Studies On Histamine's Effects

[managing]

THat is an important distinction. I once found a study that suggested that histidine could boost brain histamine w/o boosting peripheral histamine. I asked Dr. P about it, but I don't recall getting a response.

I found my exchange with Dr. P. I noted increased alertness and energy. But after awhile I started to feel really cold all the time while taking it. He suggested
"One effect that a supplement of a single amino acid can have, if the concentration in the blood is high enough, is to inhibit the synthesis of proteins, by displacing other essential amino acids. That could reduce your heat production."

Which leads me to wonder if you take it with food, or on an empty stomach? I was taking it on an empty stomach.

 

[redsun]

It is not correct that people with high histamine necessarily are thin. Especially long term, histamine is yin-yang with inflammation and both can be raised.

People with high brain histamine will have a strong tendency to be more normal weight or underweight depending on the levels assuming they aren't forcing food down or doing weight gaining type diets (which is about having tons of calories to gain weight).

I found my exchange with Dr. P. I noted increased alertness and energy. But after awhile I started to feel really cold all the time while taking it. He suggested
"One effect that a supplement of a single amino acid can have, if the concentration in the blood is high enough, is to inhibit the synthesis of proteins, by displacing other essential amino acids. That could reduce your heat production."

Which leads me to wonder if you take it with food, or on an empty stomach? I was taking it on an empty stomach.

Supplementing histidine makes me much warmer. I take it with food usually. But sometimes if I don't, I did still have a meal prior and I still don't get cold from it.

But yeh Peat makes a good point so its important to be wary. The issue would be more likely to happen when you take on an empty stomach and/or take very high doses.

I don't think that my chronic fatigue is due to low histamine because I'm often fully alert when my muscles aren't working.

Furthermore, if my chronic fatigue is caused by lactic acid buildup, histamine would worsen it by increasing glycolysis.

Then you would test blood lactate levels to know for sure. Basically everyone will have normal lactate levels at rest unless you have B1 deficiency and/or severe anemia. Histamine will not worsen lactic acid build up.

Anyways, raising histamine will never fix fatigue on its own. Some get mostly mental benefits, some get both mental and physical energy increase but its not the CFS cure. It can however help a lot. If you do have low histamine it will likely help you more with physical fatigue though.

 

[managing]

Loss of histidine decarboxylase activity in aging thymus suggests histidine/histamine role in aging.

https://www.surgjournal.com/article/0039-6060(74)90127-5/pdf

 

[Ron J]

@redsun
Do you know if histidine supplementation has any effects on water retention/puffiness/edema?
Does it have any effects on stress hormones(prolactin, cortisol, adrenaline etc.)?

 

[redsun]

Association of prescription H1 antihistamine use with obesity: Results from the National Health and Nutrition Examination Survey

"The incidence of obesity in the US has reached epidemic proportions. Previous research has shown several medications exert noticeable effects on body weight regulation. Histamine 1 (H1) receptor blockers commonly used to alleviate allergy symptoms are known to report weight gain as a possible side effect. Therefore, we investigated the association between prescription H1 antihistamine use and obesity in adults using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Adults taking prescription H1 antihistamines were matched by age and gender with controls; and compared on the basis of body measurements, plasma glucose and insulin concentrations, and lipid levels. Prescription H1 antihistamine users had a significantly higher weight, waist circumference, and insulin concentration than matched controls. The odds ratio (OR) for being overweight was increased in prescription H1 antihistamine users. H1 antihistamine use may contribute to the increased prevalence of obesity and the metabolic syndrome in adults given these medications are also commonly used as over the counter remedies."

"H1 receptor antihistamines such as cetirizine, fexofenadine, and desloratadine are among the most commonly prescribed medications for the treatment of allergies and have been shown to stimulate appetite and weight gain as side effects of treatment."

