David M. Klurfeld

Towards Establishing Dietary Reference Intakes for Eicosapentaenoic and Docosahexaenoic Acids

There is considerable interest in the impact of (n-3) long-chain PUFA in mitigating the morbidity and mortality caused by chronic diseases. In 2002, the Institute of Medicine concluded that insufficient data were available to define Dietary Reference Intakes (DRI) for eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), noting only that EPA and DHA could contribute up to 10% toward meeting the Adequate Intake for alpha-linolenic acid. Since then, substantial new evidence has emerged supporting the need to reassess this recommendation. Therefore, the Technical Committee on Dietary Lipids of the International Life Sciences Institute North America sponsored a workshop on 4-5 June 2008 to consider whether the body of evidence specific to the major chronic diseases in the United States--coronary heart disease (CHD), cancer, and cognitive decline--had evolved sufficiently to justify reconsideration of DRI for EPA+DHA. The workshop participants arrived at these conclusions: 1) consistent evidence from multiple research paradigms demonstrates a clear, inverse relation between EPA+DHA intake and risk of fatal (and possibly nonfatal) CHD, providing evidence that supports a nutritionally achievable DRI for EPA+DHA between 250 and 500 mg/d; 2) because of the demonstrated low conversion from dietary ALA, protective tissue levels of EPA+DHA can be achieved only through direct consumption of these fatty acids; 3) evidence of beneficial effects of EPA+DHA on cognitive decline are emerging but are not yet sufficient to support an intake level different from that needed to achieve CHD risk reduction; 4) EPA+DHA do not appear to reduce risk for cancer; and 5) there is no evidence that intakes of EPA+DHA in these recommended ranges are harmful.

Consumption of cereal fiber, mixtures of whole grains and bran, and whole grains and risk reduction in type 2 diabetes, obesity, and cardiovascular disease

BACKGROUNDnStudies of whole grain and chronic disease have often included bran-enriched foods and other ingredients that do not meet the current definition of whole grains. Therefore, we assessed the literature to test whether whole grains alone had benefits on these diseases.nnnOBJECTIVEnThe objective was to assess the contribution of bran or cereal fiber on the impact of whole grains on the risk of type 2 diabetes (T2D), obesity and body weight measures, and cardiovascular disease (CVD) in human studies as the basis for establishing an American Society for Nutrition (ASN) position on this subject.nnnDESIGNnWe performed a comprehensive PubMed search of human studies published from 1965 to December 2010.nnnRESULTSnMost whole-grain studies included mixtures of whole grains and foods with ≥25% bran. Prospective studies consistently showed a reduced risk of T2D with high intakes of cereal fiber or mixtures of whole grains and bran. For body weight, a limited number of prospective studies on cereal fiber and whole grains reported small but significant reductions in weight gain. For CVD, studies found reduced risk with high intakes of cereal fiber or mixtures of whole grains and bran.nnnCONCLUSIONSnThe ASN position, based on the current state of the science, is that consumption of foods rich in cereal fiber or mixtures of whole grains and bran is modestly associated with a reduced risk of obesity, T2D, and CVD. The data for whole grains alone are limited primarily because of varying definitions among epidemiologic studies of what, and how much, was included in that food category.

Dietary Reference Intakes for vitamin D: justification for a review of the 1997 values

Recent Institute of Medicine (IOM) reviews of the process for deriving Dietary Reference Intakes (DRIs) suggest that determining the need for a new nutrient review should be evaluated against criteria set a priori. After selecting the criterion of significant new and relevant research, a working group of US and Canadian government scientists used results from a systematic review and 2 conferences on vitamin D and health to evaluate whether significant new and relevant scientific evidence had become available since the 1997 IOM publication of the DRIs for vitamin D. This working group concluded that there appears to be new research meeting the criteria for 4 key DRI questions. The new research is of larger quantity and quality for the elderly than for other groups, but overall 1) adds to the bone-related and status evidence available to the 1997 DRI Committee for several of the life-stage groups, 2) identifies new outcomes with respect to risk of falls and performance measures in the elderly and potential adverse effects, and 3) provides additional information on dose-response relations between intakes and circulating 25-hydroxyvitamin D concentrations and between 25-hydroxyvitamin D concentrations and several health outcomes (ie, bone-related outcomes for all ages and risk of falls and performance measures in older adults). Members of the working group concluded that significant new and relevant research was available for reviewing the existing DRIs for vitamin D while leaving the decision of whether the new research will result in changes to the current DRIs to a future IOM-convened DRI committee.

