ETAS™ Clinical Evidence


Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry
“Isolation and structure determination of a novel compound to induce HSP70.” Amino Up Chemical sales bulletin: http://www.aminoup.co.jp/e/ 

Topic: 
Does ETAS™, a proprietary extract of Asparagus oficinalis, increase heat shock protein HSP70 in humans?

Background:

Heat shock proteins (HSPs) are intracellular proteins that are induced by various stressors (principally excess heat exposure) and are hypothesized to have anti-stress and anti-aging benefits. They help protect the body’s cellular proteins from heat damage, which would otherwise deform and denature these proteins, rendering them nonfunctional. Heat shock proteins are also stimulated by exercise and calorie restriction interventions, which are known to have life-extension effects in animal studies. In animal studies, an extraction-processed asparagus stem induced HSP70 messenger RNA expression. The extract known as ETAS™ contains compounds known as hydroxymethylfurfural derivatives, one of which is a novel compound capable of inducing HSP70 expression.

Study Type:

Human clinical intervention trial

Study Design:

Placebo-controlled. Researchers divided subjects into two equal groups, a placebo group and a treatment group. Subjects in the treatment group ingested 300 mg of ETAS™50 daily for a week.

Subjects:

14 healthy volunteers

Dosage:

150 mg of ETAS™ daily for a week

Results:

Those ingesting ETAS™ had 3 times the expression of HSP70 mRNA in white blood cells compared with before and after intake.

Conclusion:

ETAS™ increases HSP70 in human subjects. 


Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry
“Isolation and structure determination of a novel compound to induce HSP70.” 2012. Amino Up Chemical sales bulletin with excerpts from Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry:
http://www.aminoup.co.jp/e/ 

Topic: 
Can ETAS™ reduce stress by influencing heart rate variability, a sign of ANS balance?

Background:

Heat shock proteins (HSPs) are intracellular proteins that are induced by various physical stresses, principally excess heat exposure. They are hypothesized to have anti-stress effects. An extraction-processed asparagus stem known as ETASTM (proprietary extract of Asparagus oficinalis) has been found in animal studies to induce HSP70 messenger RNA expression.

Study Type:

Human clinical intervention trial

Study Design:

Researchers divided subjects into two equal groups: a placebo group and a treatment group. The treatment group ingested 400 mg of ETASTM50 daily for 4 weeks. Researchers evaluated ANS condition using a Pulse Analyzer Plus TAS9, which analyzes heart rate variability (HRV) by detecting pulse wave acceleration from a fingertip.

Subjects:

30 healthy volunteers

Dosage:

200 mg/day of ETASTM50 for 4 weeks

Results:

Supplementation with ETASTM50 improved ANS balance. 

Conclusion:

ETAS™50 reduces stress by improving heart rate variability. 


Hokkaido Information University, Ebetsu, Japan
A randomized, double-blind, placebo-controlled crossover clinical study performed at Hokkaido Information University.
Amino Up Chemical unpublished study. 

Topic: 
What is the effect of ETASTM on sleep-related physiological stress parameters?

Background:

Stress related to sleep problems results in increases in biochemical indices such as serum and salivary cortisol and chronographanin A. Will ETASTM50 improve these stress indices?

Study Type:

Human clinical intervention trial

Study Design:

Randomized, double-blind, placebo-controlled crossover study. Volunteers with sleeprelated problems took ETASTM50 or placebo. Researchers measured serum cortisol, salivary cortisol, and chromogranin A, a marker of psychological stress.

Subjects:

16 healthy male volunteers (with sleep-related problems)

Dosage:

150 mg/day of ETASTM50 for a week

Results:

Serum cortisol increased by 45% in the placebo group, whereas in the ETAS™50 group it increased by only 10%. This represents a suppression of the rise in cortisol caused by stress of roughly 80%. Salivary cortisol increased by only 47% in the ETAS™50 group compared with 75% in the control group. A marker of psychological stress known as chromogranin A decreased 2.5 times more in the ETASTM50 group compared with the control group. 

Conclusion:

ETASTM50 improves sleep-related-stress physiological indices. 


Hokkaido Information University, Ebetsu, Japan
A randomized, double-blind, placebo-controlled crossover clinical study performed at Hokkaido Information University. Amino Up Chemical unpublished study. 

Topic: 
What is the effect of ETASTM50 on sleep quality and what is its impact on mental function using the Athens Insomnia Scale?

