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• Evid Based Complement Alternat Med
• v.2016; 2016

Alkaline Water and Longevity: A Murine Study

Massimiliano magro.

1 Department of Comparative Biomedicine and Food Science, University of Padua, 35020 Legnaro, Italy

Livio Corain

2 Department of Management and Engineering, University of Padua, 36100 Vicenza, Italy

Silvia Ferro

Davide baratella, emanuela bonaiuto, vittorino corraducci, luigi salmaso, fabio vianello.

The biological effect of alkaline water consumption is object of controversy. The present paper presents a 3-year survival study on a population of 150 mice, and the data were analyzed with accelerated failure time (AFT) model. Starting from the second year of life, nonparametric survival plots suggest that mice watered with alkaline water showed a better survival than control mice. Interestingly, statistical analysis revealed that alkaline water provides higher longevity in terms of “deceleration aging factor” as it increases the survival functions when compared with control group; namely, animals belonging to the population treated with alkaline water resulted in a longer lifespan. Histological examination of mice kidneys, intestine, heart, liver, and brain revealed that no significant differences emerged among the three groups indicating that no specific pathology resulted correlated with the consumption of alkaline water. These results provide an informative and quantitative summary of survival data as a function of watering with alkaline water of long-lived mouse models.

1. Introduction

Alkaline water, often referred to as alkaline ionized water (AKW), is commercially available and is mainly proposed for electrolyte supplementation during intensive perspiration. Early studies on animal models reported that alkaline water supplementation may exert positive effects on body weight improvement and development in offspring [ 1 , 2 ]. Even biochemical markers were analyzed, suggesting that alkaline ionized water intake can cause elevation of metabolic activity. In particular, hyperkaliemia was observed in 15-week-old rats and pathological changes of necrosis in myocardial muscle were found [ 3 ].

More recently, studies were carried out on alkaline reduced water (ARW), referring to electrolyzed water produced from minerals, such as magnesium and calcium, which is characterized by supersaturated hydrogen, high pH, and a negative redox potential. This hydrogen-rich functional water has been introduced as a therapeutic strategy for health promotion and disease prevention [ 4 ].

Alkaline and electrolyzed water have been shown to exert a suppressive effect on free radical levels in living organisms, thereby resulting in disease prevention [ 5 ]. Various biological effects, such as antidiabetic and antioxidant actions [ 4 ], DNA protecting effects [ 6 ], and growth-stimulation activities [ 2 ], were documented.

Although a variety of bioactive functions have been reported, the effect of alkaline water on lifespan and longevity in vivo is still unknown. Animal alkalization has been shown to be well tolerated and to increase tumor response to metronomic chemotherapy as well the quality of life in pets with advanced cancer [ 7 ]. Therefore, we performed a study based on survival rate experiments, which play central role in aging research and are generally performed to evaluate whether specific interventions may alter the aging process and lifespan in animal models.

2. Materials and Methods

Biological effects of alkaline water were evaluated on a selected population of 150 mice (CD1, by Charles River, Oxford, UK). Pathogen-free mice were purchased and placed in a specific breeding facility. No other animal was present in the room. Contact with animal caretakers was minimized to feeding and watering. The population was divided into 3 groups, each consisting of 50 individuals, as follows:

• Group A: 50 mice conventionally fed and watered with alkaline water produced by the Water Ionizer (mod. NT010) by Asiagem (Italy). The Water Ionizer is a home treatment device for producing alkaline drinking water.
• Group B: 50 mice conventionally fed and watered with alkalized water obtained by dilution of a concentrated alkaline solution (AlkaWater by Asiagem, Italy). AlkaWater is a concentrated alkaline solution for preparing alkaline drinking water.
• Group C: 50 mice conventionally fed and watered as conventional (control group) with tap water. The local water supply was evaluated weekly for assuring the absence of toxins and pathogens. The pH values were in the 6.0–6.5 range.

All procedures involving animals were conducted in accordance with the Italian law on experimental animals and were approved by the Ethical Committee for Animal Experiments of the University of Padua and the Italian health Ministry (Aut. no. 39ter/2011). Efforts were made to minimize animal suffering.

2.1. Histological Examination

Treated aged mice were sampled postmortem and subjected to histological examination. Animals belonging to the populations treated with alkaline water, A and B, were sacrificed after 24 months and compared to mice treated with tap water. Samples from kidneys, intestine, heart, liver, and brain were fixed in 10% neutral buffered formalin, and 4  μ m sections were analyzed by optical microscopy.

2.2. Statistical Analysis

In order to investigate the biological influence of alkaline water on mouse longevity, we employed the accelerated failure time model (AFT) [ 8 ], which allows formally exploring the possible effect on survival curves of the applied three-level treatment, that is, examining the role of group membership as a covariate of lifespan. As a more robust alternative to the commonly used proportional hazards models, such as the Cox model, the use of AFT models is advised in the field of survival analysis when the goal is to investigate if a covariate may affect the lifespan in a way that the life cycle may pass more or less rapidly. In fact, whereas a proportional hazard model assumes that the effect of a covariate is constant over time, an AFT model assumes that the effect of a covariate is to accelerate or decelerate the life course.

The relevance of AFT model for biomedical studies has been already recognized in the literature [ 8 ]. With more specific reference to the issue of aging, Swindell [ 9 ] observed that some genetic manipulations were found to have a multiplicative effect on survivorship which were well characterized by the AFT model “deceleration factor.” Moreover, Swindell [ 9 ] argued also that the AFT model should be utilized more widely in aging research since it provides useful tools to maximize the insight obtained from experimental studies of mouse survivorship.

To perform all calculations, we applied a parametric survival analysis approach using a class of 3-parameter AFT distribution models implemented within the statistical software Minitab, version 17.2.1 [ 10 ]. More specifically, we employed three types of random distributions, namely, log-logistic, log-normal, and generalized Weibull.

The experiment consisted in an initial 15-day acclimatization period. After acclimatization, animals (50, group A) were watered with alkaline water (pH 8.5), obtained by the Water Ionizer (Asiagem, Italy), whereas group B animals (50) were watered with water alkalized at pH 8.5 by a concentrated alkaline solution (AlkaWater by Asiagem, Italy) for 15 days. Group C animals (50), control group, were watered with the local water supply. This period has been identified to gradually accustom the animals treated with alkaline water. At the end of the second period of acclimatization, group A and B animals were watered with alkaline water at pH 9.5 (by the Water Ionizer and by AlkaWater by Asiagem, Italy), while animals of group C were watered with local tap water.

After the first year, the most aggressive individuals were moved to other cages within the same group and an environmental enrichment protocol was employed in order to decrease the hyperactivity. This phenomenon was observed especially in animals of groups A and B.

Table 1 reported basic statistics on mice survival of treated and control animals.

Basic statistics on mice survival by treatment level.

Regarding group A, animals (50) were watered with alkaline water (pH 8.5), obtained by the Water Ionizer (Asiagem, Italy). As for group B, animals (50) were watered with water alkalized at pH 8.5 by a concentrated alkaline solution (AlkaWater by Asiagem, Italy) for 15 days. Regarding group C, animals (50), control group, were watered with the local water supply.

A first look on experimental data is provided in Figure 1 , where nonparametric hazard and survival plots seem to suggest that even if no macroscopic difference emerges, starting from the second year of life mice watered with alkaline Water Ionizer and those treated with AlkaWater overwhelmed control mice.

Nonparametric hazard and survival plots by treatment level. Group A: animals (50) were watered with alkaline water (pH 8.5), obtained by the Water Ionizer (Asiagem, Italy). Group B: animals (50) were watered with water alkalized at pH 8.5 by a concentrated alkaline solution (AlkaWater by Asiagem, Italy) for 15 days. Group C: animals (50), control group, were watered with the local water supply.

In order to explore the possible effect of different treatments, that is, to examine the role of group membership on longevity, we applied a parametric survival analysis approach using a class of 3-parameter survival distributions that represent flexible accelerated failure time, AFT models. First of all, using the Anderson-Darling goodness-of-fit statistic, we compared three specific survival distributions, that is, log-logistic (AD = 6.397), log-normal (AD = 6.519), and generalized Weibull (AD = 6.447). Since the best fitting was shown by log-logistic model, we adopted this one as final survival distribution model. The straight lines in the log-logistic distribution QQ plots (Figures 2(a) and 2(b) ) indicate that this distribution provides a suitable fit to our survival data.

QQ plots using the 3-parameter log-logistic distribution model. (a) Treatment A survival time quantiles (vertical axis) versus treatment C survival time quantiles (horizontal axis); (b) treatment B survival time quantiles (vertical axis) versus treatment C survival time quantiles (horizontal axis).

Finally, by including our treatment as covariate, we performed a parametric distribution analysis whose results are graphically represented in Figure 3 .

Distribution plot results using the 3-parameter log-logistic model. Group A: animals (50) were watered with alkaline water (pH 8.5), obtained by the Water Ionizer (Asiagem, Italy). Group B: animals (50) were watered with water alkalized at pH 8.5 by a concentrated alkaline solution (AlkaWater by Asiagem, Italy) for 15 days. Group C: animals (50), control group, were watered with the local water supply.

Starting with the second year of life, it is worth noting that both alkaline water treated groups denote a decreasing hazard curve over time, while the corresponding curve for control group is monotonically increasing. To more formally compare the treatment levels, the proposed analysis provided also suitable p values. Since the p values related on the null hypotheses of equality of location, scale and threshold parameters were, respectively, less than 0.001 (for both locations and scales) and 0.634 (for thresholds) at a 5% significance level; we can state that there is enough experimental evidence to conclude that the treatment significantly affects the mice longevity; in particular the alkaline water provides a benefit to longevity in terms of “deceleration aging factor” as it decreases the hazard functions when compared with the control group. Note that the treatment effect cannot be directly related to no one of the three distribution parameters. Anyway, using the estimated parameters, it should be possible to provide an estimate for the effect of each treatment on survivorship: setting the reference survival time to 1000, 1200, and 1400 days, Table 2 summarizes the estimated point and 95% interval survival probabilities by each treatment level.

Table of survival probabilities by treatment level. The probabilities, along with their related 95% confidence interval limits, were calculated using the normal approximation.

As final remark, it should be noted that even if our parametric AFT survival analysis was performed using the log-logistic distribution, our conclusions are consistent with results obtained using the generalized Weibull distribution, while via log-normal distribution no significant effect was found.

3.1. Histological Examination

No significant differences emerged from the histological examination among the three groups. In all examined samples, renal tissue was characterized by a mild-to-moderate lymphoplasmacytic interstitial infiltrate and few occasional glomerular changes as glomerular size reduction and increasing of Bowman's space ( Figure 4 ).

