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Laxogenin

Can a plant steroid increase strength in a safe and harmless way?

5-Alpha-Hydroxy-Laxogenin (which is usually referred to simply as Laxogenin) is a natural anabolic supplement derived from plants and has been sold by some supplement companies for a number of years. Despite its enormous potential, laxogenin has not achieved the level of popularity one might have expected for reasons we will discuss later. Based on the results of laboratory tests and as new supplier technologies emerge, it's time to take a second look at this ingredient.

What is laxogenin?

In more detail, laxogenin is a sapogenin - a steroidal component of the non-sugar part of a saponin - that is isolated from the plant Smilax Sieboldii, which resembles asparagus. This compound is a spirostanic analog of the brassinosteroid (9), which means that it belongs to a group of plant-based steroids found in small amounts in plants and foods such as pollen, seeds and leaves. Laxogenin has been shown to have a ratio of anabolic to androgenic effects similar to that of Anavar, one of the most efficient anabolic substances, without its side effects such as liver toxicity or the risk of testing positive for steroids. Laxogenin has attracted interest due to its growth-promoting activity in plants. However, poor absorbability and bioavailability have prevented users from achieving results that even come close to Anavar with the help of Laxogenin. Our goal is to give you an overview of Laxogenin so that you can decide for yourself if this compound is worth a try. We would like to point out that this article is aimed at steroid-free athletes or use during the weaning phase after using anabolic steroids. But let's be honest: you won't get prohormone-like gains with Laxogenin - the most common positive feedback is about strength gains and recovery (both after hard training sessions and after injuries). The real question is this: will this compound work for those of us not using steroids (at the moment) and are the results worth the money?

How does Laxogenin work?

Laxogenin is often compared to Oxandrolone as it is believed to have a similar ratio of anabolic to androgenic effects (2). As you may know, oxandrolone is the brand name of Anavar. Oxandrolone reduces levels of sex hormone binding globulin (SHBG), promoting higher levels of free testosterone and increased nitrogen retention, which will ultimately lead to anabolism. Oxandrolone has been shown to directly stimulate lipolysis by binding to the androgen receptor (3), reducing levels of thyroid-binding protein and promoting increased utilization of triiodothyronine (T3). It also increases the amount of red blood cells (4), resulting in increased muscle endurance. We should clarify at this point that laxogenin is not the same as oxandrolone. Laxogenin is a plant-based steroid, whereas oxandrolone is a chemically synthesized steroid. Further studies with laxogenin are needed to fully understand its effects in the human body.

When did interest in laxogenin begin?

Laxogenin came to public attention after Yahoo Sports published an article in 2007 about NFL quarterback Tim Couch, who made an impressive comeback and attributed his physical recovery to the use of laxogenin (8).Couch was the former Cleveland Browns quarterback who underwent multiple shoulder surgeries after several painful years. Unfortunately, it was almost a decade before a trustworthy source of laxogenin came onto the market, as the raw materials were often contaminated in the early years.

What are the benefits of Laxogenin? Are there any scientific studies?

To date there have been very few studies conducted and published on laxogenin, but this situation is changing. Typically, data from studies with oxandrolone or brassinosteroids are used as a proxy for laxogenin. Human studies conducted with oxandrolone have shown that this steroid can increase muscle mass and strength even without training (5). Other benefits include increased fat loss, improved insulin sensitivity and accelerated wound healing (6, 7). One theory is that the improvement in wound healing also results in faster recovery after hard and intense training sessions (7). There is also a study conducted in rats with the brassinosteroid 28-homobrassinolide (HB), which can be used as a proxy for laxogenin. In this study, HB stimulated protein synthesis while inhibiting protein degradation, which was attributed in part to an induction of AKT phosphorylation (9). AKT is a serine/threonine kinase that stimulates an increase in the levels of growth factors and the phosphoinositide-3 kinase PI3K. AKT also stimulates glucose uptake, glycogen synthesis via AKT/mTOR and the AKT/GSK-3β signaling network (10). In addition, HB stimulates a selective anabolic response with minimal androgenic side effects (9).

An interesting patent application provides further insights ...

From a relatively recent patent application titled "The phytosterols spirostane and spirostene derivatives have a wide range of uses in humans and animals (16, 17)" from 2014, we can learn about a few more claims made by the authors of this patent application.

Warning: At the time of publication of this article, this patent had not yet been granted, so these claims should be taken with a grain of salt

Claims of adaptogenic effects

The applicant of this patent claims that laxogenin acts as an adaptogen:

"As an anabolic, performance enhancing, immunoprotective and rejuvenating adaptogenic composition for animals, this composition contains an effective amount of spirostane derivatives composed of laxogenin derivatives, 5-hydroxy laxogenin derivatives and combinations thereof (16, 17)" Adaptogens are natural substances that help the body adapt to stress by exerting a "normalizing effect". This is beneficial for bodybuilders and people who train with heavy weights.

Synergistic interaction with anabolic substances?

"5-hydroxy-laxogenin and laxogenin interact synergistically with anabolic substances including anabolic steroids (16, 17)"

Claims regarding pain reduction/recovery after injury

The most interesting part of the patent is the following "case study":

"The compounds contained in this invention have the ability to reduce pain in humans and animals.

A man in his sixties had two artificial knee joints implanted due to long-standing injuries. He began taking 150 mg of laxogenin three times a day a week before the knee surgery. He reported that his pain subsided after the third day of taking it - two days before his operation. The day after his operation, he was able to completely avoid treatment with morphine. He was able to walk a little three days after the operation and was able to stand on his own and walk long distances without pain or stiffness on the seventh day after the operation. He used a liquid version of Laxogenin applied to the skin, which greatly reduced inflammation and scarring (16, 17)"

We do not know the person who applied for this patent and so far this patent has not been granted, but this information could definitely be of interest to users interested in joint supplements.

Is it possible to reduce LDL cholesterol levels?

The last claim regarding an effect in humans is worth mentioning

A 44-year-old man with a high total cholesterol level of 270 (LDL 175) reported a significant reduction in total cholesterol to a level of 230 (LDL 135) after using a combination of 7-Keto and Laxogenin (5 mg twice daily) for three months. (16, 17) What makes this interesting is the fact that such effects are often seen in users of other anabolic substances including testosterone (18), but as mentioned we are not sure where this data comes from and whether it is valid.

The patent also includes an interesting case study of two Rhodesian Ridgeback dogs that exceeded their actual life expectancy due to a rejuvenating effect possibly attributable to laxogenin, but this is outside the focus of this article.

What effects are reported?

The first thing to note is that the supplement industry has been using contaminated or adulterated laxogenin for nearly a decade, making it difficult to find trustworthy testimonials. When we look at the brands and ingredient suppliers we trust, here's what the testimonials say:

  • A useful, noticeable increase in strength can be observed (i.e. you'll be able to do two reps on the bench press with your previous 1RM weight)
  • Healing and recovery from injury is reported to be faster and joints feel "smoother".
  • 100 mg per day seems to be the ideal amount
  • Transdermal products, which are applied to the skin, appear to work better than orally ingested products. However, new capsule technologies for oral products may change this in the future. As you can see, mass gain is not one of the most common experiences. The strength-enhancing effects of laxogenin could be used to increase training volume and calorie intake and then build some strength, but this is a slightly more indirect route. This brings us to the next topic.

Who should consider using Laxogenin and who should not use it? Healthy men who train with weights are the main target group for Laxogenin use. Taking this further and considering that laxogenin primarily provides strength gains, this ingredient is best suited for three types of athletes:

  • Steroid-free athletes who compete (see the section on drug testing below)
  • Steroid users who are not currently using steroids (to maintain strength and not lose their gains)
  • Athletes who are suffering from an injury

Apart from this, of course, virtually anyone can supplement with laxogenin. img

"Laxogenin and 23-oxygenated derivatives with growth-promoting activity (11)"

A risk assessment

As for the "aggressiveness" of the effect, based on the laxogenin products currently available, we would rate this at 6 out of 10 - it is closer to the "aggressive" range and is not for absolute beginners. However, if you're not a complete natural athlete, then the risk/aggressiveness rating is closer to 2 out of 10. There's a lot crazier stuff out there in the world of hormonal anabolic agents. These risk estimates are of course no more than very rough estimates, as there are no placebo controlled, with trained athletes who have used laxogenin, nor long-term studies. However, many excellent supplements have started at this point.

How old do you have to be to use Laxogenin?

