What are potential long-term effects of isotretinoin, branded name: Accutane?

Ok first I want to say, I’m not demonizing this treatment, I’m glad it works for a good number of people.

Heck, I even took it— just before I graduated college. I was approaching 23 and had never seen any real improvement in my acne, despite trying nurmerous protocols: Proactive, oral & topical antibiotics and birth control. Spoiler alert: I had NOT tried everything for my acne.

But whether Accutane / isotretinoin works or not, it still greatly affects your internal body in ways you may not notice until later, these are my main long term concerns.

Aside from the LONG list of side effects / black box warnings for it, majority of people relapse with acne after treatment: up to 52%.

This drug works by binding to various retinoid receptors in the nucleus of the cell, acting as retinoic acid (active vitamin A) which allows it to control cell growth, differentiation and death. Isotretinoin inhibits sebaceous gland function (reduces oil production), decreases keratinization (lowering dead cell build up) & suppresses the inflammatory response. This usually speeds up cellular growth, which is why most people experience a “purging” while on the drug. Then, their acne generally clears up for a period of time or permanently.

But a drug that binds to receptors will block those receptors— in this case, natural vitamin A will be blocked from its receptors. This means time after time, this natural substance, necessary for normal functioning and essential for skin, immune health & more isn’t going to attach where it needs to.

What this means is that any vitamin A you do ingest in the hopes of balancing your internal body during treatment will be turned away. Keep in mind that retinoic acid is deficient in most people who suffer with acne, either because of genetic variants, poor digestibility, low intake or other factors. The vitamin A will be blocked out — it’s receptor or “parking space” is already taken.

Well, you may be thinking, if it’s the synthetic form of vitamin A, what’s so wrong with letting it do retinoic acid’s job, especially if it’s working?

Well for one— we didn’t actually address find out whether there’s a deficiency, nor did we address what the root cause of the deficiency is. Is there a gene variation (up to 60% of people have a variation on the BCO1 gene which causes a low conversion of beta carotene to retinoic acid). This means you can eat all the sweet potatoes and carrots you want, but you still may not have enough retinoic acid for healthy skin. But that’s the obvious issue…

Another concern is that overtime, the body may respond in a very poor way to synthetic vitamin A, and many researchers / practitioners and those who were prescribed this drug in the past are wondering whether this has long term affects on the retinoid receptors, the microbiome and the actions of converting vitamin A to retinol to retinoic acid.

* Does having a synthetic supply of vitamin A taking up your receptor spaces make your receptors less effective… or unresponsive to retinoic acid that your body later creates in the hopes of attaching and causing a reaction? This would cause major issues if you can’t get this vitamin to work in the body and it would mean an uphill battle for those with acne.

* Does it create or further perpetuate conversion issues… since the body took a hiatus from doing that? Again, causing major issues and certainly a deficiency in this vitamin.

* We know medications alter our gut microbiome— for instance, the microbiome will increase microbes that metabolize metformin (a drug for insulin resistance) while on that drug—which lowers the drug’s effectiveness, causing patients to increase their dosage in order to achieve the same effect. Could this be a similar situation with isotretinoin? Where the level of retinoic acid needed has increased due to the body adapting to metabolizing the huge supply of synthetic retinoic acid from the drug? Therefore, after discontinuing treatment, our requirements for vitamin A are much higher to achieve the same health effects on our skin and immunity? Is this perhaps the reason for relapse? And if so, does this also mean that our susceptibility to toxicity of vitamin A (yes, that exists) is also higher? And if not, where is the toxicity line for those people?

Just a critical thinker over here trying to figure out some puzzles. What do you think?

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