Plasma ascorbic to blood pressure

John
Curtis

acid concentrations relate in human subjects13

Jane M S Feldman antioxidant ofAugusta, Greene, Guifa Xi,, Elaine B Feldman,

inversely

P Moran,
G Ifames,

Leslie
and This

(ohen, Daniel study relates

ABSTRACT pressure (BP)

status GA,

and

blood

The basis related selenium

purpose of the to the and

of this literature,

study that

was the

to test

the

hypothesis, was ascorbic possible

on inversely

the acid, asso-

in 168 healthy

residents

following

BP of Georgians

usual diets. BP ranges mm Hg, and diastolic concentrations ofascorbic

were systolic (5) 84-1 52, mean 1 12 1 (D) 52-96, mean 72 1 mm Hg. Plasma acid (AA)
<

plasma values cs-tocopherol plasma

of the antioxidants and to examine the retinol and taurine

were and SBP Highest

significantly DBF (r vs AA = and lowest

inversely -0.20, -0.083C quintiles

related to SBP (r = -0.18, < 0.0 1): with regression + 1 16 and DBP -0.077C of AA differed Hg) and DBP trations smokers, significantly (69 I, 74

0.05)

ciation between with BP.

concentrations

equations + 76. in mean

2),

Downloaded from ajcn.nutrition.org by guest on July 7, 2013

Subjects
One atic

and methods
hundred sixty-eight volunteer healthy subjects normotensive were or asymptomrecruited from the

<

SBP (108 2, 1 1 3 2 mm 0.05. Plasma AA concensmokers. By deleting DBF with plasma AA Plasma selenium, retinol and taurine body Am mass index, lipoprotein

were significantly lower in the the inverse relations ofSBP and ofthe equation were cs-tocopherol:cholesterol to BP: whereas plasma triglycerides

hypertensive

and the slopes ct-tocopherol. were body not related

enhanced. ratio, gender,

Augusta, GA, region. There were 108 women and 60 men: 141 were white and 16 were black. Their ages ranged from 19 to 70
y (1

SEM:

37

1). They

were

not

taking

antihypertensive mellitus, They were were not

male cholesterol, correlated.

fat distribution, and

low density

medication and hepatic or renal consuming their

did not disease, regular

have heart or known diets and

disease, diabetes hyperlipidemia. indicated that they

cholesterol, 1993:57:213-7.

J C/in

Nutr

using supplements with ascorbic acid beyond the recommended dietary allowances (I 6). Fifty-six subjects reported taking supplements that included ascorbic acid. One subject was discovered Ascorbic a-tocopherol, acid, blood retinol, pressure, WBC antioxidants, ascorbic acid, vito be ingesting 3 g ascorbic acid/d after a high plasma concentaurine, tration (143 zmol/L) indicated that two ascorbic and 200 was assayed subjects took in the study. supplements Further inquiry containing 1 g of 500, 250, obtained from

KEY tamin

WORDS C, smokers

selenium,

Introduction
The netic, related calcium tioxidants Epidemiologic development hormonal, and hypertension (4), alcohol in relation data of hypertension nutritional to intakes can be influenced by gehave (3), aninterest. between cir-

acid and three mg, respectively.

subjects took supplements Informed consent was

factors ( 1 ). Many studies of sodium (2), potassium (6). The (BP) role ofdietary pressure is ofrecent

all subjects and the procedures followed were approved by and are in accord with the ethical standards ofthe Human Assurance Committee at the Medical College ofGeorgia. Each subject filled out a self-administered caffeine intake, alcohol ofhypertension, vitamin and/or Standardized height body and mass weight index questionnaire use, tobacco to provide use, exercise, data concerning history family

(5), and
to blood support

energy an inverse

association

culating antioxidants and blood pressure (9) in a study of normotensive Finnish was moderately inversely associated

