Sunday, July 26, 2015

Water, Energy, and the Perils of Dehydration


Posted on: Saturday, June 13th 2015 at 6:30 am

What if water, plain and simple, was the most critically lacking substance for energy and health promotion in the modern lifestyle? 
Some years ago, I read the late Dr. Fereydoon Batmanghelidj's marvelous book, Your Body's Many Cries for Water, first published in 1992 and more recently updated in 2008.  Here this Iranian-American physician made and makes a strong case that chronic low grade and usually unrecognized dehydration affects most of us in the West, attuned as we are to avoiding water as a beverage and too often choosing dehydrating caffeinated and sweetened drinks that only contribute to the problem.  After all, caffeine is a well-known diuretic, as is sugar.  We may think when we imbibe sodas, coffee, energy drinks, or for the healthier among us, even herbal teas, that we are in effect ingesting adequate "water." But as Dr. Batmanghelidj points out, such intake only makes dehydration worse, causing a greater water loss overall than we take in.  For example, for every 10 ounces of a caffeinated beverage, be it coffee, black tea, soda pop or an "energy" drink, we can lose up to 12 ounces of water, a loss contributing to, not resolving, low grade chronic dehydration.  Even the healthy favorites of non-caffeinated herbal teas dehydrate, due to the complex combination of diuretic molecules in the brew as well as the osmotic effect.



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After reading this book and the several that followed, I began to suspect that many of my patients, often diagnosed with life threatening malignancies and other serious degenerative diseases, appeared to be chronically dehydrated, though virtually none expressed any sensation of thirst.  Many, when first starting treatment with me, acknowledged that they never drank any water at all, relying instead, and mistakenly, on a variety of other beverages including dehydrating herbal teas they assumed provided for all water needs.  For many years I have routinely recommended my patients drink a minimum of 6-8 glasses of water a day in addition to whatever other liquids they might ingest such as the recommended vegetable juices.  More recently, after giving greater thought to the subject, I have been recommending now 8-10 glasses a day, along with one half teaspoon of good quality sea salt, such as Himalayan or Celtic Sea Salt.  And, I have been surprised by the unexpected results.  
Recently, one patient's cholesterol, despite intensive nutritional supplementation including those anti-cholesterol nutrients such as carnitine, etc. a proper organic diet and intensive detoxification routines, continued to rise toward the 300 level.  When I questioned him, he readily admitted that though I had suggested he consume 6-8 glasses of water daily, he assumed that the four glasses of prescribed carrot juice and a remarkable eight cups of organic herbal tea would serve as equivalents to drinking plain water, which he found tedious to do and distasteful.  When I instructed him that he immediately eliminate all herbal tea from his diet substituting instead the recommended water, within six weeks his total cholesterol dropped 63 points and his HDL, the alleged "good" cholesterol, went up considerably.  Water intake had done effectively in six weeks what many heart-friendly supplements and an ideal nutritionally replete diet had failed to do in a year.

Dr. Batmanghelidj provides an interesting explanation for such cholesterol drops, as I have now observed in my own practice.  Water certainly serves many functions in our body, as a solvent in the blood, as well as "filler" in the extra and intracellular spaces, but it also functions as a main adhesive in cell membranes, keeping them intact while yet fluid, allowing the necessary passage of molecules in and out of the cell.  As a polar molecule, water's electrically charged surfaces keep the complex molecules that make up the membrane itself in place, where they are supposed to be.  In a state of deficiency as the water level in the membranes falls, the movement of nutrients into the cells and wastes out becomes significantly less efficient, and the membrane structure itself becomes less stable.  In this situation, if chronic, the liver begins synthesizing and releasing cholesterol into the bloodstream; this lipid can then substitute for water as a last ditch adhesive in the cells, to keep their membranes functional.  So, an elevated cholesterol in the context of undiagnosed chronic water deficiency reflects the body's wisdom, rather than some random or genetic mystery.  
Dr. Batmanghelidj also makes a case that diabetes may be another result of chronic subclinical water deficiency. To understand his argument, as a start I think it would be useful to summarize, though briefly, what insulin does.  This hormone, through a complex receptor system and signal transduction in the target cells, drives glucose across membranes so it can be used by cells as an energy source.  Along with the glucose, other substances including potassium, certain amino acids, and importantly, water pass into the cell interior.  As Dr. Batmanghelidj points out, this insulin-stimulated flow of water from the extracellular to the intracellular space can be a problem with even mild dehydration, leading as it can to further depletion of the body's extracellular fluids and reduced blood volume.  Since neurons are 85% water in their healthy state and since the brain receives and requires fully 20% of our total blood supply, carrying with it oxygen and essential nutrients, the effect of vascular volume depletion can be catastrophic.  Dr. Batmanghelidj argues that to preserve its own blood supply and the integrity of its nine trillion cells, the brain, through prostaglandin and neurologic signaling, suppresses insulin synthesis and secretion.  This in turn reduces the constant flow of water into the various cells of the body, conserving water to satisfy the brain's own requirements.  Of course there's a tradeoff, reduced fluid supplies to most cells in order to meet the water demands of the central nervous system.

