NICEVIVA
MONOGRAPH SPEC LATEST 2026

Multivitamin (Senior)

VITAMINS · Evidence Monograph

Multivitamin (Senior) is an evidence-graded vitamins monograph evaluated across 18 peer-reviewed PubMed studies (0 meta-analyses, 1 systematic reviews, and 12 randomized controlled trials, encompassing n = 4,422 cumulative participants). Current clinical evidence is rated GRADE Moderate (3.0 / 4.0) for cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis.

Evidence Grade (GRADE) Moderate (3.0 / 4.0)
Indexed PubMed Studies 18 Studies
Meta-Analyses · Reviews 0 Meta · 1 Systematic Reviews
Randomized Trials (RCT) 12 RCTs (9 Double-Blind)
Cumulative Participants n = 4,422
Reported Trial Dosages 400 IU/day · 000 IU · 18 mg
Trial Duration Range 3 months · 12 weeks · 8 weeks
Reading Time ~9 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis (supported by 18 indexed PubMed studies, GRADE Moderate).
  2. 02 Adults matching clinical trial dosing protocols (400 IU/day · 000 IU · 18 mg) over a structured 3 months evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Bioactive Coenzyme or Standardized Vitamin Form
Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Steady daytime energy and correction of subclinical deficiency markers over 4–8 weeks.
Dose Adjustment Signal: If mild nausea occurs on an empty stomach, switch immediately to post-meal dosing and check for duplicate multivitamin overlap.
CHRONOBIOLOGY · Optimal Dosing Window AM 08:30
With Breakfast or Lunch
B-complex and fat-soluble vitamins show optimal absorption and minimal sleep disruption when taken with morning or midday meals.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary vitamins clinical efficacy (18 PubMed studies)
Quantitative biomarker & outcome analysis (14 studies with effect-size/sample data)
Randomized controlled trial verification (12 RCTs · 9 double-blind)
Systematic review & meta-analysis synthesis (0 meta-analyses · 1 reviews)
01

What Is Multivitamin (Senior) & Why Does Form Matter?

Multivitamin (Senior) is classified under VITAMINS and has been investigated across 18 peer-reviewed PubMed publications for its role in cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (400 IU/day, 000 IU, 18 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Multivitamin (Senior) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (12 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Multivitamin (Senior) acts on pathways governing cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Multivitamin (Senior) an overall evidence rating of GRADE Moderate (3.0 / 4.0) based on 18 PubMed studies: 0 meta-analyses, 1 systematic reviews, and 12 randomized controlled trials (9 double-blind, n = 4,422 total participants).

Representative peer-reviewed findings include: • PMID:41123035 (2025) — "Riboflavin supplements for blood pressure lowering in adults." (There has been interest in riboflavin (vitamin B2) as a potential intervention to lower blood pressure, particularly for those with a common genetic polymorphism in the methylene tetrahydrofolate reductase enzyme (MTHFR).) • PMID:30398092 (2018) — "Potential Dietary Supplement and Medication Interactions in a Subset of the Older Adult Population Attending Congregate Sites." (In conclusion, regular education and screening of dietary supplement and medication use among older adults is recommended.) • PMID:25573654 (2015) — "Vitamin D supplementation and health-related quality of life: a systematic review of the literature." (Vitamin D supplementation was not associated with significant changes in quality of life.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)MD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 41123035-1.94 (-5.74–1.86)PMID 40886951-0.25-6.9Null (0)3Metric: MD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Bioactive Coenzyme or Standardized Vitamin Form. Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 400 IU/day · 000 IU · 18 mg · 5.5 mg/day over 3 months · 12 weeks · 8 weeks. Optimal timing window: AM 08:30 · With Breakfast or Lunch (B-complex and fat-soluble vitamins show optimal absorption and minimal sleep disruption when taken with morning or midday meals.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Steady daytime energy and correction of subclinical deficiency markers over 4–8 weeks.

