IngredientsLaxogenin is a steroidal sapogenin first isolated from Smilax sieboldii Miq. Its systematic IUPAC-derived chemical name, as established through spectroscopic analysis of isolates from Smilax sieboldii rhizomes, is 3β-hydroxy-(25R)-5α-spirostan-6-one. Six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii, with their structures determined by spectroscopic analysis and hydrolysis to be 3β-hydroxy-(25R)-5α-spirostan-6-one (laxogenin) and related glycosides. The compound carries the CAS registry number 1177-71-5 and a molecular weight of 430.62 g/mol.
Laxogenin is a sapogenin — the sterol constituent of the non-sugar portion of a saponin — isolated from the plant Smilax sieboldii. The compound is a spirostanic analogue of the brassinosteroid. Sapogenins are aglycones (non-saccharide moieties) of saponins, a large family of natural products, and contain steroid or other triterpene frameworks as their key organic feature.
Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals.
Laxogenin is one of many plant-based steroids that help to promote growth in plants. It comes from the stems of Asian plants such as Smilax sieboldii, Allium schoenoprasum, Allium chinense, and Solanum unguiculatum, but only in very small amounts.
The underground stems of the Asian plant Smilax sieboldii contain approximately 0.06% laxogenin and are its main natural source. Laxogenin is also obtained from Chinese onion (Allium chinense) bulbs. Laxogenin was first identified in 1965 by a Japanese laboratory as a substance in the plant Smilax sieboldii, which is native to Japan, Korea, and China.
Smilax sieboldii Miq. is a climbing plant with prickly stems that grows in Korea, Japan, China, and Taiwan. Smilax sieboldii is a climbing shrub which mainly grows in East Asia, and South and North America.
The dietary supplement industry predominantly markets a compound called 5α-hydroxy laxogenin, which is importantly distinct from naturally occurring laxogenin. Although laxogenin has been isolated from the rhizomes of Smilax sieboldii, 5α-hydroxy laxogenin has not been isolated or reported from any natural source. Avula et al. proved 5α-hydroxy-laxogenin's synthetic origin; hence, it is not of natural, plant-derived origin.
Laxogenin in supplements is produced from the more common plant steroid diosgenin. In fact, diosgenin is used as a raw material for over 50% of synthetic steroids including progesterone, cortisone, and testosterone. 5α-hydroxy-laxogenin is a synthetic spirostane-type steroid, which is contained in dietary supplements and advertised as an anabolic agent.
As dietary supplements, laxogenin and its so-called derivative, 5-alpha-hydroxy-laxogenin, are promoted as "natural anabolics" (alternatives to anabolic steroids) for those who want to gain muscle mass while keeping body fat low. They appear on dietary supplement labels and websites with claims of increased lean muscle growth, strength, and vitality.
Laxogenin and 5α-hydroxy laxogenin are formulated commercially as oral capsules and tablets, and occasionally in topical preparations. As a plant-derived spirostane-type steroidal compound, its bioavailability is limited by poor oral absorption due to its lipophilic nature; encapsulation in cyclodextrin or liposomal delivery systems has been reported to improve absorption. In dietary supplements, you will often find 5α-hydroxy laxogenin, a synthetic version of the compound.
No traditional use of laxogenin as an isolated chemical entity has been documented; the compound was not isolated until the 1960s. Historical use is therefore attributed to preparations derived from Smilax sieboldii and related Smilax species, which contain laxogenin as one of many saponin constituents.
Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. Young leaves are harvested from the wild for local use as food. In addition, the subterranean parts have been employed in traditional folk remedies for arthritis, tumors, leprosy, psoriasis, and lumbago.
The roots and tubers of Smilax china L. have been applied not only as traditional Chinese medicine (TCM) for treatment of diuretic, rheumatic arthritic, detoxication, lumbago, gout, tumor, and inflammatory diseases, but also as food in some areas of China.
The Smilax species, which are widely dispersed throughout the world's tropical regions and the temperate zones of North America and East Asia, were commonly used as food and traditional medicine to cure inflammatory illnesses.
