Studies On Histamine's Effects

Discussion in 'Scientific Studies' started by redsun, Jun 21, 2020.

  1. redsun

    redsun Member

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    I wanted to make a single thread for myself to post histamine related studies. As Peat himself is not a fan of histamine, lumping it together with things like cortisol and serotonin, I want to stick to one thread for all studies instead of posting them each as their own seperate thread in order to respect the main stance of this community on histamine. So I will post a few now, and I can always come back here and post some more in time.

    I will provide studies and post some excerpts from them. The studies in their entirety should be available for everyone to read and look into themselves (some may only have abstracts which I will try to avoid for the most part). More practical information will be bolded.

    I want to emphasize that in someone that has very elevated histamine, raising histamine is obviously a not a good idea. So the kind of people that this applies to is those that are naturally very slender/underweight (meaning they stay thin without paying attention at all to food intake), have many histamine reactions and allergies and other histamine related disorders, etc...

    Someone who is very thin to the point of being underweight should not do something that may further reduce bodyweight. Just to emphasize, terrible digestion and food intolerance is not due to high histamine but can be related to low histamine (though raising histamine alone may or may not fix the issue).

    So we all need to be aware of ourselves and who we are and not go around lowering things that we already have too low and raising things that we already have too high. This applies to histamine, but also to everything else whatever it may be.

    If you struggle with very poor cognition/very low motivation (dopamine is clearly involved in motivation as well) and/or are overweight and have trouble maintaining a normal weight because appetite is very high, consider low brain histamine. Increasing brain histamine will help reduce appetite and increase appetite control and improve cognition/motivation, libido and sexual function overall.

    If you have questions, feel free to ask them in this thread. I didnt want to put this in the debate section, since this is not about debate. This is about providing information to those that may be struggling in large part due to chronically low histamine levels and also for those that are curious about histamine since its so easy to learn about the negatives of histamine but so I wanted to provide info for those wanting to learn about the positives of histamine.

    Some definitions

    TMN - Tuberomammillary nucleus: source of histamine pathways in the brain
    Histamine methyltransferase (HMNT) - methylates histamine using SAM, deactivating it
    HDC - Histidine Decarboxylase, synthesizes histamine from histidine

    Histamine in the brain

    "Brain histamine promotes wakefulness and orchestrates disparate behaviors and homeostatic functions. Recent evidence suggests that aberrant histamine signaling in the brain may also be a key factor in addictive behaviors and degenerative disease such as Parkinson's diseases and multiple sclerosis."

    "In fact, histamine signaling controls feeding behavior in a complex fashion and it has been considered for long, a satiety system, as brain histamine decreases the drive to consume food. In their paper, Ishizuka and Yamatodani (2012) demonstrated the fine regulation of histamine release during feeding and in taste perception. Furthermore, they showed that histamine neurons respond to both mechanical and chemical sensory input from the oral cavity, as may be expected for a danger detection system."

    Histamine and motivation

    "Here, we review evidence indicating that brain histamine plays a central role in motivation and emphasize its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control histaminergic neurons of the tuberomamillary nucleus (TMN) of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles, and food anticipatory responses."

    "The relationship between the motivation for food, arousal, and TMN activity was first studied using a model of restricted feeding. Rats placed on a feeding schedule that is restricted to a few daytime hours wake up in anticipation of mealtime. This anticipatory behavior has an important adaptive value because in nature, food may be available during the same few daily hours (Stephan, 2001), and the anticipatory physiological and behavioral activation prepares the animals to take advantage of this predictable phenomena."

    "Novelty has reinforcing properties that motivate the exploration of new environments or novel objects. Evidence indicates that this exploration depends on an intact prefrontal cortex (Daffner et al., 2000) and histamine system. It has been shown that mice lacking the enzyme histidine decarboxylase (HDC) show decreased spatial novelty-induced arousal (Parmentier et al., 2002) and reduced exploratory activity in an open field but normal habituation to the same open field (Dere et al., 2004)"

    "The nucleus accumbens (NAcc) is one site where histamine increases exploratory behavior through the activation of H1 and H2Rs (Orofino et al., 1999)."

