Effect of dietary cholesterol on plasma cholesterol concentration in subjects following reduced fat,high fibre diet.

One hundred and sixty eight subjects participated in a randomised crossover study to determine whether halving or doubling the present dietary cholesterol intake from eggs had any influence on blood cholesterol concentration in people following current dietary recommendations. During the first eight weeks all participants were advised to follow a reduced fat diet (26% total energy for hyperlipidaemic patients, 35% total energy for normolipidaemic volunteers) with an increased ratio of polyunsaturated to saturated fatty acids. This background diet was continued throughout the 16 week experimental period, during which participants ate either two or seven eggs a week. A small but significant increase in total cholesterol was seen after four weeks in the group eating seven eggs a week compared with that in the group eating two eggs a week, but this was no longer apparent after eight weeks. Previous studies suggesting that dietary cholesterol has a greater effect on the serum cholesterol concentration either have been carried out against a background of a higher fat intake or have contrasted extreme cholesterol intakes. A further reduction in dietary cholesterol seems to be unnecessary in those people who have already reduced their intake of saturated fat and increased the ratio of polyunsaturated to saturated fatty acids and fibre rich carbohydrate.     

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.     

Dietary influences on serum lipids and lipoproteins

Substantial data are available to indicate that the diet influences serum levels of cholesterol and lipoproteins. These data are derived from studies in laboratory animals, from epidemiologic studies, and from human investigations. Most research has focused on effects of diet on serum total cholesterol concentrations. In recent years, however, attention has shifted to individual lipoproteins, i.e., low density lipoproteins (LDL), high density lipoproteins (HDL), and very low density lipoproteins (VLDL). Three nutritional factors have been identified that raise serum LDL levels; these are saturated fatty acids, cholesterol itself, and excess caloric intake leading to obesity. The major cholesterol-raising saturated fatty acid in the diet is palmitic acid. Several nutrients can be substituted for saturated fatty acids to produce a reduction in LDL-cholesterol levels. These are polyunsaturated fatty acids, monounsaturated fatty acids, carbohydrates, and even one saturated fatty acid, stearic acid. The latter appears to be converted rapidly into a monounsaturated fatty acid in the body. Any of these nutrients can be used for replacement of cholesterol-raising saturated fatty acids in the diet. However, their relative effects on other metabolic processes remain to be determined fully. At present it appears that carbohydrates and monounsaturated fatty acids represent the preferred replacements for saturated fatty acids, although modest increases in polyunsaturated fatty acids and stearic acid, at the expense of cholesterol-raising saturates, probably are safe and may provide for greater variety in the diet.     

Nutritional properties of trans fatty acids

The role of trans fatty acids (TFA) present in partially hydrogenated fats widely consumed in food and their link with coronary heart disease has been examined in this review. Most of the studies carried out have been on the effects of TFA on blood-lipid profile. The perceived effects of TFA intake depend on the fat or oil with which they are compared and appears to be in between that of dietary saturated fats and monounsaturated fatty acids. When compared to saturated fat, TFA intake shows lower levels of total and LDL-cholesterol in blood. But when both TFA and saturated fatty acids are compared with cis fatty acids or native unhydrogenated oil, increase in total and LDL-cholesterol are noted. The effects of TFA on HDL-cholesterol and Lp(a) are not clearly established. The undesirable effects of TFA can be overcome by inclusion of essential fatty acids at a minimum of 2 energy per cent level in the diet. The link between trans fatty acid intake and coronary heart disease (CHD) are not unequivocally established.     

Evolutionary aspects of omega-3 fatty acids in the food supply

Information from archaeological findings and studies from modern day hunter-gatherers suggest that the Paleolithic diet is the diet we evolved on and for which our genetic profile was programmed. The Paleolithic diet is characterized by lower fat and lower saturated fat intake than Western diets; a balanced intake of omega-6 and omega-3 essential fatty acids; small amounts of trans fatty acids, contributing less than 2% of dietary energy; more green leafy vegetables and fruits providing higher levels of vitamin E and vitamin C and other antioxidants than today's diet and higher amounts of calcium and potassium but lower sodium intake. Studies on the traditional Greek diet (diet of Crete) indicate an omega-6/omega-3 ratio of about 1/1. The importance of a balanced ratio of omega-6:omega-3, a lower saturated fatty acid and lower total fat intake (30-33%), along with higher intakes of fruits and vegetables leading to increases in vitamin E and C, was tested in the Lyon Heart study. The Lyon study, based on a modified diet of Crete, confirmed the importance of omega-3 fatty acids from marine and terrestrial sources, and vitamin E and vitamin C, in the secondary prevention of coronary heart disease, and cancer mortality.     

