10 OVERHYPED PREWORKOUT SUPPLEMENTS: CURRENT CONTROVERSY!
By Robert Schinetsky
Current Controversy In our previous installment of the “Best Pre Workout Supplements”, we covered those nutrients that have a solid backing of evidence for improving human exercise performance.
Today, we look at the other side of the coin -- those ingredients commonly included in pre workouts that flat out don’t work or whose results are heavily mixed when studied in humans.
Let’s kick things off with an ingredient that’s been a pre workout staple going on 20 years...
Before L-Citrulline rose to fame, nitric oxide boosters and pump pre workouts were fueled by L-arginine.
In theory, this made sense -- Arginine is the amino acid that serves as the “fuel” for nitric oxide production. Therefore, supplementing with free form L-arginine should increase blood levels of arginine, leading to greater NO production, vasodilation, blood flow, and muscle pumps.
Unfortunately, the theory doesn’t really hold up.
Numerous studies have shown that orally supplemented l-arginine (the same form used in many pre workouts), even when dosed as high as 6g/day, has no benefit on nitric oxide production or athletic performance.[1,2,3]
This begs the question -- why is l-arginine still used extensively in pre workouts claiming to enhance the pump?
Well, preliminary research using intravenously administered l-arginine (at a massive 30g dose!) elevated nitric oxide levels in sick and healthy humans.[4,5]
The issue is that virtually every single person taking supplements to boost nitric oxide consume them orally.
When l-arginine is supplemented orally, it’s been shown to have no effect compared to an infusion of l-arginine. This is due to arginine’s poor bioavailability, which is around 20%.
When ingested, arginine is rapidly broken down by intestinal arginase and converted to ornithine and urea, which means that if you were to ingest 10g of arginine, you’d only absorb about 2g worth.
To circumvent this issue, you could consume upwards of 20-30g arginine, but that is known to come with great deal of GI distress and stomach upset, which isn’t exactly ideal pre workout.
L-citrulline on the other hand is highly bioavailable, avoids metabolization by arginase, and has been shown to improve blood flow, energy production, and exercise performance.
Much like l-arginine, BCAA supplements have been (and continue to be) one of the most popular and overhyped pre workout (or intra workout) supplements on the market.
BCAA supplements gained notoriety when it was discovered that the trio of amino acids (primarily leucine) activated mTOR -- the biological pathway that triggers muscle protein synthesis.
Additionally, the BCAAs can serve as an energy substrate in skeletal muscle, which may help to limit muscle protein breakdown as well as glycogen depletion during prolonged exercise.
Adding further fuel to the fire were a few early studies indicated that BCAA supplements may help preserve lean mass and even enhance fat loss.[9,10]
However, these studies had a few glaring errors. Namely, the protein intake of the test group was severely deficient. Furthermore, individuals in the test group consumed an amount of BCAA that’s over 10 times higher (52 grams per day!) than what you get in a conventional BCAA supplement!
On top of that, other BCAA research presented results that seem just a bit too good to be true, as it showed consuming 14g of BCAA was superior to consuming 28 grams of whey protein.
Here again, neither overall diet or protein intake was controlled or accounted for by the researchers, which is a pretty substantial oversight considering you’re trying to track increases in performance, size, and strength.
A recent narrative review published in the Journal of Nutritional Health & Food Engineering noted that:
“Despite enough evidence showing the ability of BCAAs, particularly leucine, to up-regulate muscle protein synthesis, there is no provision towards additional benefit to performance or adaptations to resistance and endurance training with supplementation. In conclusion, peri-exercise BCAA supplementation appears to be most effective only in terms of recovery between exercise sessions and the preservation of both muscle mass and muscle performance under states of hypocalorism.”
Now, there is research to indicate that BCAA supplementation may help improve recovery following exercise and reduce soreness, but a 2018 study concluded that:
“BCAA supplementation may mitigate muscle soreness following muscle-damaging exercise. However, when consumed with a diet consisting of ~1.2 g/kg/day protein, the attenuation of muscular performance decrements or corresponding plasma CK levels are likely negligible.”
Basically, if you’re consuming enough protein, the benefits of BCAA supplements are negligible.
There’s also some evidence indicating that BCAA supplementation may decrease dopamine levels.
This is due to the fact that BCAAs (leucine, in particular) competitively inhibits the dopamine precursor, L-Tyrosine.
