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Acid-Base Balance for your patients - naturally! SCIENTIFIC INFORMATION (English Translation) Acid-Base-Balance for your patients – naturally! SCIENTIFIC INFORMATION (English Translation) 2nd edition 2008 PASCOE VITAL GmbH D-35383 Giessen Tel. 0641/7960-0 · Fax 0641/7960-123 [email protected] · www.pascoe-vital.de All rights, including copying, reproduction, photomechanical reproduction and translation are reserved. 3 CONTENTS CONTENTS LATENT HYPERACIDITY ............................................................................... 6 OSTEOPOROSIS AND NUTRITION ............................................................ 26 Insidious, unnoticed, with no clinical symptoms ........................................ 6 Osteoporosis is among the 10 most economically significant widespread diseases .......................................................................... 26 PRINCIPLES OF THE ACID-BASE BALANCE ................................................... 7 Our skeleton – more than just our external frame.................................... 28 Buffer systems ensure that physiological pH-values are kept constant .......... 9 Bone fulfils an important function: it acts as a reservoir for protons and bicarbonate dispensers ............................................... 29 How an acid particle is eliminated depends upon whether it is a volatile or a fixed acid ................................................... 10 Carbon dioxide is a volatile acid and is eliminated via the lung........................................................................ 13 Protons are fixed acids and are eliminated by the kidneys....................... 13 Bone fulfils its important function as a buffer at the expense of its mineral density .............................................................. 30 Hyperacidity increases with age, but acid elimination capacity declines ................................................. 32 The connective tissue functions as the transport route between the cell and the blood .................................................... 14 When diet alone is no longer enough to protect the bones ...................... 35 The bicarbonate buffer is the most important extracellular buffer .............. 15 The excretory organs adapt their metabolism to the conditions................. 17 BASENTABS pH-balance PASCOE® – natural bicarbonate for effective deacidification ..................................... 37 WHEN THE ACID-BASE BALANCE IS DISTURBED ........................................ 20 APPENDIX ............................................................................................... 42 The pH-value becomes derailed: acidosis and alkalosis .......................... 22 Frequently asked questions .................................................................. 42 A protein-rich diet lacking in fruit and vegetables can cause latent hyperacidity..................................................................... 24 International specialist literature extract ................................................. 46 The acid burden caused by a food can be quantified: PRAL .................... 24 Glossary ........................................................................................... 56 Chronic latent acidosis causes brittle bones ........................................... 25 Literature ........................................................................................... 60 4 Bicarbonate: protective shield for the bones .......................................... 36 Food table......................................................................................... 54 5 LATENT HYPERACIDITY PRINCIPLES OF THE ACID-BASE BALANCE LATENT HYPERACIDITY PRINCIPLES OF THE ACID-BASE BALANCE Insidious, unnoticed, with no clinical symptoms The end products of metabolism in the form of hydrogen ions (protons, H+) feature thus in the acid-base theory: the concentration of hydrogen ions (protons, H+) is the measure for the pH-value. Living is a metabolic process. Our whole body undergoes continuous renewal, which can adapt dynamically to meet external demands. The energy and the nutrients required for these renewal processes are obtained from nutrition. In the course of this, depending on the metabolic status, various end products are produced, some of which must be eliminated. Acids (acid valences, protons) are one of these endproducts . Normally our body manages to dispose of these acids, because it has a variety of mechanisms for maintaining the equilibrium of the acid-base balance. The acid particles migrate from the site of their production– the cells – through the connective tissue into the blood and from here are transported to the kidneys or the lung. If excess acids are constantly being produced in our metabolism, more and more acid particles crowd on to the motorway in our body, resulting in a traffic jam in the elimination process: the acids remain in the connective tissue and overtax the body’s buffer systems. The consequences are insidious: there are no clinical symptoms as yet. The pH-value of the blood is still in the physiological range and the buffering capacity in the blood is not yet decreased. However, this is only possible because bones and muscles step in as buffers, in order to maintain the buffering capacity in the blood. This condition is known as latent acidosis, tissue acidosis or hyperacidity. We are now right in the middle of the acid-base balance of the body. Since it is regulated by a complex interaction, the main features of the process should be outlined here to provide a refresher and improve understanding: 6 pH=-log [H+] H+ pH 1 3 5 7 acid 9 neutral 11 13 alkaline Fig.1: The definition of the pH-value The lower the pH-value, the higher the concentration of free H+ ions. The pH-value scale comprises values from 0 to 14, where a pH-value of 7 is classified as neutral. In pure water (at 25 °C), 10–7 mol/L hydrogen ions are present, because water is present not only in the form of H2O, but also always to a small extent in the dissociated form, i.e. as a proton (H+) and a hydroxide ion ( OH- ). H2O H+ + OH– The negative decadic logarithm of 10–7 is pH 7. Stronger acids release more protons in solution, and strong acids release all protons; the pH-value is lowered, and the solution becomes acid. If the relative proportion of H+ ions decreases, the pH-value rises, and the solution becomes alkaline. 7 PRINCIPLES OF THE ACID-BASE BALANCE PRINCIPLES OF THE ACID-BASE BALANCE Constant pH-values in the blood, cells and the individual organs is essential, since fluctuations in the pH-value affects many metabolic processes, such as the structures of proteins and those of the connective tissue. The bioavailability of oxygen, the permeability of the membranes and the distribution of electrolytes also change depending on the pH-value. Saliva pH 6,7 – 7,2 Intracellular pH 6,9 (ca.) Skin pH 5,5 Blood plasma, connective tissue fluid pH 7,35–7,45 Milk pH 6,6– Gastric juice pH 1,2–3 Sweat pH 6,6–7,0 Pancreatic secretion pH 8,6 Urine pH 6,9 (ca.) Deviations from the physiological pH-values therefore result in serious malfunctions. In order to avoid this, the body has various regulation mechanisms: Buffer systems ensure that physiological pH-values are kept constant The pH-value is regulated both by buffer substances and by physiological processes, which include respiratory immediate control and slowly adapted renal processes. The buffer systems are closely linked and are found on an organic, intra- and extracellular level. Buffers are mixtures of weak acids and their corresponding bases, which can release or absorb release protons. This does not alter their concentration in the solution, so that the pH-value does not change. The buffer capacity is a measure of how many H+- or OH–- ions can be added without changing the pH-value. The acid burden at first causes a reduction in buffer capacity. Only when large quantities of acid are added the buffer capacity is exhausted and the pH-value changes. The buffer capacity is highest in the range around the pKS value (+/-1) of the acid. This is the pH-value at which the acid and its corresponding base are present in the same concentration. Thus it describes a state of equilibrium between acid and base. As soon as the ratio between the acid and its conjugated base shifts, the buffer capacity falls. Intestine pH 4,8–8,2 Stool in healthy person pH 5,5–6,5 Fig. 2: Physiological pH-values in our organism 8 9 PRINCIPLES OF THE ACID-BASE BALANCE PRINCIPLES OF THE ACID-BASE BALANCE How an acid particle is eliminated depends upon whether it is a volatile or a fixed acid Acids are produced in the human organism in the energy metabolism or in the renewal, degradation and construction reactions as end products. Aerobic Carbohydrates Glucose Fats Fatty acids Proteins Amino acids CO2 + H2O anaerobic Carbohydrates/Amino acids Lactic acid (lactate) Glucose