Juice Plus+OMEGA Study
Condition: Healthy
Study type: Interventional

Summary: 
      In this randomized, controlled clinical study firstly the bioavailability of fatty acids and
      micronutrients of JP+® Omega Blend will be analysed. Secondly, the effect of the constituents
      contained in the nutraceuticals on blood lipid values will be determined. Thirdly, it will be
      examined, whether a dose-dependent effect of the supplementation of JP+® Omega Blend exists.
      Fourthly, the effect of a combined consumption of JP+® Omega Blend and Juice Plus+® Orchard,
      Garden and Vineyard blend (JP+® OGV) is investigated.
    

Detailed description: 
      In this randomized, controlled clinical study firstly the bioavailability of fatty acids and
      micronutrients of JP+Omega Blend will be analysed. Secondly, the effect of the constituents
      contained in the nutraceuticals on blood lipid values will be determined. Thirdly, it will be
      examined, whether a dose-dependent effect of the supplementation of JP+ Omega Blend exists.
      Fourthly, the effect of a combined consumption of JP+ Omega Blend and Juice Plus+® Orchard,
      Garden and Vineyard blend (JP+ OGV) is investigated.

      RESEARCH QUESTIONS:

        -  To which extend will the ω-3-fatty acids, as well as certain micronutrients, such as
           carotenoids and tocopherols contained in the herbal fatty acid nutraceutical JP+® Omega
           Blend be resorbed?

        -  Are the ω-3 fatty acids bioavailable by increasing ω-3-index?

        -  Does a 4-month long supplementation with a plant-based herbal fatty acid nutraceutical
           (JP+ Omega Blend) exert a positive effect on lipid metabolism in subjects with
           suboptimal serum-lipid values?

        -  Does a dose-dependent effect on lipid profile exist in the subjects through
           supplementation of JP+ Omega Blend?

        -  Does the supply of JP+ Omega Blend combined with JP+® OGV exert different or additional
           effects on bioavailability and lipid metabolism in subjects with suboptimal serum-lipid
           values?

      HYPOTHESES

        1. We hypothesise that the ω-3-fatty acids of JP+ Omega Blend will be absorbed in
           significant amounts in a dose-dependent manner and have a good bioavailability.

        2. We pursue the hypothesis, that the supplementation of JP+Omega Blend - at different
           dosage or combined with the consumption of JP+ OGV - will cause a positive effect on
           lipid metabolism in subjects with suboptimal serum-lipid values.

        3. Additionally, we hypothesise that carotenoids and tocopherols (="micronutrients")
           contained in Juice Plus+Omega Blend will be absorbed.

      The "null-hypotheses" are in detail:

        1. The ω-3-fatty acids, contained in JP+Omega Blend, are not significantly absorbed.

        2. The ω-3-fatty acids, contained in JP+Omega Blend, show no bioavailability or no increase
           in erythrocyte ω-3-index, respectively.

        3. The supplementation of JP+ Omega Blend in different dosages and combined with the
           supplementation of JP+ OGV has no (additional) effect on lipid profile and /or
           metabolism in subjects with suboptimal serum lipid values.

        4. The carotenoids and tocopherols contained in JP+®Omega Blend are not absorbed to a
           significant extent.

      ENDPOINTS

      • Primary endpoint: Ω-3-index = bioavailability of ω-3-fatty acids

        -  Secondary endpoint: lipid profile

        -  Tertiary endpoint: absorption of micronutrients

      AIMS

      This randomised, controlled, clinical study evaluates:

        1. The bioavailability of omega-3 fatty acids of a herbal fatty acid nutraceutical (JP+®
           Omega Blend) after two and four months supplementation.

        2. The effects of a 4-month long supplementation period of JP Omega-Blend in different
           dosages or combined with a fruit, vegetable and berry juice concentrate (JP+® selection
           of fruit, vegetables, and berries) on bioavailability and lipid metabolism in subjects
           with suboptimal serum lipid values.

           MERITS

           - The data acquired within this project will provide scientifically sound information
           about absorption and bioavailability of ω-3-fatty acids contained in the herbal
           nutraceutical Juice Plus+ Omega Blend.

