21 Adult male CD Sprague–Dawley rats (388–483 g).

Randomized intervention, including 3 groups in parallel.

To investigate the effects of mineral water⊗ consumption in 10% fructose-fed Sprague–Dawley rats (Table 2, Table 3 and Table 4).

The animals were divided into 3 groups (n = 7/group), fed with standard laboratory chow diet and different drinking solutions, for 8 weeks.

SBP, DBP and HR evolution over time (over the dietary intervention period) appeared to be protected from fructose effects by mineral water ingestion until approximately half of the dietary intervention period.

SBP significantly increased with time in both fructose groups versus CONT group. DBP in FRUCTMIN rats tended to increase with time versus CONT rats.

Between weeks 1 and 5, FRUCT rats had a significantly higher HR than CONT rats. HR significantly increased with time in FRUCTMIN versus CONT rats.

Circulating aldosterone seemed to increase in FRUCT versus CONT (mineral water ingestion seemed to counteract this pattern).

Between weeks 0 and 6, FRUCTMIN rats presented significantly higher urinary sodium versus CONT and FRUCT rats.

FRUCTMIN and FRUCT rats showed significantly and similarly lower circulating magnesium than CONT rats. No differences were found in circulating chloride, phosphorous, sodium, calcium and potassium among the 3 groups.

No differences in circulating uric acid; CONT rats presented significantly higher circulating urea than FRUCT and FRUCTMIN rats.

18 Postmenopausal women (amenorrheic ≥ 1 y, aged 45–59 y), healthy and not obese (BMI < 30 Kg/m2).

With exclusion criteria.

Clinical trial, well-controlled sequential design, non-blinded.

To investigate the effects of mineral water⊗ consumption in healthy postmenopause (Table 2, Table 3 and Table 4).

The intervention comprised 2 consecutive periods of 2 months each. Participants consumed, as supplement to their usual diet, 1 L/day of control low-mineral water (CLMW) during the first period and 1 L/day of carbonic sodium-bicarbonate mineral water (CSBMW) during the second period.

CLMW: 71.1 mg/L bicarbonate, 9 mg/L sodium, 5.7 mg/L chloride, 25.2 mg/L calcium, 2.7 mg/L magnesium, 1.4 mg/L potassium, 0.2 mg/L fluoride and 15.7 mg/L sulphate; without carbonic gas. CSBMW was mainly rich in bicarbonate (2094.4 mg/L), sodium (1116.5 mg/L) and chloride (583.0 mg/L) and contained carbonic gas; its content in calcium, magnesium, potassium, fluoride and sulphate being 43.6, 5.7, 54.7, 7.9 and 49.9 mg/L, respectively. Both waters were from Vichy Catalán®.

Diet was controlled, characterized and analysed; compliance with treatments was checked.

Determinations were performed at the beginning and end of the CLMW and CSBMW periods. Blood samples were collected after 12 h of overnight fasting.

SBP and DBP did not change during the study.

18 Young volunteers (8 men and 10 women), aged > 18 and < 40 y [29 ± 8 y (mean ± SD)], moderately hypercholesterolemic (total- cholesterol > 200 mg/dL and LDL-cholesterol > 100 mg/dL); BMI 24.38 ± 4.24 Kg/m2 (mean ± SD).

With exclusion criteria.

Clinical trial, controlled sequential design, non-blinded.

To investigate whether the effects of mineral water⊗intake previously observed in healthy postmenopause were confirmed in moderately hypercholesterolemia (Table 2, Table 3 and Table 4).

Intervention lasted 2 consecutive 8-week periods. Participants consumed, as supplement to their usual diet, 1 L/day of CLMW during the first period and 1 L/day of CSBMW during the second period.

CLMW contained 104 mg/L bicarbonate, 8.7 mg/L sodium, 11 mg/L chloride, 33.4 mg/L calcium, 5.0 mg/L magnesium, 2.0 mg/L potassium, < 0.2 mg/L fluoride and 15.6 mg/L sulphate; without carbonic gas.

CSBMW was mainly rich in bicarbonate (2120 mg/L), sodium (1102 mg/L) and chloride (597 mg/L); its content in calcium, magnesium, potassium, fluoride and sulphate being 32.0, 9.4, 49.5, 0.9 and 45.3 mg/L, respectively; 3.9 g/L carbonic gas.

Both waters were from Vichy Catalán®.

Diet was controlled, characterized and analysed; compliance with treatments was checked. Participants were instructed to maintain their regular habits as well as their normal diet and exercise level.

Determinations were performed at baseline, at the end of the CLMW period and at weeks 4 and/or 8 of the CSBMW period. Blood samples were collected after a 12 h fasting period. Volunteers were instructed regarding the composition of their dinner on the evening before the analysis. At the end of both intervention periods, 24 h urine samples were collected.

Consumption of CSBMW for 4 weeks significantly decreased SBP, within normal limits, versus CLMW intake (but not for 8 weeks of ingestion); without significant differences in SBP between the fourth and the eighth weeks of CSBMW intake.

DBP pressure remained constant during the entire study.

Urinary pH and sodium and chloride were significantly higher with CSBMW versus CLMW ingestion, at the eighth week.

12 Healthy men, moderately hypercholesterolemic (2.20–3 g/L), aged 20–60 y [40.6 ± 9.4 y (mean ± SD)], BMI 18.5–25 Kg/m2 [23.1 ± 2.2 Kg/m2 (mean ± SD)].

With exclusion criteria.

Controlled, randomized, double-blinded, cross-over design, including 2 groups.

To analyze the effects of mineral water⊗consumption, with or without a standardised meal, in moderate hypercholesterolemia (Table 2 and Table 3).

