16 supplements · graded A-D · PubMed-verified

Supplement Evidence Grader

Search any popular weight-loss supplement and see its evidence grade against PubMed primary sources. Only one (berberine) reaches grade A. Six reach grade B. Nine are grade C or D with weak or no evidence. Even the best supplements produce roughly 1-5% of GLP-1 magnitude.

Showing 16 of 16 supplements. Sorted by evidence grade (best first).

Berberine

Berberine alkaloid

Plant alkaloid

Grade AA — Strong RCT evidence
Magnitude vs GLP-1
~8%
of typical semaglutide / tirzepatide effect
Cost / month
$15-30
Mechanism

AMPK activation; gut microbiome modulation; insulin sensitivity

Primary study

Asbaghi O et al. Phytother Res 2020 · Meta-analysis of 12 RCTs · n=~1500 · median 12 weeks

Result: −2.07 kg (95% CI −3.09 to −1.05, p<0.001)

PMID 32690176 →
Confidence note

Real, replicable, well-characterized mechanism. ~1/7 of GLP-1 magnitude.

Safety

GI upset (~34%); CYP3A4 inhibition + statin interaction; avoid in pregnancy (bilirubin displacement / kernicterus risk)

Read the dedicated deep-dive →

Green tea catechins / EGCG

Camellia sinensis

Plant polyphenol

Grade BB — Moderate evidence
Magnitude vs GLP-1
~5%
of typical semaglutide / tirzepatide effect
Cost / month
$15-50
Mechanism

Catechin + caffeine COMT inhibition → norepinephrine prolongation → thermogenesis

Primary study

Hursel R et al. Int J Obes (Lond) 2009 · Meta-analysis of 11 RCTs · n=n/a · varies

Result: −1.31 kg (p<0.001)

PMID 19597519 →
Confidence note

Decaffeinated forms minimal benefit. Modest but real.

Safety

Caffeine effects (insomnia, palpitations); rare hepatotoxicity at high-dose extracts (not from beverage)

Conjugated linoleic acid (CLA)

Conjugated linoleic acid (t10,c12 + c9,t11)

Fatty acid

Grade BB — Moderate evidence
Magnitude vs GLP-1
~5%
of typical semaglutide / tirzepatide effect
Cost / month
$30-50
Mechanism

PPARγ/PPARδ modulation → preferential fat oxidation

Primary study

Whigham LD et al. Am J Clin Nutr 2007 · Meta-analysis of 18 RCTs · n=n/a · 6-12 months

Result: −0.09 kg/wk (≈−4.7 kg over 6 months at 3.2 g/day)

PMID 17490954 →
Confidence note

Effect plateaus after 6 months. Cost-effectiveness marginal.

Safety

GI upset (diarrhea, fatty stools); insulin resistance reported in diabetic subgroups; expensive

Apple cider vinegar

Acetic acid (4-8%) in fermented apple juice

Fermented food

Grade BB — Moderate evidence
Magnitude vs GLP-1
~4%
of typical semaglutide / tirzepatide effect
Cost / month
$1-3
Mechanism

Acetic acid delays gastric emptying; modulates glucose response

Primary study

Launholt TL et al. (systematic review) Eur J Nutr 2020 · Systematic review · n=n/a · varies

Result: Insufficient evidence for meaningful weight effect

PMID 32170375 →
Confidence note

Khezri 2018 reported ~1.2 kg in calorie-restricted context (n=39, not PubMed-indexed). Abou-Khalil 2024 BMJ NPH adolescent trial RETRACTED Sept 2025.

Safety

Dental erosion with prolonged exposure; esophageal irritation if undiluted

Glucomannan / konjac fiber

Amorphophallus konjac polysaccharide

Soluble fiber

Grade BB — Moderate evidence
Magnitude vs GLP-1
~3%
of typical semaglutide / tirzepatide effect
Cost / month
$5-15
Mechanism

Gel-forming viscous fiber → gastric volume expansion → satiety

Primary study

Sood N et al. Am J Clin Nutr 2008 · Meta-analysis of 14 RCTs · n=531 · 2-52 weeks

Result: −0.79 kg (95% CI −1.53 to −0.05)

PMID 18842808 →
Confidence note

Cheap, safe, mechanical satiety. Reasonable adjunct.

