An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of (R)-1,3-butanediol (Avela™).

Introduction: A study was undertaken to determine the acute effects of a beverage made with Avela™ (R)-1,3-butanediol, on blood beta-hydroxybutyrate (BHB) levels (using the Keto-Mojo monitor), gastrointestinal (GI) tolerability (using the modified visual analogue scale GI Symptoms Tool), and sleepiness (using the Stanford Sleepiness Scale). Methods: Following a 12-h overnight fast, 26 healthy adults consumed one beverage containing 11.5 g of (R)-1,3-butanediol at each of 0, 30, and 60 min, culminating in a total intake of 34.5 g of (R)-1,3-butanediol. Blood BHB levels, GI tolerability, and sleepiness were assessed at baseline (0 min), and at 30, 60, 90, 120, 180, 240, and 300 min. At 240 min, a protein bar was consumed. Results: The mean (±SD) BHB fasting baseline level, maximal concentration, time at maximal concentration, and incremental area under the curve over 300 min were 0.23 ± 0.21 mmol/L, 2.10 ± 0.97 mmol/L, 133.85 ± 57.07 min, and 376.73 ± 156.76 mmol/L*min, respectively. BHB levels at each time point were significantly increased relative to baseline. In females, BHB Tmax was significantly greater (p = 0.046), and BHB iAUC0-300 min nearly significantly greater (p = 0.06) than in males. Discussion: The beverage formulated with Avela™ had no impact on sleepiness and was generally well-tolerated, with no or mild GI symptoms reported in most participants. Mild headaches were reported as an adverse event by five participants and judged possibly related to the study product in two of the participants.

Liver biomarkers in adults: Evaluation of associations with reported green tea consumption and use of green tea supplements in U.S. NHANES.

Some events of hepatotoxicity have been linked to consumption of green tea supplements. The association between consumption of green tea or green tea supplements and abnormal liver biomarkers in adults was investigated using cross-sectional data from the 2009-2014 United States National Health and Nutrition Examination Survey (U.S. NHANES). Individuals with levels of either bilirubin or GGT, ALT, AST, and/or ALP in excess of the age- and gender-specific upper limits of normal ranges were classified as having abnormal liver biomarkers. Associations between green tea or green tea supplement use (consumption vs. not) and liver function were determined using multiple logistic regression modelling. 12,289 persons were included in the green tea analyses and 12,274 in the green tea supplement analyses. The odds of having one or more abnormal liver biomarkers were significantly reduced (p = 0.01) with consumption of green tea (OR: 0.49; 95% CI: 0.28, 0.85), while no significant association (p = 0.78) was determined for consumption of green tea supplements (OR: 0.92; 95% CI: 0.52, 1.64). Based on data from the 2009-2014 U.S. NHANES, green tea consumption was associated with reduced odds of having one or more abnormal liver biomarkers; whereas, no significant association was determined with consumption of green tea supplements.

Challenges in the design, interpretation, and reporting of randomized controlled clinical studies on the health effects of whole foods.

Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole foods and opportunities for the future development of best practices are reported. Novelty: Outlines existing tools, resources, and checklists for clinical nutrition trials and provides clear and tangible steps to develop best practices for studies on whole foods.

Effects of Unsweetened Preloads and Preloads Sweetened with Caloric or Low-/No-Calorie Sweeteners on Subsequent Energy Intakes: A Systematic Review and Meta-Analysis of Controlled Human Intervention Studies.

