The Influence of Daily Grapes Intake on Sarcopenia in Postmenopausal Women
Phase: NA
Conditions: Sarcopenia
Sponsor: University of California, Davis

 
 
 
 
The influence of daily grapes’ intake on 
sarcopenia in postmenopausal women 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Document date: 08/25/2022 
 

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
 
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1) Protocol Title 
The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
Protocol Version Date: 
This is a new IRB submission 
 
2) Objectives 
 
The objective of this project is to evaluate whether the daily consumption of a 
freeze-dried table grape powder, rich in phenolic compounds, mitigates sarcopenia in 
postmenopausal women. To achieve this objective, we will pursue the following aims: 
1. 
To determine the efficacy of a freeze-dried table grape powder, rich in phenolic 
compounds, to mitigate sarcopenia parameters in postmenopausal women. 
1. 
To evaluate the effect of a freeze-dried table grape powder on key metabolic 
regulators of sarcopenia in postmenopausal women, specially irisin. 
 
We hypothesize that daily dietary supplementation with a grape powder improves health 
span, mitigates sarcopenia parameters and increases irisin plasma levels in 
postmenopausal women. 
 
The successful completion of this pilot human study will provide evidence on the benefit 
of the daily addition of table grape to the diet of healthy older women to improve 
sarcopenia by regulating some key metabolic regulators. This will provide strong 
preliminary results to apply for competitive grant (USDA) in order to expand these findings 
using a bigger sample size, multiple doses and various time-periods. 
 
 
3) Background 
 
As stated above, sarcopenia is defined as a loss of muscle strength and mass in older 
individuals. However, until recently, there has been no widely accepted definition of 

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
 
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sarcopenia that was suitable for use in research and clinical. Sarcopenia leads to fragility 
and disability, worsens the prognosis of many diseases, and significantly enhances 
morbidity and mortality. Furthermore, a higher risk of death from all causes compared 
with non-sarcopenic subjects was found in > 60 years old and mainly in > 80 years old 
(13, 14). With the increasing life expectancy and rapid growth of the aged population, 
sarcopenia is becoming an emerging public health issue with huge socioeconomic 
burden.  
In recent years, various international consensuses have brought these fundamental 
concepts to the clinical practice. 
The European Working Group on 
Sarcopenia 
in 
Older 
People 
(EWGSOP) developed a practical 
clinical definition and consensus 
diagnostic criteria for age-related 
sarcopenia, recommending the 
use of the presence of both low 
muscle mass and low muscle 
function (strength or performance) 
for diagnosis. Recently, a new 
consensus 
(EWGSOP2) 
recommended 
low 
muscle 
strength as the primary parameter 
to assess sarcopenia and new 
cut-off points to increase harmonization of sarcopenia studies (15). 
Given the above, there is an ongoing intensive search for novel therapies, including 
dietary ones that can attenuate the loss of muscle mass and strength in the elderly (10, 
16). Interestingly, a growing body of research indicate that nutritional factors can preserve 
muscle function from age-related decline. In particular, phenolic compounds, widely 
distributed in fruits including grapes, have shown beneficial effects in muscle health (17, 
18). Phenolic compounds have garnered attention because they ability to alleviate 
disease pathologies through anti-inflammatory, anti-carcinogenic and antioxidant 
Figure 2: GPE supplementation 
activates 
the 
FNDC5/Irisin 
pathway  in skeletal muscle 
from rats fed a High Fat diet.  
Rats were fed a control diet (Ctrl), 
or a High fat diet without (HF) or 
with supplementation with GPE 
(HFGPE) for 6 weeks.  (A) 
Representative 
Western 
blot 
bands for PGC-1α and FNDC5 in 
total 
fractions 
isolated 
from 
skeletal muscle. (B) Bands were 
quantified, and results for PGC-1α 
and FNDC5 were normalized by 
β-actin levels (loading control). 
(C) Irisin plasma levels were 
determined by ELISA.  Data are 
presented as means ± SEM of 
seven animals/treatment. Values 
having different superscripts are 
significantly different (p < 0.05, 
one-way ANOVA).  

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
 
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properties. However, the exact influence of grapes and grapes phenolic compounds 
mitigating sarcopenia in humans remains unexplored.  
A novel and understudied mechanism by which skeletal muscle might mediate their 
protective effect against sarcopenia is by secreting myokines. Irisin is a myokine 
regulated by peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) 
and 
released 
into 
the 
bloodstream after cleavage 
of the Fibronectin type III 
domain-containing protein 
5 (FNDC5) (Fig 1.). Recent 
studies have indicated that 
circulating 
irisin 
can 
promote skeletal muscle 
growth (12, 19, 20). Lower 
irisin concentrations have 
been 
observed 
in 
sarcopenia patients (21) 
and dialyzed patients with 
cardiovascular 
disease 
(22). Furthermore, lower 
irisin plasma levels are 
associated with sarcopenia 
in postmenopausal women 
(10).  
In a recent study, we 
have shown that phenolic 
compounds present in a 
grape pomace extract (GPE), prevent irisin downregulation in rats fed a high-fat diet and 
in L6 myotube cells. In particular, we documented that consumption of the GPE activates 
the FNDC5/irisin pathway, with a significant increase of PGC-1α and FNDC5 protein 
Figure 3: EC activates the FNDC5/Irisin pathway in L6 myotubes. 
L6 myotubes were incubated without or with 1 µM (-)-Epicatechin (EC) 
in the absence or presence of palmitate for 24 h. (A) Representative 
Western blot bands for PGC-1α and FNDC5. (B) Bands were 
quantified, and results for PGC-1α and FNDC5 were normalized by β-
actin levels (loading control). (C) Irisin concentration in the cell culture 
media following treatment. (D) Representative immunofluorescent 
images for PGC-1α (green) and FNDC5 (red) in L6 myotubes. (B) 
Images were quantified, and results for PGC-1α and FNDC5 levels are 
displayed. For all experiments, data represent means ± SEM of three 
independent experiments. Values having different superscripts are 
significantly different (p < 0.05, one-way ANOVA).  

