Brain Fuel References

BRAIN RESCUE FORMULA 

BRAIN FUEL natural energy formula has been specifically designed to improve levels of energy after brain injury, viral and/or bacterial infections, chronic fatigue and pain syndromes. 

NOTE: The natural ingredients that we included in this supplement are all one hundred percent researched and backed up by science and of pharmaceutical strength 

Sifting through the research on energy restoration it becomes clear that: 

- Increasing effectiveness, number and repair of mitochondria(the energy factories in your cells) at least seems to be one of the key factors in regaining energy levels and experience less fatigue after a concussion, stroke, post viral or other infectious condition and chronic pain. 

-  In addition to regain normal or better energy levels, key nutrients and minerals should be in place. In our modern day and age the amount of nutrients available in our daily food has dramatically declined over the last decades under the influence of the big food producing industry. 

All of these elements are covered by the ingredients in BRAIN FUEL. 

In the literature there is great focus on natural compounds and nutrients that can accomplish this fast and have been proven to work on decreasing fatigue and improving energy levels.  

Before using any of these nutrients it is however very important to keep in mind that nothing replaces the work you put in to improve sleep, circadian rhythms, blood sugar levels, stress reduction, hormesis (low levels of stress that can rebuild and strengthen your energy factories). These will always be your first resource when it comes to building a failsafe system to improve energy and decrease fatigue.  

The natural components that make up Brain Fuel are therefore an (important) aid and short cut to get to better energy levels faster and more efficiently.  

BRAIN FUEL has been specifically composed to support and promote 6 of the most efficient ways to increase energy production: 

Researchers point out that 6 things need to be addressed if you want to build more robust energy levels after: 

  • First of all, you need bigger Mitochondria. Building the size of your mitochondria so they can produce more energy is one of the most 

important factors in increasing energy levels over time. Research shows that you can remodel and improve mitochondrial size (see also the references on the supplements that aid neurogenesis). 

  • You also need more energy factories (with a difficult word called Mitochondrial Biogenesis). The more mitochondria you have, the bigger your “cellular energy-producing engine” grows, the more energy you’re able to produce. Several ingredients, in the list that follows, can stimulate this process of mitochondrial biogenesis – allowing your body to build more mitochondria from scratch. 
  • You need cofactors (chemical compounds that work indirectly or directly on and are vital for the energy production process) involved in mitochondria energy production. You can also say that these are substances that facilitate the process of mitochondria producing cellular 
  • You need to recharge NAD+ levels. NAD+ is a critical regulator of mitochondrial energy production. NAD+ supplies are rapidly depleted so you need a constant supply of new NAD+ or the precursors needed to produce NAD+. When I tell you that researchers have found NAD+ to be one of the important factors in longevity you will likely be even more interested 
  • You also need to build up your mitochondrial internal defense systems (researchers call these the so-called NRF2 and R.E. Pathways) Interestingly enough, much attention is always placed on taking antioxidants for the protection of our cells and organ systems. What is often not realized is that our cells’ internal antioxidant defense system (glutathione among other components) is hundreds of times more powerful and more important. Several of the compounds in the list that follows don’t just work as antioxidants, but even better, they build up the body’s internal cellular/mitochondrial antioxidant defense system — that makes our mitochondria more able to deal with stressors and protect themselves from damage. This ultimately means more energy because it prevents the whole system from being shut down. 
  • The last thing that is needed are components to repair and protect your cell membranes, especially those of your mitochondria. 

Research has shown that one of the most potent ways to improve energy levels is to repair the physical membranes of your mitochondria. This repair process usually takes place during the evening and night (that is why sleep quality is the number one thing you should prioritize when dealing with fatigue). 

Ingredients of BRAIN FUEL(as listed on the label): 

 

ASTHAXANTINE 

Astaxanthin is one of the most powerful non-stimulant ways to build up your cellular energy production. And it works through multiple powerful mechanisms and has a massive amount of research supporting all kinds of seemingly miraculous health benefits. Astaxanthin is the red pigment in shrimp, salmon, krill, and various other seafood, but it is originally made by algae (mainly Haematococcus Pluvialis). It is thought to be one of the most effective antioxidants known to man. It’s also one of the most powerful protectors of our cellular energy generators (our mitochondria) in existence.  Astaxanthin can: Protect mitochondria and support optimal cellular energy production. Dramatically reduce inflammation. Increase blood flow. Support heart health and reduce the oxidation of LDL.  Help modulate blood glucose. Improve cognitive function. Protect neurons from damage (and likely help prevent dementia and      neurological disease) Decrease anxiety. Decrease depression. Decrease muscle inflammation by more than 50% Improve physical endurance and exercise performance. Increase muscle strength and mobility 20 Improve the “heart-brain axis” (both mental and physical health).  Improve energy levels.  Importantly for our purposes here, astaxanthin is a unique compound because it can penetrate inside of cells and actually incorporate itself inside of mitochondrial membranes, where it protects them from damage and supports energy production. Because of that, it is one of the most powerful ingredients for supporting mitochondrial health and energy levels. Astaxanthin is must-have energy and mitochondria-supporting compound that has literally dozens of positive side effects on everything from heart health, to brain health, to eye health, to skin health, to energy levels, and much more. It is one of nature’s most powerful health and energy-supporting nutrients. (click here for references) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

REFERENCES: 

CHLORELLA 

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Lee, H.-S., Choi, C.-Y., Cho, C. & Song, Y.Attenuating effect of chlorella supplementation on oxidative stress and NFkappaB activation in peritoneal macrophages and liver of C57BL/6 mice fed onan atherogenic diet. Biosci. Biotechnol. Biochem. 67, 2083–2090 (2003). 

Panahi, Y. et al. Investigation of the effects of Chlorella vulgaris supplementation on the modulation of oxidative stress inapparently healthy smokers. Clin. Lab. 59, 579–587 (2013). 

Fallah, A. A. et al. Effect of Chlorella supplementation on cardiovascular risk factors: A meta-analysis of randomizedcontrolled trials. Clin. Nutr. 37, 1892–1901 (2018). 

Kwak, J. H. et al. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural killer cell activity and early inflammatory response (randomized, double-blinded, placebo-controlled trial). Nutr. J. 11, 53 (2012). 

Lee, I. et al. Detoxification of chlorella supplement on heterocyclic amines in Korean young adults. Environ. Toxicol. Pharmacol. 39,441–446 (2015). 

Uchikawa, T. et al. Enhanced elimination of tissue methylmercury in Parachlorella beijerinckii-fed mice. J. Toxicol. Sci. 36,121–126 (2011). 

SPIRULINA 

Ciferri, O. Spirulina, the edible microorganism. Microbiol. Rev. 47, 551–578 (1983). 

Liu, Q., Huang, Y., Zhang, R., Cai, T. & Cai, Y. Medical Application of Spirulina platensis Derived C-Phycocyanin. Evid. Based. Complement. Alternat. Med. 2016, 7803846 (2016). 

McCarty, M. F. Clinical potential of Spirulina as a source of phycocyanobilin. J. Med. Food 10, 566–570 (2007). 

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Bedard, K. & Krause, K.-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev.87, 245–313 (2007). 

McCarty, M. F., Barroso-Aranda, J. & Contreras, F.NADPH oxidase mediates glucolipotoxicity-induced beta cell dysfunction–clinical implications. Med. Hypotheses 74, 596–600 (2010). 

Nawrocka, D., Kornicka, K., Śmieszek, A. & Marycz, K. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses. Mar. Drugs 15, (2017). 

Olsson, R. & Stigendal, L. Clinical experience with isolated hyperbilirubinemia. Scand. J. Gastroenterol. 24, 617–622 (1989). 

Hinds, T. D., Jr & Stec, D. E. Bilirubin, a Cardiometabolic Signaling Molecule. Hypertension 72, 788–795 (2018). 

Horsfall, L. J., Nazareth, I., Pereira, S. P. &Petersen, I. Gilbert’s syndrome and the risk of death: a population-based cohort study. J. Gastroenterol. Hepatol. 28, 1643–1647 (2013). 

