Can antihistamines like Cimetidine, Desloratadine and Loratadine play an integrative role in cancer cure?

Antihistamines can reduce metastases, boost the immune response, improve immunotherapy treatments and increase survival times in cancer patients.

Cimetidine, or Tagamet, has been shown in research to increase cancer survival following colorectal cancer surgery, and also to  boost the immune system, particularly NK cells. 

Desloratadine and Loratadine have been shown to increase survival of both ER+ve and ER-ve breast cancer patients by more than 30 per cent, after only 12-20 weeks of use. These two drugs also boost the immune system and can improve immunotherapy outcome (11).

You should choose an antihistamine based on research. Cimetidine performed poorly with lung cancer and immunotherapy, especially against Loratadine, but even those taking no antihistamine. Cimetidine may also have oestrogen-promoting effects. It may also limit anti-coagulation drugs.

Histamines are essential to your immune system

This is a complex subject.

Histamines are a double edged sword with your immune system. They are well known to cause inflammation and allergy; but they can also help the immune system - albeit they neither attack and kill rogue cells, nor do they detoxify and clear the debris, their role is essential in terms of oiling the cogs that help it all work effectively. Histamines also play a role in brain and nervous system function, helping us respond to an attack, whether it be a chemical toxin, pathogen or physical attack. Histamine is part of the 'fight or flight' mechanism and helps us respond rapidly to these attacks (9).

So far so good.

There are 4 histamine receptors - H1, H2, H3 and H4. Attaching to one might increase blood flow to our brain; attaching to another might produce an allergic reaction on the skin, warning us that a problem exists. Under normal circumstances, we produce histamine in short bursts to respond to a threat. We then have a gene, HNMT, that denatures the histamine and restores our natural balance. Problem over.

But. Constant heightened histamine production can damage your health. People who suffer stress - their work, an abusive boss, people who have financial problems, people who suffer abuse or the constant agony of a lengthy divorce - they understand how debilitating it can be, taking a toll on their health and making them 'run down' and ill. And this is primarily because of long-term and heightened histamine production leading to chronic inflammation in the body. Just the condition for cancer to thrive.

Worse, cancer cells themselves can produce heightened levels of histamine. 2022 research (8) has shown that many tumour types produce histamine, which acts as an immunosuppressor to block immune attack in the tumour microenvironment.

Histamines are essential to cancer proliferation

It is therefore of no surprise then that high histamine levels have been found in people with breast cancer, colorectal cancer, ovarian cancer, melanoma, cervical cancer and pancreatic cancer. Indeed, cancer cells have more histamine receptors on their surface than healthy cells have, and these help inflame the cancer cell, help it spread and help cancer cells stick together to form new tumours, and stick to organs like your lungs, bones and liver.

Histamine levels also seem to increase simultaneously in peripheral tissues, almost as if they were drawing cancer cells towards them.

It begs the obvious question, could you block the action of histamine in cancer proliferation?  We.know you can employ stress management techniques. as identified by UCLA , or could you simply use an antihistamine?

Antihistamines stop cancer cells sticking and spreading

1. Cimetidine reduces metastases and increases survival times:

Cimetidine (CIM), or Tagamet, is an over-the-counted medicine which was approved by the FDA back in 1977 and so is now off patent. It is a 'histamine receptor antagonist', and is used to treat stomach and duodenal ulcers and heartburn and indigestion. Histamines cause the stomach to produce excess acid and cimetidine stops this. 

Research shows this cheap antihistamine can play an important role in preventing cancer cell walls becoming inflamed and therefore 'sticky'. One expert described this as 'like having velco patches'. The sticky cells survive in the blood stream by sticking to the blood and lymph vessel walls and then spreading; they also use the stickiness to clump together with other cancer cells and thus start a tumour. The stickiness also holds the new tumour together.  

