The Current State and Potential of Synthetic Peptides For The Performance and Health Of The General Public

 Ashley Andrews (Year 12)

Abstract

The aim of the article is to assess the current state and also the potential of synthetic peptides to increase the performance and health of the general public by analysing currently researched peptides, comparing them to already safely established supplements and taking into account the origin of the regulations around dietary supplements. If scientists can create peptides with this capability then they can be taken particularly by people at risk of adverse effects namely elderly people and it will grant the general public an increase in their quality of life. There are varying synthetic peptides which have greater potential than others to be used for the general public but in the future there will be synthetic peptides that are taken regularly by the population. However at the moment there needs to be large scale studies conducted to completely verify their benefit and safety before being pushed to the public. 

Introduction

Peptides are short chains of amino acids ranging from 2-50 amino acids in one chain linked with peptide bonds that can bind to receptors on the cell membrane of cells which cause downstream effects such as gene expression and protein synthesis[1][2]. Recently, the potential of synthetic peptide hormones has been explored and many people in the fitness industry have been promoting their anecdotal benefits with the use of synthetic peptides including BPC-157 and MK-677. 

The aim of this paper is to assess the potential of synthetic peptides being used for the benefit of performance and health to the general public without having unacceptable side effects? There has been a lot of mystery around synthetic peptides, for example the potential regenerative effects of BPC-157 and both BPC-157 and MK-677 have been banned by the World Anti Doping Agency (WADA)[3][4][5]. Reviewing the studies around select synthetic peptides will allow evaluation to be made of whether synthetic peptides should be taken as a supplement to support quality of life. 

If the research behind synthetic peptides supports their healthy usage, the general public can have a boost in their performance and health which improves their quality of life. Especially increasing the capabilities of older people such as reducing injury from their natural decrease in certain substances because of their reduced absorption so they are able to be stronger which also improves pain experienced from the lack of substances that were abundant in younger stages of life[6].

Discussion 

Differences Between Peptides and Steroids 

Steroids are known for their ability to artificially alter hormone production which causes increased muscle mass, strength and reduced inflammation[7][8]. On the other hand, they come with side effects of high blood pressure, anger issues, renal damage and erectile dysfunction due to hormone imbalances and increase in substances circulating in the blood[7][8]. Both peptides and steroids can cause a change in hormones so what is the difference between them? 

The key difference between peptides hormones and steroid hormones and their role on the body is how they perform cell signalling. Steroids are a primary messenger while peptides are a secondary messenger due to the fact of their differing solubility[9]. All steroid hormones are derived from cholesterol which causes all steroids to be lipid soluble as they are lipids themselves. This allows steroids to enter cells by simple diffusion as they are able to cross the lipid soluble phospholipid bilayer surrounding the cell so it can bind to receptors inside of the cell which directly impacts gene expression and protein synthesis[10]. Steroids are “primary” messengers as they directly impact the gene expression and protein synthesis of the protein the hormone intends to make. 

Whereas peptides are water soluble so they cannot freely enter the cell and instead need to bind to receptors on the cell membrane mainly the g pathway. This is where the peptide binds to a G protein coupled receptor (GPCR) which leads to the G protein displacing guanosine diphosphate(GDP) and instead binds to guanosine triphosphate(GTP)[11].  This causes a number of enzymes to react which causes the downstream effect of gene expression and protein synthesis of the desired protein among many other effects caused by indirect signalling[12]. Peptides are “secondary” messengers as they indirectly cause the protein synthesis of the protein the hormone intends to make. 

*Image (from nature education) shows molecule binding to GPCR which causes inactive g protein to lose GDP and gain GTP making it active.[11]

It is believed that because steroids unnaturally increase hormone levels in the body by being administered exogenously there are more side effects[13]. Whereas peptides “naturally” produce higher levels of hormones as the hormones are not being injected but instead the peptide is increasing the signal for endocrine glands to produce the desired hormone[13]. It is believed they have reduced side effects when compared to steroids however there are still side effects present that always come when the endocrine system is disrupted[14]. 

However, further research is needed to precisely indicate the differences in risks of peptides and steroids yet it is hard to generalise peptides side effects. This is because there are various peptides which all have their own differing side effects but hypothetically they could be compared with each other to produce a list of general side effects of peptides that impact hormones to inform the peptide consumer.

