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science nutrition <strong>blog</strong>

By Robert Schinetsky

 

Pre workout supplements define a supplement brand, so much so that they live (and die) based on how those products perform. As you can imagine, the pre workout category is extremely competitive with hundreds of companies (and influencers) vying for your attention, and more importantly, your hard-earned money.

This can leave consumers in a bind -- how to decide what is the best pre workout supplement amidst the increasingly polluted pre workout landscape.

Well save you a lot of time searching on Google, Amazon or in your local brick-and-mortar…

Discover AML PRE XTREME – the most advanced, science-backed pre-workout formula for explosive energy, focus, & performance. Fuel your workouts like never before!

NEW AML Pre Xtreme is the best pre workout supplement; one that utilizes the most advanced formula based on scientific research in humans.

NEW AML Pre Xtreme is designed to support increased energy, mental alertness, muscular endurance, strength, and lean body mass.

What separates NEW AML Pre Xtreme from the competition?

Youre about to find out…

AML Pre Xtreme Ingredients

L-Citrulline (10,000mg)

L-Citrulline is an amino acid found in various melons that is prized for its blood flow- and performance-enhancing benefits. Its converted to L-arginine, where its used by endothelial cells to synthesize nitric oxide (NO) via the L-arginine-NO pathway.

Increased vasodilation and blood flow may help delay fatigue by allowing greater oxygen and nutrient delivery to the working muscles to enhance strength and power expression as well as the replenishment of ATP.[1] Keep in mind that increased vasodilation and blood flow also support healthy blood pressure levels and cardiovascular health.

 Interestingly, while arginine is the direct precursor to nitric oxide, l-citrulline has been shown to be a superior option for increasing plasma levels of l-arginine compared to l-arginine supplementation and comes with less GI discomfort.[2]

Research finds that citrulline may help[3,4,5,6,7]:

      Improve VO2 kinetics

      Boost energy production

      Enhance time-to-exhaustion (TTE)

      Increase the number of repetitions performed

      Reducing the rate of perceived exertion (RPE).

 Not only can citrulline improve performance (and muscle pumps!), other research finds that it may help to reduce muscle soreness up to 40% in the hours following training.[5]

Creatine Monohydrate (5,000mg)

Among the hundreds (if not thousands) of dietary supplements available, none has the track record or body of research that creatine monohydrate has. Quite simply, it is the metric by which all other dietary supplements are judged.

Supplementation with creatine, in combination with resistance training, has been shown to support better outcomes (compared to resistance training alone) in:[8

      Energy production

      Power

      Strength output

      Lean mass gain

Creatine also supports recovery by reducing muscle damage following exercise.[9]

The International Society of Sports Nutrition position stand on creatine monohydrate emphatically states[8]:

 "Creatine monohydrate is the most effective ergogenic nutritional supplement currently available to athletes with the intent of increasing high-intensity exercise capacity and lean body mass during training…

Creatine monohydrate supplementation is not only safe, but has been reported to have a number of health benefits in healthy and diseased populations ranging from infants to the elderly. There is no compelling scientific evidence that the short- or long-term use of creatine monohydrate (up to 30 g/day for 5 years) has any detrimental effects on otherwise healthy individuals or among clinical populations who may benefit from creatine supplementation…

At present, creatine monohydrate is the most extensively studied and clinically effective form of creatine for use in nutritional supplements in terms of muscle uptake and ability to increase high-intensity exercise capacity.”

Not Just for Improving Performance and Lean Body Mass

In addition to improving athletic performance and lean mass gains, a burgeoning body of research is finding that creatine helps support cognitive function, mood, and neuroprotection. Another important point to keep in mind is that although the brain represents only 2 percent of total body weight, it uses approximately 20 percent of the bodys energy. Since the brain requires significant ATP turnover, creatine metabolism and the creatine kinase/phosphocreatine system are vital for normal brain function.[68]

A 2024 systematic review and meta-analysis published in Frontiers in Nutrition concluded that, Current evidence suggests that creatine monohydrate supplementation may confer beneficial effects on cognitive function in adults, particularly in the domains of memory, attention time, and information processing speed.”[64]

Traumatic brain injury (TBI) are detrimental to the brain in numerous ways and disrupt typical brain functioning. Its estimated that 50–60 million individuals worldwide are affected by TBIs each year, and approximately half of worlds population will sustain a TBI in their lifetime.[69] A new review in Missouri Medicine concluded that ...creatine may enhance recovery from TBI, as it directly targets derangements from such trauma.”[69] Prior research also shows that creatine supplementation reduced neuronal damage, protected against the effects of cellular energy crisis and improved cognitive and somatic symptoms.”[70]

Recently a 8-week pilot study found that creatine monohydrate helps support individuals with depression.[67]

Last, but not least, a new systematic review and meta-analysis concluded that creatine directly targets myocardial cells to protect their function and minimize injury to the heart muscle.[71]

When Should I Take Creatine?

Regarding the best” time to take creatine, some research indicates that post-workout may be slightly better than pre-workout. Still, other studies find that pre-exercise creatine may be more optimal due to increased blood flow during exercise and subsequent uptake by muscle cells.[65,66]

Keep in mind, though, that these are a limited number of studies, and the much more important factor is that creatine monohydrate is consistently taken (daily).[65,66]

To make things convenient for you, weve included a full 5,000mg of creatine monohydrate in every serving of AML Pre Xtreme. And, if you take a serving of AML Post Workout youll receive another full 5,000mg creatine monohydrate!

