Miliacin

Miliacin: A Comprehensive Reference

1. Identity and Chemical Characterization

Chemical Names and Classification

Miliacin (olean-18-en-3β-ol methyl ether) is a pentacyclic triterpene methyl ether (PTME) that is enriched in seeds of Panicum miliaceum. Miliacin, also called Panicol or Prosol, belongs to the class of organic compounds known as triterpenoids. This compound (also known as olean-18-en-3β-ol or multiflorenol) is a triterpenoid compound predominantly found in proso millet (Panicum miliaceum L.) and serves as a key chemical marker for quality control and standardization of millet-based extracts.

Its CAS registry number is 5945-45-9, and its molecular formula is C₃₁H₅₂O. Miliacin is a white odorless solid crystal practically fat- and water-insoluble. This pentacyclic triterpene alcohol has gained significant research interest due to its diverse biological activities, including hair growth promotion, anti-inflammatory properties, and antioxidant effects.

Natural Source and Botanical Origin

Miliacin is a rare triterpene, a natural compound predominantly found in millet seeds and millet-based products such as millet oil. It is the principal (approximately 99%) pentacyclic triterpene methyl ether (PTME) in broomcorn millet and is absent in other commonly cultivated species. Miliacin comprises 94.9% of pentacyclic triterpene methyl ethers (PTMEs) in millet seeds, and soils where miliacin is the sole or dominant PTME are likely to have been used to cultivate millet.

Keranat®, a patented commercial preparation built around miliacin, has been developed from a variety of millet (Panicum miliaceum L.) cultivated in France; in the Loire Valley, millet fields are grown exclusively for this ingredient. The pentacyclic triterpene miliacin is an anti-microbial compound and is resistant to decomposition by bacteria. The durability of miliacin results in its survival in high concentrations in archaeological contexts.

Distribution Within the Plant

The distribution of miliacin in the different organs of P. miliaceum has been examined in order to identify the biomass responsible for its dissemination in soils and sediments. Research has confirmed its predominant concentration in the seed and bran fractions. So far, miliacin has only been detected in millet and millet products such as millet oil.

Common Forms and Preparations

Miliacin is commercially available in several forms:

• Millet seed oil (cold-pressed or supercritical CO₂ extract): Miliacin, the major triterpenoid compound from millet grains, is extracted by the supercritical CO₂ extraction method.
• Miliacin encapsulated by polar lipids (MePL / Keranat®): Keranat™ is obtained from natural substances including miliacin, millet seeds, and lipids sourced from sunflower, wheat kernels, safflower, and rosemary; polar lipids help to encapsulate miliacin to improve its bioavailability so that it can reach the bloodstream.
• Oral supplements (capsules and liquid): These supplements, available in both liquid form and capsules, are designed to cater to consumers looking for natural ways to improve hair appearance and health.
• Topical preparations: Millet oil for external wound or skin application has also been studied, as described in the wound-healing literature below.

Analysis of miliacin content in commercial preparations uses saponification and measurement via GC-MSD (Gas Chromatography with Mass Spectrometry Detector) to precisely determine the miliacin content in millet oil.

2. Historical and Traditional Use

Archaeological Evidence of Millet Consumption

Broomcorn millet (Panicum miliaceum L.) was domesticated in northeast China by approximately 6000 BC. Genetic evidence, along with archaeobotany and palaeodietary analysis, is consistent with a single origin of cultivated P. miliaceum somewhere in northern China, by at least the 6th millennium BC.

During the Late Neolithic and Bronze Age, a majority of cereals consumed in the Zhengluo region of China were foxtail millet and proso millet; Chinese myths attribute the domestication of millet to Shennong, a legendary emperor of China, and Hou Ji, whose name means "Lord Millet." The cultivation of common millet as the earliest dry crop in East Asia has been attributed to its resistance to drought, and Asian varieties of millet made their way from China to the Black Sea region of Europe by 5000 BC.

