Accutane, also known as isotretinoin, is a powerful medication widely used to treat severe acne. While its effectiveness in clearing up stubborn acne is well-documented, many patients wonder about potential side effects, including whether Accutane can impact their weight. This article explores the relationship between Accutane and weight changes, examining the scientific evidence and discussing treatment options.
Understanding Accutane and Its Mechanism
Isotretinoin (13-cis retinoic acid) is widely used to treat severe cystic or recalcitrant acne. Acne is a chronic inflammatory disorder of the pilosebaceous units in the skin. Although it commonly affects the majority of the adolescent population, it is also prevalent in adults. The pathogenesis of acne is multifactorial and includes hormonal, inflammatory, and immunologic mechanisms. There are four processes that play a pivotal role in the formation of acne lesions: inflammatory mediators released into the skin, alteration of the keratinization process leading to comedones, increased and altered sebum production under androgen control (or increased androgen receptor sensitivity), and follicular colonization by Propionibacterium acnes.
Isotretinoin is the most potent pharmacological inhibitor of sebum secretion; it causes a reduction in the size of sebaceous glands, it causes sebocytes to appear undifferentiated, and it leads to a decrease in lipid accumulation. Sebaceous glands are present all over the human body, except on the palms of the hands and soles of the feet. They are usually found in association with hair follicles. The sebaceous gland is a holocrine gland, meaning that the glandular secretion consists of cells from the gland itself. The sebaceous gland contains two kinds of sebocytes: peripheral cells and central cells. The peripheral cells are immature cells that are cuboidal or flattened and do not contain lipids. The central cells are larger than the peripheral cells, and the majority of this size increase is due to the elevated amount of cytoplasmic lipids. Adipocytes are most like sebocytes. Both cell types have a similar physiology, which is the accumulation of lipids. Sebocytes release lipids that eventually make their way to the skin surface, while adipocyte lipids have energy-storing functions. Both adipocytes and sebocytes have similar receptors and express enzymes important for lipid production (e.g., LDL, liver X receptor (LXR), diacylglycerol acyltransferase, and SCD1).
Oral isotretinoin is generally reserved for severe, recalcitrant, nodular acne that is unresponsive to topical therapy. Its mechanism of action and side effect profile is not yet completely understood. Isotretinoin significantly decreases sebum production and growth of P. acnes; in addition, it reverses hyperkeratinization and reduces inflammation. Although it is an effective therapy for acne, isotretinoin is associated with significant adverse effects, including cheilitis, dry skin and mucous membranes, epistaxis, increased risk of cutaneous Staphylococcus aureus infections, myalgias, and pseudotumor cerebri. Frequently reported blood chemistry abnormalities in isotretinoin users include elevated levels of triglycerides and cholesterol, elevated LDL concentrations and decreased HDL concentrations.
The Conflicting Evidence: Accutane and Weight Changes
When it comes to Accutane's impact on weight, the evidence is somewhat mixed. Let's break down what we know based on scientific research and reported side effects:
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Accutane and Weight Loss: Interestingly, some evidence suggests that Accutane may be associated with weight loss in some patients. According to Mayo Clinic, weight loss is listed as a common side effect of Accutane treatment. This information is corroborated by another source, which states that "Accutane may be associated with a weight loss" during active treatment. The exact mechanism behind this potential weight loss is not fully understood. It's possible that some patients may experience changes in appetite or eating habits while on Accutane, which could contribute to weight loss. Some users also report food aversions during treatment, particularly to greasy or rich foods. Accutane can influence mood and energy levels which in some people may encourage them to eat more, but for some people it can affect motivation to cook, eat, or snack regularly. Some people on Accutane report dry mouth or altered taste perception, which can make food less enjoyable. However, it's important to note that weight loss is not a guaranteed outcome for all patients taking Accutane.
Accutane and Weight Gain: While weight loss is more commonly reported, there is also some evidence suggesting that Accutane may lead to weight gain in certain cases. Mayo Clinic also reports that Accutane may cause weight gain in some patients. However, it's crucial to understand that this is not a universal effect and may only affect a subset of individuals taking the medication. One potential mechanism that could explain weight gain in some patients is the relationship between Accutane and insulin resistance. According to a study out of Turkey, Accutane has been shown to be associated with insulin resistance. Insulin resistance is typically associated with an induction of diabetes and weight gain. However, it's important to note that this doesn't necessarily mean that all patients taking Accutane will experience insulin resistance or subsequent weight gain.
No Significant Impact on BMI During Treatment: Despite the reports of both weight loss and weight gain, it's worth noting that scientific data does not show a significant link between active Accutane treatment and changes in body mass index (BMI). This suggests that while individual patients may experience weight fluctuations, there isn't a consistent, widespread effect on weight across all Accutane users. A 2016 study investigated the effects of isotretinoin on body mass index (BMI) and certain hormones related to weight regulation. The study found no significant changes in BMI after three months of treatment. Similarly, a 2024 study assessed weight and metabolic parameters in patients undergoing isotretinoin therapy. At the correct dosage, researchers noted non-significant changes in BMI or metabolic syndrome markers among patients.
Potential Weight Changes After Stopping Accutane: Interestingly, some reports suggest that weight changes may occur after discontinuing Accutane treatment. Specifically, weight changes that Accutane causes generally stop after patients discontinue the medication. This potential post-treatment effect is something patients should be aware of and discuss with their healthcare providers.
FDA's Stance: The Food and Drug Administration (FDA) does not list weight change as a side effect of Accutane, despite rare patient reports of weight loss or gain while on the medication. This doesn't mean that weight changes don't occur in some patients, but rather that they are not considered a primary or significant side effect of the medication based on current data.
