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Blood Pressure Effects of Vitamin C

2002; Lippincott Williams & Wilkins; Volume: 40; Issue: 6 Linguagem: Inglês

10.1161/01.hyp.0000038340.95407.43

1524-4563

Laura P. Svetkey, Catherine M. Loria,

Consumer Attitudes and Food Labeling

HomeHypertensionVol. 40, No. 6Blood Pressure Effects of Vitamin C Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBBlood Pressure Effects of Vitamin CWhat's the Key Question? Laura P. Svetkey and Catherine M. Loria Laura P. SvetkeyLaura P. Svetkey From the Duke Hypertension Center and the Sarah W. Stedman Center for Nutritional Studies, Duke University Medical Center (L.P.S.), Durham, NC; and the Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute (C.M.L.), Bethesda, Md. and Catherine M. LoriaCatherine M. Loria From the Duke Hypertension Center and the Sarah W. Stedman Center for Nutritional Studies, Duke University Medical Center (L.P.S.), Durham, NC; and the Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute (C.M.L.), Bethesda, Md. Originally published14 Oct 2002https://doi.org/10.1161/01.HYP.0000038340.95407.43Hypertension. 2002;40:789–791Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 14, 2002: Previous Version 1 Some, but not all, observational data concerning diet and health suggest an inverse relationship between dietary vitamin C and cardiovascular disease (CVD) morbidity and mortality.1 If such a relationship exists, vitamin C presumably protects against CVD through its antioxidant properties, possibly by preventing lipid peroxidation. Others have suggested that vitamin C might protect against CVD through effects on blood pressure (BP) and arterial stiffness.2–6 Such an effect is suggested by epidemiologic associations noted in some populations,7 but the role of this nutrient in BP regulation remains unclear, owing to design issues and/or confounding variables. For example, a recent analysis of the prospective Western Electric study2 suggests that low antioxidant intake is associated with the rise in BP with age. In that study, intake of both vitamin C and β-carotene were combined to form an "antioxidant score," so the effect of vitamin C alone was not estimated. Even in studies that isolate vitamin C intake, results are inconclusive: not all studies demonstrate an inverse relationship between vitamin C and BP; key nutrients (eg, sodium) are not accurately measured by most diet survey methods; and more importantly, these observational studies are potentially confounded by intake of other nutrients that affect BP. For example, in the Western Electric study, the investigators did not adjust for intake of potassium, a nutrient with well-known BP-lowering effects,9 which is found in many antioxidant-rich foods. Thus, although a relationship between vitamin C intake and BP is suggested, the epidemiologic data are inconclusive.Randomized controlled trials offer many advantages over prospective observational studies, including minimizing the effects of other confounding variables. Despite these advantages, a total of 7 previous trials examining BP effects of vitamin C have been inconclusive. Two of 4 randomized trials reviewed by Ness et al8 suggest no effect. The 2 positive studies in this review were methodologically flawed: one reported BP change only in the treatment group, and the other included only 20 individuals, most of whom did not have hypertension. Two subsequent trials were negative. A third study4 was difficult to interpret, likely because of its complex design: diastolic (but not systolic) BP was inversely related to plasma ascorbate level at the end of a preceding period of vitamin C depletion, but not to ascorbate level after vitamin C repletion. In aggregate, previous clinical trials do not convincingly demonstrate BP-lowering effects of vitamin C, and the question of whether vitamin C should be recommended for prevention or treatment of hypertension remains unanswered.Unfortunately, the 2 papers in this issue5,6 do not resolve this question. Both studies are randomized controlled trials of 500 mg/day of supplemental vitamin C; yet, they have diametrically opposite results: one showing a decrease in BP6 and one showing no reduction (and perhaps an increase).5 Both studies included free-living, hypertensive and nonhypertensive adults who ate an uncontrolled diet during the study. However, these studies differed in several important ways that could have contributed to their discrepant results. The Mullan et al study,6 comparing 500 mg/day of vitamin C supplement to placebo for 1 month, showed a significant decrease in BP, of 9.9/4.4 mm Hg. This study was small (n=30) but used more precise (ie, triplicate) BP measurements. In contrast, the Kim et al study,5 comparing 500 mg/day of vitamin C to 50 mg/day of vitamin C for 5 years, showed no reduction in BP. The Kim study was larger (n=244) and therefore presumably had greater power, but it based BP estimates on a single (ie, less precise) measurement. In addition, there were differences in the prevalence of treated hypertension (≈50% in the Mullan study versus 15% in the Kim study), inclusion and exclusion criteria that may affect absorption and turnover of vitamin C (eg, smoking status), and follow-up rates (100% in the Mullan study versus 80% in the Kim study). There were also potentially important differences in baseline mean BP (≈142/84 mm Hg in the Mullan study versus 127/77 mm Hg in the Kim study). The lower baseline BP and prevalence of treated hypertension in the Kim study could account in part for the lack of BP effect, given that nonpharmacologic interventions typically have greater effects on individuals with higher BP.However, the 2 most important differences are the study populations and the duration of the treatment period. Mullan et al studied diabetics in Ireland, and Kim et al studied Japanese individuals with gastric atrophy. In addition to potential genetic differences between these 2 populations, the 2 clinical conditions may differ in vitamin C metabolism. For example, diabetes may be associated with higher vitamin C requirements for general health. In addition, neither population was selected specifically because of entry BP or the presence of hypertension. Therefore, it is difficult to know how to apply these results to the general population, to