adaptogen Whitepaper...may also impact metabolic regulators including hormones, neuropeptides, nitric oxide, cytokines, etc. that influence body’s ability to respond and re-balance.(2)

adaptogen WhitepaperBuilding a Balanced Body with Natreon’s Adaptogens

WHITE PAPER SERIES #2May 2020 | natreoninc.com

Stress Response without Adaptogen Stress Response with Adaptogen

Res

po

nse

Time

These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. 2

What is an adaptogen?Adaptogens are a unique class of botanicals that may help balance and restore the body. The term adaptogen originated in the 1960’s. The classic definition provided for adaptogens is that they have a non-specific action that increases the body’s natural resistance to stressors.(1) This is a vague description and recently, herbalists developed a new definition to encompass the therapeutic benefits of adaptogenic actives.

The new definition is a nontoxic substance and especially a natural or plant extract that is held to increase the body’s ability to resist the damaging effects of stress and promote or restore normal physiological functioning. (Figure 1) An easy way to describe an adaptogen is: a natural substance that helps the body “adapt” to stress. Adaptogenic properties are expected to support, balance and restore the body from physical, mental and emotional stressors. In addition to supporting a healthy stress response, adaptogens are consumed for a variety of health benefits including increased energy, vitality, healthy digestion and to support a healthy immune response.

ADAPTOGENA natural substance that helps the body “adapt” to stress.

Figure 1Typical stress response compared to an adaptogenic stress response.

Adaptogen

Sleep

HypothalamicPituitary

Adrenal

HPA-axis

Neuroendocrine System

Homeostasis & Allostasis

Environmental Stress

External Stress

Immune System Support


In healthy persons, the body responds to both internal and external stressors through the hypothaliamic-pituitary-adrenal axis (HPA). The HPA is a complex feedback network of neurochemicals and hormones that are part of the neuroendocrine system that controls the body’s reaction to stress, helps regulate digestion, mood and emotions, energy and the immune system. When responding to internal or external stressors, the HPA helps reset and re-balance the body.

Unfortunately, with modern stressors, many find themselves out of balance and in need of additional support to restore balance. Adaptogens have been shown to reduce the intensity and impact of stressors.(2) Adaptogens influence the central nervous system, immune functions, and may also impact metabolic regulators including hormones, neuropeptides, nitric oxide, cytokines, etc. that influence body’s ability to respond and re-balance.(2)

Figure 2Adaptogens reducing impact of stress.

Today, the term adaptogen is being used more frequently and to promote, market and recommend specific herbs but beyond the definition, what actually qualifies a natural plant or extract to be in this category? Is it defined as an adaptogen based on what it does in the body? Are the natural products being used within their therapeutic context?

Natreon, Inc. is consulting with experts to help define the adaptogen market and to ensure their clinically studied adaptogens are being utilized in a truly holistic practice of Ayurveda, starting with how the whole plant affects the whole person. Both Traditional Chinese Medicine and Traditional Ayurveda have used plants and herbs for thousands of years to improve human health. Traditionally, the whole plant or multiple parts of the plant, including leaves, roots and/or seeds, were utilized.


This history of adaptogen use provides an enormous amount of information and when harnessed safely, it is a powerful guide to the traditional adaptogen usage dose and form. When used within the traditional form, adaptogens support increased energy, vitality and relaxation. Natreon, Inc. is committed to harnessing the power of the whole plant and invest in rigorous clinical studies to continue to learn the mechanisms of action for each adaptogen and ensure the benefits are within the relevant therapeutic context of the herb.

Adaptogens provide a variety of functional benefits to support the body’s natural homeostasis. Adaptogens can provide “warming” or “cooling” effects, support digestion and offer “energizing” benefits depending on what the body needs. For example, the popular adaptogen Ashwagandha may provide “warming” properties to an individual and/or “energizing” properties to a different individual depending on the current conditions of the body (Figure 3). American ginseng is another adaptogen with multiple properties including “energizing”, “cooling” and “refreshing” depending on the needs of the body.

Natreon has developed a portfolio of standardized, clinically studied adaptogens: 1. Sensoril® Ashwagandha: reduce everyday stress & cortisol, improve sleep, energy & well-being. 2. PrimaVie® Shilajit: growth, development and maintenance of muscles, bones and skin. 3. Capros® Amla: potent antioxidant for immune and heart health.

Together these adaptogens by Natreon have been clinically studied in over 25 clinical trials resulting in a range of health benefits that support restoring and rebalancing the body. Natreon is committed to advancing the study of adaptogens and their health benefits.

Figure 3Adaptogen Classification

Commonly known as Indian Ginseng or Winter Cherry.Withania somnifera

Warming Soothing Energizing

Adaptogenic Properties

Sensoril® adapts to help the body cope with everyday stress, fatigue,

energy, focus & sleep.

