Hydrocortisone, Ascorbic Acid, and Thiamine (HAT) Therapy Decreases Oxidative Stress, Improves Cardiovascular Function, and Improves Survival in Murine Sepsis

Kim, Jiyoun; Arnaout, Leen; Remick, Daniel G.

doi:10.1097/shk.0000000000001385

Cited by 23 publications

(38 citation statements)

References 30 publications

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“…Elevated protein carbonyls have been observed previously in critically ill patients with sepsis [22]. The patients with the highest protein carbonyl values in our study had hypovitaminosis C. Interestingly, a pre-clinical animal model indicated that administration of high-dose vitamin C to mice with sepsis decreased protein carbonyl levels in the most severely ill [23]. This has not yet been demonstrated in human studies, however, based on vitamin C's potent antioxidant properties, it is possible that vitamin C administration to patients with pneumonia could decrease markers of oxidative stress.…”

Section: Discussionsupporting

confidence: 67%

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

Carr

Spencer

Dixon

et al. 2020

Preprint

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Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

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Section: Discussionsupporting

confidence: 67%

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

Carr

Spencer

Dixon

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In one clinical trial, thiamine showed a statistically significance difference at lowering the lactate level compared to the control group and, therefore, possible reduc-tion in overall mortality [41,42,47,56]. The combination of thiamine, ascorbic acid, and corticosteroids has been suggested as a potential adjunctive therapy targeted at the non-oxygen delivery-dependent mechanisms of organ dysfunction in sepsis [41,42,47,[56][57][58]. Theoretically, based on these substances' mechanisms of action, their combination may have a synergistic effect in treating patients with septic shock.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

et al. 2021

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Background: Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Methods: Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Results: Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P = 0.92; I 2 = 0%); intensive care unit (ICU) mortality (RR, 0.77; P = 0.20; I 2 = 58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I 2 =37%) or hospital length of stay (WMD: 0.57; P=0.49; I 2 =17%), and renal replacement therapy (RR, 0.64; P = 0.44; I 2 = 39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, -0.72; P=0.01; I 2 = 32%). However, a significant effect was noted for the duration of vasopressor use (WMD, -25.49; P < 0.001; I 2 = 46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. Conclusions: HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

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“…The patients with the highest protein carbonyl values measured in our study had hypovitaminosis C. Elevated oxidative stress could be both a cause and a consequence of the low vitamin C status observed in the patients. Interestingly, a pre-clinical animal model indicated that administration of high-dose vitamin C to mice with sepsis decreased protein carbonyl levels in the most severely ill [ 24 ]. This has not yet been demonstrated in human studies; however, based on the potent antioxidant properties of vitamin C, it is possible that vitamin C administration to patients with pneumonia could decrease markers of excessive oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

et al. 2020

View full text Add to dashboard Cite

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1–7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery.

show abstract

Hydrocortisone, Ascorbic Acid, and Thiamine (HAT) Therapy Decreases Oxidative Stress, Improves Cardiovascular Function, and Improves Survival in Murine Sepsis

Cited by 23 publications

References 30 publications

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress

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