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Vitamin C and Blood Pressure–An Overview

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Vitamin C and Blood Pressure–An Overview Journal of Human Hypertension (1997) 11, 343–350 1997 Stockton Press. All rights reserved 0950-9240/97 $12.00 ORIGINAL ARTICLE Vitamin C and blood pressure–an overview AR Ness1, D Chee2 and P Elliott2 1Wellcome Training Fellow in Epidemiology, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 2SR; and 2Department of Epidemiology and Public Health, Imperial College School of Medicine at St Mary’s Norfolk Place, London W2 1PG, UK Background: Laboratory and some epidemiological reported an inverse association with vitamin C intake. studies suggest that antioxidants, such as vitamin C, The two non-randomised and four randomised con- are protective for cardiovascular disease. This protec- trolled trials were all small. Of the randomised trials one tive effect may be mediated through blood pressure reported a significant decrease in BP, one a non- (BP). This is the first systematic review of epidemiolog- significant decrease and two were uninterpretable. ical studies of vitamin C and BP. Conclusions: We found a consistent cross-sectional Method: Published cross-sectional studies, prospective association between higher vitamin C intake or status studies and trials in humans were identified that exam- and lower BP, though no study controlled adequately ined the association between vitamin C intake or plasma for confounding by other dietary factors. Further cross- vitamin C levels and BP. Relevant references were sectional studies are required to establish whether an located by MEDLINE search 1966–1996, EMBASE search independent association exists. If this is shown to be 1980–1996, by searching personal bibliographies, books the case larger and longer term trials will be needed to and reviews and from citations in located articles. confirm the association is causal. Potentially the impact Results: Cross-sectional data were available from 18 on cardiovascular disease of a modest change in mean populations. Ten of 14 reported an inverse association population vitamin C intake is large. between plasma vitamin C and BP and three of four Keywords: vitamin C; blood pressure; systematic reviews Introduction Materials and methods Laboratory studies and animal experiments suggest We sought to include all relevant reports (including that oxidative modification of low density lipopro- abstracts) of cross-sectional studies, prospective tein (LDL)-cholesterol plays an important role in the studies and trials in humans that examined the early development of atherosclerotic lesions.1,2 This association between vitamin C and BP. suggestion has prompted examination of the We concluded observational studies that meas- relationship between intake of dietary antioxidants, ured either intake of vitamin C or plasma vitamin C such as vitamin C, and cardiovascular disease. levels. We excluded therefore studies that reported Although several observational studies in humans their results in terms of foods and BP even if these have reported a protective association for stroke and foods were rich sources of vitamin C. We included heart attack with increased intake of vitamin C,3–5 a only trials of vitamin C alone and excluded trials of recent systematic review concluded that overall the a combination of micro nutrients14,15 and trials of evidence is not persuasive.6 dietary change, even if the result (among others) was A putative protective effect of vitamin C on car- to increase the vitamin C intake by dietary means.16 diovascular disease could be mediated through an These studies were excluded as it would be imposs- effect on blood pressure (BP),7 or an effect on lipids,8 ible to estimate the effect of vitamin C alone. platelets9,10 or haemostatic factors.11 A number of Where several reports were made by the same studies and review articles8,12,13 have examined the group on the same study, (for example see references hypothesis that vitamin C lowers BP but to our 17 and 18), the results from what was judged to be knowledge no systematic overview has been done. the definitive report, in this case reference 18, were This report aims to fill this gap in the literature. selected. For the US NHANES I sample, two sets of analyses performed by different groups were included as they were considered to be substantially different, though the study was still only considered to have contributed one study population.19,20 How- ever, a further report on NHANES I21 was excluded Correspondence: Dr AR Ness, Institute of Public Health, Univer- sity Forvie Site, Robinson Way, Cambridge CD2 2SR, UK from the analyses as the population had been dicho- Received 18 November 1996; revised 15 January 1997; accepted tomised into