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Linus Pauling
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===Medical research and vitamin C advocacy=== {{main|Vitamin C megadosage}} [[File:Pauling Vit C Book Cover.jpg|right|150px|thumb|Pauling's book, ''How to Live Longer and Feel Better'', advocated very high intake of [[Vitamin C]].<ref>{{Cite book |last=Pauling |first=Linus |title=How to Live Longer and Feel Better |publisher=Avon Books |year=1987 |edition=1 |location=New York |ol=18076125M}}</ref>]] In 1941, at age 40, Pauling was diagnosed with [[Bright's disease]], a renal disease. Following the recommendations of [[Thomas Addis]], who actively recruited Ava Helen Pauling as "nutritionist, cook, and eventually as deputy 'doctor'", Pauling believed he was able to control the disease with Addis's then-unusual low-protein salt-free diet and vitamin supplements.<ref>{{Cite book |last=Peitzman |first=Steven J. |url=https://books.google.com/books?id=8FUDO5K1pAoC&pg=PA72 |title=Dropsy, dialysis, transplant: a short history of failing kidneys |publisher=Johns Hopkins University Press |year=2007 |isbn=978-0-8018-8734-5 |location=Baltimore |pages=72β8; 190}}</ref> Thus Pauling's initial β and intensely personal β exposure to the idea of treating disease with vitamin supplements was positive.{{citation needed|date=August 2023}} In 1965, Pauling read ''Niacin Therapy in Psychiatry'' by [[Abram Hoffer]] and theorized vitamins might have important biochemical effects unrelated to their prevention of associated deficiency diseases.<ref>{{Cite book |title=Biochemical imbalances in disease a practitioner's handbook |publisher=Singing Dragon |year=2010 |isbn=978-0-85701-028-5 |editor-last=Nicolle |editor-first=Lorraine |location=London |page=27 |editor-last2=Beirne |editor-first2=Ann Woodriff}}</ref> In 1968, Pauling published a brief paper in [[Science (journal)|''Science'']] entitled "Orthomolecular psychiatry",<ref>{{Cite journal |last=Pauling |first=Linus |date=April 1968 |title=Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease |journal=Science |volume=160 |issue=3825 |pages=265β71 |bibcode=1968Sci...160..265P |doi=10.1126/science.160.3825.265 |pmid=5641253 |s2cid=20153555}}</ref> giving a name to the popular but controversial [[megavitamin therapy]] movement of the 1970s, and advocating that "orthomolecular therapy, the provision for the individual person of the optimum concentrations of important normal constituents of the brain, may be the preferred treatment for many mentally ill patients." Pauling coined the term "orthomolecular" to refer to the practice of varying the concentration of substances normally present in the body to prevent and treat disease. His ideas formed the basis of [[orthomolecular medicine]], which is not generally practiced by conventional medical professionals and has been strongly criticized.<ref name="Cassileth">{{Cite book |last=Cassileth |first=Barrie R. |author-link=Barrie R. Cassileth |title=The alternative medicine handbook: the complete reference guide to alternative and complementary therapies |publisher=W.W. Norton |year=1998 |isbn=978-0-393-04566-6 |location=New York |pages=67}}</ref><ref name="bccancer">{{Cite web |date=February 2000 |title=Vitamin Therapy, Megadose / Orthomolecular Therapy |url=http://www.bccancer.bc.ca/PPI/UnconventionalTherapies/VitaminTherapyMegadoseOrthomolecularTherapy.htm |archive-url=https://web.archive.org/web/20070202102734/http://www.bccancer.bc.ca/PPI/UnconventionalTherapies/VitaminTherapyMegadoseOrthomolecularTherapy.htm |archive-date=February 2, 2007 |access-date=August 5, 2007 |publisher=BC Cancer Agency}}</ref> In 1973, with [[Arthur B. Robinson]] and another colleague, Pauling founded the Institute of Orthomolecular Medicine in Menlo Park, California, which was soon renamed the [[Linus Pauling Institute]] of Science and Medicine. Pauling directed research on vitamin C, but also continued his theoretical work in chemistry and physics until his death. In his last years, he became especially interested in the possible role of vitamin C in preventing [[atherosclerosis]] and published three case reports on the use of [[lysine]] and vitamin C to relieve [[angina pectoris]]. During the 1990s, Pauling put forward a comprehensive plan for the treatment of heart disease using lysine and vitamin C. In 1996, a website was created expounding Pauling's treatment which it referred to as Pauling Therapy. Proponents of Pauling Therapy believe that heart disease can be treated and even cured using only lysine and Vitamin C and without drugs or heart operations.<ref>{{Cite web |title=PaulingTherapy.com β Reversing Heart Disease w/o Drugs is Possible |url=http://www.paulingtherapy.com/ |website=www.paulingtherapy.com}}</ref> Pauling's work on [[vitamin C]] in his later years generated much controversy. He was first introduced to the concept of high-dose vitamin C by biochemist [[Irwin Stone]] in 1966. After becoming convinced of its worth, Pauling took 3 grams of vitamin C every day to prevent [[colds]].