Can Fluoroquinolones Activate Mast Cells?

Can Fluoroquinolones Activate Mast Cells?

What is the connection between fluoroquinolone toxicity and mast cell activation / histamine intolerance? Can fluoroquinolones trigger mast cell activation and histamine intolerance?

The symptoms of mast cell activation are similar to those of fluoroquinolone toxicity. According to Mastocytosis Society Canada, the symptoms of mast cell activation are:

skin lesions or sores, skin rash, spots, redness, hives, persistent fatigue, itching, flushing & severe sweating, joint, bone pain, headaches, tachycardia (racing heartrate), eyes tearing/dry, eye pain, persistent body/tissue pain, difficulty exercising, vertigo, episodes of low body temperature, unexplained Vitamin B12 deficiency, scents/odors/chemical reactions, difficult menses (females), numbness & tingling in face and extremities, skin feels on fire, unexplained anxiety, sudden drops in blood pressure, fainting, persistent diarrhea, vomiting, unexplained weight loss, cognitive impairment, sinus problems, chest pain, vision problems, hair loss, mouth sores, nausea, swelling & inflammation, odd reactions to insect stings, anesthesia difficulties, anemia, thyroid problems, decreased bone density, unexplained weakness, shortness of breath, sunlight sensitivity, temperature (hot/cold) sensitivity, difficulty with foods, drinks, anaphylactoid reactions, anaphylaxis, gastrointestinal pain, bloating, unexplained medication reactions, enlarged liver/spleen, liver/spleen/bladder/kidney pain, enlarged lymph nodes, frequent urination, recurring infections, neuropathic pain, constipation, iron deficiency, unexplained bruising, bleeding, malabsorption, intermittent tinnitus or hearing problems.

That’s a pretty comprehensive list of fluoroquinolone toxicity symptoms too. (Though, as I discussed with Dr. Wahls in episode 14 of The Floxie Hope Podcast, all of the multi-symptom, chronic diseases of modernity have more in common with each other than they don’t, and should probably all just be categorized as cellular dysfunction disorders and treated similarly.)

Several floxies who have been able to get a diagnosis from a doctor have come back with a diagnosis of mast cell activation, or a disease that is related to mast cells. For example, one floxie friend’s doctors have diagnosed him with eosinophilia, a disorder that is related to mast cells and histamine intolerance. Other floxies have been diagnosed as histamine intolerant, and instructed to go on a low-histamine diet. As noted above, many floxies have symptoms of mastocytosis, and it is possible that fluoroquinolones activate mast cells and trigger mastocytosis.

Mast cell disorders are considered to be rare, but, according to Mastocytosis Society Canada, “escalation in the prevalence of these patients worldwide has resulted in a flurry of medical research ongoing in numerous countries. This indicates that these disorders may not be rare, but rather have been commonly misidentified and unfortunately for patients worldwide, commonly undiagnosed. Since approximately 2005, every year there are new theories, classifications, and adjustments to the mastocytosis definitions due to escalation of patients presenting with these disorders worldwide.”

I found the following information connecting fluoroquinolones and mast cell activation / mastocytosis:

  • From the International Journal of Tissue Reaction’s article, Effect of levofloxacin and ciprofloxacin injection on permeability of the tail vein in mice and skin microvasculature in rats, “These results suggest that LVFX and CPFX increase vascular permeability through the induction of histamine release from mast cells in rodents.” (LVFX is levofloxacin and CPFX is ciprofloxacin.)
  • From the Journal of Pharmacy and Pharmacology’s article, Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitro, “Intravenous injection of levofloxacin and ciprofloxacin at 1–10 mg kg−1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg−1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells.” Note that in studies beagle puppies have been made lame by fluoroquinolones.
  • From the Archives of Toxicology’s article, Differential response of mast cells separated from various organs and basophils of dogs to the fluoroquinolone antimicrobial levofloxacin, “Histamine releases induced by the fluoroquinolone antimicrobial levofloxacin (LVFX) were investigated using mast cells separated from various organs and peripheral basophils of dogs, being the most susceptible species to quinolone derivatives, in both in vivo and in vitro systems. An intravenous infusion of LVFX at 30 mg/kg over a 30-min period produced endogenous histamine release from 5 min, and a maximum at 30 min, in which the plasma LVFX concentration was approximately 50 µM. A close correlation (r=0.87, n=20) between histamine and LVFX concentrations in plasma during the infusion was observed. In the in vitro study, LVFX at 30 µM or more caused histamine release from mast cells separated from the liver and skin, but not from the gastric mucosa, lung, and peripheral basophils. More exactly, the liver mast cells were most susceptible to LVFX among the organs tested. On the other hand, compound 48/80, a prototype histamine liberator, elicited the histamine release from the liver or skin mast cells at 10 µg/ml, and the calcium ionophore A23187 at 1 µM exhibited the histamine release from the mast cells derived from all organs examined. Histochemical analysis revealed that the liver and skin mast cells had positive reaction for both alcian blue and safranin staining, but the gastric mucosa and lung mast cells were only positive for alcian blue staining, indicating that LVFX preferably activated the connective tissue-type mast cells rather than the mucosal-type mast cells. The degranulation of the liver and skin mast cells brought about by either LVFX or compound 48/80, unlike the calcium ionophore A23187, was blocked by pretreatment with pertussis toxin, suggesting the involvement of pertussis toxin-sensitive G proteins. The results obtained from the canine experiments strongly suggest that LVFX induces histamine release from the connective tissue-type mast cells distributed mainly in the liver, somewhat in the cutaneous tissue, through the activation of pertussis toxin-sensitive G proteins.”

