Feeling Very Periactin

Cypro Whenever a drug has been around for many decades, and is tried and tested with few known ‘side-effects’ (yet very helpful with a long list of conditions), there’s a good chance you won’t be hearing about it from your doctor.

This statement becomes doubly true, when the reason the drug – cyproheptadine (Periactin) on this occasion – is beneficial, is (at least in part) because of its anti-serotonergic effects, when the ‘official health doctrine’ only ever sees serotonin as something wonderful to be promoted.

“Cyproheptadine is a serotonin antagonist and antihistamine agent that has been used to treat allergies, migraines, nightmares and behavioural abnormalities. It has even been used to treat sexual dysfunction cause by SSRIs. Its pharmacological action makes it an ideal agent to treat symptoms associated with increased serotonin concentrations.” (Baigel GD, 2003)

If when the drug in question is valuable, because it also helps to protect against the damaging effects of excess circulation of estrogen (the so called female hormone), medical cognitive dissonance will usually start to rise even more sharply. More likely it will go through the roof.

“Treatment of human breast cancer cells with cyproheptadine decreased the expression and transcriptional activity of ERα [Estrogen receptor alpha], thereby inhibiting estrogen-dependent cell growth.” (Takemoto Y, et al., 2016)

If you were to add to all of that, cyproheptadine’s (Periactin’s) endorphin, prolactin and growth hormone lowering, anti-cholinergic impact, what you potentially would have (rather than just some ‘outdated’ anti-histamine), is a health advice, public relations nightmare.

“Treatment of the patients suffering from Itsenko-Cushing’s disease with cyproheptadine…resulted in a decrease of the plasma beta-endorphin and beta-lipotropin, as well as a display in 60% of cases of clinical and laboratory remission.” (Slavnov VN, et al., 1985)

“The present study investigated the mechanism of action of the serotonin receptor-blocking agent cyproheptadine on PRL [prolactin] release…Our studies suggest that cyproheptadine inhibits PRL release at the pituitary level…” (Lamberts SW, et al., 1985)

“The effect of cyproheptadine on growth hormone (GH) and prolactin (Prl) secretion…was studied…GH secretion was consistently inhibited and a dose-response relationship was observed between the cyproheptadine concentrations and the amounts of GH released…cyproheptadine likewise suppressed Prl release in a dose-related manner.” (Ishibashi M, et al., 1985)

Cyproheptadine (Periactin), has in fact been studied and used over many decades, for the treatment of a variety of serious and chronic metabolic issues and illnesses, with very few known problems or ‘side-effects’.

The list of ailments it has been helpful with is long, including asthma; insomnia (and other sleep related issues); depression and anxiety; schizophrenia; post-traumatic stress disorder; migraines and cluster headaches; IBS (and other digestive issues); fertility issues; testosterone promotion; dyspeptic symptoms in children; functional abdominal pain; appetite stimulation; galactorrhea-amenorrhea syndrome; chronic spinal cord injury; serotonin syndrome; skin disorders; addiction; autism; heart issues; diabetes; hemorrhagic shock; ischemia; and a number of different kinds of cancer.

“Cyproheptadine is a relatively safe compound and may be of therapeutic benefit in treating negative symptoms of schizophrenia in combination with typical neuroleptics.” (Akhondzadeh S, et al., 1999)

“Cyproheptadine was effective in improving symptoms of functional abdominal pain, functional dyspepsia….Patients…[also] had significant improvement…abdominal migraine…IBS and…cyclic vomiting syndrome.” (Madani S, et al., 2016)

“…five cases of serotonin syndrome are reported….All patients were administered cyproheptadine (4-8 mg orally) for serotonergic signs. Three had complete resolution of signs within 2 h of administration. Another two had a residual tremor or hyperreflexia following the first dose, which resolved following a repeat dose. There were no adverse outcomes from cyproheptadine use.” (Graudins A, et al., 1998)

“In a recent study comprising 127 children between 7 and 80 months with feeding difficulties…cyproheptadine…was applied…The authors reported significant weight gain and a positive change in mealtime and feeding behaviours…” (Herpertz-Dahlmann B, 2017)

So what is it then, that makes the ‘medical world’ appear as though it is largely oblivious to this cheap and simple, first generation anti-histamine, and its multitude of beneficial effects. Do they know something that science doesn’t?

The answer to that question probably gets a little clearer, once you examine the already well understood biochemical interrelationships, between some of the inflammatory by-products and promoters of chronic stress (including histamine, serotonin, cortisol, nitric oxide and estrogen), with thyroid energy metabolism dysfunction, and compare that with ‘official’ health doctrines.

Plenty of good evidence suggests, that protecting against any of the factors involved with rising stress mentioned above, can often be enough to push things in the direction of improved metabolic function. From that point of view, one logical way of understanding ‘cypro’ (as it is often lovingly referred to) can be to see it as a kind of all purpose anti-stress, pro-thyroid, pro-metabolism substance.