The study consisted in 2 experimental periods with 8 weeks each separated by a 1-week wash-out period. Subjects consumed 1.25 L/day of 1 of the 2 sparkling mineral waters.

Saint-Yorre® (SY) water, with high-mineral content (20 fold more than the referent water); mainly rich in bicarbonate (4168 mg/L), sodium (1626 mg/L) and chloride (329 mg/L) and its content in potassium, calcium, magnesium and sulphate being 117, 85, 11 and 186 mg/L, respectively.

Ogeu® (referent water), with low-mineral content (183, 31, 48, 1, 48, 12 and 18 mg/L, respectively).

Diet was controlled and characterized. Volunteers were asked not to deviate from their regular habits during the study.

BP measurements and blood sampling were done in a first visit just before starting SY water or referent water consumption and in a second visit on the last day of SY water or referent water intake. Their effects were studied at fasting (T0) and/or during postprandial state (T30 min, T1 h, T2 h, T3 h, T4 h, T6 h and T8 h) after ingestion of a standardised meal and 0.5 L of water, at both visits for both waters.

No significant differences were found on SBP and DBP considering both treatments, both at basal or postprandial $states.

64 Normotensive participants, 56% women, aged 18–45 y [30.7 ± 7.5 y (mean ± SD)], moderately hypercholesterolemic (total-cholesterol: > 200 and < 300 mg/dL), BMI 23.2 ± 2.8 kg/m2.

With exclusion criteria.

Randomized, single-blinded, cross-over, controlled trial, including 2 groups.

To assess the effects of mineral water⊗intake in moderate hypercholesterolemia (Table 2, Table 3 and Table 4).

The intervention consisted in two 8-week periods [one water tested/period, 1 L/day (consumed as part of the usual diet, with the 2 main meals)], separated by an 8-week washout period.

Participants were allocated in 2 groups:

Diet was controlled, characterized and analysed; compliance with treatments was checked. Participants were asked to maintain their regular habits as well as their normal diet, body weight and exercise level.

Determinations were made at baseline and at the fourth and eighth weeks. Blood samples were collected after 12 h of overnight fasting.

SBP and DBP did not vary significantly throughout the trial.

Circulating aldosterone did not vary significantly throughout the trial, although it tended to decrease with CSBMW, but not with CLMW intake.

CSBMW consumption significantly increased urinary pH and decreased urinary calcium; CLMW intake did not change these parameters. Urinary potassium significantly decreased with time for both mineral waters while urinary sodium and phosphate remained stable.

20 Participants, 10 men and 10 women: 10 mildly hypertensive (BP > 140/90 mmHg; 5 black + 5 white) and 10 normotensive (BP < 140/90 mmHg; 5 black + 5 white) subjects. Aged 36 ± 9 y (mean ± SD), 20–56 y.

With exclusion criteria.

Randomized, placebo-controlled, double-blinded, cross-over trial, including 2 groups.

To test the effects of sodium bicarbonate and sodium chloride ingestion (as drinking solutions) in normotensive and mildly hypertensive subjects consuming a low-sodium diet (Table 4).

Each intervention phase lasted 11 days. In the first 4 days, participants ingested a fixed daily basal low-sodium diet aiming to achieve ion balance (60 mmol sodium, 60 mmol chloride, 60 mmol potassium and 14 mmol calcium; 80 g protein; fat and carbohydrates were adjusted for each participant).

Then, keeping the same diet, they were assigned to drink 3 L/day, for 7 days, of a mineral water⊗(Staatlich Fachingen®, 26.2 mmol/L sodium, 0.71 mmol/L potassium, 2.18 mmol/L magnesium, 3.04 mmol/L calcium, 4.23 mmol/L chloride and 33.03 mmol/L bicarbonate) or a control placebo aqueous solution (containing the same concentrations of all of the cations as the chloride salts, 36.07 mmol/L). In both regimens, total daily sodium consumption increased to 138 mmol. One month later (at least), the opposite regimen was followed.

Food and liquids provided by the research team.

Determinations were done on the fifth and twelfth day, after overnight fasting.

HR was not modulated by both treatments.

Sodium chloride-containing control water did not influence BP.

In mildly hypertensives, sodium bicarbonate-containing mineral water significantly decreased SBP but not DBP; no effect was observed in normotensives.

Both drinking regimens significantly decreased circulating renin activity in mildly hypertensives but not in normotensives; no effects were observed upon circulating aldosterone, dopamine, epinephrine and norepinephrine.

No differences were found in urinary sodium or potassium between drinking regimens (urinary sodium similarly increased with both waters; data not provided for potassium), BP groups and race. Urinary chloride consistently and significantly increased with sodium chloride-containing control water but not with sodium bicarbonate-containing mineral water; a similar significant pattern was observed for urinary calcium, although more weak (an effect of race and BP was also evident for calcium: greater in whites and mildly hypertensives than in blacks and normotensives, respectively).

Urinary urate was similar in the 2 BP groups for both dietary oral interventions; however, for both drinking solutions, it was significantly greater in whites than in blacks.

Sodium chloride-containing control water, versus sodium bicarbonate-containing mineral water, had significant, but modest, positive and negative effects on circulating chloride (in both BP groups) and bicarbonate (only in normotensives; non-significant similar pattern in hypertensives), respectively. Circulating sodium, potassium, calcium, phosphate, urate and albumin were not influenced by any of the waters tested.

17 Normotensive healthy participants (BP < 140/90 mmHg; 9 women and 8 men), aged 24–53 y (median 29 y); BMI 17.3–33.5 Kg/m2.

With exclusion criteria.