To complicate matters, deficiency in salt (sodium chloride), an essential nutrient, often accompanies and complicates subclinical as well as overt dehydration.  This is particularly true in our current medical climate, in which physicians generally ignore the importance of adequate water intake at the same time demonizing salt, ignoring the mineral's many essential biochemical functions.  Among its many responsibilities, sodium chloride is an essential component of the extracellular fluids, helping to maintain its normal osmotic state.  In salt deficiency, the extracellular "sea" becomes dilute to the point water will flow into the area of higher density within the cell, contributing to the further depletion of extracellular fluids.  But as the pancreatic beta cells reduce insulin secretion and blood glucose levels rise in response to dehydration, glucose can substitute for sodium in the extracellular space, maintaining normal osmotic balance while reducing the potentially dangerous excessive flow of water into the cells.  In this vision, diabetes serves as an appropriate response to a difficult situation, chronic dehydration, reorganizing basic physiological processes as the disease we call diabetes in order to preserve our brain health. 

Dr. Fereydoon Batmanghelidj 
In his writings, Dr. Batmanghelidj perceives diabetes as a problem primarily of insulin suppression, which helps compensates for significant water and salt deficiency.  We, however, in our office, see the situation a bit differently, and with greater complexity.
As to some background, my colleague Dr. Linda Isaacs and I offer a very intensive nutrition program for the treatment of cancer and other serious illness, involving three basic components: individualized diets, individualized supplement regimens, and "detoxification" routines such as the coffee enemas.  The diets we prescribe can range from largely plant based, raw foods (always organic of course) to an Atkins-type largely fatty red meat plan (all grass fed). We base our specific dietary and supplement recommendations on the state of the each patient's Autonomic Nervous System (ANS), that collection of neurons that regulate virtually all physiological processes including respiration, cardiovascular activity, digestion, endocrine secretion, and immune function.  Neurophysiologists further divide the Autonomic Nervous System into two branches, the Sympathetic Nervous System (SNS) and the Parasympathetic Nervous System (PNS) which work in opposition to each other but synergistically to regulate metabolism from moment to moment, as our activities, needs, and stresses change.  For example, keeping the discussion brief, when the sympathetic system fires, heart rate and blood pressure increase, and blood shunts from the digestive organs and skin to the brain.  When the parasympathetic neurons fire, an opposite series of events follows, with blood flowing more readily to the digestive system and skin, and less so to the brain.  Of course, in classical physiology the SNS represents the stress nervous system which mobilizes the body's resources to deal with any minor or major difficulty in our lives, sending blood to the brain so we can think fast and to our muscles so we can react quickly as needed, while shutting down non-essential – at least in the stressful moment – processes like digestion. In contrast, the PNS acts more as the system of repair, rebuilding, and regeneration, responsible for the breakdown of food, the absorption, assimilation, and utilization of nutrients.

