The Anti-Allergic Drug That Increases Appetite & Kills Tumors

Author: Daniel S, PhD; Last update: January 31st, 2021


Dear Friends,

With this post I would like to highlight a cheap and accessible drug that I think it is good to be aware of, given its anti-cancer potential. Its name is Cyproheptadine, it is FDA approved, and in most countries is sold over the counter.

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A first-generation antihistaminic drug, Cyproheptadine (trade name: Periactin), was initially approved in 1961 for allergic conditions but its use has been expanded to include treatment of serotonin syndrome, serotonin-induced sexual dysfunction, insomnia, headaches. One of it’s side effects is increase of appetite, and this is why sometimes it is used as an appetite stimulant in cancer patients. Indeed, it has been observed to cause weight gain in observational studies of patients with advanced cancers. On the same line, Kinshasa population, Democratic Republic of Congo has been misusing the capabilities of Cyproheptadine as an appetite stimulating drug: It is sold to people who desire to gain weight, even without medical prescription, in order to have “roundness physical appearance” (Ref.). 

It is both a histamine (H1 histamine receptors) and serotonin antagonist.

In laboratory studies it has been shown to be effective against:

  • leukaemia (Ref.)
  • myeloma (Ref.)
  • mantle cell lymphoma (Ref.)
  • colon carcinoma
  • breast cancer 
    • Treatment of human breast cancer cells (MCF7 cells) with cyproheptadine decreased the expression and transcriptional activity of ERα, thereby inhibiting estrogen-dependent cell growth (Ref.)
  • urothelial carcinoma (Ref.)
  • hepatocellular carcinoma (Ref.)

Cyproheptadine seems to accumulate the most in bile and liver (Ref.). However, as we will see below, results were obtained beyond these organs, i.e. in the lungs. 

Besides it’s anti-cancer potentials Cyproheptadine may be relevant to address Alzheimer’s disease (Ref.).

To keep things simple and because it’s anticancer mechanisms are not yet very well established, I will just sump to the facts.

Note that while there is not enough literature to establish the exact anticancer mechanism behind Cyproheptadine, note that histamine antagonists (both for H1 and H2 histamine receptors, such as Cimetidine. Loratadine, etc.) have been intensively studied during the past decade and have also been discussed on this website from time to time (e.g. here). accordingly, they are often associated with modulation of the immune cells, autophagy and metabolic modulation. So far, Cyproheptadine has been specifically associated to activation of P38 MAP kinase (Ref.) and Set7/9 (Ref.).

Case Reports in Humans

Unexpected remission of hepatocellular carcinoma (HCC) with lung metastasis to the combination therapy of thalidomide and cyproheptadine: report of two cases and a preliminary HCC cell line study

This publication reports two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC (liver and lungs) in both of them after treatment for 6 months and 6 weeks, respectively:

Case 1: A 57-year-old man with no history of alcohol consumption with a  tumour measuring 3 cm in diameter near the dome of the right lobe of liver –  diagnosis of HCC. He underwent transarterial chemoembolisation for HCC on 3 December 2007. Four months later, abdominal CT performed on 16 April 2008 (figure 1A,B) revealed that the tumour size increased to 10 cm in diameter, with the presence of lung metastasis. Doctors start to him with thalidomide (50 mg once daily) for 14 days, followed by thalidomide (50 mg twice daily) for 67 days. At the same time, they prescribed cyproheptadine (4 mg thrice daily) for his skin itching. Eighty-one days later, thalidomide was discontinued because the patient could not afford it, but cyproheptadine was continued. Abdominal CT on 18 October 2008 revealed complete remission of the liver tumour and lung metastasis (figure 2A,B).

Figure: CT of case 1 on 16 April 2008. (A) Hepatocellular carcinoma approximately 10 cm in diameter with daughter nodules. (B) Metastasis in the right lung. (In fact, bilateral lung metastases were observed). (Ref.)

