Primary Outcomes

Description: The GoStop Impulsivity Paradigm measures the ability to inhibit an already initiated response. A number of five digits are presented on a computer screen for 500ms followed by a 500ms blackout. A second number then appears for 500ms followed by a 500ms blackout. If the numbers are identical the mouse button has to be pressed before the second number disappeared. However, the response has to be with-held if a "Stop" signal appeared; that is the second number was identical but changed from black to red. If the two numbers were different then no response was required.

Measure: Go Stop Impulsivity Paradigm

Time: Change from before to after supplementation for three months

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Description: This is test of the tendency to respond in an aggressive manner. A series of cartoons are presented that present an intentionally frustrating situation. The participant reports what he or she would say in that situation. Blind the responses are assessed in terms of the extent to which the responses are aggressive in matter Note that the use of two primary outcomes reflects the aim of the study to contrast performance and questionnaire measures

Measure: Rosenzweig Picture Frustration Test

Time: Change from before to after supplementation for three months

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Secondary Outcomes

Description: The Buss-Perry Aggression Questionnaire assesses four aspects of aggressive behavior: physical aggression, verbal aggression, anger and hostility. Participants rank statements about their temperament using a 7-point Likert scale ranging from 1 (extremely uncharacteristic of me) to 7 (extremely characteristic of me).

Measure: Buss Perry Aggression Scale

Time: Change from before to after supplementation for three months

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Description: The Perceived Stress Scale assesses the extent to which stressful thoughts and feeling had been experienced during the last month. For example: "In the last month, how often have you been upset because of something that happened unexpectedly?" The participant responded on a scale ranging from 0 = Never to 4 = Very Often. An overall score is calculated.

Measure: Perceived Stress Scale

Time: Change from before to after supplementation for three months

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Description: A measure of the subjects ability to forgo initial reward for a later larger reward. The subject can choose to wait for a reward and get more points or alternatively respond more quickly and get fewer points sooner. The longer a subject waits the higher the reward; that the more points are earned. A mouse click began the task and a second resulted in a reward. Two counters display the most recent and cumulative reward over a 20 minute session. Subject are able to infer that responses at a faster rate earn smaller rewards.

Measure: Single Key Impulsivity Paradigm

Time: Change from before to after supplementation for three months

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Description: Polymorphisms associated with the metabolism and receptors of dopamine and serotonin will be related to the response to micro-nutrient supplementation

Measure: General Health Questionnaire

Time: Further analysis of existing data - considers changes from baseline to three months

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Primary Outcomes

Description: Pain will be measured follow the baseline and 20 week score using n the following assessment tools: Michigan Neuropathy Screening Instrument Norfolk Quality of Life Questionnaire Neuropathy Impairment Score - Lower Limbs Neuropathy Total Symptom Score 6 Neuropathy Pain Scale McGill Pain Questionnaire Global Impression Scale

Measure: Pain

Time: 20 weeks

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Description: Sensation will be measured follow the baseline and 20 week score using the following assessment tools: Michigan Neuropathy Screening Instrument Norfolk Quality of Life Questionnaire Neuropathy Impairment Score - Lower Limbs Neuropathy Total Symptom Score 6

Measure: Sensation

Time: 20 weeks

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Description: Disease activity will be measured by change in small fiber density of lower limbs as measured by skin biospy done at baseline and 20 weeks.

Measure: Disease activity

Time: 20 weeks

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Description: Glycemic control will be measured by change in hemoglobin A1c percentage points at baseline and 20 weeks.

Measure: Glycemic control

Time: 20 weeks

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Description: Mood will be measured by change in score using the following assessment tools at baseline and 20 weeks: Beck Depression Inventory Center for Epidemiologic Studies Depression Scale Revised

Measure: Mood

Time: 20 weeks

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Secondary Outcomes

Description: Quality of Life will be measured by change in score using the following assessment tools at baseline and 20 weeks: Norfolk Quality of Life Questionnaire MOS SF-36 Questionnaire

Measure: Quality of life

Time: 20 weeks

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Other Outcomes

Description: Acceptability of vegan diet will be measured by change in score at baseline and 20 weeks using the Eating Inventory questionnaire.

Measure: Acceptability of vegan diet

Time: 20 weeks

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Primary Outcomes

Description: Pain will be measured follow the baseline and 20 week score using the following assessment tools: Michigan Neuropathy Screening Instrument Norfolk Quality of Life Questionnaire Neuropathy Impairment Score - Lower Limbs Neuropathy Total Symptom Score 6 Neuropathy Pain Scale McGill Pain Questionnaire Global Impression Scale

Measure: Pain

Time: 20 weeks

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Secondary Outcomes

Description: Sensation will be measured follow the baseline and 20 week score using the following assessment tools: Michigan Neuropathy Screening Instrument Norfolk Quality of Life Questionnaire Neuropathy Impairment Score - Lower Limbs Neuropathy Total Symptom Score 6

Measure: Sensation

Time: 20 Weeks

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Description: Disease activity will be measured by change in galvanic skin response, as measured by Sudoscan technology. Galvanic skin response detects sweat gland function, which is an indicator of small nerve fiber function..