    "Orexin (hypocretin) neurons from the LHA, which are involved in appetitive behavior, in part because of their role in incentive saliency (Harris et al., 2005), form a well studied excitatory (Bayer et al., 2001; Eriksson et al., 2001) input to histaminergic neurons [while histamine has little effect on orexin neurons (Li et al., 2002)]. Orexin neurons may be considered a modulatory input to the TMN"

    "Orexinergic neurons, perhaps under cortical influence (Monda et al., 2004), operate through type B receptors and histamine to increase brown adipose tissue sympathetic nerve activity (Yasuda et al., 2005) and thermogenesis."

    "Regarding the histaminergic system, a reduction in H1R ligand binding in the frontal lobe of depressed patients (Kano et al., 2004) and schizophrenic patients (Iwabuchi et al., 2005) and the frontal and temporal regions of Alzheimer's disease patients (Higuchi et al., 2000) has been observed. "

    "Parkinson's disease patients have increased levels of histamine but do not have increased levels of its metabolite, telemethylhistamine, in the putamen, substantia nigra compacta, and both divisions of the globus pallidus (Rinne et al., 2002); they also have increased histamine fibers in both divisions of the substantia nigra (Anichtchik et al., 2000). However, no increase in HDC mRNA expression was found in the TMN (Shan et al., 2012b) of Parkinson's disease patients, suggesting that there is no change in histamine production."

    "Reduced H3R mRNA expression and increased histamine methyltransferase mRNA levels in the susbtantia nigra were also found in Parkinson's disease patients (Shan et al., 2012a)."

    "Pharmacological evidence also indicates a causal relationship between histamine dysfunction and apathy. Methylphenidate strongly increases extracellular levels of dopamine, noradrenaline (Berridge et al., 2006), and histamine in the rat prefrontal cortex (Horner et al., 2007) and improves apathy scores in patients with Alzheimer's disease (Padala et al., 2010), stroke (Spiegel et al., 2009), and dementia (Dolder et al., 2010). It is possible that the increase in the histamine levels by methylphenidate is secondary to the increased extracellular concentration of dopamine, as is the case for systemic methamphetamine administration (Morisset et al., 2002), because D2 brain receptor activation enhances the TMN neuronal firing frequency, histamine release, and wakefulness in freely moving rats (Yanovsky et al., 2011)."

    "A well studied example is the reliable and phasic decrease in food intake that follows a cyclic increase in estrogen in rodents and primates, including humans (Geary et al., 2001). While several hypothalamic nuclei, including the TMN, express estrogen receptors, the anorectic effect of estradiol appears to depend on its direct action on TMN neurons, in addition to the effects of corticotropin-releasing hormone on TMN neurons (Gotoh et al., 2005). Estradiol also acts on the paraventricular hypothalamic nucleus (an important anorexigenic region), which releases corticotropin-releasing hormone (Gotoh et al., 2009). Histaminergic neurons may act on ventromedial hypothalamic nucleus (VMH) neurons via H1R to decrease food intake (King, 2006)."

    "Blockade of H1R within the VMH, but not in other hypothalamic nuclei such as the paraventricular hypothalamic nucleus or the LHA, increases both meal size and duration and suppresses the activity of glucose-responsive neurons (Fukagawa et al., 1989)."

    "Rats with a strong preference for alcohol have elevated levels of brain histamine and its metabolites, as well as a higher density of histaminergic nerve fibers than rats with a lower preference for alcohol (Lintunen et al., 2001)."

    "Local administration of histamine into the NAcc increases or decreases the firing rate of the accumbens neurons (Shoblock and O'Donnell, 2000) and increases local extracellular dopamine via H1 activation of cholinergic interneurons (Prast et al., 1999), which act on presynaptic nicotinic receptors to increase dopamine release (Wonnacott et al., 2000; Galosi et al., 2001)."

    Histamine and the nervous system
    https://journals.physiology.org/doi/full/10.1152/physrev.00043.2007

    "Histamine is a transmitter in the nervous system and a signaling molecule in the gut, the skin, and the immune system. Histaminergic neurons in mammalian brain are located exclusively in the tuberomamillary nucleus of the posterior hypothalamus and send their axons all over the central nervous system. Active solely during waking, they maintain wakefulness and attention. Three of the four known histamine receptors and binding to glutamate NMDA receptors serve multiple functions in the brain, particularly control of excitability and plasticity. H1 and H2 receptor-mediated actions are mostly excitatory; H3 receptors act as inhibitory auto- and heteroreceptors. Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease."

