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Vitamin C in Plants: Novel Concepts, New Perspectives, and Outstanding Issues.
Foyer, CH, Kyndt, T, Hancock, RD
Antioxidants & redox signaling. 2020;(7):463-485
Abstract
Significance: The concept that vitamin C (l-ascorbic acid) is at the heart of the peroxide processing and redox signaling hub in plants is well established, but our knowledge of the precise mechanisms involved remains patchy at best. Recent Advances: Ascorbate participates in the multifaceted signaling pathways initiated by both reactive oxygen species (ROS) and reactive nitrogen species. Crucially, the apoplastic ascorbate/dehydroascorbate (DHA) ratio that is regulated by ascorbate oxidase (AO) sculpts the apoplastic ROS (apoROS) signal that controls polarized cell growth, biotic and abiotic defences, and cell to cell signaling, as well as exerting control over the light-dependent regulation of photosynthesis. Critical Issues: Here we re-evaluate the roles of ascorbate in photosynthesis and other processes, addressing the question of how much we really know about the regulation of ascorbate homeostasis and its functions in plants, or how AO is regulated to modulate apoROS signals. Future Directions: The role of microRNAs in the regulation of AO activity in relation to stress perception and signaling must be resolved. Similarly, the molecular characterization of ascorbate transporters and mechanistic links between photosynthetic and respiratory electron transport and ascorbate synthesis/homeostasis are a prerequisite to understanding ascorbate homeostasis and function. Similarly, there is little in vivo evidence for ascorbate functions as an enzyme cofactor.
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A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.
Harville, EW, Lewis, CE, Catov, JM, Jacobs, DR, Gross, MD, Gunderson, EP
PloS one. 2020;(2):e0229002
Abstract
BACKGROUND Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS Higher preconception antioxidant levels are not associated with better birth outcomes.
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The effect of β-carotene on the mortality of male smokers is modified by smoking and by vitamins C and E: evidence against a uniform effect of nutrient.
Hemilä, H
Journal of nutritional science. 2020;:e11
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Abstract
A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found that β-carotene supplementation increased the risk of pneumonia 4-fold in those who started smoking at the age of ≥21 years and smoked ≥21 cigarettes/d (a subgroup of 7 % of the study population). The present study hypothesised that β-carotene increases mortality in the same subgroup. The ATBC Study (1985-1993) recruited 29 133 Finnish male smokers (≥5 cigarettes/d) aged 50-69 years. Cox regression models were constructed to estimate the effect of β-carotene supplementation in subgroups. β-Carotene increased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at ≥21 years and smoked ≥21 cigarettes/d. Within this subgroup, there was strong evidence of further heterogeneity. The effect of β-carotene supplementation was further modified by dietary vitamin C intake, fruit and vegetable intake (P = 0·0004), and by vitamin E supplementation (P = 0·011). Thus, harm from β-carotene was not uniform within the study population. Interactions between β-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not be extrapolated to the general population. Heterogeneity of the β-carotene effect on mortality challenges the validity of previous meta-analyses that have pooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants and all people. Trial registration: ClinicalTrials.gov NCT00342992.
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Association of Dietary Micronutrient Intake with Pulmonary Tuberculosis Treatment Failure Rate: ACohort Study.
Xiong, K, Wang, J, Zhang, J, Hao, H, Wang, Q, Cai, J, Ma, A
Nutrients. 2020;(9)
Abstract
Malnutrition is associated with an increased risk of pulmonary tuberculosis (PTB) treatment failure. Currently, there is no effective adjunctive nutritional therapy. The current objective is to investigate the association of dietary micronutrient intake with PTB treatment outcome.A cohort study including 1834 PTB patients was conducted in Linyi, China. The dietary micronutrient intake was assessed through a three-day 24 h dietary recall questionnaire. The treatment outcome was assessed by combinations of sputum smear and computerized tomography results. A multivariate binary regression model was used to assess the associations. The final model was adjusted for potential confounding factors. A low intake of vitamin C (adjusted OR (95% CI): 1.80 (1.07, 3.04), Ptrend = 0.02) and Zn (adjusted OR (95% CI): 2.52 (1.25, 5.08), Ptrend = 0.02) was associated with a high treatment failure rate. In addition, a low intake of vitamin C and Mn was associated with a severe tuberculosis symptom, as indicated by a high TB score. A supplementation of vitamin C and Zn may be beneficial in PTB treatment. Previous meta-analysis of randomized controlled trials (RCTs) reported a null effect of Zn supplementation on PTB treatment. The effect of vitamin C supplementation should be investigated by RCTs.
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Ascorbic acid inhibits vascular remodeling induced by mental stress in overweight/obese men.