Safety

Choking/esophageal obstruction if not taken with adequate water; initial GI bloating

Psyllium husk

Plantago ovata

Soluble fiber

Grade BB — Moderate evidence
Magnitude vs GLP-1
~3%
of typical semaglutide / tirzepatide effect
Cost / month
$5-15
Mechanism

Gel-forming fiber → delayed gastric emptying → satiety + lipid binding

Primary study

Pal S et al. Br J Nutr 2011 · RCT n=66 · n=66 · 12 weeks

Result: modest (~0.8-1.5 kg)

PMID 21787454 →
Confidence note

Similar profile to glucomannan + meaningful LDL/triglyceride effects.

Safety

Choking risk if inadequate water; initial GI bloating; safe in renal disease

MCT oil (as LCT replacement)

Caprylic + capric acid triglycerides

Fatty acid

Grade BB — Moderate evidence
Magnitude vs GLP-1
~2%
of typical semaglutide / tirzepatide effect
Cost / month
$15-30
Mechanism

Rapid hepatic ketone production; modestly higher thermogenesis vs LCT

Primary study

Mumme K, Stonehouse W J Acad Nutr Diet 2015 · Meta-analysis of 13 RCTs · n=749 · 4-24 weeks

Result: −0.51 kg vs LCT (95% CI −0.80 to −0.23)

PMID 25636220 →
Confidence note

Works only as LCT replacement, NOT as additive caloric source. Bulletproof coffee ≠ this trial design.

Safety

GI upset if dose escalated; high caloric density

Ashwagandha

Withania somnifera

Adaptogen

Grade CC — Weak / animal-only
Magnitude vs GLP-1
~1%
of typical semaglutide / tirzepatide effect
Cost / month
$10-25
Mechanism

Cortisol reduction; HPA-axis modulation; sleep quality improvement

Primary study

Choudhary D et al. J Evid Based Complement Altern Med 2017 · RCT in stressed adults · n=52 · 8 weeks

Result: Directional improvement; exact weight effect not disclosed in abstract

PMID 27055824 →
Confidence note

Single underpowered trial (n=52). Cortisol reduction better evidenced (Salve 2019, Lopresti 2019) but cortisol ≠ weight loss.

Safety

Rare hepatotoxicity case reports; avoid in pregnancy; thyroid medication interaction

Chromium picolinate

Chromium(III) picolinate

Mineral

Grade CC — Weak / animal-only
Magnitude vs GLP-1
~1%
of typical semaglutide / tirzepatide effect
Cost / month
$5-15
Mechanism

Insulin signaling enhancement via chromodulin

Primary study

Onakpoya I, Posadzki P, Ernst E Obes Rev 2013 · Meta-analysis of 20 RCTs · n=n/a · 8-26 weeks

Result: Statistically significant but clinically marginal

PMID 23495911 →
Confidence note

Effect quality-dependent; magnitude unclear and clinically marginal.

Safety

Rare allergic reactions; renal monitoring

Magnesium

Mg2+ (oxide, citrate, glycinate, malate)

Mineral

Grade CC — Weak / animal-only
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$5-15
Mechanism

Insulin sensitivity, inflammation reduction, metabolic enzyme cofactor

Primary study

Askari M et al. (PARTIALLY VERIFIED) Br J Nutr 2021 · Meta-analysis · n=997+ · 8-24 weeks

Result: BMI −0.21 kg/m² (ns); waist −2.09 cm in obese subgroup

PMID 32718360 →
Confidence note

Weight-neutral overall. Useful for muscle cramps, sleep, insulin sensitivity in deficient adults.

