Nutritional Management of Heart Disease

A lecture by Robert Buist Ph.D.

I have often been asked about the efficacy of orotates and aspartates in the management and treatment of heart disease. After reading about Hans Nieper’s results and also using these mineral chelates for many years I thought it would be beneficial to share the research data with those of you who are interested:

Magnesium and Potassium in cardiovascular disease (CVD)

Normal healthy cells contain a high concentration of magnesium and potassium.  Calcium and sodium are largely extracellular minerals.  In fact, normal cells maintain an extreme calcium gradient such that calcium ion pumps and channels ensure that the cytoplasmic calcium ion concentration is only one ten thousandth that of the extracellular environment.  Intracellular magnesium controls the calcium gradient via the Mg2+-C-AMP second messenger system which carries out orders from catecholamines such as adrenaline, glycogen, ACTH, TSH, FSH, LH, vasopressin, secretin and many other hormones and neurotransmitters.

So ordered physiological control of the body depends very much upon the correct functioning of calcium and magnesium transportation and cellular gradients.

For example, if the calcium gradient fails, pathological events follow.  These include hypertension, atherosclerosis, insulin resistance, neurological disorders, soft tissue calcification and malignant transformation.  Prolonged elevation of intracellular calcium is universally toxic.  Insulin resistance is commonly associated with hyperinsulinaemia and also elevated intracellular calcium because of altered activities of the membrane cation pumps (ATPase’s – i.e. calcium-ATPase and sodium + potassium ATPase).  Diabetic cardiovascular disease with its related cardiomyopathy, hypertension and atherosclerosis is very much related to changes in membrane control of calcium and magnesium ions.  In fact, controlling the intracellular flow of magnesium, calcium, potassium and sodium ions across cell membranes of the heart and peripheral vascular system has become top priority in the prevention and treatment of cardiovascular disease.  The most effective vehicles for doing so are the intracellular mineral transporters, orotates and aspartates.  Mineral salts of these 2 ligands are unique in their ability to carry magnesium, potassium and calcium through the cell membrane with out increasing serum levels.  So let’s have a more detailed look at the nature of these orotates and aspartates.

Orotates and the Heart

Orotic acid is a major building block in the body’s manufacture of pyrimidines which together with purines form the basis of the nucleic acids which make up our DNA and RNA.  Orotic acid is specifically converted to uridine-5′-phosphate (UMP) which is subsequently converted to the nucleotides uracil, cytosine and thymidine which are incorporated into ribonucleic acid (RNA), deoxyribonucleic acid (DNA) and certain enzymes.

Administration of labelled orotic acid to animals results in the radioactive label being found in all the pyrimidines of RNA and DNA.  Histochemical examinations show orotic acid localised in the cytoplasm of cells of the spleen, bone marrow, kidneys, heart and other organs within 2-3 hours of oral administration and an exogenous dose is firstly delivered to the liver by the blood and partially by the lymph.

Further experiments with labelled formiate and glycine also showed that the addition of 1% orotic acid to the diet of rats stimulated the biosynthesis of free purine nucleotides 15 to 20 times that of the controls.  Hence, in the rat, orotic acid stimulates the biosynthesis of both pyrimidines and also purines.  The improved production of nucleic acid precursors has subsequently been shown to have a definite anabolic effect in both animals and humans especially in the area of improved protein synthesis.

Strengthening the Heart

Using animal models researchers have induced experimental myocardial hypertrophy by narrowing the abdominal aorta above the origin of the superior mesenteric artery.  The effect of administering orotic acid was then examined by measuring parameters including myocardial contractility, protein synthesis and other aspects of carbohydrate and energy metabolism.  In this situation the development of compensatory myocardial hypertrophy is a physiological adaptation to a sudden increase in work load (due to narrowing the aorta).  The subcellular mechanism, which translates overload into a biochemical message, is responsible for rapidly increasing the synthesis of nucleic acids and thus protein synthesis.  This leads to stronger and thicker heart muscle.

When orotic acid 10mg/kg/day was administered to rats who had undergone this technique the maximum developed tension in 4 day hypertrophied hearts rose from 2.28 to 3.99g/mm2 and the maximum rate of rise of tension increased from 30.9 to 47.3g/mm2 sec.  This was consistent with a rapid increase in myocardial protein synthesis, which peaked at 18 hours and was 50% higher than in control animals.

The mitotic activity of connective tissue and endothelial cells was increased together with synthesis of myosin and cytochrome C.  A detectable increase in the heart weight also occurred within 24 to 48 hours.

