- White-berry mistletoe
For Patients & Caregivers
Mistletoe therapy may improve symptoms and quality of life for cancer patients, but definitive information is still lacking.
Mistletoe is a semi-parasitic plant that grows on various host trees. Although some oral mistletoe products are sold as dietary supplements and homeopathic medicine, most scientific research has only evaluated intravenous or injected formulations that are not approved as prescription drugs in the United States.
Basic research shows that mistletoe extracts may stimulate the immune system to fight cancer. Studies in humans show that mistletoe treatment may improve symptoms and reduce side effects of cancer treatments. A few studies indicate it may also have some effects on survival. More studies are needed to see if mistletoe can be used as supportive therapy in cancer care.
To treat cancer and cancer symptoms
Laboratory and animal studies show some anticancer activity. Some human studies show that mistletoe extract can reduce symptoms from cancer treatments and that patients live longer. However, more studies are needed to confirm these effects.
To treat hepatitis
Clinical trials show conflicting results.
To treat HIV and AIDS
Some studies find that mistletoe extract can affect the immune system in HIV patients. However, there is not enough evidence to show that it can be used as a treatment.
To lower high blood pressure
Laboratory data show that mistletoe may lower blood pressure, but no studies have been done to see if it is an effective treatment for high blood pressure.
As an immune stimulant
Laboratory and animal studies as well as some human studies show that mistletoe can both modulate and stimulate the immune system.
Common: Fever, chills, elevated white blood cell count, reaction at injection site, hypersensitivity.
Less common, may indicate toxicity: Diarrhea, vomiting, headache, low blood pressure, low heart rate, fainting or passing out, increased blood sugar, itching, rash.
Most reactions were mild, but there are instances of severe toxicity and even death with self-administration or by ingesting raw mistletoe.
For Healthcare Professionals
Mistletoe is a semi-parasitic plant that grows on various host trees. Mistletoe extracts are used for a variety of conditions including cancer, HIV, hepatitis, and degenerative joint disease. Oral preparations are available as dietary supplements and homeopathic remedies. However, most clinical research has evaluated mainly parenteral formulations, which are not approved for use in the United States by the Food and Drug Administration.
Studies support the use of mistletoe to improve symptoms and quality of life, and reduce chemotherapy and radiotherapy side effects, including in pancreatic (13) (37), lung (11), colorectal (12), and breast (14) cancers. Some studies suggest it may help prolong survival (6) (8) (9) (13), but other study results are mixed (17) (18) (19) (43). Preliminary studies suggest that intravesical mistletoe extract is safe and well tolerated in patients with nonmuscle invasive bladder cancer (38), and that mistletoe extract injection may be efficacious for chemical pleurodesis in patients with malignant pleural effusion (39) (44).
In two studies with 5-year follow-ups of breast cancer patients, mistletoe did not appear to negatively influence chemotherapy efficacy (14) and appeared to continue reductions in persistent symptoms (15). In patients with advanced solid tumors, the addition of mistletoe administration allowed for higher gemcitabine doses to be used without apparent pharmacokinetic interactions (16). Concomitant mistletoe appeared to reduce adverse events from monoclonal antibody therapy (45) but not immune checkpoint inhibitors (46). Benefits with mistletoe treatment in combination with medical care have also been reported (47) (48). Large prospective studies are needed to determine safety and whether these immune-related events translate to beneficial outcomes.
Raw mistletoe contains toxic constituents. Possible adverse effects from mistletoe treatment include injection site reactions, chills, and fever (16) (20) (39) (40) (41). Long-term use may also reduce T-cell function in cancer patients (21), but the majority of reactions were mild to moderate and dose-related (22) (49).
Mistletoe inhibits CYP3A4 in vitro, so it could theoretically interact with drugs metabolized by this enzyme. However, in vitro studies show this effect only happens in very high doses and is unlikely when used in clinically relevant concentrations (10) (23) (50).
In preclinical models, mistletoe has anti-inflammation (1) and anticancer effects (3) (4) (51). Mistletoe lectins are the most investigated single component of mistletoe extracts, with cytotoxic effects attributed in part to ribosome-inactivating properties and apoptotic induction (5). In vitro studies show that lectins induce macrophage cytotoxicity, stimulate immune-cell phagocytosis, increase TNFα, IL-1, IL-2, and IL-6 cytokine secretion, and enhance cytotoxicity (29). In lymphoblastic leukemia cells, mistletoe extracts stimulate dendritic cell maturation and activation (30) and induce dose-dependent apoptosis through caspase-8 and -9 dependent pathways (26).
In animal models, triterpene-containing mistletoe extracts produced the greatest apoptotic induction (26) and improved efficacy against malignant melanoma compared with conventional extracts via reduced tumor angiogenesis (31). Viscotoxins may also be responsible for tumor-inhibiting and immune-stimulating activities (28). However, mistletoe produced both pro- and anti-proliferative effects depending on dose (32).
Mistletoe preparations induce T-helper 2 immune response, as evidenced by significant eosinophilia during treatment in patients with chronic hepatitis C (2). Mistletoe-induced immune stimulation may explain physical improvements that contribute to increased quality of life in cancer patients (5).
Common: Injection site reactions, fever (39) (40) (52), flu-like symptoms (41), leukocytosis (16) (20) (22).
Uncommon: Diarrhea, nausea (40), vomiting, headache, increased blood glucose, decreased blood pressure, syncope, generalized pruritus, urticaria (22); bradycardia , organ toxicity (33); fatigue, pain (39) (40).
Long-term use: Reduced T-cell function in cancer patients (21).
Most infusion reactions were mild to moderate and dose-related (22) (41).
Subcutaneous inflammation mimicking metastatic malignancy: In a 61-year-old breast cancer patient 2 months post-surgery, induced by mistletoe injections self-administered over 12 months (35).
Fatalities: Rare, and due to excessive ingestion of mistletoe teas (33).
Severe hypertension: Possibly related to intratumoral injection in 1 patient (41).
Hepatotoxicity: Significantly increased AST and ALT levels in a 55-year-old man with no significant medical history and a 10-day history of mild fever and brownish urine. Liver injury was related to the use of mistletoe and kudzu extracts. Values gradually returned to normal after 8 days of hospitalization (42).