UMIN-CTR Clinical Trial

Public title

Effects of 4-week continuous intake of mineral-rich water on skin condition and glycation-related indices

Acronym

Mineral Water Skin and Glycation Study

Scientific Title

Effects of continuous intake of high-mineral-content water on health indicators and skin condition: a randomized two-sequence crossover trial

Scientific Title:Acronym

Mineral Water Skin Aging Study

Region

Japan

Condition

Age-related changes in skin condition and glycation-related indices

Classification by specialty

Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study was to examine, in a randomized two-sequence crossover trial, the effects of 4-week continuous intake of an ore-derived multi-mineral concentrate (10 mL/day) on skin condition, facial blood flow, and glycation-related indices associated with advanced glycation end products (AGEs) in women aged 50-69 years. Participants were randomly allocated to sequence AB (4-week intake, 1-month washout, then 4-week non-intervention control) or sequence BA (4-week non-intervention control, 1-month washout, then 4-week intake). This study was registered retrospectively in UMIN-CTR on September 23, 2026, after study completion. The trial was registered retrospectively on 23 September 2026, after study completion, because the investigators did not recognize the requirement for prospective clinical trial registration at the time of study initiation.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Glycation-related index derived from skin autofluorescence (AF) of the right forearm (AGE-related index). In the final analysis, values at the end of each condition period were analyzed using a two-way mixed ANOVA with condition (intake/control) as a within-subject factor and sequence (AB/BA) as a between-subject factor, and the main effect of condition was evaluated. Holm correction was applied to the main effects of condition across all nine primary and secondary outcome indices. The initial registration, made retrospectively after study completion, described a within-participant comparison of changes during the control and intervention periods; the final analysis differs from that description and was not prospectively registered. [Post hoc additional analysis] After study completion, during manuscript preparation, condition-end values were additionally reanalyzed using a linear mixed-effects model (LMM) to account explicitly for period effects, in addition to the two-way mixed ANOVA described above (fixed effects: condition [intake/control], period [first/second], and sequence [AB/BA]; random effect: participant-specific random intercept; estimation: REML; test: two-sided t test with 28 degrees of freedom; multiplicity: Holm correction of the condition effects across nine outcomes; analysis population: 30 participants who completed both conditions). This LMM was adopted post hoc and was not specified before study initiation.

Key secondary outcomes

(1) Facial blood flow: FLOW, VEL, and MASS; (2) Facial skin condition: texture, skin brightness (whitening value), spots, aging index, and moisture. The analysis was the same as for the primary outcome (two-way mixed ANOVA, with Holm correction applied to the main effects of condition across all nine indices). Facial blood flow (FLOW, VEL, MASS) was measured in this study but was not listed as an outcome in the initial registration; it has been added in this correction. The post hoc LMM described for the primary outcome was also applied to these outcomes (Holm correction of the condition effects across nine outcomes). This LMM was not specified before study initiation.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Prevention

Type of intervention

Food

Interventions/Control_1

[Sequence AB] Participants consumed an ore-derived multi-mineral concentrate (10 mL/day) continuously for 4 weeks (intake condition). The timing of intake was not specified, and the concentrate could be mixed into beverages or foods. This was followed by a 1-month washout and then a 4-week non-intervention control period during which participants did not consume the study concentrate and maintained their usual diet, fluid intake, and lifestyle (control condition).

Interventions/Control_2

[Sequence BA] Participants first underwent a 4-week non-intervention control period during which they did not consume the study concentrate and maintained their usual diet, fluid intake, and lifestyle (control condition). This was followed by a 1-month washout, after which participants consumed the ore-derived multi-mineral concentrate (10 mL/day) continuously for 4 weeks (intake condition). The timing of intake was not specified, and the concentrate could be mixed into beverages or foods.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

50

years-old

<=

Age-upper limit

69

years-old

>=

Gender

Female

Key inclusion criteria

1. Women aged 50-69 years
2. Individuals who understand the study procedures and provide written informed consent
3. Individuals who are able to continuously consume the specified mineral-rich water for 4 weeks
4. Individuals who are able to participate in the scheduled assessments during the study period
5. Individuals who are able to maintain their usual lifestyle during the study period

