Recently I have seen a lot of difference of opinions on social media on these issues. There are several blogger who write on this, for example:
I was well trained at University to always work from primary sources (hence the joys of learning at least some greek, latin, french, german, danish for history courses). Bloggers are secondary and often tertiary sources – with the risk of reading more into stuff then there may actually be, or spinning the data to gain readers.
On the flip side, some of their advice comes from experience. The unfortunate aspect of experience is that there is no control for placebo effects, or anti-placebo effects, or effects due to other factors with the person.
You may also wish to read DAO and Probiotics, a prior post
To me, the primary sources are two grades:
- Individual specific studies (which suffer from a variety of bias risks)
- Review Articles (unlike bloggers, these are peer reviewed)
Wikipedia lists the following as Mast Cell Stabilizers, most are prescription drugs
- β2-adrenergic agonists
- Cromoglicic acid
- Ketotifen
- Loratadine
- Desloratadine
- Methylxanthines[citation needed]
- Olopatadine
- Rupatadine
- Mepolizumab
- Omalizumab
- Pemirolast
- Quercetin Plant Flavonol (see below)
- Nedocromil
- Azelastine
- Tranilast
- Palmitoylethanolamide
- Vitamin D[3]
The drug bank list of Histamine H1 Antagonists, Non-Sedating provides a similar link with the KEGG providing nice diagrams here, with the following enzymes:
| 07216 Catecholamine transferase inhibitors |
| 07219 Cyclooxygenase inhibitors |
| 07024 HMG-CoA reductase inhibitors |
| 07217 Renin-angiotensin system inhibitors |
| 07218 HIV protease inhibitors |
- “Aspirin enhanced histamine release from basophils via increased Syk kinase activation” [2013]
There is no evidence to suggest that sensitization against drugs occurs more frequently among patients with presumed histamine intolerance compared to patients with normal tolerance to histamine. However, preclinical data suggest interactions between some drugs and histamine catabolism. Nevertheless, the clinical relevance of these findings remains unclear as histamine in humans can be catabolized by different pathways[Editor: DAO and HNMT]. There are no drugs for which induction or worsening of histamine intolerance has been established clinically.
Drug hypersensitivity in patients with presumed histamine intolerance and mast cell activation disease [2019]
In terms of citizen science, we find some strong statistical associations for some bacteria shifts
The Review
Mast Cell Stabilizers
- Twenty-first century mast cell stabilizers [2013] See Table 1 “Naturally occurring mast cell stabilizers”
- I have a page that links to what contain various flavonoids here, with the amount (and mast cell stabilizers labelled)
- Often people work off “contains” only, ignoring the amount, for example
- Apigenin: Kumquats has 21 mg/gram and mangos 0.01 mg/gram — a 2000x difference!
- Often people work off “contains” only, ignoring the amount, for example
- Example: Apigenin
- I have a page that links to what contain various flavonoids here, with the amount (and mast cell stabilizers labelled)
- PubMed reports nothing for probiotics that have this effect. Nor for bifidobacterium, nor lactobacillus
- For Bacillus, we find evidence of histamine release [1975], exactly the wrong response
DAO Response
There are chemicals/vitamins that DAO and Histamine N-methyltransferase (HNMT) ( the key natural histamine removers) need to act upon histamines. These include:
- “Vitamin B6 is a collective term for all 3-hydroxy-2-methylpyridines which act as vitamins. Vitamin B6 substances like pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated metabolites are all equally effective. Pyridoxal-5-phosphate and pyridoxamine-5-phosphate fulfill the functions of a coenzyme in the organism [for activation of DAO].” [2014]
- Impact of oral vitamin C on histamine levels and seasickness [2014]
Note: “Histamine (p < 0.01) and DAO levels were increased after the intake of vitamin C (p < 0.001)”- The p values suggests that DAO increased significantly more than histamine.
- This may be the source of QAnon belief that citric fruits/vitamin C is bad.
- “A cross-over study in former East-Germany on patients who had infection-related asthma found that 5 g/day vitamin C decreased the proportion of participants who had bronchial hypersensitivity to histamine by 52 percentage points (95% CI: 25 to 71).” [2013]
- “copper …. did significantly increase two enzyme activities (SOD and DAO)” [1997]
- “diamine oxidase (DAO) activity were both increased (linear, p = 0.0004, 0.001, respectively) with Defatted Rice Bran…” [2019]
Negative Impacts
Caution: DAO production seems to increase with gut permeability issues (GPI). Thus something that improves GPI may not actually decrease DAO production, the change of DAO may be a side effect.
- “selenium-enriched yeast …significantly decreased the serum concentrations of diamine oxidase (DAO)” [2020] – unclear if the yeast or the selenium was the primary cause.