deficiency Fatty acids Keto acids Sulphur-containing amino acids N groups of amino acids Other catabolic processes Purines Nucleic acid Under aerobic conditions fats, proteins and carbohydrates are burned to within the cell to CO2 und H2O for the purpose of obtaining energy. The CO2 continues to be used to a minor extent in the metabolism for carboxylation reactions, but it is mainly released via the lung as a so-called volatile acid. So-called fixed acids are also produced in cell metabolism by nitrogen, sulphur and phosphorous compounds. However, these fixed acids cannot be eliminated by respiration via the lung and therefore have to be eliminated by the kidneys. Sulphuric acid (H2SO4) Ammonium ions (NH4+) Uric acid Pyrimidines Ammonium ions (NH4+) Phosphate Phosphoric acid (H3PO4) Fig.3: Metabolic end products are often acids 10 11 PRINCIPLES OF THE ACID-BASE BALANCE PRINCIPLES OF THE ACID-BASE BALANCE Carbon dioxide is a volatile acid and is eliminated via the lung Nutrition and metabolism Cheese H+ H+ H+ H+ H+ Meat/ sausage Grainproducts Milk/ yogurt H+ H+ H+ H+ Fruit/ vegetables H+ H+ H+ H+ H+ CO2 Blood pH-value HCO3- CO2 penetrates the cell membrane and after passing through the intercellular substance migrates into the blood vessels. Now an important intracellular protein buffer comes into play here: haemoglobin. CO2 diffuses from the blood into the erythrocytes and is immediately converted by carbonic anhydrase into bicarbonate and a proton. While the bicarbonate temporarily migrates into the blood plasma and can become active as a buffer substance, the ferrous haemoglobin in the erythrocytes acts as a buffer for the protons produced during their transport to the lungs. In the lungs bicarbonate again penetrates the red blood cells, where it is converted back into CO2 in the reverse reaction by carbonic anhydrase and can be eliminated by respiration as a gas. Under physiological conditions, the respiratory protons pose no problem to the body, since the corresponding base is immediately produced at the same time and is also available to the body as a buffer at the time of transport. Kidney Lung Bicarbonate buffer system HCO3- CO2 CO2 + OH- H+ H+ Protons are fixed acids and are eliminated by the kidneys H+ Protons take the following pathway to elimination: HCO3- Metabolically active cell Connective tissue Blood Connective tissue, bone and muscles Excretory organ (liver, kidney, intestine, lung, skin) Fig. 4: Physiological regulation of the blood pH-value Fig. 5: The route of protons to the kidney 12 13 PRINCIPLES OF THE ACID-BASE BALANCE PRINCIPLES OF THE ACID-BASE BALANCE In the cell system The most important intracellular buffer is the phosphate buffer; sources are for example ATP, ADP and sugar phosphates. H3PO4 H+ + H2PO4– HPO42– + 2H+ PO43– + 3 H+ The connective tissue functions as the transport route between the cell and the blood In the connective tissue On the way between the cell and the blood, the protons pass through the extracellular space (also known as: matrix, extracellular matrix, Pischinger’s space, interstitial space). The proteoglycans and glycoproteins of this connective tissue with their many negatively charged groups act as ion exchangers and stationary buffer substances. This means that protons can accumulate on these connective tissue molecules. They can “park” here until the blood and the elimination organs have enough free buffer capacity to transport the protons away. Structure of a proteoglycan H+ H+ H+ In the blood The blood buffers help to transport the protons to the excretory organs and are primarily responsible for keeping the blood pH-value constant. A high buffer capacity in the blood ensures on the one hand the stability of the blood pH is kept constant even under extreme burdens and on the other hand the removal of the protons “parked” in the connective tissue. The blood has four buffer systems altogether: the bicarbonate and phosphate buffer, the haemoglobin and plasma proteins. Many proteins can absorb and release protons; in particular the imidazole ring of the amino acid histidine. Plasma proteins are extracellular buffer proteins. The bicarbonate buffer is the most important extracellular buffer CO2 + H2O H2CO3 HCO3– + H+ The pK-value of the bicarbonate buffer is 6.1, thus below the adjusted pHvalue of 7.4 in plasma. The highest buffer capacity would thus be expected at a pH-value of 6.1. This applies to a closed system. However, the bicarbonate buffer functions as an open system in conjunction with the lungs and the kidneys: on the one hand the bicarbonate concentration is regulated by the change in respiratory frequency. On the other hand, the kidneys are flexible in adjusting their elimination rate for fixed acids. H+ H+ H+ H+ H+ H+ Negatively charged glycoproteins bind H+ in the connective tissue Fig. 6: Proton binding in the connective tissue 14 15 PRINCIPLES OF THE ACID-BASE BALANCE Lung ventilation PRINCIPLES OF THE ACID-BASE BALANCE The degradation of weak organic acid anions, such as lactate and citrate, occurs even when bicarbonates are produced, which can thus be made available for the blood buffer. Normal CO2 CO2 + H2O H2CO3 HCO3- + H+ Blood CO2 Cell metabolism Fig. 7: The bicarbonate buffer as an open system The bicarbonate buffer is the most important blood buffer, thus it can be said that the pH-value of the blood depends on the ratio HCO3– and pCO2: pH-value ~ HCO3–/pCO2 (according to Henderson-Hasselbach equation) The major importance of this buffer system lies in the fact that the two buffer components can be regulated independently of each other and by different organs: The concentration of HCO3 by the kidneys and the liver and that of CO2 by the lungs. In the liver Metabolisation of organic acids takes place in the liver. This is directly linked with nitrogen degradation. The conversion of nitrogen compounds is determined by the current pH-value: if sufficient buffer base, that is, bicarbonate is present, 2 molecules of ammonia and 2 molecules of bicarbonate are bound together into urea. However, if there is a bicarbonate deficiency, the ammonia is bound to keto acids, producing glutamine, and the buffer base is thus conserved. 16 The excretory organs adapt their metabolism to the conditions In the lung The lung is responsible in conjunction with the erythrocytes for the elimination by respiration of volatile acids in the form of CO2. The respiratory frequency can be quickly adjusted (extreme case: Kussmaul breathing). However, since one molecule of bicarbonate is used up with every proton eliminated by respiration, the buffer capacity of the blood decreases in excessive CO2 respiratory elimination. In the kidney The kidneys help to eliminate fixed acids, namely inorganic acids such as phosphoric and sulphuric acid, uric acid and ammonium ions. Only around 1 % of protons to be eliminated is eliminated in free form. The majority is regulated via the kidney buffer. The ammonia/ammonium buffer deals with around 60 % of the acids which occur: this buffer is produced in the renal cells themselves: via the enzymatic degradation of glutamine (s. Fig. 8). The second buffer in the kidney is the phosphate buffer. Around 30 % of protons are eliminated by this. H+ + HPO42– H2PO4– Bicarbonate is absorbed at the same time as the H+ elimination. 17 PRINCIPLES OF THE ACID-BASE BALANCE PRINCIPLES OF THE ACID-BASE BALANCE Ammonia/ammonium buffer Na NH3 + H+ NH4 H+ Phosphate buffer Na2HPO4 H+ Glutamin CO2 (5) H O 2 Renal cell HCO3Cl – Na+ - HCO3 Exchanger (4) K+ (1) K+ H2CO3 NH3 NH3 Stomach lumen Mucosa Blood + H+ (2) K+ H+ Pump H+ Cl – H+ Cl – NaH2PO4 (3) Cl – Parietal cell Renal cell Bicarbonate absorption HCO3- + H+ H+ CA H2O + CO2 Tubulus Na+ H+ + HCO3- Fig. 9: The alkaline flood HCO3- CA H2O + CO2 Renal cell CA -Carbonhydrase Fig. 8: The elimination of protons in the renal cell In the stomach Parietal cells in the stomach are responsible for the production of stomach acid (HCl). They are governed hormonally (e.g. gastrin, histamine) and vegetatively via the parasympathetic system (vagus nerve). 18 While hydrochloric acid is released into the stomach lumen, NaHCO3 arises at the same time and in adequate quantities. As a result the intracellular pHvalue can be kept constant. The bicarbonate is released by the parietal cells into the blood. At the same time together with mucin it forms the gastric mucosa, which can protect the cells from autodigestion. The phenomenon of the release of bicarbonate into the blood has been demonstrated in numerous studies and is described as the alkaline flood. The measurement of this alkaline flood can also be used to determine acid secretion. In the intestine After passage through the stomach, the acidic chyme is neutralised with help from the bicarbonate of pancreatic secretions. If neutralisation is not sufficient, the enzymes, which have their pH-optimum in the alkaline range at approx. pH 7-8, will not function adequately. 