Egg consumption, cardiovascular diseases and type 2 diabetes.

Eggs are rich in nutrients and a source of essential fatty- and amino acids, and the food item with highest cholesterol content. Since the 1970s dietary recommendations have advised limiting egg intake to 2-4 a week for the healthy population, and in those diagnosed with cardiovascular disease (CVD) and type 2 diabetes (T2D) an even more restricted consumption. The aim of the present paper was to assess the recommendation to lower the dietary intake of cholesterol and especially the intake of egg to reduce the risk of CVD and T2D. We performed three web-based literature searches on human studies (observational and interventional) published within the past 10 years during spring 2015. High-quality intervention studies have found nonsignificant effects of increasing the consumption of eggs on risk markers for CVD and T2D in healthy subjects and subjects with T2D. The risk associations found in the observational studies are more likely to be attributed to a dietary pattern often accompanying high egg intake and/or the cluster of other risk factors in people with high egg consumption. Dietary patterns, physical activity and genetics affect the predisposition of CVD and T2D more than a single food item as eggs. In conclusion, up to seven eggs per week can safely be consumed, but in patients with established CVD or T2D only with special emphasis on a healthy lifestyle.

Intake of ruminant trans fatty acids in the Danish population aged 1-80 years.

OBJECTIVE: To estimate the intake of ruminant trans fatty acids (TFA) in the Danish population aged 1-80 years. DESIGN: Descriptive study. SUBJECTS: A sex- and age-stratified random sample drawn from the Danish Civil Registration System. A total of 3098 participants (51% female) aged 1-80 years were included. The participation was 66%. DIETARY INFORMATION: A 7-day dietary record. RESULTS: The estimated median intake of ruminant TFA was 1.4 g/day with the 80% central range being from 0.9 to 2.1 among children aged 1-6 years and 1.6 g/day (1.0-2.4) among children aged 7-14 years. The median TFA intake was 1.8 g/day (0.9-2.9) among adults aged 15-29 years and among adults aged 30-80 years. The intake expressed as percentage of energy intake was 0.8, 0.6, 0.7, and 0.7, respectively. Dairy products were the main source of ruminant TFA. CONCLUSIONS: The median intake of ruminant TFA in the Danish population aged 1-80 years is estimated to be 1.7 g/day (0.9-2.7), corresponding to 0.7% of energy intake (0.5-1.0), with dairy products being the main source of ruminant TFA. SPONSORSHIP: The Danish Heart Foundation (Grants 02-2-9-8-22010 and 03-2-9-4-22087) and the Female Researchers in Joint Action (FREJA) programme from the Danish Medical Research Council.

Marine n-3 fatty acids, wine intake, and heart rate variability in patients referred for coronary angiography.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs) derived from fish may reduce the incidence of sudden cardiac death (SCD). In addition, wine drinking is suggested to have a protective effect against cardiovascular death. METHODS AND RESULTS: We included 291 patients referred for coronary angiography in whom ischemic heart disease was suspected and all of whom completed a food questionnaire regarding fish and wine intake. The n-3 PUFA composition of granulocyte membranes and of adipose tissue was measured. In addition, 24-hour heart rate variability (HRV) was analyzed. Fish intake was positively associated with the level of n-3 PUFAs in adipose tissue. Significant positive correlation coefficients were found between HRV indices and the levels of n-3 PUFAs in granulocytes. Wine intake was also significantly positively related to HRV, but the patients with the highest wine intake also had the highest intake of fish, as documented by a high n-3 PUFA content in adipose tissue. Multiple linear regression analysis revealed that traditional factors such as treatment with ss-blockers, smoking, age, and previous myocardial infarction were independently related to HRV, and furthermore that n-3 PUFAs (but not wine intake) were significantly independently associated with HRV. CONCLUSIONS: The close positive association between n-3 PUFAs and HRV in patients suspected of having ischemic heart disease may indicate a protective effect of n-3 PUFAs against SCD. This may partly explain the reduction in SCD observed in humans with a modest intake of n-3 PUFA. Wine intake was also positively correlated with HRV, but this correlation was no longer significant after controlling for the cellular level of n-3 PUFA.

Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy.

OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a) [apo(a)] in particular to CVD in nephropathic patients with IDDM. RESEARCH DESIGN AND METHODS: We investigated 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients matched for sex, age, diabetes duration, and BMI. RESULTS: The prevalence of CVD was 30 and 12% in patients with and without nephropathy, respectively (P < 0.001). The level of apo(a) was significantly higher in patients with nephropathy, 189 (20-2,350) U/l as compared with the normoalbuminuric group, 103 (20-1,940) U/l (P < 0.005). The prevalence of plasma apo(a) > 300 U/l (at-risk level for cardiovascular pathogenicity) was 38% (31-45) vs. 22% (16-28) in patients with and without nephropathy, respectively (P < 0.0005). In nephropathic patients, the prevalence of plasma apo(a) > 300 U/l was raised in patients with CVD (48%, 36-61%) as compared with patients without (34%, 26-42%) (P = 0.05). Furthermore, the serum concentrations of the following apolipoproteins and lipids were higher in patients with nephropathy as compared with normoalbuminuric patients: apoB 1.33 +/- 0.37 vs. 1.06 +/- 0.26 g/l; total cholesterol 5.6 +/- 1.2 vs. 4.8 +/- 0.9 mmol/l; and triglycerides 1.22 (0.31-9.87) vs. 0.77 (0.28-3.05) mmol/l, P < 0.0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P < 0.05). CONCLUSIONS: Dyslipidemia and raised plasma concentrations of apo(a), particularly > 300 U/l, may contribute to the enhanced morbidity and mortality from CVD characteristically observed in IDDM patients with diabetic nephropathy.

Marine docosenoic acid isomer distribution in the plasma of Greenland Eskimos.

The natural docosenoic acid in the human diet can be predominantly 22:1 omega 9 if of plant (generally rapeseed oil) origin, or predominantly 22:1 omega 11 if of marine origin. The fatty fatty acids of dietary fats (meals) and plasma lipids of some Greenland eskimos were examined by open-tubular gas-liquid chromatography. The dietary docosenoic acid isomer distribution pattern showed 22:1 omega 11 to be about 5 times 22:1 omega 9, a ratio typical of marine mammal fats. A similar ratio was also found in the plasma fatty acids, but with a slightly higher proportion of 22:1 omega 9. When correlated with the excellent cardiovascular health of Greenland eskimos, the docosenoic acid data suggest that current concern as to the impact of dietary docosenoic acids on the human myocardium, largely based on animal feeding studies, may be exaggerated.

The composition of the Eskimo food in north western Greenland.

In the winter of 1976 an examination of the composition of Eskimo food was carried out in north western Greenland. Duplicate specimens of diets collected from 50 adults, equal numbers of males and females, were analyzed for water, ash, protein, fat, individual fatty acids, cholesterol, and carbohydrate. The results are compared with those of typical Danish diets. Seal and the fish are predominant Eskimo food. Marked differences between Eskimo and Danish food were found. The Eskimo diets were richer in polyunsaturated fatty acids, the ratio to saturated fatty acids was 0.84 as compared with 0.24 in Danes. The polyunsaturated fatty acids were predominantly of the linolenic class (n-3) in Eskimos and the linoleic class (n-6) in Danes. Monoenes other than palmitoleic and oleic acids were high in Eskimo diets, but negligible in Danish. The results are related to previous examinations of the plasma lipids in Eskimos. The rarity of ischemic heart disease in Greenland Eskimos may partly be explained by the antithrombotic effect of the long-chained polyunsaturated fatty acids, especially eicosapentaenoic acid prevalent in diets rich in marine oils.

Fatty acid composition of the plasma lipids in Greenland Eskimos.

