Cardiovascular Health Through Vitamin C Intake

Recent findings demonstrate that vitamin C may be an essential component of cardiovascular health by preventing atherosclerosis, hypertension, and stroke.1

What is Vitamin C?

Vitamin C, or ascorbic acid, is a water-soluble vitamin, coenzyme, and cofactor in the biosynthesis of carnitine, a molecule that is required to oxidize fatty acids or convert fat in the body into energy. An adequate intake of vitamin C helps to facilitate osteoblast and osteodentin formation, synthesize catecholamines, reduce urinary folic acid excretion, and improve the absorption of dietary iron.1 Since humans lack endogenous synthesis of vitamin C, it is necessary to obtain adequate levels in the diet. Vitamin C is found in foods such as citrus fruits (oranges, kiwi, lemon, grapefruit), tomatoes, bell peppers, strawberries, white potatoes, broccoli, and green leafy vegetables and is widely available in affordable supplemental forms1,2

Vitamin C foods

The physiologic benefits of vitamin C may best be demonstrated by considering scurvy, a disease that occurs as a result of severe vitamin C deficiency. Scurvy is rare and easily treatable, but the manifestations are pronounced and include mood and behavioral changes, petechiae, ecchymoses, hyperkeratosis, coiled hairs, impaired wound healing, joint pain, and fragile bones.3,4 Perhaps most significant are the cardiovascular complications that may progress to cardiac failure or rhythm disturbances, chest pain, hypotension, syncope, cardiac tamponade, and dyspnea.3

Biological Mechanisms of Vitamin C Prevention of Cardiovascular Health

While the extreme lack of vitamin C may result in various types of cardiovascular disease, adequate dietary consumption of vitamin C has been found to promote the integrity of the endothelium and prevent hypertension, atherosclerosis, and stroke.1,3 Endothelial function is a necessary component of vascular health, lowering the risk for hypertension. Vitamin C also promotes local vasodilation during exercise, increasing skeletal muscle blood flow and oxygen consumption.5

Vitamin C also exerts an antioxidant function by radical scavenging6 of oxygen reactive oxygen species that would otherwise accumulate in cells and cause oxidative stress.1 Prior research demonstrates that higher levels of oxidative stress are linked to an increase in the production of cytokines.7 It is these antioxidant properties from vitamin C that help to prevent and treat cardiovascular diseases.6

Vitamin C and Cardiovascular Health

Shati et al. recently theorized that endotoxin-induced cardiomyopathy may be prevented by vitamin C consumption.8 They aimed to determine if vitamin C prevented lipopolysaccharide-induced heart damage by inhibiting oxidative stress cytokines. The study found that vitamin C did in fact protect against endotoxin-induced heart injury by improving the cardiomyocytes, endothelial cells, and mitochondria.8

Furthermore, there have been especially promising findings from several clinical studies examining the association that exists between hypertension and vitamin C intake and circulating levels of ascorbic acid.9,10,11,12 In a recent meta-analysis involving 11 cross-sectional studies and seven case-control studies conducted from 1990 to 2017, serum vitamin C levels in study participants with hypertension were significantly lower than in those with normotension.12 These results were supported in an independent meta-analysis in which the authors selected eight randomized controlled trials in which vitamin C intake varied from 300 to 1000 mg/day, and was supplemented for 4–24 weeks in 614 patients with hypertension.13, 8 A marked reduction in diastolic blood pressure was found in a subgroup of patients with an age of 35 years having a vitamin C supplementation of 500 mg/day for 6 weeks, while a significant reduction of both systolic blood pressure and diastolic blood pressure was observed in the subgroup of those aged 60 years.

In a meta-analysis examining the effect of vitamin C on left ventricular ejection fraction (LVEF), Hemilä et alfound vitamin C increased LVEF in both cardiac and noncardiac patients, with a strong negative association between the size of the vitamin C effect and baseline LVEF. Compared with healthy people, patients with heart failure had lower vitamin C levels unexplained by differences in dietary intake. More severe heart failure seemed associated with lower plasma vitamin C levels.14 However, Hemilä’s findings suggest further research on vitamin C and heart failure is warranted, particularly in those with low LVEF together with low vitamin C intake or low plasma levels, in addition to comparisons between different dosages and different routes of administration.14 Vitamin C has also been found to be associated with a decreased risk of ischemic stroke.15  

Clinical Implications

Vitamin C may have a key role in the mechanisms involved in the pathogenesis of cardiovascular disease. Nevertheless, major limitations must be considered when interpreting study findings that have investigated the effect of vitamin C on cardiovascular health. Dietary assessment methods such as questionnaires or food diaries tend to lack precision and accuracy and fail to consider the numerous variables that can affect vitamin C levels and overall homeostasis.16