Maruhashi, T. et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation 126, 598–603 (2012). 

Kundur, A. R., Singh, I. & Bulmer, A. C. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert’s syndrome? Atherosclerosis 239, 73–84(2015). 

Goel, A. & Aggarwal, R. Unconjugated hyper bilirubinemia: a blessing in disguise? Journal of gastroenterology and hepatology vol. 28 1687–1689 (2013). 

Tosevska, A. et al. Longer telomeres in chronic, moderate, unconjugated hyper bilirubinaemia: insights from a human study on Gilbert’s Syndrome. Sci. Rep. 6, 22300 (2016). 

MCT (medium chain triglycerides) 

Krotkiewski M. Value of VLCD supplementation with medium chain triglycerides. Int J Obes Relat Metab Disord. 2001 Sep;25(9):1393-400. doi: 10.1038/sj.ijo.0801682. PMID: 11571605. 

Papamandjaris AA, White MD, Jones PJ. Components of total energy expenditure in healthy young women are not affected after 14 days of feeding with medium-versus long-chain triglycerides. Obes Res. 1999 May;7(3):273-80. doi: 10.1002/j.1550-8528.1999.tb00406.x. PMID: 10348498. 

Papamandjaris AA, White MD, Raeini-Sarjaz M, Jones PJ. Endogenous fat oxidation during medium chain versus long chain triglyceride feeding in healthy women. Int J Obes Relat Metab Disord. 2000 Sep;24(9):1158-66. doi: 10.1038/sj.ijo.0801350. PMID: 11033985. 

CITRUS BIOFLAVANOIDS 

 

Mahmoud AM, Hernández Bautista RJ, Sandhu MA, Hussein OE. Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health. Oxid Med Cell Longev. 2019;2019:5484138. 

Kumar A, Prakash A, Dogra S. Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by D-galactose in mice. Food Chem Toxicol. 2010;48:626–32. 

Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr. 2014;5:404–17. 

Testai L, Piragine E, Piano I, Flori L, Da Pozzo E, Miragliotta V, et al. The Citrus Flavonoid Naringenin Protects the Myocardium from Ageing-Dependent Dysfunction: Potential Role of SIRT1. Oxid Med Cell Longev. 2020;2020:4650207. 

Kicinska A, Jarmuszkiewicz W. Flavonoids and Mitochondria: Activation of Cytoprotective Pathways? Molecules [Internet]. 2020;25. Available from: http://dx.doi.org/10.3390/molecules25133060 

Overdevest E, Wouters JA, Wolfs KHM, van Leeuwen JJM, Possemiers S. Citrus Flavonoid Supplementation Improves Exercise Performance in Trained Athletes. J Sports Sci Med. 2018;17:24–30. 

Martínez-Noguera FJ, Marín-Pagán C, Carlos-Vivas J, Rubio-Arias JA, Alcaraz PE. Acute Effects of Hesperidin in Oxidant/Antioxidant State Markers and Performance in Amateur Cyclists. Nutrients [Internet]. 2019;11. Available from: http://dx.doi.org/10.3390/nu11081898 

 

D-RIBOSE 

 

Pauly DF, Pepine CJ. D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000;5:249–58. 

Mahoney DE, Hiebert JB, Thimmesch A, Pierce JT, Vacek JL, Clancy RL, et al. Understanding D-Ribose and Mitochondrial Function. Adv Biosci Clin Med. 2018;6:1–5. 

Omran H, Illien S, MacCarter D, St Cyr J, Lüderitz B. D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study. Eur J Heart Fail. 2003;5:615–9. 

MacCarter D, Vijay N, Washam M, Shecterle L, Sierminski H, St Cyr JA. D-ribose aids advanced ischemic heart failure patients. Int J Cardiol. 2009;137:79–80. 

Pliml W, von Arnim T, Stäblein A, Hofmann H, Zimmer HG, Erdmann E. Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet. 1992;340:507–10. 

Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004;286:R182–8. 

Seifert JG, Brumet A, St Cyr JA. The influence of D-ribose ingestion and fitness level on performance and recovery. J Int Soc Sports Nutr. 2017;14:47. 

Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006;12:857–62. 

Gebhart B, Jorgenson JA. Benefit of ribose in a patient with fibromyalgia. Pharmacotherapy. 2004;24:1646–8. 

 

ACETHYL-L-CARNITINE 

 

Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, et al. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clin. 2014;1:12–23. 

Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, et al. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell. 2006;23:607–18. 

Kerner J, Yohannes E, Lee K, Virmani A, Koverech A, Cavazza C, et al. Acetyl-L-carnitine increases mitochondrial protein acetylation in the aged rat heart. Mech Ageing Dev. 2015;145:39–50. 

Rosca MG, Lemieux H, Hoppel CL. Mitochondria in the elderly: Is acetylcarnitine a rejuvenator? Adv Drug Deliv Rev. 2009;61:1332–42. 

Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M, Koverech A, et al. Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr. 2008;46:181–90. 

 

CREATINE 

 

Walsh B, Tonkonogi M, Söderlund K, Hultman E, Saks V, Sahlin K. The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J Physiol. 2001;537:971–8. 

Barbieri E, Guescini M, Calcabrini C, Vallorani L, Diaz AR, Fimognari C, et al. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity. Oxid Med Cell Longev. 2016;2016:5152029. 

Sestili P, Barbieri E, Martinelli C, Battistelli M, Guescini M, Vallorani L, et al. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts. Mol Nutr Food Res. 2009;53:1187–204. 

Sestili P, Barbieri E, Stocchi V. Effects of Creatine in Skeletal Muscle Cells and in Myoblasts Differentiating Under Normal or Oxidatively Stressing Conditions. Mini Rev Med Chem. 2016;16:4–11. 

Dempsey RL, Mazzone MF, Meurer LN. Does oral creatine supplementation improve strength? A meta-analysis. J Fam Pract. 2002;51:945–51. 

Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13:198–226. 

Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage F-X, Dutheil F. Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses. Sports Med. 2015;45:1285–94. 

Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage F-X, Dutheil F. Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis. Sports Med. 2017;47:163–73. 

Chilibeck PD, Kaviani M, Candow DG, Zello GA. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access J Sports Med. 2017;8:213–26. 

Swaminathan R. Magnesium metabolism and its disorders. Clin Biochem Rev. 2003;24:47–66. 

 

RESVERATROL 

Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone? Clin Biochem. 1997;30(2):91-113.  (PubMed) 

Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004;24(5A):2783-2840.  (PubMed) 

Romero-Perez AI, Ibern-Gomez M, Lamuela-Raventos RM, de La Torre-Boronat MC. Piceid, the major resveratrol derivative in grape juices. J Agric Food Chem. 1999;47(4):1533-1536.  (PubMed) 

Siemann EH, Creasey LL. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic. 1992;43(1):49-52.  

Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet. 1992;339(8808):1523-1526.  (PubMed) 

Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci. 2011;1215:9-15.  (PubMed) 

Burkon A, Somoza V. Quantification of free and protein-bound trans-resveratrol metabolites and identification of trans-resveratrol-C/O-conjugated diglucuronides - two novel resveratrol metabolites in human plasma. Mol Nutr Food Res. 2008;52(5):549-557.  (PubMed) 

Goldberg DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem. 2003;36(1):79-87.  (PubMed) 

Walle T, Hsieh F, Delegge MH, Oatis JE, Jr., Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377-1382.  (PubMed) 

Boocock DJ, Faust GE, Patel KR, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1246-1252.  (PubMed) 

Brown VA, Patel KR, Viskaduraki M, et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010;70(22):9003-9011.  (PubMed) 

Patel KR, Andreadi C, Britton RG, et al. Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. Sci Transl Med. 2013;5(205):205ra133.  (PubMed) 

Tome-Carneiro J, Larrosa M, Gonzalez-Sarrias A, Tomas-Barberan FA, Garcia-Conesa MT, Espin JC. Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des. 2013;19(34):6064-6093.  (PubMed) 

Vitaglione P, Sforza S, Galaverna G, et al. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005;49(5):495-504.  (PubMed) 

