Potential and Mechanisms of Laxogenin
Laxogenin is a muscle-building plant-derived supplement. Many athletes and bodybuilders turn to it as a safer means to gain muscle mass and enhance physical performance, seeking to avoid the typical adverse effects of prohormones and steroids. But is laxogenin even natural, is it a prohormone, or how does it work? Read on to find out.
What Is Laxogenin?
Laxogenin is a compound sold in various forms as a muscle-toning supplement. It belongs to a class of plant hormones called brassinosteroids, which have a similar structure to animal steroid hormones (including sex and stress hormones). In plants, they work to boost growth [R, R+, R].
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 [R+, R, R+, R].
However, laxogenin in supplements is produced from the more common plant steroid diosgenin. Diosgenin is usually extracted from wild yams. In fact, diosgenin is used as a raw material for over 50% of synthetic steroids including progesterone, cortisone, and testosterone [R, R+].
Although often advertised as “natural”, most supplements don’t contain laxogenin but its synthetic derivative 5a-hydroxy laxogenin (laxosterone). An analysis of 12 different supplements found that 5a-hydroxy laxogenin is always derived from synthetic laxogenin. Importantly, 5 supplements didn’t have any 5a-hydroxy laxogenin at all and 8 contained diosgenin derivatives of untested safety as contaminants [R].
- Build muscle
- Burn fat stores
- Enhance physical performance and recovery
- Lower cortisol, the stress hormone that promotes fat storage and muscle breakdown
As opposed to typical muscle-building steroids, laxogenin is not a steroid or prohormone. This means that it will not be converted to the more powerful male sex hormones testosterone and dihydrotestosterone in the body, nor does it run the risk of raising estrogen. As a result, laxogenin probably won’t cause unwanted effects such as [R+]:
- Sex hormone imbalances or testosterone suppression
- Need for post-cycle therapy (PCT) to restore testosterone production
- Testing positive for steroids in anti-doping tests
- Liver and kidney damage
However, the scientific evidence backing up the effectiveness of 5a-hydroxy laxogenin is insufficient according to sports nutrition authorities [R+].
This leaves laxogenin hanging somewhere in the grey area — not entirely natural or synthetic, not dangerous but not effective either.
Snapshot of Laxogenin
- Mostly positive reviews
- Fewer side effects than prohormones and steroids
- Commonly stacked with other supplements (epicatechin, creatine, fat burners, PCT)
- Being researched for preventing cancer, diabetes, and tissue damage
- No clinical trials and only a few animal and cell studies
- Synthetically produced
- Studies investigated similar, but different compounds
- Low-quality supplements: some don’t contain the active compound (5a-hydroxy laxogenin) and others contain other potentially unsafe ingredients
What Does Laxogenin Do?
Laxogenin is often falsely labeled as a prohormone. A prohormone is a substance that is used by to body as the building block for hormone production — hence the term PROhormone. The most popular ones are androgenic prohormones, which the body converts to testosterone or a synthetic anabolic steroid.
Since laxogenin has a steroid structure, people initially assumed that it must be a typical prohormone. However, laxogenin is a plant steroid, somewhat similar to cholesterol-derived human sex hormones. But being a unique plant-derived compound, it turned out that laxogenin affects different pathways in the body.
Human steroid hormones like testosterone act by affecting structures deep within the cell (the so-called nuclear receptor family of transcription factors). Plant steroids like laxogenin (brassinosteroids) clearly increase growth in plants, but their effects in humans and animals are much more obscure [R, R].
Since recently, though, we do know that plant steroids like laxogenin act through a completely different pathway than human steroid hormones. These plant hormones attach only to the cell surface (via receptor kinases), which sets off a signal to increase muscle building to the inside of the cell [R, R].
More specifically, several natural and synthetic brassinosteroids similar to laxogenin activate a protein (known as Akt1 or protein kinase B) that enhances muscle building and prevents the breakdown of muscle proteins (Ivia GF-1) [R, R, R].
Additionally, two natural laxogenin derivatives blocked the enzyme that breaks down cAMP (phosphodiesterase) in one study. This increases cAMP levels, which enhances fat breakdown and activates the fight-or-flight (sympathetic) response [R+, R+].
Taking everything into account, laxogenin could at best be considered a prohormone alternative. Laxogenin supplements are not really a “natural” alternative, though, but they do contain synthetically modified plant-based substances.
The complete chemical name of laxogenin is 3beta-hydroxy-25D,5alpha-spirostan-6-one. Supplements for physical enhancement contain a synthetic laxogenin derivative called 5a-hydroxy laxogenin or laxosterone [R+, R+].
Is Laxogenin legal?
Yes, laxogenin is currently classified as a dietary supplement.
Laxogenin Anabolic Effects
Laxogenin is sold as a muscle toning supplement for athletes and bodybuilders. It’s claimed to increase protein production in muscles by 200%.
In an old study in rats that hasn’t been translated from Russian, brassinosteroid derivatives with a similar structure to laxogenin increased total weight and protein content of the liver, heart, kidneys, and leg muscles (tibialis anterior) without raising the levels of sex male hormones or mimicking their effects [R].
Similarly, another natural plant brassinosteroid (homobrassinolide) increased food intake, weight gain, lean body weight, the weight of leg muscles (gastrocnemius), and physical fitness in rats. In muscle cells, both this molecule and its synthetic derivatives promoted protein production and reduced protein breakdown [R, R].