Background:

The Athens Insomnia Scale (AIS) measures psychological assessments, sleep variables, and quality-of-life variables. The scale utilizes diagnostic criteria set forth by the International Classification of Diseases (ICD-10). A questionnaire evaluates sleep quality and daily functioning.

Study Type:

Human clinical intervention trial

Study Design:

Researchers determined the degree of a sleep disorder based on psychological assessments, sleep variables, and quality-of-life variables. Subjects took ETASTM50 and filled out the AIS survey form. The eight-item questionnaire evaluates sleep onset, night and early-morning waking, sleep time, sleep quality, frequency and duration of complaints, distress caused by the experience of insomnia, and interference with daily functioning.

Subjects:

16 healthy male volunteers (with sleep-related problems)

Dosage:

150 mg of ETASTM50 daily for a week

Results:

The placebo group decreased 0.05 points on early-morning waking in the AIS, compared with a beneficial increase of 0.35 points in the ETASTM50 group, resulting in an average score 0.40 points higher than the placebo group. In the OSA sleep inventory (MA ver.) measure of sleep quality, dreaming frequency decreased by almost 2 points, but in the ETAS™50 group it increased by 5.4 points. In the Visual Analogue scale of sleep effects on health, appetite was affected negatively by 6.1 points, but in the ETASTM50 group it improved by 9.1. 

Conclusion:

Overall sleep quality and other quality-of-life measurements all improved in the ETASTM50 group, compared with the placebo group. 


Hokkaido Information University, Ebetsu, Japan
Nishihira, J., J. Takanari. The Discovery of a Novel Functional Constituent Extracted from Asparagus: Its Effectiveness for Stress Reduction, and Potential Use for Prevention of Sleep Disorders. Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu, Japan (funded by Amino Up Chemical, unpublished). 

Topic: 
Does ETASTM50 improve sleep quality and reduce stress?

Background:

HSPs (heat shock proteins) are thought to have anti-stress effects by reducing cortisol and chronographanin levels. Asparagus provides numerous health benefits, including cancer and cardiovascular disease prevention. In addition to those properties, scientists have found a novel functional molecule, asfural, isolated from an asparagus extract (ETASTM) useful for stress reduction. The isolated compound is structurally unique and induced heat shock protein (HSP) 70. In animal studies, intake of ETASTM dose-dependently ameliorated stress, reducing corticosterone, in accordance with up-regulation of HSP70. Similarly, researchers found stress decreased in a human clinical trial as HSP70 level in peripheral blood increased after the intake of ETASTM.

Study Type:

Human clinical intervention trial

Study Design:

Randomized, placebo-controlled, double-blind crossover study. Researchers used actigraphy, a reliable analyzer of sleep quality, and measured serum cortisol as well as salivary cortisol and chromogranin A.

Subjects:

16 healthy male volunteers (with sleep-related problems)

Dosage:

150 mg/day of ETASTM50 for a week

Results:

ETASTM50 was found to be a safe, well-tolerated nutritional supplement that significantly improved quality of sleep. Moreover, ETASTM50 decreased serum cortisol as well as salivary cortisol and chromogranin A. 

Conclusion:

ETASTM50 is effective for improving quality of sleep and reducing mental stress. Although the mechanism of these actions remains to be investigated, the current data strongly support that ETASTM50 would be beneficial to sustain quality of life through good sleep and stress reduction. 

Clinical Nutrition
Waki, H., et al. 2013. Effect of Enzyme-treated asparagus (ETASTM) on the Stress Response Substance in a Clinical Trial. 32:S233– S234. 

Topic: 
What is the effect of ETASTM on the stress response?

Background:

Autonomic-nervous functions can be measured by heart rate variability, levels of serum cortisol and plasma catecholamine, and concentrations of sIgA and cortisol in saliva. Will ETASTMaffect these markers of stress?

Study Type:

Human clinical intervention trial

Study Design:

Randomized, double-blind, placebo-controlled crossover trial. Subjects took ETASTM or placebo for 28 days, with a 14-day washout. Subjects filled out a questionnaire regarding their levels of energy or fatigue in a sitting position, and then did mental arithmetic to measure psychological stress. During the mental arithmetic phase, researchers measured autonomic-nervous functions using heart rate variability analyses with an active orthostatic test, and analyzed the results in real time with heart rate variability waveanalysis software. After the mental arithmetic test, researchers collected blood and saliva and performed POMS. Researchers measured levels of serum cortisol and plasma catecholamine in the blood samples and analyzed the concentration of sIgA and cortisol in saliva.

