Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies
Condition: HIV Infections; Cancer, Second Primary
MeSH terms: Neoplasms, Second Primary; Immunologic Deficiency Syndromes
Study type: Interventional

Summary: 
      We hypothesize that micronutrient fortified probiotic yogurt can improve nutritional status
      and enhance immunity parameters in subjects HIV/AIDS and other immunodeficiencies.

      We have developed a micronutrient-fortified probiotic yogurt that has safe and beneficial
      levels of micronutrients for human consumption. This has been undertaken with the guidance of
      Edward Farnworth, a senior research scientist at Agri-Food Canada-Food Research and
      Development Centre, St. Hyacinthe, Quebec

      We will now measure nutritional parameters (height, weight, serum albumin, serum nutrient
      levels, blood urea, liver function tests (AST, ALT)) to determine if there is a statistically
      significant difference between the various levels of fortified probiotic yogurt and the
      placebo on the nutritional parameters of the subjects consuming the yogurt.

      We will measure immunological parameters (CD4 lymphocyte count, CBC, levels of TNFα, IL-12,
      IL-10, and G-CSF [Kim, et.al. 2006]) in order to determine if there is a statistically
      significant difference using fortified probiotic yogurt compared to a placebo.

      In addition, we will determine if the micronutrient-fortified probiotic yogurt has a
      significant impact on the overall quality of life for the subjects using the "linear analogue
      self assessment" tool [Kaiser, et.al 2006].
    

Detailed description: 
      Drs. Reid and Hekmat have recently developed a fermented milk product (yogurt) containing
      Lactobacillus GR-1 and RC-14 and concluded that such dairy products are suitable vehicles for
      these beneficial microorganisms [Hekmat, S. & Reid, G. 2006].

      The strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 have a proven
      efficacy to treat and protect against gastrointestinal and urogenital infections [Anukam, K.
      et. al. 2006; 2007]. In one study, the supplementation of yogurt with these probiotics was
      shown to eradicate diahrea and increase the CD4 T-lymphocyte counts in HIV subjects [Anukam,
      K. et.al. 2006]. HIV infected subjects often suffer diarrheal episodes, and consequently
      experience malabsorption of certain nutrients [Cunningham-Rundles, 2000]. A study conducted
      by Cunningham et. al [2000] found that probiotic Lactobacillus plantarum 299 had a positive
      impact on the immunity of 10/17 children and on the growth of all of the children who were
      HIV-positive.

      It is estimated that 75 percent of immune function is localized in the gastrointestinal
      tract, which may explain why oral administration of probiotics is an excellent tool for
      immunomodulation [Olah, A. et. al. 2002]. In a study of 45 patients with acute pancreatitis,
      22 were given probiotic Lactobacillus plantarum 299 and 10g of oat fibre with regular enteral
      nutrition; and 23 were given a placebo in the form of regular enteral nutrition.
      Significantly fewer (n=1 versus n=7) patients in the probiotic/fibre group experienced septic
      complications requiring surgery, highlighting the safety and potential hospitalized benefits
      that could be accrued for critical care nutrition.

      A study has recently shown in 40 HIV-infected patients taking a stavudine and/or
      didanosine-based HAART regimen plus micronutrients twice daily for twelve weeks, that the
      absolute CD4 count increased by an average of 24% versus 0% in the placebo group (p=0.01).
      The mean HIV-1 RNA decreased in the micronutrient supplementation group [Kaiser, et.al.
      2006]. This is significant for the HIV/AIDS pandemic in Africa and for the many people in
      Canada living with HIV/AIDS. In addition, this may be related to other immunodeficiencies in
      hospitalized patients from chemotherapeutic and radiological treatments, organ
      transplantation, controlling diabetes, and other chronic ailments.

      Clinical malnutrition is a heterogenous group of disorders including macronutrient
      deficiencies that lead to body cell mass depletion and micronutrient deficiencies, and these
      often coexist with infectious and inflammatory processes [Hughes,S. & Kelly, P. 2006].
      Diverse factors affect bioavailability, such as the nutritional status of individuals, the
      presence in the diet of substances which facilitate or inhibit its absorption, interactions
      among micronutrients, illnesses, and chemical characteristics of the compound used for
      fortification. There is good evidence that specific micronutrients, particularly zinc and
      vitamin A, influence immunity, while iron supplementation is often not effective in Africa
      [Hughes, S. & Kelly, P. 2006].

