WNBF Pro Dr. Andrew Chappell
Straight out of the gate the following supplements are effective at increasing your exercise performance / muscle mass either directly or indirectly.
- Creatine Monohydrate
- Isotonic Sports Drinks
- Sports Gels
- Protein Powders
- Beatroot and Cherry Extract
The International Olympic Committee (IOC), International Society Of Sports Nutrition (ISSN), American College of Sports Medicine (ACSM), Australian Institute of Sport (AIS), and English Institute of Sport (EIS) consider the aforementioned effective. There’s enough evidence around dosages and improvements in performance that these supplements could be recommended by an accredited sports nutritionists and sports scientist. Now let me tell you why everything else you’re being marketed is most likely garbage.
If you’re reading this article, then you’re in the process of doing research into fitness supplements. You’re probably thinking about buying one to try out, maybe you want to gain an understanding of how it might improve your performance, or perhaps your sceptic and you’re looking for an informed source. Either way, I promise you that if you make it to the end of this article you will have a much firmer grasp of why 99% of supplements are garbage (this includes supplements out with the fitness world). This article is written for the “evidence based” trainer, the individual who wants to understand the science and apply it. If that sounds like you, then let’s get into it. If you don’t want to get into the weeds then just stick with the list of supplements above.
The problem with sports supplements
Before we talk about turkesterone we need to talk about the problem with supplements in general. The main issue people have in trying to identify if a supplement is any good or not, is the fact that they don’t understand how research works, and what constitutes good research, how to interpret research. Nor do they have the time to spend looking into it. If more people however took the time and understood how to do research, then people wouldn’t get hoodwinked by junk supplements. In this article I’m going to explain a few of research concepts to help you navigate the health and fitness research space, then I’m also going to talk about turkesterone. Probably the main reason why you came here, but first let’s talk about science.
Now, I’ve been involved in the fitness industry for over 20 years. I worked for a supplement company during my gap year. I’ve been sponsored by supplement companies as a bodybuilder. As a consumer I’ve probably tried no less than 100 different sports supplements. Personal and industry experience aside, I’m an academic. I have a bachelors in sports science, a master’s in human nutrition and a PhD in nutrition. I taught sports nutrition for 5 years before becoming an entrepreneur. Personally, I’ve published 5 different studies on sports supplements and been involved in another half dozen. It’s a topic I’ve always been into and one I know my way around.
The problem supplements have is they often lack any scientific rigour associated with them. A lack of scientific rigour however never stopped anyone selling anything though. Let’s be clear most supplements have absolutely zero scientific studies to back up their claims or justify their use. When there are studies, a lot of the time the research is underwhelming, not applicable or limited, e.g. too few studies to substantiate a claim. Turkesterone and other test boosters can easily be included on this list. Moreover, the supplement industry is not well regulated, which leaves companies or individuals free to make outrageous claims and under-dosed their products. I still can’t believe so many people got duped by the “Liver King”. Moreover, consumers caught up in marketing hype are often far too trusting of supplement companies and the influencers who market their products. Some of the time they’re literally praying on the lowest common denominator and their insecurities to sell these products.
How we work out if something works
It wasn’t until I went to university at 20 that I found out what a scientific study actually was. Before that when I did research, I thought that meant literally reading blogs. Now you can find research studies by visiting websites like PubMed and Google Scholar. These are databases that allow you to search for scientific studies. If you want to know about Turkesterone and muscle mass for example, just type it in the search bar and see how many hits you get. Now broadly speaking you can categorise research into one of two categories: observational or experimental.
Observation research: this involves large cohorts and is the domain of epidemiologists. It can be retrospective (looking backwards), or perspective (following trends over time). Public health or demographic studies like a census are observational. They provide a snapshot of information at a point of time. A health study might look at links between supplement use and mortality rates and then try to assess if there’s a link for example. These studies can identify associations and can be useful. As you can imagine there are a lot of reasons why people might live longer in a group taking supplements vs not taking them. We often say these types of studies are great for hypothesis generating, but to prove causation you need to do experiments.