Sensoril® utilizes both the leaves and roots to revitalize

the body & mind.

Ashwagandha is recommended for a variety of reasons because of its adaptogenic properties of “warming”, “soothing” and “energizing.” Ashwagandha has been used in Ayurveda for

thousands of years to promote longevity, enhance vitality, support a healthy immune response, enhance focus and to help reduce everyday stress and fatigue.


Ashwagandha

Placebo 125 mg Sensoril

0

20

40

60

p<0.01 vs

Placebo

Ove

rall

Str

ess

% C

hang

e fr

om

Bas

elin

e

Placebo 500 mg Sensoril

1 RM Squat 1 RM Bench Press0

10

20

30

Cha

nge

in K

g

p<0.01 vs

Placebo

p<0.05 vs

Placebo


Adapt with Sensoril®Recent scientific research utilizing a combination of the leaves and roots of ashwagandha in Natreon,

Inc’s Sensoril® (US 7,318,938, CA 2508478) have shown enhanced focus, helps reduce everyday stress

(Figure 4), increases muscular strength (Figure 5), supports heart health, supports healthy joints and

a healthy immune response.(3-10)

The health benefits have been attributed to an array of bioactive compounds found in the leaves and

roots of ashwagandha, unique only to Sensoril®. Withanolide glycosides found in a variety of plants

have been shown to support a healthy immune response and clinically studied to reduce everyday

stress. Withanolide glycosides have hundreds of metabolites; however, the predominant bioactives

are Withaferin A, Withaferin D and Withanone.(11-14) Withaferin A is one of the most studied

withanolides, supporting heart health, brain health and a healthy immune response.(15-20)

Research has also elucidated that the ashwagandha leaves and roots contain different

concentrations of Withaferin A.(21) Again, a combination of the leaves and roots standardized

to the most bioactive compounds in ashwagandha, ≥ 10% withanolide glycosides and not more

than 0.5% Withaferin A, found in clinically studied Sensoril® prove to provide greater health benefits

than either plant part alone.(3-10) In addition, the oligosaccharides present in Sensoril® at ≥ 32% level,

are believed to enhance bioavailability of withanolide glycosides and Withaferin A. As tradition holds,

combining both ashwagandha leaves and roots provides a holistic extract traditionally used in

Ayurveda and harnesses the power from the whole plant.

Figure 5 Sensoril® increases upper & lower body strength compared to placebo in healthy men.

Figure 4Sensoril® improves everyday stress 62% more than placebo in healthy adults.

Commonly known as mineral resin, wax or pitch.Asphaltum Punjabianum

Shilajit, an extract from Himalayan mountain rock, is another example of an adaptogen with a variety of health benefits. For thousands of years, shilajit has been used in Ayurveda with a key focus to promote male vitality and physical performance. Shilajit is also considered to be one of the most promising energizers or rejuvenators and helps reduce everyday fatigue by

supporting energy production.

Sourced from the Himalayan Mountains.

PrimaVie® helps adapt for energy, endurance and vitality.

Cooling Refreshing Energizing


Shilajit


Placebo

Total Testosterone (ng/mL) Free Testosterone (pg/mL)

500 mg PrimaVie

Cha

nges

in T

esto

ster

one

p<0.05 vs

Placebo

p<0.05 vs

Placebo

Placebo 500 mg PrimaVie

0

5

10

15

Po

st-S

upp

lem

enta

tio

n M

VIC

% D

eclin

e

p<0.05 vs

Placebo

Femur BMD Spine BMD

Placebo 500 mg PrimaVie

-3

0

3

6

% C

hang

e o

f B

one

M

iner

al D

ensi

ty (

gm

/cm

2 )

p<0.0001 vs

Placebo

p<0.0001 vs

Placebo

Adapt with PrimaVie®A standardized extract of shilajit, PrimaVie®, from Natreon Inc. (US 6,869,612), is the most clinically studied shilajit supplement

available. PrimaVie® contains the highest concentrations of bioactives, including ≥10.3% of free plus conjugated urolithin A

and urolithin B, ≥ 50% fulvic acid and with more than 40 naturally occurring microminerals. Fulvic acid has been studied

to have immune-stimulating and potent antioxidant effects.(22-24) Fulvic acid has been shown to sequester and reduce the

production of ROS(25, 26) as well as decrease the release of proinflammatory mediators.(27) Fulvic acid independently protects

mitochondrial membranes from oxidative damage,(28) allowing for healthy mitochondrial function.