Gas-liquid chromatography analyses have been carried out to investigate the composition of esterified fatty acids in the plasma lipids in 130 Greenland Eskimos, compared with those of 32 Greenland Eskimos living in Denmark and of 31 Caucasian Danes in Denmark. While the Eskimos living in Denmark did not differ substantially from other persons living in Denmark and, from what is found in other studies in Western communities, the Greenland Eskimos showed a completely different pattern. They demonstrated a much higher proportion of palmitic, palmitoleic, and timnodonic acids, while they had a markedly lower concentration of linoleic acid. The total concentration of polyunsaturated fatty acids was lower in Greenland Eskimos than in the other groups. These findings are discussed in the light of the generally accepted opinion of the beneficial effect on plasma lipid levels and on the morbidity of coronary atherosclerosis of a high dietary intake of polyunsaturated fatty acids. As plasma lipid and lipoprotein levels in Greenland Eskimos in a previous study were found markedly lower than those found in Western populations, and as coronary atherosclerosis seems to occur far less commonly among Eskimos in Greenland than among peoples in industrialized countries, it was found difficult to combine these observations with the results from the present study. If dietary differences are the main reason for the differences in plasma lipid concentrations, the results from the present study point more toward qualitative than toward quantitative differences in respect of fatty acid composition of the food.

Heart rate variability and fatty acid content of blood cell membranes: a dose-response study with n-3 fatty acids.

BACKGROUND: Dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against sudden cardiac death, an event that may be predicted by measurement of heart rate variability (HRV). OBJECTIVE: The objectives of this study were to 1) examine the correlations between the content of fatty acids in blood cell membranes (platelets and granulocytes) and HRV in healthy subjects, and 2) assess the effect on HRV of dietary intervention with n-3 PUFA in different doses. DESIGN: Sixty healthy volunteers (25 women and 35 men) were randomly assigned to 3 treatment groups in a double-blind design. Subjects received a daily supplement of either 6.6 g n-3 PUFA, 2.0 g n-3 PUFA, or placebo (olive oil). A 24-h Holter recording was obtained for each subject before supplementation and after 12 wk of supplementation; the 24-h HRV was then related to the content of fatty acids in granulocytes and platelets. RESULTS: Before supplementation, positive correlations were observed in men between the content of docosahexaenoic acid in cell membranes and HRV indexes (r = 0.50, P < 0.01), whereas such correlations were not found in women. Dietary intervention revealed a dose-dependent effect of n-3 PUFA on HRV in men, whereas no effect was found in women. CONCLUSION: The study showed a beneficial effect of n-3 PUFA on HRV in healthy men, suggesting an antiarrhythmic effect of n-3 PUFA. No such effect was observed in healthy women.

Fish oil in angina pectoris.

The effect of 12 weeks supplementation with fish oil on the number of anginal attacks and consumption of glyceryltrinitrate in 36 patients with stable angina pectoris was evaluated in a clinically controlled trial using a vegetable oil as placebo. Fish oil caused a decrease in frequency of angina, but was not significantly superior to placebo. However, due to the small sample size and a high spontaneous variation in number of anginal attacks, a risk of up to 50% of overlooking a 30% reduction in anginal attacks could be estimated. A significant inhibition of the epinephrine-induced platelet aggregation and a significant increase in intraplatelet cyclic AMP were induced by fish oil.

Cod liver oil inhibits neutrophil and monocyte chemotaxis in healthy males.

Epidemiological evidence suggests a reduced rate of chronic inflammatory diseases and ischaemic heart disease in populations with a high consumption of fish. This has been ascribed to the high content in sea food of polyunsaturated fatty acids (PUFAs), belonging to the n - 3 family. We have studied neutrophil and monocyte chemotaxis in 12 healthy males before and after 6 weeks supplementation with cod liver oil, corresponding to 5.3 g n - 3 PUFAs daily. Neutrophil and monocyte chemotaxis were investigated using the under agarose technique with N-formyl-methionyl-leucyl-phenylalanine (N-FMLP) and autologous serum as chemoattractants. Neutrophil chemotaxis towards both chemoattractants and monocyte chemotaxis towards N-FMLP were significantly reduced after supplementation with cod liver oil.

