Evaluation of Vitamin A Absorption From Fortified Bouillon

This study is being conducted to help characterize the absorption of 3 different formulations of VAP (PFH-VAP and BASF-VAP250 vs a positive control) when prepared as broth with an oil dose containing VAP or placebo (referred to as the "study treatments") and consumed by healthy adult women of reproductive age (ages 18 - 49 years).

Participants will undergo 3 treatment periods and will be blinded to treatment sequence using a 3-period, 3-treatment crossover design to receive all 3 treatments. All 3 treatment periods will include blood sampling to measure VA levels from pre- through 24 hours post-broth consumption.

• Unfortified bouillon plus vitamin A in oil (Other): Participants consume unfortified bouillon with vitamin A oil
• Bouillon fortified with vitamin A #1 plus unfortified oil (Other): Participants consume vitamin A #1 fortified bouillon plus unfortified oil
• Bouillon fortified with vitamin A #2 plus unfortified oil (Other): Participants consume vitamin A #2 fortified bouillon plus unfortified oil

Primary outcomes

• Serum retinyl ester area-under-the-effect-curve [Baseline to 8 hours]: The serum retinyl ester area-under-the-effect-curve (corrected for baseline retinyl ester concentrations) will be calculated for each treatment to determine relative absorption of vitamin A, (nmol/L*h)
• Serum retinyl ester area-under-the-effect-curve [Baseline to 24 hours]: The serum retinyl ester area-under-the-effect-curve (corrected for baseline retinyl ester concentrations) will be calculated for each treatment to determine relative absorption of vitamin A, (nmol/L*h)

Secondary outcomes

• Serum retinol maximum concentration (Cmax) [Baseline to 24 hours]: Maximum serum retinol concentration observed, (µmol/L)
• Serum retinyl ester maximum concentration (Cmax) [Baseline to 24 hours]: Maximum serum retinyl ester concentration observed, (nmol/L)
• Time to maximum serum retinol concentration (Tmax) [Baseline to 24 hours]: Time to maximum serum retinol concentration, (h)
• Time to serum retinyl ester maximum concentration (Tmax) [Baseline to 24 hours]: Time to maximum serum retinyl ester concentration, (h)

Other outcomes

• Total body vitamin A using retinol isotope dilution [Baseline]: The retinol isotope dilution test provides an estimate of total body stores of vitamin A, (umol)
• Liver vitamin A concentrations using retinol isotope dilution [Baseline]: The retinol isotope dilution test provides an estimate of liver vitamin A concentrations, (umol/g)
• C-reactive protein [Baseline]: To determine inflammation at each treatment visit, (mg/L)
• Serum carotenoids [Baseline]: Serum carotenoid concentrations will be measured using high-performance liquid chromatography at baseline for each treatment visit, (nmol/L)

Sex: Female, ages: 18 Years to 49 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy, nonpregnant women
* ≥18 and <49 years of age
* Able and willing to provide informed consent
* Body mass index (BMI) between 18.5 to 30.0 kg/m2
* Willing and able to undergo study procedures, including: repeated blood sampling, a baseline hemoglobin and pregnancy test, adherence to a low-vitamin A diet at specified times throughout the study, consumption of provided meals (specifically, a breakfast of bouillon, peanut butter, and a bagel or bread), and, except for the Screening visit, foregoing alcohol for at least 2 days before each visit and fasting for ≥8 hours before each visit

Exclusion Criteria:

* Currently pregnant
* Breastfeeding a child under 1 year of age
* Allergic to soy or peanut butter
* Current use of smoking tobacco products or any other form of nicotine
* Active eating disorder diagnosis
* Current diagnosis of acute or chronic illness, including hepatitis, Celiac's disease, Crohn's disease, and cystic fibrosis
* Moderate or severe anemia according to World Health Organization guidelines (i.e., hemoglobin ≤10.9 g/dL)
* Unable or unwilling to refrain from consuming alcohol when required
* Unable or unwilling to discontinue consumption of foods that are high in vitamin A and of vitamin A supplements when required during the study
* Taking prescription oral medication that includes a retinoid, e.g., isotretinoin/ Accutane
* Taking proton pump inhibitors.
* Unable/unwilling to avoid taking antacids during the fasting period prior to sample collection
* Unable/unwilling to fast for periods of at least 10 hours at a time
* Status relationship with a member of the study team.
* Unable to fulfill study requirements per the judgment of the investigator

• Sherry Tanumihardjo, PhD, Principal investigator, University of Wisconsin, Madison
• Bryan M Gannon, PhD, Study director, University of Wisconsin, Madison
• Luke M Funk, MD, MPH, Study director, University of Wisconsin, Madison
• Justin Chileshe, PhD, Study director, Tropical Diseases Research Centre, Zambia