Marie-Ève Labonté

Impact of dairy products on biomarkers of inflammation: a systematic review of randomized controlled nutritional intervention studies in overweight and obese adults

BACKGROUND Recent data from cross-sectional studies suggest that consumption of dairy products is inversely associated with low-grade systemic inflammation, but a cause-and-effect relation can be confirmed only with results from randomized controlled trials. OBJECTIVE We reviewed the results of randomized controlled nutritional intervention studies that have assessed the impact of dairy product consumption (ie, milk, yogurt, and/or cheese) on biomarkers of inflammation in adults (aged ≥18 y). DESIGN We performed a systematic literature search in PubMed in April 2012, which was limited to randomized controlled trials in humans published in English. Studies that included pregnant or lactating women or that did not include a low-dairy control intervention were excluded. RESULTS Eight trials that were conducted in overweight or obese adults were included in the review. The only study that had identified change in the inflammatory profile as its primary outcome measure showed that dairy food consumption improved pro- and antiinflammatory biomarker concentrations compared with the low-dairy control diet. Three of the 7 studies in which inflammation was a secondary or undefined outcome showed improvement in key inflammatory biomarkers, ie, C-reactive protein, IL-6, or TNF-α after dairy product consumption, whereas the other 4 studies showed no effect. CONCLUSIONS Dairy product consumption does not exert adverse effects on biomarkers of inflammation in overweight or obese adults. Several methodologic factors and limitations among existing studies do not allow differentiation between a beneficial or neutral impact of dairy products on inflammation. Further studies specifically designed to assess inflammation-related outcomes are warranted.

Systematic Review of the Association between Dairy Product Consumption and Risk of Cardiovascular-Related Clinical Outcomes

The objective of this systematic review was to determine if dairy product consumption is detrimental, neutral, or beneficial to cardiovascular health and if the recommendation to consume reduced-fat as opposed to regular-fat dairy is evidence-based. A systematic review of meta-analyses of prospective population studies associating dairy consumption with cardiovascular disease (CVD), coronary artery disease (CAD), stroke, hypertension, metabolic syndrome (MetS), and type 2 diabetes (T2D) was conducted on the basis of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Quality of evidence was rated by using the Grading of Recommendations Assessment, Development, and Evaluation scale. High-quality evidence supports favorable associations between total dairy intake and hypertension risk and between low-fat dairy and yogurt intake and the risk of T2D. Moderate-quality evidence suggests favorable associations between intakes of total dairy, low-fat dairy, cheese, and fermented dairy and the risk of stroke; intakes of low-fat dairy and milk and the risk of hypertension; total dairy and milk consumption and the risk of MetS; and total dairy and cheese and the risk of T2D. High- to moderate-quality evidence supports neutral associations between the consumption of total dairy, cheese, and yogurt and CVD risk; the consumption of any form of dairy, except for fermented, and CAD risk; the consumption of regular- and high-fat dairy, milk, and yogurt and stroke risk; the consumption of regular- and high-fat dairy, cheese, yogurt, and fermented dairy and hypertension risk; and the consumption of regular- and high-fat dairy, milk, and fermented dairy and T2D risk. Data from this systematic review indicate that the consumption of various forms of dairy products shows either favorable or neutral associations with cardiovascular-related clinical outcomes. The review also emphasizes that further research is urgently needed to compare the impact of low-fat with regular- and high-fat dairy on cardiovascular-related clinical outcomes in light of current recommendations to consume low-fat dairy.

Recommended dairy product intake modulates circulating fatty acid profile in healthy adults: a multi-centre cross-over study

Dairy products are rich sources of an array of fatty acids (FA) that have been shown individually and in certain clusters to exert varying effects on cardiovascular health, for which the circulating lipid profile is a powerful biomarker. Whether the profile of these FA is reflected in blood upon short terms of intake, possibly contributing to the lipid-related health impacts of dairy products, remains to be fully established. The objectives of the present study were to assess a recommended dairy product consumption in relation to circulating FA and lipid profiles, and to evaluate certain FA in dairy fat as potential biomarkers of intake. In a free-living, multi-centre, cross-over design, 124 healthy individuals consumed 3 servings/d of commercial dairy (DAIRY; 1% fat milk, 1·5% fat yogurt and 34% fat cheese) or energy-equivalent control (CONTROL; fruit and vegetable juice, cashews and a cookie) products for 4 weeks each, separated by a 4-week washout period. Plasma FA and serum lipid profiles were assessed by standard methods at the end of each dietary phase. After 4 weeks of intake, plasma levels of FA pentadecanoic acid (15 : 0) and heptadecanoic acid (17 : 0) were higher (0·26 v. 0·22% and 0·42 v. 0·39% of the total identified FA, respectively) after the DAIRY phase than after the CONTROL phase (P< 0·0001). This was accompanied by a small but significant increase in serum LDL-cholesterol levels after the DAIRY phase compared with the CONTROL phase (+0·08 mmol/l; P= 0·04). In conclusion, intake of 3 servings/d of conventional dairy products may modify certain circulating FA and lipid profiles within 4 weeks, where 15 : 0 and 17 : 0 may be potential short-term biomarkers of intake.

