Niacin: Difference between revisions

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In 1954, researchers [[Abram Hoffer]] and [[Humphry Osmond]] claimed that [[adrenochrome]], a chemical compound produced by the oxidation of adrenaline (epinephrine), is a [[neurotoxin|neurotoxic]], [[psychotomimetic]] substance and may play a role in [[schizophrenia]] and other mental illnesses.<ref name="pmid13152519">{{cite journal | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | first3 = John | last3 = Smythies| author-link3 = John Raymond Smythies | title = Schizophrenia: A New Approach. II. Result of a Year's Research | journal = [[British Journal of Psychiatry|The Journal of Mental Science]] | volume = 100 | issue = 418 | pages = 29–45 | date = January 1954 | pmid = 13152519 | doi = 10.1192/bjp.100.418.29 | eissn = 1472-1465 | issn = 0007-1250 | lccn = 89649366 | oclc = 1537306 | s2cid = 42531852 | df = dmy-all }}</ref>

In what Hoffer called the "adrenochrome hypothesis",<ref name="Hoffer2">{{cite journal | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | title = The Adrenochrome Hypothesis and Psychiatry | url = http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | access-date = 2024-03-15 | journal = [[The Journal of Orthomolecular Medicine]] | volume = 14 | issue = 1 | date = First Quarter 1999 | pages = 49–62 | archive-url = https://web.archive.org/web/20240220043758/http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | archive-date = 2024-02-20 | url-status = live | issn = 0834-4825 | oclc = 15726974 | s2cid = 41468628 | df = dmy-all}}</ref> he and Osmond in 1967 speculated that [[Megavitamin therapy|megadoses]] of [[vitamin C]] and [[niacin (nutrient)|niacin]] could cure schizophrenia by reducing brain adrenochrome.<ref name="hallucinogens">{{cite book | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | date = 1968-01-01 | title = The Hallucinogens | url = https://archive.org/details/hallucinogens0000hoff/ | url-access = registration | language = en | edition = First | publisher = [[Academic Press]] | isbn = 978-0123518507 | lccn = 66030086 | oclc = 332437 | ol = OL35255701M | access-date = 2024-03-15 | via = [[Internet Archive]] | quote= | quote-page= | quote-pages= | df = dmy-all}}</ref><ref name=hoffer94>{{cite journal | vauthors = Hoffer A | date = 1994 | title = Schizophrenia: An Evolutionary Defense Against Severe Stress | journal = Journal of Orthomolecular Medicine | volume = 9 | issue = 4 | pages = 205–2221 | url = http://orthomolecular.org/library/jom/1994/pdf/1994-v09n04-p205.pdf }}</ref> He tested this in small numbers of patients and claimed that it was frequently impressively successful.

In what Hoffer called the "adrenochrome hypothesis",<ref name="Hoffer2">{{cite journal | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | title = The Adrenochrome Hypothesis and Psychiatry | url = http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | access-date = 2024-03-15 | journal = [[The Journal of Orthomolecular Medicine]] | volume = 14 | issue = 1 | date = First Quarter 1999 | pages = 49–62 | archive-url = https://web.archive.org/web/20240220043758/http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | archive-date = 2024-02-20 | url-status = live | issn = 0834-4825 | oclc = 15726974 | s2cid = 41468628 | df = dmy-all}}</ref> he and Osmond in 1967 speculated that [[Megavitamin therapy|megadoses]] of [[vitamin C]] and [[niacin (nutrient)|niacin]] could cure schizophrenia by reducing brain adrenochrome.<ref name="hallucinogens">{{cite book | last1 = Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | date = 1968-01-01 | title = The Hallucinogens | url = https://archive.org/details/hallucinogens0000hoff/ | url-access = registration | language = en | edition = First | publisher = [[Academic Press]] | isbn = 978-0123518507 | lccn = 66030086 | oclc = 332437 | ol = OL35255701M | access-date = 2024-03-15 | via = [[Internet Archive]] | quote= | quote-page= | quote-pages= | df = dmy-all}}</ref><ref name=hoffer94>{{cite journal | vauthors = Hoffer A | date = 1994 | title = Schizophrenia: An Evolutionary Defense Against Severe Stress | journal = Journal of Orthomolecular Medicine | volume = 9 | issue = 4 | pages = 205–2221 | url = http://orthomolecular.org/library/jom/1994/pdf/1994-v09n04-p205.pdf }}</ref> He tested this in small numbers of patients and claimed that it was frequently impressively successful.<ref name=hofferj74>{{cite journal | last1 = Hoffer | first1 = John | date = 1974 | title = The Controversy Over Orthomolecular Therapy | journal = Journal of Orthomolecular Medicine | volume = 3 | issue = 3 | url = https://orthomolecular.org/library/jom/1974/pdf/1974-v03n03-p167.pdf }}</ref>

