Health effects of desalinated water: Role of electrolyte disturbance in cancer development
Introduction
In his landmark paper, Ames (1979) observed that damage to DNA appeared to be a major cause of most cancers and suggested that natural chemicals in the human diet and the tens of thousands of synthetic chemicals that have recently been introduced into the environment be tested for their ability to damage DNA. Dr. Ames advocated the use of rapid mutagenicity assays to identify environmental mutagens and carcinogens and this seminal study was responsible for shifting the scientific and regulatory emphasis to ‘mutagens as carcinogens’, and led to international quest to find individual chemicals and a few well-defined mixtures (e.g. diesel exhaust) that could be shown to be ‘complete’ carcinogens (i.e., substances that could cause cancer on their own). Advances in cancer biology subsequently revealed the limitations of this approach and have let to the multistage and “hallmarks of cancer” framework which recognizes that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce tumors and ultimately malignancies (Casey et al., 2015, Hu et al., 2015, Narayanan et al., 2015). We hypothesize that electrolyte disturbance from exposure to demineralized water can mediate the cancer microenvironment in ways that lead to procarcinogenic outcomes. This review explores the role of dysregulation in electrolyte homeostasis, one of the most recognizable features as well as one of the earliest described hallmarks of cancer (Robey et al., 2015), in enabling cancer genesis, maintenance and progression.
As freshwater resources become scarcer, communities in different parts of world have turned increasingly to “manufacturing” drinking water from desalination or demineralization of seawater. Desalination of sea water and brackish water is growing rapidly and has become the principal source of new fresh (demineralized) water in many parts of the world (Greenlee et al., 2009, Fried and Serio, 2012, Lattemann et al., 2010). As of 2013, there were more than 17,000 desalination plants located in 150 different countries. These plants produce about over 80 million cubic meters of water (21.1 billion US gallons) per day. More than 300 million people around the world rely on desalinated water for some or all their daily needs (IDA, 2015). The rate of desalination continues to grow inexorably, driven by worldwide expansion in drought (for example, in California, USA) and the need for water especially in the Arabian Gulf region and China (GWI, 2015). Desalinated water differs from natural waters in the sense that its composition can be controlled whereas natural waters have a very wide range of physical, chemical and biological characteristics that are a matter of climate, geology and chance which are tied to the health of the local population and ecosystems (WHO, 2011a, Mecawi et al., 2013). A logical question in public health is whether the ultimate composition of desalinated and other manufactured “pure” water may have a negative impact on the health of long-term consumers (WHO, 2011a, Rygaard et al., 2011). In this review, we used the “weight of evidence” approach to suggest that chronic ingestion of demineralized water is a potential risk factor for adverse health outcomes.
Chronic ingestion of demineralized water can change the ionic and molecular composition of the extracellular and intracellular fluids resulting in hyponatremia, hypokalemia, hypomagnesemia and hypocalcemia which are very common comorbidities in cancer patients. Such dysregulated electrolyte homeostasis can contribute to multiple stages of tumor development by influencing the tumor microenvironment which consists of a complex of interaction among the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages, blood vessels that feed the tumor, and soluble factors such as cytokines (Casey et al., 2015, Langie et al., 2015). Furthermore, ingestion of water with low levels of sodium, potassium, magnesium and calcium can affect the tonicity and osmolality of body fluids and hence the effective cell volume and blood pressure -- thereby creating osmotic stress. Studies on several mammalian cell lines suggest that osmotic stress, regardless of its origin, can cause DNA damage leading to chromosome aberrations; genome malfunction occasioned often is a prerequisite for the development of cancer (Langie et al., 2015, Thompson et al., 2015). This review makes a case that the cumulative effects of aberrant electrolyte homeostasis on different metabolic pathways and a variety of related systems, organs, tissues and cells can produce carcinogenic synergies. The exact mechanism that triggers the procarcinogenic effect needs to be fully explored. This review highlights possible areas for exploratory experiments to validate this hypothesis.
Children are particularly vulnerable to health risks from ingestion of demineralized water. For the most part they drink when given the opportunity and can readily over-hydrate their optimal needs by continuing to drink water or some other liquids such as soda (often low in minerals) or fruit juice (made with demineralized water). Over time, the chronic lack of optimal water intake could create metabolic conditions that can promote epigenetic changes and tumorigenesis later in life. Any delayed health effects from drinking of water by children has to be of some concern.
Section snippets
Dysregulation of water and electrolyte homeostasis after ingestion of demineralized water
Since pure desalinated water has unsavory and undesirable attributes that can affect the water distribution system, effort is generally made to stabilize and reduce its corrosivity using lime or limestone and/or some blending with groundwater (WHO, 2005, WHO, 2011b, Birnhack et al., 2011). The post-treatment processes often result in products with varying chemical characteristics and it is remarkable that currently there are few regulatory guidelines specific to the quality of desalinated water
Evidence from human studies
Experiments with laboratory animals and human volunteers, and observational data from populations supplied with desalinated water, individuals drinking reverse osmosis-treated demineralized water, and infants given beverages prepared with distilled water go back several decades (reviewed in WHO (2005)). In addition, some insights have been provided by the results of epidemiological studies where health effects were compared for populations using low-mineral (soft) water and more mineral-rich
Electrolyte dysregulation and hallmarks of cancer
The list of processes that are controlled by cell volume and osmotic stress reads like the book of life itself – it includes growth and proliferation, membrane transport, exocytosis, endocytosis, cell shape changes, hormone signaling, metabolism, excitability, neural communication, cell migration, nutrient delivery, waste filtration, necrosis and apoptosis (Casey et al., 2015, Nahta et al., 2015). These are among the common hallmarks of cancer (Hanahan and Weinberg, 2011). There are clearly
Conclusions
There is currently no "smoking gun" evidence to suggest that desalinated water in itself can cause cancer directly in terms of inducing genetic mutations. Ingestion of demineralized water, however, leads to alterations in tonicity and osmolality which can offset the osmoregulatory mechanisms, a conserved set of adaptations designed to maintain cell volume, ion transport, organic osmolyte concentration, protein structure, cell turnover, and other cellular parameters within set limits (Kültz, 2001
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