Impact of Supplementation in Improving Metabolic Health Outcomes (ISMOS) Study

This study investigates the role of multivitamin and multimineral (MVM) supplementation in improving metabolic, musculoskeletal, and mental health among midlife Asian women aged 40-60 years, a critical period marked by hormonal and physiological transitions from pre- to post-menopause. Evidence from the GUSTO cohort in Singapore has shown that higher plasma levels of vitamins B6, B9, B12, and D are associated with better metabolic profiles, insulin sensitivity, and mental wellbeing, while deficiencies are linked to increased metabolic and psychological risks. Given that vitamin insufficiency and central obesity are highly prevalent among Asian women even at lower BMI, this randomized, double-blind, placebo-controlled trial will evaluate whether 12 months of daily MVM supplementation can reduce MetaboAge and improve metabolic, mental, and muscle health outcomes compared with placebo. Findings will inform preventive strategies for extending health span and mitigating chronic disease risks among midlife women in Asia.

Study Overview

• Status: Recruiting
• Conditions: Body Composition; Mental Health; Glucose Control; Musculoskeletal Health
• Intervention / Treatment: Dietary supplement: Multivitamin/mineral study product

Detailed Description

Vitamins are essential micronutrients that regulate key metabolic pathways involved in energy metabolism, immune function, and neuronal integrity. Adequate vitamin status is critical during midlife (ages 40-60 years), a period marked by hormonal fluctuations and physiological transitions from pre- to peri- and post-menopause. These transitions profoundly affect women's metabolic, musculoskeletal, and mental health trajectories, often predisposing them to metabolic syndrome, insulin resistance, central adiposity, dyslipidaemia, and hypertension. Concurrently, declines in muscle strength, bone mineral density, and mood are frequently observed, heightening the risk of sarcopenia, osteopenia, and depressive symptoms in later life.

Emerging evidence indicates that suboptimal dietary intake or deficiency of vitamins contributes to these adverse outcomes. Vitamin D insufficiency, highly prevalent in Asia, has been linked to metabolic syndrome, insulin resistance, and mood disturbances in postmenopausal women. Similarly, low levels of B-vitamins, vitamin C, vitamin E, and folate have been associated with impaired glucose regulation, higher inflammatory burden, and poorer muscle function. While several studies in Western populations have reported positive correlations between these micronutrients and musculoskeletal or psychological health, corresponding data in Asian women remain limited despite their higher susceptibility to central obesity and metabolic dysfunction at lower BMI thresholds compared to Western populations.

Findings from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort provide novel insights into the role of vitamin status in Asian women. Plasma concentrations of vitamins B6, B9, B12, and D were associated with favorable metabolic profiles, including lower metabolic syndrome severity, improved insulin sensitivity, reduced HbA1c, and higher HDL-cholesterol. Furthermore, higher thiamine monophosphate (vitamin B1) levels correlated with greater handgrip strength, while elevated folate was inversely related to depressive symptoms and perceived stress. Importantly, these associations were more pronounced among women with a BMI ≥ 23 kg/m², emphasizing the compounded metabolic vulnerability of overweight Asian phenotypes. Collectively, these findings highlight the potential of multivitamin/multimineral (MVM) supplementation as a preventive strategy to mitigate age-related metabolic, musculoskeletal, and psychological decline during midlife.

Building on these observational findings, this randomized, double-blind, placebo-controlled trial aims to determine whether 12 months of daily MVM supplementation can improve metabolic and overall health in relatively healthy middle-aged Asian women. The trial will recruit women aged 40-60 years, a critical window for metabolic and hormonal adaptation, who are at increased risk of vitamin insufficiency, insulin resistance, and low-grade chronic inflammation. Participants will be randomized to receive either a daily MVM supplement or placebo for one year, with comprehensive assessments at baseline, 6 months, and 12 months.