Laxogenin was first identified in the 1960s as a member of a group of plant-based steroids known as brassinosteroids. The original isolation and structural elucidation were reported by Akahori and Yasuda (1963) and later by Okanishi, Akahori, and Yasuda (1965) in Chemical and Pharmaceutical Bulletin, where the full structure of laxogenin was determined from the stems of Smilax sieboldii. Laxogenin was studied by Japanese researchers as far back as the early 1960s, but it was not brought to public attention until the 1990s.
Anabolic interest in the compound emerged from a 1975 Soviet study by Syrov and Kurmukov examining the anabolic activity of 6-ketoderivatives of certain natural sapogenins, a line of research that informed later commercial development in the supplement industry. Supplement companies began using this compound in their products to give athletes a boost. Laxogenin was isolated in 1992 from rhizomes of Smilax sieboldii and is considered to be a type of steroidal sapogenin and part of a group called brassinosteroids, which are part of a group of 40 different steroids synthesized from species of plants.
Laxogenin belongs to the spirostane class of steroidal sapogenins. Its defining structural features are a spiroketal ring system (characteristic of the spirostan framework), a 6-keto group on the B ring, and a 3β-hydroxyl group. The full IUPAC-based name, 3β-hydroxy-(25R)-5α-spirostan-6-one, encodes these structural elements.
The presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were found to be critical for the anabolic activity of brassinosteroids in cell-based assays. This structure-activity relationship has relevance for understanding which laxogenin derivatives might retain biological activity.
In Smilax sieboldii, laxogenin exists not as a free aglycone but primarily as part of steroidal saponin glycosides. Six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii, and their structures were determined to include laxogenin bound to various sugar chains including glucopyranosyl and arabinopyranosyl residues. The free sapogenin (laxogenin) is released upon hydrolysis of these glycosides.
Steroidal saponins are considered to be responsible for the pharmacological properties of Smilax species. Many pharmacological in vitro and in vivo studies revealed significant biological activities, including cAMP phosphodiesterase inhibitory, anti-fungal, cytotoxic, and anti-inflammatory activities. Laxogenin glycosides displayed cAMP phosphodiesterase inhibitory activities with IC50 values in the 30–83 μM range.
The mechanisms attributed to laxogenin in the context of muscle physiology are based on research conducted largely on related brassinosteroids (particularly 28-homobrassinolide), and on in vitro assays. No peer-reviewed mechanistic study using laxogenin itself in human skeletal muscle has been published at the time of this article.
Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway.
All anabolic brassinosteroids tested in one study selectively activated the PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.
Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity. Moreover, HB showed no direct binding to the androgen receptor in vitro. These findings suggest that oral application of HB triggers a selective anabolic response with minimal or no androgenic side effects.
These findings from related brassinosteroids are frequently extrapolated to laxogenin in the supplement literature, but it must be emphasized that laxogenin itself has not been the subject of these key mechanistic studies. The generalization from 28-homobrassinolide to laxogenin remains an inference not directly validated in the published peer-reviewed literature.
Laxogenin has been proposed to inhibit cortisol binding and thereby exert anti-catabolic effects. Its primary bioactive mechanism is proposed to involve inhibition of cortisol binding and modulation of the PI3K/Akt/mTOR protein synthesis pathway at the cellular level. However, this cortisol-modulating effect has not been confirmed in peer-reviewed human or animal studies specifically using laxogenin.
To date, evidence has been missing on anabolic or androgenic activity of 5α-hydroxy-laxogenin. Researchers investigated its androgenic potential in two in vitro bioassays. While no activity was observed in the yeast androgen screen, 5α-hydroxy-laxogenin was able to trans-activate the androgen receptor in human prostate cells in a dose-dependent manner.
In a subsequent in vivo study using castrated male rats, effects were neither observed on the wet weights of the androgen target tissues (prostate, seminal vesicle, or penis) nor on the wet weights of the anabolic target tissue musculus levator ani or skeletal hindlimb muscles. Significantly higher atrophy was seen for some target tissues in the animals treated with the highest 5α-hydroxy-laxogenin dosage (36 mg/kg bw). While in silico docking supports androgen receptor binding previously observed in vitro, neither androgenic nor anabolic effects of 5α-hydroxy-laxogenin were observed in vivo in castrated male rats.
