Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double-Blind Trial in Children.

BACKGROUND: Substituting sugar-free for sugar-sweetened beverages reduces weight gain. This effect may be more pronounced in children with a high body mass index (BMI) because their sensing of kilocalories might be compromised. We investigated the impact of sugar-free versus sugary drinks separately in children with a higher and a lower initial BMI z score, and predicted caloric intakes and degree of compensation in the two groups. METHODS AND FINDINGS: This is a secondary, explorative analysis of our double-blind randomized controlled trial (RCT) which showed that replacement of one 250-mL sugary drink per day by a sugar-free drink for 18 months significantly reduced weight gain. In the 477 children who completed the trial, mean initial weights were close to the Dutch average. Only 16% were overweight and 3% obese. Weight changes were expressed as BMI z-score, i.e. as standard deviations of the BMI distribution per age and sex group. We designated the 239 children with an initial BMI z-score below the median as 'lower BMI' and the 238 children above the median as 'higher BMI'. The difference in caloric intake from experimental beverages between treatments was 86 kcal/day both in the lower and in the higher BMI group. We used a multiple linear regression and the coefficient of the interaction term (initial BMI group times treatment), indicated whether children with a lower BMI responded differently from children with a higher BMI. Statistical significance was defined as p ≤ 0.05. Relative to the sugar sweetened beverage, consumption of the sugar-free beverage for 18 months reduced the BMI z-score by 0.05 SD units within the lower BMI group and by 0.21 SD within the higher BMI group. Body weight gain was reduced by 0.62 kg in the lower BMI group and by 1.53 kg in the higher BMI group. Thus the treatment reduced the BMI z-score by 0.16 SD units more in the higher BMI group than in the lower BMI group (p = 0.04; 95% CI -0.31 to -0.01). The impact of the intervention on body weight gain differed by 0.90 kg between BMI groups (p = 0.09; 95% CI -1.95 to 0.14). In addition, we used a physiologically-based model of growth and energy balance to estimate the degree to which children had compensated for the covertly removed sugar kilocalories by increasing their intake of other foods. The model predicts that children with a lower BMI had compensated 65% (95% CI 28 to 102) of the covertly removed sugar kilocalories, whereas children with a higher BMI compensated only 13% (95% CI -37 to 63). CONCLUSIONS: The children with a BMI above the median might have a reduced tendency to compensate for changes in caloric intake. Differences in these subconscious compensatory mechanisms may be an important cause of differences in the tendency to gain weight. If further research bears this out, cutting down on the intake of sugar-sweetened drinks may benefit a large proportion of children, especially those who show a tendency to become overweight. TRIAL REGISTRATION: ClinicalTrials.gov NCT00893529.

[The Dietary Guidelines 2015 of the Health Council of the Netherlands--a commentary]. / Richtlijnen Gezondheidsraad over goede voeding 2015.

The latest dietary guidelines recommend increased consumption of vegetables, fruits and nuts; weekly consumption of beans and fish; zero intake of alcohol; reduced meat and salt consumption; water, milk or yoghurt, filtered coffee, and 3-5 daily cups of tea rather than soft drinks and fruit juice; and replacing butter with vegetable oils and soft margarine. The glycemic index is considered not useful. The totality of the guidelines can lower blood pressure substantially. Effects on LDL cholesterol may be limited because the guidelines ignore the saturated fat content of foods, and treat all dairy products as equal. Interpretation of the effects of foods in terms of their constituent parts is mostly dismissed; this is a worrisome development in an otherwise valuable report.

Can children discriminate sugar-sweetened from non-nutritively sweetened beverages and how do they like them?

BACKGROUND: Replacement of sugar-sweetened by non-nutritively sweetened beverages or water may reduce excess weight gain in children. However, it is unclear whether children like non-nutritively sweetened beverages as much as sugar-sweetened beverages. We examined whether children could taste a difference between non-nutritively sweetened beverages and matching sugar-sweetened beverages, and which of the two types of beverage they liked best. METHODS: 89 children aged 5 to 12 tasted seven non-nutritively sweetened beverages and matching sugar-sweetened beverages, for a total of 14 beverages. We used Triangle tests to check their ability to discriminate between the matched versions, and a 5-point scale to measure how much the children liked each individual beverage. RESULTS: Overall, 24% of children appeared to be genuinely capable of distinguishing between non-nutritively sweetened and sugar-sweetened beverages. The mean ± SD score for how much the children liked the non-nutritively sweetened beverages was 3.39 ± 0.7 and that for the sugar-sweetened beverages 3.39 ± 0.6 (P = 0.9) on a scale running from 1 (disgusting) to 5 (delicious). The children preferred some beverages to others irrespective of whether they were sugar-sweetened or non-nutritively sweetened (P = 0.000). Children who correctly identified which of three drinks contained the same sweetener and which one was different also showed no preference for either type. CONCLUSION: We found that about one in four children were able to discriminate between non-nutritively sweetened and sugar-sweetened beverages but children liked both varieties equally. Non-nutritively sweetened beverages may therefore be an acceptable alternative to sugar-sweetened beverages although water remains the healthiest beverage for children.

Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial.

BACKGROUND: Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer. METHODS: The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL). FINDINGS: Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: -0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58). INTERPRETATION: An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

The effect of sugar-free versus sugar-sweetened beverages on satiety, liking and wanting: an 18 month randomized double-blind trial in children.

BACKGROUND: Substituting sugar-free for sugar-sweetened beverages reduces weight gain. A possible explanation is that sugar-containing and sugar-free beverages cause the same degree of satiety. However, this has not been tested in long-term trials. METHODS: We randomized 203 children aged 7-11 years to receive 250 mL per day of an artificially sweetened sugar-free beverage or a similarly looking and tasting sugar-sweetened beverage. We measured satiety on a 5-point scale by questionnaire at 0, 6, 12 and 18 months. We calculated the change in satiety from before intake to 1 minute after intake and 15 minutes after intake. We then calculated the odds ratio that satiety increased by 1 point in the sugar-group versus the sugar-free group. We also investigated how much the children liked and wanted the beverages. RESULTS: 146 children or 72% completed the study. We found no statistically significant difference in satiety between the sugar-free and sugar-sweetened group; the adjusted odds ratio for a 1 point increase in satiety in the sugar group versus the sugar-free group was 0.77 at 1 minute (95% confidence interval, 0.46 to 1.29), and 1.44 at 15 minutes after intake (95% CI, 0.86 to 2.40). The sugar-group liked and wanted their beverage slightly more than the sugar-free group, adjusted odds ratio 1.63 (95% CI 1.05 to 2.54) and 1.65 (95% CI 1.07 to 2.55), respectively. CONCLUSIONS: Sugar-sweetened and sugar-free beverages produced similar satiety. Therefore when children are given sugar-free instead of sugar-containing drinks they might not make up the missing calories from other sources. This may explain our previous observation that children in the sugar-free group accumulated less body fat than those in the sugar group. TRIAL REGISTRATION: ClinicalTrials.gov NCT00893529 http://clinicaltrials.gov/show/NCT00893529.

[Health claims for medical foods]. / De claims van medische voeding.

Souvenaid (Nutricia, Zoetermeer, the Netherlands) is a medical food for the dietary management of early Alzheimer's disease. The mix of nutrients in this drink is suggested to have a beneficial effect on cognitive function; such implicit health claims for medical foods are not checked by government agencies. Souvenaid has been investigated in three clinical trials. The first trial showed that Souvenaid produced a significant improvement in delayed verbal recall, but not in other psychological tests. The second and largest trial showed no effect on any outcome. The third trial showed no significant effect at 12 or 24 weeks, but a significant difference in the 24-week time course of the composite memory score. None of these outcomes was clearly specified as a primary outcome at trial registration. In conclusion, there is no convincing proof that Souvenaid benefits cognitive function. Better scrutiny of the efficacy of medical foods is warranted.

[Linoleic acid and heart infarct]. / Linolzuur en hartinfarct.

A re-analysis of the Sydney Diet Heart Study (Ramsden et al., BMJ 2013) suggested that a diet high in linoleic acid increased the risk of coronary heart disease. The authors ascribe this to a lack of the omega-3 fatty acid, alpha-linolenic acid, in the oils and fats consumed. This argument has some weaknesses. Mortality in the linoleic acid group was 38 cases versus 27 in the control group (or 35 versus 28, or 39 versus 28; sources differ). The difference was significant in the current, though not in the original, publication. Conceivably, application of multiple statistical models led to chance significances. Additionally, the fats consumed by subjects in the intervention group were high in trans fats, which may have increased risk. Finally, a large recent clinical trial failed to show any benefit of linolenic acid. The conclusion is, therefore, that this re-analysis provides insufficient evidence to justify changes in current dietary recommendations.

A trial of sugar-free or sugar-sweetened beverages and body weight in children.

