We found plasma ascorbic acid concentration to be inversely associated with systolic and diastolic BP in young-adult Black and White women, independent of race, BMI, education, diet, and lifestyle factors. A 1 mg/dL (56.8 μmol/L) increase in plasma ascorbic acid levels was associated with 4.1 mmHg lower systolic blood pressure and 4.0 mmHg lower diastolic blood pressure. Plasma ascorbic acid levels in this cohort ranged from 0.22 to 3.13 mg/dL (12.5 to 177.8 μmol/L), indicating that a 1 mg/dL change in plasma ascorbic acid level is achievable in this young population.
Plasma ascorbic acid concentration was also inversely and significantly associated with change in BP during the previous year. It is particularly notable that there was very little increase in diastolic BP in persons in the highest quartile of ascorbic acid.
The magnitude of the decrease in systolic and diastolic blood pressure associated with plasma ascorbic acid is consistent with the range of values found in other cross-sectional studies [8–18]. A review by Ness  found that the blood pressure difference associated with a 50 μmol/L (0.88 mg/dL) difference in ascorbic acid concentration ranged from -2.6 to -9.4 mmHg for diastolic blood pressure, and from -3.6 to -17.8 mmHg for systolic blood pressure.
Intervention trials have been less consistent [24–37]. Many of the studies that failed to find a treatment effect have had design limitations such as no control group or no placebo control, short duration, small sample size, concomitant use of non-study dietary supplements containing vitamin C, and varying or inadequately described methods for measuring BP; or they were post-hoc analyses where change in BP was not a primary endpoint of the trial. On the other hand, some studies have found significant reductions in BP as a result of treatment with vitamin C [38–41].
The DASH study  is the major intervention trial of nutritional factors, and our results are comparable in magnitude to those of DASH. Among all participants in the DASH study, the DASH diet lowered mean systolic BP by 5.5 mmHg, and lowered mean diastolic BP by 3.0 mmHg. In the present study, the difference between the mean BP in the first and fourth quartiles of ascorbic acid concentration was 4.7 mmHg systolic, and 6.1 mmHg diastolic BP. This suggests the possibility that if the ascorbic acid concentration of those in the lower one-fourth of the distribution could be increased to the ascorbic acid concentration of those in the top one-fourth of the distribution, an effect comparable to that of the DASH diet could be achieved. The present study was not an intervention study and such an intervention effect is only a hypothesis, but one which would seem to merit follow-up.
The ranges of plasma ascorbic acid seen in our sample are very consistent with those found in the United States. We examined data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004, among women in the same age group, 18–21 years. The mean plasma ascorbic acid concentrations in the four quartiles were 0.43 mg/dL, 0.84 mg/dL, 1.14 mg/dL, and 1.59 mg/dL (24.1, 47.8, 64.8, 90.1 μmol/L). (Block, unpublished data.) In our sample those means were 0.59, 1.03, 1.36 and 1.83 mg/dL. Thus, in the present sample the first three quartiles were similar although slightly higher than those seen in representative national data. The lower two quartiles represent ascorbic acid concentrations most likely obtained from fruits, vegetables and fortified foods such as cereals. A diet rich in fruits and vegetables can produce a concentration similar to that seen in the third quartile. The concentration in the fourth quartile represents a level in which supplements containing vitamin C have made a substantial contribution.
There is substantial biologic rationale for a causal role of ascorbic acid in maintaining normal BP. Numerous oxidative mechanisms appear to be involved in the pathogenesis of hypertension [6, 7, 42]. One well-studied oxidative stress biomarker is F2-isoprostane, a vasoactive product of lipid peroxidation ; we have shown in a randomized trial that supplementation with vitamin C, but not with vitamin E, significantly reduces F2-isoprostane . Similarly inflammation, consistently associated with increased risk of cardiovascular disease, is associated with impaired endothelium-dependent vasodilation and hypertension . Bautista found a progressive increase in blood pressure with increases in high-sensitivity C-reactive protein (hsCRP), a sensitive marker of inflammation . We showed, in a randomized trial, that vitamin C but not vitamin E significantly lowered hsCRP, to an extent equivalent to that seen with statins . Thus, vitamin C may have a beneficial effect on BP by mitigating the adverse effects of inflammation and oxidative stress. Specific functions of vitamin C have also been shown. These include effects on smooth muscle contractility of peripheral blood vessels and improvement of vasomotor dysfunction , prevention of nitric oxide inhibition of release of endothelium-derived relaxing factor , and prevention of free radical inhibition of prostacyclin synthetase. Ascorbic acid may also influence BP by maintaining the normal production and biological activity of nitric oxide through enhanced recycling of tetrahydrobiopterin, a cofactor that stabilizes and sustains the activity of endothelial nitric oxide synthase [49–52].
An important limitation of this study is the fact that the results depicted in Figures 1 and 2 are cross-sectional and therefore causality cannot be inferred. Also, the data represented in Figure 3 are limited by the fact that there were no plasma ascorbic acid measurements for the 9th annual visit, and therefore the association with change in BP, while longitudinal, is not truly prospective. In interpreting our findings it is important to consider the fact that dietary variables are often correlated with one another and may be correlated with lifestyle variables. Therefore, it is possible that plasma ascorbic acid concentration is simply a marker for another variable that influences BP. However, the association persisted even after controlling for BMI, race, education, and intake of fat, sodium and antioxidants. We also evaluated the effect of controlling for other potential confounders including smoking, alcohol consumption, television or video watching, and intake of total energy, calcium, and potassium, and none diminished the strength of the association.
Nevertheless, while we cannot confidently infer causality, our findings point to the important possibility that vitamin C may influence BP even among healthy young adults. This finding is of importance because lowering BP or attenuating increases in BP in young adults may lead to lower BP in older adults, which in turn may reduce the risk of age-associated vascular events. Therefore, our findings suggest that further study of the relationship between vitamin C and BP in this young-adult population is warranted.