Randomized, non-blinded, cross-over study, including 2 groups.

To evaluate the effects of mineral water⊗ consumption in healthy normotensive subjects (Table 4).

Each arm of the study lasted 7 weeks, with a 6-week washout period. Participants ingested 0.5 L/day of Água das Pedras/Pedras Salgadas® or Vitalis® (0.25 L in the morning and 0.25 L in the afternoon).

Água das Pedras®, carbonic hypersaline (sodium and bicarbonate-rich) mineral water: 62.0 mg/L silica, 31.0 mg/L chloride, 2125.0 mg/L bicarbonate, 622.0 mg/L sodium, 28.0 mg/L magnesium, 103.0 mg/L calcium and 0.3 mg/L nitrate.

Vitalis®, hyposaline water: 10.0 mg/L silica, 7.0 mg/L chloride, < 1.0 mg/L bicarbonate, 3.8 mg/L sodium, 0.7 mg/L magnesium, 0.4 mg/L calcium and nitrate 1.2 mg/L; without carbon dioxide.

Diet was controlled, characterized and analysed; compliance with treatments was checked. Participants had no restrictions on food or other drinks ingestion but were asked to maintain their normal eating and drinking habits.

Measurements were done at the beginning and end of each treatment.

No significant differences were observed between the effects of the 2 treatments upon SBP, DBP and HR. No significant difference from baseline values was found.

None of the 2 treatments had any effect on urinary pH or sodium and potassium.

21 Healthy normotensive participants [men (n = 10) and women (n = 11)], aged 64.1 ± 3.6 y (mean ± SD; 60–72 y); BMI 26.1 ± 3.6 Kg/m2.

With exclusion criteria.

Randomized, placebo-controlled, double-blinded cross-over trial, including 3 groups.

To examine the effects of mineral water⊗ ingestion in healthy normotensive participants consuming a low-sodium diet (an oral glucose tolerance test was also done; Table 2 and Table 3).

Each phase of the study lasted 4 weeks, with a 2-week washout period (during which the volunteers kept the low-salt diet).

After reducing salt intake to below 100 mmol/day, participants were assigned to drink 1.5 L/day of:

Dietary counselling was provided and compliance with treatments was checked.

Determinations were done before the start of the study and at the end of the firstcand fourth weeks of each mineral water phase [c24 h ambulatory BP, circulating lipids and circulating glucose and insulin response to an oral glucose load (75 g) were not evaluated at this time point].

Versus baseline, mean resting BP, at weeks 1 and 4, was significantly reduced when consuming low-sodium or sodium bicarbonate-rich mineral waters but unchanged with sodium chloride-rich mineral water. At week 4, ambulatory 24 h BP was not altered by any of the 3 waters.

At weeks 1 and 4, urinary sodium was significantly reduced by the ingestion of low-sodium mineral water versus baseline, significantly increased with sodium chloride-rich and sodium bicarbonate-rich mineral water ingestion versus low-sodium mineral water and significantly reduced with sodium bicarbonate-rich mineral water ingestion versus sodium chloride-rich mineral water (and non-significantly versus baseline); urinary chloride showed a pattern similar to sodium (although not always with the same statistical significance).

At weeks 1 and 4, urinary calcium was significantly reduced by drinking low-sodium and sodium bicarbonate-rich mineral waters versus baseline (non-significantly for low-sodium mineral water at week 1); with sodium chloride-rich mineral water intake a non-significant decrease versus baseline was observed only at week 4.

At weeks 1 and 4, urinary net acid increased with sodium chloride-rich (significantly at both time points) and low-sodium mineral water ingestion (significantly only at week 1) versus baseline.

No effects were observed in circulating catecholamines and uric acid as well as in glomerular filtration rate under the 3 distinct mineral water treatments.

Although circulating renin activity, aldosterone and atrial natriuretic factor values were distinctly affected by the 3 different interventions at end of week 1, at the end of week 4 there were no differences versus baseline.

10 Patients, men (n = 4) and women (n = 6), aged 55–74 y [65 ± 6.7 y (mean ± SD)]; with moderate hypercholesterolemia (total-cholesterol > 240 mg/dL; LDL-cholesterol > 170 mg/dL).

With exclusion criteria.

Clinical sequential trial.

To evaluate the effect of a spring mineral water⊗ ingestion in moderate hypercholesterolemia (Table 2).

The study was conducted over a 9-week period. The first 3 week-period matched the dietary stabilization phase (dietary-lead-in period) that was followed by 3 weeks of active treatment with mineral water and 3 further weeks of control treatment with tap water.

During the study, the subjects were given a standard daily diet and, for each of the 2 treatments, consumed, respectively, 0.75 L of Montecatini Regina® mineral water (1540 mg/L sulphate, 136 mg/L magnesium, 5535 mg/L sodium, 9220 mg/L chloride and 677 mg/L bicarbonate) ### or tap water (no information provided regarding its composition), in the morning.

Blood sample collection was performed after 13 h of overnight fasting. Circulating lipids, ApoAI and ApoB were evaluated at T-21 (screening), T0 and every week during the 2 treatment periods [similar for circulating Lp(a) and identical for BP (no information found for circulating electrolytes)].

Feces collection was done for 24 h periods. Fecal total bile acids were evaluated on the last 3 days of the dietary-lead-in period, every day during the active treatment (five-day mean data) and once a week during the control period (similar for fecal fractionated bile acids). Gallbladder volume was evaluated just before and after water intake (at 15, 30, 45 and 60 min).

BP remained stable during the entire study.

Circulating chloride significantly increased during the active treatment period but did not show any differences between the dietary-lead-in and control periods; circulating sodium, potassium and magnesium did not change significantly during the active treatment period.