    " The name histamine for imidazolethylamine indicates an amine occurring in tissues. The presence and biological activities of histamine were detected by Sir Henry Dale and co-workers almost a century ago: contraction of smooth muscles in the gut and vasodilatation (130). The stimulation of acid secretion in the stomach (582) was also recognized early. Feldberg (172) demonstrated histamine release from mast cells in the lungs during anaphylactic shock causing constriction of the bronchi. The presence of histamine in the brain, predominantly in the gray matter, was first shown by Kwiatkowski (1941 (378), and White (1959) (814) demonstrated its formation and catabolism in the brain. The sedative “side effects” of antihistamines (68) triggered early work and suggestions for histamine as a “waking substance” (488)."

    "Histamine (CID 774) is synthesized from the amino acid histidine through oxidative decarboxylation by histidine-decarboxylase (HDC; EC 4.1.1.22), a pyridoxal 5′-phosphate (PLP)-dependent enzyme (177) found in many species and highly conserved throughout the animal kingdom from mollusc, insect, rodent, to human"

    "
    A) GLUTAMATE.

    Glutamatergic fibers from the cortex and the hypothalamus are present and glutamate excites TMN neurons, which carry both AMPA and NMDA receptors (840), and the neuronal glutamate transporter EAAC1 was detected by immunohistochemistry near histamine neurons (170). "

    "A number of NMDA antagonists increase the synthesis and turnover of histamine, indicating the possibility of an (indirect) inhibitory action through NMDA receptors on TMN neurons which express the NR1, NR2A, and NR2B NMDA receptor subtypes"

    "C) GABA.

    GABAergic inputs come from several mostly hypothalamic locations, functionally prominent with respect to sleep-waking regulation is the innervation from the ventrolateral preoptic (VLPO) area which fires high during sleep and thus suppresses the firing of histamine neurons (159, 636, 678, 703). "

    "B) CATECHOLAMINES.

    The TMN receives input from the noradrenergic cell groups including the locus coeruleus. Norepinephrine does not affect histaminergic neurons directly but effectively controls GABAergic input through α2-adrenoreceptors mediating an inhibition of IPSCs: evoked GABAergic IPSPs are reduced by norepinephrine and clonidine but not isoproterenol while exogeneously applied GABA responses remain unaffected (707). Dopamine also excites histamine neurons through D2 receptor activation (671)."

    " ATP evokes fast nondesensitizing inward currents in TMN neurons. Single-cell RT-PCR and pharmacological analysis revealed P2X2 receptors as the major receptor type that occurs in all TMN neurons (796); five further types are expressed rarely. Zn2+ acts as a bidirectional modulator of P2X2 receptors (797). Zn2+ potentiation of ATP responses is caused by slowing ATP dissociation from the receptor, while inhibition at higher concentrations of Zn2+ is related to suppression of gating. ATP, ADP, UTP, and 2MeSATP excite TMN neurons through metabotropic receptors; P2Y1 and P2Y4 are prevailing (670). "

    "Both hypocretins (1 and 2, also known as orexin A and B) excite histamine neurons through the Hcrt2 receptor and activation of NCX (163, 165, 166, 664) (Fig. 9). This action is secondary to a rise in intracellular Ca2+ that probably comes from both extra- and intracellular sources. Hypocretin neurons also express dynorphin, which can contribute to the excitation of histaminergic neurons by suppressing inhibitory GABAergic inputs (164). "

    "Neuropeptide Y (NPY)-containing fibers are found close to histaminergic neurons (734), and NPY indirectly affects histamine release (286). The appetite-stimulating stomach-derived ghrelin inhibits a potassium channel (Kir3) in cultured TMN neurons (39). Thyrotropin releasing hormone (TRH) reduces food intake (215) and sleeping time in rats and combats excessive sleepiness in canine models of narcolepsy (612). The majority of the TMN neurons are excited by TRH (673)."

    "Prostaglandin E2 activates the TMN via the EP4 receptor to induce wakefulness in rats (273). Endocannabinoids increase histamine release selectively in the TMN through CB1R but independent from modulation of GABAergic transmission (100). Histaminergic neurons may also be involved in CO2-mediated arousal (306, 527)."

