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Given the evidence of the health benefits of plant-based diets and long-chain n–3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n–3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n–3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.

Appropriate planning, execution, and reporting of statistical methods and results is critical for research transparency, validity, and reproducibility. This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition randomized controlled trials (RCTs). Readers are referred to the other NURISH (NUtrition inteRventIon reSearcH) publications for detailed information about the preparation and conduct of human nutrition RCTs. Collectively, the NURISH series outlines best practices for conducting human nutrition research.Statement of Significance: This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition, randomized, controlled trials.

Appropriate planning, execution, and reporting of statistical methods and results is critical for research transparency, validity, and reproducibility. This paper provides an overview of best practices for developing a statistical analysis plan a priori, conducting statistical analyses, and reporting statistical methods and results for human nutrition randomized controlled trials (RCTs). Readers are referred to the other NURISH (NUtrition inteRventIon reSearcH) publications for detailed information about the preparation and conduct of human nutrition RCTs. Collectively, the NURISH series outlines best practices for conducting human nutrition research.

In human nutrition randomized controlled trials (RCTs), planning, and careful execution of clinical data collection and management are vital for producing valid and reliable results. In this article, we provide an overview of best practices for biospecimen collection and analyses, and for the fundamentals of clinical data management, including preparation and study startup; data collection, entry, cleaning, and authentication; and database lock. The reader is also referred to additional resources for information to assist in the planning and conduct of human RCTs. The tools and strategies described are expected to improve the quality of data produced in human nutrition research that can, therefore, be used to support food and nutrition policies.

In human nutrition randomized controlled trials (RCTs), planning, and careful execution of clinical data collection and management are vital for producing valid and reliable results. In this article, we provide an overview of best practices for biospecimen collection and analyses, and for the fundamentals of clinical data management, including preparation and study startup; data collection, entry, cleaning, and authentication; and database lock. The reader is also referred to additional resources for information to assist in the planning and conduct of human RCTs. The tools and strategies described are expected to improve the quality of data produced in human nutrition research that can, therefore, be used to support food and nutrition policies.

The Dietary Guidelines for Americans (DGA) provide nutrition advice for Americans >2 y of age. The 2020–2025 DGA proposes a life stage approach, focusing on birth through older adulthood. Limited recommendations for beverages exist except for milk, 100% fruit juice, and alcohol. The goal of this article is to provide a better understanding of the role of beverages in the diet using current scientific evidence. A Medline search of observational studies, randomized controlled trials, and meta-analyses was undertaken using key beverage words. We highlight the role beverages can play as a part of the DGA and considered beverages not traditionally included, such as those that are phytonutrient dense. Our primary consideration for beverage consumption targeted healthy Americans aged ≥2 y. However, with the proposed expansion to the life span for the 2020–2025 DGA, we also reviewed evidence for infants and toddlers from birth to 24 mo. Examples are provided on how minor changes in beverage choices aid in meeting recommended intakes of certain nutrients. Guidance on beverage consumption may aid in development of better consumer products to meet broader dietary advice. For example, beverage products that are nutrient/phytonutrient dense and lower in sugar could be developed as alternatives to 100% juice to help meet the fruit and vegetable guidelines. Although beverages are not meant to replace foods, e.g., it is difficult to meet the requirements for vitamin E, dietary fiber, or essential fatty acids through beverages alone, beverages are important sources of nutrients and phytonutrients, phenolic acids and flavonoids in particular. When considering the micronutrients from diet alone, mean intakes of calcium (in women), potassium, and vitamins A, C, and D are below recommendations and sodium intakes are well above. Careful beverage choices could close these gaps and be considered a part of a healthy dietary pattern.

Guidelines for designing, conducting, documenting, and reporting human nutrition randomized controlled trials (RCTs) have as yet to be developed and disseminated as reference for investigators, funders, regulators, institutions, assessors, trainees, and others involved in human nutrition research. Diet-related interventions can include diet and/or behavioral manipulation, provision of foods or entire meals, or delivery of dietary components in individual food items or supplements. This Perspective introduces a series of papers that outline core principles for the design and conduct of human nutrition RCTs, documentation and reporting of all aspects of clinical trial management, and data analysis and reporting of results. Human nutrition RCTs have unique considerations delineated in these papers. Conducting them with the highest scientific rigor is essential to the development of evidence-based dietary guidance for promoting optimal health and advancing health care.