In research on the related compound 28-homobrassinolide, acute oral administration of 50–300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose. Daily chronic administration of HB (50 mg/kg for 8 weeks) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. Whether these findings extend to laxogenin specifically is not established.
When C57BL/6J mice were given a dermal wound, topical application of brassinosteroids significantly reduced wound size after 10 days of treatment. The data suggest that topical brassinosteroids accelerate the wound-healing process in part by shortening the early inflammatory phase and enhancing migration and wound repair by stimulating the PI3K/Akt pathway. Again, this work was conducted on the related brassinosteroid HB, not on laxogenin itself.
Evidence summary: Preliminary — animal and in vitro studies only; no published human clinical trials on laxogenin or 5α-hydroxy laxogenin.
Only animal and cell studies have tested laxogenin so far, and none of them used the compound found in most supplements: 5α-hydroxy laxogenin.
The most substantive published evidence in this area concerns the brassinosteroid 28-homobrassinolide, studied by Esposito et al. (2011) in the FASEB Journal. 28-Homobrassinolide (HB) stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by the PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/day for 24 days) to healthy rats fed a normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Laxogenin was not tested in this study.
There is no high-quality clinical evidence from human studies supporting any benefits of 5α-hydroxy-laxogenin. While in vitro studies suggest potential mechanisms, these findings have not been translated or validated in living organisms. Specifically, cell culture studies indicate that 5α-hydroxy-laxogenin may theoretically inhibit myostatin (MSTN) signaling pathways and reduce reactive oxygen species (ROS) in muscle cells.
These are preliminary findings from isolated cell models and molecular docking simulations, which do not equate to clinical efficacy in humans.
While animal studies and in vitro experiments suggest that brassinosteroids like 5α-hydroxy laxogenin can positively influence protein synthesis and muscle development, robust clinical trials in humans are currently lacking. A few preliminary studies indicate potential benefits for muscle health and performance, but these findings have not yet been widely replicated or confirmed in large, well-controlled human trials.
Currently 5α-hydroxy-laxogenin is not prohibited by the World Anti-Doping Agency because it doesn't meet at least two of the three WADA Code criteria for inclusion. There is unclear evidence showing that it has performance-enhancing effects in humans.
Evidence summary: Conflicting in vitro/in vivo data; no human data.
5α-hydroxy-laxogenin is a synthetic spirostane-type steroid, which is contained in dietary supplements and advertised as an anabolic agent. To date, evidence is missing on anabolic or androgenic activity of 5α-hydroxy-laxogenin. Researchers investigated its androgenic potential in two in vitro bioassays. While no activity was observed in the yeast androgen screen, 5α-hydroxy-laxogenin was able to trans-activate the androgen receptor in human prostate cells in a dose-dependent manner.
To investigate its androgenic potential in vivo, researchers treated orchiectomized rats with three different dosages of 5α-hydroxy-laxogenin for 2 weeks. Effects were neither observed on the wet weights of the androgen target tissues (prostate, seminal vesicle, or penis) nor on the wet weights of the anabolic target tissue musculus levator ani or on skeletal hindlimb muscles.
These results are in apparent conflict: 5α-hydroxy-laxogenin showed androgen receptor activation in human prostate cell lines in vitro, but no androgenic or anabolic effects were observed in the castrated rat model in vivo. The in vivo animal data do not support the androgenic activity observed in vitro at pharmacologically tested dosages.
Evidence summary: In vitro and limited animal data only.
Laxogenin has been demonstrated to have antitumor-promoting activity in a two-stage lung carcinogenesis experiment. This finding, reported in studies on saponins isolated from Allium chinense by Baba et al. (2000), showed that laxogenin from Allium chinense exhibited antitumor-promoting activities. No human clinical trials on laxogenin for oncological indications have been published.
Evidence summary: In vitro cell study only.
Smilax sieboldii has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii, researchers screened various extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. Of the isolated compounds, several significantly reduced fat accumulation in 3T3-L1 adipocytes at a concentration of 100 μM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation. These findings relate to the broader extract of S. sieboldii and have not been replicated in human trials.
Evidence summary: In vitro data only.
S. sieboldii exhibits various pharmacological activities, including antihyperlipidemic effects and cAMP phosphodiesterase inhibition. Laxogenin glycosides displayed cAMP phosphodiesterase inhibitory activities with IC50 values of 83, 34, and 32 μM, respectively. No human studies have examined this activity.