Archaeobotanical evidence reveals that millet was common in Europe from the 2nd millennium BC, when major societal and economic transformations took place in the Bronze Age. Millet is listed along with wheat in the 3rd century BC by Theophrastus in his Enquiry into Plants.

Miliacin specifically has been identified as a biomarker linking pottery vessels to millet consumption across multiple civilizations. Miliacin (olean-18-en-3β-ol methyl ether), a pentacyclic triterpene methyl ether enriched in grains of common/broomcorn millet (Panicum miliaceum), has been successfully identified in Bronze Age pottery vessels from the Korean Peninsula and northern Europe. It is readily absorbed in the walls of pottery during cooking and is highly resistant to degradation.

Palaeoethnobotanists have found evidence of the cultivation of millet in the Korean Peninsula dating to the Middle Jeulmun pottery period (around 3500–2000 BC); millet continued to be an important element in the intensive, multicropping agriculture of the Mumun pottery period (about 1500–300 BC) in Korea.

Traditional Medicinal and Ethnobotanical Use

Millet (Panicum miliaceum) and its main compound, miliacin, arouse a lot of interest in dermatological research, especially for its tissue repair and wound healing properties. The use of millet oil in traditional Eastern European folk medicine for wound care predates its formal scientific investigation. The efficacy of miliaceum (millet) oil in local application for the treatment of purulent wounds was the subject of formal study; the oil is obtained from waste products of millet processing. This reflected an older tradition of applying grain-derived oils to skin lesions across Eastern European and Russian folk healing.

Considering that miliacin, like other pentacyclic triterpenes, is rather resistant to diagenesis owing to its supposed antifungal/antibacterial role in plants, it is very likely that miliacin survives in soils formerly used for millet cultivation. This inherent antimicrobial character of miliacin may partially explain why millet preparations were historically applied to infectious or suppurating wounds.

3. Key Constituents and Active Compounds

Miliacin as the Principal Bioactive

Miliacin, the main triterpenoid from millet, is known to stimulate keratinocyte metabolism and proliferation; polar lipids are able to form vesicles with active compounds and to improve their bioavailability.

Keranat™ (the principal commercial preparation) is made with millet, a small brown wholegrain; it contains naturally occurring compounds such as linoleic acid and miliacin. Miliacin is the most important molecule within Keranat™; it is this clinically studied compound that is responsible for stimulating hair growth and increasing collagen thickness in the hair follicle.

Millet Polar Lipids (MePL)

Studies have shown that miliacin, encapsulated by the polar lipids (MePL) present in Keranat™, effectively enhances the synthesis of insulin-like growth factor (IGF-1), stimulates cell division in the hair bulb, as well as the anagen (growth) phase, and reduces the telogen (resting) phase ratio. The polar lipid matrix — derived from millet, sunflower, wheat, safflower, and rosemary — serves both as a delivery vehicle and as a bioactive component in its own right, contributing to scalp hydration.

4. Mechanisms of Action

Hair Follicle Biology: Proliferation and Growth Cycle Regulation

Miliacin, the primary triterpenoid compound isolated from millet (Panicum miliaceum L.), has demonstrated significant potential in stimulating keratinocyte metabolism and proliferation; the encapsulation of this compound within polar lipid vesicles enhances its bioavailability and cellular uptake, thereby amplifying its proliferative effects on hair follicle cells.

Studies indicate that miliacin can promote hair growth by activating the Wnt/β-catenin signaling pathway, a key regulator of the hair follicle anagen (growth) phase. Miliacin's activation of the Wnt/β-catenin pathway leads to the upregulation of downstream targets, including growth factors like Insulin-like Growth Factor 1 (IGF-1), which further stimulates the proliferation of keratinocytes in the hair bulb.

Ex vivo studies on human scalp tissue have provided quantified data on these effects. A significant increase of 14.1% in IGF-1 and an important and significant 140% stimulation of mitotic index (Ki67 positive cells) was observed in the epithelial cells of the hair bulb with miliacin/polar lipid treatment (MPL). A significant increase of 20.8% in collagen thickness was measured in the connective tissue sheath of the hair in contact with MPL.

