Do you have runaway histamine? Some natural substances may help break histamine down or prevent its release. Could they help reduce the need for antihistamines? What does the science say? Read on to find out.
What Causes Histamine Reactions?
You may have gotten here from one of our previous articles on histamine intolerance. If so, then you know that having too much histamine in your body and not enough of the enzymes that degrade it can trigger uncomfortable inflammatory symptoms.
These allergy-like symptoms can range from skin rashes to headaches, and you can manage them by avoiding histamine-rich foods and substances that activate your mast cells.
If you haven’t already read our previous posts, you may want to check them out before reading on:
- What is Histamine? Definition, Function, Receptors & DAO
- 17 Histamine Health Effects: Cognition, Inflammation & Sleep
- Histamine Intolerance Symptoms: Could You Be Sensitive
- Low Histamine Diet: Does It Work? + Who Should Try It
- Foods High & Low in Histamine + Other Mast Cell Triggers
Mast cells use an enzyme called histidine decarboxylase (HDC) to make histamine out of the amino acid histidine. They then release histamine in response to a host of different triggers, including some foods, alcohol, insect bites, and more.
Many natural compounds are being investigated for their potential to interrupt this process, either by inhibiting HDC or stabilizing mast cells and preventing them from releasing histamine. In this post, we will explore these natural antihistamines so you can find the right one for you.
Forskolin is a compound extracted from a member of the mint family called Coleus forskohlii. It is most often used to promote weight loss, but it is also great for preventing asthma. It stabilizes mast cells and relaxes muscles in the lungs comparably to two common asthma drugs, sodium cromoglycate and beclomethasone [1, 2, 3, 4, 5].
Quercetin is a plant flavonoid and antioxidant. It is recognized as one of the best natural antihistamines out there. In one human trial, quercetin even outperformed Cromolyn, a mast cell-stabilizing drug; quercetin was more effective for prevention, while Cromolyn worked more quickly once the histamine reaction had already started [6, 7].
Astragalus is a medicinal plant also known as milk vetch. Its active compound astragalin is a powerful antioxidant that can stabilize mast cells in the intestines and nasal passages, so it may be worth a try for histamine problems in the gut and nose [7, 8, 9].
In a study of 48 adults, astragalus reduced the symptoms of allergic rhinitis. The authors did not specifically test the histamine levels of the patients, but they compared the effect of the astragalus supplement to the effect of a non-sedating antihistamine and found them very similar .
Insufficient Evidence to Recommend
The substances and supplements in this section have each produced positive results in at least one human trial, but these studies have been very small, poorly designed, or contradictory in some way, and more research is required to confirm their benefit. Talk to your doctor before starting any new supplement.
4) Vitamin C
In one study, 1 g of vitamin C directly decreased histamine in all 11 volunteers that it was given to; as vitamin C levels went back down, histamine levels increased. Oral doses can generally only get your blood vitamin C level up to 70-120 micromol/L; to this end, there’s not much of a difference between 400 mg and 2.5 g of vitamin C supplements per day [11, 12, 13, 14].
5) B. longum
People with histamine intolerance tend to have fewer bacteria of the Bifidobacteriaceae family than healthy controls, suggesting a role for these bacteria in healthy histamine metabolism in humans. One species in this family, Bifidobacterium longum, effectively suppresses allergic reactions in rats; it decreases expression of the H1R and HDC genes, which code for histamine receptor 1 and the histamine-producing enzyme histidine decarboxylase, respectively. A blend including B. longum has effectively reduced histamine in human subjects [15, 16].
6) B. infantis
Bifidobacterium longum ssp. infantis was previously thought to be a separate species from B. longum. This subspecies is sometimes included in probiotic blends that have effectively reduced histamine in human subjects .
Erythropoietin (EPO) is a hormone that stimulates red blood cell production, also called erythropoiesis. In a clinical trial of people with kidney disease, 8 out of 10 experienced a significant reduction of histamine and improvement in their itching symptoms during EPO therapy. Histamine levels increased again when the patients stopped EPO [17, 18].
8) Pancreatic Enzymes
According to one human study, supplementing with pancreatic enzymes may reduce histamine levels and improve the symptoms of histamine intolerance; the mechanism of this effect is unknown, and it has only been observed in a single human trial .
