OCUFOLIN | Medical Food


OCUFOLIN
Indication: Ocufolin is a medical food indicated for the distinct nutritional requirements of individuals who have reduced innate capacity to metabolize synthetic folic acid and folate into its biologically-active form, L-methylfolate, resulting in an increased risk for vascular eye disorders. Ocufolin contains a proprietary formulation of vitamins, minerals, carotenoids, and glutathione precursors for the clinical dietary management of the metabolic imbalances underlying retinal and choroidal ischemia and their related vascular disorders. Ocufolin must be administered under medical supervision.


MECHANISM OF ACTION
Ocufolin acts by optimizing intracellular antioxidants, vitamin enzymatic co-factors, and N-Acetylcysteine levels so that impaired folate methylation is improved, restoring efficiency of the conversion of homocysteine into methionine, and reducing oxidative stress by increasing intracellular glutathione. Lower homocysteine levels and improved glutathione levels improve vascular health and are neuroprotective against the continuous high level oxidative metabolic stress experienced by the retina in general, and the macula in particular.


RETINAL AND CHOROIDAL ISCHEMIA AS A METABOLIC DEFICIENCY
Ischemia is a broad term for chronic reduced blood flow, resulting in hypoxia, energy depletion, and cell death. Reduced blood flow in the retinal and the choroidal vessels can initiate or contribute to retinal vascular conditions such as macular degeneration, retinal microaneurisms, retinal vein or artery occlusions, and vascular retinopathies, producing symptoms such as blurred or distorted vision or loss of vision.

Retinal and choroidal ischemia may be caused by systemic vascular disorders such as hypertension and atherosclerosis. Hyperhomocysteinemia, a medical condition characterized by elevated levels of homocysteine in the blood, has been identified as an independent risk factor for many systemic vascular conditions 7,8,9,10 as well as common vascular conditions of the eye including retinal vein or artery occlusions,11,12,13,14,15,16,17,18,19,20 nonarteritic anterior ischemic optic neuropathy (NAION)14 and age-related macular degeneration (AMD).21,22,23,24,25,26

Numerous human epidemiological studies have shown homocysteine levels correlate inversely and closely with plasma folate levels.10 In addition to poor diet and lifestyle factors, folate deficiencies may also result from malabsorption of dietary folates, as in the case of Celiac disease,27 Crohn’s disease,28 bariatric surgery,29 and alcoholism.30 Inborn genetic defects31 and medications may also cause interference with normal folate uptake and metabolism, ultimately reducing the availability of biologically-active L-methylfolate.31 Among such medications are dihydrofolate reductase inhibitors, sulfonamides, oral contraceptives, anticonvulsants,10,32 metformin,33 fluoexitine,34 levodopa,35 warfarin,36 proton pump inhibitors,37 and H2 antagonists.37 Intake of synthetic folic acid itself, if greater than 400 mcg daily, may also fail to be metabolized and act as a competitive inhibitor of transport of L-methylfolate.38 These same factors that affect intracellular folate uptake and metabolism are also risk factors for hyperhomocysteinemia.10


The most common genetic causes of hyperhomocysteinemia are inborn genetic variations (polymorphisms) in the Methyltetrahydrofolate Reductase (MTHFR) gene.10 The MTHFR gene produces the MTHFR enzyme that catalyzes the metabolic conversion of dietary folic acid to its bioactive form, L-methylfolate. L-methylfolate is used by the body in many biochemical pathways, most importantly in the recycling of homocysteine back into methionine. It is estimated that homozygous and compound heterozygous MTHFR genotypes are present in more than 30% of the US population 39 and therefore may have associated impaired vascular health. Specifically, research has shown that there are direct associations between polymorphisms in the MTHFR gene and elevated levels of homocysteine.40,41,42,43 The MTHFR 677TT genotype has also been shown to have a direct impact on hypertension. 86,87,88,89,90,91


The resulting systemic vascular conditions 44,45,46,47,48 and many vascular disorders of the eye include:

• Retinal vein or artery occlusions 49,50,51,52,53,54,55,56

• Retinopathy 57,58,59,60,61,62,63

• Age-related macular degeneration (AMD) 64,65,66

• Non-arteritic anterior ischemic optic neuropathy (NAION) 67


Elevated plasma levels of homocysteine have also been associated with increased oxidative stress, as measured by total antioxidant capacity.68 Homocysteine’s effect on oxidative stress is possibly due to decreased expression and/or activity of key antioxidant enzymes, as well as increased generation of damaging reactive oxygen species (ROS).69 Homocysteine specifically has been shown to promote oxidant injury to the vascular endothelium70 and subsequent endothelial dysfunction, the major pathophysiologic mechanism that causes vascular disorders.10,71 Evidence of increased oxidative stress and elevated homocysteine have been correlated with depleted levels of the endogenous antioxidant glutathione in patients with vascular eye disorders. 72,73,74