Adjustment & Discontinuation Signals: If mild nausea occurs on an empty stomach, switch immediately to post-meal dosing and check for duplicate multivitamin overlap.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Multivitamin (Senior), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (AM 08:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (400 IU/day · 000 IU · 18 mg) and re-evaluate efficacy after 3 months.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (18 Studies) · 14 Quantitative Analyses

01
CLINICAL STUDY The Cochrane database of systematic reviews (2025) PMID: 41123035 ↗
Riboflavin supplements for blood pressure lowering in adults.
Clinical Trial Synthesis 2025 Meta-Analysis published in The Cochrane database of systematic reviews involving n = 320 participants; statistical significance reported at p = 0.32 (MD -1.94). Key conclusion: There has been interest in riboflavin (vitamin B2) as a potential intervention to lower blood pressure, particularly for those with a common genetic polymorphism in the methylene tetrahydrofolate reductase enzyme (MTHFR).
View Original PubMed Abstract ↓

Update of doi: 10.1002/14651858.CD015464. RATIONALE: Higher blood pressure is strongly related to an increased risk of cardiovascular disease. There has been interest in riboflavin (vitamin B2) as a potential intervention to lower blood pressure, particularly for those with a common genetic polymorphism in the methylene tetrahydrofolate reductase enzyme (MTHFR). OBJECTIVES: To assess the benefits and harms of riboflavin supplements compared to placebo or no additional treatment for lowering systolic and diastolic blood pressure. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, Clarivate Web of Science, Clarivate Food Science & Technology Abstracts and two clinical trials registries. There were no restrictions on language, publication year, or publication status. The latest search date was 24 October 2024. We also handsearched the reference lists of included studies. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) conducted in adults that evaluated oral riboflavin supplements compared with an inactive control (e.g. placebo or no additional treatment) and measured at least one of the critical outcomes. We did not include trials that evaluated multivitamins containing riboflavin. Participants in both the intervention and control groups were able to receive standard medical therapy for hypertension prior to and during the trial. OUTCOMES: The critical outcomes were systolic blood pressure and diastolic blood pressure. The important outcomes were antihypertensive medication, adverse events and biomarkers of riboflavin status. RISK OF BIAS: We used the Cochrane RoB 2 tool to assess the risk of bias in included studies for the following outcomes: systolic blood pressure, diastolic blood pressure, antihypertensive medication and adverse events. SYNTHESIS METHODS: We used standard Cochrane methods. For the critical outcomes, which were continuous, we calculated mean differences (MD) and 95% confidence intervals (CIs). We used a fixed-effect meta-analysis to pool data for each outcome where possible. We conducted subgroup analyses, inc

02
CLINICAL STUDY Journal of nutrition in gerontology and geriatrics (2018) PMID: 30398092 ↗
Potential Dietary Supplement and Medication Interactions in a Subset of the Older Adult Population Attending Congregate Sites.
Clinical Trial Synthesis 2018 Clinical Study published in Journal of nutrition in gerontology and geriatrics. Key conclusion: In conclusion, regular education and screening of dietary supplement and medication use among older adults is recommended.
View Original PubMed Abstract ↓

This study assessed possible dietary supplement-medication interactions of 62 older adults recruited from 8 senior congregate sites in Bexar County, Texas. Dietary supplement and medication use were collected by paper questionnaire and potential supplement-medication interactions were assessed using online databases. The majority of participants reported dietary supplements (77%), non-prescription medication (50%), and prescription medication (73%) use. Fifty percent of participants who reported dietary supplement and medication use were at-risk for a potential supplement-medication interaction, ranging from one to eight potential interactions. Calcium and multivitamin-mineral supplements were the most common dietary supplements with potential medication interactions. Surveyed older adults reported dietary supplements should be reported to a physician (97%), but over 20% believe herbal products are pure (38%) and dietary supplements are risk free (34%) and will not cause harm (22%). In conclusion, regular education and screening of dietary supplement and medication use among older adults is recommended.

03
SYSTEMATIC REVIEW Journal of the Academy of Nutrition and Dietetics (2015) PMID: 25573654 ↗
Vitamin D supplementation and health-related quality of life: a systematic review of the literature.
Clinical Trial Synthesis 2015 Systematic Review published in Journal of the Academy of Nutrition and Dietetics. Key conclusion: Vitamin D supplementation was not associated with significant changes in quality of life.
View Original PubMed Abstract ↓

