Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Peer-reviewed

Research Article

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

  • Yoke Mun Chan ,

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

    cym@upm.edu.my

    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

    ⨯
  • Zalilah Mohd Shariff,

    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

    ⨯
  • Yit Siew Chin,

    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

    ⨯
  • Sazlina Shariff Ghazali,

    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

    ⨯
  • Ping Yein Lee,

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

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

    ⨯
  • Kai Sze Chan

    Roles Data curation, Investigation, Writing – review & editing

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

    ⨯

Abstract

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 η2 = 0.435), triglyceride/high-density lipoprotein concentration ratio (F(1,294) = 21.06, p = 0.023, partial η2 = 0.360), diastolic blood pressure (F(1,294) = 7.85, p = 0.046, partial η2 = 0.258) and waist circumference (F(1,294) = 9.261, p = 0.038, partial η2 = 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 η2 = 0.451) and handgrip strength F(1,294) = 27.51, p = 0.011, partial η2 = 0.448). Low density lipoprotein cholesterol concentration (F(1,294) = 1.772, p = 0.287, partial η2 = 0.014), body weight (F(1,294) = 1.985, p = 0.145, partial η2 = 0.013) and systolic blood pressure (F(1,294) = 1.656, p = 0.301, partial η2 = 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.

Results

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.

thumbnail
Download:
Table 1. Comparison of characteristics between alkaline water drinkers and non-drinkers (n = 304).

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).

thumbnail
Download:
Table 2. Influence of drinking behaviour (alkaline water drinkers vs non-drinkers) on metabolite risks (FPG, TG/HDL, LDL, SBP, DBP), anthropometric parameters (body weight, WC), sleep duration and handgrip strength.

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 η2 = 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 η2 = 0.435), TG/HDL (F(1,294) = 21.06, p = 0.023, partial η2 = 0.360), DBP (F(1,294) = 7.85, p = 0.046, partial η2 = 0.258), with no significant main effect of alkaline water drinking behaviour on LDL (F(1,294) = 1.772, p = 0.287, partial η2 = 0.014) or SBP (F(1,294) = 1.656, p = 0.301, partial η2 = 0.010). Postmenopausal women who were alkaline water drinkers had lower waist circumference (F(1,294) = 9.261, p = 0.038, partial η2 = 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 η2 = 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 η2 = 0.451) and hand grip strength (F(1,294) = 27.51, p = 0.011, partial η2 = 0.448).

Discussion

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.