The pattern of increased energy utilization associated with mechanical overload of the heart was interesting.  There were no significant changes in the glycogen content between the heart of the normal and sham operated animals, however the glycogen content increased in the hypertrophied animals from 36.4 to 49.8 and 98.2 mmoles/g in the one day and three day hypertrophied hearts respectively.  So glycogen supplies were conserved, especially under the influence of orotic acid.  Fatty acid oxidation is the preferred energy source and acts to divert most of the available glucose into glycogen.  Electron micrographs show that lipid droplets, which are normally present in heart muscle preparations, have disappeared 4 days after the induction of hypertrophy.  Orotic acid treatment of the hypertrophying myocardium made it more reliant on fatty acids, lactate and ketone body oxidations to supply energy by mechanisms that are not dependent upon high oxygen tension obviously of great benefit in the anoxic heart.  Add to these observations the fact that orotic acid has a positive inotropic effect in the hypertrophied heart by increasing the rate of protein synthesis and contractility and one can understand why so much interest has been placed on orotic acid and its salts in recent years.

Potassium and Magnesium Orotates

The major salts of orotic acid are potassium and magnesium orotate.  Some landmark studies on potassium orotate were carried out in Russia in the 1960′s.  Again using the experimental stenosis model to promote hypertrophy, Russian researchers showed that the myocardium of animals treated with potassium orotate was characterised by a uniform thickening of muscular fibres (1.5 to 2 times).  The structure of the fibres was well-identified, the striation preserved and signs of oedema and haemorrhage were in most cases absent.  The nuclei of the muscle fibres were moderately hypertrophic.  In contrast, the animals in the control group showed a marked thinning of the walls of the left ventricles.  The animals treated with potassium orotate experienced a thickening of the left ventricular walls.  Potassium orotate promoted an increase in the heart mass in the period of compensatory hypertrophy development.  This prevents the transition of the heart from the state of “concentric” hypertrophy to an “eccentric” one during the development of compensation stability.  This is important because the greater the degree of eccentric hypertrophy in patients with cardiac insufficiency the worse the prognosis.

In another Moscow study 40 out of 80 patients with acute myocardial infarction received 500mg potassium orotate 3 times daily for 40 days (while the other 40 received their standard medications).  Patients taking the orotate experienced significant reductions in heart rate, arterial blood pressure and peripheral resistance and also increases in cardiac output and coronary flow rate compared to the controls.  Of the 40 patients taking orotate only 3 died during their stay in the clinic while in the control group 10 patients died – 7 with progressing cardiac insufficiency and 2 with sudden heart stoppage.  Similar results were found with the treatment of 97 patients in the third stage cardiac insufficiency where together with considerable improvement in their general state (diminution of oedema, reduction of liver size and normalization of ECG findings) the use of 1.5g potassium orotate daily resulted in an increase in the serum levels of total protein and albumins indicating a restoration of the protein synthesizing function of the liver.  There was a double reduction in mortality in the orotate treated group (7 deaths) compared with the controls (15 deaths).

Even pre-operative patients with 4th degree cardiac insufficiency showed an improvement of heart activity, an increase in ECG voltage and a change from the tachysystolic form of fluttering arrhythmia to the bradyarrhythmic form while taking orotates.

Potassium orotate has been used in Russia for many years for the treatment of:

A. Myocardial infarction (with the objective of stimulating the synthesis of nucleic acids and protein in the non-affected parts of the myocardium and to improve myocardial contractility.

B. Chronic cardiac insufficiency of the 3rd and 4th degree.

C. Cardiac rhythm disturbances – especially extra systoles and fluttering arrhythmia.  Orotates are particularly effective in stabilising sinus rhythm after the restoration of the latter by discharge of a defibrillator.

D. Diseases of the liver and bile ducts (except true cirrhoses with signs of ascites) caused by chronic alcohol and drug ingestion and infection.

Orotates are also useful supplements during the pre- and post-operative periods for patients undergoing cardiosurgery.

Magnesium Orotate and the Pentose Pathway

Magnesium orotate has been shown to be an important activator of direct oxidation in the pentose pathway.  Tissues that are particularly dependent upon this pathway are mesenchymal in origin and include vascular walls, connective tissue, cartilage, etc.  For this reason orotates have been used extensively in the long term therapy of arteriosclerosis.

