1 Introduction

In 1994, approximately 3000 prescriptions for fluoxetine hydrochloride (Prozac) were written for infants aged younger than one year, this alarming statistic was cited in an article in the Journal of the American Medical Association, (Vol. 283 No. 8, February 23, 2000). Approximately 10 per cent of all babies are born with a maternally inherited energy-metabolic-deficiency (EMD) which they themselves can not yet verbalized in understandable terms to their caregivers

1 Introduction

In 1994, approximately 3000 prescriptions for fluoxetine hydrochloride (Prozac) were written for infants aged younger than one year, this alarming statistic was cited in an article in the Journal of the American Medical Association, (Vol. 283 No. 8, February 23, 2000). Approximately 10 per cent of all babies are born with a maternally inherited energy-metabolic-deficiency (EMD) which they themselves can not yet verbalized in understandable terms to their caregivers. Some of these energy deficient babies will be diagnosed as depressed and end up using antidepressants before their first birthday. Fortunately for these babies there are two simple and non invasive blood tests that will show us their metabolic energy levels. The costs of these two blood tests are only R62.00, but it will save thousands of rands in treatment and unmeasurable pain, despair and premature death. “Depressed newborns had higher umbilical lactate levels than vigorous newborns irrespective of the method of delivery. Umbilical cord blood levels of lactate, base deficit, and pH were measured in 452 liveborn infants. In vigorous newborns, the mean umbilical arterial and venous concentrations of lactate were lowest with elective cesarean section, higher with cesarean section performed during labor, and highest with vaginal delivery.”723

Most of these energy deficient babies will grow up and run in to inexplicable problems as adults. "At that stage I... I felt I was working under immense pressure. I was so tired and I had no energy. I had been married for a few months, my second marriage, and I wasn't feeling too well at that stage. I did have a few patients who had problems, or whom I noticed were always coming back for their Pethidine injections. They were allegedly suffering from migraine, but they clearly only came for the Pethidine. One day I just injected myself with one of these vials"32. (Dr Jaques Botha, medical doctor in treatment as an Alkogen patient for his prescription drug abuse).

In Alkogen's therapy rooms patients, of all walks of life and age groups, reveal that they are even too exhausted to pray and feel that nothing will help. Some are even too tired to express this or to accept the redeeming love of God. Others attempt in vain to make it through another day by using self-medication in the form of prohibited or undesirable chemical substances or unhealthy eating habits. Some indulge in socially inexplicable behaviour in order to feel human for a brief while. The entire process is complicated further because their beloved and significant others often do not understand their weariness of life, or can no longer put up with it. We have often labelled many of them with professional stereotypes, like depressive, alcoholic, eating disordered, hyperactive, drug-dependent, delinquent, co-dependent, chronic fatigued and many others. Few of those who provide support understand that these persons might simply lack the metabolic energy to continue. Because there is no existing concept, we can refer to them as the unfortunate persons who suffer from EMD. As will become evident in the later chapters, EMD can be defined as the physical state that develops when the body does not have enough coenzyme 1 (NAD) molecules and accompanying energy metabolic cofactors to generate enough metabolic energy on cellular level to maintain the body in a constant state of health. “Nicotinamide adenine dinucleotide (NAD), an energy "currency" of the cell, all cellular life requires it and there is a concomitant pantheon of proteins that interact with it”.762

EMD exerts a negative effect on man as a whole and therefore ought to be dealt within a multiprofessional manner. This ebook therefore specifically aims to provide deeper insight into the latest information on the body's biochemical functioning in respect of metabolic energy. We often care for the body passively, by depending on medical science to maintain it, by reframing our diseases on a psychological level or by praying and hoping for miracle cures on a spiritual level. Scientific knowledge in the biochemical field has also not yet been recorded in SELF-HELP diaries and reading material that are easily accessible, as is the case with spiritual and psychological issues. This statement merely points out that relevant and therapeutical information on the subject of biochemistry is not readily available to the public. This ebook is an attempt to, in particular, discuss the importance of NAD Therapy as a safe and natural generator of cellular energy in the treatment of EMD.

