Study to Evaluate the Efficacy of Elix's Cycle Balance and Its Impact on PMS and Menstrual Symptoms
Phase: NA
Conditions: PMS, Menstrual Pain
Sponsor: Zenchi, Inc.

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Study to evaluate the efficacy of Elix’s Cycle 
Balance and its impact on PMS and menstrual 
symptoms 
 
  
Final Version 
Date: November 9, 2021 
 
Sponsor:  
Zenchi Inc. (Elix) 
 
Contract Research Organization: Citruslabs 
 
 
 
 
 
1. Background and Purpose 
 
The menstrual cycle is a process characterized by changes in hormone levels, specifically, fluctuating 
levels of estrogen and progesterone [1]. The menstrual cycle starts with the first day of the period and 
ends with the start of the next period. Usually, a menstrual cycle lasts between 24 and 38 days but the 
actual length may vary from cycle to cycle [2]. While 28 days seems to be the conventional length of a 
menstrual cycle, only 10-15% of women have cycles of exactly 28 days [3]. In the days following 
ovulation, both estrogen and progesterone levels are falling, which results in the transition from the 
luteal to follicular phase of the cycle, and eventually, menstruation [1]. PMS (premenstrual symptoms) 
and discomfort during menstruation are two of the most common health concerns women are facing 
[10]. And, the most common symptoms can impose significant economic and personal consequences to 
women, as social events and even school or work can be missed [11]. In fact, dysmenorrhea is the 
leading cause of absenteeism in school-aged girls, and reports show that 13%-51% of women have been 
absent at least once and 5%-14% are often absent due to the severity of period pain [33].  However, 
according to a recent study conducted with 43,000 women, more than half of these women did not tell 
their family, friends, or medical care provider about their menstrual problems [4]. During menstruation, 
dysmenorrhea or pelvic cramps, and feeling tired are commonly reported issues [4, 10], while prior to 
menstruation, the most common complaints and symptoms of premenstrual syndrome (PMS) are mood 
swings, bloating, and breast tenderness [5, 12]. Typically, PMS symptoms occur up to 1-2 weeks before 
menstruation and stop when menstruation begins, or shortly thereafter. Menstruation starts at puberty 
(menarche) and stops permanently at menopause. 
 

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The test product (Elix Cycle Balance) is specifically targeting dysmenorrhea, which is a debilitating 
gynecological condition that impacts women around the world. Dysmenorrhea is the term for describing 
pain during menstrual bleeding. It indicates a cramp-like, dull, throbbing, or colicky pain that usually 
emanates from the lower abdomen, and that occurs just before and/or during menstruation[30]. The 
pain usually lasts 8-72 hours. Back and thigh pain, headache, diarrhea, nausea, and vomiting may also be 
present [31]. Other symptoms often associated with menstruation are mood swings, changes in bowel 
movements, and dizziness, or even fainting [32]. One study found that menstrual pain was reported by 
84.1% of women, with 43.1% reporting that pain occurred during every period, and 41% reporting that 
pain occurred during some periods [30]. Dysmenorrhea is associated with significant decrease in quality 
of life [35]. Women with primary dysmenorrhea have a significantly reduced quality of life, poorer 
mood, and poorer sleep quality during menstruation compared with their pain-free follicular phase and 
compared with the menstruation phase of pain-free control women [36, 37].  
  
Options for mild to moderate discomfort as a result of menstruation are primarily either hormonal 
contraception [6] or non-steroidal anti-inflammatory drugs (NSAIDs) [7, 8]. Increasingly, however, 
consumers are interested in non-hormonal treatment options as well as the potential for more plant-
based, herbal or dietary options, due to potential side effects of the above options. Dietary supplements 
capable of supporting the body as it responds to the natural fluctuations in hormone levels associated 
with menstruation are thus of significant interest for consumer wellbeing [9]. Numerous studies using 
dietary supplements have been conducted and shown to assist with menstruation-related symptoms.  
 