<ref name="frs" /> Excited by his own perceived results, he researched the clinical literature and published ''[[Vitamin C and the Common Cold (book)|Vitamin C and the Common Cold]]'' in 1970. He began a long clinical collaboration with the British cancer surgeon [[Ewan Cameron (physician)|Ewan Cameron]] in 1971 on the use of intravenous and oral vitamin C as cancer therapy for terminal patients.<ref>{{Cite web |last=Cameron |first=Ewan |author-link=Ewan Cameron |title=Cancer Bibliography: Ewan Cameron, M.D. and Vitamin C Therapy |url=http://www.doctoryourself.com/biblio_cameron.html |access-date=August 5, 2007 |publisher=Doctoryourself.com}}</ref> Cameron and Pauling wrote many technical papers and a popular book, ''Cancer and Vitamin C'', that discussed their observations. Pauling made vitamin C popular with the public<ref name="OnThisDay">{{Cite news |last=Severo |first=Richard |date=August 21, 1994 |title=Linus C. Pauling Dies at 93; Chemist and Voice for Peace |work=The New York Times |url=https://www.nytimes.com/learning/general/onthisday/bday/0228.html |access-date=June 1, 2015}}</ref> and eventually published two studies of a group of 100 allegedly [[terminal illness|terminal]] patients that claimed vitamin C increased survival by as much as four times compared to untreated patients.<ref>{{Cite journal |last1=Cameron |first1=E |author1-link=Ewan Cameron |last2=Pauling |first2=L |date=October 1976 |title=Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer |journal=Proceedings of the National Academy of Sciences |volume=73 |issue=10 |pages=3685β9 |bibcode=1976PNAS...73.3685C |doi=10.1073/pnas.73.10.3685 |pmc=431183 |pmid=1068480 |doi-access=free}}</ref><ref>{{Cite journal |last1=Cameron |first1=E |author1-link=Ewan Cameron |last2=Pauling |first2=L |date=September 1978 |title=Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer |journal=Proceedings of the National Academy of Sciences |volume=75 |issue=9 |pages=4538β42 |bibcode=1978PNAS...75.4538C |doi=10.1073/pnas.75.9.4538 |pmc=336151 |pmid=279931 |doi-access=free}}</ref> A re-evaluation of the claims in 1982 found that the patient groups were not actually comparable, with the vitamin C group being less sick on entry to the study, and judged to be "terminal" much earlier than the comparison group.<ref>{{Cite journal |last=DeWys |first=WD |year=1982 |title=How to evaluate a new treatment for cancer |journal=Your Patient and Cancer |volume=2 |issue=5 |pages=31β36}}</ref> Later clinical trials conducted by the [[Mayo Clinic]] led by oncologist [[Edward T. Creagan|Dr. Edward T. Creagan]] also concluded that high-dose (10,000 mg) vitamin C was no better than [[placebo]] at treating cancer and that there was no benefit to high-dose vitamin C.<ref>{{Cite journal |last1=Creagan |first1=ET |last2=Moertel |first2=CG |last3=O'Fallon |first3=JR |date=September 1979 |title=Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial |journal=The New England Journal of Medicine |volume=301 |issue=13 |pages=687β90 |doi=10.1056/NEJM197909273011303 |pmid=384241}}</ref><ref>{{Cite journal |last1=Moertel |first1=CG |last2=Fleming |first2=TR |last3=Creagan |first3=ET |last4=Rubin |first4=J |last5=O'Connell |first5=MJ |last6=Ames |first6=MM |date=January 1985 |title=High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison |journal=The New England Journal of Medicine |volume=312 |issue=3 |pages=137β41 |doi=10.1056/NEJM198501173120301 |pmid=3880867}}</ref><ref>{{Cite journal |last=Tschetter |first=L |display-authors=etal |year=1983 |title=A community-based study of vitamin C (ascorbic acid) in patients with advanced cancer |journal=Proceedings of the American Society of Clinical Oncology |volume=2 |page=92}}</ref> The failure of the clinical trials to demonstrate any benefit resulted in the conclusion that vitamin C was not effective in treating cancer; the medical establishment concluded that his claims that vitamin C could prevent colds or treat cancer were [[quackery]].<ref name="frs" /><ref name="PNASChen2007">{{Cite journal |last1=Chen |first1=Q |last2=Espey |first2=M. G. |last3=Sun |first3=A. Y. |last4=Lee |first4=J.