JOM Volume 26, Number 4, 2011 Editorial 155

of noradrenaline that would be converted to Does B3 Really Reduce ? . Since adrenochrome was thought to be an oxidized derivative of adrenaline, vi- tamin B3 might help to reduce the quantity of adrenochrome by simply limiting the pro- Until his death, Dr. Abram Ho!er educat- duction of adrenaline. ed clinicians for over 50 years about the need Ho!er and his team also discovered an to correctly (optimally) provide schizophren- additional biochemical property of vitamin ics with vitamin B3 (niacinamide or ). B3, that it is a precursor to nicotinamide For over 13 years I have, likewise, educated adenine dinucleotide, which is present in numerous naturopathic and medical doctors both oxidized (NAD) and reduced forms about the very same thing. Schizophrenic pa- (NADH) in the body. In the brain, adrenaline tients are less likely to get well if not provided becomes oxidized and loses one electron to with optimal doses of vitamin B3. become oxidized adrenaline. If enough NAD To understand the importance of vi- and NADH are available then the oxidized tamin B3 treatment, some background in- adrenaline is reconverted to adrenaline. "ese formation is necessary. Beginning around back and forth processes continue to occur 1952, Ho!er researched, published, and ex- in the presence of su#cient vitamin B3 coen- panded upon the adrenochrome theory of zymes. However, in the absence of su#cient .1,2 He and his colleagues, Drs. NAD and NADH, the oxidized adrenaline Osmond and Smythies, came to this theory loses an additional electron and becomes ad- by studying and researching the e!ects of renochrome. "is last reaction is irreversible, substances such as , lysergic acid and is believed to occur in much greater con- diethylamide (LSD), and – centrations in the schizophrenic brain. all of which can cause a clinical syndrome in Over the past 15 years, Smythies, Ho!er’s normal individuals that would be clinically former research colleague, noted that: indistinguishable from schizophrenia. 1. Adrenochrome’s close relatives–dop- Ho!er noticed that mescaline had a sim- aminochrome (from ) and norad- ilar chemical structure to that of adrenaline, renochrome (from noradrenaline)–are pres- and since both can be converted to indoles in ent in the human brain.3-5 the body, the potential schizophrenic toxin 2. Adrenochrome and its close relatives might be an indole derivative of adrenaline induce a combination of neurotoxic and with similar neurochemical properties to mind-mood-altering e!ects.3-5 that of mescaline or LSD. He conjectured While there are clinical studies and re- that the schizophrenic toxin was an oxidized ports demonstrating that vitamin B3 does derivative of adrenaline known as adreno- indeed help in the treatment of acute and chrome. To reduce the production of ad- chronic schizophrenia,1,2,6-8 the available data renochrome, Ho!er and his team decided is insu#cient in proving that it mitigates upon the methyl acceptor, vitamin B3. "is schizophrenic symptoms by lowering adre- vitamin had previously been used to treat nochrome concentrations in the brain. Adre- pellagra (a disease clinically indistinguish- nochrome might be present in the blood9 of able from schizophrenia), and had relevant normal human subjects or it might not be.10 biochemical properties.1,2 Ho!er and his Even though its presence in the blood has team researched the metabolism of adrena- been the subject of much debate, none of this line. "ey knew that the reaction involving proves it is in the blood (or brains) of schizo- noradrenaline to adrenaline required the ad- phrenic patients and that it is responsible dition of one methyl group. Because vitamin for schizophrenic symptoms. A urine study B3 was known to function as a methyl accep- found N-methylmetanephrine, a metabolite tor, Ho!er’s team thought that an optimum of N-methylepinephrine, in 3 of 18 psychotic dose of niacin might decrease the amount children.11 "is might suggest some increased