The articles noted above are all from animal studies, not human studies, but they show that fluoroquinolones can activate mast cells and histamine release in mammals, and it’s reasonable to think that they may do the same things to humans that they do to dogs. Also, the similarity between fluoroquinolone toxicity symptoms and mastocytosis symptoms, though not a smoking gun, indicate that further studies of the affects of fluoroquinolones on mast cells should be done.

A few good resources for people with mastocytosis, and it’s possible that floxies are in that category, are:

  1. Dr. Theoharides web site
  2. Mastocytosis Society Canada web site
  3. The Low Histamine Chef web site
  4. Alison Vickery’s web site

I suspect that mast cells are profoundly affected by fluoroquinolones and that mast cell activation is a big part of fluoroquinolone toxicity. The potential options, and mechanisms for fluoroquinolone toxicity, are mind-boggling. Add mast cell activation to the list.

 

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60 thoughts on “Can Fluoroquinolones Activate Mast Cells?

  1. Linda Livingston October 1, 2015 at 10:36 am Reply

    OMG LISA—you are a psychic! I was just talking about this with my chiro yesterday, because I have been SO congested since this started. Nonstop phlegm production. He had me order something called Daosin so take after meals. I never had a problem with foods before but I have had a lot of other allergies and it is the cumulative effect of everything. You finally reach a tipping point and your body can’t deal with anymore. I may not be able to control the pollen (and I stopped taking otc meds for that) but if I can control the food part, hopefully that will help. There is also a diet, but I looked at the list of “do nots” and it is completely unworkable. It includes everything I have been told I SHOULD eat, eg spinach, avocado, berries, sweet potatoes.. DAMN this cipro!!! Every single area of my life (Thanks for posting)

    • Lisa Bloomquist October 1, 2015 at 11:37 am Reply

      A lot of this mast cell activation stuff fits well, and it’s nice to hear that your chiro concurs. 🙂 I hope the Daosin helps! I’ve been meaning to try it. Please let me know what your response to it is. Yep, the low-histamine diet is close to impossible for most people. You can’t have leftovers for goodness sake! But there is still a lot of good info on The Low Histamine Chef web site about foods you can eat (linked above). The link to Alison Vickery’s site that is in the post is also to a list of foods that suppress histamine and mast cells, and maybe those can help.

      • Linda Livingston October 1, 2015 at 12:05 pm Reply

        will do. should get it in a couple days

  2. Lisa October 1, 2015 at 1:50 pm Reply

    Mast cells are activated by Fluoroquinolones. See recent Medical Study from December 17,2014, from John Hopkins : http://www.hopkinsmedicine.org/news/media/releases/multiple_allergic_reactions_traced_to_single_protein It unequivocally states that FLUORQUINOLONES cause a Mast Cell reaction.
    It is NO coincidence that Mast Cell Activation Disease presents with the EXACT diverse symptoms of all Floxies. In the Medical Article of March 22, 2011, published in the Journal of Hemotol Oncol, titled “Mast Cell Activation Disease: a concise practical guide for diagnostic workup and therapeutic options, It states that “Mast Cell activation disease is now appreciated to likely be considerable prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitely diagnosed major illness does not well account for the entirety of the patient’s presentation.” In that article is attached :Table 3″ which reads like a laundry list of symptoms that are caused by what is called the ‘unregulated release of mast cell mediators” . This list reads like a Floxie Symptom List. It is clear from these medical journal articles based on recent medical studies that Fluoroquinolones cause Mast Cell Activation which results in the myriad of multisystem symptoms and ‘disease’ like entities listed on Table 3.

    • Lisa Bloomquist October 1, 2015 at 5:25 pm Reply

      Thank you!!! You are wonderful and this is immensely helpful!

  3. Lisa October 1, 2015 at 1:54 pm Reply

    The Medical Article of March 22, 2011, published in the Journal of Hemotol Oncol, titled “Mast Cell Activation Disease: a concise practical guide for diagnostic workup and therapeutic options, can be found, along with the attached “Table 3” at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/ Everything listed on Table 3 is a Floxie ‘Disease/Symptom’

    • Lisa Bloomquist October 1, 2015 at 5:26 pm Reply

      Thank you so much! If you find any other articles connecting FQs to mast cells, please either post them or send them to me, if you don’t mind. I really, really, really appreciate you posting these articles!

    • Linda Livingston October 1, 2015 at 8:39 pm Reply

      are you ever right about table 3!!!!! And this explains SO much about all the new sensitivities I am having, in addition to all the other garbage. thanks

    • Linda Livingston October 3, 2015 at 9:43 am Reply

      copying this for my accupuncturist. (but like all good government sites, with the exception of slow release vitamin c, all other treatments are pharmaceutical) still, some good explanations

  4. Bobby Traina October 2, 2015 at 10:25 pm Reply

    Excellent article/hypothesis!