The treatment of schizophrenia with such potent anti-oxidants is highly contested. In 1973, the [[American Psychiatric Association]] reported methodological flaws in Hoffer's work on niacin as a schizophrenia treatment and referred to follow-up studies that did not confirm any benefits of the treatment.<ref name="APA">{{cite web | vauthors = Lipton MA, Ban TA, Kane FJ, Levine J, Mosher LR, Wittenborn R | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | publisher = American Psychiatric Association | year = 1973 | url = https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | access-date = 7 September 2020 | archive-date = 23 February 2021 | archive-url = https://web.archive.org/web/20210223194022/https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | url-status = dead }}</ref> Multiple additional studies in the United States,<ref name="ArchGenPsy">{{cite journal | doi = 10.1001/archpsyc.1973.01750330010002 |vauthors=Wittenborn JR, Weber ES, Brown M | title = Niacin in the Long-Term Treatment of Schizophrenia | journal = Archives of General Psychiatry | year = 1973 | volume = 28 | issue = 3 | pages = 308–315 | pmid = 4569673 | url = http://archpsyc.ama-assn.org/cgi/content/abstract/28/3/308}}</ref> Canada,<ref name="SZ Bull">{{cite journal | vauthors = Ban TA, Lehmann HE | title = Nicotinic Acid in the Treatment of Schizophrenia: A Summary Report | journal = Schizophrenia Bulletin | year = 1970 | volume = 1 | issue = 3 | pages = 5–7 | doi = 10.1093/schbul/1.3.5 | doi-access = free }}</ref> and Australia<ref name="ANZJP">{{cite journal |vauthors=Vaughan K, McConaghy N | s2cid = 38857700 | title = Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial | journal = Australian and New Zealand Journal of Psychiatry | year = 1999 | volume = 33 | issue = 1 | pages = 84–88 | pmid = 10197889 | doi =10.1046/j.1440-1614.1999.00527.x}}</ref> similarly failed to find benefits of megavitamin therapy to treat [[History of schizophrenia|schizophrenia]]. Hoffer~~, in~~ a ~~lengthy review article, replied~~ that the follow-up studies were poorly designed, using incorrect doses and illogical measures of whether the patients had recovered or not, and ~~voiced suspicions~~ that they had been ~~deliberately set up~~ to ~~make~~ the ~~niacin protocol look bad by~~ doctors who had ~~spoken~~ publicly ~~in support~~ of the ~~use~~ of tranquillizers and ~~wanted to make it look as if they were right~~.

The doses used were very high - 3,000 mg to 6,000 mg of niacin per day and 1,000 to 5,000 mg of vitamin C per day, with a common protocol being 3,000 mg of each, usually split into three doses.<ref name=hofferj74 /> This dose of niacin is within the range at which there is a risk of liver issues or high blood sugar. However, it is the same amount used for high cholesterol under medical supervision.

The treatment of schizophrenia with such potent anti-oxidants is highly contested. In 1973, the [[American Psychiatric Association]] reported methodological flaws in Hoffer's work on niacin as a schizophrenia treatment and referred to follow-up studies that did not confirm any benefits of the treatment.<ref name="APA">{{cite web | vauthors = Lipton MA, Ban TA, Kane FJ, Levine J, Mosher LR, Wittenborn R | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | publisher = American Psychiatric Association | year = 1973 | url = https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | access-date = 7 September 2020 | archive-date = 23 February 2021 | archive-url = https://web.archive.org/web/20210223194022/https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | url-status = dead }}</ref> Multiple additional studies in the United States,<ref name="ArchGenPsy">{{cite journal | doi = 10.1001/archpsyc.1973.01750330010002 |vauthors=Wittenborn JR, Weber ES, Brown M | title = Niacin in the Long-Term Treatment of Schizophrenia | journal = Archives of General Psychiatry | year = 1973 | volume = 28 | issue = 3 | pages = 308–315 | pmid = 4569673 | url = http://archpsyc.ama-assn.org/cgi/content/abstract/28/3/308}}</ref> Canada,<ref name="SZ Bull">{{cite journal | vauthors = Ban TA, Lehmann HE | title = Nicotinic Acid in the Treatment of Schizophrenia: A Summary Report | journal = Schizophrenia Bulletin | year = 1970 | volume = 1 | issue = 3 | pages = 5–7 | doi = 10.1093/schbul/1.3.5 | doi-access = free }}</ref> and Australia<ref name="ANZJP">{{cite journal |vauthors=Vaughan K, McConaghy N | s2cid = 38857700 | title = Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial | journal = Australian and New Zealand Journal of Psychiatry | year = 1999 | volume = 33 | issue = 1 | pages = 84–88 | pmid = 10197889 | doi =10.1046/j.1440-1614.1999.00527.x}}</ref> similarly failed to find benefits of megavitamin therapy to treat [[History of schizophrenia|schizophrenia]].

