Beyond Hydration: Natural Mineral Water and Metabolic Health

Abstract

Background: Natural mineral water (NMW) is a heterogeneous dietary exposure whose composition varies substantially among sources. Objective: This critical review examines human intervention evidence on NMW in relation to metabolic health across healthy adults and populations with hypercholesterolaemia, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) while separating direct clinical findings from mechanistic evidence. Methods: Seven principal human intervention studies were identified in the clinical synthesis. Results: Controlled studies did not show a reproducible glucose-lowering effect attributable to mineralwater composition. Selected studies nevertheless reported changes in postprandial insulin dynamics, glycoalbumin, oxidative status, gastrointestinal or microbiota-related variables, and intestinal, inflammatory, and hepatic outcomes. Calcium and magnesium in mineral water are bioavailable, but mineral absorption should not be interpreted as evidence of disease-specific efficacy. The literature is constrained by small samples, chemically dissimilar waters, heterogeneous populations, variable intervention durations, and inconsistent comparator designs. Conclusions: Accordingly, current evidence supports NMW primarily as a source-specific nutritional exposure rather than an established metabolic intervention. Future trials should use analytically characterized intervention and control waters, predefined outcomes, adequate durations, and clearly defined metabolic phenotypes to determine whether particular hydrochemical profiles produce reproducible metabolic effects.

1. Introduction

Metabolic disorders, including insulin resistance, T2DM, dyslipidaemia, and MASLD, arise from interacting disturbances in glucose and lipid metabolism, inflammation, oxidative stress, and organ-specific physiology [1,2,3]. Nutrition is central to their prevention and management, but the possible contribution of drinkingwater composition has received comparatively little attention.

NMW is a legally and hydrogeologically defined category of drinking water characterized by source-specific mineral and trace-element composition [4]. Concentrations of bicarbonate, calcium, magnesium, sodium, sulfate, silica, and other constituents vary markedly among sources [5]. Consequently, studies labelled as ‘mineralwater’ interventions may evaluate chemically different exposures.

This distinction matters because selected minerals in NMW are bioavailable. WHO guidance identifies calcium and magnesium in drinking water as nutritionally relevant constituents [6], while human absorption studies demonstrate their bioavailability from mineral water [7,8,9,10,11,12]. These findings establish nutritional exposure, but they do not show that mineral water improves metabolic disease outcomes.

The direct human literature is small and spans heterogeneous populations. Controlled studies have examined glucose and insulin responses in older adults, postmenopausal women, and hypercholesterolaemic individuals [13,14,15], while other interventions have involved patients with T2DM [16,17], healthy volunteers undergoing metabolomic and microbiome assessment [18], and patients with MASLD [19]. Across these studies, conventional glycemic outcomes have generally been neutral or inconsistent, whereas some intermediate redox, gastrointestinal, microbiota-related, inflammatory, and hepatic signals have been reported.

The limited evidence therefore does not justify treating NMW as a metabolic therapy or attributing observed responses to individual minerals. It does, however, raise a narrower question: whether particular, analytically defined water profiles can influence specific metabolic or physiological outcomes under defined experimental conditions.

This critical review evaluates human intervention evidence on NMW and metabolic health, summarizes relevant mineral-bioavailability and mechanistic evidence, and identifies methodological priorities for future research. Direct clinical findings are distinguished throughout from biological plausibility and hypothesis-generating evidence.

2. Materials and Methods

2.1. Review Design

This study was designed as a structured critical review rather than a systematic review conducted according to PRISMA. Its purpose was to evaluate the small human intervention literature on NMW and metabolic health and to interpret those findings alongside selected mechanistic evidence. The clinical synthesis included glucose and insulin regulation, cardiometabolic markers, oxidative and inflammatory outcomes, gastrointestinal and microbiota-related variables, intestinal permeability, and liver-related outcomes.

Direct human NMW interventions were treated as the primary evidence base. Mineral-bioavailability studies and the broader nutritional or mechanistic literature were used only to contextualize biological plausibility and were not treated as evidence of NMW efficacy.

2.2. Literature Search Strategy

A structured search was undertaken in PubMed/MEDLINE, Scopus, and Web of Science. The final search was conducted on 25 July 2026.