This is concerning since research indicates that fatigue appears to set in when dopamine levels start to drop while serotonin levels remain elevated.
At the end of the day, if you’re consuming enough total calories and/or dietary protein, consuming BCAA supplements pre workout is unlikely to yield any substantial improvement in performance or lean mass gains.
L-Glutamine is a conditionally essential amino acid that has been touted as a “muscle builder” and performance booster for well over a decade.
Part of the reason that glutamine is considered a “muscle building” ingredient is that it is the most abundant amino acid in the body, with ~61% of bodily stores located in skeletal muscle tissue.
Glutamine is involved in protein synthesis, and it can even serve as a sort of “fuel” for various cells in the body, including important immune system components in lymphocytes and macrophages.
Additionally, glutamine supplementation could theoretically since, in the body, glutamine can:
- Stimulate glycogen synthesis
- Limit accumulation of ammonia
- Reduce muscle damage
- Supporting Krebs (TCA) cycle function
However, a 2019 review titled Glutamine as an Anti-Fatigue Amino Acid in Sports Nutrition
“Most of the studies evaluated observed that glutamine supplementation improved some fatigue markers, such as increased glycogen synthesis and reduced ammonia accumulation, but this intervention did not increase physical performance. Thus, despite improving some fatigue parameters, glutamine supplementation seems to have limited effects on performance.”
Other previous research has shown that glutamine supplementation has absolutely no benefit on athletic performance, strength, muscle growth, or recovery.[20,21,22]
L-Glutamine also has low bioavailability and is primarily utilized by the cells lining the GI tract, which means very little of it (if any) reaches the small intestine and can subsequently be transported to the bloodstream.
Carnitine is an amino acid derivative that supports energy production and “fat burning” by way of acting as the biological taxi for fatty acids.
In case you didn’t know, long-chain fatty acids cannot enter the mitochondria on their own. They require the services of carnitine to transfer them into mitochondria for subsequent β-oxidation (the burning of fatty acids for energy).
Based on the roles of carnitine in the body, it’s thought that supplementing with additional carnitine can improve exercise performance, fat burning, and weight loss.
However, the research doesn’t really pan out as the results are mixed. Some studies find benefit, while others find no performance or lean mass improvements at all.[28,29,30]
A recent 2020 review on Carnitine supplementation also concluded that:
“Theoretically, carnitine supplementation should increase carnitine muscle content thus improving fatty acid oxidation and exercise function in healthy humans. However, so far, no scientific basis supports improvement in exercise performance for healthy individuals or athletes after carnitine supplementation.”
Another 2020 systematic review, including 11 studies, noted that:
“Twenty-four-weeks of LC supplementation did not affect muscle strength in healthy aged women, but significantly increased muscle mass, improved physical effort tolerance and cognitive function in centenarians.”
Furthermore, research indicates that healthy individuals do not need to consume supplemental l-carnitine as the liver and kidneys are capable of generating sufficient amounts from the essential amino acids lysine and methionine to meet daily needs.[24,25,26]
It’s also worth noting, like several of the other ingredients on this list, L-Carnitine suffers from poor bioavailability (between 5-15%).
Basically, carnitine may be helpful to those individuals who do not consume enough protein and/or animal products (vegans, vegetarians, elderly), but healthy individuals do not appear to need and/or benefit from L-carnitine supplementation.
There’s also the carnitine-TMAO link to consider as well.
TMAO (trimethylamine-N-oxide) is considered to be an independent and dose-dependent risk factor for cardiovascular disease (CVD). Long-term supplementation of L-carnitine has been noted to induce an increase of fasting plasma trimethylamine-N-oxide (TMAO) levels.
However, other studies in humans have noted that while L-Carnitine does increase TMAO levels, it doesn’t increase markers of atherosclerosis, inflammation, or oxidative stress.[31,32,33]
Still, researchers make it clear that “additional studies focusing on long-term supplementation and its longitudinal effect on the TMAO metabolism and cardiovascular system are needed.”
Derived from l-arginine, agmatine sulfate is commonly included alongside L-citrulline to prolong and intensify nitric oxide production, blood flow, and muscle pumps.
The reason for this is due to some research indicating that agmatine may indirectly support nitric oxide production via inhibition of arginase -- the enzyme that breaks down arginine -- as well as stimulation of endothelial nitric oxide synthase (eNOS) -- the enzyme that catalyzes NO production in the body.
