The tale of Tres Hombres: Ashwaghanda, Beta-Alanine, and Senactiv®.

By Dr. Luke Bucci, PhD


In this blog, Dr. Bucci lays out the latest research on the ingredients that are unique to OptygenHP’s formula. Both the Optygen and OptygenHP formulas share the ATPro Matrix, Chromium, and adaptogens cordyceps and rhodiola (the Optygen formula). OptygenHP adds two more adaptogens – ashwagandha and Senactiv® (which is a blend of adaptogens) – along with a kicker: beta-alanine. These additions give OptygenHP more ways to improve your performance and recovery than Optygen.

We don’t expect you to take our word for that, though. We did our homework before designing the formula, and we have the science to support those claims, including from the last few years, well after we created Optygen and OptygenHP. In the interest of staying current (and maybe indulging in a little “we told you so”), here is the latest clinical research for each additional nutrient in OptygenHP. (For more information on each ingredient, check out the Ingredient Cards for Optygen and OptygenHP on their webpages.)


For over 4,000 years, ashwagandha has been used in Ayurvedic health practices in India for many health-promoting purposes, similar to Asian Ginseng (Panax spp.). Roots are the usual part used, but increasing use of leaves and whole plants are in vogue, because all plant parts contain withanolides, the major active agents.

The latest human clinical studies support ashwagandha’s role in Ayurvedic practice, showing significant improvements in exercise performance in both sedentary persons and elite athletes. It also benefited relevant non-performance activities, including overall antistress, mental functions, QOL and sleep qualities. The daily doses showing benefits ranged from 120-1,000mg, though the higher doses in that range show no additional benefit. OptygenHP contains 150mg of ashwagandha extract standardized to alkaloids, withaferin-A, and withanolides, ensuring it’s over the baseline 120mg mark for effective dosing.

The latest research on ashwagandha

  • Improved speed, muscle strength, and neuromuscular coordination;
  • Improved oxygen capacity (cardiorespiratory endurance, VO2max);
  • Reduced muscle fatigue/exhaustion;
  • Speedier post-exercise muscle recovery (DOMS);
  • Improved QOL (Quality Of Life);
  • Reduced mental anxiety & stress;
  • Improved mental functions (cognition, psychomotor functions)
  • Better sleep;
  • Supports immune health.

Citations for Latest Ashwagandha & Endurance Exercise Reviews: Akhgarjand 2022; Bonilla 2021; Cheah 2021; Dharmasena 2020; Lopresti 2021; Perez-Gomez 2020; Speers 2021; Wal 2013.


Senactiv® is a concentrated, patented combination of two little-known adaptogens: notoginseng (Panax notoginseng) and chestnut rose hips (Rosa roxburghii) concentrated extracts. Clinical human research shows Senactiv® has an elegantly illustrated rationale for enhancing exercise performance: it boosts the complicated, hidden machinations of muscle recovery in a big way. Recent research involving three-hour cycling sessions shows that muscle repair processes immediately after exercise are increased, and that repaired muscles rebuild better for the next exercise bout.

Senactiv® accomplishes this by consistent daily intake – not just immediately after exercise is done. Muscles need to be primed for action ahead of time, not trying to sift through helpful compounds delivered when they are under difficulty and not working normally. To work properly, the active agents in Senactiv® need to be in place and ready.

The first of the two adaptogens, notoginseng, supplies essentially pure ginsenoside Rg1. This is found in other ginsengs; however, common ginseng extracts and preparations have a number of ginsenosides with competitive actions, which works for aging and health, but also washes out the properties of Rg1 by itself. Rg1 is potent and needs only a small dose (5 mg is enough as shown by human studies).

The other adaptogen, chestnut rose hips extract, also requires a relatively small dose to deliver a plethora of compounds in clinically effective quantities that work to accentuate Rg1 actions. Together, the two provide just what we look for: better performance, better muscle health, and better recovery in a small dose (50mg per serving of OptygenHP).

