Vitamin C-deficient Research Articles

VITAMIN C DEFICIENCY IN PATIENTS WITH SHOCK IS ASSOCIATED WITH POOR OUTCOMES

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The use of Vitamin C (VC) therapy in patients with septic shock has recently been explored due to its anti-oxidative and anti-inflammatory properties. However, the prevalence and impact of VC deficiency among critically-ill patients in shock is unclear. We sought to determine the prevalence of VC deficiency as well as its association on clinical outcomes. METHODS: We conducted a retrospective cohort study of patients admitted to the intensive care unit (ICU) at Kaiser Permanente Los Angeles Medical Center with a diagnosis of shock from March 1, 2018 to June 30, 2018. The study included all causes of shock defined as hypotension requiring vasopressor therapy. VC serum concentrations were collected upon admission to the ICU. Data on demographics and comorbidities were collected. We compared outcomes, including survival at 7-, 30-, and 90-days, and vasopressor free days at 30-days between VC deficient and VC sufficient subjects. Logistic regression was used to estimate odds ratios (OR). Chi-square and Fisher’s exact test were used to determine statistical significance for categorical variables. P-value <0.05 was considered statistically significant. RESULTS: The study examined 145 patients, of which, 51 were VC deficient. With VC sufficient subjects as reference, estimated risks of 7-day survival compared to VC deficient subjects were OR 2.1; 95% CI, 0.86-5.10, p= 0.10. VC deficient patients had an increased risk in 30-day mortality, OR 2.52; 95% CI 1.24-5.12, p= 0.01, compared to VC sufficient patients. VC deficient patients also had increased risk in 90-day mortality OR 3.06; 95% CI 1.5-6.24, p= 0.002, compared to VC sufficient patients. VC deficient subjects also averaged fewer vasopressor free days, [means (SD): 14.7 (11.96) vs 21.5 (10.36), OR 0.94; 95% CI 0.92-0.98, p= 0.0009]. Patients with chronic kidney disease (CKD) were four times more likely to be VC deficient, OR 4.06 (1.76-9.3), p= 0.0009. CONCLUSIONS: Medical ICU patients account for the majority of ICU cases. There is a small percentage of cardiogenic shock patients given the presence of a designated Coronary Care Unit. Prevalence of VC deficiency among the study population was five times higher than the US general population (35% vs 7%). VC deficiency was associated with decreased survival at 30 days and 90 days when compared to VC sufficient subjects. There was no significant difference in mortality at 7 days. VC deficiency was also associated with fewer vasopressor free days. History of CKD was the highest predictor for VC deficiency. Our findings suggest that VC deficient subjects presenting with shock are at greater risk for poor outcomes. Therefore, studies should further explore the use of VC therapy in subjects at higher risk. CLINICAL IMPLICATIONS: Literature has not explored mortality benefit in Vitamin C deficient patients. Thus, VC therapy in this subset of patients must be studied. DISCLOSURES: No relevant relationships by Dinora Chinchilla, source=Web Response No relevant relationships by Ngoc Ho, source=Web Response No relevant relationships by Brannen Liang, source=Web Response No relevant relationships by Kenneth Wei, source=Web Response

Vitamin C Deficiency Impairs Mineralization of Ossicle in Mice

Objectives: Vitamin C-deficient (VCD) mice develop spontaneous bone fractures and exhibit hearing loss. However, the effects on the micro-architecture of the ossicles and the underlying mechanisms have not been fully understood. In this study, we test the hypothesis that vitamin deficiency impairs osteoblast differentiation and function of the ossicles. Methods: The morphologic characteristics of the ossicles in VCD and wild-type mice were evaluated with a stereoscopic microscope. Micro-structure of the ossicles was analyzed by micro computed tomography (µCT). Osteoblast differentiation was determined by immunostaining of the bone marker gene, osteocalcin. Sound transmission along the ossicular chain was evaluated with laser Doppler vibrometer. Results: The ossicles in VCD mice demonstrated thinner bone in the manubrium of malleus and stapes footplate. µCT analyses further verified that the bone volume/total volume fraction (BV/TV) was significantly reduced in the stapes footplate (51.5 ± 3.9% vs 61.2 ± 1.5%; P &lt; .05) and the manubrium of malleus (24.9 ± 5.3% vs 39.0 ± 5.0%; P &lt; .05) in VCD mice. The expression of osteocalcin was significantly decreased in the ossicles of VCD mice (17.8 ± 3.3 vs 32.4 ± 4.7; P &lt; .05). However, the preliminary data revealed a modest change in sound transmission along the ossicular chain. Conclusions: These findings suggest that VCD decreased expression of osteoblast differentiation marker, osteocalcin, and reduced bone volume and of the ossicles without significantly altering sound transmission. These results may indicate that the pathogenesis of VCD-induced hearing loss might be due to a deficiency at the inner ear or auditory neuron level. Further studies are warranted.

