Guarana (Paullinia cupana)

guarana seed energise+ we know health

Guarana is a climbing planet, native to the Amazon with coffee bean sized seeds containing medicinal value. It has been traditionally used in South America and Amazonia to increase awareness and energy. 

Guarana contains a number of active ingredients including the stimulants caffeine, theobromine and theophylline, as well as polyphenols such as catechin and epicatechin.

Energy, stamina and physical performance

Guarana in whole seed form contains 2-6% caffeine, for which the performance enhancing effects are widely known. In a large systematic review of 46 trials in humans, caffeine was found to improve endurance performance and mean power output in athletes (1). The International Society of Sports Nutrition (ISSN) in 2021 published a comprehensive position statement describing many of the performance enhancing effects of caffeine. Aerobic exercise performance was noted as demonstrating the most significant effect size, caffeine was best taken 60 minutes before exercise, in both trained and untrained athletes (2). 

Interestingly, in the context of high concentrations of tannins Guarana’s caffeine content seems to release more slowly than pure caffeine anhydrous or coffee, reducing any jitters or crash. This is uniquely paired with a number of other stimulating methylxanthines (theophylline and theobromine) (3), leading to additional stimulation beyond the dose of caffeine administered (4). The effects of Guarana beyond caffeine were also discussed in a 2022 review (5).

Cognitive performance and mood

A systematic review of eight placebo controlled trials in humans concluded there was an improved reaction time with Guarana (6). A combination of Guarana containing only 9mg of caffeine and Panax Ginseng (another ingredient in Energise+) demonstrated increased attention as well as improved memory task performance (7). Given the small amount of caffeine, the effects are likely related to other active ingredients in Guarana and/or Panax Ginseng.

In a systematic review of 13 trials, a low/moderate dose of caffeine before/during exercise was found to improve self-reported cognition (such as attention), energy and mood (8). In a double blinded, placebo controlled, randomized trial, participants were found to be significantly better at a problem solving task if they had consumed a caffeine pill versus placebo (9).

Both Guarana (10) and caffeine (11), in separate trials, have shown positive effects on mood. These effects were in addition to cognitive or task performance effects. The Guarana trial demonstrated effects at low doses, suggesting that the effects were less likely entirely due to caffeine. In a study of men participating in treadmill running, those pre-treated with caffeine demonstrated significantly higher dopamine and B-endorphin levels than those who did not consume caffeine (12).

Antioxidant effect

Guarana also contains several polyphenols such as catechin and epicatechin (13) with demonstrated antioxidant and antimicrobial effects (14).


We have chosen a potent dose of 10:1 extract (from 4000mg dry seed per two capsule dose) standardised to 22-28% caffeine. This allows us to provide a high amount of the beneficial active ingredients in Guarana without providing excessive caffeine which would cause adverse effects in some people. We believe this is the best of both worlds.


Panax Ginseng (Panax ginseng C.A. Meyer, Asian Ginseng)

Panax Ginseng in Energise+ formula

Panax Ginseng, considered an ‘adaptogen’, has been used for thousands of years in traditional Chinese, Korean, Japanese and Western medicine. Panax means “all healing” in ancient Greek. It has been traditionally used for many purposes including to restore energy, vitality and strength.

In modern times, ginsenosides have been isolated as the main active constituents. At least 200 ginsenosides have been identified in ginseng roots, however the most abundant in Panax Ginseng are Rb1, Rb2, Rc, Rd, Re and Rg1 (15). 

Cognitive performance and neuroprotection

In addition to the combination study in the Guarana section there have been numerous trials demonstrating the effects of Panax Ginseng on mental performance. Among these, there was an improvement in mental arithmetic and feelings of mental fatigue in a placebo controlled trial (16) and improvement in cognitive tests over 6 months in those with mild cognitive impairment in another trial (17). There are also mounting studies on using Panax Ginseng for neuroprotective effects as discussed in a 2018 review (18).


