Fortified Bouillon for Vitamin A Absorption

Recruiting at 2 trial locations

Overseen By Bryan M Gannon, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Wisconsin, Madison

Must not be taking: Retinoids, Proton pump inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 periods

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as those containing retinoids (like isotretinoin/Accutane) and proton pump inhibitors. If you are taking these, you will need to discontinue them to participate.

What data supports the effectiveness of the treatment Vitamin A, Retinol, Vitamin A1 in fortified bouillon for vitamin A absorption?

Research shows that food fortification with vitamin A, such as using vitamin A-fortified cooking oil, can significantly improve vitamin A levels in children, which suggests that fortified bouillon could also be effective. Additionally, encapsulated vitamin A in food fortification has been shown to improve stability and absorption, indicating potential benefits for vitamin A absorption in fortified bouillon. ^{1 2 3 4 5}

Is fortified bouillon with vitamin A safe for human consumption?

Vitamin A has been used safely in food fortification programs to address deficiencies, and risk management tools help ensure safe levels are maintained. Concerns about high intake levels are more relevant in affluent countries, while in low-resource areas, the risk of deficiency is greater than the risk of overdose. ^{2 3 6 7 8}

How does the treatment of fortified bouillon for vitamin A absorption differ from other treatments for vitamin A deficiency?

The fortified bouillon treatment for vitamin A absorption is unique because it likely involves the use of encapsulation techniques to enhance the stability and absorption of vitamin A, similar to methods used in food fortification strategies. This approach may improve vitamin A's bioavailability compared to traditional supplements, which can degrade during storage and cooking. ^{2 7 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to measure how well different formulations of vitamin A (VA) are absorbed by the body when they are added to bouillon (broth) as vitamin A palmitate (VAP). Fortifying bouillon cubes with VA is one potential approach to addressing VA deficiency, which is a major public health issue in many low- and lower-income countries. The main question this study aims to answer is to compare the amount of VA that is absorbed by the body from three different VAP formulations that are added to bouillon. Participants will consume different formulations of VA and have multiple blood collections.

Research Team

Luke M Funk, MD, MPH

Principal Investigator

University of Wisconsin, Madison

Justin Chileshe, PhD

Principal Investigator

Tropical Diseases Research Centre, Zambia

Sherry Tanumihardjo, PhD

Principal Investigator

University of Wisconsin, Madison

Bryan M Gannon, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for healthy individuals interested in helping to find new ways to address Vitamin A deficiency. Participants will need to consume various bouillon formulations with vitamin A and undergo blood tests.

Inclusion Criteria

Healthy, nonpregnant women

Able and willing to provide informed consent

Body mass index (BMI) between 20 to 30 kg/m2

Exclusion Criteria

Currently pregnant

Breastfeeding a child under 1 year of age

Unable or unwilling to refrain from consuming alcohol when required

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 3 treatment periods with different vitamin A formulations, including blood sampling to measure vitamin A levels from pre- through 24 hours post-broth consumption

3 periods

Multiple visits for each treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vitamin A

Trial Overview The study is testing how well the body absorbs Vitamin A from three different types of fortified bouillon compared to unfortified bouillon with added vitamin A oil. It aims to identify the most effective formulation.

Participant Groups

Group I: Vitamin A #2 Experimental Treatment 1 Intervention

Bouillon fortified with vitamin A formulation #2 plus unfortified oil

Group II: Vitamin A #1 Experimental Treatment 1 Intervention

Bouillon fortified with vitamin A formulation #1 plus unfortified oil

Group III: Unfortified bouillon positive control Active Control 1 Intervention

Unfortified bouillon plus vitamin A fortified oil

Vitamin A is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Approved in European Union as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Approved in Canada as Vitamin A for:

• Vitamin A deficiency
• Prevention of night blindness
• Supportive therapy in measles

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Particles for Humanity, PBC

Industry Sponsor

Trials

1

Recruited

60+

Tropical Diseases Research Centre, Zambia

Collaborator

Trials

10

Recruited

12,800+

Findings from Research

Increased consumption of carotene-rich fruits and vegetables is associated with better vitamin A status, but this relationship is not definitively causal due to limitations in study designs and conflicting results from recent experiments.

Factors such as the type of carotene, meal composition, and individual host characteristics significantly influence the bioavailability of carotenoids and their conversion to vitamin A, indicating that more research is needed to understand these dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary carotenoids and their role in combating vitamin A deficiency: a review of the literature. de Pee, S., West, CE.[2005]

Encapsulating vitamin A in a special copolymer significantly improves its stability during cooking and storage, making it a more effective option for food fortification against vitamin A deficiency.

In a study with healthy premenopausal women, the encapsulated vitamin A was absorbed similarly to free vitamin A, suggesting that this technology can effectively deliver vitamin A in fortified foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification. Tang, W., Zhuang, J., Anselmo, AC., et al.[2023]

Vitamin A deficiency (VAD) affects around 125-130 million preschool-aged children, increasing their risk of serious health issues, but vitamin A supplementation and food fortification can significantly reduce this risk and improve child survival.

