Improving diabetic and hypertensive retinopathy with a medical food containing L-methylfolate: a preliminary report

Abstract

Background: Homocysteine and vitamin D may play a role in the development of diabetic and hypertensive retinopathy in patients with diabetes mellitus (DM) and hypertension. Supplementing food with L-methylfolate and vitamin D theoretically may improve diabetic and hypertensive retinopathy, however, the outcome of these nutritional approaches has not been fully examined. A retrospective case review was done of cases of retinopathy reversal in patients on Ocufolin™ and a similar nonprescription multivitamin, Eyefolate™. In this study, they were administered L-methylfolate (2.7 mg and 3.0 mg, respectively) and vitamin D3 (4500 IU each). These dosages are significantly above the RDA but well below levels associated with toxicity.

Case presentation: Seven patients had nonproliferative diabetic retinopathy (NPDR) and some of them had hypertension. One patient had only hypertensive retinopathy. All patients were instructed to take Ocufolin™ medical food as a food supplement. Baseline genetic testing for MTHFR polymorphisms was conducted. Fundus photography was used to document the fundus condition of the enrolled eyes in 8 NPDR patients at the initial and follow-up visits. Microaneurysms (MA) and exudates were observed to be improved in some trial patients. All subjects had one or more MTHFR polymorphisms. All had diabetic retinopathy, hypertensive retinopathy, or both. MAs were resolved, and exudates were decreased in 8/8 cases after taking the medical food. Retinal edema was found in 2/8 cases and improved or resolved in both cases after taking the medical food or the supplement. The best corrected visual activity was stable or improved in 8/8 cases.

Conclusion: We report a series of diabetic and hypertensive retinopathy cases with MTHFR polymorphisms and the improvement of retinal microvasculature (mainly MAs) in serial fundus photography after taking a medical food or supplement containing L-methylfolate and vitamin D. It appears that the use of nutritional supplements and medical foods containing L-methylfolate and vitamin D may be effective in facilitating the improvement of diabetic and hypertensive retinopathy.

Keywords: Diabetes; Homocysteine; L-methylfolate; MTHFR C677T; Microaneurysms; Retinopathy; Vitamin D.

Fig. 1

Follow-up of first case fundus photos and OCT images. The fundus photograph fewer hemorrhages and MAs after taking Eyefolate™ (a, b, c). The diabetic cystic macular edema resolved at a later visit (e) on the OCT B-scan using Zeiss Cirrus HD-OCT (Model 5000) compared to the previous visit (d). OCT: optical coherence tomography; MA: microaneurysms

Fig. 2

Follow-up of the second case fundus photos. Intra-retinal hemorrhages and 3 small MAs (black arrows) were seen in the fundus photo in OS eye (a) at the first visit. At the second visit, only 1 faint MA remained, and the hemorrhages were resolved (b) after taking Eyefolate™ for four months. MA: microaneurysms

Fig. 3

Follow-up of third case fundus photos. Some exudate leakage was found at the August 2014 visit (a). After taking Eyefolate™, the large MA (yellow arrow) was reduced and the exudate was smaller at the Dec 2014 visit (b). The MA and exudates (yellow arrow) were resolved by the January 2016 visit (c). In addition, at the November 16 visit (e), the diabetic cystic macular edema was reduced from the 2015 visit (d) and later visit

Fig. 4

Follow-up of the fourth case fundus photos. The number of retinal hemorrhages and MAs on the fundus photo declined and exudates were resolved after taking the supplements (a-c). MA: microaneurysms

Fig. 5

Follow-up of fifth case fundus photos. Baseline findings of drusen, exudates, a cotton wool spot and microaneurysms (a). MAs were smaller and the exudates and cotton wool spot resolved after taking Eyefolate™ for 5 months (b). MAs and exudates returned 3 ½ years after quitting Eyefolate™ (c). The foveal drusen did not change. MA: microaneurysms

Fig. 6

Follow-up of sixth case fundus photos. After taking Eyefolate™ then Ocufolin™, MAs, and exudates resolved. He remains free of MAs and exudates in 2/2019 (c). OS show resolution of intra-retinal hemorrhages, exudates, and MAs improved and remained stable over more than 3 years of follow up from 12/2015 through February 2019 (a-c). OD show resolution of intra-retinal hemorrhages and MAs between 12/2015 and 5/2018 (d-f). MA: microaneurysms

Fig. 7

Follow-up of seventh case fundus photos. Between September 2018 (a) and December 2018 (b), the intra-retinal hemorrhage (yellow arrow) resolved after taking Eyefolate™

Fig. 8

Follow-up of eighth case fundus photos. The top images were taken using Topcon DX fundus camera on October 10, 2017, before the patient took Ocufolin™ (a, b). Close inspection of fundus photos showed two MAs in the periphery of the superonasal quadrant OS. The bottom photos were taken using Zeiss Clarus 500 on January 17, 2019, after the patient participated in a clinical trial of Ocufolin™ for 6 months (c, d). The MAs in the superior nasal periphery of the OS eye resolved in the photo taken in January 2019

Fig. 9

Retinal blood flow velocity of the eighth case. Retinal blood flow velocity was measured during study period of 6 months when the patient took Ocufolin™