- “Tannic acid … reduced diamine oxidase (DAO) activity” [2020] ( Tea, coffee, wine, chocolate)
- ” Antimalarial drugs that inhibit histamine N-methyltransferase also inhibit putrescine catabolism in vivo and DAO activity in vitro” [1981]
- “putrescine supplement…. increase in putrescine at 1 h and in diamine oxidase (EC 1.4.3.6) activity within 3-6 h” [1986]
- “putrescine is found in virtually all foods of plant origin, and is particularly abundant in fruits and vegetables, notably citrus fruits (1,554 nmol/g) and green peppers (794 nmol/g) (9, 61). There are also high amounts of putrescine in wheat germ (705 nmol/g) and soybean sprouts (507 nmol/g) (37, 70).” [2019]
Histamine Production
Many probiotics produce histamines, for a list see our commercial probiotic list. For many probiotics, we could not find PubMed studies. Lactobacillus buchneri has been implicated in histamine-poisoning[1991].
Foods
Fermented foods are usually uncertain for which bacteria are fermenting it. As we see above, many produce histamine. Studies of commercial Kefir have found that the listed bacteria and the actual are usually in disagreement. Bottom line: no fermented food. This includes sauerkraut, soy, miso, red wine and salami[2020] [1991] .This usually extends into no left-overs, most items left in the fridge (or out) indefinitely– get covered in furry green/black coats. This extends to many cheeses [2020][1995], with Feta Cheese being a possible exception [2020]. For cheese, the same cheese name (like Stilton and Camembert cited below), from one producer may be fine and from another bad — the difference is which strains (not species) of bacteria was used. This also applies to yogurts. For “wild Culture cheeses” it is Russian Roulette for histamines.
Very fresh fish can be safe, but they are prone to producing histamine quickly once skinned [2020].
This also applies to items like nuts and beans that are not fresh.
“Citrus fruits are high in histamines” [Internet Legend?] – alas, I could not find any usable studies. I did find this
In this study, aqueous extracts of peels of best known citrus fruits namely grapefruit (Citrus paradisi), lemon (C. limon), lime (C. aurantifolia) and orange (C. sinensis) were used. Depending on polyphenols content, the extracts were graded as orange > lemon > lime > grapefruit. Effects of the extracts on the release of histamine from rat peritoneal exudate cells (PECs) was measured to know anti-allergic activity. All extracts inhibited the release of histamine from rat PECs induced by the calcium ionophore A23187
Anti-histamine release and anti-inflammatory activities of aqueous extracts of citrus fruits peels [2013]
- “Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells ” [2016]
Other Histamine Producing Foods
In researching another possible internet myth, pineapples and banana. I found a summary of a study which could easily be misread to imply histamine issues. After some effort, I found the full text of the article and shows the results of their lab tests below. The summary stated “Histamine, tyramine, noradrenaline, serotonin and other pressor amines occur in fruits and fermented foods such as bananas, pineapples, cheese and wine. ” It does not state that each is found in every fruit and fermented food
Grasping for straws?
“Abnormal association between mast cells and nerve fibers, and increased release of tryptase and histamine have also been described in IBS patients [7],” [2017] has led to the not-demonstrated belief that what improves IBS also improves histamine. i.e. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption [2019]
Highest Mast Stabilizer Foods
As mentioned above, we should not ignore the amount, fortunately the database behind Microbiome Prescription, allows us to compute across all natural mast cell stabilizers and get concrete numbers.
By amount of Mast Cell Stabilizers
| Food | mg/gram |
| Spices, parsley, dried | 4523.25 |
| Spices, celery seed | 841.05 |
| Capers, canned | 303.89 |
| Spices, saffron | 205.48 |
| Dill weed, fresh | 68.48 |
| Thyme, fresh | 47.75 |
| Elderberries, raw | 27.35 |
| Kumquats, raw | 21.87 |
| Peppermint, fresh | 18.05 |
| Cranberries, raw | 16.15 |
| Cranberries, dried, sweetened | 12.83 |
| Blueberries, cultivated (highbush), raw | 9.53 |
| Blueberries, frozen, unsweetened | 7.55 |
| Cranberry sauce, whole, canned, OCEAN SPRAY | 6.51 |
| Pitanga, (surinam-cherry), raw | 6.2 |
| Acerola, (west indian cherry), raw | 5.79 |
| Figs, raw | 5.47 |
| Currants, european black, raw | 5.16 |
| Raisins, golden seedless | 5.11 |
| Prickly pears, raw | 5.04 |
| Apples, raw, with skin | 4.27 |
| Apples, Red Delicious, raw. with skin | 3.87 |
| Blackberries, raw | 3.85 |
| Apples, Gala, raw, with skin | 3.8 |