    • Lisa Bloomquist October 3, 2015 at 7:19 am Reply

      Thanks, Bobby! I think there’s a lot to this one. I suggest looking at the links that Lisa put in the comments too.

  5. Sandra October 6, 2015 at 9:58 pm Reply

    Are these sulfa drugs?

    • Lisa Bloomquist October 7, 2015 at 9:36 am Reply

      Hi Sandra,

      No, fluoroquinolones are their own category of antibiotics. Here’s the wiki for fluoroquinolones – https://en.wikipedia.org/wiki/Quinolone. They are not related to sulfa drugs, but many (though not all) people who have adverse reactions to fluoroquinolones are also allergic to sulfa drugs.

      Regards,
      Lisa

  6. Natalie October 8, 2015 at 10:57 pm Reply

    Has anyone tried Quercetin and Bromelain ? They are all natural and are supposed to help with mast cells and inflammation. I’ve developed an auto-immune disease and was told to try them by my doctor. They are made by NOW foods and i’m sure there are other brands

    Praying they work because I can’t deal with the post nasal drip and bladder problems at this time and a few other times of the year
    Good Luck to all of us,

    Natalie

    • Linda Livingston October 8, 2015 at 11:15 pm Reply

      I have been having awful congestion…just nonstop phlegm production…back of nose, throat, lungs. I had tried quercitin because it was recommended to me by several different people for my allergies, and I am afraid it didn’t have much effect on me, if any. (That is not to say it wouldn’t work for you.) Haven’t tried bromelain. I have been experimenting with something called allerase, which seems to be helping a bit—but could get expensive. I think I will try to find a supplement that includes quercitin as well as other ingredients that should help

  7. Jason January 10, 2016 at 6:54 pm Reply

    Found this on the interwebs and wanted to share it here, not sure how accurate the info is but people suffering might want to look at it further:

    Quote “omega 3’s, vit D3, vit B6, magnesium and vitamin C can help the body maintain proper histamine balance, and well as a histamine reduced diet.”

    I find it interesting that things like D3 and MAG are being leached from the body by Cipro and they are possibly things to help balance histamine.

    Also listed were Probiotics that can potentially help, or make things worse:

    Histamine Degraders

    Bifidobacterium infantis
    Bifidobacterium longum
    Lactobacillus gasseri
    Lactobacillus rhamnosus
    Lactobacillus plantarum
    Lactobacillus salivarius

    Histamine Producers:

    E. coli
    Klebsiella pneumoniae
    Lactobacillus bulgaricus
    Lactobacillus casei
    Lactobacillus helveticus
    Lactobacillus reuteri

    • Linda January 10, 2016 at 7:44 pm Reply

      Interesting. I definitely have been having things likely related to the mast cell activation, like hives (no longer) and congestion. A LOT of congestion. After Lisa posted the piece on mast cell activation, I had tried the low histamine diet but it is SO limited and some things are virtually impossible, given my living situation (eg no reheated meals) and so restrictive and I needed to be putting on more weight. But I just finished my bottle of probiotics which had a lot of different strains and i am wondering if any of those latter ones were in it. I just started a different one that doesn’t have any of those. Lactobacillus Casei—wonder if that is from caseine, which would make sense since it is in dairy products. (Of course Lactobacillus helveticus sounds like it came from a font style 😉 ) Thanks for posting. I will be on the lookout for those now in my probiotics.

    • Linda January 10, 2016 at 7:49 pm Reply

      also the low histamine chef website has a lot of info on this too, eg quercitin, tumeric, thyme also good to inhibit mast cell activation.

  8. Jason February 8, 2016 at 7:30 pm Reply

    Dr. Jill wrote up a good article on Histamine Reactions, what can be done etc

    http://www.jillcarnahan.com/2013/11/16/histamine-intolerance-could-this-be-the-cause-of-your-problems/

    • Jason February 8, 2016 at 7:32 pm Reply

      One guess what some of the most common root causes are…..

      • Jason February 18, 2016 at 1:22 am Reply

        Here in someone else’s words, is MUCH more about the root cause I was referring to mentioned in Jill’s article, GUT.

        I found this post online from someone who has done a bunch of research and it ties MANY things together really well and all relating to the GUT (he refers to IBS specifically because it was an IBS forum BUT it applies to many other things). I’m not completely sure of its total accuracy in every statement but many things are dead on for sure.

        Anyone that took Steroids with Cipro and had a severe reaction, extra GUT damage is almost surely why or a big part of it. Here is the post:

        MY IBS can effect my brain and my brain can effect my IBS. I have had this conversation with some of the worlds leading experts in IBS. Its physically not possible for gas to effect your brain, except through neurotransmission of nerve fibers in the digestive system. Its also how the system works. Its also what they are finding out in years and years of IBS research. FYI There are very complex connections to the gut and the brain and one part of this is the emotional motor system or Limbic system. This is also connected to the HPA axis or bodies stress system. The bodies stress system is also used to FIGHT INFECTION as well as the fight or flight responce. Constant activation of this system drains the body, like draining the batteries.”Emotion involves the entire nervous system, of course. But there are two parts of the nervous system that are especially significant: The limbic system and the autonomic nervous system.

