Nutrition and the 2020 Pandemic

Patrick J. Stover and Rudi Balling

doi : 10.1146/annurev-nu-40-082120-100001

Vol. 40, 2020, pp. v–vi

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An Accidental Nutritionist

Alfred Sommer

doi : 10.1146/annurev-nutr-111919-033415

Vol. 40, 2020, pp. 1–23

My career as an accidental nutritionist began with my immersion in cholera control, a cyclone disaster, a smallpox epidemic, and formal training in ophthalmology and epidemiology. Interest in blindness prevention inexplicably led me to (re)pioneer the effects, treatment, and prevention of vitamin A deficiency, while faced with intense criticism by many leading scientists in the nutrition community. The resulting efforts by the World Health Organization and UNICEF in support of programs for the global control of vitamin A deficiency still face vocal opposition by some senior scientists, despite having been estimated to have saved tens of millions of children from unnecessary death and blindness. This entire journey was largely an accident!

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Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning

Nishan Sudheera Kalupahana, Bimba Lakmini Goonapienuwala, Naima Moustaid-Moussa

doi : 10.1146/annurev-nutr-122319-034142

Vol. 40, 2020, pp. 25–49

White adipose tissue (WAT) and brown adipose tissue (BAT) are involved in whole-body energy homeostasis and metabolic regulation. Changes to mass and function of these tissues impact glucose homeostasis and whole-body energy balance during development of obesity, weight loss, and subsequent weight regain. Omega-3 polyunsaturated fatty acids (?-3 PUFAs), which have known hypotriglyceridemic and cardioprotective effects, can also impact WAT and BAT function. In rodent models, these fatty acids alleviate obesity-associated WAT inflammation, improve energy metabolism, and increase thermogenic markers in BAT. Emerging evidence suggests that ?-3 PUFAs can also modulate gut microbiota impacting WAT function and adiposity. This review discusses molecular mechanisms, implications of these findings, translation to humans, and future work, especially with reference to the potential of these fatty acids in weight loss maintenance.

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Nutrient Control of mRNA Translation

Xin Erica Shu, Robert V. Swanda, Shu-Bing Qian

doi : 10.1146/annurev-nutr-120919-041411

Vol. 40, 2020, pp. 51–75

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

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Roles of Regulatory RNAs in Nutritional Control

Elizabeth M. McNeill and Kendal D. Hirschi

doi : 10.1146/annurev-nutr-122319-035633

Vol. 40, 2020, pp. 77–104

Small RNAs (sRNAs), including microRNAs (miRNAs), are noncoding RNA (ncRNA) molecules involved in gene regulation. sRNAs play important roles in development; however, their significance in nutritional control and as metabolic modulators is still emerging. The mechanisms by which diet impacts metabolic genes through miRNAs remain an important area of inquiry. Recent work has established how miRNAs are transported in body fluids often within exosomes, which are small cell-derived vesicles that function in intercellular communication. The abundance of other recently identified ncRNAs and new insights regarding ncRNAs as dietary bioactive compounds could remodel our understanding about how foods impact gene expression. Although controversial, some groups have shown that dietary RNAs from plants and animals (i.e., milk) are functional in consumers. In the future, regulating sRNAs either directly through dietary delivery or indirectly by altered expression of endogenous sRNA may be part of nutritional interventions for regulating metabolism.

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Calorie Restriction and Aging in Humans

Emily W. Flanagan, Jasper Most, Jacob T. Mey, Leanne M. Redman

doi : 10.1146/annurev-nutr-122319-034601

Vol. 40, 2020, pp. 105–133

Calorie restriction (CR), the reduction of dietary intake below energy requirements while maintaining optimal nutrition, is the only known nutritional intervention with the potential to attenuate aging. Evidence from observational, preclinical, and clinical trials suggests the ability to increase life span by 1–5 years with an improvement in health span and quality of life. CR moderates intrinsic processes of aging through cellular and metabolic adaptations and reducing risk for the development of many cardiometabolic diseases. Yet, implementation of CR may require unique considerations for the elderly and other specific populations. The objectives of this review are to summarize the evidence for CR to modify primary and secondary aging; present caveats for implementation in special populations; describe newer, alternative approaches that have comparative effectiveness and fewer deleterious effects; and provide thoughts on the future of this important field of study.

