Safflower Oil for Metabolic Syndrome: One Small RCT

Eight grams of safflower oil per day improved waist circumference, blood pressure, fasting glucose, and insulin resistance over 12 weeks in one double-blind, placebo-controlled trial of people with metabolic syndrome. That is an interesting result. It is not enough evidence to treat safflower oil as a proven therapy.

The biggest problem is unusually basic: the study did not specify whether it used high-linoleic or high-oleic safflower oil. Those are not interchangeable products. Until another trial identifies the oil and reproduces the results, the sensible conclusion is that safflower oil is a lead worth testing, not a supplement with reliable expected effects.

What the trial found

In a 2022 randomized, double-blind, placebo-controlled trial by Ruyvaran et al., 67 adults with metabolic syndrome received 8 g/day of safflower oil in divided doses or placebo for 12 weeks. Compared with the control group, the safflower-oil group had statistically significant improvements in five measures.

• Waist circumference fell by 2.42 ± 3.24 cm, while the control group increased by 0.97 ± 2.53 cm (p<0.001).
• Systolic blood pressure fell by 8.80 ± 9.77 mmHg, versus 2.26 ± 8.56 mmHg in controls (p=0.021).
• Diastolic blood pressure fell by 3.53 ± 7.52 mmHg, versus 0.70 ± 6.21 mmHg in controls (p=0.041).
• Fasting glucose fell by 5.03 ± 10.62 mg/dL, while it rose by 2.94 ± 7.57 mg/dL in controls (p=0.003).
• HOMA-IR, a calculated marker of insulin resistance, fell by 0.59 ± 1.43 units; it rose by 0.50 ± 1.00 units in controls (p=0.012).

Adiponectin also increased by 0.38 ± 0.99 μg/mL in the safflower group and fell by 0.09 ± 0.81 μg/mL in controls (p=0.042). Adiponectin is an adipose-derived hormone generally associated with greater insulin sensitivity and less abdominal fat.

The breadth of the signal makes the trial more compelling than a single favorable biomarker. Waist, blood pressure, glucose, and HOMA-IR point in the same direction. But statistical significance does not make each change clinically decisive. An 8.80 mmHg drop in systolic pressure could matter if it holds up; a 5.03 mg/dL fall in fasting glucose will usually not move someone across a diagnostic category by itself. HOMA-IR also lacks one universal cutoff: interpretation depends on the population. In a large U.S. cohort, Xing et al. reported sex-specific HOMA-IR cutoffs that varied across follow-up periods.

The lipid result was flat

Safflower oil did not significantly change LDL cholesterol, HDL cholesterol, total cholesterol, or triglycerides during the 12-week trial. It also did not change leptin.

This rules out using 8 g/day of safflower oil as a cholesterol treatment on the basis of this study. The null lipid result also fits the dose and context. Linoleic acid can lower LDL when it replaces saturated fat in the diet; adding roughly 8 g of oil, about 72 calories, does not necessarily displace enough saturated fat to remodel lipoproteins. A supplement added on top of the usual diet is not the same intervention as changing the fat composition of that diet.

The unchanged leptin result is harder to explain. A smaller waist often accompanies lower leptin, although the relationship is neither immediate nor exact. The mismatch could reflect measurement noise, a short study, or a waist change that did not track directly with visceral-fat loss. The trial cannot distinguish among those explanations.

The missing oil type is a reproducibility problem

Safflower oil is sold in two materially different forms. High-linoleic safflower oil contains roughly 75% linoleic acid, an omega-6 polyunsaturated fat. High-oleic safflower oil contains roughly 75% oleic acid, a monounsaturated fat. The trial publication did not say which one participants received.

That omission matters because the proposed mechanism centers on linoleic acid. Linoleic acid may act on PPAR-γ, a receptor involved in fat-cell biology and insulin signaling; PPAR-γ activity can increase adiponectin transcription. The rise in adiponectin alongside the lower HOMA-IR is compatible with that hypothesis. It does not prove the mechanism, and it certainly does not prove that any bottle labeled "safflower oil" will reproduce the result.

A replication should name the safflower-oil variant, verify its fatty-acid composition, and report whether sex or baseline metabolic status predicts response.

Response variation is a serious issue here. The standard deviations were large relative to several average changes. For systolic pressure, for example, the mean reduction was 8.80 mmHg with an SD of 9.77 mmHg. That pattern means individual outcomes probably varied substantially; an average benefit does not mean every participant benefited.

What the related PUFA evidence can—and cannot—tell us

The broader evidence gives the hypothesis some biological context, but it cannot substitute for a replicated safflower-oil trial. A 2023 randomized, double-blind crossover study by Laupsa-Borge et al. examined marine omega-3 and plant omega-6 polyunsaturated-fat supplementation in people with abdominal obesity. It found that responses in glucose-insulin and lipid measures differed by sex. That does not confirm the safflower result, but it supports the concern that pooled averages can hide different responses in men and women.

The familiar claim that omega-6 fats are automatically inflammatory also fares poorly as a blanket rule. In a 2025 randomized, double-blind crossover study, Grytten et al. found that plant omega-6 PUFA supplementation did not uniformly increase the inflammatory markers they measured compared with marine omega-3 supplementation. That provides limited short-term reassurance, not a full safety clearance for safflower oil. The available safflower evidence did not measure lipid-peroxidation products such as F2-isoprostanes, malondialdehyde, or 4-hydroxynonenal.

Conjugated linoleic acid, or CLA, is sometimes invoked as support because it is a related C18:2 fatty acid with overlapping receptor biology. That comparison has limits. A 2023 GRADE-assessed meta-analysis of CLA trials in people at cardiovascular risk found higher fasting glucose on average, by 4.49 mg/dL (95% CI, 2.39 to 6.59). CLA is not linoleic acid, and its results should not be imported as proof for safflower oil. If anything, they are a reminder that related fats can produce different clinical effects.

How this evidence compares with actual supplement research

Small dietary-oil trials can move metabolic markers over a few months. The 2026 OleoMetS randomized trial, for example, tested olive-oil polyphenols in people with metabolic syndrome. But a plausible dietary intervention is not automatically a validated one. Other supplements have reached synthesis across many trials before anyone can estimate a reasonably stable average effect. A 2025 meta-analysis of nanocurcumin pooled 20 randomized trials involving 1,394 participants; safflower oil for metabolic syndrome has one small direct trial.

Practical verdict

The Ruyvaran trial gives safflower oil a real but preliminary signal: at 8 g/day for 12 weeks, participants with metabolic syndrome had lower average waist circumference, blood pressure, fasting glucose, and HOMA-IR than controls. The study did not improve blood lipids, did not explain the unchanged leptin level, and did not identify the oil variant.

If someone chooses to test it alongside established treatment and lifestyle measures, the trial most logically points to high-linoleic safflower oil—not high-oleic oil—though that inference remains unconfirmed because the study failed to specify its product. Monitor the outcomes the study actually moved: blood pressure, waist circumference, and fasting glucose. Do not expect a cholesterol benefit from this dose, and do not treat a lack of response after 12 weeks as a reason to dose-load.

One 67-person trial can generate a useful hypothesis. It cannot tell you who will respond, whether the benefit lasts, or whether the same result survives a better-specified replication.