19 WHEN THE ACID-BASE BALANCE IS DISTURBED WHEN THE ACID-BASE BALANCE IS DISTURBED WHEN THE ACID-BASE BALANCE IS DISTURBED Lung ventilation Respiratory acidosis CO2 The physiological blood pH-value is about 7.4; the laboratory normal range has been set at pH 7.36 to 7.44. However, if the pH-value in the blood falls below 7.35, this is referred to as manifest acidosis; if the pH-value in the blood rises above 7.45, this is called manifest alkalosis. The acute condition of a disturbance in the acid-base balance can be diagnosed on the basis of its clinical symptoms and the clearly measurable deviation from the blood normal values. Manifest or clinical acidosis is life-threatening and must receive immediate intensive medical treatment. Depending on the cause of the change in the pH-value, a distinction is made between respiratory and metabolic acidosis or alkalosis. Lung ventilation CO2 + H2O H2CO3 HCO3- + H+ Blood CO2 Cell metabolism Fig. 11: Schematic diagram of respiratory acidosis Respiratory acidosis always occurs when the respiratory elimination of carbon dioxide is disturbed. The CO2 partial pressure in the alveoli and in the (arterial) blood increases, the buffer equilibrium is shifted to the right and thus an excess of H+ occurs. Metabolic acidosis CO2 CO2 + H2O H2CO3 HCO3- + H+ Blood CO2 Cell metabolism Fig. 10: Schematic diagram of metabolic acidosis If the renal elimination of H+ is less than the metabolic H+ occurrence, the lung must increase its CO2 respiratory elimination. Metabolic acidosis is the name given to metabolism-related hyperacidity. It develops as a result of an increase in the number of protons occurring in the body’s metabolism or their reduced elimination or a loss of bicarbonate. 20 21 WHEN THE ACID-BASE BALANCE IS DISTURBED WHEN THE ACID-BASE BALANCE IS DISTURBED The pH-value becomes derailed: acidosis and alkalosis ACIDOSIS ALKALOSIS The condition in which the buffering capacity of the blood is severely reduced, but no clinical symptoms are yet present, is known as compensated clinical acidosis: the acid excess is intercepted, but the body buffers fewer and fewer acid particles. The tissue acidosis or hyperacidity, also referred to as latent acidosis, characterises a situation in which the pH-value of the blood lies within the physiological normal range and also the buffering capacity of the blood is reduced only slightly or not at all as yet, but a chronic acid flood demands a high quantity of bicarbonate for buffering. In the long term, the body turns to other endogenous buffer reserves: bones and muscles. BUFFER Respiratory acidosis • Bronchial asthma • Pneumonia Respiratory alkalosis • Hyperventilation • Pregnancy Metabolic acidosis • Diabetic ketoacidosis • Anaerobic metabolism • Stomach drainage • Hepatic, pancreatic, renal insufficiency (age) • Sepsis / Inflammation • Diarrhoea • Hunger / Fasting • Intoxication Metabolic alkalosis • Increased metabolism of lactate, citrate • Loss of acid as a result of vomiting, fever A variety of symptoms are associated with hyperacidity in natural and empirical medicine. These include muscle and joint pain, increased susceptibility to allergies, inflammatory reaction or increased susceptibility to infections in the area of the mucous membranes and caries. For much of these there is as yet no scientific evidence of a causal connection. The importance of a well-regulated acid-base balance is increasingly recognised and is reflected in an everincreasing number of scientific publications in renowned scientific journals. Here osteoporosis, osteoarthritis, diabetes, gout and kidney stones are to the fore. Ongoing clinical studies continue to focus on the development of latent acidosis under severe physical stress, such as for example high-performance sports. Fig. 12: Causes of acidosis and alkalosis 22 23 WHEN THE ACID-BASE BALANCE IS DISTURBED A protein-rich diet lacking in fruit and vegetables can cause latent hyperacidity On the other hand, there is ample evidence to show that the diet plays an important role in the acid-base balance: a diet rich in meat and protein causes a permanent acid burden. Fruit and vegetables – although not vegetable foodstuffs in general– contain alkaline minerals, which form bases and thus unburden the acid-base balance. Grain products, however, are among the acidifiers. How therefore can one make reliable statements about acid burden? The acid burden caused by a food can be quantified: PRAL The scientists Thomas Remer and Friedrich Manz developed a model which is reasonably able to estimate the potential renal burden, i.e. the net acid elimination of the kidney, caused by food. From this the food source tables indicating PRAL-values (in mEq/100 g) were developed. Only the primary effects on the acid-base balance are reflected. This means: only those effects are considered which the food has on our body as a result of its chemical composition and its rate of absorption. Positive PRAL-values indicate that more acids arise in the balance as a whole than are used in the organism. According to this, cheese, meat and fish should be regarded as potent acidifiers; negative PRALvalues mean that the metabolism of these foods is base forming. Many types of fruit and vegetables are included in this group. The complete table can be consulted in the Appendix. 24 WHEN THE ACID-BASE BALANCE IS DISTURBED With the help of a similar calculation model, prehistoric diets were compared to today’s diet and analysed. Interestingly, the past diet had a far greater meat portion than today’s diet, and yet it resulted in alkaline nutrition. Our modern diet, because of its high proportion of grain products, refined sugar and hydrogenated/saturated fats and the low consumption of fresh fruit and vegetables, is unable to counteract acidic meat and protein consumption. In comparison to prehistoric diets, today’s foodstuffs are rich in sodium chloride and low in potassium and bicarbonate and their precursors. Today‘s Western nutritional habits should be regarded very critically, because they may have long-term negative effects on the health of our bones: Chronic latent acidosis causes brittle bones In 1994 Sebastian et al. reported in the renowned New England Journal of Medicine that even in normal endogenous acid production, a chronic burden exists for bone under Western nutritional patterns. This chronic burden increases the risk of osteoporosis through the loss of bone substance. Osteoporosis is a skeletal disease which is characterised by inadequate bone strength. This inadequate bone strength predisposes to an increased risk of fracture. If osteoporosis is present and one or more fractures have occurred as a consequence of the osteoporosis, this is referred to as manifest osteoporosis. 25 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION Osteoporosis is among the 10 most economically significant widespread diseases But it is not only the economic consequences which make clear the importance of the prevention of osteoporosis. In the first years, bone loss usually progresses without symptoms. But then the personal life of suffering begins for the person affected by osteoporosis; often with symptoms of the spinal column. Initially sharp back pain caused by a vertebral fracture is often not associated with the disease, because the vertebral fracture is not detected. If there are several fractures in the spinal column, the posture changes up to the extreme of hyperkyphosis (“dowager’s hump”). Respiration is restricted and gait steadiness is reduced, because the field of vision is restricted. In addition, the risk of suffering a fracture for example of the wrist increases, even in minor falls. In the worst case, the hip is broken simply by stumbling over the edge of a rug. This means long periods spent in hospital and even longer periods of recovery. One third of those affected die within the following year from the consequences of the fracture, and a further third becomes disabled. Osteoporosis is the crunch point of the Western way of life, so to speak. As well as a diet rich in meat, sausage and processed food, many of the features of our modern lifestyle are risk factors for the development of osteoporosis: smoking, lack of exercise, alcohol consumption. If hip fractures have occurred within the family, the risk for this disease also increases. Compromising our bone health means significant damage to our quality of life. An estimated 75 million people in Europe, the USA and Japan are affected by osteoporosis. On average almost one woman in four over the age of 50 and one man in eight over the age of 50 in the industrialised countries develops osteoporosis. UNO and WHO have classified it among the 10 most economically significant widespread diseases of the 21st century. The costs of osteoporosis for Germany were presented in 2006. According to this, the costs of osteoporosis amount to 5.4 billion euros annually. They are thus on a par with those caused by diabetes or ischemic heart disease. The