70 Women and men, aged 45–64 y, with borderline hypertension (SBP 15 mmHg above normal values for corresponding age, DBP ˃ 90 mmHg and within 20% of ideal BW, and with low urinary magnesium and calcium levels) and living in an area with low magnesium content in the drinking water.

With exclusion criteria.

Randomized parallel double-blinded trial, including 3 groups.

To determine the effects of the consumption of mineral water⊗ and water with added magnesium in borderline hypertension, with low urinary magnesium and calcium levels.

Subjects consumed at least 1 L/day, for 4 weeks.

The participants were allocated in 3 groups:

Dietary control was done; compliance with treatments was checked.

For analysis, volunteers with serum or urine values higher than the 75th percentile (n = 15) were excluded (a group with a sufficient body burden of minerals and not influenced by the intervention).

Determinations were done before and after intervention periods. Additionally, BP was also evaluated at week 2.

A significant decrease in SBP and DBP was found at the second and fourth weeks in the group consuming Contrex®.

Consumption of magnesium-enriched water and Contrex®significantly increased urinary magnesium, but did not change urinary calcium, at the end of the protocol.

No significant effects of treatments on circulating magnesium were detected.

None of the subjects changed their normal dietary habits during the trial.

31 Participants, aged 50–79 y (mean 62 y), 62% women, no smokers and without disease.

With exclusion criteria.

Clinical trial, with randomization, non-blinded.

To detect groups at risk for high BP and to assess the possibility to intervene in these groups with mineral water⊗.

The participants consumed 75 mL/day of mineral water (split in five doses, evenly distributed over the day and without specific relation to mealtimes), for 2 weeks.

Content per total daily dose of mineral water: 3.1 mmol magnesium, # 0.65 mmol calcium and 0.02 mmol potassium.

No data on volunteers’ dietary habits were gathered.

Determinations were undertaken at baseline and after 14 days, with and without intervention with mineral water.

At baseline, without mineral water ingestion, although positive significant associations between urinary urea and urinary calcium, magnesium and potassium were observed, the same did not happen for urinary urea versus SBP or DBP.

Consistent results for the changes over time without mineral water intervention were observed.

At baseline, without mineral water ingestion, among individuals with high urinary urea, lower urinary magnesium was significantly related to higher SBP; the same did not happen for potassium or calcium. No relationship occurred in the low urinary urea group.

Mineral water ingestion induced a small and almost significant increase in urinary magnesium and calcium.

Only among volunteers with initial high urinary urea and low urinary magnesium, mineral water intervention strongly tended to decrease DBP ## (in 4 out of 5 subjects).

5 Healthy women [aged 27–61 y #; 41 y (mean)].

Clinical trial, non-blinded.

To assess the effects of the ingestion of a mineral water⊗ in healthy subjects.

# Volunteers drank 1 L Magnesia®mineral water (204 mg/L magnesium, 39.5 mg/L calcium, 1.3 mg/L potassium and 5.4 mg/L sodium) in 30 min, on the 1st day; tests were made at 0, 2, 6, 24 and 48 h. Then, only 1 glass of water was drunk at a time by the individuals for 4 weeks, with a daily total of 1–1.5 L. Tests (but urine volume) were repeated after 1, 2, 3 and 4 weeks.

No data on volunteers’ dietary habits were collected.

Magnesia®water consumption significantly increased circulating and urinary magnesium as well as urine volume, in a specific time-dependent manner.

Circulating and urinary magnesium peaked at 6 h, slowly decreasing afterwards (until 48 h). While urinary magnesium peaked again at the end of the first week and then decreased until the end of the fourth week (but always presenting higher values than baseline), circulating magnesium returned to baseline values. Urine volume increased from 2 to 48 h.

BP, HR, ECG and circulating calcium, potassium and sodium did not vary.

Information provided in Table 1.

Information provided in Table 1.

Circulating total-triglycerides significantly increased in FRUCT versus CONT rats, but just tended to increase in FRUCTMIN versus CONT rats.

Circulating total-, LDL- and HDL-cholesterol did not differ among the 3 groups neither did the HDL-cholesterol/total-cholesterol and HDL-cholesterol/LDL-cholesterol ratios.

100 Specific pathogen-free male CD rats (100 ± 10 g).

Randomized intervention, including 3 groups in parallel.

To study the impact of hydropinic treatment with mineral water⊗in hypercholesterolemia (Table 4).

Dietary intervention lasted 4 months.

Rats were assigned into 3 groups:

IDCS water (rich in minerals) contained 485 mg/L calcium, 209 mg/L magnesium, 50.9 mg/L potassium, 1650 mg/L chloride, 793 mg/L sodium, 714 mg/L bicarbonate and 1287 mg/L sulphate. 1− and F−content amounted to 24.8 and 1.6 mg/L, respectively, in IDCS but was absent in TW.

TW (with low-mineral content) contained 49.8 mg/L calcium, 0.96 mg/L magnesium, 0.24 mg/L potassium, 3.2 mg/L chloride, 1.74 mg/L sodium, 152.9 mg/L bicarbonate and 2.14 mg/L sulphate.

During the last night of the interventions, feces were collected. At the end of the treatment, after 18 h of overnight fasting, blood samples were collected, intestinal propulsion was evaluated and bile flow (and bile composition) after biliary drainage was determined.

TC and TT rats presented significantly higher circulating total-, HDL- and LDL-cholesterol than CC rats. TT rats showed significant reductions in circulating total- and LDL-cholesterol versus TC rats (no differences were found in circulating HDL-cholesterol and total-triglycerides).