Why Metafolin® [(6S)-5-methyltetrahydrofolic acid,
calcium salt (L-methylfolate)]

Individuals with some chronic illnesses, on certain medications, or with genetic MTHFR deficiencies, cannot efficiently metabolize dietary folate or folic acid into the bioactive form of folate, L-methylfolate (Metafolin), which is required for reducing homocysteine levels. The resulting L-methylfolate insufficiency increases homocysteine levels which causes constriction of the retinal arteries which decreases retinal perfusion leading to ocular ischemia and microvascular occlusion.75,76 Oral supplementation with folates raises serum folate levels and lowers homocysteine.84  Higher serum folate levels are associated with lower homocysteine and increased retinal artery caliber.77,78  Low L-methylfolate is associated with increases in homocysteine which is directly toxic to retinal ganglion cells.79,80 Therefore, supplementation with L-methylfolate may be beneficial. Clinical studies have concluded that direct supplementation with L-methylfolate reduces homocysteine levels more effectively than folic acid.81,82 In fact, folic acid supplementation alone was shown not to reduce intracellular homocysteine. 83


L-methylfolate was especially effective in individuals with MTHFR genetic variations, as it was shown to lower homocysteine levels and improve plasma folate.84,85 Reversing these downstream effects of L-methylfolate deficiency can be critical to addressing ischemic damage to the retina. 


Dosage and Administration

The recommended adult dose of Ocufolin is one capsule orally per day (with a meal) or as recommended by your health care practitioner based on an assessment of metabolic imbalances. Ocufolin is not recommended for use with children or during pregnancy. Ocufolin must be administered under medical supervision.


Ingredients

Ocufolin is a medical food containing a proprietary blend of key vitamins, minerals, and carotenoids to help manage homocysteine levels resulting from metabolic active folate deficiencies caused by certain medical conditions, MTHFR polymorphisms, and medications. Ocufolin was also formulated to help protect retinal, choroidal, and macular tissue from oxidative stress caused by high levels of homocysteine.


Each capsule contains:

Folate (as (6S)-5-methyltetrahydrofolic acid, calcium salt, Metafolin®) 900 mcg

Vitamin C (Ascorbic Acid) 33.3 mg

Vitamin D (as Cholecalciferol) 1500 IU

Vitamin E Natural Tocopherols (as Alpha, Beta, Gamma, & Delta) 7.5 IU

Vitamin B1 (As Thiamine Hydrochloride) 1.5 mg

Vitamin B2 (Riboflavin) 10 mg

Vitamin B6 (as Pyridoxal-5-Phosphate) 3 mg

Vitamin B12 (as Methylcobalamin) 500 mcg

Pantothenic Acid (as Calcium-D-Pantothenate) 5 mg

Zinc (as Zinc Oxide) 26.6 mg

Selenium (as L- Selenomethionine) 20 mcg

Copper (as Cupric Oxide) .667 mcg

N-Acetyl Cysteine (NAC) 180 mg

Lutein 3.35 mg

Zeaxanthin 700 mcg


Other Ingredients: Capsule (Hypromellose & Gellan Gum) Dicalcium Phosphate, Rice Flour, Magnesium Stearate.

Contains Soy.

Metafolin® is a registered trademark of Merck KGaA, Darmstadt, Germany.


Contraindications

Ocufolin is contraindicated in patients with known hypersensitivity to any of the components contained in this product. Ocufolin contains folate, which may interact with certain drugs that interfere with folate absorption or metabolism of homocysteine. Consult your healthcare professional (e.g., doctor or pharmacist) for more information. If you are pregnant or breastfeeding, check with a doctor before using Ocufolin.


5. Adverse Effects

Allergic reactions to L-methylfolate are rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling, dizziness or trouble breathing. Nausea, vomiting, headache, other gastrointestinal symptoms, and rash have been associated with NAC. There are rare reports of renal stone formations with NAC. There are also rare reports of patients taking combinations of B vitamins with a history of anxiety attacks or panic disorder causing anxiety and elevation in blood pressure.


6. Please send any reported adverse effects to: report-side-effects@ocufolin.com




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