24 Jun 2022


Homocysteine: The Whole Story

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Academic level: University

Paper type: Term Paper

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Today, most people consume protein foods, like meat, in large quantities. Most of these protein foods are seen to be prestigious and are thus held high in value by the society. However, little is known by many people that the consumption of these particular foods in large amounts results in the production of homocysteine. Homocysteine is a very common amino acid in the blood of most individuals today. Having it in one’s blood system is not dangerous but having it in excess amounts is risky and could result in the eventual death of that particular individual. This is because it has been associated with causing cardiovascular diseases to people who are diagnosed with having high levels of its concentration. This paper looks at homocysteine, its history, risk factors, and how it can be maintained in the human body. 


This amino acid was discovered by Butz and du Vigneaud in the year 1932. These two scientists were furthering their study on insulin when they noticed it. Initially, they were heating methionine in sulphuric acid when they noticed that a new amino acid was being formed. This newly formed amino acid displayed chemical properties similar to those of cysteine, and they thus named it homocysteine. Later on, significant advancements were made to this discovery as homocysteine began to become an area of interest for most scientists. This further triggered the aspect of the production of homocysteine given that the body was known to produce methionine. 

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Homocysteine Metabolism 

The metabolism of homocysteine in the human body occurs only two pathways: remethylation to methionine and transsulfuration to cystathionine 1 . For the first pathway to be realized, there needs to be vitamin B12 and folate whereas, for the second, the prydoxal-5-phosphate is necessary 1 . Like in most other cases, a controller is required for this process, and the S-adenosylmethionine plays that role in this case. However, it also doubles as an inhibitor in the case where it is used to slow down the reaction of the methylenetetrahydrofolate reductase. 

The synthesizing of homocysteine takes place in a number of steps. It all begins with the receiving of an adenosine group which is obtained from the body-produced Adenosine triphosphate (ATP) 1 . This reaction is catalyzed by the use of S-adenosyl-methionine synthetase, and it results in the production of S-adenosyl methionine (SAM). The production of SAM causes the methyl group (CH3) to transfer to becoming an acceptor molecule, meaning that it can take in electrons. Once this first step has taken place, the hydrolyzation of adenosine from the previously produced ATP takes place. The result of this process is the releasing of the L-homocysteine. If this newly produced L-homocysteine reacts with tetrahydrofolate (THF), it could be reversed to L-methionine. In an alternate case, it could be converted to L-cysteine. 

Elevated Homocysteine 

In some cases, the levels of homocysteine might increase rampantly in an individual’s body. Based on the previous research, having a high concentration of homocysteine levels in one’s blood is quite hazardous and could result in serious conditions like heart attacks and strokes. This is primarily because the highly concentrated levels of homocysteine lead to the formation of plaque on arterial walls which in turn damages them, thus disrupting the transfer of blood from the heart to other parts of the body, like the brain. Again, this high levels also effect the blood platelets which are responsible for clotting 2 . The primary danger associated with this is that blood clots will be experienced from time to time. In the event that this occurs, blood will not be able to move freely in the arteries and veins. 

Causes of Elevated Homocysteine 

As it was aforementioned at the beginning of the paper, the consumption of protein foods in bulk is one of the primary causes of increased levels of homocysteine 2 . Also, the low consumption of foods that are enriched with vitamin B is a leading cause. Moreover, a person’s genetic orientation also plays a significant role in the creating of high production of homocysteine 1 . For instance, some individuals tend to have some genetic factors that have an effect on how the body absorbs and uses folic acid. For persons with such genetic problems, it is recommended that they ensure to have intake levels of more than 400 mcg as a way to counter the increasing levels of homocysteine. 

Little known to many, drinking too much coffee is also a cause of increased levels of homocysteine. The more coffee one takes, the more the body produces homocysteine. Stress is also another contributing factor. When one has stress, they induce neurotransmitters such as epinephrine and norepinephrine. The metabolism of both of transmitters takes place in the liver, and the whole process involves the use of methyl groups. Other causative factors are certain medications and kidney disease. 

