Consumption of 'Good Salt' Can Reduce Population Blood Pressure Levels, Research Finds

An increased intake of ‘good’ potassium salts could contribute significantly to improving blood pressure at the population level, according to new research. The favorable effect brought about by potassium is even estimated to be comparable with the blood pressure reduction achievable by halving the intake of ‘bad’ sodium salts (mostly from table salt).

Those are the conclusions drawn by Linda van Mierlo and her colleagues at Wageningen University, part of Wageningen UR, and Unilever in their investigation of the consumption of potassium in 21 countries. An article describing their findings appears in the journal Archives of Internal Medicine.

The risk of developing cardiovascular diseases rises as blood pressure increases. In Western countries only 20-30% of the population has ‘optimal’ blood pressure, with the systolic (maximum) pressure being lower than 120 mm Hg and the diastolic (minimum) pressure lower than 80 mm Hg. Blood pressure increases with age in most people. Men more often have a higher blood pressure than women.

Diet and lifestyle plays an important role in managing blood pressure. High intakes of sodium and low intakes of potassium have unfavorable effects on blood pressure. Therefore, reducing the consumption of sodium and increasing the consumption of potassium are both good ways to improve blood pressure.

The study carried out by food researchers from the Human Nutrition department at Wageningen University and from the Nutrition & Health department at Unilever demonstrates that the average potassium intake in 21 countries including the US, China, New Zealand, Germany and the Netherlands varies between 1.7 and 3.7 g a day. This is considerably lower than the 4.7 g a day, which has been recommended based on the positive health effects observed at this level of intake.

A hypothetical increase in the potassium intake to the recommended level would reduce the systolic blood pressure in the populations of these countries by between 1.7 and 3.2 mm Hg. This corresponds with the reduction that would occur if Western consumers were to take in 4 g of salt less per day. The intakes of both potassium and sodium are therefore of importance in preventing high blood pressure.

Earlier studies have shown that salt reduction of 3 g per day in food could reduce blood pressure and prevent 2500 deaths per year due to cardiovascular diseases in the Netherlands. In Western countries, salt consumption can be as high as 9-12 g a day whereas 5 g is the recommended amount according to WHO standards. Most household salt is to be found in processed foods such as bread, ready-made meals, soups, sauces and savory snacks and pizzas. An effective way of increasing potassium intake is to follow the guidelines for healthy nutrition more closely, including a higher consumption of vegetables and fruit. In addition, the use of mineral salts in processed foods — by which sodium is partly replaced by potassium — would contribute to an improved intake of both sodium and potassium.

ScienceDaily (Sep. 13, 2010)

China scientists show how arsenic treats blood cancer

Scientists in China have demonstrated how arsenic — a favorite murder weapon in the Middle Ages — destroys deadly blood cancer by targeting and killing specific proteins that keep the cancer alive.

“Our study showed how arsenic directly targets these proteins and kills them,” lead researcher Zhang Xiaowei at the State Key Laboratory of Medical Genomics in Shanghai, China, told Reuters.

“Unlike chemotherapy, the side effects of arsenic (in treating acute promyelocytic leukemia) are very low. There is no hair loss or suppression of bone marrow (function). We are interested in finding out how arsenic can be used in other cancers,” Zhang said by telephone.

Well known for its toxicity, arsenic was regarded in the past as the king among poisons because its symptoms are like those of cholera and can often go undetected.

In China, however, it has long served a dual purpose. Apart from intentional poisoning, it has been used for at least 2,000 years in traditional Chinese medicine.

In 1992, a group of Chinese doctors reported how they used arsenic to treat acute promyelocytic leukemia (APL), a blood and bone marrow cancer that has surprisingly high cure rates of over 90 percent in China.

However, the actual workings of arsenic and how it interacts with cancer tissues has never been clear — until Zhang and his colleagues used modern technology to find out.

In a paper published in the journal Science, Zhang and his team, which includes Health Minister Chen Zhu, described how they used modern equipment and saw how arsenic attacked specific proteins that would otherwise be keeping the cancer alive and well.

“This shows how Western technology can be used to find out about the mysteries of Chinese medicine,” Zhang said.

“Although many countries are now using arsenic to treat APL, some countries are resistant to the idea. It depends a lot on whether doctors recommend it and whether patients accept it.”

In APL, there is a drop in the production of normal red blood cells and platelets, resulting in anemia and thrombocytopenia. The bone marrow is unable to produce healthy red blood cells. Until the 1970s, APL was 100 percent fatal and there was no effective treatment.

“The clinical result of arsenic in treating APL is well-established. More than 90 percent of APL patients in China have (at least) five years of disease-free survival,” Zhang said.

