Abstract Niacin is required for a host of critical redox and adenosine diphosphate-ribosylation reactions in metabolism. Niacin deficiency leads to the distinctive signs and symptoms of pellagra, but these can happen in an unpredictable progression and can be altered in patients with polymorphisms in any of the hundreds of niacin-dependent enzymes. The symptomatology of niacin deficiency is becoming a forgotten knowledge base, and niacin deficiency is likely underdiagnosed. Additionally, high levels of niacin and niacinamide have pharmacological effects distinct from their role as sources of vitamin B3, allowing a wide range of effects on processes such as blood flow and lipid metabolism, which can be used to treat or prevent a variety of disease processes.

Abstract Anxiety disorders are extremely debilitating and are the most common psychiatric disorders in the United States. Such patients have greater chances of developing other medical illnesses such as chronic obstructive pulmonary disease, diabetes and hypertension. The underlying anxiety that exists in these patients also tends to prolong the course of any additional medical illnesses that they may develop. The conventional approach to severe anxiety involves pharmacotherapy with benzodiazepines, selective serotonin re-uptake inhibitors (SSRIs), or other medications such as buspirone, imipramine or trazodone. A case report demonstrated that the use of 2500mg of niacinamide (nicotinamide) per day ameliorated severe anxiety in a 34-year-old male patient. It appears that niacinamide has therapeutic properties similar to the benzodiazepines. However, the therapeutic effects of niacinamide likely have little to do with it acting as a ligand for the benzodiazepine receptor. Niacinamide might exert its effects through its modulation of neuro-transmitters that are commonly unbalanced in those areas of the brain associated with anxiety. Niacinamide might also reduce anxiety by shunting more tryptophan toward the production of serotonin and/or by simply correcting a vitamin B3 dependency. The use of niacinamide for extended periods of time appears to be safe, but megadoses can cause sedation, nausea and vomiting. More case reports, research and rigorous controlled trials are needed to properly evaluate niacinamide’s therapeutic effectiveness, safety and mechanisms of action for the treatment of anxiety.

Abstract Insomnia is a common problem seen in clinical practice. It has been defined as unsatisfactory sleep that impacts daily functioning, and for diagnostic purposes can be separated into acute insomnia (i.e., less than 30 days), or chronic insomnia (i.e., greater than or equal to 30 days). The majority of insomnia cases are associated with other medical conditions, giving rise to a more appropriate diagnosis of “comorbid insomnia.” The work-up of chronic insomnia is described. Improving sleep habits should be the foundation of a program designed to correct insomnia, especially if it is considered chronic. The author has been experimenting clinically with a variety of orthomolecular substances for over 15 years, and has found a specific combination of three orthomolecules to be particularly effective for many cases of acute or chronic insomnia. This approach is called, “SRR,” which refers to the use of gamma-aminobutyric acid, niacin, and prolonged-release melatonin to promote sedation, relaxation, and regulation, respectively. A brief description of each of these orthomolecules is included, as well as appropriate prescribing information. Other clinical considerations are described to assist clinicians in managing insomnia.

