Adaptogen

Herbal adaptogens concentrating active compounds while maintaining complex synergistic co-factors – supporting Adrenal/ HPA regulation, Long Term Potentiation, AMPK activation, neurogenesis, catecholamine production, tissue regeneration, and many regulatory functions.

American Ginseng (Cereboost™)

PANAX QUINQUEFOLIUS COMMON NAME

American Ginseng

TOP BENEFITS OF PANAX QUINQUEFOLIUS

  • Enhances working memory and alertness*
  • Promotes calmness*
  • Supports cognitive function and performance*

WHAT IS PANAX QUINQUEFOLIUS?

Panax quinquefolius is commonly called American ginseng, because it is native to forested regions in North America. It is the same genus as Asian ginseng (Panax ginseng) and prized for many of the same reasons. Both American and Asian ginseng contain similar active constituents called ginsenosides. The ginsenosides are thought to be responsible for many of the adaptogenic (i.e., stress and fatigue support)  and health-promoting properties associated with ginseng.[1] While there are many different ginsenosides, the most well characterized include Rb1, Rb2, Rg1, Rc, Rd, and Re. Cereboost™ is a clinically studied and standardized American ginseng root extract. In humans studies, Cereboost™ has enhanced working memory and alertness, while promoting calmness.

NEUROHACKER’S PANAX QUINQUEFOLIUS SOURCING

Cereboost™ has been used in human clinical studies, where it has enhanced alertness, working memory, and calmness.

Cereboost™ was granted the NutrAward 2010 for the Best New Ingredient of the year.

Cereboost™ is produced by Naturex, an innovator in nutraceutical products in Europe and the United States.

Cereboost™ is standardized for total ginsenoside content (10-12%), and several specific ginsenosides, including Rb1 (4-7%), Rb2 (0.2-1.5%), Rg1 (0.1-0.4%), Rc (0.5-3.5%), Rd (0.9-3.0%), and Re (0.4-3.5%). 

Cereboost™ is non-GMO, gluten-free, and vegan.

Cereboost™is a trademark of Naturex.

PANAX QUINQUEFOLIUS DOSING PRINCIPLES AND RATIONALE

We consider Panax quinquefolius to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is consistent with the studied amount in the human clinical studies for supporting working memory, alertness, and calmness.*

PANAX QUINQUEFOLIUS KEY MECHANISMS

Cognitive function

  • Supports attention [2]
  • Supports working memory [2,3]
  • Supports learning and memory [4–7]

Mood

  • Promotes calmness [2]
  • Supports mood [1,8,9]
  • Adaptogenic actions (i.e., stress resilience and anti-fatigue) [5]
  • Downregulates stress hormone levels / HPA-axis activation [1,8]

Brain function

  • Modulates cholinergic neurotransmission [1,4,5,10,11]
  • Downregulates acetylcholinesterase (AChE) activity [4]
  • Upregulates choline acetyltransferase (ChAT) expression [4]
  • Upregulates acetylcholine levels [4]
  • Modulates dopaminergic neurotransmission [12–15]
  • Modulates GABAergic neurotransmission [1,8]
  • Neuroprotective effects [1,4,5,8,10]
  • Regulates neural cytokine signaling [1,8,10,16]
  • Protects against glutamate neurotoxicity [10,17]
  • Supports neurite outgrowth, dendritic spine density, and synaptic plasticity [1,5–7]
  • Upregulates BDNF signaling [1,7,10,18]
  • Supports neurogenesis [1,10,18]

Antioxidant defenses

  • Upregulates antioxidant enzymes in the brain (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [8]
  • Replenishes glutathione (GSH) levels [8]
  • Downregulates lipid peroxidation [8]

Cardiometabolic effects

  • Supports healthy cardiometabolic parameters [19–21]
  • Supports healthy blood glucose levels [22–24]
  • Supports healthy insulin sensitivity [25]
  • Supports fat metabolism [19]
  • Supports mitochondrial enzyme complex activities [8]

 Gut microbiota

  • Regulates gut cytokine signaling [26–28]
  • Modulates gut microbiota composition [27,28]

Ergogenic effects

  • Supports high-intensity endurance performance [29,30]
  • Protects from exercise-induced muscle damage [29–31]


REFERENCES 

[1] H.J. Kim, P. Kim, C.Y. Shin, J. Ginseng Res. 37 (2013) 8–29.
[2] A. Scholey, A. Ossoukhova, L. Owen, A. Ibarra, A. Pipingas, K. He, M. Roller, C. Stough, Psychopharmacology 212 (2010) 345–356.
[3] A. Ossoukhova, L. Owen, K. Savage, M. Meyer, A. Ibarra, M. Roller, A. Pipingas, K. Wesnes, A. Scholey, Hum. Psychopharmacol. 30 (2015) 108–122.
[4] K. Shin, H. Guo, Y. Cha, Y.-H. Ban, D.W. Seo, Y. Choi, T.-S. Kim, S.-P. Lee, J.-C. Kim, E.-K. Choi, J.-M. Yon, Y.-B. Kim, Regul. Toxicol. Pharmacol. 78 (2016) 53–58.
[5] Y. Cheng, L.-H. Shen, J.-T. Zhang, Acta Pharmacol. Sin. 26 (2005) 143–149.
[6] I. Mook-Jung, H.S. Hong, J.H. Boo, K.H. Lee, S.H. Yun, M.Y. Cheong, I. Joo, K. Huh, M.W. Jung, J. Neurosci. Res. 63 (2001) 509–515.
[7] H. Zhao, Q. Li, X. Pei, Z. Zhang, R. Yang, J. Wang, Y. Li, Behav. Brain Res. 201 (2009) 311–317.
[8] P. Chanana, A. Kumar, Front. Neurosci. 10 (2016) 84.
[9] M. Chatterjee, P. Verma, G. Palit, Indian J. Exp. Biol. 48 (2010) 306–313.
[10] K. Radad, R. Moldzio, W.-D. Rausch, CNS Neurosci. Ther. 17 (2011) 761–768.
[11] C.G. Benishin, Neurochem. Int. 21 (1992) 1–5.
[12] G.-L. Wang, Y.-P. Wang, J.-Y. Zheng, L.-X. Zhang, Brain Res. 1699 (2018) 44–53.
[13] S.H. Lee, J. Hur, E.H. Lee, S.Y. Kim, Biomol. Ther. 20 (2012) 482–486.
[14] H.S. Kim, Y.T. Hong, K.W. Oh, Y.H. Seong, H.M. Rheu, D.H. Cho, S. Oh, W.K. Park, C.G. Jang, Gen. Pharmacol. 30 (1998) 783–789.
[15] H.S. Kim, K.S. Kim, K.W. Oh, Pharmacol. Biochem. Behav. 63 (1999) 407–412.
[16] C.F. Wu, X.L. Bi, J.Y. Yang, J.Y. Zhan, Y.X. Dong, J.H. Wang, J.M. Wang, R. Zhang, X. Li, Int. Immunopharmacol. 7 (2007) 313–320.
[17] Y.C. Kim, S.R. Kim, G.J. Markelonis, T.H. Oh, J. Neurosci. Res. 53 (1998) 426–432.
[18] L.-H. Shen, J.-T. Zhang, Neurol. Res. 26 (2004) 422–428.
[19] R.K. Singh, E. Lui, D. Wright, A. Taylor, M. Bakovic, Can. J. Physiol. Pharmacol. 95 (2017) 1046–1057.
[20] V. Vuksan, Z.Z. Xu, E. Jovanovski, A.L. Jenkins, U. Beljan-Zdravkovic, J.L. Sievenpiper, P. Mark Stavro, A. Zurbau, L. Duvnjak, M.Z.C. Li, Eur. J. Nutr. (2018).
[21] I. Mucalo, E. Jovanovski, D. Rahelić, V. Božikov, Z. Romić, V. Vuksan, J. Ethnopharmacol. 150 (2013) 148–153.
[22] V. Vuksan, M.P. Stavro, J.L. Sievenpiper, V.Y. Koo, E. Wong, U. Beljan-Zdravkovic, T. Francis, A.L. Jenkins, L.A. Leiter, R.G. Josse, Z. Xu, J. Am. Coll. Nutr. 19 (2000) 738–744.
[23] V. Vuksan, J.L. Sievenpiper, V.Y. Koo, T. Francis, U. Beljan-Zdravkovic, Z. Xu, E. Vidgen, Arch. Intern. Med. 160 (2000) 1009–1013.
[24] V. Vuksan, J.L. Sievenpiper, J. Wong, Z. Xu, U. Beljan-Zdravkovic, J.T. Arnason, V. Assinewe, M.P. Stavro, A.L. Jenkins, L.A. Leiter, T. Francis, Am. J. Clin. Nutr. 73 (2001) 753–758.
[25] L.R. De Souza, A.L. Jenkins, E. Jovanovski, D. Rahelić, V. Vuksan, J. Ethnopharmacol. 159 (2015) 55–61.
[26] C.-Z. Wang, H. Yao, C.-F. Zhang, L. Chen, J.-Y. Wan, W.-H. Huang, J. Zeng, Q.-H. Zhang, Z. Liu, J. Yuan, Y. Bi, C. Sava-Segal, W. Du, M. Xu, C.-S. Yuan, Int. Immunopharmacol. 64 (2018) 246–251.
[27] C.-Z. Wang, C. Yu, X.-D. Wen, L. Chen, C.-F. Zhang, T. Calway, Y. Qiu, Y. Wang, Z. Zhang, S. Anderson, Y. Wang, W. Jia, C.-S. Yuan, Cancer Prev. Res. 9 (2016) 803–811.
[28] C.-Z. Wang, W.-H. Huang, C.-F. Zhang, J.-Y. Wan, Y. Wang, C. Yu, S. Williams, T.-C. He, W. Du, M.W. Musch, E.B. Chang, C.-S. Yuan, Clin. Transl. Oncol. 20 (2018) 302–312.
[29] J. Wu, S. Saovieng, I.-S. Cheng, T. Liu, S. Hong, C.-Y. Lin, I.-C. Su, C.-Y. Huang, C.-H. Kuo, J. Ginseng Res. (2018).
[30] C.-W. Hou, S.-D. Lee, C.-L. Kao, I.-S. Cheng, Y.-N. Lin, S.-J. Chuang, C.-Y. Chen, J.L. Ivy, C.-Y. Huang, C.-H. Kuo, PLoS One 10 (2015) e0116387.
[31] M. Estaki, E.G. Noble, Appl. Physiol. Nutr. Metab. 40 (2015) 116–121.

Schisandra chinensis Fruit Extract

SCHISANDRA CHINENSIS COMMON NAME

Schisandra | Schizandra | Magnolia Berry | Five-Flavor-Fruit | Limonnik (Russian)

TOP BENEFITS OF SCHISANDRA CHINENSIS

Supports cognitive function*
Supports mood*
Supports resistance to stress*
Supports endurance capacity*
Supports sleep*

WHAT IS SCHISANDRA CHINENSIS?

The fruits of Schisandra chinensis are berries. They are one of the 50 fundamental herbs in Traditional Chinese Medicine, and have been used in traditional medicine in Japan, Korea, and Far East regions of the Russian empire. One of its common names—Five-Flavor-Fruit—is because the berries are known for possessing all five basic flavors: salty, sweet, sour, pungent (spicy), and bitter. S. chinensis fruits are considered to be an adaptogen, supporting broad resistance to stress, mental and physical performance, mood, sleep, vision, and immunity. Several of its traditional uses, including use as a tonic to counter exhaustion and support night vision, led to Russian scientists extensively studying the berries and seeds in both animals and humans from 1940-1960. As a result of this research S. chinensis gained recognition as an adaptogen in the early 1960’s in the former USSR, and has continued to be extensively studied in articles published in Russian, and more recently in English language journals. The primary active compounds in S. chinensis berries are schisandra lignans—lignans are a subgroup of non-flavonoid polyphenols that interact with gut microbiota (i.e., gut-brain axis) [1].

NEUROHACKER’S SCHISANDRA CHINENSIS SOURCING

Schisandra chinensis fruit extract is standardized to contain not less than 9% schisandrins.

Schisandra chinensis fruit extract is Non-GMO and Vegan.