The goal in writing this ebook is to provide a clear and simple account of the key ideas of NAD Therapy and its therapeutic application in energy-metabolic-deficiency related syndromes (EMDRS). Although we wanted NAD Therapy to be accessible to readers in all of the related disciplines, we could not cover all of these perspectives in detail. NAD Therapy simply starts with the normalising of the cellular energy metabolic production on mitochondrial level, resulting in an energenetic person ready for appropriate medical or psychiatric interventions, psychotherapy, pastoral counselling or any other applicable form of therapy. We also chose not to produce a rigorous formal treatment approach. We did not reach for the highest possible level of scientific integration of the various seemingly unrelated concepts. We tried to choose a level of detail that points the therapeutic inclined in the right directions without distracting from the simplicity and potential generality of the underlying ideas.

We first came to focus on what we referred to as NAD Therapy in late 1989. As you may be aware, many of the chronic ailments that human beings suffer from, tend to take root in an energy metabolic deficient cellular environment. For instance: "As the biological techniques for measuring mitochondrial function have become increasingly refined since the 70s, more than a hundred diseases have been identified as having a mitochondrial basis. Although these overt mitochondrial diseases affect only a small percentage of our population, we wonder to what degree subtle "subclinical" mitochondrial impairment may be involved in more common complaints. Are overt mitochondrial diseases just the "tip of the iceberg" of a much larger and as-yet-unidentified metabolic deficiency? The vast majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation. Oxidative phosphorylation is a highly refined and efficient system for producing the prodigious amounts of energy that are required to maintain the structure and function of the body, and regulate body temperature in warm blooded animals. Oxidative phosphorylation takes place entirely in mitochondria (tiny cellular organelles that closely resemble bacteria in both size and structure)."82

When cells are exposed to a NAD deficient environment, their structure change or they simply die and are disposed of by the body. "It is postulated that a decrease in nicotinamide adenine dinucleotide (NAD) concentration has a primary association with carcinogenesis. The following observations are presented as evidence: (1) NAD and adenosine triphosphate (ATP) concentrations are lower in cancer cells; (2) chemical carcinogens and radiation can cause a lowering of NAD concentration in precancerous cells: (3) biosynthesis of NAD in Ehrlich ascites tumor cells is altered; and (4) NAD is involved in regulating deoxyribonucleic acid (DNA) synthesis. The lowering of NAD concentration would lead to the expression of oncogene and/or virogene according to the protovirus hypothesis, and the cellular characteristics of cancer cells can also be explained through the lowering of cellular NAD."48

One of the most important aspects to note about NAD Therapy is the sheer breadth of its application. It is useful and valuable for so many different symptoms and health issues. A good way to understand NAD Therapy is to consider two of the examples and possible applications that have guided its development. These two examples share features that are so basic that they are easy to overlook.

"Because insulin was discovered in l922 and niacin in l937, no one realized the importance of NAD deficiency in diabetes, even though a small group headed by Tom Spies in l939 published their study of low NAD levels in diabetics. But a lapse of niacin research during and after World War II gave the pharmaceutical companies a voice of unquestioned authority over the new practicing clinicians who had no real experience with niacin deficiency cases and had not lived through events of the Pellagra years in the South, indeed did not recognize the symptoms of pellagra. I discuss this disease in my recent publication on the NAD Deficiency Diseases, wherein I describe the subclinical pellagras (Cleary 1986), and their response to the administration of niacin. The reason antidiabetic agents work is that they mimic the action of NAD which is very low in diabetes, causing a release of insulin from the beta cells, but they do not restore function of the mitochondrial Krebs cycle as NAD does, they do not cure this problem.639"

"Vit B3 treatment took time - often months - before it produced benefits. It was most effective with early schizophrenics - those treated within a year after onset. In cases of longer duration, it sometimes helped when combined with other treatment (sic), including electroshock. Then, late in 1965, Dr. Hoffer began to work with a new chemical, NAD, a derivative of nicotinic acid. Produced as an experimental drug, it seemed to do everything the vitamin did - but in days. Early in 1966, at a New York medical meeting, after three months of trials with NAD, Dr. Hoffer made a preliminary report. Of 17 patients treated, 13 had shown dramatic improvement. A woman hospitalized for eight years seemed almost completely recovered three days after NAD treatment began. It seemed to Dr. Hoffer that NAD was the active form of nicotinic acid; that in normal circumstances, the body converted nicotinic acid from food into NAD but that in the schizophrenic the conversion couldn't take place, with the result that large amounts of adrenaline were turned into adrenochrome. There will be further studies to clarify the NAD question.640"