The Diagnosis of Homocysteine Levels 

The levels of homocysteine are rarely tested for most individuals. However, for individuals whose families have a history of heart disease, doctors tend to order a test to determine the levels of concentration. This is determined through the conducting of a blood test. For an individual with a normal homocysteine level, the medical expectation is that it be ranging from 4.4 to 10.8 micromoles for every liter of blood in their body. In the case where the concentration per liter is above 10.8, the particular person is considered to be at a very high risk of developing complications in their heart operations. However, the diagnosis of homocysteine is rarely found around the world. Most of the places do not have the technology required to conduct the tests. Also, the test is quite expensive and is in most cases not coverable by insurance. These inconveniences persons who live on the minimum wage as they are not able to afford this particular kind of care. 

Effects of Elevated Homocysteine 

As it was previously stated, the elevation of homocysteine is very dangerous for the human beings and results in body complications, most of which result in death. One of the primary effects of elevated levels of homocysteine is that it results in the development of cardiovascular disease 1 . Over the past decade, cardiovascular diseases have been statistically said to account for a third of the total deaths experienced in the world, with the toll increasing on a yearly basis. Some of the cardiovascular diseases that are associated with the increased concentration of homocysteine include stroke, thromboembolism, myocardial infarction, and the peripheral vascular disease 1 . During the homozygous mutation of CS during most births, the homocysteine levels might increase in rampantly thus causing a severe occurrence hyperhomocysteinemia. The occurrence ratio of the disease today is one out of every 100,000 births 1 . If the condition is not given medical attendance, there is a high probability that it would result in the occurrence of other conditions, like a stroke. 

Nonetheless, high levels of homocysteine are also a causative agent for atherosclerosis 2 . It does this in three distinctive ways. It first damages the intima, interferes with clotting factors, and eventually results in the oxidation of lipoproteins with low density (LDLs). Homocysteine produces a cytotoxic on the endothelial cells of the body, an occurrence that results in reactive oxygen cells (ROS) being produced 3 . The ROS then works as an inhibitor to the production of nitric oxide that is derived from the endothelium and eventually causes damage to the cells as well as proliferates smooth muscle cells. It is with this peroxidation of lipids and the oxidation of LDL that ultimately results in atherosclerosis. Also, the formation of ROS is associated with the damage of smooth muscle cells and the causing of changes in endothelial cell function and its structural orientation. 

In another case, homocysteine has also been as one of the leading causes of carcinogenesis 4 . Cancer has been an increased occurrence in the modern day and age with individuals who develop it having limited life expectancies due to the lack of a cure. Despite there being little research to prove this phenomenon, it was found out that homocysteine played a very crucial role in it. Zhang et al. conducted a meta-analysis of previous research studies to determine the possibility of occurrence of the carcinogenesis as a result of increased levels of homocysteine and deficiency of folate. They obtained 83 case-control studies involving a total number of 35,758 individuals, with 15,046 being the actual cases and the other 20,712 being the control. In their findings, the group of researchers pointed out that high levels of homocysteine and low levels of folate were a risk factor for the development cancer but had a very little effect on the type of cancer caused 4 . 

For patients who have developed an ischemic stroke, elevated levels of homocysteine have been seen to be an indication of mortality 5 . In a case study done in 2015, it was found out that most of the individuals who had a stroke and were diagnosed with high levels of homocysteine were prone to die over a given period. In this research, a total number of 3799 patients were sourced to become participants. The level of homocysteine in their body was measured, and they were then observed over a period of 48 months (4 years). During this time, 233 of the 3799 passed away 5 . Patients who were categorically put in the highest quartile that is those with a homocysteine concentration of more than 10.8 mcg were found to be at the greatest risk of death. Individuals in the lower quartile, that is, those with a homocysteine concentration less than 10.8 mcg, were found to have a lower risk of mortality. These findings indicated that the having of high levels of homocysteine were a critical indicator for mortality of an individual. 

Treating Elevated Homocysteine 

There has been no significant progress in finding an effective treatment for homocysteine levels in the human body. However, this condition can be reduced by taking a right medical and dietary measures. For instance, a person who has been diagnosed with having high levels of homocysteine in their blood is supposed to increase their consumption of Vitamin B foods 6 . Increasing one’s consumption of foods like green leafy vegetables, grains, and fruits mitigate the production of homocysteine. Also, one should reduce their level of consumption for protein food 7 . Common foods, like meat, should not be taken in large amounts or for consecutive days. If one increases their consumption of such, they should also make sure to increase their consumption of vitamin B foods 8 . Grains are also significant in one’s diet as they result in the production of folic acid which also counters the production homocysteine. 