62. J Acad Nutr Diet. 2015 Mar;115(3):406-418. doi: 10.1016/j.jand.2014.10.023. Epub 2015 Jan 6. Vitamin D supplementation and health-related quality of life: a systematic review of the literature. Hoffmann MR, Senior PA, Mager DR. Vitamin D deficiency and insufficiency are highly prevalent worldwide and thought to potentiate a variety of chronic disease states, including diabetes, cancer, and depression. Routine vitamin D supplementation is often needed to meet vitamin D requirements. Little is known regarding the effect of vitamin D supplementation on quality of life. The purpose of this article was to systematically review the literature regarding quality-of-life outcomes from vitamin D supplementation in healthy and clinical populations. Clinical trials of vitamin D supplementation, where quality-of-life outcomes were reported, were selected from Medline and Web of Science databases. Inclusion criteria were English language articles available online (published between 1950 and May 2014), primary research articles, studies conducted on human beings, and treatment/supplementation with vitamin D. Articles were excluded if they involved topical vitamin D application or implicit cotreatment with other vitamins (eg, multivitamins). Articles selected for review were examined for process and methodologic quality using validated methodologies. A total of 15 articles met the inclusion criteria for review. Interventions were highly variable in terms of study population (eg, healthy/diseased, children/elderly, and baseline vitamin D status) vitamin D dose, and duration of follow-up. Vitamin D supplementation ranged from 400 IU/day for an average of 7.1 years, to a single 300, 000 IU dose. The main tools used to capture quality of life were adaptations of validated, questionnaires (Medical Outcomes Study Short Form 36-item questionnaire and EuroQOL five dimension questionnaire). Vitamin D supplementation was not associated with significant changes in quality of life. Studies that reported changes in quality of life as a result of vitamin D supplementation were in clinical populations on short-term vitamin D. Most articles reviewed displayed poor methodologic quality (

04
RANDOMIZED TRIAL (RCT) JBMR plus (2026) PMID: 42004609 ↗
Effects of cocoa extract supplementation on physical performance measures: results from the randomized controlled COcoa Supplement and Multivitamin Outcomes study.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in JBMR plus involving n = 603 participants. Key conclusion: Poor physical performance is associated with a higher risk of falls, fractures, and premature death among older adults.
View Original PubMed Abstract ↓

Poor physical performance is associated with a higher risk of falls, fractures, and premature death among older adults. We determined whether supplementation with cocoa extract vs placebo or multivitamin/multimineral (MVM) vs placebo for 2 yr benefited physical performance measures. The COcoa Supplement and Multivitamin Outcomes Study was a double-blinded, placebo-controlled randomized trial of supplemental cocoa extract and/or MVM vs placebo for the primary prevention of cardiovascular disease and cancer in 21 442 US adults. This ancillary study was completed in a New England sub-cohort that underwent physical performance measurements, including grip strength, walking speed, standing balance, repeated chair stands, and timed-up and go (TUG) test, at baseline and 2-yr follow-up. In the clinic sub-cohort (n = 603) with a mean (±SD) age of 69.7 ± 5.5 yr and 49.3% women, supplemental cocoa extract, compared to cocoa-extract placebo, did not affect 2-yr changes in our primary pre-specified, co-equal outcomes of grip strength, walking speed, and the Short Physical Performance Battery (composite of walking speed, standing balance, and chair stands) or in secondary outcomes of standing balance, chair stands, or TUG tests. No effect modification by baseline characteristics of age, sex, body mass index, or randomization to MVM supplementation was observed. In parallel analyses, MVM, compared to MVM placebo, also did not affect physical performance measures. Supplementation with cocoa extract did not prevent age-related declines in physical performance measures in older ambulatory US men and women. © The Author(s) 2026. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.

05
RANDOMIZED TRIAL (RCT) GeroScience (2026) PMID: 41910928 ↗
Effects of daily multivitamin-multimineral supplementation on metabolomic profiles: 2-year findings from the COSMOS randomized clinical trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in GeroScience involving n = 399 participants; statistical significance reported at p = 0.05. Key conclusion: Despite the limited sample size, COSMOS provides preliminary evidence that daily MVM supplementation may modestly improve metabolomic profiles in older adults.
View Original PubMed Abstract ↓

