A natural alternative to caffeine without the side-effects

Published: 10-Nov-2023

Mango tree leaf extracts can deliver similar benefits to caffeine but without the drawbacks, explains Nektium’s Dr Miguel Florido

In today’s fast-paced world, consumers often need to enhance their cognitive performance and focus. Many rely on caffeine to increase both energy and mental acuity, but there are growing concerns about its health impacts.

The side-effects of caffeine can include anxiety, jitters and sudden energy crashes, as well as impacting heart rate and blood pressure.1–4

A 2023 Mintel report showed that 39% of global coffee drinkers say they are now actively trying to reduce their caffeine intake.5

The rise in adolescent energy drink consumption has also prompted significant unease, with a range of adverse reactions being attributed to excessive caffeine.6

However, a Euromonitor report in 2021 highlighted the so-called “Caffeine Paradox,” with consumption continuing to grow worldwide because consumer need for effective energy still outweighs the rising concerns about stress and anxiety.7

This highlights the vast opportunity for a natural alternative that can deliver the benefits of caffeine without the negative impacts. 

Natural stimulation

In 2016, Nektium set out on a mission to find an all-natural mental and physical energy ingredient that could be used as an alternative to caffeine. We soon discovered the potential of the leaf of the mango tree (Mangifera indica).

Mango tree leaves are rich in the polyphenol, mangiferin, and other bioactives. They were described in ancient Ayurveda Sanskrit verses thousands of years ago as being beneficial in terms of treating digestive health issues such as stomach pain, diarrhoea and vomiting.

In modern times, research has shown that mangiferin has antioxidant, anti-inflammatory, immunomodulatory, antidiabetic, lipolytic, anti-bone resorption and antimicrobial qualities.8

A natural alternative to caffeine without the side-effects

It has also now emerged that mangiferin can deliver natural stimulation in much the same way as caffeine. Both have an effect on the frontal cortex and hippocampus.

The frontal cortex is responsible for acquiring and processing information, controlling memory, planning and attention, whereas the hippocampus is responsible for mood.

Research published in Food and Nutrition Sciences in 2018 showed that mango tree leaf extracts can activate cranial electrical activity and increase long-term potentiation in a remarkably similar pattern to caffeine and with an equally fast action.9

Crucially, mango tree leaf extracts are better tolerated than caffeine, have no crash effect and do not cause side-effects such as jitters, racing pulse or anxiety. 

Introducing Zynamite

Launched in 2018, Zynamite is Nektium’s patented, proprietary Mangifera indica extract —standardised to mangiferin — that has been developed from sustainably harvested mango leaves.

Research has demonstrated its ability to increase brain oxygenation, which improves the efficiency of brain cell functioning and supports neural activities.10

The aforementioned pilot study in Food and Nutrition Sciences used well-established animal models to show that the bioactive compounds in Zynamite clearly pass the blood-brain barrier to act on the central nervous system.

It highlighted the induction of long-term potentiation in a hippocampus slice preparation ex vivo after 1 week of daily administration. This long-term potentiation may involve the strengthening of synaptic connections between the neurons associated with learning and memory.

Research in Nutrients, meanwhile, showed that one dose of Zynamite is enough to significantly improve performance for at least 5 hours in a range of cognitive tasks.11

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The double-blind, placebo-controlled study tested the effects of a single 300 mg dose of Zynamite on various cognitive functions. Participants performed more accurately on the tasks that measure concentration and memory … and they were better at performing each of the mentally demanding tasks than after the placebo.

Mango leaf extracts are also an inhibitor of catechol-O-methyltransferase (COMT).12 Nektium’s scientific research unveiled mangiferin’s mechanism of action in this regard for the first time.

Mangiferin inhibits the COMT enzyme, which breaks down catecholamines. By inhibiting this enzyme, Zynamite raises the levels of dopamine — a neurotransmitter that reduces cravings and enhances the body’s detoxification response.

On the market

In 2022, we successfully concluded the first phase of securing patents for Zynamite in several primary markets. This intellectual property refers to its ability to improve alertness, concentration and memory.

In some countries, the patent includes additional effects, such as its use as an ingredient to enhance mood, reduce stress and as a replacement for caffeine.

Zynamite is also a highly adaptable ingredient that can be used in applications including tablets, capsules, powders, fizzy sticks, gummies and beverages. It has only a slight effect on the sensory profile of beverages and does not affect microbiological activity, pH and Brix levels.

