Despite mainstream medical ignorance of Kilmer McCully’s original homocysteine work four decades ago, homocysteine is now considered a risk factor for cardiovascular disease. Homocysteine is thought to increase the risk of cardiovascular disease via oxidative stress (although may also cause endothelial dysfunction independent from its pro-oxidative action). Since Denham Harman proposed the free radical theory of disease in the 1950’s, oxidative stress has been linked to a number of conditions including type 2 diabetes and hypertension. Homocysteine is often elevated in individuals with these conditions which suggests that homocysteine may be the cause of the oxidation associated with these diseases. If this is the case, then an increase in plasma homocysteine could be the cause of the increase risk of cardiovascular disease associated with ageing. The fact that oxidative stress is associated with ageing itself, may implicate homocysteine in this process in some way.
Researchers1 have measured a number of biochemical and physiological parameters in 282 subjects over 65 years in age and compared them to the same parameters in 141 subjects below 65 years of age, in order to find associations between homocysteine, oxidative stress and cardiovascular risk factors. The results showed that showed that homocysteine was higher in older individuals compared to younger individuals (2.9 versus 2.3µmol/L, respectively) and that oxidative stress was also higher in the older subjects (measured as reactive oxygen species, colorimetric method), as expected. However, when the researchers compared the older healthy subjects with younger subjects with hypertension or type 2 diabetes, they found that plasma homocysteine concentrations and malonaldehyde (MDA, measured with thiobarbituric acid reactive substance (TBARS)) plasma levels were not significantly different. Comparisons of older versus younger diabetic and hypertensive subjects revealed no significant difference in homocysteine, ROS or MDA.
These results suggest that diabetes and hypertension are conditions that accelerate the increase in plasma homocysteine levels seen with ageing. Interestingly the researcher reported that subjects over 65 did not show an increase in homocysteine levels if they had diabetes and hypertension, when compared to just diabetes or hypertension This suggests that there is a natural ceiling for homocysteine, above which plasma levels cannot rise. Because age is the major risk factor for cardiovascular disease, it stands to reason that physiological changes must accompany ageing in order for the risk of the disease to increase. Homocysteine may be one factor that leads to changes in the risk of cardiovascular disease over time. If diabetes and hypertension accelerate the natural age associated rise in homocysteine and its associated oxidative stress, this explains why such conditions increase the risk of cardiovascular disease in young healthy subjects.
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