Body Composition

Small Improvement

Three RCTs consistently demonstrate body fat reduction. A 12-week RCT (n=76) found significant reductions in visceral, subcutaneous, and total abdominal fat area with 150mg/day. A second RCT (n=80) using 12mg purified polymethoxyflavone daily reduced visceral fat significantly at 8 and 12 weeks. A 2025 RCT (n=83 analyzed) confirmed significant reductions in body fat mass, body weight, and BMI compared to placebo.

Small Decrease

Small Decrease

Small Improvement

Small Decrease

Large Increase

One large RCT (n=200) found 35 mg/day MHBA significantly reduced visceral fat area after 8 and 12 weeks and total body fat area after 12 weeks vs placebo in healthy overweight adults. Animal studies show MHBA induces thermogenesis in brown adipose tissue via sympathetic nerve activity, increasing UCP1 expression, and reduces body weight gain in diet-induced obese mice.

Moderate Decrease

Small Decrease

Small Improvement

Moderate decrease in body fat during caloric restriction

Small Increase

No effect

Three independent mouse studies showed A. iwayomogi extract attenuated high-fat diet-induced obesity. The extract acts as a direct PPARdelta ligand activating skeletal muscle fatty acid oxidation (n=9/group), suppresses adipogenic transcription factors PPARgamma2/C/EBPalpha reducing visceral adiposity and insulin resistance (n=10/group), and dose-dependently improves hypertriglyceridemia via adiponectin-AMPK pathway activation (n=8/group). All evidence is preclinical.

A pectic polysaccharide from mulberry fruit showed anti-obesity effects in an animal model (PMID:27112865). In 3T3-L1 adipocytes, mulberry fruit extract ameliorated adipogenesis via AMPK activation and microRNA modulation (PMID:32191574). Evidence is limited to one animal and one in vitro study.

Valine contributes to muscle protein synthesis as one of three BCAAs, but a 2017 critical review (Wolfe) argued that BCAAs alone cannot promote muscle protein synthesis in humans due to the requirement for all essential amino acids. Isolated valine has not been shown to independently stimulate muscle protein synthesis in human trials.

In a rat study, oral 28-homobrassinolide (20 mg/kg) increased skeletal muscle protein synthesis by approximately 15% and improved lean body mass without affecting androgenic tissues, acting via the PI3K/Akt pathway rather than the androgen receptor. A 2023 multi-level comparative analysis confirmed biological activity of 28-homobrassinolide across multiple endpoints.

Two animal studies showed anti-obesity effects with evodiamine supplementation. However, the mechanism may involve TRPV1-mediated heat perception rather than true increases in caloric expenditure. Poor oral bioavailability limits translational relevance to humans.

In vitro studies show piperine activates TRPV1 receptors and stimulates UCP1 expression via AMPK signaling in muscle cells. In mice, 0.05% piperine diet significantly decreased body weight and visceral fat over 4 weeks. However, the sole human RCT testing black pepper on 24-hour energy expenditure in overweight women found no significant thermogenic effect, suggesting preclinical results may not translate to humans.

In high-fat diet mouse models, haskap berry extract reduced body weight, adipocyte size, and abdominal/subcutaneous fat mass while increasing muscle mass by regulating SIRT1 and PGC1-alpha. A separate study confirmed decreased serum cholesterol and triacylglycerol through AMPK activation with prevention of fatty liver.

A 12-week double-blind RCT (n=80, BMI 23-30) of heat-killed L. paracasei K71 did not reach significance on the primary per-protocol analysis for fat reduction. However, subgroup analysis in participants with stable lifestyles showed significant decreases in subcutaneous fat area, visceral fat volume, body fat percentage, and hip circumference. No adverse events reported.

In rodent models, NR supplementation enhanced oxidative metabolism, activated SIRT1 and SIRT3, increased energy expenditure, reduced cholesterol, and protected against high-fat diet-induced obesity and metabolic abnormalities (Cantó et al., 2012). Reviews confirm NAD+-boosting molecules improve metabolic regulation in animal models (Rajman et al., 2018). No human obesity trials have been conducted.