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Nutritional Aspects of Spermidine

Frank Madeo, Sebastian J. Hofer, Tobias Pendl, Maria A. Bauer, Tobias Eisenberg, Didac Carmona-Gutierrez, Guido Kroemer

doi : 10.1146/annurev-nutr-120419-015419

Vol. 40, 2020, pp. 135–159

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.

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Novel Approaches for Omega-3 Fatty Acid Therapeutics: Chronic Versus Acute Administration to Protect Heart, Brain, and Spinal Cord

Hylde Zirpoli, Chuchun L. Chang, Yvon A. Carpentier, Adina T. Michael-Titus, Vadim S. Ten, Richard J. Deckelbaum

doi : 10.1146/annurev-nutr-082018-124539

Vol. 40, 2020, pp. 161–187

This article reviews novel approaches for omega-3 fatty acid (FA) therapeutics and the linked molecular mechanisms in cardiovascular and central nervous system (CNS) diseases. In vitro and in vivo research studies indicate that omega-3 FAs affect synergic mechanisms that include modulation of cell membrane fluidity, regulation of intracellular signaling pathways, and production of bioactive mediators. We compare how chronic and acute treatments with omega-3 FAs differentially trigger pathways of protection in heart, brain, and spinal cord injuries. We also summarize recent omega-3 FA randomized clinical trials and meta-analyses and discuss possible reasons for controversial results, with suggestions on improving the study design for future clinical trials. Acute treatment with omega-3 FAs offers a novel approach for preserving cardiac and neurological functions, and the combinations of acute treatment with chronic administration of omega-3 FAs might represent an additional therapeutic strategy for ameliorating adverse cardiovascular and CNS outcomes.

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Nutrition Regulates Innate Immunity in Health and Disease

Samuel Philip Nobs, Niv Zmora, Eran Elinav

doi : 10.1146/annurev-nutr-120919-094440

Vol. 40, 2020, pp. 189–219

Nutrient content and nutrient timing are considered key regulators of human health and a variety of diseases and involve complex interactions with the mucosal immune system. In particular, the innate immune system is emerging as an important signaling hub that modulates the response to nutritional signals, in part via signaling through the gut microbiota. In this review we elucidate emerging evidence that interactions between innate immunity and diet affect human metabolic health and disease, including cardiometabolic disorders, allergic diseases, autoimmune disorders, infections, and cancers. Furthermore, we discuss the potential modulatory effects of the gut microbiota on interactions between the immune system and nutrition in health and disease, namely how it relays nutritional signals to the innate immune system under specific physiological contexts. Finally, we identify key open questions and challenges to comprehensively understanding the intersection between nutrition and innate immunity and how potential nutritional, immune, and microbial therapeutics may be developed into promising future avenues of precision treatment.

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Nutritional Requirements for Sustaining Health and Performance During Exposure to Extreme Environments

Stefan M. Pasiakos

doi : 10.1146/annurev-nutr-011720-122637

Vol. 40, 2020, pp. 221–245

Dietary guidelines are formulated to meet minimum nutrient requirements, which prevent deficiencies and maintain health, growth, development, and function. These guidelines can be inadequate and contribute to disrupted homeostasis, lean body mass loss, and deteriorated performance in individuals who are working long, arduous hours with limited access to food in environmentally challenging locations. Environmental extremes can elicit physiological adjustments that alone alter nutrition requirements by upregulating energy expenditure, altering substrate metabolism, and accelerating body water and muscle protein loss. The mechanisms by which the environment, including high-altitude, heat, and cold exposure, alters nutrition requirements have been studied extensively. This contemporary review discusses physiological adjustments to environmental extremes, particularly when those adjustments alter dietary requirements.

