Food and Alcohol Behavior Study: Meaningful Enhancement

Study Overview
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Brief Summary
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This study will determine how folate supplementation affects both serum and red blood cell folate status in females ages 18 -24 years old. Additionally, this study will determine the effect of folate supplementation on mood, cognition, and sleep patterns. This study will fill a crucial gap in understanding how folate status affects a variety of health behaviors in order to better inform public health practice and prevention.

Detailed Description
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Preliminary studies conducted by the investigator's team indicate that 95.7% of previous participants (all alcohol consuming, ages 14-24), were below the threshold for red blood cell (RBC) folate status for women of childbearing potential. Understanding how the interaction of behaviors (alcohol use, nutrient supplementation, diet) contribute to sub-optimal folate status is critical to developing and expanding upon evidence-based FASD prevention programs. Notably, how nutrient supplementation might improve overall folate status in a group with poor folate status and other behaviors that confound the absorption of folate. Because the participants do not view themselves as being at risk for unwanted pregnancy, their motivation to take a supplement for a future pregnancy is very low. This team seeks to collect data on how folate supplementation might improve individually measured outcomes, like cognition and mood, so that interventions might be developed focusing on these individual outcomes. After becoming aware of the study, prospective participants will undergo a screening questionnaire for inclusion/exclusion criteria. Once the participant meets the inclusion criteria, the study will be fully explained and written informed consent will be handed out. Participants will be randomized in a single-blind manner (participant) in a 1:1 ratio to the Methyl Folate supplement (1,000 mcg, once daily) or placebo (once daily).

Official Title
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Food and Alcohol Behavior Study: Meaningful Enhancement

Conditions
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Folate Deficiency

Intervention / Treatment
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* Dietary Supplement: Methyl Folate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females restricted to those living in the United States Not currently using hormonal birth control Must experience menses Must begin the study exactly one week after the start of their menstrual cycle Folate consumption must be less than or equal to 250 micrograms of dietary folate equivalents (DFEs) Exclusion Criteria: Current use of a folate supplement