           - The results of this project will provide information about the effect of the
           supplementation of a purely herbal fatty acid product on lipid metabolism in subjects
           with suboptimal serum lipid values.

           - Data of this study will provide information about a possible dose-dependent effect of
           JP+Omega Blend supplementation and an effect of the combined supplementation of JP+Omega
           Blend and JP+ OGV on lipid metabolism and micronutrient absorption in subjects with
           suboptimal serum lipid values.

           METHODS/STUDY DESIGN

           • Study design: This clinical study is a randomized, controlled study with a
           parallel-group design.

           The recruitment phase of the study starts with initial telephone interviews of potential
           subjects about inclusion and exclusion criteria for pre-selection. Special focus will
           lie on the determination of any intake of nutritional supplements including
           antioxidants, supplements with relevant effects on redox biology, omega-3 fatty acids
           and various plant extracts and concentrates. If a supplementation with the just
           mentioned substances is conducted, a wash-out phase of at least 4 weeks has to be
           implemented before the pre-screening period. The pre-screening aims to further evaluate
           inclusion and exclusion criteria of the subjects and also focuses on the measurement of
           ω-3 indices and blood pressure.

           If inclusion criteria are met and written informed consent is given, subjects are
           randomised into one of 4 intervention groups (control group (CG; consumption of 2
           capsules of JP+ Omega Blend/d (Ω2); consumption of 4 capsules JP+ Omega Blend/d (Ω4);
           consumption of 2 capsules JP+ Omega Blend + Juice Plus+ Obst-, Gemüse- und
           Beerensaftkonzentrat with 2 capsules each /d (Ω2+OGV)). Subjects allocated to Ω2 and Ω4
           will receive the herbal fatty acid nutraceutical in the 4-month long study period
           (intervention phase), subjects allocated to Ω2+OGV will additionally receive the fruit,
           vegetable and berry juice concentrate. The control group will refrain from using any
           supplements over the course of this period and will maintain their usual eating habits.

           Subjects are asked to complete an at least 4-week long wash-out phase, before attending
           the baseline-visit. The consumption of foods, as well as medication and supplements,
           which could influence the study outcome, will be suspended (see section "nutrition").

           The measurements and examinations with eligible subjects will be conducted within the
           scope of the study visits at baseline, after 2 (midpoint) and after 4 months (end of
           study; endpoint).

           • Subjects The subjects of this study comprise 80 healthy men and women with suboptimal
           serum lipid values (see inclusion criteria).

           (NUTRITIVE) INTERVENTION

             -  Supplementation:

           A wash-out phase of at least 4 weeks, to eliminate all nutritional supplements taken
           prior to study, is followed by a 16 week long intervention phase. During this phase, the
           nutraceutical JP+ Omega Blend alone or in combination with an encapsulated fruit,
           vegetable and berry-juice concentrate (JP+Orchard, Garden and Vineyard blend; JP+OGV)
           will be supplemented. Participants allocated to the Ω2 group receive 2 capsules of JP+
           Omega Blend/d, one capsule to be taken in the morning and one in the evening together
           with a meal. The intake of two capsules per day complies with the directions of use
           given on the label of the nutraceutical, which has been available on the market since
           2016.

           Participants in the Ω4 group are instructed to consume 4 capsules of JP+ Omega Blend/d,
           two capsules along with the breakfast and two in the evening. In the Ω2+OGV group,
           participants receive 2 capsules of JP+® Omega Blend plus 2 capsules each of an
           encapsulated fruit, vegetable and berry-juice concentrate (JP+OGV) (total intake of 8
           capsules/d; 4 capsules with the breakfast meal and 4 administered with the evening
           meal). The control group does not receive any supplementation. However, the subjects in
           this group are instructed not to change dietary habits during the 4 month long study
           period, similarly to the other intervention groups.

           All participants will be provided with a sufficient amount of supplements, according to
           their randomization group.