Measure: Disease activity

Time: 20 Weeks

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Description: Glycemic control will be measured by change in hemoglobin A1c percentage points at baseline and 20 weeks.

Measure: Glycemic control

Time: 20 Weeks

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Description: Mood will be measured by change in score using the following assessment tools at baseline and 20 weeks: Beck Depression Inventory Center for Epidemiologic Studies Depression Scale Revised

Measure: Mood

Time: 20 Weeks

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Description: Quality of Life will be measured by change in score using the following assessment tools at baseline and 20 weeks: Norfolk Quality of Life Questionnaire MOS SF-36 Questionnaire

Measure: Quality of life

Time: 20 Weeks

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Other Outcomes

Description: Acceptability of vegan diet will be measured by change in score at baseline and 20 weeks using the Eating Inventory questionnaire.

Measure: Acceptability of vegan diet

Time: 20 Weeks

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Primary Outcomes

Description: The fMRI paradigm will assess evoked blood oxygen level dependent (BOLD) response to receipt of study beverages, (sweetened and unsweetened) and a tasteless solution, and logo-elicited anticipation of both beverages and tasteless solution. The paradigm is controlled by in-house scripts written in PsychoPy software. The visual stimuli will be two beverage logos, a tasteless logo, and a fixation cross. Each logo (1 seconds) signals impending delivery of 3 mL of the associated juice/tasteless over 6 seconds, with the fixation cross otherwise presented. Participants are visually instructed on when to swallow. A jitter ranging from 5 to 13 (x̅ =8) seconds follow each trial. In total, the participants are presented 24 repeats of the events of interest over 4, 7 min runs.

Measure: Percent Change in Voxel-wise Blood Oxygen Level Dependent (BOLD) Including Outliers Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to Beverage Taste and Logo

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Secondary Outcomes

Description: The investigators use resting state fMRI (rsfMRI) data to assess intrinsic functional connectivity and network analyses. Functional connectivity is commonly quantified by measuring the synchronization of low-frequency BOLD fluctuations across pairs of brain regions of interest (ROIs) via correlation coefficients (see statistical analyses). rsfMRI data is acquired in one run of 7 minutes; participants are asked to remain still with their eyes open, and to fixate on the fixation cross.

Measure: Percent Change in Voxel-wise Blood Oxygen Level Dependent (BOLD) Including Outliers Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in During Rest

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: Saliva from participants is used to extract DNA using standard salting-out and solvent precipitation methods, to yield an average of 45 µg of DNA. The TaqIA (rs1800497) assays are done using a fluorogenic 5_nuclease (Taqman, ABI) method on an ABI Prism 7000 Sequence Detection System via the allelic discrimination mode. Reactions containing 20ng of DNA are performed in 10 µl reactions with TaqMan Universal Polymerase Chain Reaction Master Mix using standard cycling conditions. Independent investigators score allele sizes; inconsistencies are reviewed and rerun when necessary. For every assay, each 96-well plate includes non-template and DNA standards of known genotype. All genotyping is performed at the UNC-CH Advanced Analytics Core

Measure: Modulation of Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to Beverage Taste and Logo by TaqIA Single Nucleotide Polymorphism Status

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: BMI (kg/m2) is calculated by collecting height and weight. Height is measured to the nearest mm using a stadiometer. Weight is assessed to the nearest 0.1 kg using digital scales with participants wearing light clothing without shoes at each assessment.

Measure: Modulation of Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to Beverage Taste and Logo by Body Mass Index (BMI)

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The primary objective of the behavioral response inhibition task is to examine motor disinhibition in response to the beverage logos and control logos. This allows for behavioral assessment of bias toward the logos and is sensitive to detect change to the intervention. Participants respond as quickly and accurately as possible with a keyboard press when shown the target logo, but withhold their responses during presentation of other logos. The task is performed twice, each time depicting one of the beverage logos as the 'target' logo. Each task consists of 48 trials. For each trial, a picture of the target logo (75% occurrence) or similar logos (25% occurrence) is presented for 500 ms. Stimuli is presented and reaction times, commission and omission errors are recorded using Presentation (Neurobehavioral Systems, Davis, CA).