According the Dr. Hans Nieper the unusual effect on arteriosclerosis is explained by the fact that magnesium orotate activates riboses in the pentose pathway and during its metabolism the liberated magnesium further activates cholesterol esterases and increases cholesterol mobilization.  This is the reason why patients may experience an increase in blood cholesterol for the first few months when taking magnesium orotate.

The following studies confirm the usefulness of magnesium orotate in the treatment of arteriosclerosis and in serum lipid reduction.

Magnesium Orotate and Blood Vessel Elasticity

115 patients suffering from arteriosclerosis or inflammatory changes in vessel behaviour were treated for 15 months with either magnesium orotate, EPL substances (essential phospholipids) or clofibrate.  Vessel elasticity was checked at intervals of 6 weeks by means of light electronic capillarography.

A total of 64 patients were treated with magnesium orotate, 34 with EPL substances and 28 with clofibrate, and their progress observed over a 15 month period at approximately 6 week intervals.  In general, they received daily doses of one of 500mg magnesium orotate, four capsules of the EPL preparation or two capsules of clofibrate 500.

The amazing results of this series of treatments were quite unexpected:

Sixty of the 64 patients taking magnesium orotate daily showed a highly normalized capillarogram within the 15 months of observation; the capillarograph curves of about half of these were then completely normal, and those of the remainder showed not the slightest resemblance to the situation before treatment.  This was true for both arteriosclerotic and arteriolitic damage to the vessels.  The 4 patients who discontinued treatment prematurely also had shown some improvement in their conditions.

In the group which received EPL substances, 21 of the original 34 patients showed a marked improvement, 11 showed no improvement and 2 discontinued treatment after 4 and 6 months respectively, with no apparent improvements in their conditions.  Only 2 out of the 34 patients showed complete reversal of their condition as demonstrated by completely apathological curves for vessel elasticity.

Of the 28 patients taking clofibrate, only 5 showed a significant improvement after 15 months of treatment.  There was no improvement in the condition of the 3 patients who discontinued treatment prematurely.

While EPL substances and magnesium orotate appeared to be completely free of unwanted side effects, and magnesium orotate even provided a sustained lessening of pectanginal pain, the treatment with clofibrate caused increased heart pains in 5 cases. One of these 5 patients, a fifty-six year old woman, complained of extreme pain, which subsided immediately upon the discontinuation of clofibrate therapy.

Many reports have been published on the use of magnesium orotate to combat arteriosclerosis.

Serum Lipid Reduction (Cholesterol and Triglycerides).

Magnesium orotate, as an activator of direct oxidation in the pentose pathway, affects tissues dependent on the pathway, such as vascular walls, connective tissue, cartilage, etc. making it effective for long term therapy in arteriosclerosis.

Early studies on magnesium orotate (200-600mg) daily demonstrated that it is more efficient in the mobilization of cholesterol esters and in the activation of cholesterol turnover than other cholesterol activators tested.

A clinical investigation of 100 hyperlipidaemic patients given 200-400mg of magnesium orotate daily showed a 32.06% reduction in plasma lipids from pretreatment levels.

A cross-over double-blind study of the lipid-reducing effects of clofibrate as compared with a clofibrate/magnesium orotate combination (450mg clofibrate with 50mg magnesium orotate) showed that the combination reduced cholesterol and triglyceride levels faster than 3 separate daily doses of 450mg of clofibrate alone during the 8 week trial period.

Another paper briefly described the results of a clinical investigation of magnesium orotate in serum lipid reduction.  The study involved two groups of hyperlipidaemic patients.  The first group of 8 patients had higher initial lipid levels and showed drops of 15.2% in cholesterol and 32.4% in triglycerides.  The second group, which included borderline hyperlipidaemic patients, had lower initial lipid levels and showed drops of 5.9% and 25.0% in cholesterol and triglycerides, respectively.  The results suggest that magnesium orotate exhibits a normalization effect in lowering lipids.

During the study the patients were instructed not to change their diet, work or sleep habits in any way.  Each patient in the study was given 900mg of magnesium orotate daily.

There was no complaint by any of the patients in the study regarding side-effects from magnesium orotate.  No toxicity or adverse reactions were noted at any time during the study due to this substance.

Apparently, the closer to “normal” the patient was in terms of lipid levels, the less effect magnesium orotate had.  This suggests that it has a “normalizing” effect on the lipids.  Such an observation is significant in that magnesium orotate could be considered as adjunctive therapy in the treatment of hyperlipidaemia when lipid-lowering drugs are undesirable.