The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure.

Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study, with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil. Each oil containing approx. 40% of n-3 and n-6 polyunsaturated fatty acids (PUFA) respectively. During the n-3 PUFA period, systolic blood pressure, plasma total lipids, triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III (AT-III) rose. Cutaneous bleeding time increased significantly. In contrast only AT-III rose during the n-6 PUFA feeding, however, more marked than during the n-3 oil period. It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases. It is in this respect superior to that of n-6 PUFA, stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted.

Dose-response studies on the effect of n-3 polyunsaturated fatty acids on lipids and haemostasis.

We have studied the dose-response effects of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA's) on lipids and haemostasis. Ten healthy males were each given 1.3 g, 4 g or 9 g of n-3 PUFA's daily for 6-week periods. Bleeding time, HDL-cholesterol and plasminogen activator inhibitor increased with the dose of n-3 PUFA. Plasma fibrinogen and triglyceride levels were reduced in a dose-dependent fashion. After ingestion of 1.3 g of n-3 PUFA's plasma fibrinogen decreased from 9 to 7 mumol/l and HDL-cholesterol increased from 1.2 to 1.3 mmol/l. The bleeding time was prolonged from 5 to 6.5 min while triglyceride levels decreased from 1.2 to 0.9 mmol/l after ingestion of 4 g of n-3 PUFA's. Dietary supplementation with the highest daily dose (9 g) reduced plasma levels of triglycerides, fibrinogen and von Willebrand factor, while bleeding time, plasminogen activator antigen, plasminogen activator inhibitor and the ratio of HDL-cholesterol to total cholesterol increased.

The effect of n-3 fatty acids on lipids and haemostasis in patients with type IIa and type IV hyperlipidaemia.

Plasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type IIa and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction.

To elucidate a possible antiarrhythmic effect of long-chained n-3 polyunsaturated fatty acids, heart rate variability was assessed in 52 patients with a previous myocardial infarction and left ventricular dysfunction. The content of n-3 polyunsaturated fatty acids in platelets was closely associated with the patient's fish-consuming habits, and a significant positive correlation was observed between the n-3 fatty acid docosahexaenoic acid and heart rate variability.

Omega-3 fatty acids. Current status in cardiovascular medicine.

Omega-3 polyunsaturated fatty acids (PUFA) reduce fasting and postprandial triglycerides, decrease platelet and leucocyte reactivity, and may slightly decrease blood pressure. Omega-3 PUFA may also beneficially influence vessel wall characteristics and blood rheology. Furthermore, these compounds have been shown to inhibit ventricular tachyarrhythmias in animals. Omega-3 PUFA may impair fibrinolysis and could lead to increased oxidation of lipoproteins. Potential adverse effects must not be neglected, but should be viewed in light of the beneficial effects of these agents. Clinical studies investigating the effects of dietary omega-3 PUFA in the prevention and treatment of cardiovascular disease (CVD) are beginning to emerge. The results have offered some promise, but further studies are needed to define the role of these agents in CVD. Long term trials and studies using omega-3 PUFA as adjuvants to conventional therapy in patients with coronary artery disease, hyperlipidaemia and hypertension may be of particular interest.

Mortality from ischaemic heart disease and cerebrovascular disease in Greenland.

Mortality 1968-83 from Ischaemic Heart Disease (IHD) and Cerebrovascular Disease (CD) was studied in native Greenlanders. Mortality from IHD was lower in Greenland than in Denmark for both males and females and especially low in Greenlandic settlements. IHD mortality decreased during the period. Mortality from CD was higher in Greenland than in Denmark with no certain time trend. Living conditions, of which a high intake of seafood may be a key factor, and/or a genetic predisposition seem to protect Greenlanders from IHD and to predispose them to CD.