The latest research on Senactiv®

  • Longer time to exhaustion;
  • 20% more total work;
  • Enhanced muscle glycogen replenishment;
  • Less free radical damage;
  • Decreased inflammatory markers by less neutrophil infiltration;
  • Brings in macrophages and increases their activity – orchestrating damage control and repair;
  • Reduced senescent cells after exercise (takes out the garbage);
  • Activation of muscle satellite cells (stems cells);
  • Increased myogenesis – making muscles stronger and better trained
  • Reduced DOMS from cycle ergometry (by a large dose of Notoginseng)

Citations for Latest Senactiv® & Endurance Exercise: Hou 2015; Lee 2021; Liang 2005; Pumpa 2013; Wu 2019 27, 2019 580, 2020. 


Beta-alanine is an amino acid that boosts muscle levels of carnosine, a major buffer of acidity formed from supramaximal anaerobic exercise, when your aerobic oxygen supply can no longer keep up with your exercise output. Thus, any physical activity that is exhausting and increases acidity in muscles benefits from increased muscle carnosine levels. Performance in long-distance running and cycling depends on the ability to develop high anaerobic power outputs during decisive moments.

When designing OptygenHP, we targeted performance in those specific moments, where races are won or lost. Steep climbs, breakaways, break chases, and particularly sprints in the finale – beta-alanine can boost performance precisely when you need a boost most, in those moments where everyone’s engine is running in the red, and whoever can dig deeper wins. Even before beta-alanine had enough human studies for a consensus, we realized that it was good for those key anaerobic race portions, and set out with our usual new product development and testing. The rest of the world is gradually catching up.

The benefits of beta-alanine for high-intensity exercise performance are also condoned by a worldwide collection of authoritative groups: Academy of Nutrition and Dietetics, American College of Sports Medicine, Australian Institute of Sports, Dietitians of Canada, International Associations of Athletics Federations, International Olympic Committee, International Society of Sports Nutrition (ISSN), National Strength and Conditioning Association (NSCA), and Sports Dietitians Australia.

Clinical research shows that muscle levels of carnosine are easily built up and maintained at lower doses (~1,000mg daily) of beta-alanine, taking at least 6-12 weeks to achieve benefits from daily supplementation. If stopped, muscle carnosine levels very slowly decrease over a period of 6 months. Daily doses with benefits ranged from 1,000-6,400mg, showing a plateau for benefits at 1,000mg. To comfortably clear that 1,000mg hurdle, OptygenHP provides 1,500mg beta-alanine per serving.

Beta-alanine also produces a non-performance effect that many of you may be familiar with. Some persons may experience paraesthesis (itching or prickly-feeling skin) soon after a dose. This is normal, short-lived, and not problematic, so go with the tingle.

The latest research on beta-alanine

  • Benefits short-term, high-intensity exercise for intermittent, repeated and continuous exercise lasting 0.5-10 minutes;
  • Benefits have been reported for combat sports, high-intensity interval training, middle distance running, military activities, racquet sports, resistance training, rowing, swimming; team sports, track cycling and more;
  • Delays fatigue and increases exercise capacity & performance;
  • Improves anaerobic endurance performance during long-duration endurance cycling/running (important for brief spurts of extreme effort at any time of an event);
  • We realized long ago (2007) that adding Beta Alanine OptygenHP gives you a bigger kick at the end of long-duration endurance events – helping you finish faster when others are lagging.

Citations for Latest Beta-Alanine & Endurance Exercise Reviews: Australian Institute of Sports 2021 March, 2021 April; Brisola 2019; Burke 2019 73, 2019 156, 2021; Caruso 2022; Close 2022; Forbes 2020; Gonzalez 2022; Hoffman 2018; Kerksick 2018; Matthews 2019; Maughan 2018 104, 2018 439; Saunders 2020, 2021; Sports Dietitians Australia 2023; Stecker 2019; Tambalis 2022; Varanoske 2019; Vicente-Salar 2022; Woitas 2022.


Both Optygen and OptygenHP were designed after extensive field testing on elite endurance athletes, with feedback guiding adjustments before launch. Each was backed up by a controlled human study on trained endurance athletes, a rarity for sports supplements (Creer 2007; Larson 2007). Feedback from users continues to be very favorable – and, as the above research summaries show, the clinical studies are also still supporting the formulae.