Effects of isocaloric (sweetness differences but constant calories) preloads and isosweet (caloric differences but constant sweetness) preloads, as well as preloads that were neither isosweet nor isocaloric (sweetness and caloric differences) on subsequent ad libitum meal and total (preload + ad libitum) energy intakes were investigated. Thirty-five crossover studies were eligible for inclusion, representing 116 comparisons (41, isocaloric; 41, isosweet; and 34, neither isosweet nor isocaloric). References of existing reviews and literature from 4 databases were searched. The calculated raw mean differences in ad libitum and total energy intakes were pooled in meta-analyses using a random-effects model and the inverse of the variance as the weighting factor. Energy intakes at an ad libitum meal were significantly lower for low-/no-calorie sweetener (LNCS)-sweetened compared with unsweetened preloads in the isocaloric comparison (-55.5 kcal; 95% CI: -82.9, -28.0 kcal; P < 0.001); however, the difference in energy intake was not significant in additional sensitivity analyses (i.e., removal of comparisons where the matrix was a capsule and when xylitol was the LNCS). For the isosweet comparison, although the pooled energy intake at the ad libitum meal was significantly greater with the LNCS-sweetened preload compared with the caloric sweetener (CS)-sweetened preload (58.5 kcal; 95% CI: 35.4, 81.7 kcal; P < 0.001), the pattern was reversed when total energy intake was considered (-132.4 kcal; 95% CI: -163.2, -101.6 kcal; P < 0.001), explained by only partial compensation from the CS-sweetened preload. The results were similar when assessing ad libitum and total energy intakes when unsweetened compared with CS-sweetened preloads were consumed. Unsweetened or LNCS-sweetened preloads appear to have similar effects on intakes when compared with one another or with CS-sweetened preloads. These findings suggest that LNCS-sweetened foods and beverages are viable alternatives to CS-sweetened foods and beverages to manage short-term energy intake.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effects of Oats and Oat Processing on Postprandial Blood Glucose and Insulin Responses.

BACKGROUND: Oats are a whole grain cereal with potentially favorable effects on the postprandial glycemic response; however, the effects of oat processing on these glycemic benefits are not well understood. OBJECTIVES: The study objective was to determine the effects of differently processed oats on the postprandial blood glucose and insulin responses relative to refined grains. METHODS: Eleven electronic databases were systematically searched to identify studies published up to and including May 2019. Randomized controlled trials comparing the postprandial blood glucose and insulin responses to oats compared with any refined grain were included, so long as the available carbohydrate content of the test meals was similar. Pooled effect sizes were computed using the difference in incremental area under the curves for blood glucose and insulin following the consumption of oats compared with the refined grain control. RESULTS: Ten publications were included, with intact oat kernels studied in 3 comparisons, thick oat flakes (>0.6 mm) in 7 comparisons, and thin/quick/instant oat flakes (≤0.6 mm) in 6 comparisons. Compared with the consumption of the refined grain control, the consumption of intact oat kernels was associated with significant reductions in postprandial blood glucose (-45.5 mmol x min/L; 95% CI: -80.1, -10.9 mmol x min/L; P = 0.010) and insulin (-4.5 nmol x min/L; 95% CI: -7.1, -1.8 nmol x min/L; P = 0.001) responses; the consumption of thick oat flakes was associated with significant reductions in postprandial blood glucose (-30.6 mmol x min/L; 95% CI: -40.4, -20.9 mmol x min/L; P < 0.001) and insulin (-3.9 nmol x min/L; 95% CI: -5.3, -2.5 nmol x min/L; P < 0.001) responses; but, the consumption of thin/quick/instant oat flakes was not associated with any effects on the postprandial blood glucose and insulin responses. CONCLUSIONS: A disruption in the structural integrity of the oat kernel is likely associated with a loss in the glycemic benefits of oats.

Effects of a Fermented Dairy Drink Containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (Lactobacillus casei CNCM I-1518) and the Standard Yogurt Cultures on the Incidence, Duration, and Severity of Common Infectious Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is considerable interest in the role of probiotics in immune function. The objective of this systematic review and meta-analysis was to assess the effects of the consumption of a fermented dairy drink containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (the previous taxonomic nomenclature was Lactobacillus casei CNCM I-1518, prior to the nomenclature change in April 2020) and the standard yogurt cultures (hereinafter referred to collectively as "FDD") on common infectious diseases (CIDs) in generally healthy children and adults. Nine literature databases were searched, and nine randomized controlled trials from eight publications were eligible for inclusion. Combined effect sizes were determined for three metrics of CID incidence, two metrics of CID duration, and one metric of CID severity. Compared to the control, the consumption of the FDD resulted in (1) a significant reduction in the odds of experiencing ≥1 CID (odds ratio (OR) (with a 95% confidence interval (CI)): 0.81 (0.66, 0.98); p = 0.029); (2) a significant reduction in mean CIDs per subject (-0.09 (-0.15, -0.04); p = 0.001); and (3) a trend towards reduced risk in cumulative CIDs (relative risk (RR): 0.91 (0.82, 1.01); p = 0.082). The consumption of the FDD had no significant effect on CID duration or severity. Based on the studies conducted thus far, these results suggest that the FDD may reduce CID incidence in the general population.