Kidney, a specific chronic nephropathy. Focal interstitial mainly lymphocytic infiltrate (upright) and a sclerotic glomerulus (middle right). Hematoxylin and Eosin.

Final diagnosis was mild chronic progressive nephropathy for the three analyzed mouse groups.

The microscopic examination of the liver revealed a multifocal nodular pattern of the parenchyma and diffuse mild-to-moderate hepatocellular cytoplasmic hydropic degeneration with multifocal binucleation in all explored animals ( Figure 5 ).

Liver, aging change. Hepatocellular abundant dishomogeneous cytoplasm, binucleation (center), variably sized nuclei, and a nuclear pseudoinclusion cyst (arrow). Hematoxylin and Eosin.

Mild-to-moderate anisokaryosis was the most relevant alteration, with few pleomorphic nuclei and frequent intranuclear pseudoinclusions and karyomegaly. A specific mild perivascular infiltrate was occasionally present. Final diagnosis was mild-to-moderate diffuse hepatopathy with multifocal hyperplastic hyperplasia.

The pulmonary parenchyma showed mild multifocal areas of interstitial thickening of the interalveolar septa due to moderate congestion and mild cellular mixed infiltrate ( Figure 6 ). Mild areas of emphysema were detected at the periphery of the parenchyma. Final diagnosis was multifocal very mild atelectasis and mild vicarious emphysema.

Lung, mild atelectasis. Very mild multifocal interstitial thickening of the alveolar septa associated with congestion and mild cellular increase. Hematoxylin and Eosin.

At the same time, no relevant histopathologic histological changes have been noticed in intestine ( Figure 7 ), brain, and heart.

Intestine. Longitudinal section of duodenum showing uniformly thin and elongated villi. Hematoxylin and Eosin.

4. Discussion

The present work presents a 3-year survival study on a population of 150 mice and the data were analyzed with accelerated failure time (AFT) model. Kaplan-Meier statistical analysis of the survival data indicates the possibility of a positive effect of alkaline water on mouse lifespan and AFT model allowed evaluating differences starting from the second year of the survival curves. These results provide an informative and quantitative summary of survival data as a function of watering with alkaline water on long-lived mouse models. It should be pointed out that, from the standpoint of aging research, this statistical approach presents appealing properties and provides valuable tools for the analysis of survival. The observation of tissues of deceased animals was performed for the assessment of the state of internal organs to be compared with similar analyses of untreated animals. The renal lesions observed at histology were specific and common for the three animal groups. Chronic progressive nephropathy has been well described as normal aging change in mice [ 11 , 12 ]. In our cases animals did not show any clinical sign of nephropathy or any other histological evidence of specific kidney disease and we ascribed the lesions to the aging process [ 11 , 12 ].

The examined livers were also affected by typical lesions of mature subjects, such as hyperplastic nodules. Furthermore, well known aging changes were individuated in the hepatocytes, such as karyomegaly, nuclear pleomorphism, and pseudoinclusions cysts [ 11 , 12 ].

5. Conclusions

A 3-year survival study on a population of 150 mice was carried out in order to investigate the biological effect of alkaline water consumption. Firstly, nonparametric hazard and survival plots suggest that mice watered with alkaline water overwhelmed control mice. Secondly, data were analyzed with accelerated failure time (AFT) model inferring that a benefit on longevity, in terms of “deceleration aging factor,” was correlated with the consumption of alkaline water. Finally, histological examination of mice kidneys, intestines, hearts, livers, and brains was performed in order to verify the risk of diseases correlated to alkaline watering. No significant damage, but aging changes, emerged; organs of alkaline watered animals resulted to be quite superimposable to controls, shedding a further light in the debate on alkaline water consumption in humans.

Acknowledgments

This paper is dedicated to the memory of Tommaso Nicoletti. The authors are grateful to Rocco Palmisano for original ideas and support. The authors would like to thank Asiagem (Italy) for partial support and Ludovico Scenna, Carlo Zatti, and Silvano Voltan for their scientific and professional contribution.

Competing Interests

The authors declare that there are no competing financial interests.

• Research article
• Open access
• Published: 28 November 2016

Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults

• Joseph Weidman 1 ,
• Ralph E. Holsworth Jr. 2 ,
• Bradley Brossman 3 ,
• Daniel J. Cho 4 ,
• John St.Cyr 5 &
• Gregory Fridman 6  

Journal of the International Society of Sports Nutrition volume  13 , Article number:  45 ( 2016 ) Cite this article

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Previous research has shown fluid replacement beverages ingested after exercise can affect hydration biomarkers. No specific hydration marker is universally accepted as an ideal rehydration parameter following strenuous exercise. Currently, changes in body mass are used as a parameter during post-exercise hydration. Additional parameters are needed to fully appreciate and better understand rehydration following strenuous exercise. This randomized, double-blind, parallel-arm trial assessed the effect of high-pH water on four biomarkers after exercise-induced dehydration.

One hundred healthy adults (50 M/50 F, 31 ± 6 years of age) were enrolled at a single clinical research center in Camden, NJ and completed this study with no adverse events. All individuals exercised in a warm environment (30 °C, 70% relative humidity) until their weight was reduced by a normally accepted level of 2.0 ± 0.2% due to perspiration, reflecting the effects of exercise in producing mild dehydration. Participants were randomized to rehydrate with an electrolyzed, high-pH (alkaline) water or standard water of equal volume (2% body weight) and assessed for an additional 2-h recovery period following exercise in order to assess any potential variations in measured parameters. The following biomarkers were assessed at baseline and during their recovery period: blood viscosity at high and low shear rates, plasma osmolality, bioimpedance, and body mass, as well as monitoring vital signs. Furthermore, a mixed model analysis was performed for additional validation.

After exercise-induced dehydration, consumption of the electrolyzed, high-pH water reduced high-shear viscosity by an average of 6.30% compared to 3.36% with standard purified water ( p  = 0.03). Other measured biomarkers (plasma osmolality, bioimpedance, and body mass change) revealed no significant difference between the two types of water for rehydration. However, a mixed model analysis validated the effect of high-pH water on high-shear viscosity when compared to standard purified water ( p  = 0.0213) after controlling for covariates such as age and baseline values.

Conclusions

A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, electrolyte water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.

Water is an essential nutrient for life, and hydration plays a critical role in human physical performance as well as in the prevention of chronic diseases. Dehydration is a well-accepted contributor to impaired human physical performance, resulting in guidelines established for fluid replacement in many professions involving significant physical activity, including athletes [ 1 ]. Performance impairments that are mediated by dehydration can produce untoward effects such as cardiovascular strain, heat strain, altered neurologic function and altered metabolic function [ 2 ].

Reductions in body mass by 2% or more due to perspiration during exercise have been well-established to be linked with impaired aerobic and physiologic performance. While this impairment involves metabolic, neurological, cardiovascular and important thermoregulatory factors, the primary limiting factor of exercise performance is cardiovascular drift, reflecting a shrinking cardiovascular reserve by reduced stroke volume and mean arterial pressure during intense or protracted exercise, coupled with an increase in heart rate [ 3 ]. Exercise-induced elevations in heart rate with a decrease in myocardial stroke volume can correlate closely with the degree of dehydration [ 2 ]. Dehydration has been shown to increase systemic vascular resistance by 17 ± 6% compared with euhydration during prolonged exercise ( p  < 0.05) [ 4 ].

Numerous studies have evaluated beverage rehydration around exercise sessions, which have included supplementation with water, coconut water, juices, teas, sodas, as well as carbohydrate, electrolyte and glycerol beverages [ 5 – 9 ]. In a majority of these studies, fluid replacement beverages were administered orally after a dehydration challenge and the rehydration abilities of specific replacement beverages were assessed using biomarkers, physical performance evaluations and subjective questionnaires. One study involving 6 healthy males suggested that higher vs. lower concentrations of a carbohydrate-electrolyte solution were more effective in restoring hydration following exercise [ 5 ]. A study of 10 soccer players reported that exercise-induced changes in body mass and plasma volume were smaller with the ingestion of a carbohydrate-glycerol beverage than a carbohydrate beverage, highlighting improved hydration with the addition of glycerol [ 6 ]. Another study which monitored hydration biomarkers showed that coconut water did not hydrate significantly better than water alone [ 7 ]. Alkaline water (ALK) has been hypothesized to be superior to standard purified water in restoring rehydration and high-shear blood viscosity during a 2-h recovery period following exercise-induced dehydration; however, specific structured studies of one or multiple biomarkers during re-hydration following exercise have not established a gold standard biomarker for recovery period. Therefore, we designed a randomized, double-blind, parallel arm research study to characterize and compare the magnitude and rate of rehydration of high-pH electrolyzed water vs. standard purified water by assessing serial levels of a specific biomarker of whole blood viscosity at high-shear rate as a primary endpoint. In addition to measuring whole blood viscosity at high shear rate, the following secondary endpoints were assessed: low-shear blood viscosity, plasma osmolality, bioimpedance, and changes in body weight.

This study, performed at the Waterfront Technology Center (Camden, NJ), was a randomized, double-blind, parallel-arm, controlled trial, which recruited 100 adult volunteers (50 male, 50 female), between 25 to 49 years of age. Eligible participants were healthy, non-smoking adults, having a body-mass index less of 29 or less and free from any medication for at least one week prior to the participation in the study. Female participants were excluded from the study if they were pregnant, breast-feeding, menstruating at the time of screening, or if they had taken oral contraceptives in the previous 3 months. Subjects were instructed to refrain from strenuous activity, alcohol, and to limit excessive caffeine intake (>2 six-ounce cups) for at least 24 h prior to their assigned arrival on the study date. This clinical study was approved by the Institutional Review Board, and written informed consent was obtained from all subjects at the time of enrollment and prior to participating in this study. The study was registered (ClinicalTrials.gov Identifier: NCT02118883) and conducted in accordance and compliance with Good Clinical Practice and the Declaration of Helsinki.

Design of study

The two different fluid replacement beverages consisted of standard bottled water as the control (CON), having a normal pH with minerals added for taste (Dasani®, The Coca-Cola Company, Atlanta, GA). The electrolyzed, high-pH ALK with added minerals for taste acted as the experimental treatment beverage (Essentia®, Essentia Water, LLC, Bothell, WA). Supplies of both water samples were stored in the same climate-controlled indoor location and covered to prevent prolonged light exposure.