Search terms combined NMW exposures (‘natural mineral water’, ‘mineral water’, ‘bicarbonate-rich mineral water’, ‘magnesium-rich mineral water’, ‘calcium-rich mineral water’, ‘sulphurous mineral water’, ‘low-mineral water’, and ‘drinking water’) with metabolic terms including ‘glucose’, ‘glycaemia’, ‘insulin’, ‘insulin resistance’, ‘type 2 diabetes’, ‘metabolic syndrome’, ‘oxidative stress’, ‘inflammation’, ‘intestinal permeability’, ‘gut microbiota’, ‘microbiome’, ‘fatty liver’, ‘MASLD’, ‘magnesium’, ‘calcium’, ‘bicarbonate’, ‘lithium’, ‘silicon’, and ‘boron’.

Reference lists of eligible primary studies and relevant reviews were also screened. The search was broadened when metabolic outcomes were reported as secondary outcomes in studies primarily addressing cardiovascular, gastrointestinal, mineral-bioavailability, or hepatic effects.

Only studies published in English were eligible for inclusion in the clinical synthesis; all identified non-English-language studies were excluded on the basis of language.

2.3. Eligibility of Human NMW Studies

Human prospective intervention studies were eligible for the clinical synthesis when they investigated naturally occurring mineral water and reported at least one metabolically relevant outcome. Randomized controlled trials, crossover studies, and prospective uncontrolled interventions were considered because the direct literature is limited.

Relevant outcomes included fasting or postprandial glucose, insulin-related measures, glycoalbumin, lipid and cardiometabolic variables, oxidative or antioxidant markers, inflammatory biomarkers, gastrointestinal function, microbiota-related outcomes, intestinal permeability, and MASLD-related hepatic outcomes.

Animal and in vitro studies, artificially formulated mineral solutions, supplementation trials, observational studies, and reviews were excluded from the primary clinical evidence synthesis; selected examples were retained only for mechanistic interpretation.

All five authors conducted independent literature searches. After duplicate removal, E.M. selected eligible studies according to the predefined criteria and extracted the relevant data. E.P. independently checked the study-selection decisions and verified the data extracted by E.M.

2.4. Data Extraction and Hydrochemical Characterization

For each eligible human intervention, E.M. extracted information on study design, population, sample size, water exposure, dose and duration, comparator, hydrochemical characteristics, metabolic outcomes, principal findings, and major limitations. E.P. independently cross-checked the data extracted by E.M. against the source publications. Hydrochemical composition was considered separately from clinical outcomes because ‘mineral water’ does not represent a single chemical exposure.

Seven principal human NMW intervention studies formed the direct clinical synthesis [13,14,15,16,17,18,19]. Because the review was not conducted using a prospectively documented systematic-review workflow, formal counts of records identified, duplicates removed, records screened, full texts assessed, and records excluded were not recorded. These counts were therefore not reconstructed retrospectively.

2.5. Evidence Synthesis

A meta-analysis was not undertaken because the interventions differ substantially in water composition, participant phenotype, duration, comparator design, and outcome assessment. Evidence was therefore synthesized narratively by metabolic domain and weighted according to study design and outcome specificity.

Randomized comparisons with a control water were given greater interpretative weight than uncontrolled before–after interventions. Direct clinical endpoints were distinguished from intermediate biomarkers and from mechanistic evidence derived outside the NMW intervention literature.

3. Clinical Evidence

3.1. Overview of the Human Evidence

The seven principal human intervention studies are summarized in Table 1. They include controlled crossover studies in healthy or metabolically at-risk adults [13,14,15], interventions in T2DM [16,17], a short metabolomic/microbiome study in healthy volunteers [18], and a longer randomized nutritional intervention in MASLD [19]. The studies differ in both hydrochemical exposure and metabolic phenotype, limiting direct comparison.

Table 1. Characteristics, metabolic outcomes, and interpretation of the seven principal human natural mineral water intervention studies.

