I.A. Brouwer

Folate intake in Europe: recommended, actual and desired intake

Objectives: To evaluate possible inconsistencies between recommended, actual and desired folate intake in European adult populations. Design: Review of dietary recommendations, of food consumption surveys, and of intervention and observational studies relating folate intake to the risk of neural tube defects and plasma homocysteine levels. Results: In Europe, mean dietary folate intake in adults is 291u2005μg/d (range 197–326) for men and 247u2005μg/d (range 168–320) for women. The recommended intakes vary between 200–300u2005μg/d (men) and 170–300u2005μg/d (women). However, women with a previous pregnancy affected by a neural tube defect (NTD), are recommended to take 4000u2005μg/d of supplemental folic acid when planning a subsequent pregnancy. For those without a history of NTD, the use of 400u2005μg/d of supplemental folic acid is the best option to prevent the occurrence of NTDs. A daily dose of 650u2005μg supplemental folic acid normalises elevated plasma homocysteine levels, which is a risk factor for cardiovascular diseases. A dietary folate intake of at least 350u2005μg/d is desired to prevent an increase in plasma homocysteine levels of the adult population in general. Conclusions: Mean dietary folate intake in Europe is in line with recommendations, but the desired dietary intake of <350u2005µg/d is only reached by a small part of studied European populations. It is considered unethical to investigate whether supplements with a dose lower than 400u2005μg/d of folic acid are also protective against NTDs. However, research to establish the lowest effective dose of dietary folate/supplemental folic acid to optimise homocysteine levels and research on the bioavailability of folate is required. This will enable the choice of a strategy to achieve desired folate intakes in the general population. In the meantime, consumption of plant foods like vegetables, fruits, and cereals should be stimulated to reach the desired level of 350u2005μg of dietary folate per day.

Lactotripeptides Show No Effect on Human Blood Pressure: Results From a Double-Blind Randomized Controlled Trial

Milk-derived peptides with ACE-inhibiting properties may have antihypertensive effects in humans. We conducted a randomized double-blind placebo-controlled trial to examine the blood pressure lowering potential of 2 ACE-inhibiting lactotripeptides, ie, Isoleucine-Proline-Proline and Valine-Proline-Proline. We included 135 Dutch subjects with elevated systolic blood pressure who were otherwise healthy and who received no current antihypertensive treatment. After a 2-week run-in period on placebo, subjects randomly received a daily dose of 200 mL dairy drink with 14 mg lactotripeptides obtained by concentrating fermented milk, enzymatic hydrolysis, or chemical synthesis, or placebo for 8 weeks, followed by a 2-week wash-out. The primary outcome was 8-week change in office systolic blood pressure. Secondary outcomes were change in diastolic blood pressure, home blood pressure, 24-hour ambulatory blood pressure, plasma ACE-activity, and plasma angiotensin II. Blood pressure at baseline was on average 142/84 mm Hg. Lactotripeptides did not significantly change systolic blood pressure (P=0.46) or diastolic blood pressure (P=0.31) compared with placebo. The mean difference (95%-CI) in systolic blood pressure response between treatment and placebo was 2.8 mm Hg (−2.6;8.2) for concentrated fermented milk lactotripeptides, −0.5 mm Hg (−6.0;5.0) for enzymatic lactotripeptides, and 1.6 mm Hg (−3.9;6.9) for synthetic lactotripeptides. Treatment neither had a significant effect on secondary outcome measures. In conclusion, the present study does not support the hypothesis of a blood pressure lowering effect of the lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline.

Trans fatty acids and cardiovascular health: research completed?

This review asks the question if further research on trans fatty acids and cardiovascular health is needed. We therefore review the evidence from human studies on trans fatty acids and cardiovascular health, and provide a quantitative review of effects of trans fatty acid intake on lipoproteins. The results show that the effect of industrially produced trans fatty acids on heart health seen in observational studies is larger than predicted from changes in lipoprotein concentrations. There is debate on the effect of ruminant trans fatty acids and cardiovascular disease. Of special interest is conjugated linoleic acid (CLA), which is produced industrially for sale as supplements. Observational studies do not show higher risks of cardiovascular disease with higher intakes of ruminant trans fatty acids. However, CLA, industrial and ruminant trans fatty acids all raise plasma low-density lipoprotein and the total to high-density lipoprotein ratio. Gram for gram, all trans fatty acids have largely the same effect on blood lipoproteins. In conclusion, the detrimental effects of industrial trans fatty acids on heart health are beyond dispute. The exact size of effect will remain hard to determine. Further research is warranted on the effects of ruminant trans fatty acids and CLA on cardiovascular disease and its risk factors.

Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects

Objective: High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of cardiovascular risk. We hypothesised that n-3 fatty acids reduce underlying inflammatory processes and consequently CRP concentrations in healthy middle-aged subjects.Design: Placebo-controlled, double-blind study.Subjects: A total of 43 men and 41 postmenopausal women aged 50–70u2009y. Before and after intervention, we measured serum CRP concentrations with an enzyme immunoassay.Interventions: Capsules with either 3.5u2009g/day fish oil (1.5u2009g/day n-3 fatty acids) or placebo for 12 weeks.Results: The median CRP change in the fish oil group did not significantly differ from that in the placebo group (0.01 vs −0.17u2009mg/l, P = 0.057).Conclusion: The currently available data —including ours— do not support that beneficial effects on CRP are involved in a mechanism explaining the protective effect on heart disease risk of n-3 fatty acids as present in fish.Sponsorship: Wageningen Centre for Food Sciences.

Effect of a High Intake of Conjugated Linoleic Acid on Lipoprotein Levels in Healthy Human Subjects

Background Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower high-density lipoprotein (HDL) cholesterol, raise low-density lipoprotein (LDL) cholesterol, and increase the risk of coronary heart disease. The effects of trans fatty acids from ruminants are less clear. We investigated the effect on blood lipids of cis-9, trans-11 conjugated linoleic acid (CLA), a trans fatty acid largely restricted to ruminant fats. Methodology/Principal Findings Sixty-one healthy women and men were sequentially fed each of three diets for three weeks, in random order, for a total of nine weeks. Diets were identical except for 7% of energy (approximately 20 g/day), which was provided either by oleic acid, by industrial trans fatty acids, or by a mixture of 80% cis-9, trans-11 and 20% trans-10, cis-12 CLA. After the oleic acid diet, mean (± SD) serum LDL cholesterol was 2.68±0.62 mmol/L compared to 3.00±0.66 mmol/L after industrial trans fatty acids (p<0.001), and 2.92±0.70 mmol/L after CLA (p<0.001). Compared to oleic acid, HDL-cholesterol was 0.05±0.12 mmol/L lower after industrial trans fatty acids (pu200a=u200a0.001) and 0.06±0.10 mmol/L lower after CLA (p<0.001). The total-to–HDL cholesterol ratio was 11.6% higher after industrial trans fatty acids (p<0.001) and 10.0% higher after CLA (p<0.001) relative to the oleic acid diet. Conclusions/Significance High intakes of an 80∶20 mixture of cis-9, trans-11 and trans-10, cis-12 CLA raise the total to HDL cholesterol ratio in healthy volunteers. The effect of CLA may be somewhat less than that of industrial trans fatty acids. Trial Registration ClinicalTrials.gov NCT00529828

Identification of potential serum biomarkers of inflammation and lipid modulation that are altered by fish oil supplementation in healthy volunteers.

Long chain n‐3 polyunsaturated fatty acids (n‐3 LCPUFA) lower risk of coronary heart disease (CHD), but mechanisms are not well understood. We used proteomics to identify human serum proteins that are altered by n‐3 LCPUFA. Such proteins could identify pathways whereby they affect CHD. Eighty‐one healthy volunteers entered a double blind randomised trial to receive 3.5u2005g of fish oil or 3.5u2005g of high oleic sunflower oil daily. Serum was collected before and after 6u2005wk of intervention. Serum was analysed by proteomics using 2‐DE. Proteins that were differentially regulated were identified by MS. We also analysed serum apolipoprotein A1 (apo A1), high‐density lipoprotein (HDL) particle size and haptoglobin. Serum levels of apo A1, apo L1, zinc‐α‐2‐glycoprotein, haptoglobin precursor, α‐1‐antitrypsin precursor, antithrombin III‐like protein, serum amyloid P component and haemopexin were significantly downregulated (all p<0.05) by fish oil compared with high oleic sunflower oil supplementation. Fish oil supplementation caused a significant shift towards the larger, more cholesterol‐rich HDL2 particle. The alterations in serum proteins and HDL size imply that fish oil activates anti‐inflammatory and lipid modulating mechanisms believed to impede the early onset of CHD. These proteins are potential diagnostic biomarkers to assess the mechanisms whereby fish oil protects against CHD in humans.