        So the Limbic system (and Emotions) are connected to the autonomic nervous system that helps control digestion, heart rate and breathing among other things. This is one reason why emotions often effect digestion. Even subtle emotions.”The hypothalamus is one of the busiest parts of the brain, and is mainly concerned with homeostasis. Homeostasis is the process of returning something to some “set point.” It works like a thermostat: When your room gets too cold, the thermostat conveys that information to the furnace and turns it on. As your room warms up and the temperature gets beyond a certain point, it sends a signal that tells the furnace to turn off. The hypothalamus is responsible for regulating your hunger, thirst, response to pain, levels of pleasure, sexual satisfaction, anger and aggressive behavior, and more. It also regulates the functioning of the parasympathetic and sympathetic nervous systems, which in turn means it regulates things like pulse, blood pressure, breathing, and arousal in response to emotional circumstances. This is also one reason why a person can get hot and cold chills before an IBS attack as well as dilated pupils, increase heart rate and breathing etc..)

        The first is the autonomic nervous system. This allows the hypothalamus to have ultimate control of things like blood pressure, heart-rate, breathing, digestion, sweating, and all the sympathetic and parasympathetic functions. “Importantly it helps regulated “It also regulates the functioning of the parasympathetic and sympathetic nervous systems. This is how it breaks down: Central nervous system, The Autonomic Nervous System, The organs (the “viscera”) of our body, such as the heart, stomach and intestines, are regulated by a part of the nervous system called the autonomic nervous system (ANS). The ANS is part of the peripheral nervous system and it controls many organs and muscles within the body. In most situations, we are unaware of the workings of the ANS because it functions in an involuntary, reflexive manner. For example, we do not notice when blood vessels change size or when our heart beats faster. However, some people can be trained to control some functions of the ANS such as heart rate or blood pressure.

        The ANS is most important in two situations: 1. In emergencies that cause stress and require us to “fight” or take “flight” (run away) and 2. In non-emergencies that allow us to “rest” and “digest.”. The ANS is divided into three parts: The sympathetic nervous system, The parasympathetic nervous system and The enteric nervous system. The enteric nervous system is part of the autonomic nervous system and is often now called the “Gut Brain” and has 100 million neurons as many as the spinal cord, so note you have two brains: one in your head and another in your gut. This is really important in IBS and how some of it fits into IBS. This complex network of nerves lines the walls of the digestive tract form the esophagus all the way down to the colon. This little brain in the gut is connected to the big brain by the Vagus nerves, bundles of nerve fibers running from the GI tract to the head. All neurotransmitters, such as serotonin (ME => GABA, etc) that are found in the brain are also present in the gut. Dr Wood has discovered that this little-brain-in-the-gut has programs that are designed for our protection and which are very much like computer programs. They respond to perceived threats in the same way that the limbic system or the emotional brain does. So the threat of a gastrointestinal infection can activate the program that increases gut contractions in order to get rid of the infection. The symptoms are abdominal cramping and diarrhea.

        Also importantly there is a cell embedded in the gut wall that is directly connected to the HPA axis and the fight or flight. Dr. Wood has determined that the type of cell found in the body and the gut, called the Mast Cell, is a key to understanding the connection of the big brain in the head with the little-brain-in-the-gut. Mast cells are involved in defense of the body. In response to certain threats or triggers, such as pollen or infection, mast cells release chemicals, such as histamine, that help to fight off the invader. Histamine is one of the chemicals that causes the symptoms of an allergy or a cold. When an infection of the gut occurs, such as food poisoning or gastroenteritis, the mast cells of the gut release histamine. The little-brain-in-the-gut interprets the mast cell signal of histamine release as a threat and calls up a protective program designed to remove the threat at the expense of symptoms: abdominal pain and diarrhea. The brain to mast cell connection has a direct clinical relevance for irritable bowel syndrome and other functional gastrointestinal syndromes. It implies a mechanism for linking allostasis and the good stress response to irritable states (e.g., abdominal pain and diarrhea) of the gut. Mast cells can be activated to release histamine in response to perceived psychological stress, whether the stressor or trigger is consciously perceived or not.

    • Linda February 8, 2016 at 8:13 pm Reply

      Hmmm. There is glutamine again. But what is unfortunate is that things like fermented foods are so GOOD for healing the gut. i also see nuts, spinach and a few other thing on the “don’t” list that are part of my very very limited diet. Guess I will try to fight it more with quercitin and C. I actually only have one or two of her listed symptoms..

      • Jason February 9, 2016 at 7:08 am Reply

        L-Glutamine will ALWAYS be brought up when the topic of Leaky Gut is being discussed, unless the person is truly uniformed

        Nuts are bad in many ways, Spinach while good in many also has some downfalls unfortunately, seems every damn food does

        Don’t underestimate the B6, P5P best form, this sucker is important for a LOT of things.

        BTW – Steroids also destroy the Microbiome, so its no surprise that everyone who was given Steroids at the same time as Cipro usually has a more severe reaction than many other people, it ALL comes down to GUT again

        p.s – Alright just come clean, you ARE following me! This is an old article yet you found my post the same day I posted it!