The Growing Regulations of Supplements

During the 20th century there had been a long battle between the Food and Drug Administration (FDA), pharmaceutical companies and the public in the regulation of the growing supplement industry.

The emerging supplement industry in the early 20th century was a disarray of misleading health claims and all sorts of ingredients were being put in supplements with no scientific evidence backing their claimed benefits.

In response to this, the Federal Food and Drugs Act was passed in 1906 which prohibited the commerce of adulterated or misbranded supplements and used seizure and prosecuting as means of enforcement[15]. The act helped settle down the unregulated industry and many manufacturers were being prosecuted from marketing misbranded products and products were being seized which contained prohibited ingredients. However, it did not stop the growing health claims that manufacturers were claiming their supplements had to the point where Dunbar (commissioner of FDA from 1944-1951) said “A considerable gap still existed between what experimental studies revealed and the health-giving claims some manufacturers were expressing”[15]. 

In response to this, the FDA introduced the Food, Drug and cosmetic act that replaced the previous act in 1938 which widened the legal description of a drug as “articles (other than food) intended to affect the structure or any function of the body”. They also later made amendments in 1962 that stated only their selected vitamins and minerals were allowed to be said to improve health and every other claim would be treated as misbranding which caused a national outrage receiving 54,000 communications in regard to the proposed rules[15]. 

The FDA also caused another national outrage when they proposed any supplement that contained more than 150% of the U.S recommended daily allowance would be considered and treated as a drug and in response received 20,000 communications but this proposal was later shut down.

Turning of the Tide

The public and pharmaceutical companies felt the FDA had stepped too far in their regulation of supplements and the first step of their retort was when the Vitamin-Mineral Amendments were passed in 1976[15]. This prohibited the FDA from limiting the potency of vitamins and minerals, prevented the government listing a supplement as a drug if the quantity exceeded a certain amount and prevented the government from preventing any combination of ingredients. 

Leading on from this, Congress passed the Nutrition Labelling and Education Act of 1990 (NLEA) which charged the FDA to validate their claims on vitamins and health outcomes in order to regulate nutritionalling labelling and they were given a deadline to complete this by[15]. However, congress was working on a law to make NLEA rules null and void and therefore the limit on health claims also null and void which was one of the most impactful acts in the history of supplements. The Dietary Supplement Health Education Act (DSHEA) was passed on 25 October 1994 because of the major role supplements played in the U.S economy due to half of the U.S population buying supplements leading to $4 billion revenue annually[15][16]. Congress wanted to increase the revenue the economy was receiving from the supplement industry so they removed premarket clearance for any dietary supplement that did not include a new dietary ingredient[17]. The FDA also had to provide evidence of a product being adulterated or misbranded before taking action which made it much harder to regulate supplements. Another major part of DSHEA was that manufacturers could make claims about their products including their structure and function if they included the disclaimer ‘These statements have not been evaluated by the Food & Drug administration. This product is not intended to diagnose, treat, cure or prevent any disease.’[18]]

*Disclaimer needed to be made on the labels of supplements that make any structural/functional claims.[19]

This allowed supplements companies to make less regulated supplements which were more dangerous because as long as the FDA did not find out the product was adulterated or misbranded then there was no harm done in the eyes of the law. The current position of the FDA is shown in the following quote “The FDA does not approve dietary supplements for safety and effectiveness or their labelling before they are sold to the public” as they do not have the authority anymore which has ultimately led to the following study[17].

How Do People Actually Know What is in Peptides?

A study published in the journal JAMA Network Open called “Presence and Quantity of Botanical Ingredients With Purported Performance-Enhancing Properties in Sports Supplements” showed some dismaying results regarding the correctness of supplements. The study found 40% of supplements did not contain detectable quantities of the ingredients listed, quantities ranged from 0.02% to 334% of the labelled quantity and 12% contained FDA prohibited ingredients[20].

The study highlights the relaxed regulations of supplements in the 21st century which has led to 89% of supplement labels not accurately declaring the ingredients in the product[20]. This means supplements should only be bought from reputable sources to increase the chance of correct labelling of supplements and experimental supplements should never be bought from unknown supplement manufactures as there is a high likelihood that it is a mix of unknown and potentially harmful ingredients instead of the desired product. 

