Regular fish oil intake tied to lower T2D risk

A prospective study evaluating individuals with prediabetes shows an inverse association between habitual fish oil intake and the risk of type 2 diabetes (T2D).

“[W]e observed that habitual fish oil supplementation was related to a 9-percent lower risk of T2D among individuals with prediabetes after adjusting for multivariable risk factors for T2D development. The inverse relationship was modified by rs780094 in GCKR and variants at glucose transporter 4 (GLUT4),” said the researchers.

The use of fish oil supplements was significantly associated with a lower risk of incident T2D after adjusting for a healthy diet score (hazard ratio [HR], 0.91; p=0.021). The inverse association was more pronounced among women (p for interaction=0.005). [Research (Wash D C) 2025:8:0683]

Fish oil intake was also inversely associated with T2D risk in the age- and sex-adjusted analyses (HR, 0.85; p<0.001). The researchers added that this was sustained after further adjustments for other demographic variables, use of other supplements and medications, and dietary factors, including oily fish, vegetable, and fruit intake.

They added that the significant inverse association did not substantially change after further adjustments for serum HbA_1c levels, C-reactive protein levels, lipid-lowering and antihypertensive agents, hormone replacement therapy, or oral contraceptive use in the sensitivity analyses.

“Our results also remained similar when we further excluded participants with extreme BMI, incident T2D cases that occurred within 2 years, persons who took any other supplements, or those with missing covariate data,” they said.

Genetic factors

There was also a significant interaction between fish oil intake and rs780094 in GCKR (p for interaction=0.049) and marginal interactions for rs174555 in FADS1 (p for interaction=0.078), rs7200543 in NTAN1 (p for interaction=0.061), and rs102275 in TMEM258 (p for interaction=0.072).

According to the researchers, these underscore the potential role of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) metabolic pathways in the benefits of fish oil.

Fish oil intake was also associated with higher plasma levels of n-3 polyunsaturated fatty acids (PUFAs), DHA, and non-DHA n-3 PUFAs, and a lower n-6/n-3 PUFA ratio (p<0.001 for all). Of note, rs1077989 in TMEM229B had significant interactions with fish oil intake on plasma levels of DHA (p for interaction=0.012) and n-3 PUFAs (p for interaction=0.036).

The inverse association between fish oil intake and n-6/n-3 PUFA ratio was substantially modified by the number of n-3 PUFA-related alleles and several specific single-nucleotide polymorphisms (p for interaction<0.001 for all).

A promising approach for T2D prevention

“[T]here is an urgent need for effective measures for improving glucose metabolism, which is the key step to preventing T2D development in prediabetes,” said the researchers.

To explore the association between fish oil supplementation and T2D development, the investigators used data from 48,358 individuals with prediabetes from the UK Biobank (mean age 59 years, 56 percent women). A third (n=16,180) of participants reported habitual fish oil intake. During an average follow-up of 7.8 years, 3,385 T2D cases were documented to have developed from prediabetes.

“[Taken together, our findings suggest that] DHA and EPA supplementation may be a promising approach for T2D prevention,” said the investigators. The results offer an in-depth understanding of the causal relationship and underlying mechanisms of the alleviative effects of marine n-3 PUFAs on hyperglycaemia in humans, they added.

“Overall, our findings offer new robust evidence on the beneficial effects of marine n-3 PUFAs on T2D prevention by targeting muscular glucose homeostasis, opening up new research avenues into pioneer treatment for enhancing GLUT4 translocation, glycogen synthesis, and aerobic glycolysis,” they concluded.