While all these substances are similar, they are not identical. It is possible that laxogenin (and its derivatives in supplements) have similar anabolic effects. But since these have not been studied yet, we are still in the dark when it comes to laxogenin’s realistic muscle-building gains.
Other Potential Laxogenin Uses
1) Fighting Cancer
Laxogenin reduced lung tumor formation in mice given a cancerogenic compound (4-NQO), [R+].
2) Lowering Blood Sugar Levels
In obese mice, a plant brassinosteroid (homobrassinolide) taken with the diet reduced blood sugar levels, sugar production in the liver, and insulin resistance. In cells, it prevented the activation of two enzymes that make sugars from proteins and fats [R].
3) Reducing Tissue Damage
In a cell study, a natural laxogenin derivative blocked the activation of an enzyme (protein tyrosine kinase) linked to tissue damage from free radicals and poor oxygen supply. This suggests laxogenin may be able to neutralize oxidative stress, which would explain its beneficial effects on muscle recovery. However, animal and human studies are needed [R, R].
Due to the risk of kidney damage, people with kidney disease (or taking drugs eliminated through urine) should avoid laxogenin and Smilax supplements [R+].
However, it’s important to note that most of these effects refer to supplements obtained from other Smilax species (e.g., sarsaparilla) that may not contain any laxogenin.
Laxogenin was safe in animal studies. However, no studies have confirmed its safety or described its side effects in humans.
Anecdotally, users reported headaches with high oral doses (~200mg).
Limitations and Caveats
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 supplements for athletes and bodybuilders (5a-hydroxy laxogenin). Instead, they tested laxogenin, natural and synthetic laxogenin derivatives, and similar compounds (other brassinosteroids, phytoecdysteroids).
The study most commonly cited by supplement manufacturers is old (1976) and hasn’t been translated from Russian.
The German Commission E for herbal medicine warns about the following potential drug interactions of supplements containing Smilax steroids [R+]:
- Increased elimination of hypnotic drugs
- Increased absorption of digoxin (used for congestive heart failure and irregular heart rate)
- Increased absorption of bismuth (used for upset stomach, heartburn, nausea, diarrhea, and ulcers)
These interactions have only been reported for supplements obtained from Smilax species other than S. sieboldii. Whether 5a-hydroxy laxogenin found in most supplements also interacts with these drugs hasn’t been confirmed.
Supplements & Formulations
Laxogenin is usually sold in capsules. Other forms include liquid emulsions and topical creams. Each serving (1 capsule, 0.5 mL liquid emulsion, or 2 mL cream) contains 25-100 mg 5a-hydroxy laxogenin. Some of the most popular laxogenin products include:
- Primavar (Primeval Labs)
- Nano Genin (Assault Nano Series)
- Anafuse (Vital Labs)
- Secreta Bridge (LGI)
- Ano-Genin (Blackstone Labs)
- STR3NGTH (Olympus Labs)
- Halo (Redcon1)
Recently, Olympus Labs launched a transdermal laxogenin called DermaSTRENGTH. The rationale was to boost laxogenin’s poor oral bioavailability.
Since the dosing data in clinical trials is nonexistent, the manufacturers and users established unofficial dosing guidelines based on trial and error.
The recommended dose is usually 100 mg/day for 4-12 week cycles, followed by an off-cycle period of 4 weeks. Some users claim that, given that laxogenin is not a prohormone or steroid, it’s not necessary to cycle it off.
Most users claim that laxogenin can be safely stacked with other substances. Some use it alongside PCT, while others take it to maintain muscle gains during their off-cycle periods.
The official published scientific research about Laxogenin tells us very little about its real-world use. To bridge the gap, here we summarized the available reviews and feedback from online communities with the attempt of teasing apart the most useful information.
Overall, laxogenin seems to have milder side effects but offers weaker gains than most bodybuilding substances, especially when compared to investigational SARMs like Ostarine. A handful of users claimed that it is as potent as Anavar (Oxandrolone), although most agreed that the effects of laxogenin are much milder.
Most laxogenin users were satisfied with its effects on muscle weight gain, physical strength and endurance, and recovery from fatigue and injuries. Although less effective than prohormone steroids, it was preferable due to its lack of adverse effects. While it worked at doses as low as 50 mg for some users, others reported no effects even at 200 mg. This could be due to the different supplement brands and their quality.
Indeed, a supplement sold as a liquid emulsion with laxogenin nanoparticles that should maximize its absorption mainly received positive reviews. Its downside is bitter taste, which users tried to mask by mixing it with juice or peanut butter.
A lot of users stacked laxogenin with other compounds, epicatechin (a natural myostatin inhibitor) being the most common choice. Users who combined both were generally satisfied and reported good lean muscle gains, fat loss, and enhanced physical performance. The high price of the supplement was the most common complaint and only one user noticed adverse effects (increased aggressiveness and sleepiness).
Some users took laxogenin during their off periods, after cycling other muscle-building compounds. They claimed that laxogenin prevented muscle loss and sustained muscle gains.
A handful of women also used laxogenin supplements. They were usually satisfied and reported good muscle toning and fat loss without the masculinizing effects of prohormones or steroids.