Folate, B6 could boost heart health for type-1 diabetics

Children with type-1 diabetes could benefit from high-dose folate and vitamin B6 supplements to boost their cardiovascular health, according to a new clinical trial.

"Effective intervention with an apparently safe, inexpensive adjunct such as folate or vitamin B6 at an early stage in childhood, in addition to optimisation of metabolic control, could have a major impact on long-term diabetic vascular complications," wrote lead author Karen MacKenzie in the journal Pediatrics (Vol. 118, pp. 242-253).

Type-1 diabetes occurs when people are not able to produce any insulin after the cells in the pancreas have been damaged, thought to be an autoimmune response.

Sixty-five percent of diabetics die from heart attack and stroke, and people with diabetes are reported to have a two to four higher chance of developing cardiovascular disease.

And the new study, from the University of Adelaide in Australia and the Wellington School of Medicine and Health Sciences in New Zealand, reports that the cardiovascular health of people with type-1 diabetics could benefit from high-dose folate and/or vitamin B6 supplements.

This is the first time, say the researchers, that such a such benefits associated with these B vitamins have been reported.

The randomised, double-blind, placebo-controlled study recruited 122 children (average age 14) with type-1 diabetes and normal blood folate levels and assigned them to one of four experimental groups: Five milligrams of folate (Sigma Pharmaceuticals) and matched placebo; 100 milligrams vitamin B6 (Rhone-Poulenc-Rorer) and matched placebo; five mg folate plus 100 mg vitamin B6; two placebo tablets.

High-resolution ultra-sound was used to measure flow-mediated dilation (FMD) at baseline, at two and four hours after the first dose, and after four and eight weeks of supplementation. FMD measures changes in the diameter of blood vessels that are associated with increased blood flow.

Two hours after the first dose of folate, FMD was found to have increased significantly from 1.88 per cent to 10.46 per cent, with no additional increase at four hours.

The vitamin B6 supplement only lead to an immediate (at two hours) effect on FMD, increasing from 4.7 per cent to 8.36 per cent, with no further changes at four hours.

No significant changes were observed for the placebo group.

After eight weeks, the researchers found that FMD was significantly increased in all three intervention groups. Folate supplementation only led to an increase in FMD of about seven per cent, while vitamin B6 led to an increase of almost five per cent.

The combined supplement of vitamin B6 and folate led to an increase in FMD of about 7.75 per cent at the end of the eight-week intervention period.

No significant differences were observed for the placebo groups.

"We have shown for the first time that, among children with type-1 diabetes and normal folate status, both high-dose folate and high-dose vitamin B6 normalise endothelial function within two hours, an effect that is maintained over eight weeks with combined [supplementation] with high-dose folate and/or vitamin B6," wrote the authors.

When the researchers considered an endothelium-independent dilation of blood vessels induced by glyceryltrinitrate no changes were observed. This result indicated that there was no effect on smooth muscle function, said MacKenzie.

The mechanism behind the benefits of high-dose B vitamin supplementation may not be due to decreasing levels of the amino acid homocysteine, say the researchers. Homocysteine has been linked by epidemiological studies to an increased risk of cardiovascular disease.

MacKenzie and her co-workers propose that the B vitamins offer benefits independent of homocysteine levels, which may be due to antioxidant effects, and possibly a direct interaction with nitric oxide synthase which boosts nitric oxide production.

Since this study is the first to report such benefits, more randomised, double-blind, placebo-controlled studies are required to confirm or refute these effects.

But these promising results led the researchers to conclude: "The possibility of long-term benefits of folate and vitamin B6 [supplementation] on vascular disease progression is an exciting prospect."

The research was welcomed by British charity Diabetes UK. Matt Hunt, head of science information for the charity told NutraIngredients.com that the study was "certainly novel".

"What is interesting is that the combination therapy appears to work immediately within i.e. within 2 hours. It warrants further investigation because endothelial dysfunction also occurs in Type 2 and there doesn't appear to be the same evidence for this treatment and adults.

"Because type 1 has autoimmune implications it is early to speculate that this is affecting mostly cardiovascular health. Diabetes UK would suggest a future area of research as T2 Kids and this combination therapy," said Hunt.