Saturated fatty acid (SFA) status and SFA intake exhibit different relations with serum total cholesterol and lipoprotein cholesterol: a mechanistic explanation centered around lifestyle-induced low-grade inflammation

We investigated the relations between fatty acid status and serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol ratio in five Tanzanian ethnic groups and one Dutch group. Total cholesterol/HDL cholesterol ratio is a widely used coronary artery disease (CAD) risk factor. Fatty acid status was determined by measurement of fatty acids in serum cholesterol esters and erythrocytes. Data reflecting the influence of fatty acid intakes on serum total cholesterol and lipoprotein cholesterol were obtained from documented intervention studies. We found that 14:0, 16:0 and saturated fatty acid (SFA) status correlates positively with total cholesterol/HDL cholesterol ratio, while their intakes were unrelated. Linoleic acid and polyunsaturated fatty acid (PUFA) status and PUFA intake exhibited negative relations with the total cholesterol/HDL cholesterol ratio. These data suggest that a high SFA status, not a high SFA intake, is associated with increased CAD risk, while both high linoleic acid status and PUFA status are associated with reduced CAD risk. Consequently, the total cholesterol/HDL cholesterol ratio is a questionable risk marker since meta-analyses of randomized controlled trials show that partial dietary replacement of SFA for linoleic acid, the dominating dietary PUFA, does not change CAD risk. We conclude that many lifestyle factors, not SFA intake alone, determine SFA status, and suggest that interaction with many other lifestyle factors determines whether SFA status has a relevant contributing effect in low-grade inflammation, lipoprotein changes and CAD risk. The present outcome may teach us to consider the health effects of the entire diet together with many nondietary lifestyle factors, opposite to the reductionist approach of studying the effects of single nutrients, SFA and PUFA included.     

Keloids in rural black South Africans. Part 2: dietary fatty acid intake and total phospholipid fatty acid profile in the blood of keloid patients

In the second part of this study, emphasis is placed on nutritional intakes (fatty acids and micronutrients) and fatty acid intake and metabolism in the blood, respectively, according to a combined 24 h recall and standardized food frequency questionnaire analyses of keloid prone patients (n=10), compared with normal black South Africans (n=80), and total phospholipid blood (plasma and red blood cell ) analyses of keloid patients (n=20), compared with normal individuals (n=20). Lipid extraction and fractionation by standard procedures, total phospholipid (TPL) separation with thin layer chromatography, and fatty acid methyl ester analyses with gas liquid chromatography techniques were used. Since nutrition may play a role in several disease disorders, the purpose of this study was to confirm or refute a role for essential fatty acids (EFAs) in the hypothesis of keloid formations stated in part 1 of this study. (1)According to the Canadian recommendation (1991), we observed that in keloid patients linoleic acid (LA) and arachidonic acid (AA) dietary intakes, as EFAs of the omega-6-series, are higher than the recommended 7-11 g/d. However, the a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary intakes, as EFAs of the omega-3 series, are lower than the recommendation of 1.1-1.5 g/d. This was also the case in the control group, where a higher dietary intake of the omega-6 fatty acids and a slightly lower dietary intake of the omega-3 fatty acids occurred. Thus, we confirm a high dietary intake of LA (as a product of organ meats, diary products and many vegetable oils) and AA (as a product of meats and egg yolks), as well as lower dietary intakes of ALA (as a product of grains, green leafy vegetables, soy oil, rapeseed oil and linseed), and EPA and DHA (as products of marine oils). Lower micronutrient intakes than the recommended dietary allowances were observed in the keloid group that may influence EFA metabolism and/or collagen synthesis. Of cardinal importance may be the lower intake of calcium in the keloid patients that may contribute to abnormal cell signal transduction in fibroblasts and consequent collagen overproduction, and the lower copper intake that may influence the immune system, or perhaps even the high magnesium intake that stimulates metabolic activity. Micronutrient deficiencies also occurred in the diets of the normal black South Africans that served as a control group. In the case of plasma TPLs, deficiency of the omega-3 EFA series (ALA, EPA and DHA) occurred, and this is in accordance with the apparent lower omega-3 EFA intake in the diets of these patients. In the case of the red blood cell TPLs, as a true and reliable source of dietary fatty acid intake and metabolism, sufficient EFAs of the omega-6 series (LA and AA) and the omega-3 series (ALA, EPA and DHA) occurred. For this study group a relative deficiency of nutritional omega-3 EFA intake apparently did occur, but was probably compensated for by blood fatty acid metabolism.     

Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse

A significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.     

Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review

Epidemiological studies in Greenland Eskimos led to the hypothesis that marine oils rich in n-3 fatty acids (also referred to as omega (omega)-3 fatty acids) are hypolipidemic and ultimately antiatherogenic. Metabolically controlled trials in which large amounts of fish oil were fed to normal volunteers and hyperlipidemic patients showed that these fatty acids (FAs) are effective at lowering plasma cholesterol and triglyceride levels. Although more recent trials using smaller, more practical doses of fish oil supplements have confirmed the hypotriglyceridemic effect, they have shown little effect on total cholesterol levels; hypertriglyceridemic patients have even experienced increases in low density lipoprotein cholesterol (LDL-C) levels of 10-20% while taking n-3 FA supplements. Discrepancies among fish oil studies regarding the effects of n-3 FAs on LDL-C levels may be understood by noting that, in the majority of studies reporting reductions in LDL-C levels, saturated fat intake was lowered when switching from the control diet to the fish oil diet. When fish oil is fed and saturated fat intake is constant, LDL-C levels either do not change or may increase. Levels of high density lipoprotein cholesterol have been found to increase slightly (about 5-10%) with fish oil intake. Plasma apolipoprotein levels change in concert with their associated lipoprotein cholesterol levels. Although the decrease in triglyceride levels appears to result from an inhibition in hepatic triglyceride synthesis, the mechanisms leading to the increases in LDL and HDL have not been determined. Finally, fatty fish or linolenic acid may serve as alternative sources of long-chain n-3 FAs, but further studies will be needed to document their hypolipidemic and/or antiatherogenic effects.     

Thematic review series: patient-oriented research. Nutritional determinants of insulin resistance

Interpreting the literature relating to the nutritional determinants of insulin resistance is complicated by the wide range of methods used to determine insulin sensitivity. Excess adiposity is unquestionably the most important determinant of insulin resistance, although the effect may be tempered by a relatively high proportion of lean body mass. Weight loss is associated with improved insulin sensitivity. Thus, diet-related factors that promote excessive energy intake may be regarded as promoters of insulin resistance. In the context of energy balance, diets characterized by high intakes of saturated fat and low intakes of dietary fiber are associated with reduced insulin sensitivity. Total fat intakes greater than the usually consumed range appear to promote insulin resistance, although the relative proportions of total fat and carbohydrate within the usual range appear unimportant. Monounsaturated fatty acids with a cis configuration and fiber-rich carbohydrate foods appear to be appropriate substitutes for saturated fatty acids and rapidly digested glycemic carbohydrates. In animal studies, n-3 unsaturated fatty acids have been shown to enhance insulin sensitivity and fructose and sucrose to increase insulin resistance. However, human data are limited. Large prospective studies currently being conducted should confirm the most appropriate macronutrient composition of diets for preventing and treating insulin resistance as well as establishing whether a range of candidate genes explains the variation in response to dietary change.     

Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome

Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m²) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes.     

N-3 vs. saturated fatty acids: Effects on the arterial wall

Cardiovascular disease is a leading cause of death worldwide. Atherosclerosis and unstable plaques are underlying causes for cardiovascular diseases. Cardiovascular disease is associated with consumption of diets high in saturated fats. In contrast there is increasing evidence that higher intakes of dietary n-3 fatty acids decrease risk for cardiovascular disease. Recent studies are beginning to clarify how n-3 compared with saturated fatty acids influence cardiovascular disease risk via pathways in the arterial wall. In this paper we will review studies that report on mechanisms whereby dietary fatty acids affect atherosclerosis through modulation of arterial wall lipid deposition, inflammation, cell proliferation, and plaque vulnerability.     