SCHISANDRA CHINENSIS DOSING PRINCIPLES AND RATIONALE

The original Russian research resulted in Schisandra chinensis being categorized as an herbal adaptogen. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response (see Neurohacker Dosing Principles). It’s important to be in this zone; it’s just as important not to be above it. The Russian research also found that the amount of the schisandra lignans given were critical when determining the dose, with very low doses of these compounds being nootropic and ergogenic. So, when an extract is standardized for higher amounts of schisandrins, lower amounts of it should be taken. Our dosing of S. chinensis is determined based on the standardization in order to provide an amount of schisandra lignans in the target range for a healthy adaptive response.

SCHISANDRA CHINENSIS KEY MECHANISMS

Adaptogen

Supports endurance and working capacity [1]

Supports resistance to stress [1–8]

Supports sleep [1]

Supports a calm mood [1,9]

Supports healthy behavioral responses to stress [3,4,7]

Brain function

Supports mental performance [1]

Supports vision [1]

Supports learning and memory [7,10–13]

Supports GABAergic neurotransmission [3,14,15]

Supports GABA-Glutamate levels [10,11,15,16]

Supports acetylcholine signaling [10,11,13]

Supports serotonin signaling [9–11,16]

Supports adrenergic signaling [9–11,16]

Supports dopamine signaling [9–11,16]

Supports sleep mechanisms [14,15,17,18] 

Downregulates acetylcholinesterase (AChE) activity [10,13]

Supports brain-derived neurotrophic factor (BDNF) [4,7]

Modulates glycogen synthase kinase 3β (GSK3β) activity [7,10] 

Supports neuroprotective functions [10–13,19,20]

Supports brain mitochondrial function [21]

Supports antioxidant defenses [10,19,21,22]

Supports phase II detoxifying/antioxidant enzymes [22]

Gut microbiota

Supports the composition of the gut microbiota [23,24]

Supports gut microbial metabolism [24]

Supports gut immune responses [24]

Immune System

Supports innate immunity [25–27]

Supports immune function during some forms of stress [2,28–30]

Supports immunomodulation (i.e., balance of immune function) [31–33]

Healthy aging and longevity

Supports mitochondrial function [19,21,34]

Supports antioxidant defenses [21,34]

Supports HSP70 chaperone [34]

Supports autophagy [35]

Supports healthy muscle and bone with aging [36,37]

Synergies

With sesamin (from sesame seeds)—another lignan—to support liver health [38] and blood fluidity [39]

With other adaptogens (e.g., Rhodiola, Siberian Ginseng) as a nootropic and immune support [40,41]


REFERENCES 

[1]A. Panossian, G. Wikman, J. Ethnopharmacol. 118 (2008) 183–212.

[2]J. Li, J. Wang, J.-Q. Shao, H. Du, Y.-T. Wang, L. Peng, Chin. J. Integr. Med. 21 (2015) 43–48.

[3]T. Yan, M. Xu, B. Wu, Z. Liao, Z. Liu, X. Zhao, K. Bi, Y. Jia, Food Funct. 7 (2016) 2811–2819.

[4]T. Yan, M. Xu, S. Wan, M. Wang, B. Wu, F. Xiao, K. Bi, Y. Jia, Psychiatry Res. 243 (2016) 135–142.

[5]Sun L.-J., Wang G.-H., Wu B., Wang J., Wang Q., Hu L.-P., Shao J.-Q., Wang Y.-T., Li J., Gu P., Lu B., Zhonghua Nan Ke Xue 15 (2009) 126–129.

[6]N. Xia, J. Li, H. Wang, J. Wang, Y. Wang, Exp. Ther. Med. 11 (2016) 353–359.

[7]T. Yan, B. He, S. Wan, M. Xu, H. Yang, F. Xiao, K. Bi, Y. Jia, Sci. Rep. 7 (2017) 6903.

[8]Xia P., Sun L.-J., Wang J., Zhonghua Nan Ke Xue 17 (2011) 472–476.

[9]W.-W. Chen, R.-R. He, Y.-F. Li, S.-B. Li, B. Tsoi, H. Kurihara, Phytomedicine 18 (2011) 1144–1147.

[10]Y. Liu, Z. Liu, M. Wei, M. Hu, K. Yue, R. Bi, S. Zhai, Z. Pi, F. Song, Z. Liu, Food Funct. 10 (2019) 432–447.

[11]B.-B. Wei, M.-Y. Liu, Z.-X. Chen, M.-J. Wei, Acta Pharmacol. Sin. 39 (2018) 616–625.

[12]N. Egashira, K. Kurauchi, K. Iwasaki, K. Mishima, K. Orito, R. Oishi, M. Fujiwara, Phytother. Res. 22 (2008) 49–52.

[13]V.V. Giridharan, R.A. Thandavarayan, S. Sato, K.M. Ko, T. Konishi, Free Radic. Res. 45 (2011) 950–958.

[14]C. Zhang, X. Mao, X. Zhao, Z. Liu, B. Liu, H. Li, K. Bi, Y. Jia, Fitoterapia 96 (2014) 123–130.

[15]N. Li, J. Liu, M. Wang, Z. Yu, K. Zhu, J. Gao, C. Wang, J. Sun, J. Chen, H. Li, Biomed. Pharmacother. 103 (2018) 509–516.

[16]B. Wei, Q. Li, R. Fan, D. Su, X. Chen, Y. Jia, K. Bi, J. Pharm. Biomed. Anal. 88 (2014) 416–422.

[17]H. Zhu, L. Zhang, G. Wang, Z. He, Y. Zhao, Y. Xu, Y. Gao, L. Zhang, J. Food Drug Anal. 24 (2016) 831–838.

[18]F. Huang, Y. Xiong, L. Xu, S. Ma, C. Dou, J. Ethnopharmacol. 110 (2007) 471–475.

[19]N. Chen, P.Y. Chiu, K.M. Ko, Biol. Pharm. Bull. 31 (2008) 1387–1391.

[20]C.-L. Li, Y.-H. Tsuang, T.-H. Tsai, Nutrients 11 (2019).

[21]K.M. Ko, N. Chen, H.Y. Leung, E.P.K. Leong, M.K.T. Poon, P.Y. Chiu, Biofactors 34 (2008) 331–342.

[22]S.Y. Park, S.J. Park, T.G. Park, S. Rajasekar, S.-J. Lee, Y.-W. Choi, Int. Immunopharmacol. 17 (2013) 415–426.

[23]M.-Y. Song, J.-H. Wang, T. Eom, H. Kim, Nutr. Res. 35 (2015) 655–663.

[24]Y. Qi, L. Chen, K. Gao, Z. Shao, X. Huo, M. Hua, S. Liu, Y. Sun, S. Li, Int. J. Biol. Macromol. 124 (2019) 627–634.

[25]M. Kortesoja, E. Karhu, E.S. Olafsdottir, J. Freysdottir, L. Hanski, Free Radic. Biol. Med. 131 (2019) 309–317.

[26]T. Zhao, Y. Feng, J. Li, R. Mao, Y. Zou, W. Feng, D. Zheng, W. Wang, Y. Chen, L. Yang, X. Wu, Int. J. Biol. Macromol. 65 (2014) 33–40.

[27]T. Zhao, G. Mao, R. Mao, Y. Zou, D. Zheng, W. Feng, Y. Ren, W. Wang, W. Zheng, J. Song, Y. Chen, L. Yang, X. Wu, Food Chem. Toxicol. 55 (2013) 609–616.

[28]L.-M. Zhao, Y.-L. Jia, M. Ma, Y.-Q. Duan, L.-H. Liu, Int. J. Biol. Macromol. 76 (2015) 63–69.

[29]J. Yu, L. Cong, C. Wang, H. Li, C. Zhang, X. Guan, P. Liu, Y. Xie, J. Chen, J. Sun, Exp. Ther. Med. 15 (2018) 4755–4762.

[30]S.-H. Tang, R.-R. He, T. Huang, C.-Z. Wang, Y.-F. Cao, Y. Zhang, H. Kurihara, J. Ethnopharmacol. 134 (2011) 141–146.

[31]Y.H. Kang, H.M. Shin, Immunopharmacol. Immunotoxicol. 34 (2012) 292–298.

[32]H. Kim, Y.-T. Ahn, Y.S. Kim, S.I. Cho, W.G. An, Pharmacogn. Mag. 10 (2014) S80–5.

[33]A.Y.S. Yip, W.T.Y. Loo, L.W.C. Chow, Biomed. Pharmacother. 61 (2007) 588–590.

[34]P.Y. Chiu, H.Y. Leung, M.K.T. Poon, K.M. Ko, Biogerontology 7 (2006) 199–210.

[35]Y. Lu, W.-J. Wang, Y.-Z. Song, Z.-Q. Liang, Pharm. Biol. 52 (2014) 1302–1307.

[36]K.-Y. Kim, S.-K. Ku, K.-W. Lee, C.-H. Song, W.G. An, J. Ethnopharmacol. 212 (2018) 175–187.

[37]J.-S. Kim, J.S. Takanche, J.-E. Kim, S.-H. Jeong, S.-H. Han, H.-K. Yi, Phytother. Res. 33 (2019) 1865–1877.

[38]H.-F. Chiu, T.-Y. Chen, Y.-T. Tzeng, C.-K. Wang, Phytother. Res. 27 (2013) 368–373.

[39]D. Tsi, A. Tan, Bioinformation 2 (2008) 249–252.

[40]G. Aslanyan, E. Amroyan, E. Gabrielyan, M. Nylander, G. Wikman, A. Panossian, Phytomedicine 17 (2010) 494–499.

[41]N. Kormosh, K. Laktionov, M. Antoshechkina, Phytother. Res. 20 (2006) 424–425.

Sirtmax® Kaempferia parviflora

Kaempferia parviflora Common Name

Black Ginger | Black Turmeric | Krachai Dam

Top Benefits of Kaempferia parviflora

  • Supports mitochondrial biogenesis, structure and function*
  • Supports muscle strength and endurance*
  • Supports metabolism & healthy blood sugar levels*
  • Supports healthy weight*
  • Supports antioxidant defenses*
  • Supports healthy aging*
  • Support cardiovascular function*
  • Supports brain function*
  • Supports reproductive health*

What is Kaempferia parviflora?

Kaempferia parviflora is found in the upper Northeastern regions of Thailand. Root extracts have a long history of use and a reputation for being a health tonic and energy enhancer (i.e., Thai ginseng). The novel active constituents are a special type of polyphenol called polymethoxyflavonoids. Sirtmax® Kaempferia parviflora root extract is standardized for polymethoxyflavonoid content.

Neurohacker’s Kaempferia parviflora Sourcing

Sirtmax® has been used in animal and human research studies.

Created by Tokiwa Phytochemicals, a leader in standardized Kaempferia parviflora supplementation. 

Highest concentration, full-spectrum root extract, with double standardization for 5,7-dimethoxyflavone (≥ 4%) along with five Kaempferia parviflora polymethoxyflavonoids (≥ 15%).

Grown in Thailand & Laos.

Sirtmax® is a registered trademark of Tokiwa Phytochemical Co., Ltd.