The test product assessed in this study is based on Chinese herbal medicine (CHM). CHM has been used 
for centuries in China and it is currently used in public hospitals in China for the treatment of primary 
dysmenorrhea. For example, a 2008 Cochrane review found promising evidence for the use of Chinese 
herbal medicine in reducing menstrual pain in the treatment of primary dysmenorrhea, compared to 
conventional medicine such as NSAIDs and the oral contraceptive pill, or even acupuncture and heat 
compression. No significant adverse effects were identified in this review, however, the findings should 
be interpreted with caution due to the generally low methodological quality of the included studies [34]. 
 
This exploratory observational trial provides the opportunity to gather information on a multi-
supplement intervention that is aiming to reduce inflammation and balance hormone levels through a 
customized all-natural blend of herbs based on individual menstrual symptoms. This study will provide 
evidence for marketing claims. 
 
There is a well-understood connection between the menstrual cycle and the immune system where the 
immune system is suppressed following ovulation, and immune activity increases during menstruation 
[13]. The increased immune activity leading to menstruation results in increased inflammatory markers 
[14, 15, 16, 17], which are also linked with higher self-reported discomfort prior to and during 
menstruation [12, 18, 19]. 
  
Many dietary supplements have been extensively studied both in-vitro and in-vivo and shown to help 
mitigate inflammatory responses [26] and investigated the role that they might play in helping ease 

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menstrual discomfort [20, 8, 9]. Specifically, many of the dietary supplements that have been studied 
have a long history in traditional medicine as treatment options for PMS, and these include extracts 
from plants such as Vitex agnus-castus or dong quai (21, 22, 23]. The biological effects of herbs have 
been shown to include affecting the central nervous system, endocrine system, the activity of 
sympathetic nerves, basal metabolic rate, the function of organs and tissues, and secretion of cytokines 
out of the body [38]. 
  
In addition to the diagnosis of a western-defined disease (such as dysmenorrhea), traditional Chinese 
medicine (TCM) doctors use a technique called pattern diagnosis to focus treatments on the 
subcategories of said disease; for example, blood stasis and cold accumulation of the uterus or blood 
and qi deficiency syndrome for dysmenorrhea [40]. The TCM pattern is determined by a TCM doctor on 
the basis of signs and symptoms displayed by the patient, their physical condition, disease status, and 
constitution, after which CHM prescriptions for treatment are given [39]. This individualization is a key 
primary requirement of traditional treatment with CHM [34]. Personalized medicine refers to the right 
treatment for the right individual at the right time and has the potential to diminish the incidence of 
drug adverse reactions, eliminate invalid therapy, improve the efficacy of treatments, ultimately, 
achieve optimal health outcomes [38]. 
 
Chinese herbal medicines (CHM) have been used to treat menstrual symptoms for centuries. There is 
strong evidence that CHM may be a suitable alternative to treat PMS and menstrual symptoms and that 
CHM is most effective when tailored to an individual’s symptoms. In a 2008 Cochrane review, thirty-nine 
randomized controlled trials studying CHM for dysmenorrhea were analyzed, involving a total of 3,475 
women in the review. Chinese herbal medicine resulted in significant improvements in pain relief, 
overall symptoms, and the use of additional medication when compared to the use of pharmaceutical 
drugs. Individualized CHM prescriptions resulted in significant improvements in pain relief, overall 
symptoms, and use of additional medication after up to three months of follow-up when compared to 
commonly used Chinese herbal health products. Chinese herbal medicine also resulted in better pain 
relief than acupuncture and heat compression. Of the 39 studies, all had an effectiveness range of 87-
100% for herbal medicine interventions. Generally, the reviewed trials reported that CHM for primary 
dysmenorrhea was safe when compared with conventional medicines [34]. 
 
Lastly, most of the dietary supplements studied have followed a “one size fits all” approach. Given the 
wide array of symptoms women experience before and during their menstruation, this approach is 
inadequate and may treat symptoms that are irrelevant. The development of dietary supplements that 
provide a customized scenario to menstrual concerns and are taken immediately prior to menstruation 
would be of significant benefit. 
  