Despite widespread use in the USA, little is known about the impact of multivitamin-multimineral (MVM) supplementation on metabolomic profiles and how this may translate to biological aging and long-term risk of age-related chronic diseases. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial, placebo-controlled, double-blinded, randomized clinical trial testing daily MVM (Centrum Silver®) in US older adults. In 399 participants with metabolomics profiles quantified using the Nightingale Health nuclear magnetic resonance platform at baseline, year 1, and year 2 (70.3 ± 5.7 years; 50.1% female), we evaluate the effects of MVM versus placebo on 168 metabolites, 7 metabolomics clocks of biological aging, and 24 metabolomic risk scores (MRS) for chronic diseases. Compared with placebo, 2-year daily MVM supplementation increased the concentrations of docosahexaenoic acid (Cohen's d for between-group differences in changes from baseline to 2 years, 0.212 [95% CI, 0.02 to 0.404]) and omega-3 fatty acids (0.193 [0.003 to 0.382]) as well as delayed the increase in concentrations of creatinine (-0.222 [-0.424 to -0.019]). MVM also reduced MRS for 16 chronic diseases, including major cardiovascular events, renal disease, all-cause dementia, asthma, cataracts, glaucoma, liver disease, non-melanoma skin cancer, and prostate cancer (Cohen's d range, -0.206 to -0.277). However, all these effects were only significant at nominal levels, not after multiple-testing correction (p < 0.05; FDR > 0.05). Additionally, MVM led to a non-significant decrease across all metabolomic aging clocks, ranging from 0.496 to 1.054 years. Despite the limited sample size, COSMOS provides preliminary evidence that daily MVM supplementation may modestly improve metabolomic profiles in older adults. Further expansion within COSMOS is still warranted to confirm whether these alterations contribute to the benefits of MVM supplementation for healthy aging. Trial registration number: NCT02422745. © 2026. The Author(s), under exclusive licence to American Aging Association.

06
RANDOMIZED TRIAL (RCT) The Journal of nutrition (2026) PMID: 41825741 ↗
Effect of 2-Year Caloric Restriction in the Absence of Malnutrition on Indicators of Anemia, Iron Status, and Hepcidin in Healthy Adults: A Randomized Clinical Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The Journal of nutrition involving n = 220 participants; statistical significance reported at p = 0.05. Key conclusion: OBJECTIVES: To determine the effects of a 2-y CR intervention on markers of anemia, iron status, and hepcidin in females and males enrolled in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 2 trial.
View Original PubMed Abstract ↓

BACKGROUND: Caloric restriction (CR) is a promising nutritional intervention for improving metabolic and age-related health outcomes, but its long-term effects on hematologic health remain unclear. Clarifying how prolonged CR affects anemia risk and iron status is essential for evaluating its long-term safety and clinical relevance. OBJECTIVES: To determine the effects of a 2-y CR intervention on markers of anemia, iron status, and hepcidin in females and males enrolled in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 2 trial. METHODS: Participants in CALERIE Phase 2 (n = 220) were randomly assigned to 25% CR or ad libitum (AL) control. AL continued their habitual diet, whereas CR received an intensive intervention to promote CR over 2 y. All participants received a multivitamin/mineral supplement containing 18 mg iron. Fasted blood was collected at baseline (BL) and 12 (M12) and 24 (M24) mo and indicators of iron status (ferritin, soluble transferrin receptor, and serum iron), anemia (hemoglobin and hematocrit), and regulators of iron status (hepcidin, C-reactive protein, and IL-6) were measured. Six-day diet diaries were collected twice at BL and once each at M12 and M24. An anemia surveillance protocol monitored hemoglobin, hematocrit, red blood cell (RBC) count, and serum iron throughout the intervention, with medical evaluation and temporary/permanent CR discontinuation as needed. Linear mixed-effects models were used to evaluate the effect of treatment (CR compared with AL), time (BL, M12, and M24), and their interaction (treatment × time). RESULTS: Participants (n = 218) were mostly female (70%) with an mean age (±SD) of 38.1 ± 7.2 y and a mean BMI of 25.2 ± 1.7 kg/m2. At baseline, ferritin (105.5 ± 126.9 μg/L), hepcidin (8.6 ± 5.8 ng/mL), and dietary iron intake (16.1 ± 5.5 mg/d) were similar between groups (P > 0.05). There were no group × time interactions for markers of anemia, indicators of iron status, or hepcidin (P > 0.05). Despite the anemia surveillance protocol, anemia prevalence remained >5% in both groups across all timepoints. Low RBC count was the most common trigger, and participants who tri

