The Problem with Oral Turkesterone and Ecdysterone

Ecdysterone and ecdysteroid containing products (including turkesterone) are rumored to have been used by the Russians during their doping scandals in the 1980s and have been commercially available in the United States since the 1990s. Overtime, these products fell out of favor but in the past year or so, they have made a massive resurgence. Numerous companies have since jumped on the bandwagon flooding the market with turkesterone and ecdysterone products trying to cash in on the hype; however, all of them fall short in one key area...

(Read more about the key differences between ecdysterone and turkesterone)

KEY POINTS 

1. Ecdysterone and turkesterone are not well absorbed when taken orally. These compounds are subjected to liver “first-pass effect” and have poor bioavailability of around 1%.¹  
2. Some supplement companies employ ineffective and dishonest means of formulating and labeling their oral ecdysterone and turkesterone products.
3. Transdermal patches are a simple and effective solution to improve absorption considerably. This formulation is a commonly used strategy in drug development to help deliver medications that are poorly absorbed.²

THE PROBLEM WITH ORALS

While the market for ecdysterone and turkesterone is growing exponentially amongst lifters, there is a big factor to consider. Recently published literature suggested that these compounds are not well absorbed orally.^1,3 These compounds have been shown to be extensively metabolized and inactivated by the liver and other organs and subsequently excreted through urine and feces without getting absorbed.³

This means the vast majority of the supplement will be wasted. Consequently, this makes getting an effective dose nearly impossible.

Currently, all existing ecdysterone and turkesterone products on the market are formulated as oral capsules. This may explain why initially the studies were so promising and also explains the reason that they fell out of favor. Most newer companies to the game are completely oblivious to the problem. Some of companies have recognized the issue and began adding fillers and other ingredients to try to remedy the poor absorption. However, these solutions are unlikely to have any meaningful effect.

Thus, an alternative solution is required for lifters to be able to maximize their results using these supplements. Transdermal patches are an ideal solution to the absorption problem faced by ecdysterone because this method of administration bypasses the liver's “first-pass effect”.

DEFINITIONS

We’ve mentioned “absorption” and “first-pass effect” already, so let’s define some terms so that we are all on the same page.

• Oral: the route of delivering medications, vitamins, minerals, and supplements by mouth.
• Transdermal: refers to the application of medications, vitamins, minerals, and supplements through the skin through the use of a patch or other device.
• Systemic circulation: in the case of metabolism, this refers to when a substance reaches the blood flow across the entire body.
• First-pass metabolism: aka the first pass effect, is a phenomenon that occurs when an oral drug or supplement is greatly reduced by the liver before it reaches the systemic circulation.
• Absorption: is the process of drug or supplement moving through the body to reach systemic circulation.^4,5 Absorption can occur at multiple different organs but primarily in the stomach and intestines.
• Bioavailability (f): is the amount of unchanged drug or supplement as measured in the blood, in this case, when taken orally vs when infused into the veins directly (IV).^4,5 This term gets thrown around frequently but has a very specific meaning in the study of pharmacokinetics. It involves measuring the area under that curve (AUC) for a concentration vs time.⁴ 

THE PATHWAY OF THE DIGESTIVE SYSTEM

Let’s take an example of someone taking an ibuprofen as a way to demonstrate the first pass effect.

Digestion first begins the mouth where chewing and saliva can break down food, or in this case until the tablet is swallowed.

1. After swallowing the tablet, the ibuprofen travels down the esophagus. The esophagus is a muscular tube that connects your throat to your stomach.
2. Next the ibuprofen enters the stomach where it gets mixed with acid and enzymes to be broken down. Before meals, the stomach can begin to churn out more acid in order to breakdown food ingested, this process can have a profound effect on the tablet.
3. The intestines (small and large) are the most important stop on this journey. Absorption primarily occurs here, with the duodenum doing a majority of the work. The pancreas will also secrete bile and enzymes to help the intestines breakdown and digest things.
4. The ibuprofen that gets absorbed into the blood stream is then sent to the liver. Here the ibuprofen will be metabolized by enzymes and be partially inactivated. This is the first pass effect. Our bodies use this process as a safety mechanism to defend from foreign substances we ingest by filtering our blood before it reaches the rest of our organs.
5. Ibuprofen molecules which are lucky enough to make it pass the liver’s metabolism will go into systemic circulation and enter the bloodstream to reach target tissues.