"The mechanism through which histamine modulates insulin function and energy expenditure has not been fully elucidated (12). Histamine promoted glucose uptake in rat, but not human adipocytes (13). In humans, insulin has been shown to up-regulate H1 receptor expression (14). H1 receptor expression is also modulated by leptin levels (15), which become elevated when insulin levels are increased. The 2005–2006 NHANES did not measure leptin levels. Perhaps the weight observed with prescription H1 antihistamine use is related to the disruption of H1 receptor expression and binding leading to impaired insulin and leptin signaling. "

H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E knockout mice

"We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)−/− mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg body wt) in drinking water. Antihistamine treatments increased body weight gain, gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but not in ApoE−/− mice. Lobular inflammation, acute inflammation, and necrosis were not affected by H1-antihistamines in either genotype. Serum biomarkers of liver injury tended to increase in antihistamine-treated wild-type mice. Serum level of glucose was increased by fexofenadine, whereas lipase was increased by cetirizine. H1-antihistamines reduced the mRNA expression of ApoE and carbohydrate response element-binding protein in wild-type mice, without altering the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid synthase, or ApoB100, in either genotype. "

"The role of histamine and H1R in regulating obesity is evident from the fact that histidine decarboxylase knockout or H1R knockout mice are obese when fed a HFD compared with control (10, 24). This finding is further supported by the report showing reduced fat accumulation and adiposity in mice infused with histamine (23)."

"Despite the comparable amounts of food and water intake, the H1-antihistamine-treated wild-type mice gained more body weight and increased deposition of gonadal fat than untreated control mice. This observation is in accordance with the findings that chronic use of H1-antihistamines exacerbates obesity in humans (30)."

 

[managing]

Association of prescription H1 antihistamine use with obesity: Results from the National Health and Nutrition Examination Survey

"The incidence of obesity in the US has reached epidemic proportions. Previous research has shown several medications exert noticeable effects on body weight regulation. Histamine 1 (H1) receptor blockers commonly used to alleviate allergy symptoms are known to report weight gain as a possible side effect. Therefore, we investigated the association between prescription H1 antihistamine use and obesity in adults using data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Adults taking prescription H1 antihistamines were matched by age and gender with controls; and compared on the basis of body measurements, plasma glucose and insulin concentrations, and lipid levels. Prescription H1 antihistamine users had a significantly higher weight, waist circumference, and insulin concentration than matched controls. The odds ratio (OR) for being overweight was increased in prescription H1 antihistamine users. H1 antihistamine use may contribute to the increased prevalence of obesity and the metabolic syndrome in adults given these medications are also commonly used as over the counter remedies."

"H1 receptor antihistamines such as cetirizine, fexofenadine, and desloratadine are among the most commonly prescribed medications for the treatment of allergies and have been shown to stimulate appetite and weight gain as side effects of treatment."

"The mechanism through which histamine modulates insulin function and energy expenditure has not been fully elucidated (12). Histamine promoted glucose uptake in rat, but not human adipocytes (13). In humans, insulin has been shown to up-regulate H1 receptor expression (14). H1 receptor expression is also modulated by leptin levels (15), which become elevated when insulin levels are increased. The 2005–2006 NHANES did not measure leptin levels. Perhaps the weight observed with prescription H1 antihistamine use is related to the disruption of H1 receptor expression and binding leading to impaired insulin and leptin signaling. "

H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E knockout mice

"We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)−/− mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg body wt) in drinking water. Antihistamine treatments increased body weight gain, gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but not in ApoE−/− mice. Lobular inflammation, acute inflammation, and necrosis were not affected by H1-antihistamines in either genotype. Serum biomarkers of liver injury tended to increase in antihistamine-treated wild-type mice. Serum level of glucose was increased by fexofenadine, whereas lipase was increased by cetirizine. H1-antihistamines reduced the mRNA expression of ApoE and carbohydrate response element-binding protein in wild-type mice, without altering the mRNA expression of sterol regulatory element-binding protein 1c, fatty acid synthase, or ApoB100, in either genotype. "

"The role of histamine and H1R in regulating obesity is evident from the fact that histidine decarboxylase knockout or H1R knockout mice are obese when fed a HFD compared with control (10, 24). This finding is further supported by the report showing reduced fat accumulation and adiposity in mice infused with histamine (23)."

"Despite the comparable amounts of food and water intake, the H1-antihistamine-treated wild-type mice gained more body weight and increased deposition of gonadal fat than untreated control mice. This observation is in accordance with the findings that chronic use of H1-antihistamines exacerbates obesity in humans (30)."