    "Histamine through H1R excites neurons in most brain regions, including brain stem (45, 367, 407) (Fig. 12), hypothalamus, thalamus (462, 694, 855), amygdala, septum (213, 828), hippocampus (445, 659), olfactory bulb (299), and cortex"

    "Classic antihistamines act at H1R (684) with well-known sedative properties (67, 407, 603). Many antidepressants or antipsychotics also bind to the H1R (336, 611)."

    "Interestingly, the absence of histamine downregulates H2R expression but not H1Rs in a tissue-specific manner (175)."

    "H2R couple to Gsα proteins to stimulate adenylyl cyclase and increase intracellular cAMP (40, 50, 197, 764), which activates protein kinase A (PKA) and the transcription factor CREB, all of which are key regulators of neuronal physiology and plasticity (35, 234, 462, 562, 563, 659). "

    "A second messenger-mediated modulation of ionotropic receptors is common for several transmitters: facilitation of NMDA receptors through PKC and a reduction of the Mg2+ block have been described as a result of H1 receptor activation (561)."

    "G. Thyroid Axis

    Systemic l-thyroxine administration, along with rises in T3 and T4 levels, increases cortical 5-HT and histamine content,"

    "Depletion of brain histamine decreases locomotion. Likewise, chronic loss of H3R function in H3R-KO mice is associated with reduced locomotion (762) and mice lacking histamine (HDC-KO), or the H1R (284) display altered ambulatory activity and reduced exploratory behavior, particularly in a novel environment (556)."

    "H1 antihistamines impair cognitive performance in humans, and this action has been largely attributed to sedative effects (723) (see above) resulting from suppression of cholinergic subcortical (334, 335, 828) and cortical activity (60, 603, 828)."

    "Histamine-deficient HDC-KO mice have elevated testicular and serum androgen levels but reduced testis weight, independent from GnRH expression, and their mating behavior and sexual arousal are strongly impaired (554). Likewise, administration of the H1 antihistamine astemizole affects testis weight and male reproductive behavior. Histamine may thus play a role in brain masculinization."

    "Hypersomnia is currently treated mainly by drugs enhancing dopaminergic effects such as amphetamines and modafinil, which can also promote wakefulness by activating TMN histamine neurons (642)."

    "Histamine- and histamine receptor-deficient animals show hyperphagia and disruption of feeding circadian rhythm and develop obesity, diabetes mellitus, hyperlipidemia, hyperinsulinemia, and disturbance of thermoregulation and cardiovascular functions (187, 311, 453, 739, 848), fundamental marks of metabolic syndromes. Behavioral and metabolic abnormalities produced by depletion of neuronal histamine from the hypothalamus mimic those of obese Zucker rats (628)."

    Increased Susceptibility to Diet-Induced Obesity in Histamine-Deficient Mice - PubMed

    "The neurotransmitter histamine is involved in the regulation of appetite and in the development of age-related obesity in mice. Furthermore, histamine is a mediator of the anorexigenic action of leptin. The aim of the present study was to investigate a possible role of histamine in the development of high-fat diet (HFD)-induced obesity."

    "Both HDC-KO and WT mice fed an HFD for 8 weeks increased their body weight significantly more than STD-fed mice. A significant difference in body weight gain between HDC-KO mice fed an HFD or an STD was seen after 2 weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. "

    "After 8 weeks epididymal adipose tissue size and plasma leptin concentration had increased significantly in HFD-fed WT and HDC-KO mice compared to their STD-fed controls."

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

    "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."

    Hypothalamic Neuronal Histamine Regulates Body Weight Through the Modulation of Diurnal Feeding Rhythm - PubMed

    "Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R), a leptin signaling pathway in the brain, regulate body weight and adiposity by affecting food intake and energy expenditure. Glucagon-like peptide-1 and/or corticotrophin-releasing hormone mediate leptin signaling to neuronal histamine. Leptin-induced suppression of food intake and upregulation of uncoupling protein-1 expression in brown adipose tissue were partially attenuated in histamine H(1)-R knockout (H(1)KO) mice. H(1)KO mice developed maturity-onset obesity. Hyperphagia and decreased energy expenditure assessed by the expression of uncoupling protein-1 mRNA were observed in older (48-wk-old) obese H(1)KO mice"

    "Early disruption of H(1)-R-mediated functions in H(1)KO mice may lead to hyperphagia and decreased energy expenditure, which may contribute to the development of obesity in these animals."