Key exclusion criteria

1. Individuals with a disease, allergy, or other health condition considered incompatible with consumption of the study product
2. Individuals planning to initiate new treatment, health foods, or supplements during the study period that may substantially affect skin condition or glycation-related indices
3. Individuals who are unable to comply with the specified intake procedure or assessment schedule
4. Individuals judged by the principal investigator or co-investigators to be inappropriate for participation in the study

Target sample size

30

Name of lead principal investigator

1st name	Shiho
Middle name
Last name	Kurosaka

Organization

Hiroshima University

Division name

Graduate School of Humanities and Social Sciences

Zip code

739-8524

Address

1-1-1 Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-8524, Japan

TEL

082-424-6844

Email

shihok@hiroshima-u.ac.jp

Name of contact person

1st name	Shiho
Middle name
Last name	Kurosaka

Organization

Hiroshima University

Division name

Graduate School of Humanities and Social Sciences

Zip code

739-8524

Address

1-1-1 Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-8524, Japan

TEL

082-424-6844

Homepage URL

Email

shihok@hiroshima-u.ac.jp

Institute

Hiroshima University

Institute

Department

Personal name

Organization

JES Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Research Ethics Committee, Graduate School of Humanities and Social Sciences, Hiroshima University

Address

1-1-1 Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-8524, Japan

Tel

082-424-6705

Email

shihok@hiroshima-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

広島大学（広島県）
Hiroshima University (Hiroshima, Japan)

Date of disclosure of the study information

2026

Year

09

Month

23

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

35

Results

30 analyzed (AB 15, BA 15). Post hoc LMM (fixed: condition, period, sequence; random participant intercept; not prespecified): intake vs control, glycation-related index -29.10 (95% CI -40.07 to -18.13; p<0.001; Holm p<0.001); texture +17.50 (6.41 to 28.59; p=0.0031; Holm p=0.0250); FLOW +1.75 (0.53 to 2.98; p=0.0067; Holm p=0.0472). Holm across 9 outcomes. All 9 outcomes and the earlier mixed ANOVA results: see Outcome measures. Not prospectively registered.

Results date posted

2026

Year

10

Month

26

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Written informed consent was obtained from 35 participants. Two did not attend the first assessment, and 33 underwent it. After the first assessment, 3 participants became unreachable. Thirty participants completed the trial and were included in the final analysis (sequence AB, n = 15; sequence BA, n = 15). The target sample size was 30.

Adverse events

Before participation, participants were informed of how to contact the research team if an adverse event occurred, the procedures for seeking medical care, and how related medical costs would be handled. No adverse events were reported by participants who could be followed up. Safety after the first assessment could not be confirmed for the 3 participants who became unreachable after the first assessment.