Lipid-reducing drugs, such as clofibrate, can produce undesirable side effects or adverse reactions.  Such reactions include nausea, vomiting, loose stools, dyspepsia, flatulence, dizziness, fatigue, muscle cramping, skin rash & pruritus.  Magnesium orotate did not produce any such side effects in any patients.

Overall, the magnesium orotate appears to be an effective and safe adjunct in reducing or normalizing serum lipids such as cholesterol and triglycerides in hyperlipidaemic patients.

Calcium Orotate for Inflammatory Vessel Disorders

Calcium orotate plays two quite unique roles in the treatment of circulatory disorders.  Firstly, it has been shown to dramatically improve circulation in inflammatory vessel disorders.  These include vessels with free radical damage (as in smokers), diabetes and disorders of rheumatic or autoimmune origin such as retinitis, nephritis, phlebitis, etc.  A heat reaction is frequently felt by patients when they start taking calcium orotate but it  only occurs when there is an inflammatory process in the vessels and subsides with time.  This does not occur with magnesium orotate.  The intensity and duration of the heat reaction depends on the seriousness of the inflammatory vessel disease.  Secondly calcium orotate has a unique ability of dissolving calcium in vessel walls, possibly by rectifying the associated inflammatory processes.  Calcification of the aorta has been reversed using just 400mg calcium orotate daily over a period of time.  Small amounts of calcium orotate together with magnesium orotate appear to act synergistically.  Nieper cites a 63 year old man who suffered for several years with severe angina and cardiac insufficiency with coronary sclerosis.  His condition improved after several months treatment with magnesium orotate but then dramatically improved with the addition of calcium orotate.

An interesting animal study from Switzerland gives further testimony to the beneficial effects of calcium orotate on cardiovascular functioning.  It examined the effects of digitalis, potassium, magnesium aspartate and calcium orotate on the ability of 14 year old dogs to run up a 14 degree slope.  The dogs could normally run up the incline an average of 14 metres before they were exhausted.  When digitalis was administered they extended this distance to 16 metres.  A combination of digitalis and potassium, magnesium aspartate increased the distance to 40 metres.  When digitalis, potassium, magnesium aspartate and calcium orotate were simultaneously given to the dogs they were able to run up the incline for more than 500 metres before stopping.  This experiment well illustrates the effects of improved calcium transport into the myocardium.  Such calcium transport is particularly relevant to elderly people who may suffer from defective calcium transit across cell membranes of the heart muscle.  These calcium ions are required to trigger the release of energy from fat and triglycerides in the heart muscle and thus keep the heart beating.  It is interesting to note that heart muscle gets a large amount of its energy from fat stores in the heart tissue (an emergency precaution in times of severe stress).  Calcium activates enzymes which release the energy stored up in these fat deposits.  Thus a good supply of calcium in the heart is essential.  Unlike most calcium supplements which in high doses may cause electrical disturbances in the heart because of calcium build-up on the myocardial cell membranes, calcium orotate goes straight through the membrane eliminating this problem.

Magnesium, Potassium Aspartates

What causes myocardial necrosis

Over the years hypercholesterolaemia has been the main focus of cardiovascular disease prevention and serum cholesterol levels have essentially become the surrogate end-point for treatment.  The popularity of the statin drugs has reinforced this approach after it was discovered that lipid-lowering diets frequently had no effect whatsoever on cholesterol levels.  The statins could actually block the body’s manufacture of cholesterol by inhibiting HMG-CoA reductase.  Fortunately cholesterol is losing its popularity as the major risk factor and we have made important steps forward in detecting other risk factors such as homocysteine and fibrinogen levels  (see Table) but we seem to have overlooked one major area that contributes to heart attacks and that is the metabolism of the myocardium (and ductile tissue of the heart).  The fact is, myocardial infarction does not always follow intense constriction of the coronary arteries, nor does it necessarily follow a complete blockage of the coronary artery due to thrombus formation at a point of severe plaque formation.  Coronary thrombosis is seen clinically in only one out of every two infarcts.  Atherosclerotic changes to the arteries as a consequence of aging also offer no statistical relationship with frequency of infarction.  Young people with clean arteries still get heart attacks.  Frequently coronary thrombosis develops only after cardiac necrosis.  Some researchers believe that only 20% of cases of myocardial necrosis are caused by occlusion of coronary vessels.  This may be because the heart starts growing collateral blood vessels when major arteries of the heart start to become blocked.  Cardiologists have found complete blockage of a coronary artery but the collaterals have taken over the function of the blocked vessel.  So necrosis does not necessarily develop even in the face of complete blockage – at least not initially.  The body can compensate by activating angiogenesis and growing new secondary vessels for many years.  A myocardial metabolic disaster rather than a blockage may explain why so many seemingly healthy people die of “sudden death”.  This is particularly relevant for the long distance runner who develops mini necrotic lesions over the myocardium due to abnormal supply of magnesium, potassium, water, oxygen or energy under the extreme conditions of an endurance sport.  These mini infarcts turn to fibrous tissue throughout the heart to the extent that the condition has been called “stone heart” syndrome as the myocardium tightens and hardens, seriously interfering with its function.  However, this is an extreme situation.  Highly stressed individuals tend to hold their breath and release adrenaline to the extent that anaerobic glycolysis is potentiated at the expense of aerobic metabolism.  Because of the attendant oxygen deficit this can result in high levels of lactic acid.  Lactic acid has also been associated with anxiety and panic attacks in such individuals.

