Sepsis
Supplements studied for sepsis.
Overview
Vitamin C (30 studies) is the most studied supplement for sepsis, with high-quality trials finding that intravenous vitamin C does not reduce organ failure, hospital stays, or mortality—and one large study suggested possible harm. Melatonin (5 studies) may shorten ventilator time and hospital stay in adults but does not clearly improve survival; newborn data are mixed.
L-Carnitine (2 studies) does not reduce overall mortality but may benefit the sickest patients. N-Acetyl Cysteine (NAC) (2 studies) may improve breathing in septic shock without lowering death rates. See the heatmap and evidence reviews below.
Effect graph
Relevant supplements
Relevant supplements sorted by DEX Score.
| Melatonin | ★★★★★ | Low |
| Vitamin C | ★★★★★ | Very Low / None |
| N-Acetyl Cysteine (NAC) | ★★★★★ | Low |
| Vitamin A | ★★★★★ | Very Low / None |
| Saccharomyces boulardii | ★★★★★ | Very Low / None |
| L-Carnitine | ★★★★★ | Very Low / None |
| Algal Oil | ★★★★★ | Very Low / None |
Studies
Find individual evidence reviews for supplements sorted by DEX Score.
7 supplements for and rated at least stars. All purchase bands. No minimum star filter.
MelatoninView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- It is unclear if melatonin helps with sepsis in newborns or adults. Some early studies in newborns give mixed results. In adults, melatonin taken by mouth or through an IV for a few days may help shorten time on ventilators and reduce hospital stay, but it does not clearly improve survival. More research is needed.
- Melatonin might help adults with sepsis recover faster in hospital but does not clearly improve survival, and more research is needed especially in newborns.
Browse 5 studies
RCTA phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in surgical patients with severe sepsis admitted to the intensive care unit2023n=14
In surgical patients with severe sepsis, IV melatonin 60 mg daily did not significantly improve redox status or inflammatory markers versus placebo.
- Effect
- No Benefit
- Duration
- 5 days
- Dose
- 60 mg/day
- Population
- Pregnant women
- Participants
- 14
RCTA pilot study on the melatonin treatment in patients with early septic shock: results of a single-center randomized controlled trial2022n=40
In 40 early septic shock patients, melatonin 50 mg for 5 nights did not significantly improve SOFA score or organ dysfunction versus placebo.
- Effect
- No Benefit
- Duration
- 5 days
- Dose
- 50 mg/day
- Population
- ALL patients
- Participants
- 40
RCTThe Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients2022n=158
An RCT of 158 hospitalized COVID-19 patients found 10 mg/day melatonin for 14 days significantly reduced thrombosis and sepsis incidence and lowered mortality vs standard care.
- Effect
- Benefit
- Duration
- 14 days
- Dose
- 10 mg/day
- Population
- Adults
- Participants
- 158
Controlled trialBeneficial effect of melatonin in the treatment of neonatal sepsis2018
In 40 neonates with sepsis, a single melatonin 20 mg dose plus antibiotics reduced sepsis markers versus antibiotics alone in a nonrandomized study.
- Effect
- Benefit
- Dose
- 20 mg/day
- Population
- Infants
Clinical trialUse of melatonin as an adjuvant therapy in neonatal sepsis2015n=25
In 50 neonates with sepsis, melatonin 20 mg as adjuvant therapy improved clinical outcomes versus antibiotics alone in a prospective trial.
- Effect
- Benefit
- Dose
- 20 mg/day
- Population
- Infants
- Participants
- 25
N-Acetyl Cysteine (NAC)View supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Some small studies show that intravenous N-acetylcysteine (NAC) may help breathing and oxygen levels in people with septic shock, but it does not seem to lower the risk of death.
- These results come from a few small studies comparing NAC to a placebo.
Browse 2 studies
RCTDoes N-acetyl-L-cysteine influence cytokine response during early human septic shock?1998n=10
In a double-blind RCT of 22 septic shock patients, NAC (150 mg/kg bolus plus infusion) did not clearly improve hemodynamics, oxygen transport, or cytokine profiles versus placebo.