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

References

  1. 1. Shirahata S, Hamasaki T, Teruya K. Advanced research on the health benefit of reduced water. Trends Food Sci Tech. 2012. 23:124–131.
  2. 2. Siener R, Jahnen A, Hesse A. Influence of a mineral water rich in calcium, magnesium and bicarbonate on urine composition and the risk of calcium oxalate crystallization. Eur J Clin Nutr. 2004. 58:270–276. 74. pmid:14749747
  3. 3. Heil DP. Acid–base balance and hydration status following consumption of mineral-based alkaline bottled water. J Int Soc Sports Nutr. 2010. 7:29. 75. pmid:20836884
  4. 4. Day RO, Liauw W, Tozer LM, McElduff P, Beckett RJ, Williams KM. A double-blind, placebo-controlled study of the short-term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women. BMC Res Notes. 2010. 3:180. pmid:20579398
  5. 5. Choi YA, Lee DH, Cho DY, Lee YJ. Outcomes Assessment of Sustainable and Innovatively Simple Lifestyle Modification at the Workplace—Drinking Electrolyzed-Reduced Water (OASIS-ERW): A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel). 2020. 9(7):564. pmid:32605142
  6. 6. Wicaksono SA, Nabyla DH, Utami SB. The Effects of Alkaline Reduced Water Administration to the Fasting Blood Glucose Levels in Patients with Type 2 Diabetes Mellitus. Pakistan J Med Health Sci. 2020. 14(3): 1260–1265.
  7. 7. Wulandari P, Suwondo A, Puji Astuti SE. Utilization of Alkaline Water as An Alternative Complementary Therapy on Triglyceride Levels Among Patients with Grade I Hypertension. IJNHS. 2020. 3(6): 662–671.
  8. 8. Agustanti D, Purbianto. Effect of Alkaline Water Consumption on Decreasing Blood Sugar Levels of Diabetes Mellitus Patients. Medico Legal Update. 2019. 234–237.
  9. 9. Rias YA, Kurniawan AL, Chang CW, Gordon CJ, Tsai HT. Synergistic Effects of Regular Walking and Alkaline Electrolyzed Water on Decreasing Inflammation and Oxidative Stress, and Increasing Quality of Life in Individuals with Type 2 Diabetes: A Community Based Randomized Controlled Trial. Antioxidants (Basel). 2020. 9(10):946. pmid:33019646
  10. 10. Tanaka Y, Saihara Y, Izumotani K, Nakamura H. Daily ingestion of alkaline electrolyzed water containing hydrogen influences human health, including gastrointestinal symptoms. Med Gas Res. 2019; 8(4):160–166. pmid:30713669
  11. 11. Hansen TH, Thomassen MT, Madsen ML, Kern T, Bak EG, Kashani A, et al. The effect of drinking water pH on the human gut microbiota and glucose regulation: results of a randomized controlled cross-over intervention. Sci Rep. 2018. 8:16626. pmid:30413727
  12. 12. Siswantoro E, Purwanto NH, Sutomo. Effectiveness of Alkali Water Consumption to Reduce Blood Sugar Levels in Diabetes Mellitus Type 2. J Diabetes Mellitus. 2017. 7:249–264.
  13. 13. Weidman J, Holsworth RE, Brossman B, Cho DJ, St Cyr J, Fridman G. Effect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults. J Int Soc Sports Nutr. 2016. 13(45). pmid:27932937
  14. 14. Gadek Z, Li Y, Shirahata S. Influence of natural reduced water on relevant tests parameters and reactive oxygen species concentration in blood of 320 diabetes patients in the prospective observation procedure. In: Iijima S., Nishijima KI. (eds) Animal Cell Technology: Basic & Applied Aspects. 2006. 14. Springer, Dordrecht.
  15. 15. Chycki J, Kurylas A, Maszczyk A, Golas A, Zajac A. Alkaline water improves exercise-induced metabolic acidosis and enhances anaerobic exercise performance in combat sport athletes. 2018. PLoS ONE 13(11): e0205708. pmid:30452459
  16. 16. Nerbrand C, Agréus L, Lenner RA, Nyberg P, Svärdsudd K. The influence of calcium and magnesium in drinking water and diet on cardiovascular risk factors in individuals living in hard and soft water areas with differences in cardiovascular mortality. BMC Public Health. 2003. 18;3:21. pmid:12814520
  17. 17. Marque S, Jacqmin-Gadda H, Dartigues JF, Commenges D. Cardiovascular mortality and calcium and magnesium in drinking water: an ecological study in elderly people. Eur J Epidemiol. 2003. 18(4):305–309. pmid:12803370
