Frank Thies

Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled trial

BACKGROUND Three daily portions of whole-grain foods could lower cardiovascular disease risk, but a comprehensive intervention trial was needed to confirm this recommendation. OBJECTIVES We aimed to assess the effects of consumption of 3 daily portions of whole-grain foods (provided as only wheat or a mixture of wheat and oats) on markers of cardiovascular disease risk in relatively high-risk individuals. DESIGN This was a randomized controlled dietary trial in middle-aged healthy individuals. After a 4-wk run-in period with a refined diet, we randomly allocated volunteers to a control (refined diet), wheat, or wheat + oats group for 12 wk. The primary outcome was a reduction of cardiovascular disease risk factors by dietary intervention with whole grains, which included lipid and inflammatory marker concentrations, insulin sensitivity, and blood pressure. RESULTS We recruited a total of 233 volunteers; 24 volunteers withdrew, and 3 volunteers were excluded. Systolic blood pressure and pulse pressure were significantly reduced by 6 and 3 mm Hg, respectively, in the whole-grain foods groups compared with the control group. Systemic markers of cardiovascular disease risk remained unchanged apart from cholesterol concentrations, which decreased slightly but significantly in the refined group. CONCLUSIONS Daily consumption of 3 portions of whole-grain foods can significantly reduce cardiovascular disease risk in middle-aged people mainly through blood pressure-lowering mechanisms. The observed decrease in systolic blood pressure could decrease the incidence of coronary artery disease and stroke by ≥15% and 25%, respectively. This trial was registered at clinicaltrials.gov as ISRCTN27657880.

Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT.

CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality. Data from randomized controlled trials are limited. OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease (CVD) risk. DESIGN We conducted a parallel-group, double-blind, placebo-controlled randomized controlled trial. Randomization was computer generated. Participants and study investigators were blinded to intervention groupings throughout the trial. SETTING The study was conducted at the Clinical Research Facility, University of Aberdeen, United Kingdom. PARTICIPANTS A total of 305 healthy postmenopausal women aged 60-70 yr were recruited for the study. INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3) or placebo randomly allocated. MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; and apolipoproteins A-1 and B100], insulin resistance (homeostatic model assessment), inflammatory biomarkers (high-sensitivity C-reactive protein, IL-6, soluble intracellular adhesion molecule-1), and blood pressure. RESULTS A total of 265 (87%) participants completed all study visits. Small differences between groups for serum apolipoprotein B100 change [repeated measures ANOVA, P=0.04; mean (sd), -1.0 (10.0) mg/dl (400 IU); -1.0 (10.0) mg/dl (1000 IU); and +0.02 (10.0) mg/dl (placebo)] were not considered clinically significant. Other systemic markers for CVD risk remained unchanged. There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose (P<0.001, linear mixed model). Mean (sd) reduction in systolic blood pressure from winter to summer was -6.6 (10.8) mm Hg. CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors. Confounding of seasonality should be recognized and addressed in future studies of vitamin D.

Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals

The management of overweight subjects by interventions aimed at reducing inflammation is highly desirable. To date, observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity. However, direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking. Therefore, this study examined lycopenes ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects. Serum was collected before and after a 12-week intervention from 54 moderately overweight, middle-aged individuals. Subjects were randomised to one of three groups: control diet (<10 mg lycopene/week), lycopene-rich diet (224-350 mg lycopene/week) and lycopene supplement (70 mg lycopene/week). HDL was subfractionated into HDL(2&3) by rapid ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum and HDL(2&3). Systemic and HDL-associated inflammation was assessed by measuring serum amyloid A (SAA) levels. HDL functionality was determined by monitoring the activities of paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT). Lycopene increased in serum and HDL(2&3) following both lycopene interventions (P<.001, for all), while SAA decreased in serum following the lycopene supplement and in HDL(3) following both lycopene interventions (P<.05 for all). PON-1 activity increased in serum and HDL(2&3) in both lycopene groups (P<.05, for all). Furthermore, the activity of CETP decreased in serum following the lycopene supplement, while the activity of LCAT increased in serum and HDL(3) following both lycopene interventions (P<.05 for all). These results demonstrate that in moderately overweight, middle-aged subjects, increasing lycopene intake leads to changes to HDL(2&3), which we suggest enhanced their antiatherogenic properties. Overall, these results show the heart-protective properties of increased lycopene intake.

Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

Effect of a tomato-rich diet on markers of cardiovascular disease risk in moderately overweight, disease-free, middle-aged adults: a randomized controlled trial

BACKGROUND Cardiovascular disease (CVD) is a major cause of mortality in the United Kingdom. Epidemiologic studies suggest that consumption of tomato-based foods may lower CVD risk. Such potential benefits have been ascribed in part to high concentrations of lycopene in the tomatoes. However, these findings have not yet been validated by comprehensive intervention trials. OBJECTIVE The aim of this study was to conduct a single-blind, randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods affects recognized biomarkers of CVD risk. DESIGN After a 4-wk run-in period with a low-tomato diet, 225 volunteers (94 men and 131 women) aged 40-65 y were randomly assigned into 1 of 3 dietary intervention groups and asked to consume a control diet (low in tomato-based foods), a high-tomato-based diet, or a control diet supplemented with lycopene capsules (10 mg/d) for 12 wk. Blood samples were collected at baseline, at 6 wk, and after the intervention and were analyzed for carotenoid and lipid profiles and inflammatory markers. Blood pressure, weight, and arterial stiffness were also measured. Dietary intake was also determined during the intervention. RESULTS None of the systemic markers (inflammatory markers, markers of insulin resistance and sensitivity) changed significantly after the dietary intervention. Moreover, lipid concentrations and arterial stiffness were also unaffected by the interventions. CONCLUSION These data indicate that a relatively high daily consumption of tomato-based products (equivalent to 32-50 mg lycopene/d) or lycopene supplements (10 mg/d) is ineffective at reducing conventional CVD risk markers in moderately overweight, healthy, middle-aged individuals. This trial was registered at isrctn.org as ISRCTN34203810.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women.

