A New Frontier In Acne Medication
Dermatological researchers are investigating a new class of medications for1 treating acne. These drugs are know as peroxisome proliferator-activated receptor agonists, or PPAR agonists (stimulants) for short. This class of new acne treatments contains both great promise and great peril. Before you use them, you need to know about their potential benefits and side effects. We’re sorry that this is a little technical, but if your doctor is prescribing you a drug called Zileuton, or if you take medication for type 2 diabetes and you have acne, this is information you need to know.
What Is A PPAR-Agonist?
A PPAR-agonist really is not a medication that causes pain and suffering to PPAR. An agonist is the opposite of an antagonist. A PPAR-agonist makes PPAR more active2. But what is PPAR?
A peroxisome is an organelle (or miniature organ) in a cell that creates enzymes that break down fats into a form that the cell can use for fuel. It also creates enzymes that enable the cell to use many of the essential amino acids. Many biologists believe that peroxisomes are “permanent symbiotes” that perform some of the functions of symbiotic bacteria but that are purely human tissue.
A peroxisome proliferator is a chemical factor that causes another part of the cell known as the endoplasmic reticulum to create new peroxisomes. These peroxisome proliferators can activate receptors that switch on metabolic processes that use fats and amino acids.
Different kinds of tissues have different kinds of peroxisome proliferator-activated receptors. The peroxisome proliferator-activated receptors-alpha are found in liver, kidney, heart, and fat cells. -Beta and -delta receptors are found in the brain and skin. -Gamma1 receptors are found all over the body. -Gamma2 receptors are found in fat tissue. -Gamma3 receptors are found in fat and in the large intestine.
The nomenclature gets a little hard to follow. What is important to remember that these compounds “flip a switch” that helps a cell use fats and protein. That can be a good thing. Sometimes it’s not.
Early PPAR-Agonists In Medicine
Medications in this class became standard treatment for diabetics about 1997. One of the early PPAR-alpha agonists was a drug called Rezulin. It activated cells in the liver to store sugar taken out of the bloodstream. At first it appeared that the drug made control of diabetes effortless. All you had to do was to take the pill and your liver stored all that sugar you otherwise would have to cut out of your diet.
It turned out that there were limits to how much sugar the liver could store, and thousands of diabetics taking the drug developed liver failure3. Hundreds died. But that didn’t stop the pharmaceutical industry from coming out with two more PPAR-alpha agonists called Actos and Avandia.
You may have heard the story about these medications. At first it seemed like they too would be miracle drugs for diabetes. What doctors did not realize until their patients started gaining 30 to 100 pounds without changing their diets was that they activated receptors that not only helped fat cells store sugar taken out of the bloodstream, but that changed stem cells into fat cells. The adult stem cells the body generates to renew blood and bone were being transformed into fat. The stem cells it uses to repair the heart were also being transformed into fat.
Diabetics became morbidly obese without eating huge amounts of food. Many developed osteoporosis or anemia or congestive heart failure. Many suffered the indignity of being blamed for their health problems, and some self-righteous doctors stopped treating their patients altogether.
Actos and Avandia now have “black box” warnings. Rezulin has been banned. So the pharmaceutical industry is now looking to reinvent this class of medications in skin care.
Antagonists For Acne
PPAR-agonists, which stimulate gene activity, have mostly turned out to be disasters. The pharmaceutical industry now is experimenting with PPAR-antagonists, which turn genes off.
One of these PPAR-antagonists is a drug called Zileuton. It switches off the genes that are involved in the creation of a class of hormones called the leukotrienes, specifically the genes for a leukotriene called LBT44.
This is the substance that causes inflammation in acne. If you don’t have inflammation, pimples begin to heal, cysts and nodules begin to shrink, and blackheads and whiteheads never get started. You might still have a problem with your pores closing because the skin in the lining of the pores grows too fast, and you still might have a problem with excessive sebum production, but one of the most important phases of the formation of acne just might be brought under control if acne patients were given Zileuton. And scientists have discovered5 that Zileuton seems to slow down skin oil production, too.
What Could Possibly Go Wrong?
When Zileuton is used to treat asthma, the most common side effect is a headache. About 1 in 4 users of Zileuton develops cluster headaches. There are also people who experience nausea6, vomiting, heartburn, or mild liver damage, as well as some who become depressed. The drug is not recommended for people who are heavy drinkers or who have a history of liver disease, and it is not known to be safe for women who are breastfeeding or pregnant.
The pharmaceutical industry did not know about the potential of Rezulin to cause deaths from liver failure before it was released and the pharmaceutical industry did not about the potential of Actos and Avandia to cause deaths from congestive heart failure before they were released. It seems like an awful risk to take Zileuton for acne.
And there are much simpler and safer (not to mention cheaper) treatments that do a better job of treating acne inflammation. One of them is salicylic acid, which is chemically related to aspirin. Salicylic acid is the only beta-hydroxy acid used in skin care. It relieves inflammation7 and redness, but that is not all.
Salicylic acid lifts the dead skin off the surface of pores. It makes the natural color of the skin more visible. It helps pores drain. It stimulates the production of collagen underneath scars to help heal them from the inside out.
You can spend $20 for a beta-hydroxy acid exfoliant that works or $200 for a PPAR-alpha antagonist that might not. The time for Zileuton in acne treatment just has not yet arrived. Wait another 10 years to make sure that it does not cause horrible side effects.
- Trivedi N.R., Cong Z., Nelson A.M., Albert A.J., Rosamilia L.L., Sivarajah S., Gilliland K.L., Liu W., Mauger D.T., Gabbay R.A., Thiboutot D.M. Peroxisome proliferator-activated receptors increase human sebum production. The Journal of Investigative Dermatology. 2006;126(9):2002-9.
- Sertznig P., Reichrath J. Peroxisome proliferator-activated receptors (PPARs) in dermatology. DermatoEndocrinology. 2011;3(3):130-5.
- Faich G.A., Moseley R.H. Troglitazone (Rezulin) and hepatic injury. Pharmacoepidemiology and Drug Safety. 2001;10(6):537-47.
- Zouboulis C.C. Zileuton, a new efficient and safe systemic anti-acne drug. DermatoEndocrinology. 2009;1(3):188–192.
- Zouboulis Ch.C., Saborowski A., Boschnakow A. Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production. Dermatology. 2005;210(1):36-8.
- Bouchette D., Preuss C.V. Zileuton. StatPearls. 2019.
- Arif T. Salicylic acid as a peeling agent: a comprehensive review. Clinical, Cosmetic, and Investigational Dermatology. 2015;8:455-61.
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