Kaempferia parviflora Dosing Principles and Rationale

We consider Kaempferia parviflora to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is within the studied range in humans.*

Kaempferia parviflora Key Mechanisms

Mitochondrial biogenesis

  • Upregulates mitochondrial number[1]
  • Upregulates Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha (PGC-1α)[1–3]
  • Upregulates transcription factors for mitochondrial biogenesis (estrogen-related receptor-α [ERRα], nuclear respiratory factor-1 [Nrf-1], and mitochondrial transcription factor A [TFAM]) through activation of PGC-1α[2]

Mitochondrial function

  • Upregulates AMP-Activated Protein Kinase (AMPK)[2,3]
  • Promotes ATP production (output of mitochondrial oxidative phosphorylation)[3]
  • Promotes mitochondrial β-oxidation (fatty acid metabolism) – upregulates peroxisome proliferator-activated receptor gamma (PPARγ) and delta (PPARδ)[2,4]

Exercise performance (ergogenic effects)

  • Supports endurance performance[1,2,5,6]
  • Supports post-exercise recovery[1]
  • Supports muscle strength[5,6]
  • Supports muscle metabolism (upregulates glycogen synthase and increases glycogen content)[1]

Metabolism

  • Supports healthy insulin sensitivity[7]
  • Promotes cell metabolism (muscle cell precursors [myoblasts] in vitro): promotes glucose uptake and the downregulation of lactic acid production; promotes the expression of glucose transporter 4 (GLUT4) and monocarboxylate transporter 1 (MCT1)[3]

Body weight

  • Downregulates fat accumulation and blood/liver lipid levels[4,7,8]
  • Promotes differentiation of brown adipocyte cells[4]
  • Upregulates uncoupling protein 1 (UCP1) in brown adipose tissue - supports thermogenesis of brown adipose tissue [4,7,8]
  • Promotes whole-body energy expenditure through activation of brown adipose tissue[7,9]
  • Promotes lean body mass[2]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])[5]

Healthy aging and longevity 

  • Upregulates SIRT-1[2,10]
  • Downregulates the production of advanced glycation end-products (AGEs)[10]

Cardiovascular function

  • Promotes healthy nitric oxide (NO) signaling pathway function[11–14]
  • Upregulates endothelial NO synthase (eNOS)[11]
  • Inhibits phosphodiesterase 5 (PDE-5), the enzyme that cleaves the NO mediator cyclic guanosine monophosphate (cGMP) to 5’GMP[15]
  • Positive effect on NO signaling pathway in cardiac tissue via upregulated cGMP levels[12]
  • Promotes vasodilation via the NO signaling pathway[13,14]

Brain function

  • Acetylcholinesterase inhibition (by the methoxyflavonoid 5,7-dimethoxyflavone [DMF])[16]
  • Neuroprotection from glutamate excitotoxicity (by the methoxyflavonoid 5‐Hydroxy‐3,7,3′,4′‐tetramethoxyflavone)[17]

Reproductive function

  • Inhibits phosphodiesterase-5 (PDE-5)15 and supports relaxation of the corpus cavernosum[18]


REFERENCES

[1] Toda K, et al. Heliyon. 2016;2(5):e00115. doi:10.1016/j.heliyon.2016.e00115
[2] Kim M-B, et al. J Med Food. 2018;21(1):30-38. doi:10.1089/jmf.2017.3989
[3] Toda K, et al. J Nat Med. 2016;70(2):163-172. doi:10.1007/s11418-015-0948-y
[4] Kobayashi H, et al. J Nat Med. 2016;70(1):54-61. doi:10.1007/s11418-015-0936-2
[5] Wattanathorn J, et al. Evid Based Complement Alternat Med. 2012;2012:732816. doi:10.1155/2012/732816
[6] Promthep K, et al. Med Sci Monit Basic Res. 2015;21:100-108. doi:10.12659/MSMBR.894301
[7] Shimada T, et al. Fitoterapia. 2011;82(8):1272-1278. doi:10.1016/j.fitote.2011.08.018
[8] Yoshino S, et al. Food Sci Nutr. 2014;2(6):634-637. doi:10.1002/fsn3.144
[9] Matsushita M, et al. J Nutr Sci Vitaminol . 2015;61(1):79-83. doi:10.3177/jnsv.61.79
[10] Nakata A, et al. Nat Prod Commun. 2014;9(9):1291-1294. PMID: 25918795.
[11] Wattanapitayakul SK, et al. J Ethnopharmacol. 2007;110(3):559-562. doi:10.1016/j.jep.2006.09.037
[12] Weerateerangkul P, et al. J Cardiovasc Pharmacol. 2012;60(3):299-309. doi:10.1097/FJC.0b013e3182609a52
[13] Tep-Areenan P, et al. Phytother Res. 2010;24(10):1520-1525. doi:10.1002/ptr.3164
[14] Tep-Areenan P, et al. Asian Biomed. 2010;4(1):103-111. doi:10.2478/abm-2010-0012
[15] Temkitthawon P, et al. J Ethnopharmacol. 2011;137(3):1437-1441. doi:10.1016/j.jep.2011.08.025
[16] Sawasdee P, et al. Phytother Res. 2009;23(12):1792-1794. doi:10.1002/ptr.2858
[17] Moon H-I, et al. Phytother Res. 2011;25(8):1215-1217. doi:10.1002/ptr.3390
[18] Jansakul C, et al. Eur J Pharmacol. 2012;691(1-3):235-244. doi:10.1016/j.ejphar.2012.07.019

Sensoril® Ashwagandha Withania somnifera Root and Leaf Extract

Withania somnifera Common Name

Ashwagandha | Indian ginseng

Top Benefits of Withania somnifera

  • Supports a healthy stress response*
  • Supports exercise performance and energy*
  • Supports healthy weight* 
  • Supports mitochondrial efficiency* 
  • Supports brain function and mental cognition* 
  • Supports sleep*

What is Withania somnifera?

Ashwagandha is an Ayurvedic herb with adaptogenic properties—it’s often referred to as “Indian ginseng.” Ashwagandha has a long history of use and has been reported to have several health-promoting effects, supporting healthy energy, metabolism, stress response, physical performance, sleep, joint health, and cognitive performance. The novel active constituents are a group of plant compounds called withanolide glycosides. Sensoril® root and lead extract is standardized for withanolide glycoside content.

Neurohacker’s Withania somnifera Sourcing

Sensoril® has been clinically tested in 10 randomized, double-blind, placebo-controlled human trials.

Created by Natreon Inc., a leader in scientifically studied and tested Ayurvedic ingredients.

Leaf and root extract triple standardized to contain a minimum of 10% withanolide glycosides, the main bioactive; a minimum of 32% oligosaccharides, which increase the bioavailability of the withanolide glycosides; and a maximum of 0.5% free withanolides (as Withaferin A).

Protected by multiple U.S. patents with self-affirmed generally recognized as safe (GRAS) status). 

Vegetarian ● Organic compliant or certified organic ● Non-GMO Allergen & Gluten-free ● Kosher & Halal certified

Withania somnifera Dosing Principles and Rationale

We consider Ashwagandha to be an herbal adaptogen, so expect it to follow hormetic dosing principles (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. So, it’s important to identify the lowest dose that can produce the desired response. Sensoril®—the standardized extract we use—produced a threshold  response in a study that gave different daily dosages—125 mg, 250 mg, 500 mg. Effect size was slightly greater for the higher doses, but most of the change was evident with the lowest dose.[1] We opted for this lower dose to be consistent with a core hormetic principle—only do or use as much as something as would be needed to stimulate the desired response.

Withania somnifera Key Mechanisms 

Mitochondrial structure and function

  • Supports mitochondrial membrane potential and structural integrity [2]
  • Protects from mitochondrial damage [2]
  • Protects from mitochondrial membrane permeabilization [3]
  • Protects from complex I-V Inhibition (protects electron transport chain and oxidative phosphorylation performance) [2,4–6]
  • Upregulates citric acid cycle enzymes [6]

Exercise performance (ergogenic effect)

  • Supports endurance performance [7,8]
  • Supports muscle strength [9,10]
  • Supports post-exercise recovery [10]

Metabolism

  • Supports healthy insulin sensitivity [11–15]
  • Supports healthy blood glucose levels [12–16]
  • Supports healthy leptin signaling [11,15]

Body weight 

  • Supports healthy body weight [11,15]
  • Supports healthy feeding behaviors [11,17]
  • Upregulates lean mass [10]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [2,4,5,16,18]
  • Replenishes glutathione (GSH) levels [2,4,16]
  • Downregulates oxidative stress and reactive oxygen species levels [2–4,19]

Cellular signaling 

  • Downregulates the expression of proinflammatory cytokines – tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), and IL-6 [11–13]

Brain function

  • Supports cognitive and psychomotor performance [20,21]
  • Supports memory, executive function, attention, and information processing speed [22]
  • Modulates GABAergic neurotransmission [23,24]
  • GABA receptor agonism [25–27] 
  • Upregulates dopamine levels [4]
  • Downregulates the basal activity levels of acetylcholine esterase [4]
  • Neuroprotective – protects from neuronal mitochondrial swelling and apoptosis; protects cognitive function (ischemia, oxidative stress) [2]
  • Protects from neurotoxicity [4,5]
  • Regulates neural cytokine signaling [11]

Sleep

  • Shortens sleep onset latency [23,28]
  • Supports sleep efficiency [28]
  • Supports quality of sleep [9,28]
  • Extends the duration of slow wave sleep [23]
  • Extends total sleep time [23]

Mood and stress response

  • Supports a calm mood [11,28]
  • Supports stress management [1,17,29]
  • Downregulates serum cortisol levels [1,17,29]

Thyroid function

  • Supports thyroid function [30–32]

Healthy aging and longevity 

  • Lifespan extension effects (Caenorhabditis elegans) [19,33]
  • Upregulates insulin-like growth factor-1 (IGF-1) signaling pathway [19,33]
  • Downregulates α-synuclein and amyloid-β aggregation [19]
  • Upregulates FOXO3A and SIRT3 [34]

REFERENCES

[1]B. Auddy, J. Hazra, A. Mitra, B. Abedon, S. Ghosal, Journal of American Nutraceutical Association 11 (2008) 50–56.

[2]A. Sood, A. Mehrotra, D.K. Dhawan, R. Sandhir, Metab. Brain Dis. 33 (2018) 1261–1274.

[3]P. Parihar, R. Shetty, P. Ghafourifar, M.S. Parihar, Cell. Mol. Biol. 62 (2016) 73–83.

[4]M.J. Manjunath, Muralidhara, J. Food Sci. Technol. 52 (2015) 1971–1981.

[5]P. Kumar, A. Kumar, J. Med. Food 12 (2009) 591–600.

[6]P. Senthilnathan, R. Padmavathi, V. Magesh, D. Sakthisekaran, Life Sci. 78 (2006) 1010–1014.

[7]J.S. Sandhu, B. Shah, S. Shenoy, S. Chauhan, G.S. Lavekar, M.M. Padhi, Int. J. Ayurveda Res. 1 (2010) 144–149.

[8]B. Choudhary, A. Shetty, D.G. Langade, Ayu 36 (2015) 63–68.

[9]A.A. Raut, N.N. Rege, F.M. Tadvi, P.V. Solanki, K.R. Kene, S.G. Shirolkar, S.N. Pandey, R.A. Vaidya, A.B. Vaidya, J. Ayurveda Integr. Med. 3 (2012) 111–114.

[10]S. Wankhede, D. Langade, K. Joshi, S.R. Sinha, S. Bhattacharyya, J. Int. Soc. Sports Nutr. 12 (2015) 43.

[11]T. Kaur, G. Kaur, J. Neuroinflammation 14 (2017) 201.

[12]M.R. Shahraki, Z. Samadi Noshahr, H. Ahmadvand, A. Nakhaie, J. Basic Clin. Physiol. Pharmacol. 27 (2016) 387–391.

[13]Z. Samadi Noshahr, M.R. Shahraki, H. Ahmadvand, D. Nourabadi, A. Nakhaei, Rep Biochem Mol Biol 3 (2015) 62–67.

[14]T. Anwer, M. Sharma, K.K. Pillai, M. Iqbal, Basic Clin. Pharmacol. Toxicol. 102 (2008) 498–503.

[15]J. Lee, J. Liu, X. Feng, M.A. Salazar Hernández, P. Mucka, D. Ibi, J.W. Choi, U. Ozcan, Nat. Med. 22 (2016) 1023–1032.

[16]T. Anwer, M. Sharma, K.K. Pillai, G. Khan, Acta Pol. Pharm. 69 (2012) 1095–1101.

[17]D. Choudhary, S. Bhattacharyya, K. Joshi, J. Evid. Based Complementary Altern. Med. 22 (2017) 96–106.

[18]S.K. Gupta, A. Dua, B.P.S. Vohra, Drug Metabol. Drug Interact. 19 (2003) 211–222.

[19]B.A. Akhoon, S. Pandey, S. Tiwari, R. Pandey, Exp. Gerontol. 78 (2016) 47–56.

[20]U. Pingali, R. Pilli, N. Fatima, Pharmacognosy Res. 6 (2014) 12–18.

[21]K.N.R. Chengappa, C.R. Bowie, P.J. Schlicht, D. Fleet, J.S. Brar, R. Jindal, J. Clin. Psychiatry 74 (2013) 1076–1083.

[22]D. Choudhary, S. Bhattacharyya, S. Bose, J. Diet. Suppl. 14 (2017) 599–612.

[23]A. Kumar, H. Kalonia, Indian J. Pharm. Sci. 70 (2008) 806–810.

[24]M. Candelario, E. Cuellar, J.M. Reyes-Ruiz, N. Darabedian, Z. Feimeng, R. Miledi, A. Russo-Neustadt, A. Limon, J. Ethnopharmacol. 171 (2015) 264–272.

[25]A.K. Mehta, P. Binkley, S.S. Gandhi, M.K. Ticku, Indian J. Med. Res. 94 (1991) 312–315.

[26]J.P. Bhattarai, S.A. Park, S.K. Han, Phytotherapy Research (2009).