Theoretically, by limiting arginase activity, blood levels of arginine should remain elevated longer promoting stronger, longer-lasting NO production, blood flow, and muscle pumps.
However, research demonstrating the NO-boosting effects of agmatine when consumed orally in humans is severely lacking.
There is some research suggesting that agmatine may have some neurological and endocrine benefits, including a reduction in perceived pain, but in terms of boosting blood flow and/or athletic performance the evidence just isn’t there yet.
Glycerol combined with water hyperhydration increases total body water when compared with water hyperhydration alone
Research has shown that glycerol ingestion may increase exercise tolerance in terms of time by approximately 24% as well as the length of time that can be spent exercising because of the improvement in physical endurance. Additionally, heart rate during exercise appears to be significantly lower following ingestion of glycerol.[36,37,38]
However, other research has found that hyperhydration with glycerol compared with hyperhydration with water alone does not improve performance.[39,40,41]
Moreover, the doses of glycerol used in these studies (between 1-1.2g/kg of bodyweight) far exceed the paltry 1-3 grams of glycerol (in the form of 65% glycerol-containing supplements) you’ll find in current pre workouts supplements.
Another potential concern is the silica content of glycerol supplements.
In case you weren’t aware, glycerol is extremely hygroscopic, meaning it loves water.
To prevent the glycerol in pre workout supplements from clumping, glycerol liquid is dried into a powder and mixed with copious amounts of silicon dioxide.
The FDA has set upper limits on the consumption of silicon dioxide not to exceed 2% of food total weight. This is mainly because amounts higher than these limits haven’t been sufficiently studied.
It’s also worth mentioning that animal studies suggest that consumption of glycerol monostearate (GMS) increases the exposure to phthalate esters, which can reduce testosterone levels.
Taurine is a conditionally essential amino acid, and an ingredient commonly found in energy drinks and many pre workout supplements.
In the body, taurine is predominantly stored in the heart, brain, and skeletal muscle tissue. It can help cells retain more water due to its osmolytic properties, and it can also act as a fairly potent antioxidant.
Similar to many of the other ingredients on this list, the research surrounding taurine supplementation and exercise performance is mixed.
Some studies indicate that taurine may improve exercise performance and support recovery from damaging and stressful exercise, while others find no significant benefit.[43,44,45,46]
Interestingly, a 2017 study found that a dose of 50 mg/kg dose of taurine outperformed caffeine, placebo, and caffeine + taurine on performance changes after repeated Wingate anaerobic capacity tests.
This evidence is further bolstered by other research noting that that the combination of taurine + caffeine does not improve performance, energy, or attention.[48,49,50,51]
These aforementioned studies (typically using energy drinks which contain taurine and caffeine) did note that the taurine + caffeine combination did reduce feelings of vigor and the stimulating effects of caffeine, likely due to taurine’s effects on GABA -- the body’s primary inhibitory (“downer”) neurotransmitter.
Furthermore, research also noted that the combination of caffeine and taurine actually increased feelings of fatigue.
Based on the current body of evidence, taurine supplementation on its own may offer benefit, but outcomes continue to be mixed regarding taurine supplementation, especially when used in combination with caffeine (as it typically is with pre workout supplements and energy drinks).
The main reason most people take pre workout supplements is for the boost in energy they provide.
This energy infusion largely comes from caffeine -- a stimulant that has been extensively studied and shown to not only be effective for improving exercise performance, but safe (when used in reasonable dosages -- 3-9mg/kg).
However, some pre workout supplements include stimulants beyond caffeine. Ones that are woefully under-researched in human beings.
Included among those stimulants that are unproven, unsafe, and/or not classified as “dietary supplements” are:
- Phenylethylamine (PEA)
- DMBA (AMP Citrate)
- Dendrobium extract
The stimulants, and the potential issues (side effects) they bring, have been discussed at length in previous articles titled:
- Stim Hype! Show Me the Science
- NEW HARVARD STUDY! HIGENAMINE CONCERNS! Stimulant In Some Pre-Workouts And Fat Burners!
Without rehashing the entirety of those previous articles, these stimulants essentially lack extensive safety/performance research in healthy human subjects.