TT rats had total-cholesterol/HDL-cholesterol, total-cholesterol/LDL-cholesterol and HDL-cholesterol/LDL-cholesterol cardiovascular risk indexes intermediate between those found for CC and TC rats.

Total fecal bile acid elimination was significantly higher in TT than in TC rats.

Intestinal propulsion was significantly higher in TT than in TC rats.

TT and TC groups displayed similar biliary elimination curves, with alike total bile acids and cholesterol content in the bile.

Information provided in Table 1.

Information provided in Table 1.

Circulating total-triglycerides, ApoAI and ApoB did not differ at the end of the 2 periods.

Circulating total- and LDL-cholesterol significantly decreased as well as cardiovascular risk indexes (total-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios), while circulating HDL-cholesterol significantly increased, after CSBMW intake versus CLMW.

Information provided in Table 1.

Information provided in Table 1.

CSBMW versus CLMW consumption significantly reduced circulating total- and LDL-cholesterol as well as cardiovascular risk indexes (total-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios) and ApoB, at the eighth week.

LDL-cholesterol/HDL-cholesterol ratio changed only between the fourth and the eighth week of CSBMW consumption. The other parameters showed a continuum reduction (ApoB not evaluated at the fourth week).

Circulating HDL-cholesterol tended to increase with CSBMW versus CLMW intake, only at the eighth week.

Circulating total-triglycerides and ApoAI as well as LDL-cholesterol/ApoB and HDL-cholesterol/ApoAI ratios remained stable with treatments.

Information provided in Table 1.

Information provided in Table 1.

No significant effects were observed with low-mineralized referent water both at fasting and postprandial states. No difference was observed between the 2 waters both at fasting and postprandial states.

At fasting state, a significant decrease in circulating total- and VLDL-triglycerides and a tendency to a decrease in circulating VLDL-cholesterol was observed after SY water consumption (a similar non-significant pattern was noticed for referent water).

At postprandial state, the results showed no significant differences either for circulating total- and VLDL-triglycerides or for circulating VLDL-, LDL- and HDL-cholesterol after SY water consumption.

Information provided in Table 1.

Information provided in Table 1.

With CLMW and CSBMW intake, and without significant differences between these groups, circulating total- and LDL-cholesterol as well as cardiovascular risk indexes (total-cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and LDL-cholesterol/ApoB ratios) significantly decreased, while circulating ApoB significantly increased, with time; circulating oxidised LDL tended to decrease with time.

Circulating HDL-cholesterol, total-triglycerides and ApoAI as well as HDL-cholesterol/ApoAI ratio remained constant throughout the trial.

Information provided in Table 1.

Information provided in Table 1.

Circulating total-triglycerides and total-, LDL- and HDL-cholesterol did not differ among the 3 different regimens (sodium-chloride-rich, sodium-bicarbonate-rich and low-sodium mineral water ingestion; results provided only for the fourth week).

Information provided in Table 1.

Information provided in Table 1.

Treatment with Montecatini Regina®water significantly reduced circulating total- and LDL-cholesterol as well as ApoB and total-cholesterol/HDL-cholesterol ratio (versus the other 2 periods). No differences were found between dietary stabilization and control periods.

Circulating HDL-cholesterol, total-triglycerides, ApoAI and Lp(a) did not significantly change during the active treatment period.

The gallbladder volume was significantly reduced with Montecatini Regina® water treatment (no significant effect with tap water treatment). Total fecal bile acids were significantly increased with Montecatini Regina®water (versus the other 2 periods).

The lithocholic/deoxycholic ratio increased from 1:9 to 3.8:6.2 with Montecatini Regina®water.

19 Healthy subjects (7 men and 12 women), aged 26–59 y [46.9 ± 11.1 y (mean ± SD)]; BMI 23.0 ± 3.2 Kg/m2(average ± SD).

With exclusion criteria.

Clinical sequential trial.

To elucidate the effects of mineral water⊗ consumption in healthy volunteers (Table 3).

Tap water (TW) and bicarbonate-rich mineral water (BMW) sequential consumption periods lasted for a week each; the sequence was repeated twice. The participants drank 0.5 L/day of TW or BMW, divided into thrice daily (30–60 min before breakfast, lunch and dinner).

BMW (from Nagayu hot spring) contained 2485 mg/L bicarbonate, 412 mg/L sodium, 182 mg/L chloride, 80 mg/L potassium, 291 mg/L magnesium, 177 mg/L calcium, 355 mg/L sulphate and 0.3 mg/L fluoride.

TW (from Nishikawa water treatment plant) contained, respectively, 28, 10, 11, < 0.1, 1.9, 6.1, 6.9 and < 0.1 mg/L. For both waters, H2 S and HS− < 0.1 mg/L.

Participants were instructed to maintain their normal dietary habits during the test. Compliance with treatments was checked.

Determinations were done on the first day of the test and last days of every week, after overnight fasting.

Apart from circulating calcium, BMW intake had no impact on circulating urate, total-, HDL- and LDL-cholesterol, total-triglycerides, sodium, chloride, magnesium and cortisol. A significant increase was reported for circulating calcium.

21 Adult men (n = 10) and women (n = 11), aged > * 18 and < 40 y [27.8 ± 4.5 y (mean ± SD)]; triglycerides < 2.82 mmol/L (250 mg/dL), moderately hypercholesterolaemic; BMI > 18 and < 30 Kg/m2 [23.8 ± 2.9 Kg/m2 (mean ± SD)]. With exclusion criteria.

Randomized, cross-over, controlled trial, including 4 groups.

To investigate the effects of mineral water⊗ consumption, with or without a standard fat-rich meal, in moderately hypercholesterolaemia (Table 3).