Optygen was introduced in 2002 and has remained the yardstick for a successful adaptogenic blend for endurance exercise. Its effects on endurance performance were determined in 2007 using highly trained distance runners by a study from Luther College (Larson 2007). After seven weeks, Optygen users showed a significant increase in time to onset of lactate threshold – 42% compared to the placebo group. Other measures, including VO2max and cortisol levels (the primary stress hormone), were numerically in favor of Optygen, but the subject numbers prevented statistical significance.

Four years after Optygen debuted, OptygenHP was introduced with even more adaptogenic support based on newly available ingredients (ashwagandha, beta-alanine, and Senactiv®). Like Optygen, empirical field-testing feedback and results from a pilot study showed OptygenHP also had benefits. In the pilot study, after eight weeks, OptygenHP significantly increased training volume, bumping it up by 27% in highly trained collegiate runners (Creer 2007). OptygenHP also significantly reduced the Stress Score Performance by 28%, including a significant 26% decrease in salivary cortisol and a 36% increase in testosterone : cortisol ratio, signifying an anti-stress effect reduced adverse overtraining/overreaching effects.


First Endurance has a policy of constant improvement, even if the original formula is successful and popular. Reports from field trials and decades of use in real life for both Optygen and OptygenHP consistently find better than normal performance and not being as fatigued at the end of long events. In short, both help you to keep training and perform at a higher level.

Optygen is a good starting point, but if you are pushing yourself to your limit, under extreme stress, and the stakes of your endurance ambitions are high, then OptygenHP provides additional adaptogenic support for improved recovery and more anaerobic power with beta-alanine. 



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Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martinez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on physical performance: systematic review and Bayesian meta-analysis. J Funct Morphol Kinesiol. 2021 Feb11;6(1):20.

Cheah KL, Norhayati MN, Yaacob LH, Rahman RA. Effect of Ashwagandha (Withania somnifera) extract on sleep: a systematic review and meta-analysis. PLoS ONE. 2021 Sep24;16(9):e025843.

Dharmasena KNA, Ramamurthy A, Joshi K, Sharma G. Review on the ergogenic effect of Withania somnifera (L.) Dunal. Int Ayurvedic Med J. 2020;Aug:4219-28.

Lopresti AL, Smith SJ. Ashwagandha (Withania somnifera) for the treatment and enhancement of mental and physical conditions: a systematic review of human trials. J Herbal Med. 2021 Aug;27:100434.

Perez-Gomez J, Villafina S, Adsuar JC, Merellano-Navarro E, Collado-Mateo D. Effects of Ashwagandha (Withania somnifera) on VO2max: a systematic review and meta-analysis. Nutrients. 2020 Apr17;12(4):1119.

Speers AB, Cabey KA, Soumyanath A, Wright KM. Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression and insomnia. Curr Neuropharmacol. 202;19(9):1468-95.

Wal P, Wal A. Am overview of Adaptogens with a special emphasis on Withania and Rhodiola, Ch 34 in Nutrition and Enhanced Sports Performance. Muscle Building, Endurance, and Strength, Bagchi D, Nair S, Sen CK, Eds., Academic Press, London, 2013, pp.343-50.

Beta Alanine

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Brisola GMP, Zagatto AM. Ergogenic effects of beta-alanine supplementation on different sports modalities: strong evidence or only incipient findings? J Strength Cond Res. 2019 Jan;33(1):253-82.

Burke LM. Nutritional approaches to counter performance constraints in high-level sports competition. Exp Physiol. 2021 Dec;106(12):2304-23.
Burke LM. Supplements for optimal sports performance. Curr Opin Physiol. 2019 Aug;10:156-65.

Burke LM, Castell LM, Casa DJ, Close GL, Costa RJS, Desbrow B, Halson SL, Lis DM, Melin AK, Peeling P, Saunders PU, Slater GJ, Sygo J, Witard OC, Bermon S, Stellingwerf T. International Association of Athletics Federations Consensus Statement 2019: nutrition for athletics. Int J Sport Nutr Exerc Metab. 2019 Mar1;29(2):73-84.