| Apples, Golden Delicious, raw, with skin | 3.69 |
| Spices, marjoram, dried | 3.5 |
| Lemons, raw, without peel | 3.07 |
| Olives, ripe, canned (small-extra large) – May be high in histamine [2000] | 2.8 |
| Rosemary, fresh | 2.55 |
| Apples, Granny Smith, raw, with skin | 2.54 |
| Cherries, sweet, raw | 2.53 |
| Mulberries, raw | 2.47 |
| Cranberry sauce, canned, sweetened | 2.44 |
| Apples, Fuji, raw, with skin | 2.36 |
| Apricots, raw | 2.26 |
| Gooseberries, raw | 2.11 |
| Applesauce, canned, unsweetened, without added ascorbic acid (includes USDA commodity) | 2 |
| Juice, lemon, canned or bottled | 1.83 |
| Plums, dried (prunes), uncooked | 1.82 |
| Kiwifruit, green, raw | 1.81 |
| Cherries, sour, red, raw | 1.71 |
| Strawberries, raw | 1.61 |
| Raspberries, raw | 1.48 |
| Jujube, raw | 1.26 |
| Raspberries, frozen, red, unsweetened | 1.14 |
| Juice, pomegranate, bottled | 1.11 |
| Apples, raw, without skin | 1.07 |
| Strawberries, frozen, unsweetened | 0.98 |
| Grapefruit, raw, pink and red, all areas | 0.94 |
| Dates, deglet noor | 0.93 |
| Sauce, pasta, spaghetti/marinara, ready-to-serve | 0.92 |
| Watermelon, raw | 0.91 |
| Oranges, raw, navels | 0.91 |
| Plums, raw | 0.9 |
| Peaches, raw | 0.88 |
| Pears, raw | 0.84 |
| Oranges, raw, all commercial varieties | 0.77 |
| Juice, grape, canned or bottled, unsweetened, without added ascorbic acid | 0.75 |
| Melons, cantaloupe, raw | 0.72 |
| Nectarines, raw | 0.69 |
| Juice, apple, canned or bottled, unsweetened, without added ascorbic acid | 0.58 |
| Olives, pickled, canned or bottled, green May be high in histamine [2000] | 0.56 |
| Juice, lime, raw | 0.51 |
By Number of different Mast Cell Stablizers
Different flavonoids may have different responses, hence the most varied should also be considered.
| Food | Flavonoids Counts |
| Raspberries, raw | 6 |
| Strawberries, frozen, unsweetened | 3 |
| Oranges, raw, all commercial varieties | 3 |
| Apples, raw, with skin | 3 |
| Blueberries, cultivated (highbush), raw | 3 |
| Blueberries, frozen, unsweetened | 3 |
| Cranberries, raw | 3 |
| Kiwifruit, green, raw | 3 |
| Lemons, raw, without peel | 3 |
| Mangos, raw | 2 |
| Melons, cantaloupe, raw | 2 |
| Oil, olive, salad or cooking | 2 |
| Cranberry sauce, canned, sweetened | 2 |
| Currants, european black, raw | 2 |
| Dill weed, fresh | 2 |
| Elderberries, raw | 2 |
| Gooseberries, raw | 2 |
| Grapefruit, raw, pink and red, all areas | 2 |
| Capers, canned | 2 |
| Cherries, sour, red, frozen, unsweetened | 2 |
| Cherries, sour, red, raw | 2 |
| Cherries, sweet, raw | 2 |
| Cranberries, dried, sweetened | 2 |
| Apricots, raw | 2 |
| Bananas, raw | 2 |
| Blackberries, raw | 2 |
| Oranges, raw, navels | 2 |
| Peaches, raw | 2 |
| Peppermint, fresh | 2 |
| Pitanga, (surinam-cherry), raw | 2 |
| Prickly pears, raw | 2 |
| Raisins, golden seedless (because of age, histamine risk) | 2 |
| Raspberries, frozen, red, unsweetened | 2 |
| Strawberries, raw | 2 |
| Thyme, fresh | 2 |
| Watermelon, raw | 2 |
| Rosemary, fresh | 2 |
| Spices, celery seed | 2 |
| Spices, parsley, dried | 2 |
| Acerola, (west indian cherry), raw | 2 |
Bottom Line
I will gladly take comments citing gold standard sources (PubMed with full test), please do not add comments about so-and-so saying something is bad. I dislike QAnon medicine.
The above should give a framework for diet and cooking, as points
- Use items high in mast cell stabilizers
- No fermented foods or left overs
- No ‘old raw’ ingredients (i.e. nuts, beans, etc) – unfortunately, most of these do not have “Picked dates” on them. Bad storage (i.e. high humidity, temperature) is also a factor.
- Dried fruit/vegetables have significant histamine risk
- Canned food is unclear, but there are cases of problems from some manufacturers[2010].
- Fresh frozen is usually fine. We buy blueberries originating at a far 4 miles away. We know that the temperature is cool when they are harvested and thus the risk of bacterial growth on them is low. Likely much lower than “fresh blueberries” at the market that was shipped from Chile and have been on display for 3 days.
- Find out when fruit, vegetables etc are delivered to your market, you want to shop the next day — avoiding all old looking items
- Peel fruits etc, immediately before consumption. Skins evolved to protect the contents from bacteria (i.e. histamine producing) growths
Whenever you hear an avoid (example list)— do your homework on it. Use PubMed exclusively. One of the best items for mast cell stabilization is Kumquats, which is on many avoid lists because it is in the citric family…. another QAnon recommendation.
IBS/Gut permeability appears to be a significant co-factor.
Evidence please! Studies, not the volume of people repeating rumors!