There are a large number of trials investigating Panax Ginseng for alleviation of fatigue. A 2020 systematic review of 8 human randomized controlled trials and 30 animal trials concluded that Panax Ginseng has beneficial effects on reduction of fatigue. It was concluded this was likely due to a number of mechanisms including antioxidant stress, regulation of carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulation of neurotransmitters in the central nervous system (19). A series of animal studies sought to understand the ginsenoside Rb1’s role in reducing fatigue. It was theorised the mechanisms relate to an increase in the content of ATP and activity of the Na-K-ATPase in skeletal muscle (20,21).

A comprehensive systematic review in 2022 discussed the role of Panax Ginseng in various chronic and age related diseases. They included 25 studies and 3190 participants. The conclusion was that Panax Ginseng has “potent therapeutic benefits that can act as a complementary treatment in managing patients with chronic diseases related to aging” (22). Some of the symptoms effectively treated in the studies included fatigue, anxiety, nausea and vomiting.

Immune system and inflammation

There is a large body of evidence investigating using different ginsenosides as anti-inflammatories ranging from neurological to respiratory conditions as summarised in a review published in 2017 (23). There has also been work to characterise the immune enhancing effects of Panax Ginseng (Red Korean Ginseng). In a 8 week placebo controlled trial of 100 participants, there were significantly increased T cells, B cells and white blood cell counts compared to placebo (24).


We have chosen a potent 10:1 Panax Ginseng extract (derived from 2000mg of dry herb per two capsule dose) with a guaranteed content of at least 6% ginsenosides. This is within the dose range used in research showing benefits and synergizes with the other ingredients in Energise+. 


Acetyl-l-carnitine (Acetyl levocarnitine hydrochloride)

Acetyl-l-carnitine (ALCAR) in Energise+ by We Know Health

Aceyl-l-carnitine (ALCAR) is an acetylated form of L-carnitine that is thought to be more easily absorbed and more readily cross the blood brain barrier, making it potentially more effective as a nootropic and in reducing brain oxidative damage (25). Carnitine functions as a carrier molecule to transfer long-chain fatty acids across the mitochondrial membrane where they can participate in brain energy production. ALCAR (unlike L-carnitine) can also support acetylcholine (a major neurotransmitter) production via transferring acetyl groups to Acetyl-CoA. 

Cognitive performance and mental fatigue

ALCAR has shown beneficial effects for mental fatigue in Chronic Fatigue Syndrome (26) and elderly patients with fatigue (27). A meta-analysis of multiple randomised controlled trials of those with mild Alzheimer’s Disease or mild cognitive impairment showed improvements compared to placebo for those treated with ALCAR (28). It has also been studied in an induced model of Parkinson’s Disease in animals, demonstrating improved cognition (29).

Antioxidant and anti-inflammatory effects

In an animal model of atherosclerosis, ALCAR administration demonstrated significant reductions in unhealthy lipids whilst elevating HDL (30). Among numerous other trials, the mechanisms of ALCAR’s antioxidant action were explored in a hypoxia model (31) as well as a chemotherapy induced cardiotoxicity model (32).


We have chosen 400mg of vegan ALCAR per two capsule dose based on many anecdotal reports in combination with the available evidence. Given ALCAR is combined with other energising and stimulating ingredients in Energise+, we felt that a higher dose could be excessive for some people. It also provides significantly more carnitine than what is found in a daily diet (especially a plant based one).


Eleuthero (Eleutherococcus senticosus, Acanthopanax senticosus, Siberian Ginseng)

Eleuthero (Siberian Ginseng) in Energise+ by We Know Health

Eleuthero is found in parts of China, Korea, Japan and Russia. Whilst it is commonly called Siberian Ginseng it contains eleutherosides instead of ginsenosides and hence is not technically a ginseng.  It is considered an ‘adaptogen’ and has been traditionally used to enhance vitality, stamina, physical performance, cognition, help manage stress and improve the immune response.