Beta Alanine (3,200mg)

Beta alanine is renowned for two things -- its ability to boost endurance and the tingles it induces. For those of you unfamiliar with beta alanine, those tingles” (technically known as paresthesia) are completely normal, and they usually subside once youre saturated with beta alanine (which usually takes between 4-8 weeks, depending on your dosing protocol).

 Higher dosages of beta alanine (greater than 3,200mg) per serving can cause more severe “tingles”, which many feel is undesirable.

As for why beta alanine is in AML Pre Xtreme…when muscles repeatedly contract (such as during a high rep set or sprint), hydrogen ions (H+) begin to accumulate in the muscle. As these ions build up, the muscle pH becomes more acidic, which eventually prevents the muscle from being able to contract.

Beta alanine is the rate-limiting precursor to carnosine synthesis, and carnosine is a formidable intracellular buffer that helps neutralize H+ ions.[9]

Essentially, supplementation with beta alanine increases carnosine concentrations in skeletal muscle tissue, thereby improving a muscles capacity to buffer H+ ions and delay the onset of fatigue. This helps athletes to complete more repetitions and more total work before succumbing to fatigue, which should result in greater gains in performance, muscle and strength over the long term.

To date, beta alanine has been studied across many athletic endeavors, including boxing, martial arts, running, high-intensity interval training, and resistance training, and shown to improve time-to-exhaustion, resistance to fatigue, and muscle growth.[10,11] 

New Study! Creatine + Beta Alanine + L-Citrulline for Better Performance

Most often dietary supplements are studied in isolation. Very rarely are they studied in combination; however, most of us take these various ergogenics in combination, not isolation.

New research published in the International Journal of Sports Physiology and Performance investigated the effects of Creatine (0.1g/kg) vs Beta Alanine (4.8g/day) vs L-Citrulline (6g) vs a combination of all three vs placebo in healthy young athletes.[72]

The athletes performed a variety of athletic tests, including short-sprint interval training (3 sets of 10 repetitions of 5-s all-out runs) sessions 3 times a week for 4 weeks. At the end of the trial, the researchers found that supplementation with the three most common pre workout ingredients, both individually and in combination, significantly improved physical and physiological performance compared to placebo.[72]

Betaine Anhydrous (2,500mg)

Betaine (trimethylglycine) is a natural osmolyte found in a number of foods common to the diet, including whole grains, shellfish, spinach, and sugar beets.[12]

It plays a key role in several aspects of human health, including the methylation of homocysteine. In fact, aside from methylfolate, betaine is the only molecule that provides methyl groups for homocysteine remethylation.[13]

Research indicates that high levels of homocysteine can be a risk factor for heart disease.[14]

As an osmolyte, betaine also helps maintain cell volume and fluid balance, which may help guard against dehydration during stressful events such as intense exercise.

Betaine also increases intracellular water, which encourages cell volumization and cellular swelling. This promotes muscle growth by way of stimulating muscle protein synthesis.

Additional research indicates that betaine supplementation may significantly increase anaerobic power, muscle protein synthesis, and body composition.[15,16,17,18,19]

Beyond its performance and physique benefits, researchers have discovered that diets high in betaine may support certain vital organs (including the heart and liver) and improve ones health.

Citrulline Nitrate (2,000mg)

Most pre workout supplements include L-citrulline to boost NO production, athletic performance, and pump. What you may not realize is that your body includes two independent pathways for nitric oxide synthesis. We’ve already mentioned the Citrulline→Arginine→NO Pathway. The other pathway is the Nitrate→Nitrite→NO pathway.

What Are Nitrates?

Nitrates are polyatomic ions composed of nitrogen and oxygen that are naturally occurring in air, soil, water, and some foods, including arugula (rocket), and spinach. In supplements, they usually come in the form of amino-bound nitrates, such as citrulline nitrate or creatine nitrate.

Why Include Nitrates in AML Pre Xtreme?

Nitrates increase vasodilation and blood flow. As we mentioned above, increased vasodilation and blood flow supports increased exercise performance and cardiovascular health.

Research on dietary nitrate or nitrate supplements find that it can boost skeletal muscle contractility, peak power output, and mean power outputs in healthy humans.[20,21]

A meta-analysis of six studies including healthy recreationally-trained men and women found that dietary nitrate significantly improved time-to-peak power.[22]

Doses used in the trials ranged from 5.6 to ~13 mmol nitrate (347.2 to 806mg of nitrate). Note: a easy way to convert mmol of nitrates to mg is: 1mmol ≅ 62mg nitrate.[23]

As potent as nitrate supplements are, its important to time their intake as they require more time to load” than other NO-enhancing supplements, such as L-Citrulline. A 2021 narrative review on the effects of nitrate supplementation on exercise concluded that, Nitrates are an effective ergogenic aid when taken acutely or chronically in the range of ~5–16.8 mmol (~300–1041 mg) 1–3 h before exercise…”[24]

AML Pre Xtreme contains 2,000mg of Citrulline Nitrate (as NO3-T®), supplying 540mg nitrate.

L-Tyrosine (2,000mg)

L-Tyrosine is an amino acid that supports the biosynthesis of the motivation and reward” molecule (dopamine) as well as several other important neurotransmitters, including epinephrine (adrenaline), and norepinephrine (noradrenaline).