Are H2 inhibitors also associated with weight gain?

 

[managing]

Do you have any thoughts (or research) differentiating histamine activity in the periphery vs in the brain?

 

[redsun]

Are H2 inhibitors also associated with weight gain?

If anything they cause weight loss because they disturb digestion and cause a lot digestive related side effects.

Do you have any thoughts (or research) differentiating histamine activity in the periphery vs in the brain?

Well 2nd generation antihistamines do not readily cross the blood brain barrier so they can help deal with allergies without disturbing brain function. Its just there's not too much you can do in enhancing histamine in the brain but not in the rest of the body except through drugs. If you took an H3 antagonist or something similar and took a 2nd generation antihistamine to reduce periphery effect maybe but seems pointless to me to mess with drugs like that.

 

[managing]

If anything they cause weight loss because they disturb digestion and cause a lot digestive related side effects.

Have you seen any of the stuff @haidut has posted about H2 (Famotidine) only reducing stomach acid in doses over 80mg/day for extended times? The reduction in ulcers is believed due to histamine having a direct role in ulceration and not reduction in stomach acid. I've found therapeutic doses as small as a few mg/day.

 

[managing]

Well 2nd generation antihistamines do not readily cross the blood brain barrier so they can help deal with allergies without disturbing brain function. Its just there's not too much you can do in enhancing histamine in the brain but not in the rest of the body except through drugs. If you took an H3 antagonist or something similar and took a 2nd generation antihistamine to reduce periphery effect maybe but seems pointless to me to mess with drugs like that.

I agree, but just out of curiosity, are there an exclusively H3 antagonists?

 

[redsun]

I agree, but just out of curiosity, are there an exclusively H3 antagonists?

Pitolisant. Also betahistine but it is also a weak H1 agonist.

 

[redsun]

Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness - PubMed

"Narcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult narcolepsy."

"All teenagers developed their disease during childhood (11.3 ± 2.4 years; 50% boys) and were 17.3 ± 0.8 years old at the time of pitolisant therapy. Pitolisant treatment was increased from 10 to 30 mg (n = 1) and 40 mg (n = 3). The adapted Epworth Sleepiness Score decreased from 14.3 ± 1.1 to 9.5 ± 2.9 (P = 0.03) with pitolisant alone to 7 ± 3.4 when combined with mazindol (n = 1), methylphenidate (n = 1), or sodium oxybate plus modafinil (n = 1). Mean sleep onset latency increased from 31 ± 14 minutes to 36 ± 8 minutes (P = 0.21) on the maintenance of wakefulness test. The severity and frequency of cataplexy were slightly improved. Adverse effects were minor (insomnia, headache, hot flushes, leg pain, and hallucinations) and transitory, except for insomnia, which persisted in 2 teenagers. The benefit was maintained after a mean of 13 months."

 

[Whichway?]

I’ve read the Pfeiffer stuff, however I’m always confused as to whether I fall in the high-histamine or low-histamine phenotype, as I seem to display definite symptoms and aspects of both.

@redsun did you have that issue, or did you clearly fit into just one camp or the other?

 

[redsun]

I’ve read the Pfeiffer stuff, however I’m always confused as to whether I fall in the high-histamine or low-histamine phenotype, as I seem to display definite symptoms and aspects of both.

@redsun did you have that issue, or did you clearly fit into just one camp or the other?

Likely because you are not either and your histamine levels are more in the normal range.

I was a clear histadelic as a child but through fad dieting for years messed up the metabolism and in the end eventual drug use to deal with my lost ability to perform in school gave me a lot of histapenic traits. It did of course deal with the cons of high histamine as well that I dealt with so much.

Eventually turned things around so its a bit simpler for me because I have the "genetics" for it. You can always take 1-2g histidine a day and see what happens. Its a brain thing more than anything else, so it helps with mental fatigue (also physical fatigue depending on the person) and improves cognitive function and it can help get a feel of where your at.

 

[redsun]

 

[Tidal]

This is a very interesting thread to me, as I appear to meet a lot of the criteria for low histamine. But then I have some aspects of high histamine as well.

