In the news: Lower Risk of DR with Higher omega-3; Metformin Lowers B12 Levels

Higher Blood Omega-3 Linked to Lower DR

Inflammation is associated with the development and progression of diabetic retinopathy (DR). Previous studies have shown that omega-3 polyunsaturated fatty acids (omega-3s) have anti-inflammatory properties and modulate capillary integrity and neovascularization.

Few studies, however, have examined the association of individual circulating levels of omega-3 with diabetic retinopathy.

In the current study(1), a research team determined the associations between the omega-3s EPA and DHA and the prevalence and severity of DR in a combined cohort of diabetic participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and Genetics of Latino Diabetic Retinopathy (GOLDR).

The investigators found that individuals with blood levels of DHA in the top 25% (4th quartile) of DHA were 17% less likely to have retinopathy compared to the lowest 25% or first quartile (p=0.009).

Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth compared to the first quartile of EPA + DHA combined and DHA alone (p=0.004 and p=0.006, respectively). No significant associations were observed between EPA alone and retinopathy.

Overall, the current findings are in line with those of the PEDIMED trial – the largest dietary intervention trial to assess the effects of the Mediterranean diet on cardiovascular disease. In PEDIMED, those who consumed at least 500 mg/day showed a 46% decreased risk in sight-threatening DR versus those consuming less.

Collectively, the results of the present study suggest that circulating levels of omega-3, particularly DHA, may be protective against developing or worsening DR. Further studies are warranted to see whether consuming more omega-3 is a viable DR prevention option in those with type 2 diabetes.

Metformin & Vitamin B12: New Insights

Decreased vitamin B12 levels is now considered to be a relatively common side effect in people taking metformin, especially for those receiving a higher dose or treated longer, or those with existing risk factors for B12 deficiency such as family history, Crohn’s, infections, vegan diets, and older age.

There are several ways that metformin could affect B12 status. The most common theory is that the drug reduces B12 absorption due to interference with the calcium-dependent binding of the intrinsic factor- vitamin B12 complex. It has also been suggested that gut microbes play a role. A newly published study(2) exploring this theory found that metformin helps certain gut bacteria accumulate their own B12 (making less B12 available to the host) by increasing transporter genes.

A recent systematic review(3) asked whether B12 supplementation could be effective in raising serum B12 levels, reducing homocysteine levels, and in reducing neuropathy in diabetics taking metformin.

The results support vitamin B12 supplementation for metformin-receiving type 2 patients. Out of 7 included studies in the review, the 5 that measured B12 found a significant increase in serum vitamin B12 level after supplementation and 2 of them showed a decrease in serum homocysteine levels. The effects on neuropathy symptoms were less clear, with 2 studies reporting improvements and 1 finding no significant effect.

References

1. Weir NL, et al. Omega-3 fatty acids are associated with decreased presence and severity of diabetic retinopathy: A combined analysis of MESA and COLDR cohorts. Retina. Epub Jan. 30, 2023.
2. Yao L, et al. The antidiabetic drug metformin aids bacteria in hijacking B12 from the environment through RcdA. Comm Biol. 6:96, 2023.
3. Pratama S, et al. The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review. Diabetes Metab Syndr. Epub Oct 16, 2022.