Glutathione and Fuel Oxidation in Aging
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 21 - 80 |
| Updated: | 2/28/2019 |
| Start Date: | October 2012 |
| End Date: | December 2019 |
Glutathione is an important antioxidant protein which protects cells from harmful oxidative
stress. Elderly humans are known to have elevated oxidative stress and deficiency of
glutathione, but it is not known whether there is deficient synthesis of glutathione in
muscle tissue of elderly humans.
Mitochondria are engines of cells where food consumed is burned to make energy. Under normal
conditions the fuel of choice in the fasted state is fat, but fasted elderly humans are not
able to oxidize fat as well as healthy young humans. Elderly humans also have the highest
incidence and prevalence of being overweight and obese, and have increased storage of fat in
liver and muscle.
This study will help determine whether
1. elderly humans have diminished synthesis of glutathione in the skeletal muscle, and
whether this can be improved by supplementing cysteine and glycine (and not an
isonitrogenous placebo) in the diet;
2. improving muscle glutathione concentrations can also improve fuel oxidation in aging;
3. improvement of intracellular glutathione concentrations will be associated with a change
in total body fat content
stress. Elderly humans are known to have elevated oxidative stress and deficiency of
glutathione, but it is not known whether there is deficient synthesis of glutathione in
muscle tissue of elderly humans.
Mitochondria are engines of cells where food consumed is burned to make energy. Under normal
conditions the fuel of choice in the fasted state is fat, but fasted elderly humans are not
able to oxidize fat as well as healthy young humans. Elderly humans also have the highest
incidence and prevalence of being overweight and obese, and have increased storage of fat in
liver and muscle.
This study will help determine whether
1. elderly humans have diminished synthesis of glutathione in the skeletal muscle, and
whether this can be improved by supplementing cysteine and glycine (and not an
isonitrogenous placebo) in the diet;
2. improving muscle glutathione concentrations can also improve fuel oxidation in aging;
3. improvement of intracellular glutathione concentrations will be associated with a change
in total body fat content
Subjects will be recruited by written informed consent on forms approved by the Institutional
Review Board of Baylor College of Medicine at the time of approval of the full protocol.
Subjects taking an nonvitamin supplements or lipid lowering medications will stop this 4
weeks before the screening labs and for the entire duration of the study. Fasted subjects
will have screening labs (blood count, HbA1c, lipid profile, liver profile, blood urea
nitrogen, Creatinine, thyroid stimulating hormone, free t4, cortisol) followed by an oral
glucose tolerance test, measures of muscle strength by dynamometry, tests of function
(including a 6-min walk test) and body composition scans to measure total body fat. On
another occasion, fasted subjects will be undergo stable isotope infusions and other studies
in the metabolic research unit to measure concentrations of amino-acids and glutathione in
red blood cells and muscle tissue, glutathione synthesis rates in muscle and red cells,
plasma and whole-body mitochondrial fatty-acid oxidation, Kreb's cycle function, urine urea
nitrogen, plasma reactive oxygen species and F2-isoprostanes, genes of glutathione synthesis
and fuel oxidation. Elderly subjects will also have magnetic resonance spectroscopy scan for
liver and muscle fat content.
Young subjects will be given dietary cysteine and glycine for 2-weeks and be restudied
2-weeks later. They are then released from the study.
Elderly subjects will be studied for 16 weeks. They will be assigned to receive either
cysteine plus glycine, or alanine in a randomized, double-blinded study design. The studies
described above will be repeated after 2 weeks and 16 weeks. Subjects will have monthly
measures of liver profile, lipid profiles, BUN and creatinine and glutathione.
Review Board of Baylor College of Medicine at the time of approval of the full protocol.
Subjects taking an nonvitamin supplements or lipid lowering medications will stop this 4
weeks before the screening labs and for the entire duration of the study. Fasted subjects
will have screening labs (blood count, HbA1c, lipid profile, liver profile, blood urea
nitrogen, Creatinine, thyroid stimulating hormone, free t4, cortisol) followed by an oral
glucose tolerance test, measures of muscle strength by dynamometry, tests of function
(including a 6-min walk test) and body composition scans to measure total body fat. On
another occasion, fasted subjects will be undergo stable isotope infusions and other studies
in the metabolic research unit to measure concentrations of amino-acids and glutathione in
red blood cells and muscle tissue, glutathione synthesis rates in muscle and red cells,
plasma and whole-body mitochondrial fatty-acid oxidation, Kreb's cycle function, urine urea
nitrogen, plasma reactive oxygen species and F2-isoprostanes, genes of glutathione synthesis
and fuel oxidation. Elderly subjects will also have magnetic resonance spectroscopy scan for
liver and muscle fat content.
Young subjects will be given dietary cysteine and glycine for 2-weeks and be restudied
2-weeks later. They are then released from the study.
Elderly subjects will be studied for 16 weeks. They will be assigned to receive either
cysteine plus glycine, or alanine in a randomized, double-blinded study design. The studies
described above will be repeated after 2 weeks and 16 weeks. Subjects will have monthly
measures of liver profile, lipid profiles, BUN and creatinine and glutathione.
Inclusion Criteria:
1. Elderly subjects: age range 61-80y.
2. Young healthy subjects: age range 21-40y
Exclusion Criteria:
1. Renal impairment (serum creatinine >1.5 mg/dL)
2. Liver impairment (liver transaminases >2x upper limit of normal)
3. Untreated/uncontrolled hyperthyroidism or hypothyroidism
4. Known hypercortisolemia
5. Known diabetes mellitus
6. Hospitalization in the past 3 months
7. BMI <27 (elderly group)
8. Elderly women on estrogen replacement
9. Known pre-existing coronary artery disease
10. Fasted plasma triglyceride >300 mg/dl (on lipid lowering medications)
11. Fasted plasma triglyceride >500 mg/dl (off lipid lowering medications)
We found this trial at
1
site
1200 Moursund Street
Houston, Texas 77030
Houston, Texas 77030
(713) 798-4951
Principal Investigator: R V Sekhar, MD
Phone: 713-798-4951
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
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