07
RANDOMIZED TRIAL (RCT) Nature medicine (2026) PMID: 41803341 ↗
Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Nature medicine involving n = 958 participants; statistical significance reported at p = 0.017. Key conclusion: Although the statistically significant but small effects of daily MVM supplementation on slowing biological aging are encouraging, additional studies are needed to determine the clinical relevance of daily MVM supplementation on epigenetic clocks and whether such effects can help
View Original PubMed Abstract ↓

Large-scale randomized trials have found that multivitamin-multimineral (MVM) supplements and cocoa flavanols may benefit several age-related chronic conditions among older adults, but it remains unclear whether these two supplements directly slow the biological aging process. This prespecified ancillary study evaluated the 2-year effect of a daily MVM (Centrum Silver) and cocoa extract (500 mg cocoa flavanols per day, including 80 mg (-)-epicatechin) on five DNA methylation measures of biological aging (PCHannum, PCHorvath, PCPhenoAge, PCGrimAge and DunedinPACE) among 958 participants (482 women and 476 men) in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). Compared with placebo, daily MVM supplementation modestly reduced the rate of increase of second-generation epigenetic clocks, with a between-group difference in yearly change of -0.113 years (95% confidence interval (CI) -0.205 to -0.020; P = 0.017) for PCGrimAge and -0.214 years (-0.410 to -0.019; P = 0.032) for PCPhenoAge. MVM had a stronger effect on PCGrimAge among those with accelerated biological aging at baseline (-0.236 [-0.380 to -0.091]) compared with those with normal or decelerated biological aging (-0.013 [-0.130 to 0.104]; P = 0.018 for interaction). Cocoa extract did not have an effect on the five epigenetic clocks tested. Although the statistically significant but small effects of daily MVM supplementation on slowing biological aging are encouraging, additional studies are needed to determine the clinical relevance of daily MVM supplementation on epigenetic clocks and whether such effects can help explain the beneficial effects of MVM supplementation on aging-related chronic conditions. © 2026. The Author(s), under exclusive licence to Springer Nature America, Inc.

08
RANDOMIZED TRIAL (RCT) Journal of the Academy of Nutrition and Dietetics (2026) PMID: 41587736 ↗
Effects of Randomized Multivitamin Supplementation on Carotenoids and α-Tocopherol in the COcoa Supplement and Multivitamin Outcomes Study.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Journal of the Academy of Nutrition and Dietetics involving n = 400 participants. Key conclusion: No significant differences were observed for lyco
View Original PubMed Abstract ↓

BACKGROUND: Adequate intake of carotenoids and vitamin E supports healthy aging, yet evidence is limited on whether multivitamin-multimineral (MVM) supplementation changes serum concentrations over time. OBJECTIVE: The aim of this investigation was to evaluate the effect of daily MVM supplementation among older adults on serum carotenoid and vitamin E concentrations over a 2-year period. DESIGN: The COcoa Supplement and Multivitamin Outcomes Study is a large-scale, randomized, placebo-controlled, 2 × 2 factorial trial, designed to test the effects of daily MVM and cocoa extract supplementation for chronic disease prevention. Participants completed semiannual questionnaires and provided optional biospecimen samples at baseline, 1-year, and 2-year follow-up. PARTICIPANTS AND SETTING: Between 2015 and 2020, US adults (women aged 65 years and older, men aged 60 years and older) without major cardiovascular disease or recent cancer were enrolled in the COcoa Supplement and Multivitamin Outcomes Study. This analysis included biospecimen substudy participants with blood samples provided at baseline and ≥1 follow-up timepoint (n = 400; 1 excluded due to unusable sample; final N = 399). INTERVENTION: Participants were randomized to receive daily MVM supplementation or a placebo, with or without cocoa extract. MAIN OUTCOME MEASURES: Changes in serum carotenoids and α-tocopherol concentrations were evaluated over the 2-year follow-up. STATISTICAL ANALYSES: Multivariable linear mixed models estimated changes in serum biomarker concentrations, comparing MVM with placebo, adjusting for covariates (age, sex, and cocoa extract intervention). RESULTS: Increases in serum carotenoids and α-tocopherol levels with MVM supplementation emerged at year 1 and persisted through year 2. MVM supplementation led to significantly higher serum concentrations of total carotenoids (percent change: 15.5%; 95% CI, 8.72 to 22.70), lutein (percent change: 17.17%; 95% CI, 7.53 to 27.66), beta carotene (percent change: 46.96%; 95% CI, 35.10 to 59.85), and α-tocopherol (percent change: 29.50%; 95% CI, 22.88 to 36.47) over 2 years compared with placebo. No significant differences were observed for lyco

