What vitamins help sepsis?

Sepsis is a life-threatening condition caused by the body’s extreme response to an infection. It can rapidly lead to tissue damage, organ failure, and death. An estimated 1.7 million adults in America develop sepsis each year, resulting in nearly 270,000 deaths. This makes sepsis a leading cause of mortality, underscoring the need for effective prevention and treatment strategies.

One area of increasing interest is the role of nutrition, particularly vitamins, in influencing sepsis outcomes. Vitamins help regulate many critical bodily processes impacted in sepsis, including immunity, inflammation, tissue repair, and antioxidant activity. Research shows certain vitamins may help prevent or treat sepsis when administered appropriately. Let’s explore what the current evidence says about vitamins and sepsis.

Vitamin C

Vitamin C is a powerful antioxidant that supports numerous cellular functions. It boosts immunity, inhibits inflammation, stabilizes endothelial barriers, and aids collagen synthesis necessary for wound healing. Multiple lines of evidence suggest vitamin C may help with sepsis treatment:

  • Sepsis often rapidly depletes vitamin C reserves due to inflammation and metabolic alterations. Patients with sepsis tend to have very low vitamin C blood levels.
  • Low vitamin C levels correlate with more severe organ dysfunction and higher mortality in sepsis.
  • Animal studies demonstrate vitamin C administration after sepsis reduces organ injury and death risk.
  • Mechanistic studies show vitamin C impacts sepsis pathways by reducing oxidative stress, stabilizing endothelium, improving vasopressor responsiveness, and modulating immune cell function.
  • Numerous clinical trials find high-dose intravenous vitamin C shortens vasopressor duration, SOFA scores, and time on mechanical ventilation for sepsis patients. A meta-analysis of 12 trials concluded vitamin C probably reduces mortality.

Based on this collective evidence, experts increasingly recommend adding intravenous vitamin C to standard sepsis care. Typical dosing is 6-10 grams per day for 3-4 days. Oral vitamin C has poor bioavailability at such high doses, so intravenous administration is preferred. Still, more research is needed to clarify optimal vitamin C dosing regimens. Overall, vitamin C shows promise as an adjunctive sepsis therapy due to its critical physiological roles, safety, and clinical trial results.

Vitamin D

Vitamin D is instrumental in regulating calcium absorption and bone health. However, vitamin D receptors are present on nearly all immune cells. Growing evidence suggests vitamin D also modulates immunity and inflammation. Vitamin D may help prevent and treat sepsis through several mechanisms:

  • Many sepsis patients are deficient in vitamin D. This correlates with higher mortality risk.
  • Vitamin D enhances production of antimicrobial peptides and anti-inflammatory cytokines.
  • Vitamin D also suppresses release of proinflammatory cytokines like tumor necrosis factor alpha and interleukin-6.
  • Vitamin D stimulates neutrophil mobility and phagocytic activity to help fight infection.
  • Through its immunomodulatory effects, vitamin D decreased mortality in animal sepsis models.
  • Several clinical studies found low vitamin D levels in sepsis patients portended worse outcomes.

These findings suggest vitamin D sufficiency may help prevent and manage sepsis complications. However, interventional trials testing vitamin D supplementation for sepsis treatment show mixed results so far. The heterogeneity of dosing strategies, sepsis severity, and timing of administration make interpretations difficult. Still, ensuring adequate vitamin D levels through screening and repletion before sepsis onset seems prudent. More research is needed to clarify if pharmacologic vitamin D doses can improve sepsis outcomes. The safety and low cost of vitamin D supplements support their consideration for repletion in deficient patients.

B Vitamins

B vitamins like thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, and cobalamin play cardinal roles in energy metabolism. Sepsis often leads to elevated metabolic demands, hypoxia, and diminished energy production. Depletion of B vitamins can therefore profoundly impact sepsis outcomes.

Thiamine deficiency is particularly prevalent and dangerous in sepsis patients. Thiamine requirements increase during critical illness due to augmented glucose metabolism. However, thiamine stores get depleted while malnutrition and alcoholism compromise thiamine intake and absorption. This makes many sepsis patients thiamine deficient. Consequences include anaerobic metabolism, high lactate, and neurological dysfunction. Multiple trials demonstrate thiamine administration reduces lactate levels, organ dysfunction scores, and mortality for septic patients.

Other B vitamin deficiencies also associated with worse sepsis prognosis include:

  • Riboflavin – linked to mitochondrial dysfunction and increased infection risk
  • Niacin – low levels predict higher mortality
  • Pyridoxine – correlated with longer ICU stays
  • Folate – predicts development of sepsis complications
  • Cobalamin – deficiency impairs immunity and methylmalonic acid clearance

Experts recommend screening for and correcting any B vitamin insufficiencies in sepsis patients. Thiamine should be promptly administered, especially prior to glucose infusion. Addressing B vitamin deficiencies may optimize metabolic function and energy production to improve sepsis outcomes. The low risk of B vitamin supplementation further supports their use in sepsis management.