Study	Population/Design	Water Exposure	Dose/Duration	Domains	Key Findings	Interpretation
Schorr et al. [13]	n = 21 older normotensive adults; randomized double-blind crossover	NaCl-rich, NaHCO3-rich, and low-sodium waters	1.5 L/day; 4 weeks/condition; 2-week washout	Glucose tolerance	No differential glucose-tolerance effect	Controlled neutral finding
Schoppen et al. [14]	n = 18 healthy postmenopausal women; randomized crossover	Two sodium-rich bicarbonated waters vs. low-mineral water	0.5 L with meal; acute	Glucose; insulin	Glucose unchanged; insulin water × time interaction	Insulin signal; no glucose-lowering effect
Toxqui & Vaquero [15]	n = 64 hypercholesterolaemic adults; randomized crossover	Sodium-bicarbonated vs. low-mineral water	1 L/day; 8 weeks/condition; 8-week washout	Glucose; lipids	Glucose/lipids decreased without water-type effect; caloric drinks also decreased	No water-specific effect; substitution may contribute
Costantino et al. [16]	n = 35 treated T2DM; randomized short-term intervention	Sulphurous water + usual therapy vs. therapy alone	14 days	Glycemia; redox	Reported favourableglycemic/redox changes	Preliminary; small, short study
Jovicic et al. [17]	n = 60 T2DM; uncontrolled before–after	Low-mineral Sneznik-1/79 water	28 days	Metabolic; bowel; dysbiosis; redox	Cholesterol, bowel, dysbiosis-related and antioxidant variables changed; no convincing glucose effect	Hypothesis-generating; no control
Murakami et al. [18]	n = 19 healthy adults; repeated short-term crossover-type protocol	Bicarbonate-rich water vs. tap water	500 mL/day; 1-week periods ×2	Glycoalbumin; metabolomics; microbiome	Glycoalbumin decreased; 19 metabolites differed; microbiome assessed	Exploratory; small, short study
Dallio et al. [19]	n = 87 MASLD; randomized nutritional intervention	Bicarbonate–sulfate–Ca–Mg water + diet vs. diet alone	400 mL/day; 12 months + 6-month washout	Barrier; inflammation; redox; liver	Favourable multidomain intestinal, inflammatory, oxidative and hepatic responses	Long-term signal; no equivalent-water control

Note: T2DM, type 2 diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; NaCl, sodium chloride; NaHCO₃, sodium bicarbonate; Ca, calcium; Mg, magnesium; n, number of participants; L/day, litres per day; mL/day, millilitres per day. Randomized comparative interventions and uncontrolled before–after studies are distinguished in the Population/Design column. Reported durations and doses refer to the respective study protocols.

3.2. Sodium Chloride- and Sodium Bicarbonate-Rich Mineral Waters

Schorr et al. investigated 21 healthy men and women aged 60–72 years in a randomized, placebo-controlled, double-blind crossover trial [13]. Following dietary sodium restriction, participants were assigned to consume 1.5 L/day of sodium chloride-rich, sodium bicarbonate-rich, or low-sodium mineral water for four weeks per condition, with two-week washout periods between phases.

The three waters differed substantially in sodium, chloride, and bicarbonate content. Despite these differences, the study did not demonstrate a differential effect of the water conditions on glucose tolerance [13].

This study provides important neutral evidence. It demonstrates that marked differences in sodium and bicarbonate exposure do not necessarily translate into measurable changes in glucose metabolism while also illustrating the value of a chemically defined controlwater design.

Schoppen et al. subsequently examined postprandial glucose and insulin physiology in 18 healthy postmenopausal women using a randomized three-way crossover design [14]. Participants consumed 0.5 L of either of two sodium-rich bicarbonated mineral waters or a low-mineral water together with a standardized fat-rich meal.

Glucose concentrations did not differ significantly among water conditions [14]. Insulin, however, showed a significant water-by-time interaction. The investigators also explored whether responses differed according to baseline insulin resistance assessed using homeostatic model assessment (HOMA) [14].

The pattern is compatible with an effect on postprandial insulin physiology rather than a direct glucose-lowering action. Nevertheless, the small sample, acute exposure, and reliance on surrogate insulin-sensitivity measures preclude conclusions about sustained improvement in insulin sensitivity.

Toxqui and Vaquero extended this question to a longer intervention in 64 moderately hypercholesterolaemic adults [15]. Participants consumed 1 L/day of either sodium-bicarbonated mineral water or low-mineral control water with the main meals for eight weeks in a randomized crossover design, with an eight-week washout between interventions.

Total cholesterol, LDL cholesterol, and glucose decreased during the intervention, but these changes were not specific to water type [15]. Participants also reduced their intake of caloric beverages, including soft drinks and fruit juice, creating an important competing explanation for part of the observed response.

Consequently, the trial does not establish a bicarbonate-specific glucose-lowering effect. Instead, it illustrates an important methodological issue: metabolic improvement occurring during a water intervention may reflect hydration or beverage substitution in addition to, or instead of, hydrochemical composition.