Dairy Product Consumption Has No Impact on Biomarkers of Inflammation among Men and Women with Low-Grade Systemic Inflammation

BACKGROUND Randomized controlled trials specifically designed to assess inflammation-related outcomes in response to dairy consumption are lacking. OBJECTIVE We investigated the impact of dairy food consumption on biomarkers of inflammation in healthy men and women with low-grade systemic inflammation. METHODS In a multicenter randomized crossover study, 112 adult men and women with high-sensitivity C-reactive protein (hs-CRP) values >1 mg/L consumed 3 servings/d of dairy (375 mL low-fat milk, 175 g low-fat yogurt, and 30 g regular-fat cheddar cheese) or energy-matched control (fruit juice, vegetable juice, cashews, and 1 cookie) products as part of prudent 4-wk diets, each separated by a 4- to 8-wk washout period. Serum concentrations of inflammation biomarkers were measured at the beginning and end of each dietary phase. Expression levels of key inflammatory genes and transcription factors in whole blood cells were assessed at the end of each diet by real-time polymerase chain reaction in a random subset of 53 subjects. RESULTS Analysis of within-diet changes (post- vs. prediet values) showed a significant reduction in hs-CRP concentrations after the control diet (-11.7%, P = 0.05) but no change after the dairy diet (-7.3%, P = 0.47). As a result, changes in hs-CRP differed between the dairy and control diets (P = 0.04). Both the control and dairy diets similarly reduced interleukin-6 concentrations compared with diet-specific baseline values (-17.6% and -19.9%, respectively; P < 0.0001 for both, P = 0.77 for between-diet comparison). No between- or within-diet difference was observed in adiponectin concentrations, and there was also no between-diet difference in the expression of inflammatory genes and transcription factors. CONCLUSION Consistent with data from previous work, these results suggest that short-term consumption of a combination of low- and high-fat dairy products as part of a healthy diet has no adverse effects on inflammation. This trial was registered at www.clinicaltrials.gov as NCT01444326.

Comprehensive Review of the Impact of Dairy Foods and Dairy Fat on Cardiometabolic Risk

Because regular-fat dairy products are a major source of cholesterol-raising saturated fatty acids (SFAs), current US and Canadian dietary guidelines for cardiovascular health recommend the consumption of low-fat dairy products. Yet, numerous randomized controlled trials (RCTs) have reported rather mixed effects of reduced- and regular-fat dairy consumption on blood lipid concentrations and on many other cardiometabolic disease risk factors, such as blood pressure and inflammation markers. Thus, the focus on low-fat dairy in current dietary guidelines is being challenged, creating confusion within health professional circles and the public. This narrative review provides perspective on the research pertaining to the impact of dairy consumption and dairy fat on traditional and emerging cardiometabolic disease risk factors. This comprehensive assessment of evidence from RCTs suggests that there is no apparent risk of potential harmful effects of dairy consumption, irrespective of the content of dairy fat, on a large array of cardiometabolic variables, including lipid-related risk factors, blood pressure, inflammation, insulin resistance, and vascular function. This suggests that the purported detrimental effects of SFAs on cardiometabolic health may in fact be nullified when they are consumed as part of complex food matrices such as those in cheese and other dairy foods. Thus, the focus on low-fat dairy products in current guidelines apparently is not entirely supported by the existing literature and may need to be revisited on the basis of this evidence. Future studies addressing key research gaps in this area will be extremely informative to better appreciate the impact of dairy food matrices, as well as dairy fat specifically, on cardiometabolic health.

Prostatic and Dietary Omega-3 Fatty Acids and Prostate Cancer Progression during Active Surveillance

The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer. Cancer Prev Res; 7(7); 766–76. ©2014 AACR.