Guidelines for designing, conducting, documenting, and reporting human nutrition randomized controlled trials (RCTs) have as yet to be developed and disseminated as reference for investigators, funders, regulators, institutions, assessors, trainees, and others involved in human nutrition research. Diet-related interventions can include diet and/or behavioral manipulation, provision of foods or entire meals, or delivery of dietary components in individual food items or supplements. This Perspective introduces a series of papers that outline core principles for the design and conduct of human nutrition RCTs, documentation and reporting of all aspects of clinical trial management, and data analysis and reporting of results. Human nutrition RCTs have unique considerations delineated in these papers. Conducting them with the highest scientific rigor is essential to the development of evidence-based dietary guidance for promoting optimal health and advancing health care.

Proteins from plant-based compared with animal-based food sources may have different effects on cardiovascular disease (CVD) risk factors. Numerous epidemiologic and intervention studies have evaluated their respective health benefits; however, it is difficult to isolate the role of plant or animal protein on CVD risk. This review evaluates the current evidence from observational and intervention studies, focusing on the specific protein-providing foods and populations studied. Dietary protein is derived from many food sources, and each provides a different composite of nonprotein compounds that can also affect CVD risk factors. Increasing the consumption of protein-rich foods also typically results in lower intakes of other nutrients, which may simultaneously influence outcomes. Given these complexities, blanket statements about plant or animal protein may be too general, and greater consideration of the specific protein food sources and the background diet is required. The potential mechanisms responsible for any specific effects of plant and animal protein are similarly multifaceted and include the amino acid content of particular foods, contributions from other nonprotein compounds provided concomitantly by the whole food, and interactions with the gut microbiome. Evidence to date is inconclusive, and additional studies are needed to further advance our understanding of the complexity of plant protein vs. animal protein comparisons. Nonetheless, current evidence supports the idea that CVD risk can be reduced by a dietary pattern that provides more plant sources of protein compared with the typical American diet and also includes animal-based protein foods that are unprocessed and low in saturated fat.

Recent dietary guidance for heart health recommends a reduction (by ∼50%) in saturated fatty acid (SFA) intake to reduce LDL cholesterol and to decrease risk of cardiovascular disease (CVD). The 2010 Dietary Guidelines for Americans recommends substituting unsaturated fat [both polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs, respectively)] for SFAs. There are many dietary options that can be implemented to replace SFAs, given the different sources of unsaturated fats in the food supply. Compelling evidence exists for the cardioprotective benefits of n–3 (ω-3) PUFAs, both marine- and plant-derived. In addition, the evidence of cardioprotective benefits of n–6 (ω-6) PUFAs is strong, whereas that for MUFAs is mixed, although there is emerging evidence of benefits. Quantitatively, lowering SFAs by 50% will require, in part, substituting food sources of n–6 and n–3 PUFAs and MUFAs for food sources of SFAs. The use of n–3 PUFAs as a replacement for SFAs will result in a shortfall in reaching the SFA goal because of the relatively low amounts that can be incorporated in the diet, even with very high n–3 PUFA substitution. SFAs also can be replaced with dietary carbohydrate and/or protein. Replacing SFAs with carbohydrate, specifically refined sources, however, has little impact on reducing CVD risk. There is evidence about the health benefits of dietary protein on CVD risk, which merits study. Dietary guidelines have advanced considerably with the “replacement of SFA with unsaturated fat message” instead of recommending decreasing SFAs alone. A key question that remains is what is the optimal mix of macronutrients to maximally reduce CVD risk.

Most health care professionals are not adequately trained to address diet and nutrition-related issues with their patients, thus missing important opportunities to ameliorate chronic diseases and improve outcomes in acute illness. In this symposium, the speakers reviewed the status of nutrition education for health care professionals in the United States, United Kingdom, and Australia. Nutrition education is not required for educating and training physicians in many countries. Nutrition education for the spectrum of health care professionals is uncoordinated, which runs contrary to the current theme of interprofessional education. The central role of competencies in guiding medical education was emphasized and the urgent need to establish competencies in nutrition-related patient care was presented. The importance of additional strategies to improve nutrition education of health care professionals was highlighted. Public health legislation such as the Patient Protection and Affordable Care Act recognizes the role of nutrition, however, to capitalize on this increasing momentum, health care professionals must be trained to deliver needed services. Thus, there is a pressing need to garner support from stakeholders to achieve this goal. Promoting a research agenda that provides outcome-based evidence on individual and public health levels is needed to improve and sustain effective interprofessional nutrition education.

Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n–3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n–3) and docosahexaenoic acid (DHA, 22:6n–3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n–3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction.