Subjects were permitted to consume food and water at will prior to the study. Following a baseline assessment, participants were asked to refrain from food or fluid intake. Baseline assessments for body mass, bioelectrical impedance and vital signs (heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), respiration rate, body temperature) were collected at the initiation of the study prior to exercise. Blood samples were collected by venipuncture for evaluation of whole blood viscosity and plasma osmolality. Following baseline measures, the subjects performed moderate aerobic exercise sessions (using their choice of a treadmill, stationary bicycle, and/or elliptical trainer) in a warm environment (30 °C, 70% relative humidity) until they reached a dehydrated state. The duration of exercise varied between subjects; however, the dehydration threshold target was standardized to 2.0 ± 0.2% body weight loss due to the effects of a period of exercise in producing mild dehydration. During the exercise period, participants dried themselves thoroughly before each body mass measurement. A disposable paper gown of known weight was provided during body mass measurements. After the exercise period was completed and a dehydrated state attained, study participants moved to a thermo-neutral environment (21 °C, 60% relative humidity), where they rested for 20 min. After this rest period, vital signs, weight and bioimpedance were assessed. In addition, blood samples were collected for assessment of blood viscosity and plasma osmolality.

A prior study, assessing the effect of oral carbohydrate solution on rates of absorption reported an approximate 3% reduction in plasma volume during a 105-min interval after beverage consumption [ 10 ]. The present study incorporated a follow-up period of 120 min, which was considered to be sufficiently long in duration to show any effect of rehydration during recovery. The 120-min follow-up period (T000 to T120 min), which followed exercise and rest, was divided into a 30-min rehydration period and a 90-min recovery period. Participants were rehydrated orally by CON or ALK (T000 to T030 min). The mass of the water consumed during the rehydration period was calculated according to a participant’s body mass change during the exercise period. The recommended amount of rehydration fluids was determined using a formula of 20 mL of oral hydration per 1 kg of subject body weight, i.e. 2% of pre-exercise, baseline body weight. Water volumes poured into containers were measured using a precision scale (Intelligent-Lab PD-3000, Intelligent Weighing Technology, Inc. Camarillo, CA) by an unblinded coordinator who had no contact with any participants or study results throughout the study. Subjects were required to consume the entire quantity of designated water following exercise ad libitum within 30 min (T000 to T030 min). Blood samples were collected for whole blood viscosity and plasma osmolality at T015 min and T030 min during this rehydration period.

Additional data were collected during the 90-min recovery period (T030 to T120 min) to fully assess any potential variations in measured parameters. Blood viscosity and plasma osmolality were assessed seven times: at baseline and at six subsequent intervals (T000, T015, T030, T060, T090, and T120 min). Bioimpedance analysis and body mass change measurements were performed five times: at baseline and at four subsequent intervals (T000, T045, T075, and T120 min). Vital signs were evaluated a total of three times: at baseline, as well as at T000 and T120 min. A flow sheet showing time points for each biomarker evaluation is represented in Fig.  1 .

Study overview (clinical study flow sheet)

Measured parameters

Whole blood viscosity.

Whole blood viscosity, the inherent resistance of blood to flow, was used as a measurement of intravascular hydration status. Blood viscosity was assessed across a physiologic range of shear rates of 1-1000 s -1 in increments of 0.1 s -1 using an automated scanning capillary tube viscometer (Hemathix SCV-200, Health Onvector, King of Prussia, PA). This instrument has been validated using rotating cone-and-plate and couette type viscometers across a range of shear rates [ 11 ]. Approximately 3 cc of whole blood were collected for each blood viscosity test. Each blood sample was processed and analyzed at 37 °C within 24 h after being collected. Blood viscosity levels were reported in millipoise units (1 centipoise [cP] = 1 millipascal-seconds [mPa•s] = 10 millipoises [mP]). Blood viscosity values, measured at a high shear rate of 300 s -1 , were reported as systolic blood viscosity, and those measured at a low shear rate of 5 s -1 were reported as diastolic blood viscosity.

Plasma osmolality

Once retrieving a blood sample, the plasma osmolality was assessed within 24 h. Each sample was centrifuged at 5 °C for 10 min at 1000 x g , and the plasma component was shipped to a reference laboratory (Laboratory Corporation of America, Burlington, NC), which performed the analysis using a freezing-point depression osmometer (Advanced Instruments, Norwood, MA).

Bioelectrical impedance

Bioelectrical impedance analysis, or bioimpedance, was performed on site using a bioimpedance analyzer (Quantum IV, RJL Systems, Clinton, MI). Subjects assumed a supine position with their arms 30° from the body and their legs not touching. Electrodes were placed on the right hand and right foot of each subject and removed after each measurement. On the subject’s hand, the signal electrode was placed on the skin of the metacarpophalangeal joint of the middle finger, and the detecting electrode was placed on skin of the wrist. On the foot, the signal electrode was placed on the skin at the base of the second toe, and the detecting electrode was placed on the skin at the top of the ankle. The following indices were recorded during each measurement: impedance, reactance, capacitance, phase angle, total body water, intracellular water, and extracellular water.

Body mass index (BMI) was measured using a digital floor scale (HealthOMeter 349KLX, Pelstar, LLC, McCook, IL). Measurements were performed using a nude, dry weight, with a dry gown of known weight provided for comfort.

Determination of sample size

The scanning capillary viscometer used to assess the primary endpoint in this study was previously employed in a preliminary study of dehydration and rehydration by high-pH alkaline water in 15 nonsmoking, apparently healthy firefighters. The variability of systolic blood viscosity measurements (high-shear viscosity) and the rehydration effect of high-pH alkaline on systolic viscosity observed in this prior study population were used to determine the sample size for this study [ 12 ]. In this firefighter trial, dehydration induced by fighting mock fires in training session with full equipment produced mean systolic viscosity values of 42.7 mP, and after rehydration, mean systolic blood viscosity was significantly reduced to 38.8 mP ( p  = 0.003). A standard deviation of 2.6 mP observed at baseline was used in determining our sample size for the present study. We postulated that high-pH ALK would demonstrate 40% greater rehydration effect than CON, that is, rehydration by CON was hypothesized to reduce mean systolic blood viscosity to 40.5 mP while ALK was hypothesized to reduce systolic blood viscosity to 38.8 mP from a dehydrated level of 42.7 mP. The present study was powered to detect such a contrast with 90% power using a type I error rate of 5%. This required 100 participants or 50 in the CON group and 50 individuals in the ALK group.

Statistical analyses

Statistical analyses were performed using SAS (Statistical Analysis System, Version 9.3, 2012, Cary, NC). The data were analyzed using both descriptive and inferential statistics. Four separate analyses were pre-planned: comparison of percent change in biomarkers, comparison of the slopes of regression lines, absolute differences, and mixed model analyses.

A comparison of the percentage change of each outcome measure was performed during the rehydration and recovery period. Such an analysis was intended to compensate for the individual differences at baseline and at T000 min values. For example, the percentage change in the endpoint parameter from T000 to T120 was computed for whole blood viscosity (WBV) as:

Mean values for each treatment group and estimates of standard errors for each enabled confidence intervals were to be computed and conclusions made based on these differences.

Fitting a line to each set of endpoint data for each variable, CON versus ALK were examined and statistical tests were conducted on the difference of the slope parameter for each line to determine if there was a significant overall treatment effect on the rate of rehydration during the recovery period. Regression procedure (PROC REG) was used in SAS to provide estimates of the best fitting line and of the slope and intercept parameters and to generate the data plots. Faster rehydration would be demonstrated for the group having a steeper slope for the line fit to the data between T000 and T120 min.

Absolute changes between baseline and each subsequent time point were also computed for each of the outcome parameters. Keeping the two assigned treatment groups separate, a plot of the mean values was performed for each of the outcome parameters at each time point starting at baseline and continuing through T120 min after commencing rehydration. By graphing each of the endpoints (y-axis) vs. time (x-axis), an initial change in the outcome measure between baseline and T000 was expected, as the latter was at or near the maximum point of dehydration and thus an expected inflection point of the endpoint parameters. Subsequently, a gradual restoration in these measures was expected as rehydration occurred. The mean value at T000 was expected to serve to indicate the dehydration level for each group. Mean and standard errors for each time point were to be computed, allowing tests at any particular time point to be made comparing the two treatment groups. Structuring 95% confidence intervals (using mean ± 1.96 S.E.) around each point enabled differences to be tested at every time point.

A final pre-planned analysis was employed for validation using a linear model approach but allowing for repeated measures generated for the outcome variables at all time points. In this analysis, a mixed model was used to specify observations at the different time points as random effects, and included fixed effects such as treatment (i.e., ALK vs. CON), age, baseline levels, and weight loss at end of exercise (%) in the analysis. Then, the treatment effect was estimated while controlling for these covariates. Using mixed model procedure (PROC MIXED) in SAS, the treatment effect comparing ALK vs. CON was tested for each of the outcome variables.

Data displays of key outcome variables at each time point starting at baseline and continuing through T120 min after start of rehydration are provided in Figs.  2 , 3 , 4 and 5 . Mean and standard errors for each time point were computed, allowing tests at any particular time point to be made comparing the two groups. Structuring 95% confidence intervals using mean ± 1.96 S.E. enabled absolute differences to be tested. As shown in Figs.  2 , 3 , 4 and 5 , the 95% confidence intervals are displayed graphically for the two treatment arms using error bars. Each pair of confidence intervals displayed for the two treatment arms observably overlapped.

Systolic blood viscosity as a function of time for CON and ALK

Diastolic blood viscosity as a function of time for CON and ALK

Plasma osmolality as a function of time for CON and ALK

Body weight as a function of time for CON and ALK

The linear mixed models account for the correlational structure inherent in these repeated measures data, as intra-individual measures are more highly correlated than inter-individual measures. Since there was only one primary endpoint and only one endpoint was used to estimate the sample size, all statistical tests were conducted at the alpha = 0.05 level; no Bonferroni correction was employed. For the mixed model analyses, a linear model approach was used while allowing for the repeated measures to be generated for outcome assessment. The treatment effect was tested while controlling for the following covariates: time point, age, dehydration weight change, a gender-treatment-arm interaction effect, as well as baseline levels for systolic blood viscosity, diastolic blood viscosity, and plasma osmolality. Analyses of all outcome variables were performed using a mixed model, which takes into account intra-individual correlations across repeated measures.

One hundred adult participants completed the study. For each subject, the study required approximately 4–8 h of time on a single study date with no follow-up visits. Table  1 shows demographics of each study arm (CON versus ALK), including average age and the number of subjects by ethnicity were similar between the two study arms. Table  2 shows baseline characteristics for each study arm prior to exercise, including systolic and diastolic blood viscosities, hematocrit, plasma osmolality, bioelectric impedance analysis, body weight, systolic and diastolic blood pressures, heart rate, respiratory rate, and body temperature. The CON and ALK subjects did not differ significantly from baseline values.