Evidence summary: In vitro data only, based on the broader Smilax genus.
Phytochemical studies revealed that steroids (spirostane and furostane skeleton) and their corresponding glycosides were present in the rhizome of S. sieboldii and had several biological activities, such as antifungal, cytotoxic, anti-inflammatory, and anti-bacterial. These activities have been observed in vitro for preparations from the plant; they have not been confirmed for isolated laxogenin in controlled human studies.
At this time there is not enough scientific information to determine an appropriate range of doses for laxogenin.
In the absence of human clinical trials, no evidence-based dosage recommendation can be made for laxogenin or 5α-hydroxy laxogenin. The following dosage information reflects what has appeared on supplement labels or in preclinical research and is presented descriptively only:
Laxogenin and 5-alpha-hydroxy-laxogenin have not been approved by the FDA for any use, and 5-alpha-hydroxy-laxogenin is on the DoD Prohibited Dietary Supplement Ingredients list. The safety of products containing either ingredient is unknown.
In October 2019, the US Food and Drug Administration (FDA) placed 5-alpha-hydroxy-laxogenin, a synthetic analog of a plant steroid marketed as a natural alternative to anabolic steroids, on the Dietary Supplement Ingredient Advisory List.
The Food and Drug Administration has confirmed through several recent warning letters that the ingredient 5-Alpha-Hydroxy-Laxogenin is not a lawful dietary ingredient.
It has been previously observed that 5α-hydroxy-laxogenin can bind to and activate the androgen receptor in a cell-based bioassay. However, as noted in Section 5.2, this in vitro finding was not reproduced at the tissue level in the in vivo rat model. The clinical relevance of androgen receptor activity at typical supplement doses in humans is therefore unknown.
A particularly significant safety concern is the presence of undeclared ingredients in products marketed as containing laxogenin or 5α-hydroxy laxogenin. Five of 12 supplements analyzed in one study did not contain any 5α-hydroxy laxogenin. In the remaining seven samples, spirostane-type synthetic artifacts were identified along with the labeled 5α-hydroxy laxogenin.
While 5α-hydroxy-laxogenin is related to the plant steroid laxogenin, there are no reports of the derivative being detected in or isolated from any natural source. 5α-hydroxy-laxogenin has been on USADA's radar because it is frequently listed on labels of products that also happen to be contaminated or spiked with performance-enhancing drugs (PEDs).
Products in which the synthetic substance 5-alpha-hydroxy-laxogenin was detected also contained other substances not disclosed on the label, including some drugs or other substances with unknown health effects. Some of those substances are prohibited for use by Service Members. Laxogenin is not prohibited for use by Service Members and should not cause a positive drug test. However, products with this ingredient on the label do not always contain laxogenin and might contain other prohibited ingredients.
Laxogenin was safe in animal studies. However, no studies have confirmed its safety in humans.
The most common side effects of Smilax supplements are stomach upset and kidney disorders. At large doses, they may cause diarrhea, excessive urination, headaches, and shock. Due to the risk of kidney damage, people with kidney disease (or taking drugs eliminated through urine) should be aware of this risk with laxogenin and Smilax supplements. However, most of these effects refer to supplements obtained from other Smilax species, such as sarsaparilla, that may not contain any laxogenin.
Despite marketing claims, there is a significant lack of scientific evidence to support the efficacy or safety of 5α-hydroxy laxogenin in humans. No clinical studies in humans or animals have been published to confirm its purported benefits or assess its safety profile.
The safety of 5-Alpha-Hydroxy-Laxogenin is unclear because the ingredient has not been tested in humans.
Despite being labelled as an unlawful ingredient by the FDA, 5α-hydroxy-laxogenin is not prohibited by WADA. Due to lack of scientific evidence of performance-enhancing properties or potential health risks to athletes, the requirements for a potential prohibition of 5α-hydroxy-laxogenin are not fulfilled. This status could change if new evidence of performance enhancement emerges.
The table below characterizes the state of evidence across each proposed area of use:
Health conditions that Laxogenin may help support.
Body systems that Laxogenin may help support.
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