Contribution of 100% Fruit Juice to Micronutrient Intakes in the United States, United Kingdom and Brazil.

The contribution of 100% fruit juice (FJ) to the total daily intakes of energy, sugars, and select vitamins and minerals and to the recommended dietary allowances (RDAs) or adequate intake (AI) of these micronutrients was assessed in individuals reporting the consumption of 100% FJ in the national dietary intake surveys of the United States (U.S.; n = 8661), the United Kingdom (UK; n = 2546) and Brazil (n = 34,003). Associations of 100% FJ intake with the odds of being overweight or obese also were assessed. Data from the U.S. National Health and Nutrition Examination Survey (2013-2014), the UK National Diet and Nutrition Survey (2012-2014), and Brazil's Pesquisa de Orçamentos Familiares (2008-2009) were used, and all analyses were limited to individuals reporting consumption of 100% FJ on at least one day of the dietary intake survey. Approximately 34%, 37%, and 42% of individuals surveyed reported the consumption of 100% FJ on at least one day of the dietary intake survey in the U.S., UK, and Brazil, respectively, and the average daily intakes of 100% FJ were 184 g, 130 g, and 249 g, respectively. Across the 3 countries, 100% FJ contributed to 3-6% of total energy intakes, 12-31% of total sugar intakes, 21-54% of total vitamin C intakes, 1-12% of total vitamin A intakes, 4-15% of total folate intakes, 7-17% of total potassium intakes, 2-7% of total calcium intakes, and 4-12% of total magnesium intakes. In a multivariate logistic regression model, juice intake was associated with a significant reduction in the odds of being overweight or obese in UK adults (OR = 0.79; 0.63, 0.99), and significant increases in the odds of being overweight or obese in UK children (OR = 1.16; 1.01, 1.33) and Brazilian adults (OR = 1.04; 1.00, 1.09). Nutrient contributions of 100% FJ vary according to regional intake levels. In all three countries studied, 100% FJ contributed to more than 5% of the RDAs for vitamin C and folate. In the U.S. and Brazil, 100% FJ contributed to more than 5% of the RDA for magnesium and more than 5% of the AI for potassium.

Determinants of Sweetness Preference: A Scoping Review of Human Studies.

Factors associated with sweetness preference are multi-faceted and incredibly complex. A scoping review was undertaken to identify determinants of sweetness preference in humans. Using an online search tool, ProQuest ™, a total of 99 publications were identified and subsequently grouped into the following categories of determinants: Age, dietary factors, reproductive hormonal factors, body weight status, heritable, weight loss, sound, personality, ethnicity and lifestyle, previous exposure, disease, and 'other' determinants. Methodologies amongst studies were heterogenous in nature (e.g., there was variability across studies in the sweetness concentrations tested, the number of different sweetness concentrations used to assess sweetness preference, and the methods utilized to measure sweetness preference), rendering interpretation of overall findings challenging; however, for certain determinants, the evidence appeared to support predictive capacity of greater sweetness preference, such as age during certain life-stages (i.e., young and old), being in a hungry versus satiated state, and heritable factors (e.g., similar sweetness preferences amongst family members). Recommendations for the design of future studies on sweetness preference determinants are provided herein, including an "investigator checklist" of criteria to consider.