PIP: Mortality from ischemic heart disease and cerebrovascular disease among native Greenlanders is studied and compared with sex-specific rates in Denmark. Living conditions, nutrition, and genetic predisposition are considered as factors influencing these causes of death.

Hyperlipoproteinemia, diabetes, and oxygen affinity of hemoglobin.

Oxyhemoglobin dissociation curves (ODC) were performed on blood from diabetic and nondiabetic subjects with and without hypertriglyceridemia. P50 at in vivo pH was slightly lower than normal in normolipemic diabetics (25.7 versus 26.6 mmHg, p less than 0.05), in spite of increased red cell 2,3-diphosphoglycerate concentration (15.4 versus 14.4 mumole/g Hg, p less than 0.025). P50 at in vivo pH in diabetics with moderately elevated very low density lipoproteins (VLDL)--Type IV hyperlipoproteinemia (HLP)--was likewise found to be slightly lower than normal (25.5 versus 26.6 mmHg, p less than 0.05). In contrast, diabetics with pronounced hyperlipemia due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons as well as VLDL (type V HLP) showed markedly increased hemoglobin--oxygen affinity (P50:21.1 versus 26.6 mmHg, p less than 0.001). The change in the ODC of normolipemic diabetics is considered to be an expresssion of the presence of an increased proportion of a hemoglobin fraction (Hb Alc) with increased oxygen affinity. The additional change in the ODC of the hyperlipemic patients is thought to be secondary to accumulation of triglyceride-rich particles for the following reasons: (1) a similar increase in oxygen affinity of hemoglobin was demonstrated in familial type I HLP of nondiabetic subjects; (2) normal red cells increased their oxygen affinity when incubated in lactescent plasma; (3) in both acquired types I and V HLP the disappearance of HLP was followed by a normalization of the ODC.

Plasma 6-keto-PGF1 alpha, thromboxane B2 and PGE2 during diabetic ketoacidosis.

In 10 patients admitted to hospital with diabetic ketoacidosis plasma prostanoids 6-keto-PGF alpha, thromboxane B2 and PGE2 were studied before treatment and following recovery. During ketoacidosis the median plasma 6-keto-PGF1 alpha and PGE2 were significantly increased compared to those of a normal reference group: 5.2 pg/ml and 3.9 pg/ml versus 1.7 pg/ml and 0.4 pg/ml (p less than 0.01 and p less than 0.05). In response to therapy both prostanoids decreased significantly towards a normal level, 6-keto-PGF1 alpha: 0.5 pg/ml p less than 0.01 and PGE2: 0.08 p less than 0.05 respectively. The changes in plasma 6-keto-PGF1 alpha were negatively correlated to changes in pH, rho: -0.7788 p = 0.0135, whereas the changes in PGE2 were positively correlated to serum creatinine at admittance, rho: 0.6976, p = 0.0368 and to the amount of intravenous fluid and insulin used during treatment, rho: 0.7500 p = 0.0126 and rho: 0.8424, p = 0.0023 respectively. Plasma thromboxane B2 concentrations were not elevated and did not change after treatment of the ketoacidosis.

Interactions between sodium salicylate and acetyl salicylic acid evaluated using ADP induced platelet aggregation and bleeding time.

1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 mumol/l and 2.5 mumol/l ADP. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsalicylic acid from inhibiting the secondary aggregation. Sodium salicylate was without effect on the bleeding time and did not inhibit the prolongation induced by acetyl salicylic acid. Our study does not lend support to the concept of an important interaction in vivo between acetyl salicylic acid and its first metabolite salicylate in man.

Verapamil does not alter platelet function in patients with recent myocardial infarction.

Reports concerning the influence of the calcium antagonist verapamil on platelet function are conflicting. In a randomized double blind trial including 52 patients with acute myocardial infarction the effect of verapamil 120 mg given perorally three times a day for three months was investigated. There were no alterations in cutaneous bleeding time, platelet aggregate ratio or platelet aggregation induced by ADP or collagen. Verapamil administered in therapeutic doses does not seem to affect platelet function in patients with ischaemic heart disease.