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Laxosterone

Table of contents

Other Names

(25R)-3beta,5alpha-Dihydroxyspirostan-6-one(3beta,5alpha,25R)-3,5-dihydroxyspirostan-6-one25R,5alpha-Spirostan-3beta,5-diol-6-one5-alpha-hydroxy laxogenin5a hydroxy laxogenin acetate5a-hydroxy laxogenin5a-hydroxy-raschogenin5a-hydroxylaxogenin5alpha-hydrolaxogenine5alpha-hydroxy laxogenin5α-hydroxy laxogeninAlpha hydroxy laxogeninBB-16Biobras-16Brassinosteroid BB-16Brassinosteroid DI-31DI-31LaxogeninSpirostan-6-one, 3,5-dihydroxy-, (3β,5α,25R)-

Synopsis

Laxosterone (Laxogenin / 5α-Hydroxy-Laxogenin): A Comprehensive Reference

1. Identity: Names, Structure, and Natural Source

1.1 The "Laxosterone" Trade Name

Laxosterone® is a registered trademark used by SYNMR Biotechnology (Shanghai) Limited to designate a standardised preparation of laxogenin derived from plant material. Laxosterone® is the trademark for a purified laxogenin preparation; because of the very low content of the compound in natural plant material, the manufacturer uses a bioconversion method to obtain highly purified laxogenin from natural plant precursors. In the broader supplement marketplace the name "Laxosterone" is therefore used interchangeably with laxogenin itself, and the two terms refer to the same core molecule. The compound that most commonly appears in commercial products labelled as "Laxosterone" or "laxogenin" is either laxogenin proper or its synthetic derivative 5α-hydroxy-laxogenin.

1.2 Chemical Identity and Classification

5α-hydroxy-laxogenin is a synthetic spirostane-type steroid contained in dietary supplements and advertised as an anabolic agent. The parent compound, laxogenin, carries the systematic name 3β-hydroxy-(25R)-5α-spirostan-6-one; its CAS registry number is 1177-71-5. Six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii; their structures were determined by spectroscopic analysis and hydrolysis and include laxogenin as the aglycone 3β-hydroxy-(25R)-5α-spirostan-6-one.

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. A study on steroidal saponins from the genus Smilax identified furostane, cholestane, spirostane, isospirostane, and pregnane type constituents; laxogenin falls under the classification of isospirostane-type saponins.

The derivative most widely marketed as an anabolic supplement is 5α-hydroxy-laxogenin, in which a hydroxyl group is added at the 5α position of the spirostane skeleton. Critically, although laxogenin has been isolated from the rhizomes of Smilax sieboldii, 5α-hydroxy-laxogenin has not been isolated or reported from any natural source.

1.3 Botanical Sources

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.

Smilax sieboldii Miq. is a climbing plant with prickly stems that grows in Korea, Japan, China, and Taiwan. 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.

Laxogenin was first identified in the 1960s as a member of a group of plant-based steroids known as brassinosteroids. The original isolation, by Akahori and Yasuda in 1963, was published in the Journal of the Pharmaceutical Society of Japan (Vol. 83, pp. 557–558). A 1992 phytochemical study at PubMed ID 1369386 confirmed that six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii, with laxogenin as one aglycone skeleton.

1.4 Common Commercial Forms and Preparations

Laxogenin is usually sold in capsules; other forms include liquid emulsions and topical creams. Standardised botanical extracts of Smilax sieboldii and proprietary blends (e.g., "Phytofuseâ„¢," which is a combination of laxogenin and soy phosphatidylcholine) are also marketed. The biodistribution of the relevant saponins across the leaf, stem, and root/rhizome of S. sieboldii has been characterised using UHPLC-QToF-MS/MS; deducing such profiles is anticipated to aid the overall product integrity of botanical dietary supplements while avoiding tedious pharmacognostic investigations and helping identify exogenous components within finished products.

2. Traditional and Historical Use

2.1 Ethnobotanical Context: The Smilax Genus

The pharmacological interest in laxogenin is inseparable from the long ethnobotanical record of the broader Smilax genus. It is important to note that historical use was of whole-plant or root preparations of Smilax species — not isolated laxogenin, which was only chemically characterised in the 1960s.

Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago.

Smilax china L. is a small vine that grows in the southern parts of China, known as Jin Gang Ten, which has a long history of indigenous use in China. It consists of fat, saponins, glucosides, gum, starch, flavonoids, tannins, and alkaloids. It has been used in traditional Chinese medicine because it has effective components such as triterpenoids, saponins, flavones, stilbenes, and organic acids. Roots are the most common part used; stems and rhizome can also be used in the form of powder or paste, raw or cooked.

