Antioxidants and Disease Outcome Observational Studies

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Observational studies correlating potential health benefits with the consumption of antioxidants are summarized in table 1.

Several epidemiologic observations indicate an inverse association between vitamin E intake and CHD. For example, the Iowa Women's Health Study (n = 34,486) [14], Nurses' Health Study (n = 87,245) [15], and Health Professionals Follow-Up Study (men only; n = 39,910) [16] revealed that subjects in the highest quintile of vitamin E consumption from food and supplements had relative CHD risks of 0.78, 0.59, and 0.59, respectively, after adjustment for confounding variables such as age. The Nurses' Health study [15] showed a decreased risk of coronary artery disease in women who took vitamin E supplements for more than 2 years. However, in this study women who took the supplements had a slightly better cardiovascular risk profile at baseline. It is also probable that people who choose the vitamin supplements had healthier lifestyle.

The National Health and Nutrition Examination Survey (NHANES) I [17] concluded that there was an inverse association of vitamin C intake in males and all causes of death and CVDs. In this study diabetes and hypertension were not included as potential confounding variables.

The Rotterdam study [18] and the Bruneck study [19] have observed the beneficial effects of carotenoid intake. However in the Rotterdam study, lifestyle variables were not taken into consideration and in the Bruneck study

1 Table 1. A select list of observational studies of the role of antioxidants s, 0 - §

Study Study Study design Antioxidants assessed Results of study d population and follow-up a time 3

Dwyer et al. [20] Los Angeles Atherosclerosis Study

573 persons aged 40-60 years

18-month follow-up

D'Odorico et al. [19] Bruneck study

Ford et al. (23)a NHANES III

392 randomly selected men and women aged 45-65 years

1,010 controls; 277 persons with impaired glucose tolerance 230 diabetic patients aged 40-74 years

5-year follow-up


Vitamin C and vitamin E intake determined by 24-hour recall, and plasma levels of antioxidants

Plasma levels of carotenoids, vitamins A and E were determined. Atherosclerosis was assessed by duplex ultrasound

Plasma level of carotenoids measured

Vitamin C supplement >857 mg/day was associated with increased intima media thickness (IMT) of the common carotid arteries; whereas vitamin E supplement of >443 IU/day was associated with reduced progression. 18-month change in IMT was inversely related to the 3 measured oxygenated carotenoids (lutein, p-cryptoxanthin, zeaxanthin) and one hydrocarbon carotenoid, a-carotene a- and p-carotene plasma levels were inversely associated with the prevalence of atherosclerosis of carotid and femoral arteries

P-Carotene and to lesser degree cryptoxanthin and lycopene were inversely correlated with the degree of glucose tolerance abnormality. All the carotenoids were inversely related to fasting insulin concentration

Klipstein-Grobusch et al. [18]a Rotterdam Study

WU1 et al. [21]a NHANES III

Mayer-Davis et al. [22]a, SLVDS

Coudray et al. [30]a EVA study

Mayer-Davis et al. [31]a, IRAS and SLVD

Sanchez-Lugo et al. [32]a, IRAS

Jacques et al. [33] Nurses' Health Study

4.802 participants of Rotterdam aged 55-95 years

237 diabetics

1.803 nondiabetics aged 40-74 years

387 type-2 diabetics aged 20-74 years

1,389 persons aged 59-71 years

520 persons from IRAS and 422 from SLVDS

1,151 persons from IRAS group aged 40-69 years

247 women aged 56-71 years

4-year follow-up


Cross-sectional and longitudinal 4-year follow-up

Cross-sectional with a 4-year follow-up

IRAS: cross-sectional; SLVDS: cross-sectional and longitudinal design Cross-sectional

10- to 12-year follow-up

Food frequency questionnaire for assessment of dietary antioxidant intake Vitamin C serum levels were assayed

24-hour dietary recall

Laboratory values of selenium, vitamin E and carotenoids were analyzed

Vitamin C assessed by food frequency interview in IRAS and 24-hour dietary recall interview in SLVDS Intake of vitamins E and C estimated from food frequency questionnaire

Intake of vitamin C was assessed by food frequency questionnaire and vitamin C supplement consumption data

