Vitamin C Deficiency-Induced Pulmonary Arterial Hypertension

Gayen, S.; Abdelrahman, Abd Almonem M.; Preston, Ioana R.; Petit, R; Hill, Nicholas S.

doi:10.1016/j.chest.2019.06.043

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…The numerous biochemical effects translate to diverse changes at the clinical level. Vitamin C deficiency is associated with many symptoms characteristic of HF (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

“…Case reports of patients with severe vitamin C deficiency have reported fatigue, dyspnea, cardiac enlargement, oedema and orthostatic hypotension, which often disappeared quite rapidly after vitamin C administration (9)(10)(11)(12)(13)(14)(15). A few animal models found that vitamin C can improve contractility and mechanical efficiency of the heart, including effects on left ventricular ejection fraction (LVEF) (16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

Hemilä

Chalker

Man

2022

Front. Cardiovasc. Med.

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BackgroundVitamin C deprivation can lead to fatigue, dyspnea, oedema and chest pain, which are also symptoms of heart failure (HF). In animal studies vitamin C has improved contractility and mechanical efficiency of the heart. Compared with healthy people, patients with HF have lower vitamin C levels, which are not explained by differences in dietary intake levels, and more severe HF seems to be associated with lower plasma vitamin C levels. This meta-analysis looks at the effect of vitamin C on left ventricular ejection fraction (LVEF).MethodsWe searched for trials reporting the effects of vitamin C on LVEF. We assessed the quality of the trials, and pooled selected trials using the inverse variance, fixed effect options. We used meta-regression to examine the association between the effect of vitamin C on LVEF level and the baseline LVEF level.ResultsWe identified 15 trials, three of which were excluded from our meta-analysis. In six cardiac trials with 246 patients, vitamin C increased LVEF on average by 12.0% (95% CI 8.1–15.9%; P < 0.001). In six non-cardiac trials including 177 participants, vitamin C increased LVEF on average by 5.3% (95% CI 2.0–8.5%; P = 0.001). In meta-regression analysis we found that the effect of vitamin C was larger in trials with the lowest baseline LVEF levels with P = 0.001 for the test of slope. The meta-regression line crossed the null effect level at a baseline LVEF level close to 70%, with progressively greater benefit from vitamin C with lower LVEF levels. Some of the included trials had methodological limitations. In a sensitivity analysis including only the four most methodologically sound cardiac trials, the effect of vitamin C was not substantially changed.ConclusionsIn this meta-analysis, vitamin C increased LVEF in both cardiac and non-cardiac patients, with a strong negative association between the size of the vitamin C effect and the baseline LVEF. Further research on vitamin C and HF should be carried out, particularly in patients who have low LVEF together with low vitamin C intake or low plasma levels. Different dosages and different routes of administration should be compared.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

Hemilä

Chalker

Man

2022

Front. Cardiovasc. Med.

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“…The above evidence fully demonstrated that 15 mg kg −1 WDNs inhibited PH‐induced RV hypertrophy and improved RV dysfunction. In addition, natural antioxidants such as GSH, [ 41 ] vitamin C, [ 42 ] and clinical drugs for PH treatment fasudil [ 43 ] were conducted for comparison. As shown in Figures S9 and S10, Supporting Information, these control treatments had a negligible therapeutic effect at the samedose as WNDs.…”

Section: Resultsmentioning

confidence: 99%

Natural Targeting Potent ROS‐Eliminating Tungsten‐Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension

Liu

Wang

Chen

et al. 2023

Adv Healthcare Materials

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Pulmonary hypertension (PH) is a disease of pulmonary artery stenosis and blockage caused by abnormal pulmonary artery smooth muscle cells (PASMCs), with high morbidity and mortality. High levels of reactive oxygen species (ROS) in pulmonary arteries play a crucial role in inducing phenotypic switch and abnormal proliferation of PASMCs. However, antioxidants are rarely approved for the treatment of PH because of a lack of targeting and low bioavailability. In this study, the presence of an enhanced permeability and retention effect (EPR)‐like effect in the pulmonary arteries of PH is revealed by tissue transmission electron microscopy (TEM). Subsequently, for the first time, tungsten‐based polyoxometalate nanodots (WNDs) are developed with potent elimination of multiple ROS for efficient treatment of PH thanks to the high proportion of reduced W5+. WNDs are effectively enriched in the pulmonary artery by intravenous injection because of the EPR‐like effect of PH, and significantly prevent the abnormal proliferation of PASMCs, greatly improve the remodeling of pulmonary arteries, and ultimately improve right heart function. In conclusion, this work provides a novel and effective solution to the dilemma of targeting ROS for the treatment of PH.

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“…Case reports of scurvy have reported hypotension, tachypnea, and tachycardia [39][40][41][42][43][44][45][46], which are important symptoms of sepsis [3,6,7]. In the case reports, vitamin C deficiency also caused dyspnea [42][43][44][45][46][47][48], chest pain [42], edema [40-43, 46, 47], petecchia and ecchymoses [39][40][41][42][43][44][45][46][47][48][49][50], fatigue [39,40,45,46] and musculoskeletal pains [40,42,47] which are also symptoms of sepsis [7]. This means that scurvy should be considered in the differential diagnosis of patients with such symptoms, in particular when plasma vitamin C levels are very low.…”

Section: Ethical Concerns With Not Treating Overt Vitamin C Deficiencymentioning

confidence: 99%

Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial

Hemilä

Chalker²

2022

Eur J Clin Nutr

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Background The LOVIT trial examined the effect of vitamin C on sepsis patients, and concluded that in adults with sepsis receiving vasopressor therapy in the ICU, those who received 4-day intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. The aim of this study was to determine whether the abrupt termination of vitamin C administration could explain the increased mortality in the vitamin C group. Methods We used Cox regression with two time periods to model the distribution of deaths over the first 11 days in the LOVIT trial. Results Compared with a uniform difference between vitamin C and placebo groups over the 11-day follow-up period, addition of a separate vitamin C effect starting from day 5 improved the fit of the Cox model (p = 0.026). There was no difference in mortality between the groups during the 4-day vitamin C administration with RR = 0.97 (95% CI: 0.65–1.44). During the week after the sudden termination of vitamin C, there were 57 deaths in the vitamin C group, but only 32 deaths in the placebo group, with RR = 1.9 (95% CI: 1.2–2.9; p = 0.004). Conclusion The increased mortality in the vitamin C group in the LOVIT trial is not explained by ongoing vitamin C administration, but by the abrupt termination of vitamin C. The LOVIT trial findings should not be interpreted as evidence against vitamin C therapy for critically ill patients.

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Vitamin C Deficiency-Induced Pulmonary Arterial Hypertension

Cited by 12 publications

References 11 publications

Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

Natural Targeting Potent ROS‐Eliminating Tungsten‐Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension

Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial

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