The most important health benefits attributed to S. china in traditional use include energy tonic, impotency and seminal disorders, chronic arthritis, secondary and tertiary syphilis, schizophrenia and epilepsy, pemphigus and skin diseases, osteoarthritis, leucorrhea or white discharge, relieving joint numbness, diabetes, and excretory system conditions.

For Smilax glabra, another species of the genus historically used in Chinese medicine, the Ben Cao Tu Jing, written by Su Song in the Song Dynasty (AD 960–1279), first recorded the plant as sweet, calm in nature, and non-toxic; the Ben Cao Gang Mu by Li Shizhen in the Ming Dynasty (AD 1368–1644) recorded that it could cure "syphilitic skin lesion." By the Qing Dynasty (AD 1636–1912), Ben Cao Bei Yao further described effects including anti-infective properties, removing rheumatism, facilitating urination, stopping diarrhea, and treating muscles and bones.

In TCM, the rhizome preparations are used as a diuretic and for treatment of rheumatic arthritic conditions; also for detoxification and treatment of gout. In Ayurveda, Siddha, and Unani medical systems, the plant is used for syphilis, skin disease, epilepsy, insanity, flatulence, dyspepsia, constipation, fever, neuralgia, rheumatism, gout, and general debility.

There is no documented traditional use for isolated laxogenin or 5α-hydroxy-laxogenin as such; these chemical entities were unknown until the mid-twentieth century. The traditional record pertains to crude botanical preparations from the Smilax genus as a whole.

3. Key Constituents and Active Compounds

3.1 The Spirostane/Brassinosteroid Class

Laxogenin belongs to the spirostane group of steroidal sapogenins. The natural occurrence of laxogenin has been shown in several Smilax species as well as in two Allium species, but there is no proof of a natural existence of 5α-hydroxy-laxogenin.

Tandem mass diagnostic fragmentation patterns of aglycones — diosgenin, sarsasapogenin/tigogenin, or laxogenin — were critical to establishing the unique nodes belonging to six groups of nineteen unknown steroidal saponins identified in S. sieboldii. Mass fragmentation analysis resulted in the identification of 6-hydroxy sapogenins, believed to be key precursors in the biogenesis of characteristic smilaxins and sieboldins, along with other saponins.

3.2 The 5α-Hydroxy-Laxogenin Derivative: Synthetic Origin

It has been shown that 5α-hydroxy-laxogenin is not naturally occurring, but rather of synthetic origin. Research by Avula et al. (2019), published in the Journal of Pharmaceutical and Biomedical Analysis, demonstrated this using hyphenated chromatography-time-of-flight mass spectrometry. One of the unlabelled contaminants found in commercial products was identified as the phytosteroid saponin diosgenin, a common starting precursor of several steroidal drugs; several synthetic derivatives of diosgenin were also identified. These findings indicate that the labelled 5α-hydroxy-laxogenin along with other spirostanes found in supplements are synthetic and signify a lack of quality controls. Additionally, an unlabelled anabolic androgenic steroid, arimistane (an aromatase inhibitor), was identified in one product. Laxogenin itself was not detected in any of the samples analysed during that investigation.

4. Mechanisms of Action

4.1 PI3K/Akt Signalling and Protein Synthesis (Brassinosteroid Class)

The mechanistic rationale most cited in supplement marketing is extrapolated from research on a related plant brassinosteroid, 28-homobrassinolide (HB), not on laxogenin itself. HB, a steroidal lactone with potent plant growth-promoting properties, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC₅₀ 4 μM), mediated in part by the PI3K/Akt signalling pathway.

Oral administration of HB (20 or 60 mg/kg/day for 24 days) to healthy rats fed a normal diet increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass compared with vehicle. Moreover, HB showed no direct binding to the androgen receptor in vitro. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibres and the cross-sectional area of type I and type IIa fibres. These findings suggest that oral application of HB triggers a selective anabolic response with minimal or no androgenic side effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.

This research (Esposito et al., FASEB Journal, 2011;25(10):3708–3719) is the primary scientific basis repeatedly invoked by the supplement industry in relation to laxogenin, despite the fact that it used HB — not laxogenin or 5α-hydroxy-laxogenin — as its test compound.

4.2 Androgen Receptor Interactions

Regarding 5α-hydroxy-laxogenin specifically, investigators using two in vitro bioassays found no activity in the yeast androgen screen, but 5α-hydroxy-laxogenin was able to trans-activate the androgen receptor in human prostate cells in a dose-dependent manner. A biphasic response was observed, with antagonistic properties at lower concentrations and agonistic effects at higher concentrations tested.