The investigators hypothesize that daily MVM supplementation for 12 months will reduce MetaboAge, a composite biomarker of metabolic aging and enhance metabolic, musculoskeletal, and mental health outcomes in midlife women compared with placebo.

Primary Objective is to examine the effect of 12-month MVM supplementation on MetaboAge among relatively healthy middle-aged Asian women.

Secondary Objectives are to;

1. Evaluate the impact of MVM supplementation versus placebo on metabolic markers (fasting glucose, insulin resistance indices, HbA1c, lipid profile, blood pressure); mental health outcomes (depressive symptoms, perceived stress, quality of life); musculoskeletal health (lean mass, fat mass distribution, bone mineral density, and handgrip strength) and circulating micronutrient and inflammatory marker levels.
2. To explore how menopausal status, baseline vitamin status, and body composition modify the observed intervention effects.

Scientific and Public Health Significance This trial is among the first in Asia to integrate multivitamin supplementation with multidimensional health outcomes; metabolic, musculoskeletal, and psychological, within the context of midlife transition. Asians are metabolically predisposed to visceral adiposity and insulin resistance even at lower BMI, placing midlife women at particularly high risk for metabolic syndrome and its sequelae. By addressing micronutrient insufficiency through a low-cost, scalable nutritional approach, this study aims to establish evidence for early preventive strategies that can extend functional health span and reduce the burden of chronic diseases among Asian women.

If proven effective, findings from this trial will support the incorporation of multivitamin supplementation or vitamin status screening into midlife health programs and community-based preventive frameworks, aligning with regional and national goals for promoting healthy longevity and metabolic resilience across the lifespan.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Johan Eriksson, MD; Phone Number: 80616604; Email: johan_eriksson@a-star.edu.sg
• Study Contact Backup: Name: Mya Thway Tint, PhD; Email: mya_thway_tint@a-star.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore, 117597
    • Recruiting
    • Institute for Human Development and Potential (IHDP)
    • Contact: Jolene Chee; Email: jolene_chee@a-star.edu.sg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women aged 40-60 years old
• Chinese, Malay or Indian
• BMI between 23.0-35.0 kg/m2
• Proficient in English language
• Willing to comply with study protocol & provide informed consent

Exclusion Criteria:

• Pregnant or planning a pregnancy
• Diagnosis with Diabetes, Polycystic Ovary Syndrome (PCOS), autoimmune diseases, chronic organ failure, severe heart disease, eating disorders and/or other medical conditions which in the PI's judgment which may affect study outcomes
• Fasting glucose value ≥ 7.0 mmol/L
• Active cancer or treatment of cancer in the last 3 years
• Participating in other nutritional intervention studies
• Taking oral corticosteroids, anti-psychotic and/or weight loss drugs
• Having planned hospitalization in the next 12 months
• Planning to have major diet changes in the next 12 months
• Taking a medically prescribed supplement(s) that contains 3 or more of the ingredients of the study product
• Taking a non-prescribed supplement(s) that contains 3 or more of the ingredients of the study product in the last 1 month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multivitamin/mineral (MVM) study product; One MVM study product to be taken once a day for 52 weeks	Dietary supplement: Multivitamin/mineral study product; Participants will be randomised into one of the two study treatment arms
Placebo Comparator: Placebo study product; One placebo study product to be taken once a day for 52 weeks	Dietary supplement: Multivitamin/mineral study product; Participants will be randomised into one of the two study treatment arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in MetaboAge	MetaboAge is a composite biomarker of metabolic aging derived from proton nuclear magnetic resonance (^1H-NMR) metabolomics profiling of serum samples. It reflects overall metabolic health and correlates with cardiometabolic risk and insulin sensitivity. The expected outcome is that daily multivitamin/multimineral (MVM) supplementation for 12 months will result in a reduction in MetaboAge compared with placebo, indicating improved metabolic profile and slower metabolic aging. The change in MetaboAge will be calculated as the difference between post-intervention and baseline values. A negative change in MetaboAge represents metabolic rejuvenation or improvement in metabolic health status.	Changes in MetaboAge over one year, including: Week 0 (Baseline), Week 26 (Midpoint) and Week 52 (Endpoint)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric Measurements	Participants will be measured for their height in m and weight in kg. Height and weight will be combined to report BMI in kg/m^2.	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Blood Pressure Measurements	Blood pressure will be measured using an automated blood pressure monitor.	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Body Composition Assessment	Body composition will be assessed using multi-frequency bioelectrical impedance analysis (BIA) with the InBody 970 (InBody Co., Seoul, Korea). Participants will be measured in a standing position using an 8-point tactile electrode system (hands and feet), and impedance will be recorded across multiple frequencies to estimate total and segmental lean mass, fat mass, and body fat percentage.	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
36-Item Short Form Survey (SF-36)	Health-related quality of life will be assessed using the 36-Item Short Form Survey (SF-36), a validated instrument measuring eight domains of physical and mental wellbeing: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain score and the overall physical and mental component summary scores will be calculated according to standardized scoring procedures. The expected outcome is that 12 months of daily multivitamin/multimineral (MVM) supplementation will lead to improvement in SF-36 scores compared with placebo, reflecting better perceived physical and mental wellbeing during the midlife transition. The change from baseline (ΔSF-36) will be computed for total and domain-specific scores, with higher positive values indicating improved quality of life.	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Menopausal Status	Menopausal Rating Scale (MRS)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Anxiety	State-Trait Anxiety Inventory (STAI)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Depression	Beck Depression Inventory (BDI)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Stress	Perceived Stress Scale (PSS)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Sleep Quality	Pittsburgh Sleep Quality Index (PSQI)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Physical Activity	International Physical Activity Questionnaire (IPAQ)	Week 0 (Baseline), Week 26 (Midpoint), Week 52 (Endpoint)
Dietary Intake	Food Frequency Questionnaire (FFQ)	Week 0 (Baseline), Week 52 (Endpoint)
Musculoskeletal assessment by peripheral quantitative CT (pQCT)	Bone mineral density and muscle quality of lower limb (Tibia) will be measured using pQCT and measurement of the non-dominant tibia will be performed using Stratec XCT-3000. Single axial scans will be acquired at 4% and 66% of tibial length, expressed as a percentage from the distal reference line, to assess bone and lower-limb muscle. Bone parameters are derived using manufacturer software with standard contouring and density thresholds to segment total and trabecular compartments at 4% and cortical bone at 66%, generating measures such as total/trabecular volumetric BMD (vBMD), cortical vBMD, cortical thickness, cross-sectional area, and strength indices. At the 66% site, soft-tissue segmentation is additionally performed to quantify calf muscle cross-sectional area (CSA), muscle density, and subcutaneous/intermuscular fat CSA, using predefined attenuation thresholds to separate muscle from adipose tissue.	From enrollment to the end of 12 months multi-vitamin supplementation.
Physical performance assessment	Physical performance will be assessed using a standardized physical performance battery that includes tests of handgrip strength, gait speed (4-meter walk test), chair stand test, and balance test. Composite physical performance scores will be derived according to established protocols, with higher scores reflecting better functional capacity and musculoskeletal health. The expected outcome is that 12 months of daily multivitamin/multimineral (MVM) supplementation will lead to improvements or maintenance of physical performance scores compared with placebo, indicating enhanced muscle strength, endurance, and coordination during the midlife transition. The change from baseline will be calculated for each test and the composite score, with positive values representing improved physical function.	From enrollment to end of 12 months multi-vitamin supplementation

Collaborators and Investigators

• Sponsor: Institute for Human Development and Potential (IHDP), Singapore
• Collaborators: HALEON

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Women; Mental health; Metabolic health; Muscle health; Multivitamin and mineral supplementation
• Additional Relevant MeSH Terms: Behavior; Personal Satisfaction; Psychological Well-Being; Geritol
• Other Study ID Numbers: 2025-064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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