Another bioactive found in PrimaVie, urolithin A is a unique

immune booster. Urolithin A is not known to be in any

food source but is the result of the transformation of

ellagic acids and ellagitannins by the gut microflora.(29)

Recent research has shown that urolithins protect the gut

by having antioxidant and antimicrobial effects and may

support a systemic anti-inflammatory response.(30)

The unique combination of actives naturally found in

PrimaVie®, clinically support its adaptogenic properties

in humans. Two human clinical trials show significant

improvements in male vitality and sexual health,

(Figure 6) (31, 32) supporting both healthy aging and

rejuvenation when consuming PrimaVie®. PrimaVie®

has been shown repeatedly to improve energy, fitness

and sports performance. (Figure 7) (33, 34) Recently

completed clinical studies have also shown PrimaVie®

improving skin health and skin permeability and

significantly improving bone mineral density in

healthy aging women. (Figure 8) (35)

The mechanisms of action for these benefits have not

been fully elucidated in clinical studies, PrimaVie® has

shown significant upregulation of collagen and other

extra-cellular matrix protein genes related to the

development, maintenance and growth of skin, skeletal

muscles and bones.(33, 35) These health benefits are unique

to PrimaVie® and the bioactive standardization found only

in PrimaVie®. Natreon Inc. continues to harness the power

of a full spectrum shilajit extract as performed in

Traditional Ayurveda to support and improve human

health within the therapeutic context of its traditional

use as an adaptogen.

Figure 7 PrimaVie® promoted the retention of maximal muscular strength in healthy men.

Figure 8 PrimaVie® increased bone mineral density in healthy aging women compared to placebo.

Figure 6PrimaVie® improves testosterone levels in healthy aging men.


Commonly known as Indian Gooseberry.Phyllanthus emblica

Amla, also known as Indian gooseberry, is an extraordinary yet little known adaptogen. In traditional Ayurveda, amla as an adaptogen supports the body’s natural balance by offering

a “cooling” effect primarily in support of healthy digestion and circulation. Amla has historically been used to promote multiple facets of heart health, including blood flow, healthy cell function

and resistance to oxidative stress.

Capros® is a heart healthy superfruit sourced from amla.

Capros® adapts to the body’s need to support healthy

digestion and energy.

Cooling Digestion Energizing


Amla


Post-Treatment

Placebo 500 mg BID Capros

p<0.001 vs

Placebo-10

0

10

20

Aug

men

tati

on

Ind

ex

% C

hang

e

250 mg BID CaprosPlacebo 500 mg BID Capros

-10

0

10

20

Nit

ric

Oxi

de

(µM

/L)

Figure 9Capros® improves endothelial function in healthy subjects compared to placebo.

Figure 10Capros® increases nitric oxide levels in diabetic subjects compared to placebo.


Polyphenol bioavailability, including tannins,

is typically very low due to limited absorption,

extensive metabolism and rapid excretion.

Capros’® unique aqueous extract preserves

the polyphenols and ensures cardio-pro-

tective benefits. Capros’® benefits to heart

health are supported by 6 clinical studies in

healthy humans and in type 2 diabetics.(36-40)

All cardiovascular clinical studies utilizing

Capros® standardized to tannins unique to

amla show a significant improvement in

endothelial function (Figure 9) and support

a healthy lipid profile.(36-39, 41) Capros® amla

also increases nitric oxide levels, a measure

of healthy blood vessel function (Figure 10)

and decreases C-reactive protein levels, a

marker of inflammation in the blood in

Type 2 Diabetic subjects. (38)

In addition to heart health, Carpos® further

supports the body’s natural balance by

protecting the body against oxidative

stress(42) and supports a healthy immune

response,(38, 41) without being a pro-oxidant.

Adapt with Capros®Natreon Inc. developed Capros®, a multi-patented (US 6,290,996, US 8,962,576, US 6,362,167)

amla extract standardized to hydrolysable tannins, emblicanin A, emblicanin B, punigluconin and

pedunculagin, classified as potent polyphenols. Polyphenols are powerful antioxidants found in a

variety of plant extracts, that have been shown to support cognitive health, digestion, heart health

and a healthy immune response.

Summary


About NatreonNatreon is a leader in nutritional ingredient innovation, quality and research. Trusted by manufacturers for over 20 years, Natreon’s patented ingredients are derived from nature and founded on evidence-based Ayurveda.

Committed to quality, its extracts are purified and standardized using proprietary process technology and controls that result in optimal levels of bioactive constituents. Natreon’s ingredients have been tested in multiple clinical and safety studies to ensure safety, efficacy and authenticity. Natreon brings storied knowledge and expertise in botanical cultivation and extraction, and its ingredients are sustainably sourced through an integrated supply chain to ensure quality and potency. Natreon has its global headquarters in New Jersey and a state-of-the-art R&D facility in Kolkata, India.

