Effects of Xoçai Antioxidant Supplements on Atherosclerosis Risk Factors
Condition: Hypertension; Dyslipidemia; Hyperglycemia
MeSH terms: Atherosclerosis; Dyslipidemias; Hyperglycemia
Study type: Interventional

Summary: 
      An antioxidant dietary supplement made from cocoa powder, and extracts of acai, grape and
      blueberry will be tested for effects on blood sugar, blood pressure, cholesterol and related
      parameters in human subjects.
    

Detailed description: 
      Background and Introduction It has long been known that increased intake of plant products
      results in reduced risk of atherosclerosis and cardiovascular disease, which are the most
      important causes of death and disability in Western societies. This protective effect has
      been found to correlate with increased plasma levels of various antioxidant vitamins along
      with the expected increased resistance of the plasma to oxidation, and reduced evidence of
      oxidation of lipoproteins and other plasma components. It also has long been understood that
      oxidized LDL, and related lipoproteins which also contain apo B-100, are a primary driving
      force in the process of atherogenesis. These two facts have led to a very strong interest in
      developing antioxidant treatments as likely effective atheropreventive measures. This quest
      has taken the form of several large, long-term interventional studies, in which patients have
      been given purified antioxidant vitamins in an effort to reduce cardiovascular events.
      Surprisingly, almost without exception these interventions have failed to show any favorable
      effects. The cause of this paradox remains unknown, but may have resulted either from the
      reliance on antioxidant vitamins, rather than other antioxidant elements in the diet, or from
      the use of highly purified products, instead of more lightly processed food elements.

      Cocoa mass (or cocoa powder in the dried form) is the edible non-fat part of the cacao bean
      which remains once the fatty cocoa butter has been removed. Cocoa mass or powder is a rich
      source of polyphenol antioxidants of the flavonoid family. The predominant flavonoids in
      cocoa are flavonols, including both the oligomeric proanthocyanidins (procyanidins and
      prodelphinidins) and the monomeric catechins and epicatechins. Recent studies have shown that
      chocolate preparations which are high in cocoa (and thus high in flavonol content) may have
      several beneficial effects on the vasculature and on various risk factors for
      atherosclerosis. These likely beneficial effects include:

        1. Increased vascular reactivity

        2. Improved arterial compliance

        3. Increased HDL-C levels,

        4. Decreased oxidation of LDL, and

        5. Reduced insulin resistance.

      Although several of these studies have compared preparations with low vs. high content of
      cocoa (or flavonols), only one study of which we are aware has tested effects of a source of
      chocolate other than a high-fat chocolate bar. Only a non-bar product can readily exclude
      cocoa butter and/or butterfat and thus be low in fat content. Meanwhile the relatively high
      fat content of a chocolate bar, even if made with high cocoa powder content (thus a "dark"
      chocolate bar) adds many calories to the product and may well reduce the beneficial effects
      of the cocoa. Apparently also, all of the preparations tested in the published studies were
      relatively high in sugar content, which also adds calories and may reduce the benefits of the
      cocoa.

      In addition there are many inconsistencies among studies of standard chocolate preparations
      regarding the above-mentioned beneficial effects (for example, studies failing to show lipid
      or anti-inflammatory effects), and these inconsistencies may relate to various issues. First,
      of all the elements in chocolate-containing foods, cocoa mass or powder appears to contain
      virtually all of the antioxidant factors. Variability in cocoa powder content, or possible
      blunting of its benefits by the addition of variable amounts of cocoa butter might variably
      reduce the beneficial effects. Second, the alkaline processing of cocoa (which is routine for
      virtually all bar and powdered chocolate products) may reduce its antioxidant content and
      activity. Thus, the variability in published results among various chocolate preparations
      could be due to differences in the degree and type of processing of the cocoa (and resulting
      differences in its antioxidant content), and/or differences in the presence of other
      components (such as fat and/or sugar) which might block beneficial effects of the cocoa.

      Açai fruit appears to have even greater content of antioxidant polyphenols (primarily as
      anthocyanins) than does cocoa mass or powder, especially when preserved from fresh açai juice
      as freeze-dried açai powder. Açai is known to contain many vitamins and minerals as well as
      some fats, and is a rich source of phytosterols. It is said to be able to lower LDL levels,
      likely because of its unsaturated and monounsaturated fat content. It is also said to have
      anti-inflammatory effects. Although processing into freeze-dried açai powder removes most of
      the fat, phytosterols and dietary fiber, the unique potential of açai appears to be primarily
      in its many anthocyanin antioxidants, which are best preserved in the freeze-dried powder.
      Unfortunately, in contrast to the many studies on chocolate, there appear to be no published
      scientific studies of physiologic effects of Açai (as an antioxidant or otherwise) in humans.
      A recent lay review of açai by Alexander G. Schauss, PhD, FACN ("Açai: The Nutritional and
      Antioxidant-Rich Amazonian Palm Tree Fruit," Sound Concepts, 2005), states that some human
      studies have been performed with açai and that the first scientific articles are currently in
      preparation. Dr Schauss does not mention, however, any detail about the methods or results of
      any such studies.