Supplementing with L-tyrosine supplies extra raw material” to support neurotransmitter and catecholamine production during stressful situations, such as a high-volume resistance training.

Dopamine: More Than Motivation & Reward

While dopamine is primarily known for its role in feelings of reward and motivation, this just begins to scratch the surface of the many ways in which this neurotransmitter affects health and well-being. It also plays an important role in mood, memory, and motor control. Research even shows that supplementing with dopamine precursors, such as L-tyrosine and mucuna pruriens (which well discuss down below, may also support increased energy expenditure and weight loss.[25,26,27]

As you might expect, deficiencies in dopamine can adversely impact motivation, performance, mood, and cognition.

Stress (such as intense exercise) can reduce dopamine stores in the brain, leading to increased feelings of fatigue and reduced athletic performance.[28]

AML Pre X-Treme contains 2,000 mg of L-Tyrosine -- the same dose used in human research trials found to enhance mental and physical performance.[29,30]

Caffeine Anhydrous (400mg)

Extreme” pre workouts often rely on a cocktail of stimulants, including hordenine, higenamine, yohimbine, DMHA, DMAA, and/or eria jarensis to provide the kick in the teeth” sensation that stim junkies crave. However, these stimulants lack the safety data or increased performance metrics of caffeine.

Caffeine is the king of psychostimulants, backed by hundreds of studies demonstrating its benefits in the areas of alertness, cognitive performance, athletic performance, energy expenditure, and weight loss.[31]

And, if youve had a poor nights sleep, a higher dose of caffeine (6mg/kg) can offset the decline in performance associated with sleep deprivation.[32]

The worlds most popular stimulant also supports the release of dopamine in the brain as well as upregulates dopamine receptor availability and affinity.[33,34]

No other stimulant touts the body of research or high safety profile that caffeine does.

At 400mg per full serving, AML Pre Xtreme provides a science-based dosage and more than enough jolt to get you mentally and physically prepared for whatever athletic endeavor lies ahead!

Velvet Bean Seed Extract (100mg)

To further support dopamine synthesis, AML Pre Xtreme includes a generous 100mg of mucuna pruriens (velvet bean), which contains a natural source of L-Dopa -- the direct precursor to dopamine.

This plant has a rich history of use in traditional medicin as a tonic and aphrodisiace due to its broad spectrum of activities. Its also been found to possess neuroprotective, anti-inflammatory, and analgesic properties.[35]

Interestingly, research in Nutrients, found that mucuna pruriens extract offered greater neuroprotective and acetylcholinesterase inhibitory activity compared to synthetic L-Dopa.[36,37]

Newly published research in Brain, Behavior & Immunity found that L-Dopa administration improved improved connectivity within a key brain reward pathway after just one week.[38]

Grape Skin Extract (100mg)

Grape skin extract is rich in a variety of polyphenols (including proanthocyanidins) which have been noted to stimulate endothelial nitric oxide synthase (eNOS) and improve oxygen delivery to working muscles.[39,40]

Studies using polyphenol-rich extracts note significant increases in average power (5%), total power output (5%), and maximal peak power output (3.7%).[41] 

Additional research notes that grape seed extract supplementation can reduce muscle damage after high intensity strength training.[42,43]

AML PreWorkout X-Treme contains 100mg grape skin extract (standardized to 30% polyphenols).

BioPerine (5mg)

BioPerine is the industry-standard black pepper extract included for its ability to improve nutrient bioavailability. Piperine, the primary bioactive in black pepper, inhibits the drug-metabolizing enzyme CYP3A4 as well as the drug transporter P-glycoprotein.[44]

Inhibition of CYP3A4 can help extend the lifespan” of various nutrients, thereby increasing their efficacy and duration of effects.

Piperine also has been noted to increase dopamine via activation of the TRPV receptor in the brain and inhibition of MAO.[45,46]

MAO (monoamine oxidase) is the enzyme that breaks down mood-boosting neurotransmitters in the body, including serotonin and dopamine. By inhibiting MAO, BioPerine may help dopamine levels remain elevated longer for greater energy, mood, and motivation!

Essential Electrolytes

Electrolytes are charged ions that help regulate fluid balance, muscle contraction/relaxation, cardiovascular function, and a whole host of other physiological processes. Two of the most important, in regards to exercise performance, are potassium and magnesium.

Research notes that potassium can soften the endothelium and increase nitric oxide production while magnesium aids vasodilation by increasing nitric oxide synthase activity.[47,48]

AML Pre Xtreme supplies 500mg Potassium (from potassium citrate) + 100mg magnesium (from magnesium citrate)

The Benefits of Citrate

Citrate forms of electrolytes have been shown to offer better bioavailability compared to other forms, such as oxide-bound electrolytes. Additionally, citrate has also been noted to improve exercise performance by buffering lactic acid accumulation in muscle cells.[49,50]

Additionally, the combination of potassium citrate, magnesium citrate, grape skin extract, L-Citrulline, and nitrates can offset the blood pressure-raising effects of caffeine in individuals that are stimulant-sensitive.

Citrate vs Sodium Bicarbonate

On February 18, 2025, The Wall Street Journal published a piece by Rachel Bachman concerning a new indoor mile world record set by Norwegian Jakob Ingebrigtsen.[51]

Within the article, Bachman states that track athletes are increasingly using sodium bicarbonate (household baking soda) for its blood buffering benefits.

