The Definitive Guide to Zynamite (Mangiferin): The Next Caffeine Replacement?

Society runs on caffeine.


It’s in our coffee, pre workout, and energy drinks.


Caffeine is even working its way into other “functional foods” like protein powders and peanut butter.


And, make no mistake, I enjoy my caffeine (and in a multitude of ways).


But, not everyone reacts well to caffeine, or can handle the ever-increasing doses that are working their way into dietary supplements and energy drinks.


As a result, a number of caffeine alternatives have been investigated over the years, with some being a bit more “effective” than others.


Notable examples of these caffeine alternatives include TeaCrine and Dynamine, both of which you’ve heard me talk about before.


Today, we’re going to cover another intriguing new caffeine alternative/replacement/synergist is Zynamite®. 

What is Zynamite®?

Zynamite® is a patent-pending proprietary extract of Mangifera indica (mango) standardized to 60% mangiferin.[1]


To date, Zynamite® has been the subject of seven clinical studies and noted for both its nootropic and sports performance benefits.

Image courtesy Nektium.

More on Mangifera indica (Mango)

Mangifera indica has long been used in ayurvedic medicine for a wide variety of ailments due to its antiseptic, astringent, diaphoretic (inducing perspiration -- “sweat”), stomachic (improves appetite or digestion), vermifuge (anti-parasitic), tonic, diuretic, and laxative properties.[2]


As a result, various parts of the plant have been used as a remedy for anaemia, asthma, bronchitis, cough, dysentery, hypertension, insomnia, rheumatism, and toothache.


The plant have also been used to treat stings, snakebites, abscesses, blisters, wonds, diarrhea, colic, liver disorders, excessive urination, tetanus and asthma.[2]

Mangiferin, the “Magic” in Mango

Mangiferin is the primary active compound in mangifera indica, found in the leaves, bark, fruit and roots. It can also be found in several other plants, including Salacia chinensis, Swertia chirata, and Hypericum aucheri.[3]

Fig. 1: Structure of Mangiferin[24]

It is a xanthone glycoside, possessing strong antioxidant, antidiabetic, hypotensive, anti-lipid peroxidation, immunomodulatory, cardiotonic, wound healing, and anti-degenerative activities.[2]


Mangiferin is also considered to be a “super antioxidant” capable of specifically protecting against free radical production via the Fenton reaction due to its iron-chelating properties.


Moreover, mangiferin can cross the blood-brain barrier and modulate neurotransmission, K+ channels and nociception. 

How Does Zynamite® Work?

Zynamite® is a catechol-o-methyltransferase (COMT) inhibitor that activates brain waves and increases Long-Term Potentiation (LTP) in a manner similar to caffeine.[21]


COMT is the enzyme that metabolizes neurotransmitters and catecholamines, including dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). It also metabolizes levodopa (L-Dopa), the direct precursor to dopamine.


By inhibiting COMT, the bioavailability of L-Dopa is significantly increased, promoting stronger, longer-lasting dopamine and norepinephrine levels in the central nervous system.


FYI, pharmaceutical-grade COMT inhibitors are also used alongside carbidopa-levodopa therapy in the treatment of symptoms of Parkinson’s disease.


Long-Term Potentiation can be thought of as the “strengthening” of synaptic connections between neurons, which benefit both space and time dependent memory.


While caffeine boosts feelings of energy, mood, and alertness via antagonism of adenosine receptors, Zynamite® acts non-selectively to modulate various CNS targets and stimulate brain activity.[1]


Animal studies note that a dose of 25 mg/kg of Zynamite® attenuates alpha2 and beta1 spectral frequencies in the brain during the first hour after administration, indicating that Zynamite has a fairly quick onset of action (again, similar to caffeine). 


Additionally the pattern of frequency changes induced by Zynamite administration mimics those observed following administration of caffeine. 

Fig. 8: Direct comparison of the frequency changes observed in the presence of Zynamite® and caffeine alone and in the presence of the combinations during the second hour after administration. Frequency ranges are depicted as coloured bar graphs on the abscissa representing delta (red), theta (orange), alpha1 (yellow), alpha2 (green), beta1a (light blue) and beta1b (dark blue) and gamma spectral power (violet) from left to right within the four brain areas as mentioned on top of the graph. Statistical significance in comparison to control (vehicle) is documented by stars: * = p < 0.10; ** = p < 0.05; *** = p < 0.01.[1]

Interestingly, you’ll notice that when Zynamite and caffeine are combined, there is a synergistic and additive effect on brain waves (but, more on that in a bit).


