The question of whether antihistamines contribute to weight gain has been a topic of interest and debate. While some studies suggest a potential link, the evidence remains complex and requires careful consideration. This article explores the available research, potential mechanisms, and practical considerations regarding antihistamine use and its possible association with weight changes.
The Rise of Obesity and Related Health Issues
The prevalence of childhood obesity has been increasing in the United States, contributing to a rise in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). According to the latest Centers for Disease Control and Prevention (CDC) data, obesity affects 18.5% of children ages 2-19 years, estimated as 13.7 million. This has led to a 2.7-fold increase in the prevalence of pediatric NAFLD and a higher incidence of metabolic syndrome.
Understanding Antihistamines and Their Mechanisms
Antihistamines are medications used to relieve allergy symptoms. They work by blocking histamine, a chemical released by the body during an allergic reaction. Histamine causes small blood vessels (capillaries) to become more permeable, allowing white blood cells to move in to attack the foreign body. It also acts as a neurotransmitter in the brain, playing a role in wakefulness.
There are two main types of antihistamines: H1 and H2 receptor blockers. Common H1 receptor blockers include diphenhydramine (Benadryl), hydroxyzine, cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra). H2 receptor blockers include famotidine and ranitidine.
Studies on Antihistamines and Weight Gain
The NHANES Study
One of the primary studies investigating the relationship between antihistamines and weight gain comes from the Journal of Obesity in 2010. This study used data from the National Health and Nutrition Examination Survey (NHANES) from 2005-2006. Researchers at Yale University School of Medicine looked at 268 adults who reported using prescription antihistamines and compared them to 599 people who did not.
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The study found that, after adjusting for gender and age, those who used prescription antihistamines had significantly greater BMI, waist circumference, and insulin levels. Specifically, antihistamine users had an average BMI of 30 compared to a BMI of 28-29 for non-users. This suggests a correlation between antihistamine use and higher weight.
However, this study has limitations:
- It is a cross-sectional study, so it cannot prove causation.
- The sample size of antihistamine users was relatively small.
- Participants were using prescription antihistamines, suggesting they may have had more severe allergies.
- The study is over a decade old, and the types of antihistamines used may differ from those used today.
- The specific H1 antihistamines used by participants were not delineated.
Pediatric NAFLD Study
A single-center retrospective cohort study on children with a diagnosis of non-alcoholic fatty liver disease (NAFLD) examined the association between antihistamine (AH) use and obesity. Of the 32 participants, 13 used antihistamines, and 19 did not. The study found that antihistamine users had a mean increase in BMI percentile per year of 1.17 compared to a decrease of 0.06 in the comparison group (p = 0.0008). Antihistamine usage correlated with a mean increase in BMI z-score of 0.23 per year, as opposed to a decrease of 0.012 in the comparison group (p = 0.0016).
This study also found an 8.3-fold increase in BMI percentile/year in female antihistamine users compared to non-antihistamine female users. In males, the corresponding BMI percentile/year change in antihistamine users was 103.8-fold (p = 0.0007, p = 0.011, respectively).
Animal Studies
Animal studies have provided additional insights into the potential mechanisms by which antihistamines might affect weight. A study by Gasheva et al. implemented daily desloratadine treatment in rats for 16 weeks, equivalent to about 8 years in human life. The study found that prolonged intake of desloratadine induced an obesity-like phenotype and signs of metabolic syndrome. Rats experienced excessive weight gain with an increase in visceral, subcutaneous fat, and intracapsular brown fat. They also had high serum triglycerides, high fasting glucose, elevated liver to body weight ratio, and liver steatosis.
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Other Studies
A study on adults with data based on the 2005-2006 National Health and Nutrition Examination Survey Studies, which included 268 adults taking prescription H1 antihistamines, mainly cetirizine and fexofenadine, along with 599 adults matched by age and gender with controls. Body measurements, glucose, insulin concentrations, and lipid profiles were monitored. Antihistamine users had higher weight, BMI, waist circumference (p < 0.001), and insulin levels (p < 0.005).
In 2019, a study by Stark et al. retrospectively reviewed a large pediatric population prescribed antibiotics, H2 receptor antagonists (H2RA), or proton pump inhibitors (PPI) in the first two years of life and reviewed rates of obesity using a Cox proportional hazards regression model. Antibiotics, H2RA, and PPI use were associated with obesity, especially when participants received a 30-day supply.
Potential Mechanisms for Weight Gain
Several mechanisms have been proposed to explain the potential link between antihistamine use and weight gain:
- Increased Appetite: Histamine is known to decrease hunger by affecting the appetite control center in the brain. Antihistamines, by blocking histamine, could interfere with the "I'm full" signal, leading to overeating.
- Sedation and Reduced Activity: Some antihistamines, particularly older ones like diphenhydramine (Benadryl), can cause drowsiness and lethargy. This can decrease physical activity and lead to fewer calories burned.
- Metabolic Changes: Animal studies suggest that antihistamines may affect metabolism, leading to increased fat storage and insulin resistance.
- Lymphatic Function: Histamine plays a vital role as an endothelium-derived relaxing factor on mesenteric lymphatic vessels (MLVs), thereby regulating MLVs’ tone and resistance to lymph flow. The blockade of histamine’s intrinsic action modifies the flow-dependent post-prandial adaptation of mesenteric lymphatic contractility and tone. Long-term use of antihistamines leads to increased resistance to lymph flow, accumulation of lipids in the mesentery, and malabsorption.
Considerations for Different Antihistamines
Not all antihistamines are created equal. Older, first-generation antihistamines like diphenhydramine are more likely to cause sedation and other side effects compared to newer, second-generation antihistamines like cetirizine, loratadine, and fexofenadine.
Some experts suggest that cetirizine (Zyrtec) may be more likely to cause tiredness than loratadine (Claritin) or fexofenadine (Allegra). If sedation is a concern, non-sedating antihistamines may be a better choice.
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Practical Advice for Managing Weight While Taking Antihistamines
If you are concerned about weight gain while taking antihistamines, consider the following:
- Consult with an Allergist: Knowing what you're allergic to makes it easier to find prescription medications without all the side effects. Allergy shots don't have side effects like antihistamines do.
- Hydration: Make sure you keep yourself well hydrated whenever you're taking allergy medications, to prevent your mind from confusing thirst with hunger.
- Healthy Diet: If allergies or allergy medications are causing you to overeat, try to indulge in healthy food. There are a number of healthy foods that provide allergy relief and fight back hunger pangs at the same time.
- Exercise: Regular physical activity can help counteract the sedative effects of some antihistamines and burn extra calories.
- Alternative Treatments: Consider using nasal sprays or eyedrops for symptom relief instead of oral antihistamines.
- Medication Review: Talk to your healthcare provider about all of your medications, including over-the-counter ones, to identify potential contributors to weight gain.
- Switching Medications: Working with your healthcare provider to determine if there might be an appropriate alternate medication option with a lower risk of weight gain.
- Monitor for Rapid Weight Gain: If you ever notice rapid weight gain, contact your healthcare provider. Weight gain from medications is typically more gradual, happening over weeks or months. Rapid weight gain could indicate a more serious problem, such as worsening heart failure.