Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.

BACKGROUND: Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. OBJECTIVES: The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. DESIGN: The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. RESULTS: Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. CONCLUSIONS: Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.     

Plasma n-3 polyunsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean and Mongolian workers

The favorable role of n-3 polyunsaturated fatty acid (PUFA) in cardiovascular disease (CVD) has been demonstrated in animal experiments and in humans in Western countries, but its effect remains controversial in Asian populations. An observational study of Japanese, Koreans and Mongolians with extended histories of remarkably different frequencies of fish intake was conducted to examine whether differences in plasma n-3 PUFA affects CVD risk factors. We conducted a cross-sectional study in workplace settings and determined body mass index (BMI), blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride (TG), glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and fatty acid composition in plasma. A total of 411 Japanese, 418 Korean and 252 Mongolian workers aged 30-60 yr participated in this study. The Japanese ate fish more frequently and had remarkably higher values of eicosapentaenoic acid, docosahexaenoic acid and n-3 PUFA, and lower values of BMI and HOMA-IR, followed by the Koreans, and then the Mongolians. In age groups, the Japanese and Koreans showed a similar tendency of increase in n-3 PUFA with increasing age. General linear measurement multivariate analysis after adjustment for gender, age, smoking, drinking, exercise habits and BMI showed n-3 PUFA was associated with HDL-C and TG in the Japanese, while it was associated with systolic blood pressure in the Koreans, and TG in the Mongolians. In conclusion, an increase in n-3 PUFA was associated with HDL-C and TG in the Japanese and Mongolians, but these beneficial effects were not constant across the three Asian ethnic groups.     

Cardiovascular disease risk factors in an Indochinese population

One hundred seventeen Indochinese adults were screened for heart disease risk factors at a San Diego community health facility during December 1986. Two levels of excess risk, moderate-high and high, were categorically defined for blood pressure, total cholesterol, cigarette smoking, and obesity. Overall, 61% were at moderate-high or high risk in at least one category, and 34% were at high risk by these criteria. Systolic blood pressure, diastolic blood pressure, and total cholesterol were positively correlated to age, and ethnicity was a significant covariate for cholesterol, body mass index, and cigarette smoking. The Hmong, compared with other Indochinese, had a significantly lower mean cholesterol level, which remained after adjusting for age and body mass. High rates of cigarette smoking were found among Vietnamese men and young Indochinese men. If confirmed, the high prevalence of heart disease risk factors in Indochinese refugees and immigrants suggests that cardiovascular health education programs are appropriate in Indochinese communities.     

Incidence and prevalence of end-stage renal disease among Ontario's James Bay Cree.

End-stage renal disease (ESRD) and chronic renal failure (CRF) among Canadian natives is more common than among the general Canadian population. The results of this study show the James Bay Cree in Northern Ontario in 1989 experienced ESRD prevalence rates 3.2 times greater than the national rate. The average annual incidence rates for 1981-1989 were 1.6 times the national rate. Methodological difficulties inherent in incidence and prevalence studies of native Canadians are examined. With tertiary treatment care facilities available only in southern urban centres, native Canadians in remote northern communities face considerable psychosocial disruption when seeking out medical assistance for ESRD such as renal dialysis services.     

Regular consumption of n-3 fatty acid-enriched pork modifies cardiovascular risk factors

The long-chain (LC) n-3 PUFA content of pork, particularly DHA, can be increased by including 15% PorcOmega (a fortified tuna fishmeal product) in pig finisher diets. The aim of the present study was to see whether this enriched pork could deliver cardiovascular health benefits to consumers. In a double-blind intervention trial, thirty-three healthy adult volunteers (sixteen female and seventeen male) were randomised to consume either n-3-enriched or regular (control) pork (a selection of five fresh cuts totalling 1000 g/week) for 12 weeks. Fasting blood samples were collected every 4 weeks and analysed for serum lipids, maximally stimulated thromboxane production and erythrocyte fatty acid composition. The n-3-enriched pork provided subjects with 1.3 g LC n-3 PUFA per week. Erythrocyte DHA levels rose 15% in the n-3 group and fell 5% in the control group over 12 weeks (P=0.001). Compared with the control group, serum TAG decreased to a greater extent in the n-3 group (P=0.02) and serum thromboxane production increased to a lesser extent (P=0.004). Changes in the latter were inversely associated with changes in incorporation of DHA into erythrocytes (r -0.54; P<0.05). Thus the modest increases in LC n-3 PUFA intake resulting from regular consumption of enriched pork can improve cardiovascular risk factors.     