    Role of dietary histidine in the prevention of obesity and metabolic syndrome

    "A recent Chinese supplementation study, in which obese middle-aged women diagnosed with metabolic syndrome received 12 weeks of supplemental histidine (2 g, twice daily) or matching placebo, achieved remarkable findings. Insulin sensitivity improved significantly in the histidine-supplemented subjects, and this may have been partially attributable to loss of body fat. Body mass index (BMI), waist circumference and body fat declined in the histidine-supplemented group relative to the placebo group; the average fat loss in the histidine group was a robust 2.71 kg. Markers of systemic inflammation such as serum tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6, non-esterified fatty acids and oxidative stress also decreased in the histidine group"

    "These intriguing findings were not altogether unexpected, as earlier rodent studies had shown that supplemental histidine tends to inhibit food intake, via an impact on the hypothalamus that is mediated by the neurotransmitter histamine. Acting via H1 receptors in the ventromedial and paraventricular hypothalamic nuclei, histamine suppresses feeding behaviour, promotes adipocyte lipolysis via sympathetic activation and raises metabolic rate. These effects are analogous to those of leptin on the brain, and indeed histamine has been shown to be a key mediator of leptin signalling in the hypothalamus. Leptin triggers histamine release in the hypothalamus, and histamine in turn prevents the downregulation of leptin receptors which mediates leptin resistance. Crucially, whether administered intraperitoneally or intraventricularly, histidine dose dependently increases hypothalamic levels of histamine as well as hypothalamic activity of histidine decarboxylase, the enzyme which converts histidine to histamine. Such administration also inhibits food consumption—an effect that is blocked in animals pretreated with an irreversible inhibitor of histidine decarboxylase"

    "Transport of histidine into the brain may depend not only on plasma histidine level but also onneutral amino acids—including the branched-chain amino acids (BCAAs)—that can compete for access to the neutral amino acid transporter that mediates their transport through the blood–brain barrier. Hence, the rate of brain histidine uptake via this transporter should be proportionate to the plasma ratio of histidine to the sum of other neutral amino acids; this sum is determined primarily by BCAA levels. This observation may be pertinent to cross-sectional studies concluding that plasma levels of BCAAs are elevated in those with type 2 diabetes, metabolic syndrome and/or obesity."

    Central Infusion of Histamine Reduces Fat Accumulation and Upregulates UCP Family in Leptin-Resistant Obese Mice - PubMed

    "Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice. Infusion of histamine (0.05 pmol x g body wt(-1) x day(-1)) into the lateral cerebroventricle (i.c.v.) for 7 successive days reduced food intake and body weight significantly in both diet-induced obesity (DIO) and db/db mice. Histamine treatment reduced body fat weight, ob gene expression, and serum leptin concentration more in the model mice than in pair-fed controls. The suppressive effect on fat deposition was significant in visceral fat but not in subcutaneous fat. Serum concentrations of glucose and/or insulin were reduced, and tests for glucose and insulin tolerance showed improvement of insulin sensitivity in those mice treated with histamine compared with pair-fed controls. On the other hand, gene expression of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 expression in white adipose tissue were upregulated more in mice with i.c.v. histamine infusion than in the pair-fed controls. "

    https://www.ncbi.nlm.nih.gov/books/NBK27916/

    Histamine synthesis in the brain is controlled by the availability of l-histidine and the activity of histidine decarboxylase
    "Figure 14-4 depicts the dynamics of histamine in mammalian brain. Although histamine is present in plasma, it does not penetrate the blood—brain barrier. Thus, histamine concentrations in the brain must be maintained by synthesis. With a Km value of 0.1 mm for L-histidine under physiological conditions, HDC is not saturated by histidine concentrations in the brain, an observation which explains the effectiveness of large systemic doses of this amino acid in raising the concentrations of histamine in the brain. The essential amino acid l-histidine is transported into the brain by a saturable, energy-dependent mechanism (see Chap. 32)"
     
  2. Lokzo

    Lokzo Member

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    Outstanding work man, thanks for sharing this.

    What's your personal experience with histamine modulating drugs/supps been like?
     