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levels compared to control and high fat diet groups (Figure 2A-B). Furthermore, 
supplementation with GPE led to the increase in irisin plasma level (Figure 2C)(11).  
In order to understand the underlying mechanism involved in the GPE-related irisin 
increased levels, we next evaluated the effects of epicatechin, one of the main flavonoids 
present in GPE, in L6 myotubes challenged with palmitate, to mimic a condition of fatty 
acids oversupply. Protein levels of PGC- 1α and FNDC5 were significantly higher in the 
EC and palmitate-treated cells, compared with palmitate-treated cells (Figure 3A-B). The 
same tendency was observed by immunocytochemical analysis of PGC-1α, while no 
differences were observed in FNDC5 fluorescence intensity among treatments (Figure 
3D-E). In addition, EC induced a 2-fold increase in irisin levels secreted to the medium 
compared with cells treated with only palmitate (Figure 3C). These data strongly indicate 
that phenolic compounds enhance irisin levels in vitro and in vivo.  
These intriguing data allow us to hypothesize that phenolic compounds present in 
grapes might have a positive effect in human health, specially preventing sarcopenia in 
elderly humans, in part, by increasing irisin levels. 
 
 
4) Enrollment Numbers 
 
We chose the “changes in plasma irisin levels” as our primary outcome to determine the 
power calculations for sample size. Based on our preliminary data (11), 5 individuals per 
group are required to reach 80% power to detect differences in irisin levels between the 
groups, at a a=0.05, using a two-sided paired T-test. We propose to enroll 7 individuals 
per group, instead of 5, in the event of a patient drop out of the study (for any unforeseen 
circumstances). In total we will have 14 subjects. 
 
 
5) Inclusion and Exclusion Criteria 
 

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Inclusion Criteria: postmenopausal women aged 60 years or older with a hand-grip 
strength media value of 16 kg or lower, normal body mass index (BMI) with values 
between 18.4 and 24.9 kg/m2, blood pressure below 130/80 mmHg, and plasma glucose 
and cholesterol concentrations below 100 and 200 mg/dl. 
 
Exclusion Criteria: history of specific muscle diseases, peripheral vascular disease, 
intermittent claudication, central and peripheral nervous system disorders, cachexia, 
active diagnosis of diabetes mellitus, myocardial infarction, stroke, liver disease, on 
dialysis or long-term steroid therapy, and/or actively receiving treatment for cancer or 
severe infection (excluding short-term antibiotic therapy), weight less than 140 pounds, 
anemia and blood donations in the past 30 days. In addition, participants should not be 
taking dietary supplements at the time of the study. 
 
6) Recruitment Methods 
We will recruit by: 1) posting flyers on campus bulletin boards; 2) listing the study on our 
departmental website that provides a list of all current departmental trials; 3) listing the 
study on campus list servers; 4) advertising in the local newspapers and 5) posting on 
social media. All recruitment material will use similar language and list a study office 
phone number, clinical coordinator email and the departmental website for clinical trials 
(Attachment A). Respondents will be contacted by phone and pre-screened. Information 
about the study will be provided during the phone interview (Attachment B). For subjects 
that are eligible and interested in enrolling in the study, an in-person screening visit 1 
appointment will be scheduled with the investigator or designee and the informed consent 
form emailed to them in advance. If the participants meet all the inclusion criteria, in the 
same visit the investigator or designee will review the informed consent form with the 
subjects, explain the study to the subjects and answer any questions prior signing the 
consent. Only once the informed consent form is signed, a diet history questionnaire 
(Attachment C) will be completed by the subjects.  
 
7) Compensation to the Subjects 
 
Subjects will be compensated at a rate roughly proportional to the inconvenience 

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incurred according to the following schedule: 
• Visit 0 (screening): $50 for inconvenience 
• Visit 1: $75 for inconvenience 
• Visit 2: $75 for inconvenience  
• Visit 3: $75 for inconvenience + $50 for study completion 
 
Subjects will be paid at the completion of their involvement in the study. The total 
compensation that a participant might earn is $325 for completion of all visits. Subjects 
that withdraw from the study early will be compensated based on the visit(s) they 
completed. 
8) Screening procedures to determine eligibility:  
 
After being pre-screened for eligibility by a phone interview, eligible potential participants 
will come to the Ragle Facility in a fasting (12 h) state for the in-person screening visit 0.  
In this visit the participants will sign an informed consent form. The subject will read the 
information carefully and will be given the opportunity to seek more information if needed. 
The investigator or designee will obtain written (signed and dated by the subject) informed 
consent from each potential participant after adequate explanation of the aims, methods 
and potential hazards of the study. The investigator or designee will also explain to the 
potential participant that his/her participation is voluntary, and he/she is free to withdraw 
from the study at any time. The investigator or designee will sign and date the consent 
form to confirm that the consent process was completed correctly. The subject will also 
be provided with the option of taking the consent form home to review prior to making 
his/her decision. The subject will be provided with a copy of his/her signed and dated 
consent form. Once consent has been obtained, the pre-screening visit will proceed. After 
the subject has signed the informed consent, an identification number (ID) will be 
assigned and entered the screening and enrollment log. A diet history questionnaire 
(Attachment C) will be complete by the participant. 
After this we will confirm if they meet the following inclusion criteria: 