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to a condition that receives a vitamin supplement (methyl folate), or a placebo group. Both the condition and placebo group will receive the same size pill once daily for 15 days and the pills will look the same. The condition group will receive a gel capsule containing the methyl folate supplement and a microcrystalline cellulose fiber. The placebo group will receive the same size gel capsule containing only the microcrystalline cellulose filler. The methyl folate supplement is the upper tolerable limit set by the Institute of Medicine. Taking more that the upper limit of 1000 mcg of methyl folate may be harmful; for this reason, it is important to discontinue vitamin use while enrolled in the study. Participants assigned to both the condition and placebo groups will be directly observed taking the pill during each daily appointment.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methyl Folate<br>Participants will receive a capsule containing 1,000 mcg methyl folate and microcrystalline cellulose orally once per day for 15 days. | Dietary Supplement: Methyl Folate<br>* 1,000 mcg methyl folate and Microcrystalline Cellulose in a capsule<br>|
| Placebo Comparator: Placebo<br>Participants will receive a microcrystalline cellulose capsule orally once per day for 15 days. | Dietary Supplement: Placebo<br>* Microcrystalline Cellulose capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red blood cell folate status | Red blood cell folate status will be analyzed through dried blood spot samples collected on Arrayit blood cards, which use linear flow chromatography to separate whole blood into erythrocyte and serum. Red blood cell folate values represent a longer-term reduction in folate consumption or increases in folate excretion. Overturn of red blood cells occurs every 4 months, therefore, red blood cell folate status will only be assessed at baseline. The WHO-recommended cutoff of <340 nmol/L will be used to assess low red blood cell folate status. | Baseline | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from baseline serum folate status at day 1 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 1 serum folate status at day 2 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 2 serum folate status at day 3 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 3 serum folate status at day 4 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 4 serum folate status at day 5 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 5 serum folate status at day 6 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 6 serum folate status at day 7 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 7 serum folate status at day 8 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 8 serum folate status at day 9 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 9 serum folate status at day 10 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 10 serum folate status at day 11 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 11 serum folate status at day 12 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 12 serum folate status at day 13 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 13 serum folate status at day 14 | 
| Change in serum folate status | Serum folate values will be analyzed through dried blood spot samples collected on Arrayit blood cards daily, which use linear flow chromatography to separate whole blood into erythrocyte and serum. The WHO-recommended cutoff of <10 nmol/L will be used to assess low serum folate status. Results will be reported as a concentration with higher values indicating improved serum folate status. | Change from day 14 serum folate status at day 15 | 
| Change in gastrointestinal symptoms | Gastrointestinal health symptoms will be assessed by a short questionnaire aimed at capturing side-effects commonly associated with oral supplementation such as nausea, vomiting, heartburn, abdominal pain, diarrhea, and constipation. | Change from baseline gastrointestinal health status at day 7 | 
| Change in gastrointestinal symptoms | Gastrointestinal health symptoms will be assessed by a short questionnaire aimed at capturing side-effects commonly associated with oral supplementation such as nausea, vomiting, heartburn, abdominal pain, diarrhea, and constipation. | Change from day 7 gastrointestinal health status at day 15 | 
| Change in dietary folate consumption | The Block Dietary Folate Equivalents (DFE) Screener: A 21-item measure validated specifically for folate. This screener measures folate intake within a 1-week time period and will be assessed throughout the study period. DFE results are given as an calculated average of micro-grams per day. DFE's above 400 micro-grams meet the RDA for the study population. | Change from baseline dietary folate consumption at day 7 | 
| Change in dietary folate consumption | The Block Dietary Folate Equivalents (DFE) Screener: A 21-item measure validated specifically for folate. This screener measures folate intake within a 1-week time period and will be assessed throughout the study period. DFE results are given as an calculated average of micro-grams per day. DFE's above 400 micro-grams meet the RDA for the study population. | Change from day 7 dietary folate consumption at day 15 | 
| Change in mood | The Patient Health Questionnaire (PHQ-9): 9-item self-report screening tool used to assess and identify symptoms related to depression. The PHQ-9 has potential scores of 0-27 with scores of 5, 10, 15, and 20 representing thresholds for mild, moderate, moderately severe, and severe depression, respectively. Positive and Negative Affect Schedule (PANAS-SF): 20-item self-report screening tool used to assess both positive and negative affect. Scores can range from 10-50, with higher scores representing higher levels of positive affect. Scores can range from 10-50, with lower scores representing lower levels of negative affect. Brief Mood Introspection Scale (BMIS): 16-adjective scale to assess pleasant-unpleasant mood (scale range of 16-64), arousal-calm mood (scale range of 12-48), positive-tired mood (scale range of 7-28), and negative-relaxed mood (scale range of 6-24). Adding up the scored items reveals where an individual lies on each of the 4 subscales. | Change from baseline mood at day 7 | 
| Change in mood | The Patient Health Questionnaire (PHQ-9): 9-item self-report screening tool used to assess and identify symptoms related to depression. The PHQ-9 has potential scores of 0-27 with scores of 5, 10, 15, and 20 representing thresholds for mild, moderate, moderately severe, and severe depression, respectively. Positive and Negative Affect Schedule (PANAS-SF): 20-item self-report screening tool used to assess both positive and negative affect. Scores can range from 10-50, with higher scores representing higher levels of positive affect. Scores can range from 10-50, with lower scores representing lower levels of negative affect. Brief Mood Introspection Scale (BMIS): 16-adjective scale to assess pleasant-unpleasant mood (scale range of 16-64), arousal-calm mood (scale range of 12-48), positive-tired mood (scale range of 7-28), and negative-relaxed mood (scale range of 6-24). Adding up the scored items reveals where an individual lies on each of the 4 subscales. | Change from day 7 mood at day 15 | 
| Change in cognition | The NIH Toolbox Cognition Battery assesses cognitive functioning. Cognitive reports include several calculated scores including Age-Corrected Standard Scores, Uncorrected Standard Scores, and Fully Corrected T-Scores. The higher the score on each cognitive test, the higher the cognitive functioning. | Change from baseline cognitive functioning at day 7 | 
| Change in cognition | The NIH Toolbox Cognition Battery assesses cognitive functioning. Cognitive reports include several calculated scores including Age-Corrected Standard Scores, Uncorrected Standard Scores, and Fully Corrected T-Scores. The higher the score on each cognitive test, the higher the cognitive functioning. | Change from day 7 cognitive functioning at day 15 | 
| Change in sleep patterns | The Oura Ring is a wellness tracker used to track an individual's nightly sleep cycle and physical activity 24 hours per day. All data is synced via a smartphone application. | Change from baseline sleep patterns at day 7 | 
| Change in sleep patterns | The Oura Ring is a wellness tracker used to track an individual's nightly sleep cycle and physical activity 24 hours per day. All data is synced via a smartphone application. | Change from day 7 sleep patterns at day 15 | 
| Change in hair, nails, and skin satisfaction | A 6 item self-report screening tool for assessing satisfaction of hair, nails, and skin. Scores can range from 0-6. Results are recorded using a likert scale and will indicate changes in physical attribute satisfaction as supplementation occurs. A higher score represents a greater satisfaction whereas a lower score represents a lower satisfaction. | Change from baseline hair, nails, and skin satisfaction at day 7 | 
| Change in hair, nails, and skin satisfaction | A 6 item self-report screening tool for assessing satisfaction of hair, nails, and skin. Scores can range from 0-6. Results are recorded using a likert scale and will indicate changes in physical attribute satisfaction as supplementation occurs. A higher score represents a greater satisfaction whereas a lower score represents a lower satisfaction. | Change from day 7 hair, nails, and skin satisfaction at day 15 |