I've done a bit of reading about CBS upregulation in the medical literature (where it's known as CBS overexpression), and I'm posting my findings here. I've also posted it on the web, with links to the studies at this site: http://web.mit.edu/london/www/cbs.html Here's the text, without the links: Upregulation of the CBS enzyme via two genetic polymorphisms has been theorized to possibly be detrimental to some people with CFS, based on the work by Dr. Amy Yasko in autism. These two polymorphisms were studied in 2000, and in that study, the Post Methionine Load (PML) test was used to determine the effects of the different polymorphism genotypes. That loading test can detect subtle defects in the transsulfuration pathway, which is affected by the CBS enzyme. The polymorphism with the greater effect was 699CàT (Y233Y). The study found that people with the TT (-/-) genotype of that polymorphism, and to a somewhat lesser degree CT, produce lower levels of homocysteine levels in response to the PML test, when compared with the CC genotype. Lower homocysteine levels from that test infers greater CBS activity. About 40% of the population has CC, 40% has CT, and 20% have TT. The other polymorphism, 1080CàT (A360A), was found to have less a significant effect, with the TT genotype only showing a significant decrease in homocysteine, if 2 other polymorphisms were excluded. Thus, 699TT seems to have the greatest affect on CBS activity. On the other hand, a similar study in 2003 on these polymoprhisms did not show a significant difference in homocysteine levels due to the different genotypes, in response to the PML test. One difference is that this new study was done on a different ethnic group, which is sometimes a factor in genetic studies. Also, while the mean age was the same in both studies, this new study had a much smaller range of ages, and did not include anyone younger than about 40 years old. This might be a factor, since CBS activity is known to decrease as a person gets older. Even more interestingly, is that a study on pregnant women in 2003 surprisingly showed an increase in basal homocysteine levels from the TT genotype, the same genotype that had the lowest homocysteine level in the 2000 study. This study did not give any possible reason for this result. In any event, even in positive studies, such as the one from 2000, and a recent one from 2007, only small changes in homocysteine levels have been observed. For example, in the latest study, basal homocysteine levels only differed by 2.7% between the CC and TT genotypes. This effect is in contrast to the effect seen in Down’s syndrome, where CBS upregulation is definitely known to occur. In one study on Down's syndrome children, basal homocysteine levels were reduced by 25%, and plasma levels of cystathionine, the product of transsulfuration, was increased by 3.8 fold. On the other hand, a later study on Down's syndrome adults did not show decreased homocysteine levels. This surprising result was theorized to be due to the fact that adults have a much lower requirement for folic acid. When folic acid was given to the Down's syndrome children, their homocysteine levels rose significantly. Thus, age may become a factor when considering the effects from CBS upregulation. The original claim that CBS upregulation might be a factor for some people with CFS, is based on work by Dr. Yasko , who claims that the CBS polymorphisms can have a significant effect for autistic children. Even if that claim is true, it's possible that it only has relevancy for children. Also, the claim may have no relevancy for CFS, due to other the fact that CFS doesn’t have many of the metabolic disturbances that exist in autism. It’s also been claimed that increased urinary taurine and ammonia can help diagnose CBS upregulation. While it's true that CBS upregulation can cause increased taurine and ammonia production, there's no evidence that measuring urinary levels is a proven way to test for this increased production. Urinary taurine is unreliable as a test for CBS upregulation, due to fact that urinary taurine is greatly dependent on other factors, such as dietary taurine intake. This likely explains why that even though a study on Down’s syndrome found a significant increase in plasma taurine, another study on Down’s syndrome found that urinary taurine levels were normal. Urinary inorganic sulfur was also not significantly different (which doesn’t confirm Dr. Yasko’s prediction of excess sulfur byproducts) . On the other hand, urinary thiosulfate was significantly increased. Thiosulfate is a metabolite of hydrogen sulfide, and CBS is one of only three enzymes known to be able to produce hydrogen sulfide, indicating that significant CBS upregulation was likely was occurring. Urinary ammonia is an even less reliable method for testing for CBS upregulation. This is because most of the ammonia in urine is produced by the kidneys for ph regulation. The ammonia that is produced in the body, is usually first converted to urea, before being excreted. This process mainly occurs in the liver, and it is quite capable of handling a large amount of ammonia. The liver has to have this ability, as it has to be able to detoxify the large amount of ammonia which is created in the body from the metabolization of amino acids. Excess ammonia, i.e., hyperammonia, only usually occurs either when liver functioning has been greatly reduced, or where a genetic defect in the urea cycle exists. Only by testing serum ammonia, can such a condition be diagnosed. In conclusion, the medical literature states that the CBS polymorphisms which supposedly cause CBS upregulation, have only very mild effects. There is no evidence that they can significantly cause any negative effects, such as overproduction of ammonia. And the medical literature doesn’t support the claim that elevated levels of urinary ammonia or taurine is indicative of CBS upregulation. Dr. Yasko claims that CBS upregulation can lead to “a lack of glutathione.” However, while glutathione is reduced in Down's syndrome, medical researchers do not believe that this is due to the CBS upregulation. Instead, they believe it is due to the overexpression of the superoxide dismutase (SOD) gene, which also occurs in Down's syndrome: “The reduced plasma glutathione observed in the children with DS most likely reflects an adaptive antioxidant response to chronic oxidative stress, resulting from SOD overexpression.” This conclusion is possibly confirmed by a lab study on CBS overexpression in mice, where even though homocysteine levels were significantly reduced by the CBS upregulation, gluathione levels were unchanged. Thus, while some of the aspects of Dr. Yasko’s treatment plan may have usefulness, we do not see support for her theories on CBS upregulation.