Vaz-da-Silva M, Loureiro AI, Falcao A, et al. Effect of food on the pharmacokinetic profile of trans-resveratrol. Int J Clin Pharmacol Ther. 2008;46(11):564-570.  (PubMed) 

la Porte C, Voduc N, Zhang G, et al. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet. 2010;49(7):449-454.  (PubMed) 

Leonard SS, Xia C, Jiang BH, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun. 2003;309(4):1017-1026.  (PubMed) 

Vlachogianni IC, Fragopoulou E, Kostakis IK, Antonopoulou S. In vitro assessment of antioxidant activity of tyrosol, resveratrol and their acetylated derivatives. Food Chem. 2015;177:165-173.  (PubMed) 

Brito P, Almeida LM, Dinis TC. The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Free Radic Res. 2002;36(6):621-631.  (PubMed) 

Frankel EN, Waterhouse AL, Kinsella JE. Inhibition of human LDL oxidation by resveratrol. Lancet. 1993;341(8852):1103-1104.  (PubMed) 

Wang H, Yang YJ, Qian HY, Zhang Q, Xu H, Li JJ. Resveratrol in cardiovascular disease: what is known from current research? Heart Fail Rev. 2012;17(3):437-448.  (PubMed) 

Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004;22(3):169-188.  (PubMed) 

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Yurdagul A, Jr., Kleinedler JJ, McInnis MC, et al. Resveratrol promotes endothelial cell wound healing under laminar shear stress through an estrogen receptor-alpha-dependent pathway. Am J Physiol Heart Circ Physiol. 2014;306(6):H797-806.  (PubMed) 

Chen ZH, Hurh YJ, Na HK, et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis. 2004;25(10):2005-2013.  (PubMed) 

Ciolino HP, Yeh GC. Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol Pharmacol. 1999;56(4):760-767.  (PubMed) 

Hsieh TC, Lu X, Wang Z, Wu JM. Induction of quinone reductase NQO1 by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Med Chem. 2006;2(3):275-285.  (PubMed) 

Chow HH, Garland LL, Hsu CH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010;3(9):1168-1175.  (PubMed) 

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Woo JH, Lim JH, Kim YH, et al. Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene. 2004;23(10):1845-1853.  (PubMed) 

Yu H, Pan C, Zhao S, Wang Z, Zhang H, Wu W. Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. Biomed Pharmacother. 2008;62(6):366-372.  (PubMed) 

Igura K, Ohta T, Kuroda Y, Kaji K. Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Lett. 2001;171(1):11-16.  (PubMed) 

Lin MT, Yen ML, Lin CY, Kuo ML. Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol. 2003;64(5):1029-1036.  (PubMed) 

Chen Y, Tseng SH. Review. Pro- and anti-angiogenesis effects of resveratrol. In Vivo. 2007;21(2):365-370.  (PubMed) 

Kanavi MR, Darjatmoko S, Wang S, et al. The sustained delivery of resveratrol or a defined grape powder inhibits new blood vessel formation in a mouse model of choroidal neovascularization. Molecules. 2014;19(11):17578-17603.  (PubMed) 

Steele VE, Hawk ET, Viner JL, Lubet RA. Mechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer. Mutat Res. 2003;523-524:137-144.  (PubMed) 

Donnelly LE, Newton R, Kennedy GE, et al. Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol. 2004;287(4):L774-783.  (PubMed) 

Pinto MC, Garcia-Barrado JA, Macias P. Resveratrol is a potent inhibitor of the dioxygenase activity of lipoxygenase. J Agric Food Chem. 1999;47(12):4842-4846.  (PubMed) 

Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci. 2007;12:4839-4854.  (PubMed) 

de la Lastra CA, Villegas I. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res. 2005;49(5):405-430.  (PubMed) 

Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014;22(3):147-151.  (PubMed) 

Stocker R, Keaney JF, Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381-1478.  (PubMed) 

Carluccio MA, Siculella L, Ancora MA, et al. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol. 2003;23(4):622-629.  (PubMed) 

Ferrero ME, Bertelli AE, Fulgenzi A, et al. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr. 1998;68(6):1208-1214.  (PubMed) 

Ekshyyan VP, Hebert VY, Khandelwal A, Dugas TR. Resveratrol inhibits rat aortic vascular smooth muscle cell proliferation via estrogen receptor dependent nitric oxide production. J Cardiovasc Pharmacol. 2007;50(1):83-93.  (PubMed) 

Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol. 2003;63(4):925-932.  (PubMed) 

Mnjoyan ZH, Fujise K. Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway. Biochem Biophys Res Commun. 2003;311(2):546-552.  (PubMed) 

Khandelwal AR, Hebert VY, Dugas TR. Essential role of ER-alpha-dependent NO production in resveratrol-mediated inhibition of restenosis. Am J Physiol Heart Circ Physiol. 2010;299(5):H1451-1458.  (PubMed) 

Duffy SJ, Vita JA. Effects of phenolics on vascular endothelial function. Curr Opin Lipidol. 2003;14(1):21-27.  (PubMed) 

Klinge CM, Blankenship KA, Risinger KE, et al. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem. 2005;280(9):7460-7468.  (PubMed) 

Klinge CM, Wickramasinghe NS, Ivanova MM, Dougherty SM. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J. 2008;22(7):2185-2197.  (PubMed) 

Takahashi S, Nakashima Y. Repeated and long-term treatment with physiological concentrations of resveratrol promotes NO production in vascular endothelial cells. Br J Nutr. 2012;107(6):774-780.  (PubMed) 

Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta. 1995;235(2):207-219.  (PubMed) 

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Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int. 2009;54(2):111-118.  (PubMed) 

 

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Kumar A, Naidu PS, Seghal N, Padi SS. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology. 2007;79(1):17-26.  (PubMed) 

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Berge G, Ovrebo S, Eilertsen E, Haugen A, Mollerup S. Analysis of resveratrol as a lung cancer chemopreventive agent in A/J mice exposed to benzo[a]pyrene. Br J Cancer. 2004;91(7):1380-1383.  (PubMed) 

Schneider Y, Duranton B, Gosse F, Schleiffer R, Seiler N, Raul F. Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutr Cancer. 2001;39(1):102-107.  (PubMed) 

Sengottuvelan M, Nalini N. Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development. Br J Nutr. 2006;96(1):145-153.  (PubMed) 

Ziegler CC, Rainwater L, Whelan J, McEntee MF. Dietary resveratrol does not affect intestinal tumorigenesis in Apc(Min/+) mice. J Nutr. 2004;134(1):5-10.  (PubMed) 

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Popat R, Plesner T, Davies F, et al. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2013;160(5):714-717.  (PubMed) 

Smoliga JM, Blanchard O. Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules. 2014;19(11):17154-17172.  (PubMed) 

PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011;342:d671.  (PubMed) 

Lippi G, Franchini M, Favaloro EJ, Targher G. Moderate red wine consumption and cardiovascular disease risk: beyond the "French paradox". Semin Thromb Hemost. 2010;36(1):59-70.  (PubMed) 

Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY. Antiartherosclerotic effects of plant flavonoids. Biomed Res Int. 2014;2014:480258.  (PubMed) 

Gronbaek M, Becker U, Johansen D, et al. Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med. 2000;133(6):411-419.  (PubMed) 

Klatsky AL, Friedman GD, Armstrong MA, Kipp H. Wine, liquor, beer, and mortality. Am J Epidemiol. 2003;158(6):585-595.  (PubMed) 

Renaud SC, Gueguen R, Siest G, Salamon R. Wine, beer, and mortality in middle-aged men from eastern France. Arch Intern Med. 1999;159(16):1865-1870.  (PubMed) 

Mukamal KJ, Conigrave KM, Mittleman MA, et al. Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Engl J Med. 2003;348(2):109-118.  (PubMed) 

Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. Bmj. 1996;312(7033):731-736.  (PubMed) 

Wannamethee SG, Shaper AG. Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. Am J Public Health. 1999;89(5):685-690.  (PubMed) 

Barefoot JC, Gronbaek M, Feaganes JR, McPherson RS, Williams RB, Siegler IC. Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study. Am J Clin Nutr. 2002;76(2):466-472.  (PubMed) 