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1- Hand-grip strength media value of 16 kg or lower: Handgrip strength will be evaluated 
by using a digital dynamometer (Grip Strength Dynamometer T.K.K.5401; Takei Co., 
Tokyo, Japan). Following are the steps of the procedure [a detailed procedure will be 
added (Attachment D)]: 
- 
The participant will be asked to seat comfortably in a standard chair with legs, back 
support and fixed arms.  
- 
The participant will be asked to rest their forearms on the arms of the chair with their 
wrist just over the end of the arm of the chair wrist in a neutral position, thumb facing 
upwards.  
- 
The person in charge of the test will demonstrate how to use the handgrip 
dynamometer. 
- 
The participant will be asked to start with the right hand.  
- 
The person in charge of the test will encourage the participant to squeeze as long 
and as tightly as possible or until the needle stops rising. Once the needle stops 
rising the participant can be instructed to stop squeezing.  
- 
The person in charge of the test will read grip strength in kilograms from the outside 
dial and record the result to the nearest 1 kg on the data entry form.  
- 
The person in charge of the test will ask the participant to repeat measurement in 
the left hand.  
- 
The participant will be asked to repeat two further measurements for each hand 
alternating sides to give three readings in total for each side.  
- 
The best of the 3 grip strength measurements will be use in statistical analyses to 
encourage the subjects to get as high a score as possible.  
- 
The person in charge will also record hand dominance, i.e. right, left or ambidextrous 
(people who can genuinely write with both hands).  
 
For those participants that meet the previous inclusion criteria the following parameters 
will be explore: 
1. 
Seated resting blood pressure. 
2. 
Weight and height.  

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3. 
A finger stick blood sample (~1-2 drop equal to ~ 100ul) will be collected to confirm 
that subjects meet the inclusion criteria for fasting levels of blood glucose and 
cholesterol, plus a hematocrit to discard anemia.  
 
 
Briefly, at Visit 0 (screening visit): 
• Subjects will arrive fasted for at least 12 h prior to this visit (water ok). 
• Informed consent will be obtained. 
• ID number will be assigned. 
• Hand grip strength test will be conduct. 
• Seated resting blood pressure will be measured. 
• Weight and height will be measured.  
• A finger stick blood sample (~1-2 drop equal to ~ 100ul) to confirm that subjects 
meet the inclusion criteria (glucose, cholesterols and hematocrit). 
• Diet history questionnaire (Attachment C) will be completed by the subjects to 
review medical history (including known positivity test for COVID-19), concomitant 
medications (including COVID-19 immunization dates), inclusion and exclusion 
criteria. 
• This visit will take approximately 2 h to complete 
 
9) Procedures Involved 
Schedule of procedures 
 
Visit 0  
Screening 
Visit 1 
Baseline  
Visit 2 
3-weeks 
visit 
Visit 3 
6-weeks 
final visit 
Informed consent 
X 
 
 
 
Inclusion / Exclusion criteria 
X 
 
 
 
Review medical history 
X 
 
 
 
Review concomitant medications 
X 
 
X 
 
Height, weight and blood 
pressure 
X 
X 
X 
X 
Finger stick  
 
X 
X 
X 
Hand grip strength test 
X 
X 
X 
X 
SPPB test 
 
X 
X 
X 

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Blood draws for plasma 
determinations  
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
Study product randomization 
 
X 
 
 
Study product intake 
 
 
X 
X 
Dispense study product for home 
 
X 
X 
 
Return unused study product and 
empty packages 
 
 
X 
X 
Dispense stool and urine 
collection kit 
 
X 
X 
 
Return stool and urine collection 
kit 
 
 
X 
X 
Adverse events assessment 
 
 
X 
X 
 
After confirmation of the inclusion/exclusion criteria enrolled subjects will be asked to 
travel to Ragle Human Nutrition Center at University of California Davis for 3 study visits: 
a baseline visit (visit 1), and a 3-week intervention visit (visit 2) and a final 6-week visit 
(visit 3) 
 
Visit 1 (baseline visit): 
On this visit, baseline measurement will be done. Fasted participants (12 h) will provide 
blood samples and complete two tests: 
Blood samples: from each participant 20 ml of blood will be extracted. The following 
parameters will be measured in plasma, (the same parameters will be measure in the 
following visits 2 and 3): 
Blood parameter 
Volume of blood needed 
Visit 1 
Visit 2 
Visit 3 
Irisin 
1200 ul 
x 
x 
x 
Glucose 
1000 ul 
x 
x 
x 
Insulin 
1200 ul 
x 
x 
x 
GLP-1/ 2, GIP 
2000 ul 
x 
x 
x 
Adiponectin, leptin and ghrelin 
3000 ul 
x 
x 
x 
Blood urea nitrogen, creatinine 
1000 ul 
x 
x 
x 
Total cholesterol, triglyceride, high-density lipoprotein 
(HDL), low-density lipoprotein 
2000 ul 
x 
x 
x 
Aspartate transaminase, Alanine transaminase 
2000 ul 
x 
x 
x 
IL-6, IL-15 
2000 ul 
x 
x 
x 
25-hydroxyvitamin D 
1000 ul 
x 
x 
x 
Hematocrit 
500 ul 
x 
x 
x 

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Total volume of blood per visit  
~ 20 ml 
20 ml 
20 ml 
20 ml 
 
After taking the blood samples a snack will be provide to the participants in order to 
complete the following tests. 
1. 
Hand-grip strength: previously describe in the screening point 
2. 
Short Physical Performance Battery (SPPB): the SPPB score will be based on 
three tests, as follows: balance test, gait speed test, and chair stand test (see 
Attachment E). Of note, these tests have been used as a predictive tool for 
possible disability and can aid in the monitoring of function in older people.  
 