Old Russian studies

Eleuthero was heavily researched (reportedly in over 2000 subjects) in the 1960s and 1970s in Russia for performance enhancement in athletes. Whilst these studies are not all available, a group in 2021 were able to access and summarise 46 of these trials. Their conclusion was that Eleuthero appears to exhibit benefits for cognitive function, physical endurance and mental endurance (33). Unfortunately we do not have access to the trials that made up this review.

Fatigue and physical performance

A 2010 placebo controlled trial in recreationally trained males over 8 weeks demonstrated improved endurance capacity and cardiovascular function (34) and an older crossover trial also demonstrated increased physical work capacity with Eleuthero versus placebo, thought to be due to improved oxygen metabolism (35). In middle aged healthy volunteers subjected to exercise a shift to burning fat for energy and subsequently preserving muscle glycogen was demonstrated (36).

In Chronic Fatigue Syndrome, those with ‘moderate fatigue’ had a statistically significant improvement versus placebo after two months of treatment (37). Additionally, in elderly patients with non-specific feelings of fatigue and weakness there were improvements in social functioning and mental health after four weeks of Eleuthero versus placebo (38).

Neuroprotection and brain effects

There are numerous animal studies investigating the mechanisms behind Eleuthero’s central effects including memory enhancement that are beyond the scope of this page (39, 40, 41, 42). Eleutheroside B or E were identified as the constituents responsible for improving memory and learning in rats (43).

An antidepressant effect was noted in mice after seven days of Eleuthero administration. This correlated with significant increases in serotonin, noradrenaline (norepinephrine) and dopamine levels (44).

Immune modulation

When administered in a lab (in vitro) to rhinovirus, respiratory syncytial virus (RSV) and Influenza A, Eleuethero had inhibitory effects on the replication of all these RNA viruses (45). A placebo controlled trial in healthy volunteers showed a significant increase in immunocompetent cells, especially T-lymphocytes after consuming Eleuthero for four weeks (46). When administered to mice before an induced endotoxic shock, Eleuthero was found to be protective by reducing the inflammatory response (47).


We have chosen a potent 15:1 Eleuthero (from 1500mg root and rhizome per two capsule dose) standardized to a guaranteed content of at least 0.8% eleutherosides. This dose provides a higher amount of active ingredient than many products that include non standardised forms which can be largely ineffective, without being so high that adverse effects could be encountered.