Based on the data, researchers suggest that at least part of Zynamite’s stimulating properties are due to activation of dopamine, since alpha2 waves are under the control of dopamine.


Researchers also noted a sustained attenuation of alpha1 spectral power during their testing, which can be interpreted as a higher state of wakefulness. 


In case you were curious, Alpha1 waves are under the control of the neurotransmitter serotonin.

Why Not Just Supplement with Mangiferin Instead of Zynamite®?

Since mangiferin is the main active compound that we’re interested in, you might be wondering why not find some generic mangiferin extract and leave the “designer” (read: more expensive) Zynamite® alone?


Well, studies show that while mangiferin can cross the blood-brain barrier, its bioavailability is greater as part of a polyherbal preparation in comparison to administration of pure, isolated Mangiferin.[4]


Based on this, researchers question whether Mangiferin alone is responsible for the stimulating effects of Zynamite®, or if it is the presence of the other “supporting cast members” present in the remaining 40% of the herbal preparation that potentiates its effects.

Benefits of Zynamite®

Increases Mental Energy

The primary reason people use caffeine is to increase their wakefulness, alertness, and/or feelings of mental energy. These wakefulness promoting properties of caffeine come as a result of adenosine antagonism.


Zynamite enhances mental energy is a “caffeine-like” manner, in that it yields similar effects on brain wave activity, but the manner in which it does this isn’t the same as caffeine, meaning it doesn’t antagonize adenosine.[1]


It works by inhibiting COMT (the enzyme that breaks down dopamine), thereby leading to sustained dopamine levels in the CNS.


A pair of randomized, double blind, placebo-controlled crossover pilot clinical trials involving 16 participant were carried out to assess potential nootropic benefits of Zynamite®. 


Subjects received either a 500mg dose of Zynamite® or placebo.[21]


Researchers found that 500mg Zynamite significantly reduced fatigue after only 90 minutes, as demonstrated by a Profile of Mood States questionnaire (POMS). 


Additionally, Zynamite® reduced stress during the Calculation Performance Tests and improved reaction time compared to placebo.[21]

During a Number Sequence Test (NST) and a Number Connection Test (NCT), subjects receiving 500mg Zynamite® had a significant activating effect on the brain compared to placebo as determined by frequency analysis of the changes in electrical activity across six brain wave frequency ranges (shown below) in the EEG of the association cortex.


Unfortunately, these two pilot studies are not accessible online save for the data published by Nektium in the White Paper on Zynamite, so it’s hard to really delve into the methods of the paper.


Fortunately, several other studies in humans have been published noting benefits with lower doses of Zynamite (more on that in a bit!)

Long-Term Potentiation (LTP)

As mentioned above, preliminary animal studies found that Zynamite increases long-term potentiation (LTP) in a manner similar to caffeine.

Interestingly, Zynamite® had a greater effect on LTP than caffeine, but the combination

of Zynamite® and caffeine demonstrated a remarkable synergy in increasing long-term potentiation.

LTP strengthens the connections between synapses, which can increase memory, learning, and attention.

Improves Athletic Performance

Excessive production of reactive oxygen and nitrogen species (RONS) during exercise can damage cellular structures, leading to inflammation, fatigue, and impairment of executive and cognitive functions. It can also hinder adaptations to exercise (effectively undercutting your efforts in the gym to get better).


These reactive oxygen and nitrogen species are generated constantly during exercise by mitochondrial respiration. 


However, two other enzymes, xanthine oxidase (or xanthine oxidoreductase; XO) and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase, also called NOX) are also contribute to the formation of RONS during exercise.


As a result, a number of antioxidants have been studied to limit the formation of RONS and improve athletic performance. However, some of these antioxidants offer a double-edged sword in that they might combat RONS and lower inflammation, but simultaneously blunt desired training adaptations (i.e. killing your gains).


Now, it’s worth mentioning that the dose of these antioxidants is important as is the form.


Lower dose, natural antioxidants (present in grape extracts, green tea, etc) seem to have less adverse effects on training adaptations than mega-doses of synthetically derived Vitamin C or E.


