ETAS Clinical Evidence 1

ETAS™ Clinical Evidence

STUDY 1

Topic Does ETAS™ 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 (ETAS™) useful for stress reduction. The isolated compound is structurally unique and induced heat shock protein (HSP) 70. In animal studies, intake of ETAS™ 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 ETAS™.

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 ETAS™ for a week

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

Conclusion ETAS™ 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 ETAS™ would be beneficial to sustain quality of life through good sleep and stress reduction.

Topic What is the effect of ETAS™ 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 ETAS™ improve these stress indices?

Study Type Human clinical intervention trial

Study Design Randomized, double-blind, placebo-controlled crossover study. Volunteers with sleep-related problems took ETAS™ or placebo. Researchers measured serum cortisol, salivary cortisol, and chromogranin A, a marker of psychological stress.

STUDY 2

STUDY 3

Journal of Nutritional Science and VitaminologyIto T, et al. Effects of Enzyme-Treated Asparagus Extract on Heat Shock Protein 70, Stress

Indices, and Sleep in Healthy Adult Men. 2014 60(4): 283-290

Subjects 16 healthy male volunteers (with sleep-related problems)

Dosage 150 mg/day of ETAS™ for a week

Results Serum cortisol increased by 45% in the placebo group, whereas in the ETAS™ 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™ group compared with 75% in the control group. A marker of psychological stress known as chromogranin A decreased 2.5 times more in the ETAS™ group compared with the control group.

Conclusion ETAS™ improves sleep-related-stress physiological indices.

Topic What is the effect of ETAS™ 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 ETAS™ 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 ETAS™ 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 ETAS™ 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™ 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 ETAS™ group it improved by 9.1.

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

ETAS Clinical Evidence 2

ETAS™ Clinical Evidence

Presented at the 35th European Society for Clinical Nutrition and Metabolism (ESPEN) Congress, Leipzig, Germany. 2013 Waki H, et al. Effect of Enzyme-treated asparagus (ETAS™) on the Stress Response Substance in a Clinical Trial

Topic The aim of this study was to examine the effectiveness of ETAS™ on the stress response and related dysphoria (feelings of unhappiness).

Background Stress effects result in fatigue and dysphoria; however, a heat-shock protein (HSP)-inducing agent may be able to counteract those effects. A fermented stem extract of asparagus known as ETASTM at relatively low dosages may have an effect in inducing the HSP response.

ETAS™ affects stress response to stressful stimuli and can be assessed experimentally through the use of a questionnaire survey of condition, sitting position, and mental arithmetic for psychological stress. The autonomic-nervous functions are measured by heart rate variability. The levels of serum cortisol and plasma catecholamine can be measured from extracted blood as further indicators of stress response. In addition, saliva can also be tested for the concentration of secretory immunoglobulin A (sIgA) and cortisol. Other indications are dysphoria stimulation due to the adverse effects of mental arithmetic.

Study Type Human clinical intervention trial

Study Design A randomized, double-blind, placebo-controlled crossover trial that used a questionnaire survey of the subject’s condition of energy or fatigue in a sitting position and utilized mental arithmetic to cause psychological stress. In the mental arithmetic phase, the autonomic-nervous functions were measured by heart rate variability analyses using an active orthostatic test and were analyzed in real time with heart rate variability wave-analysis software. After the mental arithmetic test, blood and saliva were extracted, and catecholamine stress hormones in the blood, sIgA (saliva immune factor that is reduced from stress), and cortisol in saliva were analyzed.

Subjects 25 healthy volunteers

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

Results After the mental arithmetic, the correction value of sIgA level in saliva (mg/mg) increased significantly (Day 0: 208.11 ± 168.20; Day 28: 298.66 ± 154.71). On the other hand, the levels of cortisol and catecholamine did not change.

The main subjective results of Day 0 to Day 28 in the ETAS™ group in the questionnaire survey were rated by condition in terms of “Feel tired,” “Hard to get up,” and “Feel heavy.” This was used to show the effectiveness of results. The number of answers and correct answers of the mental arithmetic increased significantly. After the mental arithmetic, two items of “depression falling” and “fatigue” in POMS showed effective results.

Conclusion These data suggest that ETAS™ intake may reduce a tired feeling in daily living and have beneficial effects in the response to dysphoria stress. ETAS™ is effective in reducing fatigue and feelings of unhappiness (dysphoria) caused by stress.

ETAS Clinical Evidence 3

ETAS™ Clinical Evidence

Journal of Food ScienceIto 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.

ETAS™ Clinical Evidence