  18. 18. Sauvant MP, Pepin D. Geographic variation of the mortality from cardiovascular disease and drinking water in a French small area (Puy de Dome). Environ Res. 2000. 84(3):219–227. pmid:11097795
  19. 19. Rubenowitz E, Axelsson G, Rylander R. Magnesium and calcium in drinking water and death from acute myocardial infarction in women. Epidemiology. 1999. 10(1):31–36. pmid:9888277
  20. 20. Rubenowitz E, Molin I, Axelsson G, Rylander R. Magnesium in drinking water in relation to morbidity and mortality from acute myocardial infarction. Epidemiology. 2000.11(4):416–421. pmid:10874548
  21. 21. Rylander R. Drinking water constituents and disease. J Nutr. 2008. 138(2):423S–425S. pmid:18203915
  22. 22. Rylander R, Arnaud MJ. Mineral water intake reduces blood pressure among subjects with low urinary magnesium and calcium levels. BMC Public Health. 2004. 56(4). pmid:15571635
  23. 23. Aini MS, Fakhrul-Razi A, Mumtazah O, Meow Chen JC. Malaysian households’ drinking water practices: A case study. International Journal of Sustainable Development & World Ecology. 2007. 14(5):503–510.
  24. 24. Ong C, Ibrahim S, Sen Gupta B. A survey of tap water quality in Kuala Lumpur. Urban Water J. 2007. 4(1):29–41.
  25. 25. Delos Reyes FSLG Mamaril ACC, Matias TJP Tronco MKV, Samson GR Javier ND, et al. The Search for the Elixir of Life: On the Therapeutic Potential of Alkaline Reduced Water in Metabolic Syndromes. Processes. 2021; 9(11):1876.
  26. 26. Izadpanah AA, Javidnia A. The Ability of a Nanofiltration Membrane to Remove Hardness and Ions from Diluted Seawater. Water. 2012; 4(2):283–294.
  27. 27. Christakis MK, Hasan H, De Souza LR, Shirreff L. The effect of menopause on metabolic syndrome: cross-sectional results from the Canadian Longitudinal Study on Aging. Menopause. 2020. 27(9):999–1009. pmid:32852451
  28. 28. Yoldemir T, Erenus M. The prevalence of metabolic syndrome in pre- and post-menopausal women attending a tertiary clinic in Turkey. Eur J Obstet Gynecol Reprod Biol. 2012. 164:172–175. pmid:22765975
  29. 29. Figueiredo Neto JA, Figueredo ED, Barbosa JB, Barbosa FF, Costa GR, Nina VJ, Nina RV. Metabolic syndrome and menopause: cross-sectional study in gynecology clinic. Arq Bras Cardiol. 2010. 95:339–345. pmid:20658092
  30. 30. Ainy E, Mirmiran P, Zahedi AS, Azizi F. Prevalence of metabolic syndrome during menopausal transition Tehranian women: Tehran Lipid and Glucose Study (TLGS). Maturitas. 2007.58:150–155. pmid:17768019
  31. 31. Kim HM, Park J, Ryu SY, Kim J. The effect of menopause on the metabolic syndrome among Korean women: the Korean National Health and Nutrition Examination Survey, 2001. Diab Care. 2007. 30:701–706. pmid:17327344
  32. 32. Tom SE, Kuh D, Guralnik JM, Mishra GD. Self-reported sleep difficulty during the menopausal transition: results from a prospective cohort study. Menopause. 2010. 17(6):1128–1135. pmid:20551846
  33. 33. Woods NF, Mitchell ES. Sleep symptoms during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women’s Health Study. Sleep. 2010. 33(4):539–549. pmid:20394324
  34. 34. Kravitz HM, Zhao X, Bromberger JT, Gold EB, Hall MH, Matthews KA, et al. Sleep disturbance during the menopausal transition in a multi-ethnic community sample of women. Sleep. 2008. 31(7):979–990. pmid:18652093
  35. 35. Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrell K, Meyer PM. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause. 10(1):19–28. pmid:12544673
  36. 36. Rathnayake N, Alwis G, Lenora J, Lekamwasam S. Factors associated with measures of sarcopenia in pre and postmenopausal women. BMC Women’s Health. 2021. 21(5). pmid:33388050
  37. 37. Park YM, Jankowski CM, Ozemek C, Hildreth KL, Kohrt WM, Moreau KL. Appendicular lean mass is lower in late compared with early perimenopausal women: potential role of FSH. J Appl Physiol. 2020. 128:5, 1373–1380. pmid:32298212
  38. 38. Khadilkar SS. Musculoskeletal Disorders and Menopause. J Obstet Gynecol India. 2019. 69:99–103. pmid:30956461