(7, 8). Salonen et al men reported that BP with concentrations of

use oforal contraceptives or steroid hormones, mineral supplement use, and demographics. anthropometric measurements ( 17) of body were (BMI, obtained in kg/m2). to enable Height calculation was measured of the while

plasma ascorbic acid and serum selenium. There was marked elevation of BP at the lowest concentrations of these nutrients (9). Other investigators in the United States and Japan have reported correlated BF (SBF) decreases nutritional motensive that the that vitamin C nutriture with both diastolic blood (10-12). in the factors subjects. amino Nuir acid McCarron consumption that taurine Studies was significantly pressure (DBP) found A and hypertensive and rats have BF (1 3-1 5). in USA. 1993 American Society that inversely and systolic significant some norfrom C were

I From the Department of Medicine. Section College ofGeorgia. Augusta, GA. 2 Supported by NHLBI MERIT award (CGH)

of Nutrition. and summer

Medical research

et al (8) of vitamins

distinguished in humans decreases Printed

reported

fellowship MCG (LC). 3 Address reprint requests to EB Feldman. Medical College of Georgia, Department of Medicine. Section of Nutrition, BG-230, Augusta, GA 309 12-3 102. Received January 21. 1992. Accepted for publication August 10, 1992. for Clinical Nutrition 213

.1,n J C/in

1993:57:213-7.

214 subjects stood erect against and wore no shoes. Weight eating shoes. Waist with the subject the upright was measured in light

MORAN bar of the height scale in the morning before clothing and without

ET SBP

AL or DBP nutrients as the dependent studied. variable and with values of each

of the

dressed

The same balance-beam scale was used on all subjects. and hip girth were measured with a tape measure and the girth assessed were read ratio was Three calculated. after by using three each using
5 mm

Results
The variables examined in the 168 subjects 152 mm were arc included in

waist-to-hip BF was other subjects digital Rochester, culated. Blood after taming ticoagulant. 800-850 samples for a-tocopherol, for total (HDL) dextran cholesterol LDL were
2 mo.

in the morning position of the from fast (143 was at -25 and and was calculated
=

rest

and taken

before while

manipulations. out NY). samples sodium The

measurements

were a Taylor (Sybron

in the seated An were heparin blood average

automated Corporation, was cal-

Table 1. The 1 ). Plasma supplement SBP (men and with respectively, mm than Hg higher
0.97).

SBP ranged from 84 to ascorbic acid concentrations users DBP than than readings those
>

Hg (mean 1 12 1 1% higher in Hg higher, subjects SBF was 3 subjects in obese in-

in nonusers. of men ofwomen women were 8 and

<

sphygmomanometer

6 mm In obese
>

BF readings subject evacuated for light acid, was

(P
with

0.02). BMI

a BMI

27.8,

27.3)

obtained

in the morning tubes conas an1 5 mm plasma exposure, selenium, assayed by using (LDL) at or EDTA

(1 14.6 2.4, 1 SEM)

than

in nonobese 2.1)

a 12- 14-h

overnight

by USP

(1 1 1.4

units/tube) centrifuged from

nonobese

DBP was 7 mm Hg higher (79 subjects (72 0.7, P = 0.001).

promptly

X g at 4 #{176}C to separate stored This retinol, cholesterol cholesterol magnesium was plasma

the plasma. #{176}C, protected

Heparinized

Plasma concentrations versely related to SBP

=

(r

of ascorbic acid = -0. 1 8, P

<

were significantly 0.05) and DBF indicated acid value, 1). Subjects acid Hg, had that

(r
for

-0.20,

<

0.01).

The

regression in the plasma by 8 mm of plasma 2 and

equations ascorbic Hg (Fig ascorbic

was assayed taurine. triglycerides. quantitated sulfate. by using cholesterol

for ascorbic EDTA after the

-

plasma precipitation

a l00-mol/L increase SBF and DBP decreased highest icantly and The and lowest different SBF

both in the signif<

High-density-lipoprotein

quintiles (108

Downloaded from ajcn.nutrition.org by guest on July 7, 2013

1 13 2 mm

0.05)