Following, the subjects will randomize into the study supplement: a) Placebo powder (46 
g placebo powder in 180 ml of water); or b) freeze-dried table grape powder (46 g grape 
powder in 180 ml of water). The supplement will be supplied to the participants to 
complete the following 3 weeks supplementation until the next visit. The investigator or 
designee will explain the details regarding the preparation and consumption of the 
supplement [a dosing protocol will be uploaded too (Attachment F)].  
Also a 24-hs food and physical activity questionary will be performed  
 
Briefly, at visit 1: 
• Subjects will arrive fasted for at least 12 h prior to this visit (water ok). 
• A finger stick blood sample will be collected (to confirm fasting). 
• Concomitant medications and accomplishing of inclusion and exclusion criteria will 
be reviewed. 
• 24-hs food and physical activity questionary 
• Seated resting blood will be measured. 
• Weight will be measured. 
• Venous blood samples will be collected for analytical determinations (20 ml). 
• A hematocrit will be performed in order to discard anemia. 
• Snack ingestion 
• Hand grip strength and SPPB test will be completed. 

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• The supplement will be provided to the subjects for a 3 weeks supplementation 
period. 
• Stool and urine collection kit and a standardized log and instructions (Attachment 
G and H) will be provided to subjects. The kits will be returned at visit 2. 
 
Visit 2 (3-weeks visit): 
Subjects will return to the Ragle Facility for the follow-up visit. This visit will take 
approximately 2 h to complete. 
Briefly, at visit 2: 
• Subjects will arrive fasted for at least 12 h prior to this visit (water ok). 
• Subjects will provide fecal and urine samples collected with the collection kit. 
• A finger stick blood sample will be collected (~1 drop).  
• Concomitant medications and accomplishing of inclusion and exclusion criteria will 
be reviewed. 
• 24-hs food and physical activity questionary 
• Seated resting blood pressure will be measured. 
• Weight will be measured. 
• Subjects will take the assigned supplement. 
• Venous blood samples will be collected (20 ml). 
• A hematocrit will be performed in order to discard anemia. 
• Snack will be provided to the participants. 
• Hand grip strength and SPPB test will be completed.  
• Enough supplement will be provided to the subjects for a 3 weeks 
supplementation period. 
• Unused and empty packages of the study product will be return. 
• Stool and urine collection kit will be provided to subjects. The kits will be returned 
at visit 3. 
 
Visit 3 (final visit): 

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Subjects will return to the Ragle Facility for the final visit. This visit will also take 
approximately 2 h to complete. 
Briefly, at visit 3: 
• Subjects will arrive fasted for at least 12 h prior to this visit (water ok). 
• Subjects will provide fecal and urine samples collected with the collection kit. 
• A finger stick blood sample will be collected (~1 drop).  
• Concomitant medications and accomplishing of inclusion and exclusion criteria will 
be reviewed. 
• 24-hs food and physical activity questionary 
• Seated resting blood pressure will be measured. 
• Weight will be measured. 
• Subjects will take the assigned supplement. 
• Venous blood samples will be collected (20 ml). 
• A hematocrit will be performed in order to discard anemia. 
• Snack will be provided to the participants. 
• Hand grip strength and SPPB test will be completed.  
• Unused and empty packages of the study product will be return. 
 
10) Study Timelines 
 
Duration of individual subject’s participation will be ~6 weeks. The study will include: 1 
visit (visit 0) for the screening process that will last approximately 2 h and 3 more visits 
(visits 1, 2 and 3) for intervention process that will last approximately 2 h each. Visit 0 will 
involve an in-person screening to obtain written informed consent and determine if 
subjects meet the inclusion/exclusion criteria. Visit 1, 2 and 3 (at 0, 3 weeks and at the 
end of the 6 weeks, respectively) will include blood sample collection and tests 
performance. 
 
11) Study Endpoints 

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Primary endpoint:  
Hand-grip strength media value of 16 kg or lower 
 
Secondary endpoints: 
Levels of Irisin as a marker of sarcopenia 
Glucose, Insulin, GLP-1, GLP-2, GIP, Adiponectin, leptin and ghrelin, Blood urea 
nitrogen, creatinine, Aspartate transaminase, Alanine transaminase, Total cholesterol, 
triglyceride, high-density lipoprotein (HDL), low-density lipoprotein, IL-6, IL-15, 25-
hydroxyvitamin D as markers of general metabolism state.  
 
12) Data and/or Specimen Management and Confidentiality 
 
Data management: The de-identified data will be analyzed for statistical significance with 
the help of the Biostatistics group at UC Davis, including univariate graphical, analytic 
summaries and bivariate relationships using box plots, scatter plots, and correlations. To 
compare participants in the two diet groups (Placebo control and freeze-dried table grape 
powder) a paired Student’s t test (two-tailed) will be used. Data involving more than two 
repeated measures, such as grip strength tasks, or irisin levels, will be assessed by 
repeated measures (ANOVA).  Differences will be considered significant at P < 0.05. 
Significant results will be also subjected to analysis of covariance (ANCOVA) to account 
for group differences at baseline and post hoc comparisons using the Bonferroni 
correction. 
 