  39. 39. Alberti KGMM Eckel RH, Grundy SM Zimmet PZ, Cleeman JI Donato KA, et al. Harmonising the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009. 120:1640–1645.
  40. 40. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.
  41. 41. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol Ser A Biol Sci Med Sci. 2001, 56, M146–M157. pmid:11253156
  42. 42. Institute for Public Health (IPH). National Health and Morbidity Survey 2014: Malaysian Adult Nutrition Survey. 2014.1:108.
  43. 43. Institute for Public Health. Report on Smoking Status among Malaysian Adults. Report of the National Health and Morbidity Survey 2015. 2015. IPH, Ministry of Health: Kuala Lumpur, Malaysia.
  44. 44. Tee ES, Noor MI, Azudin MN, Idris KI. Nutrient Composition of Malaysian Foods. 1997. 4th Ed. Institute for Medical Research, Kuala Lumpur, Malaysia.
    • 45. Energy and Nutrient Composition of Food. Singapore Food Composition Database. 2011
      • 46. Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc. 1995. 95:791–7. pmid:7797810
      • 47. Lee TT, Norimah AK, & Safiah MY. Development of Healthy Eating Index (HEI) for Malaysian adults. Proceedings of 26th Scientific Conference of the Nutrition Society of Malaysia. 2011. Kuala Lumpur, Malaysia.
      • 48. James G, Witten D, Hastie T, Tibshirani R. An Introduction to Statistical Learning: With Applications in R. 2021. 2nd Ed. Springer-Verlag New York Inc. New York, United States.
        • 49. Cohen J, Cohen P, West SG, Aiken LS. Applied multiple regression/ correlation analysis for the behavioral sciences. 2003. 3rd Ed. Lawrence Erlbaum Associates, Inc. Mahwah, New Jersey, United States.
          • 50. Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ. 2016. 354:i3857. pmid:27510511
          • 51. Ignacio RM, Kang TY, Kim CS, Kim SK, Yang YC, Sohn JH, et al. Anti-obesity effect of alkaline reduced water in high fat fed obese mice. Biol Pharm Bull. 2013. 36:1052–1059. pmid:23811554
          • 52. Yahiro T, Hara T, Matsumoto T, Ikebe E, Fife-Koshinomi N, Xu Z, et al. Long-Term Potable Effects of Alkalescent Mineral Water on Intestinal Microbiota Shift and Physical Conditioning. Evid Based Complement Alternat Med. 2019. 1–10. pmid:31827547
          • 53. Jackson K, Dressler N, Ben-Shushan RS, Meerson A, LeBaron TW, Tamir S. Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model. World J Gastroenterol. 2018. 7;24(45):5095–5108. pmid:30568387
          • 54. St-Onge MP, Gallagher D. Body composition changes with aging: The cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutr. 2010. 26(2):152–155. pmid:20004080
          • 55. Snijder MB, van Dam RM, Visser M, Seidell JC. What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol. 2006. 35(1):83–92. pmid:16339600
          • 56. Jin D, Ryu SH, Kim HW, Yang EJ, Lim SJ, Ryang YS, et al. Anti-Diabetic Effect of Alkaline-Reduced Water on OLETF Rats. Biosci, Biotechnol & Biochem. 2006. 70:1, 31–37, pmid:16428818
          • 57. Kim JM, Yokoyama K. Effects of alkaline ionized water on spontaneously diabetic GK-rats fed sucrose. Korean J Lab Anim Sci. 1997. 13, 187–190.
          • 58. Li Y, Hamasaki T, Nakamichi N, Kashiwagi T, Komatsu T, Ye J, et al. Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus. Cytotechnology. 2011. 63(2):119–31. pmid:21063772
          • 59. Watanabe T, Kishikawa Y, Shirai W. Influence of alkaline ionized water on rat erythrocyte hexokinase activity and myocardium. J Toxicol Sci. 1997. 22, 141–152. pmid:9198011
          • 60. Burgos-Morón E, Abad-Jiménez Z, Martínez de Marañón A, Iannantuoni F, Escribano-López I, López-Domènech S, et al. Relationship between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues. J Clin Med. 2019. 8(9):1385.
          • 61. Halliwell B. The wanderings of a free radical. Free Radic Biol Med. 2009. 46:531–542. pmid:19111608
          • 62. Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem. 2017. 118:3577–3585. pmid:28460155
          • 63. Eriksson JW. Metabolic stress in insulin’s target cells leads to ROS accumulation-a hypothetical common pathway causing insulin resistance. FEBS Lett. 2007. 581:3734–3742. pmid:17628546