largest proportion of the costs at 56 % arises from the in-patient treatment of more than 300,000 fractures per year. Our skeleton – more than just our external frame For many of us, our skeleton is simply our external static frame. It enables us to walk upright and, in conjunction with muscles and tendon, makes it possible for us to move. It also provides protection from injury for important organs such as the brain, the heart and the lungs. These functions are obvious, and we always become aware of them when we feel a stiffness somewhere: frozen shoulder, a strain in the back and pain in the foot for example after unaccustomed movement. In the worst case, the unexpected broken rib caused by violent sneezing, when the bone has already become brittle. But our bones fulfil more than just the obvious functions: they are storage organs for minerals, OSTEOPOROSIS AND NUTRITION There are a number of more recent studies which show the relationship between an unbalanced diet and osteoporosis: • Diet-induced subclinical acidosis is now recognised as a significant, pathophysiological factor in the development of osteoporosis (Tucker 2003). • Heaney documents how the type and quantity of protein consumed affects bone health (Heaney et al. 2007). • Thorpe et al. (2008) relate protein consumption to bone density and found that high protein consumption correlates positively, but high protein-sulphur consumption results in lower bone density. This study also highlights the fact that the type of protein is important for bone density. • There is a linear relationship between calcium elimination and net acid elimination (Fenton et al. 2008). Increasing acid elimination means higher calcium loss. 26 27 OSTEOPOROSIS AND NUTRITION which are accessed as required: almost the entire store of calcium (98 %) and around three quarters of the body’s phosphate is found in our over 200 bones. The complete stock of bones is remodelled during the entire course of life. Up until puberty, bone formation predominates, whereas in adulthood there is an equilibrium between formation and degradation, and essentially the existing bone is remodelled. Up to 20 % of bone is replaced annually. Three different cell types are involved in this bone remodelling: bone-forming osteoblasts, bone-degrading osteoclasts and osteocytes, which are responsible for the transport of nutrients. In the healthy body the activities of the osteoblasts and osteoclasts are in balance. The osteoblasts build the organic basic structure from collagen fibres and amorphous intracellular substance. The inorganic components are then stored in this organic frame: fluorapatite, carbon apatite, calcium carbonate and magnesium carbonate. The inorganic main component is hydroxylapatite Ca10(PO4) (OH) , which is essentially composed of 6 2 calcium and phosphate and forms a store for them. In total, around 65% of a bone is composed of inorganic components, 25 % of organic components and 10 % water. The regulation of bone metabolism is subject to various influences. Thus tensile and pressure loads e.g. through sport cause bone to thicken in the direction of the load and to strengthen for future stresses. The sex hormones oestrogen and testosterone also play an important role, as well as parathormone and calcitonin. The latter have an important function in ensuring a constant Ca2+ level in the blood and regulate as antagonists either the storage or the mobilisation of calcium ions in or from the bone. 28 OSTEOPOROSIS AND NUTRITION Bone fulfils an important function: it acts as a reservoir for protons and bicarbonate dispensers One aspect which has hardly featured in the standard literature to date is the important function of bone as a reservoir for protons and bicarbonate dispensers; it thus supports the acid-base balance of our organism as a buffer. Bone acts as a local buffer by collecting excess protons. In this context it is important to bear in mind that the physiological blood pH-value of arterial blood is 7.40 and that of venous blood is pH 7.36. However, the pH-value of the extracellular fluid around the bone cells is assumed to be below 7.36 and runs as a gradient depending on the metabolic activity of the cells and their distance from the next capillary. How and where does bone collect protons? There are negative charges on the surface of the bone, to which Na+, K+, und H+ ions are flexibly bound. If the pH-value falls to below 7.4 – which means of course that the absolute quantity of free H+ increases – the Na+ and K+ ions are exchanged for the free protons. The blood or the immediate extracellular fluid is relieved of the acid. However the bone loses sodium and potassium ions. At the same time calcium and carbonate is released from the bone. Around two thirds of the calcium present in the bone are firmly bound. However, one third can be released at any time into the systemic circulation. Calcium carbonate is dissolved out of this store. The carbonate ions can now buffer further protons in the blood; increased levels of calcium are eliminated renally. 29 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION Bone fulfils its important function as a buffer at the expense of its mineral density This is first of all a purely physicochemical reaction without the involvement of the bone cells. The illustration (13) shows schematically the exchange mechanism cation against proton on the surface of the bone: Ca 2+ Na+ CO32- K+ On the one hand the inhibition of bone-forming cells results in a decrease in collagen synthesis. At the same time the calcium influx is reduced, which is important for apatite formation. On the other hand acid stimulates bone-degrading osteoclasts, which are also activated by an increased release of parathormone. To sum up, this means a shift of bone remodelling processes towards bone loss; there is a loss of bone substance, which is associated with increased calcium elimination and is reflected in reduced bone density. HPO3H+ H+ H+ H+ acidosis H+ Bone H+ H+ H+ PO43- Alkaline salts Buffer acidosis 30 Ca2+ - HCO3 Fig.13: The physicochemical response in the bone metabolism to metabolic acidosis: (Krieger et al. 433) In the event of longer-term hyperacidity, cell-mediated calcium release also takes place: acid has a counter effect on the activity of the various bone cells: the activity of the osteoblasts is inhibited and that of the osteoclasts is increased. At a physiological pH-value of 7.4 the osteoclasts are practically inactive. If the pH-value falls to 7.1, their activity increases rapidly and remains at around the same level as pH-values fall. Even at a pH-value of 6.3, at which the survival rate of the osteoclasts is reduced, effective loss of bone substance takes place. Mineral Absorption CO32- Osteoporosis - H2PO4 Kidney Calcium is eliminated with the urine Ca2+ Fig. 14: Effects of chronic latent acidosis on bone metabolism 31 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION A: Blood concentration H+ 44 Blood [H+] (neq/L) Hyperacidity increases with age, but acid elimination capacity declines Hyperacidity increases with age, but acid elimination capacity declines. The problems of latent acidosis are exacerbated with increasing age. An adult with a typical Western diet already has low-grade chronic metabolic acidosis. The extent of this acidosis increases with age. Renal function also declines with the process of aging. Thus on the one hand the acid burden is increased, but on the other hand its elimination capacity declines. 42 40 38 36 34 160 140 120 100 80 60 r= 0,38 p<0,001 B: Blood concentration HCO3Plasma [HCO3-] (neq/L) GFR (ml/min/70 kg) 180 r=-0,69 p<0,001 28 26 24 22 20 20 40 60 80 Age (years) Frassetto, Morris et al., Am J Physiol (1996) 271, F1114-1122 Fig. 15: Renal elimination capacity declines with increasing age r= 0,47 p<0,001 80 100 120 140 GFR (ml/min/70 kg) 160 Frassetto, Morris et al., Am J Physiol (1996) 271, F1114-1122 Fig. 16 A+B: The effect of renal function on the concentration of H+ and HCO3- 32 33 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION When the kidney reduces the H+ elimination for a longer period, the lung can delay, but not prevent, the occurrence of acidosis. In persistent acidosis there is the threat of demineralisation of the bone. The effect of diet-related hyperacidity is thus even more pronounced on bone metabolism with increasing age and contributes to the risk of osteoporosis. This thesis is validated by the results of a worldwide survey (33 countries) on the incidence of hip fractures in women over the age of 50 (Frassetto, Nash et al. 2000). A highly significant positive correlation was shown between proportion of fruit and vegetable consumption and the occurrence of hip fractures (varied greatly between e.g. 0.8 (Nigeria) and 200 (Germany) per 100,000 inhabitants/year). A: Blood concentration H+ Blood [H+] (neq/L) 44 42 40 38 36 34 r= 0,40 p<0,002 26 In this context there is also discussion about the decrease in muscle mass as a result of exhausted glutamine reserves in the kidney cells: in order to be able to eliminate the increasing numbers of acids via the ammonia buffer, ammonia has to be produced in the intracellular metabolism. Glutamine acts as a source. If its reserves are exhausted, it receives additional deliveries from the muscle tissue. 