Data confidentiality: After obtaining written informed consent, all subjects will be assigned 
an identification number (ID) and all data and specimens will be collected from individuals 
and stored using this ID number. The key linking the subjects’ personal information to 
their laboratory results will be kept in a locked drawer in the investigator’s office. Only 
authorized research personnel will have access to the study data. People outside the 
research process will not have access to results about any one person. Staff analyzing 
the data will only have access samples identified by subjects’ ID number. The subjects’ 

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personal information (questionnaires and consent form) will be kept separately under lock 
and key in the investigator’s office 
 
 
13) Withdrawal of Subjects 
 
Possible reasons for removal include specific muscle diseases, peripheral vascular 
disease, intermittent claudication, central and peripheral nervous system disorders, 
cachexia, active diagnosis of diabetes mellitus, myocardial infarction, stroke, liver 
disease, on dialysis or long-term steroid therapy, and/or actively receiving treatment for 
cancer or severe infection (excluding short-term antibiotic therapy) that are diagnosed 
ones the subject are already enrolled in the study. If the participants start taking 
supplements. Also, if the participants experiment a remarkable increment in body weight, 
blood pressure and plasma glucose and cholesterol concentrations above 100 and 200 
mg/dl. Finally, development of anemia during the study will be another reason for removal.  
  
14) Risks to Subjects 
Venipuncture: Risks of venipuncture include some discomfort, bruising, and rarely, 
infection. Blood collections will be performed by a registered nurse to minimize 
discomfort.   
 
Blood volume: The amount of blood to be drawn during the study will be ~60 mL, collected 
over a period of 6-weeks. We will take a finger stick blood sample (~1 drop, equal to  
~100 ul) at visits 0,1, 2 and 3  and 20 mL/visit at visits 1, 2 and 3. These volumes are well 
within the recommended allocated volume for healthy adults. Nevertheless, the patients 
could experiment dizziness, nausea and physical weakness.  
  
Study products: The components of the dietary supplement and placebo are detailed in 
Attachment I and Attachment J, respectively. The dose that the participant will consume 
daily is the equivalent to a ~150 g (1.5 cups) of fresh grapes, which won’t represent a 
health risk for the participant  
 

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15) Potential Benefits to Subjects 
 
No direct benefits to the individual subjects are anticipated. However, subjects will receive 
general information regarding their overall health status.  
 
16) Provisions to Protect the Privacy Interests of Subjects 
 
Subjects will be assigned an identification number (ID) and all data and specimens will 
be collected and stored using this ID number. Personal information (name, phone number 
and email address) and consent forms will be kept in confidence and will be stored in a 
locked cabinet in the investigator’s office. The key linking the subjects’ personal 
information to their laboratory results will be kept separately in another locked drawer in 
the investigator’s office (See above for more on confidentiality).    
At the Ragle Facility, the subjects will interact with the study coordinator and trained 
research personnel. The data collection (anthropometry, blood pressure and 
venipuncture) will be performed in individual secluded rooms by trained research 
personnel. We will ensure that the subjects feel comfortable with all research procedures. 
Questions and interactions between the subjects and the research team will be kept 
private.   
 
17) Sharing of Results with Subjects 
Subjects will receive the results of their blood screen (once reviewed and approved) at 
the time of completion of the study (or early withdrawal). The research data will not be 
shared with the subjects, but a summary of the research can be provided to the subjects 
who express interest. 
 
18) Data/Specimen Banking 
All samples, including those sent out for outside analysis will have only a numerical 
identifier and date/time. Specimens to be stored on site will be kept frozen at -80°C in 
secure laboratories.  Specimens will be stored as long as they are viable for analyses; 
records of storage will be kept by the investigator’s lab staff; all records will be of the de-
identified specimens. During analyses, the de-identified data will be entered in Excel 

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files and analyzed for statistical significance using SAS in password protected 
computers.   
 
19) Multi-Site Research 
This is a single site study. 
 
20) Community-Based Participatory Research 
N/A 
 
21) Review Requirements 
Some research projects require specific IRB determinations. 
 
1. 
Are there any contractual obligations or other considerations that require IRB 
review of this research, or review at intervals other than those required by the 
Common Rule or FDA? 
☐ Yes 
☒ No 
 

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
Do not write below this line. For IRB stamp and version date only. 
 
 
1 
Title of research study: The influence of daily grapes intake on sarcopenia in 
postmenopausal women 
 
Investigator: Prof. Gerardo G. Mackenzie 
 
Why am I being invited to take part in a research study? 
We invite you to take part in this research study because we are looking for healthy 
postmenopausal women aged 60 years or older in order to study the effects of grapes on muscle 
health. 
 
What are my rights as a research subject? 
(Experimental Subject's Bill of Rights) 
 
Someone will explain this research study to you, including: 
1. 
The nature and purpose of the research study. 
2. 
The procedures to be followed. 
3. 
Supplement to be used. 
4. 
Any common or important discomforts and risks. 
5. 
Any benefits you might expect. 
6. 
Other procedures and their risks and benefits compared to this study. 
7. 
Whether or not you take part is up to you. 
8. 
You can choose without force, fraud, deceit, duress, coercion, or undue influence. 
9. 
You can choose not to take part. 
10. 
You can agree to take part now and later change your mind. 
11. 
Whatever you decide it will not be held against you. 
12. 
You can ask all the questions you want before you decide. 
13. 
If you agree to take part, you will be given a signed and dated copy of this document. 
 
