Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports

Abstract

Background In the early literature, unintentional vitamin C deficiency in humans was associated with heart failure. Experimental vitamin C deficiency in guinea pigs caused enlargement of the heart. The purpose of this study was to collect and analyze case reports on vitamin C and pulmonary hypertension. Methods We searched Pubmed and Scopus for case studies in which vitamin C deficiency was considered to be the cause of pulmonary hypertension. We selected reports in which pulmonary hypertension was diagnosed by echocardiography or catheterization, for any age, sex, or dosage of vitamin C. We extracted quantitative data for our analysis. We used the mean pulmonary artery pressure (mPAP) as the outcome of primary interest. Results We identified 32 case reports, 21 of which were published in the last 5 years. Dyspnea was reported in 69%, edema in 53% and fatigue in 28% of the patients. Vitamin C plasma levels, measured in 27 cases, were undetectable in 24 and very low in 3 cases. Diet was poor in 30 cases and 17 cases had neuropsychiatric disorders. Right ventricular enlargement was reported in 24 cases. During periods of vitamin C deficiency, the median mPAP was 48 mmHg (range 29–77 mmHg; N = 28). After the start of vitamin C administration, the median mPAP was 20 mmHg (range 12–33 mmHg; N = 18). For the latter 18 cases, mPAP was 2.4-fold (median) higher during vitamin C deficiency. Pulmonary vascular resistance (PVR) during vitamin C deficiency was reported for 9 cases, ranging from 4.1 to 41 Wood units. PVR was 9-fold (median; N = 5) higher during vitamin C deficiency than during vitamin C administration. In 8 cases, there was direct evidence that the cases were pulmonary artery hypertension (PAH). Probably the majority of the remaining cases were also PAH. Conclusions The cases analyzed in our study indicate that pulmonary hypertension can be one explanation for the reported heart failure of scurvy patients in the early literature. It would seem sensible to measure plasma vitamin C levels of patients with PH and examine the effects of vitamin C administration.

Rebound effect explains the divergence in survival after 5 days in a controlled trial on vitamin C for COVID-19 patients

“…Instead, all three trials that terminated 4-day vitamin C administration abruptly ( 6 , 8 , 9 , 17 ), provide evidence that vitamin C should not be abruptly stopped if the patients are still critically ill. Given that scurvy is a serious and potentially life-threatening disease, it is not ethical to withhold vitamin C from patients who have very low vitamin C levels ( 7 , 36 ). Nevertheless, further research of the rebound effect is needed to monitor plasma vitamin C levels in contexts that do not compromise the safety of patients.…”