Homocysteinemia

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Homocysteinemia or hyperhomocysteinemia (from Greek ὑπέρ - hyper much ; homocysteine proper name ; Greek αἷμα - haima blood ) describes elevated blood values ​​of homocysteine , a non-biogenic amino acid that occurs naturally in the human body. In recent years, hyperhomocysteinemia has been associated with various diseases.

causes

Homocysteine ​​and Genetics

Genetic polymorphism in homocysteine ​​metabolism can, under certain conditions, influence enzyme function and thus also homocysteine ​​metabolism. A change in the genetic information usually leads to a slowdown in the breakdown of homocysteine ​​and thus to an increase in the homocysteine ​​concentration in the blood. Clinically relevant polymorphisms are mainly found in the enzyme MTHFR ( methylene tetrahydrofolate reductase ). The most common mutation is the amino acid exchange alanine for valine at position 677. This form of the enzyme is thermolabile and leads to up to 50% reduced performance at 37 ° C (body temperature).

Homocysteine ​​and external factors

Due to external factors, there may be a mild to moderate increase in the homocysteine ​​concentration in the blood. It should be noted that an increase in the homocysteine ​​value is in many cases a multifactorial phenomenon. Increased homocysteine ​​levels can be found with alcohol consumption, smoking, frequent coffee consumption, sedentary lifestyle and obesity. Certain drugs can also affect homocysteine ​​levels. A deficiency in folic acid and cobalamin (which can also be caused by inflammatory processes) often leads to an increase in homocysteine ​​levels.

Homocysteine ​​as a risk factor

Elevated levels of homocysteine ​​in the blood (hyperhomocysteinemia) can cause direct toxic damage to the vascular wall and lead in various ways to an increased tendency to thrombosis . Patients with known coronary artery disease are exposed to an increased risk of cardiovascular events even with a slightly elevated homocysteine ​​level, while the data for completely healthy people is inconsistent. With a homocysteine ​​level of over 15 µmol / l, there is an increased risk in several studies.

Although folic acid and B vitamins have been shown to lower homocysteine ​​levels, the data on the vascular protective effect is inconsistent. In some cases, no effect on the risk of myocardial infarction can be shown, but it can reduce the risk of stroke (up to 25% reduction). A systematic review by the Cochrane Collaboration found that supplementing B vitamins does not play a role in the prevention of heart disease. In contrast, a meta-analysis from the same year showed that the intake of folic acid in patients with known vascular damage and high vascular risk, especially with impaired kidney function, can prevent the progression of arteriosclerosis.

A study of patients with multiple sclerosis found that homocysteine ​​levels correlated with the degree of depression. However, there was no connection with their vitamin B 12 and folic acid levels and the degree of disability, which suggests a previously unknown factor for the increased homocysteine ​​level.

Children who have suffered a stroke are significantly more likely to have a disorder in homocysteine ​​metabolism than healthy people. In pregnant women, increased homocysteine ​​concentrations correlate with an increased risk of miscarriage and the development of pregnancy complications such as eclampsia . An increase in homocysteine ​​levels in the mother's blood is also a risk factor for developing neural tube defects in the child.

Patients with mild cognitive impairment and an increased risk of Alzheimer's disease were treated with B vitamins or placebo for 2 years in a study. It was shown that the average loss of brain mass in the brain areas relevant for Alzheimer's disease was significantly lower in the B vitamin group and that this result correlated with the lowering of the increased homocysteine ​​level.

Migraine patients with aura and elevated homocysteine ​​levels benefited from vitamins B 6 , B 12 and folic acid in a placebo-controlled study . After lowering homocysteine ​​levels by 39%, migraine attacks were reduced by 50%.

An elevated homocysteine ​​level is a risk factor in the development of all stages of macular degeneration . The administration of a vitamin B complex ( vitamin B 6 - pyridoxine, vitamin B 9 - folic acid and vitamin B 12 - cyanocobalamin) lowers the homocysteine ​​level, which significantly (34%) reduces the probability of developing macular degeneration. A systematic meta-analysis indicated hyperhomocysteinemia as a risk factor for diabetic retinopathy , especially proliferative retinopathy.

In a clinical dose-finding study, different doses of vitamins B 6 , B 12 and folic acid were tested in patients with increased homocysteine ​​levels. B 6 = 50 mg, vitamin B 12 = 1 mg and folic acid = 1 mg were the most effective with an average reduction of 55%.

Laboratory diagnostics

The homocysteine ​​level in the blood is usually determined immunochemically or using HPLC . EDTA or fluoride blood is recommended as material. Since homocysteine ​​is released by red blood cells, there is an increase of approx. 10% per hour without the addition of inhibitors (special tubes). It is now possible to measure the homocysteine ​​level close to the patient ( point-of-care testing ). This makes it possible to inform the patient of the result of the examination during the doctor's visit or to initiate any treatment that may be necessary without losing any time.

