Benadryl, Allegra, Zyrtec, and Claritin are commonly available antihistamines in the United States, both over the counter and by prescription. Individuals experiencing chronic sinus congestion, runny noses, hives, or occasional insomnia recognize just how effective these medications can be in handling such conditions. Because histamine receptors are widespread in the body, these drugs can have several effects, including weight gain. In today’s article, I will help you better understand the relationship between anti-histamines and weight gain as well as how histamine intolerance/MCAS fits into the weight gain puzzle.

Why Does Histamine Cause Weight Gain? How Histamine Affects Metabolism

Histamine is a chemical involved in various bodily functions, such as regulating the immune response, acting as a neurotransmitter, controlling stomach acid production, and much more. Its role in weight gain is linked to its complex interactions with appetite regulation, metabolism, inflammation, disruption to hormone balance, and the immune system.

Histamine itself doesn’t directly cause weight gain, but it does play a key role in several bodily functions that impact our metabolism and body weight.

In the brain, particularly within the hypothalamus, histamine suppresses appetite.(*) When the action of histamine is reduced or its receptors are blocked (for example, through the use of certain antihistamines), this can lead to increased hunger, more frequent eating, and a higher intake of calories.(*)

Histamine also affects the function of fat cells, influencing fat storage and usage.(*) Therefore, blocking histamine receptors, as some antihistamines do, can result in increased fat accumulation.(*) This is in part thanks to the effect histamine has on the hormone Leptin.

Why do antihistamines cause weight gain? Histamine decreases our hunger by, in part, affecting the appetite control center in our brains(*)

Antihistamines and Weight Gain-

Antihistamines are commonly prescribed to manage symptoms of histamine intolerance including things like allergies, rashes, hives and digestive issues. While these medications are effective in reducing symptoms by blocking histamine receptors, they also come with their own set of consequences. Not only do antihistamines not treat the root cause, but taking antihistamines is known to cause significant weight gain. (*),(*),(*)

Histamine can influence weight gain through its interaction with the body’s central nervous system through our fat cells and from its effects on inflammation. (*) Histamine receptors (H1, H2, H3, H4)  are found in various parts of the body, including the brain. A 2010 research published in the Journal of Pharmacology and Experimental Therapeutics has looked at the relationship between the histamine H3 receptor and eating behavior.(*) What they found was that

In another study published in 2010 Obesity, common prescription H1 antihistamine medications, such as Claritin, Zyrtec and Allegra, contribute to weight gain.(*)

The Science of Histamine and Weight Gain

Appetite Regulation: Histamine in the hypothalamus helps suppress appetite. Blocking histamine receptors, as some antihistamines do, can reduce this suppression, leading to increased hunger and caloric intake. In other words. Antihistamines cause weight gain because they increase our hunger mechanisms.

Metabolism: Histamine also influences energy expenditure. Histamine helps regulate metabolism, aiding the body in burning calories efficiently. By affecting the central nervous system, histamines can enhance the body’s ability to burn calories efficiently.

When histamine activity is inhibited, as in the case of antihistamines, it can slow down the metabolic rate, making weight gain more likely. This is another way in which long-term use of antihistamines causes weight gain.

Gut Microbiota: Histamine intolerance (HIT) is due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO). Without proper DAO levels of histamine from foods we eat can raise to high levels. These changes to the gut microbiome, coupled with medications that are damaging to the gut microbiome, as well as DAO deficiency, can also lead to more histamine producing bacteria compared to histamine degrading gut bacteria. This is another way we see problems with histamine metabolism causing metabolic imbalances and weight gain. (*)

Fat Storage: Histamine can impact the function of fat cells directly. Blocking histamine receptors, as some antihistamines do, can result in increased fat accumulation. Using antihistamines or experiencing disruptions in normal histamine function can lead to weight gain due to their combined effects on appetite, metabolism, and fat storage.

