JOM Volume 26, Number 4, 2011 Review Article 163 Treating Dementia with Vitamin B3 and NADH Jonathan E. Prousky, ND, MSc1,2 1 Chief Naturopathic Medical O!cer, Professor, Canadian College of Naturopathic Medicine, 1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2, Tel: 416-498-1255 ext. 235, email: [email protected] 2 Editor, Journal of Orthomolecular Medicine, email: [email protected] Abstract Dementia a!ects approximately 5 million people in the United States, and about 475,000 elderly Canadians. Dementia is a debilitating and often progressive illness. "e most common type of dementia is Alzheimer’s disease, followed by vascular types. "ere 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 insu#cient intakes of niacin from diet or medical conditions that precipitate niacin de$ciency. Clini- cal reports have documented therapeutic bene$ts when patients receive optimum daily doses of niacin. Preliminary trials evaluating the reduced form of nicotinamide adenine dinucleotide (NADH) found it a safe and e!ective 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 bene$cial for patients with AD. Hopefully, the forthcoming results will encourage researchers and clinicians to study niacinamide further, and revisit the therapeu- tic potential of vitamin B3 as a safe and an e!ective treatment for dementia. Introduction functions, including language, motor skills, Among elderly patients, Alzheimer’s judgment, orientation ability, and, most disease (AD) is the most common type of notably, memory. Patients eventually lose dementia, followed by vascular types. World- themselves in the disease, unable to remem- wide, more than 30 million people su!er ber even vestiges of the lives they once lived. from AD. In the United States, AD a!ects #e cognitive declines of AD are asso- approximately 5 million people.1 About ciated with problems in the cerebral cortex 475,000 elderly Canadians have dementia, including the formation of senile plaques, with the majority of cases being attributed to neuro$brillary tangles, and granulovascular AD.2 Experts predict that the number of pa- degeneration of neurons.3 Various risk fac- tients a"icted with dementia in Canada will tors have been implicated in the suscepti- increase to 778,000 by the year 2031.2 #e bility to AD. #ese include advancing age, burden that this disease will place on health family history, apolipoprotein E epsilon 4 care systems is staggering when you consider genotype, obesity, insulin resistance, vascular that the elderly constitute the fastest growing factors, dyslipidemia, hypertension, in%am- population in all industrialized countries.1 matory markers and Down syndrome.1 Dementia is a debilitating and often #e medical treatment of AD uses ace- progressive illness characterized by intellec- tylcholinesterase inhibitors or n-methyl-d- tual decline and the loss of higher cognitive aspartic acid glutamate receptor antagonists, Prousky.indd 163 11/29/11 10:16:11 PM 164 Journal of Orthomolecular Medicine Vol 26, No 4, 2011 with the former treatment having only weak participants were reported to have pellagra evidence of bene$t on cognitive function.4 (i.e., diarrhoea, dermatitis, dementia, and Clearly there is a need to investigate other shortly thereafter, death), some participants treatments because the current crop of med- who demonstrated mental and cognitive de- ications have limited value in mitigating the clines may not have met the recommended progression and symptoms of dementia, most dietary allowance for niacin (14 mg for adult notably, AD. In this article, I will summarize females and 16 mg for adult males6). Some and comment on: (1) research linking a re- of the study participants may have had sub- duction in the incidence of AD with high clinical pellagra. dietary intakes of vitamin B3; (2) the merits #e mental signs of mild niacin de$cien- of using niacin or the reduced form of nico- cy (a.k.a., pellagra sine pellagra) often occur tinamide adenine dinucleotide (NADH) as in the absence of any dermatologic, mucous treatments for dementia; and (3) current re- membrane, or gastrointestinal symptoms.7,8 search investigating the safety and e&cacy of #e researchers did not acknowledge that niacinamide as a treatment for AD. niacin de$ciency can lead to symptoms of AD, and thereby play a role in the patho- Preventing AD with Vitamin B3 genesis of AD. Decades ago Aring and Spies Research has shown a relationship be- reported that neurasthenic symptoms in 225 tween dietary niacin and the development of mild pellagrins were ameliorated by taking AD.5 A total of 3,718 participants aged 65 300 to 600 mg of niacin every day for 1-12 years and older underwent at least two clini- days (3-6 pills, with each pill providing 100 cal assessments and provided dietary data for mg of niacin).8 #e neurasthenic symptoms analyses over a median of 5.5 years. In this reversed by niacin appeared