Hoffer and Osmond published a rebuttal saying that the follow-up studies that had failed were poorly designed, using incorrect doses, niacin without vitamin C and/or illogical measures of whether the patients had recovered or not, and that the report had misrepresented others as unsuccessful when they had actually been successful. They voiced suspicions that this was deliberate. According to Hoffer and Osmond, of the five doctors who prepared the report, Dr Lipton had repeatedly publicly denounced the megavitamin protocol (and would therefore face professional embarrassment if it was proven to be correct), Dr Ban (who was a co-author of one of the largest groups of studies) derived much of his income from grants from companies that sold tranquillizers and Dr Mosher was a follower of R. D. Laing and was firmly convinced that schizophrenia was not a biological disorder.<ref name=hofferosmond>http://www.iahf.com/orthomolecular/reply_to_apa_tfr_7.pdf</ref><ref name=hofferj74 />

The adrenochrome theory of schizophrenia waned, despite some evidence that it may be [[psychotomimetic]], as adrenochrome was not detectable in people with schizophrenia.{{citation needed|date=March 2021}}

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 In 1954, researchers [[Abram Hoffer]] and [[Humphry Osmond]] claimed that [[adrenochrome]], a chemical compound produced by the oxidation of adrenaline (epinephrine), is a [[neurotoxin|neurotoxic]], [[psychotomimetic]] substance and may play a role in [[schizophrenia]] and other mental illnesses.<ref name="pmid13152519">{{cite journal | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | first3 = John | last3 = Smythies| author-link3 = John Raymond Smythies  | title = Schizophrenia: A New Approach. II. Result of a Year's Research | journal = [[British Journal of Psychiatry|The Journal of Mental Science]] | volume = 100 | issue = 418 | pages = 29–45 | date = January 1954 | pmid = 13152519 | doi = 10.1192/bjp.100.418.29 | eissn = 1472-1465 | issn = 0007-1250 | lccn = 89649366 | oclc = 1537306 | s2cid = 42531852 | df = dmy-all }}</ref>
-In what Hoffer called the "adrenochrome hypothesis",<ref name="Hoffer2">{{cite journal | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | title = The Adrenochrome Hypothesis and Psychiatry | url = http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | access-date = 2024-03-15 | journal = [[The Journal of Orthomolecular Medicine]] | volume = 14 | issue = 1 | date = First Quarter 1999 | pages = 49–62 | archive-url = https://web.archive.org/web/20240220043758/http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | archive-date = 2024-02-20 | url-status = live | issn = 0834-4825 | oclc = 15726974 | s2cid = 41468628 | df = dmy-all}}</ref> he and Osmond in 1967 speculated that [[Megavitamin therapy|megadoses]] of [[vitamin C]] and [[niacin (nutrient)|niacin]] could cure schizophrenia by reducing brain adrenochrome.<ref name="hallucinogens">{{cite book | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | date = 1968-01-01 | title = The Hallucinogens | url = https://archive.org/details/hallucinogens0000hoff/ | url-access = registration | language = en | edition = First | publisher = [[Academic Press]] | isbn = 978-0123518507 | lccn = 66030086 | oclc = 332437 | ol = OL35255701M | access-date = 2024-03-15 | via = [[Internet Archive]] | quote= | quote-page= | quote-pages= | df = dmy-all}}</ref><ref name=hoffer94>{{cite journal | vauthors = Hoffer A | date = 1994 | title = Schizophrenia: An Evolutionary Defense Against Severe Stress | journal = Journal of Orthomolecular Medicine | volume = 9 | issue = 4 | pages = 205–2221 | url = http://orthomolecular.org/library/jom/1994/pdf/1994-v09n04-p205.pdf }}</ref>  He tested this in small numbers of patients and claimed that it was frequently impressively successful.