In silico molecular docking work in a subsequent 2025 study confirmed plausible androgen receptor binding. However, 5α-hydroxy-laxogenin is unable to act as a hydrogen bond donor to Asn705, as its ether oxygen moieties can only act as hydrogen bond acceptors. Comparable conformations of 5α-hydroxy-laxogenin, EM-5744, and DHT are nonetheless complemented by a coat of lipophilic contacts.

4.3 Rapid Biotransformation

A key mechanistic finding, potentially limiting the biological activity of 5α-hydroxy-laxogenin, relates to its metabolism. An in vitro bioassay showed androgen receptor activation, but this androgenic effect could not be confirmed in the preclinical orchiectomized rat model, which might be due to fast biotransformation into inactive metabolites. Hair analysis points to incorporation of 5α-hydroxy-laxogenin; metabolites of 5α-hydroxy-laxogenin were identified and characterised, though exact modification sites need further investigation.

In silico metabolism predicted five different metabolites resulting from hydroxylation, reduction, or oxidation. Human HepG2 cells generated five metabolites resulting from reduction or hydroxylation and from a combination of both. Three metabolites generated in vitro and an additional mono-hydroxylated metabolite were detected in the serum of rats treated daily subcutaneously for 2 weeks.

5. Scientific Evidence by Area of Use

5.1 Skeletal Muscle Growth and Anabolic Effects

Overall evidence strength: Very weak — animal/in vitro only for laxogenin; no human clinical trials.

Both the muscle-building effects and other potential uses of laxogenin have only been tested in animals and cells. Clinical trials are required to evaluate the effectiveness and side effects of laxogenin products. Additionally, none of the studies used the compound usually found in available supplements: 5α-hydroxy-laxogenin. Instead, they tested laxogenin, natural and synthetic laxogenin derivatives, and similar compounds.

In one old Russian study in rats, brassinosteroid derivatives with a similar structure to laxogenin increased total weight and protein content of the liver, heart, kidneys, and leg muscles without raising levels of sex hormones or mimicking their effects. Similarly, another plant brassinosteroid increased food intake, weight gain, lean body weight, the weight of leg muscles, and physical fitness in rats.

The study most commonly cited by supplement manufacturers is old (1976) and has not been translated from Russian.

The biological and functional claims of being the "premier natural muscle building supplements on the market" are based solely on data showing that steroid saponins derived from laxogenin exhibited plant growth-promoting activity in radishes through elongation of hypocotyls and greater weight of cotyledons (Raphanus sativus). Paradoxically, the plant growth-promoting data were insignificant, independent of tested concentrations, and identical to control experiments, yet two laxogenin analogs were identified as plant growth promoters.

In Vivo Rat Model (2025)

To investigate androgenic potential in vivo, orchiectomized rats were treated with three different dosages of 5α-hydroxy-laxogenin for 2 weeks. Effects were neither observed on the wet weights of 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. Significantly higher atrophy was seen for some target tissues in animals treated with the highest dosage (36 mg/kg bw). Neither androgenic nor anabolic effects of 5α-hydroxy-laxogenin were observed in vivo in castrated male rats.

The rat study used a modified Hershberger assay. The dosages administered to the rats were chosen based on those recommended by supplement manufacturers. The second highest dose administered to the rats (12 mg/kg bw) is equivalent to a daily human dose of 2 mg/kg bw (for a 75 kg individual), which in turn corresponds to the daily intake of 150 mg 5α-hydroxy-laxogenin advertised by dietary supplement suppliers.

Beside the possibility that the administered dosages were too low to activate the androgen receptor, the fast biotransformation of 5α-hydroxy-laxogenin into potentially inactive metabolites may also explain the lack of effects in the androgen-responsive tissues. This might also explain discrepancies between AR binding and activation observed in silico and in vitro and the lack of androgenic effects in the preclinical animal model.

In summary: no human clinical trial has been published demonstrating muscle-building efficacy for laxogenin or 5α-hydroxy-laxogenin. The sole mechanistic animal evidence for the class derives from a different brassinosteroid (HB), and the one preclinical in vivo study specifically on 5α-hydroxy-laxogenin failed to replicate anabolic effects even at supplement-equivalent doses.

5.2 Athletic Performance Enhancement

Overall evidence strength: None in humans.

5α-hydroxy-laxogenin is currently not prohibited by WADA because it does not meet at least two of the three World Anti-Doping Code criteria for inclusion. There is unclear evidence showing that it has performance-enhancing effects in humans.

