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The Acetyl-CoA theory of acne, and fibrates for treatment

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Old 07-25-2004, 02:19 PM   #1
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The Acetyl-CoA theory of acne, and fibrates for treatment

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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Old 07-25-2004, 07:20 PM   #2
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

You sort of lost me with some of the scientific theorizing. If I understood your theory correctly, you think sesamin would possibly be helpful in treating acne. Could you please respond and clarify?

Old 07-26-2004, 12:48 PM   #3
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

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.

Old 07-27-2004, 07:53 PM   #4
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

I was hoping for some input on the Acetyl-CoA acne theory - has anyone read the original article?

Old 07-30-2004, 11:04 PM   #5
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

Over the years the pathogenesis of acne vulgaris has been extensively studied including, the structure and function of the pilosebaceous follicle, the physiology of sebum, microflora in acne vulgaris, and abnormal follicular keratinization, considered to be one of the earliest events in acne formation. Despite the concerted effort of many scientists, internists, pathologists and dermatologists, the pathogenesis of acne vulgaris remains largely elusive.

In this paper, I would like to approach this problem from a different perspective. My clinical observations suggest that acne vulgaris may be closely related to the consumption of diets, which are rich in fat content. This impression is by no means novel. Textbooks do briefly mention this correlation though, more often than not, it is dismissed as irrelevant. However, my observations have led to quite the contrary conclusions. Not only is the fat content of food closely related to acne vulgaris but it forms some sort of linear relationship with the disease process. The more fat the patient consumes, the more severe will be the acne process. This observation is in line with the opinion of many dermatologists that chocolate, which is composed mainly of the creamy part of milk, and has a high degree of fat content, is bad for acne. Significantly, in this group of patients, any deliberate attempt in trying to avoid a fatty diet over a period of weeks, if not days, will often result in important compound, cholesterol, which in turn is basically synthesized from units of acetyl-CoA. In the synthetic process, the body naturally is always trying not only to reach for a normal level of androgens, but an optimal level, so as to allow the body to function at its best. However, this is not always possible, and the normal level reached may not represent the optimal level. This is natures flexible way of dealing with shortage of essential dietary elements in any form to achieve a level that is just enough to manage the present situation, leaving a variable degree of shortage from the optimal level. In the present instance, in the two groups of boys, one group may have a normal level of androgens that is falling short of the optimum. One possible explanation for this is that there is a lack of basic building blocks, the acetyl-CoAs, which deter the body from operating at peak efficiency. If this is a viable possibility, it suggests that a plentiful supply or a deficiency of acetyl-CoA in the body may play a role in the acne process. this is certainly possible. Aside from its role in the synthesis of the sex hormones, acetyl-CoA, of which Coenzyme-A is the important component, it is also important in fatty acid metabolism as an acyl carrier in the lengthening and degradation of long chain fatty acids by adding or removing acyl groups in the metabolic process.

Acne vulgaris is related to lipid metabolism as well as the sex hormones, both of which have a lot to do with Coenzyme-A. This relationship provides a reasonable ground to link up the acne process to Coenzyme-A and to investigate the pathogenesis of acne vulgaris along this line.

The Importance of Coenzyme-A

In trying to link acne vulgaris to Coenzyme-A, it is important to have a hypothesis supporting some basic facts. A closer look at Coenzyme-A may provide the evidence.

A Sharing scenario; As a coenzyme active in both fatty acid metabolism and sex hormone synthesis, Coenzyme-A is shared between two different metabolic processes. This is not uncommon in biochemical reactions in metabolism, where a coenzyme is often shared among a number of reactions. Coenzyme-A is arguably the most important coenzyme in the body, and when a coenzyme is involved in the metabolic process to such an extent as this, it becomes legitimate to ask if a shortage and deficiency is possible. To answer this, a brief look at the structure of Coenzyme-A is warranted.