 
 
 
2. Study Objectives 

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● The primary objective of this study is to assess if Elix provides relief from menstrual symptoms 
and to see if it improves accompanying symptoms such as fatigue and mood swings. 
● The secondary objective is to examine if participants experience a reduction of the usage of 
OTC NSAIDS in the treatment of primary dysmenorrhea symptoms. 
 
 
3. Study Design  
 
This is an open-label observational single-group clinical trial to study the efficacy of a commercially 
available dietary supplement and its effect on common PMS and menstrual symptoms.  
 
It is hypothesized that the dietary supplement marketed as “Elix Cycle Balance” will improve subjective 
wellbeing in trial participants by alleviating common symptoms of PMS and menstrual symptoms, such 
as cramps, bloating, and mood swings. 
 
A total of 65 participants will be recruited for the trial following screening, with the expectation that at 
least 50 participants will complete the trial. The trial will be fully remote, a technology platform will be 
utilized to screen, enroll and capture study data of the participants. The total intervention study period 
will be 3 months. Participants will be taking their customized blend of “Elix Cycle Balance” - based on the 
study intake form for the study period. 
 
The sequence of events for the participant is as follows: 
● Eligibility pre-screening (inclusion/exclusion criteria including relevant demographic and medical 
information) 
● Informed consent 
● Study intake survey 
● Test product distribution 
● Onboarding participants on a technology platform that captures data 
● Participants to complete the baseline survey 
● Participants start their customized Elix Cycle Balance blend for 3 months 
● Participants to write down any adverse or ill effects, as well as any positive effects any time after 
taking the test product 
● Participants to take a monthly survey about their symptoms 
● Participants to complete an exit survey and note any final adverse and positive events 
● Participants receive $75 compensation, as well as 3 additional months of Elix Cycle Balance after 
completion of the study 
 
3.1. Study Procedures & Product information - intervention/treatment 
 

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As an investigatory trial studying a commercially available consumer product, an open-label design is 
most appropriate to gauge real-world perceived behavior. Focusing on 3 months minimizes the strain on 
the participants while providing a significant data-gathering opportunity. Furthermore, the survey 
results acquired from participants during baseline, and then the intervention will provide insights to 
guide further trials that are placebo-controlled.  
  
Although discomfort during and prior to menstruation is extremely common and can have a moderate 
to severe impact on social and economic activities, there are few research-backed commercially 
available products to alleviate this discomfort. Many consumers are increasingly interested in dietary 
supplements to help support their bodies, and the opportunity to determine whether a commercially 
available product improves consumer wellbeing is a significant benefit to society.  
 
 
3.2. Study Procedures 
 
Individuals aged 18+ with regular menstrual cycles and moderate to severe menstrual discomfort, but 
otherwise healthy will be chosen to participate in the study (see “4. Participant Definition”). Participants 
will be advised to discontinue any other oral supplement or prescription targeting their menstruation 
prior to beginning with the study.  
 
Participants will be asked to take a study intake questionnaire before the study begins to create a 
customized blend of the test product which is used for the study.  
 
Before participants start the study, they will be asked to complete a baseline menstrual wellbeing 
survey.  
 
Each day in the morning and at night in the week prior to the menstruation, the participants will take 6 
drops of Elix Cycle Balance. Elix Cycle Balance can be taken alone or in combination with tea, water, or 
smoothies. Especially if this is the first time taking a traditional Chinese medicine product/herbs, it is 
recommended to mix the herbal formula in another beverage. Should participants present themselves 
with a sensitive stomach, it is recommended to take the drops with a meal to avoid an upset stomach. 
Participants will repeat this process for 3 months (study period) until the study is complete.  
 
After the first month (approximately 30 days) and the subsequent months thereafter, the participants 
will take a menstrual wellbeing survey to track progress. In total there will be 3 wellbeing surveys.  
 
After 3 months, participants will take their last menstrual wellbeing survey - marking the end of the 3 
months study period.  
 
Once they completed the study and last wellbeing survey, they will also complete an exit form.  
 
 
3.3. Product information - intervention/treatment 

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The dietary supplement is designed and marketed commercially to be taken in servings of 6 drops. By 
focusing the clinical trial on this use case, we will obtain the best insight into physiological responses and 
perceived wellbeing for typical consumer behavior.  
 