In a separate commentary in Science, Scott Kogan at the University of California San Francisco Cancer Center wrote that proper case selection and combination therapy with arsenic may lead to improved outcomes for treating not only promyelocytic leukemia, but other diseases as well.

“If so, an ancient medicine, revived through careful clinical and biological studies in modern times, will have an even greater impact on human health,” wrote Kogan, who was not linked to the Chinese study.

Reuters:

Selenium supplements

PillManWhy selenate rates (and selenite bites)

Since selenium (Se) was first identified as an essential trace mineral by Schwarz and Foltz in 1957, researchers have discovered that getting enough selenium in the diet just might protect against cardiovascular disease, viral infections including influenza and HIV, rheumatoid arthritis, liver disease, and some forms of cancer as well.

Selenium is now recognized as essential for a variety of bodily functions, of which perhaps the most important and certainly the best known is antioxidant defense. Selenium-binding enzymes known as glutathione peroxidases are responsible for mopping up such harmful oxidants as hydrogen peroxide and lipid peroxides. Other selenoproteins – proteins which store, carry, or utilize Se – are involved in thyroid hormone metabolism, muscle function, male fertility, and immune regulation.

A deficiency of active, Se-bound glutathione peroxidase (GPx) appears to play a crucial role in the pathology of many conditions associated with selenium deficiency. In the case of cancer, however, the story is a bit more complicated. In fact Se appears to have multiple anticancer effects, only some of them involving GPx (which can protect DNA from cancer-causing mutations). Other evidence points to an anticancer mechanism independent of enzyme-bound Se, whereby ingested Se gets rapidly converted into molecular forms toxic to cancer cells and subsequently excreted rather than stored.

In view of selenium’s multiple metabolic pathways, it’s important to recognize that all forms of Se are not equal. Selenium supplements come in two basic varieties – inorganic salts like selenate (SeO4–) and selenite (SeO3–) and newer, organic compounds like selenomethionine (SeMet). In recent years SeMet has gotten most of the press because it’s supposedly more   “bioavailable”‘ than either of the inorganic salts, in the sense that it’s better retained in the body. But is tissue retention really the best yardstick for gauging the superiority of one supplement over another? In the case of selenium, the answer is definitely no.

In one experiment, for example, rats fed high doses of either SeMet or selenite were shown to accumulate more Se from SeMet. Despite the higher tissue levels achieved with SeMet, other experiments have found SeMet to be relatively ineffective for suppressing chemically induced colon cancer. Both selenite and selenate, but not SeMet, significantly decreased the numbers of preneoplastic lesions (precursors to colon cancer) caused by feeding rats a chemical carcinogen. In a related experiment, both selenite and selenate – but not SeMet – significantly reduced the binding of the same carcinogen to DNA in rat colon. In the latter study, rats supplemented with SeMet had greater plasma and liver Se concentrations and GPx activity than those supplemented with selenite or selenate. Thus, the most “bioavailable” form of Se was the one that was least effective in preventing colon cancer.

There are clear differences between selenate and selenite as well, the most important of which is that selenite is much more toxic than selenate both in vivo and in vitro. In addition, for relatively low doses of Se fed to humans, the absorption of selenate was observed to be greater and the urinary excretion faster than that of selenite, although retention was about the same. The enhanced uptake of selenate over selenite is mediated by an active transport mechanism in the small intestine, presumably involving the same transporter protein that carries sulfate; sulfate is a close chemical cousin of selenate but not of selenite.

The increased absorption and excretion of selenate may contribute to its lower toxicity compared to selenite. On the other hand, the similar extent to which low doses of either compound are retained suggests that once absorbed, both selenate and selenite can be utilized effectively for replenishing Se stores, in agreement with previous findings.

There are further problems associated with selenite, however: “antinutritive” activities not encountered with selenate. In the presence of stomach acid, selenite is converted to selenious acid and is further converted to inactive, elemental selenium if vitamin C is taken at the same time. In addition, nutritionally important minerals such as copper are capable of forming complexes with selenide, a metabolite of selenite; the resulting mineral complexes can tie up Se and its mineral partner in a form in which both remain metabolically unavailable.

Copper and zinc have likewise been shown to inhibit the generation of DNA-damaging oxygen radicals produced when selenite interacts with the body’s natural antioxidant glutathione. The likeliest explanation for the inhibitory effect is that both copper and zinc are inactivating selenite by forming complexes with selenide, as mentioned earlier. Unlike selenite, selenate does not interact with glutathione and therefore does not directly generate toxic oxygen radicals or tie up useful minerals such as copper and zinc.