Experimental research: you come up with a hypothesis (maybe generated from your observational study), which is a theory of how the world works and then you do an experiment to test your idea. If after multiple experiments the hypothesis still rings true, you can be confident you’re onto something. Experimental research is where you really want to look to see if something works or not, this is where you get the good data.
Now experiments can be done on cells in the lab, (in vitro), or on living systems (in vivo) like animals or humans. Cell work is great for testing how things work like molecule at a cellular level. While animal models can provide a proof of principle and are usually the next step. Although there’s a lot of shared biology and there are obviously things you can do in animals you can’t do with humans, eventually you really need to prove your hypothesis in humans.
The Best Kind Of Research
The gold standard method for testing is the randomised controlled trial (RCT). RCTs randomly assign volunteers to different groups: a treatment group (supplement), and a control group (placebo) for example. By comparing the outcomes of your groups, researchers can determine whether the treatment is effective. The experiment can be a one off (acute), or over a period (longitudinally). It depends on what your testing and your research question. Placebos are essential, they allow researchers to control for the placebo effect. The placebo effect is a psychological phenomenon where a person’s performance/symptoms or condition improve because they believe they are receiving the treatment. For example, one of the trails we ran on citrulline malate identified the placebo as superior to the supplement (Chappell et al. 2021).
Okay, so you’ve got yourself a hold of some experimental research that’s peer review and it’s tested your supplement. Next you have to read the thing, papers are broken down into different sections, but what you really want to know is, what did they do, the methods, and what did they find, the results. If you understand the area then sometimes everything else is superfluous. Want you really want to know is: does the supplement helps you put on muscle when combined with resistance training? You then need to start asking questions: who was this experiment performed on? Was it on men or women, where they young or old, experienced trainers or not, did they control the conditions of effectively, did they look at appropriate outcome measures, what was the dosage they used, did they do the test on enough participants, how big was the actual effect of the supplement etc. etc. Also don’t get side-tracked a supplement trial in post-menopausal East Asian women measuring cycling performance might be interesting but the findings aren’t applicable to the 20 year old Caucasian males trying to get jacked.
Assuming you find an appropriate research study the question is, can you find more? Single studies are interesting, but science relies on reproducibility. People in different labs doing similar experiments seeing if they can replicate each other’s results. When we investigated citrulline malate for example we identified around 8 different relevant studies, as many of them had positive effect as negative effect. So, prior to launching our own investigation, we weren’t really sure if the supplement was likely to work or not. We found no effect of the supplement across two studies we performed, however to this day I still couldn’t be sure if it works or not.
If something has been researched enough you can find reviews. These are papers summarising the research on a topic and are usually a great place to start. Supplements like creatine and caffeine, have a ton of reviews all discussing mechanisms of action alongside supporting and negative studies performed in humans. They usually on balance can suggest if something is worthwhile or what still needs to be done. There are different types of reviews, systematic reviews, meta-analysis, narrative reviews etc. The meta-analysis however is often considered the best place to look if you want a summary of the evidence and a treatments effect. Once enough data has been collated and is considered of highest quality, you start to see a consensus on the effectiveness of something. B-glucan a molecule I spent much of my PhD investigating had over 50 trials performed on it before the European Food Safety Authority (EFSA) felt it appropriate to approve a very specific health claim. In the world of sport and exercise, the equivalent is the endorsement by the ISSN, ACSM or IOC is the position stand or consensus statement.
Now, it’s important to keep in mind that research is an ongoing process and new studies can change our understanding, science never stands still. Moreover, it is possible to be at the cutting edge of something and an earlier adopter. if you interpret the data and like what you see then you’re free to try it out. The key though is that you follow the data, moreover if you are an early adopter then remember until there’s enough research any claims you might make are essentially anecdote.
