Related Terms

• Azadirachta indica, Azadirachta indica ADR, Azadirachta indica A. juss, azadirachtin, azadirachtin A, bead tree, beta-sitosterol, Bioneem™, dogonyaro, holy tree, immobile, Indian lilac, isomeldenin, limonoids, margosa, margosa oil, Meliaceae (family), Neemix™, neem flowers, neem-based pesticide, neem kernel powder (NP), neem leaf alcoholic extract (NLE), neem oil, neem seed kernel, neem seed oil, Nim, NIM-76, nimba, nimbandiol, nimbin, nimbinene, nimocinol, Persian lilac, Praneem polyherbal cream, Pride of China, quercetin, village of pharmacy.

Background

• Neem has a long history of use in India. The leaf and bark extracts were recommended by herbal practitioners for gastrointestinal upsets, skin ulcers, infections and malaria. Neem twigs were used regularly as toothbrushes, and the leaf gel was used to fight periodontal disease (inflammatory disease of the gum).

• The extracts from neem often have a pungent smell similar to garlic. This is because they contain sulfurous compounds. Neem has been reported to reduce plaque formation, act as a mosquito repellent, treat psoriasis vulgaris (chronic skin disease with reddened lesions covered by silvery scales) and aid in the healing of gastroduodenal ulcers. However, there is currently insufficient evidence to recommend for or against these uses. In the United States, neem is used mainly for its antibacterial, antifungal, insect repellant, contraceptive, and hypothetical "life extension" qualities.

Scientific Evidence

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

• Abortion, analgesic (pain-reliever), anti-bacterial, anti-fertility, antifungal, anti-inflammatory, anti-malarial, antimicrobial, antimutagenic, antiparasitic, antipyretic (fever-reducing), astringent, athlete's foot, cancer, cardiac arrhythmia (irregular heartbeat), cardiovascular disease (heart disease), colds/flu, conjunctivitis (pinkeye), contraception (before and/or after sexual intercourse), coronary artery disease, cystic fibrosis, diabetes, diarrhea, enhanced immune function, fever, gastric cancer, gastric ulcers (Type 2 diabetes-induced), gingivitis, glioblastoma (malignant brain tumor), HIV/AIDS, hormonal effects (anti-androgen), hyperlipidemia (high cholesterol), hypertension (high blood pressure), insecticide (molluscicidal, nematicidal), insect repellent (sand fly), lice, life extension, liver protection, melanoma, periodontal disease (gum disease), polio virus, respiratory disorders, Reye's syndrome, scabies, sedative, sexually transmitted disease (STD), skin diseases, tonic, ulcers (chronic), virus (Dengue).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

• There is no proven safe or effective dose for neem. The bark extract in a dose of 30-60 milligrams twice daily for ten weeks by mouth has been used to treat gastroduodenal ulcers. A gel formulation containing neem extract twice a day, before bed and after breakfast, for six weeks has been used in the treatment of plaque and gingival condition. Neem cream or oil (2-5% neem oil) has shown protective effects against mosquito bites.

Children (younger than 18 years)

• There is no proven safe or effective dose for neem in children, and use is not recommended.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

• Avoid in individuals with a known allergy or hypersensitivity to neem (Azadirachta indica).

Side Effects and Warnings

• There are few scientific reports about the safety of the above ground parts of neem. Nonetheless, several cases of death in children from neem oil poisoning have been reported. Other symptoms present in these children included vomiting, drowsiness, loose stools, metabolic acidosis, anemia, Reye-like syndrome, altered sensation and consciousness, seizures, decreased responsiveness, and liver enzyme increases with evidence of liver damage.

• Taking neem bark extract by mouth for up to ten weeks appears well-tolerated in adults, as well as neem leaf extract gel for use within the mouth for up to six weeks. A 5% neem cream or 0.5-2% neem oil is also likely safe when applied on the skin as an insect repellent for up to two weeks.

• Ventricular fibrillation and cardiac arrest due to neem leaf poisoning has been reported. Neem leaf extract may also cause bradycardia (slowed heart rate), heart rate abnormalities, or low blood pressure.

• Although not well studied in humans, neem may cause increases in ammonia levels in the body or decreases in blood sugar. High concentrations of neem leaf extract may be inhibitory to thyroid function, particularly conversion of T3 and T4. Injections of neem oil may cause damage to the uterus and surrounding glands, mild transient eosinophilia (increased levels of white blood cells), and non-specific endometritis (inflammation of the lining of the uterus).

• Margosa oil causes toxic encephalopathy (degenerative brain disease) particularly in infants and young children. Drowsiness, seizures, lethargy, and extreme exhaustion followed with coma/hyporeactivity are also possible. Use cautiously in patients with liver disease.

Pregnancy and Breastfeeding

• Neem is not recommended in pregnant or breastfeeding women due to possible abortifacient (abortion inducing) and anti-implantation effects observed in animal studies. However, teratogenetic (causing malformations or defects to an embryo of foetus) effects have not been reported in animals.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

• Concomitant use of acetaminophen (Tylenol®) and neem leaf extract may cause liver toxicity. Caution is advised in patients taking other agents that may cause liver toxicity.

