CLA (Conjugated Linoleic Acid)

Overview

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of the poly‑unsaturated fatty acid linoleic acid (C18:2). It is primarily found in nature as the cis‑9, trans‑11 and trans‑10, cis‑12 isomers. CLA is marketed as a dietary supplement, mainly for its potential to modulate body composition and metabolic health.

Benefits

Body‑composition support: Meta-analyses of randomized controlled trials (RCTs) show that 3–6 g/day of CLA can modestly reduce body fat (≈0.5 kg) and increase lean mass, especially in overweight adults.
Metabolic regulation: CLA improves insulin sensitivity and lowers fasting triglycerides in some studies, likely through enhanced fatty‑acid oxidation.
Immune modulation: In vitro and animal data indicate that CLA can attenuate inflammatory cytokine production (e.g., TNF‑α, IL‑6) and may enhance vaccine‑induced antibody responses.
Bone health: Preliminary human data suggest a modest increase in bone mineral density with long-term CLA (≥12 weeks) in post‑menopausal women, possibly via osteoblast activation.
Cognitive & neuro‑protective signals: Animal models show CLA reduces oxidative stress in the hippocampus and improves memory tasks, though human data are limited.
Overall, the strongest evidence is for modest body‑composition and metabolic effects; other benefits remain exploratory.

How It Works

CLA integrates into cell membrane phospholipids, altering fluidity and influencing receptor function.
The cis‑9, trans‑11 isomer activates peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) and PPAR‑α, enhancing fatty‑acid β‑oxidation and decreasing lipogenesis via down-regulation of sterol regulatory element‑binding protein‑1c (SREBP‑1c).
CLA also inhibits adipocyte differentiation by suppressing C/EBP‑α and PPAR‑γ expression, limiting triglyceride storage.
In immune cells, CLA reduces NF‑κB activation, lowering pro-inflammatory cytokine transcription.
The trans‑10, cis‑12 isomer exerts a stronger anti‑adipogenic effect, whereas the cis‑9, trans‑11 isomer is more active in immune modulation.
Additionally, CLA metabolites (e.g., CLA‑derived prostaglandins) can influence the eicosanoid pathway, contributing to the observed anti‑inflammatory and bone‑protective actions.

Dosage

Clinical trials most often use 3 g day⁻¹ (1 g three times daily) of a mixed‑isomer CLA (≈50 % cis‑9, trans‑11 and 45 % trans‑10, cis‑12).
For body‑composition goals, 3–6 g day⁻¹ for 12–24 weeks is typical.
For metabolic or inflammatory targets, similar doses are used, but some studies use up to 9 g day⁻¹ with a higher proportion of the trans‑10, cis‑12 isomer.
Doses are taken with meals to improve absorption and reduce gastrointestinal upset.
In athletes or lean individuals, lower doses (1–2 g day⁻¹) may be sufficient for modest lean‑mass support.
Pregnant or lactating women should avoid supplementation unless advised by a clinician; pediatric dosing has not been established.

Safety & Side Effects

CLA is generally well tolerated at ≤6 g day⁻¹.
Common mild adverse effects include gastrointestinal upset (bloating, diarrhea) and occasional mild increase in liver enzymes (ALT/AST) in a small subset of users.
Long‑term high‑dose (≥10 g day⁻¹) supplementation has been linked to insulin resistance and increased oxidative stress in animal models; human data are inconclusive.
Contraindications: pregnant or lactating women, individuals with uncontrolled diabetes, or severe hepatic disease.
Potential drug interactions include anticoagulants (possible additive anti‑platelet effect) and lipid‑lowering agents (e.g., statins) where CLA may modestly alter lipid profiles.
Individuals with a history of hyperlipidemia, insulin resistance, or active cancer should consult a healthcare professional before use.

Chemistry

Conjugated linoleic acid refers to a group of isomers of C18:2 with conjugated double bonds.
The predominant isomers are:
- cis‑9, trans‑11 CLA (IUPAC: (9Z,11E)-octadeca-9,11-dienoic acid)
- trans‑10, cis‑12 CLA (IUPAC: (10E,12Z)-octadeca-10,12-dienoic acid)
Molecular formula: C₁₈H₃₀O₂; molecular weight: 280.44 g·mol⁻¹.
The conjugated double‑bond system (alternating single‑double bonds) confers a higher susceptibility to oxidation and enables interaction with PPAR receptors.
The isomers differ in the geometry (cis vs. trans) and position of the double bonds, which influences biological potency.
CLA is a lipophilic compound, soluble in oils and organic solvents, with a melting point of ~40 °C (cis‑9, trans‑11) and ~42 °C (trans‑10, cis‑12).

Sources & Quality

Naturally, CLA is present in ruminant adipose tissue and dairy products; typical concentrations are 0.5–2 % of total fatty acids in beef, lamb, and milk fat.
Commercial supplements are produced either by extraction from bovine or sheep fat using solvent‑extraction and fractionation (e.g., supercritical CO₂) to enrich the CLA isomers, or by microbial fermentation (e.g., Lactobacillus spp.) that convert linoleic acid to CLA via isomerase enzymes.
Synthetic routes using chemical isomerization of linoleic acid also exist but are less common for food‑grade products.
Quality considerations include: minimal trans‑fat contamination, verified isomer ratio (≥50 % cis‑9, trans‑11), absence of heavy‑metal residues, and third‑party testing for purity and oxidative stability (e.g., peroxide value <5 meq O₂/kg).
Standardized, high‑purity (>80 % total CLA) products are recommended for research‑grade or therapeutic use.