Barriers and Facilitators for Consumer Adherence to the Dietary Guidelines for Americans: The HEALTH Study

The majority of the US population does not meet recommendations for consumption of milk, whole grains, fruit, and vegetables. The goal of our study was to understand barriers and facilitators to adherence to the Dietary Guidelines for Americans for four nutrient-rich food groups in fifth-grade children and unrelated adult caregivers across six sites in a multistate study. A total of 281 unrelated adult caregivers (32% African American, 33% European American, and 35% Hispanic American) and 321 children (33% African American, 33% European American, and 34% Hispanic American) participated in 97 Nominal Group Technique sessions. Nominal Group Technique is a qualitative method of data collection that enables a group to generate and prioritize a large number of issues within a structure that gives everyone an equal voice. The core barriers specific to unrelated adult caregivers were lack of meal preparation skills or recipes (whole grains, fruit, vegetables); difficulty in changing eating habits (whole grains, fruit, vegetables), cost (milk, whole grains, fruit, vegetables), lack of knowledge of recommendation/portion/health benefits (milk, vegetables), and taste (milk, whole grains, vegetables). Specific to children, the core barriers were competing foods (ie, soda, junk foods, sugary foods [whole grains, milk, fruit, vegetables]), health concerns (ie, milk allergy/upset stomach [milk]), taste/flavor/smell (milk, whole grains, fruit, vegetables), forget to eat them (vegetables, fruit), and hard to consume or figure out the recommended amount (milk, fruit). For both unrelated adult caregivers and children, reported facilitators closely coincided with the barriers, highlighting modifiable conditions that could help individuals to meet the Dietary Guidelines for Americans.

Web-Enabled and Improved Software Tools and Data Are Needed to Measure Nutrient Intakes and Physical Activity for Personalized Health Research

Food intake, physical activity (PA), and genetic makeup each affect health and each factor influences the impact of the other 2 factors. Nutrigenomics describes interactions between genes and environment. Knowledge about the interplay between environment and genetics would be improved if experimental designs included measures of nutrient intake and PA. Lack of familiarity about how to analyze environmental variables and ease of access to tools and measurement instruments are 2 deterrents to these combined studies. This article describes the state of the art for measuring food intake and PA to encourage researchers to make their tools better known and more available to workers in other fields. Information presented was discussed during a workshop on this topic sponsored by the USDA, NIH, and FDA in the spring of 2009.

Research gaps in evaluating the relationship of meat and health.

Humans evolved as omnivores and it has been proposed that cooking meat allowed for evolution of larger brains that has led to our success as a species. Meat is one of the most nutrient dense foods, providing high-quality protein, heme iron, zinc, and vitamins B6 and B12. Despite these advantages, epidemiologic studies have linked consumption of red or processed meat with obesity, type 2 diabetes, cardiovascular diseases, and cancers of multiple organs. Most observational studies report small, increased relative risks. However, there are many limitations of such studies including inability to accurately estimate intake, lack of prespecified hypotheses, multiple comparisons, and confounding from many factors - including body weight, fruit/vegetable intake, physical activity, smoking, and alcohol - that correlate significantly either positively or negatively with meat intake and limit the reliability of conclusions from these studies. The observational studies are heterogeneous and do not fulfill many of the points proposed by AB Hill in 1965 for inferring causality; his most important factor was strength of the association which in dietary studies is usually <1.5 but is not considered adequate in virtually all other areas of epidemiology outside nutrition. Accepting small, statistically significant risks as real from observational associations, the field of nutrition has a long list of failures including beta-carotene and lung cancer, low-fat diets and breast cancer or heart disease that have not been confirmed in randomized trials. Moderate intake of a variety of foods that are enjoyed by people remains the best dietary advice.

