Effects of vitamin D and probiotic supplements in older people
| ISRCTN | ISRCTN10131460 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10131460 |
| IRAS number | 304233 |
| Secondary identifying numbers | IRAS 304233, CPMS 51488 |
- Submission date
- 04/04/2022
- Registration date
- 06/04/2022
- Last edited
- 17/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English Summary
Background and study aims
As we age, our immune system becomes weaker and there is an increase in inflammation which contributes to common age-related diseases. These include heart disease, metabolic disease such as type 2 diabetes, the loss of muscle mass and strength known as sarcopenia, the weakening of bones known as osteoporosis, some cancers, and possibly dementia. A weaker immune system means older people can be more susceptible to infections and some vaccines may not work as well as in younger adults.
The “healthy” bacteria in our intestine (called gut microbiota) have an influence on our immune system and inflammation. Our intestinal bacteria also change with ageing and this can result in the loss of protective function and in the movement of harmful bacterial toxins and whole bacteria from the gut into the blood. Why these changes occur and how we can improve this in ageing are not understood. What we do know is that our intestinal bacteria can be altered by our diet. They can also be altered by probiotics, which are live healthy bacteria often found in yoghurts. In this study the researchers plan to investigate whether nutritional supplements of vitamin D and a probiotic improve measures of muscles, bone, the immune system, inflammation and intestinal bacteria. The probiotic organism used is called Lactobacillus plantarum. Vitamin D has an important role in maintaining healthy bones and a healthy immune system and preventing too much inflammation and has also been seen to positively affect the intestinal bacteria. Lactobacillus plantarum is commercially available and has been seen to positively affect the intestinal barrier but its effects on the immune system and inflammation have not been tested in older people.
The researchers plan to compare the effects of using either vitamin D and Lactobacillus plantarum individually or together in combination on intestinal bacteria, the immune system and inflammation, and other measures of ageing including bones and muscles.
Who can participate?
Healthy men and women over the age of 70 years
What does the study involve?
The study involves making two visits to the Clinical Research Facility at University Hospital Southampton. Each visit will last 1.5 to 2 hours. In between visits participants will be randomly allocated to consume supplements of either placebo, vitamin D, probiotic, or vitamin D plus probiotic each day for 12 weeks.
At each clinic visit participants will be asked to answer a set of questions about their diet, quality of life, and physical activity. They will provide a blood sample for measurement of immune, inflammatory and metabolic markers as well as indicators of intestinal integrity.
In between the two visits participants will be asked to complete a daily paper diary to record ingestion of their supplement and complete a questionnaire every day about their respiratory health (if they are well they will not need to do this).
Participants will be asked to provide urine and faecal samples at the start and end of the study. On the days they provide urine samples they will complete a diary about their diet – this can be done as a paper diary or online.
What are the possible benefits and risks of participating?
Participants may benefit from positive effects on their immune system and/ or their intestinal bacteria. Knowledge gained from this study will help research and will ultimately be of use to other researchers and consumers.
With any procedure involving blood collection with a needle, there is a very small chance of infection and a chance of bleeding and bruising at the site of insertion of the needle. This will be minimised by using sterile techniques and trained members of staff.
Where is the study run from?
The University of Southampton (UK)
When is the study starting and how long is it expected to run for?
July 2018 to September 2024
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Prof. Philip Calder
pcc@soton.ac.uk
Contact information
Principal Investigator
School of Human Development and Health
Faculty of Medicine
University of Southampton
IDS Building
Tremona Road
Southampton
SO16 6YD
United Kingdom
 ORCID ID |
0000-0002-6038-710X |
|---|---|
| Phone | +44 (0)2381205250 |
| pcc@soton.ac.uk |
Study information
| Study design | Randomized controlled trial with a 2 x 2 factorial design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Prevention |
| Participant information sheet | 41487_PIS_25Mar22_V3.pdf |
| Scientific title | Influence of vitamin D and a probiotic on inflammation and gut bacteria |
| Study acronym | Nutriom |
| Study hypothesis | The objectives of this study are to identify the effect of vitamin D (calcifediol) and Lactobacillus plantarum TIFN101 alone and together on the intestinal microbiota, markers of immune function and inflammation and other health-related markers (blood lipids, body composition, muscle strength) in older adults. |
| Ethics approval(s) | Approved 25/01/2022, South Central - Hampshire A Research Ethics Committee (Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK; +44 (0)2071048033/53; hampshirea.rec@hra.nhs.uk), ref: 21/SC/0403 |
