HANS NIEPER: THE MAN BEHIND LITHIUM OROTATE
As a premed student, Hans Nieper was eager to apply the tools of physics to the study of and practice of medicine. There he sought out the works of Einstein and other theoretical physicists, including Nikola Tesla and Richard Feynman. Their research and theories pointed to the possibility that gravity, electricity, and magnetism are all manifestations of a single immensely powerful energy field that pervades all space in the universe. Unlike the static “ether” concept of traditional physics, the “vacuum field” is highly energetic and is both the source and the final destination of all forms of energy. Nieper later realized that the existence of such a field, with all of its pervasive energy, has critical implications of the practice of medicine. The more he studied the more he became convinced that the energetic functions of the human body, and the powerful influence of the vacuum field.
Over the course of his studies in medicine and physics at Mainz Nieper came to the realization that the spark of life could be traced to the energy of the vacuum field. Contrary to traditional medical belief, the electrical charge of the cell membrane is not intrinsic to the membrane itself; it is derived from the energetic vacuum field.
The importance of electricity to the proper functioning of the body—particularly of the heart—has been known almost since the dawn of medical science. There are records of physicians in ancient Greece using the electrical current produced by some species of stingrays to restart hearts. Centuries later, modern physicians use electrical paddles to do precisely the same thing.
We now know that normal cellular functions depend on the maintenance of a very precise electrical balance within the without the cell, and that relatively minor changes in that balance can have catastrophic consequences. For example, people die from diarrheal diseases like cholera, not just because the lose fluid, but because they lose electrolytes, charged particles that come from dissolved salt. Low electrolytes lead to potentially fatal disruptions in nerve and muscle function. But the addition of energy field to this picture presents an entirely new dimension to the possible causes and treatments of disease.
He opened his first outpatient consultation and treatment office at Sedanstrase 21, Hannover, Germany in 1964 where, as Hans A. Nieper, MD, he spent the next 34 developing a line of orthomolecular substances that work to balance the body’s chemistry. His protocols engage a collection of mineral transporters and nutritional supplements that are essential to restoring cellular health. Natural and nontoxic orthomolecular agents are less stressful to patients’ immune system. They also do so without the side effects of costly toxic orthodox agents.
Today these substances form the cornerstone of his clinical treatment of life-threatening chronic diseases such as bi-polar affliction. The successful results he has achieved with his patients speak for themselves.
How does Lithium Orotate work
To begin with the mineral orotates have the increased ability to enter cells. But, what do they do once they’re in? The beginning of the answer that question is that orotate salts are electrically neutral and relatively stable against dissociation, two properties crucial their ability to participate in intracellular mineral uptake and transport. The ability to dissociation (dissolve into component ions) in a solvent such as 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.
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.
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.
Just as relatively minor changes in the composition of the atmosphere have a major effect on respiration (ask anyone who has gone hiking in the oxygen-thin air of the mountains) so changes in the vacuum field, such as the presence of electrical or magnetic fields, have profound effects on the cells. Constant exposure to even a low-level electrical or magnetic field can cause enough of a disruption to alter cellular messages, disable normal repair mechanisms, or even change the expression of reproductive genes.
Much fine research has been done concerning the impact of electromagnetic fields on human cells, including important studies, at great research centers around the world. All of this research has shown, beyond a shadow of a doubt, that living cells do respond to energetic fields, and that the presence of some forms of energy can drastically alter cellular function. When coupled with other risk factors, such as poor diet, exposure to toxic chemicals and other carcinogens, and a sedentary lifestyle, constant exposure to certain types of energetic fields can pave the way for cancer, heart disease, emotional and autoimmune disorders. Humans are living conduits of (and exist because of ) the energy of the universe. This fact carries with it the possibility that we can learn to actively control this energy and use it in positive ways.