long before any large, prospective study, dietary niacin de$- other manifestations of the disease. #ese ciencies were associated with incident AD included fatigue, insomnia, anorexia, vertigo, and cognitive decline. Niacin intake from burning sensations in various parts of the foods was inversely associated with AD body, numbness, palpitation, nervousness, a (p for trend = 0.002). A higher food intake feeling of unrest and anxiety, headache, for- of niacin was associated with a slower annual getfulness, apprehension, and distractibil- rate of cognitive decline. Speci$cally, an in- ity. #ese niacin-de$ciency manifestations creased food intake of niacin slowed the an- could easily be confused with prodromal nual cognitive decline by 0.019 standardized symptoms of AD, and, if left untreated, they units per natural log increase in intake (mg), could become severe enough for a diagnosis which was statistically signi$cant (p=0.05). of AD. #e dementia of pellagra looks much #e participants in intake quintiles 2-4 had a like AD since its clinical presentation, while statistically signi$cant 70% reduction in risk varied, includes aggression, apathy, confu- compared to participants in the lowest quin- sion, depression, disorientation, hallucina- tile (median niacin intake 12.6 mg/day). #e tions, insomnia, psychosis, and seizures.9 participants in the highest quintile (median Low dietary intakes of niacin would not niacin intake 22.4 mg/day) had an 80% sta- entirely account for the increased incidence tistically signi$cant reduction in risk. of AD among the study participants. Many #ese researchers did not provide any participants had varying intakes of alcohol robust explanations as to why diagnoses of and cigarette consumption, as well as the AD increased among participants with low presence of diabetes and/or cardiovascu- dietary intakes of niacin but they did note lar disease. #ese and other possible factors that the level of dietary niacin associated could have increased the participants’ vulner- with pellagra (8.8 mg of niacin equivalents ability to niacin de$ciency during the study per 2000 kilocalories) was lower than the period (Table 1, opposite).7 range of intake for the lowest quintile (13.2- Above all, this study demonstrates that 27 mg per day). While none of the study insu&cient intake of niacin from diet or Prousky.indd 164 11/29/11 10:16:11 PM Treating Dementia with Vitamin B3 and NADH 165 Table 1. Possible causes of niacin deficiency Precipitating Factors Explanations Inadequate amount of niacin in diet Inability to procure an adequate diet (e.g., socioeco- nomic reasons), or choosing a nutritionally unbal- anced diet (e.g., due to ignorance, individual prefer- ence, or lack of advice about nutrition) Interference with ingestion Functional and organic conditions leading to an- orexia or vomiting, gastrointestinal disease, psychi- atric disorders (e.g., psychoneuroses, both organic and functional psychoses, and addiction to alcohol or other drugs), neurological and traumatic disorders that interfere with self-feeding, and oral diseases (e.g., sore mouth, or loss of teeth) Interference with bio-synthesis Inadequate intake of tryptophan, ingestion of structurally similar compounds that would inhibit the formation of niacin by substrate competition (e.g., maize), and destruction of intestinal bacteria (e.g., bowel “sterilizing” antibiotics) Interference with absorption Absence of normal digestive secretions (e.g., achlo- rhydria and obstructive jaundice), intestinal hypermotility (e.g., various types of diarrhoea), reduction in absorptive surface (e.g., disease or surgical removal of the gastrointes- tinal tract), and medications (e.g., mineral oil) Interference with utilization Problems with cellular metabolism (e.g., alcohol, general anaesthesia, and metabolic disorders such as hypothyroidism or diabetes), specific inactivation (e.g., sulphonamides exert an anti-vitamin effect by substrate competition with para-aminobenzioc acid, corn, and isoniazid) Interference with storage Any condition causing impairment of liver function would interfere with the amount of niacin retained in the body Increased excretion or loss Elevated metabolic rate (e.g., hyperthyroidism), periods of rapid growth, pregnancy and lactation, pyrexia from any cause, any condition requiring increased muscular activity, and specific treatments (e.g., high carbohy- drate diets, insulin, thyroid medication, and overuse of stimulants (such as caffeine or amphetamines) Increased nutritive requirements Urinary loss (e.g., renal disease, and diabetes), or other routes (e.g., lactation, serous exudates due to burns, and severe blood loss) Prousky.indd 165 11/29/11 10:16:11 PM 166 Journal of Orthomolecular Medicine Vol 26, No 4, 2011 conditions that can precipitate vitamin de$- if a patient’s psychiatric condition was due to ciency can increase the risks of incident AD.