Objective-To assess the effects of dietary modifications on oxidized low-density lipoprotein (LDL). Methods and Results-Thirty-seven healthy women were fed two diets. Both diets contained a reduced amount of total and saturated fat. In addition, one diet was low in vegetables and the other was high in vegetables, berries, and fruit. The dietary intake of total fat was 70 g per day at baseline and decreased to 56 g (low-fat, low-vegetable diet) and to 59 g (low-fat, high-vegetable diet). The saturated fat intake decreased from 28 g to 20 g and to 19 g, and the amount of polyunsaturated fat intake increased from 11 g to 13 g and to 19 g (baseline; low-fat, low-vegetable; low-fat, high-vegetable; respectively). The amount of oxidized LDL in plasma was determined as the content of oxidized phospholipid per ApoB-100 using a monoclonal antibody EO6 (OxLDL-EO6 See page 392There has been a vast amount of interest in pharmacological agents and antioxidants that decrease LDL oxidation in vitro 7-9 and decrease atherosclerosis in animal models in vivo. 10 The data in humans, primarily with vitamin E, however, have been disappointing, although the reasons for this have been recently discussed. 11 Interest has also been focused on non-pharmacological agents and antioxidants, such as natural foods, and their ability to affect LDL oxidation. 12,13 Data on the effects of whole diets with a high intake of fruit and vegetables on LDL oxidation are limited and conflicting. 14 -16 In the present study, we investigated how alterations in the dietary intakes of fat, vegetables, berries, and fruit affected plasma levels of antioxidants and OxLDL. We performed a crossover dietary intervention with two diets, both low in total dietary fat but one was low in vegetables and the other was high in vegetables, berries, and fruit, to find out whether a high intake of natural antioxidants influences the plasma levels of OxLDL. Methods SubjectsWe interviewed and examined 86 women, among whom 37 healthy volunteers were selected and completed the study. The inclusion criteria were: (1) body mass index (BMI) 20 to 29 kg/m 2 ; (2) blood glucose 3.7 to 6.2 mmol/L; (3) plasma cholesterol Ͻ7.0 mmol/L; (4) plasma triglycerides Ͻ3.0 mmol/L; (5) non-smoking; (6) no gastrointestinal, renal, or hepatic diseases or food allergies; (7) no use of vitamins and/or minerals for at least 6 month before the study; (8) not pregnant or lactating. Alcohol intake was assessed by an interview and from the food records. Most subjects were teetotalers and others reported occasional moderate alcohol intake. Six participants used oral contraceptives, and 3 were using postmenopausal estrogen/ progestin supplementation. The average age, height, and weight of the subjects were 43Ϯ12 years, 163Ϯ5 cm, and 63.6Ϯ6.4 kg, respectively. The study was approved by the Ethical Committee of the Faculty of Medicine, University of Oulu and followed the Declaration of Helsinki.

High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5·9 (SD 10) % (P¼0·002) and LDL cholesterol concentration by 12·9 (SD 17·0) % (P¼ 0·0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0·56, P¼ 0·009; r 0·60, P¼0·004, total and LDL, respectively), b-carotene (r 0·58, P¼ 0·005; r 0·70, P, 0·001) and g-carotene concentrations (r 0·64, P¼ 0·002; r 0·64, P¼ 0·002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P¼0·02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, b-carotene and g-carotene levels.