normotensive and hypertensive sub- 15 January 1997 groups in contrast to all the other studies considered 344 Table 1 Cross-sectional studies that reported on the observed association between vitamin C intake and BPa Population Author No. Age Inclusions Exclusions Vitamin C Confounders D SBP D DBP Notes Sex Vitamin C and blood pressure Sample of US Stanton JL 10 419 >18, Dietary Treated BP 24 h recall — — — Correlation vit C and population et al, 198219 both information Unusual diet SBP −0.03, DBP −0.04 (P,0.001 both). Sample of US Harlan WR 2055 25–74, Subset had Hypertensives 24 h recall Biochemical, — — Vit C not in models population et al, both extra socio-economic finally selected. AR Ness 198420 information variables Sweden, Lapidus L 1462 38–60, Census based CHD, refusal, 24 h recall ———Nosignificant et al Gothenburg et al, 198628 women sample interview correlation with unsatisfactory SBP. Hawaiian Joffres MR 615 61–82, Hawaii CHD, 24 h recall Age, BMI −3.6 mm Hg −1.1 mm Hg Vit C intake Japanese et al, 198729 men resident special diet, Q4 vs Q1 Q4 vs Q1 (mg/day): Japanese hypertensive. (P=0.02) (NS) Q1 0–96 ancestry Q4 602–9574 US Elderly Jacques PF, 696 60–100, Free living Hypertensive, 3 day dietary Age, sex, BMI, −10.6 mm Hg −3.2 mm Hg Vit C intake 199231 both volunteers on treat- diary smoking, (low vs high) (low vs high) (mg/day) ment that alcohol, (P=0.01) (P,0.01) ,60 vs >240 effects BP Na/K, Ca, Mg, (low) (high) PUFA Suggestion of threshold effect aThe following abbreviations are used in the tables: BMI = body mass index; Ca = calcium; Ca/P = calcium phosphate ratio; CCF = congestive cardiac failure; CHD = coronary heart disease; CVA = Stroke; DBP = diastolic blood pressure;DM = diabetes mellitus; GI = gastrointestinal; Mg = magnesium; MI = myocardial infarction; Na/K = sodium potassium ratio; NS = non significant; PAA = plasma ascorbic acid; PUFA = polyunsaturated fatty acids; Q4 vs Q1 = The difference between the highest vitamin C quartile and the lowest; RDA = recommended daily allowance; SAA = serum ascorbic acid; SBP = systolic blood pressure; Vit C = vitamin C. Table 2 Cross-sectional studies that reported on the observed association between plasma vitamin C and BPa Population Author No. Age Inclusions Exclusions Vitamin C Confounders D SBP D DBP Notes Sex Mississippi Koh ET, 304 5–80, — — Fasting PAA — — — Correlation vit C and SBP black Stewart T, both −0.12, DBP −0.11 (P,0.05 197825 both). Mississippi Koh ET, Chi 439 .34, — — Fasting PAA — — — Significant -ve correlation black and MS, 198026 both vit C and BP, but vit C white dependent variable in regression models. Japanese farm Yoshioka M et 194 30–39, Healthy Hypertensive Fasting SAA — −17.8 mm Hg −9.4 mm Hg — workers at, 198427 men per 50 mmol/L per 50 mmol/L (P,0.001) (P,0.001) Finnish men Salonen JT, 722 54, Around CHD, Fasting PAA 18 confounders −6.5 mm Hg −3.9 mm Hg Complex models. Groups of 198718 men Kuopio born hypertensive (low vs high) (low vs high) PAA (mmol/L) ,22.7 vs 1930–1931 (P,0.001) (P=0.001) . 61.6. (low) (high) AR Ness Vitamin C and blood pressure North Karelia Riemersma RA 99 44–49, Middle-aged — PAA Smoking, — — PAA did not 22 SW Finland et al, 1990 85 men Caucasian cholesterol correlate with BP. et al Scotland 131 South Italy 80 US Chinese Choi ES et al, 247 60–96, Boston area Housebound Fasting PAA Age, sex, BMI, −11 mm Hg −4.5 mm Hg 24 h recall data 199130 both volunteers In Institution smoking, for 50 mmol/L for 50 mmol/L not reported Chinese chronic disease alcohol, (P,0.01) (P=0.02) ancestry Na/K, Ca/P, physical activity US elderly Jacques PF, 696 60–100, Free living Hypertensive, Fasting PAA Age, sex, BMI, — — BP log transformed in 199232 both volunteers on treatment 3 day dietary smoking regression. Vit C and SBP that effects BP diary -ve association both sexes, DBP in women only. (Continued) 345 346 Table 2 Continued Vitamin C and blood pressure Population Author No. Age Inclusions Exclusions Vitamin C Confounders D SBP D DBP Notes Sex Poland, Moor de Burgos 102 16–63, Obese, sample Supplement Fasting PAA — −11.2 mm Hg −9 mm Hg Groups of PAA 35 Warsaw A et al, 1992 women not described takers (low vs high) (low vs high) (mmol/L) AR Ness (P,0.05) (P,0.01) ,35 vs .52. (low) (high) − − US Augusta Moran JP et al, 168 19–70, Healthy Hypertensive Fasting PAA Smokers 4.2 mm Hg 3.9 mm Hg Small number also with 3- et al 199334 both volunteers major disease excluded for 50 mmol/L for 50 mmol/L day diet and white cell AA. special diet (P,0.02) (P,0.008) supplements above RDA Seventh Day Toohey L et al, 102 mean African– Hypertensive PAA Age, waist, — — -ve correlation vit C with Adventists, 199635 age 48, Americans, on malondi- SBP −0.39 (P , 0.0001), Dallas both Seventh Day treatment aldehyde DBP −0.25 (P,0.025).
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