In defense of selenite, however, it should be noted that its metal-complexing ability does have a useful side. Selenite can counteract heavy metal toxicity by tying up mercury, cadmium, and silver in a metabolically inactive form in the same way it does with copper. This beneficial effect of selenite occurs after its reduction to selenide by interacting with glutathione within the body. Selenate, on the other hand, cannot generate selenide directly and so does not directly participate in heavy metal detoxification.

To summarize, selenate has been shown to be an effective anticarcinogen while still retaining an ability to replenish Se stores. Other Se compounds that are effective anticancer agents – whether synthetic chemicals such as triphenylselenonium chloride or organic products such as Se-rich broccoli – cannot build up the body’s reserves of Se or increase the activity of GPx. Only selenate or selenite can perform both sets of functions (anticancer activity and capacity for being stored), and of the two selenate is clearly superior because of its lower toxicity and lack of interference with metabolism of other nutrients. In other words, selenate is the one form of Se to take if you’re taking only one.

A note on dosing: The RDI (Reference Daily Intake) for selenium in this country is 70 mcg for adult males and 55 mcg for females, although other countries have set the upper limit higher. The minimum daily dose of Se that has been administered in cancer prevention studies is 200 mcg. Anecdotal reports indicate that some people have received benefit from consuming larger doses, 1000 mcg or even higher per day, with no ill effects. Although the toxicity of selenate is considerably less than that of selenite, I don’t recommend consumption of doses higher than about 10 times the RDI (let’s say higher than 800 mcg) without first consulting a health care professional.

Consuming selenate in large daily doses can also result in a transient decline in blood sugar (hypoglycemia) because selenate has insulin-like effects. The irritability, lightheadedness, and fatigue that ensue are temporary and can be counteracted by eating some carbohydrate-rich food. However, diabetics and anyone with a tendency toward hypoglycemia should monitor their Se intake and blood sugar levels carefully.

http://www.ilifelink.com/sodium_selenate_200_mcg_x_100_capsules.html

Orotates and the mineral transporters of Dr. Nieper

PillManWhat’s the best way to take mineral supplements? Picolinates? Amino acid chelates? Chelates involving other organic acids such as citrates? Whenever anyone asks my opinion on such matters, I find myself giving an answer they often don’t expect: “Try orotates” The blank looks I usually get in response tell me that most people need some educating on the subject, hence this article.

Orotates are the mineral salts of orotic acid, a natural substance found in our bodies and also in various foods including dairy products. As theorized many years ago by the pioneering German physician Hans Nieper, orotates are a component of a natural system of electrolyte carriers for distributing minerals throughout the body. (A different compartment of this same system uses amino acid complexes such as aspartates and arginates to deliver minerals.) Based on his observations of cells in culture, Nieper concluded that molecules of calcium orotate and magnesium orotate can pass through cell membranes intact without “dissociating” or breaking apart into their component ions, and thereafter release their respective ions only at specific membrane sites within the cell. Subsequently he extended this principle to include other orotates such as lithium and zinc.

Working at his clinic in Hannover, Germany, Nieper applied his unique discoveries to the treatment of diseases such as cancer, heart disease, multiple sclerosis, and rheumatoid arthritis as well as other autoimmune conditions. Over the course of more than four decades Dr. Nieper treated thousands of patients with his innovative mineral transporters, many apparently with great success. However, in later years he published relatively little in medical journals, preferring instead to reserve his time for treating patients and for presenting occasional seminars about his work to medical professionals and consumers. As a result, his discoveries have been considered controversial by mainstream medicine or simply ignored, at least until recently.

Hans Nieper died in October, 1998 at the age of 70 ironically just at a time when many of his ideas had finally begun gaining wider acceptance. Only a few weeks before his death, in fact, the collected papers from a symposium on the medical uses of magnesium orotate were published in the journal Cardiovascular Drugs and Therapy. Overall, the symposium lent credence to Nieper’s claims for the cardiovascular benefits of magnesium orotate while calling for additional human trials.

How do the orotates work?

That’s a complex question necessitating a somewhat detailed discussion of biochemistry and for this reason my explanation has been relegated to an article of its own. See How Orotates Work. For now I’ll just state my summary conclusions: There is independent scientific evidence corroborating Nieper’s theory of orotates as mineral transporters. In my judgment, the evidence tends to support Nieper’s criteria for orotate as an electrolyte carrier, namely, (1) a low dissociation constant, (2) an affinity for specific cellular systems or organs, and (3) a metabolic pathway which liberates the transported mineral within the targeted organ or system.