The study involved between 4–8 h of time for each participant, depending upon the duration of the exercise period to achieve a dehydrated state. Study participants were monitored by a registered nurse from enrollment to discharge. There were no adverse events of any kind during the study. There were also no clinically significant abnormal values among the vital signs collected and laboratory evaluations performed. Systolic blood pressure, DBP, HR, respiratory rate, and body temperature were recorded at baseline, T000, and T120 min and are summarized in Table  3 . Mean values for vital signs were similar in the two study arms. In addition, mean values with standard deviations for outcome parameters are also provided in Table  3 .

The percentage change during the rehydration period from T000 to T120 min was computed for each outcome measure, reflecting the overall magnitude of hydration during the rehydration and recovery period, following standardized exercise-induced dehydration, while compensating for inter-individual differences at baseline and T000 min. Subjects acted as their own controls, and the inter-individual variability of endpoints was moderated by dividing the difference between the subject’s dehydrated state (T000 min) and final rehydrated state (T120 min) by the value of each subject’s own dehydrated state (T000 min).

After rehydration and recovery, the average percentage change for systolic blood viscosity, measured at a high-shear rate of 300 s -1 , in subjects administered CON was 3.36%; whereas for ALK, the average percent change was 6.30% ( p  = 0.03). Nominally, ALK significantly reduced and restored high-shear blood viscosity during a 120-min rehydration period by 87.50% more than CON. After rehydration and recovery, the average percentage change for diastolic blood viscosity (measured at low-shear rate: 5 s -1 ) in subjects administered CON was 5.43%, while the mean percent change for ALK was 9.35%. Furthermore, no other outcome variables, serving as hydration markers, demonstrated a significant difference between the two treatment arms when comparing the percent change in the outcome measure during the rehydration period (T000 to T120 min, Table  4 ).

Further analyses, using PROC REG in SAS provided an estimate of the best fitting line per treatment arm, as well as the slope and intercept parameters. The period of rehydration from T000 to T120 min was used to determine the best-fit regression line for each arm and endpoint. No significant difference was detected in the slope parameter between the two treatment arms for each endpoint. This analysis of slopes was used to examine the rate of change for each endpoint parameter during the rehydration period (see Table  5 ). A significant difference between the two treatment arms would reflect a faster hydration rate. A trend was observed for mean systolic and diastolic blood viscosity levels, which decreased faster (greater negative slope) for ALK as compared with CON. Impedance, an index derived from bioelectrical impedance analysis, was observed to increase faster (greater positive slope) for ALK as compared with CON.

Figure  2 shows systolic blood viscosity changes as a function of time, where the 2 treatment groups had similar viscosity levels at baseline. The parallel slopes for the 2 study arms measured from baseline to T000 min (i.e., end of the exercise period and the beginning of the rehydration period) suggests both study arms achieved a similar rate of dehydration during exercise. After T000, when the subjects began ingestion of water, a steeper slope can be observed for the ALK group than for CON group, demonstrating an enhancement in the recovery period towards restoring pre-exercise baseline levels. By T060 min, midway through the recovery period, mean systolic viscosity levels for ALK subjects returned to the pre-exercise baseline levels, whereas the CON did not return to pre-exercise baseline levels even at T120 min. This pattern is observed visually in the graphic display and consistent with the comparison of the percent changes in systolic viscosity. However, these noted differences that were significant using a comparison of percent changes from T000 to T120 min could not be detected using absolute differences based on 95% confidence intervals, as shown in Fig.  2 , probably due to the large inter-individual variability.

Similar results were observed for diastolic blood viscosity as shown in Fig.  3 . The values at baseline were even closer for the two groups. The increases found with exercise, between baseline and T000, progressed at a similar rate for both treatment groups. Based on mean levels for diastolic viscosity, Fig.  3 shows a more pronounced rehydration rate for ALK than CON with failure to return to baseline levels for mean diastolic viscosity in the CON group by T120 min.

Using mixed model analyses, the treatment effect of ALK vs. CON was observed to be significant for systolic blood viscosity ( p  = 0.02). The treatment effect of ALK vs. CON was not observed to be significant for the other outcome measures of diastolic blood viscosity, plasma osmolality, or the bioelectrical impedance indices. The mixed model analysis appeared to confirm the significant difference in the effect of ALK on blood viscosity, showing that after controlling for the effect of multiple covariates using a mixed model, ALK had a statistically significant effect on systolic blood viscosity when compared with CON. When the analysis was repeated with the interaction of treatment-effect-by-time included as a variable in the mixed model, the treatment effect was still significant for systolic blood viscosity ( p  = 0.02) in favor of ALK; however, the interaction effect of treatment-arm-by-time-point for systolic blood viscosity was not itself significant.

This randomized, double-blinded, parallel-arm controlled study compared the rehydration effect of ALK to CON in order to characterize relative hydration efficacy and performance. A pre-planned analysis of percentage changes, starting at dehydration (T000) and ending at recovery (T120), enabled the two treatment groups to be compared while reducing the impact of inter-individual variability. For systolic blood viscosity, ALK demonstrated significantly greater rehydration than CON ( p  = 0.03), and this result was consistent with the findings using the mixed model analyses.

Interest in the study of biomarkers for hydration has intensified in recent years, however the relative utility of markers is dependent on the environment and the nature of the stimuli applied in a given study. Even in studies of responses to acute exercise-induced dehydration, a gold standard biomarker for hydration status has proved elusive [ 13 – 15 ]. Viscosity was used as the primary endpoint in this study to reflect intravascular hydration and was clearly affected by exercise-induced dehydration. Several prior studies have reported increases in blood viscosity following exercise [ 16 , 17 ]. In a study of 20 healthy adults, blood viscosity was reported to increase after 15 min of submaximal exercise [ 18 ]. In a prior clinical study of 47 endurance-trained and untrained females, mean viscosity levels after 1 h of maximal exercise were reported to be 12.6% higher, a greater magnitude increase than could be attributed to hematocrit, which rose by a mean of 8.9% [ 19 ]. Blood viscosity is not static but changes dramatically depending on shear rate. Shear rate is calculated by dividing flow velocity by lumen diameter. When blood moves quickly at the peak of systole, it is at high-shear and relatively thinner because erythrocytes are dispersed. At high shear rates, systolic viscosity is influenced by hematocrit levels and red cell deformability, whereas at low shear rates, diastolic viscosity is influenced by red cell aggregation [ 20 ]. For this reason, systolic blood viscosity may be able to provide a more direct marker of hydration status than diastolic blood viscosity.

The key difference between electrolyzed, high-pH ALK and standard drinking water purified by reverse osmosis, used as the CON in this study is the degree of alkalinity. In a study of 1136 Japanese females, Murakami et al. found acidic dietary load was independently associated with significantly increased SBP and DBP, low density lipoprotein (LDL) and total cholesterol levels, BMI, and waist circumference [ 21 ]. These researchers suggested that unfavorable metabolic cardiac risk factors may be induced by mild metabolic acidosis which increased cortisol production. Heil reported significantly increased blood pH secondary to consumption of mineral-rich ALK [ 22 ]. Separately, Heil et al. demonstrated faster and better overall hydration with ALK than CON (bottled) in ten male cyclists. Hydration markers reported therein were urine specific gravity, urine output, serum protein concentration, and water retention [ 23 ]. In both of these studies, the effects took at least one week to occur after habitual intake of alkaline water. While Heil et al. did not perform mechanistic studies, they hypothesized that blood alkalinity was shifted as a result of direct absorption of alkaline minerals into the blood and that water retention within the vasculature was improved by the absorption of additional minerals into the blood [ 22 ]. In a more recent study by the same group, it was suggested that increases in extracellular pH may influence blood flow indirectly by altering interstitial potassium concentrations [ 24 ].

Separately, a study using an exercise-induced dehydration protocol to compare the effect of two fluid replacement beverages on markers for oxidative stress showed that rehydration recovery following ingestion of either a carbohydrate-electrolyte beverage or water reduced levels of malondialdehyde, a common marker for oxidative stress, relative to plasma concentrations of malondialdehyde at a dehydrated state [ 25 ]. Disruptions in blood flow promote an oxidative state where reactive oxygen species accumulate. Red blood cells in particular are vulnerable to an oxidative environment in the human body and, as a consequence of their iron content, are capable of producing their own free radicals [ 26 ]. This process of autoxidation occurs when oxygenated hemoglobin is degraded and releases a superoxide. Concurrently, the ferrous (Fe 2+ ) state iron in hemoglobin is oxidized to ferric (Fe 3+ ) hemoglobin, producing methemoglobin which is incapable of transporting oxygen [ 27 ]. Peroxides in the body degrade hemoglobin proteins and cause erythrocytes to release heme and iron. Forces required for red cells to perfuse capillaries can cause cell membranes to leak ions, causing further damage to lipid membranes [ 28 ]. When reactive oxygen species initiate peroxidation of lipid membranes, cellular membrane proteins often become cross-linked and red cells become stiffer with less deformability [ 27 ]. Production of methemoglobin, modification and degradation of proteins, cross-linking of membrane proteins, lipid peroxidation, hemoglobin cross-linking, and impaired surface properties are all mechanisms by which oxidative stress functionally modifies red blood cells [ 26 ]. These mechanisms alter red cell properties, including reduced membrane fluidity and increased aggregation, leading to increased blood viscosity and impaired flow [ 29 ].

A separate study of 154 subjects with varying stages of diabetes mellitus and healthy controls showed that more than 76% of oxidative stress in apparently healthy subjects was associated with elevated WBV, with 95% prevalence in the prediabetes group and 92% prevalence in the diabetes group [ 30 ]. This clinical study measured markers of erythrocyte oxidative stress included erythrocyte glutathione, methemoglobin, and malondialdehyde. Associations between oxidative stress of red blood cells and altered blood viscosity in healthy subjects, as well as those with diabetes and prediabetic patients, suggest that blood viscosity may be a marker for underlying oxidative stress.

We speculate that differences in systolic viscosity levels caused by ALK vs. CON following dehydration may have been mediated by the influence of reactive oxygen species on erythrocyte membranes and their deformability. Further studies are needed to determine if high-pH ALK is directly associated to reductions in oxidative stress. With respect to plasma osmolality as a hydration marker, Armstrong in his authoritative review noted that “a single gold standard, including plasma osmolality, is not possible for all hydration assessment requirements” [ 15 ]. He stated body mass change is the most accurate assessment of hydration in real time, and his review of biomarkers, which did not include blood viscosity, suggested that the accuracy of most hydration markers is not consistently supported. Body mass changes reflect body water losses and gains secondary to sweating and water intake, respectively. Consequently, changes in mass are very frequently measured in exercise studies and serve as a benchmark for other hydration markers. Although plasma osmolality is considered among the best available indices by many researchers, none of the analyses performed in this study showed significant differences between ALK and CON on this marker. Plasma osmolality does not incorporate the influence of cellular content in the blood and is difficult to assess when total body water, fluid intake, and fluid loss are altered.