Viewed together, these three controlled studies do not show a reproducible direct glucose-lowering effect attributable specifically to sodium- or bicarbonate-rich mineral water [13,14,15]. The Schoppen study provides an interesting signal involving postprandial insulin physiology [14], but independent confirmation is required.

3.3. Evidence in Type 2 Diabetes Mellitus

Costantino et al. evaluated 35 patients with T2DM receiving pharmacological therapy [16]. Participants were randomized either to continue drug therapy alone or to receive drug therapy together with a 14-day drinking treatment using sulphurous mineral water.

The study assessed fasting blood glucose together with reactive oxygen metabolites and biological antioxidant potential [16]. The authors reported findings compatible with improvement in glycemic and redox status in the mineralwater intervention group.

This study provides direct human evidence linking sulphurous mineralwater exposure with redox-related outcomes in T2DM. Nevertheless, its evidential strength is limited by the small sample size, short duration, and thermal-treatment context. It cannot establish durable glycemic efficacy or determine which hydrochemical constituent mediated the observed response.

Jovicic et al. investigated 60 adults aged 30–60 years with confirmed T2DM who consumed low-mineral, weakly acidic water from the Sneznik-1/79 source for 28 days [17]. Outcomes were assessed before and after the four-week intervention, without a parallel controlwater group.

Total cholesterol decreased significantly, while intestinal peristalsis improved, with regular daily bowel movements reported after the intervention [17]. Dysbiosis was no longer detected in 50% of patients in whom it had been present, and antioxidant capacity improved through increases in superoxide dismutase activity and reduced glutathione [17].

These findings identify gastrointestinal and redox physiology as potentially responsive domains. However, the uncontrolled before–after design substantially restricts causal inference. Changes cannot be separated confidently from temporal effects, hydration, dietary behaviour, medication, or other aspects of the treatment setting.

The study should therefore be regarded as hypothesis-generating rather than confirmatory evidence of NMW efficacy in T2DM.

Overall, the available T2DM studies [16,17] provide preliminary evidence of changes in oxidative and gastrointestinal domains but remain insufficient to establish clinically meaningful or durable glucose-lowering efficacy.

3.4. Bicarbonate-Rich Mineral Water, Glycoalbumin, Metabolomics, and the Microbiome

Murakami et al. investigated 19 healthy volunteers who consumed 500 mL/day of commercially available tap water or bicarbonate-rich mineral water [18]. Each water was consumed for one week, and the tapwater/mineralwater sequence was repeatedtwice.

Serum glycoalbumin decreased significantly after bicarbonate-rich mineralwater consumption [18]. Blood metabolomic analysis identified 19 metabolites, including glycolysis-related metabolites and three amino acids that differed between the tapwater and bicarbonate-rich mineralwater periods. Fecal microbiome analysis was also incorporated into the experimental design [18].

The study is important because it demonstrates the potential value of combining conventional metabolic markers with metabolomics and microbiome assessment. However, its interpretation should remain conservative. The sample was small, participants were healthy, exposure periods were short, and numerous molecular outcomes were examined.

The reduction in glycoalbumin is therefore best interpreted as an exploratory metabolic signal, not as evidence that bicarbonate-rich mineral water provides established glycemic control.

3.5. MASLD and the Gut–Liver–Metabolic Interface

Dallio et al. evaluated 87 patients with MASLD in a randomized intervention [19]. Participants were allocated either to a controlled nutritional regimen combined with 400 mL/day of bicarbonate–sulfate–calcium–magnesium water consumed in the fasting state or to the controlled nutritional regimen alone.

The intervention lasted 12 months and was followed by a six-month water washout period [19]. The study simultaneously assessed intestinal permeability, systemic inflammation, oxidative stress, and MASLD-related outcomes.

This multidomain design is particularly relevant because MASLD represents a metabolic phenotype in which hepatic dysfunction, insulin resistance, oxidative stress, inflammation, and intestinal abnormalities frequently coexist. The reported findings therefore provide a clinical basis for investigating mineralwater exposure within a gut–liver–metabolic framework [19].

The trial also has important interpretative limits. The water was administered as an adjunct to nutritional therapy rather than compared with equivalent-volume control water. Consequently, the results cannot establish whether the observed effects were attributable to a specific mineral constituent, to the complete hydrochemical profile, or to interactions between water intake and the nutritional intervention.

