Many athletes and bodybuilders have turned to laxogenin because they believe it’s a safer means to gain muscles and enhance performance. But is laxogenin really safe, and how does it actually work? Read on to find out.
What Is Laxogenin?
Laxogenin is not approved by the FDA for any purpose. The available data on its efficacy is limited, mixed, and altogether considered insufficient to support medical use of any kind. Because of the lack of studies, it may also have undiscovered side effects. We do not recommend using laxogenin.
Talk to your doctor about natural and safe alternatives to laxogenin to meet your health goals.
Steroid From Plants
Laxogenin (3beta-hydroxy-25D,5alpha-spirostan-6-one) 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. In plants, they work to boost growth [1, 2].
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 [3, 4, 5, 6].
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 [7, 8].
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 5a-hydroxy laxogenin at all and 8 were contaminated with untested diosgenin [9].
Snapshot
Proponents:
- Mostly positive user reviews
- Users report fewer side effects than prohormones and steroids
- Commonly stacked with other supplements
- Being researched for cancer, diabetes, and tissue damage
Skeptics:
- No clinical trials and only a few animal and cell studies
- Incomplete safety profile & potential unknown side effects
- Synthetically produced
- Insufficient evidence for any medical use
- Low-quality and untested supplements
Putative Effects
5a-hydroxy laxogenin is typically advertised to [10, 11, 12]:
- Build muscle
- Burn fat stores
- Enhance physical performance and recovery
- Lower cortisol
As opposed to typical muscle-building steroids, laxogenin is not a steroid or prohormone. Its proponents take this to mean that it will not be converted to the more powerful male sex hormones (testosterone and dihydrotestosterone) nor run the risk of raising estrogen. However, we don’t know this, as it’s never been appropriately tested.
Furthermore, the evidence for laxogenin’s effectiveness is insufficient, according to sports nutrition authorities [12].
This leaves laxogenin hanging somewhere in the grey area: not entirely natural or synthetic, without evidence of being either dangerous or safe.
Genetics
Laxogenin possibly increases muscle building by activating AKT1. People with mutations in this messenger protein may have an altered response to laxogenin [13].
Is Laxogenin legal?
Yes, laxogenin is currently classified as a dietary supplement. However, it is not currently approved for any medical use or health claim of any kind.
How Laxogenin Works
Not a Prohormone
Laxogenin is often falsely labeled as a prohormone. A prohormone is a substance used as the building block for hormone production—hence the term PROhormone. The most popular ones are androgenic prohormones, which the body converts to testosterone.
However, laxogenin is a plant steroid, somewhat similar to cholesterol-derived human sex hormones. But being a unique plant-derived compound, laxogenin affects different pathways in the body.
Human steroid hormones like testosterone act by affecting the nuclear receptors. Plant steroids like laxogenin (brassinosteroids) clearly increase growth in plants, but their effects on humans and animals are much more obscure [14, 13].
Mechanism
Plant steroids act through a completely different pathway than human steroid hormones. They attach only to the cell surface, which sets off a signal to increase muscle building to the inside of the cell [14, 13].
More specifically, they activate a protein, known as AKT1 or protein kinase B, that enhances muscle building and prevents the breakdown of muscle proteins [14, 15, 16].
Additionally, natural laxogenin derivatives block the enzyme that breaks down cAMP (phosphodiesterase). This increases cAMP levels, enhancing fat breakdown and activating the fight-or-flight (sympathetic) response [4, 17].
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 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 the levels of sex hormones or mimicking their effects [18].
Similarly, another plant brassinosteroid increased food intake, weight gain, lean body weight, the weight of leg muscles, and physical fitness in rats. In muscle cells, both this molecule and its synthetic derivatives promoted protein production and reduced protein breakdown [13, 14].
A class of plant chemicals with a similar structure to brassinosteroids (phytoecdysteroids) increased muscle growth in animals and protein production in muscle cells [19, 20, 21, 22].
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 the muscle-building potential of laxogenin.
Overall, the evidence for laxogenin’s purported muscle-building properties is considered insufficient.
Other Potential Applications of Laxogenin
No clinical evidence supports the use of laxogenin for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
1) Cancer
Laxogenin reduced lung tumor formation in mice. Natural and synthetic laxogenin derivatives killed leukemia and colon cancer cells in 2 studies [6, 23, 24].
Other natural and synthetic brassinosteroids killed prostate cancer cells and blocked tumor growth in cell studies [25, 26].
2) Blood Sugar
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 [27].
3) Tissue Damage
In a cell study, a natural laxogenin derivative prevented 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 [28, 29].
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 available supplements: 5a-hydroxy laxogenin. Instead, they tested laxogenin, natural and synthetic laxogenin derivatives, and similar compounds.
The study most commonly cited by supplement manufacturers is old (1976) and hasn’t been translated from Russian.
Laxogenin Side Effects
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 [30, 11].
Due to the risk of kidney damage, people with kidney disease (or taking drugs eliminated through urine) should avoid laxogenin and Smilax supplements [11].
However, it’s important to note that most of these effects refer to supplements obtained from other Smilax species, such as sarsaparilla, that may not contain any laxogenin.
Laxogenin was safe in animal studies. However, no studies have confirmed its safety in humans. Anecdotally, users reported headaches with high oral doses (~200mg).
Laxogenin Dosage and Supplements
Dosage
Since there are no dosage data from clinical trials, the manufacturers and users established unofficial dosage 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 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.
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 of 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.
Takeaway
Laxogenin is a natural steroid found in different plants. Most supplements contain its synthetic derivative, 5a-hydroxy laxogenin, and untested contaminants.
Supposedly, laxogenin boosts muscle growth and fat burning without steroid-like side effects. It was safe in animal studies, but no clinical trials have tested it yet.
Based on limited research, laxogenin may stimulate muscle growth, physical fitness, and muscle recovery. It might also fight cancer and reduce blood sugar.
Users praise laxogenin for decent muscle gains and good safety. Some complain about headaches at higher doses.