Figure: CT of case 1 on 18 October 2008. (A) Complete remission of large hepatocellular carcinoma. (B) Disappearance of lung metastasis. (Ref)

Case 2: A 63-year-old man with a large liver tumour about 17 cm in diameter resected on 3 November 2010 – diagnosis of HCC. The whole abdomen CT performed on 17 April 2011 revealed no obvious liver tumour recurrence. However, the chest CT performed on 17 April 2011 revealed bilateral lung metastases, and the serum AFP level was up to 30.2 ng/ml. Subsequent chest CT performed on 26 July 2011 revealed progression of lung metastases (figure 4). The patient underwent six chemotherapy cycles with epirubicin but the response was poor and his serum AFP level increased to 122 ng/ml on 21 November 2011. Later, doctors gave him the thalidomide (50 mg once daily) from 2 December 2011. Cyproheptadine (2 mg thrice daily) was also prescribed for skin itching. The serum AFP level on 13 January 2012 was decreased to 5.5 ng/ml and the follow-up chest CT performed on 19 January 2012 revealed that bilateral lung metastases totally disappeared (figure 5).

Partial Remission of Carcinoid Tumor in Response to Cyproheptadine

“An 80-year-old woman was hospitalized at Saint Barnabas Medical Center in October 1986 with a 9-month history of diarrhea, episodic flushing and 14 kg weight loss.  Her medications included digoxin, furosemide, and cimetidine. A computed axial tomographic (CT) scan of the liver revealed several areas of decreased attenuation consistent with metastases, the largest of which measured 8x 6 cm. Cyproheptadine, 4 mg three times daily, was started. The patient’s diarrhea and flushing disappeared, her appetite increased, and she gained 10 kg. A CT scan in January 1987 showed a decrease in size and number of hepatic metastases. The largest lesion now measured 5.0 X 3.5 cm.”

The authors conclude: “On the basis of clinical response of our patient to cyproheptadine and its low incidence of side effects, this drug should be considered for formal phase II trials in patients with carcinoid tumors. In addition, the combination of the H1 blocker, cyproheptadine, and the H2 blocker, cimetidine, should also be considered for further clinical investigation.”

Significant symptoms alleviation and tumor volume reduction after combined simultaneously integrated inner-escalated boost and volumetric-modulated arc radiotherapy in a patient with unresectable bulky hepatocellular carcinoma

A HCC patient treated with radiotherapy. The patinet obtained important tumor reduction. Only latter the doctors realized that Cyproheptadine has also been prescribed for alleviating skin itching and allergic rhinitis (2 mg by mouth Q12h; prescribed since the last 2 weeks of the RT course and then persistently used for 24 months) and that Cyproheptadine may be responsibel for the outstanding response.

Update June 2022:

Another positive case report has been publsihed at the end of 2021, many months after I wrote this post: “Efficacy of Cyproheptadine Monotherapy in Hepatocellular Carcinoma With Bone Metastasis: A Case Report”

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. Particularly, cases of bone metastasis have poorer prognoses.

Case presentation: A 62-year-old woman with suspected advanced HCC accompanied by bone metastasis with severe back pain and sciatica showed disease remission after cyproheptadine monotherapy. Initially, her serum alpha fetal protein (AFP) level was high, reaching up to 17697.62 ng/ml. A dose of 4 mg cyproheptadine, 3 times a day for 17 months was prescribed as the only treatment. Within 3 months, the serum AFP level gradually normalized down to 4.3 ng/ml. Both liver biopsy and bone biopsies were subsequently performed after 2 weeks of cyproheptadine. The results showed no malignancy. During the 34 months of follow-ups, the serum AFP remained normal in the range of 1.05 to 2.86 ng/ml. The patient has survived for 5 years without back pain and sciatica thus far.

Conclusions: This is the first report to investigate a successful clinical approach in cyproheptadine monotherapy for an advanced HCC patient with bone metastasis. We recommend cyproheptadine as a potential anti-HCC agent for the treatment of HCC with bone metastasis, but more related studies such as prospectively clinical trials, and ideally randomized trials are still needed.

Studies in Humans

Hepatocellular carcinoma (HCC) – A retrospective study conducted in Taiwan also demonstrated the anti-HCC effect of Cyproheptadine in 52 sorafenib-treated patients with advanced HCC (Ref.) Patients in the combination group (including Cyproheptadine) were 76% less likely to die and 82% less likely to have progression during the 17 months of follow-up.

Figure: Overall survival curves for the two study groups. The solid line indicates the patients who received cyproheptadine; the dotted line indicates the patients who did not receive cyproheptadine (P = 0.017, log-rank test). (Ref.)

Bladder cancer: – A retrospective study conducted in Taiwan indiacates that the use of Cyproheptadine for more than 3 months has a significant effect on bladder cancer. (Ref.)