In vivo studies using anagen-synchronized mouse models have further demonstrated that miliacin-containing complexes can elongate the anagen phase. Miliacin, the major triterpenoid from millet grains extracted by the supercritical CO₂ extraction method, can affect hair growth by inducing the proliferation of hair follicle cells.

In cell culture experiments, when normal human keratinocytes derived from the foreskin were exposed to miliacin (6 mg/mL), the metabolic capacity of these cells was increased by 162% and their proliferation was also stimulated by 215%.

Anti-inflammatory Mechanisms

The available evidence strongly suggests that miliacin possesses significant anti-inflammatory properties, primarily mediated through the downregulation of pro-inflammatory cytokines and potential modulation of the NF-κB signaling pathway.

In studies of experimental Salmonella infection in mice, the protective effect of miliacin is determined by the reduction of endotoxinemia, mobilization of the Th-1 response, stimulation of IL-10 production, and limitation of IL-17 participation in the development of the inflammatory reaction.

Thanks to its strong anti-inflammatory properties, topical application of millet oil promoted rapid cleansing of wounds and significantly activated reparative processes.

Antioxidant and Lipid Peroxidation Inhibition

A plant triterpenoid miliacin prevented stress-induced activation of lipid peroxidation (LPO) and accumulation of LPO products in the blood; the inhibitory effect of miliacin was not related to direct inhibition of reactive oxygen species generation. This indicates an indirect antioxidant mechanism, likely mediated through modulation of oxidative stress signaling pathways rather than free-radical scavenging per se.

Moreover, miliacin can prevent the stress-induced activation of lipid peroxidation. Research on the efficacy of millet and wheat grain extracts has focused on the effects of antioxidation and anti-inflammation.

Cytoprotection and Immunomodulation

The effect of plant triterpenoid miliacin on dexamethasone-induced apoptosis in thymocytes and splenocytes has been studied; miliacin produced a protective effect on splenocytes by decreasing the degree of DNA fragmentation due to blockade of the cascade cell death distally to the intramembrane phosphatidylserine translocation.

Miliacin weakens the severity of salmonellosis infection course, and studies show that miliacin reduces the intensity of endotoxinemia in mice.

The expression of growth factors (IGF-1, VEGF, and FGF7) was significantly increased in the miliacin/wheat complex (MWC)-treated group compared to the control group.

5. Scientific Evidence by Area of Use

5.1 Hair Loss (Telogen Effluvium) and Hair Growth Promotion

Evidence Summary

This is the area with the most substantial and published human clinical evidence for miliacin, primarily derived from studies on the patented formulation Keranat™ (miliacin encapsulated by polar lipids, MePL).

Key Human Clinical Trial (Keophiphath et al., 2020)

The objective of the primary human clinical study was to demonstrate potential benefits of a solution of miliacin encapsulated within polar lipids (MePL) on telogen effluvium prevention and hair condition in women. After preliminary cell proliferation studies, a placebo-controlled, multicentric, randomized, double-blind trial was performed on sixty-five nonmenopausal women affected by telogen effluvium, to assess the efficacy of a 12-week oral supplementation with MePL.

Telogen and anagen densities were determined by phototrichogram analysis; scalp dryness and hair brightness were clinically evaluated using a Likert scale. The dose tested was 300 mg of Keranat™ per day (corresponding to 3.0 to 3.3 mg/day of miliacin). Key findings included:

• MePL further enhanced cell proliferation in hair bulbs from human scalp than miliacin alone, suggesting enhanced hair growth promotion.
• Scalp dryness and hair brightness improved significantly more in the MePL group than in the placebo group.
• MePL may enhance IGF-1 production, critical for normal hair cycle and growth, warranting further studies.
• 91% of those in the active supplement group observed a reduction in hair loss.

Limitations: The study enrolled only 65 participants — all nonmenopausal women with telogen effluvium — limiting generalizability to men, postmenopausal women, and other types of alopecia. The 91% figure cited in some secondary literature derives from participant self-evaluation, which is subject to reporting bias. The published study (PMID 31135099, Journal of Cosmetic Dermatology, 2020) was partly funded by the ingredient manufacturer (Robertet Group).