4 Different treatments were applied: 0.5 L of control low-mineral water (CLMW) + standard fat-rich meal, 0.5 L of carbonic sodium-bicarbonate mineral water (CSBMW) + standard fat-rich meal, 0.5 L of CLMW and 0.5 L of CSBMW.

CSBMW was rich in bicarbonate (2120 mg/L), sodium (1102 mg/L) and chloride (597 mg/L); its content in calcium, magnesium, potassium, sulphate and fluoride being 32.0, 9.4, 49.5, 45.3 and 0.9 mg/L, respectively; with carbon dioxide (3.9 g/L).

CLMW contained 104, 8.7, 11, 33.4, 5.0, 2.0, 15.6 and < 0.2 mg/L, respectively; without carbon dioxide.

Both mineral waters were from Vichy Catalán®.

Volunteers attended the clinic 4 times at 1-week intervals, having followed instructions regarding dinner composition the evening before the study and having fasted overnight for at least 12 h; compliance with dinner instructions and absence of water intake in the previous 12 h were checked.

Volunteers were allocated to a specific individual sequence of treatments (that included the 4 arms of the postprandial study) on the 1st study day.

They were instructed not to deviate from their regular habits and to maintain their normal diet, body weight, alcohol consumption and exercise level.

Blood samples were obtained at basal conditions and at postprandial times (30, 60 and 120 min).

Consumption of CSBMW without a standard fat-rich meal (versus CLMW) did not significantly affect any of the studied parameters.

With the standard fat-rich meal, a time effect was observed with both waters for circulating total-triglycerides and CCK as well as gallbladder volume.

Consumption of CSBMW + standard fat-rich meal induced a significantly lower increase in circulating total-triglycerides and CCK than intake of CLMW + standard fat-rich meal.

Consumption of CSBMW + standard fat-rich meal significantly increased gallbladder volume versus CLMW + standard fat-rich meal. Gallbladder ejection fraction was significantly lower with CSBMW + standard fat-rich meal but AUC and peak contraction amplitude (lowest gallbladder volume) were significantly higher versus CLMW + standard fat-rich meal.

69 Hyperlipidemic adults (circulating total-cholesterol and triglycerides > 200 mg/dL, LDL-cholesterol > 150 mg/dL, HDL-cholesterol < 40 mg/dL); aged 30–60 y.

Randomized controlled trial, including 2 groups in parallel.

To assess the hypolipidemic effects of a mineral water⊗intake in hyperlipidemic subjects.

32 Adults received 1 L/day of high-mineral content water for 1 month [1350 mg/L bicarbonate, 250 mg/L calcium, 48 mg/L magnesium, 150 mg/L sodium, 165 mg/L sulphate, 9 mg/L potassium]; and

37 adults received 1 L/day of low-mineral water for the same period (29 mg/L, 7 mg/L, 1.7 mg/L, 5 mg/L, 20 mg/L and 2 mg/L, respectively).

No data on volunteers’ dietary habits were evaluated.

At the end of treatment, changes in lipid profile were compared separately in each studied group or between groups.

Circulating total- and LDL-cholesterol decreased significantly in both intervention groups (with no significant differences between the 2 intervention groups).

Circulating total-triglycerides and HDL-cholesterol did not vary significantly after both interventions.

18 Healthy postmenopausal women (amenorrhoeic for at least 1 year), aged 51–59 y; BMI 26.89 ± 3.04 Kg/m2(mean ± SD); no smokers. With exclusion criteria.

Randomized, cross-over, controlled trial, including 3 groups.

To investigate the effects of drinking mineral water⊗, with a standard fat-rich meal, in healthy postmenopausal women.

3 Different treatments were applied: standard fat-rich meal + 0.5 L of 1 of the 3 mineral waters tested [sodium-bicarbonate mineral water (SBMW) 1, SBMW2 and control low-mineral water (CLMW)].

SBMW1⊗ and 2⊗were rich in bicarbonate (2094.4/2013 mg/L), sodium (1116.5/948 mg/L) and chloride (583.0/592 mg/L); their content in calcium, magnesium, potassium, sulphate and fluoride being 43.6/52.1, 5.7/9.7 mg/L, 54.7/47.7, 49.9/42.9 and 7.9/1.4 mg/L, respectively.

CLMW was low in minerals (71.1, 9.0, 5.7, 25.2, 2.7, 1.4, 15.7 and 0.2 mg/L, respectively).

All waters were from Vichy Catalán®.

Volunteers attended the laboratory facilities on 3 occasions at 2-week intervals, having followed instructions regarding dinner composition the evening before the study and having fasted overnight for at least 12 h; compliance with dinner instructions was verified with a questionnaire.

On the first study day, volunteers were assigned to a specific individual treatments sequence including the 3 arms of the postprandial study.

Volunteers were instructed not to deviate from their regular habits and to maintain their normal diet and body weight, alcohol consumption and exercise level.

Blood samples were obtained at basal conditions and at postprandial times (30, 60, 120, 240, 360 and 420 min).

Over the period of postprandial evaluation, no significant timeXwater effect was observed for any of the 4 variables evaluated (and time to peak did not significantly vary among treatments). Circulating total- and chylomicron-triglycerides showed significant water and time effects. Circulating total- and chylomicron-cholesterol showed no water effect, while a significant time effect was observed only for the latter.

Only peak concentration of circulating total-triglycerides showed a significant water effect (with both SBMW1 and 2 similarly lower versus CLMW, but no significant differences were observed among the 3 treatments).

Circulating chylomicron-cholesterol showed a similar but less intense and non-significant overall pattern of variation (both for postprandial TAUC and peak concentration).