An age of at least 18 is recommended for many products. Interestingly, scientific research conducted with the steroidal counterpart oxandrolone concludes that this steroid is safe and harmless for the treatment of delayed growth and delayed onset of puberty in boys (11, 12). In addition, there are studies conducted with older men that have shown benefits in both those who exercised and those who did not (5).

If you're just your average amateur bodybuilder who's all about muscle mass and nothing more, then it probably makes sense to spend your money on something else. Laxogenin seems to have the most benefits for athletes - and not for guys who just want to get muscular and bulky.

What about women?

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Oxandrolone has been shown to reduce fat mass in men. Can its natural counterpart produce similar results? (6) Since laxogenin has minimal or no androgen-related side effects, it should be safe for women to use. In addition, many women have used oxandrolone without any problems, which has also been confirmed by scientific studies of women training with weights (13). However, the effects of brassinosteroids may be reduced by the absence of testosterone, so women may not experience the same effects due to their much lower endogenous testosterone production.

Is Laxogenin on the banned list of any organizations? Are there any tests for the use of Laxogenin?

Laxogenin is not on the WADA list of banned substances (14). In addition, laxogenin does not increase testosterone levels, so its use is unlikely to result in a false positive doping test. However, oxandrolone is on the WADA list of banned substances and as mentioned above, although these two compounds are not identical, they do have similarities. As with all substances, if you are tested for banned performance enhancing substances, you should consult your coach or sports organization before using them.

What is the reason for the limited success of Laxogenin as a supplement?

A plant-based steroid with minimal side effects sounds too good to be real, right? Well, that all depends. Over the past decade, there have been two major issues that have damaged Laxogenin's reputation:

1. counterfeit products in the past

The first problem has to do with counterfeit raw material - in 2010 there was a lot of alleged laxogenin that wasn't really laxogenin. The solution to such problems is to only use products from reliable manufacturers who have their products independently tested. You won't believe how many supplement manufacturers don't test their raw materials.

2. poor bioavailability

The real problem with laxogenin is its poor bioavailability. Laxogenin does show an impressive effect in studies conducted with rats, but anecdotal feedback from users shows that some users respond better to Laxogenin, while others experience no or minimal effect. But why is this?

It is believed that laxogenin on its own is poorly absorbed by the human body. There are two possible solutions to this problem:

  1. A transdermal delivery, where the active ingredient is applied to the skin.
  2. Encapsulation of the laxogenin molecule in a lipid that prevents destruction during passage through the digestive tract

The first solution is the method that is currently most trusted, but the first encapsulated forms of laxogenin are already available.

How should Laxogenin be dosed?

Most supplement manufacturers offering laxogenin supplements use 25 mg of laxogenin per capsule. The typical dosage recommendation is to take one capsule three to four times a day, preferably with meals. This corresponds to a daily dose of 75 to 100 mg laxogenin. Many laxogenin supplements are recommended to be taken for 6 to 8 weeks, although it should be safe to take laxogenin over a longer period of time. However, you should monitor your progress, as it is theoretically possible that your body will become accustomed to Laxogenin over time and the effect will diminish. At this stage, it is not yet known how likely such a scenario is.

What are the potential side effects of Laxogenin?

Studies conducted with brassinosteroids report no serious side effects and there is no anecdotal feedback from users. The worst that has been reported is headache when using high doses (200 mg or more per day). This side effect has not been observed with transdermally administered laxogenin. Laxogenin appears to be a safe (albeit weaker) alternative to more aggressive prohormones once the bioavailability issues have been resolved.

Is a weaning phase (post cycle therapy) necessary?

Since the 28-homobrassinolide (HB) study conducted in rats suggests that this agent has minimal or no androgen-related side effects (9), it is unlikely that a discontinuation phase is necessary. Many users of steroids and prohormones are likely to use laxogenin even during the withdrawal phase following use of these agents.

Conclusion

Let's get back to the question of whether laxogenin can be worth using. On paper, the properties of Laxogenin seem too good to be true - a plant steroid that increases strength and lean muscle mass without androgen-related side effects and is therefore safe and harmless for both men and women. Unfortunately, laxogenin has poor oral bioavailability, but the supplement industry has now found different solutions to this problem. There is definitely a target group for this active ingredient: steroid-free athletes who need more strength, users of steroids and prohormones during the weaning phase (post cycle therapy) and injured athletes. If you belong to this group of people, then Laxogenin could be worth a try. On the other hand, if you want to get as bulky as possible to make an impression, there are probably better ways to invest your money.