McCann SE, Sempos C, Freudenheim JL, et al. Alcoholic beverage preference and characteristics of drinkers and nondrinkers in western New York (United States). Nutr Metab Cardiovasc Dis. 2003;13(1):2-11.  (PubMed) 

Mortensen EL, Jensen HH, Sanders SA, Reinisch JM. Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults. Arch Intern Med. 2001;161(15):1844-1848.  (PubMed) 

Johansen D, Friis K, Skovenborg E, Gronbaek M. Food buying habits of people who buy wine or beer: cross sectional study. Bmj. 2006;332(7540):519-522.  (PubMed) 

Ruidavets JB, Bataille V, Dallongeville J, et al. Alcohol intake and diet in France, the prominent role of lifestyle. Eur Heart J. 2004;25(13):1153-1162.  (PubMed) 

Stocker R, O'Halloran RA. Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall. Am J Clin Nutr. 2004;79(1):123-130.  (PubMed) 

De Curtis A, Murzilli S, Di Castelnuovo A, et al. Alcohol-free red wine prevents arterial thrombosis in dietary-induced hypercholesterolemic rats: experimental support for the 'French paradox'. J Thromb Haemost. 2005;3(2):346-350.  (PubMed) 

Lekakis J, Rallidis LS, Andreadou I, et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005;12(6):596-600.  (PubMed) 

Karatzi K, Karatzis E, Papamichael C, Lekakis J, Zampelas A. Effects of red wine on endothelial function: postprandial studies vs clinical trials. Nutr Metab Cardiovasc Dis. 2009;19(10):744-750.  (PubMed) 

Grover-Paez F, Zavalza-Gomez AB. Endothelial dysfunction and cardiovascular risk factors. Diabetes Res Clin Pract. 2009;84(1):1-10.  (PubMed) 

Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med. 2002;9(1):77-79.  (PubMed) 

Kirk RI, Deitch JA, Wu JM, Lerea KM. Resveratrol decreases early signaling events in washed platelets but has little effect on platalet in whole blood. Blood Cells Mol Dis. 2000;26(2):144-150.  (PubMed) 

Szewczuk LM, Forti L, Stivala LA, Penning TM. Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J Biol Chem. 2004;279(21):22727-22737.  (PubMed) 

Tsai SH, Lin-Shiau SY, Lin JK. Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Br J Pharmacol. 1999;126(3):673-680.  (PubMed) 

Fukao H, Ijiri Y, Miura M, et al. Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul Fibrinolysis. 2004;15(6):441-446.  (PubMed) 

Wang Z, Zou J, Huang Y, Cao K, Xu Y, Wu JM. Effect of resveratrol on platelet aggregation in vivo and in vitro. Chin Med J (Engl). 2002;115(3):378-380.  (PubMed) 

Wilson T, Knight TJ, Beitz DC, Lewis DS, Engen RL. Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits. Life Sci. 1996;59(1):PL15-21.  (PubMed) 

Fujitaka K, Otani H, Jo F, et al. Modified resveratrol Longevinex improves endothelial function in adults with metabolic syndrome receiving standard treatment. Nutr Res. 2011;31(11):842-847.  (PubMed) 

Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis. 2011;21(11):851-856.  (PubMed) 

Wong RH, Berry NM, Coates AM, et al. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013;31(9):1819-1827.  (PubMed) 

Agarwal B, Campen MJ, Channell MM, et al. Resveratrol for primary prevention of atherosclerosis: clinical trial evidence for improved gene expression in vascular endothelium. Int J Cardiol. 2013;166(1):246-248.  (PubMed) 

Tome-Carneiro J, Gonzalvez M, Larrosa M, et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol. 2012;110(3):356-363.  (PubMed) 

Tome-Carneiro J, Gonzalvez M, Larrosa M, et al. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol Nutr Food Res. 2012;56(5):810-821.  (PubMed) 

Tome-Carneiro J, Gonzalvez M, Larrosa M, et al. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013;27(1):37-48.  (PubMed) 

Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.  (PubMed) 

Liu Y, Ma W, Zhang P, He S, Huang D. Effect of resveratrol on blood pressure: A meta-analysis of randomized controlled trials. Clin Nutr. 2015;34(1):27-34.  (PubMed) 

Tome-Carneiro J, Gonzalvez M, Larrosa M, et al. Resveratrol in primary and secondary prevention of cardiovascular disease: a dietary and clinical perspective. Ann N Y Acad Sci. 2013;1290:37-51.  (PubMed) 

Heilbronn LK, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr. 2003;78(3):361-369.  (PubMed) 

Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000;289(5487):2126-2128.  (PubMed) 

Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425(6954):191-196.  (PubMed) 

Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430(7000):686-689.  (PubMed) 

Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006;16(3):296-300.  (PubMed) 

Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-342.  (PubMed) 

Semba RD, Ferrucci L, Bartali B, et al. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 2014;174(7):1077-1084.  (PubMed) 

Brown K, Rufini A, Gescher A. Do not throw out the resveratrol with the bath water. JAMA Intern Med. 2015;175(1):140-141.  (PubMed) 

Glaser JH. Effect of wine consumption on mortality. JAMA Intern Med. 2015;175(4):650.  (PubMed) 

Wang J, Ho L, Qin W, et al. Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2005;19(6):659-661.  (PubMed) 

Aguirre L, Fernandez-Quintela A, Arias N, Portillo MP. Resveratrol: anti-obesity mechanisms of action. Molecules. 2014;19(11):18632-18655.  (PubMed) 

Kennedy DO, Wightman EL, Reay JL, et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91(6):1590-1597.  (PubMed) 

Witte AV, Kerti L, Margulies DS, Floel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014;34(23):7862-7870.  (PubMed) 

Pasinetti GM, Wang J, Ho L, Zhao W, Dubner L. Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment. Biochim Biophys Acta. 2015;1852(6):1202-1208.  (PubMed) 

CORDYCEPS 

Lin, -Q. & Li, S.-P. Cordyceps as an Herbal Drug. in Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition (CRC Press/Taylor & Francis, 2011). 

Lo HC, al. The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin. – PubMed – NCBI. 

Hirsch, K. R., Smith-Ryan, A. E., Roelofs, E. J., Trexler, E. T. & Mock, M. G. Cordyceps militaris improves tolerance to high intensity exercise after acute and chronic supplementation. J. Suppl. 14, 42 (2017). 

REISHI 

 

Wachtel-Galor S, Yuen J, Buswell JA, Benzie IFF.Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. In: Benzie IFF,Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects.Boca Raton (FL): CRC Press/Taylor & Francis; 2012. 

Lin Z-B. Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. J Pharmacol Sci. 2005;99:144–53. 

De Marco Castro E, Calder PC, Roche HM. β-1,3/1,6-Glucansand Immunity: State of the Art and Future Directions. Mol Nutr Food Res.2020;e1901071. 

Zhong Z, Han J, Zhang J, Xiao Q, Hu J, Chen L. Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system. Drug Des Devel Ther. 2018;12:1479–89. 