As we mentioned earlier, mangiferin is a natural polyphenol that also happens to be an antioxidant as well as an inhibitor of XO and NOX.[5,6]


Based on these activities, researchers were curious to see if supplementing with mangiferin (as Zynamite) might limit RONS production and improve athletic performance.


To date, a trio of human studies have been conducted using a range of Zynamite doses.

Study #1

The first study sought to investigate the effects of Zynamite and either quercetin or luteolin, on sprint performance and recovery from ischemia-reperfusion.[7]


35 healthy subjects (18 men and 17 women) took part in the trial, but only 30 completed it (17 men and 13 women).


Participants were randomized into one of three treatments two days before the exercise test:

  • Treatment A: placebo (500 mg of maltodextrin/day)
  • Treatment B: 140 mg Zynamite and 50 mg of Luteolin per day
  • Treatment C: 140 mg Zynamite, 600 mg of Quercetin and 350 mg of tiger nut extract per day

For the exercise test, after completing a warm-up, subjects performed two 30-second Wingate tests as well as a 60-second all-out sprint with 4-minute recovery periods. 


At the end of the 60-second sprint, the circulation of both legs was instantaneously occluded for 20 seconds. 


After the 20 second occlusion period ended, circulation was reopened and the subject then had to perform a 15-second sprint. This was then followed by 10 seconds of recovery with open circulation, and a final 15-second sprint.


(Sounds rather hellacious, doesn’t it?)


Fig. 1: Experimental protocol[7]


Both Zynamite treatments improved performance in the exercise trial, but a slight edge can be obtained from the combination of Zynamite + Quercetin + Tiger nut over the combination Zynamite + Luteolin.


Moreover, brain oxygenation during the sprints was greater after Zynamite combination supplements B and C compared to placebo.


This is noteworthy as previous studies show that decreased brain oxygenation is associated with fatigue.[8] 


Zynamite supplements also enhanced peak (Wpeak) and mean (Wmean) power output by 5.0–7.0% and peak VO2 during the repeated sprints by 5.8%.


Researchers concluded that:


“In summary, this study shows that the MLE 60% mangiferin (Zynamite) has a remarkable ergogenic effect increasing muscle power in fatigued subjects, without increasing the consumption of oxygen, submaximal exercise efficiency or submaximal and maximal blood lactate concentrations. This type of response is expected for a compound acting on the central nervous system.” 


Note: Nektium Pharma supplied the supplements for this study and partly financed the experiments. However, the experiment and interpretation of the results was carried out using a double-blind design in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.[7]

Study #2

The next study investigating the effects of Zynamite® again tested it against placebo and in combination with peanut husk extract (supplying 95% luteolin) on various markers of exercise performance.[9]


12 healthy male P.E. students (age = 21.3 ± 2.1 years) took part in the double-blind, crossover design (meaning each subject spent time consuming one of the following treatments:

  • Low Dose: 140mg Zynamite® (containing 100mg mangiferin) + 50 mg peanut husk extract
  • High Dose: 420mg Zynamite® + 100 mg peanut husk extract
  • Placebo

48 hours after beginning their supplementation regimen, subjects reported to the lab to have their body composition and RMR measured.


Exercise testing for this particular study included a warm-up consisting of 8-second isokinetic sprint on a cycle ergometer followed by a 5-minute “recovery period” during which the subjects pedaled at low speed (~40 rpm) with no load.


Next, the subjects performed an incremental exercise test to determine the maximal fat oxidation (MFO) capacity.


Afterwards, they then performed a 2-minute period of unloaded pedaling.


Then, each subject had the load increased to the same intensity reached at the end of their MFO test and increased 15 Watts every minute until exhaustion in order for researchers to determine the subject’s VO2max


Upon reaching exhaustion, researchers clamped on the occlusion cuffs for 1-minute.


During this time, the subjects remained seated and silent on the cycle ergometer without pedaling. 


At the 50th second of occlusion, a 10-second countdown was initiated while the subjects got ready to sprint as fast and hard as they possibly could for 15 seconds. 


Following the one-minute ischemia, the occlusion cuff was deflated such that the men were sprinting with the circulation opened. At the end of the 15-second sprint, a second occlusion was started for 30 seconds, which was then followed by another 10 seconds of free circulation. 


At the end of the 15-second sprint, a second occlusion was started for 30 seconds, then the cuff was released and the subjects pedaled slowly at 20 watts while a 10-second countdown towards another 15-second sprint was started. 