Low-density-lipoprotein formula HDL

-

DBF (69 1 and 74 2 mm Hg, P < 0.05; Fig 2) readings. plasma mean ascorbic acid concentrations were significantly in the smokers of plasma 10 moderate and 2 heavy than in the nonsmokers. ascorbic acid and BP in with the with SBF

cholesterol

total

cholesterol X 0.16). by in

(triglycerides was assay selenium method

(30%) lower (34 vs 5 1 mol/L) (> 20 cigarettes/d) cigarette We determined the relation smokers and nonsmokers. total group, the inverse

The using tions and

plasma a colorimetric were

ascorbic Laboratory

acid

concentration acid plasma

quantified in operation concentraof Whetter the plasma

In nonsmokers, compared correlation of ascorbic acid

phosphotungstic (1 8). The by using subset

the Nutrition Ullrey

determined (19).

a fluorometric

In a random

of 82 subjects,

a-tocopherol multaneously In a random tions were

and retinol concentrations were by the HPLC method ofCatignani subset determined of 108 subjects, by the on HPLC plasma method

determined and Bieri of Hill with Demand

si(20).

TABLE 1 Study variables0 Value Age(y)(n = 168) Height(m)(n= 168) Weight (kg) (n = 168) Body mass indext (n = 168) Waist circumference (cm) (n - 167) Hip circumference (cm) (n = 167) Waist-to-hip ratio (n - 167) Systolic blood pressure (mm Hg) (n = 168) Diastolic blood pressure (mm Hg) (n = 168) Ascorbic acid (Mmol/L) (n = 168) White blood cell ascorbic acid (zg/l06 WBC) (n = 22) Selenium (Mmol/L) (n = 168) Retinol (Mmol/L) (n = 82) a-Tocopherol (Mmol/L) (n = 82) Taurine (Mmol/L) (n = 108) Total cholesterol (mmol/L) (n = 101) HDL cholesterol (mmol/L) (n = 101) LDL cholesterol (mmol/L) (n = 101) Triglycerides (mmol/L) (n = 101)
0

taurine

concentraet al (21). a coloriClinical NY). and and and one of 37.2 68.6 23.5 78.0 96.5 0.81 1 1 1.6
72.3

Cholesterol and metric-enzymatic Chemistry Three-day were highest the food weekend Minnesota and and validation nutrient obtained quintiles diaries, day. Analyzer

triglycerides method (Olympus

were determined the Olympus Corporation, (including with the certified Center records. by the values acid, subjects

0.86 (19-70) 1.05 (43.2-107.5) 0.3 (16.4-33.2)

(59.5-108) (76.2-14 1.6)

1.7 0.01 (1.5-1.95)

New dietary in the plasma

York, lowest

food-intake from ofplasma dietitian which The review intakes dietitian ofthe

records 25 subjects ascorbic instructed were

supplements) selenium, on completing University were analyzed at

0.85 0.7

0.005

(0.66-0.97)

BF. A registered

recorded was food

on two

weekdays

0.9 (84-152)
(52-96)

by the The data

Nutrition

Coordinating quantitated

in the administration computer program

0.7

50.5 1.7 (5.7-143.1)

the Minnesota blood samples tions were trations were zinc method The tical cepts, nutrient compared data were data programs Berkeley, for also

Center. The 3-d food records were repeated and were obtained. Plasma ascorbic acid concentraand white blood cell ascorbic acid concenmeasured of Denson were analyzed by using the and Bowers with the colorimetric (22). MacIntosh phenylhydracomputer (Abacus quintiles SBP Students with and DBP
t test.

repeated

17.9 1.42 I .7 23.7 60.8 1.4 3.0 1.1 are from

1.59 (0.37-33.1) 0.02 (0.39-2.38) 0.04 (0.9-2.6)

(11.7-54.1)

0.7

2.3 (26.3-147.2) 0.03 (0.8-2.4) 0.1 (1.0-5.4) 0.06 (0.3-2.7) plasma unless oth-

4.8 0.01 (2.8-7.3)

statisConfor the were The mean

Stat
CA). these

View
The subjects

II and
lowest were

Super
and

ANOVA
highest and the

concentrations evaluated

identified by using

SEM specified.

(range).

Biochemical

values

erwise

by regression

analysis,

the

t In kg/m2.

