In yesterday's post, I discussed some of the evidence that Parkinson's disease is possibly caused by defects in the energy efficiency of the mitochondria of susceptible (and poisoned) individuals. I don't mean to do a whole Parkinson's series or anything, but the post did bring up some interesting questions.
We already know that a ketogenic metabolism seems to increase energy efficiency in the brain. But what else might do the same? Well, researchers are already looking into some trials of a few compounds of interest - Coenzyme Q10 (also known as ubiquinone) and creatine. There are a few published animal studies, a few small clinical trials of CoQ10, and human trials are ongoing for both CoQ10 and creatine.
CoQ10 is an interesting vitamin/molecule. Yesterday I compared mitochondria (our cells' energy factories) to a ski resort. There are proton pumping complexes in the mitochondria that pump against a gradient, rather like the ski lift carrying skiers up the hill. Eventually the energy is used to transport electrons across membranes in the "electron transport chain" and ATP is created (skiers set free to fly down the hill). To beat the analogy to death, CoQ10 is a bit like the attendants at the top of the ski lift, making sure everyone gets off the lift okay, and guiding skiers between lifts. While small doses of CoQ10 didn't seem to help symptoms of Parkinson's large doses (1200mg) seemed mildly helpful, and even larger doses are being tried now.
Creatine is a compound made from amino acids, and basically helps the body make ATP more easily. According to the Wikipedia article, we make a lot of creatine from dietary amino acids, but about half of our creatine is taken directly from eating skeletal muscle, and the muscles of vegetarians are lower in creatine. In animal studies, supplementation with creatine (combined with CoQ10) was helpful for Parkinson's symptoms.
Anyone who reads "statin skeptic" literature knows that statins lower CoQ10 levels. A pubmed search reveals a lot of papers on the subject - questions arise as to whether statins cause heart failure due to CoQ10 depletion - the heart, like the brain, is energy-hungry, and CoQ10 depletion over time might damage the heart (the study I linked showed lower CoQ10 in statin users and worse heart failure in people with low CoQ10, but no link between statin use and worsening of heart failure...) There are also questions if the CoQ10 depletion causes ALS (Lou Gerhig's disease) and whether the CoQ10 depletion causes the known (rare) statin side effect, diabetes.
So the obvious question is - would statins cause Parkinsons? This small study found that there didn't seem to be a link between Parkinson's progression and statin use, and this brief editorial notes that in population studies, higher LDL cholesterol levels are associated with lower risk of Parkinson's disease, but in the Rotterdam study, statin use seemed to have no correlation with Parkinson's disease risk, and other small studies showed the use of cholesterol-lowering drugs was associated with a decreased risk of Parkinson's. Turns out that serum cholesterol levels (and triglycerides) are the strongest determinant of serum CoQ10 levels - the reason being that CoQ10 rides along with the lipoprotein complexes in the body. Moderate alcohol use also seems to be associated with CoQ10 increases. And the best dietary sources of CoQ10? Meat, eggs, and certain vegetables such as broccoli. Dietary intake wasn't correlated that much with serum levels, though that could be because serum levels had more to do with how much cholesterol was floating around.
What can I make of this confusing mess? CoQ10 is a powerful antioxidant, one of whose jobs is likely to protect cholesterol and triglycerides as they are transported through the scary circulatory system. People with lots of inflammation will have high triglycerides, high cholesterol, and high CoQ10. The high CoQ10 is probably protective against Parkinson's disease (and perhaps a robust amount of cholesterol is too). Statins are also antioxidant and antiinflammatory, so it is possible that those attributes make up for obliterating the cholesterol making machinery and depleting the body's CoQ10, at least in the case of Parkinson's disease. The jury, though, is still out.