- White-berry mistletoe
For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
What is it?
Mistletoe is a plant that grows on different types of trees. For example, mistletoe can grow on apple, oak, or pine trees. The leaves, berries, and stem of the mistletoe plant are used in traditional medicine for a variety of issues.
Mistletoe extracts come in supplements as capsules, liquid extracts, teas, and powder. Mistletoe injections are used in scientific research.
What are the potential uses and benefits?
Mistletoe is used:
- To treat hepatitis (swelling of the liver caused by the hepatitis C virus)
- To treat cancer
- To reduce side effects from cancer treatments
Mistletoe has other uses, but doctors haven’t studied them to see if they work.
Talk with your healthcare provider before taking mistletoe supplements. Herbal supplements are stronger than the herbs you would use in cooking.
Supplements can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.
What are the side effects?
Side effects of mistletoe injections include:
- High white blood cell counts
- Reaction at injection site (swelling, reddening of skin)
- Hypersensitivity (when your immune system overreacts to a substance)
What else do I need to know?
- Talk with your healthcare provider if you’re pregnant. Mistletoe may increase your risk of abortion.
- Do not eat raw mistletoe. It can cause vomiting, seizures, slow heart rate, and even death.
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) (53) 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, this effect only happens in very high doses and is unlikely when used in clinically relevant concentrations (10) (23) (50).
Purported Uses and Benefits
- Cancer treatment side effects
Mechanism of Action
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).
Pregnant women should not consume mistletoe due to uterine stimulant activity of tyramine and unidentified constituents (27).
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).