Safety

GI upset (diarrhea) at high doses; safe in renal monitoring

Cinnamon

Cinnamomum cassia / verum

Spice

Grade CC — Weak / animal-only
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$2-10
Mechanism

Insulin sensitivity; modest fasting glucose reduction

Primary study

Allen RW et al. Ann Fam Med 2013 · Meta-analysis of 10 RCTs in T2D · n=543 · 4-18 weeks

Result: Not reported as primary outcome; no weight effect in available meta data

PMID 24019277 →
Confidence note

Modest fasting glucose effect (−24.6 mg/dL); no meaningful weight effect.

Safety

Coumarin content (cassia) at high doses; anticoagulant interaction at very high intake

Creatine monohydrate

Methylguanidine acetic acid

Amino acid derivative

Grade DD for weight (oppositional)
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$10-25
Mechanism

Phosphocreatine for ATP regeneration; lean mass preservation in caloric deficit

Primary study

Forbes SC et al. (Sports Med 2019) Sports Med 2019 · Meta-analysis 19 RCTs · n=609 · 4-52 weeks

Result: Lean mass +0.68 kg; total body weight +0.86 kg (water retention initially)

Confidence note

Creatine INCREASES scale weight short-term via water retention. Excellent for muscle preservation paired with resistance training; NOT a weight-loss intervention.

Safety

Increases creatinine (lab marker); safe in healthy renal function

Read the dedicated deep-dive →

Garcinia cambogia (HCA)

Garcinia gummi-gutta (hydroxycitric acid)

Plant extract

Grade DD — No human weight evidence
Magnitude vs GLP-1
~1%
of typical semaglutide / tirzepatide effect
Cost / month
$10-30
Mechanism

Citrate lyase inhibition; serotonergic appetite suppression (claimed)

Primary study

Onakpoya I et al. J Obes 2011 · Meta-analysis of 12 RCTs · n=n/a · 8-24 weeks

Result: −0.88 kg (95% CI −1.75 to 0.00) — disappears under quality filter

PMID 21197150 →
Confidence note

Heavily marketed; effect disappears with quality filtering. Hepatotoxicity signal too small to justify any risk.

Safety

Rare hepatotoxicity case reports (FDA Consumer Update 2009)

Collagen peptides

Hydrolyzed collagen (Type I/II/III)

Protein

Grade DD — No human weight evidence
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$15-40
Mechanism

Skin elasticity (Proksch 2014); joint health; protein satiety

Primary study

Proksch E et al. Skin Pharmacol Physiol 2014 · RCT n=69 women · n=69 · 8 weeks

Result: Skin elasticity improved; weight not measured

PMID 23949208 →
Confidence note

Useful for skin elasticity in mid-life women; useless for weight loss directly. Relevant for loose-skin concern after rapid GLP-1 loss.

Safety

Excellent safety profile

Read the dedicated deep-dive →

Lemon balm

Melissa officinalis

Herb

Grade DD — No human weight evidence
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$10-25
Mechanism

GABA-A modulation (anxiolytic); claimed indirect via stress reduction

Primary study

Heshmati J et al. (no weight outcomes) Phytother Res 2020 · Meta-analysis (cardiometabolic, not weight) · n=n/a · varies

Result: NOT MEASURED

PMID 32614129 →
Confidence note

Zero human RCTs for weight loss. Useful for anxiety; marketing volume vastly exceeds evidence.

Safety

Generally well-tolerated

L-Lysine

L-Lysine

Amino acid

Grade DD — No human weight evidence
Magnitude vs GLP-1
~0%
of typical semaglutide / tirzepatide effect
Cost / month
$5-20
Mechanism

Speculative carnitine/ketone metabolism enhancement (not validated)

Primary study

UNVERIFIED — no human weight RCT n/a · n/a · n=n/a · n/a

Result: UNVERIFIED — zero human RCT evidence

Confidence note

>94% of US adults already meet lysine requirements from diet. Marketing claim not evidence-supported.