Perhaps the recent wave of interest in Dr. Nieper’s compounds will inspire further research on the mechanism of transport. Until then there’s plenty of evidence for the validity of Dr. Nieper’s ideas in previous publications by Nieper and other researchers. The following sections summarize these results on the medical and biological effects of the various mineral orotates, together with a brief discussion of other potential uses. Beyond that, there is direct and compelling evidence from personal experience see my article Orotates for Weight Loss, Cognitive Enhancement, and Athletic Performance for details. To give but one example, there can be little doubt about the effectiveness of Nieper’s products when the majority of people trying calcium orotate as an appetite suppressant can tell almost immediately that it works, just as Nieper said it would.

Magnesium orotate

Of all the macronutrient minerals in the human body, magnesium is the one most likely to be deficient. Magnesium deficiency has been linked to a large number of disorders, including diabetes, hypertension, dementia, and osteoporosis. Magnesium compounds are medically accepted as helpful for treating migraines, asthma, chronic lung disease, and cardiac conditions such as heart attack and arrhythmias. Magnesium orotate should be even more effective than other magnesium supplements for such conditions, in view of its enhancement of magnesium transport and its documented benefits in cardiovascular disorders.

In addition to its cholesterol-lowering and heart-energizing effects, magnesium orotate has also been reported to improve the elasticity of blood vessels. Using capillarographic recordings Dr. Nieper was able to show that a daily dose of 380 mg magnesium orotate over 15 months was sufficient to normalize or greatly improve the elasticity of peripheral blood vessels in 60 of 64 patients. Such an effect on vessel elasticity suggests the use of magnesium orotate for lowering blood pressure as well as for inhibiting arteriosclerosis.

Dr. Nieper generally combined magnesium orotate with other nutrients for optimal effect. For example, it’s known that potassium deficiency is closely linked with magnesium deficiency because magnesium ions are needed to activate an important cellular pump which regulates sodium and potassium levels. In addition, potassium orotate itself is thought to be beneficial for conditions such as cardiomyopathy and congestive heart failure (see section below on Potassium orotate). So it’s not surprising to find that Nieper recommended a combination of magnesium orotate (1.5 to 2.5 grams per day) plus potassium orotate (138 to 300 mg daily) for treating angina and coronary heart disease. He also suggested adding the pineapple enzyme bromelain (120 to 140 mg per day) to inhibit platelet aggregation and dissolve fibrin clots. The 2- and 4-year mortality rates for patients on this regimen were reportedly reduced by 90% or more compared to patients in other studies who received conventional medications.

A similar Nieper combination designed for unclogging arteries involved magnesium orotate (1 to 1.5 grams per day) together with carnitine (4 grams per day), selenium (Se-enriched yeast, 300 to 400 mcg per day), bromelain (240 mg daily), and the enzyme serrapeptase 10 to 15 mg per day). See my article on CardioPeptase for additional information.

Finally, it’s worth pointing out that magnesium orotate isn’t just for heart patients – it’s also for healthy athletes. In a double-blind, randomized study, 23 competitive triathletes were studied after 4 weeks of supplementation with placebo or magnesium orotate. Blood was collected before and after a test consisting of a 380-meter swim, a 20-km bicycle race, and a 5-km run. Compared to placebo, magnesium orotate caused a greater increase during the test in serum glucose and venous partial pressure of oxygen, and a greater decrease in serum insulin, blood acidity, and serum cortisol. The changes in glucose use and reduction in stress responses occurred without affecting the athletes’ competitive potential-quite the reverse, in fact. The exercising athletes had greater endurance as a result of the magnesium orotate supplements. By contrast, a different study in which athletes were supplemented with magnesium oxide (which is relatively poorly absorbed) reported no improvement in exercise performance, attesting to the superior uptake of magnesium in the orotate form compared to the oxide.

Potassium orotate

Potassium deficiency is not considered to be common in view of the availability of adequate amounts of this mineral in most diets. Nevertheless, potassium deficiency is known to arise as a secondary consequence of magnesium deficiency. Another cause of deficiency is the use of potassium-wasting diuretics to control high blood pressure. Disease states known to be associated with low serum or tissue potassium include diabetes, insulin resistance, and high blood pressure as well as rheumatoid arthritis and heart disease.

Dr. Nieper’s original motivation to develop orotic acid as an electrolyte carrier was inspired by results due to E. Bajusz showing that potassium orotate can prevent idiopathic myocardial necrosis in hamsters, while potassium chloride is ineffective. Nieper subsequently found that potassium orotate was highly effective for alleviating human cardiovascular diseases when combined with magnesium orotate (see discussion in the section below on Magnesium orotate). Even when administered by itself to heart attack patients, potassium orotate has been reported to result in faster recovery of myocardial contractibility than in placebo-treated controls.

Other reported applications for potassium orotate include acceleration of wound healing and enhancement of recovery and immune function following surgery. Although not an antioxidant itself, potassium orotate facilitates the tissue uptake of vitamin C from serum and increases blood levels of reduced glutathione. Finally, studies in animals have revealed antidepressant, psychostimulant, and anxiety-reducing effects associated with chronic potassium orotate administration.

Lithium orotate

Although no absolute need for lithium has yet been established in human nutrition, lithium intake can affect many different systems in the body in a positive way. Lithium is most famous for treatment of manic-depressive disorders. At high doses lithium can depress dopamine release (which tends to flatten elevated moods), while at lower doses it can stimulate serotonin synthesis (which gives an antidepressant effect). Although most people don’t need treatment for manic-depressive illness, a very large number with mild depression could benefit from low-dose lithium supplements. Recently it’s been discovered that lithium has potent neuroprotective effects as well (see the article Lithium increases gray matter in the brain). The hope now is that lithium supplements will prove capable of halting the progress of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis, among others.

Lithium is also known for its immune-enhancing and antiviral effects, especially against herpes simplex virus. It may be equally effective against measles, judging by results obtained in vitro. The downside to lithium’s immune-stimulating activity is that it can also set off autoimmune reactions in susceptible individuals. For this reason, if you suffer from an existing autoimmune disease such as rheumatoid arthritis or lupus, don’t take lithium supplements without first consulting your health care professional.

Another benefit of supplementing with lithium is its insulin-sensitizing effect. Lithium has been found to decrease blood glucose levels, especially when used in conjunction with insulin or oral glucose-lowering drugs. Results such as these have led to suggestions that lithium might be useful in treating diabetes.

As expected in view of the neurological activity of lithium compounds, Dr. Nieper found that lithium orotate in doses of 138 mg 4 to 6 times per week was effective in treating cases of depression, headaches and migraine, epilepsy, and even alcoholism. The amount of lithium contained in the doses was only a small fraction of the amount conventionally given as therapy for manic-depressive illness, thus avoiding the risk of kidney toxicity typically associated with high-dose lithium. Elsewhere Dr. Nieper reported that 5 mg of lithium in the form of orotate was roughly as effective as 100 mg of lithium in the form of carbonate, giving a 20-fold enhancement of potency thanks to efficient transport of the lithium by its orotate carrier.

Nieper’s results were subsequently confirmed in a group of 42 alcoholic patients who were followed for between 6 months and 10 years. Treatment with 138 mg of lithium orotate per day resulted not only in a marked decline in alcoholic relapses, but also in improvements in liver, cardiovascular, thyroid, and immune function. Migraines, cluster headaches, manic behavior, and seizure disorders were also reduced among this group. Eight patients reportedly developed muscle weakness, loss of appetite, and mild apathy as a result of treatment, but symptoms disappeared after the dose was reduced to 138 mg 4 to 5 times per week. The improvements in liver function appeared to be due to a synergy between lithium orotate and calcium orotate, both of which were administered to the alcoholic patients with liver disease. For more information on the treatment of liver disorders with a combination of lithium and calcium orotate, see the section below on Calcium orotate.

Note on lithium safety

As mentioned above, lithium in large doses can be toxic, especially to the kidneys. The therapeutic dose of lithium when administered as lithium carbonate is close to the toxic dose (i.e., there is a narrow therapeutic window), and for this reason blood levels and organ function need to be monitored continually. This is true only for lithium carbonate and not for lithium orotate. For example, according to the Physicians Desk Reference, the recommended dose of lithium carbonate administered for treatment of psychiatric disorders is 300 mg three to four times per day. Since each 300 mg tablet of lithium carbonate provides 56.8 mg of elemental lithium, the total amount of lithium delivered would range from 170.4 mg to 225.6 mg per day. By contrast one lithium orotate tablet delivers 5.8 mg elemental lithium, which is roughly 1/30 to 1/40 the amount delivered by the recommended daily dose of lithium carbonate. Even taking several lithium orotate tablets per day would amount to a dose well below the toxic level for lithium.

Similarly, consumers of lithium carbonate are often warned of possible toxic effects if other medications such as ACE inhibitors or diuretics are taken concurrently. Although these warnings appear to be true for pharmaceutical lithium compounds only and not for modest doses of lithium orotate, it would nevertheless be wise to consult with a health care professional for anyone contemplating taking lithium orotate concurrently with either of these medications.

Zinc orotate

Zinc deficiency has been implicated in age-related osteoporosis and, conversely, zinc supplements can speed the healing of fractures in animal models. Zinc also plays a vital role in immune function, where deficiency is associated with atrophy of the thymus, reduction in white blood cell counts, and increased susceptibility to infection. Another important role for zinc is in maintaining male reproductive function. Deficiency of zinc is associated with hypogonadism and low levels of serum testosterone, reversible upon supplementation. Zinc also appears to be important for the activity of growth hormone (GH) since GH loses effectiveness under conditions of zinc deficiency.