NCT06237959 (24-Week Randomized Controlled Trial)

A 24-week, randomized, double-blind, placebo-controlled clinical study (NCT06237959) was completed in 2023 to evaluate the efficacy and safety of Keranat™ on hair health. The trial enrolled 100 participants aged 19 to 60 years. Keranat™ 300 mg and placebo were administered in two separate daily doses for 24 weeks. Full published results for this trial were not yet available in the peer-reviewed literature as of the time of writing; the trial's registration indicates it was completed in December 2023.

Ex Vivo Studies

Numerous ex vivo studies have been undertaken to examine the effect of Keranat™ on cellular proliferation, growth factors, and collagen thickness. The quantitative results of the most cited ex vivo study are described under Mechanisms of Action above (27-3, 27-4).

A further study investigated the biological effects of a complex of millet extract and wheat extract (MWC) on hair health using human immortalized dermal papilla cells (iDPCs) for an in vitro study and an anagen-synchronized mouse model for an in vivo study.

Strength of Evidence

Moderate — but with important caveats. There is one published randomized, double-blind, placebo-controlled clinical trial in humans (Keophiphath et al., 2020), supported by mechanistically coherent ex vivo and in vitro data. However, the study population was small and restricted to a single type of hair loss (telogen effluvium) in premenopausal women. The majority of the supporting evidence is preclinical (cell culture and animal models). A larger, independent replication study is needed to confirm these findings. Industry funding of the primary clinical study also warrants cautious interpretation.

5.2 Wound Healing and Tissue Repair

Animal Studies

The efficacy of miliaceum (millet) oil in local application for the treatment of purulent wounds was studied formally; the oil is obtained from waste products of millet processing, and experiments on 55 rabbits with a model of a purulent wound demonstrated that the preparation causes a marked anti-inflammatory effect, promotes rapid cleansing of wounds from pyonecrotic contents, and significantly activates reparative processes. With the use of millet oil, the term of wound healing was reduced by 6–12 days on average compared to healing in treatment with buckthorn oil and Vishnevsky's ointment.

The effects of miliaceum oil used for topical application to trophic ulcers were studied; the oil was obtained from millet processing waste products, and experiments on 73 rats with induced trophic ulcers demonstrated that the agent under study had a marked anti-inflammatory effect and substantially activated reparative processes.

Cellular studies using thymocyte and splenocyte cultures have revealed a protective effect of miliacin from DNA fragmentation and apoptosis; animal and clinical studies with suppurating wounds in different physiopathological conditions have confirmed and deepened these first results.

Strength of Evidence

Preliminary — animal/preclinical only. The wound-healing and tissue repair evidence for miliacin is derived almost exclusively from animal models (rats, rabbits) and in vitro cell studies. No controlled human clinical trials specifically examining miliacin's effects on wound healing in human subjects have been published in peer-reviewed literature.

5.3 Immunomodulation and Infection (Salmonellosis)

Animal Studies

In one published study, the effect of miliacin on the intensity of endotoxinemia and features of cytokine production in experimental Salmonella infection was evaluated; the studies were carried out in 128 male mice divided into four groups (intact, infected, infected with solvent control, and infected with miliacin). Miliacin reduced the intensity of endotoxinemia; Salmonella infection increased spontaneous (IFN-γ) and induced (IL-12, IFN-γ, IL-17) cytokine production; miliacin ensured the most significant increase of spontaneous IL-10, IL-12, and IFN-γ production.

Strength of Evidence

Preclinical only. All evidence in this area comes from animal (murine) models. No human clinical trials have investigated miliacin specifically for infectious disease or immunological outcomes.

5.4 Antioxidant and Oxidative Stress Reduction

Animal/In Vitro Studies

A plant triterpenoid miliacin prevented stress-induced activation of lipid peroxidation (LPO) and accumulation of LPO products in the blood; the inhibitory effect of miliacin was not related to direct inhibition of reactive oxygen species generation. This study, published in the Bulletin of Experimental Biology and Medicine (2006), was conducted in animals under experimental stress conditions.