Figure: Kaplan-Meier survival curves for patients treated with Cyproheptadine users and non-Cyproheptadine users. (Ref.)

Side Effects and Toxicity

Potential adverse effects:

Potential toxicity: There are cases of cyproheptadine intoxications publsihed, associated with ingestions of cyproheptadine ranging from 0.3 to 6.5 mg/kg (Ref.). In these casee, patients presented some degree of manifestation of anticholinergic syndrome, including tachycardia, hyperthermia, decreased salivation and sweating, agitation, delirium, hallucinations (visual and tactile), mydriasis, and seizures. In such cases to reverse the symptoms treatment can include physostigmine, an acetylcholinesterase inhibitor, when necessary (Ref.).

Please read this too:

Admisnistration & Dose

The patients in the case reports above were given doses from 2mg 2x/day (that is a total of 4mg/day), up to 4mg 3x/day (that is a total of 12mg/day). These doses seem to be indeed in a safe range (Ref.). 

According to the case reports and studies cited above, Cyproheptadine has been used for minimum 3 months continuously.

Given that some of the outstanding results have been obtained when Cyproheptadine was used in combo with Thalidomide, it could make sense to add that to the treatment strategy. Thalidomide has been discussed previsouly on this website here (Ref.).


In conclusion, Cyproheptadine is a very relevant tool in the fight against cancer such as carcinoid (neuroendocrine) tumors, liver tumors or other tumor types presenting liver metastasis.

In addition, as it modulates and down regulates Estrogen Receptor, it could represent a good repurposed drug to be added into a more comprehensive anticancer treatment cocktail to fight breast cancer.

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Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients

The median overall survival was 11.0 months (95% confidence interval: 6.8–15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1–6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22–0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1–10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4–2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22–0.86). Kaplan–Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10–0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08–0.44) during the 17 months of follow-up.

Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription

SET domain containing lysine methyltransferase 7/9 (Set7/9), a histone lysine methyltransferase (HMT), also methylates non-histone proteins including estrogen receptor (ER) α. ERα methylation by Set7/9 stabilizes ERα and activates its transcriptional activities, which are involved in the carcinogenesis of breast cancer. We identified cyproheptadine, a clinically approved antiallergy drug, as a Set7/9 inhibitor in a high-throughput screen using a fluorogenic substrate-based HMT assay. Kinetic and X-ray crystallographic analyses revealed that cyproheptadine binds in the substrate-binding pocket of Set7/9 and inhibits its enzymatic activity by competing with the methyl group acceptor. Treatment of human breast cancer cells (MCF7 cells) with cyproheptadine decreased the expression and transcriptional activity of ERα, thereby inhibiting estrogen-dependent cell growth. Our findings suggest that cyproheptadine can be repurposed for breast cancer treatment or used as a starting point for the discovery of an anti-hormone breast cancer drug through lead optimization.


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22 thoughts on “The Anti-Allergic Drug That Increases Appetite & Kills Tumors

  1. Thanks so much for this information, Daniel!

    Cyproheptadine requires a prescription in the US at this time, do you have any ideas where I could get some online?

    1. Hi Daniel,
      I have history of Ulcerative Colitis, diagnosed in 2000. After 8 years treatment with a well known gastroenterologist in Mumbai, India, I started Ayurvedic treatment which provided me with lot of symptomatic relief with fewer and less severe episodes of bloody diarrhea.
      In July last year (2019), I experienced diarrhea and after Ayurvedic treatment, it came under control. But I started losing weight was passing unformed stool everyday with cramps and bowel discomfort. I also gained weight during the course of treatment.

      I have continued with herbal treatment, currently I have stabilized my bowel movement but not gained my weight back. I have lost almost 8 kg in the last 18 months.

      Should I try cyproheptadine?

      1. Dear Khalid,

        Ulcerative Colitis is considered to be an autoimmune reaction. There are three mechanisms that come in to my mind in this case that I would consider to address:

        1. Inhibit MCT1 (known as key for effective inhibitors of autoimmune reactions) – here I would consider Quercetin
        2. Increase the activity of T regulatory cells (to lower the over activity of T cells) – here I would consider NAC supplement and maybe Alpha Lipoic Acid
        3. Inhibit Glycolysis (required to lower the over activity of T cells) – here I would consider fermentation inhibitors as discussed here

        I hope this helps.