  3. OP
    redsun

    redsun Member

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    I have used as a stack daily:
    2-4g L-histidine (base, not HCL but both work of course)
    zinc (15-30mg should be the limit)
    P5P (25mg the limit)

    Some observations utilizing this stack:
    • Felt like my brain never got tired and was on the ball constantly yet it did not give the same stimulating feeling of taking a ton of caffeine at once.
    • Physical energy was somewhat increased, but mental energy and speed was especially increased.
    • Though physical energy barely changed, I wanted do things and whatever I already was doing planwise I had more zest for. Wanting/desire and having motivation for life is a big thing to me, and likely many others. Very positive, lively energy for the most part
    • Things were more enjoyable, felt very grounded in life. The increased wakefulness due to histamine brightens up your senses, especially visuals.
    • Had to be careful when I took the stack, as the meal I had and took with it would be my last. I would barely eat basically because of it.
    • Slept less and woke up easier. My muscles could be tired but my brain was wide awake.
    • I would heat up a lot at the gym, pumps also increased (I used to have barely any). Sweating increased too, which is not a positive but its whatever.
    • Doesn't make you "smarter", but makes your thinking processes better and faster and much more clear. Almost like it is allowing you to use more of your brain at once. So in that way the knowledge you do have you can utilize to a higher degree and also learning new things is MUCH easier.
    • Libido increased, though my libido wasnt a problem it just raised even more
    • Increased emotions (both positive and negative)
    I have also used folic acid sometimes, but folic acid can be converted to tetrahydrofolic acid and convert histidine to glutamic acid. So if you take folic acid, you will have histamine and more glutamate action which can be good, or without folic acid you will have mostly histamine action (some of course will be converted to glutamic acid from the folic acid you have in the body). It also helps increase histidine retention probably, but this may only apply when you are deficient in folic acid.

    Niacinamide can be used here as well as it may trigger more histamine to release. So you make it with histidine/zinc/B6, and B3 releases it. You will still release histamine normally without it, but it may make sense to take a small amount of B3 to maximize release. Debatable.
     
  4. Korven

    Korven Member

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    I feel like I tick all the boxes for high histamine:
    • Extremely hard to gain weight
    • Can digest pretty much anything without problems (though I do get gassy when certain fibers reach the colon)
    • Allergic reactions, sneezing etc
    • High motivation to do stuff
    • High libido
    • Learn things very fast, high cognition
    • History of addiction, OCD, bipolar tendencies
    In another thread you mentioned that histadelics get sick/colds/flus more often, which is definitely true in my case as well. I don't mind the high libido/motivation/cognition/digestion/, and the OCD stuff I've learned to manage so that's not a problem, but getting sick all of the time just sucks.

    ...Any tips on what to do to "dial down" histamine levels?
     
  5. OP
    redsun

    redsun Member

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    Well just keep in mind you tone down histamine everything it is responsible for tones down as well. What I would do in your case is if you feel a cold/flu come on take a highish dose of zinc (25-50mg) with 2g of vitamin C and that may stop it altogether or reduce symptoms. Vitamin C is antihistamine, zinc is important for immunity despite its pro-histamine raising effects. Zinc alone can have the opposite effects, Im not going to get into it too much but yeh Zinc + vitamin C.

    If this doesn't work. You can increase DAO via P5P, copper, vitamin C through foods which are high in them or as supplements in small doses. Also calcium and methionine rich foods would help as well. But this should not be the first approach, Try Zinc + C first in the interesting of preserving the positives.
     
  6. OP
    redsun

    redsun Member

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    H1 receptor activation stimulates tyrosine hydroxylase which is the rate limiting step in catecholamine synthesis including dopamine:

    Role of PKA and PKC in Histamine H1 Receptor-Mediated Activation of Catecholamine Neurotransmitter Synthesis - PubMed

    "Activation of the histamine H1 receptor stimulates tyrosine hydroxylase (TH) to increase catecholamine neurotransmitter synthesis in mammalian brain and adrenal tissues. Histamine non-selectively activates both H1-linked phospholipase (PL) C/inositol phosphates (IP)/diacylglycerol (DAG) signaling and adenylyl cyclase (AC)/adenosine 3',5'-cyclic monophosphate (cAMP) signaling, confounding determination of signaling events involved in H(1)-mediated TH activation. "

    Histidine administration reduces mental fatigue and improves cognitive performace (attentiveness, reaction time) in subjects with high fatigue and sleep disruption scores:

    The Effect of Histidine on Mental Fatigue and Cognitive Performance in Subjects With High Fatigue and Sleep Disruption Scores - PubMed

