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BACKGROUND: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. OBJECTIVE: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering. DESIGN: Sixty-four healthy volunteers (31 men and 33 women) with a mean (+/-SD) age of 43 +/- 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetiere (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk. RESULTS: Consumption of 1 L unfiltered coffee/d for 2 wk significantly raised fasting plasma homocysteine concentrations by 10%, from 12.8 to 14.0 micromol/L. CONCLUSIONS: Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

We reviewed the evidence from human intervention studies for the health effects of probiotic bacteria, ie, live bacteria that survive passage through the gastrointestinal tract and have beneficial effects on the host. Of the 49 studies reviewed, 26 dealt with the prevention or treatment of diarrheal disease, 9 with the prevention of cancer or of the formation of carcinogens, 7 with the lowering of serum cholesterol, and 7 with the stimulation of the immune system. The most widely studied probiotic bacteria were Lactobacillus GG (22 studies), Lactobacillus acidophilus (16 studies), Bifidobacterium bifidum (6 studies), and Enterococcus faecium (7 studies). Intake of Lactobacillus GG consistently shortened the diarrheal phase of rotavirus infection by 1 d. However, evidence for the prevention by Lactobacillus GG and other probiotics of diarrhea due to viral or bacterial infections was less strong. Effects of probiotics on the immune system are inconclusive because of the variety of outcome variables reported. Cholesterol lowering by L. acidophilus was shown in some but not all studies; cholesterol lowering by E. faecium seems to be transient. Two studies of one research group showed a smaller recurrence of bladder tumors in patients after treatment with Lactobacillus casei; these results await confirmation. The production of mutagens after a meal might be reduced by the concomitant intake of probiotics, but the relevance of this finding is unclear. In conclusion, consumption of foods containing Lactobacillus GG may shorten the course of rotavirus infection. Other health effects of probiotic bacteria have not been well established. Well-designed placebo-controlled studies with validated outcome variables are needed to determine the health effects of probiotics. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Some coffee brewing techniques raise the serum concentration of total and low-density-lipoprotein cholesterol in humans, whereas others do not. The responsible factors are the diterpene lipids cafestol and kahweol, which make up about 1% (wt:wt) of coffee beans. Diterpenes are extracted by hot water but are retained by a paper filter. This explains why filtered coffee does not affect cholesterol, whereas Scandinavian 'boiled,' cafetiere, and Turkish coffees do. We describe the identification of the cholesterol-raising factors, their effects on blood levels of lipids and liver function enzymes, and their impact on public health, based on papers published up to December 1996. [ABSTRACT FROM AUTHOR]

Flavonols are antioxidants that may reduce the risk of heart disease. Two major flavonols in the diet are quercetin and kaempferol, and their main sources in The Netherlands are tea and onions. We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans could be used as biomarkers of intake. We provided 15 subjects with strong black tea (1600 mL/d) or fried onions (129 g/d) for 3 d each in random order separated by a 4-d washout period. The tea provided 49 mg quercetin and 27 mg kaempferol daily and the onions provided 13 mg quercetin and no kaempferol. Flavonols from both foods were clearly absorbed. However, the excretion of unmodified quercetin was 0.5% of intake after tea and 1.1% after onions. Thus, the absorption of quercetin from tea was half of that from onions. The onion treatment was repeated 7-14 d later to estimate within-subject CVs as a measure of reproducibility when the same treatment is given twice. CVs for quercetin were 30% in plasma and 42% in urine. The magnitude of these variations relative to actual variations of approximately 60% between free-living subjects indicates that concentrations of quercetin in plasma and urine are applicable as biomarkers of its intake. We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Observational studies have reported many beneficial effects of vitamin and mineral supplements on cardiovascular and other diseases, but randomized controlled trials have failed to confirm these. This could be due to the failure of statistical adjustment to eliminate residual and unmeasured confounding by known risk factors. A Mendelian randomization study now suggests a similar problem for the observed beneficial effects of moderate alcohol intake. When 500,000 Chinese people were ranked by self-reported alcohol intake, stroke risk showed a U-shaped curve, risk being lowest at 1-2 units per day. However, when subjects were ranked by genetically conditioned intake, risk was lowest in abstainers and went up linearly with intake. Mendelian randomization may be more suitable for elucidating the effects of diet on health than conventional epidemiology.