The costs of the examination of approx. 20 to 30 € are normally not covered by health insurances and must be borne by the patient as a so-called IGeL service .

literature

Individual evidence

  1. ↑ M. Födinger, H. Buchmayer, G. Sunder-Plassmann: Molecular genetics of homocysteine ​​metabolism. In: Miner Electrolyte Metab. 1999; 25, pp. 269-278, PMID 10681651 .
  2. ↑ S. Bleich, K. Bleich, S. Kropp, HJ Bittermann, D. Degner, W. Sperling, E. Rüther, J. Kornhuber: Moderate alcohol consumption in social drinkers raises plasma homocysteine ​​levels: a contradiction to the "French paradox " ? In: Alcohol Alcohol. 2001; 36, pp. 189-192. PMID 11373253
  3. ^ S. Bleich, M. Carl, K. Bayerlein, U. Reulbach, T. Biermann, T. Hillemacher, D. Bönsch, J. Kornhuber: Evidence of increased homocysteine ​​levels in alcoholism: the Franconian Alcoholism Research Studies (FARS). In: Alcohol Clin Exp Res. 2005; 29, pp. 334-336. PMID 15770107
  4. ↑ M. Ploder, K. Schroecksnadel, A. Spittler, G. Neurauter, E. Roth, D. Fuchs: Moderate hyperhomocysteinemia in patients with multiple trauma and with sepsis predicts poor survival. In: Mol Med. 2010; 16, pp. 498-504.
  5. ↑ N. Weiss, C. Keller u. a .: Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia. In: Vascular medicine. Volume 7, Number 3, August 2002, pp. 227-239, ISSN  1358-863X . PMID 12553746 . (Review).
  6. ↑ E. Lonn, S. Yusuf et al. a .: Homocysteine ​​lowering with folic acid and B vitamins in vascular disease. In: New England Journal of Medicine . Volume 354, Number 15, April 2006, pp. 1567-1577. doi: 10.1056 / NEJMoa060900 . PMID 16531613 .
  7. ↑ AJ Martí-Carvajal et al .: Homocysteine ​​lowering interventions for preventing cardiovascular events. Cochrane Heart Group, 2009. doi: 10.1002 / 14651858.CD006612.pub2
  8. ↑ X. Qin, M. Xu et al. a .: Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials. In: Atherosclerosis. Volume 222, Number 2, June 2012, pp. 307-313, ISSN  1879-1484 . doi: 10.1016 / j.atherosclerosis.2011.12.007 , PMID 22209480 .
  9. ↑ B vitamins also support the therapy of depression. ( Memento from May 27, 2015 in the Internet Archive ) In: Ärztliche Praxis. Edition: December 2008.
  10. ↑ IM van Beynum et al .: Hyperhomocysteinaemia: a risk factor for ischemic stroke in children. In: Circulation . 99, 1999, pp. 2070-2072. PMID 10217643 .
  11. ↑ WL Nelen: Hyperhomocysteinaemia and human reproduction. In: Clin Chem Lab Med. 39, 2001, pp. 758-763. PMID 11592447 .
  12. ↑ B. Fowler: Disorders of homocysteine ​​metabolism. In: J Inher Met Dis. 20, 1997, pp. 270-285, PMID 9211199 .
  13. ↑ G. Douaud, H. Refsum et al. a .: Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 110, Number 23, June 2013, pp. 9523-9528, ISSN  1091-6490 . doi: 10.1073 / pnas.1301816110 . PMID 23690582 . PMC 3677457 (free full text).
  14. ^ R. Lea, N. Colson et al. a .: The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. In: Pharmacogenetics and Genomics . Volume 19, Number 6, June 2009, pp. 422-428, ISSN  1744-6872 . doi: 10.1097 / FPC.0b013e32832af5a3 . PMID 19384265 .
  15. ↑ Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2006; 244, pp. 565-569.
  16. ↑ C-reactive protein and homocysteine ​​are associated with dietary and behavioral risk factors for age-related macular degeneration. In: Nutrition. 2006; 22, pp. 441-443.
  17. ↑ Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women. The Women's Antioxidant and Folic Acid Cardiovascular Study. In: Arch Intern Med . 2009; 169 (4), pp. 335-341.
  18. ↑ C. Xu, Y. Wu, G. Liu, X. Liu, F. Wang, J. Yu: Relationship between homocysteine ​​level and diabetic retinopathy: a systematic review and meta-analysis. In: Diagnostic Pathology . Volume 9, Number 1, September 2014, p. 167 (electronic pre-publication). doi: 10.1186 / s13000-014-0167-y . PMID 25257241 . PMC 4207897 (free full text).
  19. ^ CP Siegers et al: Treatment of liver dysfunction with a new balanced diet. ( Memento of the original from February 23, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Poster published as part of the CAM-EXPO, Düsseldorf, April 2013. @1@ 2Template: Webachiv / IABot / homocysteinspiegel.de

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Methionine Metabolism  - Learning and Teaching Materials