Following this sprint, subjects performed 2.5 minutes of passive recovery on the bike. Researchers then collected a blood sample from the earlobe to measure blood lactate concentration 


After this cycle, subjects rested for 30 minutes.


During the first 20 minutes of the rest period, they laid on a stretcher. 


For the final 10 minutes, they moved back to the cycle ergometer for unloaded pedaling at low speed while the instruments were reconnected. 


At the conclusion of the 30-minute rest period, subjects performed a 30-second Wingate test followed by 4 minutes of recovery during which they pedaled at low speed with the cycle ergometer unloaded. 


At the end of this 4-minute block, subjects performed a second Wingate test. 


This second Wingate was followed by a 10-minute recovery block whereby subjects pedaled at a low 20-watt rate.


2.5 minutes into this 10-minute block, researchers collected another blood sample to measure blood lactate concentration. 


At the completion of the 10-minute recovery period, subjects performed a submaximal [(70% of the intensity reached in the incremental exercise test (Wmax)] constant-intensity time-trial to exhaustion.


Researchers noted that this last portion of the testing protocol was carried out to assess the effects of the Zynamite + Luteolin supplements on endurance capacity, since the test likely started with the subjects having very low glycogen levels -- a scenario which closely mimics conditions competitive athletes face during the final stages of endurance competitions. 


At the end of the endurance test, subjects had occlusion cuffs placed on both legs for 60 seconds. 


Again, at the 50-second mark of ischemia, researchers began a 10-second countdown which led into a final Wingate (30-second) sprint. 


At the end of this sprint, the subjects remained seated on the bike while pedaling at low speed with the cycle ergometer unloaded. 


After 2.5 minutes of recovery, another blood sample was obtained from the earlobe to measure blood lactate. 


Then the subjects moved to the stretcher and rested for 30 minutes.


As if performing this whole thing wasn’t bad enough, subjects repeated this protocol after 15 days of supplementation to determine any potential effects due to prolonged supplementation.


Afterwards, subjects then embarked on a 3–4 week washout and repeated following the crossover counterbalanced design!


Following is a graph summarizing the exercise testing:

Fig. 1: Exercise protocol[9]

Results from the Study

Researchers noted that supplementation with either Zynamite supplement did NOT affect body weight, resting metabolic rate, resting blood pressure, blood lactate concentration or heart rate.[9]


Researchers did observe that the combination of Zynamite + luteolin:

  • Enhanced exercise performance
  • Increased muscle oxygen extraction
  • Improved brain oxygenation

This last point is especially noteworthy as reduced brain oxygenation can increase production of RONS, which can combine with circulating RONS released by contracting muscles during training.[10] 


This increase in RONS and decrease in brain oxygen content could impair cognitive function during exercise, thereby reducing performance in complex tasks.[11,12]


Additionally, after 48 hours of supplementation, mean power output was 15% higher in the group receiving the polyphenol supplement than those receiving placebo.


Researchers offered up a trio of reasons why the combination of Zynamite + Luteolin may improve athletic performance following ischemia-reperfusion: 

  • Firstly, the supplements may facilitate muscle oxygen extraction as evidenced by a greater reduction in the muscle oxygenation index during the first five seconds of total occlusion of the circulation at exhaustion. 
  • Secondly, Zynamite + luteolin reduced oxygen consumption during the sprints preceded by occlusion. 
  • Thirdly, the supplement combination may promote ATP production through additional recruitment of the glycolysis, as indicated by the higher levels of blood lactate 

It’s also worth mentioning that the Zynamite + luteolin supplement enhanced mean power output during prolonged sprints carried out after 30 minutes of recovery following the incremental exercise test. 


This improvement in prolonged sprint performance was accompanied by enhanced brain oxygenation and larger muscle oxygen extraction during the sprints.[9]


Note: This study was partly financed by Nektium Pharma, who provided the phenolic compounds and participated in the experimental design. Nektium did NOT participate in the data collection, data analysis, and interpretation of results.

Study #3

The previous two studies found that the combination of Zynamite® + luteolin or quercetin improves exercise performance when ingested at least 48 hours prior to exercise. 


The most recent exercise study on Zynamite sought to determine if a single dose of the supplement could improve athletic performance. This would help determine if the effects of Zynamite® are more acute-based (a la citrulline, VASO6, nitrates, etc.) or saturation-based (e.g. creatine, beta alanine, betaine, etc.).


