Elevated Homocysteine and Eye Disease

In clinical studies elevated homocysteine is associated with an increased risk of eye disease as well as other heart disease, stroke, and possibly Alzheimer's disease with additional roles in pregnancy, depression, and osteoporosis.

Why high homocysteine levels?

It would not be surprising if, indirectly, lifestyle habits such as smoking contribute to high homocysteine levels. Smokers who have high homocysteine levels are at far greater risk of heart attacks. While this by itself is certainly not conclusive, it is true that folic acid levels are depleted by exposure to cigarette (and other) smoke.⁵

High levels of homocysteine are also directly tied to kidney disease: homocysteine levels in the blood are strongly correlated with how blood passes through the tiny filters (glomeruli) in the kidney, a process that removes toxins from the blood.⁶

Researchers suspect that high levels of homocysteine are also tied to hypothyroidism. There is an inverse connection between levels of homocysteine and thyroid hormones.^{7, 8}

Finally, researchers are also connecting high homocysteine levels to deficiencies in choline, taurine & n-acetyl-cysteine.

Learn more about causes of high homocysteine.

Homocysteine formation

Homocysteine is created as a result of the metabolism, or digestion, of proteins - homocysteine levels are higher in people who eat lots of meats and few fruits and vegetables. When the body digests protein it creates a number of amino acids, one of which is known as methionine. One of the functions of methionine is to support certain cellular activities and it does so by contributing a methyl group (a molecule made up of a carbon and 3 hydrogen atoms). Normally when this process takes place, methionine receives a return methyl group from vitamin B12 or folic acid. This is a process called remethylation. But if folic acid and/or B6 levels are inadequate, then the changed methionine remains as homocysteine.

Homocysteine can also transform into cysteine through a process that requires folic acid, and vitamins B6 and B12. Again, if someone eats a lot of meat or other protein without enough of those nutrients, then homocysteine levels can climb.³

Homocysteine and eye disease

Macular Degeneration. High levels of homocysteine in the blood have been observed with and are tied to a number of eye conditions. In a study spanning a 10 year period, and relying on blood samples taken at outset, food questionnaires, and retina photos taken 10 years later, researchers have connected these high levels with age related macular degeneration, suggesting complementary treatment with vitamin B12 and folic acid in reducing macular degeneration risk.^{2, 9}

Glaucoma. Whether high levels of homocysteine is associated with increased risk of glaucoma has been a little controversial. Researchers concluded in 2004 that there was no significant difference between patients with open-angle glaucoma and controls. However, in 2009, in a larger study, researchers looking at three groups - patients with pseudoexfoliation glaucoma, open angle glaucoma, normal tension glaucoma and controls - found that homocysteine was higher in the patients with the various forms of glaucoma, 27.1% to 30.6%.^{1, 10}

In 2014 researchers analyzed records from the 20 year Nurses' Health Study involving 120,000 people. They report that while vitamins B6 and B12 were not linked to lower rates of glaucoma, that folate was tied to a suggestive lower rate of exfoliation glaucoma - the most common kind of glaucoma.¹³

Diabetic retinopathy There have been inconsistent results connecting high homocysteine levels with diabetic retinopathy. In 2008 researchers evaluated 168 diabetic (type 2) men and women, taking pictures of the condition of their retinas and assessing plasma homocysteine levels. The patients with diabetic retinopathy had higher levels of homocysteine which were not otherwise explained (ie, by kidney failure). Their conclusion that was the homocysteine level could be a useful indicator for high risk of diabetic retinopathy in diabetic patients.¹¹

Optic neuropathy. Scientists suspect a connection between high levels of homocysteine and optic neuropathy. Research studies did find such a connection in patients with a variety of optic neuropathies, most of whom had vitamin B12 deficiencies. They concluded that high homocysteine levels were valuable indicators for these types of conditions.¹²

Homocysteine and heart disease

Early researchers were fully aware that heart disease was tied to high cholesterol. However it was also very clear that some heart attacks occurred even though the patient did not have high cholesterol. So a search was on for other culprits and high homocysteine levels were found to be one possible source. It turns out that high levels of homocysteine in the blood may be responsible for damage to the smooth walls of blood vessels making it easier for plaque to form - with or without the contribution of high cholesterol.⁴

Learn more about homocysteine and your heart.

Homocysteine and brain function

Researchers have noted that low levels of folic acid and B12 are tied to depression and Alzheimer's. In addition, such low levels seem to lessen the efficacy of anti-depressants. These low folic levels are known to trigger high homocysteine levels. Too high homocysteine levels seem to limit proper neurotransmiter and other chemical processes from occurring normally within the brain. Cognitive capacity (understanding what we see and perception of objects locations in space) is hindered by high homocysteine levels. In this regard, high homocysteine is also connected to dementia, multiple sclerosis, and Parkinson's Disease.

Homocysteine and fetal development

Researchers have known for some time that deficiencies in folic acid and other nutrients are tied to likelihood of miscarriage and other pregnancy abnormalities and so high homocysteine levels in the mother are another signal that recommended folic acid supplementation during pregnancy is doubly important. The high levels are possibly also connected to a higher risk of birth defects.

Homocysteine and osteoporosis

Homocysteine's role in contributing to the aging process is well exemplified by that fact that high homocysteine levels are implicated as a cause or contributing factor for osteoporosis.

Homocysteine and other conditions

High homocysteine levels are additionally suggested as causative factors for a number of other conditions, including strokes and birth defects.

The following also affect homocysteine levels in the blood:

• aging
• excessive stress
• deficiencies in choline, taurine & n-acetyl-cysteine

Footnotes

1. S. Bleich, J. Roedl, et al., Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. American Journal of Ophthalmology, July, 2004
2. K. Coral, R. Raman, et al., Plasma homocysteine and total thiol content in patients with exudative age-related macular degeneration, Eye, April, 2005
3. John Wiley & Sons, article on Homocysteine
4. European Heart Journal (2002) 23, 1580-1586
5. Smoking influence on the level of homocysteine and 5-methyltetrahydrofolic acid in active and non smokers, Przegl Lek [translation: Drug Overview], 2007
6. Van Guldener, Coen, et al, Why is homocysteine elevated in renal failure and what can be expected from homocysteine-lowering? Nephrology Dialysis Transplantation, May, 2006
7. Lef.org, Thyroid Regulation
8. M. Bicikova, et al, Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation, Clinical Chemistry and Laboratory Medicine, March, 2003
9. B. Gopinath, et al, Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration, American Journal of Clinical Nutrition, July, 2013
10. C.I. Clement, et al, Plasma homocysteine, MTHFR gene mutation, and open-angle glaucoma, Journal of Glaucoma, January,2009
11. L. Brazionis, et al, Homocysteine and diabetic retinopathy, Diabetes Care, January,2008
12. Stanger, et al, Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy, Clinical Chemistry and Laboratory Medicine, 2005
13. J.H. Kang, S. J. Loomis, et al, A prospective study of folate, vitamin B6, and vitamin B12 intake in relation to exfoliation glaucoma or suspected exfoliation glaucoma, JAMA Opthalmology, May, 2014.