Researchers are beginning to explore the potential of antihistamines as effective cancer drugs. Histamine can play a driving role in the cancer process, and tumors often contain large numbers of mast cells. Using antihistamines to target tumors has been found to be effective in certain circumstances.
Mast Cells
Mast cells are innate immune cells that play a key role in the body’s inflammatory response and in establishing the balance of tissue. Since inflammation has long been associated with cancer, it makes sense that when it comes to cancer, mast cells help to control various aspects of tumor biology including the growth of cells, survival and resilience of tumors, the spread of blood vessels, how invasive the tumor is, and whether and how aggressively it spreads.
Mast cells may be found in proximity to surfaces that are common portals of infection, namely in mucosa of the respiratory, digestive and urogenital tracts, and in the dermis of the skin. Mast cells may also be found in the connective tissue near vessels and nerves, making them key elements in the processes of tissue remodeling, wound healing, fibrosis and angiogenesis, and in the central nervous system where the histamine acts as a neurotransmitter. The ability of mast cells to synthesize and release potent angiogenic compounds (compounds that promote the expansion of blood vessels) such as FGF, VEGF, tryptase, and chymase is a major point linking them to cancer.
During tumor development, mast cell precursors migrate into the tumor and constitute one of the major stromal cell populations. Studies suggest that the mediators released by mast cells have both detrimental (promote tumor growth, neovascularization, immunosuppression and tumor invasion) and beneficial effects for the host (inhibiting the tumor, inducing apoptosis, stimulating inflammation, and inhibiting metastasis.)
Histamine and Cancer
One major role of mast cells is that they release a compound called histamine. Histamine has something of a bad reputation in the world of alternative medicine, but it is important to stress that it does have essential roles in the body by acting as a neurotransmitter, regulating stomach acid secretion, and playing a part in the body’s immune response.
However, histamine has many harmful effects in excess. It acts like estrogen upon certain tissues, especially the uterus, it tends to exacerbate hypoglycemia (through its acetylcholine-like actions) and it suppresses the immune system directly in multiple ways: it inhibits the production of immune cells in response to stimulation, interferes with antibody formation, and suppresses the generation of T-helper cells. According to an in vivo study performed on a melanoma xenograft model and an in vitro study using cells from mice spleen, histamine promotes cancer growth by stimulating cell division and activating suppressor T-cells that are responsible for the down regulation of the immune system. In vivo and in vitro studies with human cell lines of cancers, (breast cancer, lymphoma, leukemia, cervical, ovarian, vaginal, uterine, vulvar and colorectal cancer, and melanoma) showed that histamine is involved in the growth and invasion of cancer cells.
High levels of histamine have been associated with both the inhibition or promotion of the growth of several tumors (cervical, ovarian, vaginal, uterine, vulvar, colorectal cancer, and melanoma.) Some researchers have observed high activity of the enzyme L-histidine decarboxylase and high levels of histamine in some tumors, namely colon, breast and endometrial cancers, melanoma, and small cell lung carcinoma. It was also observed that blood levels of histamine in human patients with breast, prostate and lung malignant tumors were two or three times higher when compared with healthy ones and remained high for two months after surgery. Histamine content has been found to be unequivocally increased in ovarian, cervical and endometrial cancer when compared with adjacent normal tissues, suggesting the participation of histamine in carcinogenesis.
Antihistamines and Cancer
Antihistamines are being studied for their effects against cancer, and they have been found to be quite effective in multiple cases.
One case study found that cyproheptadine, an antihistamine that also opposes serotonin, was able to eradicate all cancer within 14 months and minimize all tumours within two weeks. In studies with liver cancer, cyproheptadine was found to induce cell cycle arrest leading to apoptosis (cancer cell death.) The antihistamine shows potential for both prevention and treatment.
Another antihistamine, cimetidine has been found to inhibit tumor growth and metastasis in several different ways: it inhibits cell adhesion of tumor cells, exerts anti angiogenic effects by the inhibition of VEGF that has been recognized as an important angiogenic factor, induces apoptosis, activates macrophages, activates the immune system through the increase of interleukin levels, increases infiltration of tumors by immune cells and inhibits immunosuppression.
Another study found that the users of desloratadine and loratadine, (antihistamines) had an improved rate of survival, regardless of other factors. Use of CAD antihistamines has been associated with a reduction of about 20%-30% in ovarian cancer mortality, a significant improvement. The unique chemical structure of CADs enables them to accumulate rapidly inside lysosomes, where they increase lysosomal pH, alter lysosomal lipid metabolism, and eventually cause lysosomal membrane permeabilization (cancer cell death.)
What are other ways to keep histamine and mast cells in check?
- Address nutrient deficiencies: Vitamin D is necessary to stabilize mast cells, and they can be activated when vitamin D is low. Zinc and magnesium are also involved in regulating the activity of mast cells and in reducing inflammation.
- Incorporate nutrients and foods that stabilize mast cells: Nutrients such as selenium, vitamin E, vitamin B6, and vitamin C, as well as herbs and spices like tulsi, (holy basil) ginger, quercetin, bromelain, and nettle.
- Reduce Stress: Under physical or psychological stress, corticotropin hormone is released, destabilizing the mast cells and causing them to release histamine.
- Optimize your circadian rhythm: Mast cells are largely regulated by circadian rhythms, making it important to get natural light, enough sleep, and avoid blue light at night.
- Make sure you have adequate progesterone levels: progesterone directly inhibits mast cell secretion, while estrogen promotes its release.