 1.6 g per kg a day [3].
Population: Trained and competitive athletes [1][3]; young adults in training [2].
Sources: [1], [2], [3]
Caveats: Small pooled samples. The ISSN position stand [4] reports body composition improvements across ages and training levels, but several of its authors disclose employment, consulting or patents tied to HMB.

Protein powderStrong

Plant protein compared with animal protein

Not shown to differ in strength by protein source. Soy matched milk protein for muscle, while non-soy plant proteins trailed animal protein in 5 trials.

The numbers and sources

Effect: In 16 RCTs, protein source did not change absolute lean mass or strength; adults under 50 gained 0.41 kg more lean mass (95% CI 0.08 to 0.74) on animal protein [5]. In 30 RCTs, plant protein produced lower muscle mass than animal protein (SMD -0.20, 95% CI -0.37 to -0.03). Soy and milk protein did not differ (SMD -0.02, 17 RCTs). Non-soy plant proteins such as rice, oat and potato trailed animal protein (SMD -0.58, 5 RCTs). Strength (14 RCTs) and physical performance (5 RCTs) did not differ [6].
Population: Adults of all ages, most with protein intakes above the RDA [5][6].
Sources: [5], [6]
Caveats: Few trials tested pea, rice or other non-soy powders, so the non-soy estimate rests on 5 trials [6].

Beta-alanineModerate

Body composition and muscle gain

Not shown to change body mass, fat mass or fat-free mass in adults in training, across 20 trials.

The numbers and sources

Effect: Across 20 RCTs (492 participants), beta-alanine did not change body mass (-0.15 kg, 95% CI -0.78 to 0.47), fat mass (-0.24 kg, 95% CI -1.16 to 0.68), body fat percentage (-0.06%) or fat-free mass (0.05 kg, 95% CI -0.71 to 0.82). Results were the same across training type, duration and dose [7].
Population: Adults in resistance, endurance or combined training [7].
Sources: [7]
Caveats: Certainty ranged from low to moderate. The authors report no funding [7].

ChromiumModerateStudied in men

Strength and muscle with resistance training

Not shown to add to strength or muscle gains from resistance training in men, in two small trials.

The numbers and sources

Effect: Over 8 weeks, strength, fat-free mass and muscle mass rose with training, and chromium chloride or picolinate did not add to the gains [10]. Over 12 weeks in older men, 924 µg a day did not add to strength, muscle size or lean mass. The placebo group gained more knee-extension power [11].
Population: 36 men [10]; 18 men aged 56 to 69 [11].
Sources: [10], [11]
Caveats: Both trials were small.

D-aspartic acidModerateStudied in men

Strength and muscle with training

Not shown to add to strength or muscle gains from resistance training in trained men over 28 days to 12 weeks.

The numbers and sources

Effect: Over 28 days of heavy resistance training, body composition and strength rose in both groups and did not differ between 3 g of D-aspartic acid and placebo [2]. Over 12 weeks of supervised training, isometric strength rose 17% and quadriceps and calf muscle size increased similarly in both groups on 6 g a day or placebo [4].
Population: Resistance-trained men [2][4].
Sources: [2], [4]
Caveats: Small samples, 22 randomized in [4].

GlutamineModerate

Athletic performance and body composition

Not shown to change lean mass, body fat or VO2max in athletes. Body weight fell about 1.4 kg.

The numbers and sources

Effect: Across 25 trials in athletes over 18, glutamine did not change lean body mass, body fat percentage or VO2max. Body weight fell by 1.36 kg (95% CI -2.55 to -0.16) [1].
Population: Athletes, 47 studies reviewed and 25 pooled [1].
Sources: [1]
Caveats: One meta-analysis. The weight change is not explained by a lean mass or fat change in the same analysis [1].

Nicotinamide ribosideModerate

Muscle and physical function

Not shown to preserve muscle mass or function in adults over 60. One trial found a longer six-minute walk in peripheral artery disease.

The numbers and sources

Effect: A meta-analysis of randomized trials in adults over 60 found no support for NR or NMN preserving muscle mass or function. NR was linked to a longer six-minute walk in peripheral artery disease, and to lower SPPB scores and slower chair stands in mild cognitive impairment [5]. In the peripheral artery disease trial, six-minute walk changed by +7.0 m on NR and -10.6 m on placebo, a difference of +17.6 m (90% CI +1.8 to +∞) at 6 months [6].
Population: Randomized trials in adults with mean ages of 60.9 to 83 [5]; 90 people with peripheral artery disease for 6 months [6].
Sources: [5], [6]
Caveats: The walking result is one trial with a one-sided interval. ChromaDex supplied the NR and placebo for it [6].

