(OMNS Dec 2, 2017) Schizophrenia is a devastating and complex disease that can include a variety of specific clinical conditions. Drugs to treat schizophrenia have not advanced much beyond the 1960s; in many cases they are not very effective, and they have severe side-effects. The problem is that the cause of schizophrenia is unknown, and precisely how the drugs affect brain circuitry is also unknown. Schizophrenia is thought to have a substantial environmental component (toxins, culture, upbringing, lifestyle, diet, etc.), but its onset is likely to be predisposed by genetic factors. Genetic analysis has recently made great progress in identifying genes that cause diseases. Many diseases that strike young adults, as schizophrenia often does, have been shown to be caused by one or just a few specific mutations. For example, some diseases that cause blindness are now known to be caused by a mutation in one or more of the genes that code for molecules in the brain essential for sight. In one recent case, gene therapy approved by the FDA to correct the mutation has restored sight in blind people. 
Pessimism about schizophrenia
However, research into the possible genetic cause of schizophrenia has not found any obvious candidate gene mutations. Part of the problem is that schizophrenia is not just one disease; it comprises a family of interrelated conditions and is diagnosed by several criteria, which implies that a variety of causes may contribute. Apparently, many gene mutations may contribute to schizophrenia, but none yet found have an influence strong enough to be the exclusive cause.
A recent presentation on solving the puzzle of schizophrenia at the Society for Neuroscience (SfN) conference in Washington DC had a pessimistic tone, explaining that there are no easy answers in the search for better treatment. No helpful novel drug treatments for schizophrenia have been found in recent years, and the lack of obvious genetic markers that are correlated with the disease presents a severe challenge. The SfN presentation, however, didn’t mention recent research into dietary causes and treatments for schizophrenia.
Niacin cures many schizophrenics
In the early 1960s, Hoffer and Osmond published studies showing that niacin (also known as nicotinic acid or vitamin B3) given at sufficiently high doses could effectively treat some schizophrenia patients.[3-7] Although Hoffer and Osmond’s theories about how niacin could treat schizophrenia were never proven sufficiently to convince the rest of the field, their results in treating thousands of patients with niacin therapy and curing many were striking. The term “orthomolecular” was coined by Linus Pauling for the use of essential nutrients such as niacin in preventing disease, and in particular, schizophrenia. Looking for more recent studies, a search on PubMed of the terms “schizophrenia niacin” returns several dozen articles. One of them asserts that some schizophrenics can be well treated with niacin, and refers to Hoffer and Osmond’s early studies, reviewing several theories about likely mechanisms.
“Abram Hoffer backed up his treatment with clearly explained biochemistry, as he had a degree in biochemistry before obtaining his MD. I personally found his presentation fascinating as well as convincing.”
(Ralph Campbell, MD)
Niacin skin test
Most people get a “niacin flush” on their skin for a few minutes when a large dose of niacin is taken orally. This is a normal consequence of niacin activating prostaglandin pathways that cause vasodilation in the skin and is not harmful. Niacin is utilized by several hundred metabolic pathways in the body, so oral niacin is taken by many to treat illness and maintain good health. To avoid the skin flush, one starts with small doses [typically 25 mg/day] and gradually increases the dose over several days to achieve a therapeutic effect. However, some schizophrenics don’t get a niacin flush with the normal doses, suggesting that they have a deficiency of niacin and likely other essential nutrients. Therefore, niacin applied to the skin or taken orally has been used as a test for predisposition to schizophrenia. Hoffer noted that in some cases where schizophrenics recovered, they reverted to a normal skin flush. A flurry of recent studies show that about one third of schizophrenics have a blunted niacin skin flush, suggesting that this test can be used as a diagnostic tool. [12-21] Several of these recent studies attempt to determine from those results what aspect of the metabolic disturbance might cause problems for the brain. Although most of these studies don’t explicitly discuss the use of niacin as a treatment, the underlying theme is that niacin treatment can help many schizophrenics.
“Dr. Abram Hoffer observed a recovery to a normal niacin-flush response in an otherwise previously flush-resistant schizophrenic. Dr. Hoffer used either niacinamide or niacin, although he favored the lipodystrophy-correcting/flush-causing niacin form more. He also recommended essential fatty acids.”