There were limitations to the study including the small sample size of 57 supplements, only taking one sample from each brand and that the supplements only included botanicals[20]. However, it does show the randomness of supplements and an indication to what other things could be happening in other categories of supplements such as experimental peptides that are less regulated than the supplements used in the study.

Further studies need to be done on a larger sample size of supplements including all categories to accurately assess the level of adulteration and misbranding of supplements currently being sold to unknowing consumers. Although some peptides could be safe, can people trust the companies selling them to produce them in a safe way where the supplement includes the right dosage of the peptide and not to mention including any other unknown ingredients?

The Gold Standard of Supplements - Creatine 

Creatine is a naturally occurring chemical produced endogenously in the liver and kidneys using amino acids and 95% of the chemical is found in the skeletal muscle[21][22]. Creatine can also be taken exogenously in the form of high creatine content foods for example salmon, steak and eggs[21]. 

Creatine benefits[21][22][23]:

• Increases muscle strength

• Increases muscle mass

• Increases recovery due to muscles having greater glycogen storage

• In animal models, creatine is neuroprotective and is observed to reduce severity of spinal cord injury

Creatine improves muscle growth by increasing water retention in muscles which is an important cellular signal for protein synthesis and therefore leads to growth of muscle cells[21]. Also, creatine allows for greater energy during intense exercise because adenosine triphosphate(ATP)  breaks down to release energy and creates the products adenosine diphosphate(ADP) + inorganic phosphate. When creatine is consumed it is converted into creatine phosphate which is then sent to the skeletal muscles and phosphorylases the ADP to form ATP by giving it an inorganic phosphate which means more energy is available for the  skeletal muscles[22][24].

Creatine is found in foods but people can not get enough creatine from their diet alone so many supplement creatine in various forms such as powders, capsules and gummies for these listed benefits[22]. Furthermore, all these benefits of creatine come without any damage to the liver or kidneys[21]. The only side effects reported are gastric problems from absorbing the creatine which can be reduced by spreading creatine intake out over the day and does not happen to most people[22]. 

Creatine acts as a role model to what peptides should be. That is having great benefits without any serious side effects. But is this what people are taking peptides for? Or are people instead not reading the research around them and thinking ‘anything is worth a try’ putting their body at unreasonable risk?

The qualities that creatine possesses should be used as a guide to the research and development(R&D) of peptides for use by the general public to result in performance and health benefits. The main quality creatine contains is that it is a substance that the body already contains and it brings benefits by simply increasing the content of this beneficial substance in the body[25]. 

Usually, supplements that affect hormones then go on to affect a multitude of other parts of the body which leads to various serious side effects, however keeping the impact to one variable tends to reduce the side effect[14]. Peptides should aim to find useful proteins in the body that the body could benefit from having more of and then manufacture easily absorbable versions of those proteins in peptide form to bring simple but effective benefits with low side effects. 

This is no doubt a basic way for the R&D of peptides and the downside is missing the potential benefits of creating peptides from more experimental methods which means people may miss out on the benefits of developing an unknown peptide which somehow has great benefits with no side effects. But scientists should avoid making those experimental peptides at the moment with a low rate of success in place of making more successful peptides that will guarantee success and improve the performance and health of the general public.

Evaluating Collagen peptides 

Collagen is the most abundant form of structural protein in the body and is vital for the structure of skin, bones, tendons and ligaments[26][27][28]. Collagen starts to decrease in the 20s and most likely by the 40s people lose 1% of collagen content per year[26]. The effects of reduced collagen is joint pain, wrinkled skin and loss of mobility in joints[26][27]. 

Collagen is found in the bones and skin of animals so it is also found in food. However, eating collagen rich foods does not directly translate into higher collagen levels as collagen cannot be absorbed in whole form and it is rather broken down by digestive enzymes into peptides and amino acids[28][29]. Collagen peptides are useful because they can be readily absorbed in the gastrointestinal tract as they are already broken down into their peptide structure[29]. 

The research around peptides have currently shown these benefits[28]:

• Increased Skin health

• Reduced Joint pain

• Reduced Bone loss

• Increased Muscle mass

• Increased Heart health

The main benefits of collagen peptides are their role in skin health and joint pain.

