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The effects of vitamin C supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis

Nosratabadi S, Ashtary-Larky D, Hosseini F, Namkhah Z, Mohammadi S, Salamat S, et al.

Diabetes Metab Syndr, 2023 Aug;17(8):102824.
PMID: 37523928 DOI: 10.1016/j.dsx.2023.102824

BACKGROUND AND AIM: It has been suggested that taking vitamin C supplements may improve glycemic control in patients with type 2 diabetes mellitus (T2DM). However, there has not been a thorough evaluation of the actual impact or certainty of the findings. This systematic review and meta-analysis was conducted to determine the effect of vitamin C supplementation on glycemic profile in T2DM patients.
METHODS: A systematic search was performed across online databases including Scopus, Web of Science, and PubMed/Medline to identify relevant randomized controlled trials (RCTs) published until July 2022. A random-effects model was applied for the meta-analysis.
RESULTS: The present meta-analysis included a total of 22 RCTs with 1447 patients diagnosed with T2DM.A pooled analysis revealed a significant decrease in levels of serum hemoglobin A1c (HbA1c), fasting insulin, and fasting blood glucose (FBG) in vitamin C-treated T2DM patients compared with their untreated counterparts. The dose-response evaluation displayed a substantial linear association between the intervention duration and changes in serum HbA1c levels. However, the analysis did not demonstrate any significant effect of vitamin C on serum values of homeostasis model assessment of insulin resistance(HOMA-IR) in diabetic patients. Subgroup analyses indicated that high-dose vitamin C administration (≥1000 mg/d) considerably decreased serum HOMA-IR levels.
CONCLUSION: These findings suggest that long-term (≥12 weeks) and high-dose vitamin C supplementation (≥1000 mg/d) may ameliorate glycemic profile in T2DM patients. However, additional high-quality RCTs are necessary to validate these results.

Matched MeSH terms: Ascorbic Acid/therapeutic use
Fulltext Vitamin C: A Review on its Role in the Management of Metabolic Syndrome

Wong SK, Chin KY, Ima-Nirwana S

Int J Med Sci, 2020;17(11):1625-1638.
PMID: 32669965 DOI: 10.7150/ijms.47103

Oxidative stress and inflammation are two interlinked events that exist simultaneously in metabolic syndrome (MetS) and its related complications. These pathophysiological processes can be easily triggered by each other. This review summarizes the current evidence from animal and human studies on the effects of vitamin C in managing MetS. In vivo studies showed promising effects of vitamin C, but most of the interventions used were in combination with other compounds. The direct effects of vitamin C remain to be elucidated. In humans, the current state of evidence revealed that lower vitamin C intake and circulating concentration were found in MetS subjects. A negative relationship was observed between vitamin C intake / concentration and the risk of MetS. Oral supplementation of vitamin C also improved MetS conditions. It has been postulated that the positive outcomes of vitamin C may be in part mediated through its anti-oxidative and anti-inflammatory properties. These observations suggest the importance of MetS patients to have an adequate intake of vitamin C through food, beverages or supplements in order to maintain its concentration in the systemic circulation and potentially reverse MetS.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
History of scurvy and use of vitamin C in critical illness: A narrative review

Dresen E, Lee ZY, Hill A, Notz Q, Patel JJ, Stoppe C

Nutr Clin Pract, 2023 Feb;38(1):46-54.
PMID: 36156315 DOI: 10.1002/ncp.10914

In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness-a condition also resulting in death of thousands in the 21st century-has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.

Matched MeSH terms: Ascorbic Acid/therapeutic use
IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis

Patel JJ, Ortiz-Reyes A, Dhaliwal R, Clarke J, Hill A, Stoppe C, et al.