In addition, several application trials are underway to ensure that Zynamite can be used in various types of functional food. Zynamite has already been used in diverse finished product innovations, including popular smart supplements and e-gaming formulations in Japan.

Sports nutrition

Recognising the fundamental importance of the mind in sports performance, we have also applied the caffeine-free and doping-free nootropic activities of Zynamite to active nutrition.

It has wide-ranging benefits for sports, which have been subjected to double-blind, randomised controlled clinical trials.

A natural alternative to caffeine without the side-effects

They show that, as well as reducing mental fatigue and improving reaction time, Zynamite improves peak power output and maximum oxygen intake during intense exercise (VO2 max) while reducing pain and helping athletes to recover faster after exhausting exercise.10,13,14

Most recently, a study in Nutrients examined the effects of Zynamite PX — which combines the ingredient with quercetin — on exercise performance and muscle adaptation.

It revealed that Zynamite PX triggers a biochemical response in skeletal muscle fibres at rest that is similar to that elicited by regular exercise. It also modifies signalling in muscle fibres during intense exercise, resulting in reduced activation of stress-sensing enzymes for improved muscle performance.15

Nature’s ignition

Zynamite is a branded mango leaf extract that can provide a natural alternative to caffeine as well as support sporting performance and recovery. Since 2018, its benefits have been demonstrated in a total of ten clinical studies and it has won six global industry awards.

Natural, safe and clean-label friendly, Zynamite is a fast-acting and experiential ingredient that can give consumers the enhanced energy they need — without the drawbacks of caffeine. 


  1. L. Klevebrant and A. Frick, “Effects of Caffeine on Anxiety and Panic Attacks in Patients with Panic Disorder: A Systematic Review and Meta-Analysis,” General Hospital Psychiatry 74, 22–31 (2022).
  2. B. Fiani, et al., “The Neurophysiology of Caffeine as a Central Nervous System Stimulant and the Resultant Effects on Cognitive Function,” The Cureus Journal of Medical Science 13(5), e15032 (2021).
  3. G. Richards and A.P. Smith, “A Review of Energy Drinks and Mental Health with a Focus on Stress, Anxiety and Depression,” Journal of Caffeine and Adenosine Research 6(2), 49–63 (2016).
  4. P.J. Green, et al., “The Effects of Caffeine on Blood Pressure and Heart Rate: A Review,” Annals of Behavioral Medicine 18(3), 201–216 (1996).
  5. www.mintel.com/food-and-drink-market-news/the-coffee-and-coffee-shop-industries-what-consumers-want-in-coffee/.
  6. L.D. Ruiz and R.E. Scherr, “Risk of Energy Drink Consumption to Adolescent Health,” American Journal of Lifestyle Medicine 13(1), 22–25 (2019).
  7. www.euromonitor.com/the-caffeine-paradox-energy-anxiety-and-the-future-of-caffeinated-beverages/report. 
  8. K.A. Shah, et al., “Mangifera indica (Mango),” Pharmacognosy Review 4(7), 42–48 (2010).
  9. W. Dimpfel, et al., “Zynamite (Mangifera indica Leaf Extract) and Caffeine Act in a Synergistic Manner on Electrophysiological Parameters of Rat Central Nervous System,” Food and Nutrition Sciences 9(5), 502–518 (2018).
  10. M. Gelabert-Rebato, 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,” Frontiers in Physiology (2018): doi:10.3389/fphys.2018.00740.
  11. E.L. Wightman, et al., “Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study,” Nutrients 12(8), 2194 (2020).
  12. L. López-Ríos, et al., “Central Nervous System Activities of Extract Mangifera indica L.,” Journal of Ethnopharmacology 260, 112996 (2020).
  13. M. Gelabert-Rebato, et al., “A Single Dose of the Mango Leaf Extract Zynamite in Combination with Quercetin Enhances Peak Power Output During Repeated Sprint Exercise in Men and Women,” Nutrients 11(11), 2592 (2019).
  14. M. Martin-Rincon, et al., “Supplementation with a Mango Leaf Extract (Zynamite) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery After Strenuous Damaging Exercise,” Nutrients 12(3), 614 (2020).
  15. M. Martinez-Canton, et al., “A Mango Leaf Extract (Zynamite) Combined with Quercetin Has Exercise-Mimetic Properties in Human Skeletal Muscle,” Nutrients 15(13), 2848 (2023).

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