Do healthy people absorb cow-derived microRNAs from drinks?
| ISRCTN | ISRCTN16329971 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16329971 |
| Secondary identifying numbers | 13755 |
- Submission date
- 01/02/2019
- Registration date
- 07/02/2019
- Last edited
- 24/01/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Recent research has identified a new type of substance naturally found in foods that may play a role in nutrition and health. This substance is called microRNA and is naturally occurring in both plants and animals. microRNAs are thought be be involved in controlling the levels of substances produced by cells. Along with other foods, milk contains microRNAs within exosomes (bubbles released by cells). This study aimed to investigate whether people absorb immune-relevant microRNAs from cow’s milk into the blood and whether these affect human immune responses.
Who can participate?
Health adults who are not pregnant, smokers or intolerant to cow's milk.
What does the study involve?
Participants drank five different drinks based on 1 litre of cow's milk or soy-based infant formula with a period of at least a week between each one. Some of the drinks contained extra cow's milk exosomes and some had the exosomes destroyed. Blood samples were taken immediately before the drink and at 3, 6 and 9 hours afterwards.
What are the possible benefits and risks of participating?
There were no direct benefits to research participants. Minimal risks were anticipated for the participants. However, potential risks included intolerance to milk, fatigue due to blood draws, and risk of bruising. No other physical, psychological, financial, etc., risks were expected. Blood draws may make someone become anxious, light-headed, nauseous, or generally uneasy. All blood draws were performed by University of Nebraska-Lincoln Health Center phlebotomists (experts in taking blood samples) who have been trained and are experienced in dealing with subjects who may become anxious during blood draw procedures.
Where is the study run from?
University of Nebraska-Lincoln (USA)
When is the study starting and how long is it expected to run for?
October 2013 to June 2019
Who is funding the study?
The Gerber Foundation (USA)
Who is the main contact?
Dr Janos Zempleni
jzempleni2@unl.edu
Contact information
Public
Department of Nutrition and Health Sciences
University of Nebraska-Lincoln
316 Leverton Hall
Lincoln
68583
United States of America
| Phone | +1 704-421-1477 |
|---|---|
| emutai@huskers.unl.edu |
Scientific
Department of Nutrition and Health Sciences
University of Nebraska-Lincoln
316C Leverton Hall
Lincoln, NE 68583-0806
USA
Lincoln
68583
United States of America
 ORCID ID |
0000-0001-5492-4661 |
|---|
Study information
| Study design | Randomized crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Bioavailability of immunomodulatory microRNAs from bovine milk exosomes and cytokine secretion by peripheral blood mononuclear cells ex vivo in humans |
| Study objectives | Immune-related miRNAs in bovine milk exosomes are bioavailable and modulate immune responses in humans. Immunomodulatory microRNAs depend on co-stimulation with concanavalin A to elicit cytokine secretion by peripheral blood mononuclear cells ex vivo in humans |
| Ethics approval(s) | Approved 10/10/2013, University of Nebraska-Lincoln Institutional Review Board (IRB) (301 Canfield, PO Box 880433, Lincoln, NE 68588-0433, USA; +1 (402) 472-3123; unlresearch@unl.edu), ref: 20131013755FB |
| Health condition(s) or problem(s) studied | Relevance of bovine milk exosomes as bioactive food compounds and use of exosomes for drug delivery. |
| Intervention | 12 healthy adults received 5 different milk meals in a randomized cross-over design, with a washout period of at least 1 week between each meal. The milk meals were 1 l of 1% fat bovine milk, 1 l of 1% fat sonicated bovine milk (exosomes depleted), 1 l of soy infant formula, 1 l of soy infant formula fortified with bovine milk exosomes, and 1 l of 1% fat sonicated bovine milk and fortified with bovine milk exosomes (exosomes containing microRNAs depleted by ultrasonication and then exosomes isolated from 1 l of bovine milk added back to the sonicated milk). Blood samples were collected before and at timed intervals after consumption of the various milk meals for analysis of bioavailability of six immune-relevant microRNAs in plasma and secretion of cytokines by peripheral blood mononuclear cells ex vivo. |
| Intervention type | Other |
| Primary outcome measure | Levels of six immune-relevant microRNA found in bovine milk exosomes in plasma using real-time quantitative polymerase chain reaction (RT-qPCR) before (0 h) and at timed intervals (3, 6,and 9 h) after a milk meal |
| Secondary outcome measures | 1. Secretion of inflammation-related cytokines by cultured human peripheral blood mononuclear cells (PBMCs) collected before and 6 h after milk consumption and stimulated with or without Concanavalin A (Con A) was assessed using a customized Milliplex Map Human Cytokine/Chemokine Magnetic Bead Panel Immunoassay 2. Secretion of cytokines by PBMCs treated ex vivo with microRNA-loaded exosomes assessed using a customized Milliplex Map Human Cytokine/Chemokine Magnetic Bead Panel Immunoassay |
| Overall study start date | 10/10/2013 |
| Completion date | 06/06/2019 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 12 |
| Key inclusion criteria | Healthy adults |
| Key exclusion criteria | 1. Pregnant women 2. Smokers 3. Persons with lactose and milk protein intolerance or gastrointestinal disorders |
| Date of first enrolment | 09/04/2015 |
| Date of final enrolment | 30/11/2017 |
Locations
Countries of recruitment
- United States of America
Study participating centre
University of Nebraska-Lincoln
316C Leverton Hall
Lincoln
68583
United States of America
Sponsor information
Other
4747 West 48th Street, Suite 153
Fremont, MI 49412-8119
Fremont
49412
United States of America
| Phone | 231-924-3175 |
|---|---|
| tgf@gerberfoundation.org | |
| Website | http://www.gerberfoundation.org/ |
"ROR" |
https://ror.org/03ggcx620 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- The Gerber Foundation, GerberFdnWMI, The Gerber Companies Foundation, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/03/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2020 | 10/06/2020 | Yes | No |
| Results article | 21/01/2022 | 24/01/2022 | Yes | No |
Editorial Notes
24/01/2022: Publication reference added.
10/06/2020: Publication reference added.