      More than 20% of older adults may have marginal or frank vitamin B12 deficiency [Park, et.al.
      2006], while folic acid is often deficient in children and reproductive aged females.
      Glutamine, arginine, fatty acids, and vitamin E provide additional benefits to
      immunocompromised persons or patients who suffer from various infections, while long-chain
      polyunsaturated n-3 fatty acids, vitamin E, vitamin C, selenium, and nucleotides can modulate
      immunity to fight infection [Field, et.al. 2002]. In order to produce energy, the use of
      glucose by nervous tissue requires vitamin B1; this vitamin modulates cognitive performance,
      especially in the elderly. Vitamin B9 preserves brain during its development and memory
      during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins
      B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters
      [Bourre, JM. 2006]. Thus, three formulations added to L. rhamnosus GR-2 supplemented yogurt,
      will be tested at the Brescia College Tasting Centre where volunteers will score the products
      for taste and texture [Hekmat, S. & Reid, G. 2006]

      Thirty test subjects will be recruited during the first four months of the study, for
      inclusion in a trial starting at the 4-6 month time-point, with completion by 10-12 months. A
      crossover study will be performed in London in which 10 HIV positive volunteers with CD4
      counts between 200 and 400 on their standard treatment (including Highly Active
      Antiretroviral Therapy), and 10 subjects with Cancer who are in the recovery stages and not
      currently receiving chemotherapy or radiation therapy, and 10 healthy adults (aged 18-30)
      will randomly be assigned to receive one cup of Yogurts 1, 2 or 3 and a control
      unsupplemented yogurt 4, daily for one month, followed by a two week washout where no yogurt
      will be consumed, then one month on the second yogurt, two weeks off etc for 162 days.
      Subjects will not be receiving antibiotics, not have any mental illness that would affect
      compliance, or not be requiring surgery during the study. No restrictions will be placed on
      subjects continuing prescribed or other remedies, but none will consume any other probiotic
      product during the study. The volunteers will be gender matched and a randomization scheme
      will ensure that subjects are blinded and different yogurts are distributed at each time
      (thus, for example two subjects will receive yogurt 1, two yogurt 2, three yogurt 3 and three
      yogurt 4 on day sample day one). The two week washout period will be used, as probiotic
      organisms do not persist for longer than that. Various measurements will be taken on the day
      of consuming the first and last batches of yogurt (days 0, 30, 44, 74, 88, 118, 132, 162).
      These will include weight, height, and from blood samples the CD4 count, CBC, levels of TNFα,
      IL-12, IL-10 and G-CSF [Kim, et.al. 2006], liver function test (AST, ALT), serum albumin,
      total protein, blood urea, serum zinc levels, serum selenium levels and HIV-1 RNA. A linear
      analogue self-assessment tool will be used to assess the subject's energy levels, daily
      activities and overall quality of life [Kaiser, et.al. 2006].

      The present project is an important step in developing new yogurts, supplemented with
      micronutrients and probiotic lactobacilli for malnourished children, adults, and seniors in
      Canada, as well as surgical, transplant, and hospitalized patients, and HIV/AIDS subjects in
      Canada and in Africa. The following formulations will be used to supplement the yogurt:

        1. The Kaiser micronutrient formula [14]: N-Acetyl cysteine (NAC) 300 mg, Acetyl
           L-carnitine 250 mg, Magnesium 92.5 mg, Alpha lipoic Acid 100 mg, Selenium 13.8 µg, Beta
           carotene + Vitamin A 5666 IU, Zinc 2.4 mg, Vitamin C 21 mg, Copper 0.225 mg, Vitamin B1
           0.3 mg, Boron 0.5 mg, Vitamin B2 0.3 mg, Potassium 1200 mg, Pantothenic acid 1.3 mg,
           Iron 3.3 mg, Niacinamide 3.8 mg, Manganese 0.5 mg, Inositol 15 mg, Biotin 7.5 µg,
           Vitamin B6 0.3 mg, Chromium 7.5 µg, Vitamin B12 0.6 µg, Molybdenum 11.3 µg, Vitamin D 52
           IU, Choline 121.9 mg, Vitamin E 5.7 IU, Bioflavonoid complex 75 mg, Folic acid 100 µg,
           L-Glutamine 25 mg, Betaine HCL 37.5 mg;

        2. A multi-component formula containing zinc 30mg, vitamins A + beta carotene 5666 IU , C
           21mg and E 5.7 IU, selenium 13.8µg, iron 3.3mg, folic acid 100µg, vitamin B12 0.6 µg,
           vitamin B6 0.3 mg, vitamin B1 0.3mg

        3. A basic supplement containing zinc 30mg, vitamins A 666 IU, vitamin C 21mg and E 5.7 IU,
           and folic acid 100µg and 16 mg docosahexaenoic acid (DHA-Omega 3 Fatty Acid) and 24mg
           eicosapentaenoic acid (EPA-Omega 3 Fatty Acid) [Austin, J. et.al 2006 & Alan DD, et.al
           2006].
    

Intervention name(s): Probiotic Yogurt B: with various micronutrients; Probiotic Yogurt A: Kaiser micronutrients; Probiotic yogurt C: with basic micronutrients; Probiotic Yogurt D: Placebo -- no added micronutrients
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 175g probiotic yogurt / day 25% RDA for each nutrient; 175g probiotic yogurt/ day 25% RDA for each nutrient; 175g yogurt/ day 25% RDA for each nutrient; 175g/day probiotic yogurt
Intervention MeSH terms: Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: micronutrients; immunodeficiency; probiotics; yogurt; Healthy; Acquired Immunodeficiency Syndrome; Complementary Therapies