- Effect
- Benefit
- Duration
- 4 hours
- Dose
- 150 mg/kg
- Population
- Patients with septic shock
- Participants
- 10
RCTInfluence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study1994n=58
A prospective double-blind RCT in 58 septic shock patients found NAC (150 mg/kg) did not improve whole-body oxygen consumption, gastric intramucosal pH, or veno-arterial PCO2.
- Effect
- No Benefit
- Dose
- 150 mg/kg
- Population
- Patients with septic shock
- Participants
- 58
Vitamin CView supplement →
Reconsider purchase·★★★★★
How we scored this▸
- Giving vitamin C through the vein does not help prevent organ failure, shorten hospital or ICU stays, or reduce death rates in people with severe infections called sepsis or septic shock.
- People with septic shock often have low vitamin C levels in their blood.
- However, several high-quality studies found no benefit of intravenous vitamin C on organ health or survival.
- One large study showed that vitamin C might even increase the risk of death or long-lasting organ problems.
- While some early research suggested combining vitamin C with other medicines might help, other studies did not find proof of this.
Browse 30 studies·12 meta-analyses
RCTHigh-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial2024n=58
An RCT in 58 septic shock patients found IV vitamin C increased catecholamine synthesis markers and reduced norepinephrine dose but not mortality.
- Effect
- No Benefit
- Duration
- 96 hours
- Dose
- 150 mg/kg
- Population
- Adults
- Participants
- 58
- Ages
- 18+
RCTAssociation of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial2023n=108
A VICTAS secondary analysis in 213 sepsis survivors found vitamin C, thiamine, and hydrocortisone did not improve and may worsen 6-month cognitive outcomes.
- Effect
- No Benefit
- Duration
- 96 hours
- Dose
- 1.5 g
- Population
- Adults
- Participants
- 108
MetaEfficacy of Ascorbic Acid, Thiamine, and Hydrocortisone Combination Therapy: Meta-analysis of Randomized Controlled Trials2023
A meta-analysis of 9 HAT therapy RCTs found no mortality benefit but significantly shorter vasopressor duration with ascorbic acid, thiamine, and hydrocortisone.
- Effect
- No Benefit
- Population
- Sepsis patients
MetaHydrocortisone Combined with Vitamin C and Thiamine in the Treatment of Sepsis/Septic Shock: A Systematic Review with Meta-Analysis and Trial Sequential Analysis2023n=1,572
A meta-analysis of 8 RCTs (1,572 patients) found hydrocortisone plus vitamin C and thiamine did not reduce sepsis mortality or improve major outcomes.
- Effect
- No Benefit
- Population
- Sepsis patients
- Participants
- 1,572
RCTIntravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial)2023n=71
The VALENCIA RCT in 71 vasoplegic shock patients found IV vitamin C (1.5 g every 6 h) did not significantly reduce vasopressor duration versus placebo.
- Effect
- No Benefit
- Duration
- 5 days
- Dose
- 1.5 g sodium ascorbate every 6 h
- Population
- Patients With Vasoplegic Shock
- Participants
- 71
RCTIV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial2023n=437
A Bayesian reanalysis of the 872-participant LOVIT trial found IV vitamin C (50 mg/kg) associated with high probability of harm for 28-day death or persistent organ dysfunction.
- Effect
- No Benefit
- Duration
- 96 hours
- Dose
- 50 mg/kg
- Population
- Adults
- Participants
- 437
MetaIV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis2023
A meta-analysis of 24 sepsis RCTs found IV vitamin C may reduce mortality (RR 0.82) and significantly improve SOFA scores after 72+ hours.
- Effect
- Benefit
- Population
- Sepsis patients
RCTMega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial2023n=30
An RCT in 30 septic shock patients found single mega-dose sodium ascorbate (60 g) did not significantly increase 24-hour urine output but reduced vasopressor dose over time.
- Effect
- No Benefit
- Dose
- 60 g sodium ascorbate over 6 h
- Population
- Patients With Septic Shock
- Participants
- 30
MetaThe outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials2023n=3,364
A meta-analysis of 18 RCTs (3,364 sepsis patients) found IV vitamin C improved SOFA score and reduced vasopressor duration but not short-term mortality.