40 healthy, physically active subjects (20 men and 20 women) took part in the double-blind crossover counterbalanced design and received each of three treatments[13]:

  • Treatment A: 140 mg of Zynamite® + 140 mg of quercetin alongside 147.7 mg of maltodextrin and 420 mg of sunflower lecithin
  • Treatment B: 140 mg of Zynamite®, 140 mg of quercetin and 2126 mg of maltodextrin
  • Treatment C (PLACEBO): 2548 mg of maltodextrin. 

For each training session, subjects performed three Wingate tests interspaced by 4 minutes of rest and ended with a final 15-second sprint after ischemia.[13]


Here’s a graph illustrating the exercise protocol:

Figure 1: Exercise protocol[13]

After all subjects completed all treatment regimens, researchers collected the data and documented that treatments A and B (the two Zynamite + Quercetin supplements) improved peak power output (PPO) during the first three sprints by 2.8 (p = 0.04) and 3.8% (p = 0.01), respectively.[13]

Figure 2: Peak Power Output[13]

Additionally, blood lactate concentration was 7.4% lower (on average) in men after the administration of treatment B compared to placebo (p = 0.03).[13]


While previous studies noted that the combination of Zynamite + quercetin improved performance, this study used a quercetin dose that was ~25–50% lower than that noted in previous research, suggesting that the combination of Zynamite + quercetin may have synergistic effects.


This is all the more noteworthy when you consider the fact raised earlier that high-dose antioxidant supplementation can impair training adaptations. Being able to use a lower dose of a powerful polyphenol may allow for the improvement of exercise performance while “toeing the line” and not blunting the beneficial adaptations to intense exercise.


Additionally, researchers noted a greater reduction of muscle tissue oxygenation during the ischemia following administration of Zynamite® combined with quercetin. 


This suggests that the combination of Zynamite + quercetin may improve mitochondrial bioenergetics during sprinting and ischemia, which are in line with previous animal studies showing that mangiferin protects mitochondrial function.[14]


Furthermore, this study found that a single dose of Zynamite (and quercetin) is enough to derive benefit, and that prolonged supplementation is not necessarily needed.


Researchers also mentioned that adding sunflower lecithin to the Zynamite®-quercetin mixture (treatment A) had no additional beneficial effects.


Note: This study was was partially financed by Nektium Pharma S.L, (the company that makes Zynamite). Nektium also participated in the experimental design, but was completely excluded from participation in data collection, data analysis and interpretation of results.[13]

Additional Benefits of Mangiferin

The following list of benefits have been noted with mangiferin supplementation, not Zynamite supplementation, specifically.


However, since Zynamite is standardized to mangiferin, and research has noted it has greater effectiveness when combined with the other botanical components naturally-occurring in mango leaves, it’s reasonable to think that some of these benefits may apply to Zynamite supplementation (provided the dose is comparable).

Neuroprotective

Mangiferin is able to cross the blood–brain barrier and has been found possibly reduce the oxidative stress observed in neurodegenerative disorders.[15]


Additionally, mangiferin has been shown to reduce intracellular Ca2+ concentrations, an activity that may contribute to its protective effects and reduce iron neurotoxicity in cells.

May Support Healthy Blood Glucose Levels

Research suggests that mangiferin may reduce blood glucose levels by inhibiting glucose absorption from the intestine. This is supported by rodent studies noting that mangiferin inhibits the glucosidase enzymes sucrase, isomaltase, and maltase which are involved in the digestion of carbohydrates into simple sugars. This enzymatic inhibition may delay or inhibit carbohydrate breakdown, thereby slowing glucose absorption from the intestine.[16,17] 


Additional animal studies find that a 50% ethanolic extract of mangifera indica leaves  at a dose of 250 mg/kg produced a significant hypoglycemic effect, both in normal and streptozotocin-induced diabetic animals. 