We believe certain patients have a strong sympathetic system, and a corresponding weak parasympathetic system.  This has relevance to our discussion, since when the sympathetic system fires, its active nerves suppress pancreatic insulin secretion while at the same time stimulating the breakdown of body proteins and storage carbohydrates into simple glucose, hence ultimately raising blood sugar.
In such patients with a strong SNS, the brain, perceiving chronic even low grade dehydration as a significant danger and physiologic stress, further activates the already hypertonic SNS, suppressing insulin release still more and encouraging glucose production.  If prolonged without resolution of the underlying dehydration, the scenario outlined by Dr. Batmanghelidj ensues, with the brain trying to maintain extracellular and essential blood volume by reducing insulin secretion and increasing the osmotic effect of glucose in the extracellular fluids.  In such patients, we prescribe a diet and supplement regiment aimed at reducing sympathetic tone, at the same time increasing PNS activity.  But if we don't also correct dehydration with adequate water intake, the SNS will keep firing, determined to keep blood flow to the brain intact.
In another group of patients we find a strong parasympathetic nervous system, and a correspondingly weak sympathetic system, and in them diabetes has a different origin, and a different course.  In contrast to the SNS, when the PNS nerves activate they directly stimulate the pancreatic beta cells to synthesize and release copious amounts of insulin into the bloodstream.  Consequently, these patients, even when healthy, tend toward high blood insulin and a lower than "normal" blood sugar, since glucose will be shunted out of the blood and into the cells rather continuously.   
With dehydration, even low grade, chronic dehydration these "Parasympathetic Dominants" as we call them, must also work to conserve extracellular fluid volume.  However, over time though they continue to secrete excess insulin, in response the receptors for the hormone situated on target cells withdraw from the membrane, neutralizing its glucose-driving effect no matter how high the insulin level goes. We end up with the paradoxical situation of high blood insulin, coupled with high blood sugar – what contemporary researchers refer to as "insulin resistance," a syndrome I associate primarily if not exclusively with an overly strong parasympathetic system.  But the end result, in a state of dehydration, is the same as insulin suppression in the "Sympathetic Dominants", less water seeping into cells and higher extracellular glucose acting as an osmotic pull to keep water where it is most needed in the bloodstream.  With these patients we prescribe a diet and supplement regimen designed to suppress the overactive PNS and stimulate the weaker SNS.  But in addition to appropriate diet and supplement programs, adequate water and with it salt are a must.

