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Stim Hype! Show Me the Science

Brian Turner

Posted on May 02 2018

By: Robert A. Schinetsky

 Without question, the most beloved and fiercely debated topic in regards to sports supplements is:

 What’s the best pre workout?

 Ask 10 people that question, and you’re guaranteed to have two very different, yet equivalently passionate answers. And who can blame them?

 There are scores of supplement companies on the market each selling their own unique blend of stimulants and performance-enhancers, but at the heart of the matter is the stimulant blend. In today’s day and age, pre workouts are all about stimulants. It’s sad to say, but that’s really all that most consumers care about when deciding what is the “best” pre workout. Stimulants are what ushered in the boom in business that the supplement industry in presently enjoying, and for better or worse, they continue to drive the formulation trends by and large in the industry.

 Now, don’t get us wrong, we’re not trying to paint stimulants in a bad light here. In fact, quite the opposite. Stimulants are one of the big reasons pre workouts are so awesome, in the first place!

 They give you the energy and motivation to get in the gym and give it your all after a long day at the office. They also help dial in your focus so you stay on point while you’re training, and they even help you last longer in your workouts, that you otherwise would.

 So, as you can see, we’re not saying stimulants are inherently bad, or even detrimental to your performance and physique goals. They’re actually a big help in your quest to get bigger, faster, leaner, and stronger.


 Not all stimulant supplements are created equal. A lot of pre workouts (as well as fat burners) on the market use a crazy combination of stimulants with little to no human safety, let alone performance, data behind them. Sure, these stimulants might feel great for a time, but where’s the human studies showing it’s actually worth including in a pre workout.

 After all, a pre workout should only contain those ingredients that actually increase performance. That’s the purpose of a pre workout (to boost performance), not something to give you just a brief energy high.

 And that brings us to the point of why we’re here today -- to discuss the best stimulants for boosting performance and burning fat. The ones that have actual data backing their claims, conducted in humans.

 So, without further adieu, let’s take a look at the best pre workout and fat burner stimulants you should be using prior to crushing it in the gym! 

Best Training & Fat Loss Stimulants


 What can be said about caffeine that most of you already don’t know by now. It’s the most widely consumed drug on the planet, and for good reason. It seemingly makes everything better….well except maybe sleep that is.

 Caffeine is the sturdy foundation upo which all of the best pre workouts are built and for good reason -- the stuff flat out delivers. Whether it be performance, focus, time-to-exhaustion, resistance to fatigue, power, and even strength, caffeine does it all, and then some.[1,2,3]

 More of Caffeine

 So, let’s dive a little deeper into how caffeine works, which we’ll explain how it can improve so many key attributes of athletic performance.

 For starters, caffeine is a naturally-occurring thermogenic methylxanthine alkaloid that operates as a powerful central nervous system (CNS) stimulant. It’s been extensively shown to increase energy expenditure, focus, lipolysis, and fat oxidation (i.e. fat burning). Due to this, caffeine is great not only as a pre workout stimulant, but also a valuable component of any effective fat burner too.

 Caffeine is able to increase cyclic AMP (cAMP) via phosphodiesterase inhibition. FYI, phosphodiesterase (PDE) are a set of enzymes that functions as “energy regulators” and by inhibiting those enzymes, caffeine can promote greater energy levels. It also blocks adenosine receptors, which contribute to caffeine’s wakefulness-promoting properties.

 Additionally, caffeine is also believed to enhance performance through a number of other mechanisms, including[1,2,4]:


        - Enhanced muscle glycogen resynthesis

        - Increased β-endorphin and catecholamine secretion

        - Improved nerve conduction velocity and motor unit recruitment

        - Reduced perception of pain perception

        - Increased permeability and mobilization of intracellular calcium

        - Reduced uptake of intracellular calcium


        Essentially, caffeine is awesome for training and improves your performance in a number of ways, probably more than ever thought.

         But caffeine isn’t the end of our list of the best proven pre workouts stimulants, it’s only the beginning...


         Seeing p-synephrine in the list might give you pause for a second and wonder why it’s included in our list of the best pre workouts stimulants. You’re probably thinking p-synephrine is more suited to a fat burner, and we won’t argue there, as p-synephrine is definitely a valuable inclusion in any top weight loss supplement, but its benefits extend beyond helping you get lean and mean. It’s also a valuable performance enhancer as well, backed by several human studies!

         Research has noted that p-synephrine increases energy expenditure, post exercise oxygen uptake, and fat oxidation, which leads to enhanced repetition performance and volume load during training. But that’s not all.