Researchers believe that this was at least in part due to the stimulation of β-cells to release insulin.[1]

Other Actions

As noted above, various studies have also noted that mangiferin administration may offer[1,19]:

  • Neuroprotective
  • Anti-viral
  • Anti-parasitic
  • Anti-inflammatory
  • Immunomodulatory
  • Anti-microbial
  • Anti-fungal
  • Anti-bacterial
  • Hepatoprotective
  • Anti-allergic
  • Antihyperlipidemic
  • Antiatherogenic
  • Monoamine oxidase (MAO)-inhibiting

This last property may be especially intriguing for supplement brands looking for an alternative to Hordenine, another MAO-inhibiting supplement that currently resides on the FDA’s Advisory (“watchdog”) list.[17]

Important Takeaways Concerning Zynamite®

  • 7 clinical studies
  • Patent-pending
  • Similar brain activity to caffeine, but different mechanism
  • Synergistic with caffeine
  • Enhanced mental energy
  • Shown in human studies to improve workouts & recovery between bouts of repeated high-intensity exercise 
  • Side-effect free
  • Self-affirmed GRAS

Is Zynamite Safe®?

To date, Zynamite® administration has demonstrated no side effects and no change in heart rate variability or blood pressure.[21]


90-day toxicology studies also find no evidence of mortality or toxic effects male and female rats even when dosing as high as 2000 mg/kg bw/day.[3]

How to Stack Zynamite®

We all love to stack supplements.


As such, it’s no surprise that many of you reading this are wondering what you could stack with Zynamite (provided you can find it in the first place, haha).


Leading the charge is none other than the consummate stimulant...

Caffeine

As we stated above, animal research notes that Zynamite is synergistic with low doses of caffeine.[1]


Researchers also noted that if most caffeine is replaced by Zynamite®, but at least 2% of caffeine is retained, a prominent increase in stimulation can still be achieved.[1]


This is especially noteworthy for individuals looking to lower their caffeine intake (or cycle off of it completely), yet still want to use something to put a little pep in their step.


It should be noted that this synergistic effect has only been shown in animal models, and more human studies are needed to confirm the initial data set.


Still, if the synergism between caffeine + Zynamite is anything like that of caffeine + TeaCrine (theacrine), I’ll be a happy (and energized) camper.

Rhodiola Rosea

Rhodiola rosea is one of my personal favorite nootropics / adaptogens. I use it damn near every day, especially for late afternoon work sessions when I don’t necessarily need or want more caffeine.


It’s been used by Russians for centuries for its anti-stress and anti-fatigue properties.


Similar to Zynamite, Rhodiola is able to increase feelings of mental energy, boost cognition, and ameliorate mental and physical fatigue in a manner different from caffeine.


Common doses of rhodiola rosea used in studies are between 200-680mg per day.[20]

  • Personally, I find a dose between 200-300 mg to be my “sweet spot”.

Tyrosine

Tyrosine is an amino acid that provides the “building blocks” necessary to support production of the neurotransmitters/catecholamines dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline).


Intense, prolonged exercise (and other stressful situations) can deplete dopamine levels in the body, which facilitates the onset of fatigue.


Since caffeine and Zynamite both impact dopamine signaling in the brain (and Zynamite acts as a COMT inhibitor), it stands to reason that supplementing with more of the substrate used to synthesize the “mood and motivation molecule” may help to stave off its decline and keep energy, mood, motivation, and focus elevated for longer.


Essentially, you could think of the Tyrosine + Zynamite stack as the dopamine equivalent of a Alpha-GPC or CDP-Choline + Huperzine A stack for enhancing acetylcholine levels in the brain.

  • Recommended Dose: 2 grams L-Tyrosine

TeaCrine

It’s no secret that I’m a fan of another caffeine “alternative”, TeaCrine.


It works similar to caffeine, in that it antagonizes adenosine receptors, but binds to the receptors in a different style than caffeine.


Caffeine binds orthosterically, which is akin to “kicking in the front door”, while TeaCrine (and Dynamine) bind allosterically, which is akin to “sneaking in a window.” 


Both accomplish the same goal (getting into the house), but the way you “feel” the experience happening (increased alertness, motivation, etc.) is markedly different.


Combining caffeine + TeaCrine has worked very well for me and many others based on anecdotal feedback. And, there’s some research to validate these “n=1” reports.[21,22]


Since caffeine, TeaCrine, and Zynamite all work via slightly different mechanisms, combining the three might be the “ultimate'' rapid-acting, long-lasting energy experience.


The combo caffeine + TeaCrine + Dynamine has been floated as being a possible “trifecta” to fast-acting, prolonged energy, but based on personal experience, and that of others who have used the three ingredients together, the trio leaves individuals feelings somewhat “flat-lined” or “unmotivated.”