+In what Hoffer called the "adrenochrome hypothesis",<ref name="Hoffer2">{{cite journal | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | title = The Adrenochrome Hypothesis and Psychiatry | url = http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | access-date = 2024-03-15 | journal = [[The Journal of Orthomolecular Medicine]] | volume = 14 | issue = 1 | date = First Quarter 1999 | pages = 49–62 | archive-url = https://web.archive.org/web/20240220043758/http://www.orthomolecular.org/library/jom/1999/articles/1999-v14n01-p049.shtml | archive-date = 2024-02-20 | url-status = live | issn = 0834-4825 | oclc = 15726974 | s2cid = 41468628 | df = dmy-all}}</ref> he and Osmond in 1967 speculated that [[Megavitamin therapy|megadoses]] of [[vitamin C]] and [[niacin (nutrient)|niacin]] could cure schizophrenia by reducing brain adrenochrome.<ref name="hallucinogens">{{cite book | last1 =  Hoffer | first1 = Abram | author-link1 = Abram Hoffer | last2 = Osmond | first2 = Humphrey | author-link2 = Humphry Osmond | date = 1968-01-01 | title = The Hallucinogens | url = https://archive.org/details/hallucinogens0000hoff/ | url-access = registration | language = en | edition = First | publisher = [[Academic Press]] | isbn = 978-0123518507 | lccn = 66030086 | oclc = 332437 | ol = OL35255701M | access-date = 2024-03-15 | via = [[Internet Archive]] | quote= | quote-page= | quote-pages= | df = dmy-all}}</ref><ref name=hoffer94>{{cite journal | vauthors = Hoffer A | date = 1994 | title = Schizophrenia: An Evolutionary Defense Against Severe Stress | journal = Journal of Orthomolecular Medicine | volume = 9 | issue = 4 | pages = 205–2221 | url = http://orthomolecular.org/library/jom/1994/pdf/1994-v09n04-p205.pdf }}</ref>  He tested this in small numbers of patients and claimed that it was frequently impressively successful.<ref name=hofferj74>{{cite journal | last1 = Hoffer | first1 = John | date = 1974 | title = The Controversy Over Orthomolecular Therapy | journal = Journal of Orthomolecular Medicine | volume = 3 | issue = 3 | url = https://orthomolecular.org/library/jom/1974/pdf/1974-v03n03-p167.pdf }}</ref>
-The treatment of schizophrenia with such potent anti-oxidants is highly contested. In 1973, the [[American Psychiatric Association]] reported methodological flaws in Hoffer's work on niacin as a schizophrenia treatment and referred to follow-up studies that did not confirm any benefits of the treatment.<ref name="APA">{{cite web | vauthors = Lipton MA, Ban TA, Kane FJ, Levine J, Mosher LR, Wittenborn R | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | publisher = American Psychiatric Association | year = 1973 | url = https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | access-date = 7 September 2020 | archive-date = 23 February 2021 | archive-url = https://web.archive.org/web/20210223194022/https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | url-status = dead }}</ref> Multiple additional studies in the United States,<ref name="ArchGenPsy">{{cite journal | doi = 10.1001/archpsyc.1973.01750330010002 |vauthors=Wittenborn JR, Weber ES, Brown M | title = Niacin in the Long-Term Treatment of Schizophrenia | journal = Archives of General Psychiatry | year = 1973 | volume = 28 | issue = 3 | pages = 308–315 | pmid = 4569673 | url = http://archpsyc.ama-assn.org/cgi/content/abstract/28/3/308}}</ref> Canada,<ref name="SZ Bull">{{cite journal | vauthors = Ban TA, Lehmann HE | title = Nicotinic Acid in the Treatment of Schizophrenia: A Summary Report | journal = Schizophrenia Bulletin | year = 1970 | volume = 1 | issue = 3 | pages = 5–7 | doi = 10.1093/schbul/1.3.5 | doi-access = free }}</ref> and Australia<ref name="ANZJP">{{cite journal |vauthors=Vaughan K, McConaghy N | s2cid = 38857700 | title = Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial | journal = Australian and New Zealand Journal of Psychiatry | year = 1999 | volume = 33 | issue = 1 | pages = 84–88 | pmid = 10197889 |  doi =10.1046/j.1440-1614.1999.00527.x}}</ref> similarly failed to find benefits of megavitamin therapy to treat [[History of schizophrenia|schizophrenia]].  Hoffer, in a lengthy review article, replied that the follow-up studies were poorly designed, using incorrect doses and illogical measures of whether the patients had recovered or not, and voiced suspicions that they had been deliberately set up to make the niacin protocol look bad by doctors who had spoken publicly in support of the use of tranquillizers and wanted to make it look as if they were right.