  1. Southward K, Rutherfurd-Markwick KJ, Ali A. The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis. Sports Med. 2018 Aug;48(8):1913-1928. doi: 10.1007/s40279-018-0939-8. Erratum in: Sports Med. 2018 Aug 9.
  2. Guest, N.S., VanDusseldorp, T.A., Nelson, M.T. et al. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr 18, 1 (2021). https://doi.org/10.1186/s12970-020-00383-4.
  3. Ádina L. Santana, Gabriela A. Macedo, Health and technological aspects of methylxanthines and polyphenols from guarana: A review, Journal of Functional Foods, Volume 47, 2018, Pages 457-468, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2018.05.048.
  4. Moustakas D, Mezzio M, Rodriguez BR, Constable MA, Mulligan ME, Voura EB. Guarana provides additional stimulation over caffeine alone in the planarian model. PLoS One. 2015 Apr 16;10(4):e0123310. doi: 10.1371/journal.pone.0123310. 
  5. Kennedy DO, Wightman EL. Mental Performance and Sport: Caffeine and Co-consumed Bioactive Ingredients. Sports Med. 2022 Dec;52(Suppl 1):69-90. doi: 10.1007/s40279-022-01796-8. Epub 2022 Nov 30.
  6. Hack, Brian & Macedo Penna, Eduardo & Talik, Tyler & Chandrashekhar, Rohan & Millard-Stafford, Mindy. (2023). Effect of Guarana (Paullinia cupana) on Cognitive Performance: A Systematic Review and Meta-Analysis. Nutrients. 15. 434. 10.3390/nu15020434. 
  7. Kennedy DO, Haskell CF, Wesnes KA, Scholey AB. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol Biochem Behav. 2004 Nov;79(3):401-11. doi: 10.1016/j.pbb.2004.07.014.
  8. Lorenzo Calvo J, Fei X, Domínguez R, Pareja-Galeano H. Caffeine and Cognitive Functions in Sports: A Systematic Review and Meta-Analysis. Nutrients. 2021 Mar 6;13(3):868. doi: 10.3390/nu13030868.
  9. Darya L. Zabelina, Paul J. Silvia, Percolating ideas: The effects of caffeine on creative thinking and problem solving, Consciousness and Cognition, Volume 79, 2020, 102899, ISSN 1053-8100, https://doi.org/10.1016/j.concog.2020.102899.
  10. Haskell CF, Kennedy DO, Wesnes KA, Milne AL, Scholey AB. A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guaraná in humans. Journal of Psychopharmacology. 2007;21(1):65-70. doi:10.1177/0269881106063815.
  11. Smith A, Sutherland D, Christopher G. Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers. Journal of Psychopharmacology. 2005;19(6):620-626. doi:10.1177/0269881105056534.
  12. Lee JB, Lee HJ, Lee SJ, Kim TW. Blood dopamine level enhanced by caffeine in men after treadmill running. Chin J Physiol. 2019 Nov-Dec;62(6):279-284. doi: 10.4103/CJP.CJP_59_19. PMID: 31793465.
  13. Marvin Carlson, Richard D Thompson, Liquid Chromatographic Determination of Methylxanthines and Catechins in Herbal Preparations Containing Guaraná, Journal of AOAC INTERNATIONAL, Volume 81, Issue 4, 1 July 1998, Pages 691–701, https://doi.org/10.1093/jaoac/81.4.691.
  14. Lucija Majhenič, Mojca Škerget, Željko Knez, Antioxidant and antimicrobial activity of guarana seed extracts, Food Chemistry, Volume 104, Issue 3, 2007, Pages 1258-1268, ISSN 0308-8146, https://doi.org/10.1016/j.foodchem.2007.01.074.
  15. Chen W, Balan P, Popovich DG. Analysis of Ginsenoside Content (Panax ginseng) from Different Regions. Molecules. 2019 Sep 26;24(19):3491. doi: 10.3390/molecules24193491.
  16. Reay JL, Kennedy DO, Scholey AB. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol. 2005 Jul;19(4):357-65. doi: 10.1177/0269881105053286.
  17. Park KC, Jin H, Zheng R, Kim S, Lee SE, Kim BH, Yim SV. Cognition enhancing effect of panax ginseng in Korean volunteers with mild cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. Transl Clin Pharmacol. 2019 Sep;27(3):92-97. doi: 10.12793/tcp.2019.27.3.92. Epub 2019 Sep 30.
  18. Kim KH, Lee D, Lee HL, Kim CE, Jung K, Kang KS. Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions. J Ginseng Res. 2018 Jul;42(3):239-247. doi: 10.1016/j.jgr.2017.03.011. Epub 2017 Apr 15. 
