Multivitamin and Mineral Supplementation and Healthy Aging (MiMIC)

The Impacts of Multivitamin and Mineral Supplementation on Cellular Metabolism and Healthy Aging

The goal of this study is to determine the impact of MVM supplementation on clinical and biochemical markers associated with healthy aging, with a particular focus on mitochondrial function and metabolism. Specifically, changes in mitochondrial respiration using isolated blood cells will be measured. This method has been used to compare with various other age-related markers of health such as physical function, gait speed, and resting metabolic rate. It is hypothesize that MVM supplementation will impact the function of blood cells. We will also explore how MVM supplementation impacts other markers of health, including serum nutrient levels, metabolomic profiles, physical function, and skeletal muscle composition and quality. These comprehensive assessments will provide insights into the potential benefits of MVM supplementation for healthy aging and address critical gaps in our understanding of its immediate effects. Further, this study will aid in the understanding of how multivitamin supplements can support heathy aging in mid-life adults, a key time to start including wellness programs in our lives.

The study cohort will consist of 150 sedentary men and women aged 40-60-years of age. A double-blind, three-arm, placebo-controlled randomized clinical trial will be conducted. Participants will receive a daily oral tablet containing one of two possible formulations of vitamins and minerals or a placebo. The three groups will be MVM "GOLD" blend formula, the US Restage MVM "US CORE", and the placebo group.

Study Overview

• Status: Recruiting
• Conditions: Healthy Aging; Multivitamin and Mineral Supplementation
• Intervention / Treatment: Dietary supplement: MVM Core Blend; Dietary supplement: MVM Gold Blend; Dietary supplement: Placebo

Detailed Description

As the global population of older adults continues to expand, it is imperative to identify accessible and evidence-based interventions to support healthy aging. Among the key biological hallmarks of aging, mitochondrial dysfunction is highly modifiable and especially responsive to lifestyle interventions such as diet and exercise. Importantly, our clinical studies demonstrate that mitochondrial bioenergetics plays a key role in the physical and cognitive abilities of older adults. Thus, identifying interventions that can improve mitochondrial bioenergetics is a promising avenue for the development of healthy aging interventions.

Multivitamin and mineral (MVM) dietary supplements have been used to support general health and nutritional status for years, particularly in older adults who are more susceptible to nutritional deficiencies due to factors such as reduced appetite, malabsorption, and polypharmacy. Observational studies consistently demonstrated that older adults exhibit higher rates of nutritional deficiencies, and that MVM supplementation may ameliorate these burdens. More recently, evidence suggests that MVM use may also confer functional health benefits; for example, the COSMOS-Mind trial demonstrated efficacy of MVM on global cognition, memory, and executive function in 2262 participants. Notably, most MVM studies are longitudinal and occur over the course of many years. A significant gap remains in understanding the acute effects of MVM supplementation on health and aging. Can rapid, measurable improvements in health be observed with MVM use? Moreover, what are the cellular mechanisms that can underlie the benefits of MVM use?

Description of Study Intervention: The study cohort will consist of 150 sedentary men and women aged 40-60-years of age. A double-blind, three-arm, placebo-controlled randomized clinical trial will be conducted. Participants will receive a daily oral tablet containing one of two possible formulations of vitamins and minerals or a placebo. The three groups will be MVM "GOLD" blend formula, the US Restage MVM "US CORE", and the placebo group. Specific formulations of the three tablets are detailed in the 2025 Stability Provisional Expiry for Centrum Gold Blend Tablets (FN-2492-0001), Centrum US Restage Blend Tablets (FN-2493-0001, and Placebo of Centrum Gold Blend Tablets (FN-0436-0231) -

Assessments:

The baseline study visit will occur at least 2 weeks after, but no more than 4 weeks after, the initial screening visit (actigraph will be deployed at screening and will be worn for 2 weeks).

At each study visit (V1, V2, V3, V4) the participant will undergo a fasted blood-draw followed by a snack break, assessment of vital signs, and physical assessments as listed below.

Sample Collection: A licensed phlebotomist will perform a venipuncture blood draw at the forearm, arm, or antecubital fossa of either arm and collect 20 ml of blood into three 10ml Acid Citrate Dextrose (ACD) tubes, one serum-separating tube (SST), and one ethylenediaminetetraacetic acid (EDTA) tube for each blood-draw visit (V1, V2, V3, V4). On visits V2 and V3, we will collect three additional ACD tubes for fresh cell assays. Our previous studies indicate that samples are stable for 8 hours at room temperature.

