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Does Apolipoprotein E Genotype Affect Flaxseed Oil Response in Type 2 Diabetes?

Clinical Bottom Line

A small RCT finds flaxseed oil reduces platelet aggregability but not other risk markers in type 2 diabetes, with no ApoE genotype effect. PICO summary and expert commentary.

Summary: In a small trial of adults with well-controlled type 2 diabetes, flaxseed oil reduced platelet aggregability versus a safflower-oil placebo but improved none of the other six cardiometabolic risk markers, and apolipoprotein E genotype had no influence on response.

PICO Summary

ElementDetail
Population32 adults with well-controlled type 2 diabetes (double-blind, placebo-controlled).
InterventionFlaxseed oil supplementation (ALA-rich) between visits.
ComparisonSafflower oil supplementation as placebo.
OutcomeSignificant reduction in platelet aggregability versus placebo; no significant effect on abdominal obesity, hypertension, hyperglycaemia, dyslipidaemia, LDL oxidation, or inflammation. No ApoE genotype effect on any outcome.

Expert Commentary

This is, by the authors’ own framing, largely a negative study, and I respect that it is reported as such rather than spun. The nutrigenomic question it set out to answer, whether ApoE genotype predicts response to flaxseed oil, returned a clean null, which is a genuinely useful thing to know even though it is not the answer anyone hoped for. The one positive signal, reduced platelet aggregability, I hold very loosely: this is 32 people, the comparator was omega-6-rich safflower oil that has its own effects, and the outcome is a surrogate with no link here to actual cardiovascular events. Everything else, glucose, lipids, blood pressure, inflammation, was unmoved. Can I use this with my patients? Essentially no. I would not recommend flaxseed oil for metabolic or cardiovascular protection on this evidence, and I would certainly not order ApoE testing to guide it. If a patient takes flaxseed oil for their own reasons it is harmless, but it is no substitute for proven antiplatelet, lipid, and glucose management. I would need event-level data before saying anything stronger.

References

Barre DE, Mizier-Barre KA, Griscti O. Thus far there are no statistically significant differences between various apolipoprotein E genotypes in the cluster of seven responsiveness to a flaxseed oil supplement in persons with type 2 diabetes. Endocr Regul. 2025;59(1):141–146. doi:10.2478/enr-2025-0016

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