BACKGROUND: The consumption of beverages that contain sugar is associated with overweight, possibly because liquid sugars do not lead to a sense of satiety, so the consumption of other foods is not reduced. However, data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain. METHODS: We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age. Participants were randomly assigned to receive 250 ml (8 oz) per day of a sugar-free, artificially sweetened beverage (sugar-free group) or a similar sugar-containing beverage that provided 104 kcal (sugar group). Beverages were distributed through schools. At 18 months, 26% of the children had stopped consuming the beverages; the data from children who did not complete the study were imputed. RESULTS: The z score for the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group; the 95% confidence interval (CI) of the difference was -0.21 to -0.05. Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group (95% CI for the difference, -1.54 to -0.48). The skinfold-thickness measurements, waist-to-height ratio, and fat mass also increased significantly less in the sugar-free group. Adverse events were minor. When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study, the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group (P=0.06). CONCLUSIONS: Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children. (Funded by the Netherlands Organization for Health Research and Development and others; DRINK ClinicalTrials.gov number, NCT00893529.).

A high intake of trans fatty acids has little effect on markers of inflammation and oxidative stress in humans.

Consumption of industrial trans fatty acids (iTFA) increases LDL cholesterol, decreases HDL cholesterol, and is strongly associated with a higher risk of cardiovascular disease (CVD). However, changes in circulating cholesterol cannot explain the entire effect. Therefore, we studied whether iTFA and conjugated linoleic acid (CLA) affect markers of inflammation and oxidative stress. Sixty-one healthy adults consumed each of 3 diets for 3 wk, in random order. Diets were identical except for 7% of energy provided by oleic acid (control diet), iTFA, or CLA. At the end of the 3 wk, we measured plasma inflammatory markers IL-6, C-reactive protein, tumor necrosis factor receptors I and II (TNF-RI and -RII), monocyte chemotactic protein-1 and E-selectin, and urinary 8-iso-PGF(2α), a marker of lipid peroxidation. Consumption of iTFA caused 4% lower TNF-RI concentrations and 6% higher E-selectin concentrations compared with oleic acid (control) and had no significant effect on other inflammatory markers. CLA did not significantly affect inflammatory markers. The urine concentration of 8-iso-PGF(2α) [geometric mean (95% CI)] was greater after the iTFA [0.54 (0.48, 0.60) nmol/mmol creatinine] and the CLA [1.2 (1.1, 1.3) nmol/mmol creatinine] diet periods than after the control period [0.45 (0.41, 0.50) nmol/mmol creatinine; P < 0.05]. In conclusion, high intakes of iTFA and CLA did not substantially affect plasma concentrations of inflammatory markers, but they increased the urine 8-iso-PGF(2α) concentration. However, it is unlikely this plays a major role in the mechanism by which iTFA increase the risk of CVD. However, more research is needed to fully understand the implications of these findings.

Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial.

BACKGROUND: Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. OBJECTIVES: The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. DESIGN: The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. RESULTS: The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrollment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. CURRENT STATUS: Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010.

Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans--a quantitative review.

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 HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA) on blood lipoproteins, and compared these with industrial trans fatty acids. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95%CI 0.044-0.066) for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95%CI 0.012-0.065) for ruminant trans fatty acids, and 0.043 (95% CI 0.012-0.074) for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids). CONCLUSIONS/SIGNIFICANCE: Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol.

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 (p = 0.001) 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.

The role of epoxidation and electrophile-responsive element-regulated gene transcription in the potentially beneficial and harmful effects of the coffee components cafestol and kahweol.

Cafestol and kahweol are diterpene compounds present in unfiltered coffees. Cafestol is known as the most potent cholesterol-raising agent that may be present in the human diet. Remarkably, the mechanisms behind this effect have only been partly resolved so far. Even less is known about the metabolic fate of cafestol and kahweol. From the structure of cafestol, carrying a furan moiety, we hypothesized that epoxidation may not only be an important biotransformation route but that this also plays a role in its effects found. In bile duct-cannulated mice, dosed with cafestol, we were able to demonstrate the presence of epoxy-glutathione (GSH) conjugates, GSH conjugates and glucuronide conjugates. In addition, it was shown that cafestol was able to induce an electrophile-responsive element (EpRE). Using a murine hepatoma cell line with a luciferase reporter gene under control of an EpRE from the human NQO1 regulatory region, we also found that metabolic activation by CYP450 enzymes is needed for EpRE induction. Furthermore, raising intracellular GSH resulted in a decrease in EpRE-mediated gene induction, whereas lowering intracellular GSH levels increased EpRE-mediated gene induction. In conclusion, evidence suggests that cafestol induces EpRE, apparently via a bioactivation process that possibly involves epoxidation of the furan ring. The epoxides themselves appear subject to conjugation with GSH. The effects on EpRE can also explain the induction of GSH which seems to be involved in the reported beneficial effects of cafestol, for example, when administered with aflatoxin B1 or other toxic or carcinogenic compounds.

Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.