    "We investigated the effects of histidine intake on the feeling of fatigue, mood states and mental task performance by performing a placebo-controlled, double-blind crossover trial. Twenty subjects with high fatigue and sleep disruption scores were asked to ingest histidine or a placebo every day for two weeks. The subjects' mood states were evaluated using the Profile of Mood States (POMS) scale and a visual analog scale (VAS) for eight feelings (fatigue, depression, carelessness, drowsiness, clear thinking, motivation, attentiveness and concentration). We also measured subjects' cognitive performance using the CogHealth test battery. The fatigue T-scores on the POMS test decreased significantly following histidine ingestion compared to placebo ingestion (p<0.05). After two weeks of histidine ingestion, the reaction time for the working memory task in the CogHealth test battery was significantly shorten compared to placebo ingestion. The VAS scores for clear thinking and for attentiveness were increased significantly following histidine ingestion compared to placebo ingestion (p<0.05). These results suggest that daily ingestion of histidine may ameliorate feelings of fatigue, increase performance during working memory tasks, and improve the clear thinking and attentiveness."
     
  7. Lokzo

    Lokzo Member

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    Phenomenal man!!

    Sounds like my experience back when I used L-Histidine!!

    I may have to run that experiment again.

    I think a lot of the benefits you're experiencing can also be related to its ability to raise Carnosine levels in the body!
     
  8. orewashin

    orewashin Member

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    I have a question about that. I remember that low-histamine people were said sweat sparsely, whereas high-histamine people were said to sweat profusely.

    I sweat sparsely, except in my armpits, whereas my father sweats profusely. I have a machine that can measure SCD (skin conductance) among other things. I once tried it with my father and my SCD was very low, whereas his was high. Which makes sense. I don't sweat much even under stress, whereas I remember how wet his forehead was when we were running late for a plane and waiting in line.

    There are differences in SCD between people, and SCD level is higher in people who have a more active cortex. From what you say about histamine increasing wakefulness, I guess it would increase arousal. I wonder if my low sweating is due to being more "go with the flow" or if it's related to low histamine. I speculated that it was due to hypothyroidism, but thyroid doesn't seem to make me sweat.

    Normally, I associate sweating with adrenalin. So then, does histamine induce sweating by increasing arousal, or does it do it through a local mechanism? Since it counteracts adrenalin, I would have trouble understanding how it can do it locally.

    Antihistaminergic and anticholinergic drugs cause a person to be unable to sweat, which is another association, but they can also work either peripherally or centrally.
     
  9. OP
    redsun

    redsun Member

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    Noradrenaline is the main one in regards to sweating and if there is enough H2 activation by histamine it will raise noradrenaline and increase sweating or make it more likely to happen. Theres a difference between noradrenaline and adrenaline. The fact that histamine will usually raise the body temp which will increase the need for sweat to cool down temps. We have to remember what the purpose of sweat is to begin with.

    I actually had high histamine as a child but messed with my metabolism with fad diets so even minor histamine boosting acts a bit stronger for me since I have the "genetics" for excess based on childhood. I sweat normally from exercise and but temp rises up and subsequently I sweat even more easily when i take histamine boosting stuff. But the same applies to anyone that raises histamine high enough.
     
  10. Hans

    Hans Member

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    Acetylcholine promotes sweating. Activation of the sympathetic nervous system stimulated the release of acetylcholine and that causes the sweating. That's why stressed people get sweating hands, feet and pits.
    Histamine can also promote the release of acetylcholine. Histaminergic Neurons Modulate Acetylcholine Release in the Ventral Striatum: Role of H3 Histamine Receptors - PubMed
     
  11. orewashin

    orewashin Member

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    Low histamine people often have high copper, which is used for making dopamine beta hydroxylase, the enzyme that converts dopamine to noradrenaline. By that logic, high histamine people should have a lack of noradrenaline.

    The body temperature explanation is probable. I recall that high histamine increases calorie burning, this would likely increase temperature.

    RP mentioned a type of hypothyroidism in which people eat lots of calories, but remain skinny and waste a lot of energy on glycolysis. He said that he himself had this issue, and when he started supplementing thyroid, his caloric requirement actually went down. Do you think this was due to high histamine?