TribulusModerateStudied in men

Strength and sport performance

Not shown to improve strength, body composition or sport performance in active men. One small trial found a larger bench press gain.

The numbers and sources

Effect: In 30 CrossFit-trained men over 6 weeks, body composition and four of five workout tests did not differ from placebo. Bench press rose 19.2% with tribulus against 8.5% with placebo [5]. A systematic review of 7 studies in physically active men found no clear benefit on muscle damage markers or hormones, some lipid improvements and no reported toxicity [4]. A review of athlete use found that tribulus alone did not improve androgen status or physical performance [9].
Population: Physically active men [4][5][9].
Sources: [4], [5], [9]
Caveats: Few and small trials.

BCAAs and EAAsLimited

Lean mass during dieting

One trial found BCAAs did not significantly reduce lean mass loss over 16 weeks of dieting in 132 adults, and a high-protein diet lost the least.

The numbers and sources

Effect: In 132 adults with overweight or obesity on a 500 kcal daily deficit for 16 weeks, lean mass fell 4.39% with BCAAs (0.1 g per kg a day), 5.39% with placebo and 3.67% with a high-protein diet (p = 0.06). Insulin sensitivity did not differ among groups [6].
Population: 132 Chinese adults aged 21 to 45 [6].
Sources: [6]
Caveats: One RCT. The high-protein diet group lost the least lean mass [6].

Turkesterone and ecdysteroneLimitedStudied in men

Muscle growth with turkesterone

One small study found no significant change in IGF-1 or resting metabolic rate within 24 hours of turkesterone in 11 young men. No muscle growth trial was located.

Compared with placebo [8]

The numbers and sources

Effect: In 11 healthy men, mean age 23, turkesterone did not significantly change serum IGF-1, resting metabolic rate, or blood lipid and carbohydrate measures at 3 or 24 hours against placebo. IGF-1 rose non-significantly on both turkesterone conditions [8].
Population: 11 healthy young men, with samples before and 3 and 24 hours after doses [8].
Sources: [8]
Caveats: One small, short study of single doses. IGF-1 and metabolic rate are markers, not muscle growth, and no training was involved [8]. Tested turkesterone products often held little or none of the labeled ingredient (see Risks) [4].

Practices

SaunaLimited

Growth hormone

Limited evidence: growth hormone rose 16-fold in 10 men during a week of twice-daily one-hour saunas, and the response declined after the third day.

The numbers and sources

Effect: In 10 healthy men exposed to an 80°C sauna for 1 hour twice a day for 7 days, serum growth hormone rose 16-fold and prolactin 2.3-fold (P < 0.01). The growth hormone response declined after the third day. Cortisol and ACTH fell slightly by the end [28].
Population: 10 healthy men, with 7 women taking part in prolactin measurements only [28].
Sources: [28]
Caveats: One 1986 study with no control group. Two hours a day at 80°C is far longer than the sessions in other studies here. No muscle, recovery or body composition outcome was measured. The authors suggest dehydration may explain the hormone release.

Cold water immersionModerate

Muscle growth from resistance training

Not shown to help muscle growth. Used after resistance training, it was associated with smaller gains in pooled trials, a difference whose interval narrowly included zero.

The numbers and sources

Effect: A meta-analysis of 8 randomized studies found smaller hypertrophy with cold water immersion plus resistance training than with training alone (comparative SMD -0.22, 95% credible interval -0.47 to 0.04), with a 95.7% probability that the difference was below zero [11]. In 21 men over 12 weeks, muscle mass increased more with active recovery, and type II fiber cross-sectional area rose 17% with active recovery and did not rise with cold immersion [9]. In 16 men over 7 weeks, the increase in type II fiber area was smaller with cold immersion (effect size -1.37) [10].
Population: Healthy adults in 8 randomized studies of at least 4 weeks [11]. 21 physically active men [9]. 16 men training 3 days a week [10].
Sources: [11], [9], [10], [6]
Caveats: The authors of the meta-analysis rated the evidence fair to poor in quality [11]. Trials were short and mostly in young men. An umbrella review also concluded that hypertrophic gains were impaired [6].

Infrared saunaLimitedStudied in women

Muscle growth and power

One trial found no added muscle growth from a 10-minute infrared sauna after training for 6 weeks in 40 female athletes. Loaded jump height improved.

The numbers and sources

Effect: Six weeks of strength and power training improved performance and muscle size in both groups. Hypertrophy measures by DXA and ultrasound showed no group by time interaction. Countermovement jump with 15% added load improved in the sauna group (interaction p = 0.002 for height and p = 0.010 for peak power) [23].
Population: 40 female team sport athletes, pair-matched to sauna (10 minutes at 50°C, 3 times a week) or control [23].
Sources: [23]
Caveats: Pair-matched, not described as randomized. One of several jump tests showed the effect.

