Histamine, Leaky Gut & Migraines: How the Gut–Brain Connection Impacts Headaches

Leaky gut can cause migraines and headaches within 1-3 hours of eating a certain "trigger."

When we think of histamine, allergies often come to mind, but emerging research suggests that histamine and gut health play surprising roles in headache and migraine patterns. New studies show that inflammation, microbiome balance, and histamine metabolism may all influence how sensitive the brain’s pain pathways become. This blog explores how histamine intolerance and leaky gut syndrome contribute to migraines, as well as how restoring balance in the body can bring lasting relief.

What is Histamine Intolerance?

Histamine intolerance occurs when the body struggles to clear histamine efficiently, causing symptoms at otherwise normal exposure levels. These may include:

• Headache or migraine

• Facial flushing, dizziness, or nasal congestion

• Digestive upset or bloating

• Hives or itchy skin

This condition is still being researched. Differences in food histamine levels, testing methods, and symptom overlap with allergies make diagnosis challenging. Still, early evidence points to a connection worth exploring, particularly when migraine symptoms appear linked to certain foods or gut issues.

What is Histamine?

Histamine is a natural chemical messenger involved in immune response, digestion, and neurotransmission. It’s produced from the amino acid histidine and broken down by enzymes (primarily diamine oxidase--DAO and histamine N-methyltransferase). If histamine builds up faster than it can be broken down, it may cause symptoms like facial flushing, nasal congestion, digestive upset, and headaches. This imbalance, known as histamine intolerance, can overlap with migraines in sensitive individuals.

The Link Between Histamine and Migraines

Research evidence: Infusing histamine directly into human subjects has been shown to reliably trigger migraine-like headaches, particularly in people already prone to migraines. Histamine acts through H₁ receptors in cranial blood vessels, leading to vasodilation and activation of the trigeminovascular system, a key pathway in migraine pain.

High histamine levels also amplify inflammation around the nerves and vessels that transmit migraine pain. Some individuals experience migraines after eating histamine-rich foods such as aged cheeses, red wine, processed meats, and fermented products.

In fact, a small double-blind study found that supplementing with DAO enzyme (which helps break down histamine) shortened migraine duration by about 1.4 hours per month, suggesting that supporting histamine clearance may improve symptoms for some patients.

What is Leaky Gut?

Leaky gut, also known as increased intestinal permeability, occurs when the lining of the small intestine becomes compromised. Normally, this lining acts as a selective barrier, allowing nutrients to pass into the bloodstream while keeping harmful substances like toxins, bacteria, and undigested food particles out. When the gut barrier is weakened (due to factors such as chronic stress, inflammation, poor diet, or imbalances in gut bacteria) these substances can “leak” into the bloodstream. This triggers systemic immune activation and low-grade inflammation, which can affect organs and tissues throughout the body, including the brain. In the context of migraines, this inflammatory cascade can sensitize pain pathways, disrupt neurotransmitter balance (like serotonin), and contribute to headache frequency and severity.

Common signs of leaky gut include:

• Bloating or food sensitivities

• Fatigue or brain fog

• Skin issues like acne or eczema

• Frequent headaches or migraines

Our Personal Experience with Leaky Gut and Migraines

Our own experience with leaky gut included ocular migraines, facial flushing and dry, irritated eyes. Our symptoms worsened with increased stress and triggering foods.

At peak "awfulness" of our leaky gut experience, certain foods would trigger an ocular migraine within 2 hours of eating. Through food journaling, we were able to pinpoint which foods we needed to take a break from and reintroduce once our gut lining had healed. We also worked with a nutritionist who specialized in functional medicine and gut health. We do not recommend trying to "figure out" leaky gut on your own.

As a reference, leaky gut may take 3-6 months of consistent work to heal.

Easy ways to support gut health at home:

• Focus on whole, unprocessed foods

• Incorporate homemade bone broth

• Reduce alcohol, sugar, and processed fats

• Manage stress (as chronic cortisol weakens the gut lining)

• Keep a food journal to track reactions

Common Food Sensitivity Groups to Pay Attention to When Journaling:

• Dairy (milk, cheese, yogurt, butter)

• Gluten/Grains (wheat, barley, rye, spelt)

• Alcohol (beer, wine, spirits)

• Soy (soy milk, tofu, soy sauce, edamame)

  • *Often contains wheat/gluten

• Peanuts & Tree Nuts (peanuts, almonds, cashews, walnuts)

• Eggs (chicken eggs, baked goods containing eggs)

• Shellfish & Fish (shrimp, crab, tuna, salmon)

• Corn (corn products, corn syrup, popcorn)

• Nightshades (tomatoes, potatoes, peppers, eggplant)

• Caffeine (coffee, tea, energy drinks, chocolate)

When you strengthen the gut, you often calm inflammation, and that can translate to fewer migraine days and better energy overall.

Practical Takeaways

If you suspect histamine or gut issues may be worsening your headaches:

• Journal the symptoms and food intake for 2–4 weeks.

• Discuss DAO enzyme or gut-lining support with your provider.

• Rule out other causes such as allergies or caffeine headaches.

• Work with a clinician who understands both the neurological and digestive aspects of migraine care.

How Stability In Wellness Can Help

At Stability In Wellness in Jupiter, FL, we help migraine sufferers address the root causes of their symptoms, not just the pain itself. While hormone or histamine fluctuations can be internal triggers, many migraines are also linked to neuromuscular tension, jaw dysfunction, and poor postural alignment. We also understand that headaches may be correlated with hormones or food sensitivities, and will refer you to the appropriate provider that can help.

If you’re looking for a natural, root-cause-focused approach to migraines, contact Stability In Wellness to schedule your evaluation today.

References

1. Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. The American Journal of Clinical Nutrition, 85(5), 1185–1196. ScienceDirect

2. Schink, M., Konturek, P. C., Tietz, E., Dieterich, W., & Zopf, Y. (2018). Microbial patterns in patients with histamine intolerance. Journal of Physiology and Pharmacology, 69(4), 579–593. PMC

3. Wantke, F., Gotz, M., & Jarisch, R. (1993). Histamine-free diet: Treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clinical and Experimental Allergy, 23(12), 982–985. AAAAI

4. Martami, F., et al. (2021). Association of intestinal permeability and gut microbiota with migraine: A case-control study. Journal of Clinical Medicine, 10(10), 2158. PubMed

5. Izquierdo-Casas, J., et al. (2018). Diamine oxidase supplementation in migraine: A randomized double-blind trial. Cephalalgia, 38(1), 155–163. PubMed

6. Mavroudi, A., et al. (2020). The role of histamine in migraine mechanisms and management. Headache: The Journal of Head and Face Pain, 60(2), 389–401. Headache Journal