Subjects:

25 subjects

Dosage:

150 mg/day of ETASTM50 for 28 days

Results:

In the ETASTM50 group, researchers noted the following results: (1) In the questionnaire responses, the items of “Feel tired,” “Hard to get up,” and “Feel heavy” showed improvement. (2) The number of answers and correct answers of the mental arithmetic increased significantly. (3) After the mental arithmetic, two items, “depression falling” and “fatigue,” in POMS showed effective results. (4) After the mental arithmetic, the correction value of sIgA level in saliva (μg/mg) increased significantly (Day 0: 208.11 ±168.20; Day 28: 298.66 ± 154.71). However, the levels of cortisol and catecholamine did not change. 

Conclusion:

ETASTM50 intake for 28 days improved speed and accuracy of mental arithmetic and increased the levels of sIgA, promoting a stress response. These data suggest that ETASTM intake may reduce feelings of fatigue in daily life and improve stress response. 

Clinical Nutrition
Waki, H., et al. 2013. Effect of Enzyme-treated asparagus (ETAS™) on the Stress Response Substance in a Clinical Trial. 32:S233– S234. 

Topic: 
Can ETAS™50 relieve stress-related dysphoria (unhappiness) and fatigue?

Background:

Stress often results in fatigue and dysphoria; however, a heat shock protein (HSP)-inducing agent may be able to counteract those effects. Can a proprietary extract of Asparagus oficinalis known as ETAS™50 at relatively low dosages have an effect in inducing the HSP response?

Study Type:

Human clinical intervention trial

Study Design:

Randomized, double-blind, placebo-controlled crossover trial. Subjects filled out a questionnaire regarding their level of energy or fatigue in a sitting position, and then did mental arithmetic to measure psychological stress. In the mental arithmetic phase, researchers assessed autonomic-nervous functions using heart rate variability analyses with an active orthostatic test, and analyzed results in real time with heart rate variability wave-analysis software. After the mental arithmetic test, they collected blood and saliva samples and analyzed catecholamine stress hormones in the blood, sIgA (saliva immune factor that is reduced from stress), and cortisol in saliva.

Subjects:

25 healthy volunteers

Dosage:

150 mg/day of ETAS™50 or a placebo for 28 days with 14-day washout period

Results:

ETAS™50 increased levels of sIgA, reduced perception of fatigue, and had a beneficial effect in response to dysphoric stress.

Conclusion:

ETAS™50 is effective in reducing fatigue and feelings of unhappiness caused by stress. 

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Journal of Food Science 

Ito T, et al. Enzyme-Treated Asparagus Extract Promotes Expression of Heat Shock Protein and Exerts Antistress Effects. 2014 Feb 5. doi: 10.1111/1750-3841.12371. 

Topic 

The effect of ETAS™ on anti-stress responses in white blood cells leukocytes) was studied in humans subjects. 

Background 

HSP70 is known to be a stress-related protein and its induction leads to cell protection. Asparagus has been used in traditional Asian medicine since ancient times for its diuretic, anti-fatigue, and metabolism enhancement effects. Asparagus extract modulates blood glucose level in diabetic rats as well as oxidant defense activity. The current study tested enhanced expression of intracellular heat shock protein 70 (HSP70) in response to ETAS™ and its anti-stress effect. The HSP70-inducing activity of ETAS™ was tested in HeLa cells, which are used for gene expression studies. 

Study Type 

Human clinical intervention trial 

Study Design 

Randomized varying dosages tested (non-placebo) 

Subjects 

20 healthy male volunteers were randomly divided into 3 groups: low-dose (ETAS™ 75 mg/d, 10 subjects, mean age; 36.0 ±2.0 y), middle-dose (ETAS™ 100 mg/d, 5 subjects, mean age; 33.6 ±2.7 y) group, and high-dose (ETAS™ 150 mg/d, 5 subjects, mean age; 33.2 ±2.4 y). 

Dosage 

100 or 150 mg/d daily for 7 days 

Results 

The mRNA expression of HSP70 in peripheral leukocytes was significantly increased at intakes of 100 or 150 mg/d, compared to the baseline levels. The expression level of HSP70 mRNA in leukocytes was assessed through real-time PCR measurement before and after 7 days. Intakes of 100 and 150 mg/d were associated with increased expression of HSP70 mRNA compared to baseline values (154.9 ±24.9% and 159.2 ±24.9%, respectively). The low-dose group had no significant increase (101.6 ±8.8%). 

Conclusion 

The outcome of the study suggested that ETAS™ might exert anti-stress effects under stressful conditions which is based on the enhancement of HSP70 expression.