Japanese Journal of Physiological Anthropology Yoto, A., et al. The Stress Reducing Effect of γ-Aminobutyric Acid and Apocynum venetum Leaf Extract on Changes in Concentration of Salivary Chromogranin A. 2009 14(3): 55.

Topic
What is the stress-reducing effect of ingesting γ-amino butyric acid (GABA), Apocynum venetum leaf extract (Venetron® or AVLE), and a combination of both?

Background
The herb from which Venetron is derived is known botanically as Apocynum venetum L. and is found in the Chinese Pharmacopoeia (as luobuma) for calming the liver, soothing nerves, and clearing heat (inflammation). Modern pharmacological studies have revealed that luobuma has many potent physiological effects, including antihypertensive, cardiotonic, antidepressant, and anti-anxiety effects — most of which are believed to be attributable to the flavonoid content. Pharmacological investigations of Venetron’s effect on neurotransmitters show Venetron produces its anxiolytic action through the GABA-ergic system (Grundmann, 2007). Venetron given in a proprietary 1:1 blend of Apocynum venetum extract and a highly bioavailable form of GABA at a dosage of 50 mg/day was tested for its effect on the reduction of a stress marker known as salivary chromogranin A (CgA) in students undergoing stress related to cognitive function. This was a double-blind, placebo-controlled crossover study to examine the stress-reducing effect of GABA, AVLE, and concurrent ingestion of both. Changes in the concentrations of CgA and cortisol in the saliva, and scores on a mental questionnaire were taken after subjects were given a stress-inducing mental task following intake.

Study Type
Human clinical intervention trial

Study Design
Double-blind, placebo-controlled crossover study

Subjects
12 students

Dosage
Venetron (a proprietary 1:1 blend of Apocynum venetum extract and a highly bioavailable form of GABA) at a dosage of 50 mg/day

Results
The 12 students who underwent a stress-inducing mental task showed a reduction in salivary CgA secretion.

Conclusion
Venetron given with bioavailable GABA reduces markers of cognitive-induced mental stress.

Venetron® brochure, Tokiwa

Topic
What was the effect of a daily dose of 50 mg of Venetron® in individuals with mild depression over 8 weeks?

Background
In 39 individuals with mild depression, Venetron was tested in a double-blind, randomized trial using 50 mg per day given as two 25-mg tablets at different times over 8 weeks. Global scores of depression and blood samples for serotonin levels were measured at base line and after 8 weeks. The changes were assessed using a 17-item Hamilton Depression (HAM-D) rating scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and comorbid anxiety symptoms.

Study Type
Human clinical intervention trial

Study Design
Global scores of depression and blood samples for serotonin levels were measured at base line and after 8 weeks. The changes were assessed using a 17-item HAM-D scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and comorbid anxiety symptoms.

Subjects
39 subjects with mild depression and symptoms of anxiety, 20 subjects in the Venetron group and 19 in the control (placebo) group.

Dosage 50 mg of Venetron per day given as two 25-mg tablets

Results
After 8 weeks of treatment, 40% of the subjects in the Venetron group showed a greater-than-10-point decrease in HAM-D scores. It should also be noted that in the Venetron group, 50% had a decrease of 50% or greater in the symptoms of depression as compared with the placebo group. There were also significant improvements of decreased anxiety and reductions of insomnia in the middle of the night and later in the sleep cycle. In the Venetron group, 50% of subjects had increased serotonin concentrations, demonstrating biochemical evidence of improvement. HAM-D scores decreased by 50 percent or greater in the Venetron group. Also, 60% of the Venetron group had a HAM-D score of 8 or less by week 8. Other symptoms that showed significant improvements within the Venetron group included middle- and late-night insomnia, work and activities, and somatic anxiety between base line and week 8. In the Venetron group, 50% of the subjects had increased serotonin concentrations, demonstrating biochemical evidence of improvement (increase of 67%; 10.6 ± 6.3 ng/mL to 17.7 ± 7.2 ng/mL). And 35% of the subjects in this group showed an increase of at least 20%.

Conclusion
Venetron significantly improved anxiety and reduced insomnia in the middle of the night and later in the sleep cycle. There was also an improvement in the biochemical index of serotonin concentrations, a marker of reduced tendency for depression and anxiety

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Venetron® brochure, Tokiwa

Topic
What effect does Venetron® have on patients with various degrees of depression?

Background Venetron has been shown to influence serotonin levels, a marker of mood health in both animal and human subjects. Venetron is an extract of Apocynum venetum rich in flavonoid bioactive compounds similar to St. John’s wort, though it differs in the type and quantity, and does not contain hypericin or hyperforin. Venetron is known to lower blood pressure and help with anxiety states. In this study, the symptoms of depression were assessed in subjects having widely varying severity using the Sheehan Disability Scale (SDS). This scale used to measure depression was developed to assess functional impairment using three interrelated areas: work/school, social, and family life. The patient is able to rate the extent that work/school, social life, and home life or family responsibilities are impaired by symptoms of depression as a composite of three self-rated items designed to measure the extent to which these three major life sectors are impaired by panic, anxiety, phobic, or depressive symptoms.

Study Type
Human clinical intervention trial

Study Design
The SDS was used to measure symptoms of depression in patients taking two 25-mg tablets a day for 14 days.

Subjects
Patients with varying states of depression

Dosage
Two 25-mg tablets twice a day Results The SDS scores of subjects improved in symptoms of depression ranging from minimal to mild depression and moderate to severe depression. The mean measurement significantly declined to the normal range after 14 days of ingestion.

