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Background: Chronic kidney disease is a major worldwide problem. Although epidemiologic and experimental studies suggest that n--3 long-chain polyunsaturated fatty acid (n--3 LCPUFA) supplementation may prevent or slow the progression of kidney disease, evidence from clinical trials is inconsistent. Objective: The objective was to combine evidence from controlled clinical trials to assess the effect of n--3 LCPUFA supplementation on the change in urine protein excretion (UPE) and on glomerular filtration rate (GFR). Design: We performed a meta-analysis of clinical trials that tested the effect of n--3 LCPUFA supplementation on UPE, a marker of kidney damage, and on GFR, a marker of kidney function. A random-effects model was used to pool SD effect size (Cohen's d) across studies. Results: Seventeen trials with 626 participants were included in the meta-analysis. Most trials focused on patients with a single underlying diagnosis: IgA nephropathy (n = 5), diabetes (n = 7), or lupus nephritis (n = 1). The dose of n--3 LCPUFAs ranged from 0.7 to 5.1 g/d, and the median follow-up was 9 mo. In the pooled analysis, there was a greater reduction in UPE in the n--3 LCPUFA group than in the control group: Cohen's d for all trials was -0.19 (95% CI: -0.34, -0.04; P = 0.01). In a patient with 1 g UPE/d, this corresponds to a reduction of 190 mg/d. Effects on GFR were reported in 12 trials. The decline in GFR was slower in the n--3 LCPUFA group than in the control group, but this effect was not significant (0.11; 95% CI: -0.07, 0.29; P = 0.24). Conclusions: In our meta-analysis, use of n--3 LCPUFA supplements reduced UPE but not the decline in GFR. However, small numbers of participants in trials, different methods of assessing proteinuria and GFR, and inconsistent data reporting limit the strength of these conclusions. Large, high-quality trials with clinical outcomes are warranted.

Background: Racial differences in cardiovascular risk factors do not fully explain the higher prevalence of lower-extremity peripheral arterial disease (PAD) in black adults. Objective: We sought to determine whether any of this excess risk may be explained by vitamin D status, which has been widely documented to be lower in blacks than in whites. Design: This population-based cross-sectional study included 2987 white and 866 black persons aged [greater than or equal to] 40 y from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index of Results: Mean ([+ or -] SEM) 25-hydroxyvitamin D [25(OH)D] concentrations were significantly lower in black than in white adults (39.2 [+ or -] 1.0 and 63.7 [+ or -] 1.1 nmol/L, respectively; P < 0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartiles of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, and 0.53; P for trend < 0.001]. In black adults, the association was nonlinear; models with cubic splines suggested evidence of greater odds for PAD and a trend for lower odds for PAD at the lowest and highest concentrations of 25(OH)D, respectively. After adjustment for racial differences in socioeconomic status and for traditional and novel risk factors, odds for PAD in black compared with white adults were reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (1.11, 2.51). After additional adjustment for 25(OH)D, the odds were further reduced to 1.33 (0.84, 2.10). Conclusions: Racial differences in vitamin D status may explain nearly one-third of the excess risk of PAD in black compared with white adults. Additional research is needed to confirm these findings.

Background: Selenium, an essential micronutrient, has received considerable attention for its antioxidant properties. In addition, selenium may affect several cardiometabolic risk factors, such as glucose homeostasis and lipid concentrations. However, the effects of selenium intake on the lipid profile in selenium-replete populations, such as the United States, are largely unknown. Objective: We examined the relation of serum selenium concentrations with serum lipids in a representative sample of US adults. Design: This was a cross-sectional analysis of 5452 men and women aged [greater than or equal to] 20 y participating in the third National Health and Nutrition Examination survey. Serum selenium was measured by atomic absorption spectrometry. Results: The multivariable adjusted differences in total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) comparing the highest with the lowest quartile of serum selenium were 16.6 mg/dL (95% CI: 11.6, 21.4 mg/dL), 10.9 mg/dL (95% CI: 6.4, 15.4 mg/dL), 3.2 mg/dL (95% CI: 1.6, 5.0 mg/dL), 8.9 mg/dL (95% CI: 5.6, 12.2 mg/dL), and 6.9 mg/dL (95% CI: 1.7, 12.1 mg/dL), respectively. Participants in the highest quartile of serum selenium had 10% higher concentrations of triacylglycerols than did participants in the lowest quartile (ratio of triacylglycerol concentrations: 1.10; 95% CI: 1.05, 1.17). The difference in the ratios of LDL cholesterol to HDL cholesterol and apo B to apo A-I that compared the highest with the lowest selenium quartiles were 0.11 (95% CI: -0.02, 0.25) and 0.03 (95% CI: 0.00, 0.06), respectively. Conclusion: Elevated serum selenium was associated with elevated serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, apo B, and apo A-I among US adults, a selenium-replete population. Experimental studies are needed to determine cause and effect relations and the potential mechanisms underlying these associations.