[27]H. Yin, D.H. Cho, S.J. Park, S.K. Han, The American Journal of Chinese Medicine 41 (2013) 1043–1051.

[28]D. Langade, S. Kanchi, J. Salve, K. Debnath, D. Ambegaokar, Cureus 11 (2019) e5797.

[29]K. Chandrasekhar, J. Kapoor, S. Anishetty, Indian J. Psychol. Med. 34 (2012) 255–262.

[30]A.K. Sharma, I. Basu, S. Singh, J. Altern. Complement. Med. 24 (2018) 243–248.

[31]J.M. Gannon, P.E. Forrest, K.N. Roy Chengappa, J. Ayurveda Integr. Med. 5 (2014) 241–245.

[32]R. Jatwa, A. Kar, Phytother. Res. 23 (2009) 1140–1145.

[33]B.A. Akhoon, L. Rathor, R. Pandey, Exp. Gerontol. 104 (2018) 113–117.

[34]R. Pradhan, R. Kumar, S. Shekhar, N. Rai, A. Ambashtha, J. Banerjee, M. Pathak, S.N. Dwivedi, S. Dey, A.B. Dey, Exp. Gerontol. 95 (2017) 9–15.

Holy Basil (Ocimum sanctum) Leaf Extract

HOLY BASIL COMMON NAME

Holy Basil | Sacred Basil | Tulsi | Tulasi

TOP BENEFITS OF HOLY BASIL

Supports a calm mood*
Supports cognitive function*
Support a healthy stress response*
Supports general immune health*

WHAT IS HOLY BASIL?

Holy Basil (Ocimum sanctum; synonym Ocimum tenuiflorum) is a culinary and medicinal aromatic herb that has been used within Ayurvedic medicine for more than 3000 years[1]. In Ayurvedic medicine holy basil is called “tulsi,” which translates as “the incomparable one.” It is one of a small number of herbs categorized as Rasayana, the category applied to elixirs and tonic herbs prized for rejuvenation and revitalization. It was believed to guard the body from stress of all types while keeping the mind sharp and the body healthy. In modern times, holy basil is categorized as an adaptogen, supporting a healthy stress response. Holy basil also supports mood, cognition and immunity. Holy basil’s bioactive molecules include ursolic acid, rosmarinic acid, eugenol, ocimumosides A and B, ocimarin, apigenin and lutein[2,3].

NEUROHACKER’S HOLY BASIL SOURCING

Holy Basil is a leaf extract standardized to contain not less than 2% ursolic acid.

Holy Basil is Non-GMO and Vegan.

HOLY BASIL DOSING PRINCIPLES AND RATIONALE

Because holy basil is an Ayurvedic Rasayana herb, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles ). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. For herbs that are adaptogens, especially when they will be used for extended periods of time, we think it’s important to identify the lowest dose that can produce many of the desired responses. Different doses of holy basil have been used in human studies. Functional benefits have occurred at low doses (~300mg) and at doses four-fold higher (1200mg). Considered collectively, human studies suggest holy basil dosing may be somewhat akin to the Pareto Principle (i.e., 80-20 rule), where 80%+ of the benefits happen at 20% of the dose. Our goal with holy basil, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogen extracts, we are likely to use less holy basil than if the only herbal adaptogen we were using was holy basil.

HOLY BASIL KEY MECHANISMS

Mood and stress response
Supports a calm mood[4–11]
Supports a positive mental-emotional bias[6,9]
Supports healthy stress hormone levels[4,7,8,12,13]

Brain function
Supports memory and learning[5,14,15]
Supports working memory[4]
Supports executive function[4]
Supports attention[6]
Supports sleep[5]
Supports serotonin signaling[16–18]
Supports dopamine signaling[16–18]
Supports adrenergic signaling[17,18]
Supports acetylcholine signaling[19,20]
Down-regulates acetylcholinesterase (AChE) activity[19,21]
Up-regulates choline acetyltransferase (ChAT) expression[14,22]
Supports brain antioxidant defenses[18,23–25]
Supports neuroprotective functions[15,18,23–27]

Immune System
Supports innate immunity[28]
Supports adaptive immunity[28–31]

General health
Supports gastroprotective functions[32,33]
Supports healthy metabolism[34,35]


REFERENCES

[1] N. Jamshidi, M.M. Cohen, Evid. Based. Complement. Alternat. Med. 2017 (2017) 9217567.
[2] P. Pattanayak, P. Behera, D. Das, S. Panda, Pharmacognosy Reviews 4 (2010) 95.
[3] P. Gupta, D.K. Yadav, K.B. Siripurapu, G. Palit, R. Maurya, J. Nat. Prod. 70 (2007) 1410–1416.
[4] S. Sampath, S.C. Mahapatra, M.M. Padhi, R. Sharma, A. Talwar, Indian J. Physiol. Pharmacol. 59 (2015) 69–77.
[5] R.C. Saxena, R. Singh, P. Kumar, M.P.S. Negi, V.S. Saxena, P. Geetharani, J.J. Allan, K. Venkateshwarlu, Evid. Based. Complement. Alternat. Med. 2012 (2012) 894509.
[6] D. Bhattacharyya, T.K. Sur, U. Jana, P.K. Debnath, Nepal Med. Coll. J. 10 (2008) 176–179.
[7] E. Jothie Richard, R. Illuri, B. Bethapudi, S. Anandhakumar, A. Bhaskar, C. Chinampudur Velusami, D. Mundkinajeddu, A. Agarwal, Phytother. Res. 30 (2016) 805–814.
[8] R. Archana, A. Namasivayam, J. Ethnopharmacol. 73 (2000) 81–85.
[9] M. Chatterjee, P. Verma, R. Maurya, G. Palit, Pharm. Biol. 49 (2011) 477–483.
[10] L. Mohan, U.S.C. Rao, H.N. Gopalakrishna, V. Nair, Evid. Based. Complement. Alternat. Med. 2011 (2011).
[11] L.R. Bathala, C.V. Rao, S. Manjunath, S. Vinuta, R. Vemulapalli, J. Contemp. Dent. Pract. 13 (2012) 782–786.
[12] R. Archana, A. Namasivayam, Phytother. Res. 16 (2002) 579–580.
[13] K. Sembulingam, P. Sembulingam, A. Namasivayam, Indian J. Physiol. Pharmacol. 41 (1997) 139–143.
[14] D.L. Kusindarta, H. Wihadmadyatami, A.R. Jadi, S. Karnati, G. Lochnit, P. Hening, A. Haryanto, M.B. Auriva, M. Purwaningrum, Research in Veterinary Science 118 (2018) 431–438.
[15] S.C. Sarangi, S.S. Pattnaik, J. Katyal, T. Kaleekal, A.K. Dinda, J. Ethnopharmacol. 249 (2020) 112389.
[16] J. Samson, R. Sheela Devi, R. Ravindran, M. Senthilvelan, Pharmacol. Biochem. Behav. 83 (2006) 67–75.
[17] R. Ravindran, S.D. Rathinasamy, J. Samson, M. Senthilvelan, J. Pharmacol. Sci. 98 (2005) 354–360.
[18] A. Ahmad, N. Rasheed, K. Chand, R. Maurya, N. Banu, G. Palit, Indian J. Med. Res. 135 (2012) 548.
[19] K. Sembulingam, P. Sembulingam, A. Namasivayam, J. Ethnopharmacol. 96 (2005) 477–482.
[20] D.L. Kusindarta, H. Wihadmadyatami, A. Haryanto, Veterinary World 11 (2018) 135–140.
[21] V.V. Giridharan, R.A. Thandavarayan, V. Mani, T. Ashok Dundapa, K. Watanabe, T. Konishi, J. Med. Food 14 (2011) 912–919.
[22] P. Hening, M.B. Mataram Auriva, N. Wijayanti, D.L. Kusindarta, H. Wihadmadyatami, Vet World 11 (2018) 1237–1243.
[23] S.U. Yanpallewar, S. Rai, M. Kumar, S.B. Acharya, Pharmacol. Biochem. Behav. 79 (2004) 155–164.
[24] A. Ahmad, M.M. Khan, S.S. Raza, H. Javed, M. Ashafaq, F. Islam, M.M. Safhi, F. Islam, Neurol. Sci. 33 (2012) 1239–1247.
[25] J. Samson, R. Sheeladevi, R. Ravindran, Neurotoxicology 28 (2007) 679–685.
[26] H. Joshi, M. Parle, Indian J. Exp. Biol. 44 (2006) 133–136.
[27] Y.H. Siddique, M. Faisal, F. Naz, S. Jyoti, Rahul, Chin. J. Nat. Med. 12 (2014) 777–781.
[28] S. Mondal, S. Varma, V.D. Bamola, S.N. Naik, B.R. Mirdha, M.M. Padhi, N. Mehta, S.C. Mahapatra, J. Ethnopharmacol. 136 (2011) 452–456.
[29] A. Goel, D.K. Singh, S. Kumar, A.K. Bhatia, Asian Pac. J. Trop. Med. 3 (2010) 8–12.
[30] C.R. Jeba, R. Vaidyanathan, G. Rameshkumar, Int J on Pharmaceutical and Biomed Res 2 (2011) 33–38.
[31] P. Kaur, Robin, V.O. Makanjuola, R. Arora, B. Singh, S. Arora, Biomedicine & Pharmacotherapy 95 (2017) 1815–1829.
[32] R.K. Goel, K. Sairam, M. Dorababu, T. Prabha, C.V. Rao, Indian J. Exp. Biol. 43 (2005) 715–721.
[33] S. Mandal, D.N. Das, K. De, K. Ray, G. Roy, S.B. Chaudhuri, C.C. Sahana, M.K.Chowdhuri, Indian J. Physiol. Pharmacol. 37 (1993) 91–92.
[34] S. Satapathy, N. Das, D. Bandyopadhyay, S.C. Mahapatra, D.S. Sahu, M. Meda, Indian J. Clin. Biochem. 32 (2017) 357–363.
[35] P. Agrawal, V. Rai, R.B. Singh, Int. J. Clin. Pharmacol. Ther. 34 (1996) 406–409.

Panax ginseng Root Extract

COMMON NAME

Ginseng | Korean ginseng | Asian ginseng | Ginseng radix

TOP BENEFITS OF PANAX GINSENG ROOT EXTRACT

  • Supports general immune health*
  • Supports upper respiratory health*
  • Supports cognitive function*

WHAT IS PANAX GINSENG ROOT EXTRACT?

The roots of Panax ginseng have been used for thousands of years in China, Korea, and Japan. In these traditions, it was used as a Qi tonic to promote strength, restore vitality, support energy, and to quiet the spirit. “Panax” means “all-healing” in Greek. It is aptly named, based on both its traditional uses and modern scientific research[1]. P. ginseng is characterized as an adaptogen—it is used for invigorating and fortifying in times of higher stress or greater demands. P. ginseng is also used for supporting the capacity for mental and physical work. A great deal of the research on it P. ginseng has been related to the immune system, where it acts as an immune adaptogen, supporting both the innate and adaptive immune systems[2]. The main bioactive compounds of Panax ginseng are ginsenosides[3].

NEUROHACKER’S PANAX GINSENG  ROOT EXTRACT SOURCING

Panax ginseng Root Extract is made from dried roots extracted according to the European Pharmacopoeia. 

Panax ginseng Root Extract is a 3-4:1 extract standardized to contain not less than 4% ginsenosides.

Panax ginseng Root Extract is non-GMO, Halal, Kosher, gluten-free, and vegan.

PANAX GINSENG  ROOT EXTRACT DOSING PRINCIPLES AND RATIONALE

Because Panax ginseng is an adaptogen, we consider dosing to follow hormetic principles (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone. The established daily dose range for Panax ginseng root extracts standardized for 4% ginsenosides is 40-200 mg. Our dosage is consistent with this established dosage range.