There is also the concern that supplements listing these ingredients on their respective Supplement Facts Panel don’t actually label claims, which is backed up by studies showing just that.[52,53,54,55]
Ketone supplements have steadily risen in popularity in recent years, in large part due to the surge in popularity of ultra-low/no carb diets, including keto and carnivore.
To highlight the points made in those previous articles…
Ketone supplements supply the body with exogenous forms of ketone bodies, specifically beta-hydroxybutyrate (BHB).
In the absence of glucose (the body’s preferred source of energy), BHB serves as the main energy source for cells, in the brain as well as skeletal muscle tissue.
Researchers estimate that a keto-adapted individual can produce 150+ grams of ketones daily after adapting to a complete fast, and between 50-100 grams per day on a properly constructed ketogenic diet.
BHB is also known to[5,57,58]:
- Combat oxidative stress
- Reduce inflammation
- Support cognition in individuals with neurological disorders
When you also take into consideration that BHB is capable of delivering more energy per unit of oxygen consumed than either glucose or fatty acids (the two fuels typically used by skeletal muscles during exercise), it stands to reason that consuming more of them in the peri-workout window would improve performance via greater energy production.
Unfortunately, when it comes to boosting exercise performance, the data does not really support the use of exogenous ketone supplements (BHB salts and ketone esters).
In particular, supplementation with exogenous ketones is noted to[59,60]:
- Result in decreased average power output
- Inhibit the use of glycogen
- Offer no improvement in cognitive performance following exercise
A 2017 review on Ketone Bodies and Exercise Performance concluded that:
“...there is currently no evidence to support the use of ketone bodies as an ergogenic aid under conditions where optimal evidence based nutritional strategies are applied.”
Until more research is published noting improvements in performance following ketone supplementation, it simply doesn’t make sense to supplement with them pre workout.
Seeing this on the list might cause you to blink twice as whenever you hear about antioxidants, it’s usually in reference to how good they are for you on account of their ability to help prevent or delay various types of cell damage brought on by reactive oxygen and nitrogen species (RONS).
And while this is certainly true, and antioxidants due serve a very important purpose, if you want to maximize the benefits of intense exercise, you may want to avoid taking high doses of antioxidants around your training.
You see, what makes antioxidants so great is also their downfall -- their ability to suppress free radicals and inflammation.
Intense exercise serves as a powerful (and beneficial) stressor to the body that generates free radicals, and it also causes acute inflammation in the working muscle tissue. Specifically, RONS can act as intracellular messengers that induce changes in cell function and regulate gene expression.
To date, the majority of studies investigating antioxidant supplementation and exercise is focused on minimizing exercise-induced muscle damage, oxidative stress, and inflammation, which would help athletes recover faster from training, but may not necessarily improve their adaptations to intense exercise.
In other words, high dose antioxidants taken around training might help you recover better and experience less damage to skeletal muscle tissue, but it could also blunt/hinder the body’s ability to improve and grow bigger/stronger.
More specifically, research indicates that high-dose supplementation with potent antioxidants, including vitamin C and E, may negate some of the beneficial effects of exercise, especially in regards to insulin signaling and glucose metabolism.
Additional research notes that antioxidants may delay recovery, reduce performance, and impair strength and hypertrophy gains.[65,66,67,72]
Moreover, a recent 2020 systematic review and meta-analysis titled “The Effects of Strength Training Combined with Vitamin C and E Supplementation on Skeletal Muscle Mass and Strength: A Systematic Review and Meta-Analysis” concluded that:
“Most of the evidence suggests that this kind of supplementation does not potentiate muscle growth and could possibly attenuate hypertrophy over time.”
It is worth noting that there are studies noting improvements in exercise performance with acute supplementation of antioxidants.[69,70,71]
Still, if you’re looking to maximize the adaptations to be had from resistance training or other forms of strenuous exercise, it may be best to avoid high-dose antioxidants in the peri-workout window.
Now, we should also mention, this doesn’t include natural sources of polyphenols and flavonoids, such as grape seed extract, pine bark extract, etc. These natural sources of antioxidants do not appear to be as detrimental to exercise adaptations as high-dose synthetic antioxidants.[73,74]
There is an endless supply of pre workout supplements on the market, and with each passing day/week, more enter the space.
But, not all pre workout supplements are created equal (or are even legal!).