How Supplement Companies Actually Do Research
With all that in mind, now let me give you an example of the level of scientific scrutiny that typical goes into the development of a supplement. Someone somewhere has identified an ingredient they’d liked to develop into a supplement. Or in other words they’ve found some ingredient that has some potentially bioactive molecule. Perhaps this molecule does something in a plant, insect, or bacteria, this might even have been shown to be the case, using cells. The supplement researcher looks at their textbook containing biochemical pathway and rationalises, maybe this molecule can do the same thing in humans. They rationalise perhaps this might lead to an increase/decrease in some anabolic pathway or catabolic process. They then make the supposition that having more of this molecule is therefore probably a good thing for humans, and hey presto you have yourself a sports supplement! What you’ve got is a hypothesis. You need to do an experiment to see if it works or not. This type of textbook mechanistic reasoning doesn’t constitute a proof of principle or evidence. Moreover indirect effects don’t always translate into real world performance. A 1% increase in oxygen delivery to working muscles might make zero difference to muscle mass obtained in a 12-week resistance training study. You need to be able to prove your ideas work in the real world rather than just on paper or a cell line.
Let’s talk Testboosters
Turkesterone fits into the category of test boosters or potentially pro-hormones/SARMS. It’s important to point out that Pro-hormones/SARMS are effectively steroids and shouldn’t be considered sports supplements. Now we all know testosterone helps build muscle. People inject it, they work out, they eat protein, and they get larger muscles. I wrote a whole article on how much of an edge steroid give you, if you want to read it then click here to check it out (https://proprepcoaching.com/science-of-bodybuilding/steroids-in-sports-how-much-of-an-edge/). Testosterone is produced by the testes and injecting it causes the testes to shrink. The reason for the testes shrinking is that testosterone is regulated by a negative feedback loop involving the hypothalamus, pituitary gland, and testes. See the diagram below for an explanation of this.
The hypothalamus, a small area in the brain, produces gonadotropin-releasing hormone (GnRH) which stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones then travel to the testes, where they stimulate the Leydig cells to produce testosterone. The testosterone in turn travels through the bloodstream and reaches the hypothalamus and pituitary gland. The hypothalamus and pituitary gland detect the rise in testosterone, and respond by decreasing the release of GnRH and LH, respectively, which subsequently decrease the production of testosterone by the testes. This keeps the levels of testosterone in the body within a healthy range, which is essential for maintaining the proper function of the reproductive system, as well as for overall health.
Testosterone boosters aim to increase the body’s own natural production of testosterone or by suppressing the production or oestrogen. They work by interacting with the testosterone pathway at some point either providing more molecules to help manufactory the hormones required or by acting as constitute parts in the pathway. The third possibility and this is more reflective of a pro-hormone/SARM is they can directly interact with muscle cells performing the same action as testosterone. The problem of all this is the negative feedback loop explained above limits their effectiveness. I could think of circumstances where they may be effective to elevated a depressed natural levels, however once testosterone is boosted to a critical level, the body’s own natural production is then down regulated. As a result, any effect from these products is likely short lived and what you really want to know is does it work over a 12 to 24 weeks training cycle and does it have any effect on healthy young men trying to build muscle mass.
So what about Turkesterone?
Turkesterone is a phytoecdysteroid which found in several plant species including Ajuga turkestanica, Vitex species, Triticum aestivum, and Rhaponticum acaule. Phytoecdysteroids are similar to ecdysteroid, and beta-ecdysteroid. These ecydsteroids are involved in malting and reproduction in arthropods (which includes things like scorpions, crabs, and spiders). The prefix Phyto refers to the fact that turkesterone is a plant derived ecydsteroids. At face value plant poisons involved in causing anthropods to excessively malt and die aren’t something you’d immediately suspect would be bioactive in a human. There are obvious biological differences, between humans, insects and plants. There’ is however shared biology, otherwise we couldn’t develop drugs from plants, and things like anti-depressants wouldn’t work in lobsters (or so Jordan Peterson said so). Interestingly, ecydseterone is on the WADA watch list although being on the watch list doesn’t always constitute an effective supplement as Bezuglov et al. (2021) points out.
