Understanding Antihistamines: Definition, Types and Side Effects

Picture it: Springtime. The birds are singing their songs in the trees and all the glorious spring flowers are in bloom. But so are your allergies.

Your nose is running like it has a bus to catch and your eyes are red, teary, and itchy. So you reach for the box of antihistamine medication you keep in the bathroom cabinet for some relief.

Antihistamines are a crucial class of medications used to manage allergies and histamine reactions. They play a vital role in alleviating symptoms associated with various allergic conditions, providing relief to millions of people worldwide. 

There’s no doubt they are a God-send for anyone who has ever suffered allergic reactions when histamine levels rise to neutralize the offending pollen or food chemical.

As with all things, though, there is another side to the story. It’s especially important to understand the impact of antihistamine drugs on your body if you have a histamine disorder.

In this comprehensive guide, we'll help you understand what antihistamines are, the different types available, and how they work. We’ll also take a look at their potential side effects and what to watch out for if you have histamine intolerance.

 

What is Histamine?

Are you ready for a crash course in histamine physiology? Before you can understand antihistamine medication, you should probably know what histamine is. 

First off, histamine is a biogenic amine. That is, it’s a chemical naturally produced by a variety of cells throughout the body. 

Histamine has many functions in several areas, including (1):

• Acting as a chemical messenger between the immune system and other cells.
• Stomach acid secretion.
• Digestion.
• Blood cell production.
• Regulating your sleep-wake cycles (your circadian rhythm).
• Cognition and brain function.
• Plays a key role in the body’s inflammatory response.

 

When is Histamine Released?

Although histamine’s functions range from aiding digestion to supporting healthy sleep patterns, it is most well known for its role in triggering allergic reactions. 

When your immune cells detect a potential threat like pollen or a foreign chemical, they release histamine into the bloodstream. In turn, histamine sounds the alarm, setting off a chain of events to neutralize the problem.

Let’s go back to our springtime example. It’s a wonderful time of year when nature springs (excuse the pun) back to life. But for many people, it means seasonal allergies. In this case, the pollen from flowering plants is picked up by the wind and we can’t avoid inhaling it.

For people with pollen allergies, the immune system kicks into high gear. The proteins in the pollen trigger the release of histamine which causes a runny nose, sneezing, and watery, itchy eyes.

A histamine reaction can be triggered by any number of things including food, medication, and dust particles. Your body also responds in a variety of ways from bloating to diarrhea, heart palpitations to high blood pressure, and headaches to hives.

 

The Role of Histamine Receptors in Allergic Reactions

For histamine to cause an immune response it must bind to a specific location on the cells. These sites are called histamine receptors of which there are four different kinds—H1, H2, H3, and H4 (2). 

It can be compared to a lock-and-key mechanism, where histamine is the key that slots into the histamine receptor, or lock, and turns on a specific immune response.

The type of reaction you experience depends on which receptor the histamine binds to:

H1 Receptors are responsible for your typical allergic reactions causing symptoms like itching, flushing, low blood pressure, rapid heart rate, and difficulty breathing. They are located in many different tissues throughout the body including nerves, airways, and blood vessels.

H2 Receptors occur mostly in the gut, smooth muscle cells, and the heart. When histamine binds to these sites it causes gastric acid secretion, headaches, vascular permeability, and low blood pressure.

H3 Receptors are found in the brain and spinal cord. They influence the release of neurotransmitters like serotonin and dopamine which affect your mood and behavior. They are also involved in body temperature changes.

H4 Receptors are involved in the regulation of all other immune cells, activating their functions as well as inhibiting them.

 

Understanding Antihistamine Medications

Now, with a basic understanding of what histamine is and how it works in your body, we can move on and find out how antihistamine medication works.

Antihistamines are exactly what their name suggests—substances used to treat allergy symptoms by blocking the effects of histamine. They do so by binding to either the H1 or H2 histamine receptors (3).

 

Types of Antihistamines

Older H1 histamine blockers, referred to as first-generation antihistamines, often cause drowsiness and are usually used for short-term allergy relief or as sleep aids. Newer H1 blocking medications are called second-generation antihistamines. They are less likely to make you drowsy, making them the preferred choice for daily use. 

H1 Antihistamines are used to treat the following allergic reactions:

• Hay fever or allergic rhinitis - sneezing, itchy nose, watery and itchy eyes, coughing, and trouble breathing.
• Allergic conjunctivitis - burning, itchy, puffy, red, or watering eyes. 
• Allergic skin reactions - itchy skin, rash, burning, or blisters.
• Sinusitis - headache, pain in the sinus cavities, runny nose, and post-nasal drip.
• Urticaria - itchy and swelling on the skin resulting in hives.
• Angioedema - swelling under the skin.
• Atopic dermatitis or eczema - dry, itchy, and inflamed skin.
• Bronchitis - swelling of the airways, making it difficult to breathe.
• Motion sickness
• Nausea
• Vomiting

H2 Antihistamines are useful in the following conditions:

• Peptic ulcer
• Acid reflux
• Gastritis

Antihistamines are available in various forms, including oral tablets, liquids, nasal sprays, and eye drops. While generally safe for most people, it's important to consult with a healthcare professional before you take any new medication.