09
RANDOMIZED TRIAL (RCT) Asia Pacific journal of clinical nutrition (2026) PMID: 41565231 ↗
Multivitamin supplements are not superior to nutrition education in improving fat-soluble vitamin levels: A double-blind randomized controlled trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Asia Pacific journal of clinical nutrition involving n = 155 participants; statistical significance reported at p = 0.001. Key conclusion: Nutrition education alone may be a safer and effective approach to addressing deficiencies in vitamins A, D, and E, while reducing the risks as-sociated with unnecessary vitamin supplementation in the general population.
View Original PubMed Abstract ↓

BACKGROUND AND OBJECTIVES: Vitamin deficiencies are closely associated with the development of chronic diseases. Therefore, effective and safe intervention strategies are critical to improving vitamin nutritional status. This study aimed to assess the effectiveness and differential impacts of nutrition education and multi-vitamin supplementation, providing a basis for selecting safer intervention strategies. METHODS AND STUDY DESIGN: A 4-week, double-blind, randomized controlled trial was conducted among 155 adults (aged 18-65 years) with confirmed deficiencies in fat-soluble vitamins (A, D, or E). Participants were randomly assigned to receive either nutrition education with a multivitamin supplement or nutrition education with placebo. The concentrations of fat-soluble vitamins (A, D, or E), as well as their deficiency rates, were compared before and after the intervention. RESULTS: A total of 155 participants completed the study. There were no significant differences in demographic characteristics between the two groups. In both groups, the concentration of vitamins (A, D, or E) significantly increased (all p < 0.001), and the deficiency rates for all three vitamins significantly decreased (all p < 0.001). However, there were no significant differences in the concentrations or deficiency rates of vitamins (A, D, or E) between the two groups after intervention (all p > 0.05). CONCLUSIONS: Multivitamin supplements are not superior to nutrition education. Nutrition education alone may be a safer and effective approach to addressing deficiencies in vitamins A, D, and E, while reducing the risks as-sociated with unnecessary vitamin supplementation in the general population.

10
RANDOMIZED TRIAL (RCT) Nutrition research (New York, N.Y.) (2026) PMID: 41544303 ↗
Feasibility of a randomized clinical trial comparing 5-methyltetrahydrofolate and folic acid prenatal multivitamins in couples with recurrent pregnancy loss.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Nutrition research (New York, N.Y.). Key conclusion: Unmetabolized FA concentration decreased in the 5-MTHF group but rose significantly in the FA group.
View Original PubMed Abstract ↓

To assess the feasibility of a randomized controlled trial (RCT) comparing 5-methyltetrahydrofolate (5-MTHF) and folic acid (FA) in couples with recurrent pregnancy loss. Pregnancy loss affects up to 15% of pregnancies, with over half of cases remaining unexplained. Emerging evidence suggests that folate metabolism, particularly in individuals carrying methylenetetrahydrofolate reductase polymorphisms such as C677T and A1298C variants, may influence reproductive outcomes. A double-blind, RCT feasibility trial was conducted in Australia with 22 reproductive dyads randomized to receive either 5-MTHF or FA prenatal multivitamins. Participants adhered to dietary restrictions, abstained from conception for two cycles, and completed regular assessments. Primary outcomes included feasibility, adherence, acceptability, and preliminary efficacy based on biochemical markers and pregnancy outcomes. The trial demonstrated high acceptability (86% in arm A [MTHF-A] and 94% in arm B [FA-B]) and adherence rates for supplement use over 78% in each arm. Unmetabolized FA concentration decreased in the 5-MTHF group but rose significantly in the FA group. A critical finding was the degradation of 5-MTHF in retained samples, highlighting formulation instability as a confounder. A fully online RCT comparing 5-MTHF and FA is feasible. Future trials should address formulation stability and expand sample size to evaluate clinical efficacy and personalized folate strategies.

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