Homocysteine, an sulfur amino acid, has been used over and over again marker for cardiovascular events. However, it is complicated so Jacob Selhub is going to talk about its particulars this morning at American College of Nutrition conference in New York City.
He starts by going through all the metabolic pathways that homocysteine is involved in, with methionine and SAM, as well as serving as a source for cysteine.
Hyperhomocysteinemia, he says, is caused by deficiencies in CBS, MTHFR, or in enzymes of B12 metabolism.
He tells the story about how back in 1969, pathologist McCully was studying how two children died of hyperhomocysteinemia. The pathology was identical, but causes were different.
The pathologies were arteriosclerosis. Even low levels of homocysteine was responsible for CVD. At the time, the idea was not accepted because the focus was on cholesterol.
But newer data showed that homocysteine is strongly associated with higher CVD and stroke incidence (Wilcken, 1976; others). Also, higher risk of incident dementia (Shesadri et al, NEJM).
Basically, the summary is that fasting homocysteine levels are now a well-established factor in vascular disease.
So, how do we lower homocysteine?
Selhub et al (JAMA 1993) established a relationship between B vitamin status and plasma homocysteine levels, specifically B6, B12, and folate. These decrease levels of homocysteine.
Clinical trials? There have been a few, he says. In randomized controlled trials of folic acid supplementation, most showed lower homocysteine, but did not help cardiovascular disease (no benefit) (Miller et al Am J Card 2010).
He notes that hyperhomocysteinemia is related to other factors too. Being male is higher risk factor. It’s very complicated, and he shows us more pathways again.
In the next decade, he says we need to look at the B vitamin pathways as a way to understand the disease.