        • Linda February 9, 2016 at 2:56 pm

          It’s a crap shoot which posts I see. I don’t check in all the time, and when I do sometimes I just scroll and stop. It’s not a very scientific method ;).

          I am reading Dr Jay Cohen’s last book which is terrific, although I disagree with some stuff he says, like in limited situations steroids are ok, as well as other pharmaceuticals. But the rest should be MANDATORY reading for all doctors.

          Can’t give up nuts…one of my last treats. I think my gut is not too bad anymore though.

  9. Jason February 11, 2016 at 1:37 pm Reply

    Methylation tie-in

    http://www.drkaslow.com/html/histadelia.html

    There is B6 again….

    The article ties a bunch of stuff together, even Adrenal Fatigue. I have been having low Methylation issues myself as of late and as it turns out, a histamine response it seems as well. Took some Methionine & B6 yesterday and today and so far I am better.

    • Jason February 11, 2016 at 1:38 pm Reply
    • Jason February 11, 2016 at 8:42 pm Reply

      I’m thinking here that the Quins can cause or exasperate “Under-Methylation” in people (I’ve posted many times in the past that these people are more prone to being Floxed in the first place), which raises Histamine levels and does a bunch of other nasty things too.

      Here is good article on Methylation in general, 3rd section relates to what I am talking about and also “Part 2” near the end.

      http://www.enzymestuff.com/methylation.htm

      If people are having trouble discerning what this all this info means (and there is a LOT there), here is a quote to help

      “One way histamine is de-activated (eliminated) is by receiving a methyl group from SAMe. So if there is low methylation, there is low SAMe, and the histamine levels are higher because of the lack of methyl groups to deactivate it.”

      —-

      This is why I took what I did (and really there are more things to take to support Methylation as well but this was my “quick fix”) the last 2 days and feel better, WAY better actually, I was undermethylating and had low dopamine and high histamine, which is now more balanced

      Here is another interesting quote pointing to GUT again:

      “Where does this histamine come from?
      One source is when the amino acid histidine looses a carboxyl group. Some bacteria can faciliate this conversion too. So if you have a bacteria overgrowth, it may be using up histidine and converting it to more histamine”

      One more, directly related to Quins and their damaging ways again:

      “Another way to reduce histamine levels is to supply antioxidants, too many free radicals provoke histamine reactions.”

      • Linda February 11, 2016 at 9:40 pm Reply

        sounds Greek to me. I can wade through legal stuff but when it comes to medical—yikes. So other than the b6 what is another quick fix to try for over=production of histamine? you mention antioxidants but I already think I am taking a lot.

        • Jason February 11, 2016 at 11:06 pm

          Quick fix is do what I did, take Methionine and B6 (B6 is also good for Anxiety/Gaba see there for more info on why), or you can take Sam-E also.

          Either one of these will add “Methyl Donors” to the Methylation cycle, and if someone is undermethylating thus low on Methyl Donors and thus also higher in Histamine, doing this should provide some relief (It did for me, I was having an excessive phlegm response from left over cold germ [that appeared to be not going away but really it was a histamine excess from under methylation] and some itchy skin issues and even a bad rash, well, it was a very itchy spot small rash that I scratched so much it turned into a big rash….).

          Pay attention to how you feel directly after, if taken on empty stomach, you will know within 60 minutes the effect. If you feel WAY more edgy after, then you may not have been low on Methyl Donors (and could even be high). If your brain feels like it has no “gas in the tank” before taking it and then gets new life after (=my reaction), then you were most likely low.

          ===========

          Note also what one article said about potential treatment:

          “In addition calcium helps release the bodies store of histamine, while Zinc aids the calcium-methionine program and provide sufficient relief. Typical treatment includes the following nutrients in high doses: calcium, magnesium, Vit B6, Vit C, zinc and methionine.”

          ——–

          I thought you in particular might find this quote from one of the articles linked interesting:

          “Many patients with obsessive-compulsive tendencies, “oppositional-defiant disorder,” or seasonal depression are under-methylated, which is associated with low serotonin levels. Often with inhalant allergies, frequent headaches, perfectionism, competitiveness and other distinctive symptoms and traits. Tend to be very low in calcium, magnesium, methionine, and vitamin B-6 with excessive levels of folic acid. People with histadelia often have a positive effect from SSRIs and other serotonin-enhancing medications (Paxil, Zoloft, Prozac, Celexa, Lexapro, Effexor, etc.) because methylation is a step in the manufacture of mood stabilizing neurotransmitters. Unfortunately, histadelics often have nasty side effects with these medications.

          Histamine excess can be manifest as asthma, vasomotor rhinitis, allergic skin disorders with pruritis, excess stomach acid production (acts as a gastric hormone to stimulate flow of stomach acid), saliva, tears, and thin nasal and bronchial secretions, and certain types of vascular headaches. This is the basis of anti-histamine medications. Excessive histamine results because of the inadequate methylation in liver detoxification. Histamine opposes adrenalin in its effects and as expected fatigue occurs just as it occurs in adrenal exhaustion.”