Antioxidant Vitamins A, E, and Selenium

Sepsis induces the rapid release of reactive oxygen species, contributing to cellular injury and organ dysfunction. Depletion of antioxidant defenses likely precipitates further oxidative damage. Restoring antioxidant capacity could therefore help mitigate complications. The antioxidant vitamins A, E, and selenium may have utility in sepsis treatment.

  • Vitamin A supports epithelial barrier integrity and immune cell differentiation. Low vitamin A levels occur in sepsis and associate with greater mortality.
  • Vitamin E scavenges free radicals and stabilizes cell membranes. Sepsis patients often exhibit vitamin E deficiency.
  • Selenium boosts activity of antioxidant selenoproteins like glutathione peroxidase. Selenium levels decrease in sepsis.

Animal studies demonstrate antioxidant vitamin therapy reduces sepsis mortality. However, human trials show less consistent benefit. Earlier antioxidant supplementation may better replenish stores before extensive oxidant damage occurs. Still, some studies found increased risk of mortality, so caution is warranted. Overall the antioxidant vitamins show plausible mechanistic rationale but require more research to determine their role in sepsis treatment.


Zinc serves as a cofactor for numerous enzymes and signaling molecules related to immunity, antioxidant function, and tissue repair. Sepsis prompts excessive inflammation and oxidant release which can rapidly deplete zinc reserves.

  • Animal models find zinc supplementation ameliorates sepsis-induced inflammation and mortality.
  • Zinc administration improved endothelial function and reduced oxidative injury in human endotoxemia experiments.
  • Small clinical studies show zinc provided during sepsis correlated with reduced complication rates and mortality.
  • Conversely, low zinc levels portended worse outcomes.

Given its importance for enzymes vital for antioxidant activity, immune cell function, and tissue repair, zinc repletion may support recovery in sepsis patients. More research is still needed to determine optimal zinc dosing. But zinc administration appears relatively safe and trials indicate potential for therapeutic benefit.

Other Vitamins

A few other vitamins show initial links to sepsis outcomes, but await more substantive evidence:

  • Vitamin K assists with blood clotting and coagulation. Sepsis often leads to coagulation abnormalities. Small studies find low vitamin K levels associate with organ dysfunction and higher mortality risk in sepsis patients.
  • Biotin aids carboxylase enzyme function involved in gluconeogenesis and fat metabolism. A minority of critically ill patients develop biotin deficiency, which could theoretically impact sepsis metabolism.
  • Vitamin B12 helps regulate methylmalonic acid levels. Elevated methylmalonic acid occurs in sepsis and correlates with hypoperfusion and mortality. However, B12 itself lacks clear links to sepsis outcomes so far.

While these vitamins exhibit plausible connections to sepsis pathology, current evidence does not yet support recommendations for their routine use in sepsis treatment. Larger controlled trials are needed.

Key Considerations for Vitamin Supplementation in Sepsis

The emerging yet incomplete evidence for vitamins in sepsis treatment raises several key considerations:

  • Screening for and correcting vitamin deficiencies prior to sepsis onset seems highly prudent. This may help optimize vitamin status and resilience before an infectious crisis.
  • The common deficiencies seen in sepsis patients (vitamins C, D, thiamine, etc) provide rationale for their repletion during sepsis treatment. However, optimal dosing remains unclear.
  • Improperly timed or excessively high vitamin doses could potentially cause harm in some cases. More research is still needed to refine regimens.
  • Intravenous administration attains more consistent and higher vitamin levels than enteral supplementation for acutely ill patients.
  • Vitamins act synergistically, suggesting combinations may be more beneficial than individual vitamins alone.
  • Vitamins should only be given alongside standard sepsis care like antibiotics, vasopressors, ventilation, etc. They are adjunctive, not standalone.

Overall, vitamins show significant promise for mitigating sepsis by supporting key physiological processes undermined by sepsis pathology. Further research to illuminate optimal formulations, combinations, timing, and dosing will help translate vitamins’ theoretical benefit into clear clinical improvements for sepsis patients.


Sepsis is a complex, devastating syndrome requiring multi-pronged treatment approaches. Certain vitamins like vitamin C, vitamin D, thiamine, and zinc may help prevent sepsis complications and mortality when administered correctly during sepsis treatment. They support immune function, antioxidant capacity, tissue healing, and energy metabolism which are all impaired in sepsis. While questions remain about optimal regimens, vitamins are relatively low-risk adjuncts with emerging evidence of benefit. Vitamin status should be assessed in sepsis patients and deficiencies corrected. Further research is still needed to refine the roles of vitamin supplementation in sepsis. Some of the most compelling evidence supports IV vitamin C and thiamine. Overall, vitamins may serve as safe, inexpensive additions to standard care in the ongoing quest to improve sepsis outcomes.

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