- Effect
- No Benefit
- Dose
- 25–100 mg/kg
- Population
- Sepsis patients
- Participants
- 3,364
MetaClinical efficacy and safety of vitamin C in the treatment of septic shock patients: systematic review and meta-analysis2022n=1,423
A meta-analysis of 13 studies (1,423 sepsis patients) found IV vitamin C did not reduce hospital or ICU mortality or improve 72-hour SOFA scores.
- Effect
- No Benefit
- Population
- Septic shock patients
- Participants
- 1,423
RCTEvaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy2022n=124
An RCT in 124 septic shock patients found IV vitamin C monotherapy did not significantly reduce 28-day mortality (26.7% vs 40.6%; p=0.10).
- Effect
- No Benefit
- Dose
- 1,000 mg bolus + 250 mg/h IV vitamin C for 96 h
- Population
- Adults
- Participants
- 124
RCTIntravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit2022n=872
A study of 863 patients who had been in the ICU for no longer than 24 hours, who had proven or suspected infection found that IV vitamin C (50 mg/kg/bw every 6 hours for 96 hours) increased the risk of death or persistent organ dysfunction by 21% (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01) after 28 days. Patients were sourced from 35 adult medical-surgical ICUs in Canada, France, and New Zealand. The primary outcome was a composite of death or persistent organ dysfunction (Use of vasopressors, invasive mechanical ventilation or new renal-replacement therapy). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group. After 28 days, patients taking vitamin C had a 17% greater risk of death and a 30% greater risk of persistent organ dysfunction.
- Effect
- No Benefit
- Duration
- 96 hours
- Dose
- 50 mg/day
- Population
- Adults
- Participants
- 872
- Ages
- 18+
MetaIV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis2022n=2,490
A meta-analysis of 15 trials (2,490 critically ill patients) found high-dose IV vitamin C monotherapy may reduce mortality (RR 0.70); low-dose showed no benefit.
- Effect
- Benefit
- Population
- Critically ill patients
- Participants
- 2,490
MetaParenteral Vitamin C in Patients with Severe Infection: A Systematic Review2022n=4,915
A systematic review of 41 RCTs (4,915 patients) found parenteral vitamin C may reduce early mortality in low-certainty analyses but not in low-bias trials.
- Effect
- Benefit
- Population
- Adults
- Participants
- 4,915
MetaThe impact of vitamin C-containing treatment on the mortality of patients with sepsis: A systematic review and meta-analysis of randomized controlled trials2022n=2,985
A meta-analysis of 16 RCTs (2,985 sepsis patients) found adjunctive vitamin C did not reduce 28-day, ICU, or in-hospital mortality.
- Effect
- No Benefit
- Population
- Patients with sepsis
- Participants
- 2,985
MetaVitamin C, Thiamine, and Hydrocortisone in the Treatment of Sepsis: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials2022n=839
A meta-analysis of 839 sepsis patients found vitamin C, thiamine, and hydrocortisone did not reduce mortality but lowered day-3 SOFA score.
- Effect
- No Benefit
- Population
- Sepsis patients
- Participants
- 839
- Ages
- 18+
MetaEffect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials2021n=1,737
A meta-analysis of 11 RCTs (1,737 sepsis patients) found high-dose IV vitamin C did not lower mortality but shortened vasopressor use and improved SOFA at 72–96 hours.
- Effect
- No Benefit
- Population
- Patients with sepsis
- Participants
- 1,737
- Ages
- 18+
RCTEffect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial2021n=252
The VICTAS trial in 501 sepsis patients found vitamin C, thiamine, and hydrocortisone did not increase ventilator- and vasopressor-free days versus placebo.
- Effect
- No Benefit
- Duration
- 96 hours
- Dose
- 1.5 g
- Population
- Adults
- Participants
- 252
- Ages
- 18+
MetaEfficacy of intravenous vitamin C intervention for septic patients: A systematic review and meta-analysis based on randomized controlled trials2021n=1,400
A meta-analysis of 10 sepsis RCTs (1,400 patients) found IV vitamin C monotherapy may reduce short-term mortality (RR 0.61) and improve SOFA at 72 hours.