Table: Heart Diease Risk Factors and associated Factors

Conventional Factors                        New Factors

Hyperlipidaemia                                   Low HDL

Smoking                                               Elevated small dense LDL

Diabetes mellitus                                  Elevated lipoprotein (a)

Hypertension                                        Hyperhomocyst(e)inaemia

Age                                                       Low antioxidant status

Gender                                                 Apolipoprotein E gene variants

Obesity (in particular abdominal

obesity)                                                Anticardiolipin antibodies

Increased waist/hip ratio                       Factor V Leiden

Menopause                                           Protein C deficiency

Fatty diet                                               Protein S deficiency

Lack of exercise                                   Antithrombin III deficiency

Sedentary lifestyle                                Elevated platelet activation

Family history                                       High fibrinogen concentration

Oral contraceptives                               High factor VII

History of coronary heart disease         Genetic polymorphism

Left ventricular hypertrophy                   Lipoprotein lipase gene

Stromelysin gene

Fibrinogen gene

Plasminogen activator

Inhibitor gene

Factor II gene


Hans Selye who pioneered so many of the original animal studies on the effects of stress on the body and proposed the General Adaptation Syndrome – the mechanism by which animals adapt to a stressful environment – also proposed that metabolic insufficiency of the myocardium involving myocardial injury in the presence of anoxia and in the absence of occlusion, may be one of the causes of infarction.  He also understood that coronary thrombosis could be caused by myocardial necrosis as necrotic tissue itself was well known for its coagulant properties.  Myocardial infarction could also be caused by electrically-induced circulatory damage in the absence of occlusion.

So what is the mechanism by which metabolic insufficiency rather than blockage results in destruction of heart cells (myocardial necrosis) and heart attacks (myocardial infarction)?

Metabolic changes in the myocardium

When a coronary artery is experimentally ligated, the oxygen supply to the heart is interrupted and there is a decrease in pH and an increase in intracellular acidity.  This same metabolic acidosis can also result from oxygen deprivation or utilization, metabolic deficiencies, metabolic damage or disruption with the mitochondrial oxidative phosphorylation process which gives rise to ATP, the energy source of the heart.  Accompanying any of these metabolic changes is a tendency for lactate to build up  in myocardial cells and as the intracellular pH drops, lysozomes become increasingly unstable.  If the myocardial lysozomal enzymes become active, a chain reaction can result in further destabilization of other lysozomes, which can eventually lead to a massive cardiac necrosis and infarction.

Magnesium and potassium protect the myocardium

Selye found that potassium and magnesium chlorides had a marked protective action against experimentally-induced myocardial necrosis.  The magnesium ions appeared to activate phosphatases and other esterases essential to cell metabolism while potassium ions facilitated the correction of electrically disturbed cell potentials.  In this way severe disturbances of oxidative cell metabolism caused by oxygen deficiency could be overcome.  The only problem was that parenteral use of large quantities of potassium and magnesium chlorides could lead to: (1) increased dangers of depolarization of the myocardium with high levels of potassium (especially in patients suffering from infarction)  and (2) a sudden lowering of blood pressure with high blood magnesium.

Other researchers found that intracellular magnesium sulphate could be life-saving.  Parsons, for example, here in Australia, treated over 100 patients suffering from coronary heart disease with magnesium sulphate (and of which at least one third had acute myocardial infarctions) with only one death.  This compares favourably with the previous year when of 196 cases admitted and treated with routine anticoagulants, sixty died.