Additional prospective randomized clinical trials involving large populations are necessary to identify accurate vitamin C doses and determine whether supplementation is effective in preventing or treating cardiovascular diseases. Moreover, the ideal route of administration, optimal targets, and dietary supplementation of antioxidant elements are needed for standardized and reproducible data when evaluating vitamin C status, for example, from blood samples of fasting individuals.17,18 According to Rowe and Lykkesfeldt, blood samples of vitamin C levels may be reliable indicators, although they involve considerable fluctuation following the ingestion of food or supplements and can only be obtained in fasted conditions.17 While ascorbate is rapidly oxidized ex vivo, the resulting oxidation products are quickly metabolized or degraded, and therefore, meticulous handling of samples is key for valid and reliable vitamin C measures. 19

1. Morelli MB, Gambardella J, Castellanos V, Trimarco V, Santulli G. Vitamin C and Cardiovascular Disease: An Update. Antioxidants (Basel). 2020;9(12):1227. Published 2020 Dec 3. doi:10.3390/antiox9121227

2. Tan B.L, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front. Pharmacol. 2018;9:1162. doi: 10.3389/fphar.2018.01162.

3. Byard RW, Maxwell-Stewart H. Scurvy-Characteristic Features and Forensic Issues. Am J Forensic Med Pathol. 2019;40(1):43-46. doi:10.1097/PAF.0000000000000442

4. Carpenter KJ. The discovery of vitamin C. Ann Nutr Metab. 2012;61(3):259-264. doi:10.1159/000343121

5. Richards JC, Crecelius AR, Larson DG, Dinenno FA. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults. Am. J. Physiol. Heart Circ. Physiol. 2015, 309, H360–H368.

6. Ingles DP, Cruz Rodriguez JB, Garcia H. Supplemental vitamins and minerals for cardiovascular disease prevention and treatment. Curr. Cardiol. Rep. 2020;22:22. doi: 10.1007/s11886-020-1270-1.

7. Chen CY, Huang YL, Lin TH. Association between oxidative stress and cytokine production in nickel-treated rats. Arch. Biochem. Biophys. 1998;356:127–132. doi: 10.1006/abbi.1998.0761.

8. Shati AA, Zaki MSA, Alqahtani YA, et al. Antioxidant Activity of Vitamin C against LPS-Induced Septic Cardiomyopathy by Down-Regulation of Oxidative Stress and Inflammation. Curr Issues Mol Biol. 2022;44(5):2387-2400. Published 2022 May 23. doi:10.3390/cimb44050163

9. Al-Khudairy, L, Flowers N, Wheelhouse R, et al. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 2017, 3, CD011114.

10. Gambardella J, Morelli MB, Wang XJ, Santulli G. Pathophysiological mechanisms underlying the beneficial effects of physical activity in hypertension. J. Clin. Hypertens. 2020, 22, 291–295.

11. Matarese A, Gambardella J, Sardu C, Santulli G. miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19. Biomedicines 2020, 8, 462.

12. Ran L, Zhao W, Tan X, et al. Association between Serum Vitamin C and the Blood Pressure: A Systematic Review and Meta-Analysis of Observational Studies. Cardiovasc. Ther. 2020, 2020, 4940673

13. Guan Y, Dai P, Wang HE. Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis. Medicine. 2020;99:e19274.

14. Hemilä H, Chalker E, de Man AME. Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis. Front Cardiovasc Med. 2022;9:789729. Published 2022 Feb 25. doi:10.3389/fcvm.2022.789729

15. Buijsse B, Jacobs DR Jr, Steffen LM, Kromhout D, Gross MD. Plasma Ascorbic Acid, A Priori Diet Quality Score, and Incident Hypertension: A Prospective Cohort Study. PLoS ONE 2015, 10, e0144920.

16. Michels AJ, Frei B. Myths, artifacts, and fatal flaws: Identifying limitations and opportunities in vitamin C research. Nutrients 2013, 5, 5161–5192.

17. Rowe S, Carr AC. Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern? Nutrients 2020, 12, 2008.

18. Lykkesfeldt J. On the effect of vitamin C intake on human health: How to (mis)interpret the clinical evidence. Redox Biol. 2020, 34, 101532.

19. Dewhirst RA, Fry SC. The oxidation of dehydroascorbic acid and 2,3-diketogulonate by distinct reactive oxygen species. Biochem. J. 2018, 475, 3451–3470.

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