As is well known, one of the major roles for zinc in human nutrition is its antioxidant activity. Increasing zinc intake may protect against conditions associated with both oxidant stress and zinc deficiency, such as diabetes. Zinc deficiency is known to be associated with an increased prevalence of coronary artery disease as well as diabetes, and with several associated risk factors including hypertension, hypertriglyceridemia, and insulin resistance (syndrome X).

In view of the association of zinc deficiency with diabetes, it’s not surprising to learn that zinc orotate stabilizes blood glucose and reduces the need for insulin in diabetics, according to Dr. Nieper. In addition, zinc orotate and other zinc compounds synergize with sulfur-containing antioxidants (sulfhydryls) to protect against free radical-induced tissue injury, a result which may have relevance to the treatment of diabetes as well as other diseases of increased oxidative stress.

Calcium orotate

Treatment or prevention of osteoporosis is one of the main applications for calcium supplements generally and for calcium orotate in particular. Dr. Nieper specifically cited its effectiveness in treating both inflammatory and osteoporotic decalcification and in relieving pain resulting from osteoporosis of the spine. In another paper Nieper reported successful recalcification of malignant bone tumors (thereby preventing further metastases) with calcium orotate in 10 out of 13 subjects. He also found that a daily oral dose of about 600 mg was sufficient to reverse bone loss caused by radiological therapy in cancer patients, an effect documented by X-ray photos of several subjects before and after treatment with calcium orotate. A further paper reported on the benefits of calcium orotate in treating joint diseases such as arthritis and spondylitis. On the basis of results such as these, it seems likely that calcium orotate can also have a beneficial impact on the degenerative bone changes characteristic of osteoarthritis. (For information on an orotate formulation optimized for bone health, see description below of Osteo Forte Orotate.)

But calcium orotate has many other uses as well. In his remarkable paper of 1969 Dr. Nieper reported his observations after dispensing more than 38,000 doses of calcium orotate to a large number of patients over the course of a year. Nieper found that low-dose calcium orotate was effective in treating severe refractory psoriasis, lowering blood pressure in cases of arteritis and arteriosclerosis, relieving angina pectoris, and ameliorating cases of multiple sclerosis, disseminated encephalitis, retinitis, chronic hepatitis, and colitis. The dosages employed varied from about 300 to 1000 mg calcium orotate per day. No side effects were noted except for a loss of appetite among obese chronic overeaters, some of whom were able to lose a substantial amount of excess weight.

In subsequent research Nieper reported achieving complete remissions of chronic, aggressive hepatitis in 14 patients treated with 3 grams of calcium orotate per day for 2 years; 4 of these patients also required cortisone therapy, although at a decreased dosage. Nieper found that an optimal therapeutic effect was achieved after a period of 9 to 18 months of daily supplementation, but not earlier. However, with a regimen of 2 grams calcium orotate plus 138 mg lithium orotate per day, the same beneficial results could be achieved in cases of hepatitis and cirrhosis in only 2 to 3 months. This research should be re-investigated in view of the emerging global health crisis of hepatitis C.

Around 1975 Dr. Nieper began treating lupus erythematosus patients with calcium orotate. He found that a dose of 1 to 2.5 grams was surprisingly effective when administered over a period of at least one year, even in advanced cases with pulmonary constriction, pleural effusions, or cardiomyopathy. Therapy also involved low-dose prednisone and a variety of nutrients to promote adrenal steroid synthesis, such as selenium and vitamins C and D2, as well as other calcium and magnesium salts. An account of one patient’s successful response to therapy with calcium orotate and other Nieper compounds can be found in an article available from the Brewer Science Library. In addition Nieper found that multiple sclerosis sometimes accompanies lupus, so it’s not surprising that his protocol for treating MS is strikingly similar to that for treating lupus. He recommended a dose of 1 gram calcium orotate per day for MS patients, with a higher dose given to those patients with a tendency toward migraine-like headaches.

Osteo Forte orotate

The benefits of calcium orotate for healthy bone metabolism can be amplified by adding a variety of other minerals. Magnesium, manganese, zinc, and boron are all known to act in concert with vitamin D and calcium. Osteo Forte Orotate combines calcium, zinc, and magnesium orotates with other nutrients in a synergistic formulation optimal for maintaining bone health.

List of essential minerals

An “essential mineral” is a chemical element that is required by organisms for survival or at least for health. The elements carbon, hydrogen, nitrogen, and oxygen, however, are excluded from the list because they are so omnipresent that they were never recognized as minerals.