Rationale and design of a randomised controlled clinical trial on supplemental intake of n-3 fatty acids and incidence of cardiac arrhythmia: SOFA

Background: Evidence from earlier studies indicates that intake of very long-chain n-3 polyunsaturated fatty acids (n-3 PUFA, also named omega-3 fatty acids) as present in fish oil reduces the risk of sudden death. Sudden death forms a major part of mortality from cardiovascular disease and is in most cases a direct consequence of cardiac arrhythmia. n-3 PUFA may exert their protective effect through reducing the susceptibility for cardiac arrhythmia.Objective: To investigate the effect of n-3 PUFA on the incidence of recurrent ventricular arrhythmia. This paper presents the rationale, design and methods of the Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) and discusses problems encountered in conducting a multicentre clinical trial on food.Design: A randomised, parallel, placebo-controlled, double blind intervention study, which obeys the guidelines for Good Clinical Practice.Setting: Multiple cardiology centres in Europe.Subjects: A total of 500 patients with an implantable cardioverter defibrillator (ICD). An ICD detects, treats and stores cardiac arrhythmic events in its memory chip.Interventions: Patients receive either 2u2009g/day of fish oil, containing approximately 450u2009mg eicosapentaenoic acid and 350u2009mg docosahexaenoic acid, or placebo for 12 months.Primary outcome: Spontaneous ventricular tachyarrhythmias as recorded by the ICD or all-cause mortality.Conclusion: SOFA is designed to answer the question whether intake of n-3 PUFA from fish—a regular food ingredient—can reduce the incidence of life-threatening cardiac arrhythmia. If this proves to be true, increasing the intake of n–3 PUFA could be an easy, effective and safe measure to prevent fatal arrhythmia in the general population.Sponsorship: Wageningen Centre for Food Sciences. Wageningen Centre for Food Sciences is an alliance of major Dutch food industries, TNO nutrition and Food Research, Zeist, the Netherlands, and Wageningen University and Research Centre, Wageningen, the Netherlands, with financial support by the Dutch Government.

Association between n-3 fatty acid status in blood and electrocardiographic predictors of arrhythmia risk in healthy volunteers ☆

pattern of the inferior-posterior wall. This abnormality likely occurs because of external compression of the inferoposterior wall by an elevated diaphragm, which in turn is caused by high intra-abdominal pressures from organomegaly and/or ascites. Paradoxical inferior-posterior wall motion should not be confused with ischemia or intrinsic abnormality of the myocardium on echocardiography. Furthermore, it should alert the echocardiographer of the possible presence of elevated intra-abdominal pressures and advanced liver disease.

Antiarrhythmic effects of n-3 fatty acids: evidence from human studies

Purpose of review N-3 fatty acids from fish reduce cardiovascular mortality including sudden cardiac death. In this paper, the authors discuss the results of human studies with regard to the hypothesis that n-3 fatty acids reduce the risk of fatal coronary heart disease through antiarrhythmic effects. Recent findings Results from two recent clinical trials do not support a protective effect of n-3 fatty acids. In light of the earlier published bulk of evidence that n-3 fatty acids reduce cardiovascular mortality and sudden cardiac death, it is hard to explain these findings. Two recent observational studies confirmed that intake of n-3 fatty acids from fish is associated with less cardiovascular disease in the general population. They indicated that the protective effect of a fish meal may depend on the n-3 fatty acid content or preparation method and suggested a protective effect on arrhythmia rather than on atherosclerosis. Intervention studies on electrophysiological predictors of arrhythmia do not clearly confirm a beneficial effect of n-3 fatty acids. However, most of these studies were small or performed in healthy populations. Summary The available evidence still suggests that n-3 fatty acids may prevent fatal cardiac arrhythmia, but more conclusive studies are urgently needed.

Intake of very long chain n‐3 fatty acids from fish and the incidence of heart failure: the Rotterdam Study

Evidence is accumulating for a cardioprotective effect of fish or its n‐3 fatty acids, eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). We examined EPA plus DHA and fish intake in relation to incident heart failure in the population‐based Rotterdam Study.