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build-up of epinephrine (i.e., adrenaline) me- is done on the adrenochrome hypothesis tabolites in the blood, but this does not prove of schizophrenia, we should seriously con- the presence of adrenaline metabolites in the sider alternative viewpoints into vitamin B3’s brain. Data that loosely suggests the possi- mechanism of action. bility that adrenochrome might be present in the human brain comes from an animal ex- periment that identi$ed aminochrome (i.e., a mixture of adrenochrome and noradreno- chrome) in the rat brain.12 Jonathan E. Prousky, ND, MSc "e majority of supportive data on the Editor psychotomimetic properties of adreno- chrome came from studies where normal References and/or psychiatric patients were given adre- 1. Ho!er A: Vitamin B3 & Schizophrenia. Discov- nochrome experimentally.5 For example, the ery, Recovery, Controversy. Kingston, ON: Quarry Press, Inc; 1998: 28-76. $rst-generation antipsychotic medications 2. Ho!er A: Adventures In . !e Scienti"c reduce schizophrenic symptoms by blocking Memoirs of Dr. Abram Ho#er. Caledon, ON: KOS dopamine-type 2 receptors within the brain. Publishing Inc; 2005:50-99. "ey are not, however, correcting for an over- 3. Smythies JR: Endogenous neurotoxins relevant to production of dopamine within the brain. schizophrenia. J R Soc Med, 1996; 89: 679-680. 4. Smythies JR: Oxidative reactions and schizophre- Likewise, vitamin B3’s bene$cial therapeutic nia: a review-discussion. Schizophr Res, 1997; 24: e!ects do not prove that it counteracts adre- 357-364. nochrome’s psychotomimetic properties by 5. Smythies JR: "e adrenochrome hypothesis of diminishing its production and/or the double schizophrenia revisited. Neurotox Res, 2002; 4: oxidation of adrenaline. Conclusions drawn 147-150. 6. Ho!er A, Osmond H, Callbeck MJ, et al: Treat- from these sources of data have not proven ment of schizophrenia with nicotinic acid and anything causal, except that adrenochrome nicotinamide. J Clin Exp Psychopath, 1957; 18: might be implicated in some aspect of the 131-158. disorder, or adrenochrome might not be. We 7. Ho!er A: Niacin !erapy In Psychiatry. Spring- must entertain the possibility that vitamin $eld, IL: Charles C "omas; 1962; 35-71. 8. Ho!er A: Chronic schizophrenic patients treated B3’s therapeutic e!ects might have nothing ten years of more. J Orthomol Med, 1994; 9: 7-37. to do with adrenochrome alteration. 9. Ho!er A, Payza AN: "e presence of adreno- Vitamin B3 remains an important asset chrome in blood. Am J Psychiat, 1960; 116: 664. to those practicing orthomolecular medicine. 10. Szara S, Axelrod J, Perlin S: Is adrenochrome Without Ho!er’s dedication, perseverance, present in the blood. Am J Psychiat, 1958; 115: 162-163. and proli$c writings, the therapeutic uses of 11. Perry TL: N-Methylmetanephrine: Excretion by vitamin B3 would likely have been forgotten. Juvenile Psychotics. Science, 1963; 139: 587-589. Vitamin B3 de$nitely has value in helping 12. Macarthur H, Westfall TC, Riley DP, et al: Inacti- to assuage the devastation of schizophrenia. vation of catecholamines by superoxide gives new I believe it is therapeutic precisely because insights on the pathogenesis of septic shock. Proc Natl Acad Sci USA, 2000; 97: 9753-9758. of its global physiologic (i.e., likely increases 13. Miller CL, Llenos IC, Dulay JR, et al: Upregula- brain vasodilatation) and metabolic e!ects tion of the initiating step of the kynurenine path- (i.e., enhances oxidative phosphorylation) way in postmortem anterior cingulate cortex from – some of which oppose several side e!ects individuals with schizophrenia and bipolar disor- induced from $rst and second generation der. Brain Res, 2006; 1073-1074: 25-37. 14. Miller CL, Dulay JR: "e high-a#nity niacin re- antipsychotic medication (e.g., cognitive im- ceptor HM74A is decreased in the anterior cin- pairment, fatigue, hypercholesterolemia, and gulate cortex of individuals with schizophrenia. weight gain). On the other hand, newer pub- Brain Res Bull, 2008; 77: 33-41. lications have discovered intriguing links be- tween niacin status, tryptophan metabolism and schizophrenia.13,14 Until more research

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