I don't mean to take over this thread but years ago I took psychiatric drugs which has made me anhedonic and ruined my life. I can't catch colds unless I take a specific herb now. I have no motivation, no interest in anything, emotional numbness, strong derealization/depersonalization, memory impairment. In fact the only real occasion this let up was when I was forced to abruptly quit amitriptyline due to heart palpitations.

I suddenly got flu symptoms and felt like my brain woke up and reconnected, it was miraculous.

Someone suggested this effect could be due to histamine sensitization and I think it could be true. I often feel as if I'm not even conscious now. When I took just a small dose of cyproheptadine in the past, I felt like I was sleeping or unconscious whilst awake and far worse.

So I think tricyclics have messed up my histamine receptors somehow and it isn't active enough in my brain. I know amitriptyline has some of the most powerful antihistamine effects and I was on a high dose.
I also have dysautonomia and CFS type symptoms from taking these drugs with excess saliva and stomach acid ,which is probably contradicting -but that could be more to do with acetylcholine. I do get tingling in my head and my nostril is constantly inflamed as well.

Anyway i've been taking l histidine for a week but haven't noticed anything yet- I was taking it on an empty stomach. Maybe I should add p5p and zinc? Taken both in the past to no effect. I also take levothyroxine for my thyroid which I read raises histamine in the brain but doesn't help me.

However I'm convinced histamine is a major factor for me in some way. Especially after what I've read online and in this thread.

I might even have had high-ish histamine before because I met at least some of that criteria.

I still can't lose some of the weight I put on from amitriptyline , where as I would have easily before. Along with the fact I always want to eat now. Before I was rarely ever that hungry. I also have more body hair and prior to taking amitriptyline, I didn't have that much body hair at all. I was always quite skinny.

I want to experiment.
Does histidine have to be taken with food?
Unfortunately pitolisant is just too expensive and hard to get ahold of. Do you think it would be worth trying betahistine or is it too weak?
I just wish I could safely recreate histamine sensitization to test out my theory..

One last question: what relationship does histidine or histamine have with testosterone and cortisol?

 

[redsun]

This is a very interesting thread to me, as I appear to meet a lot of the criteria for low histamine. But then I have some aspects of high histamine as well.

I don't mean to take over this thread but years ago I took psychiatric drugs which has made me anhedonic and ruined my life. I can't catch colds unless I take a specific herb now. I have no motivation, no interest in anything, emotional numbness, strong derealization/depersonalization, memory impairment. In fact the only real occasion this let up was when I was forced to abruptly quit amitriptyline due to heart palpitations.

I suddenly got flu symptoms and felt like my brain woke up and reconnected, it was miraculous.

Someone suggested this effect could be due to histamine sensitization and I think it could be true. I often feel as if I'm not even conscious now. When I took just a small dose of cyproheptadine in the past, I felt like I was sleeping or unconscious whilst awake and far worse.

So I think tricyclics have messed up my histamine receptors somehow and it isn't active enough in my brain. I know amitriptyline has some of the most powerful antihistamine effects and I was on a high dose.
I also have dysautonomia and CFS type symptoms from taking these drugs with excess saliva and stomach acid ,which is probably contradicting -but that could be more to do with acetylcholine. I do get tingling in my head and my nostril is constantly inflamed as well.

Anyway i've been taking l histidine for a week but haven't noticed anything yet- I was taking it on an empty stomach. Maybe I should add p5p and zinc? Taken both in the past to no effect. I also take levothyroxine for my thyroid which I read raises histamine in the brain but doesn't help me.

However I'm convinced histamine is a major factor for me in some way. Especially after what I've read online and in this thread.

I might even have had high-ish histamine before because I met at least some of that criteria.

I still can't lose some of the weight I put on from amitriptyline , where as I would have easily before. Along with the fact I always want to eat now. Before I was rarely ever that hungry. I also have more body hair and prior to taking amitriptyline, I didn't have that much body hair at all. I was always quite skinny.

