Patients faced with looming vision loss are motivated – and oftentimes desperate – to prevent disease progression and preserve their remaining visual acuity. As a result, millions have been spent on supplements for eye health and vision preservation.
Store shelves and internet ads promote products, some with vague claims of “protecting” or “maintaining” eye health. Therefore, as physicians, its vital to have knowledge of these supplements (along with the supporting science) to help patients avoid the often ineffective, sometimes dangerous, act of self-medication.
Looking back at AREDS
Two studies AREDS (Age-Related Eye Disease Study) and AREDS2, found that an antioxidant supplement could limit free radical cell damage in age-related macular degeneration (AMD) in certain patients. In AREDS, a high-dose combination of vitamins C and E, beta carotene and zinc oxide, with a dash of copper, was shown to effectively reduce the risk of worsening macular degeneration and severe vision loss by 25% over a period of six years.1-2 The AREDS2 formulation was just as effective, but the low zinc replaced the beta carotene (which increased lung cancer rates in smokers), with lutein and zeaxanthin.3
However, the AREDS formulations did not demonstrate benefits for all patients across all stages of AMD – it only slowed progression for those with intermediate AMD, or with the advanced form in only one eye. In addition, the AREDS formulations do not prevent AMD, and they’re not a cure . . . these things are rarely noted on package labels. Therefore, it’s important to counsel patients.
Backing benefits with science
Supplying micronutrients to the aging eye is often hampered because of altered microcirculation and problems at the blood-retina-barrier. To investigate this issue, US-ophthalmologist Craig Brown and Swiss chemist Martin Ulmann reviewed all the available – yet somewhat fragmented – knowledge regarding dietary supplements. They also brought a team together of leading experts from varying fields.
From this, Mr. Ulmann’s start-up company Aprofol AG was created; and OCUFOLIN® forte, an FSMP (food for special medical purposes), was optimized for the European- and Asian market. OCUFOLIN® uses the highest quality forms of each ingredient, at doses based on current best practices, all within a lipophilic matrix.
In a recent pilot study, OCUFOLIN® demonstrated effectiveness in lowering homocysteine, a known risk factor for vascular retinal disease. Additionally, the study showed a strong trend toward an increase in retinal blood flow and surprisingly, a significant decrease in intraocular pressure.4
“In patients with chronic ocular diseases like age-related macular degeneration or diabetic retinopathy, reduced microcirculation and elevated homocysteine levels are common,” explained Mr. Ulmann. Therefore, eliminating local micronutrient deficiencies would have tremendous potential as a safe way to delay or stop progression of serious eye diseases, such as diabetic retinopathy (DR) or AMD.
One micronutrient family in particular was singled out by Mr. Ulmann: folates. There are more than 100 naturally occurring folate compounds found in various foods and circulating through the body; its synthetic form, folic acid, is used in many dietary supplements and in food fortification. The universal natural form of folate is L-methylfolate, the only form able to cross the blood-brain-barrier and the blood-retina-barrier. As a chemist, he recognized the highly variable properties of various forms of folate in the lab, and was intrigued to uncover the different behaviors of each of the folate forms in the body – and more specifically, in the eye.
Mr. Ulmann’s investigations were supported by recent work from Stover et al., which confirms the need for supplementation in disease-induced micronutrient deficiency.5 The study reports that it “often cannot be addressed by nutrient intakes derived from a whole food-based diet alone.” Low folate status may be caused by low dietary intake, poor absorption of ingested folate, and alteration of folate metabolism due to genetic defects or drug interactions. Similar effects are also recognized for vitamins B12 and D.
According to Mr. Ulmann, his product OCUFOLIN® shows science-backed benefits: “It is a science-based FSMP developed by, and under the guidance of, ophthalmologists and chemists. It’s specifically designed for the dietary management of patients with a metabolic disorder and underlying retinal and choroidal ischemia, resulting in microvascular alterations.”
As Singh et al.6, noted: “We know that both AMD and DR patient types have elevated levels of homocysteine, but also low folate or vitamin B12 levels. We know that elevated homocysteine levels, along with oxidative stress, have been associated in the etiology of several vascular diseases that can lead to the development of choroidal neovascular membranes (CNV) in AMD.”
Mr. Ulmann explained further: “Elevated homocysteine levels and oxidative stress indicate a metabolic imbalance. A deficiency in L-methylfolate is inversely correlated to elevated homocysteine levels. Oxidative stress impairs the enzymatic homocysteine metabolism. As a consequence of elevated homocysteine levels, micro vessels are impaired in exchanging nutrients and metabolites, leading to deposits . . . and consequently inflammation in the eye.”
Referencing the 2013 work by Fonseca et al.7, he added: “The formulation is based on the AREDS formulation, B-vitamins of the Metanx study and complemented with vitamin D, as well as intracellular antioxidants.”
OCUFOLIN® forte is a specific formulation that supplies individuals (suffering from a deficit, or an impaired metabolic capacity, in forming L-methylfolate) with the necessary co-factors in the respective dosage to maintain a normal level of L-methylfolate. In addition, the reduction of homocysteine is supported by zinc and intracellular antioxidants to optimize the biochemical cascade.
In the pilot study at the University of Vienna4, 24 diabetic subjects (type I and II) took one capsule of OCUFOLIN® forte each day over a period of 12 weeks. During the study period, homocysteine-levels decreased from 14.2 to 9.6 µmol/L (32%), which is greater than the mean 25% reduction reported by the HLT (Homocysteine Lowering Trialists). In addition, there was a trend toward an increase in total retinal blood flow and it was found to significantly reduce intraocular pressure.
Ready to go the extra mile, Mr. Ulmann said: “We want to confirm the results of the Vienna pilot study in a larger placebo-controlled study and improve our understanding of the mechanisms of the microcirculation in the eye. In view of the still limited possibilities for patients with early or intermediate AMD and DR, we want to eliminate underlying deficiencies known as risk factors. OCUFOLIN® is a safe, premium food product now available for patients with harmful eye diseases.”
References:
1 Age-Related Eye Disease Study Research Group. A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss: AREDS Report No. 8. Arch Ophthalmol. 2001;119(10):1417-1436.
2 Age-Related Eye Disease Study Research Group. A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Cataract and Vision Loss: AREDS Report No. 9. Arch Ophthalmol. 2001;119(10):1439-1452.
3 AREDS2 Research Group, Chew EY, Clemons T, et al. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology. 2012;119(11):2282-2289.
4 Homocysteine Lowering Trialists’ Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr. 2005;82(4):806-812.
5 Stover PJ, Durga J, Field MS. Folate nutrition and blood-brain barrier dysfunction. Curr Opin Biotechnol. 2017;44:146-152.
6 Singh M, Tyagi S. Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal. Medical Hypotheses. 2017 (105): 17-21.
7 Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013;126(2):141-149.
