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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 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

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.govNCT01974570.

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.

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.

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

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&ndash, 2014), the UK National Diet and Nutrition Survey (2012&ndash, 2014), and Brazil&rsquo, s Pesquisa de Or&ccedil, amentos Familiares (2008&ndash, 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&ndash, 6% of total energy intakes, 12&ndash, 31% of total sugar intakes, 21&ndash, 54% of total vitamin C intakes, 1&ndash, 12% of total vitamin A intakes, 4&ndash, 15% of total folate intakes, 7&ndash, 17% of total potassium intakes, 2&ndash, 7% of total calcium intakes, and 4&ndash, 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.

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

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.

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 β-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 1–2 h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8–3.1 h for β-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.

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.

Purpose To determine if plant stanols and plant sterols differ with respect to their low-density lipoprotein cholesterol (LDL-CH) lowering efficacies across a continuous dose range. Methods Dose-response relationships were evaluated separately for plant stanols and plant sterols and reductions in LDL-CH, using a first-order elimination function. Results Altogether, 113 publications and 1 unpublished study report (representing 182 strata) complied with the pre-defined inclusion and exclusion criteria and were included in the assessment. The maximal LDL-CH reductions for plant stanols (16.4%) and plant stanol ester (17.1%) were significantly greater than the maximal LDL-CH reductions for plant sterols (8.3%) and plant sterol ester (8.4%). These findings persisted in several additional analyses. Discussion and conclusions Intakes of plant stanols in excess of the recommended 2g/day dose are associated with additional and dose-dependent reductions in LDL-CH, possibly resulting in further reductions in the risk of coronary heart disease (CHD).

The objective of the present study was to determine whether the consumption of ≥ 250 v. 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 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.

Objective The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. Methods In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. Results Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma β-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. Conclusions Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.

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 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.

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 1000 μl/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 1000 μl/kg bw/day, the highest dose tested.

The objectives of this review were to determine whether the long-chain omega-3 fatty acids eicosapentaenoic acid and/or docosahexaenoic acid dose-dependently reduce fasting serum triglycerides (TG) and, if so, to create a mathematical model that may be used to predict potential percent reductions in fasting serum TG levels at the recommended intakes of 200-500 mg/day. The assessment included 15 randomized controlled trials that met pre-defined inclusion and exclusion criteria. Across these 15 studies, the dose-response was modeled using a first-order elimination curve. The response variable was defined as percent change from baseline in fasting serum TG, adjusted for the placebo effect. A weighting factor equal to the product of each study's sample size and quality score was used. Using the equation of the dose-response curve, predicted reductions in fasting serum TG levels at the recommended long-chain omega-3 fatty acid intakes of 200-500 mg/day are 3.1 to 7.2%.

Recently published literature has been reviewed to determine whether lycopene, beta-carotene, alpha-carotene, and beta-cryptoxanthin are associated with reductions in cancer risk and whether study findings differ by study design. A total of 57 publications meeting pre-defined inclusion and exclusion criteria were identified, with the majority (55) being observational studies. None of the intervention studies supported a significant reduction in cancer risk with carotenoid (beta-carotene) supplementation. The majority of observational studies did not support significant reductions in cancer risk with increased carotenoid dietary intakes/circulating levels. A larger percentage of case-control studies supported significant associations between increased dietary intakes/circulating levels of carotenoids relative to prospective (cohort and nested case-control) studies. Compared to prospective studies, case-control studies cannot be used to establish temporality and may be more susceptible to selection and recall biases. Thus, diet-disease relationships suggested by case-control studies should ideally be confirmed by additional evidence from prospective studies.

We summarize here the evidence indicating that carbon from alpha-linolenate and linoleate is readily recycled into newly synthesized lipids. This pathway consumes the majority of these fatty acids that is not beta-oxidized as a fuel. Docosahexaenoate undergoes less beta-oxidation and carbon recycling than do alpha-linolenate or linoleate, but is it still actively metabolized by this pathway? Among polyunsaturates, arachidonate appears to undergo the least beta-oxidation and carbon recycling, an observation that may help account for the resistance of brain membranes to loss of arachidonate during dietary deficiency of n-6 polyunsaturates. Preliminary evidence suggests that de novo lipid synthesis consumes carbon from alpha-linolenate and linoleate in preference to palmitate, but this merits systematic study. Active beta-oxidation and carbon recycling of 18-carbon polyunsaturates does not diminish the importance of being able to convert alpha-linolenate and linoleate to long-chain polyunsaturates but suggests that a broad perspective is required in studying the metabolism of polyunsaturates in general and alpha-linolenate and linoleate in particular.

High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p < 0.05), but not in children on a ketogenic diet. Children who were on the ketogenic diet for longer periods of time had a significantly lower fasting breath acetone (R(2) = 0.55, p = 0.014). In one child on the ketogenic diet, breath acetone was determined hourly over a 9-h period, both by gas chromatography and by a prototype hand-held breath acetone analyzer. Preliminary results using this hand-held breath acetone analyzer are encouraging. Breath acetone may be a useful tool in examining the relationship between ketosis and seizure control and enhancing our understanding of the mechanism of the ketogenic diet.

We are thankful for the insight provided by Maki and Rains regarding our recent work titled “Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid dose-dependently reduce fasting serum triglycerides.”1 Maki and Rains raised two important issues relevant to our dose-response assessment. First, they suggested that a clear tracking of excluded studies and reasons for their exclusion should have been included in our manuscript to enable the reader to assess the potential for study-selection bias. Second, they raised questions regarding the omission of two of the largest fish oil intervention studies, the GISSI Prevention2 and GISSI Heart Failure3 trials. Each of these issues is discussed sequentially. The literature search described in our publication resulted in the identification of over 10,000 titles, despite attempts to limit the search to studies conducted in humans. This is reflective of the substantial amount of information that has been published on the topic of long-chain omega-3 fatty acids. The literature filtration process consisted of two steps: 1) abstracts of titles determined to be potentially relevant were reviewed; and 2) full-length articles of abstracts determined to be potentially relevant were reviewed. At each of these steps, the study inclusion and exclusion criteria listed in the first table of our publication1 were applied. The studies that were excluded, and the reasons for their exclusion, were tracked only from the point of full-length article review, given the substantial number of titles and abstracts reviewed. To be included in our dose-response assessment, one of …