Within 1 hour of sampling, blood will be processed to separate blood components. Blood will be spun and components will be frozen, incuding platelets and PBMCs from all four blood-draw visits (V1-V4) for frozen respirometry. During V1 (baseline) and V3 (week 12) visits, live cells will be isolated for fresh respirometry. Fresh respirometry will include platelets, PBMCs, monocytes, and lymphocytes.

Clinical Laboratory Measurements: tubes of whole blood will be provided to the UCSD Center for Advanced Laboratory Medicine (CALM) Labs as well as the Associated Regional and University Pathologists, Inc (ARUP) Laboratories in Salt Lake City, UT to run various blood tests, including: compete blood count, comprehensive metabolic panel, c-reactive protein, sedimentation rate, lipid panel, and serum levels of cortisol, vitamins D, B12, B6, E, C, and beta-carotene.

Assessment of Vital Signs: Measurements of height, weight, heart rate, and blood pressure will be administered by trained study staff.

Wireless Activity Monitor: Objective assessments of physical activity will be measured using the ActiGraph GT3X+ accelerometer (ActiGraph, LLC; Pensacola, FL). The GT3X+ is a lightweight (19g) triaxial solid state accelerometer, with a dynamic range of +/- 6g and a user-specified sampling rate of 30-100hz (in 10hz increments) (19). The device is approximately 2''x2'x0.5'' in size and is worn on the hip attached to a belt around the waist. The device has 512MB of non-volatile flash memory and a 3.7V prismatic lithium-ion battery allowing for 40 days of raw acceleration data to be collected at 30Hz.

This method employs the seven-step algorithm identified as best-practice for the collection, processing, and summarization of PA accelerometer data collected with wearable systems (20). We will provide wear time instructions, and a brief self-report wear time log for participants to note periods that the device was taken off. Participants will be asked to wear the ActiGraph for seven days and will be prompted twice via telephone during the monitoring period (wear days 2 and 5) to assist with compliance. Upon return, we will immediately download and screen ActiGraph data by hour for completeness and possible irregularities/malfunction according to best practice recommendations (21).

Accelerometer outcome variables include (i) mean minutes per day of sedentary time, (ii) mean minutes per day of light intensity physical activity, and (iii) minutes per week of moderate-to-vigorous intensity physical activity (MVPA). Additional variables will also be computed based on patterns of how sedentary time and MVPA is accumulated (e.g., minutes of sedentary time per day occurring in bouts ≥30 minutes; minutes per week of MVPA occurring in bouts of ≥ 10 minutes).

Grip Strength: Hand grip strength will be measured in both hands using an adjustable grip strength dynamometer (BL5001 Hydraulic Hand Dynamometer). Participants will have a chance to familiarize themselves with the measurement by making a submaximal effort on both hands to feel how the instrument will react. For the assessment, the participant will stand and hold the dynamometer in their hand with their arm down at their side. The participant will be instructed to take a deep breath in and squeeze as hard as possible as they exhale. The measurement will be repeated twice on each hand, alternating between each side, and the highest score for each hand will be recorded to the nearest kilogram.

Submaximal Graded Exercise Test: Participants will undergo Submaximal Graded Exercise Test (GXT) on a treadmill at EPARC under the supervision of a trained exercise physiologist. Participants will complete a walking protocol at a self-selected speed, with the treadmill incline increasing every two minutes to progressively increase cardiovascular demand. The test will continue until the participant reaches 85% of their age-predicted maximal heart rate (calculated as 220 bpm - age) or experiences volitional fatigue, whichever occurs first.

The test itself is expected to last approximately 5-10 minutes, excluding warm-up and recovery periods, with the total session lasting about 20 minutes. For the first visit (V1), we will closely monitor blood pressure and heart rate before, during, and after the test, including at least five minutes into recovery and again before the participant leaves the lab. If there is a risk detected during blood pressure monitoring, (systolic >200, or an increase in diastolic during exercise), then BP monitoring will continue throughout all visits. For every visit, continuous heart rate monitoring will be performed via Polar chest strap, and ratings of perceived exertion (RPE) will be collected at regular intervals during the test.

In the unlikely event of a cardiac event or medical emergency, EPARC staff are trained in emergency procedures, and an automated external defibrillator (AED) and supplemental oxygen are available on-site. The protocol aligns with standardized exercise testing guidelines to provide reliable and meaningful physiological data while prioritizing participant safety.