A Randomized, Double-Blind, Placebo-Controlled, Multicentre Trial of the Effects of a Shrimp Protein Hydrolysate on Blood Pressure.

In this randomized, double-blind, placebo-controlled, multicentre, parallel, 8-week study, the efficacy of a daily dose of 1200 mg of protein hydrolysate from Coldwater Shrimp (Pandalus borealis) on ambulatory and office blood pressure was investigated in 144 free-living adults with mild to moderate hypertension. The primary outcomes of the study were daytime ambulatory systolic blood pressure and office blood pressure. During the 8-week intervention period and in the intention-to-treat analysis (n=144), there were significant reductions in the group consuming the shrimp-derived protein hydrolysate relative to the placebo group in daytime ambulatory systolic blood pressure at 4 weeks (p=0.014) and at 8 weeks (p=0.002), and in office systolic blood pressure at 2 weeks (p=0.031) and 4 weeks (p=0.010), with a trend toward significance at 8 weeks (p=0.087). By 8 weeks, significant and favourable improvements in the group consuming the shrimp-derived protein hydrolysate relative to the placebo group were also observed for several secondary outcomes, including 24-hour ambulatory systolic and diastolic blood pressure, daytime ambulatory diastolic blood pressure, and daytime and 24-hour ambulatory mean arterial pressure. Also by Week 8, there was a statistically significant difference between groups in the distribution of subjects across National Institutes of Health-defined blood pressure categories (i.e., Normotensive, Prehypertensive, Stage 1 hypertension, and Stage 2 hypertension), with a more favourable distribution in the shrimp-derived protein hydrolysate group than in the placebo group (p=0.006). Based on exploratory analyses conducted only in participants in the shrimp-derived protein hydrolysate group, angiotensin II levels were significantly reduced relative to baseline. This study is registered at ClinicalTrials.gov NCT01974570.

A Narrative Review of Childhood Picky Eating and Its Relationship to Food Intakes, Nutritional Status, and Growth.

A main characteristic of children perceived as picky eaters is their tendency to avoid certain foods or food groups. The goal of this narrative review is to provide an overview of published studies that have examined whether picky eating in childhood is in fact associated with measurable differences in food and/or nutrient intakes and growth. While picky eaters appear to consume less vegetables compared to non-picky eaters, no consistent differences were observed for the intakes of other food groups or the intakes of energy, macronutrients and dietary fiber. Although, in some studies, picky eaters had lower intakes of certain vitamins and minerals, the levels consumed generally exceeded the recommended values, suggesting nutritional requirements are being met. No consistent relationship between childhood picky eating and growth status was observed, although significant differences in body weight/growth between picky and non-picky eaters were most discernible in studies where multiple defining criteria were used to identify picky eating. The research area would benefit from the adoption of a uniform definition of picky eating. More longitudinal assessments are also required to understand the long-term impact of picky eating on nutritional status and growth.

The effects of whole-grain compared with refined wheat, rice, and rye on the postprandial blood glucose response: a systematic review and meta-analysis of randomized controlled trials.

Background: Whole grains are often referred to collectively, despite differences in their composition, physical structure, processing, and potential health benefits. Objective: The aim of this study was to compare the postprandial blood glucose response of whole-grain with refined wheat, rice, or rye, while controlling for the food delivery matrix and the processing of the grain (e.g., grinding, germination). Design: Eleven electronic databases were systematically searched to identify studies published up to and including November 2017. Randomized controlled trials comparing the effects of whole-grain wheat, rice, or rye with those of each grain's refined counterpart on postprandial blood glucose area under the curve (AUC) were included. Pooled effect sizes were computed by using the difference in the blood glucose AUC after the consumption of the whole compared with the refined grain. Results: Twenty publications were included, with 10, 14, and 5 strata (or active-control comparisons) on whole-grain wheat, rice, and rye, respectively. The consumption of ground (wholemeal) wheat, compared with white wheat, was not associated with a significant reduction in blood glucose AUC (-6.7 mmol/L ⋅ min; 95% CI: -25.1, 11.7 mmol/L ⋅ min; P = 0.477). The consumption of wholemeal rye, compared with endosperm rye, was not associated with a significant reduction in blood glucose AUC (-5.5 mmol/L ⋅ min; 95% CI: -24.8, 13.8 mmol/L ⋅ min; P = 0.576). The consumption of intact (whole-grain) rice, compared with white rice, was associated with a significant reduction in blood glucose AUC (-40.5 mmol/L ⋅ min; 95% CI: -59.6, -21.3 mmol/L ⋅ min; P < 0.001). Conclusions: Compared with white rice, whole-grain rice significantly attenuates the postprandial blood glucose response. In most of the studies on wheat and rye, the postprandial blood glucose responses to foods formulated with wholemeal compared with refined flours were compared. Whether reductions in the blood glucose AUC can be achieved with whole-grain (as opposed to wholemeal) wheat and rye requires further investigation.

Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease.

Context: Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed. Objective: The aim of this review was to systematically assess the effects of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric patients with NAFLD. Data Sources: The online information service ProQuest Dialog was used to search 8 literature databases. Study Selection: Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could be isolated were eligible for inclusion. Data Extraction: The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and data transcriptions and study quality assessments were conducted in duplicate. Each effect size was expressed as the weighted mean difference and 95%CI, using a random-effects model and the inverse of the variance as a weighting factor. Results: Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy), and in steatosis score (assessed via ultrasonography). Histological measures of disease [which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were unaffected by n-3 LC-PUFA supplementation. Conclusions: Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD. Additional trials are needed to better understand the effects of n-3 LC-PUFAs on histological outcomes in patients with NASH. Systematic Review Registration: PROSPERO CRD42017055951.

An Appetite for Modernizing the Regulatory Framework for Protein Content Claims in Canada.

The need for protein-rich plant-based foods continues as dietary guidelines emphasize their contribution to healthy dietary patterns that prevent chronic disease and promote environmental sustainability. However, the Canadian Food and Drug Regulations provide a regulatory framework that can prevent Canadian consumers from identifying protein-rich plant-based foods. In Canada, protein nutrient content claims are based on the protein efficiency ratio (PER) and protein rating method, which is based on a rat growth bioassay. PERs are not additive, and the protein rating of a food is underpinned by its Reasonable Daily Intake. The restrictive nature of Canada's requirements for supporting protein claims therefore presents challenges for Canadian consumers to adapt to a rapidly changing food environment. This commentary will present two options for modernizing the regulatory framework for protein content claims in Canada. The first and preferred option advocates that protein quality not be considered in the determination of the eligibility of a food for protein content claims. The second and less preferred option, an interim solution, is a framework for adopting the protein digestibility corrected amino acid score as the official method for supporting protein content and quality claims and harmonizes Canada's regulatory framework with that of the USA.

The effects of almond consumption on fasting blood lipid levels: a systematic review and meta-analysis of randomised controlled trials.

A systematic review and meta-analysis of randomised controlled trials was undertaken to determine the effects of almond consumption on blood lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), TAG and the ratios of TC:HDL-C and LDL-C:HDL-C. Following a comprehensive search of the scientific literature, a total of eighteen relevant publications and twenty-seven almond-control datasets were identified. Across the studies, the mean differences in the effect for each blood lipid parameter (i.e. the control-adjusted values) were pooled in a meta-analysis using a random-effects model. It was determined that TC, LDL-C and TAG were significantly reduced by -0·153 mmol/l (P < 0·001), -0·124 mmol/l (P = 0·001) and -0·067 mmol/l (P = 0·042), respectively, and that HDL-C was not affected (-0·017 mmol/l; P = 0·207). These results are aligned with data from prospective observational studies and a recent large-scale intervention study in which it was demonstrated that the consumption of nuts reduces the risk of heart disease. The consumption of nuts as part of a healthy diet should be encouraged to help in the maintenance of healthy blood lipid levels and to reduce the risk of heart disease.

