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This study tests the effectiveness of dietary interventions that have the possibility to improve markers of gut health and improve general well-being. This study will allow healthcare professionals to learn how dietary interventions involving fasting can affect health. Food is increasingly recognized as a core component of preventive and ameliorative health care. Juice fasting has quickly become one of the most popular self-prescribed dietary interventions in the United States. A wide variety of juice fasts are available in the popular market; a popular variation is the three-day juice fast. The purpose of this study is to assess the effects of a three-day juice fast on certain markers of age-related disease and bio-markers of longevity. In particular, this study will assess certain epigenetic markers, which measure how the environment (including diet) can change the way that genes are expressed without changing the genes themselves. The study will also assess the microbiome, and inflammatory and glycemic markers.
Up to 30 participants will be enrolled in the study and will be randomized into one of the three arms: the "juice fasting" arm, the "juice plus ad hoc" arm, and the "caloric restriction" arm. Participants will come into the lab for an initial visit, during which they will complete questionnaires on their usual diet and demographics and will be informed about their assignment to one of the three arms.
In all three arms, the three-day diet intervention will be preceded and followed by three days of self-conducted elimination diet. The pre-intervention diet will encourage participants to eat a healthy, light diet for three days (basic instructions: eat only fresh raw or cooked fruits and vegetables (preferably organic), whole grains and eggs; drink 8 glasses of water a day; avoid or eliminate alcohol, caffeine, sugar, processed foods, dairy, red meat, and gluten). The post- intervention diet will instruct participants to gradually return to eating solid foods, and limit strenuous exercise (basic instructions: follow a diet similar to the pre-intervention elimination diet; day 1 after the intervention: eat fruits & green vegetables, and drink 8 glasses of water; day 2 add in: nuts, gluten-free grains like whole oats, quinoa, or brown rice; day 3 add in: organic meats, fish, & gluten-containing grains).
Biological samples and self-reported outcomes will be collected at four time points: baseline (prior to the first elimination diet period), pre-intervention (after the elimination diet and before the three-day intervention), post-intervention (after the intervention), and 14-day post- intervention. At each time point, participants will complete questionnaire on quality of life (PROMIS - Global Health Scale, which is an NIH measure on an individual's' overall physical and psychological well-being; see appendix) and collect their stool samples. Participants will be provided self-administered tool kits and be taught how to collect the stool sample at their first lab visit. At each of the four time points, the research assistant will coordinate the collection of cheek swabs, saliva samples, and blood spot samples. Biometrics will also be collected at each time point (weight, waist circumference, and blood pressure).
Over the course of the study, participants will be instructed to keep a diet diary days one through nine to record their daily dietary intake. During the intervention period, the research team will also contact the participants for daily check-ins. Participants will not need to record diet data for the remaining 11 days of the post-intervention period.
At the conclusion of the study, participants will bring back the final biological samples (stool wipe and saliva), provide the set of samples, and be debriefed about the purposes of the study.
The biological samples collected will then be processed and assayed for microbiome, methylation, inflammatory markers, and glycemic markers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Juice fast | Experimental | In the "juice fasting" arm, participants will be given vegetable/fruit pressed juices and be instructed to engage in a three-day juice fast diet totaling 800-900 kcal-per-day. The specific juices will be assigned for each day in order to maintain the calorie level. |
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| Caloric restriction via Plant-based meals | Experimental | In the "caloric restriction diet" arm, participants will be on a whole-food plant-based diet totaling 800-900 kcal-per-day (matching the daily calories of juice fasting). |
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| Juice plus ad hoc | Experimental | In the "juice plus ad hoc" arm, participants will be given the same juice for three days but continue with their usual diet in addition to the juice. For this arm, there is no restriction of caloric intake or restriction to liquid only. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Juice | Dietary Supplement | Participants will be drinking 800-900 kcal/day in cold-pressed juices. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change DNA Methylation at Day 7 | The ratio of methylated signal to total signal and the M-value (log2 ratio of methylated signal over unmethylated signal) will be determined for each interrogated locus using Illumina's Infinium Methylation EPIC BeadChip | This outcome will be measured on day 7 of the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline DNA Methylation | The ratio of methylated signal to total signal and the M-value (log2 ratio of methylated signal over unmethylated signal) will be determined for each interrogated locus using Illumina's Infinium Methylation EPIC BeadChip | This outcome will be measured on day 1 of the study. |
