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CLA

Evidence Fact Sheet

Conjugated Linoleic Acid

CLA (conjugated linoleic acid) is a family of linoleic-acid isomers (mainly c9,t11 and t10,c12) studied for body composition via SCD-1 inhibition and PPAR-gamma/AMPK signaling. Sold at roughly 3.2-6.4 g/day; GRAS in the US, no authorized EFSA health claim (all claims rejected).

Also known as: Conjugated Linoleic Acid · c9,t11-CLA · t10,c12-CLA · Tonalin · Clarinol

Overview

CLA (Conjugated Linoleic Acid) is a group of positional/geometric isomers of linoleic acid, with the c9,t11 and t10,c12 forms being the most studied; commercial mixed-isomer products are marketed as Tonalin and Clarinol. Proposed mechanisms from preclinical work include inhibition of stearoyl-CoA desaturase (SCD-1), AMPK activation, PPAR-gamma modulation, and downregulation of adipocyte lipoprotein lipase, framing its research interest in adipose lipid storage and body composition. Body-composition research trials and meta-analyses have most often used mixed isomers at about 3.2-6.4 g/day over 6-12 months (educational reference, not a recommendation). Regulatory status: a dietary supplement under DSHEA with GRAS Notices (GRN 521, GRN 232) receiving "no questions" letters in the US, saleable in the EU as a food supplement and within Brazil's sports-nutrition framework, but with NO authorized EFSA health claim — all CLA claims were rejected. It is described here as a research-studied ingredient, not a fat-loss product or disease treatment.

Mechanism of Action

SCD-1 (stearoyl-CoA desaturase) inhibition · AMPK activation · PPAR-gamma modulation · NF-kappaB suppression · Lipoprotein lipase (LPL) downregulation in adipocytes

Body systems: Body Composition · Musculoskeletal · Immune System · Endocrine & Metabolic

Evidence-Based Benefits

Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — CLA is not characterized as a treatment for any disease.

Body Composition / Fat Mass

Meta-analysis supported
  • 70 RCTs96 effect sizes · 4,159 participants
  • -0.44 kgfat mass · 95% CI -0.66,-0.23
  • -0.77 %body fat % · P<0.001

In the largest pooled analysis to date, CLA supplementation was associated with small, statistically significant reductions in body mass, fat mass, and body-fat percentage and a small increase in fat-free mass. The authors stress these effects were small and that high-quality studies failed to show CLA's body-fat-lowering properties — a finding the page reports as modest, not as a fat-loss product.

Reported effect: Fat mass WMD -0.44 kg (95% CI -0.66, -0.23, P<0.001); body fat percentage WMD -0.77% (95% CI -1.09, -0.45, P<0.001); body mass WMD -0.35 (95% CI -0.54, -0.15, P<0.001); fat-free mass WMD +0.27 (95% CI 0.09, 0.45, P=0.003); 70 RCTs, 96 effect sizes, 4,159 participants.

“CLA supplementation significantly reduced BM (weighted mean difference (WMD): -0·35, 95 % CI (-0·54, -0·15), P < 0·001), FM (WMD: -0·44, 95 % CI (-0·66, -0·23), P < 0·001), BFP (WMD: -0·77 %, 95 % CI (-1·09, -0·45), P < 0·001) ... increased FFM (WMD: 0·27, 95 % CI (0·09, 0·45), P = 0·003). ... data from high-quality studies failed to show CLA's body fat-lowering properties.”

Source: PMID 37671495 · Asbaghi 2024 · Br J Nutr

Long-Term Body Composition (24-Month RCT)

Null / no benefit RCT supported
  • 134 of 157completers · 24 months
  • 3.4 g/dayCLA dose · extension phase

In a 24-month randomized, double-blind, placebo-controlled trial, no fat or body-weight change occurred in the groups given CLA during the initial 12 months, while the placebo group itself showed modest reductions — an honest negative for a longer-duration individual trial. This is one of the few multi-year human safety/efficacy datasets for CLA.

Reported effect: No significant body-composition change on CLA over the initial 12 months; placebo group reduced body weight and body fat mass by -1.6 ± 3.2 kg and -1.7 ± 2.8 kg respectively; 134 of 157 participants completed the 24-month trial; 3.4 g CLA/day in the extension phase.

“Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo.”

Source: PMID 15795434 · Gaullier 2005 · J Nutr

Plasma Lipid Profile

Null / no benefit Meta-analysis supported
  • 56 RCTs73 effect sizes
  • 1.76triglycerides WMD · CI -1.65,5.19 (ns)
  • 0.49LDL-C WMD · CI -0.75,2.74 (ns)

A meta-analysis of CLA on blood lipids found no significant effect on triglycerides, total cholesterol, or LDL-cholesterol, with confidence intervals crossing the null; only HDL-cholesterol changed significantly. The overall picture is largely null for the cardiometabolic lipid markers most users are interested in.

Reported effect: No significant change in triglycerides (WMD 1.76; 95% CI -1.65, 5.19), total cholesterol (WMD 0.86; 95% CI -0.42, 2.26) or LDL-C (WMD 0.49; 95% CI -0.75, 2.74); HDL-C changed significantly (WMD -0.40; 95% CI -0.72, -0.07); 56 RCTs with 73 effect sizes.

“CLA supplementation significantly alter triglycerides (TG) (WMD: 1.76; 95% CI: -1.65, 5.19) ... total cholesterols (TC) (WMD: 0.86; 95% CI: -0.42, 2.26) ... low-density lipoprotein cholesterols (LDL-C) (WMD: 0.49; 95% CI: -0.75, 2.74) ... CLA supplementation significantly increased the density lipoprotein cholesterol (HDL-C) (WMD: -0.40; 95% CI: -0.72, -0.07).”