This might be due to the fact that all three ingredients are targeting the same receptors in the CNS (adenosine).


By attacking energy enhancement from three different directions, the caffeine + TeaCrine + Zynamite trio may offer a better solution than the Caffeine + TeaCrine + Dynamine combo.

  • Suggested Dosing: 
    • Caffeine: 50-200mg (depending on personal preference)
    • TeaCrine: 100-125mg TeaCrine
    • Zynamite: 140-200mg 

Where to Find Zynamite

Zynamite is still relatively new to the North American market, which can make finding it rather difficult, but not entirely impossible.


The makers of AZOTH have created a new nootropic supplement called Total Focus, containing:

The Bottom Line on Zynamite

Zynamite is a standardized extract of mangifera indica standardized to >60% mangiferin.


Mangifera indica has been used for centuries in traditional medicine for a wide variety of disorders and ailments due to the diverse array of effects its bioactives offer.


Studies to date show that Zynamite offers fast-acting improvements to both mental and physical endeavors, both on its own and when used in combination with other well-studied compounds, including caffeine and quercetin.


The ingredient is still very new, but the current body of evidence seems very intriguing.


Going forward it would be nice to see future human research compare similar doses of Zynamite to caffeine to placebo as well as to a combo of Zynamite + caffeine on measures of mental and physical performance to see if Zynamite can possibly contend as caffeine “replacement” and to better identify a “sweet spot” dose for the two compounds used together.

References

  1. Dimpfel, W., Wiebe, J., Gericke, N. and Schombert, L. (2018) Zynamite® (Mangifera indica Leaf Extract) and Caffeine Act in a Synergistic Manner on Electrophysiological Parame- ters of Rat Central Nervous System. Food and Nutrition Sciences, 9, 502-518. https://doi.org/10.4236/fns.2018.95039
  2. Shah KA, Patel MB, Patel RJ, Parmar PK. Mangifera indica (mango). Pharmacogn Rev. 2010;4(7):42–48. doi:10.4103/0973-7847.65325
  3. Reddeman, R. A., Glávits, R., Endres, J. R., Clewell, A. E., Hirka, G., Vértesi, A., Szakonyiné, I. P. (2019). A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin. Journal of Toxicology, 2019, 4763015. https://doi.org/10.1155/2019/4763015
  4. Kamalla, A.K., Ramasamy, M.K., Inampudi, R.J., Dubey, G.P., Agrawal, A. and Kalliapan, I. (2015) Comparative Pharmacokinetic Study of Mangiferin after Oral Administration of Pure Mangiferin and US Patented Polyherbal Formulation to Rats. AAPS PharmSciTech, 16, 250-8. https://doi.org/10.1208/s12249-014-0206-8
  5. Pinto M.M., Sousa M.E., Nascimento M.S. Xanthone derivatives: New insights in biological activities. Curr. Med. Chem. 2005;12:2517–2538. doi: 10.2174/092986705774370691. 
  6. Niu Y., Liu J., Liu H.Y., Gao L.H., Feng G.H., Liu X., Li L. Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity. Pharm. Biol. 2016;54:1680–1686. doi: 10.3109/13880209.2015.1120322.
  7. Gelabert-Rebato M, Wiebe JC, Martin-Rincon M, et al. Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans. Front Physiol. 2018;9:740. Published 2018 Jun 8. doi:10.3389/fphys.2018.00740
  8. Smith K. J., Billaut F. (2010). Influence of cerebral and muscle oxygenation on repeated-sprint ability. Eur. J. Appl. Physiol. 109, 989–999. 10.1007/s00421-010-1444-4
  9. Gelabert-Rebato M, Wiebe JC, Martin-Rincon M, et al. Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men. Nutrients. 2019;11(2):344. Published 2019 Feb 6. doi:10.3390/nu11020344
  10. Radak Z., Suzuki K., Higuchi M., Balogh L., Boldogh I., Koltai E. Physical exercise, reactive oxygen species and neuroprotection. Free Radic. Biol. Med. 2016;98:187–196. doi: 10.1016/j.freeradbiomed.2016.01.024.
  11. Racinais S., Wilson M.G., Gaoua N., Periard J.D. Heat acclimation has a protective effect on the central but not peripheral nervous system. J. Appl. Physiol. (1985) 2017;123:816–824. doi: 10.1152/japplphysiol.00430.2017. 
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