PLASMA

ASCORBIC

ACID

AND

BLOOD

PRESSURE
150

215

E
E
LU
U)

E
E
LU

130

110

Cl) LU

LU

a.
0

a.
0
-j

90

0
0
-j

0 0

70

0
-j

ICl) U)

SYSTOLIC

DIASTOLIC

a)

FIG 2. Individual measurements ofsystolic (left) and diastolic (right) blood pressure in subjects in the lowest (0) and highest (#{149}) quintiles of plasma ascorbic acid concentration. Shaded areas represent 1 SD about the mean blood pressure (horizontal line). The lowest quintile of plasma ascorbic acid was 5.6-24.5 Mmol/L: the highest quintile ofplasma ascorbic acid was 85. 1-143 Mmol/L. The mean blood pressures ofsubjects in the lowest and highest quintiles differ significantly (P < 0.05).

Downloaded from ajcn.nutrition.org by guest on July 7, 2013

E E
LU Cl)

Variables respectively, girth, r < 0.001), cholesterol

=

that (Table 0.37, plasma (r

=

were

significantly 2) included
<

related body-fat

to SBP distribution
=

and/or

DBP,

U)
LU

(waist-hip
<

a.
0 0 0
-J

0.32: P cholesterol
0.25, 0.3 1;

0.001). BMI (r (r = 0.28, 0.32;

<

0.39, 0.40: P 0.01), LDL (r

=

0.01

),

and

triglycerides

0.20, in-

0
-J

P<0.05).
We also carried out multiple-linear-regression analysis. cluding data from all subjects, and DBP with plasma ascorbic Partial correlation with BMI (P
=

I.U) 4 0

of the association between SBF acid, BMI, and total cholesterol. were significant for SBP and 0.0001) and total cholesterol were increased excluded, inversely the value DBP

coefficients 0.001, P When

(P
of

0.03,

0.01).

smokers acid

the Vitamin C (tmoIes/L)

coefficient

for ascorbic

to correlate

FIG 1 . Relationship between plasma ascorbic acid and systolic and diastolic blood pressure in men (#{149}) and women (s). The solid lines represent the regression equations, which were significant for systolic (P = 0.02) and diastolic blood pressures (P = 0.008).

TABLE 2 Correlation antioxidant

coefficients and blood

of anthropometric lipid concentrations

measurements with blood

and blood pressure Diastolic blood pressure

0.400 0.320

was

increased
=

to r

-0.25
for SBP

(P

0.002) greater The

and than

for DBF the that ofthe

increased slope of the total per Body mass index (n = 168) Waist-to-hip ratio (Fl = 167) Plasma ascorbic acid (n = 168) White blood cell ascorbic acid (I = 122) Retinol (1 = 82) a-Tocopherol (n = 82) Selenium (n = 168) Taurine (F? = 108) Total cholesterol (n = 101 ) HDL cholesterol (n = 101) LDL cholesterol (a = 10 1) Triglycerides (n = 101) *P= t P P
< <

Systolic blood pressure

0.390

to r
study

-0.27
population,

(P
equation

0.0009). indicating acid

In the was

nonsmokers,

regression 100 zmol/L equation in DBP

for the in SBP

0.37

a 12-mm

Hg decline slope

-0.181 -0.26
0.24t

-0.20j -0.26
0.22t

ascorbic

(P

0.002).

regression

for DBP similarly was greater per 100 Mmol/L ascorbic acid (P

with a 10-mm decline = 0.0009). In the smok-

ers, the relation ofplasma compared with nonsmokers, (r = 0.75, SBP: r = 0.67, was positive (P from the highest ofplasma SBP 107

ascorbic to SBP and DBP was reversed, so that the correlations were positive DBP) and the slope of the regression When lowest smokers were deleted (3 smokers) quintiles BP was enhanced: 0.001) and DBP 69 ascorbic distribution acid

0.009, P = 0.004). (3 smokers) and

ascorbic 2 and

acid, the difference 1 15 2 mm Hg Hg (P

<

in their

0.01 0.10 0 0.28t 0.02 0.25j 0.16

0.06 0.12 -0.03 0.324 -0.07 0.3 1j 0.20t

(P
The

1 and

76 2 mm

0.01).
<

plasma

<0.001.
0.05.

concentrations were (waist-hip ratio): r

inversely -0.3, P

related 0.002.

to body-fat

0.01.