| Condition | Older people (aged 70+ years) living in the community |
| Intervention | Participants will be given IDs from 001 to 104. These IDs have been randomly allocated to treatment groups using a randomisation programme, with randomisation stratified for sex based upon a 50:50 distribution. 1. Control 2. Vitamin D (calcifediol) 10 micrograms/day 3. Lactobacillus plantarum TIFN101 5 billion colony forming units/day 4. Both vitamin D (calcifediol) and Lactobacillus plantarum TIFN101 Interventions will be delivered as capsules in blister packs with two capsules to be taken each day for 12 weeks. |
| Intervention type | Supplement |
| Primary outcome measure | Measured at study entry and exit (week 12): 1. Serum 25-hydroxyvitamin D3 concentration (nmol/l) measured by immunoassay 2. Colonisation with the probiotic organism detected in faeces (number of organisms per g faeces) measured by 16S RNA 3. Serum CRP concentration measured by ELISA (mg/dl) |
| Secondary outcome measures | All measured at study entry and exit (12 weeks) 1. Blood immune cell phenotypes (number of each cell type per microlitre of blood) measured by flow cytometry 2. Plasma inflammatory markers (mg/l) measured by immunoassay 3. Faecal microbiome taxonomy (numbers of different organisms per g faeces) measured by 16S RNA 4. Weight (kg), body mass index (kg/m²), body fat mass (kg and % body weight), body lean mass (kg and % body weight), mid arm upper circumference (cm), waist circumference (cm), hip circumference (cm), waist:hip ratio, measured by weighing scales, tape measure and bioelectric impedance 5. Hand grip strength (kg) measured using a dynamometer 6. Dietary intake (amounts of foods and nutrients) measured using the EPIC food frequency questionnaire and intake24 recall 7. Quality of life (questionnaire plus visual analog scale) measured using the EQ5D5L questionnaire 8. Physical activity measured using the Physical Activity Scale for the Elderly (PASE) questionnaire 9. Respiratory symptoms measured using the Wisconsin Upper Respiratory Symptom Survey (WURSS) 10. Blood glucose (mml/l), insulin (U/l) and HOMA-IR measured by enzyme-linked colorimetric assays 11. Blood lipids (total, LDL and HDL cholesterol, triglycerides; all mmol/l) measured by enzyme-linked colorimetric assays 12. Blood adipokines (leptin, adiponectin, leptin/adiponectin ratio, visfatin and resistin; mg/l) measured by ELISA 13. Blood markers of intestinal barrier integrity (mg/l) measured by ELISA 14. Blood PTH (pg/ml) and calcium (mg/dl), as markers of vitamin D homeostasis 15. Faecal metabolome measured by nuclear magnetic resonance (NMR) 16. Urinary metabolome measured by NMR |
| Overall study start date | 31/07/2018 |
| Overall study end date | 30/09/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Senior |
| Lower age limit | 70 Years |
| Sex | Both |
| Target number of participants | 104 |
| Total final enrolment | 78 |
| Participant inclusion criteria | 1. Community dwelling males and females aged 70+ years 2. Body mass index 18.5-35 kg/m² 3. Willing to adhere to the study protocol 4. Able to provide written informed consent |
| Participant exclusion criteria | 1. Living in a care or nursing home 2. Diagnosed with diabetes or other metabolic and endocrine disorders 3. Presence of active gastrointestinal disease (coeliac disease, Crohn’s disease, diagnosed IBD etc), autoimmune disease, or inflammatory disease (lupus, rheumatoid arthritis, multiple sclerosis) 4. Use of prescribed medicine to control inflammation (e.g. non-steroidal anti-inflammatory drugs; NSAIDs) or prescribed vitamin D or calcium+vitamin D or regular use of over-the-counter NSAIDs 5. Use of dietary supplements (will allow a 4-week washout period) 6. Use of probiotic drinks or yoghurts (will allow a 4-week washout period) 7. Blood donation in the previous 3 months 8. Participation in any other clinical trial in the previous 3 months |
| Recruitment start date | 21/04/2022 |
| Recruitment end date | 31/05/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
IDS Building
Tremona Road
Southampton
SO16 6YD
United Kingdom
Sponsor information
University/education
University Road
Southampton
SO17 1BJ
England
United Kingdom
| Phone | +44 (0)2380595058 |
|---|---|
| rgoinfo@soton.ac.uk | |
| Website | https://www.southampton.ac.uk |
"ROR" |
https://ror.org/01ryk1543 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in high-impact peer-reviewed journals. |
| IPD sharing plan | The anonymised datasets generated during and/or analysed during the current study will be available upon request from Philip Calder (pcc@soton.ac.uk) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 3 | 25/03/2022 | 05/04/2022 | No | Yes |
| Protocol file | version 3 | 21/11/2022 | 16/02/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
17/12/2024: The intention to publish date was changed from 31/12/2024 to 30/06/2025.
15/03/2024: Total final enrolment added. The overall trial end date was changed from 31/03/2024 to 30/09/2024.
10/07/2023: The overall end date was changed from 31/12/2023 to 31/03/2024.
17/02/2023: The following changes were made to the trial record:
1. IPD sharing statement added.
2. The recruitment end date was changed from 31/10/2022 to 31/05/2023.
3. The overall trial end date was changed from 30/09/2023 to 31/12/2023.
4. The intention to publish date was changed from 01/06/2024 to 31/12/2024.
16/02/2023: Protocol file uploaded (not peer reviewed).
05/05/2022: Internal review.
05/04/2022: Trial's existence confirmed by the HRA.