 

CHAGA 

 

A.G. Atanasov, B. Waltenberger, E.M. Pferschy-Wenzig, T. Linder, C. Wawrosch, P. Uhrin, V. Temml, L. Wang, S. Schwaiger, E.H. Heiss, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol. Adv. (2015 

C. Chen, W. Zheng, X. Gao, X. Xiang, D. Sun, J. Wei, C. Chu. Aqueous extract of Inonotus bliquus (Fr.) Pilat Hymenochaetaceae) significantly inhibits the growth of Sarcoma 180 by inducing apoptosis. Am. J. Pharmacol. Toxicol. (2007) 

S.H. Lee, H.S. Hwang, J.W. Yun. Antitumor activity of water extract of a mushroom, Inonotus obliquus, against HT-29 human colon cancer cells. Phyther. Res. (2009) 

Z. Li, J. Mei, L. Jiang, C. Geng, Q. Li, X. Yao, J. Cao. Chaga medicinal mushroom inonotus obliquus (Agaricomycetes) polysaccharides suppress tacrine- induced apoptosis by reactive oxygen species-scavenging and mitochondrial pathway in hepg2 cells. Int. J. Med. Mushrooms (2019) 

L. Ma, H. Chen, P. Dong, X. Lu. Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Food Chem. (2013) 

Jehane Eid, Biswadeep Das. Molecular insights and cell cycle assessment upon exposure to Chaga (Inonotus obliquus) mushroom polysaccharides in zebrafish (Danio rerio). Sci. Rep., 10 (7406) (2020) 

Jehane Eid, Majdah Al-Tuwaijri. Chaga mushroom (Inonotus Obliquus) inhibits growth of lung adenocarcinoma (A549) cells but not aspergillus fumigatus. Curr. Topics Nutraceutical. Res., 16 (4) (2018), pp. 289-296 

 

PANAX GINSENG 

 

Huang Y, Kwan KKL, Leung KW, Yao P, Wang H, Dong TT, et al. Ginseng extracts modulate mitochondrial bioenergetics of live cardiomyoblasts: a functional comparison of different extraction solvents. J Ginseng Res. 2019;43:517–26. 

Jin T-Y, Rong P-Q, Liang H-Y, Zhang P-P, Zheng G-Q, Lin Y. Clinical and Preclinical Systematic Review of Panax ginseng C. A. Mey and Its Compounds for Fatigue. Front Pharmacol. 2020;11:1031. 

Lee N, Lee S-H, Yoo H-R, Yoo HS. Anti-Fatigue Effects of Enzyme-Modified Ginseng Extract: A Randomized, Double-Blind, Placebo-Controlled Trial. J Altern Complement Med. 2016;22:859–64. 

Kim H-G, Cho J-H, Yoo S-R, Lee J-S, Han J-M, Lee N-H, et al. Antifatigue Effects of Panax ginseng C.A. Meyer: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS One [Internet]. Public Library of Science; 2013 [cited 2019 Nov 25];8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629193/ 

 

ASHWAGHANDA 

 

Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8:208–13. 

Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. 2014;20:901–8. 

Andrade C. Ashwagandha for anxiety disorders. World J. Biol. Psychiatry. 2009. p. 686–7. 

Zahiruddin S, Basist P, Parveen A, Parveen R, Khan W, Gaurav, et al. Ashwagandha in brain disorders: A review of recent developments. J Ethnopharmacol. 2020;257:112876. 

Lee D-H, Ahn J, Jang Y-J, Seo H-D, Ha T-Y, Kim MJ, et al. Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle. Nutrients [Internet]. 2020;12. Available from: http://dx.doi.org/10.3390/nu12020431 

Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine . 2019;98:e17186. 

Deshpande A, Irani N, Balkrishnan R, Benny IR. A randomized, double blind, placebo controlled study to evaluate the effects of ashwagandha (Withania somnifera) extract on sleep quality in healthy adults. Sleep Med. 2020;72:28–36. 

Salve J, Pate S, Debnath K, Langade D. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus. 2019;11:e6466. 

Langade D, Kanchi S, Salve J, Debnath K, Ambegaokar D. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Cureus. 2019;11:e5797. 

Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34:255–62. 

Fuladi S, Emami SA, Mohammadpour AH, Karimani A, Manteghi AA, Sahebkar A. Assessment of Withania somnifera root extract efficacy in patients with generalized anxiety disorder: A randomized double-blind placebo-controlled trial. Curr Clin Pharmacol [Internet]. 2020; Available from: http://dx.doi.org/10.2174/1574884715666200413120413 

 

 

RHODIOLA 

Ma G-P, Zheng Q, Xu M-B, Zhou X-L, Lu L, Li Z-X, et al. Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms. Front Pharmacol. 2018;9:1415. 

Li Y, Pham V, Bui M, Song L, Wu C, Walia A, et al. Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention. Curr Pharmacol Rep. 2017;3:384–95. 

Edwards D, Heufelder A, Zimmermann A. Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms–results of an open-label study. Phytother Res. 2012;26:1220–5. 

Kasper S, Dienel A. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms. Neuropsychiatr Dis Treat. 2017;13:889–98. 

Lekomtseva Y, Zhukova I, Wacker A. Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial. Complement Med Res. 2017;24:46–52. 

Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin VV. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. 2000;7:85–9. 

Shevtsov VA, Zholus BI, Shervarly VI, Vol’skij VB, Korovin YP, Khristich MP, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. 2003;10:95–105. 

Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009;75:105–12. 

Cropley M, Banks AP, Boyle J. The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms. Phytother Res. 2015;29:1934–9. 

Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61:343–8 

 

TURMERIC 

Burge, K., Gunasekaran, A., Eckert, J. & Chaaban,H. Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms ofProtection. Int. J. Mol. Sci. 20, (2019). 

Ng, Q. X. et al. A Meta-Analysis of the Clinical Useof Curcumin for Irritable Bowel Syndrome (IBS). J. Clin. Med. Res. 7, (2018). 

Ghosh, S. S., He, H., Wang, J., Gehr, T. W. &Ghosh, S. Curcumin-mediated regulation of intestinal barrier function: Themechanism underlying its beneficial effects. Tissue Barriers 6, e1425085(2018). 

Peterson, C. T. et al. Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. J Evid Based Integr Med 23,2515690X18790725 (2018). 

Di Meo, F., Margarucci, S., Galderisi, U., Crispi, S.& Peluso, G. Curcumin, Gut Microbiota, and Neuroprotection. Nutrients 11,(2019). 

Hewlings, S. J. & Kalman, D. S. Curcumin: A Reviewof Its’ Effects on Human Health. Foods 6, (2017). 

Soto-Urquieta, M. G. et al. Curcumin restoresmitochondrial functions and decreases lipid peroxidation in liver and kidneysof diabetic db/db mice. Biol. Res. 47, 74 (2014). 

 

QUERCETINE 

 

de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF. Quercetin and the mitochondria: A mechanistic view. Biotechnol Adv. 2016;34:532–49. 

Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1071–7. 

Pelletier DM, Lacerte G, Goulet EDB. Effects of quercetin supplementation on endurance performance and maximal oxygen consumption: a meta-analysis. Int J Sport Nutr Exerc Metab. 2013;23:73–82. 

Kressler J, Millard-Stafford M, Warren GL. Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Med Sci Sports Exerc. 2011;43:2396–404. 

Ou Q, Zheng Z, Zhao Y, Lin W. Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials. Int J Food Sci Nutr. 2020;71:152–63. 

Mohammadi-Sartang M, Mazloom Z, Sherafatmanesh S, Ghorbani M, Firoozi D. Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2017;71:1033–9. 

Tabrizi R, Tamtaji OR, Mirhosseini N, Lankarani KB, Akbari M, Heydari ST, et al. The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2020;60:1855–68. 

Guo W, Gong X, Li M. Quercetin Actions on Lipid Profiles in Overweight and Obese Individuals: A Systematic Review and Meta-Analysis. Curr Pharm Des. 2019;25:3087–95. 

Sahebkar A. Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2017;57:666–76. 

Tamtaji OR, Milajerdi A, Dadgostar E, Kolahdooz F, Chamani M, Amirani E, et al. The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Curr Pharm Des. 2019;25:1372–84. 

Serban M-C, Sahebkar A, Zanchetti A, Mikhailidis DP, Howard G, Antal D, et al. Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc [Internet]. 2016;5. Available from: http://dx.doi.org/10.1161/JAHA.115.002713 

Riva A, Ronchi M, Petrangolini G, Bosisio S, Allegrini P. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin. Eur J Drug Metab Pharmacokinet. 2019;44:169–77. 

 

AMLA 

Husain, I. et al. Exploring the multifacetedneuroprotective actions of Emblica officinalis (Amla): a review. Metab. BrainDis. 34, 957–965 (2019). 

Baliga, M. S. & Dsouza, J. J. Amla (Emblicaofficinalis Gaertn), a wonder berry in the treatment and prevention of cancer.Eur. J. Cancer Prev. 20, 225–239 (2011). 