The inflammatory things, including serotonin, histamine and estrogen, as well as endotoxin, prolactin, nitric oxide and lactic acid, are (in a variety of different ways) physiologically related, and have a tendency to promote each other.

When stress is high, and when thyroid function is sub-optimal, many factors combine to create what can become a vicious circle type effect, which involves many of the stress, disease and degeneration promoting substances.

Stress uses up sugar supplies rapidly, and when glycogen stores run low, cortisol and adrenaline rise in order to convert muscle tissue into sugar, and release fat out of storage as alternative fuel.

Relying on cortisol (or stress) to provide energy via the breakdown of muscle and the release of fat (made up increasingly of polyunsaturated fatty acids), has many inflammatory anti-thyroid effects.

Polyunsaturated fats (PUFAs) are a far greater part of modern diets than ever before, and as consumption goes up, more is stored in the tissue over time, and this increases the amount of PUFAs in the composition of fat released into circulation under stress.

When thyroid metabolism is suppressed and energy systems are interfered with, the resulting increased release of the polyunsaturated free fatty acids, is one of a number of things that then can cause a slowing of digestive processes, enabling bacteria to feed and grow in number. This can lead to a rise in exposure to bacterial endotoxin, which adds momentum to a metabolically suppressed, inflammatory scenario. This is often especially true, when sugar intake (or fuel generally) is being restricted.

People often get away with restricting fuel intake for long periods of time, but relying upon the stress response can have many unintended consequences. The stress substances promote each other in an almost unlimited number of different ways.

Thyroid suppression promotes bacterial endotoxin, and endotoxin can encourage histamine release. Histamine can increase nitric oxide. More nitric oxide (NO) leads to more prostaglandin production, and more inflammation. Histamine can itself be inflammatory. Endotoxin also promotes cortisol, serotonin and estrogen, and serotonin and estrogen increase cortisol. Estrogen induces NO production, and promotes a rise in serotonin and endorphin levels.

Serotonin mediates the actions of estrogen. Estrogen stimulates growth hormone production, and serotonin stimulates acetylcholine release. Acetylcholine increases NO, growth hormone, cortisol, histamine and prostaglandins. Prostaglandins can promote histamine, estrogen and beta-endorphin. Rising levels of these substances either directly or indirectly, interfere with energy metabolism and promote stress, inflammation, and disease.

Cyproheptadine has been shown to be able to protect against bacterial endotoxin, histamine, cortisol, serotonin, estrogen, acetylcholine, growth hormone, beta-endorphin, as well as being able to prevent the synthesis from free fatty acids, of the prostaglandins.

Isn’t it weird that something that reduces exposure to so many ‘happiness promoting’ substances, could be so beneficial.

“Endotoxic shock…was produced by i.v. injection of LPS…[cyproheptadine] strongly inhibits LPS-induced TNF alpha gene expression, and [has] a beneficial antishock effect…” (Wang LZ, et al., 1999)

“…results suggest that the anti-inflammatory activity of cyproheptadine is presumably due to its anti-5-hydroxytryptamine effect and the inhibition of synthesis or release of prostaglandin E.” (Tan JQ, et al., 1989)

“Cyproheptadine…improve[s] glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by…antiserotoninergic properties.” (Ferrari C, et al., 1979)

By protecting against endotoxin, estrogen, and serotonin for example, cyproheptadine helps to take the strain off the liver, allowing it to better carry out detoxification functions. This further reduces circulation of the metabolism interfering (stress and inflammation promoting) substances, including estrogen. Improving liver function is crucial for proper thyroid and mitochondrial energy system function, and for protection against stress and disease.

Excessive exposure to the byproducts of the breakdown of PUFAs (including the inflammatory prostaglandins), and chronically high circulation of endotoxin, serotonin, cortisol and estrogen, damages the liver, and has been demonstrated to be involved in the development of cancer, including liver, breast, colon, prostate and pancreatic cancer. Histamine, growth hormone, acetylcholine and prolactin, have also been shown to be involved in the promotion of cancer, as well as numerous other disease processes.

“…histamine content increased unequivocally in other human cancer types such as ovarian, cervical and endometrial carcinoma in comparison with their adjoining normal tissues suggesting the participation of histamine in carcinogenesis.” (Medina VA, et al., 2010)

“Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance.” (Subramani R, et al., 2017)

“Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth…tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources…” (Spindel ER. 2016)

“…prolactin can increase tumor growth rates and the number of metastases, as well as induce both estrogen receptor +(ER) and ER–tumors…the available data support the hypothesis that prolactin increases risk of breast cancer.” (Tworoger SS, et al., 2006)

There’s a lot of good reasons to look at cyproheptadine (Periactin), when it comes to protection against diseases like cancer, or just for the improvement of metabolic health in general. By protecting against the promoters of stress and inflammation, it can go a long way towards stopping spiraling degeneration and disease issues, redirecting to improved metabolic function for healing and recovery.