The findings should therefore be considered promising but specific to the investigated water, dose, treatment context, and MASLD phenotype.

3.6. Overall Interpretation of the Clinical Evidence

Across controlled studies, NMW has not demonstrated a reproducible glucose-lowering effect [13,14,15]. Signals have instead appeared in selected intermediate domains, including postprandial insulin physiology [14], glycoalbumin and metabolomics [18], redox status [16,17], gastrointestinal or microbiota-related variables [17,18], and intestinal, inflammatory, and hepatic outcomes in MASLD [19]. These findings are preliminary and cannot establish a common effect across chemically different waters.

3.7. Hydrochemical Heterogeneity

Hydrochemical differences among the intervention waters are summarized in Table 2. Waters described as bicarbonate-rich, sulphurous, low-mineral, or multi-mineral differ in accompanying ions, total mineralization, pH, carbonation, and source-specific constituents. Observed outcomes should therefore be attributed to the tested water profile rather than to a dominant ion unless the study design isolates that constituent.

Table 2. Hydrochemical profiles and principal constituents of mineral waters investigated in human metabolic intervention studies.

Study	Water Profile	Key Constituents	Interpretation
Schorr et al. [13]	NaCl-rich/NaHCO3-rich vs. low-sodium	Na+, Cl−, HCO3−	Distinct sodium profiles
Schoppen et al. [14]	Two sodium-rich bicarbonated vs. low-mineral	HCO3−, Na+	Acute bicarbonated/sodium-rich comparison
Toxqui & Vaquero [15]	Sodium-bicarbonated vs. low-mineral	HCO3−, Na+ + matrix	Chronic comparison; bicarbonate not isolated
Costantino et al. [16]	Sulphurous mineral water	Sulfur species + matrix	Distinct redox-oriented exposure
Jovicic et al. [17]	Low-mineral, weakly acidic Sneznik-1/79	Low mineralization; source profile	Source-specific low-mineral exposure
Murakami et al. [18]	Bicarbonate-rich vs. tap water	HCO3− + matrix	Bicarbonate not isolated
Dallio et al. [19]	Bicarbonate–sulfate–Ca–Mg	HCO3−, SO42−, Ca2+, Mg2+	Complex multi-ion exposure

Note: NaCl, sodium chloride; NaHCO₃, sodium bicarbonate; Na⁺, sodium ion; Cl⁻, chloride ion; HCO₃⁻, bicarbonate ion; SO₄²⁻, sulfate ion; Ca²⁺, calcium ion; Mg²⁺, magnesium ion; Ca, calcium; Mg, magnesium. Constituent profiles are qualitative descriptions, not measured concentrations; no concentration units are implied. “Matrix” refers to the full hydrochemical composition of the water.

4. Biological Plausibility and Supporting Evidence

4.1. Interpreting Mechanistic Evidence

Mechanistic evidence can help explain why selected NMW interventions might affect metabolic biomarkers, but it cannot establish efficacy. Table 3 therefore separates established nutritional effects, direct human NMW signals, biologically plausible pathways, and hypothesis-generating relationships.

Table 3. Mechanistic pathways, mineralwater exposures, supporting evidence, and strength of interpretation.

Pathway	Exposure	Rationale	Direct NMW Evidence	Interpretation
Mineral bioavailability	Mg, Ca	Absorbable dietary minerals	Human absorption studies [7,8,9,10,11,12]	Established nutritional effect
Insulin regulation	Mg; water matrix	Mg participates in insulin/glucose pathways [20,21]	Postprandial insulin signal [14]	Plausible; limited direct evidence
Glucose regulation	Bicarbonate-rich/other profiles	Possible insulin/mineral-mediated effects	Glucose outcomes inconsistent [13,14,15,16,17]; glycoalbumin signal [18]	No reproducible glucose-lowering efficacy
Acid–base physiology	HCO3−	Bicarbonate affects acid–base physiology [22]	Bicarbonate-rich waters studied [13,14,15,18]	Plausible; metabolically unconfirmed
Oxidative/redox	Sulphurous/multi-mineral profiles	Oxidative stress is relevant to T2DM [23,24,25]	Redox responses [16,17,18]	Repeated signal; significance unresolved
Inflammation	Multi-component/indirect	Inflammation contributes to insulin resistance [26]	Inflammatory outcomes in MASLD [19]	Promising; limited evidence
Intestinal function	Complete water profile	GI physiology may affect metabolic/microbial milieu	Bowel-function changes [17]	Needs controlled replication
Gut microbiota	Complete profile	Microbiota associated with T2DM [27,28]	Microbiota/dysbiosis outcomes [17,19]	Hypothesis-generating
Intestinal barrier	Multi-component	Barrier dysfunction may promote inflammation [29]	Permeability outcomes in MASLD [18,19]	Emerging; mediation unproven
Gut–liver axis	Multi-mineral exposure	Gut, inflammation and liver are interconnected [30,31]	Intestinal/hepatic responses in MASLD [18,19]	Promising integrative hypothesis
Insulin resistance	Complete profile	Hepatic/peripheral substrate dysregulation [32,33]	No gold-standard insulin-sensitivity evidence	Directly unestablished
Trace elements	Lithium, silicon, boron	Potential metabolic/redox/microbiome roles [34]	No isolated causal human NMW evidence	Hypothesis-generating