          • 64. Katakami N. Mechanism of Development of Atherosclerosis and Cardiovascular Disease in Diabetes Mellitus. J Atheroscler Thromb. 2018. 25(1):27–39. pmid:28966336
          • 65. Ogawa S, Shimizu M, Nako K, Okamura M, Ohsaki Y, Kabayama S, et al. Clinical Study on the Insulin Resistance Improvement Effects of Electrolyzed Hydrogen Rich Water in Type 2 Diabetes Patients: A Multicenter Prospective Double-Blind Randomized Control Trial. SSRN. 2019.
          • 66. Masuda K, Tanaka Y, Kanehisa M, Ninomiya T, Inoue A, Higuma H, et al. Natural reduced water suppressed anxiety and protected the heightened oxidative stress in rats. Neuropsychiatr Dis Treat. 2017. 8(13):2357–2362. pmid:28932120
          • 67. Shirahata S, Kabayama S, Nakano M, Miura T, Kusumoto K, Gotoh M, et al. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochem Biophys Res Commun. 1997. 8;234(1):269–74. pmid:9169001
          • 68. Jassim EQ, Aqeel Ch H. Effect of alkaline water and /or magnetic water on some physiological characteristic in broiler chicken. J Entomol Zool Stud. 2017. 5(5): 1643–1647.
          • 69. Salemi S, Dermanaky Farahani H, Moradi B., Sharif Moghadasi. Effect of Alkaline Water on the Lipid Profile of Wistar Rats. Nutr Food Sci Res. 2014. 1(1) 119.
          • 70. Abe M, Sato S, Toh K, Hamasaki T, Nakamichi N, Teruya K, et al. Suppressive effect of ERW on lipid peroxidaton and plasma triglyceride level. Kamihira M et al. (eds.), Animal Cell Technology: Basic & Applied Aspects. 2010. 15, Springer, Dordrecht: 315–321.
          • 71. Osada K, Li Y, Hamasaki T, Abe M, Nakamichi N, Teruya K, et al. Anti-diabetic effects of Hita Tenryosui water, a natural reduced water. Kamihira M et al. (eds.), Animal Cell Technology: Basic & Applied Aspects. 2010. 15, Springer, Dordrecht: 307–313.
          • 72. Huang KC, Yang CC, Lee KT, Chien CT. Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water. Kidney Intern. 2003. 64(2): 704–714. pmid:12846769
          • 73. Fonseca MIH, da Silva IT, Ferreira SRG. Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women? Diabetol Metab Syndr. 2017. 9, 22. pmid:28405227
          • 74. Cífková R, Krajčoviechová A. Dyslipidemia and cardiovascular disease in women. Curr Cardiol Rep. 2015. 17:609. pmid:26026998
          • 75. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007. 30;115(4):450–458. pmid:17190864
          • 76. Prasad M, Sara J, Widmer RJ, Lennon R, Lerman LO, Lerman A. Triglyceride and Triglyceride/ HDL (High Density Lipoprotein) Ratio Predict Major Adverse Cardiovascular Outcomes in Women With Non-Obstructive Coronary Artery Disease. J Am Heart Assoc. 2019. 7;8(9):e009442. pmid:31014162
          • 77. Dobiásová M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem. 2001. 34(7):583–588. pmid:11738396
          • 78. Bittner V, Johnson BD, Zineh I, Rogers WJ, Vido D, Marroquin OC, et al. The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J. 2009. 157(3):548–555. pmid:19249427
          • 79. Wu H, Xiong L, Xu Q, Wu J, Huang R, Guo Q, et al. Higher serum triglyceride to high-density lipoprotein cholesterol ratio was associated with increased cardiovascular mortality in female patients on peritoneal dialysis. Nutr Metab Cardiovasc Dis. 2015. 25(8):749–755. pmid:26084271
          • 80. Nam KW, Kwon HM, Jeong HY, Park JH, Kwon H, Jeong SM. High triglyceride/HDL cholesterol ratio is associated with silent brain infarcts in a healthy population. BMC Neurol. 2019. 19:147. pmid:31266453
          • 81. Deng QW, Wang H, Sun CZ, Xing FL, Zhang HQ, Zuo L, et al. Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke. Eur J Neurol. 2017. 24(2):283–291. pmid:27862659
          • 82. Turak O, Afşar B, Ozcan F, Öksüz F, Mendi MA, Yayla Ç, et al. The Role of Plasma Triglyceride/High-Density Lipoprotein Cholesterol Ratio to Predict New Cardiovascular Events in Essential Hypertensive Patients. J Clin Hypertens (Greenwich). 2016. 18(8):772–777. pmid:26694089