However, large doses of sodium bicarbonate are required, and high intakes often lead to severe GI distress. Citrate supplements, on the other hand, are preferable to sodium bicarbonate because it does not have adverse effects on the gastrointestinal system.[52]

And, research has shown that sodium citrate appears to be a better option than sodium bicarbonate in terms of performance and adverse effects (headaches, GI distress, etc.).[53]

Folate(1360mcg) Folic Acid (800mcg)

Folic Acid (folate) is an essential B-vitamin required for numerous biological processes, including the production of BH4 (tetrahydrobiopterin) -- a cofactor required for dopamine synthesis.

Research notes an association between low dopamine levels (which are linked to depression) and low intakes of folic acid.[54]

Folic acid supplementation supports dopamine production by providing the body with necessary substrate required to build the enzyme which is considered the rate-limiting” step in the synthesis of dopamine.[55]

BH4 is also required for nitric oxide production.[56]

Essentially, folic acid is a key supporting actor” thats often overlooked by competitors. It affects both dopamine and nitric oxide (NO), which (both) can impact exercise performance.

Whats Not in AML Pre Xtreme

Gray” area stimulants

As we mentioned above, AML Pre Xtreme does NOT include illegal and/or unsafe stimulants that are commonly found in competitor extreme” pre workouts, such as:

      DMAA

      DMHA

      AMP Citrate

      Dendrobium

      Hordenine

      Higenamine

      M-synephrine

      Noopept

      Juglans Regia extract

      Eria jarensis extract

For more information on why these stimulants are not included in any AML supplements, read our article titled: Stimulant Warning: "Stim Bombs: Cracked Out!”

No Acetylcholine Precursors

Acetylcholine is an important neurotransmitter involved in learning, memory, and the mind-muscle connection. The neurotransmitter dopamine also plays an essential (yet overlooked) role in exercise where it helps to motivate people and help them push harder during intense physical activity (thereby allowing for greater performance and results).

Nevertheless, pre workout supplements frequently contain acetylcholine precursors, such as choline bitartrate, choline citrate or alpha-GPC, and neglect to include dopamine precursors.

What many individuals dont realize is that acetylcholine-support supplements may increase levels of trimethylamine N-oxide (TMAO) -- a metabolite of choline that has been associated with increased cardiovascular events, such as stroke.[57,58]

Landmark research published on November 24, 2021 in JAMA found that that use of Alpha-GPC was associated with a higher 10-year incident stroke risk in a dose-response manner after adjusting for traditional cerebrovascular risk factors.[75] More specifically, individuals supplementing with α-GPC vs not supplementing with it had a 46% higher risk of stroke.[75]

Another review on Alpha-GPC supplementation, published in December 2021 concluded that ...GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement.”[76]

Most recently, research in Frontiers in Pharmacology found that TMAO may contribute to the development of prostate cancer as it promotes the proliferation and migration of prostate cancer cells by activating the p38 pathway and increasing HMOX1 expression.[77] Based on these findings, the team of researchers conclude that reducing choline intake through dietary intervention may delay the onset and progression of prostate cancer, presenting significant clinical application value.”[77]

For these reasons, AML Pre Xtreme does NOT contain acetylcholine precursors, like Alpha-GPC. We suggest getting choline, an essential nutrient, from the diet. Eggs or CDP-choline are less prone to be converted to TMA and TMAO than other forms of supplemental choline[59]

No Glycerol

Glycerol is prized for its ability to hyper hydrate” muscle cells, due to its prominent osmolytic properties. The ingredient gained popularity among endurance athletes who frequently add glycerol (in the form of a 20% glycerol solution) to their drinks during and around training.

However, the research on glycerol and performance is mixed.[60,61]

Moreover, the doses of glycerol used in these studies (1.2 g/kg body weight) far exceed the 1-3 grams of glycerol (in the form of 65% glycerol-containing supplements) that youll find in pre workouts.[62,63] FYI, for a 170-lb male (77.27 kg), youd need to consume upwards of 92 grams of glycerol to achieve the hyperhydration and endurance benefits associated with glycerol supplementation.

No Taurine

Taurine is an inhibitory amino acid that serves many functions in the body, including those of an osmolyte and an antioxidant. It also influences the inhibitory neurotransmitter GABA, which could impede muscle excitation, force production, mental energy, or motivation.

Furthermore, several case reports have shown that the combination of caffeine + taurine in energy drinks can cause elevated blood pressure, ventricular arrhythmias in sensitive individuals and sudden death![73,74]

For these reasons, taurine is not included in AML Pre Xtreme. It is best taken as a health-supporting dietary supplement without co-ingestion of caffeine.

AML Pre Xtreme: The Best Pre Workout Supplement

Pre workout supplements are a dime-a-dozen. They can be found in virtually any big box grocery store, club store, or online retailer. When deciding which supplement to purchase, there are many factors to consider, including your budget, supplement facts panel, the company releasing the supplement, and where that supplement was manufactured.

AML Pre Xtreme spares no expense -- using premium ingredients backed by research in humans. No other supplement can match this advanced scientific formula.

For optimal exercise performance & results, consume AML Pre Xtreme 1 hour before exercise. For added recovery and growth, take a serving of AML Post Workout immediately after training, before a post workout meal that provides all the essential amino acids.