Evaluation of the relation between n-3 and n-6 fatty acid status and parity in nonpregnant women from the Netherlands

BACKGROUND: We previously observed an inverse relation between parity and docosahexaenoic acid (DHA) status in pregnant women in the Netherlands. This implies that maternal DHA status may not fully normalize after a mature pregnancy. OBJECTIVE: The objective was to investigate the relation between the essential fatty acid status (in particular the DHA status) of nonpregnant women and the number of completed pregnancies and whether the number of previous pregnancies is associated with a lower DHA status in women from the Netherlands. DESIGN: This was a cross-sectional study of 129 healthy nonpregnant women who completed 0, 1, 2, 3, or 4 mature, uncomplicated, singleton pregnancies. RESULTS: The relative amount of DHA in the plasma phospholipids of nulliparous women and of mothers who completed 1-4 pregnancies (duration since last pregnancy: 3.9 +/- 2.4 y) was not significantly different; a significant correlation between parity and the percentage of DHA in the phospholipids was not observed either. The percentage of DHA in the phospholipids of erythrocytes of mothers was significantly lower than the percentage in the erythrocytes of the nulliparas (P = 0.013), but no significant correlation between the percentage of DHA in the phospholipids of erythrocytes and parity was found. The time interval between the different pregnancies did not influence maternal DHA status. CONCLUSIONS: No relation was found between DHA status and parity in the nonpregnant Dutch women whose last pregnancy was completed > or = 1 y previously. Maternal DHA status, as reflected in plasma and erythrocyte phospholipids, probably normalized within 1 y after the last partus. Whether this is true for other tissues remains to be determined.     

Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats

PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.     

Impact of foods enriched with n-3 long-chain polyunsaturated fatty acids on erythrocyte n-3 levels and cardiovascular risk factors

Consumption of fish or fish oils rich in the n-3 long chain PUFA EPA and DHA may improve multiple risk factors for CVD. The objective of this study was to determine whether regular consumption of foods enriched with n-3 long-chain PUFA can improve n-3 long-chain PUFA status (erythrocytes) and cardiovascular health. Overweight volunteers with high levels of triacylglycerols (TG; >1.6 mmol/l) were enrolled in a 6-month dietary intervention trial conducted in Adelaide (n 47) and Perth (n 39), and randomised to consume control foods or n-3-enriched foods to achieve an EPA + DHA intake of 1 g/d. Test foods were substituted for equivalent foods in their regular diet. Erythrocyte fatty acids, plasma TG and other CVD risk factors were monitored at 0, 3 and 6 months. There were no significant differences between groups for blood pressure, arterial compliance, glucose, insulin, lipids, C-reactive protein (CRP) or urinary 11-dehydro-thromboxane B2 (TXB2) over 6 months, even though regular consumption of n-3-enriched foods increased EPA + DHA intake from 0.2 to 1.0 g/d. However, the n-3 long-chain PUFA content of erythrocytes increased by 35 and 53 % at 3 and 6 months, respectively, in subjects consuming the n-3-enriched foods. These increases were positively associated with measures of arterial compliance and negatively associated with serum CRP and urinary 11-dehydro-TXB2 excretion. Sustainable increases in dietary intakes and erythrocyte levels of n-3 long-chain PUFA can be achieved through regular consumption of suitably enriched processed foods. Such increases may be associated with reduced CV risk.     

Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status but not bone mass in piglets

Dietary (n-6) and (n-3) fatty acids have been implicated as important regulators of bone metabolism. The main objective of this research was to define the response of whole-body growth, fatty acid status and bone mass to a reduced dietary (n-6):(n-3) fatty acid ratio. A secondary objective was to determine whether there is an amount of fat x fatty acid ratio interaction for these outcomes. Piglets (n = 32) were randomized to 1 of 4 diets: group 1: [30 g fat/L + (n-6):(n-3) ratio 4.5:1]; group 2: [30 g fat/L + (n-6):(n-3) ratio 9.0:1]; group 3: [60 g fat/L + (n-6):(n-3) ratio 4.5:1]; and group 4: [60 g fat/L + (n-6):(n-3) ratio 9.0:1]. After 21 d, outcomes assessed included growth, fatty acid status and bone mass and metabolism. Growth and bone mass did not differ among the four groups nor did arachidonic acid (AA as g/100 g fatty acids) in plasma, adipose and brain. Piglets fed diets 1 and 3 with the lower (n-6):(n-3) ratio had lower liver AA (P < 0.001). Those fed diets 1 and 2 containing 30 g fat/L had lower docosahexaenoic acid (DHA as g/100 g fatty acids) in liver (P < 0.001), plasma (P = 0.019) and adipose tissue (P = 0.045). However, piglets fed diets 1 and 3 had higher (P < 0.001) brain DHA than those fed diets with a higher (n-6):(n-3) ratio. Higher plasma DHA was associated with less bone resorption (r = -0.44, P = 0.01). Therefore, elevation of dietary (n-3) fatty acids supports growth and fatty acid status while not compromising bone mass. The results may be of relevance to the nutritional management of preterm infants whose DHA status is often too low and bone resorption too high.     