those with hypertension or high-normal BP, or to other at-risk groups.An equally important difference between these 2 studies is the duration of treatment: 1 month in the Mullan study and 5 years in the Kim study. Disregarding other differences in study design, this difference might lead us to conclude that short-term treatment leads to BP reduction, but this effect either is not sustained or is overwhelmed by the typical rise in BP with aging. If vitamin C, or any intervention, is to be effective in preventing and/or controlling hypertension, a sustained effect is critically important. Either scenario—short-term treatment leading to long-term BP reduction or persistence of BP effects as long as treatment is continued—is acceptable, although the latter is biologically more likely to occur. We must keep in mind that the lack of a significant long-term effect in the Kim study could have been confounded by a relatively high dropout rate or by other factors such as changes in weight over time. It is not possible to determine whether there was a short-term effect in the Kim study or whether the BP effect observed in the Mullan study would have persisted if the treatment had been continued. In any case, at this time it is impossible to conclude that vitamin C has a sustained BP-lowering effect.The discovery of a nutrient supplement that lowers BP would make widespread changes in dietary intake aimed at lowering BP unnecessary, but experience suggests that we are unlikely to find such a magic bullet. In fact, there appears to be little evidence that supplements of individual nutrients are sufficiently effective in preventing or controlling high BP. Despite a large body of epidemiologic literature suggesting that high intake of potassium, magnesium and calcium are protective against high BP, trials of these individual nutrients have generally been disappointing. A meta-analysis of potassium supplement studies suggests a reduction in SBP of ≈3/2 mm Hg.9 A meta-analysis of calcium supplement studies suggest an even smaller effect ( 60 years have high BP; those without high BP have an estimated 90% life-time risk of developing it; and individuals of any age with high-normal BP that would not currently be treated pharmacologically are at significant excess CVD risk from their above-optimal BP. From a public health and clinical perspective, the key question is how to optimize dietary patterns to prevent and treat high BP.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Laura P. Svetkey, Box 3075, Duke University Medical Center, Durham, NC 27710. E-mail [email protected] References 1 Loria CM. Vitamin C status and cardiovascular disease: a review of prospective studies. In: Frei B, Traber M, eds. The Antioxidant Vitamins C and E. Champaign, Ill: AOCS Press. In press.Google Scholar2 Stamler J, Liu K, Ruth KJ, Pryer J, Greenland P. Eight-year blood pressure change in middle-aged men: relationship to multiple nutrients. Hypertension. 2002; 39: 1000–1006.LinkGoogle Scholar3 Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney JF Jr, Vita JA. Treatment of hypertension with ascorbic acid. Lancet. 1999; 354: 2048–2049.CrossrefMedlineGoogle Scholar4 Block G, Mangel AR, Norkus EP, Patterson BH, Levander OA, Taylor PR. Ascorbic acid status and subsequent diastolic and systolic blood pressure. Hypertension. 2001; 37: 261–267.CrossrefMedlineGoogle Scholar5 Kim MK, Sasaki S, Okubo S, Hayashi M, Tsugane S. Lack of long-term effect of vitamin C supplementation on blood pressure. Hypertension. 2002; 40: 797–803.LinkGoogle Scholar6 Mullan BA, Young IS, Fee H, McCance DR. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension. 2002; 40: 804–809.LinkGoogle Scholar7 Bates CJ, Walmsley CM, Prentice A, Finch S. Does vitamin C reduce blood pressure? Results of a large study of people aged 65 or older. J Hypertens. 1998; 16: 925–932.CrossrefMedlineGoogle Scholar8 Ness AR, Chee D, Elliott P. Vitamin C and blood pressure: an overview. J Hum Hypertens. 1997; 11: 343–350.CrossrefMedlineGoogle Scholar9 Whelton P He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, Klag MJ. Effects of oral potassium on blood pressure: meta-analysis of randomized controlled clinical trials. JAMA. 1997; 277: 1624–1632.CrossrefMedlineGoogle Scholar10 Allender PS, Cutler JA, Follmann D, Cappuccio FP, Pryer J, Elliott P. dietary calcium and blood pressure: a meta-analysis of randomized clinical trials. Ann Intern Med. 1996; 124: 825–831.CrossrefMedlineGoogle Scholar11 The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase I. JAMA. 1992; 267: 1213–1220.CrossrefMedlineGoogle Scholar12 Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin P-H, Karanja N, for the DASH Collaborative Research Group. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med. 1997; 336: 1117–1124.CrossrefMedlineGoogle Scholar13 Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER III, Simons Morton DG, Karanja N, Lin P-H, for the DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001; 344: 3–10.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Montezano A and Touyz R (2014) Reactive Oxygen Species, Vascular Disease, and Hypertension Systems Biology of Free Radicals and Antioxidants, 10.1007/978-3-642-30018-9_56, (1123-1154), . Mohanlal V, Parsa A and Weir M (2012) Role of dietary therapies in the prevention and treatment of hypertension, Nature Reviews Nephrology, 10.1038/nrneph.2012.91, 8:7, (413-422), Online publication date: 1-Jul-2012. Miller III E and Juraschek S (2012) Effects of Minerals, Antioxidants and Micronutrients on Blood Pressure Nutrition, Lifestyle Factors, and Blood Pressure, 10.1201/b12280-4, Online publication date: 26-Jun-2012. 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Halliwell B and Whiteman M (2009) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? , British Journal of Pharmacology, 10.1038/sj.bjp.0705776, 142:2, (231-255), Online publication date: 1-May-2004. &NA; (2003) The question remains: can ascorbic acid lower BP?, Inpharma Weekly, 10.2165/00128413-200313710-00048, &NA;:1371/1372, (20), Online publication date: 1-Jan-2003. December 2002Vol 40, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/01.HYP.0000038340.95407.43PMID: 12468557 Originally publishedOctober 14, 2002 PDF download Advertisement SubjectsClinical StudiesDiet and NutritionHypertension