Krishnaveni, M. & Mirunalini, S. Therapeuticpotential of Phyllanthus emblica (amla): the ayurvedic wonder. J. Basic Clin.Physiol. Pharmacol. 21, 93–105 (2010). 

Akhtar, M. S., Ramzan, A., Ali, A. & Ahmad, M.Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipidprofile of normal subjects and type 2 diabetic patients. Int. J. Food Sci.Nutr. 62, 609–616 (2011). 

Kapoor, M. P., Suzuki, K., Derek, T., Ozeki, M. &Okubo, T. Clinical evaluation of Emblica Officinalis Gatertn (Amla) in healthyhuman subjects: Health benefits and safety results from a randomized,double-blind, crossover placebo-controlled study. Contemp Clin Trials Commun17, 100499 (2020). 

Upadya, H. et al. A randomized, double blind, placebocontrolled, multicenter clinical trial to assess the efficacy and safety ofEmblica officinalis extract in patients with dyslipidemia. BMC Complement.Altern. Med. 19, 27 (2019). 

Usharani, P., Fatima, N. & Muralidhar, N. Effectsof Phyllanthus emblica extract on endothelial dysfunction and biomarkers ofoxidative stress in patients with type 2 diabetes mellitus: a randomized,double-blind, controlled study. Diabetes Metab. Syndr. Obes. 6, 275–284 (2013). 

Usharani, P., Merugu, P. L. & Nutalapati, C.Evaluation of the effects of a standardized aqueous extract of Phyllanthusemblica fruits on endothelial dysfunction, oxidative stress, systemicinflammation and lipid profile in subjects with metabolic syndrome: arandomised, double blind, placebo controlled clinical study. BMC Complement.Altern. Med. 19, 97 (2019). 

Gopa, B., Bhatt, J. & Hemavathi, K. G. Acomparative clinical study of hypolipidemic efficacy of Amla (Emblica officinalis)with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitor simvastatin.Indian J. Pharmacol. 44, 238–242 (2012). 

Karkon Varnosfaderani, S. et al. Efficacy and safetyof Amla (Phyllanthus emblica L.) in non-erosive reflux disease: a double-blind,randomized, placebo-controlled clinical trial. J. Integr. Med. 16, 126–131(2018). 

L-THEANINE 

W.W. Deng, S. Ogita, H. Ashihara. Ethylamine content and theanine biosynthesis in different organs of Camellia sinensis seedlings. Z Naturforsch C, 64 (5–6) (2009), pp. 387-390 

L. Scheid, S. Ellinger, B. Alteheld, H. Herholz, J. Ellinger, T. Henn, et al. Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea. J Nutr, 142 (12) (2012), pp. 2091-2096 

Y. Sadzuka, Y. Yamashita, S. Kishimoto, S. Fukushima, Y. Takeuchi, T. Sonobe. Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea. Yakugaku Zasshi, 122 (11) (2002), pp. 995-999 

H.S. Cho, S. Kim, S.Y. Lee, J.A. Park, S.J. Kim, H.S. Chun. Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology, 29 (4) (2008), pp. 656-662 

T. Yamada, T. Terashima, K. Wada, S. Ueda, M. Ito, T. Okubo, et al. Theanine, γ-glutamylethylamide, increases neurotransmission concentrations and neurotrophin mRNA levels in the brain during lactation. Life Sci, 81 (2007), pp. 1247-1255 

X. Tian, L. Sun, L. Gou, X. Ling, Y. Feng, L. Wang, et al. Protective effect of L-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res, 1503 (2013), pp. 24-32 

M.J. Desai, M.S. Gill, W.H. Hsu, D.W. Armstrong.Pharmacokinetics of theanine enantiomers in rats.Chirality, 17 (3) (2005), pp. 154-162 

H. Tsuge, S. Sano, T. Hayakawa, T. Kakuda, T. Unno. Theanine, gamma-glutamylethylamide, is metabolized by renal phosphate-independent glutaminase. Biochim Biophys Acta, 1620 (2003), pp. 47-53 

P. Nathan, K. Lu, M. Gray, C. Oliver. The neuropharmacology of L-theanine (N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother, 6 (2) (2006), pp. 21-30 

T. Kakuda, A. Nozawa, A. Sugimoto, H. Niino. Inhibition by theanine of binding of (3H) AMPA, (3H) kainate, and (3H) MDL 105, 519 to glutamate receptors. Biosci Biotechnol Biochem, 66 (12) (2002), pp. 2683-2686 

T. Kakuda. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull, 25 (12) (2002), pp. 1513-1518 

T. Kakuda. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res, 64 (2) (2011), pp. 162-168 

C. Wakabayashi, T. Numakawa, M. Ninomiya, S. Chiba, H. Kunugi. Behavioral and molecular evidence for psychotropic effects in L-theanine. Psychopharmacology, 219 (4) (2012), pp. 1099-1109 

 

N-ACETHYL-CYSTEINE 

Pizzorno J. Glutathione! Integr Med . 2014;13:8–12. 

Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007;7:355–9. 

Pendyala L, Creaven PJ. Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Cancer Epidemiol Biomarkers Prev. 1995;4:245–51. 

Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, et al. The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials. Eur J Pharmacol. 2020;884:173368. 

Polyak E, Ostrovsky J, Peng M, Dingley SD, Tsukikawa M, Kwon YJ, et al. N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease. Mol Genet Metab. 2018;123:449–62. 

Aparicio-Trejo OE, Reyes-Fermín LM, Briones-Herrera A, Tapia E, León-Contreras JC, Hernández-Pando R, et al. Protective effects of N-acetyl-cysteine in mitochondria bioenergetics, oxidative stress, dynamics and S-glutathionylation alterations in acute kidney damage induced by folic acid. Free Radic Biol Med. 2019;130:379–96. 

Sandhir R, Sood A, Mehrotra A, Kamboj SS. N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington’s disease. Neurodegener Dis. 2012;9:145–57. 

Wright DJ, Renoir T, Smith ZM, Frazier AE, Francis PS, Thorburn DR, et al. N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington’s disease. Transl Psychiatry. 2015;5:e492. 

 

ALPHA-GPC 

Abbiati G, Fossati T, Lachmann G, Bergamaschi M, Castiglioni C. Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-L-alpha-glycerylphosphorylcholine. Eur J Drug Metab Pharmacokinet. 1993;18:173–80. 

Chin EWM, Goh ELK. Modulating neuronal plasticity with choline. Neural Regeneration Res. 2019;14:1697–8. 

Blusztajn JK, Slack BE, Mellott TJ. Neuroprotective Actions of Dietary Choline. Nutrients [Internet]. 2017;9. Available from: http://dx.doi.org/10.3390/nu9080815 

Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? J Neurol Sci. 2007;257:264–9. 

 

WILD BLUEBERRY 

 

Tan, L. et al. Investigation on the Role of BDNF inthe Benefits of Blueberry Extracts for the Improvement of Learning and Memoryin Alzheimer’s Disease Mouse Model. J. Alzheimers. Dis. 56, 629–640 (2017). 

Rendeiro, C. et al. Blueberry supplementation inducesspatial memory improvements and region-specific regulation of hippocampal BDNFmRNA expression in young rats. Psychopharmacology 223, 319–330 (2012). 

Bensalem, J. et al. Polyphenol-rich extract from grapeand blueberry attenuates cognitive decline and improves neuronal function inaged mice. J. Nutr. Sci. 7, e19 (2018). 

Winter, A. N. & Bickford, P. C. Anthocyanins andTheir Metabolites as Therapeutic Agents for Neurodegenerative Disease.Antioxidants (Basel) 8, (2019). 

Krikorian, R. et al. Blueberry supplementationimproves memory in older adults. J. Agric. Food Chem. 58, 3996–4000 (2010). 

Bowtell, J. L., Aboo-Bakkar, Z., Conway, M. E., Adlam,A.-L. R. & Fulford, J. Enhanced task-related brain activation and restingperfusion in healthy older adults after chronic blueberry supplementation.Appl. Physiol. Nutr. Metab. 42, 773–779 (2017). 