Source: PMID 36438733 · Asbaghi 2022 · Front Nutr

Inflammation (C-Reactive Protein)

Null / no benefit Meta-analysis supported

A meta-analysis found that CLA supplementation significantly INCREASED serum C-reactive protein, a marker of inflammation — a proinflammatory signal rather than a benefit. This honest negative is consistent with EFSA's rejection of CLA fat claims on grounds of accompanying inflammation.

Effect size: not quantified on this page — see the linked study below for the reported figures.

Source: PMID 28556504 · Mazidi 2017 · Cardiovasc Ther

Insulin Sensitivity (T10,c12 Isomer Signal)

Null / no benefit RCT supported
  • n=9overweight adults · 12 weeks
  • 4 g/dayCLA dose
  • p≤0.05insulin sensitivity decreased

In a small mechanistic trial in overweight adults, 12 weeks of CLA significantly decreased insulin sensitivity, with increased glucose and insulin area-under-the-curve during an oral glucose tolerance test and increased skeletal-muscle ceramide. This supports the isomer-specific (t10,c12) safety signal flagged in the card and is an honest negative for metabolic outcomes; the small sample limits its weight.

Reported effect: Insulin sensitivity significantly decreased (p≤0.05) after CLA, with significant increase in glucose and insulin AUC during OGTT (p≤0.005) and increased skeletal-muscle ceramide; 9 overweight non-diabetic participants, 4 g/day for 12 weeks.

“Insulin sensitivity was significantly decreased (p<or=0.05) following CLA supplementation, with a significant increase in glucose and insulin area under the curve during an oral glucose tolerance test (p<or=0.005).”

Source: PMID 17510671 · Thrush 2007 · Appl Physiol Nutr Metab

Dosage (research context · not a recommendation)

3.2-6.4 g/day mixed isomers in body-composition RCTs (most meta-analyzed trials 3.2-6.4 g/day, 6-12 months; educational reference, not a recommendation)

Regulatory Status · 4 Markets

US · FDA
Dietary supplement under DSHEA; GRAS — FDA GRAS Notices GRN 521 and GRN 232 both received 'no questions' letters (GRN 153 and GRN 148 ceased). No FDA-authorized health claim; structure/function statements permitted with DSHEA disclaimer.
EU · EFSA
Market access permitted as food supplement, but NO authorized EFSA health claim. All Art.13.1 claims (body fat, lean body mass, immune, etc.) were rejected in 2010, and the Clarinol/Tonalin Art.13.5 body-fat application was rejected (EFSA Journal J.3953, 2015 — EFSA concluded CLA-associated fat reduction was accompanied by increased lipid peroxidation and inflammation, not a beneficial physiological effect).
CN · China
Not listed in China's health-food (SAMR) raw-material catalog; available only via cross-border e-commerce channels; no domestic conventional-food or health-food approval identified.
BR · ANVISA
Saleable within the sports-nutrition category (RDC 243/2018 dietary supplement framework / IN 28/2018 pathway). No IN 28/2018 Anexo V alegação funcional specific to CLA.

Safety

Generally tolerable in trials; GI discomfort most common. ISOMER-SPECIFIC SAFETY SIGNAL: mixed CLA lowered insulin sensitivity in overweight non-diabetic adults (Thrush 2007 PMID 17510671 · muscle ceramide accumulation); raised CRP / lowered HDL have been reported in other CLA trials (esp. obese / T2DM populations). Mild ALT elevation / hepatic steatosis markers reported. Long-term safety beyond ~24 months not well characterized; not characterized for pregnancy/lactation. Educational only; not intended to diagnose, treat, cure, or prevent disease.

Goals: weight-management

Lifestyles: athletic-performance

References

PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.

  1. PMID 37671495 · Asbaghi 2024 · Br J Nutr — Body Composition / Fat Mass
  2. PMID 15795434 · Gaullier 2005 · J Nutr — Long-Term Body Composition (24-Month RCT)
  3. PMID 36438733 · Asbaghi 2022 · Front Nutr — Plasma Lipid Profile
  4. PMID 28556504 · Mazidi 2017 · Cardiovasc Ther — Inflammation (C-Reactive Protein)
  5. PMID 17510671 · Thrush 2007 · Appl Physiol Nutr Metab — Insulin Sensitivity (T10,c12 Isomer Signal)

Frequently Asked Questions

1. Does CLA actually reduce body fat?

The largest meta-analysis (70 RCTs, 4,159 participants) found small, statistically significant reductions — fat mass WMD -0.44 kg and body-fat percentage -0.77% — but the authors emphasize the effects were small and that high-quality studies failed to show CLA's body-fat-lowering properties. A separate 24-month RCT (3.4 g/day) found no fat or body-weight change on CLA over its initial 12 months. The evidence describes a modest research finding, not a reliable fat-loss effect.

2. What dose of CLA was used in the research?

Body-composition trials and meta-analyses most often used mixed-isomer CLA at about 3.2-6.4 g/day over 6-12 months, and the 24-month trial above used 3.4 g/day in its extension phase. These figures describe the doses studied for educational reference and are not a dosing recommendation.

3. Is CLA approved for any health claim?

In the US it is a dietary supplement under DSHEA with GRAS Notices (GRN 521, GRN 232) that received 'no questions' letters, but there is no FDA-authorized health claim. In the EU it is saleable as a food supplement, yet has NO authorized EFSA health claim — all CLA claims (body fat, lean mass, immune) were rejected. Only structure/function statements with the DSHEA disclaimer are permitted in the US.

Last evidence review: 2026-06-13

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