Pyridoxal-5′-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients

Molina-López, Jorge; Florea, Daniela; Quintero-Osso, Bartolomé; Cruz, A. Pérez de la; Rodrı́guez-Elvira, Manuel; Pozo, Elena

doi:10.1016/j.clnu.2015.04.022

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…According to the homocysteine cycle, the elimination of homocysteine is geared towards the formation of methionine through the increase of this vitamin (vit B12) and not towards the formation of cysteine. In addition, epidemiological evidence indicates that patients with inflammation have significantly lower blood levels of pyridoxal 5′-phosphate PLP (vit B6) than control subjects [17–19]. According to this study, there is a positive correlation between Glu and vit B12; that is to say, Glu accumulates when vit B12 increases, since cysteine is not available for the gamma-glutamylcysteine synthetase to act to form gamma-glutamylcysteine, as shown in Fig.…”

Section: Discussionmentioning

confidence: 62%

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

et al. 2019

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Aim The aim of this study was to evaluate oxidative stress from glutathione depletion in critically ill patients with a septic shock through the abnormal presence of pyroglutamic acid (PyroGlu) in the urine (indirectly) and through its serum level (directly). Methods This was a prospective analytical study of 28 critically ill patients with a septic shock who were monitored from admission (initial) to 3 days of stay (final) in the intensive care unit (ICU). Data collected included PyroGlu and glutamic acid (Glu) using liquid chromatography/mass spectrometry, and glutathione peroxidase (GPX) activity with a colorimetric assay. The differences in Glu, PyroGlu, and GPX activity between the septic shock group and healthy control group serving as reference values were evaluated using the Mann–Whitney test. The correlations between Glu, PyroGlu, and GPX activity and clinical outcomes were determined using Spearman’s correlation coefficient. Results In patients with septic shock, serum and urine PyroGlu levels were higher, erythrocyte GPX activity/gr Hb was lower, and urine Glu levels were lower compared to healthy control reference values, for both initial and final values. Initial serum Glu levels were also lower. Serum PyroGlu levels had a correlation with both initial and final serum Glu levels; levels also correlated in the urine. Initial serum Glu correlated with the days of mechanical ventilation ( P = 0.016) and the days of ICU stay ( P = 0.05). Urine Glu/mg creatinine correlated with APACHE II ( P = 0.030). This positive correlation observed for serum Glu was not observed for PyroGlu. Conclusions The current study found that septic patients have higher levels of PyroGlu, lower levels of Glu, and lower erythrocyte GPX activity, suggesting that these biomarkers could be used as an indicator of glutathione depletion. In addition, Glu is related to severity parameters. This study can guide future studies on the importance of monitoring the levels of pyroglutamic acidosis in critical patients with septic shock in order to preserve the oxidative status and its evolution during the stay in the ICU.

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Section: Discussionmentioning

confidence: 62%

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

et al. 2019

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“…A deficiency of these co‐factors results in HHcy because Hcy remethylation is “blocked” (Figure ) . Cobalamine has been the subject of considerable recent investigations in the context of oxidative stress . The results of these studies suggest that even a modest reduction in vitamin B 12 levels will cause an elevation of plasma Hcy and that HHcy is a symptom of a possible vitamin B 12 deficiency.…”

Section: Introductionmentioning

confidence: 99%

Vitamin B complex mitigates cardiac dysfunction in high‐methionine diet‐induced hyperhomocysteinemia

Jeremić

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Živković

et al. 2018

Clin Exp Pharma Physio

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This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.

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“…In a study investigating the relationship between critical illness and inflammatory markers in 103 critically ill patients and 44 healthy control subjects, only pyridoxine deficiency was found to be correlated with inflammation, whereas thiamin and riboflavin were not correlated . We did not record inflammatory markers that may have an effect on thiamin levels.…”

Section: Discussionmentioning

confidence: 92%

Thiamin Status in Adults Receiving Chronic Diuretic Therapy Prior to Admission to a Medical Intensive Care Unit: A Pilot Study

et al. 2019

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Background: The aim of the study was to determine serum thiamin concentrations in critically ill medical patients who required chronic diuretic drug treatment before admission to a medical intensive care unit (ICU). Methods: This prospective study was performed in a medical ICU. Subjects who received diuretic drug therapy for at least 6 months prior to ICU admission constituted the diuretic group. The control group was clinically matched adults admitted to the same ICU but without a history of diuretic therapy. Results: A total of 50 subjects were included (25 subjects in each of the diuretic and control groups). In the diuretic group, daily dose of furosemide prior to admission was 40 mg/d (range of 20-160 mg/d). In all subjects, the ICU admission baseline blood thiamin concentrations were 31.2 ± 27.1 ng/mL. In the diuretic group, the baseline whole blood thiamin level was significantly lower compared with levels in the control group (15.5 ± 10.7 vs 46.8 ± 29.5 ng/mL; P < 0.001). On day 2 after entry, thiamin levels remained low (23.2 ± 15.4 ng/mL in the diuretic group vs 49 ± 38 ng/mL in the control group; P = 0.003). Low thiamin levels were found in 96% of patients at baseline and in 72% of patients on the second day in the diuretic group. Conclusion: Adults receiving chronic diuretic therapy and then requiring medical ICU care commonly exhibit thiamin depletion on admission to the ICU and during the initial days of ICU care. (Nutr Clin Pract. 2019;34:565-571)

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Pyridoxal-5′-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients

Cited by 23 publications

References 32 publications

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock

Vitamin B complex mitigates cardiac dysfunction in high‐methionine diet‐induced hyperhomocysteinemia

Thiamin Status in Adults Receiving Chronic Diuretic Therapy Prior to Admission to a Medical Intensive Care Unit: A Pilot Study

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