24 When diet alone is no longer enough to protect the bones Plasma [HCO3-] (neq/L) B: Blood concentration HCO328 22 20 r= 0,40 p<0,002 20 40 Age (years) 60 80 Even if the population has become more diet-conscious according to a nutritional report of 2004, and the requirement of the German Nutrition Society (DGE) – five portions of fruit and vegetables a day – has in many cases sunk in, the implementation stills leaves a lot to be desired, partly because today’s lifestyle has booked a regular date with fast food meals. Mineral bicarbonate can help to supplement our diet so that hyperacidity can be avoided or counteracted. Fig. 17 A+B: The effect of renal function on the concentration of H+ and HCO3- 34 35 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION Bicarbonate is the body’s own natural, main buffer substance BASENTABS pH-balance PASCOE® – natural bicarbonate for effective deacidification Because: Bicarbonate is produced during the absorption of nutrients from the parietal cells and is released in the duodenum to neutralise stomach juices. In addition, bicarbonate is necessary as a buffering substance in the blood and is constantly used here. As a result, carbon dioxide is produced, which is eliminated by respiration via the lungs. In order to keep the bicarbonate pool of the organism at a constant level, it has to be continually replenished. Ideally directly, in the form of bicarbonate. BASENTABS pH-balance PASCOE® fulfil all the requirements for professional, effective deacidification. They are a mineral dietary supplement and contain a balanced alkaline mixture of bicarbonates and carbonates with the additional of alkaline magnesium. Calcium and magnesium are present in an ideal ratio of 3:1. Thus in addition to the natural blood buffer bicarbonate they also provide the important building block calcium to maintain bone health: BASENTABS pH-balance PASCOE® work exactly like the body’s own bicarbonate. The body’s own bicarbonate is the most important physiological buffer substance and is thus ideal for naturally reducing the intracellular and extracellular acid burden. Bicarbonate does not have to be metabolised first in order to be effective. Bicarbonate: protective shield for the bones The positive effect of bicarbonate on bone health has been proved by numerous scientific studies: • An improvement in the bone density of postmenopausal women was demonstrated after supplementation of bicarbonate (Sebastian, Harris et al. 1994). After 18 days of supplementation of oral sodium bicarbonate the clearly negative balance for calcium and phosphorus was reduced. A decline in bone loss and an increase in bone formation were measured with the aid of metabolic markers of bone metabolism. BASENTABS pH-balance PASCOE® have a very high acid-binding capacity (16.12/g) particularly in comparison with “lifestyle preparations” such as Basica hot and cold powder (3.45/g), Basica vital (0.82/g), Basica instant (0.75/g) and Basica compact tablets (10.82/g) (measurement of PASCOE September 2008). • In a 3-year study the same group showed that this effect lasted for a long period of time (Frassetto, Morris et al. 2005). • An intervention study with high and low protein consumption also showed that administration of sodium carbonate at a level of 5.85 g per day halts calcium loss. • Bicarbonate clearly reduced calcium elimination and bone loss in men and women over the age of 50 years. Bicarbonate can thus protect against latent acidosis and reverse a negative balance in calcium elimination. In this way bicarbonate can prevent loss of bone substance. 36 37 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION Productt/Manufactur Acid-binding capacity (SBK) United States Pharmacopeia XXX, Method 301 (as at: September 2008) PASCOE VITAL PASCOE VITAL Delta pronatura M.C.M. Klosterfrau Frisenius Medical Care Delta pronatura Protina Pharm. Nestmann Pharma Nestmann Pharma Protina Pharm. Protina Pharm. Protina Pharm. Protina Pharm. 16,55 16,14 13,95 12,52 4,75 3,45 BASENTABS PASCOE BULLRICHs VITAL (powder) TAXOFIT Basis plus (tablets) 11,82 BICANORM (tablets) 11,73 BULLRICHs VITAL (tablets) 10,82 9,20 BASENPULVER PASCOE BASICA Compact (tablets) NEMABAS (tablets) • Bicarbonates support the natural alkaline flood, which occurs in the blood physiologically after meals. Citrates are removed from the blood circulation very quickly after being taken. • Bicarbonates remove acids which have accumulated in the connective tissue. Citrates are not suitable for reducing this acid burden. • Citrates have to be metabolised; they are as it were a preliminary stage of bicarbonate and also have a calorie burden. • Bicarbonates therefore act more quickly than citrates. • Bicarbonates are safe: the body has a high capacity to regulate bicarbonate floods. NEMABAS (citrate powder) BASICA hot + cold (powder) BASENTABS pH-balance PASCOE® are 0,82 BASICA VITAL • small tablets and therefore easy to swallow 0,75 BASICA (instant) • free from flavourings, colourants and preservatives, 0,44 BASICA (Sport) 0 There are also products on the market for nutritional supplements which are composed on the basis of alkaline citrates. Bicarbonates have many advantages in comparison with these: 2 4 6 • sugar, lactose, and gluten free 8 10 12 14 16 18 Acid-binding capacity (milli equivalente / g) Fig. 18: The acid-binding capacity of BASENTABS pH-balance PASCOE® • suitable for children older than 4 years • permitted for use in pregnant and lactating women • low-calorie (less than 1 kcal per daily dose) Each pack of BASENTABS pH-balance PASCOE® also contains 21 pH-teststrips to determine the pH-value of the urine. These are used to • very quickly and simply establish whether an acid-base imbalance is present and • directly check success after taking BASENTABS pH-balance PASCOE®. 38 39 OSTEOPOROSIS AND NUTRITION OSTEOPOROSIS AND NUTRITION This is how to produce the daily profile of the urine pH-values: Between three and five urine pH-measurements should be taken spread over the course of the day: Ideally the values lie within the white curve. Before breakfast and in the evening the values are in the acid range. This is normal. During the day however they should be in the alkaline range, i.e. higher than the pH-value of 7. The pH-values fluctuate in the course of the day. If the pHvalues are in the acid range during the day as well, this is a clear indication that the patient is hyperacidic or the kidneys can eliminate only insufficient acid. pH 5.6 – 6.8 = acid pH 7.0 = neutral pH 7.2 – 8.0 = alkaline pH values BASENTABS pH-balance PASCOE® and BASENPULVER pH-balance PASCOE® supply important minerals such as calcium, magnesium, sodium and potassium, for cell function, the muscles and to strengthen the bones. One daily dose (6 tablets) supplies almost half the daily calcium requirement and more than half the daily magnesium requirement. For optimum efficacy 2-3 BASENTABS pH-balance PASCOE® are taken 3 times daily after meals with plenty of fluid. BASENPULVER pH-balance PASCOE® is stirred into water and drunk once daily. Time of day Fig 19: Daily profile of urine pH-value 40 41 APPENDIX I Frequently asked questions When should alkaline agents be taken? Whether alkaline supplements should be taken with food or strictly outwith mealtimes is a subject which is variously propagated and discussed. Taking them with meals does cause partial neutralisation of the necessary stomach acid and an increased development of carbon monoxide in the stomach, which can manifest as eructation. But it has the advantage of the bicarbonate and the minerals being mixed with the food, so that physiological conditions prevail for the absorption of nutritional components. Practitioners have observed that adding alkaline agents to food is well tolerated by most people– something like a rebound effect is assumed, that is, stimulated gastric juice production after neutralisation. Nevertheless it is generally recommended that they are taken after meals so that – especially in subacid patients – there is no danger of neutralisation of stomach acid. How can I detect if my patient is hyperacidic? There are various possibilities for detecting hyperacidity. However, there is unfortunately no direct diagnosis of the acid burden of the connective tissue. Acid-base titration according to Sander 5 urine samples are taken at defined times and sent in a shipping tube with a stabilising agent to a laboratory, which carries out the acid-base titration according to Sander. Here the buffering capacity of the urine is measured, which allows conclusions to be drawn about the buffer reserves of the whole organism. A diurnal curve is produced from the measured values (rhythmic change of the acid-base flood) and the average acidity quotient (indication of the degree of acid burden) is calculated. 