Improving Diabetic and Hypertensive Retinopathy with a Medical Food Containing L-methylfolate: a Preliminary Report

Overview

Journal Eye Vis (Lond)

Publisher Biomed Central

Specialty Ophthalmology

Date 2019 Aug 1

PMID 31363484

Citations 11

Authors

Jianhua Wang

Craig Brown

Ce Shi

Justin Townsend

Giovana Rosa Gameiro

Peng Wang

Hong Jiang

Affiliations

Soon will be listed here.

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.

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References

Botto L, Yang Q . 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000; 151(9):862-77. DOI: 10.1093/oxfordjournals.aje.a010290. View

Noma H, Funatsu H, Yamashita H, Kitano S, Mishima H, Hori S . Regulation of angiogenesis in diabetic retinopathy: possible balance between vascular endothelial growth factor and endostatin. Arch Ophthalmol. 2002; 120(8):1075-80. DOI: 10.1001/archopht.120.8.1075. View

Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S . MTHFR gene polymorphism as a risk factor for diabetic retinopathy in type 2 diabetic patients without serum creatinine elevation. Diabetes Care. 2003; 26(2):547-8. DOI: 10.2337/diacare.26.2.547-a. View

Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M . Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003; 40(8):619-25. PMC: 1735571. DOI: 10.1136/jmg.40.8.619. View

Hassan A, Hunt B, OSullivan M, Bell R, DSouza R, Jeffery S . Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain. 2003; 127(Pt 1):212-9. DOI: 10.1093/brain/awh023. View

Qi Z, Hoffman G, Kurtycz D, Yu J . Prevalence of the C677T substitution of the methylenetetrahydrofolate reductase (MTHFR) gene in Wisconsin. Genet Med. 2003; 5(6):458-9. DOI: 10.1097/01.gim.0000095001.12570.a8. View

Roybal C, Yang S, Sun C, Hurtado D, Vander Jagt D, Townes T . Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004; 279(15):14844-52. DOI: 10.1074/jbc.M312948200. View

Goldstein M, Leibovitch I, Yeffimov I, Gavendo S, Sela B, Loewenstein A . Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy. Eye (Lond). 2004; 18(5):460-5. DOI: 10.1038/sj.eye.6700702. View

Atta H, El-Rehani M, Raheim S, Galal A . Lowering homocysteine decreases levels and expression of VEGF(165) and endostatin. J Surg Res. 2007; 146(2):202-10. DOI: 10.1016/j.jss.2007.04.038. View

10.

Klein B . Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007; 14(4):179-83. DOI: 10.1080/09286580701396720. View

11.

Brazionis L, Rowley Sr K, Itsiopoulos C, Harper C, ODea K . Homocysteine and diabetic retinopathy. Diabetes Care. 2007; 31(1):50-6. DOI: 10.2337/dc07-0632. View

12.

Maeda M, Yamamoto I, Fukuda M, Motomura T, Nishida M, Nonen S . MTHFR gene polymorphism is susceptible to diabetic retinopathy but not to diabetic nephropathy in Japanese type 2 diabetic patients. J Diabetes Complications. 2008; 22(2):119-25. DOI: 10.1016/j.jdiacomp.2006.12.002. View

13.

Coral K, Angayarkanni N, Gomathy N, Bharathselvi M, Pukhraj R, Rupak R . Homocysteine levels in the vitreous of proliferative diabetic retinopathy and rhegmatogenous retinal detachment: its modulating role on lysyl oxidase. Invest Ophthalmol Vis Sci. 2009; 50(8):3607-12. DOI: 10.1167/iovs.08-2667. View

14.

Nunes S, Pires I, Rosa A, Duarte L, Bernardes R, Cunha-Vaz J . Microaneurysm turnover is a biomarker for diabetic retinopathy progression to clinically significant macular edema: findings for type 2 diabetics with nonproliferative retinopathy. Ophthalmologica. 2009; 223(5):292-7. DOI: 10.1159/000213639. View

15.

Grauslund J, Green A, Sjolie A . Blindness in a 25-year follow-up of a population-based cohort of Danish type 1 diabetic patients. Ophthalmology. 2009; 116(11):2170-4. DOI: 10.1016/j.ophtha.2009.04.043. View

16.

Gopinath B, Wang J, Flood V, Burlutsky G, Wong T, Mitchell P . The associations between blood levels of homocysteine, folate, vitamin B12, and retinal vascular caliber. Am J Ophthalmol. 2009; 148(6):902-9. DOI: 10.1016/j.ajo.2009.07.018. View

17.

Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L . Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011; 58(2):186-92. PMC: 3896949. DOI: 10.1016/j.jacc.2011.02.051. View

18.

Ola M, Nawaz M, Siddiquei M, Al-Amro S, Abu El-Asrar A . Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complications. 2012; 26(1):56-64. DOI: 10.1016/j.jdiacomp.2011.11.004. View

19.

Yau J, Rogers S, Kawasaki R, Lamoureux E, Kowalski J, Bek T . Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012; 35(3):556-64. PMC: 3322721. DOI: 10.2337/dc11-1909. View

20.

Mrad M, Wathek C, Saleh M, Baatour M, Rannen R, Lamine K . Association of methylenetetrahydrofolate reductase (A1298C and C677T) polymorphisms with retinal vein occlusion in Tunisian patients. Transfus Apher Sci. 2014; 50(2):283-7. DOI: 10.1016/j.transci.2013.12.016. View