Which OTC supplement ingredients have randomized controlled trial data for modest weight loss, and what are their effect sizes?

1. Which ingredients have RCT evidence and the headline effect sizes

A 111‑trial network meta‑analysis pooled randomized trials across 18 nutraceuticals and reported high‑certainty evidence for spirulina with mean difference (MD) −1.77 kg (95% CI −2.77 to −0.78) and moderate‑certainty signals for psyllium (MD −3.70 kg, 95% CI −5.18 to −2.22), chitosan (MD −1.70 kg, 95% CI −2.62 to −0.78), curcumin (MD −0.82 kg, glucomannan (MD −1.36 kg), green tea (MD −1.25 kg) and Nigella sativa (MD −2.09 kg) versus placebo or control across trials of variable duration (weeks to months) ^[1]. Green coffee bean extract and chlorogenic acids have also been found to reduce body weight in meta‑analysis of 15 RCTs, though the reviews emphasize short durations (1–12 weeks) and heterogeneity in doses ^[2].

2. OTC orlistat: the nonprescription “drug” that still delivers modestly

Orlistat, available OTC as Alli (60 mg), has consistent randomized trial data showing a modest effect when combined with lifestyle measures; the landmark XENDOS trial (n=3,305) reported about 2.4% total body weight loss after four years with orlistat versus placebo, and orlistat’s mechanism—intestinal lipase inhibition—explains predictable GI side effects and vitamin‑absorption considerations ^{[4] [3]}.

3. Multi‑ingredient and single small trials: promising signals but limited generalizability

Some multi‑ingredient formulations and single‑ingredient RCTs report larger effects in brief trials (for example a 12‑week MDIs trial and company‑reported product studies), but these are typically small, short, or not independently replicated; the MDPI trial of a multi‑ingredient supplement showed changes over 12 weeks in a young overweight sample but cannot be generalized without larger replication ^[5]. Marketing claims from manufacturers (highlighted in industry blogs) sometimes overstate results relative to the broader literature and should be weighed against independent peer‑reviewed data ^{[3] [6]}.

4. Safety, heterogeneity and the limits of “modest”

Safety concerns and product variability are recurring caveats: fiber supplements can cause GI symptoms; choline/betaine trials have shown mixed metabolic effects; and supplement adulteration with unlisted pharmaceuticals has been documented in the category, so third‑party testing and clinician oversight are prudent ^{[2] [3] [7]}. Trials vary widely in dose, formulation, participant BMI and duration, producing heterogeneity that limits direct comparison and weakens causal confidence for many ingredients ^{[1] [2]}.

5. How these effects compare to prescription anti‑obesity drugs

Even the better OTC signals are small compared with modern prescription agents: recent meta‑analyses of approved pharmacotherapies (semaglutide, tirzepatide) show far larger percentage body‑weight reductions than the single‑digit kilogram differences reported for nutraceuticals and fibers; guideline‑level evidence now favors pharmacologic agents for larger, sustained weight loss in clinical populations ^{[8] [9]}.

6. Bottom line and reporting caveats

Randomized evidence supports small, clinically modest average weight loss for a short list of OTC ingredients—spirulina, psyllium, glucomannan, green tea/coffee extracts, chitosan, curcumin and Nigella sativa—with effect sizes typically in the range of about 0.8–3.7 kg versus control over weeks to months, while orlistat yields modest multi‑year benefit ^{[1] [4] [2]}. Many trials are small, short, or industry‑linked; independent replication, standardized dosing, longer follow‑up and transparent safety reporting remain the critical gaps in the OTC landscape ^{[5] [3]}.