 
How is this research funded? 
This research is being funded by California Table Grape Commission. 

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
Do not write below this line. For IRB stamp and version date only. 
 
 
2 
Who can I talk to? 
If you have questions, concerns, or complaints, or think the research has hurt you, you may talk 
to the research director: Prof. Gerardo Mackenzie 530-752-2140 
This research has been reviewed by an Institutional Review Board (IRB). Information to help you 
understand research is on-line at https://research.ucdavis.edu/policiescompliance/irb- admin. 
You may talk to a IRB staff member by phone: (916) 703-9158, by email: hs- 
irbeducation@ucdavis.edu, or by mail: 2921 Stockton Blvd, Suite 1400, Room 1429, 
Sacramento, CA 95817 for any of the following: 
 
Your questions, concerns, or complaints are not being answered by the research 
team.  
You cannot reach the research team. 
You want to talk to someone other than the research 
team.  
You have questions about your rights as a research 
subject.  
You want to get information or give input about this 
research. 
 
Why is this research being done? 
 
The purpose of the study is to assess the consumption of freeze-dried table grape powder on 
the muscle strength of post-menopausal women. 
 
How long will the research last? 
We expect that you will be in this research study for about 6 weeks. During the 6 weeks you will 
be asked to consume daily a beverage containing either: (A) Placebo powder (46 g placebo 
powder in 180 ml of water, equal to about 6 ounces); or (B) freeze-dried table grape powder (46 
g freeze-dried table grape powder in 180 ml of water, equal to about 6 ounces). In addition, we 
will ask you to come to 4 visits of about 2 hours each: a screening visit (visit # 0), a baseline visit 

Study: The influence of daily grapes’ intake on sarcopenia in postmenopausal women 
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(visit # 1) a mid-term visit (3 weeks, visit # 2: data and sample collection) and a final visit (6 
weeks, visit # 3: data and sample collection) 
 
How many people will be studied? 
We expect about 14 people to complete the research study. 
 
What happens if I say yes, I want to be in this research? 
If you decide to participate in this research study, you will be asked to complete this visit (visit 0) 
and 3 extra study visits scheduled as follows: 
 
Visit 0 
Visit 1 
Visit 2 
Visit 3 
Today 
Screening visit 
Baseline visit 
 
Week 0 
Follow up visit 
 
Week 3 
Final visit 
 
Week 6 
 
 
Below, we describe the procedures and commitments that are required for this study: 
 
At visit 0 (screening visit): 
 
• You will be asked to stop consuming food or beverages for at least 12 hours the day 
before of this visit (we have explained this to you in the telephone screening). During 
this fasting period, you will be able to drink as much water as you need. 
• You will arrive to the Ragle Facility fasted. 
 
• You will remain at the Ragle Facility for the duration of this visit (about 2 hours). 
 
• You will read and sign the informed consent. 
 
• You will perform a hand grip strength test (explained below). 
• Resting blood pressure will be measured. 
• Weight and height will be measured. 
• A finger stick blood sample will be taken (about 1-2 drops) to confirm if you meet the 

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inclusion criteria for fasting levels of blood glucose, cholesterol, and hematocrit. 
• You will complete a diet history questionnaire, concomitant medications (including 
COVID-19 immunization dates), inclusion and exclusion criteria. 
 
At visit 1 (baseline visit): 
 
• You will not consume any food or beverages for at least 12 hours the day before 
your visit. During this fasting period, you may drink as much water as you wish. 
• You will arrive to the Ragle Facility fasted. 
 
• You will remain at the Ragle Facility for the duration of this visit (about 2 hours). 
 
• A finger stick blood sample (about 1 drop) will be collected upon arrival to confirm you are 
fasting. If you are not sufficiently fasted, you will be asked to reschedule the visit for a 
future day. 
• We will check the medications you take and whether you meet the inclusion and exclusion 
criteria. 
• We will perform a 24-hs food and exercise questionary. 
• Blood pressure will be measured. 
• Weight will be measured. 
• A blood sample will be collected (20 ml, equal to about 1.5 tablespoon) in order to measure 
the parameters that we will study. 
• A snack will be provided to you. 
• Hand grip strength and Short Physical Performance Battery (SPPB) test will be completed 
(both explained below). 
• We will provide you with the study product to consume for the next 3 weeks. 
• You also will receive a stool and urine collection kit and instructions in order to collect 
samples that you will bring to the next visit. You will be asked to collect a stool sample 
within 16 hours before visit 2 and to bring the container with sample on the day of visit. 
For urine collection you will fill a 120 ml cup (we will provide the cup and instructions) 
with the first urine of the morning from the same day of visit 2. Both samples can be 

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kept in the fridge until the visit. We will repeat this at the following visit, so in total you 
will provide 1 sample of urine and 1 sample of stool twice during the protocol. 
 
At visit 2 (Follow-up visit week 3): 
 
 
• You will not consume food or beverages for at least 12 hours the day before your 
visit. During this fasting period, you may drink as much water as you wish. 
• You will arrive to the Ragle Facility fasted. 
 
• You will remain at the Ragle Facility for the duration of this visit (about 2 hours). 
 