Caruso G. Unveiling the hidden therapeutic potential of carnosine, a molecule with a multimodal mechanism of action: a position paper. Molecules. 2022 May20;27(10):3303.

Close GL, Kasper AM, Walsh NP, Maughan RJ. “Food first but not always food only”: recommendations for using dietary supplements in sports. Int J Sport Nutr Exerc Metab. 2022 Mar12;32(5):371-86.

Forbes SC, Candow DG, Smith-Ryan AE, Hirsch KR, Roberts MD, VanDusseldorp TA, Stratton MT, Kaviani M, Little JP. Supplements and nutritional interventions to augment high-intensity interval training physiological and performance adaptations – a narrative review. Nutrients. 2020 Jan31;12(2):390.

Gonzalez DE, McAllister MJ, Waldman HS, Ferrando AA, Joyce J, Barringer ND, Dawes JJ, Kieffer AJ, Harvey T, Kerksick CM, Stout JR, Ziegenfuss TN, Zapp A, Tartar JL, Heileson JL, VanDusseldorp TA, Kalman DS, Campbell BI, Antonio J, Kreider RB. International society of sports nutrition position stand: tactical athlete nutrition. J Int Soc Sports Nutr. 2022;19(1):267-315.

Hoffman JR, Varanoske A, Stout JR. Effects of beta-alanine supplementation on carnosine elevation and physiological performance. Adv Food Nutr Res. 2018;84:183-206.

Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jager R, Collins R, Cooke M, Davis JN, Galvan E, Greenwood M, Lowery LM, Wildman R, Antonio J, Kreider RB. ISSN exercise & sports review update: research & recommendations. J Int Soc Sports Nutr. 2018 Aug1;15(1):38.

Matthews JJ, Artioli GG, Turner MD, Sale C. The physiological roles of carnosine and beta-alanine in exercising human skeletal muscle. Med Sci Sports Exerc. 2019 Oct;51(10):2098-108.

Maughan RJ, Burke LM, Dvorak J, Larson-Meyer DE, Peeling P, Phillips SM, Rawson ES, Walsh NP, Garthe I, Geyer H, Meeusen R, van Loon L, Shirreffs SM, Spriet LL, Stuart M, Vernec A, Currell K, Ali VM, Budgett RGM, Ljungqvist A, Mountjoy M, Pitsiladis Y, Soligard T, Erdener U, Engebretsen L. IOC Consensus Statement: dietary supplements and the high-performance athlete. Int J Sport Nutr Exerc Metab. 2018 Mar1;28(2):104-25.

Maughan RJ, Burke LM, Dvorak J, Larson-Meyer DE, Peeling P, Phillips SM, Rawson ES, Walsh NP, Garthe I, Geyer H, Meeusen R, van Loon L, Shirreffs SM, Spriet LL, Stuart M, Vernec A, Currell K, Ali VM, Budgett RGM, Ljungqvist A, Mountjoy M, Pitsiladis Y, Soligard T, Erdener U, Engebretsen L. IOC Consensus Statement: dietary supplements and the high-performance athlete. Br J Sports Med. 2018 Apr;52(7):439-55.

Saunders B, McNaughton LR, Siegler J. Editorial: Nutritional buffering strategies to improve exercise capacity and performance. Front Nutr. 2021 Mar25;8:669102.

Saunders B, Virgile A, Elliott-Sale KJ, Artioli GG, Swinton PA, Dolan E, Roschel H, Sale C, Gualano B. Infographic: a systematic review and meta-analysis of the effect of beta-alanine supplementation on exercise capacity and performance. Br J Sports Med. 2020 Aug;54(15):925-6.