Advanced Molecular Labs prides itself on using ingredients in its pre workouts with solid scientific backing conducted in humans.
When choosing which products to spend your hard-earned money on, choose products formulated using ingredients that are backed by legitimate research studies.
- Liu T-H, Wu C-L, Chiang C-W, Lo Y-W, Tseng H-F, Chang C-K. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J Nutr Biochem. 2009;20(6):462-468. doi:10.1016/j.jnutbio.2008.05.005.
- Alvares TS, Conte-Junior CA, Silva JT, Paschoalin VMF. L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation. Nutr Res. 2014;34(1):31-39. doi:10.1016/j.nutres.2013.10.006.
- Robinson TM, Sewell DA, Greenhaff PL. L-arginine ingestion after rest and exercise: effects on glucose disposal. Medicine and science in sports and exercise. 2003;35(8):1309-1315.
- Bode-Böger SM, Böger RH, Galland A, Tsikas D, Frölich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic–pharmacodynamic relationship. British Journal of Clinical Pharmacology. 1998;46(5):489-497. doi:10.1046/j.1365-2125.1998.00803.x.
- Bode-Boger SM, Boger RH, Alfke H, et al. L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study. Circulation. 1996;93(1):85-90.
- Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British journal of clinical pharmacology. 2008;65(1):51-59.
- Lynch CJ. Role of leucine in the regulation of mTOR by amino acids: revelations from structure-activity studies. J Nutr. 2001;131(3):861S-865S. http://jn.nutrition.org/content/131/3/861S.long
- Mero, A. (1999). Leucine supplementation and intensive training. Sports Medicine (Auckland, N.Z.), 27(6), 347–358.
- Wolfe, RR; “Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?”; J Int Soc Sports Nutr; 14(1):30; 2017;
- Howatson G, Hoad M, Goodall S, Tallent J, Bell PG, French DN; “Exercise-induced muscle damage is reduced in resistance-trained males by branched chain amino acids: a randomized, double-blind, placebo controlled study”; Journal of the International Society of Sports Nutrition; 9:20; 2012;
- Stoppani, Jim, et al; “Consuming a supplement containing branched-chain amino acids during a resistance-training program increases lean mass, muscle strength and fat loss”; Journal of the International Society of Sports Nutrition; 2009; 6(Suppl 1):P1;
- Freund H, Hoover HC, Atamian S, Fischer JE; “Infusion of the Branched Chain Amino Acids in Postoperative Patients: Anticatabolic Properties. Annals of Surgery”; 1979; 190(1):18-23;
- Fedewa MV, Spencer SO, Williams TD, Becker ZE, Fuqua CA. Effect of branched-Chain Amino Acid Supplementation on Muscle Soreness following Exercise: A Meta-Analysis. Int J Vitam Nutr Res. 2019 Nov;89(5-6):348-356. doi: 10.1024/0300-9831/a000543. Epub 2019 Apr 2. PMID: 30938579.
- VanDusseldorp TA, Escobar KA, Johnson KE, et al. Effect of Branched-Chain Amino Acid Supplementation on Recovery Following Acute Eccentric Exercise. Nutrients. 2018;10(10):1389. Published 2018 Oct 1. doi:10.3390/nu10101389
- Neuhaus AH, Goldberg TE, Hassoun Y, et al. Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects. Schizophrenia research. 2009;111(0):167-173. doi:10.1016/j.schres.2009.03.023.
- Heijnen S, Hommel B, Kibele A, Colzato LS. Neuromodulation of Aerobic Exercise-A Review. Front Psychol. 2016;6:1890. Published 2016 Jan 7. doi:10.3389/fpsyg.2015.01890
- Mourier A, Bigard AX, de Kerviler E, Roger B, Legrand H, Guezennec CY. Combined effects of caloric restriction and branched-chain amino acid supplementation on body composition and exercise performance in elite wrestlers. Int J Sports Med. 1997 Jan;18(1):47-55. doi: 10.1055/s-2007-972594. PMID: 9059905.
- Morse T, Willoughby DS. Efficacy of BCAA supplementation for exercise performance and recovery: a narrative review. J Nutr Health Food Eng.2019;9(3):128‒ DOI: 10.15406/jnhfe.2019.09.00337
- Coqueiro AY, Rogero MM, Tirapegui J. Glutamine as an Anti-Fatigue Amino Acid in Sports Nutrition. Nutrients. 2019;11(4):863. Published 2019 Apr 17. doi:10.3390/nu11040863
- GC, Phillips. "Glutamine: the Nonessential Amino Acid for Performance Enhancement. - PubMed - NCBI." National Center for Biotechnology Information.
