Neem (Azadirachta indica)

Category

Herbs & Supplements

Synonyms

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.

Evidence

DISCLAIMER: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Dental plaque (oral bacteria): Neem has been found to have anti-plaque properties and antimicrobial activity against oral pathogens. Comparisons of neem to the prescription drug chlorhexidine have reported significant results. Additional study is needed in this area to draw a firm recommendation.
Grade: C

Mosquito repellent: Neem oil and neem cream have showed protective effects against mosquito bites from various species. Further research is necessary before a conclusion can be reached.
Grade: C

Psoriasis vulgaris: Limited human data is available, and early study suggests no benefit. Therefore, there is insufficient evidence to recommend for or against the use of neem for the treatment of psoriasis vulgaris (chronic skin disease).
Grade: C

Ulcers (gastroduodenal): Protective and healing effects on gastroduodenal ulcers have been reported in a preliminary human study. However, comparisons to other agents used for this purpose such as proton pump inhibitors or H2-antagonsits have not been conducted. Therefore, there is insufficient evidence to recommend for or against the use of neem for gastroduodenal ulcers.
Grade: C

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. 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 healthcare provider. There may be other proposed uses that are not listed below.
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

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

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

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

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.

Attribution

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Tracee Abrams, PharmD (University of Rhode Island); Heather Boon BScPhm, PhD (University of Toronto); Cathy DeFranco Kirkwood, MPH, CCCJS-MAC (MD Anderson Cancer Center); Karta Purkh Singh Khalsa, CDN, RH (University of Texas); Phuong Ngo, PharmD (Massachusetts General Hospital); Erica Seamon, PharmD (Nova Southeastern University); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration); Jen Woods, BS (Northeastern University).

Bibliography

DISCLAIMER: 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.

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.

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.

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.

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.

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.

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

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.

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.

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

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.

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. .

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. .

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

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

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.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.