PANAX GINSENG KEY MECHANISMS

Immune function

  • Supports general immune health[4–8]
  • Supports innate immunity[4,9–16]
  • Supports adaptive immunity[4,5,9–12,15–17]
  • Supports cellular intrinsic immune defenses[18–25] 
  • Supports mucosal immunity[26,27]
  • Supports immune tolerance[28–34] 
  • Supports healthy dendritic cell function[10]
  • Supports healthy natural killer cell function[4,9,11–16]
  • Supports healthy macrophage function[9,11,35]
  • Supports healthy T cell function[9–11,15]
  • Supports healthy B cell function[4,5,11,12,15–17,36]
  • Supports immune signaling[5,9,11,27,37–40]
  • Supports immune organ function[38]

Gut microbiota

  • Supports gut microbiota[27,41,42]

Brain function

  • Supports cognitive performance[43–51]
  • Supports against mental fatigue[43,44]
  • Supports brain metabolism[52]
  • Supports neuroprotection[53–56]

Healthy aging

  • Supports antioxidant defenses[38,54,57–61]
  • Supports Nrf2 signaling[9,51,62–66]
  • Supports phase II detox enzymes[9]
  • Supports autophagy[53,67–77]
  • Supports AMPK signaling[68,78]
  • Supports mitochondrial function[61,74,79–86]
  • Supports healthy blood glucose levels[43,44,87]
  • Modulates advanced glycation end product (AGE) production[57,59,60,88–92]

REFERENCES

[1]A.R. Bilia, M.C. Bergonzi, J. Ginseng Res. 44 (2020) 179–193.
[2] S.-W. Kang, H.-Y. Min, Journal of Ginseng Research 36 (2012) 354–368.
[3] K.W. Leung, A.S.-T. Wong, Chin. Med. 5 (2010) 20.
[4] F. Scaglione, G. Cattaneo, M. Alessandria, R. Cogo, Drugs Exp. Clin. Res. 22 (1996) 65–72.
[5] F.S. Quan, R.W. Compans, Y.-K. Cho, S.-M. Kang, Vaccine 25 (2007) 272–282.
[6] F. Scaglione, K. Weiser, M. Alessandria, Clin. Drug Investig. 21 (2001) 41–45.
[7] J.K. Seida, T. Durec, S. Kuhle, Evid. Based. Complement. Alternat. Med. 2011 (2011) 282151.
[8] J.-W. Jung, H.-R. Kang, G.-E. Ji, M.-S. Park, W.-J. Song, M.-H. Kim, J.-W. Kwon, T.-W. Kim, H.-W. Park, S.-H. Cho, K.-U. Min, Allergy Asthma Immunol. Res. 3 (2011) 103–110.
[9] L.-X. Chen, Y.-L. Qi, Z. Qi, K. Gao, R.-Z. Gong, Z.-J. Shao, S.-X. Liu, S.-S. Li, Y.-S. Sun, Molecules 24 (2019).
[10] M. Takei, E. Tachikawa, A. Umeyama, Biomark. Insights 3 (2008) 269–286.
[11] L.-X. He, J.-W. Ren, R. Liu, Q.-H. Chen, J. Zhao, X. Wu, Z.-F. Zhang, J.-B. Wang, G. Pettinato, Y. Li, Food Funct. 8 (2017) 3523–3532.
[12] Y.H. Jie, S. Cammisuli, M. Baggiolini, Agents Actions 15 (1984) 386–391.
[13] K. Takeda, K. Okumura, Evid. Based. Complement. Alternat. Med. 2015 (2015) 603198.
[14] J.Y. Kim, D.R. Germolec, M.I. Luster, Immunopharmacol. Immunotoxicol. 12 (1990) 257–276.
[15] C.-J. Liou, W.-C. Huang, J. Tseng, Immunopharmacol. Immunotoxicol. 28 (2006) 227–240.
[16] V.K. Singh, S.S. Agarwal, B.M. Gupta, Planta Med. 50 (1984) 462–465.
[17] C.-J. Liou, W.-C. Huang, J. Tseng, Am. J. Chin. Med. 33 (2005) 651–661.
[18] S. Wright, E. Altman, J. Microbiol. Biotechnol. 30 (2020) 101–108.
[19] E.H. Park, J. Yum, K.B. Ku, H.M. Kim, Y.M. Kang, J.C. Kim, J.A. Kim, Y.K. Kang, S.H. Seo, J. Ginseng Res. 38 (2014) 40–46.
[20] Y. Wang, Y.-J. Jung, K.-H. Kim, Y. Kwon, Y.-J. Kim, Z. Zhang, H.-S. Kang, B.-Z. Wang, F.-S. Quan, S.-M. Kang, Viruses 10 (2018).
[21] S.Y. Yin, H.J. Kim, H.-J. Kim, Biol. Pharm. Bull. 36 (2013) 1002–1007.
[22] D.-G. Yoo, M.-C. Kim, M.-K. Park, J.-M. Song, F.-S. Quan, K.-M. Park, Y.-K. Cho, S.-M. Kang, J. Med. Food 15 (2012) 855–862.
[23] D.-G. Yoo, M.-C. Kim, M.-K. Park, K.-M. Park, F.-S. Quan, J.-M. Song, J.J. Wee, B.-Z. Wang, Y.-K. Cho, R.W. Compans, S.-M. Kang, PLoS One 7 (2012) e33678.
[24] J.S. Lee, Y.-N. Lee, Y.-T. Lee, H.S. Hwang, K.-H. Kim, E.-J. Ko, M.-C. Kim, S.-M. Kang, Nutrients 7 (2015) 1021–1036.
[25] J.S. Lee, E.-J. Ko, H.S. Hwang, Y.-N. Lee, Y.-M. Kwon, M.-C. Kim, S.-M. Kang, Int. J. Mol. Med. 34 (2014) 183–190.
[26] M. Sumiyoshi, M. Sakanaka, Y. Kimura, J. Ethnopharmacol. 132 (2010) 206–212.
[27] Y. Sun, S. Chen, R. Wei, X. Xie, C. Wang, S. Fan, X. Zhang, J. Su, J. Liu, W. Jia, X. Wang, Food Funct. 9 (2018) 3547–3556.
[28] J.-I. Lee, K.S. Park, I.-H. Cho, J. Ginseng Res. 43 (2019) 342–348.
[29] J. Kim, H. Byeon, K. Im, H. Min, Food Sci. Biotechnol. 27 (2018) 227–232.
[30] M.J. Lee, M. Jang, J. Choi, B.S. Chang, D.Y. Kim, S.-H. Kim, Y.-S. Kwak, S. Oh, J.-H. Lee, B.-J. Chang, S.-Y. Nah, I.-H. Cho, Mol. Neurobiol. 53 (2016) 1977–2002.
[31] J. Jhun, J. Lee, J.-K. Byun, E.-K. Kim, J.-W. Woo, J.-H. Lee, S.-K. Kwok, J.-H. Ju, K.-S. Park, H.-Y. Kim, S.H. Park, M.-L. Cho, Mediators Inflamm. 2014 (2014) 351856.
[32] G.N. Oh, S.W. Son, J. Ginseng Res. 36 (2012) 391–395.
[33] J.-K. Kim, J.-Y. Kim, S.-E. Jang, M.-S. Choi, H.-M. Jang, H.-H. Yoo, D.-H. Kim, Am. J. Chin. Med. 46 (2018) 1879–1897.
[34] S.B. Heo, S.W. Lim, J.Y. Jhun, M.L. Cho, B.H. Chung, C.W. Yang, J. Ginseng Res. 40 (2016) 18–27.
[35] J. Hao, H. Hu, J. Liu, X. Wang, X. Liu, J. Wang, M. Niu, Y. Zhao, X. Xiao, Evid. Based. Complement. Alternat. Med. 2019 (2019) 3630260.
[36] M.L. Xu, H.J. Kim, Y.R. Choi, H.-J. Kim, J. Ginseng Res. 36 (2012) 396–402.
[37] M. Pannacci, V. Lucini, F. Colleoni, C. Martucci, S. Grosso, P. Sacerdote, F. Scaglione, Brain Behav. Immun. 20 (2006) 546–551.
[38] J. Sun, L. Zhang, J. Zhang, R. Ran, Y. Shao, J. Li, D. Jia, Y. Zhang, M. Zhang, L. Wang, Y. Wang, Int. Immunopharmacol. 58 (2018) 94–102.
[39] H. Mohammadi, A. Hadi, H. Kord-Varkaneh, A. Arab, M. Afshari, A.J.R. Ferguson, E. Ghaedi, Phytother. Res. 33 (2019) 1991–2001.
[40] H.L. Jung, H.E. Kwak, S.S. Kim, Y.C. Kim, C.D. Lee, H.K. Byurn, H.Y. Kang, Am. J. Chin. Med. 39 (2011) 441–450.
[41] M.-Y. Song, B.-S. Kim, H. Kim, J. Ginseng Res. 38 (2014) 106–115.
[42] Sun Y.-F., Zhang X., Wang X.-Y., Jia W., Zhongguo Zhong Yao Za Zhi 43 (2018) 3927–3932.
[43] J.L. Reay, D.O. Kennedy, A.B. Scholey, J. Psychopharmacol. 19 (2005) 357–365.
[44] J.L. Reay, D.O. Kennedy, A.B. Scholey, J. Psychopharmacol. 20 (2006) 771–781.
[45] S.I. Sünram-Lea, R.J. Birchall, K.A. Wesnes, O. Petrini, Curr. Top. Nutraceutical Res. 3 (2005) 65–74.
[46] D.O. Kennedy, C.F. Haskell, K.A. Wesnes, A.B. Scholey, Pharmacol. Biochem. Behav. 79 (2004) 401–411.
[47] D.O. Kennedy, A.B. Scholey, K.A. Wesnes, Physiol. Behav. 75 (2002) 739–751.
[48] A.B. Scholey, D.O. Kennedy, Hum. Psychopharmacol. 17 (2002) 35–44.
[49] D.O. Kennedy, A.B. Scholey, K.A. Wesnes, Nutr. Neurosci. 4 (2001) 295–310.
[50] L. D’Angelo, R. Grimaldi, M. Caravaggi, M. Marcoli, E. Perucca, S. Lecchini, G.M. Frigo, A. Crema, J. Ethnopharmacol. 16 (1986) 15–22.
[51] Y. Lee, S. Oh, J. Ginseng Res. 39 (2015) 250–256.
[52] M.M. Samira, M.A. Attia, M. Allam, O. Elwan, J. Int. Med. Res. 13 (1985) 342–348.
[53] Y. Li, F. Wang, Y. Luo, J. Surg. Res. 207 (2017) 181–189.
[54] X. Tan, J. Gu, B. Zhao, S. Wang, J. Yuan, C. Wang, J. Chen, J. Liu, L. Feng, X. Jia, J. Ginseng Res. 39 (2015) 116–124.
[55] D. Kim, H. Jeon, S. Ryu, S. Koo, K.-T. Ha, S. Kim, PLoS One 11 (2016) e0164906.
[56] J.M. Van Kampen, D.B. Baranowski, C.A. Shaw, D.G. Kay, Exp. Gerontol. 50 (2014) 95–105.
[57] J. Li, D. Cai, X. Yao, Y. Zhang, L. Chen, P. Jing, L. Wang, Y. Wang, Int. J. Mol. Sci. 17 (2016).
[58] S. Park, C.-S. Kim, J. Min, S.H. Lee, Y.-S. Jung, J. Nutr. Sci. Vitaminol. 60 (2014) 159–166.
[59] H.Y. Kim, K.S. Kang, N. Yamabe, T. Yokozawa, Am. J. Chin. Med. 36 (2008) 989–1004.
[60] K.S. Kang, N. Yamabe, H.Y. Kim, J.H. Park, T. Yokozawa, Eur. J. Pharmacol. 591 (2008) 266–272.
[61] E. González-Burgos, C. Fernández-Moriano, R. Lozano, I. Iglesias, M.P. Gómez-Serranillos, Food Chem. Toxicol. 109 (2017) 38–47.
[62] G. Carota, M. Raffaele, V. Sorrenti, L. Salerno, V. Pittalà, S. Intagliata, Fitoterapia 139 (2019) 104370.
[63] L. Liu, M.G. Kelly, E.L. Wierzbicki, I.C. Escober-Nario, M.K. Vollmer, S. Doré, Antioxidants (Basel) 8 (2019).
[64] L. Liu, M.K. Vollmer, A.S. Ahmad, V.M. Fernandez, H. Kim, S. Doré, Free Radic. Biol. Med. 131 (2019) 98–114.
[65] C.Y. Kim, B. Kang, H.J. Suh, H.-S. Choi, Biomed. Pharmacother. 108 (2018) 1507–1516.
[66] C.L.L. Saw, A.Y. Yang, D.C. Cheng, S.S.-S. Boyanapalli, Z.-Y. Su, T.O. Khor, S. Gao, J. Wang, Z.-H. Jiang, A.-N.T. Kong, Chem. Res. Toxicol. 25 (2012) 1574–1580.
[67] H.-H. Park, S.-W. Choi, G.J. Lee, Y.-D. Kim, H.-J. Noh, S.-J. Oh, I. Yoo, Y.-J. Ha, G.-B. Koo, S.-S. Hong, S.W. Kwon, Y.-S. Kim, J. Ginseng Res. 43 (2019) 86–94.
[68] Y. Chung, S. Jeong, H.S. Choi, S. Ro, J.S. Lee, J.K. Park, Anim Cells Syst (Seoul) 22 (2018) 382–389.
[69] Z.-M. Xu, C.-B. Li, Q.-L. Liu, P. Li, H. Yang, Int. J. Mol. Sci. 19 (2018).
[70] P. Zhou, W. Xie, Y. Luo, S. Lu, Z. Dai, R. Wang, X. Zhang, G. Li, G. Sun, X. Sun, Molecules 23 (2018).
[71] X.-Y. Zhang, K. Sun, Q. Zhu, T. Song, Y. Liu, Kaohsiung J. Med. Sci. 33 (2017) 535–542.
[72] P. Wang, C. Lin, S. Wu, K. Huang, Y. Wang, X. Bao, F. Zhang, Z. Huang, H. Teng, Cell. Mol. Neurobiol. 38 (2018) 679–690.
[73] S.W. Lim, L. Jin, K. Luo, J. Jin, C.W. Yang, Lab. Invest. 97 (2017) 1271–1281.
[74] J.-H. Moon, J.-H. Lee, Y.-J. Lee, S.-Y. Park, Oncotarget 7 (2016) 85697–85708.
[75] X. Zheng, W. Chen, H. Hou, J. Li, H. Li, X. Sun, L. Zhao, X. Li, Biomed. Pharmacother. 85 (2017) 620–626.
[76] D.-G. Kim, K.H. Jung, D.-G. Lee, J.-H. Yoon, K.S. Choi, S.W. Kwon, H.-M. Shen, M.J. Morgan, S.-S. Hong, Y.-S. Kim, Oncotarget 5 (2014) 4438–4451.
[77] S.W. Lim, K.C. Doh, L. Jin, J. Jin, S.G. Piao, S.B. Heo, B.H. Chung, C.W. Yang, Nephrology 19 (2014) 490–499.
[78] H.-S. Yoo, J.M. Kim, E. Jo, C.-K. Cho, S.-Y. Lee, H.S. Kang, M.-G. Lee, P.-Y. Yang, I.-S. Jang, Oncol. Rep. 37 (2017) 3287–3296.
[79] Y. Zhang, X. Yang, S. Wang, S. Song, J. Agric. Food Chem. 67 (2019) 10048–10058.
[80] S.J. Shin, S.G. Jeon, J.-I. Kim, Y.-O. Jeong, S. Kim, Y.H. Park, S.-K. Lee, H.H. Park, S.B. Hong, S. Oh, J.-Y. Hwang, H.S. Kim, H. Park, Y. Nam, Y.Y. Lee, J.-J. Kim, S.-H. Park, J.-S. Kim, M. Moon, Int. J. Mol. Sci. 20 (2019).
[81] J.-K. Park, J.-Y. Shim, A.-R. Cho, M.-R. Cho, Y.-J. Lee, J. Med. Food 21 (2018) 544–550.
[82] L. Bao, X. Cai, J. Wang, Y. Zhang, B. Sun, Y. Li, Nutrients 8 (2016).
[83] X.-T. Li, R. Chen, L.-M. Jin, H.-Y. Chen, Am. J. Chin. Med. 37 (2009) 1139–1152.
[84] A.C. Cabral de Oliveira, A.C. Perez, J.G. Prieto, I.D.G. Duarte, A.I. Alvarez, J. Ethnopharmacol. 97 (2005) 211–214.
[85] J. Voces, A.C. Cabral de Oliveira, J.G. Prieto, L. Vila, A.C. Perez, I.D.G. Duarte, A.I. Alvarez, Braz. J. Med. Biol. Res. 37 (2004) 1863–1871.
[86] Y. Fu, L.L. Ji, J. Nutr. 133 (2003) 3603–3609.
[87] J.L. Reay, D.O. Kennedy, A.B. Scholey, Br. J. Nutr. 96 (2006) 639–642.
[88] C.-S. Kim, K. Jo, J.S. Kim, M.-K. Pyo, J. Kim, BMC Complement. Altern. Med. 17 (2017) 430.
[89] K.S. Kang, J. Ham, Y.-J. Kim, J.H. Park, E.-J. Cho, N. Yamabe, J. Ginseng Res. 37 (2013) 379–388.
[90] H.Y. Quan, D.Y. Kim, S.H. Chung, J. Ginseng Res. 37 (2013) 187–193.
[91] H.Y. Kim, K.S. Kang, N. Yamabe, R. Nagai, T. Yokozawa, J. Agric. Food Chem. 55 (2007) 8491–8497.
[92] K.S. Kang, H.Y. Kim, N. Yamabe, R. Nagai, T. Yokozawa, Biol. Pharm. Bull. 29 (2006) 1678–1684.