         There’s also some data to show that the effects of p-synephrine are further enhanced with the addition of caffeine.[4,5] Stacking caffeine with p-synephrine yields faster, more powerful repetitions all with no additional perceived exertion or lactate accumulation![4]

         Now, that you know why you want p-synephrine in your pre workouts and fat burners, let’s take a deeper look at how it works.

        More on p-Synephrine

         For starters, you’re probably wondering why there’s a “p” in front of synephrine, when nearly everyone referring to the ingredients simply calls is “synephrine”.

         The “p” in front of synephrine stands for “para” and refers to the para-substituted hydroxy group attached to the synephrine molecule. Another variation you might see is “m-synephrine”, a.k.a. phenylephrine. The “m” stands for methyl, and indicates there’s a hydroxyl group in the meta-position on the benzene ring as opposed to the para position with p-synephrine.

        Why is this important?

        Though letter differences may seem small, the difference in actions are astounding.

         To kick things off, pSynephrine is a naturally-occurring phenylethylamine derivative present in bitter orange (Citrus aurantium). m-synephrine, on the other hand, does not occur naturally in plants.

         P-synephrine can also be synthesized in your body using the exact same pathways involved in the production of catecholamines. The reason p-synephrine first gained popularity in fat burners was due to its structural similarities to another very popular fat loss ingredient, ephedrine. It’s also worth noting that ephedrine does not contain a para-substituted hydroxy group.

         But the addition of the parahydroxygroup is a great thing, for a couple of reasons. First and foremost, p-synephrine has the ability to cross the blood-brain barrier, and it also does NOT impact cardiovascular system parameters (i.e increased blood pressure), which can’t be said of the more dangerous (and banned) stimulants that are ephedrine and m-synephrine.

         So, how does p-synephrine work exactly?

         Well, as opposed to ephedrine and m-synephrine, p-synephrine has extremely low (basically no) binding affinity for α-1 and α-2 as well as β-1 and β-2 adrenoreceptors.[7]. But, it does agonize the β-3 adrenoreceptor , which leads to increased metabolic rate, lipolysis, and potentially even reduced food intake, and its from these actions that synephrine offers its performance-boosting benefits.

         Regarding safety, studies have used doses up to 3 mg/kg and not witnessed any adverse side effects. What was documented, however, was increased fat oxidation rates during exercise, which basically means it increases the amount of fat your burning as fuel during exercise.

         When you add this to the fact that p-synephrine gets more effective with the addition of caffeine, you begin to understand why these two compounds are the best pre workout stimulants available!

        Phenylethylamine (PEA)

         In the post-ephedrine/DMAA era, supplement companies have explored a number of different ingredients that simulate the energy, focus, and euphoria of the now-banned stimulants. One of the top choices turning up in more and more pre workouts and fat burners is phenylethylamine (PEA).

         Naturally synthesized in the brain, PEA is a powerful catecholamine that stimulates the central nervous system, enhances neurotransmitter release and activity, and induces a strong sense of euphoria.[8] While PEA might sound like the heir apparent to the much beloved designer stims of yesteryear, all it’s cracked up to be.

         First, the “euphoric” sensations many attribute to PEA last a very brief amount of time (i.e. less than 15 minutes), meaning you might get a quick boost in energy, confidence, or motivation, but it’s gone before you really ever have time put that increased sense of purpose to good use, which means it doesn’t really make much sense for inclusion in a pre workout or fat burner. Furthermore, the evidence is far from conclusive whether or not PEA actually enhances fat loss, further questioning its use in any fat burning formula.[9]

         Second, and possibly more alarming, is that chronic use of PEA may to downregulation of key receptors in the brain, meaning that the more you supplement with PEA, the more your body will reduce its natural production of the powerful catecholamine, potentially leading to dependency issues in later years.

         Suffice it to say, PEA is far from an ideal , let alone “the best”, stimulant to look for in your favorite sports supplements.


        Often found alongside PEA in many supplements is hordenine, an alkaloid naturally occuring in a number of common plants, including barley. The reason hordenine is paired so frequently with PEA is that hordenine functions as a mild monoamine oxidase inhibitor (MAOIs). MAO is an enzyme that breaks down monoamine neurotransmitters and hormones such as norepinephrine (noradrenaline) and epinephrine (adrenaline). By deactivating MAO, you can increase the longevity of these potent neurochemicals, leading to prolonged energy, focus, motivation, and mood.