 


 

© Published by Advanced Research Media, Inc., 2022

© Reprinted with permission from Advanced Research Media, Inc.

 

 

References

1.     Gonzalez AM, Townsend JR, Pinzone AG, Hoffman JR. Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature. Nutrients. 2023 Jan 28;15(3):660. doi: 10.3390/nu15030660. PMID: 36771366; PMCID: PMC9921013.

2.     Curis E., et. al; Citrulline and the gut;”; Current Opinion in Clinical Nutrition and Metabolic Care; September 2007

3.     Wax, B., Kavazis, A. N., Weldon, K., & Sperlak, J. (2015). Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. Journal of Strength and Conditioning Research, 29(3), 786–792. https://doi.org/10.1519/JSC.0000000000000670

4.     Glenn, J. M., Gray, M., Wethington, L. N., Stone, M. S., Stewart, R. W. J., & Moyen, N. E. (2017). Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. European Journal of Nutrition, 56(2), 775–784. https://doi.org/10.1007/s00394-015-1124-6

5.     Perez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research, 24(5), 1215–1222.

6.     Bailey SJ, Blackwell JR, Lord T, et al. L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol 119: 385–395, 2015

7.     Suzuki T, Morita M, Kobayashi Y, Kamimura A. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. J Int Soc Sports Nutr 13: 6, 2016.

8.     Kreider, R.B., Kalman, D.S., Antonio, J. et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14, 18 (2017). https://doi.org/10.1186/s12970-017-0173-z

9.     Cooke, M.B., Rybalka, E., Williams, A.D. et al. Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals. J Int Soc Sports Nutr 6, 13 (2009). https://doi.org/10.1186/1550-2783-6-13

10.  Smith AE, Walter AA, Graef JL, Kendall KL, Moon JR, Lockwood CM, Fukuda DH, Beck TW, Cramer JT, Stout JR. Effects of beta-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial. J Int Soc Sports Nutr. 2009 Feb 11;6:5. doi: 10.1186/1550-2783-6-5. PMID: 19210788; PMCID: PMC2649036.

11.  Trexler ET, Smith-Ryan AE, Stout JR, Hoffman JR, Wilborn CD, Sale C, Kreider RB, Jäger R, Earnest CP, Bannock L, Campbell B, Kalman D, Ziegenfuss TN, Antonio J. International society of sports nutrition position stand: Beta-Alanine. J Int Soc Sports Nutr. 2015 Jul 15;12:30. doi: 10.1186/s12970-015-0090-y. PMID: 26175657; PMCID: PMC4501114

12.  Stuart AS Craig, Betaine in human nutrition, The American Journal of Clinical Nutrition, Volume 80, Issue 3, November 2004, Pages 539–549, https://doi.org/10.1093/ajcn/80.3.539

13.  Dobrijević D, Pastor K, Nastić N, Özogul F, Krulj J, Kokić B, Bartkiene E, Rocha JM, Kojić J. Betaine as a Functional Ingredient: Metabolism, Health-Promoting Attributes, Food Sources, Applications and Analysis Methods. Molecules. 2023 Jun 17;28(12):4824. doi: 10.3390/molecules28124824. PMID: 37375378; PMCID: PMC10302777.

14.  Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. Published 2015 Jan 10. doi:10.1186/1475-2891-14-6]

15.  Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD. Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr. 2009;6:7. Published 2009 Feb 27. doi:10.1186/1550-2783-6-7

16.  Cholewa, J.M., Hudson, A., Cicholski, T. et al. The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial. J Int Soc Sports Nutr 15, 37 (2018). https://doi.org/10.1186/s12970-018-0243-x

17.  Cholewa, J. M., Wyszczelska-Rokiel, M., Glowacki, R., Jakubowski, H., Matthews, T., Wood, R., Paolone, V. (2013). Effects of betaine on body composition, performance, and homocysteine thiolactone. Journal of the International Society of Sports Nutrition, 10(1), 39. https://doi.org/10.1186/1550-2783-10-39

18.  Gao, X., Zhang, H., Guo, X., Li, K., Li, S., & Li, D. (2019). Effect of betaine on reducing body fat—A systematic review and meta-analysis of randomized controlled trials. Nutrients, 11(10), 2480. https://doi.org/10.3390/nu11102480

19.  Apicella, Jenna M., "The Effect of Betaine Supplementation on Performance and Muscle Mechanisms" (2011). Master's Theses. 109. https://opencommons.uconn.edu/gs_theses/109

20.  Esen O, Dobbin N, Callaghan MJ. The Effect of Dietary Nitrate on the Contractile Properties of Human Skeletal Muscle: A Systematic Review and Meta-Analysis. J Am Nutr Assoc. 2023 May-Jun;42(4):327-338. doi: 10.1080/07315724.2022.2037475. Epub 2022 May 23. PMID: 35604074

21.  Alsharif NS, Clifford T, Alhebshi A, Rowland SN, Bailey SJ. Effects of Dietary Nitrate Supplementation on Performance during Single and Repeated Bouts of Short-Duration High-Intensity Exercise: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Antioxidants (Basel). 2023 May 31;12(6):1194. doi: 10.3390/antiox12061194. PMID: 37371924; PMCID: PMC10294948.