Though I found the clinical results of increasing water impressive, I became intrigued by my patients reporting significant improvement in their overall energy as well as their cognition, often within days of upping their water while at the same time reducing ingestion of dehydrating liquids like tea.  I began to suspect a fair amount of fatigue – both severe in Chronic Fatigue Syndrome, and less so in the typical malaise reported by so many in this day and age – has, as a significant component, chronic low-grade dehydration.
My clinical observations led me to an intensive review of the literature on cellular energetics, both academic and more popular, including the books of Dr. Batmanghelidj, many of them well-referenced.  I began to suspect that everything I had been taught about the subject of water in my highly "sophisticated" biochemistry courses in medical school may have been very much misguided.  Of course, it has been long dogma, for at least 50 years that our cells synthesize the energy they need from the breakdown of food stuffs, including complex carbohydrates, proteins, and fatty acids into glucose, a six carbon sugar.  Ultimately, or so the teaching goes, each molecule of glucose provided either directly from diet or indirectly from the conversion of certain amino acids and fatty acid break down products, gets channeled into glycolysis, a series of ten complex reactions occurring within the cell cytoplasm.  This sequence of molecular events ultimately reduces glucose to the two carbon molecule pyruvate.  In the process, two molecules of adenosine triphosphate (ATP), the cell's main storage molecule for potential energy, form.  In ATP, potential energy resides in what are called "high energy phosphate" chemical bonds, where it is held in reserve until released.   I might add that biochemists consider a two molecule production of ATP trivial for all the complicated enzymatic efforts involved in these initial steps of glucose metabolism. 
From this point, the pyruvate enzymatically transforms into another two carbon molecule, acetyl-Coenzyme A, which then gets directed into one of the many mitochondria, those small organelles sitting within the cell cytoplasm considered as the main site of energy synthesis in mammalian cells.   As an aside, mitochondria have a distinct micro-structure, with two membranes encasing the organelle interior, or matrix, and containing its own unique mitochondrial DNA that in us comes only from our mothers.
Here in the mitochondrial matrix the pyruvate offspring acetyl-Coenzyme A goes through a second series of eight chemical reactions known collectively as the citric acid or Krebs cycle, yielding another two molecules of ATP, still a paltry amount for all the complicated biochemistry.  But then quickly, in yet another series of complex series of steps known as oxidative phosphorylation occurring on the mitochondrial membrane, hydrogen atoms released from the breakdown of glucose enzymatically convert into positively charged hydrogen ions and a single negatively charged electron.  This electron passes in turn through a series of electron transport reactions yielding an additional and now substantial 34 ATP molecules.  Think of relay runners passing the baton in turn, as the electrons move along the steps of oxidative phosphorylation.  So in total, each single molecule of glucose travelling into the glycolysis-citric acid cycle-oxidative phosphorylation pathways forms a total of 38 ATP molecules – long thought, in fact thought even today, to be the main and the only source of energy to drive the thousands of cellular reactions occurring each second.
In essence, this hypothesis taught as fact, this construct – and that's all it is, a construct - assumes at its core that our food either directly or indirectly provides the molecule glucose needed as the starting point for these reactions.  There is, or so I was taught, no other way for our cells to synthesize usable energy and survive, other than from the breakdown of the materials we ingest as food.
Instinctively, I began to question this traditional view of cellular energetics, observing over and over again the rapid improvement in energy in my patients with an increase not in food, but in water.  How could that be?  
As a first point, biochemists state in the citric acid cycle the step-wise reactions of acetyl-Coenzyme A release 20 neutral-charge hydrogen atoms, whose further reduction into hydrogen ions and an electron allows for the large numbers of ATP molecules synthesized during oxidative phosphorylation.  But where one might ask, do these hydrogen atoms, absolutely critical for the creation of adequate ATP in this process, come from?   They come from one place, and one place only, water.  In the chemical process known as hydrolysis, water – which is remember, two hydrogens combined with one molecule of oxygen - reacts with those molecules originating from the metabolism of glucose, releasing the hydrogen atoms so crucial in the succeeding steps in the ATP production line. In retrospect, knowing what I know now, it is interesting to note that in the textbooks, the authors when discussing cellular glucose metabolism invariably mention water almost in passing, as some secondary player in the process.  Yet it is far more, it is absolutely critical, as critical as glucose itself, for without adequate water insufficient hydrogen atoms will be available to produce the high levels of storage ATP energy needed to fuel every reaction in every cell in the body.  
From my own clinical observations and from Dr. Batmanghelidj's writings, I suspected low grade chronic dehydration – which he reports and which I believe as well – affects the great majority of us Americans.  This overall subclinical deficiency curtails water availability even at the level of the cell cytoplasm and mitochondria, in turn reducing production of ATP and leading to all manner of disability, from chronic fatigue to, Dr. Batmanghelidj argues, auto immune disease, even cancer.  This shouldn't be surprising, since in one sense disease, whatever its form and whatever the name the experts give to it, represents at its core a state of cellular energy inefficiency.  
I suspected the rapid improvement in energy in many of my patients reflected an improvement in the water mechanics inside the cell, particularly in those neurons within the brain.  The brain weighs a mere two and a half or so pounds, yet uses 20-25% of all the body's energy output, making it a highly metabolically active organ.  And its nerve cells consist of 85% water, in contrast to most other body cells whose water content falls somewhat lower, at 75%.  Again, though physiologists and biochemists have long known this fact, they present this information as an aside in the textbooks, without editorial comment, where here comment would be useful.  The brain needs water, a lot of water, to manufacture the enormous amounts of ATP needed to fuel its complex regulatory activities.  Even slight borderline subclinical dehydration that reduces the water content of these neurons inevitably will play havoc on glucose metabolism, ATP production and ultimately on cellular energetics, leading, I believe, to at one end of the spectrum a mild state of fatigue, depression, malaise, and at the other end of more serious water deficiency, neurological disease such as Parkinson's, even Alzheimer's.  
The story gets even more interesting, beyond the pivotal role of water in the breakdown of food-derived glucose in our various cells.  I must give credit to Sayer, who has done a masterful job presenting evidence that scientists such as Gerald Pollack now question, as have I and Dr. Batmanghelidj before me had, this standard model of cellular energetics requiring glucose from foodstuffs as the penultimate starting point.  Some now suspect that in another hydrolysis event, in this case the reaction of water with melanin pigment found in the retina of our eyes and throughout our skin, may provide a far greater supply of ATP than that created from the breakdown of foodstuffs and the metabolism of glucose in the usual sequence of glycolysis-citric acid cycle-oxidative phosphorylation.
I agree with the very smart scientists proposing this alternative melanin pathway to energy formation having little to do with food – but much to do with water - but also suspect there exists an additional ATP manufacturing scheme found not just in the eye and skin, but in every cell in our body, all 100 trillion of them.  It has been long known that the interior of the cell, loaded as it is with all manner of proteins, peptides, fats, and electrolytes, particularly the positively charged potassium and its adjuvant negative chloride, exhibits a higher osmolality, that is, it is denser than the surrounding extracellular fluid that baths all cells and which contains sodium as its main positive ion. Scientists have precisely calculated this ratio of the density of the cell interior compared to the exterior extracellular fluid in a healthy cell at 1.1 to 0.8. Consequently, water, which will invariably flow from a solution of lesser concentration to a solution of greater concentration across a permeable membrane, will tend to pass continually into our cells, bringing along with it sodium while pushing potassium out.  This is a constant process, 24 hours a day.  To survive, our cells must expel the extra water and sodium, while drawing in the lost potassium.