Strength of Evidence

Preclinical only. Antioxidant activity has been demonstrated in animal stress models and by the general properties attributed to pentacyclic triterpenes. No dedicated human clinical trials have evaluated miliacin as a standalone antioxidant supplement.

5.5 Lipid Metabolism and Liver Function

Some studies suggest that miliacin may have a protective effect on liver function and may help regulate lipid metabolism. While preclinical research is encouraging, clinical studies in humans remain limited; current evidence supports the traditional use of millet-based diets for metabolic and cardiovascular health, but the specific contributions of miliacin require further validation through well-designed human trials.

Strength of Evidence

Very preliminary. Evidence for effects on liver function and lipid metabolism is limited to cell and animal models. No human trials have been published.

6. Body Systems and Health Areas Associated with Miliacin

• Integumentary system (hair follicles and scalp): The best-supported area of activity. In dermatological and hair biology research, miliacin has been shown to stimulate the proliferation of keratinocytes and hair bulb cells.
• Immune system: Beyond hair research, miliacin exhibits immunomodulatory properties. It has been studied in the context of lymphocyte apoptosis protection and experimental infection.
• Connective tissue (extracellular matrix): Miliacin associated with polar lipids acts on the dermal papilla where it stimulates IGF-1 growth factor production and renewal of keratinocytes in the hair bulb; it also increases the thickness of extracellular matrix of the connective tissue sheaths.
• Oxidative stress pathways: Miliacin modulates lipid peroxidation and has cytoprotective activity against oxidative cell death, as demonstrated in preclinical studies.
• Hepatic/metabolic system: Preliminary preclinical evidence suggests possible effects on liver function and lipid metabolism, but these require clinical validation.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are drawn directly from published or registered clinical studies; they are not recommendations.

• 300 mg/day Keranat™ (oral capsules): A double-blind clinical trial was carried out with 65 women who consumed 300 mg of Keranat™ every day for three months. This dose corresponds to approximately 3.0 to 3.3 mg/day of miliacin, as standardized in the millet oil soft capsule formulation.
• 300 mg/day in two divided doses (24-week study): Keranat™ 300 mg and placebo were administered in two separate daily doses for 24 weeks in the NCT06237959 registered trial.
• Capsule unit dose: Keranat™ capsules contain 150 mg of proso millet and wheat extract, with two capsules per day making up the 300 mg daily dose used in clinical study protocols.
• Cell culture concentration: When normal human keratinocytes were exposed to miliacin at 6 mg/mL, the metabolic capacity of the cells was increased by 162% and proliferation was stimulated by 215% — this is an in vitro concentration used in mechanistic research, not an oral dose.

8. Safety Considerations and Interactions

Observed Safety Profile in Clinical Studies

The NCT06237959 trial was specifically designed as a 24-week, randomized, double-blind, placebo-controlled study to evaluate both the efficacy and safety of Keranat™ on hair health. No serious adverse events attributable to Keranat™ were reported in the published clinical literature available at the time of writing. The ingredient is derived from food-grade, organically cultivated millet.

Millet Allergen Considerations

Millet (Panicum miliaceum) is generally recognized as a food crop rather than a common allergen, though millet-seed hypersensitivity has been reported in the dermatological literature in isolated cases. Individuals with known cereal grain hypersensitivity should be aware that miliacin preparations are derived from millet seed.

Interaction with Methotrexate

The natural triterpenoid miliacin has been studied for its capacity to prevent methotrexate-induced oxidative stress and normalize the expression of genes encoding the cytochrome P-450 2E1 isoform and glutathione reductase in the liver. This preclinical finding suggests a possible interaction with CYP2E1-metabolized drugs, though no human pharmacokinetic interaction data exist; this remains a theoretical concern based on animal data only.