It is important to note the latest research findings regarding niacin and nicotinamide. It appears that most of the therapeutical benefits ascribe to these compounds are actually only possible by means of its conversion to NAD in the cells. For example: “The beneficial effects of nicotinamide for the treatment of HIV infection appear to be linked to cellular utilization of NAD. Nicotinamide appears to be void of any cell-free reverse-transcriptase inhibition or virucidal activities. However, several cell-associated observations link HIV, nicotinamide, and NAD. HIV-infected cells demonstrate an increase in the ADP ribosylation of proteins, a phenomenon in which NAD is used as the ADP-ribose donator to covalently modify proteins. As a general feature, nicotinamide inhibits ADP ribosylation reactions. Protein ADP ribosylation can occur in the nucleus, in the cytoplasm, and on the cell surface of lymphocytes. PARP is a nuclear enzyme that catalyzes the formation of ADP-ribosepolymers that attach to multiple different proteins. The activity of PARP is critical to the integration of foreign DNA, including proviral DNA; inhibition or absence of this enzyme interrupts the HIV life cycle. Along with poly-ADP ribosylation, monoribosylation steps also involve proteins in cells, including the ADP ribosylation of both HIV Tat protein and cellular defence. The antimicrobial action of nicotinamide might also work through the modulation of certain histone deactylase reactions (i.e.,Sir2 proteins) that use NAD in the silencing of chromosomal DNA”.767

The role of NAD in the therapeutic functions of other medications also becomes available with latest research: “We recently developed a class of novel antitumor agents that elicit a potent growth-inhibitory response in many tumor cells cultured in vitro. WK175, a member of this class, was chosen as a model compound that showed strong in vitro efficacy. WK175 interferes with the intracellular steady-state level of NAD(+), resulting in a decreased cellular NAD(+) concentration. We found that WK175 induces apoptotic cell death without any DNA-damaging effect... These results imply that decreased NAD(+) concentration initiates the apoptotic cascade, resulting in the antitumor effect of WK175.”772

The pioneering work of the world renown Dr. Hoffer with NAD and its precursors, as recorded in various books and articles, was the main cornerstone in the development of EMD and NAD Therapy. He is deservedly recognized as one of the five individuals who pioneered the new medicine for the 21st century. "Once again, the synthesis of a new idea that incorporated biochemical genetic individuality, nutritional modulation of gene expression, and functional physiology resulted in a leap forward into the field of biologically based psychiatry. These five individuals pioneered the new medicine for the 21st century. The recognition that our genes do not determine our disease, but instruct us regarding the optimal environment for health represents a major shift in medical thinking. The acceptance of this model within the medical paradigm is no longer in question. It is just a question of how long it will take for this model to be fully integrated within the standard practice of medicine. The contributions of Archibald Garrod, Linus Pauling, Roger Williams, Hans Selye, and Abram Hoffer have created a force of change that cannot be held back, because truth is its own vector".651

Many concepts, dealt with briefly in this ebook, are relatively new and those who require more information should refer to this ebook's bibliography. For instance: “Fifty years ago, in the early days of biology, so little was known about the cell that all of the proteins outside of its nucleus were grouped into one big "cytoplasmic soup." Now, as the list of known cellular ingredients continues to expand beyond the capacity of any recipe card, two Rockefeller University scientists are taking a step back to ask whether there might be a better way to organize the current thinking about a particularly important class of proteins inherent to all living cells”.793 The aim of this ebook is not to provide a comprehensive review of each theme addressed, but only brief and introductory notes and guidelines are provided to stimulate the reader's own research. This is unavoidable, since the literature on NAD and other energy metabolic related concepts consist of thousands of scientific articles, which one person cannot assimilate meaningfully, during the course of a lifetime. Therefore only a selection is presented, to stimulate further research.