- Effect
- Benefit
- Population
- Patients with sepsis
- Participants
- 1,400
RCTHydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis2021n=1,427
A meta-analysis of 9 HAT RCTs (1,427 sepsis patients) found the combination improved SOFA at 72 hours and reduced vasopressor duration but not mortality.
- Effect
- No Benefit
- Population
- Patients with sepsis and septic shock
- Participants
- 1,427
MetaVitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis2021
A meta-analysis of 48 studies found IV vitamin C associated with 19% lower in-hospital mortality and 0.76 fewer ICU days in critically ill patients.
- Effect
- Benefit
- Population
- Critically ill patients
RCTCombination therapy of vitamin C and thiamine for septic shock: a multi-centre, double-blinded randomized, controlled study2020n=111
The ATESS trial in 111 septic shock patients found early vitamin C plus thiamine did not improve organ failure scores versus placebo over 72 hours.
- Effect
- No Benefit
- Dose
- 50 mg/kg
- Population
- Adults
- Participants
- 111
RCTCombined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial2020n=40
An RCT in 80 sepsis patients found hydrocortisone, vitamin C, and thiamine did not reduce 28-day mortality but improved 72-hour SOFA scores.
- Effect
- No Benefit
- Duration
- 7 days
- Dose
- 1.5 g vitamin C every 6 h for 4 days
- Population
- Patients with sepsis
- Participants
- 40
RCTEffect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial2020n=103
The ACTS trial in 205 septic shock patients found ascorbic acid, corticosteroids, and thiamine did not reduce SOFA score, kidney failure, or 30-day mortality.
- Effect
- No Benefit
- Duration
- 4 days
- Dose
- 1500 mg
- Population
- Women
- Participants
- 103
- Ages
- 18+
RCTEffect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial2020n=109
The VITAMINS trial in 216 septic shock patients found adding vitamin C and thiamine to hydrocortisone did not shorten time alive and vasopressor-free over 7 days.
- Effect
- No Benefit
- Duration
- 7 days
- Dose
- 1.5 g vitamin C + 50 mg hydrocortisone + 200 mg thiamine every 6 h
- Population
- Patients With Septic Shock
- Participants
- 109
- Avg age
- ~62
ObservationalHydrocortisone-Ascorbic Acid-Thiamine Use Associated with Lower Mortality in Pediatric Septic Shock2020
An observational study reported hydrocortisone, ascorbic acid, and thiamine associated with lower mortality in pediatric septic shock; abstract provided limited detail.
- Population
- Children
RCTOutcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial2020n=69
The ORANGES trial in 137 sepsis patients found HAT therapy shortened shock reversal time (27 vs 53 hours) but did not improve SOFA or mortality.
- Effect
- Benefit
- Population
- Patients with sepsis and septic shock
- Participants
- 69
RCTEffect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial2019n=167
The CITRIS-ALI trial in 167 sepsis/ARDS patients found 96-hour IV vitamin C did not improve organ failure scores or inflammatory markers versus placebo.
- Effect
- No Benefit
- Dose
- 50 mg/kg
- Population
- Patients with sepsis
- Participants
- 167
- Avg age
- ~55
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study2017n=47
A retrospective before-after study in 47 sepsis patients reported IV vitamin C, hydrocortisone, and thiamine associated with lower mortality (8.5% vs 40.4%).
- Effect
- Benefit
- Duration
- 7 months
- Population
- Patients With Severe Sepsis And Septic Shock
- Participants
- 47
ObservationalHypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes2017n=24
In 44 critically ill patients, 74% had low vitamin C despite standard nutrition; septic shock patients had lower levels than non-septic patients.
- Duration
- 4 days
- Dose
- 125 mg/day
- Population
- Critically ill patients
- Participants
- 24
- Ages
- 18+
L-CarnitineView supplement →
Do not purchase·★★★★★
How we scored this▸
- Meta-analyses of several small studies found that giving L-carnitine by intravenous infusion to patients with sepsis does not reduce death rates at 28 days or 1 year overall.
