Homocysteine and Eye Health: Are You at Risk?

June 25, 2017 | Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

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Homocysteine and Eye Health: Are You at Risk?
It is well known that elevated homocysteine increases the risk for heart attack, stroke, or blood clots. Did you know however, that elevated homocysteine levels impact eye health? There are several eye disorders linked with elevated homocysteine. Knowledge of this principle and its proper management may help reduce the risk and severity of glaucoma, macular degeneration, numerous other eye disorders and even diabetic retinopathy.

What Is Homocysteine?

Homocysteine is an amino acid. Levels increase in the body when the metabolism of the amino acids, cysteine to methionine and back to cysteine is impaired and in part related to the methylation cycle. Elevated homocysteine acts like an abrasive molecule against the delicate inner blood vessel lining. Elevated homocysteine levels are known to contribute to plaque formation on blood vessel walls and include the vast network of blood vessels within the eyes. The eyes require a steady supply of glucose and nutrients. An intricate, detailed web of blood vessels and capillaries is present in the eyes to get nutrients in and waste products out. If homocysteine is elevated, it becomes abrasive to these vessels and causes plaque build-up. Several eye disorders have been found to occur as a result. It is worth paying attention to this.

Nutrient Deficiencies Increase Homocysteine

Nutrients are essential to manage homocysteine and the methylation cycle. The most important nutrients are the coenzyme forms of vitamin B6, B12, and folate. Other nutrients like magnesium, vitamin B2, N-acetyl-cysteine, taurine, omega-3 DHA, choline and trimethylglycine (TMG) are also needed for the process of methylation and homocysteine management. Inadequate amounts of any one of these nutrients may lead to a build-up of homocysteine and impaired methylation.

Medications and Other Factors Increase Homocysteine

Numerous factors can increase risk for elevated homocysteine. These include smoking and prescription drugs like birth control pills, methotrexate, cholestyramine, carbamazepine/Tegretol, proton pump inhibitors/stomach acid blockers, metformin, and phenytoin. Drugs may rob the body of nutrients that are needed for healthy homocysteine management and methylation. Kidney disease, certain cancers, Alzheimer’s disease, hypothyroidism, alcohol, estrogen deficiency, H. pylori bacterial overgrowth, and increased age can lead to elevated homocysteine levels. Women tend to have higher homocysteine levels than men. Processed and canned foods compared to fresh foods lack adequate amounts B12, folate, and other required nutrients for the body to manage homocysteine. Strict vegans who consume no meat, fish, or dairy are at high risk for elevated homocysteine, because vitamin B12 is naturally found only in animal foods. Even high stress is considered a factor for elevated homocysteine and eye disorders due to depletion of nutrients from stress.

Homocysteine Tests

Homocysteine blood tests may not be routinely ordered in “fast food” health care. You may have to ask for it. It is a valuable test just like hemoglobin A1C to measure blood sugar or CRP (C-reactive protein) to measure inflammation. Evaluate it at least once per year or more frequently if you are at high risk. It is generally used to evaluate cardiovascular and stroke risks in adults and may sometimes be used to help evaluate vitamin B12 or folate status. It is a routine test for newborns as inborn genetic disorders may cause seriously elevated homocysteine and severe illness. Consider the impact though on how you can help manage eye health if you know your homocysteine number. Homocysteine lab values at15 µmol/L and higher are recognized as elevated, however optimal lab values for homocysteine are equal to or less than 7.2 µmol/L. If you know your lab value, it may help you reduce the risk of cardiovascular disease and stroke risk, as each 3.0 point increase above 7.2, the risk for heart attack increases by 35 percent. Studies described below will help us see that fine-tune management of homocysteine may help reduce the risk of eye disease and further damage to vision.