      Blueberries, grapes and peppers have natural antioxidants, albeit in far lesser quantities
      than acai. With the exception of grapes, the in vivo effects of these antioxidant-rich fruits
      on human subjects have been very little studied. Research into the intake of alcoholic and
      non-alcoholic grape products (both from lighter- and darker-colored grapes) has shown
      significant antioxidant effects, especially with dark grapes. Any effects of grapes on
      atherosclerosis or its many standard risk factors remain controversial at best, and in many
      cases are unknown. Given the encouraging scientific data regarding antioxidant and vascular
      effects of cocoa and grapes in human subjects, further studies of non-vitamin
      antioxidant-rich food products are clearly warranted.

      The study product, Xoçai Activ drink , has been carefully designed to try to maximize
      antioxidant content and effects in a pleasant-tasting natural food product. It achieves this
      by (1) including many ingredients with naturally high antioxidant content, cocoa powder, and
      Acai, grape and blueberry powders. (2) minimizing the processing of its components, and (3)
      eliminating added fat both to minimize potential interference with the likely favorable
      effects of its main ingredients, and to minimize its total caloric content.

      In light of the high antioxidant content (manifested as high ORAC, etc.) of Xoçai Activ it is
      a prime candidate for studies of antioxidant effects in humans in vivo. If this study can
      show significant effects on clinical-relevant endpoints, such as lipids, glucose tolerance,
      blood pressure, or vascular function, it would indicate that clinical disease can be
      prevented with antioxidant supplement therapy.

      Objectives:

      Hypotheses

      We hypothesize that when given to human subjects:

        1. Xoçai Activ will have dose-dependent antioxidant effects in human subjects

        2. Xoçai Activ will improve several atherosclerosis risk factors in a dose-dependent
           manner:

      Specific Aims We will perform an open-label pilot dose-response study which we will test our
      hypotheses by measuring various individual factors related to the above aims.

      All of the study parameters will be measured at baseline and at the end of two treatment
      periods of two weeks each, one at low dose (1 square three times/d) and high dose (two
      squares three times/d). The study will last about 5 weeks, counting the screening portion.

      Patient Selection Criteria Subjects for the study will be up to 5 men and 5 women. All
      subjects will be from 18-79 years of age, with a body mass index <35, and of good general
      health. Subjects will be excluded if they regularly use lipid-altering medications (including
      niacin over 100 mg/d and DHA/EPA over one gram/d), alcohol, tobacco or antioxidant
      supplements (other than a standard multiple vitamin) and if they have a history of active
      liver, renal, or thyroid disease, or active cancer.

      Study Design:

      The study will be done with up to 10 subjects with endpoints measured at screening, baseline
      and then every 2 weeks for 4 weeks of treatment. The first two weeks of the study,
      participants will be instructed to drink three one-ounce servings of Xocai Activ a day. The
      second two weeks, participants will be instructed to drink three three-ounce servings of
      Xocai Activ a day (nine ounces daily). Subjects will be carefully instructed how to mix the
      dry Xocai Activ powder with the correct amount of water so that the proper amount of Xocai
      Activ will be consumed during both the low- and high-dose periods. There will be a total of 7
      clinic visits with a total of 470 mL of blood taken.

      Due to the difficulty in preparing placebo interventions, this study will not be
      double-blinded. We will however, blind the measurement of all laboratory assays.

      Study Endpoints:

      All blood and urine will be taken, and all vascular and body composition measurements will be
      performed after a 12-hour overnight fast twice during the baseline period and twice at the
      end of each 2-week period of intervention.

      Diet: Subjects will have their routine diet assessed between the two baseline visits, and at
      the end of the study by means of a 3-day food record. They will be instructed to consume no
      antioxidant supplements, and to minimize consumption of high antioxidant foods (chocolate,
      blueberries, red grapes, etc.) during the study.

      Laboratory measurements: Antioxidant levels and activity are a primary endpoint of the study
      and will be measured at baseline and in each dose in each subject.

      Vascular measurements: Blood pressure and vascular function should be favorably affected by
      Xoçai, and they will be measured by standard, established methods in our research clinic.

      Body composition: We anticipate that the effects of Xoçai may be determined in part by body
      composition, in that more obese subjects, who have greater abnormalities in oxidation,
      inflammation, lipids and vascular function, will have a greater response. We will measure
      body composition by percent body fat by bioelectrical impedance.

      Study data will be obtained in the laboratory by Dr. Nanjee and will be analyzed by all
      investigators. Confidentiality will be maintained by not divulging personal information
      beyond those directly involved in subject contact and data collection, and by maintaining
      hard copies of subject records in locked files. Computer files with personal information
      identifying subjects will be kept exclusively in secure password-protected computer files.
      Data analysis will be performed using files identifying patients only by subject number.
    

Intervention name(s): Xocai Activ drink
Intervention type(s): Dietary Supplement
Intervention description(s): proprietary blend of cocoa powder and extracts of acai, grape and blueberry
Other intervention name(s): Xocai Activ drink;; cocoa powder,; acai extract,; grape extract,; blueberry extract
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Primary purpose: Prevention
Keywords: blood pressure; dyslipidemia; hyperglycemia