Study Population:
Healthy, postmenopausal (> 1 year from last menstrual cycle) adult females (at birth), >
55 years of age with obesity (≥ 30 BMI)
Objectives/Purpose of the Study:
Worldwide rates of obesity increased from 100 million to 764 million between 1980 and
2021. During the same time frame, a five-fold increase in Type 2 diabetes (T2DM) was
reported. Increases were similar across the globe with older individuals at greatest risk
of obesity and related metabolic dysfunction. Central obesity is well known to be both a
manifestation and driver of metabolic syndrome with similar prevalence worldwide. Older,
post-menopausal females, in particular, are at increased risk of developing central
obesity due to a reduction in endogenous ovarian hormone production. Novel multi-modal
therapies are needed to address central obesity-related metabolic dysfunction in
post-menopausal females. However, current therapeutic methods lack specificity and
propose universal solutions to a multi-factorial disorder requiring an individualized,
precision medicine approach. More concerning, is the lack of rigorous, scientific
evidence to support conventional dietary therapies for reducing aging-related central
obesity and associated metabolic dysfunction. Targeting multiple biological pathways that
are related to individual behavioral determinants (caloric intake) and biological aging
markers (estrogen levels) may identify more precise therapies in post-menopausal female
adults with obesity.
Recently, advanced glycation end-products (AGEs) were identified as potential drivers of
obesity-related impaired metabolic function. In a series of in vitro and in vivo
experiments, a combination of GRAS compounds that function synergistically to improve
metabolic health and extend lifespan [(alpha lipoic acid, pyridoxamine, nicotinamide,
piperine and thiamine (i.e. GLY-LOW)] were examined. Supplementation with GLY-LOW was
shown to detoxify methylglyoxal (MGO), a reactive precursor to AGEs. In addition, GLY-LOW
supplementation reduced caloric intake and glycolysis, reprogramed metabolism, and
increased insulin sensitivity and mTor signaling in the hypothalamus of the mice. In
female animals GLY-LOW supplementation reversed aging-related declines in estrogen and
related female hormones. Studies in humans are needed to translate these findings and
explore the feasibility, utility and efficacy of GLY-LOW supplementation in
post-menopausal women with obesity toward improving aging-related impairments. These
include increased metabolic disease risk and insufficiency, impaired physical function,
osteoporosis, reduced fitness levels, cognitive impairment, systemic inflammation and
premature biological aging. Interestingly, results of a novel biological aging
assessment, retina scan, were recently shown to be associated with metabolic dysfunction
via inflammatory pathways. The effect of GLY-LOW supplementation on these obesity and
biological age-related impairments in post-menopausal adult female humans with obesity is
unknown.
Study Site:
The Hoskinson Health and Wellness Clinic (HHWC) focuses on your whole health for your
whole life, and provides a proactive, not reactive, personalized and integrated,
multi-component solution to age-related increases in obesity and associated declines in
metabolic health. The HHWC utilizes functional, precision medicine to identify unhealthy
aging biomarkers and genetic vulnerabilities, and innovative medical technology to both
diagnose and manage aging-related metabolic, physical and cognitive impairments.
State-of-the-art assessments identify targets for tailored programming including diet
instruction, nutrition education and supplementation, fitness counseling and training.