Daily life

Strength trainingStrong

Muscle strength, lean mass and physical function

Shown to raise muscle strength by a large amount and lean mass by about 1.1 kg in older adults in pooled trials, with small gains in everyday physical function.

Compared with control groups in randomized trials [9]; before training, in the same people, in randomized and nonrandomized studies [10][11]

The numbers and sources

Effect: Progressive resistance training had a large effect on strength (SMD 0.84, 95% CI 0.67 to 1.00, 73 trials), a small effect on physical ability (SMD 0.14), a gait speed gain of 0.08 m/s and a moderate to large effect on rising from a chair (SMD -0.94) [9]. Strength rose 29% in leg press, 24% in chest press, 33% in knee extension and 25% in lat pull, more with higher intensity [10]. Lean body mass rose 1.1 kg (95% CI 0.9 to 1.2), more with higher volume and less in older participants [11].
Population: 6,700 older adults in 121 trials, mostly training 2 to 3 times a week at high intensity [9]. 1,079 adults 50 and older in 47 studies [10]. 1,328 adults 50 and older in 49 studies [11].
Sources: [9], [10], [11]
Caveats: Heterogeneity was high (I² 84% for lean mass) [11]. The two strength and lean mass reviews included nonrandomized studies and before-and-after changes [10][11].

Food and drink

Red meat and processed meatLimited

Muscle and strength with resistance training in older adults

Mixed results: one trial in older women found more lean mass and strength with lean red meat during training, while a larger trial found no added gain.

Compared with a daily serving of pasta or rice [5]; rice, pasta or potato on training days [6]

The numbers and sources

Effect: In women aged 60 to 90 doing resistance training twice a week, about 160 g of cooked lean red meat 6 days a week gave greater gains in total lean mass (0.45 kg, 95% CI 0.07 to 0.84), leg lean mass and strength (18%), and a 10% greater rise in IGF-1, over 4 months [5]. In adults 65 or older training 3 days a week, lean red meat on training days did not add to gains in lean mass, thigh muscle, strength or executive function over 24 weeks. Arm lean mass, gait speed and muscle density improved slightly more [6].
Population: 100 women in 15 retirement villages, cluster randomized [5]. 154 community-dwelling adults aged 65 or older [6].
Sources: [5], [6]
Caveats: Two trials from the same research group with different results. Both combined meat with exercise, so neither tests meat alone.

Diets

High-protein dietStrong

Lean mass during weight loss

Shown to keep about 0.3 to 0.4 kg more lean mass during calorie-restricted weight loss than standard-protein diets, including in adults over 50.

Compared with diets with less protein

The numbers and sources

Effect: Energy-restricted high-protein diets reduced the loss of fat-free mass by 0.43 kg (95% CI 0.09 to 0.78) and of resting energy expenditure by 595.5 kJ a day against standard-protein diets [1]. Protein above the RDA reduced lean mass loss during energy restriction by 0.36 kg (95% CI 0.06 to 0.67, 14 comparisons) and added 0.77 kg with resistance training (95% CI 0.23 to 1.31), with no effect when people neither dieted nor trained (0.08 kg, 95% CI -0.59 to 0.75) [2]. In a network meta-analysis of 83 articles, high-protein diets raised lean body mass 0.34 kg against normal-protein diets (95% CI 0.11 to 0.57) [3]. In adults over 50, higher protein during weight loss kept more lean mass and lost more fat [4].
Population: 1,063 adults in 24 trials lasting a mean of 12.1 weeks [1]; healthy adults in 18 trials of at least 6 weeks [2]; adults in randomized trials [3]; adults over 50 in 20 RCTs [4].
Sources: [1], [2], [3], [4]
Caveats: A 2026 review of 22 trials in adults without kidney disease found no significant change in fat-free mass [5]. The abstract of [4] gives no effect sizes.

Lab markers

Serum creatinineLimitedStudied in men

Type 2 diabetes at low levels

Limited evidence: one Japanese cohort of 8,570 men linked creatinine of 0.40 to 0.60 mg/dL to about twice the odds of type 2 diabetes over 4 years.

The numbers and sources

Effect: During 4 years, 877 men developed type 2 diabetes. Men with a creatinine of 0.40 to 0.60 mg/dL had an adjusted odds ratio of 1.91 (95% CI 1.44 to 2.54) against men at 0.71 to 0.80 mg/dL. The authors treat low creatinine as a possible stand-in for low skeletal muscle mass [8].
Population: 8,570 Japanese men aged 40 to 55 without diabetes at entry [8].
Sources: [8]
Caveats: One observational cohort of men in one country. Muscle mass was not measured, so the link to muscle is the authors' interpretation [8].