Despite its labelling as an unlawful ingredient of dietary supplements, which might further contain other non-labelled performance-enhancing drugs according to the FDA and a related warning by the US Anti-Doping Agency (USADA), 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 are not fulfilled.

5.3 Anticancer Activity

Overall evidence strength: Preclinical (animal and cell) only; no human data.

Laxogenin reduced lung tumour formation in mice. Natural and synthetic laxogenin derivatives killed leukaemia and colon cancer cells in two studies. Other natural and synthetic brassinosteroids killed prostate cancer cells and blocked tumour growth in cell studies.

According to animal and cell studies, laxogenin and similar compounds may combat cancer, lower blood sugar, and prevent tissue damage caused by oxidative stress. Human studies, however, are sorely lacking.

5.4 Blood Glucose and Metabolic Effects

Overall evidence strength: Preclinical only.

In obese mice, a plant brassinosteroid (homobrassinolide) reduced blood sugar levels, sugar production in the liver, and insulin resistance. In cells, it prevented the activation of two enzymes that make sugar from protein and fat. These findings involve a related compound, not laxogenin itself, and have not been replicated in human trials.

5.5 Antioxidant/Cytoprotective Activity

Overall evidence strength: Single cell-study; no human data.

In a cell study, a natural laxogenin derivative prevented tissue damage from free radicals and poor oxygen supply. No further translational research in humans has been published.

5.6 Anti-Obesity (Adipogenesis Inhibition)

Overall evidence strength: Single in vitro study in S. sieboldii extracts; no human data.

To evaluate anti-obesity effects of S. sieboldii, researchers screened methylene chloride, ethyl acetate, aqueous-saturated n-butanol, and ethanol extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes using the 3T3-L1 cell line with Oil Red O staining as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the ethanol extract resulted in the isolation of 19 secondary metabolites, including a new α-hydroxy acid derivative and two new lanostane-type triterpenoids. This study examined whole-plant extracts, not isolated laxogenin, and was confined to cell culture.

6. Body Systems and Health Areas Associated with Laxogenin

  • Musculoskeletal system: Proposed as a stimulant of skeletal muscle protein synthesis and inhibitor of protein degradation, based on extrapolation from the brassinosteroid class. No human clinical evidence.
  • Endocrine system: In vitro data show dose-dependent androgen receptor transactivation in human prostate cells, with antagonistic properties at lower concentrations and agonistic effects at higher concentrations. In vivo data in castrated rats showed no androgenic or anabolic endpoints were affected.
  • Oncology (preclinical): Laxogenin and derivatives have shown preliminary antiproliferative effects in leukaemia and colon cancer cell lines, and reduction of lung tumour formation in murine models. Evidence is entirely preclinical.
  • Metabolic system: A structurally related brassinosteroid reduced blood glucose and insulin resistance in obese mice. Not tested in humans, and not tested as laxogenin specifically.
  • Immune/anti-inflammatory: The broader Smilax genus has a traditional anti-inflammatory indication. Smilax species were commonly used as food and traditional medicine to cure inflammatory illnesses. Specific anti-inflammatory mechanisms for isolated laxogenin in humans are not established.

7. Dosage Forms and Reported Dosages

There are no established human clinical trial dosages for laxogenin or 5α-hydroxy-laxogenin. Since there are no dosage data from clinical trials, manufacturers and users have established unofficial dosage guidelines based on trial and error.

The following dosages appear in non-clinical or consumer-facing contexts and are reported here purely as a description of what has been used, not as recommendations:

  • The dose most commonly referenced by users and manufacturers is 100 mg/day for cycles of 4–12 weeks, followed by an off-cycle period of 4 weeks.
  • Laxogenin is usually sold in capsules; other forms include liquid emulsions and topical creams.

In the 2025 preclinical rat study, the dosages administered to rats were chosen based on those recommended by dietary supplement manufacturers; the second highest dose (12 mg/kg bw in rats) is equivalent to a daily human dose of approximately 2 mg/kg bw for a 75 kg individual, which corresponds to the 150 mg/day intake advertised by supplement suppliers.

In the FASEB Journal study on the structurally related brassinosteroid HB, doses of 20 or 60 mg/kg/day were administered orally to healthy rats for 24 days. These doses are far above the human-equivalent amounts marketed in commercial supplements and involved a different compound entirely.

8. Safety Considerations, Regulatory Status, and Adulteration Concerns

8.1 Regulatory Status

Laxogenin and 5α-hydroxy-laxogenin have not been approved by the FDA for any use, and 5α-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 placed 5α-hydroxy-laxogenin, a synthetic analog of a plant steroid that is marketed as a natural alternative to anabolic steroids, on the Dietary Supplement Ingredient Advisory List to alert the public that it does not appear to be a lawful supplement ingredient.