42 APPENDIX I Blood gas analysis according to ASTRUP This method allows very precise conclusions to be drawn about the acid-base balance, but it has the disadvantage that he parameters to be examined are very unstable and therefore the sample must be examined at once. Anion gap in serum (also in 24 h urine) Sodium and potassium ions make up 95 % of serum cations. Chloride and bicarbonate ions represent 85 % of serum anions. The difference between measurable cations and anions is referred to as the anion gap, which corresponds mainly to organic and inorganic acids, phosphate and anionic proteins. Acidosis results in an enlargement of the anion gap, and alkalosis in a reduction. Provocation test This test was described at the beginning of the last century by van Slyke: One tablespoon of bicarbonate, taken in the morning, must cause clear alkalisation of the urine in the course of the following hours. If the urine pH-value does not change, hyperacidity is assumed, because this is a sign that the body urgently needs the buffer base and is therefore retaining it. Daily profile of the urine pH-values Measuring the urine pH-value is a practicable and low-cost option, if only of limited validity. One-off measurements of pH-value have no validity. A daily profile should be produced with at least 5 urine pH-measurements: upon rising, 2–3 hours after main meals, before lunch and in the evening. The measured pH-values should fluctuate clearly, that is, be subject to a Circadian rhythm (around pH7); if the pH-value is permanently below 7, or is rigidity detected (the pH does not fluctuate at all in the course of the day), then this is a clear sign that the patient is hyperacidic or the kidneys can eliminate only insufficient acid. 43 APPENDIX I The daily profile should be produced over several days, and in addition the time and type of meals should be documented. Why do some alkaline powders not taste good? Alkaline mineral salts naturally taste somewhat soapy. Of course it is possible to add substances to the agents which change the taste. However, this restricts the alkaline effect to some extent, and the risk of intolerance is increased. If the user has a strong aversion to the taste, taking the agents with fruit juice or similar is a good alternative. Does everything which tastes sour also have an acidifying effect on the organism? APPENDIX I Sugar and coffee: acid- or alkali-forming? Sugar is shown in the food table as a neutral food. However, in public discussion sugar is often denounced as an acid-forming food. So what is the truth? In the food table according to Remer and Manz, the so-called PRAL-values are listed. They indicate the estimated potential renal acid load (PRAL in mEq/100 g). Only the primary effects on the acid-base balance are reflected. This means that only those effects are considered which the food has on our body as a result of its chemical composition and its rate of absorption. Secondary effects of the food such as the effect of sugar on the intestinal flora cannot be taken into account here. The effects of coffee on the vegetative nervous system and the consequences for the metabolism are also not considered here. A foodstuff is acid-forming when more acid than alkaline compounds are formed during its metabolism. This taste is not decisive here. Thus both lemons and pickled cabbage are alkali-forming, whereas sugar, cereals, eggs, meat and cheese, which do not taste sour, are acid-forming. The liver produces bicarbonate from weak organic acids – but only under aerobic conditions. They therefore have an alkali-forming, and not an acidifying, action. Can one overdose on alkaline agents and thus become alkaline? Clinically manifest cases of alkalosis have only been described as metabolic or respiratory alkalosis. There are no indications that these states can be achieved by alimentary administration. The body has many mechanisms for eliminating surplus of alimentary alkalis. In particular the kidneys have a high capacity to eliminate excess bicarbonate. The lungs and the liver also affect the concentration of bicarbonate. 44 45 APPENDIX II APPENDIX II Origins and evolution of the Western diet: health implications for the 21st century Origins and evolution of the Western diet: health implications for the 21st century. Cordain et al., Am J Clin Nutr 81:341-354 (2005) There is growing awareness that the profound changes in the environment (e.g., in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry 10,000 years ago occurred too recently on an evolutionary time scale for the human body to adjust. Many of the so-called diseases of civilization have emerged in conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral human diets: 1. glycaemic load 5. acid-base balance 2. fatty acid composition 6. sodium-potassium ratio 3. macronutrient composition 7. fibre content 4. micronutrient density The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization. 46 The effects of acid on bone The effects of acid on bone. Bushinsky, D. A. and K. K. Frick (2000). Curr Opin Nephrol Hypertens 9(4): 369-79. A constant systemic pH-value is necessary to maintain stable physiological conditions. However, in a number of diseases (such as chronic diarrhoea, renal insufficiency etc.) the acid levels increase or the alkaline level is reduced, resulting in metabolic acidosis, which can only be corrected by the elimination of acid. The bone makes a substantial contribution to the maintenance of stable pH conditions by releasing alkaline minerals, but the long-term cost is the mineral content and the stability of the bone. In an acute metabolic acidosis the buffer function of bone can be confirmed in vivo by the release of sodium, potassium, calcium and carbonation from the bone and by the increase in the serum calcium concentration. Because 98% of the total calcium content is in bone and, for example, in the case of renal insufficiency intestinal calcium reabsorption is not increased, an increase in the serum calcium concentration in metabolic acidosis is primarily the result of release of calcium from bone. This paper describes the measurement of the effects of acid on bone with the assistance of an in vitro test model. In conjunction with the postulated buffer function of the bone, metabolic acidosis changes the composition of minerals in the bone. The decrease of sodium, potassium, carbonate and phosphate results in buffering of acid and therefore an increase in the systemic pH-value in physiological conditions. The altered bone mineral composition is primarily caused by physical-chemical solution processes, and where the effects of acid are prolonged also by changes in the function of bone cells. The bone exercises its buffer function at the cost of its store of minerals. 47 APPENDIX II Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline Effect of age on blood acid-base composition in adult humans: role of agerelated renal functional decline. Frassetto, L. A., R. C. Morris, Jr., et al. (1996). Am J Physiol 271(6 Pt 2): F1114-22. The acid-base balance is primarily regulated by acid excretion from the kidneys, which are able to adapt to the endogenous net acid load resulting from nutrition. Because renal function is significantly reduced with increasing age, age-related metabolic acidosis can be expected, which over the long term, can result in serious diseases such as osteoporosis. This study was conducted to establish a relationship with age, based on evaluation of acid-base parameters of the blood and to investigate the effects on regulation of the acid-base balance. Method: 64 patients (39 men, 25 women) aged between 17 and 74 years received one of nine diets with different endogenous acid production (approx. 25-150 mEq/day). After a preliminary phase of an average of 11 days, blood samples were taken in the steady-state phase and the following parameters were tested: pH, carbon dioxide partial pressure (pCO2), carbon dioxide (CO2), sodium, potassium, chloride and creatinine. The urine samples taken at the same time were tested for the following: pH, carbon dioxide (CO2), ammonium ions (NH4+), titratable acids, sodium, potassium, chloride, inorganic phosphate and creatinine. The bicarbonate concentration in the two sample types was calculated from the total carbon dioxide content and the pH with the Henderson-Hasselbach equation. The renal net acid excretion (NAE) was measured from the total of titratable acids and ammonium ions less the bicarbonate concentration in the urine. The glomerular filtration rate (GFR) of the kidneys, based on a 70 kg person, was determined from the 24 h creatinine clearance. 