        • Linda February 11, 2016 at 11:39 pm

          cool. thanks. will try on empty stomach. over production of phlegm has been one of the continuing, non-abating problems. tried low-histamine (almost impossible) diet, acupuncture, other stuff. I had been on b6 but stopped. maybe I will try that first. thanks

        • Jason February 12, 2016 at 7:48 am

          You’re welcome hope it helps, it definitely will IF Under-Methylation is an issue for you, and a root cause for the high Histamine, I got instant relief myself but it may take a few days or up to a week for others

          However, B6 alone will not do it, it is important and usually an important co-factor for many things including in this case, but you need an important Methyl Donor and B6 is not that.

          Sam-E can be a little pricey, Methionine is CHEAP, and especially if you buy from the probably THE BEST place to buy supplements in the World

          Less than $3! This is the one I took http://www.swansonvitamins.com/swanson-premium-pure-l-methionine-500-mg-30-caps

          Note it is an “essential” Amino Acid, so the body cannot synthesize it and thus it must be obtained from the diet or supplementation

        • Linda February 12, 2016 at 10:16 am

          Thanks…yeah, methionine might be a better way to go too since SAMe can have some undesirable side effects. Hate to add any more supplements at this point, but I will def try this when I start weaning off others…thanks

        • Jason February 12, 2016 at 8:01 am

          I should note too that I find the effect of Methionine to be less pronounced than that of Sam-E, Sam-E is a like a supercharger for my brain and can go too far

          Also, 500mg is probably a big dose of Methionine, if you have not done so already buy some empty capsules they come in VERY handy in many situations like this one, I split mine into two 250mg caps, and as with any “new” supp its always good to start slower

  10. Jason February 16, 2016 at 2:43 pm Reply

    I’ve just done even more reading on this, and really amazing I never realized Histamine was such a strong indicator of Methylation, one expert says you can just test that alone to see if someone is Under or Over-Methylating.

    I’m just reporting here as well, that my Histamine response is completely GONE. I am classic Under-Methylator and have been my whole life, for whatever reason getting sick seemed to make it worse bring on a very strong Histamine response to the point it really got my attention. 2 – 3 days of Methionine and B6 was enough to support my Meth Cycle and get the Histamine down, right after the first dose there was a HUGE difference too as I mentioned.

    More on Methylation coming tomorrow in separate article, its estimated that 40-45% of the population are Under-Methylators, I personally estimate that 80 – 95% of Floxies are.

    Found this to be a good graphic

    • Jason February 16, 2016 at 2:48 pm Reply

      Oh and I ate 2 Bananas yesterday and had the Histamine response come back a little, looked it up, YEP, they are not a Histamine containing food BUT they cause Histamine release. 😦 Guess I have to pay more attention to this when my Methylation is in the shitter

    • Linda February 16, 2016 at 6:45 pm Reply

      cool. I’m gonna try methionone and b-6. Thanks for the tip. (Used DMAO –did nothing for me unfortunately.)

  11. Jason February 16, 2016 at 2:58 pm Reply

    Here is another link with a bunch of good info discussing this:

    http://secondopinionphysician.com/tag/undermethylation/

    One quote:

    Diamine Oxidase DAO
    This is an important enzyme that naturally lowers histamine levels in the body. DAO can be provided as a supplement to lower histamine levels. Symptoms of low DAO includes:
    · Skin irritations – hives, itching, rashes, eczema, psoriasis, and acne
    · Headaches
    · Painful menstrual periods
    · Gastrointestinal symptoms
    · Intolerance to fermented foods and alcohol
    · Mucous in sinuses
    · Asthma

    Supplements and OTC meds that increase DAO levels include:
    · Vitamin C
    · Vitamin B6
    · Pancreatic enzymes
    · Benadryl

    Foods and meds that inhibit DAO
    · Alcohol
    · Curcumin (turmeric)
    · Cimetidine – an antihistamine

    ——

    PS – Not giving up my Tomatoes I don’t care!

    • Linda February 16, 2016 at 6:45 pm Reply

      Not giving up my bananas! 🙂

  12. Jason February 18, 2016 at 2:17 am Reply

    Apparently Fluoride (thus Fluorine) can also activate Mass Cells through Calcium:

    “Calcium triggers the secretion of histamine from mast cells after previous exposure to sodium fluoride. The secretory process can be divided into a fluoride-activation step and a calcium-induced secretory step. It was observed that the fluoride-activation step is accompanied by an elevation of cAMP levels within the cells. The attained high levels of cAMP persist during histamine release. It was further found that catecholamines do not markedly alter the fluoride-induced histamine release. It was also confirmed that the second, but not the first, step in sodium fluoride-induced histamine secretion is inhibited by theophylline.[22] Vasodilation and increased permeability of capillaries are a result of both H1 and H2 receptor types”

  13. Jason February 18, 2016 at 2:19 am Reply

    Tons of info here, note this guy is smart and does lots of research, but he is not as smart as he thinks he is:

    http://selfhacked.com/2014/08/01/deal-histamine/

  14. […] The tie-in of methylation and histamine is interesting too. Most floxies have symptoms of histamine intolerance. More information about that can be found in this post – https://floxiehope.com/2015/10/01/can-fluoroquinolones-activate-mast-cells/ […]

    • Jason February 18, 2016 at 10:59 am Reply

      Actually what Carol posted and was copied there at that link you gave is NOT entirely accurate, I will be correcting the short-comings there. I’ve covered some of the Methylation tie-in already right on this page.