Sports Dietitians Australia. Beta-Alanine (B-alanine) Factsheet. Sports Dietitians Australia. 2023. [β-alanine/ ]

Stecker RA, Harty PS, Jagim AR, Candow DG, Kerksick CM. Timing of ergogenic aids and micronutrients on muscle and exercise performance. J Int Soc Sports Nutr. 2019 Sep2;16(1):37.
Tambalis KD, Arnaoutis G. Nutrition ergogenic supplements regulate blood pH – an update. Eur J Fitness Nutr Sport Med Studies. 2022;3(1):1-25.
Varanoske AN, Stout JR, Hoffman JR. Effects of beta-alanine supplementation and intramuscular carnosine content on exercise performance and health, Ch 28 in Nutrition and Enhanced Sports Performance. Muscle Building, Endurance, and Strength, Bagchi D, Nair S, Sen CK, Eds., 2nd ed., Academic Press, London, 2019, pp. 327-45.

Vicente-Salar N, Fuster-Munoz E, Martinez-Rodriguez A. Nutritional ergogenic aids in combat sports: a systematic review and eta-analysis. Nutrients. 2022 Jun22;14(13):2588.

Woitas LR, Ribas JW. Major clinical findings of beta-alanine in sports performance: a systematic review. Int J Nutrology. 2022 May;15(2):1-6.


Hou CW, Lee SD, Kao CL, Cheng IS, Lin YN, Chaung SJ, Chen CY, Ivy JL, Huang CY, Kuo CH. Improved inflammatory balance of human skeletal muscle during exercise after supplementations of the ginseng-based steroid Rg1. PLoS ONE. 2015 Jan24;10(1):e0116387.

Lee TXY, Wu J, Jean WH, Condello G, Alkhatib A, Hsieh CC, Hsieh YW, Huang CY, Kuo CH. Reduced stem cell aging in human skeletal muscle is enhanced by ginsenoside Rg1. Aging (Albany NY). 2021 Jun28;139120:1657-76.,
Liang MTC, Podolka TD, Chuang WJ. Panax notoginseng supplementation enhances physical performance during endurance exercise. J Strength Cond Res. 2005 Feb;19(1):108-14.

Pumpa KL, Fallon KE, Bensoussan A, Papalia S. The effects of Panax notoginseng on delayed onset muscle soreness and muscle damage in well-trained males: a double blind randomised controlled trial.  Complement Ther Med. 2013 Jun;21(3):131-40.

Wu J, Cheng IS, Saovieng S, Jean WH, Kao CL, Liu YY, Huang CY, Lee TXY, Ivy JL, Kuo CH. Aerobic exercise induces tumor suppressor p16INK4a expression of endothelial progenitor cells in human skeletal muscle. Aging (Albany NY). 2020 Oct31;12(20):20226-34.

Wu J, Saovieng S, Cheng IS, Jensen J, Jean WH, Alkhatib A, Kao CL, Huang CY, Kuo CH. Satellite cells depletion in exercising human skeletal muscle is restored by ginseng component Rg1 supplementation. J Funct Foods. 2019 Jul;58:27-33.

Wu J, Saovieng S, Cheng IS, Liu T, Hong S, Lin CY, Su IC, Huang CY, Kuo CH. Ginsenoside Rg1 supplementation clears senescence-associated beta-galactosidase in exercising human skeletal muscle. J Ginseng Res. 2019 Oct;43(4):580-8.

Optygen & OptygenHP

Creer A. The effect of commercial herbal-based supplementation on running performance during a competitive season in collegiate distance runners: a pilot study. South Dakota University, 2007: Report to First Endurance.

Larson KR. Supplementation using a commercial herbal-based product (Opytgen) may increase running performance in highly trained collegiate distance runners: a pilot study. Report, Luther College, 2007.

February 25, 2023 — Luke Bucci


Luke said:

Bob – I did a lengthy & devoted search for answering your questions, but there is not enough research to determine if there are or are not interactions. In general when taking Rx drugs and contemplating using herbal products (like Optygen), your physician or health care provider should be informed and consulted about possible interactions, and their advice followed.
I wish I could have a more useful answer.
Luke R. Bucci, PhD CCN CNS

Bob said:

Are there any potential interactions between the ingredients of Optygen and statins like rosuvastatin and ezetimibe?

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