216 significantly cholesterol evidence that with no longer vitamin SBP

MORAN

ET

AL with the reduced plasma the metabolite theory that concentraof prostacyantioxifree at lower be-

(P

0.04)

and

with

DBP with in the

(P
DBP. data

0.03); Further set inwas ap-

correlated C among

significantly 12 variables

concentrations were associated tions of 6-keto-prostaglandin-F-la, din. This observation supports dants enhance radicals and concentrations Trout (23) blood pressure the production peroxides, which

dietary

dependently negatively parent by factor analysis There selenium, plasma food diaries was retinol, no significant or taurine indicated the a-tocopherol,

influences (data not association the ratio mean

BP in nonsmokers provided). between The dietary BP and data ofa-tocopherol

ofprostacyclin by scavenging inhibit prostacyclin synthetase acid may

plasma from 3-d

to cholesterol, intake of vitamin

above a certain threshold. suggested that plasma ascorbic in part by altering a positive (a-GTP) leukotrienc reported

concentrations. daily

metabolism,

C exclusive ofsupplements was I 22 1 1 . I zg. Intake plements) did not correlate trations nor with blood plasma did BP, possibly cell ascorbic ascorbic not correlate ber. White related to
<

was 86 10.6 mg and of selenium of these antioxidants (diet plus supsignificantly with plasma concenbecause ofthe lower subject were numdirectly 0.43, acid concentrations acid concentrations significantly with

cause earlier work a-glutamyltranspeptidase sociation between Ascorbic acid such as sodium. in hypertensive

association between serum and BP and a negative asa-GTP other

plasma ascorbic acid and may affect BP by influencing Koh patients that

( I 2).
nutrients,

( 10) proposed
by lowering the hypotensive

that ascorbic acid is effective sodium content in the blood. function ofascorbic release from acid nerve of low intake of

(r
BP.

She also may

suggested from

0.05),

but

result

decreasing

norepinephrine

endings and exchangeable

from the adrenal sodium content ascorbic acid

medulla in consequence in the circulation. may simply reflect the

Discussion
This in healthy study indicates Georgians that with plasma SBP
<

Thus, ascorbic 160 mm acid concentrations DBP

<

serum

other important nutrients and dietary fiber. These 100 consumption ascorbic acid of fruits and in hypertensive

that influence BP, such nutrients increase with vegetables subjects

as potassium the frequent of the

Downloaded from ajcn.nutrition.org by guest on July 7, 2013

Hg and

mm Hg (no treatment) were inversely related to SBP and DBP. The results agree with previous reports that have described a similar relationship. A recent review of the world literature included seven studies involving > 12 000 acid SBP relied of the subjects centration stances, the status Several of plasma nutriture and DBP. on 24-h subjects. from the United States, Finland, subjects (23). In all the populations, inversely included correlated > 10 000 the ascorbic but plasma acid data and Japan, ascorbic both and intake 1 700

(1 2). The lower intake may reflect in part

close association of ascorbic acid and potassium tassium consumption and its relation to sodium important nutrient influences on BP (3). Several small intervention studies using vitamin various effects on BP. Ascorbic acid supplementation

intake (8). Pointake are other C have yielded mg

was significantly The largest study dietary Such recalls data are

with people acid

( 1000

to estimate imprecise

d for 3 mo) reduced both SBP and DBP in 23 mildly hypertensive women (10). A study cited by Trout (23) of I 2 mildly hypertensive tation cited subjects supplemented a decrease with 1000 mg ascorbic Ascorbic of healthy itself acid acid/d young enhances for 6 women the wk only revealed in SBP. supplemen-

from

have related BP to the fasting as the indicator of ascorbic in contrast of other theories ascorbic to this study. nutrients that may have been proposed acid concentrations