 

Over-the-Counter Antihistamines

Many antihistamine drugs are available over the counter, making them easily accessible for managing common allergies. These medications are suitable for treating mild to moderate allergy symptoms and can be used as needed or daily during allergy seasons.

 

Prescription Antihistamines

In some cases, stronger prescription antihistamines may be necessary. These are typically recommended for severe allergies or when over-the-counter options prove ineffective. A healthcare provider can determine if prescription antihistamine medication is appropriate based on your symptoms and medical history.

 

Natural Antihistamines

Natural antihistamines are compounds found in certain foods and herbs that may help reduce allergy symptoms without the need for over-the-counter medications. Some popular natural antihistamines include quercetin, found in apples, onions, and berries; bromelain, an enzyme in pineapple; and stinging nettle, a plant used in traditional medicine (4,5). 

Other potentially beneficial options include vitamin C-rich foods like bell peppers, as well as butterbur and spirulina supplements (6). Green tea, with its antioxidant properties, may also help alleviate allergy symptoms (7). 

While these natural alternatives can be highly effective for some people, while maintaining strong potency and efficacy, it's important to always consult with a healthcare professional before making any changes to your supplement and medication routine, particularly if you're experiencing severe reactions.

 

Side Effects of Antihistamines

Most drugs can potentially cause side effects in some people. Antihistamines are no exception. Common side effects of prescription and over-the-counter antihistamines can vary depending on the type and your individual response to them (8). They include:

• Drowsiness: Especially common with first-generation antihistamines.
• Dry mouth, eyes, and nose
• Blurred vision
• Constipation 
• Difficulty urinating
• Dizziness
• Headache
• Increased appetite and weight gain
• Thickening of mucus in the airways

Less common but more serious side effects of antihistamine drugs can include:

• Rapid heart rate
• Confusion or agitation (particularly in older adults)
• Difficulty concentrating
• Mood changes
• Tremors
• Seizures (rare)

Long-term use or overuse of antihistamine drugs may lead to:

• Increased tolerance and reduced effectiveness.
• Rebound congestion— especially with nasal sprays.
• Potential cognitive decline in older adults has been observed with long-term use of first-generation antihistamines.

It's important to note that second-generation antihistamines generally have fewer side effects than first-generation ones. Always follow recommended dosages and consult a healthcare provider if side effects persist or worsen.

Additionally, consulting your healthcare professional about switching to natural antihistamines can be a viable option for minimizing the side-effects and long-term effects of prescription or over-the-counter antihistamine medications.

 

How Antihistamines Affect Histamine Intolerance

If you have histamine intolerance or histamine sensitivity, you're likely wondering if antihistamine drugs are useful for lowering high histamine levels. The answer to this question is complex (9). 

Even though your symptoms may be similar to the typical characteristics of allergic reactions, your histamine reaction can occur even without the usual triggers. That’s because histamine intolerance is a condition where the body has difficulty breaking down histamine, leading to an accumulation. 

Sometimes, you may even experience what is referred to as a "histamine dump," where the body releases large amounts of histamine, causing severe symptoms, including headaches, digestive issues, and skin reactions. 

Histamine sensitivity and antihistamine medication have a complicated relationship (10). On the one hand, the drugs can provide temporary relief for some of your symptoms, such as headaches, hives, or nasal congestion. 

On the other hand, simply blocking histamine receptors is not a cure. Antihistamines don't address the root cause of histamine intolerance—insufficient production of diamine oxidase (DAO), the enzyme responsible for breaking down histamine.

Furthermore, regular use of antihistamines might mask underlying histamine intolerance, potentially delaying proper diagnosis and treatment, which is hard enough to get as it is.

Finally, you may even react poorly to certain antihistamines, as some of these medications can inhibit DAO activity, making the situation worse.

For some people with histamine intolerance, antihistamines might be part of a broader management strategy that includes dietary changes, enzyme supplementation, and identifying trigger factors.

Once again, discussing natural alternatives with your doctor may minimize the negative outcomes of this. It's important to keep in mind that even when it comes to natural alternatives, you want to look for specifics such as antihistamines that stabilize mast cells which provides greater regulation and homeostasis within the body, compared to simply blocking the release of histamine using histamine blockers, which may produce a rebound reaction once the drug is ceased.

 

Managing Histamine Levels

In short, relying on prescription or over-the-counter antihistamines as your sole method for managing histamine intolerance is generally not recommended. Managing histamine levels involves a multi-faceted approach, of which the main points are highlighted below:

#1 Low-histamine diet

Some foods naturally contain high levels of histamine. They include aged cheeses, fermented products, cured meats and certain vegetables.

Other foods, like citrus fruits, tomatoes and chocolate, trigger the release of histamine in your body.

The more of these foods you eat, the higher your histamine levels, and the more likely you are to experience a symptom flareup. 