Elix is a customized blend of 21 herbs that target several symptoms for PMS and menstrual issues so 
that users find relief after a time of a maximum of 3 months. The ingredients are sourced from the most 
potent part of every plant. The blends include  
● Angelica Sinensis, a powerful anti-inflammatory that’s proven to reduce uterine spasms (or 
cramps), regenerate blood cells, stimulate circulation, as well as immune response;  
● Atractylodes, an acute and chronic anti-inflammatory agent, as well as a powerful hormone 
balancer, proven to ease a wide range of menstrual symptoms and boost immune health;  
● Bugleweed, a thyroid-regulating plant that assists in alleviating menstrual symptoms, as well as 
providing relief from pain and anxiety;  
● Bupleurum, a powerful herb with immunoregulatory actions that supports pain, depression, and 
stress relief associated with premenstrual syndrome (PMS) and menopause;  
● Corydalis, a potent pain reliever that is proven to ease uterine and upper abdomen cramping, 
and relieves insomnia due to pain; 
● Cyperus, for regulating menstruation and  reducing symptoms such as cramps, breast 
tenderness, and mood  changes; 
● Gardenia, which is  proven to reduce cramping, minimize headaches, combat acne, and 
moderate mood swings; 
● Ginger, which is clinically  proven to ease menstrual cramps as well as reduce nausea & bloating, 
and has anti-inflammatory & antimicrobial properties which support immune and respiratory 
function;  
● Licorice, great for abdominal discomfort, and ideal for treating menstrual cramping. It has been 
shown to relieve digestive discomfort and regulate bowel movement. It is also an antiviral and 
antimicrobial harmonizer, supporting how immune-boosting herbs work together in formulas;   
● Mint, an effective,  natural pain reliever that’s been shown to reduce stress and even help with 
PCOS. Mint is also a potent antioxidant and antibacterial 
● Motherwort, used for thousands of years in China, relieves menstrual pain by enhancing blood 
flow to the uterus and regulating stress hormones;  
● Moutan Cortex, has a powerful ability to reduce inflammation and promote blood flow, making 
it an excellent  treatment for severe menstrual cramps; 
● Poria, an edible mushroom that suppresses inflammation (reducing menstrual cramps) and 
protects nerve cells (alleviating depression and boosting mood);  
● Rehmannia, sometimes referred to as Chinese foxglove, is a flowering plant and adaptogen, 
known to support the circulatory system, to regulate blood production, and fight fatigue. It’s a 
proven antioxidant, anti-inflammatory, and antidepressant, all of which aid with PMS symptoms.   
● Red Ginseng Root, known for tonifying qi and regulating the central nervous system. A popular 
adaptogen, it’s great for balancing stress and improving mental function. 

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● Safflower, which reduces inflammation, promotes blood circulation, and is especially great for 
regulating an irregular menstrual cycle; 
● Skullcap, which reduces the inflammation and spasms that cause menstrual cramps, while 
cooling and calming the body and mind. With antiviral and anti-inflammatory properties, this 
herb is  widely used in China to treat influenza and pneumonia, amongst other ailments;  
● Szechuan Lovage Root is widely used for its ability to boost blood circulation and reduce 
inflammation,  which is how it effectively minimizes menstrual cramping;  
● Toosendan Fruit, a wonderful antioxidant and adaptogen, which helps your body adapt to a 
variety of stresses,  which is especially useful during menstruation; 
● Vitex Berry, an ideal hormone balancer—especially  in cases of estrogen dominance—and helps 
keep the menstrual cycle regular; 
● Water Plantain Root, commonly used to aid the body of heat by clearing dampness and 
promoting detox through urination;  
● White Peony is proven to reduce pain and cramping while promoting peaceful sleep during 
menstruation;  
● Magnesium is used to relax the smooth muscle of the uterus and reduce inflammation, 
specifically the prostaglandins that cause painful cramps (dysmenorrhea). 
 