22.  Tan, R.; Cass, J.K.; Lincoln, I.G.; Wideen, L.E.; Nicholl, M.J.; Molnar, T.J.; Gough, L.A.; Bailey, S.J.; Pennell, A. Effects of Dietary Nitrate Supplementation on High-Intensity Cycling Sprint Performance in Recreationally Active Adults: A Systematic Review and Meta-Analysis. Nutrients 2024, 16, 2764. https://doi.org/10.3390/nu16162764

23.  Lidder S, Webb AJ. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway. Br J Clin Pharmacol. 2013 Mar;75(3):677-96. doi: 10.1111/j.1365-2125.2012.04420.x. PMID: 22882425; PMCID: PMC3575935.

24.  Macuh M, Knap B. Effects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review. Nutrients. 2021 Sep 13;13(9):3183. doi: 10.3390/nu13093183. PMID: 34579061; PMCID: PMC8465461.

25.  Hull KM and Maher TJ. Effects of L-tyrosine on mixed-acting sympathomimetic-induced pressor actions. Pharmacol Biochem Behav 1992;43, 1047-1052.

26.  Tharakan B, Dhanasekaran M, et al. Anti-Parkinson botanical Mucuna pruriens prevents levodopa induced plasmid and genomic DNA damage. Phytother Res 2007;21, 1124-1126.

27.  Katzenschlager R, Evans A, et al. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry 2004;75, 1672-1677.

28.  Selasi Attipoe, Stacey A. Zeno, Courtney Lee, Cindy Crawford, Raheleh Khorsan, Avi R. Walter, Patricia A. Deuster, Tyrosine for Mitigating Stress and Enhancing Performance in Healthy Adult Humans, a Rapid Evidence Assessment of the Literature, Military Medicine, Volume 180, Issue 7, July 2015, Pages 754–765, https://doi.org/10.7205/MILMED-D-14-00594]

29.  Selasi et al.; Steenbergen, L., Sellaro, R., Hommel, B., & Colzato, L. S. (2015). Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance. Neuropsychologia, 69, 50–55. https://doi.org/10.1016/j.neuropsychologia.2015.01.022

30.  Jongkees, B. J., Hommel, B., Kuhn, S., & Colzato, L. S. (2015). Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review. Journal of Psychiatric Research, 70, 50–57. https://doi.org/10.1016/j.jpsychires.2015.08.01

31.  Saremi M, Shahriari F, Hemmatinafar M, Rezaei R, Niknam A, Nordvall M, Wong A, Bagheri R. Low-Dose Caffeine Supplementation Is a Valuable Strategy for Increasing Time to Exhaustion, Explosive Power, and Reducing Muscle Soreness in Professional Male Kickboxers. Curr Dev Nutr. 2024 Dec 21;9(1):104538. doi: 10.1016/j.cdnut.2024.104538. PMID: 39886079; PMCID: PMC11780082.

32.  Tsai YS, Chen TT, Chan YC, Huang CC, Lai TF, Liao Y, Metcalfe RS, Chen YC, Wang HS. Acute caffeine supplementation offsets the impairment in 10-km running performance following one night of partial sleep deprivation: a randomized controlled crossover trial. Eur J Appl Physiol. 2025 Mar;125(3):825-835. doi: 10.1007/s00421-024-05638-5. Epub 2024 Oct 22. PMID: 39438312.

33.  Volkow ND, Wang G-J, Logan J, et al. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain. Translational Psychiatry. 2015;5(4):e549-. doi:10.1038/tp.2015.46.

34.  Grgic, J., Trexler, E.T., Lazinica, B. et al. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr 15, 11 (2018) doi:10.1186/s12970-018-0216-0

35.  Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The Magic Velvet Bean of Mucuna pruriens. Journal of Traditional and Complementary Medicine. 2012;2(4):331-339.

36.  Kamkaen, N.; Chittasupho, C.; Vorarat, S.; Tadtong, S.; Phrompittayarat, W.; Okonogi, S.; Kwankhao, P. Mucuna pruriens Seed Aqueous Extract Improved Neuroprotective and Acetylcholinesterase Inhibitory Effects Compared with Synthetic L-Dopa. Molecules 2022, 27, 3131. https://doi.org/10.3390/molecules27103131

37.  Tambasco N, Romoli M, Calabresi P. Levodopa in Parkinson's Disease: Current Status and Future Developments. Curr Neuropharmacol. 2018;16(8):1239-1252. doi: 10.2174/1570159X15666170510143821. PMID: 28494719; PMCID: PMC6187751.

38.  Bekhbat M, Li Z, Dunlop BW, Treadway MT, Mehta ND, Revill KP, Lucido MJ, Hong C, Ashchi A, Wommack EC, Goldsmith DR, Haroon E, Miller AH, Felger JC. Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation. Brain Behav Immun. 2025 Mar;125:240-248. doi: 10.1016/j.bbi.2024.12.026. Epub 2024 Dec 16. PMID: 39694342; PMCID: PMC11903141.

39.  Feng Z, Wei RB, Hong Q, Cui SY, Chen XM. Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium. Cell Biol Int. 2010 Oct;34(10):1055-61. doi: 10.1042/CBI20100054. PMID: 20513234.

40.  Shariffi, B., Dillon, K., Gillum, T., Boyer, W., Sullivan, S., Lee, E., & Kim, J. K. (2022). Effect of Combined Grape Seed Extract and L-Citrulline Supplementation on Hemodynamic Responses to Exercise in Young Males. Journal of Dietary Supplements, 20(4), 531–542. https://doi.org/10.1080/19390211.2021.2023246

41.  Cases J, Romain C, Marín-Pagán C, et al. Supplementation with a Polyphenol-Rich Extract, PerfLoad®, Improves Physical Performance during High-Intensity Exercise: A Randomized, Double Blind, Crossover Trial. Nutrients. 2017;9(4):421. doi:10.3390/nu9040421.