High (3-carotene intake but not vitamin C or E was associated with decreased incidence of myocardial infarction After adjustment for covariates, mean concentration of serum vitamin C did not differ according to diabetes status

No protective effect of antioxidant intake on diabetic retinopathy. Potential harmful effect of vitamin E and carotenoid in certain subset of diabetics Selenium and vitamin E levels were increased in those subjects with lipemia. In diabetics and hypertensive subjects the carotenoids were reduced Vitamin C intake did not seem to be associated with CVD risk among diabetics

Intake of vitamins E and C had no correlation with insulin sensitivity

Use of vitamin C supplements for more than 10 years was associated with a 77% lower prevalence of early lens opacities and 83% lower prevalence of moderate lens opacities

Table 1. (continued)


Kushi et al. [14] Iowa Women's Health Study

Study population


Post-menopausal women aged 55-69 years

Study design and follow-up time

7-year follow-up

Losonczy et al. [24]a, EPESE


aged 67-105 years

Gaziano et al. [25] Massachusetts Health Care Panel Study

1,299 elderly Mean of 4.75

Massachusetts years follow-up residents who were 66 years or older

Salonen et al. [26]a Kuopio Ischaemic Heart Disease Risk Factor study

944 men aged 42-60 years

4-year follow-up

Knekt et al. [27] 5,133 Finnish Longitudinal study men and women with a 14-year aged 30-60 years follow-up

Antioxidants assessed Results of study

Dietary intake of vitamins A, E and C from food sources and supplements was evaluated with a questionnaire

Vitamin E and C supplements taken was determined by medication and supplementation history

Dietary carotene intake was assessed with a food diary

Plasma concentration of a-tocopherol was measured

Carotene, vitamins C and and E consumption were estimated by the dietary history

Vitamin E intake was found to be protective against CAD. Vitamin C and A intake had no impact on CAD

All cause mortality and CAD mortality was reduced in those taking a-tocopherol vs. those who were not. Simultaneous use of vitamin C and E was associated with lower risk of mortality

Fatal myocardial infarction was lower among those who were in the highest quartile for consumption of carotene-containing food

There was an inverse association observed between the a-tocopherol and the risk of developing diabetes mellitus Inverse relationship between dietary vitamin E and coronary mortality was observed. Some inverse correlation of coronary

Professionals Study

Shoff et al. [28]a Beaver Dam Eye Study

Stampfer et al. [15] Nurses' Health Study

Enstrom et al. [17] NHANESI

Gey and Puska [29] Ischemic heart disease in cross-cultural epidemiology

39,910 US male health professionals 40-75 years of age

2,152 participants aged 43-84 years

87,245 female nurses aged 34-59 years

11,348 non-institutionalized US adults aged 25-74 years

Groups of about 100 apparently healthy males aged 40-49 years from different regions of Europe

4-year follow-up


8-year follow-up

10-year follow-up


Carotene, vitamins C and E assessed with questionnaires

Intake of vitamins E, C and carotene was determined with dietary questionnaires

Vitamins E, C and carotene intake assessed with questionnaires

Vitamin C intake measured with food frequency and supplement questionnaire

Plasma levels of vitamins A, C, E, ß-carotene, and selenium mortality for vitamin C and carotenoids was observed only in women

Higher intake of supplemental and possibly dietary vitamin E was associated with a significantly lower risk of CAD

In people with diabetes no association between HbA1c and vitamins E, C and p-carotene intake was found Women who took vitamin E for more than 2 years were at decreased risk of CAD

Inverse association between vitamin C intake and all cause mortality and CVD in males. No definite relation between vitamin C consumption and individual cancers Plasma levels of vitamins E and A were inversely related to the risk of ischemic heart disease

Reproduced with some modifications from Hasanain and Mooradian [3].

CAD = Coronary artery disease; CVD = cardiovascular disease; EPESE = Established Population for Epidemiologic Studies of the Elderly; EVA = Etude du Vieillissement Arterial; HbA1c = hemoglobin A1c; IRAS = Insulin Resistance Atherosclerosis Study; NHANES = National Health and Nutrition Examination Survey; SLVD = San Luis Valley Diabetes Study. aThese studies included a significant number of subjects with diabetes or insulin resistance.

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