 
4. Participant Definition 
 
A total of 65 individuals will be recruited through Citruslabs for this study. Patients who meet the 
following eligibility requirements will be introduced to the study by online pre-selection. All potential 
study participants (who are pre-selected) will be screened for eligibility by an online pre-screener prior 
to joining the study. Additionally, all participants will receive a study onboarding onto the technology 
platform that is used to capture the data for this study.  
 
 
4.1. Inclusion Criteria 
 
Individuals will be included in the study if all of the following criteria are met: 
● Female aged 18-36 
● Self-reported moderate to severe discomfort during menstruation, related to pelvic 
cramps, bloating, mood swings, or fatigue 
● May experience regular or irregular menstrual cycle 
● May be on birth control 
● Must know or can estimate the date of the next cycle/period 
● May find blood clots in menstrual blood 
● Must be in good health (doesn’t report any medical conditions asked in the screening 
questionnaire) 
● Following a stable, consistent diet regimen  

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● Follow a stable, consistent exercise regimen and are willing, for the duration of the 
study, to not decrease or increase the amount of exercise in their regimen  
● Agree to refrain from any lifestyle changes that may affect their menstrual cycle for the 
duration of the study (for example, getting on or off hormonal birth control, reducing 
the amount of exercise) 
● Follow a stable consistent regimen when using any other interventions, such as 
massage, chiropractic medicine, or acupuncture; agree not to increase or decrease the 
number of their other interventions 
● Willingness to adhere to the dietary supplement regimen 
● Willingness to refrain from any other dietary supplements targeting the menstrual cycle 
during the study period 
● Is able to communicate in English 
● Is willing and able to share feedback via the used technology portal  
● Must provide written informed consent (ICF) 
 
4.2. Exclusion Criteria 
 
Individuals will be excluded from the study if any of the following criteria are met: 
● Don’t experience a menstrual cycle 
● Can’t estimate the onset of their next menstrual cycle 
● Don’t experience menstrual cramping 
● Follow an extreme diet intervention 
● Experienced severe weight loss in the past 3 months prior to study participation  
● Usage of any medication or herbal remedies/supplements which can affect the 
menstrual cycle 
● If currently taking allowed supplements, the dosage needs to remain the same 
throughout the entirety of the study  
● Food intolerances/allergies that require an EpiPen  
● Known allergic reaction to any of the test product ingredients 
● Currently pregnant, want to become pregnant for the duration of the study, or who are 
breastfeeding 
● Previous users of Elix Cycle Balance 
● Having more than 3 alcoholic drinks a day 
● Have been diagnosed with the following conditions: PCOS, Endometriosis, PMDD, 
Adenomyosis, Hashimoto’s, anorexia, bulimia, orthorexia, binge eating, any other eating 
disorder 
● Smokers 
● Not been on a stable dose of birth control for the past 6 months 
 
5. Patient Enrollment 

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5.1. Informed Consent 
 
In compliance with CFR 50.25, and the Declaration of Helsinki, no patient shall be enrolled in an 
investigation without the provision of adequate informed consent. Citruslabs and the Principal 
Investigator are responsible for ensuring that no patient is included in the study without adequate 
informed consent being provided. 
 
All ICFs must have a favorable opinion of the ethics committee. Consent of a patient needs to be 
obtained from the patients themselves and documented on an ICF. 
 
The Investigator or trained designee preliminarily screens to determine if a patient generally meets the 
eligibility criteria for the study. If so, the Investigator or trained designee shall offer study participation 
to those patients. If the patient agrees to participate, s/he will sign the informed consent document. 
 
5.2. Patient Screening 
 
After signing the informed consent documents, the patient will be screened for eligibility and will be 
listed on the Screening and Enrollment Log. The date of screening, the results of screening (included or 
not) and the primary reason for not including the patient (e.g., does not satisfy eligibility criteria,) will be 
recorded on this log. The original log is to be retained at the Citruslabs office and a summary of 
recruitment (de-identified) sent to Elix regularly during enrollment. 
 
5.3. Patient Identification Numbering 
 
The patient ID numbers will be assigned after consent is obtained. The patient number will become the 
unique identifier of the patient and will be recorded on each page of the completed surveys. For 
example, the first three (3) participants enrolled will be identified as 00-001, 00-002, 00-003. Once a 
patient identification number is assigned, it may not be reused.  
 