References

  1. Iglesias-Arteaga, Martín A; "A convenient procedure for the synthesis of 3b-hydroxy-6-oxo-5a-steroids. Application to the synthesis of laxogenin"; J. Braz. Chem. Soc. vol.16 no.3a São Paulo; May/June 2005; Retrieved from http://www.scielo.br/scielo.php?pid=S0103-50532005000300011&script=sci_arttext
  2. Syrov, V; "Experimental study of the anabolic activity of 6-ketoderivatives of certain natural sapogenins"; Farmakologiia i Toksikologiia; 39(5):631-5; Sep-Oct 1976; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1028596
  3. Demling, R; "Oxandrolone, an anabolic steroid, significantly increases the rate of weight gain in the recovery phase after major burns"; The Journal of Trauma; 43(1):47-51; July 1997; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9253907
  4. Kahn, N, et al; "Effects of oxandrolone, an anabolic steroid, on hemostasis"; American Journal of Hematology; 81(2):95-100; February 2006; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16432848
  5. Schroeder, E; "Treatment with oxandrolone and the durability of effects in older men"; Journal of Applied Physiology;96(3):1055-62; March 2004; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14578370
  6. Schroeder, E, et al; "Effects of Androgen Therapy on Adipose Tissue and Metabolism in Older Men"; The Journal of Clinical Endocrinology & Metabolism; Volume 89, Issue 10; July 8, 2004; Retrieved from http://press.endocrine.org/doi/10.1210/jc.2004-0784
  7. Demling, R; "Oxandrolone, an anabolic steroid, enhances the healing of a cutaneous wound in the rat"; Wound Repair and Regeneration: Official Publication of the Wound Healing Society and the European Tissue Repair Society; 8(2):97-102; March-April 2000; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10810035
  8. Peter, Josh; "Weird Science: Tim Couch Investigation. Part 4: The Comeback"; Yahoo Sports, August 28, 2007; Retrieved from https://sports.yahoo.com/nfl/news?slug=jo-part4couch082807
  9. Debora E et al; "Anabolic effect of plant brassinosteroid"; The Journal of the Federation of American Societies for Experimental Biology; 25(10): 3708-3719; October 2011; Retrieved from http://www.fasebj.org/content/25/10/3708
  10. Robey, R. Brooks, and Nissim Hay; "Is Akt the 'Warburg kinase'?-Akt-Energy Metabolism Interactions and Oncogenesis"; Seminars in cancer biology 19.1; 2009; Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814453/
  11. Stanhope, R et al; "Double Blind Placebo Controlled Trial of Low Dose Oxandrolone in the Treatment of Boys with Constitutional Delay of Growth and Puberty"; Archives of Disease in Childhood; 63.5: 501-505; 1988; Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1778902/
  12. Wilson, D, et al; "Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group"; Pediatrics; 96(6):1095-100; December 1995; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7491227
  13. Mavros, Y, et al; "Oxandrolone Augmentation of Resistance Training in Older Women: A Randomized Trial"; Medicine and Science in Sports and Exercise; 47(11):2257-67; November 2015; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25899102
  14. World Anti-Doping Agency; "January 2016 Prohibited List"; January 1, 2016; Retrieved from https://wada-main-prod.s3.amazonaws.com/resources/files/wada-2016-prohibited-list-en.pdf
  15. Olympus Labs; Laxogenin HPLC Lab Test; December 16, 2015; Retrieved from https://blog.priceplow.com/wp-content/uploads/olympus-labs-laxogenin-hplc-test-20151216.pdf
  16. Fasciola, Andre Armel; "Phytosterol spirostane and spirostene derivatives having a wide variety of utilities in humans and other animals"; US Patent & Trademark Office; September 18, 2014; Retrieved from http://appft1.uspto.gov/netacgi/nph-Parser?
  17. Fasciola, Andre Armel; "Phytosterol spirostane and spirostene derivatives having a wide variety of utilities in humans and other animals"; Google Patents; September 18, 2014; Retrieved from https://www.google.com/patents/US20140274978
  18. Zgliczynski, S, et al; "Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men"; Atherosclerosis; 121(1):35-43; March 1996; Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8678922