Sedation: If you have taken an antihistamine, then you know how they can relax and sedate the body. I don’t know about you, but if I was sedated I’m not exactly in the mood to do a 5,000-calorie row, go for a run, or perform a bunch of kettlebell swings. Some antihistamines may cause sedation, leading to decreased levels of physical activity leading to fewer calories being burned. More calories being taken in with fewer calories being burned is a surefire way of gaining weight.

Adipocyte Function: Histamine receptors are present on fat cells (adipocytes). Through these receptors, histamine can impact adipocyte function, influencing how fat is stored used or not used for energy. I’ll talk more about this in the section below as it relates to Leptin.

Inflammation and Immunity: Chronic, low-grade inflammation is linked to weight gain and obesity. Histamine, being an immune mediator, can influence inflammatory responses throughout the body.

Hormones- Through various Cross-Talk mechanisms, not only will Hormonal imbalances in the Adrenal Glands, Sex Hormones, Thyroid and Leptin cause Histamine intolerance and Mast Cell Activation, but Mast cell Activation and Histamine intolerance can affect these hormones.

Persistent excess histamine release (e.g., due to allergies, inflammatory conditions, or histamine Intolerance) can promote chronic inflammation, thereby contributing to weight gain. Chronic inflammation is not the only way that histamine can play a role in weight gain, lets take a look at some of the other ways histamine is connected to weight gain.

Histamine Intolerance, Estrogen Dominance and Weight Gain

Estrogen dominance describes a state where there is an excess of estrogen relative to progesterone. This imbalance can occur due to various factors, such as hormonal imbalances, environmental estrogens (xenoestrogens), or insufficient progesterone production.

Common symptoms of estrogen dominance include weight gain (particularly in the hips and thighs), mood swings, PCOS, menstrual irregularities, bloating, and headaches. These symptoms can also overlap with those related to histamine intolerance, such as inflammation, swelling, and digestive issues.

Those undergoing hormone replacement therapy, might notice that managing their weight becomes more difficult because hormone replacement therapy increases the risk of developing estrogne dominance. How does estrogen dominance tie into histamine levels? Here it is… Both estrogen and histamine can amplify each other’s effects. Elevated estrogen levels can increase histamine release by mast cells, which in turn can exacerbate symptoms of histamine intolerance.

High levels of histamine can lead to increased inflammation in the body. Estrogen dominance is also associated with a pro-inflammatory state, which can exacerbate symptoms tied to both conditions.

Estrogen dominance can directly affect weight gain. Estrogen influences fat distribution in the body and can promote the storage of fat in tissues.(*) As such, women, particularly those with conditions like polycystic ovary syndrome (PCOS) or endometriosis or woman on birth control pills. You Can learn more about the connection between estrogen and Histamine here.

Histamine Intolerance Your Thyroid and Weight Gain

Histamine intolerance and hypothyroidism are also interconnected more than you might think. The symptoms of histamine intolerance (headaches, digestive issues, skin rashes, fatigue) can overlap with those of hypothyroidism (fatigue, depression, digestive disturbances, heart palpitations, weight gain, menstrual cycle changes, and sleep disturbances ). This similarity can make it challenging to identify and treat both conditions accurately.

Histamine is metabolized primarily by the enzyme diamine oxidase (DAO). Thyroid hormones can influence the production and activity of DAO.(*) Hypothyroidism can result in decreased DAO activity, leading to impaired histamine breakdown and, consequently, increased levels of histamine throughout body.

You can learn more about natural ways to support DAO levels here.

Some studies suggest that Histamine can interfere with thyroid hormone production by inhibiting the enzyme’s activity that converts thyroxine (T4) to the active form of thyroid hormone, triiodothyronine (T3).(*) This is called Low T3 and after Hashimotos disease, its one of the most overlooked reasons hypothyroid symptoms. 

