The Gut-brain Axis in Food Reward and Alcohol Consumption
Condition: Impulsivity; Alcohol Consumption
MeSH terms: Alcohol Drinking; Impulsive Behavior
Study type: Interventional

Summary: 
      The aims of this project are to:

        1. Determine if 3-weeks dietary supplementation with NOPE-EGCG (PhosphoLEANtm, 85mg
           NOPE+50mg EGCG per capsule) versus a placebo will improve performance on impulsivity,
           go/no-go tasks and negative outcome learning in heavy drinkers.

        2. Evaluate whether supplementation with NOPE-EGCG versus placebo results in reductions in
           alcohol consumption.

        3. Preliminary data in the rodent model suggests that rats treated with OEA shift
           preference for lower fat test stimuli. In aim 3 we will Determine if 3-weeks of
           supplementation with PhosphoLEAN shifts fat preference towards lower fat test puddings.
    

Detailed description: 
      Similarities in striatocortical pathway dysfunction have been noted for alcoholism and
      obesity. In prior studies we have demonstrated an inverse relationship between body mass
      index and response in the dorsal striatum (DS) during consumption of a palatable
      milkshake[1]. We have also shown that the magnitude of the reduced response predicts weight
      gain, especially in individuals who carry a copy of the A1 allele of the taq1A
      polymorphism[1]. Since the A1 allele is associated with reduced striatal D2 receptors [2-7],
      this finding implicates the dopamine system in the reduced blood oxygen level dependent
      (BOLD) response. Our results also indicate that this reduced response is a consequence,
      rather than a cause of obesity, since gaining weight [8], but not risk for obesity [9] (by
      virtue of parental obesity), is associated with reduced DS response to palatable food. Taken
      together the results indicate that increased adiposity is associated with blunted DS response
      to palatable food that may reflect altered dopamine signaling. More recently we determined
      that reduced DS responses in overweight and obese subjects are associated with increased
      impulsivity measured with the BIS-11 and a go no/no-go task [10]. Heavy drinkers are also
      more likely to be impulsive [11]. In preliminary analyses of data on over 300 individuals
      assessed with the clinical core battery in the Center for the Translational Neuroscience of
      Alcoholism (CTNA), we found that higher scores on the BIS-11 and other measures of
      impulsivity were associated with greater alcohol consumption.

      Related to these findings in humans, preliminary work in rodents shows that exogenous
      administration of N-Acylethanolamines, such as oleoylethanolamine (OEA) can normalize
      high-fat diet induced dopamine decreases in DS. Human testing of OEA supplementation is
      possible based on the availability of a dietary supplement containing the OEA precursor
      NOPE-EGCG ((PhosphoLEANtm, 85mg NOPE+50mg EGCG per capsule). PhosphoLEAN has been shown to
      enhance adherence to dietary advice in overweight healthy subjects [12-14]. We therefore
      propose a pilot study to test whether PhosphoLEAN will improve performance on impulsivity,
      go/no-go tasks and negative outcome learning. Specifically, we will recruit heavy drinkers
      because they are more likely to be impulsive [11]. Phospholean may improve negative
      reinforcement learning in this population. This may lead to reductions in drinking as well.
      We will also explore whether the supplement leads to reductions in alcohol consumption and
      preference for high fat foods.
    

Intervention name(s): Phospholean; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Phospholean supplied by Cheminutra (White Bear Lake, MN). PhosphoLean® N-Oleoyl-PE + EGCG (NOPE + EGCG) is a proprietary phosphobioflavonic complex of N-oleoyl-phosphatidyl-ethanolamine (NOPE), which contains oleoyl ethanolamine (OEA) bound to phosphatidylethanolamine (PE), and epigallocatechin gallate (EGCG).
PhosphoLean® 40P is a dietary ingredient under the Dietary Supplement Health and Education Act (DSHEA) regulations of the US FDA (1994).; Placebo consists of rice flour
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: sweet and fat preference