        Kind regards,

  2. Very interesting Daniel! like all your contributions!
    It has low molecular weight and many serotonin inhibitors such as sertraline and fluoxetine have action in brain tumors …
    Weight gain for many cachexia patients is already very positive.

    1. Dear Kanzanc,

      Thank you for your question. Indeed, it can block the action of acetylcholine and serotonin, that nerves and muscles use to communicate with one another. As a result it can cause drowsiness. Due to this action, it can also inhibit cortisol release which is good

      Your point is very good. Many drugs come with side effects, specifically at doses required to induce anti-cancer effects. We should always check if a drug produces side effects that are not suitable with an existing condition and if there is any interaction between a drug to be added and drugs already in use. This is why it is advised that patients always check with a medically trained person before starting to use a drug.

      In the end, it will be a decision based on the risks and potential rewards. In general, I think the side effects coming from a drug typically used against allergic reactions should be acceptable when dealing with advanced cancer, unless this drug hits a very sensitive spot for a specific patient.

      Note: the post above (and all on this website) should not be seen as and is not intended to be medical advice. Instead, I consolidate research that should be used as input for the discussion with the medical doctor in order to define treatments strategies with higher chance for a positive outcome.

      Kind regards,

  3. Dear Daniel

    Thank you so much for sharing that article.Very insightful, as ever.

    I would appreciate the chance to ask for your advice with regards to the treatment that I am currently undertaking. This is in related to colon polyps (benign) that have been surgically removed. However, a recent biopsy rendered a malign formation – adenocarcinoma colo-rectal 8140/3 (NOS) which is lined up for radio therapy and surgical removal.

    I would appreciate if you could please spare a few thoughts around a suitable treatment that could help prevent the evolution and further formation of such polyps. Happy to give me more details, as needed. Looking forward to your thoughts either as a reply to this post or, should you prefer, by direct email.

    Much appreciated your help.

    Thank you.

    Kind Regards
    Corneliu (66yrs, Bucharest, Romania)

    1. Dear Corneliu,

      Thank you for your question.

      The must have in my view before and after surgery of colorectal tumors are:

      – Cimetidine 800mg/day
      – Mebendazole 200mg/day
      – Quercetin 1-3g/day
      – Vitamin D3 5000ui to 10.000ui/day
      – Artemisinin and/or Artemisia Annua

      The nice to have:

      – Metformin 1000mg/day or Berberine 1500mg/day
      – Curcumin 5000mg to 7000mg/day

      I would take a break a few days before intervention and about one week after intervention to avoid bleeding due to the blood thinning effects of some of the above.

      The top priority from the above is Cimetidine. If not available in Romania, you may find it in Germany with prescription or on e-Bay as an over the counter drug coming from the USA under the name Tagamet.

      I hope this helps.

      Kind regards,

      1. Daniel, many thanks indeed for your valuable reply.

        Couple of additional questions, if I may.

        1- my current treatment comprises of Acetazolamida (250mg), Omeprazol (10mg) and Metformin (500mg), three times daily x three times a week. I am also supplementing with cur curcumin, probiotic and digestive enzymes.
        I am waiting for the result for heavy metals for chelation and serum zonulin. I did the ALCAT-100 test for food intolerance. In addition, intravenous vitamin C 25 grams, twice a week and sodium selenite infusion once a week.

        Could you please let me know of your views to the above?

        2 – Secondly, the virus tracing: cytomegalovirus, epstein-barr, varicella-zooster, the values ​​for IgG are very high and increase at intervals of several months, which showed a reinfection, IgM values ​​being in the range.

        Could this be also a cause for the polyp formation and, if so, what would be your recommendation?

        Thank you

        Kind Regards

        1. Dear Corneliu,

          My view on those you mentioned:

          1. Acetozolamide, Omeprazole and Metformin will help to support radio
          Curcumin shoudl be in high enough dose.
          Probiotics are good indeed and same for digestive enzymes but as general support.
          Vitamin C in high dose from time to time is very good.
          On sodium selenite I have no special opinion.

          2. In my view, cancer is an infectious disease more than we think. In addition, it is known that many types of cancers are triggered by viruses. So I would clearly consider using some strong anti virals in cycles (such as Ivermectin) and constantly others such as Berberine, Artemisinin and Quercetin.