 

 

Boespflug, E. L. et al. Enhanced neural activationwith blueberry supplementation in mild cognitive impairment. Nutr. Neurosci.21, 297–305 (2018). 

Whyte, A. R., Cheng, N., Fromentin, E. & Williams,C. M. A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safetyand Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild BlueberryExtract (ThinkBlueTM) in Maintenance of Episodic and Working Memory in OlderAdults. Nutrients 10, (2018). 

Bergland, A. K. et al. Effects of AnthocyaninSupplementation on Serum Lipids, Glucose, Markers of Inflammation and Cognitionin Adults With Increased Risk of Dementia – A Pilot Study. Front. Genet. 10,536 (2019). 

Whyte, A. R., Cheng, N., Butler, L. T., Lamport, D. J.& Williams, C. M. Flavonoid-Rich Mixed Berries Maintain and ImproveCognitive Function Over a 6 h Period in Young Healthy Adults. Nutrients 11,(2019). 

Kent, K., Charlton, K. E., Netzel, M. & Fanning,K. Food-based anthocyanin intake and cognitive outcomes in human interventiontrials: a systematic review. J. Hum. Nutr. Diet. 30, 260–274 (2017). 

Ma, L., Sun, Z., Zeng, Y., Luo, M. & Yang, J.Molecular Mechanism and Health Role of Functional Ingredients in Blueberry forChronic Disease in Human Beings. Int. J. Mol. Sci. 19, (2018). 

MAGNESIUM 

 

Igamberdiev AU, Kleczkowski LA. Optimization of ATP synthase function in mitochondria and chloroplasts via the adenylate kinase equilibrium. Front Plant Sci. 2015;6:10. 

Pilchova I, Klacanova K, Tatarkova Z, Kaplan P, Racay P. The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions. Oxid Med Cell Longev. 2017;2017:6797460. 

Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, et al. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clin. 2014;1:12–23. 

 

NIACIN/ NIACINAMIDE 

 

Greg Kelly. ND, (2019) NAD: INTRODUCTION TO AN IMPORTANT HEALTHSPAN MOLECULE 

Klimova, , Novotny, M. & Kuca, K. Anti-Aging Drugs – Prospect of Longer Life? Curr. Med. Chem. 25, 1946–1953 (2018). 

Park, A. Scientists Can Reverse DNA Aging in Mice. Time https://time.com/4711023/how-to-keep-yourdna-from-aging/ (2017). 

Dölle, C., Skoge, R. H., Vanlinden, M. R. & Ziegler, M. NAD biosynthesis in humans–enzymes, metabolites and therapeutic Curr. Top. Med. Chem. 13, 2907–2917 (2013). 

PHOSPHATIDYL SERINE 

 

Nicolson GL, Ash ME. Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelles and restoring function. Biochim Biophys Acta. 2014;1838:1657–79. 

Nicolson GL, Rosenblatt S, de Mattos GF, Settineri R, Breeding PC, Ellithorpe RR, et al. Clinical Uses of Membrane Lipid Replacement Supplements in Restoring Membrane Function and Reducing Fatigue in Chronic Diseases and Cancer. Discoveries (Craiova). 2016;4:e54. 

Agadjanyan M, Vasilevko V, Ghochikyan A, Berns P, Kesslak P, Settineri RA, et al. Nutritional Supplement (NT FactorTM) Restores Mitochondrial Function and Reduces Moderately Severe Fatigue in Aged Subjects. J Chronic Fatigue Syndr. Taylor & Francis; 2003;11:23–36. 

 

SHILAJIT 

 

Meena, H., Pandey, H. K., Arya, M. C. & Ahmed, Z. Shilajit: A panacea for high-altitude problems. Int. J. Ayurveda Res. 1, 37–40(2010). 

Agarwal, S. P., Khanna, R., Karmarkar, R., Anwer, M.K. & Khar, R. K. Shilajit: a review. Phytother. Res. 21, 401–405 (2007). 

Pandit, S. et al. Clinical evaluation of purified Shilajiton testosterone levels in healthy volunteers. Andrologia 48, 570–575 (2016). 

Biswas, T. K. et al. Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia. Andrologia 42,48–56 (2010). 

Das, A. et al. The Human Skeletal Muscle Transcriptomein Response to Oral Shilajit Supplementation. J. Med. Food 19, 701–709 (2016). 

ALPHA LIPOIC ACID 

 

Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009;1790:1149–60. 

Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C. Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging. Clin Nutr. 2005;24:794–800. 

Long J, Gao F, Tong L, Cotman CW, Ames BN, Liu J. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. Neurochem Res. 2009;34:755–63. 

Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99:1876–81. 

Pershadsingh HA. Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome. Expert Opin Investig Drugs. 2007;16:291–302. 

Chen W-L, Kang C-H, Wang S-G, Lee H-M. α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase. Diabetologia. 2012;55:1824–35. 

Carbonelli MG, Di Renzo L, Bigioni M, Di Daniele N, De Lorenzo A, Fusco MA. Alpha-lipoic acid supplementation: a tool for obesity therapy? Curr Pharm Des. 2010;16:840–6. 

Koh EH, Lee WJ, Lee SA, Kim EH, Cho EH, Jeong E, et al. Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med. 2011;124:85.e1–8. 

Li N, Yan W, Hu X, Huang Y, Wang F, Zhang W, et al. Effects of oral α-lipoic acid administration on body weight in overweight or obese subjects: a crossover randomized, double-blind, placebo-controlled trial. Clin Endocrinol . 2017;86:680–7. 

Breithaupt-Grögler K, Niebch G, Schneider E, Erb K, Hermann R, Blume HH, et al. Dose-proportionality of oral thioctic acid–coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci. 1999;8:57–65. 

 

CO-ENZYME Q10 

 

Cordero MD, Moreno-Fernández AM, deMiguel M, Bonal P, Campa F, Jiménez-Jiménez LM, et al. Coenzyme Q10 distribution in blood is altered in patients with fibromyalgia. Clin Biochem. 2009;42:732–5. 

Di Pierro F, Rossi A, Consensi A, Giacomelli C, Bazzichi L. Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study. Clin Exp Rheumatol. 2017;35 Suppl 105:20–7. 

Cordero MD, Alcocer-Gómez E, de Miguel M, Culic O, Carrión AM, Alvarez-Suarez JM, et al. Can coenzyme q10 improve clinical and molecular parameters in fibromyalgia? Antioxid Redox Signal. 2013;19:1356–61. 

Jafari M, Mousavi SM, Asgharzadeh A, Yazdani N. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews. Indian Heart J. 2018;70 Suppl 1:S111–7. 

DiNicolantonio JJ, Bhutani J, McCarty MF, O’Keefe JH. Coenzyme Q10 for the treatment of heart failure: a review of the literature. Open Heart. 2015;2:e000326. 

Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial. Nutr Neurosci. 2016;19:138–43. 

Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Khodadadi B, Jazayeri S, et al. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci. 2015;18:169–76. 

Castro-Marrero J, Cordero MD, Segundo MJ, Sáez-Francàs N, Calvo N, Román-Malo L, et al. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015;22:679–85. 

Fukuda S, Nojima J, Kajimoto O, Yamaguti K, Nakatomi Y, Kuratsune H, et al. Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome. Biofactors. 2016;42:431–40. 

Mizuno K, Tanaka M, Nozaki S, Mizuma H, Ataka S, Tahara T, et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition. 2008;24:293–9. 

Castro-Marrero J, Sáez-Francàs N, Segundo MJ, Calvo N, Faro M, Aliste L, et al. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial. Clin Nutr. 2016;35:826–34. 

Mizuno K, Sasaki AT, Watanabe K, Watanabe Y. Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals. Nutrients [Internet]. 2020;12. Available from: http://dx.doi.org/10.3390/nu12061640 

Sarmiento A, Diaz-Castro J, Pulido-Moran M, Moreno-Fernandez J, Kajarabille N, Chirosa I, et al. Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. Biofactors. 2016;42:612–22. 

 

GREEN TEA 

 

Singhal K, Raj N, Gupta K, Singh S. Probable benefits of green tea with genetic implications. J Oral Maxillofac Pathol. 2017;21:107–14. 

