Do Antihistamines Cause Weight Gain?

One important element of helping patients who are seeking to manage their weight is to understand the potential side effects of non-weight-loss-related medications they take. There’s a good chance you have patients who take antihistamines: the Asthma and Allergy Foundation of America reports that more than 82 million people in the U.S. were diagnosed with seasonal allergic rhinitis in 2024, and about half of those who seek treatment rely on over-the-counter or prescription antihistamines. A widely cited and publicized research paper from 2010 linked antihistamines to weight gain. What have we learned since then, and how should that shape the way you counsel patients about their options?

What Does the Research Say About Antihistamines and Weight Gain?

The short answer: the available research suggests a correlation between antihistamine use and higher body weight, but not established causation. Two studies anchor the evidence — a cross-sectional NHANES analysis from 2010 in adults and a small 2020 pediatric study — and both should be read with their limitations in mind.

The primary study demonstrating the relationship between antihistamines and weight gain was published in the journal Obesity in 2010. It used the 2005-2006 National Health and Nutrition Examination Survey (NHANES) data set to study the issue. The NHANES is an annual health survey that the National Center for Health Statistics (NCHS) conducts in person across the U.S., then makes the data available to the public for research.

For the 2010 study, Yale School of Medicine researchers looked at NHANES data on 268 adults (174 female and 94 male) who reported the use of prescription antihistamines such as Zyrtec and Allegra and compared them to 599 people (401 female and 198 male) who did not. (Note that Zyrec and Allegra were available only by prescription at that time. They are both now available over the counter.)

The researchers looked at differences in body mass index (BMI), cholesterol, and glucose levels. After a statistical adjustment for gender and age, they found that those who used prescription antihistamines displayed significantly greater BMI, waist circumference, and insulin levels but no differences were seen between cholesterol and fasting glucose levels. This demonstrates a correlation between using antihistamines and higher weight.

Specifically, antihistamine users had an average BMI of 30 versus a BMI of 28-29 for men and women who did not use the drugs. In pounds, men who used antihistamines had an average weight of 214 pounds versus 192, and women had an average of 176 pounds versus 166 pounds.

This seems to suggest that antihistamines could be a factor in weight gain. However, the vital thing to note is that this is a cross-sectional study, and just because antihistamine use and weight gain are related, it doesn’t mean one causes the other. Also, the study looked at only prescription antihistamines such as Zyrtec and Allegra, and today, there are many other options available.

Further Research on Antihistamines and Weight Gain in Children

A small but more recent study published in the journal Children explored BMI in Hispanic children taking antihistamines.

The study divided 32 children with non-alcoholic fatty liver disease (NAFLD) into two groups: 13 who used antihistamines and 19 who did not. The BMI of those who used antihistamines increased by an average of 1.17 per year, compared with 0.06 in those who did not use them. There was no difference in triglycerides, glucose, and liver enzymes. The researchers concluded that antihistamine use increases BMI percentiles over time and is associated with obesity in children.

Aside from this small study, there is not much new evidence of the correlation since the 2010 study.

Why Might Antihistamines Cause Weight Gain?

Histamine is a signaling molecule with a physiological role well beyond the allergic cascade: among other things, it helps regulate appetite and satiety in the hypothalamus and plays a central role in maintaining wakefulness. Blocking histamine at the H1 receptor is what makes antihistamines effective against allergy symptoms, but the same blockade has downstream effects on hunger signaling and alertness that plausibly translate into modest weight gain over time.

Because histamine decreases hunger in part by acting on the appetite control center in the brain, an antihistamine can have the opposite effect, interfering with satiety signals and contributing to overeating. H1 antihistamines also affect wakefulness, which is why first-generation agents such as diphenhydramine (Benadryl), chlorpheniramine, dimenhydrinate (Dramamine), and doxylamine (Unisom) tend to cause drowsiness and are sometimes prescribed for insomnia. That sedation can translate into reduced physical activity and lower daily energy expenditure.

Second-generation antihistamines — cetirizine (Zyrtec), desloratadine (Clarinex), fexofenadine (Allegra), and loratadine (Claritin) — are designed to minimize CNS penetration and sedation, and are generally considered safe for long-term use. Even so, cetirizine metabolites can produce a mild sedative effect in some patients. Antihistamines are also a common ingredient in multi-symptom cold and flu products, which is worth keeping in mind when reviewing what a patient is actually taking.

Which Antihistamines Are Most Likely to Cause Weight Gain?

There haven’t been any head-to-head studies comparing which antihistamines cause weight gain. The NHANES study did not single out any one specific antihistamine.

We can speculate that drowsiness caused by first-generation antihistamines could lead to reduced physical activity, so if drowsiness is an issue, second-generation medications would be preferred.Additionally, we know that anything that causes drowsiness by crossing the blood brain barrier likely affects the hypothalamic histamine receptors, modifying hunger signaling. Since weight gain is typically slow and based on many factors, using antihistamines for a longer period of time might contribute to weight gain more than using them briefly

In addition to antihistamines, antipsychotics like Zyprexa (olanzapine) have a significant antihistamine effect and are well known to result in dramatic weight gain.

Antihistamine Alternatives for Allergy and Cold Treatment

When a patient seeks treatment for allergy symptoms, make them aware of the risk for weight gain, especially if they are seeking a long-term solution. Instead, consider steering them toward nasal and ophthalmic antihistamines or topical corticosteroid sprays, many of which are available over the counter. If an oral antihistamine is an important part of the treatment plan, try to reach for a second generation, least sedation option for the shortest duration possible.

The common cold (and other viruses) may also prompt people to take antihistamines. There may be better options. Pediatrician Brittany Chan, MD, speaking to the American Medical Association, says that antihistamines are not proven to treat colds in children and can lead to hyperactivity. Instead, she advises giving honey to children over age one.

Adults with colds should select treatments that address only the symptoms they’re experiencing.

Managing Weight While Taking Antihistamines

Remind patients that, while taking antihistamines long-term, it’s a good idea to monitor weight, caloric intake and get adequate exercise.

Clinical Takeaways for Physicians

While occasionally taking a Benadryl for sleep probably won’t lead to significant weight gain, chronic use, especially of the first-generation antihistamines, can interfere with weight loss efforts. If a patient needs an antihistamine, reach for a second-generation product for the shortest duration of treatment.