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Vitamin A and Retinoic Acid in Cognition and Cognitive Disease

Marta U. Wo?oszynowska-Fraser, Azita Kouchmeshky, Peter McCaffery

doi : 10.1146/annurev-nutr-122319-034227

Vol. 40, 2020, pp. 247–272

The history of vitamin A goes back over one hundred years, but our realization of its importance for the brain and cognition is much more recent. The brain is more efficient than other target tissues at converting vitamin A to retinoic acid (RA), which activates retinoic acid receptors (RARs). RARs regulate transcription, but their function in the cytoplasm to control nongenomic actions is also crucial. Controlled synthesis of RA is essential for regulating synaptic plasticity in regions of the brain involved in learning and memory, such as the hippocampus. Vitamin A deficiency results in a deterioration of these functions, and failure of RA signaling is perhaps associated with normal cognitive decline with age as well as with Alzheimer's disease. Further, several psychiatric and developmental disorders that disrupt cognition are also linked with vitamin A and point to their possible treatment with vitamin A or RA.

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The Role of Diet in Cancer Prevention and Chemotherapy Efficacy

Steven D. Mittelman

doi : 10.1146/annurev-nutr-013120-041149

Vol. 40, 2020, pp. 273–297

Despite great advances in treatment, cancer remains a leading cause of death worldwide. Diet can greatly impact health, while caloric restriction and fasting have putative benefits for disease prevention and longevity. Strong epidemiological associations exist between obesity and cancer, whereas healthy diets can reduce cancer risk. However, less is known about how diet might impact cancer once it has been diagnosed and particularly how diet can impact cancer treatment. In the present review, we discuss the links between obesity, diet, and cancer. We explore potential mechanisms by which diet can improve cancer outcomes, including through hormonal, metabolic, and immune/inflammatory effects, and present the limited clinical research that has been published in this arena. Though data are sparse, diet intervention may reduce toxicity, improve chemotherapy efficacy, and lower the risk of long-term complications in cancer patients. Thus, it is important that we understand and expand the science of this important but complex adjunctive cancer treatment strategy.

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Short Bowel Syndrome: A Paradigm for Intestinal Adaptation to Nutrition?

Johanne Le Beyec, Lore Billiauws, André Bado, Francisca Joly, Maude Le Gall

doi : 10.1146/annurev-nutr-011720-122203

Vol. 40, 2020, pp. 299–321

Short bowel syndrome (SBS) is a rare disease that results from extensive resection of the intestine. When the remaining absorption surface of the intestine cannot absorb enough macronutrients, micronutrients, and water, SBS results in intestinal failure (IF). Patients with SBS who suffer from IF require parenteral nutrition for survival, but long-term parenteral nutrition may lead to complications such as catheter sepsis and metabolic diseases. Spontaneous intestinal adaptation occurs weeks to months after resection, resulting in hyperplasia of the remnant gut, modification of gut hormone levels, dysbiosis, and hyperphagia. Oral nutrition and presence of the colon are two major positive drivers for this adaptation. This review aims to summarize the current knowledge of the mechanisms underlying spontaneous intestinal adaptation, particularly in response to modifications of luminal content, including nutrients. In the future, dietary manipulations could be used to treat SBS.

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From Birth and Throughout Life: Fungal Microbiota in Nutrition and Metabolic Health

William D. Fiers, Irina Leonardi, Iliyan D. Iliev

doi : 10.1146/annurev-nutr-013120-043659

Vol. 40, 2020, pp. 323–343

The human gastrointestinal tract is home to a vibrant, diverse ecosystem of prokaryotic and eukaryotic microorganisms. The gut fungi (mycobiota) have recently risen to prominence due to their ability to modulate host immunity. Colonization of the gut occurs through a combination of vertical transmission from the maternal mycobiota and environmental and dietary exposure. Data from human and animal studies demonstrate that nutrition strongly affects the mycobiota composition and that changes in the fungal communities can aggravate metabolic diseases. The mechanisms pertaining to the mycobiota's influence on host health, pathology, and resident gastrointestinal communities through intrakingdom, transkingdom, and immune cross talk are beginning to come into focus, setting the stage for a new chapter in microbiota–host interactions. Herein, we examine the inception, maturation, and dietary modulation of gastrointestinal and nutritional fungal communities and inspect their impact on metabolic diseases in humans.

