systematic reviewEvidence: limited
Plaque and gingivitis: neem mouthrinse (systematic review)
3 RCTs (206 records screened, searches to Feb 2015) comparing neem mouthrinse with chlorhexidine mouthrinse in people with gingivitis; no meta-analysis because of heterogeneity. Authors from AIIMS New Delhi and Davangere
The included trials reported that neem mouthrinse was as effective as chlorhexidine as an adjunct to toothbrushing for reducing plaque and gingival inflammation. The authors call the evidence lacking and in need of high-quality trials.[9]
Limitations: Only 3 trials; quality of reporting and methods were generally flawed with unclear risk of bias.
systematic reviewEvidence: limited
Dental plaque and gingivitis: plant extracts compared (systematic review)
47 trials of medicinal plant extracts as dental and periodontal antibiofilm agents (964 records screened); Azadirachta indica in 4 studies
Neem extracts showed efficacy similar to chlorhexidine for plaque and gingival scores in the four studies. The authors say more studies are needed to understand clinical relevance.[10]
Limitations: Neem results are a small part of a wider review, and the abstract gives no effect sizes for neem.
meta-analysisEvidence: limited
Plaque and gingivitis: miswak (pooled)
10 RCTs of miswak chewing sticks from Salvadora persica or Azadirachta indica, 9 pooled; GRADE assessment
Miswak was comparable with a toothbrush for plaque (SMD 0.39, 95% CI -0.05 to 0.83) and gingivitis scores, and as an adjunct to toothbrushing was more effective for plaque (SMD 0.68) and gingivitis (SMD 0.66).[11]
Limitations: Mixes two plant sources, so the result cannot be assigned to neem alone; included studies under-reported brushing method and frequency.
RCTEvidence: limited
Mouthwash vs chlorhexidine and tea (Indian trial)
n=30 healthy volunteers aged 18-25 at Jodhpur Dental College, 10 per group: 0.2% chlorhexidine, 2% neem or 0.5% tea mouthwash; up to 3 weeks; blinded
Plaque and gingival scores fell in all groups. Neem and tea showed gingival effects better than chlorhexidine (P < 0.05); the 0.5% tea mouthwash had the greatest anti-plaque effect, more than neem or chlorhexidine.[12]
Limitations: Only 10 people per arm; healthy young volunteers; the chlorhexidine arm stopped after week 2.
RCTEvidence: limited
Mouthwash vs chlorhexidine (Indian crossover trial)
n=40 participants aged 18-35, double-blind crossover, 2% neem mouthwash vs 0.2% chlorhexidine with a 1-week washout
Plaque fell slightly in both phases with no significant difference between mouthwashes; the gingival index fell in both groups. The authors conclude neem can be an alternative to chlorhexidine.[13]
Limitations: Small; the abstract gives short follow-up and does not separate a neem-specific effect from the group-wide change.
RCTEvidence: preliminary
Toothpaste (Indian trial)
n=30 first-year dental students, randomised double-blind, neem toothpaste vs control toothpaste
Plaque index and gingival index were significantly different between test and control groups after use. The authors suggest neem toothpaste as an adjunct for oral hygiene.[14]
Limitations: Small student sample; the abstract does not give the duration or effect sizes.
RCTEvidence: limited
Dental gel (Manipal, India)
Males aged 20-30, 6 weeks; mucoadhesive gel with neem leaf extract (25 mg/g) vs 0.2% chlorhexidine mouthwash as positive control
The gel significantly reduced plaque index and salivary bacterial count (P < 0.05) compared with the control group, as the authors report.[15]
Limitations: Males aged 20-30 only; sample size is not given in the abstract; the comparator was a chlorhexidine mouthwash used as a positive control, so the abstract does not describe a placebo.
otherEvidence: preliminary
Mutans streptococci and early caries (Manipal, India)
2-month study of neem mouthwash (with and without alcohol) against chlorhexidine; salivary S. mutans and lactobacilli counts
S. mutans was inhibited by neem mouthwashes and by chlorhexidine; lactobacilli were inhibited by chlorhexidine alone. The authors call their data initial and say longer clinical trials are essential.[16]
Limitations: 2001 study with sparse methods reported in the abstract; the claim of reversing incipient carious lesions rests on that early data.