A significant water effect was observed only in TAUC of circulating total- and chylomicron-triglycerides [circulating total-triglycerides significantly lower with SBMW2 intake versus CLMW (SBMW1 and 2 consumption behaving similarly); chylomicron-triglycerides similarly lower with SBMW1 and 2 ingestion versus CLMW, but with no significant differences among the 3 treatments].

40 Postmenopausal women with functional dyspepsia and/or constipation (amenorrhoeic for at least 1 year) [aged 61.2 ± 1.8 to 64.0 ± 1.4 y; BMI 24.0 ± 0.6 to 24.9 ± 0.9 Kg/m2, for CTRL and THW groups, respectively (mean ± SE)].

With exclusion criteria.

Non-blinded controlled trial, including 2 groups.

To investigate the effect of drinking thermal mineral⊗water (THW) in postmenopause (Table 4).

Interventions lasted 12 d; 0.5 L of each water (THW and tap water) was ingested every day in the morning, in the fasted state.

The THW group (n = 20) drank Acqua Santa of Chianciano Terme®, at a temperature of 33 °C (730 mg/L bicarbonate, 29.4 mg/L chloride, 41 mg/L sodium, 180 mg/L magnesium, 840 mg/L calcium, 7 mg/L potassium, 2 mg/L fluoride, 1840 mg/L sulphate; with 537 cc/L carbon dioxide).

The control group (CTRL; n = 20) drank Rome tap water at a temperature of 10–12 °C (6.5 mg/L chloride, 5.5 mg/L sodium, 19 mg/L magnesium, 98 mg/L calcium, 3 mg/L potassium, 0.2 mg/L fluoride, 15 mg/L sulphate).

On days 1 and 13, after an overnight fasting and before drinking water, procedures were done. Additionally, daily, body weight measurements and stool diary filling in were done.

Daily diet was controlled, characterized and analysed.

No effects were observed within each group or between groups in circulating lipid profile (total-triglycerides, total-, HDL- and LDL-cholesterol).

Gallbladder volume and circulating total bile acids did not significantly differ between THW and CTRL groups both at baseline and at the end of the study.

Gallbladder volume was significantly smaller at the end of the study than at baseline in THW group but not in CTRL group while circulating total bile acids were higher.

THW group with significantly higher number of daily bowel movements versus CTRL group.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose seemed to increase in FRUCT versus CONT rats.

Circulating insulin and leptin significantly increased in FRUCT versus CONT group.

Insulin sensitivity index strongly tended to decrease in FRUCT versus CONT rats.

Mineral water ingestion appeared to counteract all the above-mentioned fructose-induced effects.

42 Male Wistar rats with STZ-induced diabetes.

Randomized intervention, with 6 groups in parallel.

To investigate the effects of mineral water⊗ on cardiac fibrosis in diabetic rats (Table 4).

The intervention lasted 7 weeks; rats were divided into:

Mineral water composition: chloride 1560 mg/L, sodium 1300 mg/L, sulphate 844 mg/L, calcium 403 mg/L, bicarbonate 180 mg/L, magnesium 49 mg/L, fluoride 1.5 mg/L and potassium 2 mg/L (also with a sulfuric degree of 8.4 mg/L).

Overall, no differences were observed with control rats versus the 2 treatments groups: only circulating insulin significantly decreased in NaHS versus mineral water group.

Diabetic rats had significantly higher circulating glucose and HbA1C than normal controls; the opposite for circulating insulin, C-peptide and IGF-I.

Mineral water intake by or NaHS injection to diabetic rats significantly reduced circulating glucose and HbA1C versus diabetic rats; the opposite for circulating insulin, C-peptide and IGF-I.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose significantly decreased in CSBMW versus CLMW intake.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose strongly tended to decrease with CSBMW versus CLMW intake, similarly at the fourth and eighth weeks.

Circulating insulin remained constant with treatments.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose remained constant with treatments with referent and SY waters, both at fasting and postprandial states.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose significantly decreased with time, equally with CLMW and CSBMW ingestion.

Circulating insulin remained constant throughout the trial.

Information provided in Table 1.

Information provided in Table 1.

Circulating glucose and insulin levels, as well as their AUC (in the oral glucose tolerance test), did not differ among the 3 different regimens (sodium-chloride-rich, sodium-bicarbonate-rich and low-sodium mineral water ingestion), at any of the time points evaluated.

Information provided in Table 2.

Information provided in Table 2.

Circulating glycoalbumin significantly decreased during BMW versus TW interventions.

Circulating glucosed and insulin as well as HOMAR were not different between TW and BMW interventions. dIn serum, unlike in plasma, glucose slightly tended to be lowered during BMW versus TW treatments.

Information provided in Table 2.

Information provided in Table 2.

Circulating insulin remained constant with the treatments without food. When waters were consumed with the standard fat-rich meal, circulating insulin was non-significantly lower with CSBWM versus CLMW intake (at all time points).

Circulating glucose did not change with consumption of the waters alone or with the standard fat-rich meal.

With the standard fat-rich meal, a time effect was observed with both waters for circulating insulin, but not for circulating glucose.

18 Healthy postmenopausal women (amenorrhoeic for at least 1 year), aged 51–59 y [55.5 ± 2.28 y (mean ± SD)]. BMI < 30 Kg/m2 [26.88 ± 3.04 Kg/m2(mean ± SD)]; no smokers.

With exclusion criteria.

Randomized, cross-over, non-blinded controlled trial, including 3 groups.

To study the effects of mineral water⊗ intake, with a standard fat-rich meal in healthy postmenopause.