I want to experiment.
Does histidine have to be taken with food?
Unfortunately pitolisant is just too expensive and hard to get ahold of. Do you think it would be worth trying betahistine or is it too weak?
I just wish I could safely recreate histamine sensitization to test out my theory..

One last question: what relationship does histidine or histamine have with testosterone and cortisol?

If you have taken psychiatric drugs or other drugs in general, you need to look into possible nutrient depletion of the drugs you have taken. Often B vitamins can be depleted, minerals. Amitriptyline for example can possibly deplete/affect riboflavin metabolism as well as other vitamins. This alone can screw up your iron metabolism, antioxidant status (B2 is vital for glutathione), energy metabolism, and is either directly or indirectly involved in neurotransmitter metabolism for most NTs. Glutathione redox is vital for neurotransmitter function.

B2 and copper are necessary for breaking down serotonin via MAO-A which can contribute this. You may be in a high serotonin state because you lack riboflavin (or copper) and this will destroy motivation, energy, keep you a parasympathetic type state. B2 is also necessary for iron absorption (iron = dopamine).

These are just examples, you can easily be missing other things as well. Other drugs can affect other nutrients or systems. You need to spend time and research these things that you have taken because taking histamine boosting supplements when you can have multiple deficiencies and dysregulations due to drugs is likely not going to yield results because even when you raise histamine, if you have problems with other neurotransmitters being imbalanced (too high/too low) you will not fix anything.

Guidelines while you look into this is eating nutrient dense but especially mineral dense foods.

The most mineral dense foods are liver, oysters, red meats, organs in general, potatoes, tropical fruits, etc... Red meat should be a significant portion and eaten daily in the diet, its too valuable not to have.

If you are deficient in folates (or have problems with folate metabolism because you depleted other vitamins) due to drugs or what not, this can deplete histidine. Strong acid and saliva flow likely means you may be okay in that department. B complex alongside correct diet may help you out.

But the main point I want to get at is you likely multiple dysfunctions due to drugs, not just related to histaminergic neurotransmission, but possibly glutamatergic, dopaminergic, overall low sympathetic activity, deficiencies which could be causing or exacerbating all or some of these... List goes on.

Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline - PubMed

 

[czecha]

This is a very interesting thread to me, as I appear to meet a lot of the criteria for low histamine. But then I have some aspects of high histamine as well.

I don't mean to take over this thread but years ago I took psychiatric drugs which has made me anhedonic and ruined my life. I can't catch colds unless I take a specific herb now. I have no motivation, no interest in anything, emotional numbness, strong derealization/depersonalization, memory impairment. In fact the only real occasion this let up was when I was forced to abruptly quit amitriptyline due to heart palpitations.

I suddenly got flu symptoms and felt like my brain woke up and reconnected, it was miraculous.

Someone suggested this effect could be due to histamine sensitization and I think it could be true. I often feel as if I'm not even conscious now. When I took just a small dose of cyproheptadine in the past, I felt like I was sleeping or unconscious whilst awake and far worse.

So I think tricyclics have messed up my histamine receptors somehow and it isn't active enough in my brain. I know amitriptyline has some of the most powerful antihistamine effects and I was on a high dose.
I also have dysautonomia and CFS type symptoms from taking these drugs with excess saliva and stomach acid ,which is probably contradicting -but that could be more to do with acetylcholine. I do get tingling in my head and my nostril is constantly inflamed as well.

Anyway i've been taking l histidine for a week but haven't noticed anything yet- I was taking it on an empty stomach. Maybe I should add p5p and zinc? Taken both in the past to no effect. I also take levothyroxine for my thyroid which I read raises histamine in the brain but doesn't help me.

However I'm convinced histamine is a major factor for me in some way. Especially after what I've read online and in this thread.

I might even have had high-ish histamine before because I met at least some of that criteria.

I still can't lose some of the weight I put on from amitriptyline , where as I would have easily before. Along with the fact I always want to eat now. Before I was rarely ever that hungry. I also have more body hair and prior to taking amitriptyline, I didn't have that much body hair at all. I was always quite skinny.

I want to experiment.
Does histidine have to be taken with food?
Unfortunately pitolisant is just too expensive and hard to get ahold of. Do you think it would be worth trying betahistine or is it too weak?
I just wish I could safely recreate histamine sensitization to test out my theory..

