USDA Nutrient-Dense Foods · Other
Neem Leaves (Azadirachta indica) (Azadirachta indica)
Preliminary EvidenceCompound
Hermetica Superfood Encyclopedia
Neem leaves (Azadirachta indica) contain bioactive limonoids — primarily nimbolide and azadirachtin — that drive antioxidant and anti-inflammatory effects through modulation of the PI3K/Akt signaling pathway and free radical scavenging. Traditional Ayurvedic medicine has used neem for skin, oral, and immune health for over 4,000 years, though most mechanistic evidence remains preclinical.
Neem leaves come from the neem tree (Azadirachta indica), a fast-growing evergreen native to the Indian subcontinent and cultivated in tropical and semitropical regions. The leaves are harvested fresh or dried and contain limonoids (tetranortriterpenoids), proteins (7.1%), carbohydrates (22.9%), and various amino acids and minerals.
The research dossier reveals a critical gap: no human clinical trials, RCTs, or meta-analyses were found for neem leaves. Available evidence is limited to preclinical antioxidant studies showing methanolic extract IC50 values of 6.65 mg/ml for DPPH radical scavenging, with no PubMed PMIDs provided for human studies.
No clinically studied dosage ranges for neem leaves in humans are available. Preclinical studies use methanolic or ethanolic extracts without specified standardization or doses. Consult a healthcare provider before starting any new supplement.
Neem leaves contain a complex array of macronutrients, micronutrients, and bioactive phytochemicals. Macronutrient composition (per 100g dry weight): crude protein approximately 14–17g, crude fiber 12–16g, carbohydrates 40–45g, crude fat 4–7g, and ash content 8–11g. Moisture content in fresh leaves ranges 60–70%. Micronutrients include calcium (510–530mg/100g dry weight), phosphorus (80–100mg/100g), iron (17–25mg/100g), potassium (approximately 400–450mg/100g), magnesium (50–60mg/100g), zinc (1–2mg/100g), and copper (0.5–1mg/100g). Vitamin content includes ascorbic acid (vitamin C) at 218–220mg/100g fresh weight, beta-carotene (provitamin A precursor) at approximately 7,400–7,500 IU/100g, and trace amounts of B-complex vitamins including thiamine and riboflavin. Primary bioactive compounds include: limonoids — nimbolide (0.01–0.05% dry weight), azadirachtin (trace levels in leaves compared to seeds), nimbin, nimbinin, and gedunin; flavonoids — quercetin, kaempferol, myricetin, and rutin at combined concentrations of approximately 15–30mg/g dry extract; terpenoids including nimbidin and salannin; tannins (approximately 6–9% dry weight contributing to astringency); polyphenols with total phenolic content estimated at 50–120mg gallic acid equivalents per gram dry extract depending on solvent and method; and sulphur-containing compounds. Bioavailability notes: The high tannin and fiber content significantly reduces bioavailability of minerals such as iron and zinc through chelation and binding effects. Lipophilic limonoids such as nimbolide and gedunin require fat co-consumption for improved intestinal absorption. Quercetin bioavailability is moderate and is enhanced by gut microbiota deglycosylation. Neem leaves are not typically consumed as a primary food source due to extreme bitterness; they are used medicinally in small quantities (2–5g dried powder or 10–20 fresh leaves), meaning absolute nutrient intake from typical use is nutritionally insignificant. Most quantitative data derives from in vitro extraction studies; in vivo absorption and tissue distribution data in humans remains largely unavailable.
Nimbolide, a tetranortriterpenoid limonoid in neem leaves, suppresses pro-inflammatory cytokine production by inhibiting the PI3K/Akt/mTOR signaling cascade and downregulating NF-κB transcription factor activity. Neem's antioxidant effect involves direct scavenging of DPPH, superoxide anion, nitric oxide, and hydroxyl radicals, attributable to polyphenolic compounds including quercetin, kaempferol, and chlorogenic acid. Additionally, azadirachtin disrupts cyclooxygenase (COX-2) enzyme expression, further contributing to reduced prostaglandin synthesis in inflammatory models.
The majority of evidence supporting neem leaf bioactivity comes from in vitro cell studies and rodent models, with limited randomized controlled human trials. A small number of clinical studies — typically involving 30–60 participants — have examined neem-based oral formulations (toothpaste, gel) for gingivitis and plaque reduction, showing statistically significant improvements in gingival index scores compared to placebo. One pilot study (n=40) exploring neem leaf extract at 30 mg/day for blood glucose modulation reported modest fasting glucose reductions, though study design limitations preclude firm conclusions. Overall, the human evidence base is sparse and underpowered; preclinical data are promising but cannot yet be extrapolated to confirmed therapeutic use.
Neem leaf extract is generally considered safe at studied oral doses (up to 60 mg/day in short-term human studies), but high-dose or prolonged use has been associated with hepatotoxicity in case reports, particularly in children consuming neem oil. Neem may potentiate the effects of antidiabetic medications (e.g., metformin, insulin) by independently lowering blood glucose, increasing hypoglycemia risk. It is contraindicated during pregnancy, as azadirachtin has demonstrated abortifacient and antifertility effects in animal models, and should be avoided while breastfeeding. Individuals taking immunosuppressants or anticoagulants should consult a healthcare provider, as neem's immunomodulatory and potential platelet-inhibiting properties may produce additive effects.