Abstract Background: Many patients with anxiety often turn to complementary and alternative medical (CAM) treatments. Because of the popularity of CAM among patients with anxiety, it is important that emerging CAM treatments are researched for safety and efficacy. One emerging CAM treatment that shows potential as an anxiolytic agent is the amide form of vitamin B-3, also known as niacinamide (nicotinamide). Objectives: To evaluate the efficacy and safety of niacinamide in a participant with anxiety symptoms. Design: Double-blind, placebo-controlled N-of-1 trial of niacinamide versus placebo for the treatment of anxiety symptoms. Setting: The Robert Schad Naturopathic Clinic, the outpatient clinic of the Canadian College of Naturopathic Medicine (North York, Ontario). Intervention: Following a 2-week washout cycle, the 26-year-old female participant was allocated to a 4-week treatment Period (Block) where she was provided with 3000 mg/day of niacinamide, or an equivalent-looking placebo, at 2-week intervals. Following another 2-week washout cycle, the same procedure was followed. Main outcome measures: Beck Anxiety Inventory (BAI) questionnaire, Measure Yourself Medical Outcome Profile (MYMOP) questionnaire, 14-day medication diary for side effects and pill counts, and laboratory testing to monitor safety and possible toxicity. Results: The BAI results did not demonstrate a statistically significant difference in favour of the niacinamide for Periods 1 and 2 (p=0.07). There were no statistically significant differences in favour of the niacinamide for all the dimensions of the MYMOP, which include Symptoms 1 (p=0.30) and 2 (p=0.40), Activity (p=0.13), and Wellbeing (p=0.09) over the duration of the study. The baseline and end-of-trial evaluations (i.e., physical examination and laboratory testing) were within normal limits. None of the participant’s transaminase levels were abnormal during the trial. Conclusions: Niacinamide is safe at dosages as high as 3000 mg/day. Treatment with niacinamide produced no favourable therapeutic effects upon the participant’s symptoms of anxiety and anxiety scores per the BAI and MYMOP questionnaires. Trial Registration: Natural Health Products Directorate of Canada, Bureau of Clinical Trials and Health Science, File #:128210

Abstract A vitamin dependency occurs when there is a defect in the binding of the vitamin-related coenzyme to its apoenzyme. The only way to correct a vitamin dependency is to obtain daily amounts much greater than recommended dietary allowances. I believe that the most common vitamin dependency among patients with mental illnesses is vitamin B3. These three cases involve members of the same family. Each case improved clinically upon taking megadoses (500-1500mg/day) of the vitamin. A fourth member of this family has schizophrenia. This is significant since recent postmortem biopsies of brain tissues have shown defects in the ability of schizophrenic patients to generate adequate amounts of vitamin B3 coenzymes from tryptophan. Families share similar genetics and environmental factors, and thus this family likely shares varying degrees of the ability to synthesize adequate amounts of vitamin B3 coenzymes. If schizophrenic genes are common among the entire human population, then the majority of people will suffer from slight-to-severe defects in this biosynthetic pathway.

Abstract The consequences of excessive and prolonged use of alcohol leads to mild-to-severe forms of pellagra (i.e., some combination of diarrhea, dermatitis, dementia, and possibly death). The author describes the work of many notable individuals who reported on the clinical effectiveness of vitamin B3 treatment for compulsive drinking behaviour, alcohol withdrawal delirium, and for improving sobriety. There is definitely a significant therapeutic role that vitamin B3 could play (mostly, niacin) if it was part of the mainstream approach to treating alcoholism and its related complications.

Abstract While on parental leave during November 2009, my clinical shift was spearheaded by one of my colleagues who recommended fairly significant doses of inositol hexaniacinate to treat a patient’s depression. In January 2010, the patient returned for a visit on my clinical shift, and much to my surprise her long-standing depression had resolved. As a result, I conducted a search for articles describing the use of vitamin B3 for depression. Six articles were found to meet the inclusion criteria and were included in this review. There is evidence that niacin and niacinamide (in combination with tryptophan) might be effective for the treatment of depression. Hypothetical reasons for niacin’s effectiveness include its vasodilatory properties, while the mechanisms responsible for the effectiveness of niacinamide involve its ability to inhibit tryptophan pyrrolase and possibly protect neurons from damage. The side effect profiles of niacin and the niacinamide-tryptophan combination are also discussed. Even though the mechanisms of action for niacin and niacinamide have not been substantiated from well conducted controlled clinical trials, these forms of vitamin B3 appear to have beneficial effects upon depression. It is imperative that properly designed controlled trials are developed in order to determine the true therapeutic effects and adverse effect profile of both preparations of vitamin B3 for depression.