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Drinking Water in the United States: Implications of Water Safety, Access, and Consumption

Anisha I. Patel, Christina E. Hecht, Angie Cradock, Marc A. Edwards, Lorrene D. Ritchie

doi : 10.1146/annurev-nutr-122319-035707

Vol. 40, 2020, pp. 345–373

Recent water quality crises in the United States, and recognition of the health importance of drinking water in lieu of sugar-sweetened beverages, have raised interest in water safety, access, and consumption. This review uses a socioecological lens to examine these topics across the life course. We review water intakes in the United States relative to requirements, including variation by age and race/ethnicity. We describe US regulations that seek to ensure that drinking water is safe to consume for most Americans and discuss strategies to reduce drinking water exposure to lead, a high-profile regulated drinking water contaminant. We discuss programs, policies, and environmental interventions that foster effective drinking water access, a concept that encompasses key elements needed to improve water intake. We conclude with recommendations for research, policies, regulations, and practices needed to ensure optimal water intake by all in the United States and elsewhere.

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All Children Thrive: Integration of Nutrition and Early Childhood Development

Maureen M. Black, Angela C.B. Trude, Chessa K. Lutter

doi : 10.1146/annurev-nutr-120219-023757

Vol. 40, 2020, pp. 375–406

Building on the successes of child survival, we review the evidence needed to ensure both that children who survive also thrive and that recommendations promote equity, with no child left behind. To illustrate the critical roles played by nutrition and child development, we revise the Conceptual Framework for the Causes of Malnutrition and Death and the Nurturing Care Framework to create the Conceptual Framework of All Children Surviving and Thriving. The revised framework highlights the goals of child growth and development, supported by health, nutrition, learning, responsive caregiving, and security and safety. We review the challenges posed by undernutrition, stunting, micronutrient deficiencies, overweight, and children not reaching their developmental potential. Although integrated nutrition–childhood development interventions have shown promising effects, most have not been implemented at scale. Implementation science that investigates how and why integrated interventions work in real life, along with the acceptability, feasibility, cost, coverage, and sustainability of the interventions, is needed to ensure equity for all children thriving.

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Policy Progress in Reducing Sodium in the American Diet, 2010–2019

Aviva A. Musicus, Vivica I. Kraak, Sara N. Bleich

doi : 10.1146/annurev-nutr-122319-040249

Vol. 40, 2020, pp. 407–435

Most Americans consume dietary sodium exceeding age-specific government-recommended targets of 1,500–2,300 mg/day per person. The majority (71%) of US dietary sodium comes from restaurant and packaged foods. Excess sodium intake contributes to hypertension and cardiovascular disease, which is the leading cause of death in the United States. This review summarizes evidence for policy progress to reduce sodium in the US food supply and the American diet. We provide a historical overview of US sodium-reduction policy (1969–2010), then examine progress toward implementing the 2010 National Academy of Medicine (NAM) sodium report's recommendations (2010–2019). Results suggest that the US Food and Drug Administration made no progress in setting mandatory sodium-reduction standards, industry made some progress in meeting voluntary targets, and other stakeholders made some progress on sodium-reduction actions. Insights from countries that have significantly reduced population sodium intake offer strategies to accelerate US progress toward implementing the NAM sodium-reduction recommendations in the future.

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Impacts and Echoes: The Lasting Influence of the White House Conference on Food, Nutrition, and Health

Catherine E. Woteki, Brandon L. Kramer, Samantha Cohen, and Vicki A. Lancaster

doi : 10.1146/annurev-nutr-121619-045319

Vol. 40, 2020, pp. 437–461

The 1969 White House Conference on Food, Nutrition, and Health had a significant influence on the direction of food and nutrition policy in the United States. The conference produced recommendations leading to federal legislation and programs to alleviate hunger and malnutrition, improve consumers’ nutrition knowledge through education and labeling, and monitor the nutritional status of the population. Fifty years later, its legacy was revisited at a conference convened by Harvard University and Tufts University. This article reviews the literature contributing to the first author's keynote speech at the conference, its influencers, and its influences. We focus on the highlights of five domains that set the stage for the conference: the social environment, the food environment, nutrition science, public health data, and policy events. We briefly describe the conference, its proposed directions, and its lasting legacy in these five domains.

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