Our cell membranes possess an elaborate series of enzymes taught to all first year medical students as the sodium-potassium ATP pump, which requires high energy ATP molecules to fuel the reverse expulsion of water and sodium out of cells.  However, my well-intentioned professors, at least in my experience, failed to teach a fact that I find so crucial to understanding cellular energetics.  As it turns out, the movement of water into cells through the membrane, as Dr. Batmanghelidj reports from the literature, operates as a microscopic hydroelectric turbine, yielding in the rapid flow more ATP than the process consumes!  As an analogy, in a hydroelectric dam the high speed plunging of water down an elevation gradient from higher ground to lower creates energy that can easily be converted into what we call hydroelectricity, energy from water.  On a smaller scale at the cell membranes a similar process plays out, endlessly during the life of every cell in our every organ.  This constant flow of water into cells isn't, as I had thought based on my medical school learnings, just an inconvenience, a problem that fortunately our cells have solved with the ATP pump, it may very well turn out to be our most significant source of ATP energy.  Dr. Batmanghelidj believes up to 90% of all energy stored as ATP comes not from the breakdown of glucose, but from the hydroelectric processes in these cation pumps at the cell surface.
A further point warrants mention, illustrating the important, crucial role of water in the energy mechanics of the cell.  As should be clear by this point, in all our cells ATP represents the primary repository of potential energy used in all cellular processes.  There are, to be fair, other, less significant sources such as GTP, guanosine triphosphate that like ATP, stores potential energy in phosphate bonds.  But whether we consider ATP or GTP or both, these two molecules release energy as needed through, once again, hydrolysis, the reaction of these molecules with water.  Interestingly, the researchers George and colleagues (as discussed by Dr. Batmanghelidj) calculated the actual total energy released from the hydrolysis of ATP with water.  ATP itself, in its high-energy phosphate bond, contains the equivalent of 600 units of energy relatively speaking.  However, the hydrolysis of ATP to ADP (adenosine diphosphate) eventually releases a total of 6,435 units of usable, available energy, more than ten times the amount contained as potential energy in ATP itself.  In effect, the very reaction of hydrolysis releases far more energy than is contained in the high energy bond itself.

So, in summary, water seems to be at the center of cell energetics. This is true whether we stick to the traditional view of ATP production from the metabolism of glucose, a process in which hydrolysis of water yields the lion's share of ATP, or adopt more contemporary positions that that water mechanics, and water energetics, involve far more than the traditionalists teach.  We must today, in addition to the glycolysis pathways, consider the creation of ATP at various other points and in various other processes, including the hydrolysis of melanin and at the hydroelectric cation pumps of the cell membrane.  Then there is the hydrolysis of ATP itself, in which the sum total of energy released due to water exponentially exceeds the potential energy contained within the molecular bonds. 


If we allow that water provides the spark for energy creation, we must then reconsider the potentially short and long term catastrophic effects of even borderline dehydration that compromises cellular energetics, cellular efficiency, and inevitably, our own health. Dr. Batmanghelidj insists we all need to cut out all caffeine containing and most other non-water fluids, substituting instead a full 8-10 eight ounce glasses of plain water daily, including WITH meals contrary to popular teaching.  In addition, he recommends we also ingest for each 10 glasses of water one-half teaspoon of good quality mineral-containing sea salt, such as Celtic or Himalayan, available in any health food store.  With increased water intake, we will lose salt, an essential nutrient, so we need to make up the difference.  And please, don't rely on your sense of thirst to determine water needs – in chronic dehydration, from which most of us suffer, our thirst thermostat in the brain down regulates so we learn not be thirsty, even when we need water.  Forget the traditional teachings that we should drink only when we are thirsty, and that salt is our enemy.  Both ideas, both principles should be discarded forever.  And as Dr. Batmanghelidj reports and as I can confirm, I have seen patients with chronic high blood pressure on multiple medications including diuretics, whose blood pressure went down and the medications were discarded when they increased their water and gradually, even their salt intake.  But that is

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