- Candow DG , et al. "Effect of Glutamine Supplementation Combined with Resistance Training in Young Adult - PubMed - NCBI." National Center for Biotechnology Information.
- Ramezani Ahmadi A, et al. The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials . Clin Nutr. (2018)
- Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta. 2016;1863(10):2422-2435. doi:10.1016/j.bbamcr.2016.01.023
- Rebouche CJ. Carnitine. In: Modern Nutrition in Health and Disease, 9th Edition (edited by Shils ME, Olson JA, Shike M, Ross, AC). Lippincott Williams and Wilkins, New York, 1999, pp. 505-12.
- The editors. Carnitine: lessons from one hundred years of research. Ann NY Acad Sci 2004;1033:ix-xi.
- National Research Council. Food and Nutrition Board. Recommended Dietary Allowances, 10th Edition. National Academy Press, Washington, DC, 1989.
- Gnoni A, Longo S, Gnoni GV, Giudetti AM. Carnitine in Human Muscle Bioenergetics: Can Carnitine Supplementation Improve Physical Exercise?. Molecules. 2020;25(1):182. Published 2020 Jan 1. doi:10.3390/molecules25010182
- Shannon CE, Ghasemi R, Greenhaff PL, Stephens FB. Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training. Scand J Med Sci Sports. 2018 Jan;28(1):107-115. doi: 10.1111/sms.12885. Epub 2017 May 12. PMID: 28345160.
- Koozehchian MS, Daneshfar A, Fallah E, et al. Effects of nine weeks L-Carnitine supplementation on exercise performance, anaerobic power, and exercise-induced oxidative stress in resistance-trained males. J Exerc Nutrition Biochem. 2018;22(4):7-19. doi:10.20463/jenb.2018.0026
- Sawicka, A.K., Renzi, G. & Olek, R.A. The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr 17, 49 (2020). https://doi.org/10.1186/s12970-020-00377-2
- Samulak JJ, Sawicka AK, Hartmane D, Grinberga S, Pugovics O, Lysiak-Szydlowska W, Olek RA. L-Carnitine supplementation increases Trimethylamine-N-oxide but not markers of atherosclerosis in healthy aged women. Ann Nutr Metab. 2019;74(1):11–7. https://doi.org/10.1159/000495037.
- Olek RA, Samulak JJ, Sawicka AK, Hartmane D, Grinberga S, Pugovics O, Lysiak-Szydlowska W. Increased Trimethylamine N-oxide is not associated with oxidative stress markers in healthy aged women. Oxidative Med Cell Longev. 2019;2019:6247169. https://doi.org/10.1155/2019/6247169.
- Fukami K, Yamagishi S, Sakai K, Kaida Y, Yokoro M, Ueda S, Wada Y, Takeuchi M, Shimizu M, Yamazaki H, et al. Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients. J Cardiovasc Pharmacol. 2015;65(3):289–95. https://doi.org/10.1097/FJC.0000000000000197.
- Mun CH, Lee WT, Park KA, Lee JE. Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. Anat Cell Biol. 2010;43(3):230-40.
- Keynan O , et al. "Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial- PubMed - NCBI." National Center for Biotechnology Information.
- Burelle Y, Massıcotte D, Lussıer M, Lavoıe C, Hıllaıre-Marcel C, Peronnet F. Oxidation of [13C] glycerol ingested along with glucose during prolonged exercise. J Appl Physiol. 2001;90:1685–1690.
- Montner P, Stark DM, Riedesel ML, Murata G, Robergs R, Timms M, Chick TW. Pre-exercise glycerol hydration improves cycling endurance time. Int J Sports Med. 1996;17:27–33.
- Coutts A, Reaburn P, Mummery K, Holmes M. The effect of glycerol hyperhydration on Olympic distance triathlon performance in high ambient temperatures. Int J Sport Nutr Exer Metabol. 2002;12:105–119.
- Pense M, Turnagöl H. Effects of Glycerol-Induced Hyperhydration on Cardiovascular Functions and Endurance Performance in Athletes During the Course of Treadmill Exercise Performed at High Temperatures. World Appl Sci J. 2011;12:1114–1124.