Few year‐long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1‐year double‐blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25‐dihydroxyvitamin D[1,25(OH)2D], N‐terminal propeptide of type 1 collagen [P1NP], C‐terminal telopeptide of type I collagen [CTX], and fibroblast growth factor‐23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25‐hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was −4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored.

A systematic review of salicylates in foods: Estimated daily intake of a Scottish population

Several studies suggest that natural salicylates in plant-based foods may benefit health. However, large variation in published values of the salicylate content of foods means that relating dietary intakes to disease risk is problematical. Consequently, we have systematically reviewed the available literature using prescribed selection criteria. By combining these literature values with in-house analysis, we have constructed a food composition database describing median salicylate values for 27 different types of fruits, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages. Application of a validated food frequency questionnaire estimated median dietary intakes of 4.42 (range 2.90-6.27) and 3.16 (2.35-4.89) mg/day for Scottish males and females, respectively. Major dietary sources of salicylates were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non-alcoholic beverages including fruit juices (13%), tomato-based sauces (12%) and vegetables (9%). Application of the database to populations with differing dietary habits and disease risk profiles may provide further evidence for the role of dietary salicylates in the prevention of chronic diseases.

Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease

OBJECTIVE Omega-3 fatty acids have been shown to reduce platelet and endothelial activation in patients with or at risk of cardiac disease. We aimed to determine if Omega-3 fatty acid supplementation in addition to best medical therapy can reduce the increased platelet and endothelial activity that is present in patients with intermittent claudication. METHODS One hundred and fifty patients who were receiving aspirin and statin therapy were recruited into a randomised cross-over double blind study involving 6 week supplementation with OMACOR fish oil (850-882 mg eicosapentaenoic and docosahexaenoic acid) versus placebo. A 12 week washout period occurred between treatments. Patients with diabetes were excluded. For each outcome a random effects model was fitted in which treatment and period were fixed effects and patients were random effects. RESULTS Omega-3 supplementation had no effect on the primary outcome measure von Willebrand factor. Similarly Omega-3 supplementation resulted in no change in unstimulated or stimulated P-selectin expression and fibrinogen binding, or platelet aggregation (Ultegra point of care). Pulse wave velocity was also unchanged. High-sensitivity C-reactive protein, s-ICAM and IL-6 were also unchanged. CONCLUSION Supplementation with Omega-3 fatty acids had no affect on platelet and endothelial activation or markers of inflammation in patients with peripheral arterial disease.

Fish oil supplementation reduces markers of oxidative stress but not muscle soreness after eccentric exercise.

Due to the potential anti-inflammatory properties of fish-derived long chain n-3 fatty acids, it has been suggested that athletes should regularly consume fish oils-although evidence in support of this recommendation is not clear. While fish oils can positively modulate immune function, it remains possible that, due to their high number of double bonds, there may be concurrent increases in lipid peroxidation. The current study aims to investigate the effect of fish oil supplementation on exercise-induced markers of oxidative stress and muscle damage. Twenty males underwent a 6-week double-blind randomized placebo-controlled supplementation trial involving two groups (fish oil or placebo). After supplementation, participants undertook 200 repetitions of eccentric knee contractions. Blood samples were taken presupplementation, postsupplementation, immediately, 24, 48, and 72 hr postexercise and muscle soreness/maximal voluntary contraction (MVC) assessed. There were no differences in creatine kinase, protein carbonyls, endogenous DNA damage, muscle soreness or MVC between groups. Plasma thiobarbituric acid reactive substances (TBARS) were lower (p < .05) at 48 and 72 hr post exercise and H2O2 stimulated DNA damage was lower (p < .05) immediately postexercise in the fish oil, compared with the control group. The current study demonstrates that fish oil supplementation reduces selected markers of oxidative stress after a single bout of eccentric exercise.

Fish oil supplementation augments post-exercise immune function in young males

PURPOSE Fish oils and related fatty acid components have anti-inflammatory properties, with beneficial effects against various disorders such as cardiovascular disease. A single bout of exercise can alter immune function. However, the effects of fish oil on immune function after a single bout of exercise are currently unknown. This study investigated the effect of supplementation with fish oil on the immune response to an acute bout of endurance exercise. METHODS Sixteen male subjects underwent a six week double blind randomised placebo controlled supplementation trial involving two groups (fish oil or placebo oil, 3g/day). They attended for two visits, the first involving a maximal exercise test and the second involving a 1-h bout of endurance exercise on a cycle ergometer at 70% (V)O(2peak). Blood samples were taken pre-supplementation, pre-exercise (post-supplementation), immediately, 1 and 3h post-exercise. Samples were analysed for plasma IL-6, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and cortisol; peripheral blood mononuclear cell (PBMC) IL-2, IL-4 and IFN-γ production; neutrophil phagocytosis/oxidative burst; and natural killer (NK) cell cytotoxic activity. RESULTS Post-supplementation EPA concentration was increased (P=0.0127) in the fish oil group. At 3h post-exercise PBMC IL-2 (P=0.0067) and NK cell activity (P=0.0163) was greater in the fish oil compared with the control group. However, PBMC IL-4 and IFN-γ productions, plasma IL-6 and cortisol concentrations, as well as neutrophil activity were unaffected by fish oil supplementation. CONCLUSION The current study demonstrates that fish oil supplementation reduces increases PBMC IL-2 production and NK cell cytotoxic activity in the recovery period after exercise.