Both magnesium and potassium are intracellular minerals found at concentrations of 800 and 1400% higher respectively inside the cell compared with the serum.  These concentrations are maintained via active transport systems or by cation counter-transport.  Calcium, on the other hand, must be maintained at an even greater ionic gradient with the intracellular calcium ion concentrations one ten thousandth that of the extracellular environment.  In myocardia hypoxia these electrolyte gradients fail and the concentration of intracellular sodium and calcium rises and the magnesium and potassium falls.  One standard approach is the use of calcium channel blockers to try to rectify this situation but an alternative to this drug approach is the use of intracellular potassium and magnesium delivery.

It was the understanding of these ionic gradients and the need for specific transportation of potassium and magnesium to the inside of the cells that gave rise to the concept of mineral transporters such as the orotates and aspartates.  Both ligands have the ability to tightly bind cations and transport them to the intracellular environment of cells.  Dr. Hans Neiper was one of the pioneers in the use of intracellular electrolyte transport therapy for cell hypoxia.  In both Germany and France, potassium and magnesium aspartates have been used in the clinic and in private practice to facilitate recovery from fatigue, metabolic insufficiency, particularly hepatic, and for prophylaxis and therapy of angina and myocardial infarction.

It should be noted that all the positive effects of using a 50% mixture of potassium aspartate and magnesium aspartate could not be reproduced using a simple mixture of free aspartic acid with potassium and magnesium chloride, nor from using sodium aspartate, sodium + magnesium aspartate or potassium + magnesium chloride.  In fact a mixture of potassium + magnesium L-aspartates could not produce the required effects produced by a 50% mixture of potassium and magnesium salts of D,L-aspartic acid.

The pharmacological studies illustrating this point are as follows:

A. When the coronary artery of a rabbit is ligated an experimental infarct is obtained as shown by a pronounced ST depression on the ECG.  After potassium aspartate is injected the ECG tracing reverts to normal for about 3 minutes.  After injection of a 50 mixture K,Mg Aspartates the normalising effect lasts for one or more hours.

B.  An isolated heart continues to function for a few hours when perfused with an oxygenated buffer solution.  Interruption of oxygenation leads to rapid deterioration of cardiac activity within 90 seconds, but the addition of K,Mg Aspartates in a 1:10,000 concentration enables the heart contractions to last for 225 seconds, i.e. this specific mixture of potassium,magnesium aspartates allows the myocardium to function more efficiently and for a longer period of time with minimum oxygen.

Biochemical studies with K,Mg aspartates

Patients with coronary heart disease are frequently found to have deficient cellular oxidation which leads to high serum lactate levels and low levels of the krebs cycle intermediate – alpha ketoglutarate.  These biochemical changes indicate that the tricarboxylic acid cycle in the mitochondria is underperforming and hence energy creation via oxidative phosphorylation.  This situation has frequently been shown to worsen after administration of the cardiac glycosides such as digitalis.

However, experimental studies have shown that a 1g injection of K,Mg Aspartates rapidly increases the pyruvate/lactate ratio and restores cellular oxidative processes in patients taking cardiac glycosides and in those taking no medication.  For example, average serum values in one group of patients untreated with cardiac glycosides is as follows:  Lactic acid 10.3mg% (after 1g K,Mg Aspartates – 1.25mg%); pyruvic acid 0.82mg% (after – 0.134mg%); alpha-ketoglutarate 0.154mg% (after 0.02mg%).  Free aspartic acid and potassium and magnesium chloride showed no such activity.

Another electrolyte transporter, potassium and magnesium 2-amino-ethyl phosphate (AEP) also modified the pyruvate/lactate ratio toward normal but had no effect on the alpha ketoglutarate level.

Clinical aspects of potassium

It is very difficult to accurately determine the intracellular potassium and magnesium levels, especially in the myocardium, though high levels of these 2 intracellular minerals are necessary to prevent myocardial necrosis.  A flattened T wave or lengthening of the QT interval of the ECG can give some indication but large series of patients with severe hypokalaemia have not demonstrated ECG changes.  It has been hypothesized by Nieper and Blumberger that ECG changes may be more a reflection of the difference between intra-and extra-cellular potassium levels.  In general though a decrease in serum potassium below 17.8mg/100mg (4.5mEq) is accompanied by a greater danger of myocardial infarction, especially in young and middle aged men.  Thirty patients less than 50 years of age who had already suffered from angina pains and some with myocardial infarcts had average potassium levels below 16.5mg%.  Nieper warned, however, that ordinary potassium supplements (such as potassium chloride, Slow K) would first cause a one-sided loading of the extracellular environment.  The only way around this problem is the use of electrolyte transport therapy which can lead to an increase in intra- and extracellular potassium in physiological proportions.