Bioelectrical impedance analysis has been widely used to assess hydration status. This tool allows for the determination of water volumes throughout various fluid compartments of the body. There were no treatment arm effects when comparing ALK with CON on any of the bioimpedance indices in our study. It is possible that acute dehydration and rehydration consistent within this present study (2% body mass) failed to accurately predict changes in body water that were otherwise able to be determined by assessing body mass changes. Further, in athletes with low baseline body fat, small body water changes may be mistakenly reported as body fat changes by bioimpedance testing [ 31 ]. Changes in extracellular volume and osmolality may also impair the accuracy of bioelectrical impedance assessments [ 32 ].

This study was designed to characterize differences between ALK and CON in terms of intravascular hydration as quantified by serial changes in systolic blood viscosity following exercise-induced dehydration. Drinking high-pH ALK was shown to reduce systolic blood viscosity significantly more than CON consumption following exercise-induced dehydration, when comparing the percent change in WBV from a dehydrated state to 120 min after rehydration and recovery. A mixed model analyses validated this significant treatment effect for high-pH ALK on systolic blood viscosity vs. CON. Absolute differences at multiple time points did not demonstrate any significant differences; however the subjective observed benefit may be attributed to the high variability of WBV measurements in the study groups.

Abbreviations

Alkaline water

Body mass index

Diastolic blood pressure

Low density lipoprotein

Mixed model procedure

Regression procedure

Statistical analysis system

Systolic blood pressure

Whole blood viscosity.

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Acknowledgements

We thank Samuel Lee, Joylyn Martinez-Davis, Angela Nelson, Lisa Abate, Justin Johnson and Esther Lee for their assistance in the coordination and implementation of this clinical study.

This research study was supported by a grant from Essentia Water, and alkaline bottled water for the study was provided by Essentia Water. Essentia Water was not involved in any on-site data collection or the analysis and interpretation of data.

Availability of data material

The data set is held confidential pursuant to an agreement between the sponsor of this study and the research parties. However, the study was registered (ClinicalTrials.gov Identifier: NCT02118883) and conducted in accordance and compliance with Good Clinical Practice and the Declaration of Helsinki.

Authors’ contributions

Authors’ contributions were as follows: JJW, REH, GF, and DJC designed the research; DJC supervised the research nurse coordinators and phlebotomists in the implementation of the study; BB analyzed the data; JJW, GF, DJC drafted the manuscript and DJC and JAS edited the manuscript. All co-authors read and approved the final version of the manuscript.

Competing interests

The following authors have declared competing interests. REH reports having received consulting fees and stock options from Essentia Water. DJC, JJW and BB report having received consulting fees from Rheovector. JAS reports having received a fee for editing the manuscript. GF reports no conflicts of interest.

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Not applicable. There are no individual names or their personal data from this study represented in this manuscript.

Ethics approval and consent to participate

This clinical study was approved by the Institutional Review Board, and written informed consent was obtained from all subjects at the time of enrollment and prior to participating in this study. The study was registered (ClinicalTrials.gov Identifier: NCT02118883) and conducted in accordance and compliance with Good Clinical Practice and the Declaration of Helsinki.

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Weidman, J., Holsworth, R.E., Brossman, B. et al. Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults. J Int Soc Sports Nutr 13 , 45 (2016). https://doi.org/10.1186/s12970-016-0153-8

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Associations of alkaline water with metabolic risks, sleep quality, muscle strength: A cross-sectional study among postmenopausal women

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliations Faculty of Medicine and Health Sciences, Department of Dietetics, Universiti Putra Malaysia (UPM), Serdang, Malaysia, Faculty of Medicine and Health Sciences, Research Center of Excellence Nutrition and Non-Communicable Diseases, Universiti Putra Malaysia (UPM), Serdang, Malaysia, Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia

Roles Conceptualization, Formal analysis, Methodology, Resources, Supervision, Writing – review & editing

Affiliation Faculty of Medicine and Health Sciences, Department of Nutrition, Universiti Putra Malaysia (UPM), Serdang, Malaysia

Roles Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – review & editing

Affiliations Faculty of Medicine and Health Sciences, Research Center of Excellence Nutrition and Non-Communicable Diseases, Universiti Putra Malaysia (UPM), Serdang, Malaysia, Faculty of Medicine and Health Sciences, Department of Nutrition, Universiti Putra Malaysia (UPM), Serdang, Malaysia

Roles Conceptualization, Methodology, Resources, Supervision, Writing – review & editing

Affiliation Faculty of Medicine and Health Sciences, Department of Family Medicine, Universiti Putra Malaysia (UPM), Serdang, Malaysia

Affiliation Faculty of Medicine, UMeHealth Unit, Universiti Malaya (UM), Kuala Lumpur, Malaysia

Roles Data curation, Investigation, Writing – review & editing

Affiliation Faculty of Medicine and Health Sciences, Department of Dietetics, Universiti Putra Malaysia (UPM), Serdang, Malaysia

• Yoke Mun Chan, 
• Zalilah Mohd Shariff, 
• Yit Siew Chin, 
• Sazlina Shariff Ghazali, 
• Ping Yein Lee, 
• Kai Sze Chan

• Published: October 31, 2022
• https://doi.org/10.1371/journal.pone.0275640
• Reader Comments

Much has been claimed on the health benefits of alkaline water including metabolic syndrome (MetS) and its features with scarcity of scientific evidence. Methods: This cross-sectional comparative study was conducted to determine whether regular consumption of alkaline water confers health advantage on blood metabolites, anthropometric measures, sleep quality and muscle strength among postmenopausal women. A total of 304 community-dwelling postmenopausal women were recruited with comparable proportion of regular drinkers of alkaline water and non-drinkers. Participants were ascertained on dietary intake, lifestyle factors, anthropometric and biochemical measurements. Diagnosis of MetS was made according to Joint Interim Statement definition. A total of 47.7% of the participants met MS criteria, with a significant lower proportion of MetS among the alkaline water drinkers. The observed lower fasting plasma glucose (F(1,294) = 24.20, p = 0.025, partial η 2 = 0.435), triglyceride/high-density lipoprotein concentration ratio (F(1,294) = 21.06, p = 0.023, partial η 2 = 0.360), diastolic blood pressure (F(1,294) = 7.85, p = 0.046, partial η 2 = 0.258) and waist circumference (F(1,294) = 9.261, p = 0.038, partial η 2 = 0.263) in the alkaline water drinkers could be considered as favourable outcomes of regular consumption of alkaline water. In addition, water alkalization improved duration of sleep (F(1,294) = 32.05, p = 0.007, partial η 2 = 0.451) and handgrip strength F(1,294) = 27.51, p = 0.011, partial η 2 = 0.448). Low density lipoprotein cholesterol concentration (F(1,294) = 1.772, p = 0.287, partial η 2 = 0.014), body weight (F(1,294) = 1.985, p = 0.145, partial η 2 = 0.013) and systolic blood pressure (F(1,294) = 1.656, p = 0.301, partial η 2 = 0.010) were comparable between the two different water drinking behaviours. In conclusion, drinking adequate of water is paramount for public health with access to good quality drinking water remains a critical issue. While consumption of alkaline water may be considered as a source of easy-to implement lifestyle to modulate metabolic features, sleep duration and muscle strength, further studies are warranted for unravelling the precise mechanism of alkaline water consumption on the improvement and prevention of MetS and its individual features, muscle strength and sleep duration as well as identification of full spectrum of individuals that could benefit from its consumption.

Citation: Chan YM, Shariff ZM, Chin YS, Ghazali SS, Lee PY, Chan KS (2022) Associations of alkaline water with metabolic risks, sleep quality, muscle strength: A cross-sectional study among postmenopausal women. PLoS ONE 17(10): e0275640. https://doi.org/10.1371/journal.pone.0275640

Editor: Kenta Matsumura, University of Toyama: Toyama Daigaku, JAPAN

Received: May 21, 2021; Accepted: September 20, 2022; Published: October 31, 2022

Copyright: © 2022 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The funder (Universiti Putra Malaysia) provided financial research grant and support in the form of salaries for authors [YMC, ZMS, YSC, SSG], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. One of the authors, YMC received financial research fund from CUCKOO International (MAL) Pte Ltd. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The fund recipient, YMC did not involve in the consultancy, patents, products in development or marketed products of the funder. The financial assistant does not alter our adherence to PLOS ONE policies on sharing data and materials.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Alkaline water has higher pH than normal drinking water, contains alkaline minerals and negative oxidation reduction potential. Several methods can be used to activate water such as electrolysis, light irradiation, ultra-sonication, treatment with a magnetic field, bubbling with gases, collision, strong water flow, and treatment with specific mineral or rocks [ 1 ]. Despite human body pH is tightly regulated, the habitual consumption of mineral water or beverages with added bicarbonate has been shown to have beneficial effects in terms of increasing of urinary pH [ 2 – 4 ].

The effectiveness of alkaline water has gained increased recognition in health and nutrition. The application of alkaline water in the field of agriculture and medical care field was first initiated in the 1954 and 1960, and recognized for its beneficial effect on chronic diarrhea, indigestion, abnormal gastrointestinal fermentation, antacid and hyperacidity [ 1 ]. Several studies were conducted to assess the effectiveness of alkaline water in reducing the risk of metabolic syndrome (MS) or its traits [ 5 – 14 ] or other health outcomes [ 10 – 11 , 15 ], with conflicting results reported.

Earlier studies found inverse association between cardiovascular diseases with increased consumption of water containing the mineral salts of calcium and magnesium [ 16 – 18 ], especially among the women [ 19 ]. Case-control study also demonstrated that consumption of water greater than 8mg/L of mineral salt, magnesium was associated with reduced risk of mortality from the myocardial infarction [ 20 ]. Besides, epidemiological studies in Sweden also demonstrated that consumption of water with magnesium and bicarbonate with concentration of 110mg/L were at lower risk of myocardial infarction [ 21 ], which was attributed to the decreased of urinary excretion of minerals, regulated by acid conditions in the body. Clinical study intervening mild hypertensive patients with drinking water containing 403mg/L hydrogen carbonate abled to reduce the blood pressure [ 22 ].

With its geographical location at the tropical region, water is abundantly available in Malaysia throughout the year, with both surface and ground water are used as drinking water after necessary treatment. In the Klang Valley Malaysia (Selangor, Kuala Lumpur and Putrajaya), most of the tap water supply comes from surface water sources that include rivers, lakes and reservoirs. Nevertheless, the pollution in rivers and lakes has become worsen in the recent years. The decrease in the quality of tap water because of pollution of the global environment over time has become a major social problem, whereby concern over tap water quality has led to the expansion of water filtration plants and had encouraged the marketing of filtered water, including filtered alkaline water. Earlier studies reported that 50–85% households had water filter fitted to their kitchen supply [ 23 , 24 ], depends on the geographical area. These figures are believed to be higher nowadays with the reduced confidence among consumers on tap water quality as well as the increased awareness on drinking water quality among consumers [ 24 ]. Alkaline water generation has progressed and advanced in development. Besides electrolysis, alkaline minerals, nanoparticles [ 25 ] and nanofiltration membranes [ 26 ] are new technologies applied in the production of alkaline water in the water industries. To the best of knowledge, most of the previous work on alkaline water was generated using electrolysis, with little is known on the effectiveness of alkaline water generated by other technologies.