Cimetidine seems particularly useful in limiting cancer spread as a result of colorectal cancer surgery or biopsy - it greatly increased survival. Other successful studies have taken place with melanoma, renal cell carcinoma, gastric cancer and prostate cancer. For example, there is some evidence CIM helps restrict spread in cases of melanoma and might even boost white cell count and improve the effectiveness of the drug cyclophospamide too.

In a 2002 study by Matsumoto, where 800 mg of cimetidine per day was given for 1 year to people who had undergone colorectal cancer surgery 2 weeks previously and were starting chemotherapy (5-FU), the 10 year survival rose from 49.8% in the control group to 84.6% in the cimetidine group. 

The velcro-like stickiness is caused by E-selectin. Cimetidine is proven to block E-selectin. As the research said,

"Thus Tagamet (Cimetidine) reduces the histamine-derived inflammation of cancer cells and reduces metastases and cancer spread, the main cause of cancer death."

Cimetidine consistently shows increases in cancer survival times

The first report of cimetidine's use with cancer was an article in The Lancet in 1979 (1: 882-883) which reported that it possessed anti-tumour abilities. It had been used with a lung cancer patient. Several studies with mice followed until another Lancet report showed it effective with melanoma patients, where it cleared up the ulceration of tumours.

A number of papers then appeared in the New England Journal of Medicine and The Lancet showing its effectiveness amongst patients after colorectal cancer operations, either used on its own or in conjunction with standard treatments. By 2002 the British Journal of Cancer reported a trial with 64 patients. The group without cimetidine showed a 10-year survival of 49.8, whereas the group also taking cimetidine had a 10-year survival of 84.6 per cent. In the group with the most aggressive cancers the figures were, without 23 per cent; with 85 per cent! The important conclusion was to give the drug before and during surgery.

This conclusion was reinforced by two studies one from Japan (Fujita Health University; Matsumoto; Lancet 1995; 346: 115) where the group taking cimetidine with the chemotherapy 5-FU had a 4-year survival of 96.3 per cent compared to the group on chemo only, of 68.8 per cent. The cimetidine was given before the surgery. However, in a Danish study where it was started 3 weeks after surgery there was no benefit over the control group.

So, while the general evidence is clear and positive, there is some debate over whether you should take Cimetidine before or immediately after surgery.

Cimetidine may boost immune response too

In our article (2), Can Surgery Spread Cancer? we looked at various ways in which surgery might cause metastatic activity. Cimetidine may help reduce this in two ways - not just by its histamine-preventing activity stopping cells clumping together, but it appears to boost the immune system as well.

In 1997 the journal Cancer (80: 15-21) reported a study by Adams and Morris where again the cimetidine was given before and during colorectal surgery. They looked at white blood lymphocytes before and after the surgery. Those patients taking the cimetidine showed an improvement in lymphocyte levels in more than half the subjects, whereas the placebo boosted the levels in under a quarter of the control group. Equally important was the follow up where 3-year survival was in line with the findings at the time of surgery. It is possible that this immune response is an independent benefit. It is thought that antihistamines have a strong effect on cytokines. Other studies have looked at prostate cancer and found similar improved survival figures.

Cimetidine can enhance the activity of natural killer (NK) cells, particularly in patients with chronic lymphocytic leukemia (B-CLL), where NK activity is often low or absent (6). 

However, there is some concern that Cimetidine may increase oestradiol levels and should not be used with breast cancer or prostate cancer (7).

2. Antihistamines like Desloratadine and Loratadine (Claritin) also increase survival times

All anti-histamines were not created equal. Cimetidine is an H2 antagonist, like ranitidine, and is primarily used for acid reflux. Antihistamines like Desloratadine are H1 antagonists and used typically for allergies.

Researchers from Lund Medical School in Sweden (1) reviewed 61,627 women who had Breast cancer between 2006 and 2013.  including those who simultaneously took a second generation H1 antihistamine (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine). When comparing users of Desloratadine and Loratadine with non-users a significant survival improvement was seen for the users of 30 per cent or more. Desloratadine provided the best results; Loratadine was not far behind. This result was independent of Er status and age.