          Kind regards,

        2. Dear sir, where do you get Sodium Selenite inj, I want to import Sodium Selenite inj in india from your doctor, can you give me the doctors whatsapp number & personal email id. Thank you so much, my email id [email protected]
          Warm regards

      2. So what if you have access to both of the must have list and nice to have list, would it be beneficial to take the Metformin with the Cimetidine and Mebendazole along with everything else? Also, does Metformin have a synergistic effect when taken with Mebendazole in inhibiting tumor growth and is there any research behind that combination of medications or is it theoretical based on the anti tumor effects that each of those drugs have when taken individually because I’ve seen plenty of published research on each of those taken by themselves but nothing on them taken together so I’m curious if anyone has seen anything about the possible benefits of taking those drugs taken together?

  4. Thank you, Daniel. This is very helpful. One last question, if I may:

    The Glutadione Transferase determination test shows the current efficiency at only 2/3 of total, implying that toxins are not released and retained at cellular level. Exposure to heavy metals and viruses that are not released, could this be a root cause of the inflammation and ultimately cancer polyp formation. If so, would you have views with regards to possible medication or treatment that would help with cellular detoxification?

    Many thanks indeed.

    Kind Regards

    1. apologies, one correction – Glutadione Transferase determination test shows the current efficiency at only 1/3 of total and not at 2/3 as erroneously stated above. thank you

    2. HI Corneliu,

      It’s difficult to make a statement on if GTS lower activity is the origin of the cancer cell occurrence. At least, what we know is that in cancer cells GTS is over active. If you feel this is a relevant way for you, you could search for drugs and/or supplements that activate GTS and autophagy. Also, you could consider NAC. All these I would do them far from any radio or chemo that you may do.

      I do believe that there is a good chance that viruses are at the origin but not sure if taking this route would add major value on that line. I mentioned in my previous response what I think could help.

      Kind regards,

  5. I recently had a glucose psychosis incident with my mother suffering breast cancer. She started forgetting where she had placed things, and accused others of staling. Also started hiding her belongings.

    I was giving her Metformin, Vit C, Aspirin and Loratadine (switched from already prescribed Montek LC).
    Turning off Loratadine stopped the psychosis. Apparently, it reduces G6PD, which is required by the brain to retrieve memories.

    Thankfully, her cancer tumor is now miniscule in size with the above regimen, and my personal observation says that Loratadine was a big contributor in this reeduction. So, I am in peace.
    While searching for another medicine to fight cancer, I came across this article. And Cyproheptadine too reduces G6PD.

    So, fair warning to everyone – watch out for G6PD levels when treating with Cyproheptadine or Loratadine. Also, watch out for signs of increased forgetfulness, and any other psychotic behaviour. It took Loratadine about 5-6 weeks to bring around psychosis in my mother. So, a treatment regimen of one or two weeks of Cyproheptadine / Loratadin, followed by a change in medication to allow G6PD levels to recover should prove reasonable.

    1. Hi!

      I also use Loratadine for my father for about 6 months now and I just noticed he starts to forget things.
      Kind of strange how I just your post today.

      How can I measure the G6PD levels? Is it a blood test?
      Many thanks!

  6. Hi Daniel,
    My brother has colorectal with mets to his liver and he has ascites. He is being treated with chemo. I heard about cyrophetadine on a facebook group that it is good for liver mets and then came across this article you posted. When I was looking up cyrophetadine I also came across this article Cyproheptadine-Induced Acute Liver Failure . So now I am like hmm confusing. What do you think about this had you ever seen this pdf? thanks

    1. Dear Barnettan,

      Thank you for your question.

      As also stated in the article, this is a rare side effect of the drug: “Regardless of its mechanism, clinicians should be aware of the rare but life-threatening hepatotoxicity from cyproheptadine so that rapid withdrawal of the drug can be initiated, and clinical recovery can begin.”

      To me, this example of a side effect highlights the fact that no matter what supplement or drug we take, because everyone is different, we always need to move towards the target dose step by step (during several days to a few weeks time frame) as we introduce new drugs/supplements. When doing that, we can identify side effects early and be able to stop the drugs before that becomes a major issue.

      As discussed in the Vitamin C page in this website, even high dose Vitamin C can have strong negative effects on a category of patients. So important side effects can happen with every drug. This is why it is important we introduce the in a safe manner.

      I hope this helps.

      Kind regards,

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