In a double blind, randomised, placebo controlled trial with 1000 mg of collagen peptide supplementation taken once daily. There was significant improvement in skin hydration in 6 weeks and significant improvement in skin elasticity and wrinkling in 12 weeks in women aged 40-60 with photoaged skin[30]. 

Studies show improved joint pain and functionality with peptide supplementation but also an increase in fat free mass(FFM) and a decrease in fat mass[28]. The increase in FFM is due to the increase in surrounding connective tissue because collagen has a vital role in its formation28]. Collagen also reduces bone loss due to bones being mostly made of collagen giving them structure and strength.

The less researched benefits of collagen peptides such as better heart health is due to collagen providing structure to arteries and with reduced collagen could lead to arteries becoming less flexible and elastic which could lead to atherosclerosis[29].

There are other theorised benefits namely better brain health, gut health and weight loss but there are no studies supporting these benefits so trials need to be conducted to investigate these claims[29]. 

Collagen peptides are a very promising supplement as they haven been shown to mostly have no adverse events related to their consumption and the only adverse effects reported are nausea, bloating and heartburn which are not consistent in all studies[29]. 

Collagen peptides are a beneficial supplement for ageing and older people because of their role in the bones, tendons and ligaments to reduce the effects of reduced collagen including increased joint pain, decreased joint mobility and worse skin health by replacing the lost collagen[28]. Collagen peptides should be given to older people to improve bones, ligaments and muscle. 

The elderly population is particularly vulnerable to osteoporosis due to their decreasing levels of collagen that plays an important role in bone structure and strength[26]. This could lead to harmful consequences including bone fractures[31]. A large-scale study needs to be conducted on the effect of collagen peptide supplementation in elderly populations at varying dosages to assess the relationship between collagen levels and the direct consequences of osteoporosis such as bone fractures. If the study shows an effective inverse relationship between increased collagen levels in elderly people and bone fractures between the placebo and test group. Then collagen peptides can be used by all elderly people to be less at risk of osteoporosis and also in patients dealing with osteoporosis to reduce risk of bone fractures. 

Evaluating BPC-157 

Body protecting compound (BPC) contains 15 amino acids and is made synthetically with the main ingredient being from a protein in the gastric fluid of humans[32]. 

BPC-157 is a largely experimental peptide that has shown great benefits in rodents and cultured cells for its regenerative effects[33]. However, there is a lack of evidence in human trials which means there is less known about the potential side effects it has and if the benefits can also be seen in humans[32][33][34]. 

The currently observed benefits of BPC-157[32]:

• Promoting angiogenesis to create more red blood cells which could encourage healing and recovery

• Promoting production of collagen and fibroblasts which are important to tendons, joints and muscles

• Quicker repair and recovery of muscles and joints

However the potential benefits of BPC-157 has been mistaken for proven success which has led to people injecting BPC-157 into themselves with no knowing of short or long term side effects. The potential side effects could be nausea, dizziness, headache and inflammation at site of injection but there is no knowing the full side effects because of the lack of human trials[32]. Also, BPC-157 was banned in 2022 by WADA under the category of non-exempt substances and on the 6th October 2023 BPC-157 was moved into category 2 by the FDA meaning it is harder to obtain a prescription for the compound but did not give a reason to why it was moved[3][35].

Further research needs to be done on humans to have an idea what BPC-157 actually does as results in rodents and cultured cells do not directly extend to humans well. However, I believe BPC-157 has good potential as an experimental peptide because of the fact that it does not affect hormone levels and instead promotes already existing functions of the body. This means it should have less effects as it is not tampering with the whole body instead it is taking the path of supplements such as creatine and collagen peptides which instead aim for processes that the body would benefit from being increased and targeting only that to bring benefits with reduced side effects. 

Evaluating MK-677 

MK-677 is an experimental peptide that acts as a growth hormone secretagogue which attracts many people to take the peptide as human growth hormone(HGH) is seen as favourable to performance[36][37].

In current studies, MK-677 benefits have been seen as having benefits such as increased FFM, decreased LDL, longer REM sleep and functional lower extremity improvement post hip fracture in elderly individuals[36]. However the problem with MK-677 is that nearly all studies are non representative for the people who would be taking MK-677. The studies feature mostly elderly, obese and children with stunted growth but it is not being tested on the young and healthy population that would take this so the side effects are not known and none of the long term effects are known[39].