• A finger stick blood sample (about 1 drop) will be collected upon arrival to confirm you are 
fasting. If you are not sufficiently fasted, you will be asked to reschedule the visit for a 
future day. 
• You will provide the fecal and urine samples that you collected the night before and that 
morning, respectively. 
• We will check the medications you take and whether you meet the inclusion and exclusion 
criteria. 
• We will perform a 24-hs food and exercise questionary. 
• Blood pressure will be measured. 
• Weight will be measured. 
• A blood sample will be collected (20 ml, equal to about 1.5 tablespoon). 
• A snack will be provided to you. 
• We will measure your hand grip strength and an SPPB test will be completed. 
• We will provide you with more study product for the final 3 weeks.  
• You will return the empty packages of study product consumed in the last 3 weeks. 
• 
We will provide you with new stool and urine collection kits and you will be asked to bring 
the samples to the next visit. 
At visit 3 (Final visit week 6): 
 

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• You will not consume any food or beverages for at least 12 hours the day before 
your visit. During this fasting period, you may drink as much water as you wish.You 
will arrive to the Ragle Facility fasted. 
 
• You will remain at the Ragle Facility for the duration of this visit (about 2 hours). 
 
• A finger stick blood sample (about 1 drop) will be collected upon arrival to confirm you are 
fasting. If you are not sufficiently fasted, you will be asked to reschedule the visit for a 
future day. 
• You will provide fecal and urine samples that you collected the night before and that 
morning, respectively. 
• We will check your medications and whether you meet the inclusion and exclusion 
criteria. 
• We will perform a 24-hs food and exercise questionary. 
• Blood pressure will be measured. 
• Weight will be measured. 
• Blood samples will be collected (20 ml, equal to about 1.5 tablespoon). 
• A snack will be provided to you. 
• We will measure your hand grip strength and an SPPB test will be completed. 
• You will return the unused study product and the empty packages of study product 
consumed in the last 3 weeks. 
 
 
Starting from visit 1 and throughout the study, we will also ask you to limit the consumption of 
some foods that contain high concentrations of polyphenols. We will ask you to limit your 
consumption of blueberries, blackberries, bilberries, cherries, grapes, grape juice, pomegranate, 
raspberries, huckleberries, strawberries to less than ½ cup per day.  We will also ask you to 
drink less than 1 glass of red wine, and less than 3 cups of tea or coffee, and to consume less 
than 10 g (about 0.35 ounces) of chocolate per day. 
On each visit you will be asked to perform a handgrip strength test as follows: you will be asked 

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to sit comfortably in a standard chair with legs, back support, and fixed arms. An assistant will 
show you how to use the handgrip dynamometer.  You will be encouraged to squeeze the 
dynamometer as long and as tightly as possible or until the needle stops rising. We will measure 
your hand strength in both hands 3 times.   At visits 1, 2 and 3 you will also be asked to 
perform an SPPB test,  which is based on three easy tests: (1) A balance test: you will be asked 
first to stand with your feet together, side-by-side, for about 10 seconds, then to stand with the 
side of the heel of one foot touching the big toe of the other foot for about 10 seconds,  and finally 
to stand with the heel of one foot in front of and touching the toes of the other foot for about 10 
seconds. (2) A gait speed test: you will be asked to twice walk to the other end of the course at 
your usual speed, just as if you were walking down the street to go to the store. (3) A chair stand 
test: you will be asked to stand up from a chair without using your arms 6 times. 
 
For the study visits you will go to the Ragle Human Nutrition Center at University of California 
Davis. During the visit 0 screening process, the investigator or designee will read and explain to 
you all the details of the study.  You may ask all the questions you may have about the study.  If 
you agree with all the terms and have received answers to all your questions, you will be asked 
to sign the informed consent form. An identification number (ID) will be assigned for you. You 
will be asked to complete a diet history questionnaire. We will then measure your resting blood 
pressure, weight and height, and a blood sample will be collected to confirm that you meet the 
inclusion criteria for fasting levels of blood glucose, cholesterol, and hematocrit. Once you are 
enrolled in the study, you will be randomly assigned to two different supplement groups, 
consuming either a placebo powder (46 g placebo powder); or a freeze-dried table grape 
powder (46 g grape powder). The group will be chosen by chance, like flipping a coin. Neither 
you nor the study investigator will choose what supplement you will get. You will have an equal 
chance of being in either group. The study product will be provided to you during visits 1 and 2 
and you will be asked to consume it every day for 6 weeks by dissolving it in 180 ml of water 
(about 6 ounces). We will provide you with the supplement in powdered form in an appropriate 
container and you will be asked to reconstitute the powder with water in a glass/container and 
then mix it and consume it within 30 min from reconstitution. 

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What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible to: 
 
1. 
Follow the procedures in preparation for the study visits. 
2. 
Participate in 4 study visits of about 2 hours each. 
3. 
Complete a health and habits questionnaire. 
4. 
Take the study supplement daily. 
5. 
Provide blood samples: 20 ml, equal to about 1.5 tablespoon,  at visits 1, 2 and 3. 
6. 
Provide a finger stick blood sample (about 1 drop) at visits 0, 1, 2 and 3. 
7. 
Perform the hand grip test at visits 0,1, 2 and 3 and the SPPB test at visits1, 2 and 3. 
8. 
Perform the stool and urine sample collection. 
9. 
Follow the diet restrictions that we detailed for you. 
 
What happens if I do not want to be in this research? 
You may decide not to take part in the research and it will not be held against you. 
 
What happens if I say yes, but I change my mind later? 
You can leave the research at any time and it will not be held against you. 
 
If you decide to leave the research, contact the investigator so that the investigator can be aware 
of that. 
If you stop being in the research, already collected data may not be removed from the study 
database. 
 