Effect of Fluorosis on Liver Cells of VC Deficient and Wild Type Mice

For decades, mouse and other rodents have been used for the study of oxidative or related studies such as the effect of fluoride. It is known that rodents normally synthesize their own vitamin C (VC) due to the presence of a key enzyme in ascorbic acid synthesis, l-gulono-lactone-γ-oxidase (Gulo), while humans do not have the capacity of VC synthesis due to the deletion of most parts of the GULO gene. The spontaneous fracture (sfx) mouse recently emerged as a model for study of VC deficiency. We investigated the effect of fluoride on liver cells from wild type Balb/c and sfx mice. We found that activities of SOD, GPx, and CAT were reduced in both wild type and sfx mice; however, the amount of reduction in the sfx cells is more than that in Balb/c cells. In addition, while both cells increased MDA, the increase in the sfx cells is greater than that in Balb/c cells. Gene networks of Sod, Gpx, and Cat in the liver of humans and mice are also different. Our study suggests that reaction to fluoride in vitamin C deficient mice might be different from that of wild type mice.

Morphological and Biochemical Changes in Lenses of Guinea Pigs after Vitamin-C-Deficient Diet and UV-B Radiation

The effect of ultraviolet B (UV-B) radiation and a vitamin-C-deficient (VCD) diet on guinea pig lenses was investigated. The initial lens changes in the VCD group were observed by slit-lamp examination 6 weeks after the start of the VCD treatment; after 12 weeks the changes in the posterior subcapsular region became more prominent, and the dissociation around the posterior suture became wider and slightly deeper toward the posterior cortex. The high concentration of lens oxidized glutathione (GSSG), and the low ratio of reduced glutathione (GSH) to oxidized glutathione (GSH/GSSG) on the lens posterior region correlated with density changes in the corresponding layers as measured by Scheimpflug images with linear microdensitometry. It is suggested that the strong oxidative stress of the VCD diet caused the damage at the posterior part of the lens. UV-B radiation appeared to accelerate cataract progression in lenses that lack vitamin C.

A histological and biochemical study of the effect of vitamin C-deficiency on induction of amelogenesis in hamster molars in vitro

Second maxillary molars of hamsters were cultured in the presence or absence of 250μg/ml vitamin C for periods up to 12 days. At various days, cultured expiants were studied with histological and biochemical methods to investigate effects of vitamin C-deficiency on matrix production and mineralization in vitro. As biochemical parameters for protein synthesis and mineralization, uptake and incorporation of [ 3H]-proline, 45Ca and 32PO 4 were used. To discriminate between synthesis of collagenous and non-collagenous proteins digestion of the [ 3H]-proline-labelled material by purified collagenase and its degree of hydroxylation were measured. Histologically, in control explants cultured with vitamin C, normal dentinogenesis, amelogenesis and mineralization in vitro were observed. In the vitamin C-deficient expiants, odontoblasts produced an abnormal predentine matrix and de-differentiated. Eventually, this matrix mineralized aspecifically. In the presence of this abnormal matrix, ameloblasts failed to differentiate, which suggests that a cell-matrix type of interaction is involved in the differentiation of the pre-ameloblasts. Biochemically, in the vitamin C-deficient explants protein synthesis and collagen synthesis were reduced by about the same extent; the in-vitro produced collagens appeared under-hydroxylated and could, in degraded form, easily be extracted in formic acid. An increase of [ 3H]-proline solubility in formic acid in the control explants, however, paralleled enamel matrix production and was attributed to the solubilization of proline-rich enamel matrix proteins. The production of acid insoluble phosphate was not affected by vitamin C-deficiency. The uptakes of 45Ca and 32PO 4 were retarded and the molar Ca:PO 4 uptake ratio was lower, reflecting the histologically observed aspecific mineralization.