- Inder WJ, Swanney MP, Donald RA, Prickett TC, Hellemans J. The effect of glycerol and desmopressin on exercise performance and hydration in triathletes. Med Sci Sports Exer. 1998;30:1263–1269.
- Magal M, Webster MJ, Sistrunk LE, Whitehead MT, Evans RK, Boyd JC. Comparison of glycerol and water hyperhydration regimens on tennisrelated performance. Med Sci Sports Exer. 2003;35:150–156.
- Gao HT, Xu R, Cao WX, et al. Food Emulsifier Glycerin Monostearate Increases Internal Exposure Levels of Six Priority Controlled Phthalate Esters and Exacerbates Their Male Reproductive Toxicities in Rats. PLoS One. 2016;11(8):e0161253. Published 2016 Aug 30. doi:10.1371/journal.pone.0161253
- Balshaw TG, Bampouras TM, Barry TJ, Sparks SA. The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners. Amino Acids. 2013;44(2):555– doi: 10.1007/s00726-012-1372-1. [PubMed] [CrossRef] [Google Scholar]
- Waldron, M., Patterson, S.D. & Jeffries, O. Oral taurine improves critical power and severe-intensity exercise tolerance. Amino Acids 51, 1433–1441 (2019). https://doi.org/10.1007/s00726-019-02775-6
- Rutherford JA, Spriet LL, Stellingwerff T. The effect of acute taurine ingestion on endurance performance and metabolism in well-trained cyclists. Int J Sport Nutr Exerc Metab. 2010;20(4):322–329. doi: 10.1123/ijsnem.20.4.322. [PubMed] [CrossRef] [Google Scholar]
- Milioni F, Malta Ede S, Rocha LG, Mesquita CA, De Freitas EC, Zagatto AM. Acute administration of high doses of taurine does not substantially improve high-intensity running performance and the effect on maximal accumulated oxygen deficit is unclear. Appl Physiol Nutr Metab. 2016;41(5):498–503. doi: 10.1139/apnm-2015-0435.
- Warnock R, Jeffries O, Patterson S, Waldron M. The effects of caffeine, taurine, or caffeine-taurine coingestion on repeat-sprint cycling performance and physiological responses. Int J Sports Physiol Perform. 2017;12(10):1341–1347. doi: 10.1123/ijspp.2016-0570.
- Jeffries, O., Hill, J., Patterson, S. D., & Waldron, M. (2017). Energy Drink Doses Of Caffeine And Taurine Have A Null Or Negative Effect On Sprint Performance. The Journal of Strength & Conditioning Research
- Bichler, A., Swenson, A., & Harris, M. A. (2006). A combination of caffeine and taurine has no effect on short term memory but induces changes in heart rate and mean arterial blood pressure. Amino Acids, 31(4), 471–476. https://doi.org/10.1007/s00726-005-0302-x
- Giles, G. E., Mahoney, C. R., Brunye, T. T., Gardony, A. L., Taylor, H. A., & Kanarek, R. B. (2012). Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose. Pharmacology, Biochemistry, and Behavior, 102(4), 569–577. https://doi.org/10.1016/j.pbb.2012.07.004
- Peacock A, Martin FH, Carr A. Energy drink ingredients. Contribution of caffeine and taurine to performance outcomes. Appetite. 2013;64:1–4
- Cohen, P.A., Travis, J.C. and Venhuis, B.J. (2014), A methamphetamine analog (N,α‐diethyl‐phenylethylamine) identified in a mainstream dietary supplement. Drug Test. Analysis, 6: 805-807. doi:1002/dta.1578
- Catalani V, Prilutskaya M, Al-Imam A, et al. Octodrine: New Questions and Challenges in Sport Supplements. Brain Sci. 2018;8(2):34. Published 2018 Feb 20. doi:10.3390/brainsci8020034
- Cohen PA, Travis JC, Keizers PHJ, Deuster P, Venhuis BJ. Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylamylamine (1,3-DMAA) and 1,3-dimethylbutylamine (1,3-DMBA). Clin Toxicol (Phila). 2018 Jun;56(6):421-426. doi: 10.1080/15563650.2017.1398328. Epub 2017 Nov 8. PMID: 29115866.