42.  Kim J, So WY. Effects of acute grape seed extract supplementation on muscle damage after eccentric exercise: A randomized, controlled clinical trial. J Exerc Sci Fit. 2019;17(2):77-79. doi:10.1016/j.jesf.2019.01.001

43.  Kim, J., & Stebbins, C. L. (2018). Effects of Grape Seed Extract Supplementation on Exercise Performance in Athletes, 2(2017), 2017–2018. https://doi.org/10.31031/RISM.2018.02.000531

44.  Bhardwaj, R. K., Glaeser, H., Becquemont, L., Klotz, U., Gupta, S. K., & Fromm, M. F. (2002). Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and  CYP3A4. The Journal of Pharmacology and Experimental Therapeutics, 302(2), 645–650. https://doi.org/10.1124/jpet.102.034728

45.  McNamara FN, Randall A, Gunthorpe MJ. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol. 2005;144(6):781–790. doi:10.1038/sj.bjp.0706040

46.  Lee, S. A., Hong, S. S., Han, X. H., Hwang, J. S., Oh, G. J., Lee, K. S., Ro, J. S. (2005). Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chemical & Pharmaceutical Bulletin, 53(7), 832–835.

47.  Oberleithner H, Callies C, Kusche-Vihrog K, et al. Potassium softens vascular endothelium and increases nitric oxide release. Proc Natl Acad Sci U S A. 2009;106(8):2829–2834. doi:10.1073/pnas.0813069106.

48.  Howard, A. B., Alexander, R. W., & Taylor, W. R. (1995). Effects of magnesium on nitric oxide synthase activity in endothelial cells. The American Journal of Physiology, 269(3 Pt 1), C612-8. https://doi.org/10.1152/ajpcell.1995.269.3.C612

49.  Sodium citrate ingestion and its effects on maximal anaerobic exercise of different durations. McNaughton LR, et al., 1992. European Journal of Applied Physiology and Occupational Physiology, 64(1), 36-41

50.  Sodium citrate and anaerobic performance: implications of dosage. McNaughton LR. Eur J Appl Physiol Occup Physiol. 1990;61(5-6):392-7.

51.  https://www.wsj.com/sports/olympics/indoor-mile-world-record-yared-nuguse-jakob-ingebrigtsen-7a67dfce

52.  Urwin C.S., Snow R.J., Condo D., Snipe R., Wadley G.D., Carr A.J. Factors influencing blood alkalosis and other physiological responses, gastrointestinal symptoms, and exercise performance following sodium citrate supplementation: a review. Int J Sport Nutr Exerc Metabol. 2021;31:168–186.

53.  Requena B., Zabala M., Padial P., Feriche B. Sodium bicarbonate and sodium citrate: ergogenic aids? J Strength Condit Res. 2005;19:213–224

54.  Coppen, A., & Bolander-Gouaille, C. (2005). Treatment of depression: time to consider folic acid and vitamin B12. Journal of Psychopharmacology, 19(1), 59–65. https://doi.org/10.1177/0269881105048899

55.  Homma, D., Katoh, S., Tokuoka, H., & Ichinose, H. (2013). The role of tetrahydrobiopterin and catecholamines in the developmental regulation of tyrosine hydroxylase level in the brain. Journal of Neurochemistry, 126(1), 70–81. https://doi.org/10.1111/jnc.12287

56.  Crabtree MJ, Hale AB, Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. Free Radical Biology & Medicine. 2011;50(11):1639-1646. doi:10.1016/j.freeradbiomed.2011.03.010.

57.  Cho CE, Aardema NDJ, Bunnell ML, Larson DP, Aguilar SS, Bergeson JR, Malysheva OV, Caudill MA, Lefevre M. Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men. Nutrients. 2020 Jul 25;12(8):2220. doi: 10.3390/nu12082220. PMID: 32722424; PMCID: PMC7468900.

58.  Wilcox J, Skye SM, Graham B, Zabell A, Li XS, Li L, Shelkay S, Fu X, Neale S, O'Laughlin C, Peterson K, Hazen SL, Tang WHW. Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. Am J Med. 2021 Sep;134(9):1160-1169.e3. doi: 10.1016/j.amjmed.2021.03.016. Epub 2021 Apr 17. PMID: 33872583; PMCID: PMC8410632.

59.  Synoradzki K, Grieb P. Citicoline: A Superior Form of Choline?. Nutrients. 2019;11(7):1569. Published 2019 Jul 12. doi:10.3390/nu11071569

60.  McKenna ZJ, Gillum TL. Effects of Exercise Induced Dehydration and Glycerol Rehydration on Anaerobic Power in Male Collegiate Wrestlers. J Strength Cond Res. 2017;31(11):2965-2968. doi:10.1519/JSC.0000000000001871

61.  Patlar S, Yalçin H, Boyali E. The effect of glycerol supplements on aerobic and anaerobic performance of athletes and sedentary subjects. J Hum Kinet. 2012;34:69-79. doi:10.2478/v10078-012-0065-x

62.  Patlar S, Yalçin H, Boyali E. The effect of glycerol supplements on aerobic and anaerobic performance of athletes and sedentary subjects. J Hum Kinet. 2012 Oct;34:69-79. doi: 10.2478/v10078-012-0065-x. Epub 2012 Oct 23. PMID: 23487412; PMCID: PMC3590833.