 
 
 
5.4. Process for Discontinuation of Patient Participation 
 
Patient participation may discontinue through major protocol deviation, withdrawal, or death. The 
participant is free to withdraw from the study at any time. In all instances of patient discontinuation 
after obtaining Informed Consent, an End of Study/Withdrawal form is required to be submitted by the 
patient to Citruslabs, and this will ultimately be reported to Elix. 
 
5.5. Payment for Participants 
 

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Upon completion of the study, patients will be compensated for their time with $75 in the form of an 
Amazon gift card, plus receive 3 additional months of Elix Cycle Balance after the study is complete 
(total value $200+). 
 
 
 
6. Data Management 
 
All documents relevant to the study, including completed ICFs, will be hosted on a secure online portal. 
The ICFs will be completed via HelloSign, and will be transferred to the online portal, using a secured 
data transfer system on the online portal. Survey records will be stored within the online portal and Elix 
has access to the de-identified data set. After completion of the study, all data will be saved to a secured 
internal network at Elix. User access to the directory is controlled through user-level role-based security. 
All data will be anonymized during analysis. 
 
 
6.1. Privacy/Confidentiality  
 
Data will be stored encrypted on a secured online portal that uses the HIPAA compliant AWS servers. All 
patients will be de-identified and labeled using a coding system (00-01, 00-02, 00-03, etc.) 
 
 
7. Data Analysis 
 
To better document and elicit the key concepts, all recorded open-text responses to surveys will be 
analyzed using qualitative analysis software. 
 
Responses to clinical outcome measures will be normalized and analyzed using the appropriate 
statistical test. This will allow for estimation of an effect size for future studies, and initial indicative 
directional evidence of differences between groups. However, as a feasibility study, it is not anticipated 
that these tests would be powered to detect (at a statistically significant level) anything other than a 
large clinically significant effect.  
 
Any adverse events will be listed and reported using descriptive statistics by group.  
8. Risks Assessment 
 
The dietary supplements selected for this study are well tolerated, and the daily doses are within the 
FDA tolerated upper limits (where relevant). Minimal risk is foreseen for participants through their 
participation in the study. The most common side effect of dietary supplementation is gastrointestinal 
distress (for example, diarrhea) as a result of very high doses, particularly if a study participant has a 
previously unrecognized allergy or sensitivity. Should participants know that they have a sensitive 
stomach, it is recommended to take Elix Cycle Balance with a meal. Generally, participants are advised 
to take Elix Cycle balance with some fluid.  Additionally, there is the possibility that participants may 

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experience rashes or hives, as well as headaches. Should these symptoms not dissolve after 3 days, 
participants will be advised to discontinue with the study.  
 
In terms of confidentiality, there are minimal risks as all study participant information will be de-
identified. Since this is a virtual study, no confidential or protected information would be taken outside 
of the standard. There is a slight financial risk to the participants in the rare event that the above 
complications occur requiring additional medical care.  
 
 
9. Benefits Assessment 
 
The benefits of using Elix that will be assessed within the scope of this study include: 
● Brighter color of the menstrual blood  
● Canceling fewer plans // missing on less work/productivity 
● Decrease bloating  
● Help regulate cycle 
● Improve PMS symptoms overall  
● Improvement of digestive function 
● Increase energy & reduce fatigue  
● Less clotting  
● Fewer mood swings  
● Lighter/less heavy periods 
● Reduction of back pain 
● Reduction of cramps 
● Reduction of headache and menstrual migraines 
● Increase libido  
● Fewer body aches  
● Less hormonal acne  
● More balanced cycle 
● Reduction in anxiety/stress 
 
Participants are also contributing to the development and improvement of PMS and menstrual 
treatments, which some consider a benefit.  
 
 
 
10. Payment and Remuneration  
 
Upon completion of the study, patients will be compensated for their time with $75 in the form of an 
Amazon gift card, plus receive 3 additional months on Elix Cycle Balance after the study is complete 
(total value $200). 
 

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