In this respect K,Mg Aspartate is ideal because if the magnesium status of the body is low it is difficult for the body to maintain normal levels of potassium, sodium and calcium.  Magnesium is actually the key to maintaining the body’s balance of the major electrolytes.  Thus, if potassium chloride supplements are administered to a body deficient in magnesium, the effectiveness of the supplement is diminished dramatically.  This is why K,Mg Aspartate is an obvious solution for patients with low potassium or magnesium status or malfunction of the active transporting mechanisms that are responsible for maintaining high intracellular potassium and magnesium aspartates.

Clinical applications of K,Mg aspartates

The most important indications for the use of K,Mg Aspartates is in the prevention and treatment of metabolic disturbances of the myocardium especially those associated with hypoxia.  The following studies by Drs Nieper and Blumberger illustrate these conclusions:

1. Chronic treatment of angina pectoris or myocardial infarction

Eighty four patients suffering from angina pain and or previous episodes of myocardial damage were treated with electrolyte transport therapy.  Twenty one had experienced infarcts more than 6 weeks previously.  The group were administered doses of 1-1.5g K,Mg Aspartates for periods of up to 18 months.  Intracellular normalization of electrolytes usually occurred within 2-4 days and resulted in clinical improvement which included reduction of chest pain and increase in exercise tolerance.

Nieper says “an important symptom of coronary insufficiency conditioned by myocardial hypoxia is a disturbance of repolarization, with potassium depletion, after each contraction.  Cellular repolarization is identifiable by a rapid accumulation of potassium after contraction.  Abnormal return of excitability is indicated on the ECG by flattening of the T wave.  Improvement in myocardial metabolism leads to improvement in repolarization, as indicated by increased steepness of the T wave. Aspartate therapy is effective also when the serum potassium concentration is not lower than normal, but depletion of cellular (intracellular) potassium may be expected..  Observations made over many months showed uniformity in the return of excitability.  The pain of angina pectoris subsided almost completely after aspartate therapy”.

2. Acute treatment of angina and infarction

Of 45 recent myocardial infarcts, 25 cases served as controls (receiving anticoagulants) and 20 received 2g/day K,Mg Aspartates initially in their regular IV infusions followed by 2g/day orally over a minimum period of 6 months, and continuing for up to 2 years.  Compared to the control group, the treated group showed considerable reduction in pain during the first 24 hours, a clear reduction of anxiety and agitation, more rapid ECG improvements and a more rapid drop in SGOT.  Though the group was small there were 9 complete recoveries in the aspartate-treated group (45%) compared with 2 (8%) in the controls.

Treatment of ventricular extrasystoles

K,Mg Aspartates are similar in action to magnesium orotate in their ability to improve or completely eliminate extrasystoles in nearly 50% of cases.  The best therapeutic results were obtained for ventricular extrasystoles, especially when associated with glycoside therapy or in the presence of hypokalaemia or where there was an infarct history. “Atrium fibrillation, atrio-ventricular dissociation and shifting pacemaker, however, do not benefit from this therapy.  Simultaneous myocardial infarct, heart block (provided cardiac glycoside treatment is avoided) or severe bradycardias are not contraindications to aspartate therapy.  In fact one of the most important aspects of K,Mg Aspartate therapy is its lack of toxicity and adverse side effects.  Rare gastrointestinal upsets have been observed.

Like the orotates, the aspartates have that unique ability to penetrate the  membranes  of cells, delivering both cations and aspartate ligands to the intracellular metabolic processes.  In this way the extracellular-intracellular gradient can be re-established more rapidly and efficiently, avoiding thereby the risk of sudden myocardial depolarization due to too high an extracellular electrolyte concentration following excessive potassium supplementation or after IV administration of large quantities of potassium ions in particular

Using stimulated striated muscle (gastrocnemius) researchers have also shown with aspartates:

A.   a higher concentration of ATP,

B.   a nine-fold increase in residual creatine phosphate,

C.   higher potassium and lower sodium intracellular levels,


D.   a greater contraction amplitude and a faster recovery.

The increase in ATP levels could explain the return of cardiac excitability in infarct patients.


