Histamine is well known for its involvement in the immune response and as an instigator of inflammation. When mast cells containing histamine burst during the immune response, histamine is released setting off a cascade of symptoms such as the upper respiratory symptoms we associate with allergies, and skin irritations such as redness and itching. The lesser known roles of histamine are as a neurotransmitter that can affect sleep-wake cycles, and as a regulator of digestive function. Urinary testing provides clinically relevant information about histamine’s neurotransmitter and digestive effects. This can cause much confusion for providers as salivary results often differ from those in blood and may not correlate with symptoms of hay fever or food allergies. To help dispel common misconceptions about histamine we have compiled the most frequently asked questions related to urinary histamine testing.
What do elevations or depressions of histamine in urine indicate?
Urinary testing can give insight into the neurotransmitter functions of histamine. Histamine is an excitatory neurotransmitter involved in the sleep/wake cycle. Adequate levels promote wakefulness, a balanced circadian rhythm and learning and memory. Elevated histamine might contribute to anxiety or irritability or interfere with sleep. Low histamine can result in drowsiness and may affect digestive function and appetite control, learning, memory and mood.
Why does my patient with asthma/hives/allergy symptoms not have elevated urinary histamine?
Histamine levels in urine do not reliably correlate with allergic or inflammatory responses. Histamine released from basophilic and mastocytic cells is rapidly metabolized and excreted in other metabolic forms. Studies attempting to correlate urinary histamine to allergy or inflammatory symptoms have resulted in conflicting conclusions. During adverse reaction to foods, one study showed elevated urinary histamine, while another study did not. During asthma attack, one study found decreased histamine levels, while other studies showed increased levels. Differing results may be related to proximity of testing to symptoms. However, there are currently no studies that have investigated the best time to test urinary histamine following allergy or inflammatory symptoms. As of now, urinary histamine can not be used to evaluate these types of symptoms and whole blood testing may be a better option for this purpose.
Why did my patient have elevated whole blood histamine but normal urinary histamine even though they were tested on the same day?
It is typical to see differences in histamine levels when comparing different types of samples taken simultaneously. Most of the histamine released eventually gets methylated or deaminated, so only a small proportion of free histamine remains in the urine. Examples of the discrepancy between histamine tested from different fluids abound:
In one study, patients with asthma had normal blood and urine histamine but elevations in plasma. When given corticosteroids, the whole blood histamine was reduced and plasma levels normalized.
A research subject experiencing a severe allergic reaction to food had normal urine histamine and elevated plasma histamine.
If whole blood histamine is measured later in the day after urinary histamine is measured in the morning prior to any food intake, that could explain different results. Mucosal histamine reflected in urine is often low in fasting states when HCl is low. Histamine levels increase as the day progresses and HCl increases.
Which foods might elevate histamine?
The following foods have been shown to elevate urinary histamine:
- Cheeses: Parmesan, blue, Roquefort
- Vegetables: spinach, eggplant
- Red wines: Chianti, Burgundy
In general, foods containing high amounts of histamine include: alcohol, fermented beverages and foods, dried fruit, avocado, processed and smoked meat and aged cheeses. Additionally, the enzyme diamine oxidase (DAO), one of the enzymes responsible for breaking down histamine, is inactivated by alcohol and black or green tea. Certain medications can alter DAO production including NSAIDs, antidepressants, immune modulators, antiarrhythmics, and H2 blockers contributing to higher levels of histamine.
Can a specific disease or condition be responsible for elevated histamine in urine?
The available research reveals that the following diagnoses correlate with elevated histamine:
- Interstitial cystitis
- Urticarial pigmentosa
- Hyperemesis gravidarum
- Hartnup Disease (a.k.a. pellagra-like dermatitis)
Elevated histamine is not diagnostic of any of these conditions, but having one of these diagnoses can explain an elevation.
How can I help address elevated or depressed histamine levels for my patient?
Elevated histamine levels can be normalized by supplementing DAO, anti-inflammatory botanicals, MSM, and the cofactors for metabolism and conversion – SAMe, B2, and pyridoxal-5-phosphate (P5P). Depressed histamine levels can be boosted by supplementing the precursor histidine and by giving the cofactors for metabolism and conversion, P5P and SAMe.
Test your patients neurotransmitter balance now with the NeuroBasic Profile. Or delve further into neurotransmitter metabolism with the Comprehensive Neurotransmitter Profile.