Note: NMW, natural mineral water; Mg, magnesium; Ca, calcium; HCO₃⁻, bicarbonate ion; T2DM, type 2 diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; GI, gastrointestinal. Mechanistic plausibility and biomarker associations do not establish clinical efficacy or identify an individual causal mineral.

4.2. Mineral Bioavailability and Insulin-Related Physiology

Magnesium and calcium from mineral water are bioavailable in humans [7,8,9,10,11,12]. Magnesium is relevant to insulin signalling and glucose metabolism [20], and supplementation trials suggest improvements in selected glucose-metabolism outcomes in metabolically at-risk populations [21]. These data support biological plausibility but do not demonstrate that magnesium-containing NMW improves insulin sensitivity. Calcium should similarly be regarded as a bioavailable component of the water matrix rather than a proven glucose-lowering constituent [35].

4.3. Bicarbonate, Redox, and Inflammatory Pathways

Bicarbonate-rich waters can influence acid–base physiology [22], but epidemiological associations between dietary acid load and T2DM risk [36] are not equivalent to evidence from NMW interventions. Direct studies of bicarbonated waters have produced neutral glucose findings alongside selected insulin or glycoalbumin signals [14,15,19].

Oxidative stress and chronic low-grade inflammation are relevant to insulin resistance and metabolic disease [23,24,25,26]. Redox-related outcomes have changed in some T2DM and MASLD interventions [16,17,18,19], while inflammatory outcomes were assessed in the MASLD study [19]. These observations warrant replication but do not identify a specific antioxidant or anti-inflammatory action of NMW.

4.4. Intestinal, Microbiota, and Gut–Liver Pathways

Gut microbial activity, intestinal-barrier function, inflammation, and hepatic metabolism are interconnected in metabolic disease [27,28,29,30,31]. NMW studies have reported bowel-function or dysbiosis-related changes [17], incorporated fecal microbiome analysis [18], and assessed intestinal permeability together with inflammatory and hepatic outcomes in MASLD [19]. These findings remain exploratory; changes in microbiota or intestinal biomarkers do not establish mediation of metabolic effects.

4.5. Insulin Resistance and Trace-Element Context

Insulin resistance is a systemic process involving liver, skeletal muscle, and adipose tissue [32]. Most NMW studies have relied on conventional biochemical outcomes or surrogate indices rather than gold-standard insulin-sensitivity methods, which limits mechanistic inference [37].

Natural waters may also contain lithium, silicon, boron, and other trace elements. Their potential metabolic, redox, and microbiome-related roles have been reviewed [34], and trace-element status has been associated with metabolic phenotypes in observational research [38]. No human NMW intervention has isolated lithium, silicon, boron, or another trace element as the causal factor underlying a metabolic response.

4.6. Implications for Mechanistic Research

The mechanistic literature supports targeted hypotheses rather than a unified hydrochemical–phenotypic mechanism. Future studies should therefore prespecify a chemically defined exposure, a plausible pathway, and a clinically relevant outcome rather than infer mechanisms retrospectively from heterogeneous results.

The principal mechanistic pathways and supporting evidence are summarized in Table 3.