Crit Care Med, 2022 Mar 01;50(3):e304-e312.
PMID: 34637420 DOI: 10.1097/CCM.0000000000005320

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients.
DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials.
STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients.
DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.
DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C.
CONCLUSIONS: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
Intravenous ascorbic acid as a treatment for severe jellyfish stings

Kumar S, Miranda-Massari JR, Gonzalez MJ, Riordan HD

P R Health Sci J, 2004 Jun;23(2):125-6.
PMID: 15377062

We report a case of jellyfish envenomation in a 39 year old male. He was stung extensively on both lower limbs by an unidentified jellyfish. This occurred in shallow waters of a beach in the vicinity of Labuan Island, Malaysia. The patient received ambulatory treatment with parenteral and oral ascorbate with remarkable recovery.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
Fulltext Ascorbic acid protects against restraint stress-induced memory deficits in Wistar rats

Kumar RS, Narayanan SN, Nayak S

Clinics (Sao Paulo), 2009;64(12):1211-7.
PMID: 20037710 DOI: 10.1590/S1807-59322009001200012

Chronic stress has been shown to cause oxidative damage in the central nervous system. Although stress-induced impairments in learning and memory have been studied extensively, very few studies have investigated possible ways to prevent their ill effects. The present work was designed to study the protective effects of ascorbic acid in memory loss induced by chronic restraint stress.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
Effects of ascorbic acid on impaired vascular reactivity in aortas isolated from age-matched hypertensive and diabetic rats

Ajay M, Mustafa MR

Vascul. Pharmacol., 2006 Aug;45(2):127-33.
PMID: 16807125 DOI: 10.1016/j.vph.2006.05.001

Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched spontaneously hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor-mediated contractions induced by phenylephrine (PE) were augmented in diabetic (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/-6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was without any significant effects on the vascular responses to ACh, SNP and PE in aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that observed in normal aortic rings, but this enhancement in ACh-induced relaxations was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid markedly attenuated contractions induced by PE in aortic rings from both SHR (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally, following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid attenuated PE-induced contractions in all aortic ring types studied. These results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor agonists in diabetic arteries is independent of endothelial nitric oxide dysfunction; (2) ascorbic acid directly modulates contractile responses of hypertensive and diabetic rat aortas, likely through mechanisms in part independent of preservation of endothelium-derived nitric oxide.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
Fulltext Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial

Ellulu MS, Rahmat A, Patimah I, Khaza'ai H, Abed Y

Drug Des Devel Ther, 2015;9:3405-12.
PMID: 26170625 DOI: 10.2147/DDDT.S83144

Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.

Matched MeSH terms: Ascorbic Acid/therapeutic use*
The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)

Siti HN, Kamisah Y, Kamsiah J

Vascul. Pharmacol., 2015 Aug;71:40-56.
PMID: 25869516 DOI: 10.1016/j.vph.2015.03.005

The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing results of antioxidant therapy for cardiovascular risk factors in large-scale long-term randomised controlled trials. Apart from the limitations of our knowledge, limitations in methodology and assessment of the body's endogenous and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic effects of antioxidant and anti-inflammation that are shown by some well-established antihypertensive agents and statins partly support the idea of using antioxidants in vascular diseases as still relevant. This review aims to provide an overview of the links between oxidative stress, vascular inflammation, endothelial dysfunction and cardiovascular risk factors, importantly focusing on blood pressure regulation and atherosclerosis. In view of the potential benefits of antioxidants, this review will also examine the proposed role of vitamin C, vitamin E and polyphenols in cardiovascular diseases as well as the success or failure of antioxidant therapy for cardiovascular diseases in clinical trials.

Matched MeSH terms: Ascorbic Acid/therapeutic use
Fulltext Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, et al.

Am J Clin Nutr, 2016 Feb;103(2):454-64.
PMID: 26791185 DOI: 10.3945/ajcn.114.101659

BACKGROUND: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.
OBJECTIVE: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.
DESIGN: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.
RESULTS: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).
CONCLUSION: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

Matched MeSH terms: Ascorbic Acid/therapeutic use