           Participants randomized into Ω2 receive 2 containers (with 60 capsules each) of the
           supplement at baseline and another 2 containers at the midpoint visit after 8 weeks. Ω4
           participants receive twice the amount of the JP+Omega Blend capsules. Subjects in Ω2+OGV
           receive the same amount of JP+ Omega Blend capsules as Ω2 plus 2 containers each
           (containing 120 capsules) of JP+fruit, vegetable and berry juice concentrate.

           In total 2 backups will be retained for each intervention group and stored at room
           temperature. One full backup remains at the testing facility (Institute for
           Pathophysiology and Immunology), the second backup will be stored at Green Beat
           (Institute of Nutrient Research and Sport Nutrition). Thus, even in the case of the
           cancellation of a study visit (alternative visit scheduled within two weeks; elimination
           from the study after a longer period of absence from the visits), capsules should be
           available in sufficient amounts.

           Compliance: All participants will be asked to return the containers with the remaining
           capsules at the midpoint and endpoint visit. The capsules will be counted to determine
           the compliance of capsule intake.

           • Composition of the herbal omega-3 fatty acid nutraceutical

           Ingredients Amount per serving pro (2 capsules) Calories 15 kcal Total fat 1,5 g
           Proprietary blend of algal oil, pomegranate seed oil, sea buckthorn berry oil, raspberry
           seed oil, safflower seed oil, tomato seed oil 1354 mg

           Typically providing the following fatty acid profile:

           Total Omega Blend 925 mg Omega-3 375 mg DHA 175 mg EPA 100 mg ALA 50 mg Omega 5 + 7
           Fettsäuren 250 mg Omega 6 + 9 Fettsäuren 300 mg Other Ingredients: Tapioca pullulan,
           silicon dioxide, orange oil, vanilla oil, rosemary oil.

           Ingredients: DHA- and EPA-enriched oil of the micro algae Schizochytrium sp. (with high
           oleic sunflower oil, antioxidant: rosemary extract, Tocopherol-rich extracs,
           ascorbylpalmitate), pomegranate seed oil 17 %, coating agent: pullulan; raspberry seed
           oil 11,5 %, sea buckthorn oil 9 %, release agent: silicon dioxide; high oleic safflower
           seed oil, tomatoe seed oil, orange oil, vanilla oil, antioxidant: rosemary extract.

             -  Composition of the Juice Plus+ Orchard, Garden and Vineyard blend Juice Plus+® is
                an encapsulated, powdered juice concentrate derived from 36 different fruits,
                vegetables and berries including juice and pulp from concord grape, blueberry,
                cranberry, blackberry, bilberry, raspberry, redcurrant, blackcurrant, elderberry,
                green tea, ginger root, grape seed, artichoke leaf, cocoa, pomegranate, apple,
                orange, pineapple, cranberry, peach, acerola cherry, papaya, beet root, date,
                prune, carrot, parsley, beet, kale, broccoli, cabbage, tomato, spinach, sugar beet,
                garlic, as well as oat bran and rice bran. Six capsules (two of each Juice Plus+®
                OGV, respectively) of the nutraceutical provide 9.5 mg beta-carotene, 214 mg
                vitamin C, 60 mg vitamin E, 600 mcg folate and 63 kJ per day (= 6 capsules). The
                nutraceutical is distributed by the Juice Plus Company/NSA LLC, Collierville, TN,
                USA and manufactured for Europe by Natural Alternitives International (NAI), Manno,
                Switzerland.

             -  Nutrition Subjects are instructed to implement a wash-out phase of any nutritional
                supplements and medication recently taken that could influence the outcome
                parameters of the study (especially omega-3 fatty acid supplements, plant extracts
                and concentrates). This phase should be implemented for at least 4 weeks of
                duration and will be standardized for nutrition intake of omega-3 fatty acid rich
                foods. Subjects are instructed to limit the intake of fish to maximal 1
                portion/week, limit the intake of certain oils and nuts to maximal 1 Tbsp./d of
                rapeseed oil and 1 Tsp./d of linseed oil, hempseed oil, walnut oil; maximal 1
                portion of nuts and seeds (25g)/d), as well as reduce the consumption if fruits and
                vegetables to maximal 3 portions/d (of which 2 portions may be vegetables).