Rhodiola rosea Root

Scientific Name:
Rhodiola rosea

RHODIOLA ROSEA COMMON NAME

Golden Root | Arctic Root | Roseroot

TOP BENEFITS OF RHODIOLA ROSEA

Supports brain health and cognitive performance *
Supports adaptation to stress *
Supports mood °

WHAT IS RHODIOLA ROSEA?

Rhodiola rosea is an adaptogenic herb with a long history of folk use in Russia, Scandinavia, Baltic countries, and Asia. Its traditional uses included being a tonic to help counter fatigue and enhance the capacity for mental and physical work performance. R. rosea grows in cold regions and in mountainous parts of Europe through Central Asia. This ability to adapt to extreme temperatures and environments may be part of the reason R. rosea was studied (and eventually categorized as an adaptogen) by Russian researchers. Decades of research support this adaptogenic categorization, with R. rosea supporting resistance to a variety of different types of stressors. R. rosea contains many biologically active substances; Its rosavins (rosavin, rosin, and rosarian) and salidroside are the major bioactive compounds for producing standardized extracts. Rhodiola rosea main uses are in helping with adaptation to physically and mentally fatiguing circumstances and supporting energy, alertness, concentration, mental stamina, and mood.

NEUROHACKER’S RHODIOLA ROSEA SOURCING

Rhodiola rosea is an extract made from the plant's roots and uses about a 50:1 herb to extract ratio.  
Rhodiola rosea root extract is standardized to contain not less than 3% rosavins and 1% salidroside.
Rhodiola rosea root extract is non-GMO and vegan.

RHODIOLA ROSEA DOSING PRINCIPLES AND RATIONALE

We consider Rhodiola rosea to be an herbal adaptogen, so expect it to follow hormetic dosing principles. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response (see Neurohacker Dosing Principles) and don’t follow “more is better” dosing principles. This is consistent with the comparative dosing information on R. rosea root, where for example, a dose of 370 mg supported capacity for mental work, while a higher dose had similar (but not greater) benefits [1]. Standardized R. rosea root extracts have most commonly been used in human studies at doses ranging from 100 mg to 400 mg/day—in the nootropic community a dose between 150-300 mg a day is commonly used. We use a dose within this range.

KEY MECHANISMS

Brain and cognitive function
Supports attention, capacity for mental work, and resistance to mental fatigue [1–6]
Supports mental and physical performance during stress [1–4]
Supports a healthy mood [7–9]
Supports serotonin levels [10]
Supports neuroplasticity and neurogenesis [11,12]
Supports neuroprotective functions [13–18]
Supports healthy levels of stress hormones and other stress response mediators [2,19–22]
Supports β-endorphin signaling [22,23]
Influences monoamine oxidase (MAO) A and B [24,25]
Influences acetylcholinesterase [13,25]

Physical stamina
Supports resistance to physical fatigue [3]
Supports endurance performance [26]
Supports exercise-induced antioxidant defenses [27]
 
Healthy aging
Supports mitochondrial function [17,28,29]
Supports antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX], glutathione reductase [GR]) [13,15,27,30]
Supports glutathione and thioredoxin levels [15,17]
Extends lifespan (Drosophila melanogaster and Caenorhabditis elegans) [31–33]

Synergies
Ginkgo biloba for cognitive function [34]
Saffron for mood support [35]


REFERENCES

[1]V.A. Shevtsov, B.I. Zholus, V.I. Shervarly, V.B. Vol’skij, Y.P. Korovin, M.P. Khristich, N.A. Roslyakova, G. Wikman, Phytomedicine 10 (2003) 95–105.
[2]E.M. Olsson, B. von Schéele, A.G. Panossian, Planta Med. 75 (2009) 105–112.
[3]A.A. Spasov, G.K. Wikman, V.B. Mandrikov, I.A. Mironova, V.V. Neumoin, Phytomedicine 7 (2000) 85–89.
[4]V. Darbinyan, A. Kteyan, A. Panossian, E. Gabrielian, G. Wikman, H. Wagner, Phytomedicine 7 (2000) 365–371.
[5]D. Edwards, A. Heufelder, A. Zimmermann, Phytother. Res. 26 (2012) 1220–1225.
[6]T. Koop, A. Dienel, M. Heldmann, T.F. Münte, Phytother. Res. 34 (2020) 3287–3297.
[7]M. Cropley, A.P. Banks, J. Boyle, Phytother. Res. 29 (2015) 1934–1939.
[8]A. Bystritsky, L. Kerwin, J.D. Feusner, J. Altern. Complement. Med. 14 (2008) 175–180.
[9]V. Darbinyan, G. Aslanyan, E. Amroyan, E. Gabrielyan, C. Malmström, A. Panossian, Nord. J. Psychiatry 61 (2007) 343–348.
[10]C. Mannucci, M. Navarra, E. Calzavara, A.P. Caputi, G. Calapai, Phytomedicine 19 (2012) 1117–1124.
[11]Q.G. Chen, Y.S. Zeng, Z.Q. Qu, J.Y. Tang, Y.J. Qin, P. Chung, R. Wong, U. Hägg, Phytomedicine 16 (2009) 830–838.
[12]C. Concerto, C. Infortuna, M.R.A. Muscatello, A. Bruno, R. Zoccali, E. Chusid, E. Aguglia, F. Battaglia, Complement. Ther. Med. 41 (2018) 141–146.
[13]J. Zhang, Y.-F. Zhen, Pu-Bu-Ci-Ren, L.-G. Song, W.-N. Kong, T.-M. Shao, X. Li, X.-Q. Chai, Behav. Brain Res. 244 (2013) 70–81.
[14]Z.-Q. Qu, Y. Zhou, Y.-S. Zeng, Y.-K. Lin, Y. Li, Z.-Q. Zhong, W.Y. Chan, PLoS One 7 (2012) e29641.
[15]Z.-Q. Qu, Y. Zhou, Y.-S. Zeng, Y. Li, P. Chung, Biomed. Environ. Sci. 22 (2009) 318–326.
[16]S.I. Jang, H.O. Pae, B.M. Choi, G.S. Oh, S. Jeong, H.J. Lee, H.Y. Kim, K.J. Kang, Y.G. Yun, Y.C. Kim, H.T. Chung, Immunopharmacol. Immunotoxicol. 25 (2003) 295–304.
[17]L. Zhang, H. Yu, X. Zhao, X. Lin, C. Tan, G. Cao, Z. Wang, Neurochem. Int. 57 (2010) 547–555.
[18]D.R. Palumbo, F. Occhiuto, F. Spadaro, C. Circosta, Phytother. Res. 26 (2012) 878–883.
[19]A. Panossian, M. Hambardzumyan, A. Hovhanissyan, G. Wikman, Drug Target Insights 2 (2007) 39–54.
[20]A. Panossian, G. Wikman, P. Kaur, A. Asea, Front. Neurosci. 6 (2012) 6.
[21]A. Panossian, G. Wikman, Pharmaceuticals 3 (2010) 188–224.
[22]I.B. Lishmanov, Z.V. Trifonova, A.N. Tsibin, L.V. Maslova, L.A. Dement’eva, Biull. Eksp. Biol. Med. 103 (1987) 422–424.
[23]G.S. Kelly, Altern. Med. Rev. 6 (2001) 293–302.
[24]D. van Diermen, A. Marston, J. Bravo, M. Reist, P.-A. Carrupt, K. Hostettmann, J. Ethnopharmacol. 122 (2009) 397–401.
[25]D. van Diermen, A. Marston, J. Bravo, M. Reist, P.A. Carrupt, K. Hostettmann, Planta Med. 74 (2008) PA202.
[26]K. De Bock, B.O. Eijnde, M. Ramaekers, P. Hespel, Int. J. Sport Nutr. Exerc. Metab. 14 (2004) 298–307.
[27]J. Xu, Y. Li, Mol. Med. Rep. 6 (2012) 1195–1198.
[28]S. Yu, M. Liu, X. Gu, F. Ding, Cell. Mol. Neurobiol. 28 (2008) 1067–1078.
[29]H. Zhong, H. Xin, L.-X. Wu, Y.-Z. Zhu, J. Pharmacol. Sci. 114 (2010) 399–408.
[30]Y. Zhu, Y.-P. Shi, D. Wu, Y.-J. Ji, X. Wang, H.-L. Chen, S.-S. Wu, D.-J. Huang, W. Jiang, DNA Cell Biol. 30 (2011) 809–819.
[31]S.E. Schriner, A. Abrahamyan, A. Avanessian, I. Bussel, S. Maler, M. Gazarian, M.A. Holmbeck, M. Jafari, Free Radic. Res. 43 (2009) 836–843.
[32]M. Jafari, J.S. Felgner, I.I. Bussel, T. Hutchili, B. Khodayari, M.R. Rose, C. Vince-Cruz, L.D. Mueller, Rejuvenation Res. 10 (2007) 587–602.
[33]F.A.C. Wiegant, S. Surinova, E. Ytsma, M. Langelaar-Makkinje, G. Wikman, J.A. Post, Biogerontology 10 (2009) 27–42.
[34]H.M. Al-Kuraishy, J Intercult Ethnopharmacol 5 (2016) 7–13.
[35]M. Bangratz, S.A. Abdellah, A. Berlin, C. Blondeau, A. Guilbot, M. Dubourdeaux, P. Lemoine, Neuropsychiatr. Dis. Treat. 14 (2018) 1821.