Solubility and Bioavailability Challenges

Miliacin is a white odorless solid crystal practically fat- and water-insoluble. This physicochemical characteristic limits its absorption when delivered as an unformulated powder. The encapsulation of miliacin within polar lipid vesicles enhances its bioavailability and cellular uptake, thereby amplifying its proliferative effects on hair follicle cells. Patented encapsulation systems have been developed specifically to increase the effectiveness and bioavailability of Keranat® miliacin. Consumers purchasing unformulated millet oil products should be aware that the miliacin content and its bioavailability may vary significantly compared to the standardized encapsulated preparations studied clinically.

Purity and Analytical Standardization

In order to ensure that millet oil in supplements actually contains the claimed amount of miliacin, a thorough analysis of the oil to identify its ingredients is necessary. Reliable analytical techniques — including saponification and GC-MSD measurement — allow for precise determination of miliacin content with a detection limit in plant oils of 1 mg/kg. Absence of standardized miliacin content testing in some commercial products means that actual miliacin doses delivered may differ from label claims.

Populations Not Studied

Published clinical evidence for miliacin is derived exclusively from adult women with telogen effluvium. No clinical studies have been conducted in men, children, pregnant or breastfeeding individuals, or persons with pathological alopecia subtypes other than telogen effluvium. Extrapolation of efficacy or safety data to these populations is not supported by available evidence.

References

• Keophiphath M, et al. "Miliacin encapsulated by polar lipids stimulates cell proliferation in hair bulb and improves telogen effluvium in women." J Cosmet Dermatol. 2020 Feb;19(2):485-493. PMID: 31135099
• Miliacin Associated with Polar Lipids: Effect on Growth Factors Excretion and Extracellular Matrix of the Dermal Papilla Hair Follicle Model Maintained in Survival Conditions — ResearchGate
• Lee et al. "Effects of the Complex of Panicum miliaceum Extract and Triticum aestivum Extract on Hair Condition." Nutrients. 2023 Oct;15(20):4411. PMC10609892
• Panfilova TV, et al. "Effect of the Triterpenoid Miliacin on the Sensitivity of Lymphocytes in the Thymus and Spleen to Dexamethasone-Induced Apoptosis." Bull Exp Biol Med. 2003;136:336–339
• Panfilova TV, Shtil' AA, Frolov BA. "Triterpenoid miliacin inhibits stress-induced lipid peroxidation." Bull Exp Biol Med. 2006;141:685–687
• [Mechanisms of realization of protective effect of miliacin during experimental Salmonella infection: effect of endotoxinemia and cytokine production]. PubMed PMID: 25536765
• [Effect of miliacin oil on the healing of purulent wounds]. PubMed PMID: 2082266
• ClinicalTrials.gov NCT06237959: Evaluate the Efficacy and Safety of Proso Millet and Wheat Extract (Keranat™) on Hair Health
• NCT06237959 Protocol Document — Clinical Background on Miliacin
• Bortolini S, et al. "Direct evidence from lipid residue analysis for the routine consumption of millet in Early Medieval Italy." J Archaeol Sci. 2018
• Thermal desorption GC/MS on human dental calculus detected minute millet consumption in medieval Ukraine. Scientific Reports. 2025
• Bossard N, et al. "Distribution of miliacin (olean-18-en-3β-ol methyl ether) and related compounds in broomcorn millet (Panicum miliaceum) and other reputed sources." Org Geochem. 2013
• Heron C, et al. "First molecular and isotopic evidence of millet processing in prehistoric pottery vessels." PubMed PMID: 28004742
• Filipović D, et al. "New AMS 14C dates track the arrival and spread of broomcorn millet cultivation and agricultural change in prehistoric Europe." Scientific Reports. 2020
• Lu H, et al. "Earliest domestication of common millet (Panicum miliaceum) in East Asia extended to 10,000 years ago." PNAS. 2009
• Hunt H, et al. "Genetic evidence for a western Chinese origin of broomcorn millet (Panicum miliaceum)." PMC6236650
• GALAB Laboratories GmbH: "GALAB offers a new, advanced method for the determination of Miliacin." 2024
• Robertet Group: "Keranat® — Our Ingredient." Official ingredient page