         The theory with may neurohackers is that by stacking hordenine with PEA, you can prolong the euphoric effects of the stimulant by preventing MAO from gobbling it all up. In theory this makes sense, but again, all isn’t perfect with hordenine.

         MAOIs can come with a number of adverse side effects including increased blood pressure, heart rate and respiratory rate, due to the long-lasting effects of adrenaline, noradrenaline, etc. Now, hordenine isn’t nearly as potent as some prescription-grade MAOs or even tyramine, a precursor of hordenine, as hordenine only interacts with a specific subset of MAO enzymes, but still there are risks with hordenine.

         One animal study found that when horses were injected with hordenine, they experienced rapid heart rate, respiratory distress (i.e. difficulty breathing), and increased body temperature.[11] But it doesn’t end there, hordenine stimulates release of gastrin, the hormone that stimulates production and release of stomach acid.[12] This is especially concerning if you have stomach ulcers or a history of gastroesophageal reflux (GERD), as constantly supplementing with hordenine could lead to severe GI bleeding. And to top it all off, hordenine could result in you testing positive on a drug screen for opiates. Now, it would be a false-positive, but how many employers are willing to give the benefit of the doubt in the current opioid epidemic plaguing the United States?

         No matter which way you spin it, hordenine has not rightful place in a serious pre workout or fat burner for any number of reasons, but especially when you consider it has no human safety studies and could be potentially dangerous or toxic!

         When you take it all together, deciding which stimulates you should and shouldn’t use in your sports supplements is a no-brainer. Select stimulates that have been well-researched in humans and shown to be not only beneficial, but SAFE!!!

         To get your stimulant fix and boost your results, the only place you need to turn for the truth is Advanced Molecular Labs.

        AML Pre Workout + Thermo Heat -- Stimulant Perfection

        When you’ve grown tired of all the latest designer stim fad sweeping the industry, and you’re ready to start using real stimulants, backed by human trials confirming their effectiveness, you need look no further than Advanced Molecular Labs for any stimulant fix!

         Advanced Molecular Labs utilizes only those stimulants proven in human research trials to boost performance and accelerate fat loss.

         AML Pre Workout harness the raw power of 400mg pure caffeine anhydrous and surrounds it with a host of focus boosters and performance maximizers that combine to yield the consummate pre workout training supplement

         Thermo Heat combines the energy and metabolism throttling effects of caffeine alongside the fat-torching properties of p-synephrine in one unbeatable, weight loss product.




        1. Goldstein ER, Ziegenfuss T, Kalman D, et al. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr. 2010;7(1):5. doi:10.1186/1550-2783-7-5.
        2. Warren GL, Park ND, Maresca RD, McKibans KI, Millard-Stafford ML. Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med Sci Sports Exerc. 2010;42(7):1375-1387. doi:10.1249/MSS.0b013e3181cabbd8.
        3. Grgic, J., Trexler, E. T., Lazinica, B., & Pedisic, Z. (2018). Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. Journal of the International Society of Sports Nutrition, 15(1), 11.
        4. Ratamess NA, Bush JA, Kang J, et al. The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance. Journal of the International Society of Sports Nutrition. 2015;12:35. doi:10.1186/s12970-015-0096-5.
        5. Ratamess NA, Bush JA, Kang J, et al. The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise. J Am Coll Nutr. 2016;35(8):657-669. doi:10.1080/07315724.2016.1150223.
        6. Sidney J. Stohs, Harry G. Preuss, and Mohd Shara, “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects,” Oxidative Medicine and Cellular Longevity, vol. 2011, Article ID 482973, 9 pages, 2011.
        7. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid Med Cell Longev. 2011;2011:1–9. doi: 10.1155/2011/482973.
        8. Paetsch PR, Greenshaw AJ. Downregulation of beta-adrenergic and dopaminergic receptors induced by 2-phenylethylamine. Cell Mol Neurobiol 1993;13:203-15.
        9. Hoffman JR, Kang J, et al. Thermogenic effect of an acute ingestion of a weight loss supplement. J Int Soc Sports Nutr 2009;6:1-9
        10. Nedergaard OA, Westermann E. Action of various sympathomimetic amines on the isolated stripped vas deferens of the guinea-pig. Br J Pharmacol. (1968)
        11. Frank M, et al. Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse. Equine Vet J 1990;Nov;22(6):437-41.
        12. Singh AK, et al. Screening and confirmation of drugs in urine: interference of hordenine with the immunoassays and thin layer chromatography methods. Forensic Sci Int 1992;Apr;54(1):9-22.