Loratadine use has also been shown to increase lung cancer survival by reducing tumour-associated inflammation (10). Research showed that the H1 decreased the death rate from 58% down to 40%.

Of some surprise has been the finding (11) that H1 over-the-counter antihistamines may significantly improve how well patients respond to immunotherapy treatments (both PD-1 and PD-L1).

In a second study on lung cancer (12) with immunotherapy drugs, the median progression-free survival was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival was 32.8 months in the experimental group and 18.1 months in the control group.

BUT - choose your antihistamine carefully - 

Those patients who only received H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines.  Worse, patients in the control group who did not receive any antihistamines had a longer mPFS and mOS than those who received H2 antihistamines like cimetidine. 

Repurposed drugs for Oncology (ReDo) such as Antihistamines seem able to reduce metastases, improve immune response and increase survival times

Although the exact method of action is not 100% clear, there is more than enough research now to suggest using any of these inexpensive drugs such as Cimetidine or Desloratadine and Loratadine is of significant benefit to people with cancer. There are a good number of scientific reviews on the Internet, for example for Cimetidine (5) explaining how histamines enhance cancer growth nd disturb the immune response and spread and how anti-histamines can block these actions. 

Anti-histamines reduce cancer membrane velcro patches by blocking histamine receptor sites; and have immuno-modulating action increasing immune response, They thus reduce cancer growth, cancer metastases and increase survival. We believe all our readers should consider the use of antihistamines as part of their Integrative Cancer Treatment Programme.

We do not believe Loratadine should be taken for more than 10 weeks in any year as there is a study showing that long-term use (but not short-term use) can increase breast cancer risk. 

Go to: 10 ways to improve your chemotherapy success and reduce side-effects

Other articles that you may find interesting are:

1. A diet for Chemotherapy
2. Immunotherapy overview
3. A to Z Guide to Complementary Therapies

Go to: Return to the CANCERactive drug list

FURTHER READING

Reference

1. Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival; Ildikó Fritz et al; Acta Oncol, 2020 Sep;59(9):1103-1109.
2. Can Surgery Spread Cancer even if you are only having a biopsy -
3. Cimetidine as an effective anti-cancer drug http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268104/
4. Aspirin and cancer
5. Repurposing drugs in oncology (ReDO)—cimetidine as an anti-cancer agent; Pan Pantziarka et al;  Ecancermedicalscience. 2014 Nov 26;8:485.
6. Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia; John I Allen et al;  Washington U Medicine
7. Cimetidine inhibits catechol estrogen metabolism in women; Jon J. Michnovicz, Richard A. Galbraith; Metabolism Volume 40, Issue 2, February 1991, Pages 170-174
8. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1; Hongzhong Li et al; Cancer Cell, 2022 Jan 10;40(1):36-52.e9.
9. Role of Histamine in Modulating the Immune Response and Inflammation; Anna Cláudia Calvielli Castelo Branco et al; Mediators Inflamm. 2018 Aug 27;2018:9524075
10. Loratidine is associated with improved prognosis and exerts antineoplastic effects via apoptotic and pyroptotic crosstalk in lung cancer; Xiwen Liu et al; J Exp Clin Cancer Res 43, 5 (2024).
11. Boost Your Cancer Immunotherapy: How Common Antihistamines May Improve Treatment Success; Vikas P. Sukhatme;  Emory University
12. Association of concomitant H1 antihistamine and immune checkpoint inhibitor therapy on survival outcome and safety in patients with advanced primary lung cancer: a cohort study; Wei-Hong Zhang et al; TLCR Vol 13, No 10 (October 31, 2024) https://tlcr.amegroups.org/article/view/92203/html

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* NB.Cimetidine (Tagamet) may inhibit the action of anti-coagulent drugs - and so you should always consult your doctor before taking it.