One of the latest non-invasive technique used to predict and avoid heart attack by early detection is high speed gated coronary computer topography (high speed GCCT).  Using this technique, the calcium content of arterial plaque can be detected even if present in minute amounts.  Sophisticated software is employed to quantify the amount of calcium – and hence plaque- in the arteries, producing a Calcium Score.

The Calcium Score

The Calcium Score is an accurate marker to the amount of disease present.  Angiography – once the gold standard test for heart disease – cannot detect the earliest stages of atherosclerosis.  Even a stress test cannot pick up flow-reducing lesions.  Many heart attacks are caused by spontaneous rupture of the plaque in arteries that may be only 50% narrowed.  The calcium score gives an immediate indication of preclinical signs of coronary artery disease.

Low Calcium Score

If a patient’s Calcium Score is zero, it is a cause for celebration because it means the risk of having a heart attack is negligible.  If it is low, the disease process has been detected early and treatment can be started which can reverse or at least halt the process.

Medium or High Calcium Score

If the Calcium Score is high and the patient is free of symptoms this is an immediate indication that aggressive therapy needs to be undertaken and further tests should be carried out.  The Calcium Score is also a good objective measure that can be used to monitor a patient’s progress.


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Coenzyme Q10 treatment in serious heart failure.


Several non-invasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular  (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients   received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized   double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the   pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit   from adjunctive treatment with coenzyme Q10.

Munkholm H, Hansen HH, Rasmussen K.

Coenzyme Q10 treatment in serious heart failure.

Biofactors 9(2-4), 285-9 1999

CoQ10 for Congestive Heart Failure


Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive heart failure  (CHF), even when traditional medical therapy is successful. Adjunctive therapy with Q10 may allow   for a reduction of other pharmacological therapies, improvement in quality of life, and a decrease in the incidence of cardiac complications in congestive heart failure. However, dosing, clinical application, bioavailability and dissolution of CoQ10 deserve careful scrutiny whenever employing the nutrient. The assessment of blood levels in ‘therapeutic failures’ appears warranted.

Sinatra ST.

Refractory congestive heart failure successfully managed with high dose coenzyme Q10  administration.

Mol Aspects Med 18 Suppl(), S299-305 (1997)

Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction.


The effects of oral treatment with coenzyme Q10 (120 mg/d) were  (intervention group A) and 71 (placebo group B) patients with acute myocardial infarction (AMI). After treatment, angina pectoris (9.5 vs. 28.1), total arrhythmias (9.5% vs. 25.3%), and poor left ventricular function (8.2% vs. 22.5%) were significantly (P < 0.05) reduced in the coenzyme Q group than placebo group. Total cardiac events, including cardiac deaths and nonfatal infarction, were also significantly reduced in the coenzyme Q10 group compared with the placebo group (15.0% vs. 30.9%, P < 0.02). The extent of cardiac disease, elevation in cardiac enzymes, and oxidative stress at entry to the study were comparable between the two groups. Lipid peroxides, diene conjugates, and malondialdehyde, which are indicators of oxidative stress, showed a greater reduction in the treatment group than in the placebo group. The antioxidants vitamin A, E, and C and beta-carotene, which were lower initially after AMI, increased more in the coenzyme Q10 group than in the placebo group.  These findings suggest that coenzyme Q10 can provide rapid protective effects in patients with AMI if administered within 3 days of the onset of symptoms. More studies in a larger number of   patients and long-term follow-up are needed to confirm our results.

Singh RB, Wander GS, Rastogi A et al.

Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction.

Cardiovasc Drugs Ther 12(4), 347-53 (1998)

Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease.


In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential  hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.

Singh RB, Niaz MA, Rastogi SS et al.

Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease.

J Hum Hypertens 13(3), 203-8 (1999)

Interaction between warfarin and coenzyme Q10


Coenzyme Q10 (Ubidecarenone) is marketed as a dietary supplement. Drug interaction between coenzyme Q10 and warfarin has previously been reported. In the present case, a 72-year-old female treated with warfarin showed less responsiveness to warfarin than previously. It appeared she had taken coenzyme Q10, and when this was stopped, her responsiveness to warfarin was the same as before. Coenzyme Q10 is chemically similar to K-vitamins, which may explain the interaction with warfarin. Patients in treatment with warfarin should be aware of the possible risk of treatment failure when taking coenzyme Q10. The need for questioning patients concerning not   only medications but also use of dietary supplements and alternative medications is emphasised.

Landbo C, Almdal TP.

Interaction between warfarin and coenzyme Q10

Ugeskr Laeger 160(22), 3226-7 (1998)

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