- However, in patients with more severe illness (high SOFA scores), L-carnitine reduced the risk of death at 1 year by about one-third.
- Because of mixed results, more research is needed to confirm if L-carnitine helps the sickest sepsis patients survive.
Browse 2 studies·2 meta-analyses
MetaThe supplementation of L-carnitine in septic shock patients: Systematic review and meta-analysis2022n=275
A meta-analysis of septic shock trials (275 participants) found insufficient evidence that L-carnitine reduces mortality versus placebo or usual care.
- Effect
- No Benefit
- Population
- Adults
- Participants
- 275
- Ages
- 18+
MetaThe Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials2020
A systematic review and meta-analysis found L-carnitine may reduce mortality in septic patients, but evidence remained inconclusive for 28-day and 1-year mortality endpoints.
- Effect
- No Benefit
- Population
- Adults with sepsis
Saccharomyces boulardiiView supplement →
Do not purchase·★★★★★
How we scored this▸
- Giving the probiotic Saccharomyces boulardii by mouth does not reduce the risk of sepsis in preterm babies.
- A review of five studies found that doses of 100–200 mg per kilogram of body weight daily did not lower the chance of infection compared to no treatment or placebo.
Browse 1 study·1 meta-analysis
MetaEffect and Safety of Saccharomyces boulardii for Neonatal Necrotizing Enterocolitis in Pre-term Infants: A Systematic Review and Meta-Analysis2021n=1,264
A meta-analysis found S. boulardii reduced NEC stage ≥II, sepsis, and mortality in preterm infants versus placebo.
- Effect
- No Benefit
- Population
- Infants
- Participants
- 1,264
Vitamin AView supplement →
Do not purchase·★★★★★
How we scored this▸
- Giving premature babies vitamin A by mouth soon after birth does not lower their chance of developing sepsis.
- Studies show no difference in infection rates between babies receiving vitamin A supplements and those who do not.
Browse 1 study·1 meta-analysis
MetaEnteral Low-Dose Vitamin A Supplementation in Preterm or Low Birth Weight Infants to Prevent Morbidity and Mortality: a Systematic Review and Meta-analysis2022n=36
A meta-analysis of 4 trials (800 very low birth weight infants) found low-dose enteral vitamin A increased serum retinol but had no effect on mortality, sepsis, BPD, or hospital stay.
- Effect
- No Benefit
- Duration
- 26–32 weeks
- Dose
- ≤10000 IU/day vitamin A
- Population
- Infants
- Participants
- 36
Algal OilView supplement →
Do not purchase·★★★★★
How we scored this▸
- Giving DHA-enriched algal oil to breastfeeding mothers of very premature babies does not appear to lower the risk of sepsis (serious infection) in their babies.
Browse 1 study
RCTEffect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial2020n=528
An RCT in 528 breastfed preterm infants found maternal DHA 1.2 g/day did not improve bronchopulmonary dysplasia-free survival at 36 weeks; BPD was actually more common in the DHA group (41.7% vs 31.4%).
- Effect
- No Benefit
- Duration
- 36 weeks postmenstrual age
- Dose
- 1.2 g/day
- Population
- Women
- Participants
- 528
Evidence visualised
Same ratings as above, aggregated so you can see coverage and imbalance.
| Supplement | DEX | Studies | Meta-analyses | Share |
|---|---|---|---|---|
| Vitamin C | ★★★★★44% | 30 | 12 | 71% |
| Melatonin | ★★★★★52% | 5 | 0 | 12% |
| L-Carnitine | ★★★★★36% | 2 | 2 | 5% |
| N-Acetyl Cysteine (NAC) | ★★★★★44% | 2 | 0 | 5% |
| Algal Oil | ★★★★★32% | 1 | 0 | 2% |
| Saccharomyces boulardii | ★★★★★36% | 1 | 1 | 2% |
| Vitamin A | ★★★★★36% | 1 | 1 | 2% |