Assessment of Intakes and Patterns of Cooked Oatmeal Consumption in the U.S. Using Data from the National Health and Nutrition Examination Surveys.

The objective of the present study was to characterize the consumption of cooked oatmeal in the United States (U.S.) and to determine whether oatmeal consumption is associated with body mass index (BMI). To estimate current intakes of cooked oatmeal in the various age and gender population groups, we used dietary intake data from Day 1 of the U.S. 2009-2010 and 2011-2012 National Health and Nutrition Examination Surveys (NHANES). We also used dietary intake data from Day 1 of the U.S. 2003-2012 NHANES to assess associations between intakes of cooked oatmeal (in g/kg body weight) and NHANES cycle (2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012), age category (3-11 years, 12-18 years, 19-44 years, 45 years+), gender, and BMI classification (underweight, normal weight, overweight, or obese), using a multiple linear regression model. A consumer of oatmeal was defined as any individual who reported the consumption of any amount of oatmeal on Day 1 of the survey. Approximately 6% of the total population consumed oatmeal, with an average intake of 238 g/day of cooked oatmeal among consumers. The greatest prevalence of oatmeal consumption was in infants (14.3%) and older female adults (11.1%). Amongst oatmeal consumers, underweight, normal weight, and overweight individuals consumed significantly more oatmeal than obese individuals. Oatmeal was consumed almost exclusively at breakfast and, among consumers, contributed an average of 54.3% of the energy consumed at breakfast across all age groups examined. The association between oatmeal consumption and BMI is interesting and requires confirmation in future clinical studies.

Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.

13-Week oral toxicity study of oil derived from squid (Todarodes pacificus) in Sprague-Dawley rats.

Recommendations to increase the consumption of the long-chain omega-3 fatty acids are challenged by the global problem of declining fish stocks. Non-traditional and more sustainable sources of the long-chain omega-3 fatty acids are needed. Squid (Todarodes pacificus) represents a uniquely sustainable source of these fatty acids. A 13-week oral toxicity study was conducted in male and female Sprague-Dawley rats administered either 0, 250, 500, or 1000µl/kg body weight (bw)/day of a refined squid oil. All of the rats survived through to the end of the study. All of the rats grew normally and had normal clinical and ophthalmic observations. No signs of toxicity were evident from clinical chemistry, hematology, and urinalysis data measured. No abnormal findings attributable to exposure to purified squid oil were observed following the necropsy of male and female rats and the histopathological examination of the organs. The no-observed-adverse-effect level for refined squid oil was determined to be 1000µl/kg bw/day, the highest dose tested.

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects.

Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of ß-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2h, reaching 3.30 mM and 1.19 mM for ß-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1h for ß-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.

Impact of low v. moderate intakes of long-chain n-3 fatty acids on risk of coronary heart disease.

The objective of the present study was to determine whether the consumption of ≥ 250 v. < 250 mg of the long-chain n-3 fatty acids (n-3 LCFA) per d is associated with a reduction in the risk of fatal and non-fatal CHD in individuals with no prior history of CHD. A comprehensive and systematic review of the published scientific literature resulted in the identification of eight prospective studies (seven cohorts and one nested case-control study) that met predefined inclusion criteria. Relative to the consumption of < 250 mg n-3 LCFA per d, the consumption of ≥ 250 mg/d was associated with a significant 35·1 % reduction in the risk of sudden cardiac death and a near-significant 16·6 % reduction in the risk of total fatal coronary events, while the risk of non-fatal myocardial infarction was not significantly reduced. In several meta-analyses, which were based on US studies, risk of CHD death was found to be dose-dependently reduced by the n-3 LCFA, with further risk reductions observed with intakes in excess of 250 mg/d. Prospective observational and intervention data from Japan, where intake of fish is very high, suggest that n-3 LCFA intakes of 900 to 1000 mg/d and greater may confer protection against non-fatal myocardial infarction. Thus, the intake of 250 mg n-3 LCFA per d may, indeed, be a minimum target to be achieved by the general population for the promotion of cardiovascular health.