| Change DNA Methylation at Day 4 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Melinda Ring, MD, FACP | Osher Center for Integrative Medicine at Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20518700 | Background | Redman LM, Ravussin E. Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid Redox Signal. 2011 Jan 15;14(2):275-87. doi: 10.1089/ars.2010.3253. Epub 2010 Aug 28. | |
| 20395504 | Background | Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010 Apr 16;328(5976):321-6. doi: 10.1126/science.1172539. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | May 23, 2018 | Jul 11, 2018 | ICF_000.pdf |
| Prot | Yes | No | No | Study Protocol | May 22, 2018 | Jul 24, 2018 | Prot_001.pdf |
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| Caloric restriction via Plant-based meals | Behavioral | Participants' caloric intake will be limited to 800-900 kcal/day. |
|
| Plant-based meal | Dietary Supplement | Participants will be eating ~900 kcal/day in pre-prepared plant-based meals. |
|
The ratio of methylated signal to total signal and the M-value (log2 ratio of methylated signal over unmethylated signal) will be determined for each interrogated locus using Illumina's Infinium Methylation EPIC BeadChip |
| This outcome will be measured on day 4 of the study. |
| Change DNA Methylation at Day 21 | The ratio of methylated signal to total signal and the M-value (log2 ratio of methylated signal over unmethylated signal) will be determined for each interrogated locus using Illumina's Infinium Methylation EPIC BeadChip | This outcome will be measured on day 21 of the study. |
| PROMIS Global Health self-report | The PROMIS Global Health measures assess an individual's physical, mental, and social health. The measures are generic, rather than disease-specific, and often use an "In General" item context as it is intended to globally reflect individuals' assessment of their health. and psychological well-being | This outcome will be measured on day 1 of the study. |
| PROMIS Global Health self-report, repeatable | The PROMIS Global Health self-report, described in Outcome 5, will be administered daily during the active portion of the study. | This outcome will be measured on day 4 of the study. |
| PROMIS Global Health self-report, repeatable | The PROMIS Global Health self-report, described in Outcome 5, will be administered daily during the active portion of the study. | This outcome will be measured on day 5 of the study. |
| PROMIS Global Health self-report, repeatable | The PROMIS Global Health self-report, described in Outcome 5, will be administered daily during the active portion of the study. | This outcome will be measured on day 6 of the study. |
| Baseline Blood Pressure | The investigators will measure systolic and diastolic blood pressure, which will be measured manually using a stethoscope and blood pressure cuff. | This outcome will be measured on day 1 of the study. |
| Blood Pressure at Day 4 | The investigators will measure systolic and diastolic blood pressure, which will be measured manually using a stethoscope and blood pressure cuff. | This outcome will be measured on day 4 of the study. |
| Change in Blood Pressure at Day 7 | The investigators will measure systolic and diastolic blood pressure, which will be measured manually using a stethoscope and blood pressure cuff. | This outcome will be measured on day 7 of the study. |
| Change in Blood Pressure at Day 21 | The investigators will measure systolic and diastolic blood pressure, which will be measured manually using a stethoscope and blood pressure cuff. | This outcome will be measured on day 21 of the study. |
| Baseline Waist Circumference | Waist circumference will be measured according to CDC guidelines: the participant will stand, and a tape measure will be placed horizontally around their middle, just above the hip bones. | This outcome will be measured on day 1 of the study. |
| Waist Circumference at Day 4 | Waist circumference will be measured according to CDC guidelines: the participant will stand, and a tape measure will be placed horizontally around their middle, just above the hip bones. | This outcome will be measured on day 4 of the study. |
| Change in Waist Circumference at Day 7 | Waist circumference will be measured according to CDC guidelines: the participant will stand, and a tape measure will be placed horizontally around their middle, just above the hip bones. | This outcome will be measured on day 7 of the study. |
| Change in Waist Circumference at Day 21 | Waist circumference will be measured according to CDC guidelines: the participant will stand, and a tape measure will be placed horizontally around their middle, just above the hip bones. | This outcome will be measured on day 21 of the study. |
| Baseline Weight | Weight will be measured using a digital scale and recorded in pounds | This outcome will be measured on day 1 of the study. |
| Weight at Day 4 | Weight will be measured using a digital scale and recorded in pounds | This outcome will be measured on day 4 of the study. |
| Change in Weight at Day 7 | Weight will be measured using a digital scale and recorded in pounds | This outcome will be measured on day 7 of the study. |