ascorbic acid constatus. In most indid not report

the investigators

did not change by Koh (10). been suggested

BP in a study that

relate to blood pressure. to explain the association with BP. The role

It has of

hypertension

ascorbic acid as an antioxidant and its effect on other nutrients have been emphasized. As an antioxidant, ascorbic acid influences prostaglandin production, which in turn affects blood pressure. Some prostaglandins, such as prostacyclin (PGI-2), are vasodilators and are therefore hypotensive. Other prostaglandins arc rated vasoconstrictors, fatty acids like (PUFAs), to autooxidation. and cause the and peroxidized antioxidants that thromboxane are synthesized linolcic and Oxygen formation fats can prevent especially A-2 (TXA-2) from acid, hydrogen and and polyunsatuPUFAs peroxide are hypertensive. are susceptible Prostaglandins

metabolism of ascorbic acid (1 2), such as the effect ascribed to smoking and plasma ascorbic acid concentrations. The present study confirmed a significantly lower concentration of plasma ascorbic acid concentration in smokers as has been demonstrated in numerous for and factors alcohol centrations proposed increased turnover impaired studies. that (age, to explain metabolism sex, This race, association affect BMI, Conflicting persists serum dietary despite ascorbic ascorbic mechanisms studies with acid have correction acid conintake, been revealed increased found independently

consumption).

the effect ofsmoking. Some ofascorbic acid in smokers, urinary absorption

can act on PUFAs malondialdehyde, ofTXA-2. lipids may dence that According aqueous-phase Thus,

of free radicals and retard the production the autooxidation of

and increased ascorbic acid

excretion. Other studies but normal turnover acid concentrations distribution of body

(27).
were infat (BMI

In this study, plasma ascorbic versely related to measures and and waist-hip ratio). correlated with BP. viously relation ciation centrations to have These Plasma indexes ascorbic

have an antihypertensive antioxidants increase to Frei ct al (25), antioxidant protects also spares Ascorbic

effect. There is some cvithe production of PGI-2 (24). ascorbate is the most effective blood plasma. Ascorbate peroxihas anwith videtectable which also

for obesity were significantly acid has been reported prewith obesity (1 1). This the selenium assoconThese

a negative results have with not correlate

relationship been with reported study

in human

is as yet unexplained. concerning plasma or smoking. ofselenium did BP. In this

not only completely dative damage but tioxidant activity. tamin E to prevent cascade (26). Low

the lipids from a-tocopherol, acid works

Conflicting

synergistically

BP, obesity,

the autooxidation concentrations

of PUFAs in a radical of ascorbic acid lead to deE, which ascorbic acid

results are similar to those of a Dutch no relation ofselcnium to BP but reported concentrations in smokers. Other studies selenium concentrations with BP in humans (9).

study (28) that showed lower plasma selenium reported that serum

creased conversion of vitamin E radical to vitamin may cause an increase in peroxidized fats. Salonen et al (9) found that decreased plasma

were moderately inversely associated Data from our laboratory revealed that

PLASMA the mean In contrast of BP with taurine the BP of selenium-depleted higher than to other amino the studies acid that taurine, hypertensive reported and

ASCORBIC rats was rats

ACID signif(29).

AND

BLOOD

PRESSURE

217
T, Chuman Y. Inverse association of serum blood pressure or rate of hypertension in years. Int I Vitam Nutr Res 1984:54:343-

icantly

BP ofselenium-supplementcd an inverse a reduction 3 1), no

association in BP with with

12. Yoshioka M, Matsushita ascorbic acid level and male adults aged 30-39
7.

supplementation

(1 3, 1 5, 30, in this study. in 168 healthy

association

taurine and BP was found SBP and DBP measured

Augustans

consuming

their usual diets were significantly plasma concentrations ofascorbic in the (5 mm) vitamin reduced lowest quintile of plasma higher than BP C. Plasma ascorbic by 30% in smokers.

inversely related to their acid. The mean BP in subjects ascorbic acid was highest were acid significantly quintile significantly values of

in subjects in the acid concentrations Plasma ascorbic and distribution indexes ofobesity selenium, retinol, not