Batista, GMS, Rocha, HNM, Storch, AS, Garcia, VP, Teixeira, GF, Mentzinger, J, Gomes, EAC, Velasco, LL, Nóbrega, ACL, Rocha, NG
Life sciences. 2020;:117554
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Abstract
BACKGROUND Mental stress (MS) is related to endothelial dysfunction in overweight/obese men. It is believed that the pro-oxidant profile, associated with an imbalance in the vascular remodeling process, may contribute to deleterious effects of MS on endothelial function. However, it is unknown whether administration of ascorbic acid (AA), a potent antioxidant, can prevent oxidative and remodeling dysfunction during MS in these subjects. METHODS Fourteen overweight/obese grade I men (27 ± 7 years; 29.7 ± 2.6 kg·m-2) underwent the Stroop Color Word Test for 5 min to induce MS after AA (3 g) or placebo (PL, 0.9% NaCl) intravenous infusions. Venous blood samples were collected at baseline and the last minute of MS to measure nitrite concentration (chemiluminescence), protein carbonylation, thiobarbituric acid reactive substances (TBARS) and catalase activity (colorimetric assays), superoxide dismutase (SOD; immunoenzymatic assay), activities of active/inactive (pro) forms of metalloproteinases-9 and -2 (MMP; zymography) and its respective tissue inhibitors concentration (TIMP-1 and TIMP-2; immunoenzymatic assays). RESULTS At baseline, MMP-9 activity (p < 0.01), the MMP-9/proMMP-9 ratio (p = 0.02) and TIMP-1 concentration (p = 0.05) were reduced, whereas proMPP-9 activity was increased (p = 0.02) after AA compared to PL infusion. After PL infusion, MS increased protein carbonylation (p < 0.01), catalase (p < 0.01), and the MMP-9/proMMP-9 ratio (p = 0.04) when compared to baseline. AA infusion reduced protein carbonylation (p = 0.02), MMP-9 activity (p < 0.01), and MMP-9/pro-MMP-9 ratio (p < 0.01), while SOD (p = 0.04 vs baseline), proMPP-9 (p < 0.01 vs PL), MMP-2 (p < 0.01 vs PL) and TIMP-2 (p = 0.02 vs baseline) remained elevated during MS. CONCLUSIONS AA appears to minimize the oxidative imbalance and vascular remodeling induced by MS.
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The Role of Vitamin C in Two Distinct Physiological States: Physical Activity and Sleep.
Otocka-Kmiecik, A, Król, A
Nutrients. 2020;(12)
Abstract
This paper is a literature overview of the complex relationship between vitamin C and two opposing physiological states, physical activity and sleep. The evidence suggests a clinically important bidirectional association between these two phenomena mediated by different physiological mechanisms. With this in mind, and knowing that both states share a connection with oxidative stress, we discuss the existing body of evidence to answer the question of whether vitamin C supplementation can be beneficial in the context of sleep health and key aspects of physical activity, such as performance, metabolic changes, and antioxidant function. We analyze the effect of ascorbic acid on the main sleep components, sleep duration and quality, focusing on the most common disorders: insomnia, obstructive sleep apnea, and restless legs syndrome. Deeper understanding of those interactions has implications for both public health and clinical practice.
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Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation.
Wang, MX, Win, SS, Pang, J
The American journal of tropical medicine and hygiene. 2020;(1):86-99
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Abstract
The common cold had resulted in significant economic and social burden worldwide. The effect of vitamin C on preventing common cold in healthy adults has been investigated extensively, but not that of other micronutrients. Thus, we aim to assess the effects of providing micronutrients singly through oral means, on cold incidence, and/or management (in terms of cold duration and symptom severity) in healthy adults from systematically searched randomized controlled trials. From four electronic databases, 660 identified studies were screened and data were extracted from 20 studies (zinc, 10; vitamin D, 8; and vitamins A and E, 2). The quality of selected studies was assessed using the Cochrane risk of bias tool and certainty in the outcomes was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. The review found that micronutrients supplementation, except vitamin C, may not prevent cold incidence or reduce symptom severity among healthy adults. However, zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults.
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Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia.