Homocysteine and Macular Degeneration

Age-related macular degeneration, both wet and dry forms, has been linked to elevated homocysteine. In one study, researchers found that patients with a blood level of homocysteine 14.19 +/- 3.11 micromol/L compared to controls had much higher levels of age related macular degeneration. Blood levels of vitamin B12 were found to be low. A review study demonstrates cumulative evidence from several studies that elevated homocysteine levels are a significant risk factor for age-related macular degeneration. Results showed that individuals with age-related macular degeneration had a homocysteine level 2.67 μmol/L higher than controls. It also showed that depending on the type of macular degeneration (wet or dry), folate or vitamin B12 were lower than the controls. A common type of macular degenerative disease called polypoidal choroidal vasculopathy (PCV) is found predominantly in African-American, Asian, and Caucasian populations. Blurred vision, dim vision, and central or near-central loss of vision may occur in PCV and was linked with high levels of homocysteine and another inflammatory compound, C-reactive protein. It was found that for each 1 µmol/L increase of homocysteine in the blood above 9.8, there was a 1.5 fold increase in PCV macular degeneration likelihood compared to other healthy individuals. Keep in mind that 9.8 - 15 is within the normal homocysteine reference range, but is outside the optimal range. These studies demonstrated that it didn’t take drastically elevated amounts of homocysteine compared to the control subjects’ homocysteine levels to develop macular degeneration. The studies also showed that even slightly lower levels of vitamin B12 and folate can significantly increase the risks of these eye disorders. This type of information provides impetus for us to strive towards optimal levels of homocysteine.

Homocysteine and Retina Deterioration, Glaucoma, Diabetic Retinopathy

The recently published Nurses’ Health Study compared more than 20 years of data. A group of disorders (PEXS and PEXG) that affect the eye with retinal deterioration or glaucoma were found to have high levels of homocysteine. PEXS and PEXG are systemic disorders but manifest with symptoms primarily with the eyes. In these disorders, small fibers and proteins build up to cause glaucoma or blood clots within the retina. Low levels of folate and elevated homocysteine levels were found compared to healthy individuals. Individuals who took a multiple vitamin had considerably less risk and disease development. In other retina disorders, like blood clots in the retinal vein or retinal vein occlusion have been linked with elevated homocysteine. Diabetic retinopathy is a major cause for new onset of blindness in diabetic adults. Elevated homocysteine is part of the underlying pathology and a significant reason for the progression into loss of sight. Diabetic retinopathy due to elevated homocysteine may even be induced by the common diabetes drug metformin. Metformin is linked with elevated homocysteine due to its effect on stripping out the very nutrients needed to process homocysteine and manage methylation. Scientists recommend that diabetics get periodic checks on homocysteine levels to manage the progression of diabetic retinopathy and prevent blindness. We will see below that diabetic retinopathy, homocysteine, and methylation gene defects are part of a bigger picture of long-term damage unless there is intervention.

Homocysteine, Methylation Defects and Eye Disorders

A brief look at homocysteine and methylation gene defects will help dig in a little deeper with prevention and more thorough management of eye disease. Methylation defects or common genetic SNPs that impair homocysteine metabolism are an underlying concern for eye health and hundreds of other disorders. Lab tests are available through your health care provider or ancestral DNA commercial tests that map your 23 chromosomes and ancestral history. These tests identify key genes related with impaired methylation (and homocysteine) status and genetic risks. If you know the genes, then you can make more informed choices on whether certain forms of vitamin B12, B6, B2, folate or choline, etc. are needed in higher amounts to manage the genetic SNPs that impair methylation, homocysteine, and support healthy eyes and aging. This is the future of medicine with epigenetics that affects quality aging and lifespan. One of the most important genes related to methylation and homocysteine metabolism relates to the MTHFR C677T gene. A recent study evaluated the MTHFR methylation gene defect or SNP and the risk for glaucoma. Individuals who had the MTHFR C677T gene polymorphism were significantly more likely to develop primary open angle glaucoma. The journal JAMA Opthamology March 2016 found that those with the MTHFR genetic SNPs were three times more likely to develop cataracts and have high levels of homocysteine. Other studies show that even mildly elevated levels of homocysteine and MTHFR gene mutations may lead to central retinal vein occlusion and pigmentary glaucoma. Recognition of elevated homocysteine levels, methylation defects, family or personal history of these eye disorders is critically relevant as prevention is of utmost importance. At the top of the list is prevention of diabetic retinopathy because millions of people worldwide with diabetes are at risk for blindness. The goal is to intervene before the disease process gets locked in. One method of intervention is managing homocysteine levels, methylation, oxidative stress, and key nutrients to prevent a process called “metabolic memory”.