The FDA has since issued multiple warning letters to supplement manufacturers. In one such letter (May 2022), the FDA stated: 5α-hydroxy-laxogenin is not generally recognised as safe under its conditions of use in dietary supplement products. The labels of products declared 5α-hydroxy-laxogenin as a dietary ingredient; however, 5α-hydroxy-laxogenin is not a dietary ingredient. Because 5α-hydroxy-laxogenin does not qualify as a dietary ingredient and is not GRAS or otherwise exempt from the food additive definition, products containing it are adulterated under the FD&C Act because they contain an unsafe food additive.

8.2 Product Adulteration

A major and documented safety concern with commercial products labelled as containing laxogenin or 5α-hydroxy-laxogenin is contamination with undisclosed and potentially harmful substances.

Products in which the synthetic substance 5α-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.

While 5α-hydroxy-laxogenin is related to the plant steroid laxogenin, there are no reports of the 5α-hydroxy-laxogenin derivative being detected in or isolated from any natural source. 5α-hydroxy-laxogenin has been on USADA's radar for some time because it is frequently listed on labels of products that also happen to be contaminated or spiked with performance-enhancing drugs (PEDs).

Five supplements did not contain any 5α-hydroxy-laxogenin, whereas in the remaining seven samples, spirostane-type contaminants were identified along with the labelled 5α-hydroxy-laxogenin. One of the unlabelled contaminants was identified as diosgenin, a common starting precursor of several steroidal drugs. Several synthetic derivatives of diosgenin were identified in the eight products. These findings indicate that the labelled 5α-hydroxy-laxogenin along with other spirostanes found in supplements are synthetic and signify a lack of quality controls.

8.3 Safety Signal: Androgen Receptor Activity

The observed androgenic potential of higher 5α-hydroxy-laxogenin concentrations raises possible safety concerns regarding reproductive organs (e.g., the prostate). Besides the androgenic activity, further investigations should focus on potential anabolic activities of 5α-hydroxy-laxogenin.

The safety of 5α-hydroxy-laxogenin is unclear because the ingredient has not been tested in humans.

8.4 Human Safety Data

Laxogenin was safe in animal studies; however, no studies have confirmed its safety in humans. Anecdotally, users report headaches with high oral doses (~200 mg).

Laxogenin is a plant-based steroid that may offer some anabolic effects with minimal risk of side effects according to some sources; however, there is very limited research that can confirm the long-term safety profile of laxogenin.

8.5 WADA and Anti-Doping Status

Despite its labelling as an unlawful ingredient of dietary supplements and related warnings by the FDA and USADA, 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.

Laxogenin (the natural parent compound) is not prohibited for use by Service Members and should not cause a positive drug test.

8.6 Drug and Supplement Interactions

No formal drug-interaction studies for laxogenin or 5α-hydroxy-laxogenin have been published in the peer-reviewed literature. Given the documented adulteration of commercial products with substances including aromatase inhibitors and other undisclosed performance-enhancing drugs, illegally added, undeclared dietary supplement ingredients represent one way of unintentional exposure to substances that are prohibited by WADA, and adulterated dietary supplements can also be a health risk for elite and recreational athletes.

9. Summary of Evidence Quality

The totality of the published scientific literature as of mid-2026 supports the following characterisation:

  • No human clinical trials on laxogenin or 5α-hydroxy-laxogenin for any indication have been published.
  • The anabolic claims for the supplement rest primarily on extrapolation from preclinical data on a different brassinosteroid (28-homobrassinolide), and from an untranslated 1970s Soviet study on sapogenin derivatives.
  • Both the muscle-building effects and other potential uses of laxogenin have only been tested in animals and cells. Clinical trials are required to evaluate the effectiveness and side effects of laxogenin products. Additionally, none of the studies used the compound usually found in available supplements: 5α-hydroxy-laxogenin. Instead, they tested laxogenin, natural and synthetic laxogenin derivatives, and similar compounds.
  • The one published, peer-reviewed in vivo animal study directly on 5α-hydroxy-laxogenin (Keiler et al., Drug Testing and Analysis, 2025) found neither androgenic nor anabolic effects of 5α-hydroxy-laxogenin in vivo in castrated male rats.
  • 5α-hydroxy-laxogenin is a synthetically produced compound — not a natural plant product — and is considered an unlawful dietary supplement ingredient by the FDA.

References

Health Conditions

Health conditions that Laxosterone may help support.

  • No conditions available.

Body Systems

Body systems that Laxosterone may help support.

  • No body systems available.
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