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Factors Influencing Weight Changes During Accutane Treatment
Several factors can contribute to weight changes experienced by individuals undergoing Accutane treatment:
Changes in Dietary Habits: Accutane is a fat-soluble medication, meaning it is best absorbed when taken with dietary fat. Dr. Howell says that he often advises his patients to take their medication with a high-fat meal to improve effectiveness. In response, some users may deliberately increase their daily fat intake-sometimes significantly-to meet this requirement.
Fatigue and Reduced Physical Activity: Many Accutane users report feeling more tired or sluggish than usual. In fact, fatigue has been documented in up to 3% of people taking isotretinoin, according to clinical data. If you’re feeling consistently low on energy, you may find yourself eating more, exercising less or being more sedentary overall. Muscle aches and joint discomfort are among the more common side effects of Accutane, affecting as many as 20% of users. While usually mild and temporary, this discomfort can interfere with your motivation to work out or stay physically active.
Mood Alterations: Although very rare, Accutane has been associated with changes in a person’s mood. When this occurs, it can also disrupt sleep, alter appetite, and lead to emotional eating or loss of motivation to stay active-all of which may contribute to weight gain.
Metabolic Effects: Accutane has been shown to affect cholesterol levels and blood sugar in some users, suggesting a potential influence on metabolism. Although the link between isotretinoin and metabolic rate isn’t fully understood, some researchers speculate that the medication might alter how the body processes glucose and stores fat.
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Alcohol Consumption: Patients on Accutane are strongly advised to avoid alcohol because the medication can increase liver strain. As a result, those who used to drink regularly might cut out alcohol completely during their course. This can have a significant caloric impact, especially if alcohol was consumed frequently or in large amounts. Without alcohol, hangovers are no longer an issue, which means many people stop engaging in “hangover eating” - like ordering fast food or snacking heavily the day after drinking.
Appetite Changes: Many people experience side effects like nausea, stomach discomfort, or a reduced appetite while on Accutane. These symptoms, although usually mild, can lead to eating less throughout the day or skipping meals altogether.
The Role of Adipokines: Leptin, Adiponectin, and Ghrelin
Adipose tissue is a major site for storage of vitamin A derivates (collectively named retinoids); therefore, it plays an active role in their homeostasis and metabolism. Moreover, adipose tissue is a known target organ for retinoic acid as retinoid and retinoid X receptors are expressed in adipose tissue. In addition, white adipose tissue acts as an endocrine organ and produces a variety of hormones (adipocytokines), including leptin, adiponectin, tumor necrosis factor α (TNF-α) and angiotensin II (Ang II), all of which influence lipid metabolism, systemic insulin sensitivity and inflammation.
Adiponectin: Adiponectin is an adipocyte-derived hormone that plays a role in insulin function and energy homeostasis. Early studies indicated that adiponectin has an anti-inflammatory effect on endothelial cells by inhibiting the following: nuclear factor κB activation, TNF-induced adhesion-molecule expression, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule-1 (E-selectin), and intracellular adhesion molecule-1. Adiponectin induces the secretion of some anti-inflammatory cytokines (e.g. interleukin (IL)-10 and IL-1 receptor antagonist) by human monocytes, macrophages and dendritic cells. Adiponectin can also suppress the production of interferon-γ, while pro-inflammatory mediators, such as TNF-α and IL-6, inhibit adiponectin gene expression. There are only 3 published studies relating isotretinoin treatment and adiponectin blood level. All of these reports indicate that isotretinoin treatment leads to elevated levels of adiponectin.
Leptin: Leptin is a 167 amino acid protein with a molecular weight of 16 kDa; it is mainly produced by the adipocytes that stem from the obese gene. Leptin levels are directly proportional to fat mass. It is involved in the regulation of appetite and energy expenditure via hypothalamic-mediated effects. In addition, it plays a role in carbohydrate and lipid metabolism. Published data indicate that leptin levels are increased following acute infection and in chronic inflammation, which suggests that leptin may actively participate in the immune network and host defense.
Ghrelin: Ghrelin is a recently-discovered orexigenic hormone that is primarily secreted by the stomach and duodenum; it has been implicated in both mealtime hunger and the long-term regulation of body weight. Ghrelin is currently recognized as the main endogenous ligand for growth hormone secretagogue receptors as well as other regulatory factors in growth hormone secretion and energy balance. The levels of circulating ghrelin increase under conditions of starvation and in anorexia nervosa, but decrease under conditions of feeding and in obesity. Ghrelin and leptin may have opposite actions in the regulation of body weight. Recently, it was reported that ghrelin exerts anti-inflammatory and immunoregulatory actions by inhibiting Ang II-induced expression of IL-8, TNF-α and monocyte chemoattractant protein-1 (MCP-1).
Monitoring and Management of Weight Changes During Accutane Treatment
Given the potential for weight changes and other side effects, patients taking Accutane should maintain open and frequent communication with their healthcare providers. Regular check-ups and monitoring can help identify any significant weight changes or other side effects early on, allowing for appropriate adjustments to treatment if necessary.
Dr. Howell recommends monitoring how Accutane affects you by keeping a symptom journal or using a tracking app to log physical and emotional changes throughout treatment - including weight, mood, appetite, and energy levels. Tracking these details consistently can help you identify patterns early and give your dermatologist valuable insight during follow-up appointments.
Other Important Considerations During Accutane Treatment
While weight changes are a concern for many patients, Accutane can have other side effects to look out for. These may include dry skin, chapped lips, joint pain, and changes in blood lipid levels. Patients should be aware of all potential side effects and report any concerning symptoms to their healthcare provider promptly. It is very important that anyone who is pregnant, who is planning to become pregnant, or who may become pregnant accidentally does not take Accutane. This is because Accutane may cause: miscarriage, congenital disabilities, premature labor or death in babies.
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