A single double-blind RCT in 46 healthy young men found both 25 and 200 mg/day for 60 days increased muscle mass and decreased fat mass, with concurrent increases in free testosterone, IGF-1, and erythropoietin. Awaits replication.

No effect

A single animal study found C3G increased whole body energy metabolism by upregulating brown adipose tissue mitochondrial function in mice. No replication studies or human data available.

One human study found that a combination herbal preparation containing damiana (with yerba mate and guarana) delayed gastric emptying and promoted weight loss in overweight patients. Effects cannot be attributed to damiana alone due to the multi-ingredient formulation.

In high-fat-diet obese rats, olfactory stimulation (inhalation) with fennel essential oil decreased body weight, body fat, and visceral fat, and improved lipid metabolism markers and blood pressure. A separate study in dyslipidemic rats showed fennel volatile oils improved oxidative stress and inflammatory markers with superior anti-inflammatory properties.

An open-label pilot study (n=24, ages 55-75) observed significant reductions in body weight and body fat percentage after 12 weeks of 480mg Enzogenol with vitamin C. No placebo control and confounded by vitamin C co-administration.

In animal models, OEA promotes fatty acid oxidation through PPARα activation, the same nuclear receptor targeted by fibrate drugs. Rodent studies show increased lipid metabolism markers following OEA administration (PMID:25832022). No human supplementation data available.

No effect

No effect

No effect

Higenamine is widely marketed as a fat-burning supplement based on its beta-2 adrenergic agonist mechanism, which theoretically promotes lipolysis. An analytical study (PMID:30188222) found higenamine doses up to 62 mg per serving in US weight-loss supplements, with none accurately labeled. However, no animal or human studies among available evidence directly measured fat oxidation or body composition changes. The fat-burning claim remains entirely theoretical and unproven.

In a 2026 animal study, threonic acid synergized with intermittent fasting to reduce body weight and food intake in diet-induced obese mice (n=6/group). Threonic acid suppressed hypothalamic NPY and AGRP neuropeptides and competed with glucose for GLUT3 transporter uptake, suggesting a novel appetite-regulation mechanism. No human trials exist.

In rodent models, ecdysteroids from Rhaponticum carthamoides have shown effects on protein synthesis, and in vitro studies suggest activation of the Akt/mTOR pathway in muscle cells without androgen receptor binding. No quality human clinical trials have validated these effects.

A small pilot RCT (Garrison & Chambliss 2006, n=28 completers) of Relora (Magnolia + Phellodendron combination) found the treatment group maintained weight while placebo gained 1.5 kg over 6 weeks. In a separate OA study (Oben et al. 2009), the Phellodendron + Citrus combination produced 5.1% weight loss in overweight subjects (p<0.001). Both used combination products, limiting attribution to Phellodendron alone.

In vitro studies show piceatannol inhibits adipocyte differentiation by modulating mitotic clonal expansion and insulin receptor-dependent signaling during early-phase adipogenesis (PMID:22298784). Animal studies support anti-obesity effects through inhibition of lipid accumulation.

Two Phase 3 clinical trials demonstrated significant reduction in visceral adipose tissue in HIV patients with lipodystrophy, maintained through 52 weeks of treatment.

Clinical trials demonstrated significant reductions in waist circumference and trunk fat in patients with HIV-associated lipodystrophy.

Ipamorelin treatment showed dose-dependent effects on body weight gain in animal models, consistent with growth hormone-mediated anabolic effects.

Maximum tetanic muscle tension was significantly increased in animals receiving ipamorelin combined with glucocorticoids, counteracting steroid-induced muscle weakness.

MOTS-c acts as an exercise-induced mitochondrial-encoded regulator of muscle homeostasis, reducing myostatin and muscle atrophy signaling pathways.