The reason why thryoid function is so important to those with MCAS and Histamine intolerance has to do with thyroid hormones affect   the clearance of histamine from the body. Lower levels of thyroid hormones as in the case of hypothyroidism could contribute to increased histamine levels, leading to symptoms of histamine intolerance. Another way thyroid problems are tied into MCAS and Histamine Intolerance has do with our friend inflammation.

Hypothyroidism is often associated with increased systemic inflammation. We already know that histamine can cause inflammation throughout the body, but inflammation can also activate mast cells whicn then degranulate (release of histamine).

The number one cause of Hypothyroidism in the United states is autoimmune conditions, better known as Hashimoto’s thyroiditis. Autoimmune conditions can lead to increased mast cell activity and histamine release.

Chronic inflammation and immune dysregulation can contribute to both histamine intolerance and thyroid dysfunction. The more sluggish your thyroid becomes (Hypothyroidism), the more weight you gain.

Histamine Intolerance and Adrenal Glands

Histamine is also influenced by our adrenal glands and specificaly cortisol. High cortisol levels can significantly influence histamine levels and mast cell activation in the body in several ways.

Cortisol is a hormone produced by the adrenal glands in response to stress. One of cortisol major jobs is to modulate the immune response and reduce inflammation.

When cortisol levels are normal and within a healthy range, Cortisol has an inhibitory effect on mast cell degranulation. This means that it has a stablizing affect on mast cells and prevents them from rupturing and releasing all their inflammatory chemicals. But what happens when cortisol levels are not normal?, what if your doctor tested your cortisol levels and they came back elevated? Lets take a look at what happens when you have high cortisol levels

High Cortisol and Mast Cells

Unders chronic stress (as see with high levels of cortisol), the affects on mast cells are very different. High cortisol levels contribute to mast cell activation and symptoms such as difficulty breathing, rapid drop in blood pressure, and swelling of the throat, sneezing, itching, and nasal congestion, gastrointestinal issues, and neurological disturbances.

High cortisol is also associated with inflammation which is why high cortisol levels have a catabolic affect on the body (Breakdown).  Chronic inflammation can increase the number of mast cells in tissues.

Understanding this relationship is crucial for managing stress-related health issues, histamine intolerance, and allergic responses. 

You Can learn more about the affects of High Cortisol on Mast Cells and Histamine intolerance here

Histamine Intolerance and Leptin

Chronic inflammation is linked to both leptin resistance and obesity. Histamine’s role in inflammation has also now been shown to affect leptin signaling pathways.(*)

In conditions characterized by high leptin levels due to obesity, the inflammatory response may be activated further, potentially creating a feed-forward loop where both histamine and leptin interact in promoting inflammation and metabolic dysregulation.

Both histamine and leptin act within the central nervous system. Histamine is a neurotransmitter that can modulate neuronal circuits involved in feeding behavior. Leptin also acts in the brain to exert its effects on appetite and energy expenditure.(*)

Interactions between histamine and Leptin may occur at the level of central nervous system signaling, impacting both appetite regulation and energy balance.(*)

Studies also show that high level of Histamine as in the case of histamine intolerance can influence leptin’s role in appetite regulation through pathways involving appetite suppression, leptin sensitivity, inflammation, and central nervous system interactions. 

Here’s What You Need To Remember About Histamine and Weight Gain

Understanding histamine intolerance and its impact on weight gain necessitates a comprehensive investigation. Understanding our metabolism, Hormone levels, stress levels, Leptin resistance, Thyroid support, medications and Gut micobiome health.

This interconnected web of factors highlights the complexity of weight management among those struggling with weight gain caused by antihistamine or histamine intolerance. Effective management often requires a multi-faceted approach, addressing underlying imbalances and making thoughtful adjustments to diet  lifestyle and medication you are using.

Working with Certified Functional Medicine Practitioner If you have histamine intolerance and MCAS are critical first steps and the good news is with proper testing and treatment, managing histamine levels and addressing related metabolic and hormonal issues, individuals can better navigate the challenges of weight management and improve their overall well-being.