Conclusion
Venetron improves depression in patients with varying degrees of symptom severity as measured by the Sheehan self-assessment scale.

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Venetron® brochure, Tokiwa

Topic
What have been the results of Venetron® in case studies of patients having depression, PMS, anxiety, and/or insomnia?

Background
Case studies of Venetron have shown very good results in patients with depressive PMS disorders and in younger and older depressed patients. Venetron has been used in the clinical setting in Japan and as the botanical drug Apocynum venetum, recorded in the 2005 Pharmacopeia of the People’s Republic of China to treat neurasthenia, palpitation, insomnia, edema with oliguria, hypertension, and nephritic edema.

Study Type
Human clinical intervention trial

Study Design
Case studies

Subjects
One 29-year-old woman with PMS, a 39-year-old woman with PMS, a 55-year-old woman, a man, 36 years old, and two older men, one 66 and the other 75 years of age

Dosage
50 mg

Results
In the 29-year-old woman with PMS, 50 mg of Venetron day for 1 month reduced melancholy and overeating. In the 39-year-old woman with PMS taking 25 mg of Venetron for 2 weeks before menses and over a 3-month period, emotional symptoms such as irritability and depression improved. The 36-year-old man given 50 mg a day for 6 months had improvements in concentration and was more optimistic. The 55-year-old woman given 50 mg a day had decrease in fatigue and grief. The 66- and the 75-year-old men, using 50 mg a day after 2 weeks, both had decreases in frequency of waking up throughout the night and had deeper sleep.

Conclusion
Case studies have also shown very good results in patients with depressive PMS disorders and in younger and older depressed patients. The types of symptoms that improved include melancholy, overeating, emotional symptoms such as irritability, difficulty in concentrating, optimistic outlook, fatigue and grief, and improvements in sleep.

Journal of Nutritional Science and Vitaminology                                                                                                                                                                                                                                                                                                                                                                                                                                            Yamatsu A., et al. “The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract.” 2015 61(2):182–187.                                   
Topic
What is the sleep-improvement effect of oral ingestion of a daily dose of 100 mg of γ-aminobutyric acid (GABA), 50 mg of Apocynum venetum leaf extract (Venetron® or AVLE), and a combination of both?

Background
Sleep disorder insomnia is a serious health problem and becoming a matter of public concern. GABA produced by natural fermentation is an inhibitory transmitter of the central nervous system. GABA has been shown to relieve anxiety, reduce psychological stress, and promote relaxation.  AVLE, derived from Apocynum venetum leaf, is an herb found in central and northwestern China. Flavonoids such as hyperoside and isoquercitrin in AVLE showed antidepressant, anti-anxiety effects, as well as anti-hypertensive activities.                                                                                           This study was a single-blind, placebo-controlled trial. In 16 subjects with suspected sleep disorder, GABA at a dose of 100 mg and AVLE at a dose of 50 mg in gelatin capsules were given 30 minutes before going to bed every day either separately or in combination, for a test period of 1 week each. The study consisted of two test periods with a washout period (1 week) in between. An electroencephalogram (EEG) measurement was used to reveal the effect of oral intake of GABA and AVLE on sleep. Sleep quality was evaluated in 4 stages: wakefulness, rapid eye movement (REM) sleep, light non-REM sleep (stage N1 and N2), and deep non-REM sleep (stage N3). Sleep latency, or how long it takes to fall asleep, was also measured in the 16 subjects to evaluate the effect of ingesting GABA and AVLE on sleep disorder.                                                                                                     
Study Type
Single-blind, placebo-controlled trial.                                                                                                                                                                                                        
Study Design
The 16 subjects were divided into 4 groups of 4 people in each group (groups 1 to 4). The study consisted of 2 test periods (1 week each) with a washout period (1 week) in between. In the first test period, the subjects from groups 1 to 4 ingested GABA, AVLE, GABA & AVLE, and a placebo, respectively, 30 minutes before going to bed every day. In the second test period, subjects ingested different samples from the first period to make sure each sample group consisted of 8 subjects.  All the subjects were asked to maintain their lifestyle patterns during the test period. On EEG measurement days, alcohol and drugs such as cold medicine and hypnotics were prohibited to ensure the accuracy of the test. In addition, foods and drinks such as coffee and tea that may affect natural sleep were prohibited 2 hours before going to bed. A visual analog scale (VAS) was used to rate the subjects’ feeling with respect to ease of falling asleep, feeling on awakening, and satisfaction with sleep the day after the EEG measurement. The Pittsburgh Sleep Quality Index (PSQI) test was used to evaluate overall sleep quality.

Subjects
16 subjects with an average age of 36.8±8.9 years and PSQI scores at 6 or greater than 6, who were suspected of having some kind of sleep disorder.

Dosage
100 mg of GABA, 50 mg of AVLE gelatin capsules either separately or in combination.

Results
GABA alone at the dose of 100 mg shortened sleep latency by 5.3 minutes after administration, which showed a weak tendency toward difference (p = 0.13). AVLE alone at the dose of 50 mg significantly increased non-REM sleep time by 7.6% (p = 0.01). The combination of GABA and AVLE shortened sleep latency by 4.3 minutes and increased non-REM sleep time by 5.1%. The VAS questionnaires and PSQI showed that the combination of GABA and AVLE improved satisfaction, with a weak trend (p = 0.18), and AVLE improved subjective sleep quality, with a tendency toward difference (p = 0.10). 

Conclusion
Consuming GABA and AVLE simultaneously may help shorten sleep latency and increase non-REM sleep time, and ultimately improve sleep quality and satisfaction.