Background: Plasma apolipoprotein B (apo B) and VLDL and LDL with apolipoprotein C-III (apo C-III) are independent risk factors for cardiovascular disease (CVD). Dietary intake affects lipoprotein concentration and composition related to those apolipoproteins. Objective: We studied differences in apo B lipoproteins with and without apo C-III after 3 healthy diets based on the Dietary Approaches to Stop Hypertension Trial diet. Design: Healthy participants (n = 162) were fed each of 3 healthy diets for 6 wk in a crossover design. Diets differed by emphasis of either carbohydrate (Carb), unsaturated fat (Unsat), or protein (Prot). Blood was collected at baseline and after diets for analysis. Results: Compared with the Carb diet, the Prot diet reduced plasma apo B and triglycerides in VLDL with apo C-III (16%, P = 0.07; 11%, P = 0.05, respectively) and apo B in LDL with apo C-III (16%, P = 0.04). Compared with the Unsat diet, the Prot diet reduced triglycerides in VLDL with apo C-III (16%, P = 0.02). Compared with baseline (subjects' usual diet was higher in saturated fat), the Prot diet reduced apo B in LDL with apo C-III (11%, P = 0.05), and all 3 diets reduced plasma total apo B (6-10%, P < 0.05) and apo B in the major type of LDL, LDL without apo C-III (8-10%, P < 0.01). All 3 diets reduced the ratio of apo C-III to apo E in VLDL. Conclusions: Substituting protein for carbohydrate in the context of a healthy dietary pattern reduced atherogenic apo C-III-containing LDL and its precursor, apo C-III- containing VLDL, resulting in the most favorable profile of apo B lipoproteins. In addition, compared with a typical high-saturated fat diet, healthy diets that emphasize carbohydrate, protein, or unsaturated fat reduce plasma total and LDL apo B and produce a lower more metabolically favorable ratio of apo C-III to apo E.

Background: Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques. Objective: The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression. Design: We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, [beta]-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group. Results: In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins. Conclusion: Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events. KEY WORDS Meta-analysis, antioxidants, folate, B vitamins, atherosclerosis, prevention

Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a meta-analysis of the dose-response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials. Patients: 135 967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d). Data Sources: PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied. Data Extraction: 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available. Data Synthesis: 9 of 11 trials testing high-dosage vitamin E ([greater than or equal to] 400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10 000 persons (95% CI, 3 to 74 per 10 000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was -16 per 10 000 persons (CI, -41 to 10 per 10 000 persons; P > 0.2). A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. Limitations: High-dosage ([greater than or equal to] 400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult. Conclusion: High-dosage ([greater than or equal to] 400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.

Background: Lipid peroxidation may be important in the pathogenesis of atherosclerosis, particularly in its earliest stages. Evidence predominantly from in vitro studies suggests that antioxidant vitamins can prevent lipid peroxidation and that vitamin C and vitamin E have synergistic effects. However, in vivo evidence in support of these hypotheses is sparse. Objective: The objective was to determine the effects of vitamin C and vitamin E, alone or in combination, on in vivo lipid peroxidation. Design: We conducted a placebo-controlled, 2 x 2 factorial trial of vitamin C (500 mg ascorbate/d) and vitamin E (400 IU RRR-[alpha]-tocopheryl acetate/d) supplementation in 184 nonsmokers. The mean duration of supplementation was 2 mo. The outcome measures were changes from baseline in urinary 8-isoprostaglandin [F.sub.2[alpha]], urinary malondialdehyde + 4-hydroxyalkenals, and serum oxygen-radical absorbance capacity. Results: The within-group mean changes (and 95% CIs) in urinary 8-iso-prostaglandin [F.sub.2[alpha]] (pg/mg creatinine) were 9.0 (-125.1, 143.1), -150.0 (-275.4,-24.6), -141.3 (-230.5, -52.1), and -112.5 (-234.8, 9.8) in the placebo, vitamin C alone, vitamin E alone, and vitamins C + E groups, respectively. No synergistic effect of these 2 vitamins on urinary 8-iso-prostaglandin [F.sub.2[alpha]] was observed (P = 0.12). Neither vitamin had an effect on urinary malondialdehyde + 4-hydroxyalkenals. Vitamin C, but not vitamin E, increased serum oxygen-radical absorbance capacity (P = 0.01). Conclusions: Supplementation with vitamin C or vitamin E alone reduced lipid peroxidation to a similar extent. Supplementation with a combination of vitamins C and E conferred no benefit beyond that of either vitamin alone. KEY WORDS Antioxidants, vitamin C, vitamin E, free radicals, lipid peroxidation, malondialdehyde, prostaglandins, oxygen-radical absorbance capacity, [F.sub.2]-isoprostanes

Researchers conducted a study to compare the effects of a 12-week moderate-intensity aerobic exercise program and T'ai chi program of light activity on blood pressure. They concluded that both programs may have similar effects on blood pressure. Consequently, these forms of activity may prove helpful in reducing blood pressure in older persons.