Fujita T, Ando K, Noda H, Ito Y, Sato Y. Effects of increased adrenomedullary activity and taurine in young patients with borderline hypertension. Circulation 1987;75:525-32. 14. Ogawa M, Takahara A, Ishijima M, Tazaki S. Decrease of plasma sulfur amino acids in essential hypertension. Ipn Circ I 1985:49: 12 17-24. 1 5. Inque A, Takahashi H, Lee L, et al. Retardation ofthe development ofhypertension in DOCA salt rats by taurine supplement. Cardiovasc Res 1988;22:35 1-8.
13.

were

inversely related to measures and waist-hip ratio). These correlated a-tocopherol nificant reported tions ulation These with BP. Plasma to cholesterol, to BP. intake nor more did

ofbody fat (BMI were significantly the showed ratio of no sigtheir concentrapoprisk and 3-d

a-tocopherol, and taurine with to expand people should

relationship dietary of antioxidants measurements to include

In a subset correlate BP. a basis and studies

of 25 subjects, blood

16. National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press, 1989. 17. Feldman EB. Essentials ofclinical nutrition. Philadelphia: FA Davis Co. 1988:64-8. 18. Kyaw A. A simple colorimetric method for ascorbic acid determination in blood plasma. Clin Chim Acta 1978:86:153-7. 19. Whetter mining 20. PA, UlIrey, DE. Improved selenium. I Assoc OffAnal fluorometric method Chem. 1978;61:927-30. for deter-

with provide blacks

the study at higher be designed

older

of hypertension. undertaken plementation

Intervention to evaluate in healthy

the effects subjects.

on BP of ascorbic If suggestive, these

acid supshould be of paas

B

21.

extended to a double-blind, randomized controlled study tients with mild to moderate uncomplicated hypertension part of a nonpharmacologic intervention trial (32).

22.

References
EB. Essentials ofclinical nutrition. Philadelphia: FA Davis Company, 1988:455-7. 2. Elliott P. Observational studies of salt and blood pressure. Hypertension 199l:17(Suppl 1):I-3-8. 3. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis ofpublished trials. I Hypertens
1991:9:465-73. 4. 1. Feldman

23. 24.

Catignani GL. Bieri 1G. Simultaneous determination ofretinol and a-tocopherol in serum or plasma by liquid chromatography. Clin Chem 1983:29:708-12. Hill DW, Walters FH, Wilson TD, Stuart ID. High performance liquid chromatographic determination of amino acids in the picomole range. Anal Chem 1979:51:1338-41. Denson KW, Bowers EF. The determination of ascorbic acid in white blood cells. A comparison ofWBC ascorbic acid and phenolic acid excretion in elderly patients. Clin Sd 1961:21:157-62. Trout DL. Vitamin C and cardiovascular risk factors. Am I Clin
Nutr 1991:53:3225-55.

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Mikami calcium
515.

H, Ogihara intervention

T, Tabuchi Y. Blood pressure response to dietary in humans. Am I Hypertens 1990:3:1475-

Smith RS. Nutrition, hypertension and cardiovascular disease. Gilroy, CA: The Lyncean Press, 1984:2-7. 25. Frei B, England L, Ames B. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989:86:637781. 26. Gey KF, Stahelin HB, Puska P. Evans A. Relationship of plasma level ofvitamin C to mortality from ischemic heart disease. Annals of the New York Academy of Sciences, 1987:498: 1 10-23. 27. 28. Schectman G, Byrd IC, Gruchow HW. The influence of smoking on vitamin C status in adults. Am I Public Health 1989:79:158-62. Bukkens AU, deVos N, Kok Fl, Schouten EG, deBruijn AM, Hofman A. Selenium status and cardiovascular risk factors in healthy Dutch subjects. I Am Coll Nutr 1990:9:128-35. Feldman EB, Carroll RM, Martin WD, Russell BS, Hames CG. Selenium status and blood pressure in the spontaneously hypertensive rat. In: Combs GF Jr. Spallholz JE, Levander OA. Oldfield JE, eds. Selenium in biology and medicine. Part A. New York: AVI, 1987:
38 1-92.

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