The few side effects currently seen are decreased insulin sensitivity, transient increase in cortisol and prolactin and appetite, musculoskeletal pain and fluid retention and even one study was stopped as there was indication that MK-677 might increase risk of congestive heart failure (CHF) as 6.5% of patients developed CHF while only 1.7% of the placebo group experienced CHF[36]. 

Because MK-677 is a growth hormone secretagogue that releases HGH it is possible to extrapolate research for HGH onto MK-677. Although HGH may have benefits in particular more lean mass, increased fat loss and higher sprinting speed there is no difference in strength power or VO2 max[37][38]. In addition, there are common side effects of increased HGH including edema, fatigue and potentially decreased exercise capacity[37]. Finally most of the data about HGH benefits on normal people are inconclusive or negative for HGH increasing performance so using HGH as a performance enhancer is just not worth it as results are inconsistent[37].

Furthermore, the function and side effects of MK-677 cannot  be trusted but also the manufactures cannot be trusted due to the way MK-677 and other peptides such as BPC-157 are sold. Selling peptides as a dietary supplement is illegal therefore manufacturers use loopholes by labelling products such as “research chemicals” or “not for human use” to sell peptides that most likely are ending up in the hands of people for human use[40]. Due to the earlier discourse about how supplements are regulated it increases the chance that peptides such as BPC-157 and MK-677 are dangerous even in their isolated form but may also be mixed with other ingredients which may increase the risk of potential harm to the user. 

There is barely any evidence on what MK-677 does in healthy normal populations therefore it is not a valid peptide to use and because the main benefit is that it is a growth hormone secretagogue so it is not far removed from the steroid growth hormone[36]. It is not viable for the performance and health of the general public as it has great potential risks by tampering with the endocrine system with little benefit because of the unproven benefits of excess HGH[37][38].

The Side Effect Paradox when Dealing with Hormones 

There seems to be a limiter on how much humans can artificially improve their performance and health without the side effects outweighing the benefits. For example, Anabolic androgenic steroids and corticosteroids both have great benefits for example increased muscle building potential and reducing inflammation respectively so why can people not continually use these steroids for these positives[7][8]? 

This is because they change hormone levels in the body also known as endocrine disruption which leads to hormone imbalances which get more severe the longer they are taken which lead to side effects including depression, erectile dysfunction and fatigue[14]. 

These are also known as endocrine disrupting chemicals(EDC) which are natural or human-made chemicals that mimic, block or interfere with the body's hormones which are part of the endocrine system[41]. In addition, most EDCs seem to damage the kidney and liver seemingly due to the fact the liver needs to remove excess hormones from the body and the kidney needs to filter the steroids leading to damage of both[42][43]. 

This is the main problem with anything that changes hormones as they are all endocrine disrupting which subsequently lead to the same side effects that make the benefits not worth it[44]. This is why creatine and collagen peptides are effective supplements due to the fact it increases a chemical that is already present in the body without affecting hormones which allows it to yield all its benefits without having many side effects.

In the search for peptides that will have performance and health benefits, it is favourable to focus on peptides that do not have a hormonal effect in particular BPC-157 which is comparable to creatine rather than an MK-677 which carries out the mostly same end outcome as just injecting the steroid growth hormone but it is in peptide form but being in peptide form does not exempt users of MK-677 suffering side effects of increased growth hormone[37][38]. Collagen peptides and BPC-157 therefore have a greater potential than MK-677 as supplements to benefit the general public.

Snake Oil Salesman? 

Many of the articles published about peptides come from anti ageing clinics and peptide therapy companies which talk favourably about peptides they sell while coincidentally not talking about much of the side effects. Although not all companies selling peptides are represented by this, some consumers have unknowingly read biased articles about peptides and believed they had barely any side effects which resulted in more sales for these peptide companies. Why would these companies who readily hand out peptides with anyone who books a consultation with them be non-biased about products that affect their business and their livelihood[34][45]?

In addition to this most research papers are funded commercially by supplement companies wanting positive outcomes for their supplement[28]. The research can still be treated as valid as they do not change their methodology to show unrepresentative results but definitely potential bias can arise due to the source of funding. The consumers interested in peptides for performance and health need to read the literature on the peptides they are interested in rather than reading articles from perhaps biased supplement companies to understand what they are putting into their body to make sure they stay safe.

