The Effect of AyuFlex® Supplementation on Joint Health
The Effect of AyuFlex® Supplementation on Joint Health
The purpose of this 12-week, prospective study is to determine the effects of oral
 supplementation with AyuFlex® (an over-the-counter dietary supplement) on joint mobility,
 joint comfort and functional capacity in healthy overweight subjects.
This interventional study is a 12-week, randomized, double-blind, placebo and dose-response
 controlled clinical trial (in 3 parallel groups) of male and female subjects without active
 osteoarthritis of the knee to be recruited at a single investigational center in the U.S. A
 two-week placebo lead-in period will precede the study to enhance statistical power.
 One-hundred and five (105) overweight, apparently healthy subjects, pre-screened using health
 history questionnaires, vital signs, blood work and a standardized lower extremity exercise
 performance test will be randomized to one of three groups for 84 days: placebo, AyuFlex1
 (500 mg/d) or AyuFlex2 (1000 mg/d). AyuFlex is an organic, non-GMO, over-the-counter joint
 health product derived from the edible fruits of Terminalia chebula.
Inclusion Criteria:

 -  Healthy male or female volunteers >35 to <70 years of age.

 -  Non-smoker.

 -  Body Mass Index (BMI) greater than 30 kg/m2 and less than 45 kg/m2 at screening.

 -  Willing to maintain current background dietary and physical activity pattern
 throughout study period.

 -  Knee joint:

 -  No knee joint discomfort at rest.

 -  Experience knee joint discomfort with activity or exercise within the last 2
 weeks of at least 30 mm out of 100mm on VAS rating for "knee discomfort with
 activity or exercise at any time over the last 3 weeks".

 -  Must achieve a rating of at least 30mm on a 100mm VAS at any point throughout the
 standardized lower extremity exercise performance screening test (Screening test
 = 3 sets of 10-12 repetitions on seated knee extension machine + 3-minute walk
 test at maximal walking velocity).

 -  Non-pregnant, non-lactating females who agree to use effective contraceptive methods
 throughout the course of the study.

 -  Females of childbearing potential must agree to use one of the following acceptable
 birth control methods:

 1. Surgically sterile (hysterectomy or bilateral oophorectomy);

 2. Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior
 to study initiation);

 3. Intrauterine device (IUD) in place for at least 3 months;

 4. Abstinence (not having sexual intercourse);

 5. Barrier method (condom or diaphragm) with spermicide for at least 14 days prior
 to screening and through study completion;

 6. Vasectomized partner.

 -  Able to understand study procedures and provide signed informed consent, and
 authorizes release of relevant health information to study investigator.

 -  Normally active and otherwise judged to be in good health on the basis of medical
 history and physical examination.

 -  Females of childbearing potential must have a negative urine pregnancy test at
 screening.

 Exclusion Criteria:

 -  Subjects with an established diagnosis of inflammatory joint disorder or
 osteoarthritis per ACR (American College of Rheumatology) guidelines.

 -  Currently taking, or chronic use within 30 days of anti-inflammatory supplements,
 Boswellia, Curcumin, Omega-3 fatty acids, Glucosamine, Chondroitin, MSM, or Collagen
 supplements of any type.

 -  Daily use of NSAIDs (non-steroidal anti-inflammatory drugs); however, daily use of 81
 mg of aspirin (not > 81 mg) for cardioprotection is allowed.

 -  Upon physical screening by the medical staff, any subject with signs of overt nutrient
 deficiencies or metabolic abnormalities such as anemia. This will also need to be
 included in the screening assessment.

 -  Subjects with a history of knee or hip joint replacement surgery, or any hip or back
 pain which interferes with walking or exercise testing utilized throughout the study.

 -  Glucocorticoid (Corticosteroid) injection, hyaluronic acid injection, prolotherapy, or
 PRP (platelet rich plasma) injection, bone marrow or other regenerative injection in
 affected knee within 6 months prior to enrollment in study.

 -  Individual has any recent illness or condition (within 6 months of screening) that the
 Investigator believes would interfere with his or her ability to provide informed
 consent, comply with the study protocol, or might confound the interpretation of the
 study results or put the person at undue risk.

 -  Known or suspected pregnancy, planned pregnancy, or lactation.

 -  If the subjects has been treated for any psychiatric illness or hospitalized for such
 within the past year, upon PI discretion, will be excluded from the study.

 -  History of allergic reaction or known sensitivity to Terminalia chebula or other
 chemically related botanical/ herbal products or supplements.

 -  Any food allergy, intolerance, restriction or special diet that, in the opinion of the
 Investigator, could contraindicate the subject's participation in this study.

 -  Vital sign abnormalities (seated, resting systolic blood pressure lower than 90 or
 higher than 150 mmHg, diastolic blood pressure lower than 50 or higher than 100 mmHg,
 or heart rate less than 50 or more than 110 bpm) at screening.

 -  History or clinically significant gastrointestinal disorder, (eg, inflammatory bowel
 diseases), presence of any gastrointestinal pathology, persistent gastrointestinal
 symptoms (eg, diarrhea, vomiting), liver or kidney disease, gastric bypass, gastric
 stapling, use of Lapband, or other conditions known to interfere with the absorption,
 distribution, metabolism, or excretion of dietary supplements.

 -  History of active neurological, endocrine, cardiovascular, pulmonary, hematological,
 immunologic/ autoimmune, psychiatric, or metabolic disease that is considered
 clinically significant by the PI.

 -  Recent history of (within past 12 months), or strong potential for, alcohol or
 substance abuse. Alcohol abuse will be defined as >14 drinks per week (1 drink = 12 oz
 beer, 5.0 oz wine, or 1.5 oz distilled spirits).

 -  Exposure to any investigational agent or drug product within 30 days prior to study
 entry.

 -  Subjects who have any physical disability which could interfere with their ability to
 perform the functional performance measures included in this protocol.

 -  Individual has a condition the Investigator believes would interfere with the ability
 to provide informed consent or comply with study instructions, or that might confound
 the interpretation of the study results or put the patient at undue risk.