A recent Egyptian study found FAS intake significantly reduced circulating serum Hcy and sortilin, suggesting it “could have a possible contribution in the primary prevention of cardiovascular events in diabetic patients”, researchers say.
Both compounds are biomarkers for cardiovascular events in diabetic patients and correlate to insulin resistance, dyslipidemia, and poor control of the disease.
In the present study, FAS was linked to significant decreases in homocysteine and sortilin serum levels (28.2% and 33.7% respectively), as well as chronic inflammation (linked to heart disease), compared to the placebo.
As a result, the authors maintain Hcy and sortilin could be used as therapeutic targets for T2DM treatment and help clinicians identify cardiovascular risks in diabetic patients.
Pathological indicators
Hyperhomocysteinemia is 1.9-times more likely to lead to death in T2DM patients than in healthy individuals. T2DM patients exhibit raised levels of circulating Hcy, in contrast to non-diabetic individuals, and folic acid is considered an essential factor in determining plasma Hcy concentrations.
FAS lowers the Hcy level by increasing the 5-methyltetrahydrofolate intracellular pool, which may improve diabetic outcomes and decrease cardiovascular events.
Meanwhile, sortilin is linked to several pathological processes including inflammation and calcification of arterial wall, insulin resistance, and disrupted lipoprotein metabolism.
It is also associated with low-density lipoprotein cholesterol (LDL-C) levels and risk of developing atherosclerosis and also appears to be a key factor in
hepatic and muscular response to insulin - indicating a link between insulin resistance and hypercholesterolemia, the authors write.
Furthermore, sortilin correlates with the incidence of major adverse cardiovascular events in T2DM, according to a previous study.
Study protocol
The double-blind trial involved 100 male and female participants aged 45 to 75 years and chosen at random from patients attending the Damanhour National Medical Institute.
Inclusion criteria for patients was confirmed diagnosis of T2DM and treatment with metformin (1500 mg daily for more than six months) at baseline.
Patients were divided into two groups and received either the placebo or a 5 mg daily dose of folic acid for 12 weeks.
The folic acid group showed no significant difference in baseline characteristics compared to the placebo group.
Adherence to study protocol was determined through regular questioning about average tablets intake per week throughout the study period.
Positive results
The present study revealed significantly higher levels of hs-CRP at the baseline assessment of studied patients. Researchers noted a substantial positive correlation of hs-CRP and sortilin among study patients.
Furthermore, measurements for circulating serum homocysteine demonstrated substantial reductions in the intervention group.
After three months, significant changes were noted between groups regarding fasting blood glucose (FBG), glycated haemoglobin (HbA1c), and insulin resistance. On the other hand, there was no significant changes in insulin levels in either group.
Participants in the intervention group experienced an 8.7% decrease in fasting blood glucose, 13.7% decrease in serum insulin, and 21.7% decrease in measurements of insulin resistance.
Conversely, there were no significant changes in lipid profiles at the end of the 12-week intervention.
The mean BMI of the participants in each group did not change after folic acid supplementation.
Physiological mechanisms
The authors proposed several mechanisms to explain the effect of folic acid on the pathogenesis of insulin resistance and T2DM. Reductions in Hcy, from folic acid intake, may suppress glycogen production, resulting in insulin resistance and hyperglycaemia, the authors write.
Folic acid has also been linked to endothelial dysfunction, which is beneficial to glycometabolism, they explain.
“Folic acid improves endothelial dysfunction induced by high Hcy by preventing nitric oxide synthase dysfunction.”
In addition, lower Hcy reduces oxidative stress and systemic inflammation, “which can disrupt insulin signalling and diminish release of insulin from pancreatic cell ß”, they say.
Given the low sample size and short follow-up, the authors assert that an extension to the work and further large-scale studies are warranted.
Source: Nutrition & Diabetes
Published online: doi.org/10.1038/s41387-022-00210-6
‘Folic acid effect on homocysteine, sortilin levels and glycemic control in type 2 diabetes mellitus patients’
Noha M. El-khodary et al.