We recommend against using pancreatic enzymes without a doctor’s recommendation.
The methylxanthines are a group of related compounds that include caffeine, theobromine, and theophylline. Xanthine occurs naturally in the human body, while the methylxanthines, which stabilize mast cells, are under investigation as potential asthma treatments. Human trials on theophylline found that it was successfully absorbed into the bloodstream and opened up the airways of asthmatic patients; the authors attributed this effect to the inhibition or stabilization of mast cells [20, 21].
Dietary sources of methylxanthines include coffee, tea, chocolate, maté, and guarana. You can drink coffee, eat chocolate, or supplement with theobromine, but attempting to supplement with theophylline is not recommended, as adverse cardiac effects are possible [22, 23, 24, 25].
Note, however, that chocolate also contains some histamine, and researchers suspect that it may encourage histamine release. The net effect of cocoa is unknown; we recommend that you test your own individual response and see what it does for you. Note, also, that organic chocolate contains fewer biogenic amines than non-organic chocolate [26, 19, 27].
Animal & Cell Studies (Lacking Evidence)
No clinical evidence supports the approaches listed below to prevent or treat histamine reactions. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
Fisetin is a flavonoid pigment found in strawberries and apples. This compound reduces histamine release by preventing IgE from binding to and activating mast cells. It’s a good choice if you suffer from allergies. Plus, it may promote longevity [7, 28, 29].
Luteolin is a flavonoid found in celery, parsley, and broccoli. It stabilizes mast cells and suppresses inflammation in the lungs and nose, which makes it another good choice for asthma and seasonal allergies [30, 31, 32, 33].
Epigallocatechin gallate (EGCG) is a polyphenol found mainly in green tea. Besides stabilizing mast cells, EGCG has the added benefit of reducing the number of mast cells present at any time [36, 37].
EGCG also inactivates histidine decarboxylase (HDC), the enzyme that makes histamine. Finally, it prevents mast cells from dividing and traveling out of the bloodstream and into other tissues .
Kaempferol is a polyphenol found in cruciferous vegetables, Delphinium plants, witch hazel, and grapefruit. Like many other polyphenols on this list, it prevents mast cells from releasing histamine [39, 7].
Rutin is an antioxidant and anti-inflammatory flavonoid found in large quantities in buckwheat, apples, and passion flower. It stabilizes mast cells, reduces inflammation, and strengthens blood vessels [7, 42, 43, 44].
Theanine is an amino acid found most abundantly in green and black tea and some fungi. Unlike most chemicals, it can cross the blood-brain barrier and act directly on the brain, where it increases serotonin, dopamine, and GABA levels in humans. In animals, theanine has also been found to stabilize mast cells and prevent histamine release, but this effect has not been investigated in humans yet [45, 46, 47, 48].
A bitter compound found in grapefruit, naringenin inhibited histidine decarboxylase and prevented histamine from being formed in cells. Naringenin also has broader anti-inflammatory effects that are being investigated for their potential to help prevent liver damage and metabolic syndrome [49, 50].
Curcumin, a yellow compound found in turmeric, is one of the strongest plant-based anti-inflammatories. It suppresses an overactive immune system, which makes it a great supplement to fight allergies and autoimmunity; specifically, it prevents mast cells from releasing histamine [51, 52].
In a mouse study, curcumin reduced the activity of diamine oxidase (DAO), the enzyme that breaks down histamine in the blood. However, in this case, lower DAO in the blood might simply mean that cells in the intestinal lining were exposed to less histamine and, thus, needed to release less DAO .
Reishi is a fan-shaped mushroom that is believed by some to enhance the immune response. In cell and animal studies, it has shown some promise in preventing mast cells from releasing histamine, but these effects have not translated to any reliable evidence in humans [54, 55, 56].
21) Chinese Skullcap
The roots of the Chinese skullcap, a plant from the mint family, are important in traditional Chinese medicine. This plant’s active compounds significantly reduced histamine release in rat studies [57, 58, 56].
Eleuthero, also known as Siberian ginseng, is a staple of traditional medicine in the Far East. In rats, an extract of eleuthero reduces mast cell activity and prevents histamine release in cell and animal studies [59, 60, 61].
Tulsi, otherwise known as holy basil, is an aromatic herb best known in Ayurvedic medicine as a tonic for stress and inflammation. In rats, tulsi seed oil blocked histamine release from mast cells [62, 63, 64].
Mucuna pruriens, also known as velvet bean, is a natural source of the dopamine precursor L-DOPA, a strong inhibitor of histidine decarboxylase (HDC) in cell studies. It is unclear whether mucuna supplements would act as antihistamines in either animals or humans .
25) Vitamin B6
Vitamin B6 supports DAO production, but it also increases histidine decarboxylase (HDC), and may, therefore, increase total histamine production. Generally speaking, this vitamin is required for a healthy histamine metabolism. You may want to talk to your doctor about whether you might be deficient in B6 [11, 66].
26) L. plantarum
Palmitoylethanolamide, or PEA, is a fatty acid already found in your body. PEA is best known for its potential as a natural painkiller, but it also prevents histamine release from mast cells. It may be especially good for eczema and skin allergies .
S-adenosyl-L-methionine, also known as SAM-e, is a compound that naturally occurs in your body and which donates methyl groups during methylation processes. Histamine N-methyltransferase (HMNT) inactivates histamine by methylating it; SAM-e might help HMNT work more efficiently [69, 70].
According to some studies, SAM-e supplementation does not increase histamine breakdown if the body already has sufficient SAM-e. However, many of these are decades-old mouse studies; we haven’t been able to find recent human studies to clearly answer the question .
Carnosine is a naturally-occurring compound made from the amino acids beta-alanine and histidine. It is abundant in high-quality meat and inhibits histidine decarboxylase, thereby preventing new histamine from being formed, in cell studies [72, 73].
In pigs, however, carnosine inhibits diamine oxidase, which breaks histamine down in the gut. The net effect of carnosine on histamine in the human body is unknown; there are better antihistamine choices on this list .
N-acetyl cysteine (NAC) is an amino acid supplement and a strong antioxidant. In one cell study, it strongly inhibited histidine decarboxylase, the enzyme that makes histamine. But in other cell-based studies, it increased histamine release; this may explain some of NAC’s side effects [72, 75, 76].
NAC is a powerful and healthy supplement that you should consider if you have issues with oxidative stress as well as histamine, but it probably isn’t the best option solely for histamine intolerance.
Valine is an essential amino acid, meaning that we cannot make our own and therefore need to consume it in our diets. Valine weakly inhibits histidine decarboxylase (HDC) in cell studies, though we don’t know its role in histamine metabolism in animals or humans. It’s important to make sure you get plenty in your diet; you can get valine from most foods, including meat, grains, vegetables, and milk and dairy products [77, 72, 78].
If you have runaway histamine problems, you may want to talk to your doctor about plant-based antioxidants, herbal supplements, vitamins, probiotics, and some other compounds that might help you manage your symptoms without a big price tag.
These natural antihistamines include forskolin, quercetin, astragalus, vitamin C, and probiotics containing Bifidobacterium longum. These supplements and nutrients may inhibit the enzyme that creates histamine, prevent mast cells from releasing histamine, or help your body break more histamine down, but the research is limited. Always discuss new supplements with your doctor.
A Note on Synthetic & Pharmaceutical Antihistamines
Sometimes, pharmaceutical antihistamines are required to effectively and specifically control histamine reactions. Discuss these drugs with your doctor.
Antihistamines (H1-receptor antagonists) block type 1 histamine receptors to reduce the effects of circulating histamine .
Fexofenadine (Allegra) is a drug that doesn’t cause drowsiness because it doesn’t cross the blood-brain barrier as efficiently as first-generation antihistamines like Benadryl (diphenhydramine) [80, 81, 79].
People taking Allegra at normal dosages don’t experience significant adverse effects when compared to a placebo .
Benadryl, an H1 receptor antagonist that also increases diamine oxidase (DAO) production, is better taken at night since it induces sleepiness. In fact, it is also sometimes used as an occasional sleep aid [83, 84].
Benadryl may also decrease anxiety and increase serotonin in the brain, similar to SSRI antidepressants. In fact, many antidepressants and antipsychotics were developed based on its chemical structure .