48 APPENDIX II Results: There is a significant correlation between the age and the acid-base balance of the blood in adults. With increasing age less acid is eliminated renally and less bicarbonate is reabsorbed from the primary urine. The pH of the blood increases easily within the normal range and the bicarbonate concentration in the blood decreases. A metabolic acidosis develops slowly with increasing age and the chronic acid overload of the organism increases with it. The age-related change in the acid-base composition of the blood is independent of the diet-related acid load and has a significant correlation with glomerular filtration rate as a marker of kidney function. A slight metabolic acidosis can develop with a normal diet as a result of a slight decrease in the glomerular filtration rate. An initially diet-related metabolic acidosis can become more serious with increasing age and accelerate physiological changes such as bone and muscular metabolism and renal function. Older people in particular must therefore be aware of a correct acid-base balance and sufficient intake of alkaline nutrition. 49 APPENDIX II Dietary intake and bone status with aging Dietary intake and bone status with aging Tucker, K. L. (2003). Curr Pharm Des 9(32): 2687-704. Osteoporosis and related fractures represent major public health problems that are expected to increase dramatically in importance as the population ages. Dietary risk factors are particularly important, as they are modifiable. However, most of the attention to dietary risk factors for osteoporosis has focused almost exclusively on calcium and vitamin D. Recently, there has been considerable interest in the effects of a variety of other nutrients on bone status. These include minerals (magnesium, potassium, copper, zinc, silicon, sodium), vitamins (C, K, B12, A) and macronutrients (protein, fatty acids, sugars). In addition, foods and food components, including milk, fruit and vegetables, soy products, carbonated beverages, mineral water, dietary fibre, alcohol and caffeine have recently been examined. Prevention of osteoporosis by nutrition is a very complex topic. Previous results have in some cases been contradictory. There is a great need to understand the interactions of these factors within diets and on bone metabolism. Genetic factors, which result in different reactions in different individuals, increase the complexity of these effects. Intensive research will perhaps make a more realistic contribution in future to making effective recommendations for nutrition and prevention of bone loss and osteoporosis in the aging population. Intake of fruits and vegetables: implications for bone health Intake of fruits and vegetables: implications for bone health. Proc Nutr Soc 62:889-899 (2003) New SA, Proc Nutr Soc 62:889-899 (2003) 1. Reviewed by IPEV© www.ipev.de APPENDIX II focus of increasing attention in literature in recent years. The role of bone in the acid-base balance is of great interest in the area of osteoporosis. Natural (e.g. starvation), pathological (diabetic acidosis) and experimental (intake of ammonium chloride) states of acid load and hyperacidity are accompanied by hypercalciuria and a negative calcium balance. The detrimental effect of acid from the diet on bone minerals has only recently been demonstrated. The most important findings: The net acid production depends on nutrition and there is a quantitative relationship between the volume of acid produced (indicated in the urine) and the volume of acid-forming substances in the diet. The exact mechanisms of the destructive effects that acid has on the bone are well-known. It has been demonstrated that a metabolic acidosis promotes bone reabsorption by activation of mature osteoklasts and inhibits the growth of new bone by osteoblasts. It has also been confirmed that excess acid directly induces physical-chemical release of calcium from the bone. It is surprising that for more than 30 years bone has been known to be the source of buffer substances that are involved in maintaining the pH environment in the organism and also in defending the system against malfunctions in the acid-base balance. However, only recently has the possibility of a positive relationship between high intake of fruit and vegetables and the indices for healthy bone been investigated. The potential damaging influence of special nutrition has been investigated based on the potential acid loading on the kidneys, which is particularly high with many grains, some types of cheese and animal products. Some studies conducted in the population published over the past ten years have demonstrated that consumption of fruit and vegetables and intake of potassium has a beneficial effect on the axial and peripheral bone mass and bone metabolism in older men and in women before and after menopause. A detailed analysis of those types of fruit and vegetables that have the greatest direct influence on bone would appear necessary. Background: The health benefits of high fruit and vegetable consumption and the influence of this nutrition group on a variety of diseases have been the 50 51 APPENDIX II The results of the DASH (Dietary Approaches to Stopping Hypertension) and DASH potassium intervention studies provide additional reinforcement of the positive relationship between fruit and vegetable consumption and bone health. The DASH studies show that nutrition rich in fruit and vegetables with low-fat dairy products and low consumption of red meat was associated with a significant decrease in blood pressure compared to control groups, and that the renal calcium excretion was reduced as a result of reduction of the acid loading by increased consumption of fruit and vegetables. The DASH sodium intervention study investigated three volumes of sodium consumption (50, 100 and 150 nmol/l). It demonstrated that the DASH diet reduced bone growth by 8-10% and bone reabsorption by 16-18% and sodium does not significantly influence the markers for bone metabolism. The effects of a normal endogenous acid production on the bone were investigated at the in vivo or cellular level in observations of clinical applications. It was demonstrated that renal calcium and phosphate excretion decreased and the calcium balance was overall less negative when alkaline potassium carbonate was administered. APPENDIX II The data does not support the assumption that nutrition protein damages the bone, because even women in the quartile with the lowest protein intake consumed protein volumes significantly above the average daily requirement (82.5 g/day). The data demonstrate that the nutritional potassium is the deciding component. For example, nutrition types that have a lower acid loading are associated with better indices for healthy bone. Further studies: calcium plays a critical role in connection with the balance of the beneficial and damaging effects of protein on the bone. Calcium supplements may be beneficial for bone not only because of the additional supply of minerals but also because of the consumption of additional alkaline salts. Therefore, there is an urgent need to consider fruit and vegetable consumption and the change of alkaline supplements in intervention studies on bone health that evaluate the risk of fracture as the end point. Study of the existing data on nutrition, bone mass and bone metabolism appears to be required to investigate the specific influence of the acid content of nutrition on bone. Evidence: Determination of the acid-base balance of the consumed nutrition is a useful method of making a quantitative determination of the relationship between the acid-base balance and bone health. Consumption of a normal Western diet results in a minor metabolic acidosis, which is recorded by the endogenous net acid production (NEAP), which is not the result of carbonic acid, and varies depending on nutrition. Frassetto et al., Am J Clin Nutr 68:576-583 (1998) postulated a simplified model for testing the net acid content of the nutrition by the ratio of acid-forming protein (from sulphate excretion) and the alkalising effect of potassium (from the supply of salts of weak organic acids such as citrate). If this theory is applied to the baseline and longitudinally derived data sets of the Aberdeen Prospective Screening Study, it demonstrates that women with the lowest endogenous net acid production have a higher bone density in the lumbar vertebrae and hip bones and the renal excretion of the bone markers pyridinoline and desoxypyridinoline is lower. 