The increasing prevalence of MS is especially evident in Asia including Malaysia. Several studies in Europe and Asia have demonstrated an association between onset of menopause and higher risk of MetS, independent of aging [ 27 – 31 ] in postmenopausal women. Menopausal women, with declining estrogen levels, is considered particularly vulnerable with regard to impaired sleep quality [ 32 – 35 ] and muscle strength [ 36 – 38 ].

On the other hand, despite the increase usage of alkaline water in Malaysian households, with health claims on metabolic syndrome and its metabolites, studies to date provide limited information on its evidence. This was the impetus that prompted the current investigation to compare the metabolic risks, sleep quality and muscle strength between alkaline water drinkers and non-drinkers among postmenopausal women.

Materials and methods

This was an analytical cross-sectional study conducted on community-dwelling postmenopausal women in Kuala Lumpur and Selangor, Malaysia. A total of 304 participants comprised of 148 alkaline water drinkers and 156 non-alkaline water drinkers were recruited. While non-alkaline water drinkers were recruited from various community settings including senior citizen clubs and word of mouth, alkaline water drinkers were identified and screened from the contact list provided by the alkaline water company [CUCKOO International (MAL) Pte Ltd]. The alkaline water was produced using alkaline balls and nanofiltration concept which function to retain certain mineral such as calcium and magnesium selectively from water source. Inclusion criteria included women with at least five years postmenopausal, not on hormonal replacement therapy and absence from severe diseases. While non-alkaline water drinkers were defined as participants who have not been consuming alkaline water for at least past two months, alkaline water drinkers were eligible if they consumed alkaline water on regular basis (at least 1L/day for the past two months prior to data collection). The institutional ethics board of Universiti Putra Malaysia approved this study and written informed consent were obtained from all participants prior to study commencement with anonymity and data confidentiality guaranteed.

Metabolic risk

Measurements, including anthropometric parameters, systolic and diastolic blood pressure, fasting blood glucose and fasting lipid profile were taken. Weight and height were measured using a calibrated digital weighing scale and stadiometer, respectively. Waist circumference was measured with a circumference measurement tape. Waist was defined as the narrowest circumference between the iliac crest and the costal margin (lower rib), and hip was the widest circumference between the waist and thigh. Trained researchers conducted all measurements with routine monitoring and quality checks. Blood pressure was measured following five minutes seated rest using automatic blood pressure monitor (Omron Matsusaka Co. Ltd, Matsusaka, Japan). Blood samples for biochemical analyses were collected from participants by venipuncture following 8 hours of fasting for fasting blood sugar (FBS), triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol concentration (LDL-C), using enzymatic assay kits. Presence of metabolic syndrome was ascertained as per the Joint Interim Statement (JIS) definition [ 39 ] which requires three out of five of the following risk factors: Central obesity (waist circumference of more than 80 cm), hypertension (130 mm Hg for systolic BP or 85 mm Hg for diastolic BP) or on hypertensive medication, raised FBS (5.6 mmol/L) or on diabetic medication, raised fasting TG (1.7 mmol/L) and Low HDL-C (<1.3 mmol/L). Cardiometabolic health markers assessed were the individual MetS components included in the Joint Interim Statement.

Sleep quality

Sleep quality of participants was evaluated using the universal recognised sleep measures, the Pittsburgh Sleep Quality Index questionnaire [ 40 ]. Besides the individual’s perception of sleep quality, participants were assessed on the duration of sleep, habitual sleep efficiency, use of sleep medication, presence of sleep latency (defined as duration used to fall asleep), sleep disturbances (defined as any reason which may affect respondent’s sleep), or daytime dysfunction to allow the determination of sleep quality. Each component was weighted equally on a 3-point Likert scale, with a score of “0” indicated no difficulty, while a score of “3” indicated severe difficulty. The score from each component was summed up to yield the sleeping quality index score, which can range from 0 (no difficulty) to 21 (severe difficulty in all areas).

As a proxy measure of muscle strength, handgrip strength (HGS) of the participants was measured by using a dynamometer on the dominant hand, following standard protocol. Prior to the measurement, participants were asked if they had known upper-extremity impairments that could influence the measurement of hand grip strength. During the measurement, participants were asked to grip the hand dynamometer with the maximum force continuously for 2 to 3 seconds on a verbal statement: ‘Squeeze as hard as you can’. Two measurements were taken with a rest break of approximately 30 seconds was given between each grip. The HGS was measured in kg to one decimal point and the average of two attempts was calculated and used in further analysis. Classification of handgrip strength was according to the cut-off value proposed by Fried et al. (2001) [ 41 ], stratified by sex and Body Mass Index of participants.

Dietary intakes of respondents were assessed using a validated semi-quantitative food frequency questionnaire adapted from the Malaysian Adult Nutrition Survey 2014 [ 42 ]. The questionnaire covers 165 food items frequently consumed among Malaysian, along with their standard portion sizes. Participants indicated the typical frequency of consumption of foods and average amount (in household measures, eg cup, bowl, spoons) to allow the estimation of food intake over the past month [ 43 ]. Portion sizes were then converted to grams, based on the published household measurement. Nutrient data (protein, phosphorus, potassium, magnesium and calcium) were then analysed using Nutritionist Pro™ Diet Analysis (Version 3.2, 2007, Axxya Systems, Stafford, TX, USA) software, with Nutrient Composition of Malaysia Foods [ 44 ] and Singapore Food Composition Database [ 45 ] as the primary databases. Dietary Acid Load of the participants was calculated using potential renal acid load (PRAL) [ 46 ], an equation based on the ionic balance of the nutrients and intestinal absorption rates of protein and four main minerals (phosphorus, potassium, magnesium and calcium) as well as the sulphate production from the protein metabolism [ 46 ] as below:

            PRAL (mEq/d) = 0.49 protein (g/d) + 0.037 phosphorus (mg/d) - 0.021 potassium (mg/d) - 0.026 magnesium (mg/d) - 0.013 calcium (mg/d)

Besides dietary acid load, dietary quality index (DQI) of the participants was ascertained according to the Healthy Eating Index for Malaysia (HEI-M), which was developed and validated among Malaysian population [ 47 ]. The DQI consists of six components which assessed the compliance of participants with the food group intake based on Malaysian Dietary Guidelines (MDG) 2020. The score for each component was ranged from 0 (lack of compliance) to 10 (full compliance), and the score was calculated proportionately for the in-between responses. The overall diet quality for participant was then determined by adding the score for each component and computing a composite score with the following formula: (total score of 6 components / 6 × 10) × 100%. Based on the composite score, diet quality was classified into poor (<51%), improvement required (51% - 80%) or good (81% and above) [ 47 ].

Statistical analyses

Data was analysed using IBM SPSS Statistics 24 software (SPSS Inc., Chicago, IL, USA). Descriptive statistics were presented as frequency and percentage for categorical variables while as mean and standard deviation for continuous variables. Independence tests were performed to determine the mean differences on age, metabolic profile (fasting plasma glucose, systolic and diastolic blood pressures, low density lipoprotein concentration, triglycerides / HDL ratio), lifestyle characteristics (sleep quality, sleep duration), dietary quality, anthropometric measures (waist circumference, weight, BMI) and muscle strength between the alkaline water drinkers and non-drinkers. Multivariate analysis of covariance (MANCOVA) was performed to determine whether alkaline water consumption augments metabolic risks (fasting plasma glucose, systolic and diastolic blood pressures, low density lipoprotein concentration, triglycerides / HDL ratio), anthropometric measures (waist circumference, body weight), sleep duration and handgrip strength, with age and physical activity as the covariates of the model. Before the exploratory data analysis were carried out, data was cleaned to delineate any possibility of wrongly entered data, missing data or outliers. Assumptions for Independence t test and Multivariate analysis of covariance (MANCOVA), namely normality, homogeneity linearity and multicollinearity (for MANCOVA) were performed. Data normalities were verified graphically (Q-Q scatter plots) and numerically (Kolmogorov–Smirnov test, skewness and kurtosis). The homogeneity of regression slots and the equality of variances were performed using Levene’s test. Linearity of correlations between dependent and independent variables were confirmed with residual plot. Multicollinearity refers to the situation that independent variables are highly correlated. In this study, multicollinearity was examined by “variance inflation factor” (VIF) values whereby VIF value that exceeds 5 or 10 indicates a problematic amount of collinearity [ 48 ]. Besides VIF, the researchers examined the correlations between the variables considering a correlation of greater than 0.37 as large [ 49 ]. Sleep quality, % body fat and BMI were correlated closely with sleep duration (r = 0.72), waist circumference (r = 0.78) and body weight (r = 0.84), and with VIFs more than 5, respectively. Considering sleep duration (sleep quality), waist circumference (% body fat), and body weight (BMI) are structural multicollinearities, sleep quality, % body fat and BMI were removed from the MANCOVA model. All assumptions for the inferential test and the covariate were met. Statistical significance was set at p<0.05.

Mean age of participants was 68 years old ( Table 1 ). Employment rate was low with less than 15% of the participants are working. Despite the mean MET value exceeded the recommendation of the current physical guidelines and achieved at least 600 metabolic equivalent minutes (MET minutes), which is equivalent to a minimum of 150 minutes of moderate to vigorous intensity activities or 75 minutes of vigorous intensity activities PA per week, only slightly more than half of the participants met the recommendations for physical activity. This was coupled with none of the participants was either moderately active (4000–7999 MET-min/week) or highly active (≥ 8000 MET-min/week). Mean HGS was 18.1 kg, with approximately 6 in 10 of the elderly had poor grip strength. Mean duration of sleeping was approximately 5 hour 30 minutes, with more than 40% of the postmenopausal women had sleep duration of less than 5 hours and between 5–6 hours per day, respectively. This was coupled with approximately two-third of the participants were poor sleepers. Approximately one in two participants had MS. Elevated blood pressure was the most dominant component of MS (53.0%), followed by excessive waist circumference (50.3%). Approximately 60% and 40% of the participants had abnormal serum HDL and triglycerides, respectively, which out-numbered the proportion of participants with elevated blood glucose.

