Ocufolin® Selected Nutrigenomic Bibliography


Ocufolin® is a medical food intended to address the metabolic conditions that underly ischemia and small vessel vasculopathy of the visual system. Numerous studies have demonstrated the benefits of administering doses of certain natural vitamins and antioxidants in higher amounts than possible through a balanced diet. This is particularly so for individuals with genetic abnormalities of their methylation metabolism, individuals with malabsorption syndromes, and other individuals with higher han normal needs for these nutrients.

Metabolic dysfunction preceeds structural damage. Addressing metabolic dysfunction early, may reduce the severity of later structural damage. With respect to the visual system, metabolic demands for oxygen, glucose, and essential vitamin nutrients are the highest of any other tissues in the body. Metabolic and structural damage leads to loss of vision. There is evidence that early intervention with these vitamins and nutrients to address ischemia and oxidative stress may be neuroprotective for the different parts of the visual system and sometimes modestly improve vision.

Medical foods are designed to deliver high doses of natural nutrients to correct underlying metabolic abnormalities that impair function. With respect to the visual system, this includes the metabolism of the conjunctiva, the retina, the optic nerve, and the visual cortex which together form the visual system. The delivery system for all nutrients and anti-oxidants, as well as the removal of waste products are the capillaries, small arteries, and venules of the visual system. Excess homocysteine is associated with vasoconstriction, ischemia, occlusion, eventually loss of these capillaries, arterioles, and venules causing gradual tissue atrophy and vision loss. Reducing homocysteine also increases blood flow and appears to be most beneficial for the small vessels of the central nervous system, which includes the visual system.

The following bibliography lists several studies of the benefits of Ocufolin® where impaired blood flow is involved. These findings may be applied to clinical situations involving diabetic retinopathy, hypertensive retinopathy, retinal artery occlusion, retinal vein occlusion, low tension glaucoma, Flammer syndrome, and neuro-protection of the optic nerve and it's connections into the visual cortex of the brain. Improving blood flow, adressing ischemia, and addressing homocystiene elevation may be of benefit for patients with a wide range of small vessel vascular conditions in the eye and cortical tissues of the visual

These studies have appeared in many respected journals including: Advances in Ophthalmology Practice and Research, American Journal of Hypertension, BMJ Open Diabetes Research Care, Clinical Ophthalmology, Eye and Vision, Journal of Clinical Hypertension, Journal of Clinical Medicine, Journal of Clinical Research in Ophthalmology, Microvascular Research, Molecular Vision, Pharmacogenomics and Personalized Medicine, and Theraputic Advances in Ophthalmology. Additional references are cited of important nutrigenomic reviews concerning these issues.


Improving diabetic and hypertensive retinopathy with a medical food containing L-methylfolate: a preliminary report. Wang J, Brown C, Shi C, Townsend J, Gameiro GR, Wang P, Jiang H.

Nutritional and medical food therapies for diabetic retinopathy. Shi C, Wang P, Airen S, Brown C, Liu Z, Townsend JH, Wang J, Jiang H.

Improved conjunctival microcirculation in diabetic retinopathy patients with MTHFR polymorphisms after Ocufolin™ Administration. Liu Z, Jiang H, Townsend JH, Wang J.

Improved Retinal Microcirculation in Mild Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms Who Received the Medical Food, Ocufolin®. Clin Ophthalmol. Liu Z, Jiang H, Townsend JH, Wang J.

Effects of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms on Retinal Tissue Perfusion in Mild Diabetic Retinopathy Patients Receiving the Medical Food, Ocufolin®. Hong Jiang, Zhiping Liu, Justin H Townsend & Jianhua Wang

Effects of Ocufolin on retinal microvasculature in patients with mild non-proliferative diabetic retinopathy carrying polymorphisms of the MTHFR gene. Liu Z, Jiang H, Townsend JH, Wang J.