RCTEvidence: preliminary
Five-herb mouthwash after periodontal therapy (Kerala, India)
Two RCTs (CTRI-registered): 50 people with periodontitis randomised to a mouthwash of five plant extracts (amla, haritaki, bibhitaki, mulethi and neem) or chlorhexidine for 2 weeks; a second study in radiation-induced mucositis versus soda saline
Bleeding, plaque and pocket depth fell significantly in both periodontitis groups. The herbal group reported less severe radiation mucositis and less analgesic need. Pain, dry mouth and antibiotic use did not differ significantly.[17]
Limitations: A five-plant formula, so no effect can be assigned to neem; preliminary trials.
RCTEvidence: limited
Root canal irrigant: pain and endotoxin (Cairo)
n=50 adults with necrotic lower molars, parallel double-blind; neem irrigant vs 2.5% sodium hypochlorite during endodontic therapy; pain at 6-48 h
Pain scores were lower with neem at every time point but significantly so only at 24 hours after instrumentation (P = 0.012). Both irrigants reduced endotoxin (18% neem, 8% hypochlorite); neither removed it completely.[18]
Limitations: Single centre, 50 patients; a procedure-specific irrigant, not an oral or topical consumer product.
RCTEvidence: moderate
Type 2 diabetes on metformin (Indian RCT)
n=80 people with type 2 diabetes already on metformin, Nizam's Institute of Medical Sciences, Hyderabad; standardised aqueous leaf-and-twig extract 125, 250 or 500 mg twice daily vs placebo, 12 weeks, double-blind
At all three doses the extract lowered post-meal and fasting glucose, HbA1c (for example 7.78% to 6.26% at 500 mg) and insulin resistance versus placebo, and improved endothelial function and inflammatory and oxidative markers. It did not change platelet aggregation or lipids.[19]
Limitations: One branded extract, 12 weeks, surrogate markers; reported by the same research group as the metabolic-syndrome trial, so the two are not independent confirmations.
RCTEvidence: limited
Metabolic syndrome (Indian RCT)
80 adults with metabolic syndrome, 20 per group; the same type of aqueous extract at 125, 250 or 500 mg twice daily vs placebo for 12 weeks; CTRI-registered
The extract dose-dependently improved fasting and post-meal glucose, insulin resistance, HbA1c, endothelial function and most inflammatory and oxidative markers over time.[20]
Limitations: Small groups; the abstract does not give effect sizes; surrogate markers; one research group.
RCTEvidence: preliminary
Prophylaxis in COVID-19 contacts (AIIA pilot, India)
n=190 healthcare workers or relatives of COVID-19 patients, single centre, double-blind placebo-controlled; 50 mg proprietary neem-leaf extract capsule twice daily for 28 days, follow-up to day 56
13 people tested positive (all asymptomatic). Among the 154 who completed per protocol, 3 in the neem group and 8 in the placebo group tested positive (relative risk 0.45). Adverse events were minimal and grade 1-2.[21]
Limitations: A pilot with very few events, so the estimate is imprecise; proprietary extract; outcome was a positive test in asymptomatic people; the authors call for further trials.
otherEvidence: preliminary
Gastric acid and duodenal ulcer (Kolkata, India)
Patients with acid-related problems and gastroduodenal ulcers took neem bark aqueous extract: 30 mg twice daily for 10 days (acid secretion) and 30-60 mg twice daily for up to 10 weeks (ulcers)
Gastric acid secretion fell by 77% after 10 days, and duodenal ulcers were reported as almost completely healed on barium meal or endoscopy at 10 weeks. Liver, kidney and blood markers stayed close to control values.[22, 5]
Limitations: The abstract describes no placebo or randomised comparison, and the group is small; MSK calls it 'a small study' and says more human studies are needed.
otherEvidence: preliminary
Head lice (Egypt)
60 heavily infested children aged 4-15 treated with a neem seed extract shampoo, left on for 5, 10, 15 or 30 minutes
The authors report that the shampoo was highly effective against all stages of head lice, with no differences between 10, 15 and 30 minutes and no skin irritation seen.[23]
Limitations: No comparison group described; an extract shampoo, not a plain preparation.
RCTEvidence: limited
Sand-flea infestation (tungiasis, Kenya)
n=96 children aged 6-14; topical 20% neem seed oil in coconut oil vs 0.05% potassium permanganate foot bath; fleas monitored for 6 days
Neem plus coconut oil killed about 40% of embedded fleas by day 6 and did not beat the potassium permanganate standard on that main outcome. Secondary outcomes (abnormal flea development, acute skin pathology, pain-free children) favoured the neem mixture.[24]
Limitations: Proof-of-principle trial with a short follow-up; topical seed oil on the skin of children, not an oral preparation.
These studies explain possible mechanisms. They do not show the same effect in people.