Is there any way being in this study could be bad for me? 
This is a minimal risk research study. That means that the risks of participating are no more 
likely or serious than those you encounter in everyday activities. The possible risks or 
discomforts include: 

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1. 
Blood drawing can result in bruising, mild discomfort, and rarely, an infection where the 
needle enters the skin. There is also a possibility of dizziness, nausea, and physical 
weakness. 
2. 
The supplement is a lyophilizate powder made with fresh grapes. You could experience 
some minor intestinal discomfort related to ingestion of the grape powder. 
3. 
If you have food allergies associated with any ingredients in the study products, you 
should inform the study staff so that your health is not put at risk. Food allergies can be 
dangerous.  You should not participate in this study if you have specific food allergies 
associated with the components in the study supplement. 
4. 
Loss of confidentiality is a potential risk; however, every measure will be taken to ensure 
that your protected health information is kept safe. Study records are kept behind 
locked doors and on secure servers to which only a limited number of trained study staff 
members have access. 
 
Will being in this study help me in any way? 
We cannot promise any benefits to you from your taking part in this research. 
 
What happens to the information collected for the research? 
Efforts will be made to limit use or disclosure of your personal information, including research 
study and medical records, to people who have a need to review this information. We cannot 
promise complete confidentiality. Organizations that may inspect and copy your information 
include the IRB, the California Table Grape Commission, and other University of California 
representatives responsible for the management or oversight of this study 
If you agree to participate in this research study, a signed copy of this consent document and 
the privacy authorization form may be filed in your electronic medical record (EMR) and your 
study participation may be added to your EMR. This information will be used for your care and 
for healthcare operations, which may include billing and payment. Federal and state privacy laws 
give patients the right to access information about their care and study contained in their medical 
record. During this study, you may not be able to access certain information related to this study 

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in your EMR until the study is complete to ensure that the study remains unbiased. By consenting 
to participate in this study, you are also consenting to this possible temporary withholding of your 
research records. 
The sponsor, monitors, and auditors will be given direct access to your research records to run 
and oversee the study. We may publish the results of this research. However, we will keep your 
name and other identifying information confidential. In addition, the IRB and the Food and Drug 
Administration (FDA) will be given direct access to your research records to ensure proper 
oversight of the study. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
 
Can I be removed from the research without my OK? 
The person in charge of the research study or the sponsor can remove you from the research 
study without your approval. Possible reasons for removal include: Specific muscle diseases, 
peripheral vascular disease, intermittent claudication, central and peripheral nervous system 
disorders, cachexia, active diagnosis of diabetes mellitus, myocardial infarction, stroke, liver 
disease, on dialysis or long-term steroid therapy, and/or actively receiving treatment for cancer 
or severe infection (excluding short-term antibiotic therapy) that are diagnosed after the subject 
is already enrolled in the study. You may also be removed if you start taking supplements after 
the start of the study, if you develop anemia, if you experience a remarkable change in body 
weight, blood pressure, glucose or cholesterol plasma levels, or you make any blood donations 
within 30 days before the start of the study. 
 
What else do I need to know? 
There is no charge for you to take part in this study. Neither you nor your insurance carrier will 
be charged for your taking part in the research. All costs associated with the study will be paid 
by the sponsor/department. 

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If you are injured as a result of being in this study, the University of California will provide the 
necessary medical treatment. Depending on the circumstances, the costs of the treatment may 
be covered by the University or the study sponsor or may be billed to your insurance company 
just like other medical costs. 
Due to the coronavirus public health crisis, the federal government issued a Declaration under 
the Public Readiness and Emergency Preparedness (PREP) Act. If the Declaration applies, it 
limits your right to sue and recover for losses from the researchers, healthcare providers, any 
study sponsor or manufacturer or distributor involved with the study, including the University of 
California, while participating in this clinical study. However, the federal government has a 
program that may provide compensation to you or your family for certain claims if you experience 
serious physical injuries or death and these costs are not covered by other payors. To find out 
more 
about 
this 
“Countermeasures 
Injury 
Compensation 
Program” 
go 
to 
https://www.hrsa.gov/cicp/about/index.html or call 1-855-266-2427. 
 
Will I be paid or receive anything for being in this study? 
We will pay you a total $325 if you complete the full study.  If you leave the study early, we will 
pay you the following prorated amounts for each visit of the study you complete:  
• Visit 0 (screening): $50 
• Visit 1: $75  
• Visit 2: $75  
• Visit 3: $75 + $50 for study completion 
 
You may be asked for your social security number for payment purposes. It will not be used for 
any other reason without your permission.  
 
If you receive $600 or more during a calendar year from the University for taking part in research, 
you may receive a 1099 for tax reporting purposes. Reimbursements for travel and other 
expenses are not included in this amount. 

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Biospecimens (such as blood, urine, and stool) collected from you for this study and/or 
information obtained from your biospecimens may be used in this research or other research 
and shared with other organizations. You will not share in any commercial value or profit derived 
from the use of your biospecimens and/or information obtained from them. 
 
Are there other research opportunities? 
 
 
If you are interested in being contacted for future research, please write your phone number 
and/or email. This is completely optional. 
 
(initials) Yes, I am willing to be contacted for future research studies. My phone number 
and/or email is:  
. 
 
Signature Block for Capable Adult 
Your signature documents your permission to take part in this research. 
 
 
 
Signature of subject 
Date 
 
 
 
Printed name of subject 
 
 
 
Signature of person obtaining consent 
Date 
 
 
 
Printed name of person obtaining consent 
 
 
 
 
Assigned participant ID#:__________________ 
 

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