  15. Jason March 1, 2016 at 4:56 pm Reply

    Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.

    http://www.ncbi.nlm.nih.gov/pubmed/22470478

  16. Lisa Bloomquist March 19, 2016 at 1:08 pm Reply
    • Linda March 19, 2016 at 1:22 pm Reply

      Ugh. Hate histamines! And it is so frustrating because everything that is considered bad (high histamine) is basically the diet I have finally winnowed down to after cutting out stuff I could no longer eat. I would have to live on air and water to follow this diet. (not to mention things like fermented foods that are so good for the gut NOT being allowed, and nuts which is basically the only snack I can now have, and lemons which I have every morning.) It is just too much sometimes. Tried DAO and it did nothing. Guess I will try some other supplements to add to the 20 I now take for other issues. 😦

      • Jason March 27, 2016 at 11:11 pm Reply

        That is quite a good article on high Histamine Lisa posted, did you read it all Linda? I wanted to post about this earlier but I am supposed to be on Hiatus….

        Did you notice for example:

        “People suffering from HIT may display highly diverse symptoms. Every person has individual weak spots (ME => ie lungs for you), which may be afflicted earlier than other parts in the body.” (ME => and greater afflicted than other areas, they left that obvious part out)

        “Histamine is involved in panic events by causing a closing of the airways in the lungs. When released in the lungs, histamine causes the airways to swell shut in an attempt to close the door on offending allergens and keep them out. Panic attack periods are known for the sense of weight or contraction on the lungs.”(ME=>HELLO!)

        “Insomnia, problems falling asleep or sleeping through the night, only superficial catnapping without deep sleep, dreamlessness”

        “Noise sensitivity, search for tranquility and uneventfulness, vulnerability for sensory overload” (ME =>This was you in the beginning)

        (More Anxiety stuff) “susceptibility to stress, impaired ability to withstand stress, Tension, nervousness, jumpiness (also without external cause), restlessness, tingling sensation, feeling of caffeine overdose, Palpitation (stronger heart beat caused by a release of adrenaline), Racing heart”

        “Melancholia, sadness, weepiness (ME=>YEP that is you), depressive moods, depressions (often without visible cause), Thoughts of suicide”

        “Painful/burning bladder, desire to void, frequent urination (similar to bacterial bladder infection)” (ME=>jeepers how many Floxies think they have a UTI but never do, that was you too)

        The following 3 from another article I’m sure you know this first one but JIC: “While nuts do not contain histamine, they do contain histidine. Peanut, sesame, almond, pistachio, pine, and walnut have the highest levels of histidine among the nuts. Histidine, an amino acid, can be used by some gut bacteria to produce histamine. In other words, nuts can raise histamine levels indirectly.”

        “In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations.” (ME=> this can be part of the depersonalization and general psychosis that many experience as well)

        “Methionine supplements lower blood levels of histamine by increasing histamine breakdown.” (ME=> its a simple Methyl Donor to get the cycle going)

        —-

        So much more there too, as Lisa said in the article high histamine really mimics FQ Toxicity well, and I think it is playing a bigger role here than we realize, and I also have come to think “being Floxed” throws someone into “Undermethylation status” by using up/robbing all their Methyl Donors and probably triggering some of their Genetics like MTHFR etc, which of course means HIGH HISTAMINE as we see from some of the links above. Also of course as I’ve posted before I am quite sure most Floxies are UnderMethylators to begin with, many have MTHFR and other related SNP issues etc.

        PLEASE Linda I am thinking you did not try the Methionine and P5P (B6) yet, from Swanson this is like $15 combined and it could possibly shut down your breathing issues, Crying spells, Anxiety and more. I told you I used it myself successfully to bring down my own Histamine levels from undermethylation, it worked in a day or two for me but might likely take longer for you. This is not some shot in the dark, this is all well documented stuff and looks like your best bet of relief IMO. Also, be sure to look into the SIBO link above on February 18, 2016 at 11:02 am, and other websites on it if you think it is possible because SIBO is another root cause of high histamine, and will be common in Floxies unfortunately as well (and SIBO is another root cause of Leaky Gut which we know is all too common in Floxies)

        === Also for Steph someone please email her link to this article and post below ====

        http://davidjernigan.blogspot.ca/2015_07_01_archive.html?m=1

        “Tourette’s Syndrome.”

        Steph: I know Steph said she does not have this (though not sure why) before but it is very related to what she is going though, and given all the other stuff we know this could be big for her as well. That and there was something similar I posted for her before (can’t recall what is was now unfortunately), Iodine hopefully she bought it and tested herself like the patch test and tried it etc, of course her Gut is at the crux of this which she knows, and the old post from Rene to her about Taurine and another thing or two was also important, hopefully she kept that post and will get tested or try it.

        • Linda March 28, 2016 at 10:54 am

          OK, yeah I did see that and I have been doing the b6 and methianone….for a couple weeks now. No difference yet…..thanks

        • Linda March 28, 2016 at 10:55 am

          FYI the breathing is not lung related. Likely mitochondrial damage to the heart muscle. Lungs are doing fine. Breathing all around is way way better…just ocassional blips.”