           Before each of the fasted blood samples the participant's nutrition will be strictly
           standardized. Each of the subjects is instructed to protocol complete nutrition in the
           last 3 days before the baseline visit (and blood sample). Those protocols will be
           examined by a trained dietician and provide guidance for the participants. By this they
           can repeat the protocol and therefore reproduce the same nutritional intake in the days
           before the subsequent blood samples both at midpoint and endpoint visit.

           Dietary records developed by Green Beat are used, which have already been successfully
           established in different scientific studies. Additionally, these protocols collect
           information on physical activity, sleeping behaviour, as well as stress and well-being.
           All subjects receive a thorough instruction by a dietician on how to fill in the
           protocol.

           Summary of measures to standardize participant's nutrition:

             -  max. 2 portions of fish/week

             -  max. 3 portions of vegetables & fruit /d (of which max. 2 portions can be
                vegetables)

             -  nuts and seeds: max. 1 portion (25g) / d

             -  high quality, cold pressed oils: max. 1 Tbsp. rapeseed oil and 1 Tsp. per day of
                linseed oil, hempseed oil, walnut oil

           EVALUATION/STATISTICS Per protocol analyses will be performed with SPSS for Windows
           Software, Version 22.0. Data will be presented as mean ± SD. The randomisation of the
           subjects into the intervention groups will be considered during data analysis.
           Statistical significance is set at P < 0.05. The Shapiro-Wilk test will be used to
           determine normal distribution. Baseline characteristics (weight, age, gender, BMI etc.)
           of subjects will be determined by means of descriptive statistics and will be displayed
           graphically or in tables.

           Comparison of the mean values of baseline parameters among the 4 intervention groups
           will be done by analysis of variance, ANOVA. If data are normally distributed and
           variance homogeneity is fulfilled, student's t-test will be the main statistical test
           used to compare baseline and endpoint parameters in the respective group or to determine
           differences between baseline and midpoint, as well as midpoint and endpoint
           measurements. If it is not possible to use metrical data, non-parametric tests will be
           used (Wilcoxon rank sum test).

           One and two factorial repeated measures analysis of variance (ANOVA) are used to perform
           within and between group analysis for the factors "time" and "treatment", respectively.
           If the detected differences between the groups are significant, Tukey's post hoc test
           and Bonferroni correction will be used to determine the localization of the differences.
           In the case of the use of non-parametrical tests, Friedman Test (within group) and
           Kruskal Wallis test (between group) will be used for analysis.
    

Intervention name(s): control group; Omega2; Omega4; Omega2+OGV
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): no supplements given for 16 weeks, after 4 week washout of all supplements and dietetic products; 2 capsules of JP+® Omega/d for 16 weeks, after 4 week washout of all supplements and dietetic products; 4 capsules of JP+® Omega/d for 16 weeks, after 4 week washout of all supplements and dietetic products; 2 capsules of JP+® Omega/d plus 2 capsules each of an encapsulated fruit, vegetable and berry-juice concentrate (6 capsules) for 16 weeks, after 4 week washout of all supplements and dietetic products
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: subjects are randomised into one of 4 intervention groups (control group (CG; consumption of 2 capsules of JP+® Omega Blend/d (Ω2); consumption of 4 capsules JP+® Omega Blend/d (Ω4); consumption of 2 capsules JP+® Omega Blend + Juice Plus+® fruit, vegetable and berry juice concentrate with 2 capsules each /d (Ω2+OGV)). Subjects allocated to Ω2 and Ω4 will receive the herbal fatty acid nutraceutical in the 4-month long study period (intervention phase), subjects allocated to Ω2+OGV will additionally receive the fruit, vegetable and berry juice concentrate. The control group will refrain from using any supplements over the course of this period and will maintain their usual eating habits.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Omega-fatty-acids; Absorption; Bioavailability; Fruit & Vegetable concentrate; Lipid Metabolism