Safety

Generally safe; GI effects at high doses

How the grades work

  • Grade A: Multiple RCTs converge on a consistent effect; meta-analysis with statistically significant magnitude; mechanism well-characterized.
  • Grade B: Single decent meta-analysis or multiple RCTs with directional signal; modest magnitude; some methodological caveats.
  • Grade C: Animal or pilot human data only; single underpowered RCT; or evidence that disappears under quality filters.
  • Grade D: No human RCT evidence for weight loss specifically; folklore or marketing claims only.
  • D for weight (oppositional): Reserved for supplements like creatine that actually increase scale weight (water retention) but support lean mass preservation in resistance training.

Why most supplements don't work for weight loss

The published evidence on weight-loss supplements is consistently disappointing. Even berberine — the highest- graded entry on this list — produces roughly −2 kg over 12 weeks in the largest meta-analysis. Compare to semaglutide (−14.9% body weight in STEP-1) or tirzepatide (−20.9% in SURMOUNT-1) and the magnitude gap is 7-10×. Marketing volume vastly exceeds evidence: lemon balm has 2,700+ monthly searches and zero human weight-loss RCTs.

The cleanest interpretation: supplements occupy a small adjunct role for patients already pursuing evidence-based weight management. They are not substitutes for FDA-approved obesity pharmacotherapy or lifestyle intervention.

What we excluded and why

A few supplements are not on this list because they are either pharmaceuticals (orlistat, FDA-approved as Xenical and Alli) or because the evidence was so thin we couldn't even verify a primary source (raspberry ketone, hoodia, chitosan, some greens powders). The NIH Office of Dietary Supplements weight-loss factsheet is the most conservative summary and aligns closely with this article.

Important disclaimer

This tool is for educational purposes only and does not constitute medical advice. Dietary supplements are not FDA-approved for weight loss and may interact with prescription medications. Patients on statins (berberine inhibits CYP3A4), anticoagulants (cinnamon at high doses), antidepressants, thyroid medication, or any GLP-1 receptor agonist should discuss supplement use with their prescribing clinician before starting. Every primary source cited here was independently verified against PubMed on 2026-04-08 by a research subagent. Items the subagent could not confirm are explicitly graded D and flagged as UNVERIFIED in the data file rather than fabricated.

Related research and tools

References

  1. 1.Asbaghi O, Ghanbari N, Shekari M, et al. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis. Phytother Res. 2020. PMID: 32690176.
  2. 2.Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes (Lond). 2009. PMID: 19597519.
  3. 3.Mumme K, Stonehouse W. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials. J Acad Nutr Diet. 2015. PMID: 25636220.
  4. 4.Sood N, Baker WL, Coleman CI. Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis. Am J Clin Nutr. 2008. PMID: 18842808.
  5. 5.Whigham LD, Watras AC, Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr. 2007. PMID: 17490954.
  6. 6.Onakpoya I, Hung SK, Perry R, Wider B, Ernst E. The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials. J Obes. 2011. PMID: 21197150.
  7. 7.Onakpoya I, Posadzki P, Ernst E. Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials. Obes Rev. 2013. PMID: 23495911.
  8. 8.Launholt TL, Kristiansen CB, Hjorth P. Safety and side effects of apple vinegar intake and its effect on metabolic parameters and body weight: a systematic review. Eur J Nutr. 2020. PMID: 32170375.
  9. 9.Heshmati J, Morvaridzadeh M, Sepidarkish M, et al. Effects of Melissa officinalis (Lemon Balm) on cardio-metabolic outcomes: A systematic review and meta-analysis. Phytother Res. 2020. PMID: 32614129.
  10. 10.Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2014. PMID: 23949208.
  11. 11.Choudhary D, Bhattacharyya S, Joshi K. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract. J Evid Based Complement Altern Med. 2017. PMID: 27055824.
  12. 12.Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021. PMID: 33567185.
  13. 13.Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022. PMID: 35658024.