Measure: Change in Stop Signal Reaction Time to Logo as Measured in Behavioral Response Inhibition Task

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: All visual analog scales are presented on an iPad screen and completed one at a time. The scale is assessing response to taste after the participant consumes a small amount of the beverage. Perceived pleasantness of, and desire to consume the two juices is measured using adapted labeled hedonic scales at pre-/post-intervention. Pleasantness is phrased 'How pleasant is this taste' and anchored by (-100) 'most unpleasant imaginable' to (100) 'most pleasant imaginable', and 'neutral' (0) in the middle. Desire follows a similar pattern using 'desire to consume' as the phrasing. Pleasantness and desire of the assigned juice is also evaluated at the 9 intervention assessments. Perceived hunger is assessed via cross-modal visual analog scales, anchored by (-100) 'I am not hungry at all' to (100) 'I have never been more hungry'. The change score is calculated from the slope of ratings plotted by time.

Measure: Change score in Visual Analog Scale Ratings of Beverage Perceptual Measures

Time: Baseline Assessment; Intervention Visits 1-9, 3 weeks; Post-Intervention Assessment, approx. 5 weeks post baseline

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Description: The Food Frequency Questionnaire (FFQ) is a self-reported checklist of 76 foods and beverages with a frequency response section. Subjects report generally how often each item is consumed over a two-week period of time. The six possible responses are 1= never in the last two weeks, 2= 1-3 times in the last 2 weeks, 3= 4-6 times in the last 2 weeks, 4= 7-9 times in the last two weeks, 5= 10-13 times in the last 2 weeks, 6= daily or more in the last two weeks. Response information is used to estimate daily caloric intake (number of kcal) and macronutrient content (percent calories from carbohydrate/fat/protein). Food pattern is assessed as an aggregate of these measures. Changes in food pattern will be assessed as a difference from baseline to post-intervention assessment.

Measure: Change in Food Pattern From Baseline to Post-Intervention Assessment by Food Frequency Questionnaire

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: To better capture variation in regular beverage intake patterns, the Beverage Intake Questionnaire is administered which queries directly about intake of all types of beverages. Similar to the Food Frequency Questionnaire, subjects report generally how often each item is consumed over a two-week period of time. The possible responses are 1= never in the last two weeks, 2= 1-3 times in the last 2 weeks, 3= 4-6 times in the last 2 weeks, 4= 7-9 times in the last two weeks, 5= 10-13 times in the last 2 weeks, 6= daily or more in the last two weeks. Responses information is used to estimate daily caloric intake from beverages (number of kcal) and macronutrient content (number of calories from carbohydrate/fat/protein). Changes in beverage intake are assessed as a difference from baseline to post-intervention assessment.

Measure: Change in Beverage Intake Pattern From Baseline to Post-Intervention Assessment by Beverage Intake Questionnaire

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Minnesota Leisure-Time Activity Questionnaire measures leisure time activities (both free time and domestic chores). The raw scores are indexed to a key of activity and intensity codes, which are then utilized to calculate an Activity Metabolic Index (AMI). A healthy AMI have an intensity code of 6.0 while an unhealthy AMI have intensity codes of 4.0 or less. It has shown to correlate with energy expenditure (r = .73) measured via doubly-labeled water. Changes in physical activity are assessed as a difference from baseline to post-intervention assessment.

Measure: Change in Physical Activity From Baseline to Post-Intervention Assessment by Minnesota Leisure-Time Activity Questionnaire

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rate the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Restrained Eating subscale consisted of 10 items and the scores range from 10 (worse outcome) to 50 (better outcome). The change is calculated as the difference between scores at Baseline and Post-Intervention Assessment.

Measure: Change in Restrained Eating Subscale Score as measured on Dutch Eating Behavior Questionnaire

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Food Craving Inventory is a 28-item instrument measuring the frequency over the past month of general cravings and cravings for specific types of foods, namely: high fats, sweets, carbohydrates/starches, and fast-food fats. Subjects rate how often they have experienced a craving for each food on a 5-point frequency scale, where 1=never, 2=rarely (once or twice), 3=sometimes, 4= often, 5= always/almost every day. Food craving score is calculated as a total sum, and the change score is calculated from the difference between baseline to post-intervention assessment.

Measure: Change in Food Craving as assessed by the Food Craving Inventory (FCI) Score Changes of Food Pattern From Baseline by Food Frequency Questionnaire During the Intervention

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Power of Food scale assesses reported appetitive drive, food reward responsivity, sensitivity to food cues in the environment, and the frequency of food-related thoughts. The 21-item scale prompts subjects to rate how much they agree with statements about hedonic hunger on a 5-point scale, where 1=do not agree at all, 2=agree a little, 3=agree somewhat, 4=agree, and 5=strongly agree. The change in total PFS score will be calculated from the difference between baseline to post-intervention assessment.