Recent risk management tools allow for the safe use of vitamin A in food fortification, ensuring that populations in low-resource countries can increase their intake without exceeding safe limits, especially since carotenoid sources pose no overdose risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts? Kraemer, K., Waelti, M., de Pee, S., et al.[2019]

A systematic review of 14 randomized control trials involving 6153 children showed that vitamin A fortified foods significantly increase serum retinol levels, indicating improved vitamin A status.

The effect size of vitamin A fortification was moderate (Standard Mean Difference of 0.47), but there was substantial variability in the results across studies, suggesting that factors influencing the effectiveness of fortification may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis approach on vitamin A fortified foods and its effect on retinol concentration in under 10 year children. Mendu, VVR., Nair, KPM., Athe, R.[2020]

A 6-month study involving 542 Filipino children showed that those consuming vitamin A-fortified coconut cooking oil had a significantly greater increase in serum retinol levels compared to those in control groups, indicating improved vitamin A status.

The study highlighted that combining vitamin A-fortified cooking oil with other vitamin A-rich foods is essential for maximizing serum retinol concentration, suggesting a need for promoting both to effectively combat vitamin A deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vitamin A-fortified coconut cooking oil on the serum retinol concentration of Filipino children 4-7 years old. Candelaria, LV., Magsadia, CR., Velasco, RE., et al.[2017]

The study analyzed dietary intake data from 68,962 subjects to determine the maximum safe fortification levels (MSFL) for vitamin A in various demographic groups, revealing that women aged 50 and older had the highest MSFL at 2011.5 µgRE/1000 KJ, while teenage boys had the lowest at 1078.5 µgRE/1000 KJ.

The findings suggest that current fortification levels in foods are safe, with a very low risk of vitamin A overconsumption, as the proposed fortification levels for various food products exceed current national standards in China.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Risk assessment of fortification level for vitamin A in food in China]. Han, JH., Li, XY., Li, YP.[2012]

In a 4-year study of milk products from New York State, only 44.5% of samples met the required vitamin A fortification levels, indicating a significant issue with compliance in reduced fat milk products.

For vitamin D, 47.7% of samples were within the acceptable range, suggesting that while some products are adequately fortified, many still fall short, primarily due to underfortification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluid milk vitamin fortification compliance in New York State. Murphy, SC., Whited, LJ., Rosenberry, LC., et al.[2006]

Mildly oxidized palm oil, when fortified with vitamin A, showed no loss of vitamin A content after two months of storage, making it a suitable option for fortification programs.

In contrast, highly oxidized palm oil experienced a significant 46% decline in vitamin A content during storage, highlighting the importance of using less oxidized oils to maintain vitamin A stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Palm Oil as a Suitable Vegetable Oil for Vitamin A Fortification Programs. Pignitter, M., Hernler, N., Zaunschirm, M., et al.[2018]

A randomized-controlled trial involving 7-9 month old infants in Ghana showed that home fortification with micronutrient powder, including vitamin A, did not significantly change the vitamin A status of infants after 5 months, indicating that both groups had adequate vitamin A reserves.

The study utilized the MRDR and (13)C-RID tests to assess vitamin A status, revealing that these methods provided more comprehensive insights into vitamin A levels than serum retinol concentrations alone, which may not accurately reflect true vitamin A deficiency due to inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin A status and body pool size of infants before and after consuming fortified home-based complementary foods. Newton, S., Owusu-Agyei, S., Asante, KP., et al.[2020]

A new liposome/β-lactoglobulin formulation has been developed that effectively encapsulates Vitamin A, protecting it from oxidation and improving its solubility, which are key challenges in its application.

In vivo tests in mice showed that this new delivery system enhances the bioavailability of Vitamin A, suggesting it could be a promising method for food fortification to address Vitamin A deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo assessment of vitamin A encapsulation in a liposome-protein delivery system. Rovoli, M., Pappas, I., Lalas, S., et al.[2019]

Lipid nanoparticles were successfully developed to encapsulate vitamin A, enhancing its stability and bioaccessibility for food fortification, with 80% of the vitamin reaching the intestine during digestion.

The nanoparticles maintained their size and vitamin content under food processing conditions and showed no toxicity in cell tests, indicating they are safe for use in food applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoencapsulation approaches for oral delivery of vitamin A. Resende, D., Costa Lima, SA., Reis, S.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Dietary carotenoids and their role in combating vitamin A deficiency: a review of the literature. [2005]

2. United States pubmed.ncbi.nlm.nih.gov

Enhanced stability and clinical absorption of a form of encapsulated vitamin A for food fortification. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts? [2019]

4. England pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis approach on vitamin A fortified foods and its effect on retinol concentration in under 10 year children. [2020]

5. China pubmed.ncbi.nlm.nih.gov

The effect of vitamin A-fortified coconut cooking oil on the serum retinol concentration of Filipino children 4-7 years old. [2017]

6. China pubmed.ncbi.nlm.nih.gov

[Risk assessment of fortification level for vitamin A in food in China]. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

Fluid milk vitamin fortification compliance in New York State. [2006]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Palm Oil as a Suitable Vegetable Oil for Vitamin A Fortification Programs. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Vitamin A status and body pool size of infants before and after consuming fortified home-based complementary foods. [2020]

10. England pubmed.ncbi.nlm.nih.gov

In vitro and in vivo assessment of vitamin A encapsulation in a liposome-protein delivery system. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Nanoencapsulation approaches for oral delivery of vitamin A. [2021]