Data from randomized controlled trials (RCTs) provide the strongest evidence for establishing relations between exposures, including dietary exposures, and health outcomes. However, not all diet and health outcome relations can be practically or ethically evaluated by using RCTs; therefore, many dietary recommendations are supported by evidence primarily from observational data, particularly those from prospective cohort studies. Although such evidence is of critical importance, limitations are often underappreciated by nutrition scientists and policymakers. This editorial review is intended to 1) highlight some of these limitations of observational evidence for diet-disease relations, including imprecise exposure quantification, collinearity among dietary exposures, displacement/substitution effects, healthy/unhealthy consumer bias, residual confounding, and effect modification; and 2) advocate for greater caution in the communication of dietary recommendations for which RCT evidence of clinical event reduction after dietary intervention is not available.

Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present in most other fruit. Basic research has suggested a number of potential mechanisms of action of cranberry bioactives, although further molecular studies are necessary. Human studies on the health effects of cranberry products have focused principally on urinary tract and cardiovascular health, with some attention also directed to oral health and gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the recurrence of urinary tract infections is important because a nutritional approach to this condition could lower the use of antibiotic treatment and the consequent development of resistance to these drugs. There is encouraging, but limited, evidence of a cardioprotective effect of cranberries mediated via actions on antioxidant capacity and lipoprotein profiles. The mixed outcomes from clinical studies with cranberry products could result from interventions testing a variety of products, often uncharacterized in their composition of bioactives, using different doses and regimens, as well as the absence of a biomarker for compliance to the protocol. Daily consumption of a variety of fruit is necessary to achieve a healthy dietary pattern, meet recommendations for micronutrient intake, and promote the intake of a diversity of phytochemicals. Berry fruit, including cranberries, represent a rich source of phenolic bioactives that may contribute to human health.

This paper summarizes presentations given at the 2011 Experimental Biology meetings about the latest research and a paleoanthropological perspective pertaining to the relationship between dietary cholesterol intake and cardiovascular disease risk. For much of the past 50 years, a great deal of the scientific literature regarding dietary fat and cholesterol intake has indicated a strong positive correlation with heart disease. In recent years, however, there have been a number of epidemiological studies that did not support a relationship between cholesterol intake and cardiovascular disease. Further, a number of recent clinical trials that looked at the effects of long-term egg consumption (as a vehicle for dietary cholesterol) reported no negative impact on various indices of cardiovascular health and disease. Coupled with data indicating that the impact of lowering dietary cholesterol intake on serum LDL levels is small compared with other dietary and lifestyle factors, there is a need to consider how otherwise healthy foods can be incorporated in the diet to meet current dietary cholesterol recommendations. Because eggs are a healthful food, it is particularly important that sensible strategies be recommended for inclusions of eggs in a healthy diet.

Dietary SFA and cholesterol are major targets for reducing plasma total and LDL cholesterol as a strategy to decrease cardiovascular disease risk. However, many studies show that excess adiposity attenuates the expected lipid and lipoprotein response to a plasma cholesterol–lowering diet. Diets low in SFA and cholesterol are less effective in improving the lipid profile in obese individuals and in patients with metabolic syndrome. In contrast, lean persons are more responsive to reductions in dietary SFA and cholesterol. Multiple mechanisms likely contribute to the altered plasma lipid responses to dietary changes in individuals with excess adiposity. The greater rate of hepatic cholesterol synthesis in obese individuals suppresses the expression of hepatic LDL receptors (LDLR), thereby reducing hepatic LDL uptake. Insulin resistance develops as a result of adipose-tissue induced inflammation, causing significant changes in enzymes necessary for normal lipid metabolism. In addition, the LDLR-mediated uptake in obesity is attenuated by alterations in neuroendocrine regulation of hormonal secretions (e.g. growth hormone, thyroid hormone, and cortisol) as well as the unique gut microbiota, the latter of which appears to affect lipid absorption. Reducing adipose tissue mass, especially from the abdominal region, is an effective strategy to improve the lipid response to dietary interventions by reducing inflammation, enhancing insulin sensitivity, and improving LDLR binding. Thus, normalizing adipose tissue mass is an important goal for maximizing the diet response to a plasma cholesterol–lowering diet.

This article summarizes presentations from “Insights and Perspectives on Dietary Modifications to Reduce the Risk of Cardiovascular Disease,” a symposium held at the ASN Annual Meeting and Scientific Sessions in conjunction with Experimental Biology 2014 in San Diego, CA on 26 April 2014. Presenters reviewed historic and current evidence on the relation between diet and cardiovascular disease (CVD) to identify gaps in knowledge, discuss the promises and pitfalls of macronutrient replacement strategies in the diet, and suggest various options for issuing dietary guidance aimed at reducing the burden of CVD morbidity and mortality. Observational studies and clinical trials indicate that overall diet quality have a marked impact on health benefits, which is shifting the emphasis on recommending healthful dietary patterns to focusing only on single nutrients or foods.