To limit the amount of histamine in your system it is best to avoid these foods and focus on fresh, unprocessed foods and proper food storage to prevent histamine buildup.

Click on the button below to get a comprehensive low-histamine food list to get you started on your healing journey.

 

 

Get the low histamine foods list

 

 

#2 Enzyme supplementation

Diamine oxidase supplements can help break down histamine in the digestive tract. They are useful for managing histamine levels and preventing symptoms when you take them before consuming a histamine-containing meal.

 

#3 Identify and address triggers

The best way to figure out what causes your symptoms is to keep a food and symptom diary. Also include factors such as stress, medication, and potential environmental triggers. You can get one free with my low histamine foods list by clicking above.

 

#4 Support gut health

Since a significant part of your immune system is found in the gut, taking care of your digestive health is one of the first steps to overcoming histamine intolerance. Low-histamine probiotics may help balance gut bacteria and reduce histamine production. It's important to avoid using just any probiotic blend, as most strains do naturally produce histamine which can be problematic for those with histamine intolerance. Opt only for low histamine strains to ensure you're rebalancing your microbiome in a way that's right for you.

 

#4 Lifestyle modifications

Stress, sleep, and exercise affect your immune system and can make your histamine intolerance worse. Manage stress through techniques like meditation or yoga, get enough sleep to support overall health and histamine regulation, and choose exercise that doesn’t trigger a cascade of histamine-producing reactions.

 

#5 Medication management

Some medications affect histamine levels. Certain painkillers, heart medication, metformin, and antidepressants are just some of the drugs that can trigger histamine intolerance symptoms. Work with your healthcare provider to adjust medications that may affect histamine levels.

Everyone’s experience of histamine intolerance is different. While the core management techniques listed above may bring some relief from your symptoms, there are other aspects you may need to consider. It is also not a static condition with a single cure. The multifaceted nature of the condition means you may have to adjust your management plan over time.

Trying to overcome histamine intolerance on your own can be overwhelming. Discussing with a healthcare provider or registered dietitian experienced in histamine intolerance, or using a guided approach for solving histamine intolerance is a helpful way to get your strategy in check and ensure you keep moving forward with your health.

 

Antihistamines Alone are not a Cure for Histamine Intolerance

Antihistamine drugs are a handy way of stopping allergic reactions in their tracks for many people. Yet, if you have histamine intolerance, the solution is not so simple.

Histamine medication prevents the immune signal from binding to histamine receptors. In this way, it can no longer initiate an immune response. Normally, this isn’t a problem because DAO enzymes deactivate the histamine.

When histamine is prevented from unlocking an allergic reaction when you have histamine sensitivity, it causes a build up of histamine, which, in turn, triggers more severe symptoms.

While antihistamines can be part of your management strategy, you must also consider a low histamine diet, stress management, the type of medication you take, and gut health. 

Additionally, opting for a natural anti-histamine that works through the stabilization of mast cells can prevent a rebound effect and optimize positive outcomes.

Remember, a holistic approach to histamine intolerance is the best way to reduce histamine levels in your body and bring about healing.

 

References

 

1. National Center for Biotechnology Information. (2019). Histamine and histamine intolerance. In StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557790/

2. Kumar, P., & Allam, M. (2018). Histamine intolerance: A comprehensive review. Journal of Clinical Medicine, 7(10), 1-12. https://doi.org/10.3390/jcm7100332

3. Santos, J., & Kuehn, B. (2018). Histamine intolerance: Pathophysiology, diagnosis, and management. In StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK538188/

4. Gibson, P. R., & Muir, J. G. (2019). Food intolerance: A review. Gastroenterology & Hepatology, 15(2), 85-97. https://doi.org/10.1016/j.gastrohep.2018.12.003

5. Gomez, J. M., & Velasco, C. (2020). The role of histamine in gastrointestinal disorders. International Journal of Molecular Sciences, 21(4), 1-15. https://doi.org/10.3390/ijms21041016

6. Nguyen, H., & Lee, J. H. (2023). Advances in histamine research: Implications for therapy. Frontiers in Pharmacology, 14, 1-12. https://doi.org/10.3389/fphar.2023.9970132

7. Li, L., & Zhang, Y. (2024). Histamine intolerance and its impact on quality of life: A review. BJP Open, 5(1), 1-10. https://doi.org/10.1186/s43088-024-00464-2

8. Mayo Clinic. (2023). Antihistamine (oral route, parenteral route, rectal route) side effects. Retrieved from https://www.mayoclinic.org/drugs-supplements/antihistamine-oral-route-parenteral-route-rectal-route/side-effects/drg-20070373

9. Gonzalez, C., & De La Torre, M. (2015). Histamine: Histamine intoxication and intolerance. Allergologia et Immunopathologia, 43(4), 409-417. https://doi.org/10.1016/j.aller.2015.01.003

10. Choi, Y., & Kim, J. (2023). Treatments of histamine intolerance: Antihistamine and beyond. Molecules, 12(3), 454. https://doi.org/10.3390/molecules12030454