Effects of low-fat and/or high fruit-and-vegetable diets on plasma levels of 8-Isoprostane-F2α in the nutrition and breast health study

Abstract: Dietary patterns that involve both a decrease in fat and an increase in fruit and vegetable (FV) intake may decrease cancer risks. In this study, a total of 122 premenopausal women with a family history of breast cancer were randomized into one of four diets for 12 mo: nonintervention, low-fat (15% of energy from fat), high-FV (9 servings/d), and combination low-fat/high-FV. Fasting blood samples were obtained at baseline and after 3, 6, and 12 mo. Levels of 8-isoprostane-F2α in plasma were determined by immunoassay kits. Statistical analyses indicated that levels of 8-isoprostane-F2α decreased significantly with time in the low-fat arm, which is the only intervention that resulted in weight loss; there were no significant changes in the other three diet arms. It is unlikely that this is due to changes in levels of blood lipids because there was little change over time in plasma total cholesterol, high-density lipoprotein, low-density lipoprotein (LDL), or triglyceride levels in any diet arm, although mean LDL did decrease slightly in women who reduced fat intake after adjustment for change in body mass index (BMI). Levels of baseline 8-isoprostane-F2α were significantly higher in obese women than in overweight or normal weight women, and change in BMI was significantly correlated with change in 8-isoprostane-F2α levels. These results indicate that low-fat diets or high-FV diets are unlikely to affect plasma levels of 8-isoprostane-F2α in healthy, premenopausal women who do not lose weight during dietary change.

Integrating the Totality of Food and Nutrition Evidence for Public Health Decision Making and Communication

The interpretation and integration of epidemiological studies detecting weak associations (RR <2) with data from other study designs (e.g., animal models and human intervention trials) is both challenging and vital for making science-based dietary recommendations in the nutrition and food safety communities. The 2008 ILSI North America “Decision-Making for Recommendations and Communication Based on Totality of Food-Related Research” workshop provided an overview of epidemiological methods, and case-study examples of how weak associations have been incorporated into decision making for nutritional recommendations. Based on the workshop presentations and dialogue among the participants, three clear strategies were provided for the use of weak associations in informing nutritional recommendations for optimal health. First, enable more effective integration of data from all sources through the use of genetic and nutritional biomarkers; second, minimize the risk of bias and confounding through the adoption of rigorous quality-control standards, greater emphasis on the replication of study results, and better integration of results from independent studies, perhaps using adaptive study designs and Bayesian meta-analysis methods; and third, emphasize more effective and truthful communication to the public about the evolving understanding of the often complex relationship between nutrition, lifestyle, and optimal health.

Achieving a transparent, actionable framework for public-private partnerships for food and nutrition research

Officers and other representatives of more than a dozen food-, nutrition-, and health-related scientific societies and organizations, food industry scientists, and staff of the USDA, the CDC, the Food and Drug Administration, and the NIH convened on 8 December 2014 in Washington, DC, to reach a consensus among individuals participating on guiding principles for the development of research-oriented, food- and nutrition-related public-private partnerships. During the daylong working meeting, participants discussed and revised 12 previously published guidelines to ensure integrity in the conduct of food and nutrition research collaborations among public, nonprofit, and private sectors. They agreed to reconvene periodically to reassess the public-private partnership principles. This article presents the guiding principles and potential benefits, outlines key discussion points, and articulates points of agreement and reservation.

Clinical Research Strategies for Fructose Metabolism

Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. NIH and USDA sponsored a workshop on 13-14 November 2012, Research Strategies for Fructose Metabolism, to identify important scientific questions and parameters to be considered while designing clinical studies. Research is needed to ascertain whether there is an obesogenic role for fructose-containing sugars via effects on eating behavior and energy balance and whether there is a dose threshold beyond which these sugars promote progression toward diabetes and liver and cardiovascular disease, especially in susceptible populations. Studies tend to fall into 2 categories, and design criteria for each are described. Mechanistic studies are meant to validate observations made in animals or to elucidate the pathways of fructose metabolism in humans. These highly controlled studies often compare the pure monosaccharides glucose and fructose. Other studies are focused on clinically significant disease outcomes or health behaviors attributable to amounts of fructose-containing sugars typically found in the American diet. These are designed to test hypotheses generated from short-term mechanistic or epidemiologic studies and provide data for health policy. Discussion brought out the opinion that, although many mechanistic questions concerning the metabolism of monosaccharide sugars in humans remain to be addressed experimentally in small highly controlled studies, health outcomes research meant to inform health policy should use large, long-term studies using combinations of sugars found in the typical American diet rather than pure fructose or glucose.