Why Antihistamines Cause Weight Gain

Antihistamines can be great at relieving allergy symptoms such as sneezing, runny nose, and itchy, watery eyes. While the drugs are generally regarded as safe, they are not without side effects.

One possible side effect—and one that people don't often think about—is the risk of weight gain with over-the-counter antihistamines like Allegra (fexofenadine) and Zyrtec (cetirizine).

Woman unhappy looking at a scale
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This article explores the association between antihistamines and weight gain and offers some rational explanations as to why this occurs.

What Are Antihistamines?

Antihistamines are medications that are commonly used to treat allergic rhinitis (hay fever), allergic conjunctivitis (allergy-related eye inflammation), and other allergy symptoms. They work by blocking the actions of histamine, a chemical released by the immune system in response to certain triggers.

Histamine is normally released when the body detects something that is harmful, such as an infection. Histamine is also important to the regulation of many bodily functions, including blood pressure, digestion, and the sleep-wake cycle.

However, when histamine is released inappropriately, such as during an allergy, it can cause itching, rash, breathing problems, and other adverse symptoms. Histamine is the primary cause of allergy symptoms.

Antihistamines work by binding to histamine receptors on the brain, spinal cord, smooth muscles, and other tissues of the body. Without these attachment points, histamine cannot act on the body and cause allergy symptoms.

Antihistamine and Weight Gain

Older antihistamines, such as Benadryl (diphenhydramine), are known to cause significant side effects such as drowsiness.

Newer antihistamines, like Allegra, were seen to be an advance in treatment, alleviating symptoms without the accompanying drowsiness. Even so, newer antihistamines like Allegra and Zyrtec are known to cause side effects like nausea, diarrhea, headache, back pain, and lethargy.

In recent years, another side effect has been added to the list: weight gain.

According to a 2010 study published in the journal Obesity, people who regularly take antihistamines are more likely to be overweight or obese than those who did not.

Of the almost 900 people involved in the study, prolonged antihistamine use was associated with a roughly 10% increase in weight, body mass index (BMI), and waist circumference, The risk was seen to be greatest with newer generation drugs like Allegra, Zyrtec, Claritin (loratadine), Clarinex (desloratadine), and Xyzal (levocetirizine).

BMI is a dated, flawed measure. It does not take into account factors such as body composition, ethnicity, sex, race, and age. 
Even though it is a biased measure, BMI is still widely used in the medical community because it’s an inexpensive and quick way to analyze a person’s potential health status and outcomes.

A 202O in the journal Children similarly concluded that the prolonged use of antihistamines in children was associated with a two-fold increase in BMI per year compared to kids who didn't take antihistamines.

The risk of weight gain is not entirely unknown with antihistamines. Older antihistamines such as Periactin (cyproheptadine) have long been used to increase appetite and weight gain in underweight children and people undergoing chemotherapy.

Possible Causes

The cause of the weight gain among antihistamine users is unclear. Some researchers theorize that antihistamines indirectly promote weight gain by increasing appetite). It is also possible that lethargy (the lack of energy) reported among antihistamine users can lead to reduced physical activity and increased weight.

Other scientists contend that the effect is more direct. According to a 2019 study from Texas A&M University, the prolonged use of Clarinex is associated with an increased risk of high cholesterol, high blood sugar, and insulin resistance.

It has been suggested that these metabolic changes cause weight gain by increasing subcutaneous fat in the abdomen and so-called "brown fat" that the body normally uses to insulate itself from cold.


Antihistamines are a class of drugs that are used to treat allergy symptoms. While newer-generation antihistamines like Allegra and Zyrtec are less likely to cause drowsiness than older drugs like Benadryl, they have been linked to an increased risk of weight gain in some users.

Some studies suggest that the prolonged use of newer-generation antihistamines can significantly increase body weight and waist circumference compared to people who don't use antihistamines. Even children who take antihistamines appear to be affected.

The cause of the weight gain is unknown. Some experts contend that antihistamines can indirectly cause weight gain by increasing appetite and lowering energy levels. Others believe that antihistamines cause metabolic changes that directly increase fat reserves in the body.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Ratliff JC, Barber JA, Palmese LB, Reutenauer EL, Tek C. Association of prescription H1 antihistamine use with obesity: results from the National Health and Nutrition Examination Survey. Obesity (Silver Spring). 2010;18(12):2398-400. doi:10.1038/oby.2010.176

  2. Saad M, Syed S, Ilyas M, Gashev AA. Antihistamines increase body mass index percentiles and Z-scores in Hispanic children. Children (Basel). 2020 Dec;7(12):305. doi:10.3390/children7120305

  3. Couluris M, Mayer J, Freyer D, Sandler E, Xu P, Krischer J. The effect of cyproheptadine hydrochloride (Periactin) and megestrol acetate (Megace) on weight in children with cancer/ treatment-related cachexia. J Pediatr Hematol Oncol. 2008 November; 30(11): 791-797. doi:10.1097/MPH.0b013e3181864a5e

  4. Gasheva OY, Nizamutdinova T, Hargrove L, et al. Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome. Am J Physiol Gastrointest Liver Physiol. 2019 Jan 1; 316(1):G217–27. doi:10.1152/ajpgi.00321.2018

By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.