Serum creatinineLimited

Death in intensive care at low levels

Limited evidence: one cohort of 11,291 intensive care patients linked a baseline creatinine of 0.6 mg/dL or below to about 2.6 times the odds of death.

The numbers and sources

Effect: After adjustment for predicted mortality, age, sex, surgery and body mass index, the odds ratio for death in hospital was 2.59 (95% CI 1.82 to 3.61) for a baseline creatinine of 0.6 mg/dL or below and 1.28 (1.03 to 1.60) for 0.6 to 0.8 mg/dL. Median baseline creatinine was 1.1 mg/dL. The authors treat low creatinine as a marker of low muscle mass [9].
Population: 11,291 adults admitted to three intensive care units at two hospitals from 2003 to 2006, 1,185 deaths in hospital [9].
Sources: [9]
Caveats: Retrospective, in critically ill patients, so it does not describe a low result in a person who is well. Muscle mass was not measured [9].

IGF-1Strong

Body composition and adverse events in trials of growth hormone

Shown in trials of growth hormone to shift fat and lean mass by about 2 kg in older adults, with more swelling, joint pain and carpal tunnel syndrome.

The numbers and sources

Effect: IGF-1 manages the effects of growth hormone in the body [1], and these trials gave growth hormone without aiming at an IGF-1 level. In community-dwelling adults with a mean age of 69 who were not being treated for a specific illness, growth hormone lowered fat mass by 2.1 kg (95% CI 1.35 to 2.8) and raised lean mass by 2.1 kg (1.3 to 2.9), with no change in weight, bone density or most blood lipids. Treated people were more likely to have soft tissue swelling, joint pain, carpal tunnel syndrome and breast growth in men, and somewhat more likely to develop diabetes or impaired fasting glucose [10]. In adults with confirmed growth hormone deficiency, it lowered weight by 2.31 kg (1.96 to 2.66) and body fat by 2.56 kg (2.16 to 2.97) and raised lean mass by 1.38 kg (1.10 to 1.65). Swelling had a relative risk of 6.07 (4.34 to 8.48) and joint stiffness 4.17 (1.4 to 12.38), with no significant change in bone density. Quality of life improved in 11 of 16 trials [11].
Population: 220 treated participants in 18 study populations, mean treatment 27 weeks [10]. More than 3,400 patients in 54 randomized trials [11].
Sources: [10], [11], [1]
Caveats: A marker that tracks an outcome is not always one whose correction changes it. Low IGF-1 went with more deaths in cohorts, and these trials measured body composition, not deaths. The trials in older adults were small and short [10].

DHEA sulfate (DHEA-S)Strong

Body composition, physical performance and quality of life in trials that raised DHEA-S

Not shown to change body composition, physical performance, sexual function or quality of life in a meaningful way when DHEA-S was raised with DHEA in older adults.

The numbers and sources

Effect: In a 2-year trial in older adults with low DHEA-S, DHEA raised the level by a median of 3.4 µg/mL in men and 3.8 µg/mL in women, which is 340 and 380 µg/dL. It had no significant effect on body composition, and did not change peak oxygen consumption, muscle strength, insulin sensitivity or quality of life. Bone density rose at the femoral neck in men and at the ultradistal radius in women [8]. Across 25 trials in older men, DHEA reduced fat mass slightly (standardized mean difference -0.35, 95% CI -0.65 to -0.05), an effect that disappeared after adjusting for the rise in testosterone and estradiol, with no effect on blood lipids, blood sugar, bone, sexual function or quality of life [9]. A review of 8 trials called the effect on muscle strength and physical function inconclusive [10]. In postmenopausal women, 23 trials found no significant improvement in libido or sexual function (0.35, -0.02 to 0.73) and no significant effect on lipids, glucose, weight or bone density [11]. A Cochrane review found no improvement in quality of life (0.16, -0.03 to 0.34) and more androgenic side effects, mainly acne (odds ratio 3.77, 1.36 to 10.4) [12].
Population: 87 older men and 57 older women with low DHEA-S, treated for 2 years [8]. 1,353 older men in 25 trials, mean follow-up 36 weeks [9]. 661 adults aged 50 or older in 8 trials [10]. 1,188 postmenopausal women in 23 trials [11]. 1,273 women in 28 trials [12].
Sources: [8], [9], [10], [11], [12]
Caveats: A marker that tracks an outcome is not always one whose correction changes it. Low DHEA-S went with more deaths in cohorts. The trials measured body composition, function and quality of life, not deaths. The reviewers of the trials in women rated confidence in the evidence as low [11].