A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes

Mol Vis. 2020 Apr 24:26:326-333. eCollection 2020.


Purpose: The aim of the present study was to investigate the effect of a three-month dietary supplementation with a methylfolate formulation on homocysteine plasma concentrations and ocular blood flow parameters in patients with diabetes.

Methods: Twenty-four patients with diabetes received a dietary supplement (Oculofolin, Aprofol AG, Switzerland) containing 900 µg L‑methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients for three consecutive months. The patients' plasma homocysteine concentration and retinal blood flow were assessed at baseline and after three months of folate intake. Retinal blood flow was measured using a custom-built dual-beam Doppler optical coherence tomography (OCT) system. In addition, flicker-induced retinal vasodilatation was assessed by means of a commercially available dynamic vessel analyzer (IMEDOS, Jena, Germany).

Results: Supplementation was well tolerated by all patients. After three months, plasma homocysteine concentration significantly decreased from 14.2 ± 9.3 to 9.6 ± 6.6 µmol/L (p < 0.001). In addition, a tendency toward an increased total retinal blood flow from 36.8 ± 12.9 to 39.2 ± 10.8 µl/min was observed, but this effect did not reach the level of significance (p = 0.11). Supplementation had no effect on retinal vessel diameter or flicker-induced vasodilatation.

Conclusions: The present data show that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes. This is of importance because higher homocysteine plasma levels have been found to be associated with an increased risk of vascular associated systemic diseases and eye diseases. Whether systemic methylfolate supplementation affects retinal perfusion must be studied in a larger population.

Trial registration: ClinicalTrials.gov NCT03997032.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Circulation / drug effects*
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / diet therapy
  • Dietary Supplements
  • Female
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Retina / drug effects*
  • Retina / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / physiology
  • Tetrahydrofolates / administration & dosage*
  • Tetrahydrofolates / blood
  • Tomography, Optical Coherence
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / analogs & derivatives
  • Vitamins / administration & dosage*


  • Tetrahydrofolates
  • Vitamins
  • Homocysteine
  • mecobalamin
  • Vitamin B 12
  • 5-methyltetrahydrofolate

Associated data

  • ClinicalTrials.gov/NCT03997032