DISCUSSION
This systematic review and meta-analysis support a significant inverse association between total water intake and risk of CVD mortality. Moreover, total water intake was inversely linked with all-cause and CVD mortality in a linear and non-linear dose-response manner.
Water affects numerous physiological processes and, therefore, its net effects on health outcomes is important. There is substantial evidence that mild dehydration may account for many morbidities. The previous meta-analyses have focused mainly on individual fluid intakes with risk of mortality and total water intake has received less attention[21]. To the best of our knowledge, this is the first meta-analysis of prospective cohort studies that examined the association between water intake and risk of mortality. In the current study, total water intake was associated with a lower risk of CVD mortality. In line with our, a review revealed that good hydration reduces the risk of hypertension, fatal coronary heart disease, venous thromboembolism, and cerebral infarct. Further study indicated serum sodium as a risk factor for CVDs and give additional support to recommendations for dietary salt restriction and adequate water intake as preventives of CVD. Moreover, finding from earlier meta-analyses have documented that coffee and tea consumption as total fluid subtypes were associated with a lower risk of CVD mortality[7, 8, 21, 22]. However, it must be kept in mind that tea and coffee are mild diuretics and thus may raise blood viscosity which could increase the risk of mortality. Therefore, these inverse associations might be attributed to biologically active factors in tea and coffee. The inverse association between total fluid intake and cardiovascular mortality might be explained by reduced risk of inflammation and coagulation which are considered as major risk factors for the development of cardiovascular diseases. In our study total and drinking water was not associated with all-cause mortality. This might be attributed to the consumption of fluids other than water such as caffeinated beverages or high energy drinks which can cause a rapid elevation in blood viscosity after consumption.
In the context of our findings, it must be kept in mind individual fluids contain diverse biologically active components that may also account for the association between water intake and mortality. Also, other conditions such as medications and higher salt intake should be taken into account which can affect the fluid balance and in result alter the risk of mortality.
Exact mechanisms underlying the relation between water intake and mortality risk are not completely understood. Concerns about recommendations for high water intake have been based on the assumption that low fluid intake is associated with dehydration which can induce inflammation and physiological dysfunction in the body. Evidence has shown that chronic dehydration is associated with a higher risk of certain diseases, such as cardiovascular disease[5]. Besides, chronic dehydration may be related to increasing levels of hemorrhagic factors[23, 24]. Elevation coagulation factors along with high blood viscosity, fibrinogen, and hematocrit levels are correlated with coronary heart disease[25-29]. They respond to circadian changes in hydration, daily activity, and medication such as diuretics[30-33]. Moreover, raising of serum sodium within the physiological range as a result of dehydration can lead to vascular changes by stimulating inflammatory signaling in endothelial cells and promote atherosclerosis. Another theory concerns arginine vasopressin (AVP), which regulates the water balance in the body. AVP also has vasoconstrictive effects, and there is evidence that elevated plasma levels have adverse effects on blood pressure and ventricular function[34, 35]. Increased water intake, suppresses plasma AVP, and exert other hemodynamic effects[36-38].
Strengths and weaknesses of the study: The present meta-analysis has several strengths. First, the relatively large number of participants and deaths included, allowed us to quantitatively assess the association of water intake and risk of mortality, thus making it more powerful than any single study. Second, a dose-response analysis was conducted to evaluate the linear and non-linear relations. Third, because all included studies had a prospective design, the influence of recall and selection bias is minimized that are common in case-control studies. Fourth, in the significant relations of our study low heterogeneity among studies was seen which further confirms our results. Finally, we evaluated the associations separately for total and drinking water intake as the exposure of interest. These data provide the most comprehensive insight into the association between water intake and risk of mortality based on the current evidence. Our findings also need to be interpreted in the context of some limitations, most of them are common to observational studies and meta-analyses. Residual or unmeasured confounding factors may have affected the magnitude of the association between water intake and mortality. Although most studies had controlled for potential confounders, some did not control the analyses for dietary intake of other nutrients and some others did not consider total energy intake and BMI as covariates. Lack of control for such factors might affect the independent association of water intake with mortality. Also, some studies in this review did not report sufficient information to be included in the dose-response meta-analysis. Also, different methods were used for water intake assessment including FFQ and dietary recall in the included cohorts. Measurement errors in dietary assessment are inevitable and would have could alter the associations with water intake. As we considered studies on apparently healthy populations, our conclusions about water intake cannot be generalized to those with specific diseases such as hemodialysis, CKD, and ARDS patients, in which fluid imbalance is more prevalent in them.