Persistence of Metabolic Memory and Intervention with Nutrients

Recent studies have shown that type 2 diabetics can still develop vascular complications like diabetic retinopathy even with aggressive blood sugar control and a reduction in blood sugar numbers. This is thought to be due to “metabolic memory”. Metabolic memory is a hypothesis that suggests that elevated blood sugar turns on dysfunctional patterns in gene signals and leads to damaged mitochondria, genetic SNPs or altered methylation patterns, and chronic inflammation. As cells divide and mature with aging, the metabolic memory pattern continues down the path of tissue breakdown. Cells don’t revert back to a healthy state, rather further tissue aging and dysfunction occurs like diabetic retinopathy and loss of sight even when the hemoglobin A1C and daily blood sugars have improved. Tissues continue to breakdown despite controlled blood sugars because gene signals were turned dysfunctional that involved methylation defects and other stressors. In order to stop this metabolic memory phenomenon from occurring with diabetic complications like elevated homocysteine and diabetic retinopathy, researchers have turned to several antioxidants and nutrients. These include high dose folate and biotin, along with taurine, r-alpha lipoic acid, N-acetyl-l-cysteine, astaxanthin, zinc, glycine, and melatonin. Inadequate levels of these nutrients affect methylation status which leads to elevated homocysteine. Cutting-edge research suggests that impaired methylation is one cause for unhealthy metabolic memory. Impaired methylation may be reflected by elevated homocysteine levels or MTHFR methylation testing. Therefore, if you know your homocysteine level, methylation status, and hemoglobin A1C (a marker for long-term blood sugar levels) status as you age, you can potentially and substantially reduce the risk of diabetic complications like diabetic retinopathy, blindness, intervene and likely prevent negative metabolic memory.


Managing eye health is more than just sun glasses, prescription eyewear changes, managing computer eye strain, blue light/LED exposures, and the occasional allergy or dry eyes lubrication drops. Eyes are complex tissues rich in nerves and blood vessels and are affected by things that cause inflammatory damage, like homocysteine. Homocysteine is one compound that we can measure and use the knowledge to help reduce eye disease risk. Strive toward optimal levels of homocysteine with a level of 7.2 or lower. Homocysteine levels directly relate with methylation and require several key nutrients. These critical nutrients are folate, vitamin B12, B6, B2, choline, N-acetyl-l-cysteine, magnesium, taurine, trimethylglycine, and choline. Coenzyme forms of B vitamins are preferred for homocysteine and methylation. This is seen as B6 as pyridoxal 5-phosphate, B12 as methylcobalamin and adenosylcobalamin, and folate versus the non-active or synthetic forms seen as pyridoxine HCl, cyanocobalamin, and folic acid respectively. Other helpful nutrients include r-alpha lipoic acid, astaxanthin, zinc, magnesium, DHA, and melatonin. Exercise and a diet rich in dark green leafy vegetables helps homocysteine and methylation. Just like it is important to know other common lab values like hemoglobin A1C, C-reactive protein, or vitamin D levels, homocysteine measurement can help provide solid information about risks. When was the last time you had your homocysteine levels checked? When was the last time your eye doctor asked you about homocysteine and your methylation status? Get ahead of the game before you need aggressive management with eye disease and “metabolic memory” kicks in.

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