Conclusion 

Peptides have a great potential for their benefit in performance and health for the general population and some have great research around them such as collagen peptides. On the other hand, consumers should show great caution when buying peptides as it is an industry with relaxed regulation and the potential of shady manufactures to make use of these regulations to miss dose products and not even include the correct ingredients in the product is likely. Experimental peptides such as BPC-157 with not much research around them need to be further researched before being commercially distributed and should not be promoted using anecdotal evidence as their side effects can vary greatly and not all peptides have equal side effects. Hormonal changing peptides including MK-677 should be avoided due to their great potential of serious side effects with not much benefits to be had. 

Bibliography

[1] Forbes, Jessica, and Karthik Krishnamurthy. “Biochemistry, Peptide.” National Library of Medicine, August 28, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562260/. 

[2]Khavinson, Vladimir Khatskelevich, Irina Grigor’evna Popovich, Natalia Sergeevna Linkova, Ekaterina Sergeevna Mironova, and Anastasiia Romanovna Ilina. “Peptide Regulation of Gene Expression: A Systematic Review.” Molecules 26, no. 22 (November 1, 2021): 7053. https://doi.org/10.3390/molecules26227053. 

[3]“2022 Prohibited List - World Anti-Doping Agency.” World Anti Doping Agency, January 1, 2022. https://www.wada-ama.org/sites/default/files/resources/files/2022list_explanatory_note_final_en.pdf. 

[4]“Summary of Major Modifications and Explanatory Notes.” World anti-doping agency, January 1, 2024. https://www.wada-ama.org/sites/default/files/2023-09/2024list_explanatory_list_en_final_22_september_2023.pdf. 

[5] Pfiffner, Morgan, and Nick Milazzo. “BPC-157 Benefits, Dosage, and Side Effects.” Examine, November 15, 2023. https://examine.com/supplements/bpc-157/. 

[6] Mangoni, A. A., and S. H. Jackson. “Age‐related Changes in Pharmacokinetics and Pharmacodynamics: Basic Principles and Practical Applications.” British Journal of Clinical Pharmacology 57, no. 1 (January 1, 2004): 6–14. https://doi.org/10.1046/j.1365-2125.2003.02007.x. 

[7] “Steroids.” Versus Arthritis, 2023. https://versusarthritis.org/about-arthritis/treatments/drugs/steroids/. 

[8] Albano, Giuseppe Davide, Francesco Amico, Giuseppe Cocimano, Aldo Liberto, Francesca Maglietta, Massimiliano Esposito, Giuseppe Li Rosi, Nunzio Di Nunno, Monica Salerno, and Angelo Montana. “Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review.” Healthcare 9, no. 1 (January 1, 2021): 97. https://doi.org/10.3390/healthcare9010097. 

[9]Reyes, Pedro, Muhammad A. Ashraf, and Kristen N. Brown. “Physiology, Cellular Messengers - Statpearls - NCBI Bookshelf.” National Library of Medicine, April 24, 2023. https://www.ncbi.nlm.nih.gov/books/NBK538154/. 

[10]Jakoi, Emma. “Duke University Medical School.” Histology. Accessed January 2, 2024. https://histology.oit.duke.edu/. 

[11]​​“GPCR.” Scitable. Accessed January 2, 2024. https://www.nature.com/scitable/topicpage/gpcr-14047471/. 

[12]Khavinson, Vladimir Khatskelevich, Irina Grigor’evna Popovich, Natalia Sergeevna Linkova, Ekaterina Sergeevna Mironova, and Anastasiia Romanovna Ilina. “Peptide Regulation of Gene Expression: A Systematic Review.” Molecules 26, no. 22 (November 1, 2021): 7053. https://doi.org/10.3390/molecules26227053. 

[13]“What Is the Difference between Peptides and Steroids?” Advanced ChemTech, April 29, 2021. https://www.advancedchemtech.com/what-is-the-difference-between-peptides-and-steroids/#:~:text=The%20main%20difference%2C%20however%2C%20is,bodybuilders%20still%20use%20steroids%20instead. 