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.     

Dietary linoleic acid has no effect on arachidonic acid,but increases n-6 eicosadienoic acid,and lowers dihomo-γ-linolenic and eicosapentaenoic acid in plasma of adult men

High intakes of linoleic acid (LA,18:2n-6) have raised concern due to possible increase in arachidonic acid (ARA, 20:4n-6) synthesis, and inhibition of alpha linolenic acid (ALA, 18:3n-3) desaturation to eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). In healthy men, 10.5% energy compared to 3.8% energy LA with 1% energy ALA increased plasma phospholipid LA and 20:2n-6, the elongation product of LA, and decreased EPA, with no change in ARA. However, LA was inversely related to ARA at both 10.5% energy and 3.8% energy LA, (r=?0.761, r=?0.817, p<0.001, respectively). A two-fold variability in ARA among individuals was not explained by the dietary LA, ARA, ALA, or fish intake. Our results confirm LA requirements for ARA synthesis is low, <3.8% energy, and they suggest current LA intakes saturate Δ-6 desaturation and adversely affect n-3 fatty acid metabolism. Factors other than n-6 fatty acid intake are important modifiers of plasma ARA.     

APOA2 ?256T>C polymorphism interacts with saturated fatty acids intake to affect anthropometric and hormonal variables in type 2 diabetic patients

Recent studies have established the interaction between APOA2 −256T>C polymorphism and dietary saturated fatty acids intake in relation to obesity on healthy individuals. In the current study, we investigate the effects of this interaction on anthropometric variables and serum levels of leptin and ghrelin in patients with type 2 diabetes. In this cross-sectional study, 737 patients with type 2 diabetes mellitus (290 males and 447 females) were recruited from diabetes clinics in Tehran. The usual dietary intake of all participants during the last year was obtained by validated semiquantitative food frequency questionnaire. APOA2 genotyping was performed by real-time PCR on genomic DNA. No significant relation was obtained by univariate analysis between anthropometric variables and APOA2 genotypes. However, after adjusting for age, gender, physical activity and total energy intake, we identified a significant interaction between APOA2-saturated fatty acids intake and body mass index (BMI). After adjusting for potential confounders, serum levels of ghrelin in CC genotype patients were significantly higher than T allele carriers (p = 0.03), whereas the case with leptin did not reveal a significant difference. The result of this study confirmed the interaction between APOA2 −256T>C polymorphism and SFAs intake with BMI in type 2 diabetic patients. In fact, homozygous patients for the C allele with high saturated fatty acids intake had higher BMI. The APOA2 −256T>C polymorphism was associated with elevated levels of serum ghrelin.     

Spectrum of effects of dietary long-chain fatty acids on rat intestinal glucose and lipid uptake

Isocaloric modification in the ratio of dietary polyunsaturated-to-saturated fatty acids influences intestinal uptake of actively and passively transported nutrients. This study was undertaken to determine which dietary fatty acid was responsible for these alterations in absorption. Adult female rats were fed isocaloric semisynthetic diets high in palmitic and stearic acids (SFA), oleic acid (OA), linoleic acid (LA), or linolenic acid (LNA). An in vitro technique was used to measure the uptake of varying concentrations of glucose as well as a series of fatty acids and cholesterol. Jejunal uptake of 40 mM glucose was highest in rats fed SFA and lowest in those fed LA; ileal glucose uptake was similar in OA, LA, and LNA, but was lowest in SFA. Jejunal uptake of medium-chain fatty acids (8:0-12:0) was higher in OA than in other diet groups; ileal uptake of medium-chain fatty acids was unaffected by diet. Jejunal and ileal uptake of 18:2 was higher in LNA than in SFA or OA; the uptake of the other long-chain saturated or unsaturated fatty acids was unchanged by diet. The ileal but not the jejunal uptake of cholesterol was increased in LA as compared with SFA or OA, and reduced in LNA as compared with LA. These transport changes were not explained by differences in the animals' food consumption, body weight gain, intestinal mass, or mucosal surface area. We postulate that these diet-induced transport alterations may be mediated via changes in brush border membrane phospholipid fatty acyl composition. Thus, intestinal transport of nutrients may be varied by isocaloric changes in the dietary content of individual fatty acids.     