(W. Todd Penberthy, PhD)
Many schizophrenic patients have severe nutrient dependencies that can be treated with niacin and other vitamins and nutrients. Several recent studies review the evidence for a benefit from good nutrition (niacin, other B vitamins, vitamin C and D, omega-3 fatty acids, etc.) on brain function. [22-29]
The use of niacin therapy for testing and treatment of schizophrenia and many other conditions appears to be rapidly expanding. It is inexpensive and widely used for health, but can also help those in desperate need of treatment. For a therapeutic effect, Hoffer recommended gradually increasing doses up to 3,000 mg/day of niacin in divided doses, along with 2,000 mg/day or more of vitamin C and other essential nutrients. For some people, high doses can cause temporary side effects, so many people take niacin for its health benefit at lower doses (500 – 1,000 mg/day). Niacinamide has similar benefits but does not cause the skin flush. For more on the benefits of niacin, dosing, and possible contra-indications please refer to Hoffer’s book “Niacin: the Real Story” .
It is straightforward to understand the historical bias against niacin therapy for schizophrenia. Niacin is inexpensive and can’t be patented. And it is known to be effective at preventing heart disease. One can imagine that the drug industry is working to make a form of niacin or a niacin-like drug that can produce profits. [30, 31]
1. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016 Jul 2;388:86-97. https://www.ncbi.nlm.nih.gov/pubmed/26777917
2. Ledford H. FDA advisers back gene therapy for rare form of blindness. Nature. 2017 Oct 12;550:314. https://www.nature.com/news/fda-advisers-back-gene-therapy-for-rare-form-of-blindness-1.22819
3. Hoffer AF, Osmond H, Smythies, Schizophrenia: a New Approach. II. Results of a Year’s Research. J. Mental Sci. 100: 29-45, 1954. https://www.ncbi.nlm.nih.gov/pubmed/13152519
4. Hoffer A, Osmond H. Treatment of schizophrenia with nicotinic acid: a ten-year follow-up. Acta Psychiat Scand 1964, 40: 171-189. https://www.ncbi.nlm.nih.gov/pubmed/14235254
5. Niacin and Schizophrenia: History and Opportunity. http://orthomolecular.org/resources/omns/v10n18.shtml
6. To Give Credit Where Credit is Due. http://orthomolecular.org/resources/omns/v13n05.shtml
7. Abram Hoffer Centenary. http://orthomolecular.org/resources/omns/v13n19.shtml
8. Pauling L. Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease. Science. 1968 Apr 19;160:265-271. https://www.ncbi.nlm.nih.gov/pubmed/5641253 https://profiles.nlm.nih.gov/ps/access/MMBBJQ.pdf
9. Xu XJ, Jiang GS. Niacin-respondent subset of schizophrenia — a therapeutic review. Eur Rev Med Pharmacol Sci. 2015;19:988-997. https://www.ncbi.nlm.nih.gov/pubmed/25855923
10. Hoffer A, Saul AW, Foster HD. Niacin: The Real Story: Learn about the Wonderful Healing Properties of Niacin. Basic Health Publications, Inc; 2015. ISBN-13: 978-1591202752.
11. Hoffer A. Adventures in Psychiatry: The Scientific Memoirs of Dr. Abram Hoffer. KOS Publishing, 2005. ISBN-13: 978-0973194562.