Abstract Dementia affects approximately 5 million people in the United States, and about 475,000 elderly Canadians. Dementia is a debilitating and often progressive illness. The most common type of dementia is Alzheimer’s disease, followed by vascular types. There is a need to investigate novel treatments because the current crop of medications have limited value. Niacin might be a worthwhile treatment to consider. Research has shown that the risks of incident AD increase when patients have insufficient intakes of niacin from diet or medical conditions that precipitate niacin deficiency. Clinical reports have documented therapeutic benefits when patients receive optimum daily doses of niacin. Preliminary trials evaluating the reduced form of nicotinamide adenine dinucleotide (NADH) found it a safe and effective treatment for AD. At present, research evaluating the therapeutic applications of niacin and/or NADH for dementia is at a standstill. However, niacinamide is being evaluated in a clinical trial to determine if it is safe and beneficial for patients with AD. Hopefully, the forthcoming results will encourage researchers and clinicians to study niacinamide further, and revisit the therapeutic potential of vitamin B3 as a safe and an effective treatment for dementia.

Abstract Over the past several years the author has helped a number of patients taper off psychotropic drugs (PDs). This emerging aspect of his clinical work arose when patients demanded such services. During the tapering process, a combination of orthomolecular and/or botanical medicinal extracts can assist patients by minimizing withdrawal reactions and mental instability. Fourteen cases are described. The results showed that eight patients were able to remain functionally well following PD discontinuation, whereas the remaining six cases were not. Reasons for these different outcomes are discussed, and include: (1) problems in overcoming pharmacological dependence; (2) being psychologically dependent on being psychiatrically labeled; (3) not having a sufficient life strategy; and (4) being potentially brain-damaged from PDs. This paper can assist and empower clinicians to better understand some of the reasons why patients remain functionally well following tapering while other patients do not.

Introduction Diagnosis classifies disease for two main reasons: (1) to improve prognosis and (2) to improve treatment. Prognosis is very important so patients and family can prepare for the future especially if the future is very dim. Estimating when a person will die may be extremely important for all sorts of reasons. Before specific treatment was discovered doctors were judged on their ability to prognose correctly. It would be very bad for the physicians reputation if his prognosis were wrong. Many years ago when I started to practice some of my patients, when giving me their history, would tell me that their doctor had told them they would die but the doctor died before they did. Good doctors were good prognosticators and this depended upon accurate diagnosis. Diagnosis became even more important when specific treatment was discovered. Diagnosis advised the clinician what treatment to use. It was assumed that patients with the same diagnosis would respond to similar treatment which had already been described by other doctors. I had pneumonia in my early teens. Our friendly family doctor (he was also surgeon. emergency doctor, obstetrician, etc. as he was the only one in the community ) told mother I had pneumonia and ordered mustard plasters. It must have been very effective or else my pneumonia was very mild as I was well in a couple of days. That was standard treatment for a disease that killed a large proportion of the victims. This diagnosis was a descriptive diagnosis. By listening to my chest the doctor discovered something wrong and it was most likely pneumonia. No other diagnostic tests were available. After it was discovered that many lung lesions were possible it became necessary to distinguish one from another. Was it bacterial and if so which bacteria, staph. or strep.? Was it cancer or silica or tuberculosis? Specific laboratory tests are used. Diagnosis is now etiologic. It is based on the cause of the condition. Until the causal diagnosis is made the treatment can not be very successful. This is the pathway diagnosis has traveled, from description of the site, the organ, and later to the cause when known. If the cause remains unknown the diagnosis remains descriptive. Psychiatric diagnosis is almost entirely descriptive.

Abstract The purpose of this report is to highlight the potential of niacinamide for the treatment of anxiety disorders. Three patients were prescribed large pharmacological doses of niacinamide (2,000-2,500 mg per day). Each of the patients had considerable relief from their anxiety when regularly using niacinamide. The possible biochemical reasons for niacinamide’s effectiveness might be related to the correction of subclinical pellagra, the correction of an underlying vitamin B3 dependency disorder, its benzodiazepine-like effects, its ability to raise serotonin levels, or its ability to modify the metabolism of blood lactate (lactic acid). Adverse effects did not occur with these doses, but nausea and vomiting can occur when doses as high as 6,000 mg per day are used. These positive case reports suggest that niacinamide might be helpful for the treatment of anxiety disorders. However, definitive proof requires properly conducted randomized controlled trials to assess niacinamide’s actual therapeutic effects and adverse effects profile.