The well-established essential minerals are:

  • calcium
  • chlorine
  • chromium
  • cobalt
  • copper
  • iodine
  • iron
  • magnesium
  • manganese
  • molybdenum
  • phosphorus
  • potassium
  • selenium
  • silicon
  • sodium
  • sulfur
  • zinc

In addition, the following elements are suspected to be essential minerals:

  • boron
  • nickel
  • tin
  • vanadium

Circumstantial evidence suggests that the following elements might also be essential, despite the reputation many of them have for being merely toxic 1:

  • aluminum
  • arsenic
  • bromine
  • cadmium
  • germanium
  • lead
  • lithium
  • rubidium

How orotates work – The biochemistry of 'vitamin B13'

PillManThis article addresses two biochemical puzzles about the mineral orotates: how they get into cells and what they do once they’re in.

We begin with the fact that the orotate salts are electrically neutral and relatively stable against dissociation, properties that seem to be crucial for the ability of orotates to participate in intracellular mineral uptake and transport. Dissociation is the process that takes place when a salt is dissolved in a solvent such as water and breaks up into its component ions. Table salt dissolved in water, for example, dissociates into sodium and chloride ions. At physiological pH the orotate salts are much more stable than table salt and will not readily dissociate into free orotic acid plus a mineral ion.

Free orotic acid (OA) itself is known to get into cells by simply leaking (diffusing) through cell membranes, rather than by being actively transported. But diffusion is a relatively inefficient process, which limits the amount of OA that can enter a cell. By contrast, uracil – a compound almost identical to OA, only minus the carboxylic acid group – is taken up efficiently by a transporter protein that binds to uracil molecules and drags them into the cell. This transporter appears to be specific for uracil or similar molecules which are uncharged, but not for uracil’s close cousin OA (which is negatively charged at body pH).

Bind the orotic acid with a mineral, however, and you end up with a stable electrically neutral salt. This property is just what is needed for OA along with its bound mineral to be taken up directly by the uracil transporter. At the same time, neutralizing the charge on OA makes the resulting complex more lipophilic or “fat-loving” than free OA; as a result, the stable orotate complex would be expected to diffuse more easily through the lipid membranes of cells. Essentially just such a mechanism was proposed by Nieper for enhancing the diffusion of mineral ions across cell membranes. Either way – via enhanced diffusion or active transport – complexing a mineral with orotate results in increased uptake of both components of the complex by cells.

That’s still not the whole story of orotate, however. Here and there in his papers, Nieper gives tantalizing clues about the role of the “pentose phosphate pathway” or PPP in mediating the effects of his mineral orotates. The PPP is a well-known biochemical cycle which, among other vital functions, is responsible for synthesizing D-ribose 5-phosphate. D-ribose is of course the sugar which gets incorporated into nucleotides (a process known as ribosylation) and ultimately into RNA/DNA. Was Nieper attempting to signal a deep connection between the ribosylation of orotate and its activity as a mineral transporter?

The answer is yes. To see what Dr. Nieper was hinting at, we need some additional background information on OA, also known as vitamin B13.

Although orotic acid isn’t officially considered a vitamin these days, over 40 years ago it was found to have growth-promoting, vitamin-like properties when added to the diets of laboratory animals. Subsequent nutritional studies in humans and animals revealed that OA has a “sparing” effect on vitamin B12, meaning that supplemental OA can partially compensate for B12 deficiency. OA also appears to have a direct effect on folate metabolism.

Many of the vitamin-like effects of OA are undoubtedly due to its role in RNA and DNA synthesis. (B12 and folate are also involved in DNA synthesis, but at a point downstream from where OA comes in.) Our bodies produce OA as an intermediate in the manufacture of the pyrimidine bases uracil, cytosine, and thymine. Together, these pyrimidines constitute half of the bases needed for RNA/DNA, the other half coming from the purine bases adenine and guanine which are synthesized independently of OA.

The enzyme orotate phosphoribosyltransferase (OPRTase), which is found in organisms ranging from yeast to humans, is responsible for catalyzing the first step in the conversion of orotic acid into uridine. It does so by facilitating the attachment of a ribose plus phosphate group to OA. The net result is the formation of a molecule named OMP (orotidine 5′-monophosphate), which in turn is the immediate precursor to UMP (uridine 5′-monophosphate).

Because the enzyme OPRTase requires magnesium ions for its activity, some researchers wondered whether a magnesium complex of orotic acid might be involved in binding orotate to the enzyme. They found that the true substrate for OPRTase is not orotate itself but rather a magnesium orotate complex. The fact that the complex is electrically neutral compared to the negatively charged orotate ion means that the complex is more easily transportable to the active site of the enzyme. These researchers suggested that the magnesium complex helps position orotate within the enzyme in the proper orientation for conversion to OMP. In the process the magnesium ion in the complex gets exchanged with the magnesium ion bound to the active site of the enzyme, the net result being that one magnesium ion is released.