[14]professional. “Hormonal Imbalance: Ca.” Cleveland Clinic, April 4, 2022. https://my.clevelandclinic.org/health/diseases/22673-hormonal-imbalance. 

[15]Swann, John P. “The History of Efforts to Regulate Dietary Supplements in the USA.” Drug Testing and Analysis 8, no. 3–4 (November 23, 2015): 271–82. https://doi.org/10.1002/dta.1919. 

[16] “Dietary Supplements.” U.S. Food and Drug Administration, June 3, 2023. https://www.fda.gov/food/dietary-supplements. 

[17] “Understanding Dietary Supplements - U.S. Food and Drug Administration.” U.S Food and Drug Administration, May 2022. https://www.fda.gov/media/158337/download?attachment. 

[18]“Structure/Function Claims.” U.S. Food and Drug Administration, July 3, 2022. https://www.fda.gov/food/food-labeling-nutrition/structurefunction-claims#:~:text=If%20a%20dietary%20supplement%20label,legally%20make%20such%20a%20claim. 

[19]“Creatine Gummies 3000mg, Creatine Monohydrate Gummies ... - Amazon.Co.Uk.” Amazon. Accessed January 2, 2024. https://www.amazon.co.uk/Creatine-Gummies-Monohydrate-Strength-Natural/dp/B0C8TSBRL3. 

[20] Cohen, Pieter A., Bharathi Avula, Kumar Katragunta, John C. Travis, and Ikhlas Khan. “Presence and Quantity of Botanical Ingredients with Purported Performance-Enhancing Properties in Sports Supplements.” JAMA Network Open 6, no. 7 (July 17, 2023). https://doi.org/10.1001/jamanetworkopen.2023.23879. 

[21] Antonio, Jose, Darren G. Candow, Scott C. Forbes, Bruno Gualano, Andrew R. Jagim, Richard B. Kreider, Eric S. Rawson, et al. “Common Questions and Misconceptions about Creatine Supplementation: What Does the Scientific Evidence Really Show?” Journal of the International Society of Sports Nutrition 18, no. 1 (February 8, 2021). https://doi.org/10.1186/s12970-021-00412-w. 

[22] Cooper, Edward, and Christian Finn. “What Is Creatine and Should You Be Using It? - Men’s Health.” Men’s Health, June 15, 2023. https://www.menshealth.com/uk/building-muscle/a750240/what-is-creatine/. 

[23]Chen, Kuan-Lin, Chin Hsu, Hang-Cheng Chen, Jian-Yu Chen, Sheng-Yan Yu, and Yi-Jie Shiu. “Creatine Supplementation for Muscle Growth: A Scoping Review of Randomized Clinical Trials from 2012 to 2021.” Nutrients 14, no. 6 (March 16, 2022): 1255. https://doi.org/10.3390/nu14061255. 

[24] “Creatine.” Cleveland Clinic, April 26, 2023. https://my.clevelandclinic.org/health/treatments/17674-creatine. 

[25]“Creatine.” Cleveland Clinic, 2020. https://my.clevelandclinic.org/health/treatments/17674-creatine. 

[26] Czerwony, Beth. “Everything You Should Know About Collagen Peptides.” Cleveland Clinic, December 23, 2021. https://health.clevelandclinic.org/what-do-collagen-peptides-do. 

[27]“Collagen: What It Is, Types, Function & Benefits.” Cleveland Clinic, May 23, 2022. https://my.clevelandclinic.org/health/articles/23089-collagen. 

[28] Khatri, Mishti, Robert J. Naughton, Tom Clifford, Liam D. Harper, and Liam Corr. “The Effects of Collagen Peptide Supplementation on Body Composition, Collagen Synthesis, and Recovery from Joint Injury and Exercise: A Systematic Review.” Amino Acids 53, no. 10 (September 7, 2021): 1493–1506. https://doi.org/10.1007/s00726-021-03072-x. 

[29] Walle, Gavin Van De, and Brianna Elliot. “Health Benefits of Collagen: Pros, Cons, and More.” Healthline, January 2, 2023. https://www.healthline.com/nutrition/collagen-benefits#benefits. 

[30] hKim, Do-Un, Hee-Chul Chung, Jia Choi, Yasuo Sakai, and Boo-Yong Lee. “Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.” Nutrients 10, no. 7 (June 26, 2018): 826. https://doi.org/10.3390/nu10070826. 