Obesity modifies the relations between serum markers of dairy fats and inflammation and oxidative stress among adolescents

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.     

Dietary recommendations for the community towards the postponement of coronary heart disease.

The public has recently been confronted with many, often conflicting, recommendations about diet and reducing the risk of coronary heart disease (CHD). Dietary recommendations to the community designed to lower the risk of CHD should be specific, clear, and brief. People should be advised to reduce their intake of foods that are high in saturated fats and replace these partially with foods that are relatively high in polyunsaturated fats. This will lower both total fat and dietary cholesterol intakes and will also change the ratio of polyunsaturated to saturated fats.     

Associations between copper and zinc intakes from diet and mortality from cardiovascular disease in a large population-based prospective cohort study

Several studies have related cardiovascular disease (CVD) to serum concentrations of copper and zinc but not to their dietary intakes. We thought to examine the association between dietary intakes of copper and zinc with risk of mortality from CVD in a prospective study encompassing 58,646 healthy Japanese men and women aged 40-79 years. The intakes of copper and zinc were determined by a validated self-administered food frequency questionnaire, and their associations with risk of mortality from CVD were evaluated by Cox proportional hazard modelling. During 965, 970 person-years of follow-up between 1989-2009, we documented 3,388 CVD deaths [1,514 from stroke, 702 from coronary heart disease (CHD) and 1,172 from other CVD]. Copper intake was not associated with CHD mortality; however, the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality from stroke, other CVD and total CVD in the highest versus the lowest quintiles of copper intake among men were 1.78 (1.16-2.77; P-trend=0.007), 1.61 (1.01-2.81; P-trend =0.03) and 1.63 (1.21-2.33; P-trend=0.001), respectively, and those among women were 1.49 (1.00-2.19; P-trend=0.04), 1.59 (1.09-2.55; P-trend =0.02) and 1.36 (1.06-1.69; P-trend=0.01), respectively. Higher intakes of zinc was inversely associated with mortality from CHD in men; 0.68 (0.58-1.03; P-trend=0.05) but not women; 1.13 (0.71- 1.49; P-trend=0.61). No associations were observed with other mortality endpoints. In conclusion, dietary copper intake was positively associated with mortality from CVD in both genders; whereas, higher dietary zinc intake was inversely associated with mortality from CHD in men but not women.     

Dietary modulation of lipid metabolism and mechanical performance of the heart

Sudden Cardiac Death resulting from sustained ventricular fibrillation or malignant cardiac arrhythmia has been linked to the type of dietary fat intake in several economically well developed countries where high levels of saturated fatty acids are common. Experimental studies with the small non-human primate marmoset monkey have clearly demonstrated the health benefit of substituting polyunsaturated fatty acids (PUFA's) for dietary saturated fatty acids. Heart rate and blood pressure are lowered, while the left ventricular ejection fraction and the electrical threshold for the induction of ventricular fibrillation are both increased after prolonged feeding of PUFA enriched diets. All these changes in heart function reduce the risk of developing malignant cardiac arrhythmias.The fatty acid composition of cardiac membrane phospholipids is profoundly altered by these changes in dietary lipid intake. In particular the proportions of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexae noic acid (DHA) are altered in such a way that the production of myocardial eicosanoids is affected. Although the changes in proportion of these long-chain PUFA's in cardiac phosphatidyl ethanolamine and phosphatidyl inositol are not identical, the shift in balance between these substrates or inhibitors of cyclo-oxygenase activity leads to relatively greater production of prostacyclin (PGI₂) than thromboxane (TXA₂).The effect of the omega-3 PUFA's of fish oil is proportionally greater than that of linoleic acid (LA; 18:2, 6) rich sunflower seed oil, particularly during ischaemia, and probably reflects the different nutritionally induced changes in cardiac membrane fatty acid composition by these different types of dietary PUFA's. (Mol Cell Biochem 116: 19–25, 1992).