- Cohen PA, Travis JC, Keizers PHJ, Boyer FE, Venhuis BJ. The stimulant higenamine in weight loss and sports supplements. Clin Toxicol (Phila). 2019 Feb;57(2):125-130. doi: 10.1080/15563650.2018.1497171. Epub 2018 Sep 6. PMID: 30188222.
- Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT. Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life. 2017 May;69(5):305-314. doi: 10.1002/iub.1627. Epub 2017 Apr 3. PMID: 28371201.
- Haces ML, Hernández-Fonseca K, Medina-Campos ON, Montiel T, Pedraza-Chaverri J, Massieu L. Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions. Exp Neurol. 2008 May;211(1):85-96. doi: 10.1016/j.expneurol.2007.12.029. Epub 2008 Jan 26. PMID: 18339375.
- Yamanashi, T., Iwata, M., Kamiya, N. et al. Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. Sci Rep 7, 7677 (2017). https://doi.org/10.1038/s41598-017-08055-1
- O’Malley, T., Myette-Cote, E., Durrer, C., & Little, J. P. (2017). Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Applied Physiology, Nutrition, and Metabolism, 42(10), 1031–1035. https://doi.org/10.1139/apnm-2016-0641
- Waldman, H. S., Basham, S. A., Price, F. G., Smith, J. W., Chander, H., Knight, A. C. McAllister, M. J. (2018). Exogenous ketone salts do not improve cognitive responses after a high-intensity exercise protocol in healthy college-aged males. Applied Physiology, Nutrition, and Metabolism, 43(7), 711–717. https://doi.org/10.1139/apnm-2017-0724
- Pinckaers PJM, Churchward-Venne TA, Bailey D, van Loon LJC. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Medicine (Auckland, N.z). 2017;47(3):383-391. doi:10.1007/s40279-016-0577-y.
- Griffiths K, Aggarwal BB, Singh RB, Buttar HS, Wilson D, De Meester F. Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention. Diseases. 2016;4(3):28. Published 2016 Aug 1. doi:10.3390/diseases4030028
- Bentley DJ, Ackerman J, Clifford T, et al. Acute and Chronic Effects of Antioxidant Supplementation on Exercise Performance. In: Lamprecht M, editor. Antioxidants in Sport Nutrition. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 9. Available from: https://www.ncbi.nlm.nih.gov/books/NBK299045/
- Ristow M, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. (2009)
- Gomez-Cabrera MC, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. (2008)
- Close GL, et al. Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr. (2006)
- Webb R, et al. The Ability of Exercise-Associated Oxidative Stress to Trigger Redox-Sensitive Signalling Responses. Antioxidants (Basel). (2017)
- Dutra MT, Martins WR, Ribeiro ALA, Bottaro M. The Effects of Strength Training Combined with Vitamin C and E Supplementation on Skeletal Muscle Mass and Strength: A Systematic Review and Meta-Analysis. J Sports Med (Hindawi Publ Corp). 2020 Jan 8;2020:3505209. doi: 10.1155/2020/3505209. PMID: 31970196; PMCID: PMC6973181.
- Medved I, Brown M. J, Bjorksten A. R, McKenna M. J. Effects of intravenous N-acetylcysteine infusion on time to fatigue and potassium regulation during prolonged cycling exercise. Journal of Applied Physiology. 2004;96:211–217.
- McKenna M. J, Medved I, Goodman C. A. et al. N-acetylcysteine attenuates the decline in muscle Na+ , K+-pump activity and delays fatigue during prolonged exercise in humans. The Journal of Physiology. 2006;576:279–288.
- MacRae H SH, Mefferd K. M. Dietary antioxidant supplementation combined with quercetin improves cycling time trial performance. International Journal of Sport Nutrition and Exercise Metabolism. 2006;16:405–419.
- Paulsen G, Cumming KT, Holden G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol. 2014;592(8):1887-1901. doi:10.1113/jphysiol.2013.267419
- Lafay S, Jan C, Nardon K. et al. Grape extract improves antioxidant status and physical performance in elite male athletes. Journal of Sports Science and Medicine. 2009;8:468–480.
- Jong K K, Charles L S. Effects of Grape Seed Extract Supplementation on Exercise Performance in Athletes. Res Inves Sports Med. 2(1). RISM.000531.2018. DOI: 10.31031/RISM.2018.02.000531