KSM-66 Ashwagandha®​ (​Withania somnifera​) Root Extract

WITHANIA SOMNIFERA COMMON NAME

Ashwagandha | Indian ginseng

TOP BENEFITS OF WITHANIA SOMNIFERA

Supports sleep*
Supports stress relief*
Supports memory and cognition*
Supports muscle strength and endurance*
Supports sexual health*
Supports a healthy body weight*
Supports thyroid health*

WHAT IS WITHANIA SOMNIFERA

Withania somnifera is commonly called ashwagandha. Ashwagandha (i.e., Indian ginseng) is a Rasayana—the category of elixirs and tonic herbs prized by the branch of Ayurvedic medicine concerned with rejuvenation and focused on promoting a youthful state of physical and mental health. Ashwagandha holds a prominent place among the Rasayana herbs, where it was used for many reasons including as general tonic and to infuse energy and vigor in circumstances characterized by exhaustion or a lack of physical energy. A key attribute is that ashwagandha promotes balance. As the English name Indian ginseng implies, ashwagandha was believed to share some of the attributes of ginseng, in essence supporting multiple areas of health and well-being, especially under conditions characterized by increased stress. Herbs that produce these types of nonspecific resistance to and recovery from stress—and which typically also support general well-being, healthy energy, and homeostasis—are called adaptogens. Among its studied benefits, ashwagandha supports sleep quality, relaxation, muscle recovery, cognitive function, immunity and a healthier stress response.

NEUROHACKER’S WITHANIA SOMNIFERA SOURCING

KSM-66 Ashwagandha® was the product of 14 years of R&D. It is the most researched brand of ashwagandha, with a research focus on what happens in healthy people when they take the ingredient.

Created by Ixoreal Biomed Inc., the world's ashwagandha experts. Ixoreal owns the entire production chain from farm to the finished ingredient, allowing them to deliver high-quality ashwagandha with batch-to-batch consistency.

KSM-66 Ashwagandha® is a “full-spectrum” root extract, which means it is designed to maintain the balance of the various constituents found in the root. It is standardized for ≥5% withanolides and <0.1% withaferin A.

KSM-66 Ashwagandha® has won awards as an innovative ingredient and for sports nutrition. It has also qualified for an extensive number of certifications including Organic, Non-GMO, GRAS, Vegan and Gluten-Free.

KSM-66 Ashwagandha® is a registered trademark of Ixoreal Biomed Inc.

WITHANIA SOMNIFERA DOSING PRINCIPLES AND RATIONALE

We consider Withania somnifera (i.e., ashwagandha) to be an herbal adaptogen, so expect it to follow hormetic dosing principles. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. Based on studies where different doses have been given in the same study, we also consider ashwagandha dosing to be somewhat akin to the Pareto Principle (i.e., 80-20 rule), because much of the benefits have occurred at a lower dose, and relatively modest additional gains are achieved at doses two- to four-fold higher (see Neurohacker Dosing Principles). Because of both of these reasons, it’s important to identify the lowest dose that can produce many of the desired responses when using ashwagandha. Since we also use ashwagandha in more than one product, it’s also important to us to ensure that a user taking several of our products will not inadvertently take too much ashwagandha. The most common dose of KSM-66 Ashwagandha® in human studies has been 300 mg taken twice a day (i.e., 600 mg a day total). We consider this to be the upper end of the total amount of daily ashwagandha that we’d want a customer to take over a long period of time, and 300 mg to be the maximum at a given time of day (i.e., if being taken at dinner as an example). We consider the lower end of the beneficial range to be about 125-150 mg depending on the ashwagandha extract being used.

WITHANIA SOMNIFERA KEY MECHANISMS

Sleep

Supports sleep onset[1,2]

Supports sleep efficiency[1]

Supports quality of sleep[1,3]

Supports slow-wave sleep[2]

Supports total sleep time[2]

Mood and stress

Supports a calm mood[1,4]

Supports stress management[5–7]

Supports health cortisol levels[5–7]

Brain function

Supports cognitive and psychomotor performance[8,9]

Supports memory, executive function, attention, and information processing speed[10]

Supports GABAergic neurotransmission[2,11]

Supports GABA receptor signaling[12–14]

Supports dopamine levels[15]

Downregulates the basal activity levels of acetylcholine esterase[15]

Supports neuroprotection – protects from neuronal mitochondrial swelling and apoptosis; protects cognitive function (ischemia, oxidative stress)[16]
Protects from neurotoxicity[15,17]

Immune system

Supports innate immunity[18–22]

Supports adaptive immunity[18,19,22–31]

Supports immune system communication[22,32–34]

Mitochondrial function

Supports mitochondrial membrane potential and structural integrity[16]

Protects from mitochondrial damage[16]

Protects from mitochondrial membrane permeabilization[35]

Protects from complex I-V Inhibition (protects electron transport chain and oxidative phosphorylation performance)[15–17,36]

Supports citric acid cycle enzymes[36]

Exercise and sports

Supports endurance performance[37,38]

Supports muscle strength[39,40]

Supports post-exercise recovery[40]

Metabolic function

Supports healthy insulin sensitivity[4,41–44]

Supports healthy blood glucose levels[41–45]

Supports healthy leptin signaling[4,44]

Supports healthy body weight[4,44]

Supports healthy feeding behaviors[4,5]

Supports lean mass[40]

Antioxidant defenses

Supports antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT],glutathione peroxidase [GPx])[15–17,45,46]

Replenishes glutathione (GSH) levels[15,16,45]

Counters oxidative stress and reactive oxygen species levels[15,16,35,47]

Cellular signaling

Downregulates the expression of some cytokines including tumor necrosis factor alpha(TNFα), interleukin 1 beta (IL-1β), and IL-6[4,41,42]

Thyroid function

Supports thyroid function[48–50]

Healthy aging and longevity

Lifespan extension effects (Caenorhabditis elegans)[47,51]

Upregulates insulin-like growth factor-1 (IGF-1) signaling pathway[47,51]

Downregulates α-synuclein and amyloid-β aggregation[47]

Upregulates FOXO3A and SIRT3[52]

REFRENCES

[1]  D. Langade, S. Kanchi, J. Salve, K. Debnath, D. Ambegaokar, Cureus 11 (2019)e5797.
[2]  A. Kumar, H. Kalonia, Indian J. Pharm. Sci. 70 (2008) 806–810.
[3]  A.A. Raut, N.N. Rege, F.M. Tadvi, P.V. Solanki, K.R. Kene, S.G. Shirolkar, S.N. Pandey, R.A. Vaidya, A.B. Vaidya, J. Ayurveda Integr. Med. 3 (2012) 111–114.
[4]  T. Kaur, G. Kaur, J. Neuroinflammation 14 (2017) 201.
[5]  D. Choudhary, S. Bhattacharyya, K. Joshi, J. Evid. Based Complementary Altern. Med. 22 (2017) 96–106.
[6]  K. Chandrasekhar, J. Kapoor, S. Anishetty, Indian J. Psychol. Med. 34 (2012)255–262.
[7]  B. Auddy, J. Hazra, A. Mitra, B. Abedon, S. Ghosal, Journal of AmericanNutraceutical Association 11 (2008) 50–56.
[8]  U. Pingali, R. Pilli, N. Fatima, Pharmacognosy Res. 6 (2014) 12–18.
[9]  K.N.R. Chengappa, C.R. Bowie, P.J. Schlicht, D. Fleet, J.S. Brar, R. Jindal, J. Clin. Psychiatry 74 (2013) 1076–1083.
[10]  D. Choudhary, S. Bhattacharyya, S. Bose, J. Diet. Suppl. 14 (2017) 599–612.
[11]  M. Candelario, E. Cuellar, J.M. Reyes-Ruiz, N. Darabedian, Z. Feimeng, R. Miledi, A. Russo-Neustadt, A. Limon, J. Ethnopharmacol. 171 (2015) 264–272.
[12]  A.K. Mehta, P. Binkley, S.S. Gandhi, M.K. Ticku, Indian J. Med. Res. 94 (1991) 312–315.
[13]  J.P. Bhattarai, S.A. Park, S.K. Han, Phytotherapy Research (2009).
[14]  H. Yin, D.H. Cho, S.J. Park, S.K. Han, The American Journal of Chinese Medicine 41 (2013) 1043–1051.
[15]  M.J. Manjunath, Muralidhara, J. Food Sci. Technol. 52 (2015) 1971–1981.
[16]  A. Sood, A. Mehrotra, D.K. Dhawan, R. Sandhir, Metab. Brain Dis. 33 (2018) 1261–1274.
[17]  P. Kumar, A. Kumar, J. Med. Food 12 (2009) 591–600.
[18]  L. Davis, G. Kuttan, J. Exp. Clin. Cancer Res. 21 (2002) 585–590.
[19]  J. Mikolai, A. Erlandsen, A. Murison, K.A. Brown, W.L. Gregory, P. Raman-Caplan, H.L. Zwickey, J. Altern. Complement. Med. 15 (2009) 423–430.
[20]  J. Bhat, A. Damle, P.P. Vaishnav, R. Albers, M. Joshi, G. Banerjee, Phytother. Res. 24 (2010) 129–135.
[21]  A. Barua, M.J. Bradaric, P. Bitterman, J.S. Abramowicz, S. Sharma, S. Basu, H. Lopez, J.M. Bahr, Am. J. Reprod. Immunol. 70 (2013) 538–550.
[22]  F. Malik, A. Kumar, S. Bhushan, D.M. Mondhe, H.C. Pal, R. Sharma, A. Khajuria, S. Singh, G. Singh, A.K. Saxena, K.A. Suri, G.N. Qazi, J. Singh, Eur. J. Cancer 45 (2009) 1494–1509.
[23]  L. Davis, G. Kuttan, J. Ethnopharmacol. 71 (2000) 193–200.
[24]  M. Gautam, S.S. Diwanay, S. Gairola, Y.S. Shinde, S.S. Jadhav, B.K. Patwardhan, Int. Immunopharmacol. 4 (2004) 841–849.
[25]  S. Bani, M. Gautam, F.A. Sheikh, B. Khan, N.K. Satti, K.A. Suri, G.N. Qazi, B. Patwardhan, J. Ethnopharmacol. 107 (2006) 107–115.
[26]  F. Malik, J. Singh, A. Khajuria, K.A. Suri, N.K. Satti, S. Singh, M.K. Kaul, A. Kumar, A. Bhatia, G.N. Qazi, Life Sci. 80 (2007) 1525–1538.
[27]  G. Muralikrishnan, A.K. Dinda, F. Shakeel, Immunol. Invest. 39 (2010) 688–698.
[28]  K. Yamada, P. Hung, T.K. Park, P.J. Park, B.O. Lim, J. Ethnopharmacol. 137 (2011) 231–235.
[29]  S.K. Latheef, K. Dhama, H.A. Samad, M.Y. Wani, M.A. Kumar, M. Palanivelu, Y.S. Malik, S.D. Singh, R. Singh, Virusdisease 28 (2017) 115–120.
[30]  S.P. Maurya, B.K. Das, R. Singh, S. Tyagi, Clin. Immunol. 203 (2019) 122–124.
[31]  R. Kumar, J. Rai, N.C. Kajal, P. Devi, Indian J. Tuberc. 65 (2018) 246–251.
[32]  B. Khan, S.F. Ahmad, S. Bani, A. Kaul, K.A. Suri, N.K. Satti, M. Athar, G.N. Qazi, Int. Immunopharmacol. 6 (2006) 1394–1403.
[33]  C.D.P. Tripathi, P.K. Kushawaha, R.S. Sangwan, C. Mandal, S.Misra-Bhattacharya, A. Dube, Phytomedicine 24 (2017) 87–95.
[34]  T. Kaur, H. Singh, R. Mishra, S. Manchanda, M. Gupta, V. Saini, A. Sharma, G.Kaur, Mol. Cell. Biochem. 427 (2017) 91–101.
[35]  P. Parihar, R. Shetty, P. Ghafourifar, M.S. Parihar, Cell. Mol. Biol. 62 (2016) 73–83.
[36]  P. Senthilnathan, R. Padmavathi, V. Magesh, D. Sakthisekaran, Life Sci. 78 (2006) 1010–1014.
[37]  J.S. Sandhu, B. Shah, S. Shenoy, S. Chauhan, G.S. Lavekar, M.M. Padhi, Int. J. Ayurveda Res. 1 (2010) 144–149.
[38]  B. Choudhary, A. Shetty, D.G. Langade, Ayu 36 (2015) 63–68.
[39]  A.A. Raut, N.N. Rege, F.M. Tadvi, P.V. Solanki, K.R. Kene, S.G. Shirolkar, S.N. Pandey, R.A. Vaidya, A.B. Vaidya, J. Ayurveda Integr. Med. 3 (2012) 111–114.
[40]  S. Wankhede, D. Langade, K. Joshi, S.R. Sinha, S. Bhattacharyya, J. Int. Soc. Sports Nutr. 12 (2015) 43.
[41]  M.R. Shahraki, Z. Samadi Noshahr, H. Ahmadvand, A. Nakhaie, J. Basic Clin. Physiol. Pharmacol. 27 (2016) 387–391.
[42]  Z. Samadi Noshahr, M.R. Shahraki, H. Ahmadvand, D. Nourabadi, A. Nakhaei, Rep Biochem Mol Biol 3 (2015) 62–67.
[43]  T. Anwer, M. Sharma, K.K. Pillai, M. Iqbal, Basic Clin. Pharmacol. Toxicol. 102 (2008) 498–503.
[44]  J. Lee, J. Liu, X. Feng, M.A. Salazar Hernández, P. Mucka, D. Ibi, J.W. Choi, U. Ozcan, Nat. Med. 22 (2016) 1023–1032.
[45]  T. Anwer, M. Sharma, K.K. Pillai, G. Khan, Acta Pol. Pharm. 69 (2012) 1095–1101.
[46]  S.K. Gupta, A. Dua, B.P.S. Vohra, Drug Metabol. Drug Interact. 19 (2003) 211–222.
[47]  B.A. Akhoon, S. Pandey, S. Tiwari, R. Pandey, Exp. Gerontol. 78 (2016) 47–56.
[48]  A.K. Sharma, I. Basu, S. Singh, J. Altern. Complement. Med. 24 (2018) 243–248.
[49]  J.M. Gannon, P.E. Forrest, K.N. Roy Chengappa, J. Ayurveda Integr. Med. 5 (2014) 241–245.
[50]  R. Jatwa, A. Kar, Phytother. Res. 23 (2009) 1140–1145.
[51]  B.A. Akhoon, L. Rathor, R. Pandey, Exp. Gerontol. 104 (2018) 113–117.
[52]  R. Pradhan, R. Kumar, S. Shekhar, N. Rai, A. Ambashtha, J. Banerjee, M. Pathak, S.N. Dwivedi, S. Dey, A.B. Dey, Exp. Gerontol. 95 (2017) 9–15.