Suzuki Y, Miyoshi N, Isemura M. Health-promoting effects of green tea. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88:88–101. 

Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chin Med. 2010;5:13. 

Ortiz-López L, Márquez-Valadez B, Gómez-Sánchez A, Silva-Lucero MDC, Torres-Pérez M, Téllez-Ballesteros RI, et al. Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro. Neuroscience. 2016;322:208–20. 

Pervin M, Unno K, Ohishi T, Tanabe H, Miyoshi N, Nakamura Y. Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases. Molecules [Internet]. 2018;23. Available from: http://dx.doi.org/10.3390/molecules23061297 

Babu PVA, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem. 2008;15:1840–50. 

Bhardwaj P, Khanna D. Green tea catechins: defensive role in cardiovascular disorders. Chin J Nat Med. 2013;11:345–53. 

Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: a mechanistic review. J Nutr Biochem. 2011;22:1–7. 

Hursel R, Westerterp-Plantenga MS. Catechin- and caffeine-rich teas for control of body weight in humans. Am J Clin Nutr. 2013;98:1682S – 1693S. 

Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes . 2009;33:956–61. 

Cooper R, Morré DJ, Morré DM. Medicinal benefits of green tea: part II. review of anticancer properties. J Altern Complement Med. 2005;11:639–52. 

Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr. 2013;98:1667S – 1675S. 

Park J-H, Bae J-H, Im S-S, Song D-K. Green tea and type 2 diabetes. Integr Med Res. 2014;3:4–10. 

Oliveira MR de, Nabavi SF, Daglia M, Rastrelli L, Nabavi SM. Epigallocatechin gallate and mitochondria-A story of life and death. Pharmacol Res. 2016;104:70–85. 

Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, et al. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal. 2009;11:469–80. 

Most J, Timmers S, Warnke I, Jocken JW, van Boekschoten M, de Groot P, et al. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. Am J Clin Nutr. 2016;104:215–27. 

Jurgens TM, Whelan AM, Killian L, Doucette S, Kirk S, Foy E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database Syst Rev. 2012;12:CD008650. 

Baladia E, Basulto J, Manera M, Martínez R, Calbet D. [Effect of green tea or green tea extract consumption on body weight and body composition; systematic review and meta-analysis]. Nutr Hosp. 2014;29:479–90. 

Zhong X, Zhang T, Liu Y, Wei X, Zhang X, Qin Y, et al. Short-term weight-centric effects of tea or tea extract in patients with metabolic syndrome: a meta-analysis of randomized controlled trials. Nutr Diabetes. 2015;5:e160. 

Vázquez Cisneros LC, López-Uriarte P, López-Espinoza A, Navarro Meza M, Espinoza-Gallardo AC, Guzmán Aburto MB. Effects of green tea and its epigallocatechin (EGCG) content on body weight and fat mass in humans: a systematic review. Nutr Hosp. 2017;34:731–7. 

Hibi M, Takase H, Iwasaki M, Osaki N, Katsuragi Y. Efficacy of tea catechin-rich beverages to reduce abdominal adiposity and metabolic syndrome risks in obese and overweight subjects: a pooled analysis of 6 human trials. Nutr Res. 2018;55:1–10. 

 

PQQ (pyrroloquinone) 

 

Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010;285:142–52. 

Saihara K, Kamikubo R, Ikemoto K, Uchida K, Akagawa M. Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α Signaling Pathway. Biochemistry. 2017;56:6615–25. 

Hwang P, Willoughby DS. Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise. J Am Coll Nutr. 2018;37:738–48. 

Nakano M, Yamamoto T, Okamura H, Tsuda A, Kowatari Y. Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep. Functional Foods in Health and Disease. 2012;2:307–24. 

Harris CB, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013;24:2076–84. 

 

ASTHAXANTINE 

 

Naguib YM. Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000;48:1150–4. 

Kidd P. Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev. 2011;16:355–64. 

Kim SH, Kim H. Inhibitory Effect of Astaxanthin on Oxidative Stress-Induced Mitochondrial Dysfunction-A Mini-Review. Nutrients [Internet]. 2018;10. Available from: http://dx.doi.org/10.3390/nu10091137 

Yu T, Dohl J, Chen Y, Gasier HG, Deuster PA. Astaxanthin but not quercetin preserves mitochondrial integrity and function, ameliorates oxidative stress, and reduces heat-induced skeletal muscle injury. J Cell Physiol. 2019;234:13292–302. 

Krestinina O, Baburina Y, Krestinin R, Odinokova I, Fadeeva I, Sotnikova L. Astaxanthin Prevents Mitochondrial Impairment Induced by Isoproterenol in Isolated Rat Heart Mitochondria. Antioxidants (Basel) [Internet]. 2020;9.  

Sztretye M, Dienes B, Gönczi M, Czirják T, Csernoch L, Dux L, et al. Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging. Oxid Med Cell Longev. 2019;2019:3849692. 

Liu SZ, Ali AS, Campbell MD, Kilroy K, Shankland EG, Roshanravan B, et al. Building strength, endurance, and mobility using an astaxanthin formulation with functional training in elderly. J Cachexia Sarcopenia Muscle. 2018;9:826–33. 

Malmsten CL, Lignell A. Dietary Supplementation with Astaxanthin-Rich Algal Meal Improves Strength Endurance–A Double Blind Placebo Controlled Study on Male Students–. Carotenoid Sci. 2008;13:20–2. 

Fleischmann C, Horowitz M, Yanovich R, Raz H, Heled Y. Asthaxanthin Improves Aerobic Exercise Recovery Without Affecting Heat Tolerance in Humans. Front Sports Act Living. 2019;1:17. 

Djordjevic B, Baralic I, Kotur-Stevuljevic J, Stefanovic A, Ivanisevic J, Radivojevic N, et al. Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. J Sports Med Phys Fitness. 2012;52:382–92. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Frequently Asked Questions

What is the average delivery time?

All of our products are manufactured with care in Europe and shipped out of Germany. Within Europe, the average shipping time is 2-5 working days with Express Shipping and 5-10 working days with Standard shipping. Due to COVID-19, there might be some unexpected carrier delays. 

How do I know if these supplements actually work?

Our supplements are backed by years of research by a team of neurologists and specialists in the health care industry. We want to make sure to deliver the highest quality possible and create products that actually work. See our References to check out the sources that have been used during the production process of our supplements. 

Can I take these supplements during pregnancy?

Our supplement is 100% natural and medicine-free. However, we recommend to always consult your doctor before taking any dietary supplements whilst pregnant (or planning to be). 

Can I take these supplements whilst on birth control?

Please always consult with your health care professional before taking any supplement whilst on prescription medication. 

Do I need to follow a specific diet for these supplements to work?

We definitely recommend to keep a healthy diet, work out regularly and make sure to get enough sleep for optimal results of our product. As science shows, a balanced lifestyle combined with high quality supplements can actually result in improvements.   

How long does a bottle last?

One bottle of Repair & Protect contains 180 capsules. Our average recommended daily intake is 1-3 capsules daily (with a meal), and could be increased (in extreme cases) all the way up to six capsules per day. Therefore, a bottle lasts a month on average. 

Are your products natural?

All of our supplements have been tested thoroughly and are 100% natural. They consist of vitamins, minerals and more ingredients that are proven to improve brain health. 

Are the supplements allergy-proof?

Our Repair & Protect formula does not contain any gluten, milk, or nuts. There is no artificial flavouring or smell added. Lastly, there are no added sugars. 

Where do I keep the bottle in my house? In what temperature?

This product has to be kept out of direct sunlight and is best to be kept in room temperature (23C or 73F). 

What is brain.rehab exactly?

This company, Brainrescue, is part of Brain.rehab (www.brain.rehab), which was founded by a stroke survivor and a functional neurologist. Together, they strive to make the world a better place for brain-injured people. Their mission is to deliver customised training and help for people with brain trauma. The importance of dietary supplements and food is extremely significant in this process. After years of research and development, our team of health care professionals has come up with several supplement formulas that actually work. Check out the About Us page for more information about the founders.