Guest Article 

Homocysteine Levels: The Risk of High Homocysteine

High homocysteine levels increase the risk of many diseases. Hyperhomocysteinemia as a cause of disease. Lowering homocysteine with vitamins.

What is Homocysteine?

Homocysteine is an amino acid, which is not found in food, but is a metabolic product created by the body when proteins are broken down. 

It also occurs as a short-term intermediary product in the methionine metabolism, where normally it is quickly used up. It is in this process that vitamin B12 is important, which is why there is a close connection between homocysteine and vitamin B12. 

A small quantity of homocysteine is present in the blood plasma of every human: whether it has a damaging effect on certain bodily processes depends, among other things, on the concentration of the amino acid.

What Causes an Increased Homocysteine Level?

An elevated homocysteine level can be attributed to two causes:

  1. Genetics: one in three people have an increased homocysteine level genetically.

  2. Vitamin deficiency: in the remaining cases, the increased value is caused by a deficiency of vitamins B12, B6 and folic acid, which are involved in the metabolic processes in which homocysteine is broken down.

How do High Homocysteine Levels Effect the Body?

Homocysteine has an adverse effect on the body in a number of ways.

Direct Toxic Effect and Oxygen Radicals

There is evidence that homocysteine has a direct toxic effect on the mitochondria and subsequently disturbs the oxidative phosphorylation processes. This leads to an intracellular accumulation of harmful oxygen radicals (hydrogen peroxide, H202).

Inhibits Nitric Oxide Formation

At the same time, homocysteine also reduces the formation of nitrogen monoxide. Nitric oxide (NO) has a strong vasodilatory effect, while H202 damages or destroys the inner walls of the arteries. These small injuries lead to clotting processes with accumulation of blood platelets and fibrin. In addition, fatty substances also accumulate on the inner walls of the arteries and plaque forms. 

Plaque in the Arteries 

The more plaque is deposited on the inner walls of the arteries, the more the blood flow is impeded. If plaque particles come loose and block smaller vessels, this can even lead to blood clots. In the worst case, this can lead to myocardial infarction, stroke or deep vein thrombosis. Arteriosclerosis can damage not only the heart and brain, but other organs as well. 

Diseases such as diabetes are also adversely effected by increased homocysteine levels. 

High Homocysteine as Underlying Cause for Diseases

Increased homocysteine levels play a potentially causal role in various diseases. Here, exact correlations are currently under research, as the role of homocysteine remains the subject of scientific debate.

Cardiovascular Diseases 

A statistical correlation between an elevated homocysteine level and the risk of suffering from cardiovascular disease has been scientifically proven several times (1). However, this does not clarify the causal relationship, since study results concentrate on the statistical frequency of the occurrence of a heart attack with an elevated homocysteine level (2). 

Stroke

Scientific results also suggest the influence of elevated homocysteine levels on the occurrence of so-called cerebrovascular complications – mostly strokes (3, 4). 

Alzheimer’s and Dementia

Due to the potentially damaging effects on brain performance, elevated homocysteine levels may also increase the risk of Alzheimer’s disease and dementia (5). 

Macular Degeneration

A study by the ophthalmologist Dr Jost Elborg from Wiesbaden, which involved 196 patients, came to the conclusion that homocysteine is an important risk factor for the development of age-related macular degeneration. Other studies also support this result (6). 

Bone Health

Two research studies conducted throughout Europe found a clear correlation between bone loss and elevated homocysteine levels. In the Rotterdam Study and Longitudinal Aging Study, for example, Van Meurs identified hyperhomocysteinemia (HHCY) as a strong and independent risk factor for osteoporotic fractures in older people (7). 

Homocysteine: Cause or Marker?

Yet is homocysteine actually the cause of these diseases or rather a markers of a vitamin deficiency, which is the real cause? Homocysteine is probably both cause and marker. It is itself a pathogenic factor and an indication of vitamin deficiency. What is more, the mechanisms of each of these diseases are very different and cannot all be lumped together. 

When investigating the question of whether homocysteine is a cause or a marker, it must therefore be proven that there is a direct relationship between the occurrence of the factor and the development of the disease. There are several studies that prove this.

In osteoporosis, for example, the activity of osteoclasts (bone-degrading cells) outweighs that of osteoblasts (bone-forming cells). In their research, Herrmann et al. have cultivated osteoclasts and osteoblasts in cell cultures and added increasing amounts of homocysteine (HCY) to the culture medium. Through this they were able to show that the activity of osteoclasts increases with rising HCY concentration in the medium (absorption activity, tartrate-resistant acid phosphatase as osteoclast marker and cathepsin K were measured) (8). A clear dose-response relationship was thus established. Another link in the chain of evidence are experiments showing that hyperhomocysteinemia (HHCY) induces osteoporosis (9).

In their tests on hyperhomocysteinemic patients with high risk of fracture, Sato et al. from Japan have also managed to prove that the lowering of the homocysteine level with folic acid and vitamin B12 over 2 years significantly reduces the risk of fracture, compared to controls (10). 

Numerous other studies have demonstrated the dose-response relationship between homocysteine and common diseases such as dementia, Alzheimer’s and strokes.

Avoiding High Homocysteine Levels

High levels of homocysteine can be avoided by ensuring a sufficient supply of B12, B6 and folic acid – all of which are involved in processes that break down homocysteine. Especially vitamin B12 and folic acid play a key role here.

Guest Author

Prof. Dr med. habil. Dr rer. nat. Wolfgang Herrmann
Dr Wolfgang Hermann is head of the Department of Clinical Chemistry and Laboratory Medicine at Saarland University Hospital. He conducts research on homocysteine, is a featured expert in the homocysteine network (www.homocystein-netzwerk.de) and previously chaired the world congress “Hyperhomocysteinemia” in Saarbrücken. 

 Sources

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  2. Mager A(1), Orvin K, Koren-Morag N, Lev IE, Assali A, Kornowski R, Shohat M, Battler A, Hasdai D. Impact of homocysteine-lowering vitamin therapy on long-term outcome of patients with coronary artery disease. Am J Cardiol. 2009 Sep 15;104(6):745-9. doi: 10.1016/j.amjcard.2009.05.011.
  3. Casas, Juan P., et al. Homocysteine and stroke: evidence on a causal link from mendelian randomisation. The lancet, 2005, 365. Jg., Nr. 9455, S. 224-232.
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  5. Obeid, Rima; Herrmann, Wolfgang. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS letters, 2006, 580. Jg., Nr. 13, S. 2994-3005.
  6. Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med. 2009 Feb 23;169(4):335-41. doi: 10.1001/archinternmed.2008.574.
  7. Van Meurs, J.B.J., Dhonukshe-Rutten, R.A.M., Pluijm, S.M.F., Van der Klift, M., De Jonge, R., Lindemans, J., De Groot, L.C.P.G.M., Hofman, A., Witteman, J.C.M. (2004). Homocysteine levels and the risk of osteoporotic fracture. The New England Journal of Medicine, vol. 350, 20, 2033-2041.
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