For more information, visit: www.natreoninc.com

In summary, adaptogens provide a variety of functional benefits to support the body’s natural homeostasis and to truly provide therapeutic benefits, the whole plant or extract must be evaluated.

Natreon Inc.’s ongoing research both in vitro and human clinical trials will continue to support the proper use, dose and delivery form for adaptogens. Natreon, Inc. is leading the industry in adaptogen research to ensure the ingredients are being utilized in a truly holistic practice of Ayurveda and they are committed to harnessing the power of the whole plant.


References1. Brekhman II & Dardymov IV. 1969. Anna Rev Pharmacol. 9:419-430.2. Ray, A. et al. 2016. J Pharma Reports. 1(2).3. Auddy, B. et al. 2008. J Amer Nutra Assoc. 11(1):50-56.4. Pilli, R. et al. 2016. Int J Basic & Clin Pharma. 5(3):873-8785. Pingali U. et al. 2013. Curr Topics Nutra Res. 11(4):151-158.6. Pingali U. et al. 2014. Pharmacognosy Res. 6:12-18.7. Ramakanth, G. et al. 2016. J Ayurveda Integr Med. 7(3):151–157.8. Usharani, P. et al. 2014. Int J Ayur. Pharma. Res. 2(3):22-23. 9. Usharani2, P et al. 2014. Int. J Pharma. Sci Res. 5(7):2687-2697.10. Ziegenfuss, T. et al. Nutrients. 2018. 10:1807.11. Devi PU. 1996. Indian J Exp Biol. 34: 927-932.12. Kalani A. et al. 2012. BMJ Case Rep 2012.13. Kuboyama T. 2014. Biol Pharm Bull. 37:892-897.14. Sinha P & Ostrand-Rosenberg S. 2013. Cancer Immunol Immunother. 62:1663-1673.15. Grin B. et al. 2012. PLOS ONE 7: e39065. doi:10.1371/journal.pone.0039065.16. Hahm ER. et al. 2011. PLOS ONE 6: e23354. Doi: 10.1371/journal.pone.0023354. 17. Malik F. et al. 2007. Life Sci 80:1525-1538.18. Shah N. et al. 2009. Cancer Sci 100:1740-1747.19. Widodo N. et al. 2007. Clin Cancer Res 13: 2298-2306.20. Yang ES. et al. 2011. Chem Biol Interact 190:9-15.21. Kaul, S. 2016. PLOS ONE: DOI:10.1371/journal.pone.0166945.22. Sharma, P. et al. 2003. Anc Sci Life. 23(2): 114-9.23. Carrasco-Gallardo, C. et al. 2012. Int J Alzheimers Dis. Article ID: 674142.24. Winkler, J. and Ghosh, S. 2018. J Diab Res. Article ID: 5391014.25. Rodriguez, E.C. et al. 2011. J Food, Agri & Enviro. 9: 123–127.26. Visser, S.A. 1987. Sci Total Enviro. 62: 347-354.27. Junek, R. et al. 2009. Phytomed. 16(5): 470-476.28. Ghosal S. Shilajit in Perspective. 2006. Oxford, U.K.: Narosa Publishing House.29. Cerda, B. et al. 2005. J Agri Food Chem. 53(14): 5571-5576.30. Espin, J.C. et al. 2013. Evid-Based Comp Alt Med. Article ID: 270418.31. Pandit, S. et al. 2016. Andrologia. 48: 570-575.32. Biswas, T. et al. 2009. Andrologia. 42:48-56.33. Das, A. et al. 2016. J Med. Food. 19(7): 701-709.34. Keller, J. et al. 2019. J Int Soc Sports Nut. 16(3).35. Das, A. et al. 2019. J Amer Coll Nut. 38(6).36. Fatima, N. et al. 2013. Phcog Res. 6(1):29-35.37. Fatima2, N et al. 2013. Phytomedicine. 21(5):579-585.38. Usharani, P. et al. 2013. Diabetes, Meta Syn, Obesity: Targets and Therapy. 6:1-10.39. Usharani, P. et al. 2017. IJPSR. 8(10):4138-4146.40. Usharani, P. et al. 2019. BMC Comp Alt Med. 19:9741. Khanna, S. et al. 2015. J Med. Food. 18(4):415-420.42. Chaudhuri, R & Puccetti, G. 2002. Cosmetics & Toiletries Magazine. 117(9):43-56.

This whitepaper is intended to provide scientific and educational information only and should not be considered medical advice. Brand manufacturers should consult with their counsel as to whether

claims are properly substantiated and for appropriate structure function claims.

Documents

adaptogen Whitepaper...may also impact metabolic regulators including hormones, neuropeptides, nitric oxide, cytokines, etc. that influence body’s ability to respond and re-balance.(2)