-H. |last5=Krishna |first5=M. C. |last6=Shacter |first6=E. |last7=Choyke |first7=P. L. |last8=Pooput |first8=C. |last9=Kirk |first9=K. L. |last10=Buettner |first10=G. R. |last11=Levine |first11=M. |display-authors=etal |year=2007 |title=Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo |journal=Proceedings of the National Academy of Sciences |volume=104 |issue=21 |pages=8749β54 |bibcode=2007PNAS..104.8749C |doi=10.1073/pnas.0702854104 |pmc=1885574 |pmid=17502596 |doi-access=free}}</ref> Pauling denounced the conclusions of these studies and handling of the final study as "fraud and deliberate misrepresentation",<ref>{{Cite web |last=Goertzel |first=Ted |author-link=Ted Goertzel |year=1996 |title=Analyzing Pauling's Personality: A Three Generational, Three Decade Project |url=http://oregonstate.edu/dept/Special_Collections/subpages/ahp/1995symposium/goertzel.html |url-status=dead |archive-url=https://web.archive.org/web/20071014174038/http://oregonstate.edu/dept/Special_Collections/subpages/ahp/1995symposium/goertzel.html |archive-date=October 14, 2007 |access-date=August 5, 2007 |publisher=Special Collections, Oregon State University Libraries}}</ref><ref name="Golem">{{Cite book |last1=Pinch |first1=Trevor |author1-link=Trevor Pinch |title=Dr. Golem: how to think about medicine |last2=Collins |first2=Harry M. |publisher=[[University of Chicago Press]] |year=2005 |isbn=978-0-226-11366-1 |location=Chicago |pages=89β111 |chapter=Alternative Medicine: The Cases of Vitamin C and Cancer |chapter-url=http://www.press.uchicago.edu/Misc/Chicago/113663.html}}</ref> and criticized the studies for using oral, rather than [[intravenous therapy|intravenous]] vitamin C<ref>{{Cite journal |last=Levine |first=M |display-authors=etal |year=2006 |title=Intravenously administered vitamin C as cancer therapy: three cases |journal=[[Canadian Medical Association Journal|CMAJ]] |volume=174 |issue=7 |pages=937β942 |doi=10.1503/cmaj.050346 |pmc=1405876 |pmid=16567755}}</ref> (which was the dosing method used for the first ten days of Pauling's original study<ref name=PNASChen2007/>). Pauling also criticised the Mayo Clinic studies because the controls were taking vitamin C during the trial, and because the duration of the treatment with vitamin C was short; Pauling advocated continued high-dose vitamin C for the rest of the cancer patient's life whereas the Mayo Clinic patients in the second trial were treated with vitamin C for a median of 2.5 months.<ref>{{Cite book |last=Pauling |first=Linus |url=https://archive.org/details/howtolivelongerf00paul/page/173 |title=How to Live Longer and Feel Better |publisher=[[W. H. Freeman and Company|Freeman]] |year=1986 |isbn=978-0-7167-1781-2 |location=New York |pages=[https://archive.org/details/howtolivelongerf00paul/page/173 173β175]}}</ref> Ultimately the negative findings of the Mayo Clinic studies ended general interest in vitamin C as a treatment for cancer.<ref name = Golem/> Despite this, Pauling continued to promote vitamin C for treating cancer and the common cold, working with [[The Institutes for the Achievement of Human Potential]] to use vitamin C in the treatment of brain-injured children.<ref name="Pauling1978">{{Cite journal |last=Pauling |first=L |date=November 1978 |title=Orthomolecular enhancement of human development |url=https://profiles.nlm.nih.gov/MM/B/B/K/G/_/mmbbkg.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://profiles.nlm.nih.gov/MM/B/B/K/G/_/mmbbkg.pdf |archive-date=October 9, 2022 |url-status=live |journal=Human Neurological Development |pages=47β51 |editor=Ralph Pelligra}}</ref> He later collaborated with the Canadian physician [[Abram Hoffer]] on a micronutrient regime, including high-dose vitamin C, as adjunctive cancer therapy.<ref>{{Cite web |last1=Saul |first1=Andrew W. |last2=Dr. Abram Hoffer |title=Abram Hoffer, M.D., PhD 50 Years of Megavitamin Research, Practice and Publication |url=http://www.doctoryourself.com/biblio_hoffer.html |access-date=August 5, 2007 |publisher=Doctoryourself.com}}</ref> A 2009 review also noted differences between the studies, such as the Mayo Clinic not using intravenous Vitamin C, and suggested further studies into the role of vitamin C when given intravenously.<ref name="Cancerreevaluated">{{Cite journal |last1=Ohno |first1=S |last2=Ohno |first2=Y |last3=Suzuki |first3=N |last4=Soma |first4=G |last5=Inoue |first5=M |year=2009 |title=High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer |journal=Anticancer Research |volume=29 |issue=3 |pages=809β15 |pmid=19414313}}</ref> Results from most clinical trials suggest that modest vitamin C supplementation alone or with other nutrients offers no benefit in the prevention of cancer.<ref name="Oncologist">{{Cite journal |last1=Jacobs |first1=Carmel |last2=Hutton |first2=Brian |last3=Ng |first3=Terry |last4=Shorr |first4=Risa |last5=Clemons |first5=Mark |date=2015 |title=Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer? A Systematic Review |journal=The Oncologist |volume=20 |issue=2 |pages=210β223 |doi=10.1634/theoncologist.2014-0381 |pmc=4319640 |pmid=25601965}}</ref><ref name="NIHFactsheet">{{Cite web |title=Vitamin C Fact Sheet for Health Professionals |url=http://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/ |access-date=June 2, 2015 |website=National Institutes of Health}}</ref>
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