The HHWC proposes to conduct a series of clinical studies using these state-of-the-art
measures of aging-related parameters. Initially, we aim to translate the findings of
GLY-LOW supplementation in animals to a cohort of healthy, postmenopausal females at
birth with obesity by conducting a one-group, no-placebo comparer, pre post intervention
clinical trial. Additionally, we propose to examine the specific effect of
supplementation by GLY-LOW on biological aging via retina scan. The objectives of the
proposed pilot study are:
I. Conduct a 6-month pilot study to examine the feasibility, utility and efficacy of
GLY-LOW supplementation in a total of 40 postmenopausal female born adults > 55 years
with obesity (≥ 30 BMI)
Ia. Examine alterations in self-reported caloric intake and the following health and
biological aging, parameters prior to and after 6 months of GLY-LOW supplementation:
Self-reported Caloric Intake
Metabolic disease risk
Cardiovascular disease risk
Metabolic assessments
Hormones
Physical Function and Fitness
Muscular strength
Cognitive Function and Depression assessments
Systemic inflammation
Biological aging
Safety parameters (also every 2 months during the intervention; ECG at baseline and
2 months only)
Compliance measures (pill counts and interviews every 2 months during the
intervention)
Trial Design:
One group, no-placebo comparer, pre post intervention clinical trial
Randomization and Blinding:
The one group, no-placebo comparer pilot study will not require randomization. Study data
managers and biostatisticians will be blinded to basic demographic and clinical
characteristics (e.g. female, postmenopausal) of the study population and the overall
purpose of the trial.
Initial Recruitment/Screening, Enrollment, and Baseline Evaluation:
Recruitment, screening and enrollment will occur during the first eight weeks of the
study. Approximately 40 participants will be screened and enrolled into the study.
Participation in the baseline evaluation will occur during weeks 9-12. Recruitment will
be by referrals, personal interview, brochure mail-outs to area physicians, community
center flyers and presentations, presentations at civic meetings, mass media
announcements, social media posts, as well as clinic screenings as currently used in our
existing studies and clinical services at the Hoskinson Health and Wellness Center. The
plan is described below:
Potential study participants will be provided with a general information handout or
link to our website regarding the study and contact information for participation.
Study personnel will receive phone, email inquiries or website inquiries and conduct
a pre-screening interview and complete a checklist to determine eligibility.
Study personnel and/or other medical staff will then conduct the IRB-approved
informed consent procedures and begin the screening process for study participants.
An explanation of all procedures, potential risks, temporary side effects,
anticipated benefits, and alternative methods (nutrition and fitness counseling,
weight loss pharmaceuticals or nutraceuticals, other anti-aging therapeutics) will
be given to the study participant. Confidentiality is assured as well as the right
not to participate or to withdraw at any time. The signature of the study
participant will be obtained on the consent form. A copy of the forms will be given
to each study participant. Assurance that all questions have been answered about the
study testing is obtained from the participants. Names and telephone numbers of
contact persons on the medical team are given to each study participant for use if
future questions arise.
General health screenings will then be performed by qualified medical staff. A
medical physical evaluation to verify eligibility will be performed at the
intervention baseline visits and a list of current medications will be required.
After clearance by the study physician, the study participant will receive the first
set of baseline measurements The study coordinator will schedule the second day of
baseline measurements with the study participant. The study participant will be
advised to fast for at least 12 hours prior to the second day of baseline testing
Treatment, Dosage and Dosing regimen of the GLY-LOW supplement:
This supplement is available for over-the-counter purchase. Each capsule is a combination
of vitamins and natural products: Vitamin B1 (100mg); Vitamin B6 (50mg); Niacin (200mg);
Alpha Lipoic Acid (150mg); and Piperine (15mg). Each participant will take this
supplement daily in a pill form orally once in the morning. The test product will be two
capsules a day with breakfast between 7:00 - 11:00 AM. The chosen doses were based on
dose conversion from mice to humans and the prior data on safety for each of the
compounds in humans.
Expected Duration of Subject Participation:
34 weeks
Available Alternative Treatments:
Available alternative treatments offered at the HHWC include nutrition and fitness
counseling, weight loss pharmaceuticals or nutraceuticals, other anti-aging therapeutics.
Study participants will be provided with information concerning these alternative
treatment therapies during the consent procedures.
Follow-up Assessments:
The study participant will attend a follow-up safety assessment visit every two
months and will participate in blood tests and MSQ. ECG will be assessed at baseline
and 2 months only.
The study participants will attend one follow-up assessment after 6 months of
receiving the study supplement (GLY-LOW). Baseline measurements will be repeated
during these follow-up assessments in order to examine the effectiveness of the
intervention.