Discussions that mention gemfibrozil

Acne board


I can take you for a long ride here, but instead I'd like to know what has been said on this topic and see if we can't toss some things around.

The Coenzyme-A theory in a nutshell: Coenzyme-A must be present in sufficient amounts to carry out its function in both fatty acid metabolism and sex hormone synthesis. CoA is synthesized from cystine, ATP, and pantothenic acid.

The theory is that if there is insufficient CoA to efficiently carry out these functions, than it will tend to be used to synthesize sex hormones at the expense of fatty acid metabolism causing fatty acids to accumulate in the sebacious glands. Pantothenic acid is proposed to be the limiting reagent in CoA synthesis, and supplementation has shown some anecdotal support.

But there's more to this fatty acid metabolism theory, and now I am going to take you for a ride so buckle up.

Glucose and fatty acids serve as the primary source for skeletal muscle metabolism, and fuel selection operates in a pendulum fashion; that is, if one is to metabolise large amounts of glucose, later the pendulum will swing the other way to metabolise large amounts of fatty acids (1).

Now when the pendulum is swinging so that fatty acids are being metabolised, large amounts of Acetyl-CoA are produced. Imagine the pendulum now swinging so that glucose is being metabolised. In short, what happens is that Acetyl-CoA is metabolised to Manoyl-CoA. It is the Acetyl/Manoyl ratio that determines nutrient usage at rest.

My proposal in my own mind agrees with every single acne theory to date: it is the pendulum theory of acne. It agrees with dietary measures: if one metabolizes a high amount of glucose in a short characteristic time frame, Acetyl/Manoyl ratio decreases, and the pendulum "swings left," Acetyl-CoA is depleted, and fatty acids accumulate into sebacious glands. If one opts to go on a ketogenic (Atkins) diet, there is not sufficient glucose to deplete Acetyl-CoA levels, and there is sufficient Acetyl-CoA to both mediate sex hormone synthesis and metabolize fatty acids.

What about those who tend not to respond to dietary measures alone? Enter patothenic acid. This works for many but not all, because pantothenic acid does not translate directly into greater Acetyl/Manoyl ratio. According to the theory acne sufferers have considerably low Acetyl-CoA levels constantly, or at least enough to cause breakouts. Low levels of Acetyl-CoA do not translate specifically into a metabolic morphism (fat, skinny, hyper/hypothyroid, etc.). Well, I am lying but the implications here, albeit interesting, are far beyond the scope of our purposes here.

I would like some help on expounding my pendulum jargon unless it is already on paper somewhere, or you may opt to help me find the fallacy in this argument.

But there is a hook in the title. Fibrates for acne treatment? Yes, indeed. I don't know how deep I should go with this one. In short, fibrates are PPAR-alpha agonists used for the treatment of high triglycerides mainly in diabetics. It increases fatty acid metabolism and one of the side effects is an increase in acetyl-CoA levels. The only fibrate that generally doesn't cause this is gemfibrozil, but most any other fibrate does. If you don't want to use mexican pharmaceuticals, you can find a natural PPAR-alpha agonist which has shown to have similar side effects (by the same mode of action... it should really just be "effects"). This natural PPAR-alpha agonist is "sesamin," a lignan found in very low concentrations on the inside of a sesame seed. It is extracted and concentrated mainly in asia and mainly for liver detoxification, antioxidant properties, and (by some unknown mechanism) "beutifies the skin." Did you catch that? The theory previously was that sesamin recycled vitamin E and this is how it exerted its effects on the skin. I'm proposing something that conviniently fits right in place with my pendulum theory and opens the door to the PPAR-alpha agonist centric treatment of acne.

A FAS (fatty acid synthase) inhibitor actually decreases excess acetyl-CoA levels. Here's where things get interesting. EGCG in green tea is a 5AR inhibitor, inhibiting DHT conversion. EGC in green tea is a FAS inhibitor. My second proposal is that if you seek to treat your skin with green tea extract, you opt to use one standardized for EGCG instead of EGC. Hydroxycitrate is the other readily available FAS inhibitor.

Side effects of fibrate treatment: Fibrates as stated are useful for decreasing triglycerides and generally this will in a roundabout way help endomorphs (overweight) maintain a lower bodyfat phenotype by increasing insulin sensitivity, leptin transport, and a myraid of other (mostly good) things. The accumulation of acetyl-CoA can be a problem in terms of health, but my proposal is that those with acne are low in acetyl-CoA to begin with. An excess of acetyl-CoA will cause excessive hunger and the dose would then be decreased or a FAS inhibitor added (although now we are antagonizing intended effects, so the former is a better cotrol methd). If you know a diabetic who takes fibrates, note that they have a hard time controlling their appetite even though they maintain leaner than before treatment. Other side effects of fibrate use include muscle tissue wasting or weakness, cardiac cell death, and decreased testosterone synthesis. All of these are directly dose-dependent. Please don't interpret this as medical advice, or advice at all. Only theory to kick around.

If one in "theory" wanted to try this, the good news is that side effects tend to be insignificant and/or take years to materialize, but the fibrate action itself is instant and acetyl-CoA elevation will happen in less than a week. Again, this is anecdote, not medical advice. I would like to see what happens if someone were to administer a fibrate in large enough dose to induce the excessive hunger (indicating excess Acetyl-CoA) and test this theory.

I could be blowing smoke this is why I'd like to hear some other ideas.

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sesamin has reportedly been used to improve skin health (references are not allowed on this website apparently). The reason sesamin lignan was thought to improve skin was due to its vitamin E regenerating (recycling) effects. I do not believe this and I proposed a different mode of action which fits the Acetyl-CoA theory and my modification of said theory.

Unfortunately sesamin has not been studied specifically for skin health and the acetyl-CoA effects are unknown. Just like gemfibrozil, which is a PPAR-alpha agonist, it can be "poor" at increasing Acetyl-CoA deposits. Traditionally sesamin has not been used in large enough quantities to have "fibrate-like" effects but just recently it has been concentrated to 60%+ by folume in reasonable prices ($1/day or so for nearly fibrate-like action). But there has indeed been plenty of clinical studies done on fibric acid derivatives (pharmaceuticals) that will obviously elevate Acetyl-CoA levels.

The wingnut is that this Acetyl-CoA theory depends not only on total Acetyl-CoA levels, but Acetyl/Manoyl ratio. I believe that the fibrates will work to both increase Acetyl-CoA absolute values and increase Acetyl/Manoyl ratio.

I am not proposing that sesamin work. I have 60mL of 60% sesamin and I'm going to take 3g per day but I am also changing my diet around all the time so I really need more than n=1 for any statistical evaluation.