52 53 APPENDIX III APPENDIX III Food Table – PRAL-Values Estimated acidic stress* of 114 frequently consumed foods and beverages (per 100 g).Modified from Remer and Manz. Journal of the American Dietetic Association 1995; 95: 791-797. *PRAL = Potential Renal Acid Load per 100 g of the food, expressed in mEq = physico-chemical material unit. Grain products rye mixed-grain bread 4,0 rye bread 4,1 wheat mixed-grain bread 3,8 wheat bread 1,8 white bread 3,7 Cornflakes 6,0 rye crisp bread 3,3 egg noodles 6,4 oat flakes 10,7 rice, unhusked 12,5 rice, husked 4,6 parboiled rice 1,7 rye wholemeal flour 5,9 PRAL-values reflect the level of acid-load: distinctive negativ value = highly alkaline distinctive positiv value = highly acidic Blue = alkali-forming foods Orange = acid-forming foods walnuts 6,8 herring 7,0 watermelons -1,9 trout, roasted, steamed 10,8 broccoli -1,2 peas spring carrots -4,9 Fruits nuts and fruit juices cauliflower -4,0 -2,2 celery -5,2 apple juice, unsweetened normal-strength beer apples, 15 sorts, with skin, average -2,2 Coca-Cola apricots -4,8 bananas -5,5 chicory -2,0 cucumbers -0,8 aubergine -3,4 leek -1,8 ettuce, average of 4 sorts -2,5 iceberg lettuce -1,6 mushrooms -1,4 onions -1,5 peppers -1,4 potatoes -4,0 blackcurrants 1,2 -6,5 Beverages -0,2 1,1 egg yolk 23,4 0,4 curd cheese 11,1 cacao, made of skimmed milk (3.5%) -0,4 corned beef, tinned 13,2 full fat soft cheese 4,3 19,2 frankfurter 6,7 hard cheese, average of 4 sorts coffee, infusion, 5 min. -1,4 liver sausage 10,6 vanilla ice-cream 0,6 -1,8 luncheon meat, tinned 10,2 pasteurised and sterilised 1,1 lean pork 7,9 whole milk 0,7 rump steak, lean and fat 8,8 Parmesan cheese 34,2 11,6 natural cheese spread 28,7 salami turkey 9,9 9,0 whole milk fruit yoghurt 1,2 veal natural whole milk yoghurt 1,5 cherries -3,6 grapefruit juice, unsweetened -1,0 mineral water (Apollinaris) hazelnuts -2,8 mineral water (Volvic) -0,1 kiwi -4,1 red wine -2,4 lemon juice -2,5 -0,3 -2,9 Indian tea, infusion radish -3,7 spinach -14,0 oranges -2,7 Fats and oils tomato juice -2,8 peaches -2,4 butter 0,6 tomatoes -3,1 peanuts, untreated 8,3 margarine -0,5 -4,6 -2,9 olive oil, sunflower oil 0,0 dry white wine -1,2 7,3 wheat flour 6,9 courgette wholemeal wheat flour 8,2 Pulses pears, 3 sorts, with skin, average green beans -3,1 pineapple -2,7 Fish 3,5 raisins -21,0 cod fillet 7,1 strawberries -2,2 haddock 6,8 54 egg white 8,7 orange juice, unsweetened lentils, green and brown, dried 8,2 7,8 wholemeal spaghetti -0,4 chicken egg chicken 6,5 asparagus 1,2 lean beef spaghetti Vegetables Meat and sausages fresh and sour cream Milk, milk products and eggs buttermilk 0,5 camembert 14,6 Cheddar, reduced fat content 26,4 Gouda cheese 18,6 full fat cottage cheese 8,7 Sugar, preserves and sweets milk chocolate 2,4 honey -0,3 Madeira cake 3,7 jam -1,5 white sugar -0,1 55 APPENDIX IV APPENDIX IV Glossar Acids Bases According to Brönstedt, acids are proton donors. This means they release hydrogen ions (H+) in solutions. According to Brönstedt, bases are proton acceptors. This means they gain hydrogen ions in solutions. Acid-base balance Buffer This describes the regulation of protons and blood buffer which is so critical for the functioning of the organism. It is a physiological term which takes into account both absolute quantities of acids and bases and their reserves as well as buffer capacity and/or acid-binding capacity. Buffers are mixtures of weak acids and their corresponding bases, which can release or gain protons without any change in their concentration in the solution, i.e. without their pH-value changing. Buffer capacity is at its highest in the region around pK (+/-1) of the acid, i.e. when acid and base are at almost the same concentration. Acid-base equilibrium This is a purely physicochemical term indicating the relative ratio of H+ and OH- without taking the absolute quantities of the ions into account. For example, blood pH is maintained in equilibrium at pH 7.35-7.45. Outside this range, acid-base equilibrium of the blood is disturbed. Acidosis and alkalosis Buffer capacity Buffer capacity is a measure of how many H+ or OH- ions can be added without changing the pH-value. Because of acid stress, initially buffer capacity is merely reduced. Only when large quantities of acid are added buffer capacity is exhausted and changes in pH occur. Acidosis and alkalosis should be considered as emergencies in intensive medicine. A distinction is made between different forms of acidosis and alkalosis. Compensated acidosis/alkalosis Respiratory acidosis Metabolic acidosis Occurs, when CO2 elimination is decreased (pulmonary function disorders, medicines such as opioids, benzodiazepines) Caused by severe renal, intestinal or metabolic disorders For example: diabetic ketoacidosis opioids, benzodiazepines This is the ion remaining after a disassociated acid has released its proton (H2CO3 H+ + HCO3-). Respiratory alkalosis Metabolic alkalosis Develops as a result of hyperventilation i.e. too high CO2 elimination, which is often psychogenic but may also result from various underlying diseases Is caused by hyperventilation and loss of protons among other factors, as a result of vomiting or gastric drainage 56 Exhaustion of the buffer capacity in the blood. Conjugate base 57 APPENDIX IV APPENDIX IV Glossar Henderson-Hasselbach equation pH The Henderson-Hasselbach equation is also known as the buffer equation and describes the acid-base balance of a partly dissociated, therefore weak, acid or base in aqueous solution. Using this equation, the pH-value of the bicarbonate buffer can be calculated as follows: pH=pKA + log (concentration HCO3-/concentration CO2).The pKA-value of the bicarbonate buffer is 6.1. A pH-value of 7.4 is achieved when bicarbonate concentration is 20 times higher than that of CO2. For log 20 = 1.3, which used in the equation yields pH = 6.1 + 1.3 = 7.4. The physiological concentration of bicarbonate is approx. 24 mmol/l and that of CO2 in the blood 1.2 mmol/l. The definition of pH is the negative base 10 logarithm of the hydrogen ions in a solution. The lower the pH-value, the higher the concentration of free H+ ions. A pH-value of 7 is considered to be neutral. In pure water (at 25o C), 10-7 mol/l hydrogen ions are present, because water does not exist only in the form of H2O, but is always present to a minor degree in its disassociated form, i.e. as proton (H+) and hydroxide ion (OH-). H2O H+ + OHThe negative base 10 logarithm of 10-7 is pH 7. If the relative proportion of H+ ions decreases, pH-value increases and the solution becomes alkaline. Intracellular acidosis Protons cannot be transported into the extracellular space as cell metabolism is insufficient. However, this is difficult to detect. Latent acidosis, acid stress This does not refer to clinically manifest acidosis but to acid stress in tissues and cells and/or incipient exhaustion of the buffer reserves. To differentiate between this and pathological acidosis, it is more convenient to talk in terms of acid stress or hyperacidity of the organism. Chronic acid stress can have various consequences for health. pCO2 value The abbreviation pCO2 value stands for the partial pressure of carbon dioxide and indicates how much carbohydrate is dissolved in the blood. 58 pKa This is the pH-value at which the acid and its conjugate base are present at the same concentration. It describes a state of equilibrium between acid and base. In the case of pure water, pH-value is also equivalent to pK-value. The pK-value is always a specific constant for the corresponding acid-base pair. When an acid releases more than one H+ ion, there are multiple pK-values. Standard bicarbonate To determine standard bicarbonate, a blood sample must be examined at 37oC, 100% acid saturation and a partial CO2 pressure of 40 mm Hg. Reference values: 24 mmol/l. Standard bicarbonate is unchanged in respiratory disorders. It deviates when a non-respiratory disorder is present. 59 APPENDIX V APPENDIX V Literature • Arnett, T. (2003). 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Morris: Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors; American Journal of Clinical Nutrition Vol 76, 2002: pp 1308-1316 • Silbernagl, Despopoulos, Taschenatlas der Physiologie, 1991 • Silbernagel, Lang, Gay, Rothenburger, Taschenatlas der Pathophysiologie, 2007 Worlitschek, Michael: Praxis des Säure-Base-Haushaltes, 1991 61 APPENDIX V NOTES • Thews, G., Mutschler, E., Scahible H.G., Vaupel, P. (2007): Anatomie, Physiologie, Pathophysiologie des Menschen, Wissenschaftliche VerlagsgesellschaftmbH, Stuttgart • Marsh, A. G., T. V. Sanchez, et al. (1988). „Vegetarian lifestyle and bone mineral density.“ Am J Clin Nutr 48(3 Suppl): 837-41. • Thorpe, M., Mojtahedi, M.C., Chapman-Novakofski, K, McAuley, E., Evans, E.M. (2008): “A positive Association of lumbar spine bone mineral density with dietary protein is suppressed by a negative association with protein sulphur.” Am J Clin Nutr 138:1349-1354 • Tucker, K. L. (2003). „Dietary intake and bone status with aging.“ Curr Pharm Des 9(32): 2687-704. • Tucker, K. L., M. T. Hannan, et al. (1999). „Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women.“ Am J Clin Nutr 69(4): 727-36. • van Limburg Stirum, J. (2008): Moderne Säuren-Basen-Medizin, Hippokrates Verlag PASCOE VITAL GmbH · Schiffenberger Weg 55 · D-35383 Giessen Tel. 0641/7960-0 · Fax 0641/7960-109 · [email protected] · www.pascoe-vital.de 62 63 PASCOE VITAL GmbH · D-35383 Giessen Tel. 0641/7960-0 · Fax: 0641/7960-123 · [email protected] · www.pascoe-vital.de