Nerolidol
Also known as: 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol, Peru balsam, penetrol, trans-nerolidol, cis-nerolidol, Nerolidol
Overview
Nerolidol is a naturally occurring sesquiterpene alcohol found in the essential oils of various plants, including neroli, ginger, jasmine, and tea tree. It is a volatile compound that contributes to floral and woody aromas. Research indicates its potential pharmacological properties, such as anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and skin penetration enhancement effects. It is also utilized in cosmetics and as an insect repellent. Nerolidol is lipophilic and volatile, existing in two isomeric forms (cis and trans). Preclinical studies suggest rapid absorption and clearance in animal models. The current research on nerolidol is primarily in the preclinical and early clinical stages, with most studies conducted in vitro or on animals, and limited human data available. The quality of evidence is moderate, consisting mainly of experimental studies with few randomized controlled trials and no large-scale meta-analyses specifically on nerolidol as a supplement ingredient.
Benefits
Nerolidol has demonstrated several potential benefits in preclinical studies. It exhibits significant anti-thrombotic and vascular protective effects, as shown in animal models where it protected against diesel exhaust particle (DEP)-induced peripheral thrombosis, endothelial dysfunction, systemic inflammation, oxidative stress, and DNA damage, suggesting cardiovascular protective potential. It also acts as an anti-inflammatory and antioxidant agent, reducing markers of systemic inflammation (e.g., TNF-α, IL-6) and oxidative stress (e.g., malondialdehyde). Some animal studies indicate neuroprotective and sedative properties, possibly by modulating oxidative stress and inflammatory pathways. Secondary effects observed in experimental studies include antimicrobial, anti-parasitic, anti-biofilm, anti-ulcer, and skin penetration enhancement. However, robust human clinical trials are lacking, meaning these benefits are not yet confirmed in human populations. Quantitative effect sizes are not well-established due to the limited number of human randomized controlled trials, though existing animal studies show statistically significant biochemical and physiological improvements. Pharmacokinetic studies in rodents indicate rapid absorption with peak plasma concentrations within 20-30 minutes and rapid clearance within 2-12 hours.
How it works
Nerolidol exerts its effects primarily through antioxidant and anti-inflammatory mechanisms. It scavenges free radicals, thereby reducing oxidative stress markers in the body. It modulates inflammatory pathways by downregulating pro-inflammatory cytokines such as TNF-α and IL-6. In vascular tissues, it may also inhibit apoptosis and DNA damage pathways. While the exact molecular targets are not fully elucidated, its actions likely involve the modulation of NF-κB signaling and the activity of oxidative stress enzymes like SOD, catalase, and GPX. Nerolidol interacts with various body systems, including the cardiovascular system (affecting vascular endothelium), the immune system (modulating inflammatory cytokines), the nervous system (contributing to neuroprotection), and the skin (acting as a penetration enhancer). Animal studies show rapid absorption, with peak plasma levels occurring within 20-30 minutes after oral or intraperitoneal administration, though human bioavailability and metabolism remain unclear.
Side effects
The overall safety assessment for nerolidol is limited due to a lack of comprehensive human safety data. Preclinical studies suggest low toxicity at the doses tested in animals, and no significant adverse effects have been reported in these animal models. However, common, uncommon, or rare side effects in humans are not well documented. Drug interactions are currently unknown, but due to its observed effects on coagulation and inflammation in preclinical studies, potential interactions with anticoagulants or anti-inflammatory drugs should be considered. Contraindications for nerolidol use are not established due to the absence of human clinical data. Furthermore, its safety in special populations, such as pregnant women, children, or individuals with chronic diseases, has not been established, and caution is advised in these groups until more research is available.
Dosage
The minimum effective dose for nerolidol in humans has not been established. Animal studies have utilized a wide range of doses, from 25 mg/kg (intraperitoneal) to 1000 mg/kg (oral) in mice and rats. Optimal dosage ranges for human use are currently unknown and require further human clinical trials. Similarly, the maximum safe dose has not been defined; while high doses in animals did not show acute toxicity, long-term safety in any species remains uninvestigated. Due to its rapid absorption and short half-life observed in animal studies, if used therapeutically, nerolidol might require multiple daily doses to maintain consistent levels. It has been studied via oral and intraperitoneal routes in animals, and topical formulations are used for skin penetration enhancement. Its lipophilicity suggests that co-administration with fats might enhance its absorption. No specific cofactors are identified as necessary for its efficacy.
FAQs
Is nerolidol safe for human consumption?
Human safety data are insufficient. Preclinical studies suggest low toxicity, but clinical trials are needed to confirm its safety for human consumption.
What are the expected benefits?
Based on animal studies, potential benefits include antioxidant, anti-inflammatory, vascular protective, and neuroprotective effects. Human efficacy is not yet confirmed.
How quickly does it work?
Animal pharmacokinetics indicate peak plasma levels within 20-30 minutes, but the timing of clinical effects in humans is currently unknown.
Can it interact with medications?
Potentially yes, especially with blood thinners and anti-inflammatory drugs, due to its observed effects on coagulation and inflammation, but clinical data are lacking.
Is it effective as a standalone supplement?
Evidence is preliminary and based on preclinical studies. More rigorous human trials are needed to determine its effectiveness as a standalone supplement.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11940484/ – This experimental animal study investigated nerolidol's protective effects against diesel exhaust particle (DEP)-induced damage. It found that nerolidol ameliorated DEP-induced thrombosis, endothelial dysfunction, inflammation, oxidative stress, and DNA damage in mice and rats, suggesting significant cardiovascular protective potential. The study provides strong preclinical evidence for nerolidol's therapeutic properties, though it notes limitations in sample size for some sub-studies and the absence of human data.
- https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2021.704180/full – This animal study explored nerolidol's neuroprotective and anti-inflammatory effects. It demonstrated that nerolidol reduced oxidative stress markers and inflammatory cytokines in mice, indicating potential neuroprotective properties. The research provides biochemical validation for nerolidol's effects on the nervous system, but it is limited by being an animal model without human clinical outcomes.