The medical community has known about the first pass effect for decades and certain routes of administering substances can bypass our liver’s first pass effect. Eventually, the blood will circulate back to the liver to be filtered but skipping this first pass greatly increases how much substance reach systemic circulation.²

When a pharmaceutical company is trying to develop a medication that is not able to be taken effectively orally, they look to other means of delivering their medication. It's why some medications like testosterone, used for hormone replacement therapy, are primarily given through injections. But knowing that injections are not always practical, sometimes they need a more convenient solution.

WHAT ARE TRANSDERMAL PATCHES?

Similar to nicotine patches, a transdermal patch can simply be removed from their packaging and applied on to our skin. These devices usually have an adhesive layer that sticks to our skin, and a matrix layer that holds the ingredients. The ingredients are gradually released and diffuse through the skin directly into the bloodstream.

The skin is made up of multiple layers including the epidermis and dermis. Veins can be found just deep to the dermis, so once molecules diffuse through this layer of the skin, they enter the bloodstream. The largest challenge in transdermal delivery is for molecules to pass through is the stratum corneum. Because of this, not all supplements and medications are good candidates for being used in a transdermal patch, and contenders must meet certain physical and chemical properties such as lipophilicity molecular weight.^6,7 Most transdermal patches also employ skin penetrating inactive ingredients which help substances to pass through these barriers. Regardless of these difficulties, the right compounds will have a massive improvement in bioavailability using these strategies. 

Using transdermal patches means we can skip our digestive system entirely and ecdysterone can enter to the bloodstream without having to go through our liver first.

Transdermal patches are a convenient method of delivering vitamins, minerals, and supplements to your body without having to ingest them. Rather than choking down a bunch of pills to be subjected to your stomach and digestive tract, you can absorb them directly through your skin.

While it’s rare to see products available over-the-counter using transdermal technology, in the pharmaceutical industry this formulation is a go-to solution for medicines that have poor oral absorption.⁸ This technology has been applied to pain-relief medications, hormones, and many others for decades. Simply put, it’s an effective solution to the absorption problem that is faced by Ecdysterone and Turkesterone.

REFERENCES:

1. Dinan L, Dioh W, Veillet S, Lafont R. 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases. Biomedicines. 2021; 9(5):492. https://doi.org/10.3390/biomedicines9050492
2. Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum. Pharmaceutics. 2015;7(4):438-470. Published 2015 Oct 22. doi:10.3390/pharmaceutics7040438
3. Dinan L, Balducci C, Guibout L, et al. Ecdysteroid metabolism in mammals: The fate of ingested 20-hydroxyecdysone in mice and rats. J Steroid Biochem Mol Biol. 2021;212:105896. doi:10.1016/j.jsbmb.2021.105896.
4. Kimura T, Higaki K. Gastrointestinal transit and drug absorption. Biol Pharm Bull. 2002;25(2):149-164. doi:10.1248/bpb.25.149
5. Paul, A. (2019). Drug Absorption and Bioavailability. In: Raj, G., Raveendran, R. (eds) Introduction to Basics of Pharmacology and Toxicology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9779-1_5
6. Chagas CM, Moss S, Alisaraie L. Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski's Rule of Five. Int J Pharm. 2018;549(1-2):133-149. doi:10.1016/j.ijpharm.2018.07.046
7. Singh I, Morris AP. Performance of transdermal therapeutic systems: Effects of biological factors. Int J Pharm Investig. 2011;1(1):4-9. doi:10.4103/2230-973X.76721
8. Adrian S. Dobs, A. Wayne Meikle, Stefan Arver, Steven W. Sanders, Kim E. Caramelli, Norman A. Mazer, Pharmacokinetics, Efficacy, and Safety of a Permeation-Enhanced Testosterone Transdermal System in Comparison with Bi-Weekly Injections of Testosterone Enanthate for the Treatment of Hypogonadal Men, The Journal of Clinical Endocrinology & Metabolism, Volume 84, Issue 10, 1 October 1999, Pages 3469–3478, https://doi.org/10.1210/jcem.84.10.6078