Impact of JuicePlus+ on the Health Status of an Overweight Stressed Population
Condition: Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      The purpose of this study is to determine if a dried fruit and vegetable supplement (Juice
      Plus+) can alter the gut microbiome and improve gut permeability and inflammatory levels in
      an obese, stressed population.

      The microbiome and its component genes are long known as critical determinants of the
      nutritional value of the food we eat. Recently, it has become clear that the composition of
      this microbiome and its metabolites influences the host immune system, thereby altering host
      physiology. Both obesity and chronic stress have been shown to have an altered gut
      microbiome; both these conditions also lead to increased systemic inflammatory molecules that
      can lead to an increased risk for type 2 diabetes and other diseases caused by chronic
      inflammation.

      Juice Plus+ consumed by an overweight population combined with an eight week exercise regime
      showed decreased markers of protein/lipid oxidation (ox-LDL), total lipid oxidation (TOS) and
      lowered systemic concentrations of the inflammatory cytokine, TNF-α. As systemic cytokines
      are altered by the composition of the gut microbiome, this study proposes to determine if
      this decrease in inflammation by Juice Plus+ is due to a change in the species composition
      and metabolism of the microbiome. This question is particularly relevant for populations with
      high inflammatory loads resulting from excess weight in addition to increased psychological
      stress.

      The investigators propose to determine 1) how Juice Plus+ consumption alters the microbiome
      species composition and metabolism, 2) if there is an alteration in intestinal permeability
      with the consumption of Juice Plus+ and 3) do these alterations coincide with lower systemic
      markers of inflammation and oxidative stress among individuals who are psychologically
      stressed and overweight. The investigators will use a randomized, placebo-controlled design
      with a cohort of overweight, female, critical care health care professionals. Subjects will
      receive the supplements or placebo for sixteen weeks. At the end of 16 weeks, the cohort
      receiving the supplement will be randomized to also receive a meal replacement component or
      follow their normal diet for an additional 4 weeks. Stool and a fasting blood sample will be
      collected at the beginning of the study (baseline) and 8, 16 and 20 weeks later. At each time
      point, subjects will also consume a cocktail of glucose, mannitol and lactulose and a second
      blood draw performed to look at absorption of these molecules.
    

Detailed description: 
      An anticipated eighty critical care, female health care professionals will be recruited. This
      population has been shown to have a high occupational stress load and have increased risk for
      post-traumatic stress disorder (PTSD). The subjects will be premenopausal, overweight/obese
      (Body Mass Index -BMI : 25 - 40 kg/m2) and between the ages of 25-50 years.

      Exclusion criteria include smoking of any sort, smokeless tobacco use, chronic or excessive
      alcohol consumption (>1 drink per day), pregnancy or lactation, recent surgery or illness,
      diabetes, heart disease, use of antibiotics or medications (other than medication deemed not
      to impact outcome measures in this protocol-medication use will be reviewed on a case by case
      basis by the principal investigator).

      Health history, medication and dietary supplement questionnaires will be completed by all
      subjects to determine eligibility. A health and perceived stress questionnaire will also be
      completed at each sampling period. Characteristics of stool will also be recorded for the
      three days prior to sampling using the Bristol criteria.

      All food and drink intake will be recorded for the 7-day period prior to providing the first
      sample (baseline). Subjects will repeat this procedure at each sampling period. During the
      initial recording period, subjects will be asked to consume foods that represent their usual
      diet, with no more than a combined 4 fruit and vegetable servings each day, and be instructed
      to attempt to mimic the same diet during the 7 day periods each sampling period.

      Diet records will be analyzed using nutrition software and the data will be used for analysis
      purposes as needed. Subjects will be encouraged to consume their usual diet throughout the
      study period.

      Subjects will be weighed and total body composition determined using Dual-energy X-ray
      absorptiometry (DXA) for baseline subject characterization. Prior to the DXA scan a pregnancy
      test will be performed to confirm that the subject is not pregnant.