Doctors can play a major role in reducing obesity in the community, but that requires an unconventional approach. Treatment of individual patients with diet or drugs is largely ineffective. In contrast, comprehensive community interventions such as one pioneered by EPODE in France have successfully reduced the prevalence of corpulence in children. Such a community approach requires simultaneously engagement by town governments, retailers, associations, restaurants, caterers, media, schools and kindergartens to cooperate in improving diets, reducing caloric intake and increasing activity. Physicians are by far the most highly trusted source of information when it comes to health matters. Therefore, a few words from a doctor at the right time and in the right place, e.g. at a city council meeting, could tip the scales. Individual doctors cannot cure patients' obesity by themselves in their offices, but a few hours per year spent on persuading key stakeholders might help to turn the tide on obesity in the community.

Taking fish oil supplements in the third trimester of pregnancy was associated with significantly less wheezing or asthma in the child at the age of 3-5 years, according to a randomized clinical trial by Bisgaard et al., NEJM 2017. However, the results of this study should be interpreted with caution. The primary end points were modified at a late stage in the study, and two primary end points, eczema in the first 3 years of life and allergic sensitization at 18 months of age, were demoted to secondary end points, and showed no significant effect of treatment. Furthermore, the age range for the published primary end point, persistent wheeze, differed from that in the protocol. Additional concerns include the emphasis on outcomes by omega-3 fatty acid levels in the blood, a post hoc subgroup analysis not included in the protocol. In our opinion, this study does not justify advising routine fish oil supplements in pregnancy.

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 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.

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.

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.

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.

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.

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.

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.

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.).

Probiotics are microbes that are claimed to promote health and well-being when added to foods. However, the European Food Safety Authority (EFSA) has so far advised negatively about health claims for probiotics. Companies and scientists have protested against these rejections, sometimes in vigorous language. I argue that EFSA could not have acted differently, given EU regulations and the lack of convincing evidence for some of the claimed effects of probiotics on human health and well-being. One EU regulation that makes it hard to demonstrate the benefits of probiotics is the prohibition of medical claims, i.e. claims that a food prevents or cures a disease. If this prohibition did not exist, manufacturers of nutritional treatments might circumvent the costly procedures required for drugs, and market their products to ill people without thorough proof that they are effective and safe. However, the prohibition is also a legal fiction, because promotion of health and prevention of disease is largely the same thing. EFSA has recently indicated that it will allow health claims based on the ability of probiotics to reduce infections. To a certain extent, this abolishes the distinction between health claims and medical claims. It remains to be seen if probiotics producers can convince EFSA that their products prevent or cure infections and other diseases in humans.

Background: Intake of sugar-sweetened beverages is associated with overweight in observational studies. A possible explanation is that liquid sugars do not satiate and that their intake is not compensated by reduced caloric intake from other foods. However, evidence from intervention studies for this hypothesis is inconclusive because previous studies were not blinded. Hence results may have been influenced by expectations and behavioral cues rather than by physiological mechanisms., Methods: We designed the Double-blind, Randomized INtervention study in Kids (DRINK) to examine the effect on body weight of covertly replacing sugar-sweetened by sugar-free beverages. Children were only eligible if they habitually drank sugar-sweetened beverages. We recruited 642 healthy children (mean age 8.2, range 4.8-11.9). We designed, tested and produced custom-made beverages containing 10% sugar and sugar-free beverages with the same sweet taste and look. Children receive one 250 mL can of study beverage daily for 18 months. We perform body measurements at 0, 6, 12 and 18 months. The primary outcome is the z-score of BMI for age. The maximum predicted difference in this score between groups is 0.72, which corresponds with a difference in body weight of 2.3 kg., Discussion: The double-blind design eliminates behavioral factors that affect body weight. If children gain less body fat when drinking sugar-free than when drinking sugar-sweetened beverages that would show that liquid sugar indeed bypasses biological satiation mechanisms. It would also suggest that a reduction in liquid sugars could decrease body fat more effectively than reduction of other calorie sources., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.