Further, the consumption of coffee needs to be reduced. If at all one has to consume coffee, they should ensure that they only take limited amounts and avoid making it a habit. It is also critical to moderate stress. Whereas stress is unavoidable, controlling it is quite easy to do. Doing breathing exercises, engaging in mind-body exercises, and also consulting professional therapy are ways to do away with stress. 


In conclusion, homocysteine is a least considered amino acid that has very high chances of causing mortality. Its occurrence in the body and the increased concentrations is merely as a result of human activity in terms of dietary planning. However, some other individuals have it as a result of genetic heritance. Significantly, no treatment will be provided in hospitals to do away with the levels of the amino acid. The only way to go about it is to practice healthy feeding habits. Given the implications it has on the human body, there is a great need for individuals to get the concern over the kind of meals they feed themselves. Avoiding protein foods, or rarely eating them is a way to ensure that the concentrations are drastically reduced. Additionally, doing away with stress by engaging in breathing exercises as well as mind-body exercise is also a way of ensuring that the homocysteine is kept to a minimum. Coffee, which is one of the most common beverage drinks today should also be minimized at all costs. 


Ganguly, P, Alam, S. Role of homocysteine in the development of cardiovascular disease. Nutrition Journal. 2015; 14 (6). Available from: doi: 10.1186/1475-2891-14-6 [Accessed 20 th April 2015]. 

Mech, A. W, Farah, A. Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: a randomized, double-blind, placebo-controlled study. The Journal of Clinical Psychiatry . 2016; 77(5): 668-671. Available from doi: 10.4088/JCP.15m10166 [Accessed 20 th April 2015]. 

Yang, X., Xu, H., Hao, Y., Zhao, L., Cai, X., Tian, J., Zhang, M., Han, X., Ma, S., Cao, J., & Jiang, Y. Endoplasmic reticulum oxidoreductin 1a mediated hepatic endoplasmic reticulum stress in homocysteine-induced atherosclerosis. Acta Biochimica et Biophysica Sinica . 2014; 46(10), 902-910. Available at: DOI: 10.1093/abbs/gmu081 [Accessed 20 th April 2015]. 

Zhang, D., Wen, X., Wu, W., Guo, Y., & Cui, W. Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case control studies involving 35,758 individuals. PLOS . 2015. Available at: doi: 10.1371/journal.pone. 0123423 [Accessed 20 th April 2015]. 

Shi, Z., Guan, Y., Huo, Y., Liu, S., Zhang, M., Lu, H., Yue, W., Wang, J., & Ji, Y. Elevated total homocysteine levels in acute ischemic stroke are associated with long-term mortality. Stroke . 2015; 46(9), 2419-2425. Available at: doi: 10.1161/STROKEAHA.115.009136 [Accessed 20 th April 2015]. 

Hernandez-Betancor, I., Martin-Ponce, E., Martinez-Riera, A., Vina-Rodriguez, J., Gonzalez-Reimers, E., de la Viego-Prieto, M., & Santolaria, F. Prognostic value of serum homocysteine levels in elderly hospitalized patients. Nutricion Hospitalaria . 2015; 31(6), 2590-2597. doi: 10.3305/nh.2015.31.6.9011 [Accessed 20 th April 2015]. 

Towfigi, A., Arshi, B., Markovic, D., Ovbiagele, B. Homocysteine lowering therapy and risk of recurrent stroke, myocardial infarction, and death: the impact of age in the VISP trial. Cerebrovascular Diseases . 2014; 37(4), 263-267. doi: 10.1159/000360153 [Accessed 20 th April 2015]. 

Smith, D., de Jager, C., Refsum, H., & Rosenberg, I. Homocysteine lowering, B vitamins and cognitive aging. The American Journal of Clinical Nutrition . 2015; 101(2), 415-416. doi: 10.3945/ajcn.114.098467 [Accessed 20 th April 2015]. 

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StudyBounty. (2023, September 15). Homocysteine: The Whole Story.


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