        • Jason March 28, 2016 at 11:14 am

          Hi Linda, damn 2 weeks “should” have produced results if Methylation was a big issue for the Histamine for you I would think, although I could be missing something, but I guess it seems like something else might be behind it then, maybe Sibo or something else or combo of things

          GREAT news on the breathing then! I don’t really “buy” the mitochondrial damage to the heart muscle theory so much, seems like a really outside chance that would be behind a breathing issue, but just IMO of course

          Good healing to you, hopefully you continue to go in a positive direction, if only poor Steph, Jwinn and some other long time and severe sufferers could also that would be such great news, it breaks my heart thinking about these people and I wish I had more time to stick around to try and help everyone but I am severely tapped out

        • Linda March 28, 2016 at 11:28 am

          Actually the mito damge to heart muscle was suggested by someone who actually does research on FLQs and it makes sense to me. The only other thing I think it could be , which also makes a huge amount of sense, is damage to the autonomic nervous system—it is like I am breathing ok and then a door slides across (“OK—You’ve had enough air!”) WEird feeling that is hard to explain.

          Yeah, I am with you Jason…I so want for everyone to get out of this friggin nightmare. I hope Jwinn has success next week (or whenvever that is) and I am in touch with Steph by email and so have a soft spot for her. I hope her new neurologist has a light bulb moment.

          And I hope YOU find the perfect job. Thanks for letting us know you are OK. You were so missed!!! And I’m serious…maybe you should think about naturopath school (or acupuncture/chinese medicine…?)

        • Jason March 28, 2016 at 12:51 pm

          Unfortunately I don’t think there is a good chance Neurologist will help so much, hopefully but I would think a good Functional Doc would have more insight into what is going on for Steph

          Thx Linda I need all the well wishes and prayers I can get my CV is not good, and I have certainly not ruled out a position in the Health field one way or another 🙂

  17. Jason November 2, 2016 at 10:59 am Reply
    • Jason November 2, 2016 at 11:01 am Reply

      This is why I like the Functional Model and am studying the Modules, ROOT cause

  18. AndyP November 5, 2016 at 2:45 pm Reply

    I’ve only found one other floxie that has almost identical,symptoms to me and we are both in the UK
    We have had a lot of very bad reactions to most of the normal diet and supplement approaches to cipro poisoning and got talking about mast cell degradation as our symptoms are very close
    I can write on my skin with very little pressure ,I can’t really shower anymore the water hurts my skin so bad for hours afterwards and that’s with a filter fitted and aloe Vera chemical,free wash and almost cold water.Clothes hurt my skin I cancel the fibres from them,I never stop itching ever head to toe.And I have chronic non stop burning and nerve pain head to toe.
    I,also have severe symptoms of internal,cystitis and burning when I pee ,mast cell degradation in recent studies has been linked to internal cystitis
    If anybody with similar symptoms want to reach out to us to see how we are dealing with this please get in touch
    Oxylation and low histamine foods seems to be a key in the puzzle but as always only part of the answer
    Basically our floxing has turned us into the most severe cases of fibro ever ! But as we keep,saying we ain’t dead yet

  19. AndyP November 5, 2016 at 2:53 pm Reply

    Just like to add drugs that are on a mast cell degradation medical,journal list are
    NSAIDs ,opioids,morphine,codeien and many others
    Drugs to treat mast cell and histamine problems are the old school,antihistamine tangamet
    I took them all in large amounts before I realised I was floxed after every one I felt worse but obviously didn’t know why
    I also seem to react very badly to magnesium,Epsom salt baths just made me worse and worse as time went on again I didn’t realise before it was to late
    Jason maybe with your knowledge you could help us work this all out and choose the right path to healing

    • Jason November 7, 2016 at 1:00 am Reply

      Hi Andy. Sorry to hear you are going through all this. Glad to hear you realized the Epsoms were not helping, they are definitely not for everyone for a few reasons, even just Magnesium in a small number of cases can give trouble until the root of why is determined

      There is quite a bit of info on this page for Mast Cell stuff, I actually just learnt about one more thing today that might help but need to research it more, basically it is to help heal the Gut in these cases, and Gut is a huge key for most if not all Floxies.

      If you have not seen it yet, you should find more helpful info on this page below and I have added 20+ comments to the bottom, including common relapse and flare triggers and a bunch more info, and then links to other pages also full of important info. If you decide it is all too overwhelming and too much info and want help to sift through it all and figure out which info best applies to you I am currently still doing private consults for a very low rate. I have learned a great deal more in the last 12 months since all of these postings but most of the info is still relevant, I just know a LOT more now. Good healing to you Andy

      https://floxiehope.com/2015/10/12/im-floxed-now-what/

      • AndyP November 7, 2016 at 3:20 am Reply

        Hi Jason please let me know how to contact you off the site Andy

        • Jason November 7, 2016 at 8:55 am

          Hi Andy. Sorry I forgot to mention in my last comment, that my contact info is in the link I put there, near the end of the 2nd comment on the page.

  20. AndyP November 7, 2016 at 10:40 am Reply

    Sorry can’t find it please email me at p3rkles@hotmail.com

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