Measure: Change in Hedonic Hunger as assessed by the Power of Food Scale (PFS) Score

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Yale Food Addiction Scale (YFAS) is designed to identify participants who exhibit signs of possible food addiction to specific foods. The 9-item questionnaire is based on substance dependence criteria in the DSM-IV-TR, as well as on scales that are used to assess behavioral addictions. Subjects rate how often they have experienced a possible food addictive behavior on a 5-point frequency scale, where 0=never, 1=once a month, 2=2-4 times per month, 3= 2-3 times per week, 4= 4+ times per week. The change in total score is calculated from the difference between baseline to post-intervention assessment

Measure: Change in Food Habits as assessed by the Yale Food Addiction Scale

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Barratt Impulsiveness Scale is one of the most commonly used self-report measures of impulsivity. This instrument comprises 15 items that assess three independent sub-dimensions of impulsivity: (a) Attention; (b) Non-planning; (c) Motor. Collectively, the three sub-dimensions represent a total impulsivity score. Items are statements about behavior and participants rate each item are scored from 1 (Rarely/Never) to 4 (Almost Always/Always). The change in total score is calculated from the difference between baseline to post-intervention assessment.

Measure: Change in General Impulsivity as assessed by the Barrett Impulsiveness Scale

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ) is a self-reported instrument that includes 48 yes/no questions divided into two subscales: Sensitivity to Reward (SR) and Sensitivity to Punishment (SP). Items statements about behavior, and participants will rate each item are scored from 1 (Definitely True) to 5 (Definitely False). The change in total score is calculated from the difference between baseline to post-intervention assessment.

Measure: Change in General Sensitivity to Reward and Sensitivity to Punishment as assessed by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire.

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Description: The BIS/BAS scales are designed to assess individual differences in the sensitivity of two systems: A behavioral avoidance (or inhibition) system (BIS) and a behavioral approach system (BAS). The questionnaire includes 24 items. Items are statements about behavior and participants rate each item are scored from 1 (very true for me) to 4 (very false for me). The change in total score is calculated from the difference between baseline to post-intervention assessment.

Measure: Change in Behavioral Approach and Behavioral Inhibition as assessed by the BIS/BAS Scales

Time: Baseline Assessment; Post-Intervention Assessment, approx. 5 weeks post

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Primary Outcomes

Description: TFE-Q was developed by Stunkard and Messic (1985) to access three dimensions of human eating behavior: Cognitive Restriction (CR), Eating Disorder (AD) and Emotional Eating (AE). Originally made up of 51 items and reduced in the TFEQ-18, TFEQ-18, TFEQ-21 versions. We will use the TFEQ-21. The average obtained from the sum of the questions for each domain was converted to a scale ranging from 0 to 100. Evaluates dysfunctional eating behavior. Cognitive restriction: limitation of food intake for weight control; Uncontrolled Food: Tendency to lose control over eating from hunger or when exposed to external environments, even in the absence of physiological hunger; Emotional Eating: Susceptible to eating in response to emotional stress or negative mood.

Measure: Three Factor Eating Questionnaire 21

Time: 6 mouths

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Secondary Outcomes

Description: measured by scale

Measure: weight

Time: up to 2 weeks

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Description: measured by measuring tape

Measure: waist circumference.

Time: up to 2 weeks

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Description: - FCQ-T consists of 39 statements and was developed to access food cravings aspects over time and in various situations, considering them as a (usual) trait behavior of the respondent. Higher scores in this questionnaire are related to a more exaggerated eating. - FCQ-S is composed of 15 statements and is a tool sensitive to changes in contextual, psychological and physiological states in response to specific situations (such as stressful events or food deprivation), considering the food craving as a (sporadic) state behavior of the respondent. Higher scores in this questionnaire are associated with greater food deprivation, negative eating-related experiences and a greater susceptibility to triggers that lead to eating. Totals of both tools for the full subscales and their dimensions are calculated by adding the corresponding scores of each statement.

Measure: State and Trait Food-Cravings Questionnaires (FCQ-s e FCQ-t)

Time: 6 mouths

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Description: Hunger and satiety measured by the 100 mm Analog-Visual Scale (VAS), whose zero corresponds to the absence of hunger or appetite and 100 mm hunger or maximum appetite. Patients should report hunger, hunger or satiety for most of the last 24 hours.

Measure: Hunger and satiety diary

Time: up to 24 hours

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Description: Appetite measured by means of the 100 mm Analog-Visual Scale (VAS), whose zero corresponds to the absence of appetite and 100 mm or maximum appetite. Patients should report nonspecific appetite for sweet or salty most of the last 24 hours.

Measure: Appetite Diary

Time: up to 24 hours

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