Dual-energy X-ray Absorptiometry (DXA) Bone Mineral Density/Content (BMD/BMC) and Body Composition BMD/BMC and body composition will be assessed by dual energy x-ray absorptiometry (DXA) on a Prodigy Advance densitometer (GE/Lunar, Madison, WI). Densitometry will be performed by the same technician certified by the State of California Radiologic Health Branch. The scan sites include the spine (L1-L4), proximal femur (femoral neck and total hip), and whole body. The DXA whole body scans will be used to determine whole body BMD/BMC as well as body composition (fat and fat-free mass, and %fat). The total time required for subject positioning and scanning of the spine and hip is about 5 minutes, and ~6 minutes for the total body, in standard scan mode. Radiation exposure for all 3 scans is approximately 8-10 μSv (0.8-1.0 mRem), which is approximately equal to a day of background exposure. Since the long-term effects of exposure to a fetus are not known, pregnant women will not be scanned. Quality assurance tests are performed each morning of testing. The mean coefficient of variation (% CV) in our laboratory, based on precision studies of 30 individuals measured twice on the same day is: 0.64% for the total hip, 1.39 for femoral neck, 0.82% for the spine (L1-L4), 0.85% for total body BMD, 1.89% for total body fat mass, and 0.7% for total lean mass.

Subject Preparation Subjects are instructed, prior to the day of their scan, to dress in single-layer, loose clothing free of any metal, plastic, or similar materials, including all jewelry as well as leather or other dense fabrics. Women are encouraged to wear a halter-top or something similar. Subjects should be normally hydrated, and if they take a calcium supplement, not to take it on the day of their scan. Scans should not be done within 10-14 days following medical testing requiring any contrast agent.

Weekly Electronic Surveys: Weekly electronic surveys will be sent using REDCap. Electronic surveys will include the Diet Quality Questionnaire (DQQ), Warwick-Edinburgh Mental Well-Being Scale (WEMWBS), Short Form Survey (SF-36) quality of life survey, SATED sleep survey, and Pittsburgh Sleep Quality Index (PSQI) [sleep surveys are only administered monthly]. Participants will fill out an electronic adherence log each week to keep track of study compliance.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lina Scandalis, PhD; Phone Number: 18588226443; Email: Lscandalis@health.ucsd.edu
• Study Contact Backup: Name: David Wing, PhD; Phone Number: 8585349317; Email: dwing@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California, San Diego
      • Contact: Lina Scandalis, PhD; Phone Number: 18588226443; Email: Lscandalis@health.ucsd.edu
      • Contact: David Wing, PhD; Email: dwing@health.ucsd.edu
      • Principal Investigator: Anthony Molina, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. IPAQ-SF categorical score of low or moderate physical activity (indicating sedentary lifestyle).
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Between 40-60 years of age
4. BMI ≥18.5 and ≤32 kg/m2
5. Weight stable for the prior 6 weeks

Exclusion Criteria:

1. Is pregnant or nursing.
2. Current smoker.
3. Diabetes (FPG > 180 mg/dL or A1c>8)
4. Heart or cardiovascular condition, including coronary artery disease, congestive heart failure, diagnosed abnormality of heart rhythm, atrial fibrillation and/or a history of myocardial infarction
5. Cancer or history of cancer within the past 5 years
6. Sensory or physical impairment that would prevent participation
7. Parkinson's disease, multiple sclerosis or other neurological condition, including a previous stroke, that may be causing impaired muscle function or mobility
8. Consistent use of any multivitamin and mineral supplement use, or any supplement that may interfere with measurements or biological outcomes (including but not limited to: NAD+ supplements, MitoQ)
9. Individuals with drug interactions as determined by the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MVM Core Blend; This is a modification to currently marketed Centrum Adult in which select nutrients have been removed or lowered to provide a better consumer experience. This will be consumed once per day for the duration of the study.	Dietary supplement: MVM Core Blend; Consists of a pill containing a 22-ingredient blend of vitamins and minerals 1 pill will be taken daily, 7 days/week for 12 weeks
Experimental: MVM Gold Blend; Because Centrum is a global multivitamin/multimineral brand, it has numerous product formulations for different regions/markets around the world. To better harmonize these formulations across key markets, a 'core' blend of vitamins and minerals has been designed at levels that can be leveraged across different markets - this is internally being referred to as the MVM "GOLD" Blend formula. This will be consumed once per day for the duration of the study.	Dietary supplement: MVM Gold Blend; Pills, participants will take contain a 17-ingredient blend of vitamins and minerals. Instructions: 1 pill each day, 7 days/week for 12 weeks
Placebo Comparator: Placebo; The placebo is a pill of the same color, size, and density as the experimental pills. It contains no vitamins or minerals. It will be administered once a day as the experimental pills.	Dietary supplement: Placebo; Pill contains no vitamins or minerals. 1 pill will be taken daily, 7 days/week, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PBMC Respiratory Capacity by Oxymetry	Multivitamin and mineral supplementation may have an impact on blood cell bioenergetics. The high-resolution Oroboros Oxygraph 2k as well as high throughput Seahorse will be used to measure maximal oxidative phosphorylation (Max OXPHOS) in freshly prepared PBMCs. Max OXPHOS is the highest measured rate of mitochondrial ATP production and is measured in picomols of oxygen per time weight, or pmol/s*mg. This measurement will be taken at baseline and after completion of the study supplementation.	From enrollment to the end of study at 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentrations of dietary Vitamins B6 and E	Dietary nutrients will be measured from two study time points: baseline and study completion. Serum nutrient levels to be measured are Vitamins B6 and E are measured by automated analyzer and are reported in mg/L.	From enrollment to end of study period at 14 weeks
Serum concentrations of Vitamin C and Beta-Carotene	Dietary nutrients will be measured from two study time points: baseline and study completion. Serum nutrient levels to be measured are Vitamins c and Beta carotene and are measured by automated analyzer. These are reported in mg/Dl.	Measures are taken from baseline to end of study at 14 weeks
Serum concentrations of Vitamins D and B12	Dietary nutrients will be measured from two study time points: baseline and study completion. Serum nutrient levels to be measured are Vitamins D and B12 and are measured by automated analyzer. These are reported in pg/mL.	Measurements are taken from baseline to the end of the study at week 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of Grip Strength by hand-held dynamometer	Strength will be measured by hand grip in both hands using an adjustable grip strength dynamometer (BL5001 Hydraulic Hand Dynamometer). Participants will have a chance to familiarize themselves with the measurement by making a submaximal effort on both hands to feel how the instrument will react. For the assessment, the participant will stand and hold the dynamometer in their hand with their arm down at their side. The participant will be instructed to take a deep breath in and squeeze as hard as possible as they exhale. The measurement will be repeated twice on each hand, alternating between each side, and the highest score for each hand will be recorded to the nearest kg.	From enrollment to the end of study at 14 weeks
Changes in self-reported measures of Diet Quality	Computer adapted testing measure, Diet History Questionnaire (DHQ III), a general population dietary survey that queries food intake frequency and portion size. It is scored numerically from 0 to 100, with higher scores indicating better diet quality.	From enrollment to the end of treatment at 14 weeks.
Cardiovascular Function	Submaximal Graded Exercise Test (GXT) on a treadmill will be conducted at EPARC under the supervision of a trained exercise physiologist. Participants will complete a walking protocol at a self-selected speed, with the treadmill incline increasing every two minutes to progressively increase cardiovascular demand. The test will continue until the participant reaches 85% of their age-predicted maximal heart rate (calculated as 220 bpm - age) or experiences volitional fatigue, whichever occurs first.	From enrollment to the end of study period at 14 weeks.
Physical Activity	Objective assessments of physical activity will be measured using the ActiGraph accelerometer , a lightweight instrument that is worn on the hip attached to a belt around the waist. Instructions will be provided, and a brief self-report wear time log for participants to note periods that the device was taken off. Participants will be asked to wear the ActiGraph for seven days and will be prompted twice via telephone during the monitoring period (wear days 2 and 5) to assist with compliance. Upon return, we will immediately download data outcome variables which include (i) mean minutes per day of sedentary time, (ii) mean minutes per day of light intensity physical activity, and (iii) minutes per week of moderate-to-vigorous intensity physical activity (MVPA).	From enrollment until 2 weeks and again in weeks 13 and 14.
Changes in self reported measures of well being	Computer adapted testing measure, Warwick-Edinburgh Mental Well-being Scale (WEMWBS) , 14 items using a 5-point Likert scale (none of the time, rarely, some of the time, often,a all of the time). Each item is scored on a numeric scale from 1-5 with the summing of the scores ranging from 14 to 70. A higher test score indicates greater positive mental well being.	Weekly from enrollment to end of study at 14 weeks
Changes in health related quality of life	Computer adapted testing measure, Short Form Health Survey (SF-36), is a 36 items evaluating physical functioning, role limitations, bodily pain, general health perceptions, vitality, social functioning, role limitations, and mental health. Each item is cored from 0 to 100, and a higher score defines a more positive health state.	Weekly from enrollment to end of study at 14 weeks
Changes in Sleep health	Computer adapted testing measure, Satisfaction, Alertness, Timing, Efficiency, and Duration (SATED), is a 5 items covering sleep Satisfaction, Alertness, Timing, Efficiency, and Duration. The score ranges from 0 to 10, with a higher score indicating better sleep health.	Weekly from enrollment to end of study at 14 weeks
Changes in Sleep quality	Computer adapted testing measure, Pittsburgh Sleep Quality Index (PSQI), is a 19 item questionnaire querying subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The score ranges from 0 to 21 with higher scores indicating poorer sleep quality.	Weekly from enrollment to end of study at 14 weeks