Coenzyme-A is formed from adenosine triphosphate, cysteine, and pantothenic acid. Of these pantothenic acid is the only component that is a vitamin, and must be provided from our dietary intake. Could there be an insufficient intake of pantothenic acid resulting in a deficiency in Coenzyme-A, which would leave the body unable to cope with all the reactions, that it has to perform with that all-important coenzyme? Conventional wisdom does not think so. It is suggested that pantothenic acid, being ubiquitous, can be had from whatever kind of food that is taken in, and that there is no question as to its deficiency in our body. However, a deficiency is still possible. After all, when so many reactions are dependent on the same agent, its demand must be tremendous. Shortage under such circumstances is not entirely impossible

Old 07-30-2004, 11:06 PM   #6
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

The Crucial Question and the New Theory

If the question of deficiency of Coenzyme-A does come up, how does it affect acne, knowing its importance in fatty acid metabolism and sex hormone synthesis? This is the crucial question. This is where the new hypothesis on the pathogenesis of acne vulgaris is based, and this is where it diverges from conventional medical ideas. The author's proposed hypothesis for the pathogenesis of acne vulgaris is that the disease process is not caused by androgens, or any other sex hormones, but rather, the disease process results from a defect in lipid metabolism that is secondary to a deficiency in pantothenic acid, hence Coenzyme-A. Coenzyme-A, in carrying out its function efficiently both as an agent in fatty acid metabolism and an agent in androgen and sex hormone synthesis, has to be present in sufficient amounts, and anything less than sufficient will result in some compromise.

Mother Nature's Choice

Faced with the dilemma of a shortage of Coenzyme-A the body will tend to make a choice that is to the best advantage of the individual. The body does so by largely maintaining the functionally more important reaction, while at the same time slowing down the lesser important one. The choice here is a relatively simple one. Nature will seek to take care of the synthesis of hormones first, because continuation of the species depends on the development of the sex organs. Fatty acid metabolism is, for the time being, at least in part halted. Lipids start to accumulate in the sebaceous glands, sebum excretion is increased, and acne begins to appear. When there is enough Coenzyme-A in the body, however, both reactions will be well taken care of. There are enough sex hormones for the sex organs to develop. The lipids in the sebaceous glands are completely metabolized by sufficient Coenzyme-A, and there will be no unwanted lipid in the glands and little sebum will be excreted to cause acne vulgaris.

The Mystery Revealed

The mechanism proposed above may be the reason why two groups of adolescent boys both with a normal blood level of androgen may exhibit differences in the incidence of acne. The group with acne is the one that has not enough pantothenic acid in the body, whereas in the other group, pantothenic acid levels are not deficient.

This new theory seems to work well here, and can be tested in other metabolic situations. In the case in which endogenous androgen stimulates acne, whereas exogenous does not, the reasoning for the observation is the same. Any endogenous androgen synthesis will require the participation of extra amount of pantothenic acid. This will channel off some of those that are doing the work of fatty acid metabolism. Consequently, fatty acid metabolism becomes less efficient and the individual is more prone to have acne.

Today, the percentage of adult women that have acne is increasing. Some of these women may not have had acne as teenagers, and are surprised to find that they have to deal with this unpleasant problem during their adult years. Acne can have profound psychological and social effects on adults, just as it does in teenagers.

Many women in their 30s and 40s experience high levels of life stress because they shoulder the multiple burdens of career, child rearing, and housework, and often the responsibility of caring for their own aging parents. Perhaps this increasing level of stress has contributed to the rising incidence of acne in adult women.


Acne vulgaris of adulthood is similar to teenage acne. The pilosebaceous units of the face, chest, and back can be involved. The primary lesion of acne is the "microcomedo." A microscopic plug develops due to the presence of thickened and impacted keratin (dead cells) and excess oil production (sebum). More and more of the keratin and sebum back up behind this plug and form a distended follicular pore. This results in either an open comedo (blackhead) or a closed comedo (whitehead). The enlarged pilosebaceous structure allows Propionibacterium acne's, an anaerobic diphtheroid, to proliferate. Propionibacterium acne's contributes to the breakdown of lipids to free fatty acids, which are highly inflammatory. The distended follicle can rupture, causing further inflammation and the development of papules, pustules and nodules.

Acne Rosacea

Another skin disease that simulates and can coexist with acne vulgaris is acne rosacea. This skin problem is common in women, most often between the ages of 30 and 50. The face, especially the middle third, is erythematous and flushed. Multiple telangiectasias are frequently present. Small papules and pustules, which may look similar to those seen in acne vulgaris, are common, but the microcomedo component of acne vulgaris is absent in blepharitis. Rosacea keratitis is less common, but potentially vision-threatening. Rosacea is another skin disorder that is frequently stress related.