Outcome measures

Primary outcome: AF-derived glycation-related index of right forearm skin. Secondary outcomes: facial blood flow (FLOW, VEL, MASS) and facial skin condition (texture, skin brightness, spots, aging index, moisture). Nine indices in total.
[Initial analysis results, as entered in the Results field at the correction of October 26, 2026] Thirty participants were analyzed (AB, n=15; BA, n=15). In a two-way mixed ANOVA (condition x sequence), the intake condition showed a lower forearm AF-derived glycation-related index than control (difference -29.10, p<0.001) and a higher texture score (+17.50, p=0.0031) and facial blood flow FLOW (+1.753, p=0.0067). These three remained significant after Holm correction across nine indices. This analysis was not prospectively registered. (In the update of November 4, 2026, the Results field was revised to report the LMM below, and this earlier text was moved to this Outcome measures field.)
[Post hoc additional analysis: linear mixed-effects model (LMM)] After study completion, during manuscript preparation, condition-end values were reanalyzed using an LMM to account explicitly for period effects, in addition to the previously reported two-way mixed ANOVA. Fixed effects: condition (intake/control), period (first/second), and sequence (AB/BA). Random effect: participant-specific random intercept. Estimation: REML. Test: two-sided t test with 28 degrees of freedom. Multiplicity: Holm correction of the condition effects across nine outcomes. Analysis population: 30 participants who completed both conditions. This LMM was adopted post hoc and was not specified before study initiation.
LMM results (intake minus control; 95% CI; p; Holm-adjusted p): glycation-related index -29.10 (-40.07 to -18.13; p<0.001; <0.001); texture +17.50 (6.41 to 28.59; p=0.0031; 0.0250); FLOW +1.75 (0.53 to 2.98; p=0.0067; 0.0472); VEL +0.045 (-0.00002 to 0.09002; p=0.0501; 0.2004); MASS +16.20 (-192.23 to 224.63; p=0.8746; 1.000); spots -2.97 (-9.86 to 3.92; p=0.3853; 1.000); moisture (hydration) -1.87 (-10.76 to 7.03; p=0.6707; 1.000); skin brightness -5.23 (-9.28 to -1.19; p=0.0131; 0.0783); aging index (composite aging-related score) -9.43 (-17.31 to -1.56; p=0.0206; 0.1031). Only the glycation-related index, texture, and FLOW remained significant after Holm correction. Skin brightness and the aging index were moved to a supplementary table in the manuscript by a post hoc reporting decision after data inspection, but remain in the nine-outcome Holm family.
Exploratory period-effect p values (not adjusted for multiplicity): glycation-related index 0.0789, texture 0.7190, FLOW 0.9035, skin brightness 0.0038, aging index 0.0354. The period-effect analysis is exploratory and does not demonstrate the absence of carryover; no measurement was taken immediately before the second period.
[Update of the analysis completion date (November 4, 2026)] The initial analysis was completed by 31 July 2026. Subsequently, an additional post hoc analysis using a linear mixed-effects model (LMM) was conducted and completed on 4 November 2026. The analysis completion date was therefore updated to reflect the final additional analysis. The LMM was not prespecified.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2026

Year

09

Month

23

Day

Date of IRB

2026

Year

01

Month

08

Day

Anticipated trial start date

2026

Year

02

Month

15

Day

Last follow-up date

2026

Year

05

Month

31

Day

Date of closure to data entry

2026

Year

06

Month

30

Day

Date trial data considered complete

2026

Year

06

Month

30

Day

Date analysis concluded

2026

Year

11

Month

04

Day

Other related information

[Retrospective registration] This trial was conducted from February 15, 2026 (first assessment) to May 31, 2026 (final assessment) and was first registered in UMIN-CTR on September 23, 2026, after study completion (retrospective registration). Ethics application: December 15, 2025; approval: January 8, 2026, Research Ethics Committee, Graduate School of Humanities and Social Sciences, Hiroshima University (HR-ES-003712).
[Correction of initial entry errors] At initial registration, the study design, intervention sequence, anticipated start and end dates, and recruitment status were entered incorrectly, so the record appeared to show a study starting after registration. The study was planned and conducted from the outset as a randomized two-sequence (AB/BA) crossover trial. This update corrects those entries; the initial registration date and the retrospective status are unchanged. The displayed date of protocol fixation (September 23, 2026) is not the actual date the protocol was finalized.
[Outcomes] Facial blood flow (FLOW, VEL, MASS) was measured but omitted from the initial registration and has been added.
[Analysis] The initial registration described a comparison of changes in each period. The final analysis used a two-way mixed ANOVA (condition, within-subject; sequence, between-subject) assessing main effects and their interaction, with Holm correction across nine indices. This analysis was not prospectively registered.
[Funding/COI] Funded by collaborative research funds provided to Hiroshima University by JES Co., Ltd., which has a commercial interest in the evaluated product. JES Co., Ltd. provided funding and the study product but had no role in study design, recruitment, allocation, intervention, measurement, data management, analysis, or interpretation.
[Reason for retrospective registration] See Narrative objectives. [Post hoc LMM and update of analysis completion date, Nov 2026] See Primary/Key secondary outcomes, Results and Outcome measures.

Registered date

2026

Year

09

Month

23

Day

Last modified on

2026

Year

11

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072153