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https://doi.org/10.1371/journal.pone.0275640.t001

Overall, there were no significant differences on the mean age, years of education, employment status and gross monthly family income between the regular alkaline water drinkers and non-drinkers. Regular alkaline water drinkers had significant lower body weight and % body fat. On the other hand, they have significant higher muscle strength than their non-alkaline water drinker counterparts. Meanwhile, non-alkaline water drinkers had poorer sleep quality and significant shorter duration of sleep, with regular alkaline water drinkers had significant longer sleep duration of approximately 70 minutes per day. There was no significant difference on physical activity between the two groups (t = 1.87, p >0.05, df = 304). Dietary quality scores and dietary acid load were comparable between the non-alkaline water drinkers and their counterparts. With regards to metabolic syndrome, there was smaller proportion of regular alkaline water drinkers presented with metabolic syndrome (41.2% vs 53.8%). While diastolic blood pressure was comparable between the two groups, non-alkaline water drinkers had significant higher waist circumference and fasting blood glucose ( p <0.05). It is noteworthy that TG/HDL ratio was significantly lower among alkaline water drinkers (t = 2.01, p <0.05, df = 304), despite a comparable of serum HDL between the groups, attributed to the higher serum triglycerides among the non-alkaline water drinkers (t = 2.30, p <0.05, df = 304).

A one-way multivariate analysis of covariance (MANCOVA) was performed to determine the influence of drinking behaviour (alkaline water drinkers vs non-drinkers) on the nine primary outcome variables: i) fasting plasma glucose, ii) TG/HDL, iii) LDL, iv) SDP, v) DBP, vi) waist circumference, vii) body weight, viii) sleep duration, and ix) hand grip strength, after controlling for age and physical activity level as covariates in the model ( Table 2 ).

https://doi.org/10.1371/journal.pone.0275640.t002

Overall, the model was statistically significant, indicating differences between the two water drinking behaviour after controlling for covariates ( F (8,296) = 3.25, p = 0.025, partial η 2 = 0.310). A significant main effect of drinking behaviour (drinker vs non-drinkers) was found for FBG ( F (1,294) = 24.20, p = 0.025, partial η 2 = 0.435), TG/HDL ( F (1,294) = 21.06, p = 0.023, partial η 2 = 0.360), DBP ( F (1,294) = 7.85, p = 0.046, partial η 2 = 0.258), with no significant main effect of alkaline water drinking behaviour on LDL ( F (1,294) = 1.772, p = 0.287, partial η 2 = 0.014) or SBP ( F (1,294) = 1.656, p = 0.301, partial η 2 = 0.010). Postmenopausal women who were alkaline water drinkers had lower waist circumference ( F (1,294) = 9.261, p = 0.038, partial η 2 = 0.263), but there was no statistically significant difference between the alkaline water drinking groups on the body weight after controlling for covariates ( F (1,294) = 1.985, p = 0.145, partial η 2 = 0.013). On the other hand, there were significant main effects of drinking behaviour on sleep duration ( F (1,294) = 32.05, p = 0.007, partial η 2 = 0.451) and hand grip strength ( F (1,294) = 27.51, p = 0.011, partial η 2 = 0.448).

The main result of this study is that alkaline water drinking among postmenopausal women had significantly lower metabolite risks (fasting plasma glucose, TG/HDL, diastolic blood pressure, waist circumference), longer sleep duration and stronger handgrip strength. There was no significant difference on LDL, systolic blood pressure and body weight with alkaline water drinking.

This is the first study comparing features between alkaline drinkers and non-drinkers. In lieu of lacking similar study for comparison, we compared our findings on metabolic risks with prospective and interventional trials. Anti-obesity effects of alkaline water have been reported in animal models [ 51 , 52 ] with inconsistency in other [ 53 ]. There is little compelling evidence on alkaline water consumption and obesity in human, with findings had been reported as both positive [ 5 ] or neutral [ 13 ]. Current findings on the obesity indexes (body weight, body weight status, % body fat and waist circumference) deserve further elaboration. While the universal proxy measure of obesity, mean BMI was comparable between the two groups, alkaline water drinkers in general has significant lower body weight, waist circumference and % body fat, however alkaline water drinking only had significant main effect on waist circumference but not other obesity indices including body weight. Body mass index and body weight do not take into account the distribution of fat mass and cannot discriminate fat mass from lean mass, which is of particular importance in older individuals, as the distribution of body fat changes with age [ 54 ], even in the absence of changes in body weight. On the other hand, waist circumference is strongly correlate with abdominal obesity and is a commonly used clinical measure of body fat distribution [ 55 ]. It was hypothesized alkaline water might have influenced the production of leptin or adiponectin, induced lipolysis in adipocytes, downregulated the expression of transcription factors in the adipogenesis pathway, or reduced lipid accumulation by affecting the expression of genes, such as fatty acid synthase and lipoprotein lipase during preadipocytes differentiation [ 5 ]. In light of the expanding global burden of obesity on socioeconomic and health care, more work is warranted to delineate the relationship between consumption of alkaline water and risk of abdominal obesity.

In the present study, we found that alkaline drinkers have lower serum fasting blood glucose and triglycerides which add evidence to the scarcity of data on this aspect in human trials. Previous human studies showed alkaline water supplementation ameliorated blood glucose [ 9 , 12 , 14 ] and HbA1c [ 14 ] significantly, which was incongruent with human [ 5 , 10 – 11 ] or animal studies [ 53 , 56 – 58 ]. Earlier, it was hypothesized that alkaline water could substantially increase the activity of hexokinase, which is a pivotal enzyme inducing the reduction of blood glucose levels [ 59 ]. More recently, evidence is growing that oxidative stress plays a key role in the aetiology and pathophysiology of diabetes [ 60 – 62 ], involved in chronic hyperglycaemia-induced insulin resistance [ 63 ] and vascular complications [ 64 ]. The actual protective mechanism of alkaline water is yet to be elucidated but it could be attributed to its active atomic hydrogen that has a high reducing ability which may participate in redox reactions and contributing to increasing levels of antioxidants [ 65 ]. This was confirmed by recent study that intervention of alkaline water on patients with diabetes mellitus was associated with lower level of oxidative stress and inflammatory markers [ 9 ], which represents the first human trial on alkaline water supplementation, with more evidence available from animal models [ 51 , 66 ] or at laboratory testing [ 67 ]. Different from Gadek et al. (2006) [ 14 ], Rias et al. (2019) [ 9 ] and Siswantoro, Purwanto & Sutomo (2017) [ 12 ] whose participants were patients with diabetes mellitus, our participants were entirely healthy postmenopausal women, hence this finding shed light on the possible health benefit of alkaline water on healthy individual, which should be confirmed with more human trials. It is worth noting that earlier mentioned clinical trials were relatively short (ranged from six days to eight weeks), at which the positive outcomes should be confirmed with longer intervention or prospective studies.

Studies on the effectiveness of alkaline water on lipid profiles had been scarce. Our findings did not find significant differences on HDL profiles between alkaline water drinkers and non-drinkers. These findings echo recent studies in Korea and Indonesia [ 5 , 6 ]. Although mean LDL concentration was comparable between alkaline and non-alkaline water drinkers at bivariate analysis, alkaline water drinking favours lower LDL at the MANCOVA analysis after controlling for covariates. On the other hand, the role of alkaline water had been rather consistently positive for triglycerides in animal models [ 68 – 70 ], which was absent in human studies. Our finding on serum triglyceride is consistent with some previous accounts [ 7 , 56 , 71 ] and discrepant with others [ 5 , 6 , 10 , 72 ]. Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men [ 73 ], possibly attributed to the deterioration of lipid profile which becomes more atherogenic among postmenopausal women than their premenopausal counterparts [ 74 ]. Numerous studies showed elevated triglyceride increased risk of coronary artery disease in postmenopausal women [ 75 ] and play a key role in predicting cardiovascular disease in women [ 76 ]. On the other hand, growing body of evidence is suggesting the ratio of TG/HDL-C as an easily obtainable atherogenic marker [ 77 ] and predictor of all‐cause mortality [ 78 ]. Elevated ratio of TG/HDL has also been associated with poor cardiovascular outcomes in patients with chronic kidney, silent brain infarct, ischemic stroke, cardiovascular disease [ 79 – 82 ] and mortality [ 83 ]. Our findings were the only study indicating consumption of alkaline water led to lower ratio of TG/HDL, which should be confirmed with further prospective studies. It is imperative to highlight that absolute or ‘global’ approach to assessing and managing CVD risk has the potential to prevent twice as many deaths from coronary heart disease when compared with treating individual risk factors, such as blood pressure or cholesterol. More works are warranted to delineate the effectiveness of alkaline water on lipid profiles as well as CVD risks.

Alkaline water drinking has mixed findings on blood pressures, whereby significant main effect was only reported for diastolic but not systolic blood pressure. Inconsistency in findings were documented in earlier studies [ 13 , 84 – 86 ]. The later researchers speculated the use of alkaline water as the hemodialysis solution may counteract with the action by radical oxygen species and potent vasoconstrictor such as peroxynitrite and lead to vasodilation [ 84 ]. A recent animal study reported alkaline water may downregulating oxidative stress and inhibiting inflammation, leading to lower blood pressure [ 87 ]. Essential elements such as calcium and magnesium are generally higher in filtered alkaline water, which is speculated to contribute to lower blood pressure as well. As hypertensive is one of the major causes of morbidity and mortality and affects a considerable proportion of the population, with many more are underdiagnosed, the use of alkaline water can be considered as a simple lifestyle modification to modulate blood pressure. Before such recommendation is made, extensive and quality studies are needed.

Our findings that drinkers of alkaline water had significant longer sleep duration deserve more in-depth elaboration, in lieu of the societal trend toward less sleep and poorer quality sleep is a common feature in many developed countries [ 88 – 90 ] and developing countries [ 91 , 92 ]. Poor sleep quality including sleep disturbance and short sleep duration are often associated with unfavourable health outcomes including mental, physical and cognitive health [ 93 ]. Recent study showed that alkaline water consumption improved sleep quality of adults in Japan [ 10 ], however comparison between group was not available, and make it difficult to determine if any effect is due to the different intervention received or simply a result of practice. Earlier studies showed elevation of inflammation and oxidative stress are common features among sleep disordered populations [ 94 ] while consumption of kiwi (rich in vitamin A, vitamin E and serotonin) [ 95 ] and tart cherry juice (rich in vitamins A and C) [ 96 ] promoted better sleep, with inconsistencies exist [ 97 ]. More recent studies reported a direct relationship between sleep duration and quality, with fruit and vegetable intake [ 98 , 99 ] or polyphenol-rich foods (i.e., black tea and cocoa products) [ 100 , 101 ], which are known antioxidants. Acknowledging the size of the sleep problem in the modern societies and the scarcity of data, more works are needed to delineate the positive effect of alkaline water on sleep quality.

