Daily Intake of Multivitamin & Mineral Supplementation Effects on Biological Age of Relatively Healthy Middle-aged Individuals

Micronutrients, such as vitamins and minerals, are required to sustain fundamental physiological processes in individuals. As individuals age, the risk of having suboptimal levels of micronutrients increases due to several age-related changes affecting their digestion and assimilation processes. Suboptimal levels of micronutrients have been associated with increased risk of chronic diseases and accelerated ageing. Three years intake of a multivitamin and mineral supplement (MVM) improved global cognition, episodic memory and executive function in older adults. Furthermore, suboptimal micronutrient levels have been associated with a higher biological age, and diet and lifestyle interventions might lower the biological age measured by methylation clocks. Therefore, further evaluation is warranted to determine if MVM supplementation could improve the biological age and clinical outcomes in individuals with a higher biological age.

Accelerated ageing, characterized by a reduced function of multiple organ systems, can be measured by biological, clinical and digital biomarkers of aging. These biomarkers of aging are used to express the biological age of individuals. A higher biological age is not only associated with suboptimal micronutrients levels, but can also be reduced through lifestyle intervention, dietary intervention and nutrient supplementation. A frequently used biological biomarker of ageing is DNA methylation (DNAm) status, which is measured using a set of algorithm known as DNAm clock. This value has been accepted as a good indicator to capture fundamental molecular processes tied to the ageing process. Several studies using Vitamin D, Vitamin B12, and Vitamin C and E have shown positively modify DNAm clock, thus biological age. Henceforth, this study aims to determine if MVM supplementation can reduce the biological age in participants who are biologically older as assessed by DNAm clock.

Rationale for Study Population Middle aged individuals with a high biological age have a high risk of age-releated disesases. Efforts are being made to prevent the development and incidence of age-related diseases and therewith to reduce healthcare costs. Relatively healthy (no chronic disease), middle-aged (40-60 (inclusive) years old) individuals with a biological age higher than their chronological age will be included in this randomized, double-blinded, placebo-controlled trial.

Rationale for Study Design CEDIRA is a randomized, double-blinded, placebo-controlled trial including relatively healthy middle-aged individuals with a higher biological age to evaluate the effect of MVM supplementation for 12 months on biological age and other clinical and biological characteristics such as micronutrient levels in blood, anthropometrics, glucose control, lipid profile, cognition, muscle strength, skin health, lifestyle behaviour, and quality of life.

Eligibility Criteria:
Inclusion Criteria

Participants will be recruited if they fall in the following categories:

1. Relatively healthy middle aged (40-60 years) man or woman;
2. Completed the pre-screening requirements and has managed to schedule the screening visit;
3. Met the randomization criteria after the screening visit i.e., your biological age (as measured by blood DNA methylation) is greater than the chronological age;
4. Able to attend all 4 research visits for screening and research data collection at the NUHS Centre for Healthy Longevity (CHL) at Alexandra Hospital or MD11, National University of Singapore.
5. Willing to wear an OURA ring for 14 consecutive days after each study visits.
6. Willing to download study platform application into their mobile phone throughout the study period.

Exclusion Criteria

Participants will NOT be recruited if they fall in any one or more of the following categories:

1. BMI lower than 18 kg/m2 or higher than or equal to 30 kg/m2 \[25\];
2. Pre-existing, or history of major cardiovascular diseases (coronary artery disease, heart failure, stroke, peripheral vascular disease, pulmonary hypertension), severe/uncontrolled hypertension (more than 1 prescribed medication), rheumatic heart disease, congenital heart disease, deep vein thrombosis, pulmonary embolism;
3. Type 1 diabetes and Type 2 diabetes;
4. Active cancer or treatment of cancer in the last 3 years;
5. Chronic obstructive pulmonary disease (COPD), severe asthma (taking daily medications);
6. Pregnant women or women planning pregnancy in the next 12 months;
7. Multiple sclerosis or autoimmune/immune deficiency diseases such as Rheumatic arthritis, HIV, Crohn's disease;
8. Recent history of sepsis or infection (within 3 months of in-patient hospitalisation);
9. Any psychiatric disease or neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Lewy body dementia, and any eating disorders;
10. Hepatitis and liver cirrhosis (independent of severity);
11. Severe kidney disease (GFR less than 30 ml/min/1.73 m2);
12. Skin disease (on systemic medication);
13. Individuals who are on another trial that requires them taking similar or partially similar investigational product (Appendix 1);
14. Individuals who are advised by their medical practitioner to take a MVM supplement;
15. Refuse to stop taking any non-prescribed supplements that contain the investigational product (Appendix 1) within one month before the screening visit and during the study period;
16. Taking a medically prescribed supplements that contains 2 or more of the ingredients of the investigational product (Appendix 1);
17. Individuals with planned hospitalization in the next 12 months;
18. Any serious medical illness which in the PI's judgment may jeopardise the participant by his or her participation in this study or may hamper his or her ability to perform and complete procedures required in the study.