Effect of Omega-3 and Probiotic Dietary Supplements on Elevated High Sensitivity C-reactive Protein (Hs-CRP) as a Marker of Low-grade Inflammation

• Probiotic, Omega-3, Vitamin D supplement (Dietary supplement): The first supplement we would like to assess is named VNP and is composed by Omega-3 Active and vitamin D. It contains a total of 1100 mg fish oils: 640 mg Omega-3 and with 300 mg eicosapentaenoic acid (EPA), 220 mg docosahexaenoic acid (DHA) plus 200 IU Vitamin D per daily dose (2 capsules). The second supplement we investigate is four-strain probiotics combination based on the commercially available formulation HOWARU® by DuPont; two capsules containing 10 billion CFU total (supplied by Pfizer but manufactured by Danisco, DuPont). The probiotic specific composition, contains equal amounts of each strain per capsule (1.25 x 109 CFU each): Bifidobacterium lactis Bi-07, Lactobacillus paracasei Lpc-37, Lactobacillus acidophilus NCFM, Bifidobacterium lactis Bl-04. One capsule contains 5 billion CFU (Swedish milliards).
• Placebo (Dietary supplement): Placebo generated for probiotic and omega-3/vitamin D supplements

Primary outcomes

• hs-CRP [baseline, 4 weeks (mid-study), 8 weeks (study end)]: Decrease in overall body inflammation measured by at least 15% reduction in hs-CRP levels in blood

Sex: All, ages: 25 Years to 80 Years

Inclusion Criteria:

* 65-80 years old for elderly arms
* 25-65 years old for obese arms
* screening hs-CRP of 1.5-6 mg/L for elderly
* screening hs-CRP of 2-10 mg/L for obese
* BMI 18.5-27 for elderly
* BMI 28-40 for obese
* Signed informed consent prior to any study related procedures
* Prospect to start the study the latest 6 weeks after the screening visit although preferably as soon as they receive the screening results
* Willing to abstain from regular consumption of probiotic supplements, products containing probiotic bacteria
* Willing to abstain from regular consumption of medication known to alter gastrointestinal functions for at least 4 weeks prior to the time of the study inclusion
* Willing to fast at least 5 hours during the sugar-permeability-test and receive a standardised breakfast (e.g. Cereal bar) or other standardised meal
* Accepting to drink at least 1.5 litres of provided water in one day, during the two time points where the sugar test is performed

Exclusion Criteria:

1. Diagnosis of type 1 and/or type 2 diabetes
2. Current or within 4 weeks use of probiotic supplement prior to inclusion
3. More than 4 hours/week exercise habits
4. Immobile, defined as the inability to participate in all study related procedures
5. Dietary intake of fatty fish, fish oils containing omega-3 or pure omega- 3 supplements more than 2 times/week
6. History of complicated gastrointestinal surgery
7. Diagnosed Inflammatory Bowel Disease (IBD)
8. Current diagnosis of psychiatric disease/s or syndromes
9. Systemic use of antibiotics and/or steroid medication in the last 4 months prior to inclusion time
10. Use of any NSAID (Non-Steroidal Anti-Inflammatory Drugs) more than 3 times a week for the last 2 months and any time 3 days prior inclusion or at any time 3 days prior the barrier function test
11. Consumption of any NSAID up until 7 days prior to inclusion
12. Any condition which could interfere with the intestinal barrier function (e.g. gluten sensitivity, lactose intolerance, celiac disease, IBS, IBD) as decided by the principal investigators´ discretion
13. Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion.
14. Regular smoking, use of snuff, nicotine or e-cigarette use
15. Regular use, for more than three times a week for the last 2 months and any time 7 days prior to inclusion, of medications which according to the principal investigator can have an anti-inflammatory effect or affect in any way the intestinal barrier function or have an impact on the study analysis (e.g. laxatives, anti-diarrheal, anti-cholinergic).
16. Any disorder which according to the principal investigator can have an anti-inflammatory effect and/or can affect the intestinal barrier function, or that can impact an adequate analysis of the study outcomes
17. After being included in the study, starting with a medication/treatment or medical intervention that could potentially influence the study participation and/or the study analysis (e.g. the event of a fracture)
18. Radical change in diet (e.g. becoming vegetarian or if they discover that they are lactose intolerant) during the study period
19. Allergic to fish
20. Allergic to milk- or soy protein

• Robert JM Brummer, Prof MD PhD, Principal investigator, Örebro University, Sweden