      Subjects will be randomly assigned to supplement or the placebo capsules. The intervention
      will start between days 1 and 5 of the menstrual cycle to avoid confounding factors due to
      menstrual cycle hormone variation. The capsules are to be taken with a meal in the morning
      and in the evening with 3 capsules at each time, for a total of 6 capsules/day for a 20 week
      period. At the beginning of the 17th week, subjects consuming the supplement will be
      randomized with one group adding the "Complete" meal replacement component that will replace
      the first meal of the day and the second group following their normal diet.

      Initial Laboratory Visit: screening visit During the initial visit to the laboratory,
      subjects will complete the informed consent form, health history, medication and dietary
      supplement usage and perceived stress questionnaires. Subjects' heart rate and blood
      pressure, height, weight, waist, and hip circumference will be measured. A pregnancy test
      will be performed to confirm that the subject is not pregnant. Body composition will be
      determined via DXA to determine body composition, as increased visceral fat is causative in
      obesity-induced inflammation. Upon completion of this screening visit, subjects will be
      scheduled for their initial testing visit.

      Test Visit Procedures For each condition (supplement and placebo), subjects will report to
      the lab a total of three times. Subjects that continue on with the "Complete"
      meal-replacement phase of the study will report to the lab one additional time. Subjects will
      collect their stool during the 24 hours prior to reporting to the lab on each test occasion
      (or as close as possible to that time point). Subjects will report to the lab in a 10 hour
      fasted state, without having performed strenuous activity within the prior 48 hours. Subjects
      will have been instructed to obtain at least 7 hours of sleep during the night prior to
      testing. No supplement or placebo will be taken prior to blood collection, as described
      below.

      Stool Collection Stool samples will be collected by subjects during the 24 hours immediately
      before reporting to the lab on each test occasion (or as close as possible to this time
      point). Subjects will be instructed to line the pail with the biohazard bag, complete a bowel
      movement in the bag, seal the bag with the zip tie, and place the bag in the insulated cooler
      bag with two freezer packs. The pail, biohazard bag, zip tie, insulated cooler and freezer
      packs will be provided by the investigator. Verbal and written instructions for collection,
      storage, and delivery of the stool samples will be available to each participant. Upon
      receipt by investigators, these samples will be stored at -70 degrees Celsius until
      processing. All sample handling will occur in the fume hood and universal precautions will be
      observed to minimize the risk of infection. Following publication of the study results,
      remaining stool samples will be disposed of properly as biohazard waste.

      Blood Collection Blood samples (approximately 20 ml; 4 teaspoons) will be taken from subjects
      via venipuncture (by someone skilled in collecting blood). After the first blood draw,
      subjects will consume a cocktail of glucose, lactulose and mannitol. Another blood sample (3
      ml) will be collected 90 minutes after ingestion of this cocktail. The purpose of consuming
      this cocktail and collecting a second blood sample is to determine the impact of the
      treatment on glucose tolerance and also its effect on intestinal permeability.

      The collected blood samples will be processed and stored in multiple aliquots at -70 degrees
      Celsius until analyzed. Following publication of the study results, remaining blood samples
      will be disposed of properly as biohazard waste. Universal precautions will be observed to
      minimize the risk of infection or injury to either the subject or the phlebotomist. Potential
      risks for this procedure include soreness around the sampling site, bruising, and infection.

      White Blood Cell Harvest White blood cells will be harvested from the collected whole blood
      using a density gradient (Ficoll) and stored in multiple aliquots at -70 degrees Celsius
      until analyzed. Following publication of the study results, remaining cell samples will be
      disposed of properly as biohazard waste. Universal precautions will be observed to minimize
      the risk of infection or contamination.

      Dietary Intake and Records All subjects will be asked to consume their usual diet throughout
      the study period and be instructed to attempt to mimic the same diet during the 7 days prior
      to sampling. Subjects will record all food and drink consumed during the 7 days prior to each
      sampling day.
    

Intervention name(s): Juice Plus+; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Dried fruit and vegetable juice capsule.; Placebo capsule
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science