  19. Jin TY, Rong PQ, Liang HY, Zhang PP, Zheng GQ, Lin Y. Clinical and Preclinical Systematic Review of Panax ginseng C. A. Mey and Its Compounds for Fatigue. Front Pharmacol. 2020 Jul 17;11:1031. doi: 10.3389/fphar.2020.01031. 
  20. Tan S, Zhou F, Li N, Dong Q, Zhang X, Ye X, Guo J, Chen B, Yu Z. Anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection in rat. Biol Pharm Bull. 2013;36(10):1634-9. doi: 10.1248/bpb.b13-00522. Epub 2013 Aug 6. PMID: 23924778.
  21. Tan SJ, Li N, Zhou F, Dong QT, Zhang XD, Chen BC, Yu Z. Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome. J Surg Res. 2014 Oct;191(2):344-9. doi: 10.1016/j.jss.2014.04.042. Epub 2014 May 2. PMID: 24881470.
  22. Bárbara de Oliveira Zanuso, Ana Rita de Oliveira dos Santos, Vitor Fernando Bordin Miola, Leila M. Guissoni Campos, Caio Sergio Galina Spilla, Sandra Maria Barbalho, Panax ginseng and aging related disorders: A systematic review, Experimental Gerontology, Volume 161, 2022, 111731, ISSN 0531-5565, https://doi.org/10.1016/j.exger.2022.111731. 
  23. Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 2017 Oct;41(4):435-443. doi: 10.1016/j.jgr.2016.08.004. Epub 2016 Aug 18.
  24. Sun Hee Hyun, Ha-Young Ahn, Hyeong-Jun Kim, Sung Won Kim, Seung-Ho So, Gyo In, Chae-Kyu Park, Chang-Kyun Han, Immuno-enhancement effects of Korean Red Ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial, Journal of Ginseng Research, Volume 45, Issue 1, 2021, Pages 191-198, ISSN 1226-8453, https://doi.org/10.1016/j.jgr.2020.08.003.
  25. Liu J, Head E, Kuratsune H, Cotman CW, Ames BN. Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann N Y Acad Sci. 2004 Nov;1033:117-31. doi: 10.1196/annals.1320.011.
  26. Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 Mar-Apr;66(2):276-82. doi: 10.1097/01.psy.0000116249.60477.e9. 
  27. Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M, Koverech A, Neri S, Vacante M, Cammalleri L, Motta M. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr. 2008 Mar-Apr;46(2):181-90. doi: 10.1016/j.archger.2007.03.012. Epub 2007 Jul 20.
  28. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71. doi: 10.1097/00004850-200303000-00001.
  29. Singh S, Mishra A, Srivastava N, Shukla R, Shukla S. Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats. Mol Neurobiol. 2018 Jan;55(1):583-602. doi: 10.1007/s12035-016-0293-5. Epub 2016 Dec 14.
  30. Wang S, Xu J, Zheng J, Zhang X, Shao J, Zhao L, Hao J. Anti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats. Med Sci Monit. 2020 Jan 16;26:e920250. doi: 10.12659/MSM.920250. 
  31. Barhwal K, Hota SK, Jain V, Prasad D, Singh SB, Ilavazhagan G. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation. Neuroscience. 2009 Jun 30;161(2):501-14. doi: 10.1016/j.neuroscience.2009.02.086. Epub 2009 Mar 24.
  32. Bayrak S, Aktaş S, Altun Z, Çakir Y, Tütüncü M, Kum Özşengezer S, Yilmaz O, Olgun N. Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity. J Int Med Res. 2020 Aug;48(8):300060520951393. doi: 10.1177/0300060520951393.
  33. Sophia Gerontakos, Amy Taylor, Alena Yu Avdeeva, Veronika A. Shikova, Olga N. Pozharitskaya, David Casteleijn, Jon Wardle, Alexander N. Shikov, Findings of Russian literature on the clinical application of Eleutherococcus senticosus (Rupr. & Maxim.): A narrative review, Journal of Ethnopharmacology, Volume 278, 2021, 114274, ISSN 0378-8741, https://doi.org/10.1016/j.jep.2021.114274.
  34. Kuo J, Chen KW, Cheng IS, Tsai PH, Lu YJ, Lee NY. The effect of eight weeks of supplementation with Eleutherococcus senticosus on endurance capacity and metabolism in human. Chin J Physiol. 2010 Apr 30;53(2):105-11. doi: 10.4077/cjp.2010.amk018. 
  35. Asano K, Takahashi T, Miyashita M, Matsuzaka A, Muramatsu S, Kuboyama M, Kugo H, Imai J. Effect of Eleutherococcus senticosus extract on human physical working capacity. Planta Med. 1986 Jun;(3):175-7.
  36. Wu Y, Wang X, Li M, Compbell TC. [Effect of Ciwujia (Radix Acanthopanacis senticosus) preparation on exercise performance under constant endurance load for elderly]. Wei Sheng Yan Jiu. 1998 Nov 30;27(6):421-4.