The global vitamin and supplement industry is expected to be worth $278 billion by 2024. “Wellness” as a concept and industry, which often includes vitamin and supplement use, is heavily promoted by celebrities, athletes, and social media stars. IV therapy lounges are all the rage and have popped up in many major cities, and IV therapy is also offered in many naturopathic clinics. If you look online, there are all sorts of claims for what vitamins, minerals, and supplements can do, including treating Parkinson’s, macular degeneration, fibromyalgia, depression, “adrenal fatigue,” and the catch-all “detoxification”.

Potential Harms from Vitamins and Supplements

  • Geller et al. (2015) estimated that there are 23,000 ED visits and over 2,000 admissions annually for adverse events related to supplement use
    • Common reasons for taking supplements were weight loss and energy
    • Common side effects included palpitations, chest pain, and tachycardia
  • Most harms occur from vitamins and other minerals when taken in massive doses
    • Ex: Taking niacin (B6) is one method recommended online to beat a urine drug test
      • At doses of 1g/day elevated liver enzymes
      • 2-3g/day and higher niacin toxicity
        • Hepatic dysfunction → can progress to fulminant hepatic failure
        • Case report of TTP and DIC
  • Weight loss supplements are varied but some common adverse events can include:
    • Hepatotoxicity (ex. Green tea extract, orlistat)
    • Serotonin syndrome (ex. Garcinia cambogia, Hydroxycut)
    • Mania/Psychosis (ex. Garcinia cambogia, Hydroxycut, Ma-huang [a natural source of ephedrine])


Potential Benefits from Vitamins and Supplements

  • Vitamin D has been suggested as a treatment for various painful conditions
    • Basit et al. (2016) suggested a single dose of Vit D3 600,000 IU IM led to a significant improvement in symptoms of peripheral neuropathy after 10 weeks and that patients did not need to be Vit D deficient to experience benefit
    • Hirani et al. (2012) found that in adults over 65 in England, moderate to severe chronic pain was associated with low Vit D levels
    • Lasco et al. (2012) found in a small RCT that a single dose of Vit D 300,000 IU IM given prior to menstruation reduced dysmenorrhea for up to 2 months
  • A Cochrane review from 2015 by Straube et al. looked at Vitamin D and chronic pain
    • Found 10 studies and a total of 811 patients with various painful conditions (e.g. rheumatoid arthritis, osteoarthritis, polymyalgia rheumatica, non-specific MSK pain, fibromyalgia)
    • Various doses and routes of Vitamin D
    • No convincing benefit found, but poor quality of studies and significant heterogeneity, so they concluded more studies were needed

Vitamin C, Thiamine, and Steroids for Sepsis

A brief overview: at the end of 2016, Paul Marik published a study in Chest that outlined his use of IV Vitamin C, Thiamine, and Steroids to treat severe sepsis and septic shock. A press release by Eastern Virginia Medical School and Sentara Healthcare then led to a story being published on NPR on March 23rd 2017. This story got picked up by other media outlets and was all over FOAMed and social media. It has become extremely controversial and many people have expressed their skepticism, but there have been reports of patients’ families specifically requesting it.

The Study:

  • Retrospective, single-centre, propensity-matched, before-and-after study
  • 47 adults with severe sepsis/septic shock in each group (the first 3 “pivotal cases” were removed from study)
  • Intervention:
    • Vitamin C 1.5 g IV q6h x 4 days or until ICU discharge
    • Hydrocortisone 50 mg IV q6h x 7 days or until ICU discharge, then 3 day taper
    • Thaimine 200 mg IV q12h x 4 days or until ICU discharge
  • Control:
    • Hydrocortisone 50 mg IV q6h per current guidelines (attending’s discretion)
  • Both groups:
    • Broad spectrum antibiotics
    • Fluid restrictive resuscitation
    • Norepinephrine early
    • Lung-protective ventilator strategy
    • Enteral nutrition once clinically stable
    • Permissive hyperglycaemia
    • No routine stress ulcer prophylaxis
  • Results:
    • Primary outcome (mortality): 40.4% control vs 8.5% intervention
      • Absolute difference: 31.9%
      • NNT 4
    • Secondary outcomes (only significant listed):
      • Duration of pressors: 54.9 hours vs 18.3 hours
      • Renal Replacement Therapy: 37% vs 10%
      • 72h delta SOFA score: 0.9 vs 4.8


Criticisms of the study include its retrospective, non-randomized, non-blinded study design, as well as it being at a single centre with a small number of patients. There was a higher mortality rate in the control group than found in recent sepsis trials which leads to concerns about external validity. Not to mention, many feel that this is all “too good to be true” and will end up like previous sepsis “miracle cures” like activated protein c, methylene blue, hemofiltration, etc.

Supporting Evidence:

  • Vitamin C
    • Safe in sepsis (Fowler et al. 2014)
    • In sepsis, levels fall (Wilson 2009)
    • In sepsis, levels only correct with large doses (3 g/day) (de Grooth et al. 2016)
    • May restore sensitivity to glucocorticoids (Marik 2016)
    • Pre-op may prevent etomidate-induced adrenal suppression (Das et al. 2016, Nooraei et al. 2016)
    • Required for catecholamine synthesis (Carr et al. 2015)
    • Necessary for cortisol synthesis (Marik 2016)
    • Reduces resuscitation fluid volumes in severe burns (Tanaka et al. 2000)
    • Leads to dose-dependent reduction in SOFA scores (Fowler et al. 2014)
    • Reduces dose & duration of pressors (Zabet et al. 2016)
    • Levels correlate with multi-organ failure & death (Wilson 2009)
    • Vitamin C+E reduced multi-organ failure in sick surgical patients (Nathens et al. 2002)
    • Decreased mortality from 64% to 14% in surgical sepsis (Zabet et al. 2016)
  • Thiamine
    • Levels low in sepsis associated with mortality  (Manzanares & Hardy 2011)
    • Cofactor for pyruvate dehydrogenase and other enzymes (Kreb’s cycle).
    • Thiamine deficiency is associated with lactic acidosis
    • Reduces lactate & mortality in thiamine deficient septic patients (Donnino et al. 2016)
    • May prevent calcium oxalate formation (potential side effect of Vitamin C) (Marik 2016)

Marik’s protocol isn’t quite ready to be adopted widely, although there are reports of physicians going ahead with some of their patients. There are RCTs being planned from Greece, Australia/New Zealand, and the US.


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