63.  van Rosendal SP, Osborne MA, Fassett RG, Coombes JS. Guidelines for glycerol use in hyperhydration and rehydration associated with exercise. Sports Med. 2010 Feb 1;40(2):113-29. doi: 10.2165/11530760-000000000-00000. PMID: 20092365.

64.  Xu C, Bi S, Zhang W, Luo L. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024 Jul 12;11:1424972. doi: 10.3389/fnut.2024.1424972. Erratum in: Front Nutr. 2025 Feb 17;12:1570800. doi: 10.3389/fnut.2025.1570800. PMID: 39070254; PMCID: PMC11275561

65.  Candow, D. G., Forbes, S. C., Roberts, M. D., Roy, B. D., Antonio, J., Smith-Ryan, A. E., Rawson, E. S., Gualano, B., & Roschel, H. (2022). Creatine OClock: Does Timing of Ingestion Really Influence Muscle Mass and Performance? Frontiers in Sports and Active Living, 4(May), 1–8. https://doi.org/10.3389/fspor.2022.893714

66.  Ribeiro F, Longobardi I, Perim P, Duarte B, Ferreira P, Gualano B, Roschel H, Saunders B. Timing of Creatine Supplementation around Exercise: A Real Concern? Nutrients. 2021 Aug 19;13(8):2844. doi: 10.3390/nu13082844. PMID: 34445003; PMCID: PMC8401986.

67.  Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. Eur Neuropsychopharmacol. 2025 Jan;90:28-35. doi: 10.1016/j.euroneuro.2024.10.004. Epub 2024 Nov 1. PMID: 39488067.

68.  Institute of Medicine (US) Committee on Nutrition, Trauma, and the Brain; Erdman J, Oria M, Pillsbury L, editors. Nutrition and Traumatic Brain Injury: Improving Acute and Subacute Health Outcomes in Military Personnel. Washington (DC): National Academies Press (US); 2011. 10, Creatine. Available from: https://www.ncbi.nlm.nih.gov/books/NBK209321/

69.  Vietor FI, Sticher K, Ashraf KH. The Pathophysiology of Traumatic Brain Injuries and the Rationale Behind Creatine Supplementation as a Potential Therapy: A Review. Mo Med. 2025 Jan-Feb;122(1):60-66. PMID: 39958598; PMCID: PMC11827660.

70.  Ainsley Dean PJ, Arikan G, Opitz B, Sterr A. Potential for use of creatine supplementation following mild traumatic brain injury. Concussion. 2017 Mar 21;2(2):CNC34. doi: 10.2217/cnc-2016-0016. PMID: 30202575; PMCID: PMC6094347.

71.  Wang L, Chen S-F, Huang X-W, Wu Z-Y, Zhang Q-M (2025) Efficacy and safety of creatine phosphate sodium in the treatment of viral myocarditis: A systematic review and meta-analysis. PLoS ONE 20(1): e0317498. https://doi.org/10.1371/journal.pone.0317498

72.  Li M, Sheykhlouvand M. Effects of Combined Versus Single Supplementation of Creatine, Beta-Alanine, and L-Citrulline During Short Sprint Interval Training on Basketball Players' Performance: A Double-Blind Randomized Placebo-Controlled Trial. Int J Sports Physiol Perform. 2025 Feb 25;20(4):559-567. doi: 10.1123/ijspp.2024-0310. PMID: 40010353.

73.  Shah SA, Szeto AH, Farewell R, Shek A, Fan D, Quach KN, Bhattacharyya M, Elmiari J, Chan W, O'Dell K, Nguyen N, McGaughey TJ, Nasir JM, Kaul S. Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial. J Am Heart Assoc. 2019 Jun 4;8(11):e011318. doi: 10.1161/JAHA.118.011318. Epub 2019 May 29. PMID: 31137991; PMCID: PMC6585360.

74.  Ellermann C, Hakenes T, Wolfes J, Wegner FK, Willy K, Leitz P, Rath B, Eckardt L, Frommeyer G. Cardiovascular risk of energy drinks: Caffeine and taurine facilitate ventricular arrhythmias in a sensitive whole-heart model. J Cardiovasc Electrophysiol. 2022 Jun;33(6):1290-1297. doi: 10.1111/jce.15458. Epub 2022 Mar 27. PMID: 35304782.

75.  Lee G, Choi S, Chang J, et al. Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years. JAMA Netw Open. 2021;4(11):e2136008. doi:10.1001/jamanetworkopen.2021.36008

76.  Wang Z, Hazen J, Jia X, et al. The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis. Int J Mol Sci. 2021;22(24):13477. Published 2021 Dec 15. doi:10.3390/ijms222413477

77.  Zhou Y, Lv J, Jin S, Fu C, Liu B, Shen Y, Li M, Zhang Y, Feng N. Gut microbiota derived metabolite trimethylamine N-oxide influences prostate cancer progression via the p38/HMOX1 pathway. Front Pharmacol. 2025 Jan 9;15:1526051. doi: 10.3389/fphar.2024.1526051. PMID: 39850572; PMCID: PMC11754881.