Dr. Paul Marik: Critical Care, Vitamin C and Repurposed Drugs

Deep-Dive Articles

Who Paul Marik Is

Marik’s first documented clinical research comes from Johannesburg: a 1990 study of early death after heart attack at J.G. Strijdom Hospital, followed by work in the intensive care unit of Baragwanath Hospital in Soweto, including a randomised trial of once-daily against twice-daily dosing of the antibiotic amikacin in critically ill adults and children. He then moved to the Victoria Hospital Research Institute in London, Ontario, where with William J. Sibbald he published a 1993 paper in JAMA on stored-blood transfusion in patients with sepsis.

In the United States he worked in critical care at Mercy Hospital of Pittsburgh and the University of Pittsburgh. Thomas Jefferson University recruited him from Pittsburgh, and from 2005 to 2008 he directed its Division of Pulmonary and Critical Care Medicine, with the main task of building critical care medicine at its university hospital. From 2009 he was professor of medicine and chief of the Division of Pulmonary and Critical Care Medicine at Eastern Virginia Medical School in Norfolk; that is the affiliation on his papers from 2009 to 2021, including the 2017 vitamin C sepsis study.

In April 2020 he co-founded the Front Line COVID-19 Critical Care Alliance (FLCCC), a panel of critical-care doctors who, in their own words, formed the group after early reports of COVID-19 respiratory failure showed “inexplicably high mortality rates”. Since then his writing has turned increasingly to cancer: the book Cancer Care (first edition 2023, second edition 2024), a 2023 review of cancer metabolism with Halma and Tuszynski, guides on repurposed drugs and diet in cancer, and his own newsletter, subtitled “Effective Treatments using Diet, Repurposed Drugs and Nutraceuticals”.

His Work on One Page

A single idea runs through most of Marik’s work: that cheap, widely available agents, used together so that each targets a different part of a disease process, can do what single expensive drugs have not. In his 2018 review he describes the hydrocortisone, ascorbic acid and thiamine protocol as “based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host’s response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death.” He notes in the same paper that more than 100 sepsis drugs aimed at a single target had failed.

Fluids and steroids in intensive care. Before his vitamin C work, Marik was known for arguing from pooled data that central venous pressure — a pressure reading long used to decide whether a patient needs more fluid — does not predict whether the patient will respond to fluid, and for favouring dynamic tests instead. He was first author of a 2008 international consensus statement on corticosteroid insufficiency in critically ill adults, and with Bellomo he described the high blood sugar of acute illness as “an essential survival response”.

Vitamin C in sepsis. Marik writes that vitamin C acts as a “stress hormone” alongside cortisol and the catecholamines (stress hormones such as adrenaline), and that “Humans (and anthropoid apes) have lost the ability to synthesize vitamin C and therefore have an impaired stress response.” His 2017 before-and-after study compared 47 patients given intravenous vitamin C, hydrocortisone and thiamine with 47 treated in the preceding seven months, and reported hospital deaths of 8.5% against 40.4%. The authors called for further studies; the randomised trials that followed are set out on the vitamin C sepsis deep-dive page.

COVID-19. Marik and his co-authors described the lung phase of COVID-19 as an organizing pneumonia with immune dysregulation, clotting and injury to small blood vessels, and wrote that the core treatment “includes the combination of methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+ protocol)”, with other agents added around it.

Cancer. In Cancer Care Marik writes that he read “more than 1800 peer-reviewed papers” and ranks repurposed drugs and supplements in four tiers, as additions to an oncologist’s treatment. “I want to be clear that I am not suggesting I have found a cure for cancer,” he writes, “nor am I the first to propose using repurposed drugs for cancer.” He also states: “There is no evidence that cancer is caused by or related to any parasitic disease.” Following Otto Warburg and Thomas Seyfried, he treats cancer as mainly a metabolic disease, and calls dietary calorie (glucose) restriction “the most important and central approach to the metabolic treatment of cancers”.