“there are over 400 different phytoecdysteroids isolated from plants with at least 4 different types of potentially active turkesterone”
After searching via PubMed, Google Scholar, Examine.com, Google Search and then looking at references in the studies identified, I identify 7 relative studies. There are more, but I was looking for studies related to improvements in muscle mass or performance related to ecydsterone. Five of the studies were in rodents, and 2 were in humans. I also found 4 review articles. What’s more it isn’t clear from any of these studies if they’re looking at ecydsterone, phytoecdystrone or beta-ecdysterone and that’s a problem, the nomenclature is all over the place. So we don’t actually know if these studies are investigating turkosterone or some other type of ecydsteroid. When you research B-vitamins you look at specific ones (1,2,3,4,5,6,9,or 12), they don’t all do the same things. That aside if you read the rodent studies, 5 are from the same lab and author, while the only one showing no effect is from the different lab. The rodent studies are performed on healthly mice, castrated rats, diabetic rats and geriatric rats. Again, useful for a proof of principle, but results aren’t necessarily applicable. As for the human trials, both contradict each other, one found a positive effect, the other found no effect. So let’s look at these the human trials:
Wilborn et al. 2006
45 healthy males with at least one year of resistance training under their belt, aged of 20 were recruited. The subjects were placed in one of four (11 per group) treatments: placebo; 800mg/day of methoxyisoflavone; 30mg of 20-hydroxyecdysone (turkesterone); or 500 mg of sulfo-polysacharides. The participants embarked on a 4 day per week upper and lower body training program for 8 weeks. At baseline, week 4 and week 8 the researchers took bloods and performed a battery of tests. The researchers found no difference between the placebo or any of the supplement groups on: fat free mass, body fat %, 1 RM bench press or leg press, sprint peak power, active testosterone, free testosterone, cortisol, urea nitrogen, and creatinine. There was no difference in anything they measured. Now you can point to limitations in this study, these are free living individuals after all. However, the good thing about this study is the fact it was longitudinal, randomised and they tested a huge number of relevant variables like muscle mass and strength. They also tested this supplement in a population of people likely to use it.
Isenmann et al. 2019
This study was similar, although they did some on muscle cells in a lab also. 40 male participants, aged 25 with at least 1 year of training took part in a 10 week training study. The product they tested was called Peak Ecdysone (you can buy it). This is a Beta-Ecdysterone and not Turkosterone, although it’s purported to acts similarly to Turkosterone. Once again we had 4 groups: placebo, Ec1 (ecdysterone 12mg, 200mg leucine ), Ec2 (ecydsterone 48mg, 800 mg leucine), control (ecdysterone 12mg, 200mg leucine, And no training). So a higher dose was used here, 4 times the amount suggested by the manufacturer. Bloods and performance testing was done initially at 5 weeks and week 11. They found no difference in bodyweight between groups, however the high dose group managed to gained 2kg more muscle mass compared to the placebo group, while the placebo group managed to lose 0.35kg of muscle mass. This seems unusual particularly since the control group (which did no exercise) managed to increase their muscle mass over the same period. There was no difference in counter measure jump or 1RM back squat, although there was a difference in bench press 1RM strength between the placebo and both treatment groups. The placebo group did improved their counter measure jump, back squat, and bench press though despite losing muscle mass. Looking at the bloods there was no difference between the groups in testosterone, luteinizing hormone or thyroid hormone between any of the groups, although IGF-1 was higher in the treatment groups.
These results are somewhat messy, based on both studies it seems clear that the ecdysterone supplements do not affecting testosterone. Looking at the cell line part of the study, they found muscle satellite cells treated with the ecydterone grew to a similar degree as dehydrotesterone. This shows which shows in principle that if you can get it in there, it may have some effect of course the question is always, what constitutes a physiologically relevant amount. It also suggests it may be more likely to work like a prohormone/SARM than a natural testosterone booster.
So what are we to make of all this?