Carr, AC, Spencer, E, Das, A, Meijer, N, Lauren, C, MacPherson, S, Chambers, ST
Nutrients. 2020;(6)
Abstract
Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein carbonyls and thiobarbituric acid reactive substances) were assessed in association with febrile neutropenia. The vitamin C status of the study participants decreased from 44 ± 7 µmol/L to 29 ± 5 µmol/L by week one (p = 0.001) and 19 ± 6 µmol/L by week two (p < 0.001), by which time all of the participants had undergone a febrile episode. By week four, vitamin C status had increased to 37 ± 10 µmol/L (p = 0.1). Pre-transplantation, the cohort comprised 19% with hypovitaminosis C (i.e., <23 µmol/L) and 8% with deficiency (i.e., <11 µmol/L). At week one, those with hypovitaminosis C had increased to 38%, and at week two, 72% had hypovitaminosis C, and 34% had outright deficiency. C-reactive protein concentrations increased from 3.5 ± 1.8 mg/L to 20 ± 11 mg/L at week one (p = 0.002), and 119 ± 25 mg/L at week two (p < 0.001), corresponding to the development of febrile neutropenia in the patients. By week four, these values had dropped to 17 ± 8 mg/L (p < 0.001). There was a significant inverse correlation between C-reactive protein concentrations and vitamin C status (r = -0.424, p < 0.001). Lipid oxidation (thiobarbituric acid reactive substances (TBARS)) increased significantly from 2.0 ± 0.3 µmol/L at baseline to 3.3 ± 0.6 µmol/L by week one (p < 0.001), and remained elevated at week two (p = 0.003), returning to baseline concentrations by week four (p = 0.3). Overall, the lowest mean vitamin C values (recorded at week two) corresponded with the highest mean C-reactive protein values and lowest mean neutrophil counts. Thus, depleted vitamin C status in the HSCT patients coincides with febrile neutropenia and elevated inflammation and oxidative stress.
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The effect of vitamin C supplementation in the last month of pregnancy on neonatal bilirubin levels; A double-blind randomized clinical trial.
Khadem Al-Hosseini, M, Rahideh, ST, Saadati, A, Rahmati, N, Azadeh, F, Janani, L, Shidfar, F
Complementary therapies in medicine. 2020;:102359
Abstract
OBJECTIVES Jaundice is a typical condition in the neonatal period, particularly in the Asian continent. Drowsiness and disruption of breastfeeding, behavioral and neurological disorders, hearing loss and mental retardation are the results of impairment in controlling it. The increase in oxidant substances can stimulate the heme oxygenase enzyme and increase the conversion of heme to bilirubin. In some studies, vitamin C levels in the blood of infants with hyperbilirubinemia were lower than in healthy infants. DESIGN In this double-blind clinical trial study, 144 healthy pregnant women aged 20-40 years who were in 34th weeks of gestation were randomly divided into intervention, and control groups and until the end of pregnancy, they took a 500 mg tablet of vitamin C or placebo (Preparation of starch) daily. Demographic information, dietary intake, and physical activity level of the participants were also evaluated. The total blood bilirubin level was measured on the fifth day after birth using a sample of the neonatal heel. Statistical analysis was performed using SPSS software version 22. In this study P-value < 0. 05 was considered significant. RESULTS Of the 144 participants, 128 of them completed the intervention. There was no significant difference between the two groups at the level of vitamin C intake through diet, and anthropometric indices, but the total bilirubin level in the neonates of the two groups was statistically different (P = 0.02). CONCLUSION Vitamin C supplementation in the last month of pregnancy had a significant effect on neonatal bilirubin level and decreased it significantly.
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Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis.
Guan, Y, Dai, P, Wang, H
Medicine. 2020;(8):e19274
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BACKGROUND Vitamin C as a supplement to treat hypertension has been proposed. However, it remains controversial whether vitamin C can improve blood pressure in patients with primary hypertension. OBJECTIVES To analyze the effect of vitamin C (VitC) supplementation on systolic (SBP) and diastolic (DBP) blood pressure in patients with essential hypertension. METHODS We searched the Chinese Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WANFANG Data, Cochrane Library, National Library of Medicine's PubMed, EMBASE, and other databases until June 2019. Eight RCTs involving 614 participants were analyzed. SBP and DBP before and after VitC supplementation were compared between the intervention and control groups. The risk of bias of individual studies was assessed using the Cochrane Collaboration risk of bias tool. Two reviewers selected studies independently of each other. The Cochrane Collaboration Review Manager 5.3 was used to perform the meta-analysis. RESULTS There was a significant difference in the change of SBP (weighted mean difference [WMD] = -4.09; 95% confidence interval [CI] -5.56, -2.62; P < .001) and DBP (WMD = -2.30; 95% CI -4.27, -.331; P = .02) between the groups. Further, there was a significant difference in the SBP (WMD = -3.75, 95% CI -6.24, -1.26, P = .003) and DBP (WMD = -3.29, 95% CI -5.98, -.60, P = .02) for the subgroup with an age ≥60 years and that with ≥35 participants. In the subgroup analysis, result for SBP with a study duration ≥6 weeks was statistically significant different (WMD = -4.77; 95% CI -6.46, -3.08; P < .001). For an intervention dose of VitC ≥500 mg daily, SBP was statistically significant (WMD = -5.01; 95% CI -8.55, -1.48; P = .005). CONCLUSION VitC supplementation resulted in a significant reduction of blood pressure in patients with essential hypertension.