High plasma total homocysteine (tHcy), low dietary intake of folate and other B vitamins, and genetic polymorphisms related to metabolism of homocysteine may interactively contribute to the risk of cardiovascular disease. We investigated whether known mutations in genes regulating homocysteine metabolism affect the responsiveness of serum folate and plasma tHcy to high intake of natural folate from food. Healthy females (n = 37) aged 22-57 y volunteered to participate in a crossover dietary intervention with two 5-wk diet periods (low and high folate diets). Concentrations of serum and RBC folate, serum vitamin B-12 and plasma tHcy were measured at baseline and at the end of each diet period. The prevalences of C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene, 844ins68 of cystathionine beta-synthase (CBS) gene and A2756G mutation of methionine synthase (MS) gene were determined. Compared with the low folate diet, the high folate diet increased the serum folate concentration by 85% (P < 0.001), 77% (P < 0.001) and 55% (P < 0.05) in the subjects with the genotypes C/C (n = 19), C/T (n = 13) and T/T (n = 5), respectively, of the MTHFR gene. Also, the plasma tHcy of the subjects with the genotypes C/C, C/T and T/T was decreased by 11% (P < 0.001), 15% (P < 0.01) and 18% (P < 0.05), respectively, during the high folate diet period. The subjects carrying the G2756 allele of the MS gene (n = 15) had a more extensive reduction (P < 0.05) of plasma tHcy during the high folate diet period than the subjects with the genotype A/A (n = 22). The 844ins68 of CBS gene did not affect plasma tHcy concentrations or diet responsiveness. In conclusion, diet responsiveness of plasma homocysteine may be genetically regulated.

High plasma total homocysteine (tHcy) concentration is reported to be a risk factor for vascular diseases. We investigated the extent to which serum folate and plasma tHcy respond to a high intake of natural folate from food. Thirty-seven healthy females volunteered to participate in a crossover dietary intervention. The study included a baseline period and two 5-week diet periods (low-and high-folate diets) with a 3-week washout in between. The low-folate diet contained one serving of both vegetables and fruit/d, while during the high-folate diet the subjects ate at least seven servings of vegetables, berries, and citrus fruit/d. Serum and erythrocyte (RBC) folate, serum vitamin B 12 , and plasma tHcy concentrations were measured at the baseline and at the end of each diet period. The mean concentrations of serum and RBC folate were 11·0 (SD 3·0) nmol/l and 412 (SD 120) nmol/l at the end of the low-folate diet and 78 (95 % CI 62, 94) % and 14 (95 % CI 8, 20) % higher in response to the high-folate diet (P, 0·001). The serum concentration of vitamin B 12 remained unchanged during the intervention. The mean plasma tHcy concentration was 8·0 mmol/l at the end of the low-folate diet and decreased by 13 (95 % CI 9, 18) % in response to the high-folate diet (P,0·001). In conclusion, a diet high in fresh berries, citrus fruit, and vegetables effectively increases serum and RBC folate and decreases plasma homocysteine.

Paraoxonase-1 (PON1), a HDL-associated enzyme, may protect against the development of atherosclerosis. Serum PON1 activity and PON1-mediated capacity of HDL to prevent lipoprotein oxidation are modulated by two common polymorphisms at positions 192 (Gln-->Arg) and 55 (Leu-->Met) of the PON1 gene. We studied the effect of dietary modifications on PON1 activity and the role of PON1 gene polymorphisms in the response. A controlled, crossover dietary intervention of two 5-wk periods was conducted in 37 healthy, nonsmoking women. The two study diets were either low or high in vegetables, and thus in natural antioxidants, with some differences in fatty acid contents. The mean plasma total (-8%, P < 0.001), LDL (-7%, P < 0.01) and HDL (-7%, P < 0.001%) cholesterol, and apolipoprotein A-I (-8%, P < 0.001) concentrations were lower after the high vegetable diet period than after the low vegetable diet period. Also, the serum PON1 activity was lower (P < 0.05) after the high vegetable compared with the low vegetable diet period. The reduction of PON1 activity correlated with the reduction in HDL cholesterol (r = 0.35, P < 0.05). High baseline PON1 activity was related to the presence of the PON1(192Arg) allele (P < 0.001) and PON1(55Leu/Leu) genotype (P < 0.001). The reduction of PON1 activity due to the high vegetable diet was greatest among the women with the PON1(192Arg) allele (P < 0.05) and PON1(55Leu/Leu) genotype (P < 0.05). In conclusion, a diet high in vegetables, berries and fruit reduces PON1 activity, and the response is modulated by the genetic variance of PON1.