Diabetes & Homocysteine

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. Schmidl D, Howorka K, Szegedi S, Stjepanek K, Puchner S, Bata A, Scheschy U, Aschinger G, Werkmeister RM, Schmetterer L, Garhofer G.

Homocystiene & Hypertension & Stroke

New evidence for homocysteine lowering for management of treatment-resistant hypertension. Elias MF, Brown CJ.

Medical foods for lowering homocysteine in hypertensive patients. Elias MF, Brown CJ.

Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. Brown C, Wang J, Jiang H, Elias MF.

Glaucoma: Lowering Retinal Venous Pressure

The effects of vitamin supplementation containing L-methylfolate (Ocufolin® forte) on retinal venous pressure and homocysteine plasma levels in patients with glaucoma. Devogelaere T and Schötzau A.

Low Tension Glaucoma

Role of ocular blood flow in normal tension glaucoma. Xingdi Wu, Katarzyna Konieczka, Xin Liu, Min Chen, Ke Yao, Kaijun Wang, Josef Flammer.

Treatment of Glaucoma Patients with Flammer Syndrome. Konieczka K, Flammer J.

Measuring and Treating Retinal Venous Pressure: Effort and Benefit. Flammer J.

Diagnosis and therapy of primary vascular dysregulation and Flammer syndrome in glaucoma patients. Flammer J, Konieczka K.

Normal tension glaucoma: Prevalence, etiology and treatment. Ayoub G, Luo Y, Lam DMK

Ischemia from Retinal Vascular Hypertension in Normal Tension Glaucoma: Neuroprotective Role of Folate. Ayoub G, Luo Y

Small Vessel Perfusion

Improving blood flow and protecting the eye. Smith AD.

Retinal Artery Occlusion

Preservation of retinal structure and function after cilioretinal artery occlusion: a case report. Brown CJ.

Retinal Vein Occlusion

Case series of retinal vein occlusions showing early recovery using oral l-methylfolate. Baker S, Baker D, Baker R, Brown CJ.


AREDS and AREDS2 Research Groups. Dietary Nutrient Intake and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2. Agrón E, Mares J, Clemons TE, Swaroop A, Chew EY, Keenan TDL.

Age-related macular degeneration. Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC, Wong WT, Chew EY.

Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE.

Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration. Samra YA, Kira D, Rajpurohit P, Mohamed R, Owen LA, Shakoor A, Kim IK, DeAngelis MM, Sheibani N, Al-Shabrawey M, Tawfik A.

Folate Bioavailability & BBB

Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. Wollack JB, Makori B, Ahlawat S, Koneru R, Picinich SC, Smith A, Goldman ID, Qiu A, Cole PD, Glod J, Kamen B.

Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Willems FF, Boers GH, Blom HJ, Aengevaeren WR, Verheugt FW.

Homocystiene & Disease of the Visual System

Homocysteine - from disease biomarker to disease prevention. Smith AD, Refsum H.

Homocysteine Induces Inflammation in Retina and Brain. Elsherbiny NM, Sharma I, Kira D, Alhusban S, Samra YA, Jadeja R, Martin P, Al-Shabrawey M, Tawfik A.

Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy. Srivastav K, Saxena S, Mahdi AA, Shukla RK, Meyer CH, Akduman L, Khanna VK.

Combined branch retinal artery and vein occlusion in hyperhomocysteinemia. Sengupta S.

Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease. Cahill M, Karabatzaki M, Meleady R, Refsum H, Ueland P, Shields D, Mooney D, Graham I.

B12 & Diabetic Retinopathy

Effects of oral administration of mecobalamin (Methycobal) on the oscillatory potential in the scotopic ERG in diabetic retinopathy. Tamai A, Yamana T, Fujinaga Y.

Meta-analysis of Serum Vitamin B12 Levels and Diabetic Retinopathy in Type 2 Diabetes. Yang X, Hu R, Zhu Y, Wang Z, Hou Y, Su K, He X, Song G.

B12 & Stroke

B vitamins in stroke prevention: time to reconsider. Spence JD, Yi Q, Hankey GJ.