Interactions between dietary n-3 fatty acids and genetic variants and risk of disease

Nutritional genomics has undergone rapid development and the concept is now very popular with the general public. Therefore, there is increasing demand for knowledge on adapting dietary composition to the genome. Our aim has been to undertake a systematic review so as to find out the level of evidence existing on whether the effects of n-3 fatty acids on health can be modulated by genetic variation. A systematic literature search was conducted on studies that jointly analyse the effect of one or more genetic variants in candidate genes and n-3 fatty acids. Both observational and experimental studies were included. Results are classified in accordance with whether the study was undertaken on intermediate phenotypes (plasma lipid concentrations, glucose, inflammation markers, anthropometric measurements) or disease phenotypes (cancer, cardiovascular diseases, metabolic syndrome, etc) and whether it was experimental or observational. A wide diversity of genetic variants and little consistency in the publication of replication studies was found. Greater consistency was observed in studies that involved the FADS1 and FADS2 locus in the determination of n-3 fatty acid concentrations in biological samples. Most of the studies were designed to measure gene-diet interactions and not diet-gene interactions. Despite the fact that multiple studies have shown statistically significant interactions between n-3 fatty acids and certain genetic variants on intermediate and disease phenotypes, the individual level of evidence is very low and recommendations cannot be made on increasing or reducing the intake of n-3 fatty acids based on each individual's genotype.     

Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease

Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be appreciated that linoleic acid does not reflect the functions of dihomo-gamma-linolenic and arachidonic acid, and that the endogenous rate of conversion of linoleic to arachidonic acid is slow (Hassam et al. 1975, 1977; Phylactos et al. 1994; Harbige et al. 1995). In addition to effects of dietary fatty acids on immunoregulation, inflammation as a consequence of immune activation in autoimmune disease may also be an important mechanism of action whereby dietary fatty acids modulate disease activity. In conclusion, regulation of gene expression, signal transduction pathways, production of eicosanoids and cytokines, and the action of antioxidant enzymes are all mechanisms by which dietary n-6 and n-3 fatty acids may exert effects on the immune system and autoimmune disease. Probably the most significant of these mechanisms in relation to our current understanding of immunoregulation and inflammation would appear to be via fatty acid effects on cytokines. The amount, type and balance of dietary fatty acids and associated antioxidant nutrients appear to impact on the immune system to produce immune-deviation or immunosuppressive effects, and to reduce immune-mediated inflammation which will in turn affect the susceptibility to, or severity of, autoimmune disease.     

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.     

Cardiovascular disease risk factors and menopausal status in midlife women from the former Soviet Union

The purpose of this cross-sectional analysis is to examine modifiable CVD risk factors in relation to menopausal status, age, and length of residence in the U.S. of midlife women from the former Soviet Union. The analysis includes baseline data for 193 women, aged 40-70, who lived in the U.S. fewer than 8 years and were enrolled in an ongoing four-year study of post-immigration health and behavior change. Data collection was conducted in women's homes or other community locations. The presence of seven health risk indicators (obesity, dyslipidemia, high blood pressure, diabetes mellitus, sedentary lifestyle, smoking, and excessive alcohol use) was assessed. In addition, Framingham 10 year risk scores for heart disease, and the presence of metabolic syndrome, were calculated using recent National Cholesterol Education Program (ATP-III) guidelines. Consistent with the age distribution, 60% of the women were postmenopausal. Four risk indicators (obesity, dyslipidemia, high blood pressure, and sedentary lifestyle) were identified as significant areas of concern. Although the Framingham risk scores did not seem excessively high, almost 25% of the women had metabolic syndrome. Older and postmenopausal women had significantly higher scores on all risk estimates. When age and menopausal status were held constant, menopausal status remained an independent contributor for the number of CVD risk indicators. Issues specific to this group of women because of their pre- and post-migration lifestyles are discussed in relation to their CVD risk status.