• Due to possible hypotensive (blood pressure lowering) effects, neem should be used cautiously with other hypotensive agents.

• Neem leaf extract may inhibit the clastogenic activity of cyclophosphamide (Cytoxan®) and mitomycin C. Patients taking chemotherapy agents should use neem with caution.

• Neem may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. Neem had synergistic activity with dillapiol, a cytochrome P450 3A4 inhibitor. Theoretically, neem may have synergistic activity with other cytochrome P450 3A4 inhibitors. Patients using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

• The combination of a low dose of neem leaf extract and a low dose of morphine produced an increased loss of pain sensation. Theoretically, neem and some opiate analgesics (pain relievers) may work together (synergistically) for a positive interaction, although a qualified healthcare professional, including a pharmacist should be consulted before combining therapies.

• Neem may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

• The use of neem extract and quinine hydrochloride has been reported to have positive (synergistic) effects in the spermicidal activity of these agents. Quinines are often used in the treatment of malaria.

Interactions with Herbs and Dietary Supplements

• Neem may lower blood sugar levels. Caution is advised in patients with diabetes (high blood sugar) or hypoglycemia (low blood sugar), and in those taking herbs or supplements that may also lower blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary. Blood glucose levels may require monitoring, and doses may need adjustment.

• Neem may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. Neem had synergistic activity with dillapiol, a cytochrome P450 3A4 inhibitor. Theoretically, neem may have synergistic activity with other cytochrome P450 3A4 inhibitors. Patients using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

• Administration of garlic and neem leaf extracts may decrease the formation of lipid peroxides and enhance the levels of antioxidants and detoxifying enzymes in stomach, as well as in the liver and circulation.

• Due to possible hypotensive (blood pressure lowering) effects, neem should be used cautiously with other hypotensive herbs and supplements.

Author Information

• This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Arivazhagan S, Velmurugan B, Bhuvaneswari V, and Nagini S. Effects of aqueous extracts of garlic (Allium sativum) and neem (Azadirachta indica) leaf on hepatic and blood oxidant-antioxidant status during experimental gastric carcinogenesis. J Med Food 2004;7(3):334-339. View Abstract

2. Bandyopadhyay U, Biswas K, Sengupta A, et al. Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer. Life Sci. 10-29-2004;75(24):2867-2878. View Abstract

3. Bhanwra S, Singh J, Khosla P. Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats. Indian J Physiol Pharmacol 2000;44(1):64-68. View Abstract

4. Garg S, Talwar GP, Upadhyay SN. Immunocontraceptive activity guided fractionation and characterization of active constituents of neem (Azadirachta indica) seed extracts. J Ethnopharmacol 1998;60(3):235-246. View Abstract

5. Mukherjee S, Garg S, Talwar GP. Early post implantation contraceptive effects of a purified fraction of neem (Azadirachta indica) seeds, given orally in rats: possible mechanisms involved. J Ethnopharmacol 11-30-1999;67(3):287-296. View Abstract

6. Omar S, Zhang J, MacKinnon S, et al. Traditionally-used antimalarials from the Meliaceae. Curr Top Med Chem 2003;3(2):133-139. View Abstract

7. Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel--a 6-week clinical study. J.Ethnopharmacol. 2004;90(1):99-103. View Abstract

8. Pai MR, Acharya LD, Udupa N. The effect of two different dental gels and a mouthwash on plaque and gingival scores: a six-week clinical study. Int.Dent.J 2004;54(4):219-223. View Abstract

9. Panda S, Kar A. How safe is neem extract with respect to thyroid function in male mice? Pharmacol Res 2000;41(4):419-422. View Abstract

10. Patel J, Hemavathi K, Bhatt Jagat D. Study of the antinociceptive effect of neem leaf extract and its interaction with morphine in mice. Indian J Pharmacol 2005;37(1):37-38.

11. Raizada RB, Srivastava MK, Kaushal RA, et al. Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats. Food Chem Toxicol. 2001;39(5):477-483. View Abstract.

12. SaiRam M, Ilavazhagan G, Sharma SK, et al. Anti-microbial activity of a new vaginal contraceptive NIM-76 from neem oil (Azadirachta indica). J Ethnopharmacol 2000;71(3):377-382. View Abstract.

13. Siddiqui BS, Afshan F, Gulzar T, et al. Tetracyclic triterpenoids from the leaves of Azadirachta indica. Phytochemistry 2004;65(16):2363-2367. View Abstract

14. Sinniah D, Baskaran G. Margosa oil poisoning as a cause of Reye's syndrome. Lancet 2-28-1981;1(8218):487-489. View Abstract

15. Vanka A, Tandon S, Rao SR, et al. The effect of indigenous Neem Azadirachta indica [correction of (Adirachta indica)] mouth wash on Streptococcus mutans and lactobacilli growth. Indian J.Dent.Res. 2001;12(3):133-144. View Abstract