Timeline at a Glance

• 1990 — Publishes a prospective study of 233 heart-attack patients from the Department of Medicine, J.G. Strijdom Hospital, Johannesburg.
• 1991–1993 — Works in the intensive care unit of Baragwanath Hospital, Soweto; publishes an amikacin dosing trial and a study of the unit’s use.
• 1993 — With William J. Sibbald in London, Ontario, publishes a JAMA study of stored-blood transfusion in sepsis.
• 2001 — Publishes a review of aspiration pneumonitis and aspiration pneumonia in the New England Journal of Medicine, and the first edition of Handbook of Evidence-Based Critical Care.
• 2005–2008 — Director of the Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia.
• 2008 — Publishes “the tale of seven mares” review on central venous pressure, and leads an international consensus statement on corticosteroid insufficiency in critical illness.
• 2009 — Begins as professor of medicine and chief of pulmonary and critical care medicine at Eastern Virginia Medical School, Norfolk.
• 2010 and 2015 — Second edition of the handbook, then the third edition, retitled Evidence-Based Critical Care.
• 2017 — Publishes the before-and-after study of hydrocortisone, vitamin C and thiamine in severe sepsis and septic shock in Chest.
• April 2020 — Co-founds the Front Line COVID-19 Critical Care Alliance; the scientific rationale for the methylprednisolone, ascorbic acid, thiamine and heparin protocol follows the same year.
• 2022 — With his co-authors, publishes a revised clinical and scientific rationale for that hospital protocol.
• 2023 — Publishes the first edition of Cancer Care and a review of cancer metabolism in Nutrients.
• 2024 — Publishes the second edition of Cancer Care, with a revised ranking of agents.
• 2025–2026 — Writes further guides on repurposed drugs, cancer stem cells and diet in cancer, and a newsletter on diet and metabolic health.

Key Research Papers

1. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344(9):665-71. — PubMed PMID: 11228282
2. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008;134(1):172-8. — PubMed PMID: 18628220
3. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937-49. — PubMed PMID: 18496365
4. Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response! Crit Care. 2013;17(2):305. — PubMed PMID: 23470218
5. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017;151(6):1229-1238. — PubMed PMID: 27940189
6. Marik PE. Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid. Nutrients. 2018;10(11):1762. — PubMed PMID: 30441816
7. Marik PE, Liggett A. Adding an orange to the banana bag: vitamin C deficiency is common in alcohol use disorders. Crit Care. 2019;23(1):165. — PubMed PMID: 31077227
8. Marik PE. Vitamin C: an essential “stress hormone” during sepsis. J Thorac Dis. 2020;12(Suppl 1):S84-S88. — PubMed PMID: 32148930
9. Marik PE, Kory P, Varon J, Iglesias J, Meduri GU. MATH+ protocol for the treatment of SARS-CoV-2 infection: the scientific rationale. Expert Rev Anti Infect Ther. 2021;19(2):129-135. — PubMed PMID: 32809870
10. Kory P, Meduri GU, Iglesias J, Varon J, Cadegiani FA, Marik PE. “MATH+” Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale. J Clin Med Res. 2022;14(2):53-79. — PubMed PMID: 35317360
11. Halma MTJ, Tuszynski JA, Marik PE. Cancer Metabolism as a Therapeutic Target and Review of Interventions. Nutrients. 2023;15(19):4245. — PubMed PMID: 37836529

PubMed Topic Searches

1. All PubMed papers by Marik PE
2. Marik PE, vitamin C and sepsis
3. Marik PE and fluid responsiveness
4. Marik PE and corticosteroids in critical illness
5. Marik PE and COVID-19

Further Reading

• Marik PE. Handbook of Evidence-Based Critical Care. Springer; 2001. — DOI: 10.1007/978-3-642-86943-3
• Marik PE. Handbook of Evidence-Based Critical Care. 2nd ed. Springer; 2010. — DOI: 10.1007/978-1-4419-5923-2
• Marik PE. Evidence-Based Critical Care. 3rd ed. Springer; 2015. — DOI: 10.1007/978-3-319-11020-2
• Marik PE. Cancer Care: The Role of Repurposed Drugs and Metabolic Interventions in Treating Cancer (free PDF and summary)
• Paul Marik — his newsletter on diet, repurposed drugs and nutraceuticals

Connections

• Paul Marik: Life and Career
• The HAT Protocol: Vitamin C, Thiamine and Hydrocortisone in Sepsis
• MATH+ and Paul Marik’s COVID-19 Treatment Protocols
• Cancer Care: Paul Marik’s Book on Repurposed Drugs
• Paul Marik’s Metabolic Approach to Cancer
• Paul Marik’s Critical Care Research and Textbooks
• Contemporary Practitioners
• Notable Doctors
• Sepsis
• Vitamin C
• Vitamin B1 (Thiamine)
• Ivermectin
• Ketogenic Diet
• Frederick Klenner

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