It sounds almost too good to be true. Dr. Paul Marik, the Chief of Pulmonary and Critical Care Medicine at Eastern Virginia Medical School, in Norfolk, Virginia, has found that a cocktail of intravenous vitamin C and corticosteroids, along with a little bit of thiamine, may be a cure for sepsis, which is a major cause of death. (Sepsis killed Patty Duke and Muhammad Ali.) Many physicians are skeptical of Marik’s claim, for two reasons. First, they have heard a lot of nonsense about vitamin C over the years. Second, they have been trained to wait for the results of a double-blind randomized controlled trial before they make any change in how they practice medicine. As a result, they may be slow to adopt Marik’s protocol. But if they hesitate, they will miss the chance to save lives. Physicians have nothing to lose by trying the Marik’s protocol. Patients have everything to lose if their physician hesitates.
Marik’s breakthrough came in January of 2016, as he struggled to save the life of a 48-year-old woman suffering from overwhelming sepsis. He had recently read that vitamin C might be a useful treatment for sepsis. He recalled that steroids, which are commonly used for treating sepsis, might work well in concert with vitamin C. So he ordered that the patient be given a combination of steroids and vitamin C intravenously. Within hours, she started to recover. Two days later, she was well enough to leave the intensive care unit. Then, Marik and his colleagues used the same treatment on two more patients who seemed destined to die of sepsis. Those patients also recovered. At that point, Marik and his team adopted the combination therapy as standard practice. They eventually added a small dose of thiamine to the protocol, because sepsis patients are also often deficient in thiamine. Since then, they have not seen a single patient die of sepsis. (However, some did die of the underlying disease that led to sepsis.)
Marik’s claims have been supported by an adequately powered clinical study. However, that study was retrospective. It compared 47 consecutive septic patients treated with his protocol to 47 septic patients who had been treated before his institution began using the protocol. Only 4 of the 47 patients treated with the vitamin C protocol died, as compared with 19 of the 47 patients in the control group (P<.001). Most importantly, none of the patients in the treatment group developed progressive organ failure. That finding suggests that the treatment is effective against the sepsis, in particular.
Marik’s claim makes biological sense. In 2012, Wilson and Wu explained the mechanisms by which vitamin C could improve microvascular function in sepsis patients. They explained that the vitamin C would have to be given intravenously to provide adequate ascorbate concentrations in plasma and tissue. In 2015, Carr et al pointed out that septic patients present with hypovitaminosis C and explained that the enzymes that are involved in the synthesis of norepinephrine and vasopressin require vitamin C as a cofactor for optimal activity.
Some methodological purists may quibble about the supposed “flaws” of the design of Marik’s study. They may insist on a prospective, randomized, placebo-controlled study before they adopt the vitamin C protocol. Yet such a study would violate a basic principle of medical research ethics. Researchers are not supposed to assign patients with a serious illness to different treatment arms unless there is real uncertainty about which of the treatments would be better. This principle is called clinical equipoise. Yet there is no real uncertainty. The probability that the results of the retrospective study were due to random chance are less than one in a thousand. Nor was there any reason to suspect that the differences in outcome were due to any confounding variables. Nor are there any serious safety concerns about adding vitamin C and some thiamine to the commonly used corticosteroid treatment for sepsis.
Regulatory agencies typically require drug companies to do double-blind, randomized controlled trials to support a new drug application. Yet there are some exceptions. For example, the Food and Drug Administration approved lepirudin (Refludan®) for anticoagulation in patients with heparin-induced thrombocytopenia on the basis of a clinical trial that used historical controls, rather than assigning patients to a placebo treatment that would have threatened life and limb.
So we now know that a vitamin C, which is a cheap, easily available product with a long history of safe use, is probably the key to the successful treatment of a major cause of death. The medical profession will be judged by how fast or how slowly it acts on this information.
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