Practicality of Intermittent Fasting and Its Effect on Markers of Aging and Oxidative Stress

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT02132091
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute on Aging (NIA) (NIH)
• Enrollment: 37
• Location: 1
• Arms: 2
• Duration (Months): 8
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

Healthy volunteers will be recruited to participate in a ten-week double-blinded crossover trial. The trial will consist of two, three-week periods of intermittent fasting, where subjects receive either antioxidant supplementation or placebo, the ordering of which will be randomly determined. A one-week preconditioning will precede each invention period, and a two week "wash-out" period will follow the first intervention period. Serum-based assays will be performed to assess levels of reactive oxidant species, antioxidant genes, sirtuins, and markers of mitochondrial biogenesis and aging.

The investigators hypothesize that an intermittent fasting diet in healthy young volunteers will improve these markers of cellular aging and that these beneficial effects will be abrogated by the supplementation of antioxidants. This study is a proof-of-principle study that will shed light on the mechanism and effects of IF as an anti-aging dietary intervention in the absence of weight loss. It will inform the design of dietary interventions that are both effective in improving markers of aging and feasible for patients to practice on a long-term basis.

Condition or Disease	Intervention/Treatment	Phase
Aging; Metabolism	Other: Intermittent Fasting; Dietary Supplement: 400 IU Vitamin E; Dietary Supplement: 1000 mg Vitamin C	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Effect of Intermittent Fasting on Adaptive Oxidative Stress Response and Mitochondrial Biogenesis
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intermittent Fasting Intermittent Fasting	Other: Intermittent Fasting; The intermittent fasting paradigm used in this study will require participants to alternate between days of feasting (175% of normal caloric intake) and fasting ( 25% of normal caloric intake). Food will be provided by University of Florida Clinical Research Center with macronutrient composition prepared according to the 2010 Dietary Guidelines for Americans.
Experimental: Intermittent Fasting + Antioxidants Intermittent Fasting; 400 IU Vitamin E; 1000 mg Vitamin C	Other: Intermittent Fasting; The intermittent fasting paradigm used in this study will require participants to alternate between days of feasting (175% of normal caloric intake) and fasting ( 25% of normal caloric intake). Food will be provided by University of Florida Clinical Research Center with macronutrient composition prepared according to the 2010 Dietary Guidelines for Americans.; Dietary Supplement: 400 IU Vitamin E; once each day in morning; oral pill form; Dietary Supplement: 1000 mg Vitamin C; 500mg twice each day; morning and evening; oral pill form

Outcome Measures

Primary Outcome Measures

1. SOD2 gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note: SOD2 = Superoxide-dismutase-2

2. SOD2 gene expression (antioxidant supplementation) [3 weeks]

   Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note: SOD2 = Superoxide-dismutase-2

Secondary Outcome Measures

1. GPx1 gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note: GPx1 = Glutathione peroxidase 1

2. SIRT1 gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note SIRT1 = Sirtuin 1

3. SIRT3 gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note SIRT3 = Sirtuin 3

4. mTFA gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note: mTFA = mitochondrial transcription factor a

5. NRF1 gene expression (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note NRF1 = Nuclear respiratory factor 1

6. 8oxodG ratio (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using DNA extracted from venous blood. Note: 8oxodG = 8-oxo-7,8-dihydro-2'-deoxyguanosine/2-deoxyguanosine

7. 8oxoG ratio (intermittent fasting) [3 weeks]

   Observational outcome examines difference in expression between a normal diet and a 3-week intermittent fasting diet using RNA extracted from venous blood. Note: 8oxoG ratio = 8-oxo-7,8 dihydroguanosine/guanosine

8. GPx1 gene expression (antioxidant supplementation) [3 weeks]

   Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note: GPx1 = Glutathione peroxidase 1

9. SIRT1 gene expression (antioxidant supplementation) [3 weeks]

   Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note SIRT1 = Sirtuin 1

10. SIRT3 gene expression (antioxidant supplementation) [3 weeks]

    Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note SIRT3 = Sirtuin 3

11. mFTA gene expression (antioxidant supplementation) [3 weeks]

    Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note: mTFA = mitochondrial transcription factor a

12. NRF1 gene expression (antioxidant supplementation) [3 weeks]

    Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note NRF1 = Nuclear respiratory factor 1

13. 8oxodG ratio (antioxidant supplementation) [3 weeks]

    Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using DNA extracted from venous blood. Note: 8oxodG ratio = 8-oxo-7,8-dihydro-2'-deoxyguanosine/2-deoxyguanosine

14. 8oxoG ratio (antioxidant supplementation) [3 weeks]

    Experimental outcome examining differences between intermittent fasting with supplementation of antioxidants and intermittent fasting alone using RNA extracted from venous blood. Note: 8oxoG ratio = 8-oxo-7,8 dihydroguanosine/guanosine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body mass index in the range of 20.0-30.0 kg/m2;

• Age between 19 and 30;

• Stable weight (change <±10%) for 3 months immediately prior to the study

• No history of metabolic disorders (e.g. non-diabetic), cardiovascular disease, or thyroid dysfunction

• No past or present eating disorders

• No acute or chronic inflammatory disorder

• No more than moderate physical activity (i.e.,<3 hour/week of light exercise sessions for the past 3 months)

• No current medications to regulate blood sugar or lipids

• Not donated blood within 56 days of study start date

• No food allergies

• No dietary restrictions (e.g. vegetarianism and vegan)

• No heavy drinking (more than 15 drinks/week)

• No use of tobacco or recreational drugs within past 3 months

• Access to a microwave or stove

• Access to refrigeration

Exclusion Criteria:

• Inflexibility of schedule such that subject cannot attend blood draw appointments

• Unwillingness to pick-up and eat only study-provided food during the 8 weeks in which it is provided and for unwillingness to abstain from travel (>48hrs) during these same 8 weeks of the trial (travel is permitted during wash-out period)

• Unwillingness to abstain from tobacco, alcohol, recreational drugs, resveratrol or antioxidant supplements (other than study-provided) for the duration of study

• Women who are pregnant, breast-feeding or trying to become pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610

Sponsors and Collaborators

• University of Florida
• National Institutes of Health (NIH)
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Mark L Brantly, MD, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02132091
• Other Study ID Numbers: IRB772011; TL1TR000066; UL1TR000064; 1P30AG028740
• First Posted: May 6, 2014
• Last Update Posted: Dec 14, 2015
• Last Verified: Dec 1, 2015

• Keywords provided by University of Florida: Sirtuins; Calorie Restriction; Intermittent Fasting; Antioxidant; Aging; Metabolism; Mitochondria; Oxidative Stress
• Additional relevant MeSH terms: Vitamins; Ascorbic Acid; Vitamin E

Study Results

No Results Posted as of Dec 14, 2015