In the present study, with the comparable dietary quality scores and dietary acid load between the two groups, it is reasonable to assume that any beneficial effects of alkalinity towards metabolic are likely to attribute by the alkaline water consumption. One of the study limitations was we did not analyse or incorporate the minerals content of water drank in the calculation of dietary acid load of participants as the mineral contents of tap water varies according to geographical locations and depends on the mineral compositions of the soil and pollutants such as heavy metal [ 102 ]. Future studies should also consider the level of antioxidants present in alkaline water. We acknowledge that the alkaline water in previous published work was produced by electrolysis. The investigated alkaline water was acquired using a different mechanism, namely alkaline balls and nanofiltration membrane concept which function to retain certain mineral such as calcium and magnesium selectively from water source, reduces [H+] and increases [OH-], and leads to an overall rising of water pH. These preliminary data suggested consumption of alkaline water produced using other technology concept demonstrated comparable results with electrolyzed reduced alkaline water. Considering the limited information on its evidence, future work is warranted to compare the effectiveness of different water treatment in acquiring alkaline water. The cross-sectional study design limits our ability to draw predictive conclusions, hence longer intervention or prospective studies are needed to delineate the benefits of alkaline water drinking in the future studies.

Conclusions

Alkaline water consumption may be considered as a source of easy-to implement lifestyle to modulate metabolic features. However further studies are warranted for unravelling the full spectrum of individuals that could benefit from its consumption. Additionally, the precise mechanism of alkaline water consumption on the improvement and prevention of diseases such as metabolic syndrome and its individual features are not fully elucidated, hence the necessity of studies addressing its broad effect on health status improvement and mechanism merit further studies.

Supporting information

S1 questionnaire..

https://doi.org/10.1371/journal.pone.0275640.s001

Acknowledgments

We would like to thank all volunteers who participated in the study. We thank Dr Poh Ying Lim for the assistance on statistical analysis

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Joint and pain boost: Gout treatment could be enhanced by alkaline water: RCT

14-May-2024 - Last updated on 14-May-2024 at 01:34 GMT

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Researchers in China found that alkaline water reduced symptoms of chronic gouty arthritis suffers in an RCT.

“Alkaline water, particularly at high concentrations, effectively alleviated pain, reduced joint swelling, enhanced daily activities, and improved joint motion in chronic gouty arthritis treatment,” wrote the researchers in Medicine ​.

“It significantly reduced key inflammatory markers (C-reactive protein, interleukin-1β, tumor necrosis factor-α) and serum uric acid levels, suggesting its potential as a valuable adjunct in gout management.” ​

Currently, the treatment of chronic gouty arthritis focuses primarily on lowering uric acid levels and managing acute attacks. Traditional medications like allopurinol and benzbromarone are effective in controlling uric acid levels but may cause side effects such as gastrointestinal reactions and liver or kidney damage with long-term use. Hence, exploring safer, less adverse supplementary treatments has become a research focus in recent years.

Alkaline water, a non-pharmacological supplementary treatment, has gained attention for its potential to regulate body fluid pH, possibly aiding in improving urid acid solubility and excretion, which helps to lower blood uric acid levels. Alkaline water may also alleviate inflammation and pain caused by gout, improving quality of life.

For this one-year trial, researchers recruited 400 patients with chronic arthritis. They were between 18 to 70 years old and received treatment at the Gout Department of Guangdong Provincial Hydropower Hospital from September 2021 to September 2023.

The participants were randomly allocated to either the control group or the experimental group.

Those in the control group adhered to a low-purine diet and consumed 2000 mL water daily to facilitate uric acid excretion. During acute phases, affected joints were moderately rested, and strenuous exercise or exposure to cold environments were avoided. As medication, they took a 40-gram dose of febuxostat (brand name: Uloric, produced by Jiangsu Wanbang Biochemical Pharmaceutical Group Co., Ltd.). The medication was taken once daily to lower hyperuricemia (high uric acid in the blood).

Those in the experimental group were divided into three groups. They all had the same medical treatment as those in the control group, but they adhered to a normal diet. They also took varying concentrations of 2,000 mL alkaline water per day: one group took a low pH concentration of 8.0–8.2, the second group took a medium concentration of 8.3–8.5, and the last group took a high concentration of 8.8–9.

At the end of the trial, participants were assessed for pain, degree of improvement in joint swelling, and quality of life. They were also assessed via their biochemical markers (serum uric acid, creatinine, urea nitrogen), which indicated the impact of treatment on uric acid metabolism. Their inflammatory markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) were also measured.

The researchers found that those who took a high concentration of alkaline water had significantly reduced pain, and they had the greatest improvement in joint swelling reduction.

All participants who took the alkaline water could also move their joints more freely, engaging in daily activities previously hindered by pain and stiffness. Both their biochemical and inflammatory markers also saw a notable decrease.

“In this study, we particularly focused on key indicators such as CRP, ESR, IL-1β, and TNF-α to assess the impact of alkaline water on the inflammatory response in patients with gouty arthritis. The results showed significant improvements in these inflammatory markers among patients consuming alkaline water compared to the control group, especially in levels of CRP and IL-1β. This finding supports the hypothesis that alkaline water alleviates the inflammatory response in gouty arthritis,” ​ concluded the researchers.

However, they said it is critical to use the appropriate concentration of alkaline water. This research examined varying concentrations and found that all levels, particularly the high concentration, were effective. But the safety and side effects of this treatment warrant attention.

“While no significant safety concerns were observed in this study, further long-term clinical research is necessary to assess the long-term safety and tolerance of alkaline water. Moreover, when used in combination with conventional Western medication, careful monitoring of drug interactions and adverse reactions is crucial to ensure treatment safety,” ​ said the researchers.

Source: Medicine ​

DOI: https://doi.org/10.1097/MD.0000000000037589 ​  

“Assessment of the efficacy of alkaline water in conjunction with conventional medication for the treatment of chronic gouty arthritis: A randomized controlled study” ​

Authors: Wu, Yong; Pang, Shuwen MD et al ​.

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The Hydrogen Stream: Asahi Kasei to test alkaline water electrolyzer

Japan’s Asahi Kasei is testing a new alkaline water electrolyzer, while China has started developing its first 100 kg vehicle-mounted liquid hydrogen system.

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Asahi Kasei  and partners celebrated the official opening of a new hydrogen pilot plant in Kawasaki, Japan. The commercial-scale facility will test its alkaline water electrolyzer, which is optimized for the production of green hydrogen. “The trial operation of four 0.8 MW modules is another milestone toward the realization of a commercial multi-module 100 MW-class alkaline water electrolysis system for green hydrogen production,” said the Japanese company in an emailed note.

China Aerospace Science and Technology Corp. ( CASC ) has developed China's first 100 kg, vehicle-mounted liquid hydrogen system. The system will allow hydrogen-powered heavy trucks to achieve a range of more than 1,000 km with just one charge. “Compared to its predecessor, the system boasts a 20% increase in effective volume within the same overall dimensions while cutting costs by more than 30%,” said  CASC. 

New Mexico Governor   Michelle Lujan Grisham is in Rotterdam for the 2024 World Hydrogen Summit to convince manufacturing companies to invest in the US state. “We’ve created an incredible hydrogen policy landscape in our state that is supportive on the supply side and demand side , and global energy leaders are taking notice,”  said  Lujan Grisham in a press release. 

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Nikola has opened its latest HYLA high-pressure modular refueling station and facility in southern California. “This launch is yet another pivotal milestone in Nikola’s strategic plan, aiming to establish a network of up to nine refueling solutions by mid-2024, with a total of 14 operational sites slated for completion by year-end, which include a combination of HYLA modular fuelers and partner stations such as FirstElement Fuels’ in the Port of Oakland,” said the company.

Fortescue has started developing a $550 million green hydrogen production venture in the United States. It is the first of the Australian company’s planned green energy investments in North America. “The US has made serious strides in attracting global investment in green hydrogen and decarbonization projects, like Fortescue’s solar and wind-powered Arizona Hydrogen facility,” said Fortescue Executive Chair and Founder Andrew Forrest, arguing that the US government has to further support the hydrogen sector.

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Sergio Matalucci

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Carbon aims to start 500 MW pilot production at module factory in France

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Synthesis, characterization, and evaluation of the antimicrobial, cytotoxic properties of alkaline earth metal complexes containing the nucleobase guanine

• Original Paper
• Published: 11 May 2024

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• Saiful Islam 1 ,
• Asaduzzaman 1 ,
• Hasina Akhter Simol 2 &
• Pradip K. Bakshi 1  

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Alkaline earth metal (Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ ) complexes of guanine (Gu), a purine-based nucleobase were synthesized. The characterization of these complexes involved elemental analysis (CHN), determination of metal and chloride contents, FTIR, UV–Visible, 1 H-NMR spectroscopy, thermal analysis (TGA, DSC), molar conductance, and PXRD measurements. Based on the elemental analysis, the molecular formulae of the complexes were proposed as [Mg(Gu) 2 Cl 2 ]·4H 2 O, [Ca(Gu) 2 Cl 2 ]·3H 2 O, [Sr(Gu) 3 Cl 2 ]·5H 2 O and [Ba(Gu) 3 Cl 2 ](Gu)·5H 2 O. The molar conductance measurement showed that the complexes were non-electrolytic. The mode of chelation of guanine through N(7) and O(6) sites was explained using FTIR and 1 H-NMR spectral analysis. Thermal analysis in a nitrogen atmosphere showed that the complexes were fairly stable up to 100 °C, with decomposition starting above this temperature and indicating the presence of hydrated water. The crystallite size, microstrain, and dislocation density of the complexes were determined using XRD data. The antibacterial and antifungal activities of guanine and its complexes were screened against five gram-positive, eight gram-negative bacteria, and three fungi. Guanine did not exhibit any antibacterial activity, while the metal complexes showed significant antibacterial and antifungal activities. In vitro cytotoxicity testing revealed that the alkaline earth metal complexes exhibited potential cytotoxic activity, with LC 50 values ranging from 18.55 to 40.61 µg mL −1 . HeLa cervical cancer cell lines were used to investigate the anticancer activity of metal complexes, and each complex demonstrated cytotoxicity toward HeLa cell lines.

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The authors are grateful to the Department of Pharmacy, State University of Bangladesh for providing laboratory support to carry out the biological activity of the complexes.

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Islam, S., Asaduzzaman, Simol, H.A. et al. Synthesis, characterization, and evaluation of the antimicrobial, cytotoxic properties of alkaline earth metal complexes containing the nucleobase guanine. Chem. Pap. (2024). https://doi.org/10.1007/s11696-024-03494-3

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Staple crops equipped for alkaline soils

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