“We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with…cyproheptadine….originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines.” (Feng YM, et al., 2012)

“In…myeloma and leukemia, cyproheptadine inhibited tumor growth without significant toxicity. Cyproheptadine-induced apoptosis…cyproheptadine represents a lead for a novel therapeutic agent for the treatment of malignancy.” (Mao X, et al., 2008)

“Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent…in several human cancers…results provide evidence that cyproheptadine is a suitable therapeutic agent for the treatment of UC [urothelial carcinoma]…” (Hsieh HY, et al., 2016)

Cyproheptadine has been used to promote the production of cholesterol and testosterone. By protecting against stress and inflammatory issues, and by encouraging thyroid metabolism, it makes sense that it also assists in the production of the other highly protective anti-aging substances, including pregnenolone, progesterone and DHEA.

If it were to become widely accepted that reducing serotonin and estrogen issues for instance, is an important part of a metabolism enhancing, general disease protective strategy, and that this can be achieved with the assistance of a very cheap, safe, and easily available anti-histamine, it might not be good for business.

An all purpose medicine like Periactin, would interfere with the sale of a large number of the most profitable pharmaceutical products on the market, including the serotonin promoting, so called anti-depressants, as well as estrogen increasing drugs, even various highly priced forms of chemotherapy.

And just imagine how damaging the acceptance of science, contradicting ‘official’ treatment methodologies for diseases like cancer and depression, could be to the status quo.

In any case, not everyone reacts well to even the safest drugs, and some prefer not to take them unless absolutely necessary. Cyrpoheptadine has some potential dopamine lowering effects, and can also cause drowsiness, at least at first. For those who’d rather not use it, it’s possible to replicate some of the stress lowering effects of cyproheptadine with dietary and other pro-thyroid means.

Unfortunately there is probably as much (if not more) confusion and misinformation surrounding what is and isn’t a healthy pro-metabolic anti-stress diet, as there is with regards to the harmful and helpful effects of different pharmaceutical products.

Most people aren’t aware of the fact that there is plenty of good quality biological evidence demonstrating a strong relationship between improvements in thyroid energy metabolism, and overall stress reduction and disease protection.

As metabolism improves and stress and inflammation are reduced, chronically high levels of the stress substances (including serotonin, estrogen, cortisol, and histamine) are reduced systemically, rising locally and temporarily as required. Improved production of the protective hormones (pregnenolone, progesterone, testosterone and DHEA) tends to go hand in hand with better thyroid performance.

Sugar intake plays a fundamental role in the fueling of thyroid energy metabolism. Sufficient sugar consumption keeps cortisol low, and inhibits the release of PUFAs into circulation. Sugar helps to promote digestion and liver function, reducing inflammation, keeping endotoxin, serotonin and estrogen under control, and assisting in the production of cholesterol and other disease protective substances.

By protecting against stress, sugar prevents excessive catabolization of muscle tissue, reducing circulating tryptophan (as well as the mobilization of other inflammatory amino acids), and protecting against excessive serotonin.

A diet avoiding PUFAs, with enough protein from milk, cheese and gelatin, and plenty of sugar from sweet ripe juicy fruits, fruit juice, honey and white sugar, can help improve thyroid metabolism, and protect against the damaging effects of stress and inflammation (limiting exposure to serotonin, estrogen, histamine and other stress substances), potentially leading to similar results as cyproheptadine use.

Some other things that have been shown to help in similar or related ways, include lysine, theanine, certain antibiotics, activated charcoal, carrot salad, famotidine, very well cooked mushrooms, coconut oil, methylene blue, aspirin, niacinamide, glycine, caffeine and numerous other anti-stress pro-metabolic substances.

I’m not a doctor or a scientist, and I’m not here to make drug recommendations. But if you look more closely at the available science, you’ll find lots of valid evidence that largely gets ignored (perhaps because it contradicts official health guidelines), helping to explain why many modern treatment approaches, cause more harm than good.

Cyproheptadine (Periactin) is more than just a simple anti-histamine. It’s a good reminder that there is something seriously wrong with a lot of what is called ‘science’ or ‘medicine’ today. Perhaps that’s why almost nobody ever finds out about it.

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3 Responses

  1. Avatar Elie says:

    Is there a concern of cyproheptadine resistance with long term usage?

    I try to manage some of my histamine / mast cell problems with it few times a week in small dosages and it works well. It pretty much healed my IBS with half a dose, few times per week.

    Any insight that you can uncover there? Will it have withdrawal symptoms?

    Thanks for all you do. Thanks a whole lot.

  2. DanM@cowseatgrass DanM@cowseatgrass says:

    I’m no expert on the subject of withdrawal symptoms, but I have taken it for years at a time without a break and stopped without any noticeable symptoms. It probably depends on individual metabolism. Anxiety can also be a factor. Ray Peat says that it’s good to take breaks from using it.

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