Well if you read the review papers Das et al (2021) points out that there are over 400 different phytoecdysteroids isolated from plants with at least 4 different types of potentially active turkesterone (turkesterone 22-acetate, 22 oxo-turkesterone, 11-hydroxy-Δ24-capitasterone and turkesterone 20,22-acetonide). They also point out at least 12 different potential uses for phytoecdysteroids including but not limited to: antioxidants, anti-inflammatories, antibacterial, antiviral, antifungal, anticancer, antidiabetic, anabolic etc. As the paper points out though despite the potential of these molecules there’s very little in the way of in vivo or clinical studies and that a great deal of replication work is needed to confirm their pharmacological, or in this case sporting performance potential. At this point you really must agree with the authors of the review. Ecydsteroids, they’re interesting, but no serious sports scientist or nutritionist is going to recommend them until there’s more data to support the use. Two studies showing contradicting results isn’t really going to cut It. Perhaps in ten year’s time when there’s a dozen studies on it we can make a more informed decision, but for now at least I’m out. Ultimately guys this is the problem with most supplements. Once you peel back the curtain and start looking, what you often find isn’t exactly inspiring, usually it’s like this, a handful of trials with conflicting results. If it seems too good to be true, it usually is.
- Chappell, A.J., Allwood, D.M., Johns, R., Brown, S., Sultana, K., Anand, A. and Simper, T., 2018. Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. Journal of the International Society of Sports Nutrition, 15(1), p.42.
- Syrov, V.N. and Kurmukov, A.G., 1976. Anabolic activity of phytoecdysone-ecdysterone isolated from Rhaponticum carthamoides (Willd.) Iljin. Farmakologiia i toksikologiia, 39(6), pp.690-693.
- Syrov, V.N. and Kurmukov, A.G., 1976. The anabolic properties of turkesterone phytoecdysone and turkesterone tetraacetate in experiments on male rats. Problemy endokrinologii, 22(3), pp.107-112.
- Syrov, V.N., Kurmukov, A.G. and Sakhibov, A.D., 1978. Effect of turkesterone and nerobol on the activity of the protein synthesizing system of mouse liver. Voprosy meditsinskoi khimii, 24(4), pp.456-460.
- Chermnykh, N.S., Shimanovskiĭ, N.L., Shutko, G.V. and Syrov, V.N., 1988. The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles. Farmakologiia i toksikologiia, 51(6), pp.57-60.
- Lawrence, M.M., Zwetsloot, K.A., Arthur, S.T., Sherman, C.A., Huot, J.R., Badmaev, V., Grace, M., Lila, M.A., Nieman, D.C. and Shanely, R.A., 2021. Phytoecdysteroids do not have anabolic effects in skeletal muscle in sedentary aging mice. International journal of environmental research and public health, 18(2), p.370.
- Wilborn, C.D., Taylor, L.W., Campbell, B.I., Kerksick, C., Rasmussen, C.J., Greenwood, M. and Kreider, R.B., 2006. Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males. Journal of the International Society of Sports Nutrition, 3(2), p.19.
- Isenmann, E., Ambrosio, G., Joseph, J.F., Mazzarino, M., de la Torre, X., Zimmer, P., Kazlauskas, R., Goebel, C., Botrè, F., Diel, P. and Parr, M.K., 2019. Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Archives of toxicology, 93, pp.1807-1816.
- Lafont, R. and Dinan, L., 2003. Practical uses for ecdysteroids in mammals including humans: and update. Journal of insect science, 3(1), p.7.
- Parr, M.K., Botrè, F., Naß, A., Hengevoss, J. and Diel, P., 2015. Ecdysteroids: A novel class of anabolic agents?. Biology of sport, 32(2), pp.169-173.
- Das, N., Mishra, S.K., Bishayee, A., Ali, E.S. and Bishayee, A., 2021. The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review. Acta Pharmaceutica Sinica B, 11(7), pp.1740-1766.
- Bezuglov, E., Talibov, O., Butovskiy, M., Khaitin, V., Achkasov, E., Waśkiewicz, Z. and Lazarev, A., 2021. The inclusion in WADA prohibited list is not always supported by scientific evidence: a narrative review. Asian Journal of Sports Medicine, 12(2).