Hydroxychloroquine, known by the brand name Plaquenil®, is a medication primarily used to treat malaria and autoimmune diseases such as lupus and rheumatoid arthritis. While not explicitly approved for weight loss, emerging research explores its potential effects on appetite and metabolism. This article examines the relationship between Plaquenil® and weight loss, considering its mechanisms of action, clinical studies, and potential side effects.
Understanding Hydroxychloroquine (Plaquenil®)
Hydroxychloroquine sulfate (HCQS) is a synthetic relative of chloroquine, sharing a similar quinoline ring structure responsible for its bitter taste. It has anti-parasitic and anti-inflammatory properties, making it effective in preventing and treating malaria and autoimmune conditions.
The Bitter Taste Receptor Connection
Bitter flavors often signal spoiled or toxic substances, triggering an aversive response mediated by taste 2 receptors (TAS2Rs). These receptors are not limited to the tongue; they are also found in various tissues throughout the body, including enteroendocrine cells (EECs) in the gastrointestinal (GI) tract. When bitter compounds from ingested food or drugs like HCQS interact with these TAS2Rs in the GI tract, they can elicit a repulsive reaction, potentially delaying gastric emptying and reducing food intake.
Hydroxychloroquine's Impact on Appetite Hormones
The reaction caused by bitter tastants in the GI tract is linked to altered secretion of appetite-regulating hormones. Studies have shown that bitter agonists can affect the secretion of both anorexigenic (appetite-suppressing) and orexigenic (appetite-stimulating) hormones, such as acyl-ghrelin and motilin.
Acyl-Ghrelin and Motilin
Acyl-ghrelin, the active form of ghrelin, is primarily released in the stomach and stimulates food intake. Motilin, produced by M-cells mainly in the duodenum, plays a role in stomach motility and is associated with hunger sensations. Research suggests that bitter compounds can reduce plasma motilin concentration, potentially leading to reduced hunger sensations.
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Clinical Evidence: Hydroxychloroquine and Appetite
A double-blind, randomized, crossover study involving lean adult women investigated the effects of oral HCQS ingestion on appetite and hormone release. Participants received either 400 mg of HCQS or a placebo. The study found that HCQS tended to reduce hunger at the time of interest and decreased acyl-ghrelin plasma concentrations.
Study Design and Methodology
The study, approved by the Leuven University Hospital Medical Ethics Committee, included ten healthy lean female volunteers with BMIs between 18 and 25 kg/m2. Participants were not dieting and had stable body weights. They received two tablets of Plaquenil® (400 mg HCQS) or placebo in a double-blinded, crossover fashion. Blood samples were collected to measure motilin, acyl-ghrelin, insulin, and blood glucose levels. Appetite-related sensations were scored using visual analog scales (VAS).
Results and Observations
The study revealed that HCQS tended to reduce hunger scores 50-60 minutes after ingestion. Acyl-ghrelin plasma concentrations also decreased. However, no significant effect was found on subsequent milkshake intake. These results suggest that HCQS may influence appetite-regulating hormones, potentially impacting hunger sensations.
Hydroxychloroquine and Metabolic Effects
Beyond its potential impact on appetite, hydroxychloroquine has been suggested to have beneficial effects on lipid profiles and insulin sensitivity. This could contribute to lowering cardiovascular risk, particularly in patients with systemic lupus erythematosus (SLE).
Impact on Insulin Sensitivity and Lipid Metabolism
Research indicates that hydroxychloroquine can improve blood lipid and glucose levels. Studies in mice fed with a high-fat diet (HFD) have shown that hydroxychloroquine reduces weight, hepatic steatosis, glucose, and insulin resistance. It also downregulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) in the liver, a key regulator of lipid metabolism.
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Animal Studies: Mechanisms of Action
Animal studies provide insights into the potential mechanisms by which hydroxychloroquine may influence metabolism. For instance, experiments with HFD-induced obese mice demonstrated that hydroxychloroquine treatment led to improved glucose tolerance and insulin sensitivity. The treatment also reduced levels of free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C).
Hepatic Effects
Hydroxychloroquine has been shown to improve hepatic ectopic lipid accumulation in HFD-induced obese mice. It reduces liver lipid levels and inhibits the expression of pro-inflammatory cytokines in liver tissues. Additionally, it increases the phosphorylation of Akt and insulin receptor substrate-1 (IRS-1), critical mediators of the insulin signaling pathway.
Clinical Considerations and Side Effects
While hydroxychloroquine may offer potential benefits for weight management and metabolic health, it is essential to consider its potential side effects and clinical considerations.
Common Side Effects
Common side effects of hydroxychloroquine include abdominal pain, diarrhea, nausea, and vomiting. Mild side effects may also include changes in hair color, dizziness, fatigue, headache, loss of appetite, skin itching, and rash. These side effects are usually temporary and can be managed.
Serious Side Effects
Serious side effects, though less common, can include skin problems, ear problems, mental health issues, muscle or nerve problems, protein in the urine (a sign of kidney problems), low levels of blood cells, low blood sugar, seizures, eye problems, heart problems, and liver problems.
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Long-Term Side Effects
Long-term use of hydroxychloroquine may lead to side effects that persist even after discontinuing the medication. These can include low levels of blood cells, muscle or nerve problems, eye problems (such as retinal damage), and heart problems (such as cardiomyopathy).
Precautions and Contraindications
Hydroxychloroquine can cause harmful effects in individuals with certain pre-existing conditions. It is crucial to discuss your health history with your doctor before starting the medication. Conditions of concern include eye problems, heart problems, liver problems, kidney problems, muscle or nerve problems, psoriasis, diabetes, low blood levels of potassium or magnesium, mental health conditions, certain inherited conditions, and previous allergic reactions to hydroxychloroquine.
Hydroxychloroquine and Weight Changes: What the Evidence Suggests
While weight loss has been reported as a side effect of hydroxychloroquine, weight gain is not typically associated with the drug. The appetite-suppressing effects of hydroxychloroquine may contribute to weight loss in some individuals.
MyLupusTeam Survey
A survey on MyLupusTeam explored the experiences of individuals taking hydroxychloroquine and concerned about weight changes. Some members reported weight loss associated with nausea and diarrhea, while others experienced weight gain due to fatigue and muscle weakness, making exercise difficult.
Weight Gain and Lupus Management
It is important to note that other lupus treatments, such as corticosteroids and antidepressants, are well-known to cause weight gain. Lupus itself may also contribute to weight gain through symptoms like lupus nephritis, muscle or joint pain, and severe fatigue.
Practical Recommendations for Managing Weight While on Hydroxychloroquine
If you are taking hydroxychloroquine and concerned about weight changes, consider the following recommendations:
- Exercise as You’re Able: Engage in low-impact activities such as yoga, swimming, cycling, and walking to improve cardiovascular health, reduce inflammation, and boost mental health.
- Eat as Well as Possible: Follow a balanced diet that includes fruits, vegetables, whole grains, lean protein, and healthy fats.
- Consult with Healthcare Professionals: Discuss any weight changes or concerns with your doctor or a registered dietitian to develop a personalized management plan.
- Monitor Side Effects: Keep track of any side effects you experience and share this information with your doctor to adjust your treatment plan if needed.