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: HALEON
• Investigators: Principal Investigator: Anthony Molina, PhD, UC San Diego

Publications and helpful links

General Publications

• Gonzalez-Armenta JL, Bergstrom J, Lee J, Furdui CM, Nicklas BJ, Molina AJA. Serum factors mediate changes in mitochondrial bioenergetics associated with diet and exercise interventions. Geroscience. 2024 Feb;46(1):349-365. doi: 10.1007/s11357-023-00855-w. Epub 2023 Jun 27.
• Gonzalez-Armenta JL, Gao Z, Appt SE, Vitolins MZ, Michalson KT, Register TC, Shively CA, Molina AJA. Skeletal Muscle Mitochondrial Respiration Is Elevated in Female Cynomolgus Macaques Fed a Western Compared with a Mediterranean Diet. J Nutr. 2019 Sep 1;149(9):1493-1502. doi: 10.1093/jn/nxz092.
• Kramer PA, Coen PM, Cawthon PM, Distefano G, Cummings SR, Goodpaster BH, Hepple RT, Kritchevsky SB, Shankland EG, Marcinek DJ, Toledo FGS, Duchowny KA, Ramos SV, Harrison S, Newman AB, Molina AJA. Skeletal Muscle Energetics Explain the Sex Disparity in Mobility Impairment in the Study of Muscle, Mobility and Aging. J Gerontol A Biol Sci Med Sci. 2024 Apr 1;79(4):glad283. doi: 10.1093/gerona/glad283.
• Scandalis L, Kitzman DW, Nicklas BJ, Lyles M, Brubaker P, Nelson MB, Gordon M, Stone J, Bergstrom J, Neufer PD, Gnaiger E, Molina AJA. Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. 2023 Jun 1;8(6):575-584. doi: 10.1001/jamacardio.2023.0957.
• Mahapatra G, Gao Z, Bateman JR 3rd, Lockhart SN, Bergstrom J, DeWitt AR, Piloso JE, Kramer PA, Gonzalez-Armenta JL, Amick KA, Casanova R, Craft S, Molina AJA. Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer's disease. Alzheimers Dement. 2023 Apr;19(4):1466-1478. doi: 10.1002/alz.12731. Epub 2022 Jul 23.
• Tyrrell DJ, Bharadwaj MS, Van Horn CG, Kritchevsky SB, Nicklas BJ, Molina AJ. Respirometric Profiling of Muscle Mitochondria and Blood Cells Are Associated With Differences in Gait Speed Among Community-Dwelling Older Adults. J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1394-9. doi: 10.1093/gerona/glu096. Epub 2014 Jul 16.
• Wallace TC, Frankenfeld CL, Frei B, Shah AV, Yu CR, van Klinken BJ, Adeleke M. Multivitamin/Multimineral Supplement Use is Associated with Increased Micronutrient Intakes and Biomarkers and Decreased Prevalence of Inadequacies and Deficiencies in Middle-Aged and Older Adults in the United States. J Nutr Gerontol Geriatr. 2019 Oct-Dec;38(4):307-328. doi: 10.1080/21551197.2019.1656135. Epub 2019 Sep 10.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 9, 2025
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: mitochondria; Supplements; healthy aging; Respirometry; Cellular metabolism; Multivitamin and mineral supplements
• Other Study ID Numbers: 812601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan to make IPD available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No