One last question: what relationship does histidine or histamine have with testosterone and cortisol?

interesting, do you drink lots of coffee?
I have a similar story of depersonalization and no motivation.

i drink lots of coffee, like 5 cups a day.

last time I took a break from cofee, I got flu like symptoms after 2 days. They completely vanished after 1 cup again, in a matter of minutes. I wonder if histamine was at play here?

i did not notice any other positive changes because due to the flu like symptoms, I just felt like ***t, and my coffee withdrawal was only 2 days

time to take another coffee break and fight through the flu symptoms I guess, to see if that changes my brain

 

[redsun]

interesting, do you drink lots of coffee?
I have a similar story of depersonalization and no motivation.

i drink lots of coffee, like 5 cups a day.

last time I took a break from cofee, I got flu like symptoms after 2 days. They completely vanished after 1 cup again, in a matter of minutes. I wonder if histamine was at play here?

i did not notice any other positive changes because due to the flu like symptoms, I just felt like ***t, and my coffee withdrawal was only 2 days

time to take another coffee break and fight through the flu symptoms I guess, to see if that changes my brain

Question has been asked quite a few times actually, I posted in this thread explaining it:
Coffee Completely Reversing Flu Symptoms In A Matter Of Minutes?

 

[Tidal]

If you have taken psychiatric drugs or other drugs in general, you need to look into possible nutrient depletion of the drugs you have taken. Often B vitamins can be depleted, minerals. Amitriptyline for example can possibly deplete/affect riboflavin metabolism as well as other vitamins. This alone can screw up your iron metabolism, antioxidant status (B2 is vital for glutathione), energy metabolism, and is either directly or indirectly involved in neurotransmitter metabolism for most NTs. Glutathione redox is vital for neurotransmitter function.

B2 and copper are necessary for breaking down serotonin via MAO-A which can contribute this. You may be in a high serotonin state because you lack riboflavin (or copper) and this will destroy motivation, energy, keep you a parasympathetic type state. B2 is also necessary for iron absorption (iron = dopamine).

These are just examples, you can easily be missing other things as well. Other drugs can affect other nutrients or systems. You need to spend time and research these things that you have taken because taking histamine boosting supplements when you can have multiple deficiencies and dysregulations due to drugs is likely not going to yield results because even when you raise histamine, if you have problems with other neurotransmitters being imbalanced (too high/too low) you will not fix anything.

Guidelines while you look into this is eating nutrient dense but especially mineral dense foods.

The most mineral dense foods are liver, oysters, red meats, organs in general, potatoes, tropical fruits, etc... Red meat should be a significant portion and eaten daily in the diet, its too valuable not to have.

If you are deficient in folates (or have problems with folate metabolism because you depleted other vitamins) due to drugs or what not, this can deplete histidine. Strong acid and saliva flow likely means you may be okay in that department. B complex alongside correct diet may help you out.

But the main point I want to get at is you likely multiple dysfunctions due to drugs, not just related to histaminergic neurotransmission, but possibly glutamatergic, dopaminergic, overall low sympathetic activity, deficiencies which could be causing or exacerbating all or some of these... List goes on.

Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline - PubMed

Hi. Yes, I realized that I had vitamin deficiencies afterwards and took steps to tackle it. I take folic acid,b12 and I've tried all the b vitamins at one time or other, including riboflavin.

When it comes to copper, a hair mineral test gave me a low score but suggested I had hidden toxicity.

I'm definitely in a high serotonin state I think; just taking inositol really crashed my cognition previously and gave me terrible muscle spasms which still plague me.

Does histamine help to control sympathetic nerve tone? That test I took also suggested I was stuck in a parasympathetic state.

I'm looking chiefly at histamine due to my symptoms, that past window, and the fact it acts as a huge neuromodulator which can impact other systems. Also the fact I don't show flu symptoms normally.

I don't think it's as simple as just increasing histamine though.

I'm looking at the H3 receptor as a possible culprit given its complex role in the brain. For instance, I learnt that H3 receptors exert control over dopamine receptors, which is pretty big.