Lion’s Mane

Scientific Name:
Hericium erinaceus

Overview:
Lion’s Mane is a mushroom with neuroprotective and nootropic effects. Lion’s Mane can improve memory and reasoning.

Scientific Name:
Hericium erinaceus

Mechanisms:

  • Increases NGF levels in the brain – enhanced neuronal growth, regeneration and synaptic plasticity[1]
  • Improves myelination – enhanced neuronal communication and nerve regeneration[2]
  • Increases long-term synaptic potentiation – improved memory[3,4]
  • Decreases glutamatergic transmission – decreased neuronal excitability and excitotoxicity[3,4]
  • Protects neurons from endoplasmic reticulum stress[3,4]
  • Anxiolytic[5]
  • Anti-inflammatory effects[6]
REFERENCES

[1] Lai PL, et al (2013). Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int J Med Mushrooms, 15(6):539-54. doi: 10.1615/IntJMedMushr.v15.i6.30
[2] Kolotushkina EV, et al (2003). The influence of Hericium erinaceus extract on myelination process in vitro. Fiziol Zh, 49(1):38-45. PMID: 12675022
[3] Phan CW, et al (2015). Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol, 35(3):355-68. doi: 10.3109/07388551.2014.887649
[4] Sabaratnam V, et al (2013). Neuronal health – can culinary and medicinal mushrooms help? J Tradit Complement Med, 3(1):62-8. doi: 10.4103/2225-4110.106549
[5] Nagano M, et al (2010). Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res, 31(4):231-7. doi: 10.2220/biomedres.31.231
[6] Geng Y, et al (2014). Anti-inflammatory activity of mycelial extracts from medicinal mushrooms. Int J Med Mushrooms, 16(4):319-25. doi: 
10.1615/IntJMedMushrooms.v16.i4.20

LJ100® Eurycoma longifolia Root Extract

COMMON NAME

Tongkat Ali | Malaysian Ginseng | Longjack

TOP BENEFITS OF EURYCOMA LONGIFOLIA ROOT EXTRACT

  • Supports general immune health*
  • Supports mood and stress* 
  • Supports men’s health*
  • Supports muscle performance*

WHAT IS EURYCOMA LONGIFOLIA ROOT EXTRACT?

Eurycoma longifolia grows in rainforests throughout Southeast Asian. Its common name is Tongkat Ali (translates as Ali’s walking stick), which refers to its use as a tonic for male virility. It’s sometimes called “Malaysian ginseng,” because similar to ginseng, it’s regarded as an adaptogen that supports resistance to and recovery from stress of all types. The roots are used for many purposes that fit within the adaptogen category including supporting mood, overcoming fatigue, enhancing exercise, and promoting vigor with aging. E. longifolia can also be considered as an immune adaptogen, enhancing overall immunological vigor of the adaptive immune system. E. longifolia contains several bioactive compounds including quassinoids (e.g., eurycolactone, eurycomalactone, eurycomanol, eurycomanone, and eurycomaoside), alkaloids, flavonoids, triterpenes, and glycoproteins[1,2]

NEUROHACKER’S EURYCOMA LONGIFOLIA ROOT EXTRACT SOURCING

LJ100® is backed by strong science; it is the most extensively studied Eurycoma longifolia root extract and has been used in a dozen human clinical studies. 

LJ100® is produced using a patented extraction technology to create an extract standardized to 40% glyco saponins, >22% eurypeptide, and  0.8-2% eurycomanone.

LJ100® is made from wild-crafted Tongkat Ali root from the rainforests of Malaysia utilizing sustainable harvesting and fair-trade practices. 

LJ100® is GRAS, Kosher & Halal certified, non-allergenic, non-GMO, gluten-free and organic compliant.

LJ100® is the registered trademark of HP Ingredients Corp. LJ100® is the result of an innovative collaboration between MIT and the Government of Malaysia.

EURYCOMA LONGIFOLIA ROOT EXTRACT DOSING PRINCIPLES AND RATIONALE

Because Eurycoma longifolia is an adaptogen, we consider dosing to follow hormetic principles (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone. In human studies, LJ100®, a standardized Eurycoma longifolia root extract, has been given in doses ranging from 50 to 400 mg—the most common doses have been 100-200mg. Our dosage of LJ100® will be within the most commonly studied dosage range and is consistent with the dose recommended by the supplier.

EURYCOMA LONGIFOLIA ROOT EXTRACT KEY MECHANISMS

Immune function

  • Supports immunological vigor[3]
  • Supports adaptive immunity[3,4]
  • Supports T cell function[3]
  • Supports immune signaling[5–7]

Mood and stress

  • Supports vitality, emotional well-being, and social functioning[4,8]
  • Supports stress management[4,8]
  • Supports healthy behavioral and cognitive responses to stress[9]

Exercise

  • Supports muscle strength and power[10–13]
  • Supports peak power output[11]

Hormone function

  • Supports healthy testosterone levels[8,14–16]
  • Sex healthy sex hormone-binding globulin (SHBG) levels[16]
  • Supports healthy cortisol and DHEA stress hormone levels[8,16]

Men’s health

  • Supports sperm quality[17,18]
  • Supports erectile function[18]
  • Supports libido[18]

Synergies

  • Polygonum minus for supporting men’s health[19]

REFERENCES

[1] S.U. Rehman, K. Choe, H.H. Yoo, Molecules 21 (2016) 331.
[2] R. Bhat, A.A. Karim, Fitoterapia 81 (2010) 669–679.
[3] A. George, N. Suzuki, A.B. Abas, K. Mohri, M. Utsuyama, K. Hirokawa, T. Takara, Phytother. Res. 30 (2016) 627–635.
[4] A. George, J. Udani, N.Z. Abidin, A. Yusof, Food Nutr. Res. 62 (2018).
[5] Y.M. Han, S.-U. Woo, M.S. Choi, Y.N. Park, S.H. Kim, H. Yim, H.H. Yoo, Arch. Pharm. Res. 39 (2016) 421–428.
[6] T.V.A. Tran, C. Malainer, S. Schwaiger, A.G. Atanasov, E.H. Heiss, V.M. Dirsch, H. Stuppner, J. Nat. Prod. 77 (2014) 483–488.
[7] J. Ruan, Z. Li, Y. Zhang, Y. Chen, M. Liu, L. Han, Y. Zhang, T. Wang, Molecules 24 (2019).
[8] S.M. Talbott, J.A. Talbott, A. George, M. Pugh, J. Int. Soc. Sports Nutr. 10 (2013) 28.
[9] H.H. Ang, H.S. Cheang, Jpn. J. Pharmacol. 79 (1999) 497–500.
[10] R.R. Henkel, R. Wang, S.H. Bassett, T. Chen, N. Liu, Y. Zhu, M.I. Tambi, Phytother. Res. 28 (2014) 544–550.
[11] C. Chen, F. Ooi, N.A. Kasim, M. Asari, International Journal of Preventive Medicine 10 (2019) 118.
[12] F.K. Ooi, H.A. Mohamed, C.K. Chen, M.A. Asari, IJERSS 2 (2015) 1–10.
[13] S. Hamzah, A. Yusof, Br. J. Sports Med. 37 (2003) 464–470.
[14] M.I.B.M. Tambi, M.K. Imran, R.R. Henkel, Andrologia 44 Suppl 1 (2012) 226–230.
[15] R.R. Henkel, R. Wang, S.H. Bassett, T. Chen, N. Liu, Y. Zhu, M.I. Tambi, Phytother. Res. 28 (2014) 544–550.
[16] M.I.M. Tambi, J.M. Saad, in: First Asian Andrology Forum In Shanghai China, 2002.
[17] M. Tambi, M.K. Imran, Asian J. Androl. (2010).
[18] S.B. Ismail, W.M.Z. Wan Mohammad, A. George, N.H. Nik Hussain, Z.M. Musthapa Kamal, E. Liske, Evid. Based. Complement. Alternat. Med. 2012 (2012) 429268.
[19] J.K. Udani, A.A. George, M. Musthapa, M.N. Pakdaman, A. Abas, Evidence-Based Complementary and Alternative Medicine 2014 (2014) 1–10.