Background: Several lines of evidence suggest that supplementation of diet with omega-3 polyunsaturated fatty acids ([omega]-3 PUFA), commonly referred to as fish oils, may reduce blood pressure (BP). However, most clinical trials of [omega]-3 PUFA supplementation have been of insufficient size to detect relevant BP changes. Methods: We conducted a meta-analysis of 17 controlled clinical trials of [omega]-3 PUFA supplementation. To estimate an overall effect of [omega]-3 PUFA supplementation on BP, we calculated the net BP change in each trial (BP [DELTA] in [omega]-3 PUFA group minus BP [DELTA] in control group), which was then weighted according to the inverse of the variance. Results: In the 11 trials that enrolled normotensive individuals (n=728), [omega]-3 PUFA supplementation led to significant reductions of systolic BP (SBP) and diastolic BP (DBP) in two and one trials, respectively. In the six studies that enrolled untreated hypertensives (n=291), significant reductions of SBP and DBP were present in two and four trials, respectively. Weighted, pooled estimates of SBP and DBP change (mm Hg) with 95% confidence intervals were - 1. 0 (-2.0 to 0.0) and -0.5 (-1.2 to +0.2) in the trials of normotensives, and -5.5 (-8.1 to - 2.9) and -3.5 (-5.0 to - 2.1) in the trials of untreated hypertensives. In 13 of 17 studies, trial duration was less than 3 months. Doses of [omega]-3 PUFA tended to be high (average dose >3 g/d in 11 trials). The magnitude of BP reduction was greatest at high BP but was not significantly associated with dose of [omega]-3 PUFA. Side effects, most commonly eructation and a fishy taste, occurred more frequently in [omega]-3 PUFA participants than in control participants (28% vs 13%, P

Background: Low serum levels of [Beta]-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with [Beta]-carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum [Beta]-carotene level and disease risk. Methods: We used data from 14470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum [Beta]-carotene and markers of inflammation (C-reactive protein and white blood cell count). Results: After adjustment for [Beta]-carotene intake and other factors, geometric mean levels of serum [Beta]-carotene for individuals with undetectable ([is less than] 0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL), and clinically elevated ([is greater than or equal to] 1.0 mg/dL) C-reactive protein levels were 18.0, 115.1, and 13.6 [micro]g/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 [micro]g/dL in ex-smokers; and 11.3, 10.2, and 9.4 [micro]g/dL in current smokers (P [is less than] .001 for all). In corresponding analyses, white blood cell count was also inversely related to serum [Beta]-carotene concentration (P [is less than] .05 for all). Conclusions: The strong and inverse association of serum [Beta]-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum [Beta]-carotene concentration and disease risk might be confounded by inflammation. More broadly, for [Beta]-carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels. Arch Intern Med. 2001;161:1903-1908

Background: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. Objective: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. Design: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: [is less than or equal to] 6.7 mmol/L ([is less than or equal to] 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. Results: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL(-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P [is less than] 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P [is less than] 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. Conclusions: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study. Am J Clin Nutr 2001;74:80-9. KEY WORDS Diet, plasma total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol, feeding study, Dietary Approaches to Stop Hypertension Trial, DASH

Background: It is unclear whether obesity and age modify or confound relations between abdominal adiposity and metabolic risk factors for type 2 diabetes. Objective: Our objective was assess the consistency of relations between abdominal adiposity and glycemic variables across discrete categories of obesity and age. Design: We performed a stratified analysis of prevalence data from a rural screening initiative in British Columbia, Canada. Subjects were Salishan Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age: 18-80 y; body mass index (BMI, in kg/[m sup.2]): 17.0-48.2]. We measured waist-to-hip ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb [A.sub.1c]), and 2-h glucose concentrations (2 categories); and BMI (4 categories). BMI and age-specific odds ratios (ORs) and 95% CIs were calculated. Results: WHR-glycemic variable relations were not consistent across BMI and age strata. Risks associated with high WHR were: for persons with BMIs from 25 to 29, elevated insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb [A.sub.1c] (OR: 16.23; 95% CI: 2.04, 101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations [OR: indeterminate [sup.+][infinity]; 95% CI: 1.89, [sup.+][infinity]; and, for persons aged 35-49 y, elevated Hb[A.sub.1c] (OR: [sup.+][infinity]; 95% CI: 3.17, [sup.+][infinity] and 2-h glucose (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. Conclusions: WHR discriminates risk of type 2 diabetes in overweight but not obese individuals. Abdominal adiposity is associated with elevated insulin concentrations in younger age groups and with impaired glucose control in middle-aged groups, suggesting metabolic staging by age on a continuum from insulin resistance to impaired glucose tolerance. Am J Clin Nutr 1999;69:455-60. KEY WORDS Type 2 diabetes, North American Indians, body fat distribution, obesity, abdominal adiposity, waist-to-hip ratio, body mass index