So far, so good. Following up on Nieper’s hint, we see that orotate-and specifically magnesium orotate-can interact with the pentose phosphate pathway (PPP) to generate OMP and ultimately uridine. But Nieper also pointed out that the mineral-transport activity of the orotates does not necessarily have anything to do with the formation of RNA or DNA. To resolve this apparent contradiction, we must seek out an additional metabolic role for orotate independent of RNA/DNA synthesis

In fact, not all the uridine formed from orotic acid does wind up in RNA or DNA. There are other vital roles for orotic acid and uridine in the body-for example, OA gets taken up by red blood cells where it is rapidly converted to UDP-glucose by way of OPRTase and other enzymes. Here UDP is the nucleotide uridine diphosphate. The red blood cells can then act as a storage and distribution pool for delivering glucose and uridine to tissues such as brain, heart, and skeletal muscle. Because UDP-glucose is a precursor for glycogen (a storage form of glucose), the delivery of UDP-glucose to heart muscle and its conversion there to glycogen might account for some of the cardioprotective effects of orotic acid.

Which brings us right back to Dr. Nieper’s work.

Based on the available scientific evidence, it seems clear that magnesium orotate can get channeled directly into OMP synthesis and ultimately into UDP-glucose, which can then resupply a heart under stress with carbohydrates and nucleotides. Thus a mechanism exists for explaining why magnesium orotate works even better than orotic acid for heart conditions. In contrast, some of the mineral orotates such as copper and nickel either inhibit OPRTase or, in the case of calcium orotate, neither activate nor inhibit the enzyme. This suggests that the body preferentially uses magnesium orotate for promoting uridine synthesis. In a sense, complexing OA with magnesium magnifies the “vitamin-like” properties of vitamin B13.

Another effect of magnesium orotate is to inhibit the development of atherosclerosis when administered orally to humans or experimental animals. The animal study in particular tells us that magnesium orotate performs better than orotic acid, which in turn outperforms magnesium chloride, in inhibiting atherosclerotic changes caused by high levels of cholesterol in the diet. In other words, a synergy exists between magnesium and orotic acid such that the complex they form – magnesium orotate – is more potent than either one alone. Dr. Nieper explained this effect by suggesting that when OA in the magnesium orotate complex is coupled with ribose (ribosylated) in the walls of blood vessels, the magnesium ion is liberated during this process and becomes locally available for activating cholesterol-metabolizing enzymes.

The increase in potency of magnesium in going from a chloride salt to an orotate salt is notable and certainly consistent with Nieper’s ideas about orotate as a mineral transporter. But notice that orotic acid also increases in potency in going from free OA to its magnesium complex, an enhancement consistent with the idea that magnesium orotate gets preferentially directed toward uridine synthesis by OPRTase. It is just this combination of properties – enhanced transport of magnesium, itself known for its anti-atherosclerotic and anti-cholesterol effects, and enhanced synthesis of uridine from orotic acid –  that makes magnesium orotate so helpful for treating cardiovascular disorders.

By contrast, the very similar compound calcium orotate has none of the effectiveness of magnesium orotate in lowering serum cholesterol, although it does have other characteristics beneficial for treating arterial disease. The difference in activity between magnesium and calcium orotate can best be explained by the specific effects of magnesium in activating cholesterol turnover as well as by the specificity of magnesium orotate-but not calcium orotate-for activating OPRTase.

As the preceding example shows, the various mineral orotates are likely to be targeted to distinct metabolic pathways in specific tissues. Another example is provided by an experiment involving lithium metabolism in the brain. Lithium is well known for its ability to moderate manic-depressive illness. In an experiment to evaluate lithium-induced changes in brain metabolism, rats were injected with a solution of lithium chloride daily for two weeks. One hour after the last lithium treatment all rats received an injection of radiolabeled orotic acid into the cerebral ventricles. At various intervals thereafter RNA was extracted from rat brains, separated into fractions, and analyzed for radioactivity. The results showed that lithium increases RNA turnover markedly in brain (but not in other tissues such as liver). The authors suggested that lithium acts at the membrane level and that the effects on RNA metabolism are due to changes in the transport of radiolabeled orotic acid-an explanation entirely consistent with Nieper’s idea that lithium combines with OA to yield a transportable complex.

In summary, the evidence tends to support Nieper’s criteria for orotate as an electrolyte carrier, namely, (1) a low dissociation constant, (2) an affinity for specific cellular systems or organs, and (3) a metabolic pathway which liberates the transported mineral within the targeted organ or system.