| Change in Weight at Day 21 | Weight will be measured using a digital scale and recorded in pounds | This outcome will be measured on day 21 of the study. |
| Baseline C-Reactive Protein | C-reactive protein (CRP) is a blood test marker for inflammation in the body. | This outcome will be measured on day 1 of the study |
| C-Reactive Protein at Day 4 | C-reactive protein (CRP) is a blood test marker for inflammation in the body. | This outcome will be measured on day 4 of the study |
| Change in C-Reactive Protein at Day 7 | C-reactive protein (CRP) is a blood test marker for inflammation in the body. | This outcome will be measured on day 7 of the study |
| Change in C-Reactive Protein at Day 21 | C-reactive protein (CRP) is a blood test marker for inflammation in the body. | This outcome will be measured on day 21 of the study |
| Baseline Interleukin-6 | Interleukin-6 (IL-6) is an endogenous chemical which is active in inflammation, and in B cell maturation. Besides being an immune protein, it is also a pyrogen, and is responsible for fever in autoimmune, infectious or non-infectious disease. | This outcome will be measured on day 1 of the study. |
| Interleukin-6 at Day 4 | Interleukin-6 (IL-6) is an endogenous chemical which is active in inflammation, and in B cell maturation. Besides being an immune protein, it is also a pyrogen, and is responsible for fever in autoimmune, infectious or non-infectious disease. | This outcome will be measured on day 4 of the study. |
| Change in Interleukin-6 at Day 7 | Interleukin-6 (IL-6) is an endogenous chemical which is active in inflammation, and in B cell maturation. Besides being an immune protein, it is also a pyrogen, and is responsible for fever in autoimmune, infectious or non-infectious disease. | This outcome will be measured on day 7 of the study. |
| Change in Interleukin-6 at Day 21 | Interleukin-6 (IL-6) is an endogenous chemical which is active in inflammation, and in B cell maturation. Besides being an immune protein, it is also a pyrogen, and is responsible for fever in autoimmune, infectious or non-infectious disease. | This outcome will be measured on day 21 of the study. |
| Baseline Insulin Level | A fasting insulin test will show fasting blood sugar levels. | This outcome will be measured on day 1 of the study. |
| Insulin Level at Day 4 | A fasting insulin test will show fasting blood sugar levels. | This outcome will be measured on day 4 of the study. |
| Change in Insulin Level at Day 7 | A fasting insulin test will show fasting blood sugar levels. | This outcome will be measured on day 7 of the study. |
| Change in Insulin Level at Day 21 | A fasting insulin test will show fasting blood sugar levels. | This outcome will be measured on day 21 of the study. |
| Baseline Leptin | Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Leptin production is under neuroendocrine control so that serum concentrations vary directly with the amount of triglycerides stored in adipose tissue depots. | This outcome will be measured on day 1 of the study. |
| Leptin at Day 4 | Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Leptin production is under neuroendocrine control so that serum concentrations vary directly with the amount of triglycerides stored in adipose tissue depots. | This outcome will be measured on day 4 of the study. |
| Change in Leptin at Day 7 | Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Leptin production is under neuroendocrine control so that serum concentrations vary directly with the amount of triglycerides stored in adipose tissue depots. | This outcome will be measured on day 7 of the study. |
| Change in Leptin at Day 21 | Leptin is an adipocyte-derived hormone that is essential for normal body weight regulation. Leptin production is under neuroendocrine control so that serum concentrations vary directly with the amount of triglycerides stored in adipose tissue depots. | This outcome will be measured on day 21 of the study. |
| Baseline Gut microbiota | 16S rRNA amplicon library created for taxonomic annotation analysis. | This outcome will be measured on day 1 of the study. |
| Gut microbiota at Day 4 | 16S rRNA amplicon library created for taxonomic annotation analysis. | This outcome will be measured on day 4 of the study. |
| Change in Gut microbiota at Day 7 | 16S rRNA amplicon library created for taxonomic annotation analysis. | This outcome will be measured on day 7 of the study. |
| Change in Gut microbiota at Day 21 | 16S rRNA amplicon library created for taxonomic annotation analysis. | This outcome will be measured on day 21 of the study. |
| Background | Henning SM, Shao P, Qing-Yi L, Yang J, Huang J, Ru-Po L, Thames G, Heber D, Li Z. Health effects of 3-day fruit and vegetable juice fasting. Advanced Nutrition, 7(48A), 2016. |
| 23522825 | Background | Rink SM, Mendola P, Mumford SL, Poudrier JK, Browne RW, Wactawski-Wende J, Perkins NJ, Schisterman EF. Self-report of fruit and vegetable intake that meets the 5 a day recommendation is associated with reduced levels of oxidative stress biomarkers and increased levels of antioxidant defense in premenopausal women. J Acad Nutr Diet. 2013 Jun;113(6):776-85. doi: 10.1016/j.jand.2013.01.019. Epub 2013 Mar 19. |
| 28273863 | Background | Zheng J, Zhou Y, Li S, Zhang P, Zhou T, Xu DP, Li HB. Effects and Mechanisms of Fruit and Vegetable Juices on Cardiovascular Diseases. Int J Mol Sci. 2017 Mar 4;18(3):555. doi: 10.3390/ijms18030555. |