Uridine as an Approach to Reducing Side Effects and Complications from Antiretroviral Therapy

Here are some of the articles discussing the use of uridine to treat lipoatrophy or lactic acidosis that can occur in some people taking antiretroviral medications to suppress HIV:

http://scholar.google.com/scholar?num=100&hl=en&lr=&q=uridine+mitochondrial+HIV

The explanation is that some of the antiretroviral medications, more than others, can inhibit DNA polymerase-gamma (the mitochondrial DNA polymerase isoform), lead to reductions in copy number, and thereby reduce the expression of the respiratory chain enzymes (leading to reductions in mitochondrial functioning, thereby reducing uridine biosynthesis, in a vicious cycle). Uridine has been shown to help liver function and lipoatrophy in people who have side effects from antiretroviral medications.

The studies have talked about different dose regimens, and those are relevant to any context in which one would be using uridine. There's elevation of the pyrimidine pools that can persist for relatively long periods of time, and the doses have generally been 18 grams for three consecutive days each month or 18 grams every other day. The studies on people with genetic disorders that are responsive to uridine suggest that the large doses required in those people are not elevating the pyrimidine pools, after a certain point. I tend to think it's because part of the benefit comes from the uracil and ribose-1-phosphate production in combination with the elevated pyrimidine pools. Ribose has not generally been shown to substitute for uridine, but the "non-pyrimidine" effect of high-dose uridine, given regularly, might suggest that some low-level purine replacement would potentiate the effect of uridine. There are articles showing that combinations of purines and pyrimidines, given to animals, helps repair mitochondrial damage to the liver and intestinal tract. In some of those articles, the doses of purines were larger, in terms of molar ratios and mg/d of purines, than the doses of pyrimidines. ATP depletion, from mitochondrial dysfunction, can produce purine depletion by disinhibiting AMP deaminase, among other mechanisms.