          • 83. Zhou Y, Yang G, He H, Pan X, Peng W, Chai X. Triglyceride/High-Density Lipoprotein Cholesterol Ratio Is Associated with In-Hospital Mortality in Acute Type B Aortic Dissection. Biomed Res Int. 2020. 5419846. pmid:32337256
          • 84. Yang EJ, Kim JR, Ryang YS, Kim DH, Deung YK, Park SK, et al. A Clinical Trial of Orally Administered Alkaline Reduced Water. J Exp Biomed Sci. 2007. 13(2): 83–89.
          • 85. Nakayama M, Kabayama S, Nakano H, Zhu WJ, Terawaki H, Nakayama K, et al. Biological Effects of Electrolyzed Water in Hemodialysis. Nephron Clin Pract. 2009.112:c9–c15. pmid:19342864
          • 86. Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant. 2010. 25(9):3026–3033. pmid:20388631
          • 87. Sun Q, Xin F, Wen X, Lu C, Chen R, Ruan G. Protective Effects of Different Kinds of Filtered Water on Hypertensive Mouse by Suppressing Oxidative Stress and Inflammation. Oxid Med Cell Longev. 2018. 2917387. pmid:30622665
          • 88. Adams R, Appleton S, Taylor A, McEvory D, Antic N. Report to the Sleep Health Foundation: 2016 Sleep Health Survey of Australian Adults. 2016. The Adelaide Institute for Sleep Health; The University of Adelaide: Adelaide, Australia.
            • 89. Ferrie JE, Shipley MJ, Cappuccio FP, Brunner E, Miller MA, Kumari M, et al. A prospective study of change in sleep duration: associations with mortality in the Whitehall II cohort. Sleep. 2007. 30(12):1659–1666. pmid:18246975
            • 90. Engeda J, Mezuk B, Ratliff S, Ning Y. Association between duration and quality of sleep and the risk of pre-diabetes: evidence from NHANES. Diab Med. 2013. 30(6):676–680. pmid:23425048
            • 91. Farah NMF, Teh SY, Mohd Rasdi HF. Self-Reported Sleep Quality Using the Malay Version of the Pittsburgh Sleep Quality Index (PSQI-M) In Malaysian Adults. Int J Environ Res Public Health. 2019. 27;16(23):4750. pmid:31783607
            • 92. Wang YM, Chen HG, Song M, Xu SJ, Yu LL, Wang L, et al. Prevalence of insomnia and its risk factors in older individuals: a community-based study in four cities of Hebei Province, China. Sleep Med. 2016. 19:116–22. pmid:27198956
            • 93. Gadie A, Shafto M, Leng Y, Kievit RA. How are age-related differences in sleep quality associated with health outcomes? An epidemiological investigation in a UK cohort of 2406 adults. BMJ Open. 2017. 7:e014920. pmid:28760786
            • 94. Lavie L. Oxidative stress—a unifying paradigm in obstructive sleep apnea and comorbidities. Prog Cardiovasc Dis. 2009. 51(4):303–312. pmid:19110132
            • 95. Lin HH, Tsai PS, Fang SC, Liu JF. Effect of kiwifruit consumption on sleep quality in adults with sleep problems. Asia Pac J Clin Nutr. 2011. 20:169–174. pmid:21669584
            • 96. Howatson G, Bell PG, Tallent J, Middleton B, McHugh MP, Ellis J. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2012;51(8):909–916. pmid:22038497
            • 97. Kanagasabai T, Ardern CI. Inflammation, Oxidative Stress, and Antioxidants Contribute to Selected Sleep Quality and Cardiometabolic Health Relationships: A Cross-Sectional Study. Mediators Inflamm. 2015. 824589. pmid:26568665
            • 98. Noorwali E, Cade JE, Burley VJ, Hardie LJ. The relationship between sleep duration and fruit/vegetable intakes in UK adults: A cross-sectional study from the National Diet and Nutrition Survey. BMJ Open. 2018. 8:e020810. pmid:29703857
            • 99. Jansen EC, She R, Rukstalis MM, Alexander GL. Sleep Duration and Quality in Relation to Fruit and Vegetable Intake of US Young Adults: A Secondary Analysis. Int J Behav Med. 2020. 1–12. pmid:32016881
            • 100. Zhao W, Li Y, Ma W, Ge Y, Huang Y. A study on quality components and sleep-promoting effects of GABA black tea. Food Funct. 2015. 6:3393–3398. pmid:26290415
            • 101. Socci V, Tempesta D, Desideri G, De Gennaro L, Ferrara M. Enhancing Human Cognition with Cocoa Flavonoids. Front. Nutr. 2017. 4 pmid:28560212
            • 102. Azrina A, Khoo HE, Mohd Aizat I, Amin I, Muhammad Rizal R. Evaluation of Minerals Content of Drinking Water in Malaysia. Sci World J. 2012. pmid:22649292