    It doesn't say much about why skin conductance (sweating, particularly in the hands and feet) is correlated so strongly with arousal. So it's something different, like noradrenaline activating sweating in the brain stem.

    The image I'm getting is that histamine mainly increases sweating through higher calorie consumption. Yet, you also said that histamine is highly involved with arousal in the CNS, so you're saying it increases sweating both ways?

    So acetylcholine again. But in the other thread, you mentioned that my symptoms are probably from acetylcholine, and I still sweat very little.

    Furthermore, anticholinergic drugs inhibit sweating and they are used for hyperhidrosis.

    Since neurotransmitters are used for different purposes, maybe it does cause sweating through a certain pathway, but I was thinking about something more generalized.
     
  12. Hans

    Hans Member

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    That's why I mentioned in the previous thread that it could be something else, such as swelling that's pinching a nerve.
    It's best to look at all the symptoms of elevated/low acetylcholine and what might be causing it to be elevated/low and then fix that instead of directly modulating it.
     
  13. OP
    redsun

    redsun Member

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    Its not as simple as copper causing low histamine. You can be sufficient in copper, and you can still be a histadelic. And you dont necessarily have to be high in copper to have low histamine, though excess copper will cause low histamine especially chronically. There is a genetic component, but there is also the fact that if you cant make or can't make enough histamine, you will also have low histamine. So its not about just breaking it down, its about how much you can make as well.

    Genetically you can have HMNT, DAO variations or something else that can affect it. This is what I have seen in these books, reason for histadelia is unknown or blamed on genetics. Histapenia can be poor diet, high copper, etc... Chronic/severe inflammatory conditions can also deplete histidine theoretically and thus reduce histamine.

    Is it a coincidence why after severe physical injuries (that thus lead to lots of swelling/inflammation) many people gain weight more readily. Physical activity being reduced and the risk of depression because of the injury can trigger emotional eating, but it could also be histidine depletion causing low histamine eventually.

    Its possible Ray Peat had elevated histamine when he was young and could partly explain that. Most children and teenagers do and also they have higher thyroids.

    higher metabolism = higher calorie consumption and this also comes with heightened arousal/awareness and more CNS stimulation so I wouldn't say it is seperate. Body temp would also be higher so need for sweating would increase based on the environment you are in.

    Here's a little excerpt from Pfeiffer's book that is related:

    Screenshot_20200625-182452_Drive.jpg
     
  14. orewashin

    orewashin Member

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    I remember reading that. I knew a woman who had a very dry mouth, but her vagina was wet or had a normal degree of wetness. But I didn't know many people with severe physical injuries. She gained a lot of weight following a relative's death, so that might be seen as a severe injury.

    Histidine is kept in muscle tissue and readily liberated by cortisol, so why would there be histidine depletion, unlike collagen protein depletion, which would make more sense considering that collagen isn't kept in large amounts in muscle tissue?
     
  15. OP
    redsun

    redsun Member

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    Depends on age, as the younger you are the better lubrication will work. Dry mouth can be caused by a lot of things, medications she could have been taking, caffeine in coffee (many women have blood made of coffee nowadays), lack of proper hydration (water and electrolyte intake), etc...

    Severe emotional pain can be just as damaging as a severe injury to the whole organism depending on how long it takes for the individual to accept it and move on.

    As for histidine depletion, any essential and conditionally essential amino acid can easily become depleted including histidine because it cannot be made in the body. Whatever you have it is from food. The prime amino acids contained in collagen are glycine, proline (and thus hydroxyproline).

    Glycine can be synthesized but synthesis is not enough to meet daily needs and thus glycine in the diet is needed. Theoretically glycine can be used up faster in tissue injuries and the demand for it would increase. But proline is non-essential since it can synthesized from l-glutamate.
     
  16. orewashin

    orewashin Member

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    What are the purest histidine, zinc, and P5P supplements that you know of?
     
  17. OP
    redsun

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    Bulksupplements provides L-histidine as L-histidine base or L-histidine HCL. I use base as that is just histidine and nothing else so the exact measurements provided is what you are getting as histidine and HCL is factored in there. No other ingredients in there either.

    I generally think pure encapsulations for P5P and zinc are pretty good as cleaner products but I am sure there are others on market that are similar.
     
  18. managing

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    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.
     
  19. managing

    managing Member

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    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.
     
  20. orewashin

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    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.
     
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