+The doses used were very high - 3,000 mg to 6,000 mg of niacin per day and 1,000 to 5,000 mg of vitamin C per day, with a common protocol being 3,000 mg of each, usually split into three doses.<ref name=hofferj74 />  This dose of niacin is within the range at which there is a risk of liver issues or high blood sugar.  However, it is the same amount used for high cholesterol under medical supervision.
+The treatment of schizophrenia with such potent anti-oxidants is highly contested. In 1973, the [[American Psychiatric Association]] reported methodological flaws in Hoffer's work on niacin as a schizophrenia treatment and referred to follow-up studies that did not confirm any benefits of the treatment.<ref name="APA">{{cite web | vauthors = Lipton MA, Ban TA, Kane FJ, Levine J, Mosher LR, Wittenborn R | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | publisher = American Psychiatric Association | year = 1973 | url = https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | access-date = 7 September 2020 | archive-date = 23 February 2021 | archive-url = https://web.archive.org/web/20210223194022/https://www.old.quackwatch.org/01QuackeryRelatedTopics/apa_megavitamin.pdf | url-status = dead }}</ref> Multiple additional studies in the United States,<ref name="ArchGenPsy">{{cite journal | doi = 10.1001/archpsyc.1973.01750330010002 |vauthors=Wittenborn JR, Weber ES, Brown M | title = Niacin in the Long-Term Treatment of Schizophrenia | journal = Archives of General Psychiatry | year = 1973 | volume = 28 | issue = 3 | pages = 308–315 | pmid = 4569673 | url = http://archpsyc.ama-assn.org/cgi/content/abstract/28/3/308}}</ref> Canada,<ref name="SZ Bull">{{cite journal | vauthors = Ban TA, Lehmann HE | title = Nicotinic Acid in the Treatment of Schizophrenia: A Summary Report | journal = Schizophrenia Bulletin | year = 1970 | volume = 1 | issue = 3 | pages = 5–7 | doi = 10.1093/schbul/1.3.5 | doi-access = free }}</ref> and Australia<ref name="ANZJP">{{cite journal |vauthors=Vaughan K, McConaghy N | s2cid = 38857700 | title = Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial | journal = Australian and New Zealand Journal of Psychiatry | year = 1999 | volume = 33 | issue = 1 | pages = 84–88 | pmid = 10197889 |  doi =10.1046/j.1440-1614.1999.00527.x}}</ref> similarly failed to find benefits of megavitamin therapy to treat [[History of schizophrenia|schizophrenia]].
+Hoffer and Osmond published a rebuttal saying that the follow-up studies that had failed were poorly designed, using incorrect doses, niacin without vitamin C and/or illogical measures of whether the patients had recovered or not, and that the report had misrepresented others as unsuccessful when they had actually been successful.  They voiced suspicions that this was deliberate.  According to Hoffer and Osmond, of the five doctors who prepared the report, Dr Lipton had repeatedly publicly denounced the megavitamin protocol (and would therefore face professional embarrassment if it was proven to be correct), Dr Ban (who was a co-author of one of the largest groups of studies) derived much of his income from grants from companies that sold tranquillizers and Dr Mosher was a follower of R. D. Laing and was firmly convinced that schizophrenia was not a biological disorder.<ref name=hofferosmond>http://www.iahf.com/orthomolecular/reply_to_apa_tfr_7.pdf</ref><ref name=hofferj74 />
 The adrenochrome theory of schizophrenia waned, despite some evidence that it may be [[psychotomimetic]], as adrenochrome was not detectable in people with schizophrenia.{{citation needed|date=March 2021}}