What about premenstrual flare? In the luteal phase of the menstrual cycle, progesterone in is secreted abundantly by the corpus lutcum. This naturally will take up a lot of pantothenic acid from the body's pantothenic pool leading to a re-distribution of the vitamin and putting enormous pressure on fatty acid metabolism. When this metabolic process is not performing satisfactorily, lipid begins to accumulate in the sebaccous glands, an increase in sebum is excreted, and acne follows. That is why even thought progesterone has no effect on sebaceous gland activity, an increasing level of progesterone in the late stage of the luteal phase leaves the acne patient with a prominent flare.

Similarly, this may explain why eunuchs rarely exhibit acne. Since so few sex hormones are secreted, the pantothenic acid pool can deploy a more significant portion of its reserve to metabolize fatty acids. When this is efficiently done, little sebum is excreted, and no acne is formed.

This theory also explains the paradoxical problem of equal sex hormones that counts. Both males and females need sex hormones for the development of sex organs and the secondary sexual characteristics. The only difference is that in the male, the female sex hormones predominate. Apparently the synthesis of sex hormones uses a large portion of the pantothenic acid pool, leaning a relative shortage of it to efficiently metabolize fatty acids. The result is that acne starts to erupt, at the same time the sex organs begin to develop at puberty.

The reason acne first erupts at puberty is not, therefore, endocrinological, but rather secondary to the deployment of a substantial amount of pantothenic acid for the purposes of synthesis of sex hormones, leaving a relative deficiency for fatty acid metabolism. The size of this pantothenic acid pool and the ability with which the individual can deploy reserves from the pool varies and is likely to be influenced by genetic and dietary factors.

In conditions in which there is an increase in secretion of any hormone whose synthesis requires the participation of pantothenic acid, acne may erupt. This is frequently seen with those hormone secreting tumours of the ovary, testis and the adrenals. The rapid decline in incidence of acne after adolescence can also be explained. After the sex organs are fully developed, less sex hormones are required, leaving an adequate supply of pantothenic acid to serve the function of fatty acid metabolism. When this function is efficiently accomplished, sebum secretion dries up, and acne starts to fade.

Old 08-01-2004, 05:59 AM   #7
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

i cant believe i actually read all that, how boring has my life gotten lol.

anyways, thank you for posting that... and i was hoping you could answer a few questions.

1. you seem to encourage the use of pantothenic acid (b5)... what would you say is the recommended dosage per day.

2. how do you feel about taking coenzyme-A supplements vs. taking b5 supplements.

3. will you continue to update? hehe

Old 08-01-2004, 07:47 PM   #8
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

I don't specifically encourage it. Feedback has shown that it works and I like to have at least some model explanation for how it works, whether right or wrong, to test.

I have no idea what CoA supplementation would do, if anything. If there were a singular solution one would think it has been stumbled upon by now. 10+ grams/day acetyl-CoA for comparison? interesting experiment- could get pricey.

I could update, but every time I tighten up my diet and get more vigilant against my acne, it responds with more vigor.

Old 08-02-2004, 04:50 AM   #9
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

"acne vulgaris may be closely related to the consumption of diets, which are rich in fat content"

Do you mean only certain types of fat? I am vegetarian and had always followed a low fat diet. When I started looking into dietary changes to treat acne, I increased my fat intake significantly. I was led to believe that GLA, ALA and linoleic acid may inhibit 5-alpha-reductase, and that EFAs also thin sebum, making it much less likely that sebum will create blockages. (I get through flax oil, olive oil, evening primrose, nuts, etc every day). I think these changes to my diet were intrumental in curing my acne.

Last edited by pimgenet; 08-02-2004 at 04:51 AM.

Old 08-02-2004, 06:28 AM   #10
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

Eskimos ate whole fat seal and whale grease and did not have acne. However this was natural grease unprocessed.

Old 08-02-2004, 10:07 PM   #11
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

I did not write that statement.. I don't even agree with it. I think that serum fat and glucose levels are what become important. We are not eskimos, either.

So blood triacylglycerides and free fatty acids could play a role. We know that fish oil and other polyunsaturates have tendency to inhibit DGAT and FAS (by a transcriptional relation). So eating fat does not necessarily cause high blood fats or it could not be important, but it's hard to say because we are all different in this respect.

Old 10-18-2004, 07:58 PM   #12
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Re: The Acetyl-CoA theory of acne, and fibrates for treatment

Wow... I can't believe I missed when this was first posted =( Oh well, I've coming to the same conclusion to, that the more severe your acne is the more important the avoidance of specific carbohydrates and specific fats become.

Thanks for the read

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