3 Different treatments were applied: standard fat-rich meal + 0.5 L of 1 of the 3 mineral waters tested [sodium-bicarbonate mineral water (SBMW) 1, SBMW2 and control low-mineral water (CLMW)].

SBMW1⊗ and 2⊗ were rich in bicarbonate (2094.4/2013 mg/L), sodium (1116.5/948 mg/L) and chloride (583.0/592 mg/L). Their content in calcium, magnesium, potassium, sulphate and fluoride was 43.6/52.1, 5.7/9.7, 54.7/47.7, 49.9/42.9 and 7.9/1.4 mg/L, respectively.

CLMW was low in minerals (71.1, 9.0, 5.7, 25.2, 2.7, 1.4, 15.7 and 0.2 mg/L, respectively).

Both waters were from Vichy Catalán®.

Volunteers attended the laboratory facilities on 3 occasions at 2-week intervals, after 12 h of overnight fasting. Written instructions were provided regarding dinner composition the evening before the study and compliance with dinner instructions was checked.

Volunteers were assigned to an individual sequence of treatments including all 3 waters.

Volunteers were instructed not to deviate from their regular habits and to maintain their normal diet and exercise level.

Blood samples were obtained at basal and at postprandial times (30, 60, 120 min).

Glycemia did not change along the postprandial period for any of the 3 waters tested.

Postprandial circulating insulin and glucose peak concentrations as well as time to peak did not differ for all 3 waters.

At 120 min, SBMW1 ingestion significantly lower postprandial circulating insulin versus CLMW (at this point, a similar non-significant pattern was found for SBMW2 versus CLMW but no difference was found between SBMW1 and SBMW2). At 30 min, it showed non-significant higher values with both SBMW1 and SBMW2 versus CLMW intake.

Postprandial circulating insulin showed significant time for all 3 waters and waterxtime effects, depending on HOMA values: it showed significantly different responses to mineral water intake depending on HOMA values. It showed nearly significant different postprandial responses between HOMA n-tile 1 and 3. HOMA3 group showed higher postprandial circulating insulin at 30 min than in HOMA1 and 2 groups (particularly for SBMW1 intake).

With SBMW1 ingestion, postprandial circulating glucose in HOMA3 group was also slightly higher versus SBMW2 and CLMW intake.

HOMA and QUICKY were significantly correlated and equally valid to assess differences in glucose and insulin metabolism. All women presented an adequate insulin metabolism based on HOMA data.

Information provided in Table 1.

Information provided in Table 1.

Overall, on each separate week (week by week), body weight and food ingestion displayed similar values for all groups.

Week by week, fluid ingestion was significantly higher in both fructose-fed groups versus CONT group, without any significant difference between FRUCT and FRUCTMIN groups.

Week by week, total energy ingestion was significantly higher for both fructose-fed groups versus CONT group, without any significant difference between FRUCT and FRUCTMIN groups.

With time (over the 8-week period), a significantly higher and similar body weight increase in FRUCT and FRUCTMIN versus CONT rats occurred.

With time, FRUCTMIN rats decreased food ingestion significantly more than CONT rats and presented a trend towards a higher decrease than FRUCT rats.

With time, fluid ingestion increased significantly for FRUCTMIN versus CONT and FRUCT rats.

With time, total energy ingestion decreased similarly for all groups.

Information provided in Table 2.

Information provided in Table 2.

TT rats with statistically higher body weight increase than TC rats.

TT and TC rats grew significantly less than CC rats.

Information provided in Table 3.

Information provided in Table 3.

Body weight of diabetic rats was significantly lower than of controls.

Body weight of diabetic rats + mineral water was similar to controls and significantly higher than of diabetic rats (similarly for diabetic rats + NaHS, although more weak).

Information provided in Table 1.

Information provided in Table 1.

Body weight and BMI remained constant during the study. WC did not differ between the 2 treatment periods.

Dietary energy intake remained constant throughout the entire study. The protein, carbohydrate, fat (including lipid profile), cholesterol and fiber intakes did not differ between the 2 treatment periods.

Information provided in Table 1.

Information provided in Table 1.

Body weight, BMI and WC remained constant during the study.

Dietary energy intake did not vary during the entire study. No changes in protein, carbohydrate, fat, cholesterol, plant phytosterol and fiber intakes, and the type of fat ingested did not differ between the 2 intervention periods.

Information provided in Table 1.

Information provided in Table 1.

BMI and WC did not vary throughout the trial. Men exhibited significantly higher WC than women.

No significant timexwater effects were observed upon nutrients intake except for saturated fat (opposite trend in CSBMW versus CLMW group) and for sodium (CSBMW was a source of this nutrient).

A time effect was noticed for energy and carbohydrates intakes from beverages, while lipids, protein, and alcohol intakes remained unchanged. Soft drinks and fruit juice intakes significantly decreased in both treatments, while total fluid intake significantly increased with both mineral waters.

Information provided in Table 1.

Information provided in Table 1.

None of the 2 treatments had any effect on body weight.

Information provided in Table 1.

Information provided in Table 1.

None of the 2 treatments had any effect on body weight and BMI.

Normal dietary habits did not change during the trial.

Information provided in Table 2.

Information provided in Table 2.

Body weight was similar in THW and CTRL groups both at baseline and at the end of the study. Similarly, no change in body weight was observed at the end of the study versus baseline when each group was individually considered.

The number of pasta, meat and vegetable portions consumed during the study was significantly higher (approximately 2-fold) but bread consumption was significantly lower (half the amount) in THW versus CTRL group. No intergroup difference was found with regard to fish, pizza, legume, fruit, dessert, soft drink, milk, dairy product and espresso coffee consumption.