Happy Friday! I actually have a whole stack of interesting papers from email and links (as usual) - Paleo Wunderkind Jamie Scott sent me an email about homocysteine and anger earlier this week, and the papers are pretty cool.
Quick and catchy brand new tune by Girls - Honey Bunny (right click to open in new tab)
All right. Homocysteine. If you recall, in protein we eat an amino acid named methionine. Methionine plus various derivatives of the B vitamins, including folic acid vitamin B6 and vitamin B12 helps us make all sorts of stuff from other proteins like DNA, neurotransmitters, etc. Lots of important stuff. Homocysteine is an intermediate in the pathway, that is supposed to be recycled back into methionine (see this diagram) so that the cycle can begin again. Older people and men are likely to have higher homocysteine. Older folks also tend to eat less B vitamins. And folks with hyperinsulinemia are also more likely to have high homocysteine (if you really want your mind blown, check out this anonymous commenter who sounds and awful lot like Dr. K on my latest Psychology Today post linking insulin, homocysteine, selenium, B vitamins, choline, NAC and basically all the pathology of disease in Western Civilization.) Those who are obese are also more likely to have high homocysteine (in some studies but not in others), even with normal serum B6, B12, and folate levels (3).
If you don't have all the B vitamins in the right amounts, or if you are on medications that change the effectiveness of the enzymes in this pathway, or if you are one of 10% of of folks genetically deficient in the MTHFR enzyme, you will end up with extra homocysteine hanging about. And that, my friends, is not good. It's a bit murky, but homocysteine is thought to do all sorts of bad things, like stiffen arteries and increase the proliferation of smooth muscle cells leading to high blood pressure and increased risk of stroke. Homocysteine is also thought to be associated with joint and cartilage stiffness, weak bones, and is probably directly neurotoxic. High homocysteine is associated with increased risk of heart attacks both in baseline healthy folks and in people with previous heart disease, and it is thought to directly damage the blood vessel endothelium and is also probably prothrombic (2). High homocysteine (indicative of an inefficient folate cycle) (the actual level that is high is greater or equal to 11.3 micromol/L, in case you were wondering) means may be low in SAMe. SAMe (as we discussed earlier) is needed in the brain to make many neurotransmitters.
Over the years, high homocysteine has also been associated with anger (1). In fact, each 10 point increase in the Hostility and Hostility Direction Questionnaire is associated with a 2.9 micromol/L increase in homocysteine. Women under psychologic stress have higher levels of homocysteine also. Homocysteine has been investigated a number of times with respect to major depressive disorder, and it was found that only those with the disorder who also have anger attacks (approximately 40%) had significantly higher levels of homocysteine.
Anger on its own is also highly correlated with risk of heart attack. In one study of Koreans getting treatment for blocked coronary arteries, 60% of the patients met criteria for significant hostility on standard scales. This is in contrast to a much lower hostility score in healthy Koreans or Americans using the same scale. Both hostility and homocysteine level correlated with earlier return to the hospital with a new coronary event when the Korean patients were followed over time.
All right. So that is just a whole truckload of correlations, without a lot of explanation. And in the papers, there are some interesting suggestions (that the stress hormones deplete the B vitamins, thus raising homocysteine, that homocysteine is directly neurotoxic, causing anger. That homocysteine is associated with higher levels of pro-oxidants and represents an inflammatory state, also neurotoxic.
In the end we have the same prescription to address all the correlations and genetic variations - eat a healthy, nutrient rich diet. Avoid obesity and stress, or engage in stress reduction. Keep your folate cycle humming, and a lot of good things fall into place. Once it is out of whack, a cornucopia of bad juju starts to happen.