The Impact of a Phytochemical Supplement on "Metabolic Aging" in Older Overweight Adults Relative to Young Lean Adults

Brief Summary

Detailed Description

Advanced age is associated with reduced mitochondrial capacity and altered metabolomic signatures relative to those at younger ages. We hypothesize that supplemental fruit and vegetable phytochemicals will slow or reverse signs of metabolic aging by enhancing mitochondrial capacity in older, overweight/obese adults as well as shift their metabolomic signature toward those of younger, leaner adults. To test this hypothesis, we will pursue the following specific aims in a controlled feeding trial to diminish the confounding effect of concurrent and confounding dietary factors. Specific Aim 1: To determine the extent to which supplemental fruit and vegetable concentrates will shift the mitochondrial capacity of peripheral blood mononuclear cells in older, overweight older adults toward that of young, lean adults. Specific Aim 2: To determine the extent to which supplemental fruit and vegetable concentrates will shift the plasma metabolomic signature of older, overweight adults toward that of young, lean adults. The experimental design is a randomized, double-blind, placebo-controlled, parallel design, controlled feeding trial. This trial will enroll 40 older adults, as well as 20 younger adults to serve as a reference, to complete the study. They will be generally healthy. The older adults will be ≥55 y and have BMI \>27.0 and \<35 kg/m2, and the younger adults will be 18-30 y and have BMI \>18.5 and \<27 kg/m2. The older subjects will be randomized to receive either placebo (PLA) or fruit/vegetable supplement (FVS) for 6 weeks after a 2-wk run-in period. The younger adults serving as the reference group for the older subjects will only participate in the run-in period and will not receive any dietary supplements. During the whole study, including the run-in period, all subjects will consume provided meals. The total duration of the trial will be \~10 weeks for the older subjects, including screening, 2-wk run-in, and 6 wk of intervention, as well as \~4 weeks for the younger subjects including screening and 2-wk run-in. In addition to consuming the provided meals for 6 weeks, the older volunteers will take an assigned supplement daily. Blood samples of the older volunteers will be collected at the end of the run-in and the end of the 6-wk intervention. These same samples will only be collected from the younger volunteers at the end of the run-in period. Older subjects will be randomly assigned to receive one of the supplements (PLA vs. FVS) after their eligibility is confirmed. A randomization scheme will be prepared by a biostatistician using a standardized computer program for two treatment groups using a parallel design. The study supplements will be generously provided by Juice PLUS (Collierville, TN). A matching placebo product will be manufactured by the Juice PLUS under the FDA GMP guidelines. The main ingredient of the placebo will be microcrystalline cellulose-containing 0.5% magnesium stearate. The Juice PLUS products that will be used in this intervention have been marketed in the US. Microcrystalline cellulose and magnesium stearate have a GRAS status under FDA Code of Federal Regulations (CFR) title 21. FVS in a capsule form will be the combination of Juice Plus+ Garden Blend, Juice Plus+ Orchard Blend, and Juice Plus+ Berry Blend. All Juice Plus+ supplements contain a fine, granular powder, mainly from botanical ingredients. This powder is encapsulated in a size 00 gelatin capsule. These three formulas will be blended to produce a uniform brown powder and packaged into study opaque capsules. Juice Plus+ Garden Blend consists of vegetable juice powder and pulp from carrot, parsley, beet, kale, broccoli, cabbage, spinach, oat, rice, and tomato; gelatin, glucomannan, calcium ascorbate, mixed tocopherols, calcium carbonate, garlic powder, Spirulina Pacifica, natural mixed carotenoids, natural enzyme blend, Lactobacillus acidophilus, folic acid. The powder looks pale green in color and smells like cabbage. Juice Plus+ Orchard Blend consists of fruit juice powder and pulp from apple, orange, pineapple, cranberry, peach, acerola cherry, beet, prune, date, and papaya; gelatin, calcium ascorbate, citrus pectin, citrus bioflavonoids, glucomannan, natural mixed carotenoids, natural enzyme blend, bromelain, papain, mixed tocopherols, Lactobacillus acidophilus, folic acid. The powder looks pink in color and smells like apple/cranberry. Juice Plus+ Berry Blend consists of fruit juice and pulp powder of Concord grape, blueberry, cranberry, blackberry, bilberry, raspberry, black currant, elderberry, cocoa powder, pomegranate powder, green tea, ginger root, grape seed, and artichoke leaf powder, gelatin, mixed tocopherols, calcium ascorbate, natural enzyme blend, silicon dioxide, vegetable-derived magnesium stearate, citrus bioflavonoids from tangerine, folic acid. The powder looks purple in color and smells faintly of berry and cocoa. During the trial, older subjects will be required to attend 1 screening visit and 3 study visits over 10 weeks, and younger subjects will be required to attend 1 screening visit and 2 study visits over 4 weeks. An initial screening visit (Visit 1) is employed to obtain informed consent and determine each subject's eligibility. A blood sample will be collected only if the subject is fasting \>12 hours. At Visit 2, subjects will begin to consume the provided meals for 2 weeks during the run-in period. At Visit 3, all subjects will be asked to arrive at the study site after fasting for \>12 h, blood will be collected. For younger subjects, the study will complete at end of Visit 3. Older subjects will be randomly assigned to one of 2 supplements, starting on the next day of Visit 3 for 6 weeks. They will be instructed to take 3 capsules each with breakfast and dinner. At Visit 4 (final visit), older subjects will be asked to arrive at the study site after fasting for \>12 h, blood will be collected for analyses. Younger and older subjects will consume provided meals for 2 and 8 weeks. The study meals will be designed to be comparable to a diet that most average Americans are consuming. Subjects may consume the study meals longer than 2 or 8 weeks because of a visit scheduling conflict or other unexpected events.

Primary Outcomes

Secondary Outcomes

• metabolomics(at end of 6-week intervention)