12. Smesny S, Berger G, Rosburg T, et al. Potential use of the topical niacin skin test in early psychosis — a combined approach using optical reflection spectroscopy and a descriptive rating scale. Psychiatr Res. 2003 May-Jun;37:237-247. https://www.ncbi.nlm.nih.gov/pubmed/12650743
13. Messamore E. Niacin subsensitivity is associated with functional impairment in schizophrenia. Schizophr Res. 2012 May;137(1-3):180-4. https://www.ncbi.nlm.nih.gov/pubmed/22445461
14. Lien YJ, Huang SS, Liu CM, et al. A genome-wide quantitative linkage scan of niacin skin flush response in families with schizophrenia. Schizophr Bull. 2013 Jan;39:68-76. https://www.ncbi.nlm.nih.gov/pubmed/21653277
15. Nilsson BM, Holm G, Hultman CM, Ekselius L. Cognition and autonomic function in schizophrenia: inferior cognitive test performance in electrodermal and niacin skin flush non-responders. Eur Psychiatry. 2015 Jan;30:8-13. https://www.ncbi.nlm.nih.gov/pubmed/25169443
16. Berger GE, Smesny S, Sch”fer MR, et al. Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis. PLoS One. 2016 Feb 19;11(2):e0148429. https://www.ncbi.nlm.nih.gov/pubmed/26894921
17. Yao JK, Dougherty GG Jr, Gautier CH, Haas GL, Condray R, Kasckow JW, Kisslinger BL, Gurklis JA, Messamore E. Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia. Schizophr Bull. 2016 Mar;42(2):369-376. https://www.ncbi.nlm.nih.gov/pubmed/26371338
18. Sun L, Yang X, Jiang J, et al. Identification of the Niacin-Blunted Subgroup of Schizophrenia Patients from Mood Disorders and Healthy Individuals in Chinese Population. Schizophr Bull. 2017 Oct 25. https://www.ncbi.nlm.nih.gov/pubmed/29077970
19. Langbein K, Schmidt U, Schack S, et al. State marker properties of niacin skin sensitivity in ultra-high risk groups for psychosis – An optical reflection spectroscopy study. Schizophr Res. 2017 Jun 8. pii: S0920-9964(17)30335-3. https://www.ncbi.nlm.nih.gov/pubmed/28602647
20. Ross BM. Methylnicotinate stimulated prostaglandin synthesis in patients with schizophrenia: A preliminary investigation. Prostaglandins Leukot Essent Fatty Acids. 2017 May 19. pii: S0952-3278(16)30227-7. https://www.ncbi.nlm.nih.gov/pubmed/28552466
21. Messamore E. The niacin response biomarker as a schizophrenia endophenotype: A status update. Prostaglandins Leukot Essent Fatty Acids. 2017 Jun 30. pii: S0952-3278(16)30249-6. https://www.ncbi.nlm.nih.gov/pubmed/28688777
22. Lim SY, Kim EJ, Kim A, et al. Nutritional Factors Affecting Mental Health. Clin Nutr Res. 2016 Jul; 5:143-52. https://www.ncbi.nlm.nih.gov/pubmed/27482518
23. Kim EJ, Lim SY, Lee HJ, et al. Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with schizophrenia and the development of dietary guidelines for schizophrenia. Nutr Res. 2017 Sep;45:10-18. https://www.ncbi.nlm.nih.gov/pubmed/29037327
24. Pawelczyk T, Piatkowska-Janko E, Bogorodzki P, et al. Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia: A secondary outcome analysis of the OFFER randomized controlled study. Schizophr Res. 2017 Oct 24. pii: S0920-9964(17)30621-7. https://www.ncbi.nlm.nih.gov/pubmed/29079060
25. Marx W, Moseley G, Berk M, Jacka F. Nutritional psychiatry: the present state of the evidence. Proc Nutr Soc. 2017 Nov;76:427-436. https://www.ncbi.nlm.nih.gov/pubmed/28942748
26. Cieslak K, Feingold J, Antonius D, et al. Low vitamin D levels predict clinical features of schizophrenia. Schizophr Res. 2014 Nov;159:543-545. https://www.ncbi.nlm.nih.gov/pubmed/25311777 .
27. Chiang M, Natarajan R, Fan X. Vitamin D in schizophrenia: a clinical review. Evid Based Ment Health. 2016 Feb;19:6-9. https://www.ncbi.nlm.nih.gov/pubmed/26767392 .
28. Akinlade KS, Olaniyan OA, Lasebikan VO, Rahamon SK. Vitamin D Levels in Different Severity Groups of Schizophrenia. Front Psychiatry. 2017 Jun 13;8:105. https://www.ncbi.nlm.nih.gov/pubmed/28659835 .
29. Berridge MJ. Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism and schizophrenia). Am J Physiol Cell Physiol. 2017 Oct 25:ajpcell.00188.2017.https://www.ncbi.nlm.nih.gov/pubmed/29070492 .
30. Goel H, Dunbar RL. Niacin Alternatives for Dyslipidemia: Fool’s Gold or Gold Mine? Part II: Novel Niacin Mimetics. Curr Atheroscler Rep. 2016 Apr;18:17. https://www.ncbi.nlm.nih.gov/pubmed/26932224 .
31. Dunbar RL, Goel H, Tuteja S, et al. Measuring niacin-associated skin toxicity (NASTy) stigmata along with symptoms to aid development of niacin mimetics. J Lipid Res. 2017 Apr;58:783-797. https://www.ncbi.nlm.nih.gov/pubmed/28119443 .
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