5. Discussion

5.1. What the Current Evidence Supports

The available human literature supports a restrained conclusion. Controlled trials do not demonstrate a consistent glucose-lowering effect attributable to NMW composition [13,14,15]. Some interventions report changes in insulin-related, glycoalbumin, redox, gastrointestinal, microbiota-related, inflammatory, or hepatic variables [14,16,17,18], but these findings are heterogeneous and generally unreplicated.

This pattern is consistent with the earlier review of mineral water and metabolic-syndrome features, which also emphasized heterogeneity and difficulty attributing effects to individual minerals [39]. The present synthesis extends that observation across a broader set of metabolic phenotypes while avoiding the inference that hydrochemical differences necessarily explain between-study differences.

5.2. Hydration, Composition, and Sources of Heterogeneity

A major interpretative challenge is separating hydrochemical effects from hydration and beverage substitution. In the Toxqui and Vaquero trial, cardiometabolic changes occurred alongside reduced intake of soft drinks and fruit juice and were not specific to the sodium-bicarbonated water [15]. Observational evidence likewise suggests that replacing caloric beverages with water may be more relevant than water intake itself for diabetes risk [40].

Water composition remains important for exposure definition but not yet as an established effect modifier. Chemically distinct waters, different doses and durations, and populations ranging from healthy adults to T2DM and MASLD make cross-study comparison difficult. Future trials should therefore report full analytical composition and use equivalent-volume control waters when the aim is to isolate composition-related effects.

Because the intervention waters contain multiple dissolved constituents, any observed response reflects exposure to the complete water matrix. Without composition-matched, equivalent-volume control waters, effects cannot generally be attributed to individual minerals or ions.

5.3. Clinical and Research Implications

Current evidence does not justify recommending a specific NMW for treatment of insulin resistance, T2DM, MASLD, or related metabolic disorders. Established implications are narrower: water can replace energy-containing beverages [15,40], and selected mineral waters can contribute bioavailable calcium and magnesium [7,8,9,10,11,12,41,42].

Future studies should prioritize adequately powered randomized designs, analytically characterized intervention and control waters, predefined primary metabolic outcomes, and clearly characterized participants. Mechanistic endpoints should be selected prospectively and linked to clinically interpretable outcomes rather than treated as independent evidence of benefit.

Replication is particularly important. A reproducible response across independently sourced waters with comparable chemical characteristics would provide stronger evidence for a composition-related effect than additional single-source exploratory studies.

6. Strengths and Limitations

A strength of this review is the explicit separation of direct human NMW evidence from mineral-bioavailability and the broader mechanistic literature. It also evaluates the intervention waters as chemically distinct exposures rather than assuming that all NMWs are equivalent.

The principal limitation is the small and heterogeneous direct evidence base. Samples are generally modest, populations and outcomes differ substantially, and some interventions lack equivalent control water or were not primarily designed to assess metabolic endpoints [13,14,15,16,17,18,19].

These design limitations reduce confidence in the direction, magnitude, and reproducibility of reported effects. In T2DM [13,14,15,16,18], short interventions and the absence of a control group in one study limit causal interpretation; in MASLD [19], the absence of an equivalent-water comparator prevents separation of water-composition effects from the accompanying dietary intervention. The findings in both populations therefore remain preliminary.

The review itself is a structured critical review rather than a PRISMA systematic review. The search was designed to support critical synthesis of the sparse literature, and the mechanistic discussion necessarily draws on evidence outside direct NMW interventions. Accordingly, completeness of study identification cannot be guaranteed, and mechanistic plausibility should not be interpreted as causal evidence.

Publication bias, selective outcome reporting, and multiplicity are additional concerns in small exploratory studies. These limitations, together with the absence of reproducible effects on major glycemic outcomes, require conservative interpretation.

7. Conclusions

Human evidence does not establish NMW as a treatment for metabolic disease or demonstrate a reproducible glucose-lowering effect. Selected studies report potentially relevant changes in insulin-related, redox, gastrointestinal, microbiota-related, inflammatory, and hepatic domains, but these signals are preliminary and heterogeneous.

The most defensible conclusion is that NMW should be treated as a source-specific nutritional exposure whose composition must be defined analytically. Whether particular hydrochemical profiles produce clinically meaningful metabolic effects remains uncertain.

Future research should test narrowly specified hypotheses using characterized intervention and control waters, adequate sample sizes and durations, predefined outcomes, and well-defined metabolic phenotypes. Until such evidence is replicated, clinical claims beyond hydration and mineral contribution are not warranted.