[31]“Osteoporosis.” National Institute of Arthritis and Musculoskeletal and Skin Diseases, December 2022. https://www.niams.nih.gov/health-topics/osteoporosis#:~:text=Osteoporosis%20is%20a%20bone%20disease,of%20fractures%20(broken%20bones). 

[32]Atanasovski, Aleksandar. “How Is the BPC 157 Peptide Used in Muscle, Tissue, and Joint Recovery?: Concierge Md La.” Concierge MD - Mobile Medical Services, 2022. https://conciergemdla.com/blog/bpc-157-peptide-muscles-joints/#:~:text=Angiogenesis%20is%20one%20of%20the,%2C%20recovery%2C%20and%20overall%20health. 

[33]Pfiffner, Morgan, and Nick Milazzo. “BPC-157 Benefits, Dosage, and Side Effects.” Examine, November 15, 2023. https://examine.com/supplements/bpc-157/. 

[34]Nickel, Beck. “BPC-157 Peptide Side Effects: Anti-Aging Northwest.” Anti-Aging Northwest, 2022. https://antiagingnorthwest.com/bpc-157-peptide-side-effects-what-you-need-to-know/. 

[35]Alana, Jessica. “The FDA Banning Compounding Pharmacies from Prescribing Peptides: What This Really Means.” LinkedIn, November 9, 2023. https://www.linkedin.com/pulse/fda-banning-compounding-pharmacies-from-prescribing-peptides-alana-p2wif/. 

[36]Sigalos, John T., and Alexander W. Pastuszak. “The Safety and Efficacy of Growth Hormone Secretagogues.” Sexual Medicine Reviews 6, no. 1 (January 1, 2018): 45–53. https://doi.org/10.1016/j.sxmr.2017.02.004. 

[37]Siebert, David M., and Ashwin L. Rao. “The Use and Abuse of Human Growth Hormone in Sports.” Sports Health: A Multidisciplinary Approach 10, no. 5 (2018): 419–26. https://doi.org/10.1177/1941738118782688. 

[38]Holt, Richard I, and Ken K Ho. “The Use and Abuse of Growth Hormone in Sports.” Endocrine Reviews 40, no. 4 (June 10, 2019): 1163–85. https://doi.org/10.1210/er.2018-00265. 

[39]Svensson, J., C. Ohlsson, J.‐O. Jansson, G. Murphy, D. Wyss, D. Krupa, K. Cerchio, et al. “Treatment with the Oral Growth Hormone Secretagogue Mk‐677 Increases Markers of Bone Formation and Bone Resorption in Obese Young Males.” Journal of Bone and Mineral Research 13, no. 7 (December 4, 2009): 1158–66. https://doi.org/10.1359/jbmr.1998.13.7.1158. 

[40]Matthews, Michael. “Are Bodybuilding Peptides a Safe and Effective Alternative to Steroids?: Legion.” Legion Athletics, 2023. https://legionathletics.com/peptides-bodybuilding/. 

[41]“Endocrine Disruptors.” National Institute of Environmental Health Sciences, June 2, 2023. https://www.niehs.nih.gov/health/topics/agents/endocrine. 

[42]“Hormone Imbalance & Your Liver: What You Need to Know.” SFI Health, 2023. https://www.flordis.com.au/health-insights/liver-health-detox/hormone-imbalance-and-the-liver/#:~:text=How%20does%20the%20liver%20relate,by%20a%20range%20of%20factors. 

[43]Valdivielso, José Manuel, Conxita Jacobs-Cachá, and María José Soler. “Sex Hormones and Their Influence on Chronic Kidney Disease.” Current Opinion in Nephrology and Hypertension 28, no. 1 (January 28, 2019): 1–9. https://doi.org/10.1097/mnh.0000000000000463. 

[44]Susanne Hiller-Sturmhofel and Andrzej Bartke. “The Endocrine System” Alcohol Health and Research World, no. 22(1998): 153-164

[45]Nickel, Beck. “Is Peptide Therapy Safe? - Anti-Aging Northwest.” Anti-Aging Northwest, 2021. https://antiagingnorthwest.com/is-peptide-therapy-safe/.