Dietary medium-chain triglyceride supplementation has no effect on apolipoprotein B-48 and apolipoprotein B-100 kinetics in insulin-resistant men

BACKGROUND Medium-chain triglyceride (MCT) supplements are used by clinicians to treat patients with severe hypertriglyceridemia who are at risk of pancreatitis. However, the potential mechanisms underlying the effects of MCT on triglyceride-rich lipoprotein (TRL) metabolism have not yet been thoroughly examined in humans. OBJECTIVE This double-blind randomized crossover study compared the impact of 4 wk of supplementation with 20 g MCT oil/d or 20 g corn oil/d on the kinetics of apolipoprotein (apo) B-48-containing TRLs and apo B-100-containing very-low-density lipoprotein (VLDL), as well as on the expression of key intestinal genes involved in lipid metabolism in 28 obese, insulin-resistant men. DESIGN The in vivo kinetics of TRL apo B-48 and VLDL apo B-100 were assessed by using a primed-constant infusion of l-[5,5,5-d3]leucine for 12 h in the fed state. Real-time polymerase chain reaction quantification was performed on duodenal biopsy samples taken at the end of each phase of supplementation. RESULTS Compared with corn oil, MCT supplements had no significant effect on plasma lipoprotein profile or TRL apo B-48 and VLDL apo B-100 kinetics. Positive correlations were observed between the intestinal expression of several key genes involved in lipoprotein metabolism in a subgroup of participants (n = 16) after MCT supplementation. However, there was no difference between MCT and the corn oil control supplement in the intestinal messenger RNA expression levels of these key genes. CONCLUSION These data indicate that short-term supplementation with MCT has a neutral effect on TRL apo B-48 and VLDL apo B-100 kinetics and on the intestinal expression of genes involved in lipid and fatty acid metabolism in men with insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT01806142.

Adding MUFA to a dietary portfolio of cholesterol-lowering foods reduces apoAI fractional catabolic rate in subjects with dyslipidaemia

The present randomised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia. A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks. Subjects were then randomly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks. MUFA substituted 13·0% of total energy from carbohydrate (CHO) in the high-MUFA dietary portfolio. Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed, constant infusion of [2H3]leucine and multicompartmental modelling. The high-MUFA dietary portfolio resulted in higher apoAI pool size (PS) compared with the low-MUFA dietary portfolio (15·9% between-diet difference, P¼0·03). This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate (FCR) after the high-MUFA diet (25·6%, P¼0·02 v. pre-diet values), with no significant change in production rate. The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio (228·5% between-diet that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate. Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate, thus potentiating further the well-known cholesterol-lowering effect of this diet.

Population-based study of high plasma C-reactive protein concentrations among the Inuit of Nunavik.

Background . The shift away from traditional lifestyle in the Inuit population over the past few decades has been associated with an increased prevalence of coronary heart disease (CHD) risk factors such as obesity, high blood pressure (BP) and diabetes. However, the impact of this transition on the pro-inflammatory marker high-sensitivity C-reactive protein (hs-CRP) has not been documented. Objectives . To examine the prevalence of elevated plasma hs-CRP concentrations in Inuit from Nunavik in the province of Quebec (Canada) and identify anthropometric, biochemical and lifestyle risk factors associated with elevated hs-CRP. Design . A population-representative sample of 801 Inuit residents from 14 villages of Nunavik, aged between 18 and 74 years, was included in the analyses. Subjects participated in a clinical session and completed questionnaires on lifestyle. Multivariate logistic regression was used to determine risk factors for elevated hs-CRP. Results . Elevated plasma hs-CRP concentrations (≥2 mg/L) were present in 32.7% (95% confidence interval (CI) 29.5–35.8) of the Inuit adult population and were more prevalent among women than among men (36.7% vs. 29.0%, p=0.007). Multivariate logistic regression analysis indicated that every 1 mmHg increase in systolic BP was associated with a 3% increase in the odds of having hs-CRP concentrations ≥2 mg/L in the Inuit population (95% CI 1.01–1.04). The combination of older age (≥50 vs. <30 years) and elevated waist circumference (gender-specific cut-off values) in a multivariate logistic model was also associated with a 13.3-fold increase in the odds of having plasma hs-CRP concentrations ≥2 mg/L (95% CI 5.8–30.9). Conclusions . These data indicate that elevated hs-CRP is relatively prevalent among Inuit with values that are similar to those seen in Canadian Caucasian populations. Sex, age, waist circumference and systolic BP are major factors that increase the risk of this inflammatory phenotype among Inuit from Nunavik, despite their different lifestyle background compared with Caucasians. To access the supplementary material to this article please see Supplementary files under Article Tools online

Dietary assessment is a critical element of health research – Perspective from the Partnership for Advancing Nutritional and Dietary Assessment in Canada

Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions.