Nutritional care is the first-line therapy for many conditions

Abstract

Nutritional care, medical nutrition, or nutrition therapy were developed based on the concept of nutritional support. Although the term “nutritional support” mainly indicates supplementation of insufficient nutrients, the concept of nutritional care or medical nutrition implies additional goals that may include metabolic and immune function regulation and treatment of malnutrition in the context of underlying diseases. The ambitious goal of nutritional care is to ultimately improve nutritional status, clinical outcomes, and quality of life (QoL), to prolong survival time, and to reduce medical costs. Although nutritional care plays an important role in the treatment of disease-related malnutrition, its actual clinical and medical value has been underestimated for a long time. Nutritional care has been indeed long considered an auxiliary or supportive therapy, with low priority in routine clinical practice. Nevertheless, in recent years an increasing number of consensus opinions have proposed that nutrition care should be recommended as a basic treatment and first-line therapy for multiple diseases and should be given equal attention as other treatments, such as surgery and drugs. Here, we will provide examples of three main conditions for implementation of optimal nutrition and nutritional care: replacement of nutrient deficiencies and treatment of metabolic abnormalities; treatment of disease and aging-related malnutrition; prevention of non-communicable disease (NCD), with particular regard to cardiometabolic diseases. Nutrition, health, and disease: a fundamental relationship Unhealthy food and nutrition may cause disease, whereas healthy and balanced food intake plays a key role in disease prevention and health preservation. Besides their fundamental role in maintenance of cell, tissue and body mass and composition, a variety of nutrients are essential for growth and development, cellular function, energy production, and immune defense.[1] For instance, evolution of the immune system, diet as well as microbiome are interconnected, and selected foods and dietary metabolites modulate immune cells and inflammation both directly and indirectly. Appropriate diets can therefore improve the treatment and prognosis of chronic autoimmune diseases through inflammatory and immunomodulatory effects. In general, specific foods and diets as well as medical nutrition preparations for nutritional therapy may provide effective treatment options for several diseases, including but not limited to malnutrition. Substantial progress in nutrition research has occurred in recent years. New studies provided selected cause-effect demonstrations, identified quantitative etiologic effects, indicated heterogeneity, and improved our understanding of optimal intakes of major dietary factors also in disease conditions. These findings conversely contributed to informed disease impact estimation and have the potential to improve policy and priority planning.[2,3] Although substantial work is still ahead, evidence-based nutrition and nutritional care shows increasing potential to preserve and improve human health and QoL, together and as potential alternative to other drug treatments.[4,5] Nutrition care for nutrient deficiency and dysmetabolic disorders Nutrient deficiency or excess, nutritional metabolic dysfunction or disorders, and nutrient imbalance can all lead to disease. The harm of disease-associated nutrient deficiency and the benefits of nutrition care are obvious. As a major example, maternal undernutrition contributes to fetal growth restriction, which increases the risk of neonatal death. Undernutrition in the aggregate—fetal growth restriction, stunting, wasting, and micronutrient deficiencies including vitamin A and zinc along with suboptimum breastfeeding—is the cause of 3.1 million child deaths annually, and it accounted for 45% of all child deaths in 2011.[6] Deficiencies in iodine and iron, together with stunting, can contribute to children not reaching their developmental potential. There is growing evidence that sustained improvements in early life and adult pre-pregnancy nutrition could improve birth outcomes in offspring,[7] and vitamin D and omega-3 fatty acid supplementation during pregnancy may be protective against early childhood wheezing.[8] As a major early example of nutrition care for selected nutrient deficiencies, since vitamin D was first described almost a century ago, vitamin D preparations have been successfully used as a public health intervention to prevent nutritional rickets.[9] In the context of metabolic disorders, numerous diseases caused by abnormalities in nutritional metabolism can be cured by nutrition care and a special medical diet. For example, phenylalanine is toxic to immature nerve cells and impedes intellectual development. Food for special medical purpose (FSMP), including milk powder, rice, wheaten food, and other foods that remove phenylalanine, is the best therapeutic approach for children with phenylketonuria, which is characterized by lack of enzymes that metabolize phenylalanine, to avoid nerve damage and improve intellectual development.[10] Glutaric acidemia, which presents with specific catabolic deficiencies of amino acid or fatty acid metabolism, can also be treated with adequate FSMPs.[11] Nutrition care for disease- and aging-related malnutrition Most chronic and acute diseases may lead to malnutrition through combined low food intake, physical inactivity, and metabolic derangements.[12] The latter include inflammation, oxidative stress, and insulin resistance, with altered macro- and micronutrient metabolism, altered energy metabolism, increased energy expenditure, all leading to catabolism and loss of body and muscle mass. Disease-related malnutrition (DRM) has major physical, psychological, and clinically relevant adverse effects, including but not limited to immune dysfunction,[13] impaired muscle function and disabilities with loss of autonomy, decreased bone mass, anemia, and reduced cognitive function. These complications further lead to poor prognosis, including poor wound healing, increased infection rates, impaired tolerance to therapy, increased complications related to disease progression and therapy, delayed recovery with increased length of stay during hospitalization, reduced QoL, and, eventually, increased mortality.[14,15] During the coronavirus disease 2019 (COVID-19) pandemic, the important role of malnutrition in worsening risk of infection and disease outcomes has been unfortunately confirmed to be also a major component of disease burden in acute, infectious conditions, also in the presence of obesity.[16,17] Hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) are at nutritional risk,[18] and nutritional management can significantly improve patient outcomes.[19,20] Notably, despite existing discrepancies, a deficiency of vitamin D or selenium may inhibit immune defenses against COVID-19 and cause progression to severe disease.[21] DRM in acute and chronic diseases also significantly enhances the economic burden of healthcare. It has been reported that in the United States, DRM in patients with selected diseases including stroke, coronary heart failure, chronic obstructive pulmonary disease (COPD), dementia, depression, and breast and colorectal cancer leads to direct medical costs of $15.5 billion. Indirect medical and social economic costs, such as missed work, need for personal care and caregivers, lead to total costs up to $156.7 billion per year.[22] In the European Union, the economic cost of cardiovascular disease is €192 billion annually in direct and indirect health care costs.[23] Aging is a major risk factor for chronic diseases and disabilities, with major impact on social and health care expenditures in the presence of increasing life expectancy worldwide. Aging per se is also a cause of malnutrition through loss of skeletal muscle mass and function (sarcopenia), spontaneous reduction in food intake, and enhanced social and economic challenges.[24] Healthy lifestyle including balanced dietary intake with optimal protein and calcium provision and vitamin D sufficiency, as well as physical activity with resistance exercise may delay the onset of sarcopenia and aging-related diseases, and they may limit the nutritional impact of established disease conditions.[25] Selected dietary patterns such as adherence to Mediterranean diet may be associated with lower health risks and preserved cognitive function.[26,27] Several studies show that nutrition care can significantly shorten hospital stays, reduce medical costs, improve clinical outcomes and QoL, and may prolong survival in older patients and in patients with miscellaneous disease conditions.[28–30] In more than 1 million inpatients, oral nutritional supplements (ONS) shortened hospitalization stays by 21%, reduced medical costs by 21.6%, and reduced the 30-day rehospitalization rate by 6.7%.[31] Also importantly, older patients may benefit more from nutrition care.[32] Nutritional care is also reported to be beneficial in community residents and home care patients. In one study, ONSs reduced the infection rate and risk of falls, improved physical activity function and QoL, and extended adjusted QoL years.[33] From the health-economic point of view, it was calculated that $1 invested in nutritional care may save $52 in future potential healthcare resources.[31] In another report, nutrition care was estimated to save $580 million in direct medical costs annually in patients with sepsis, gastrointestinal tumors, hospital infections, surgical complications, and pancreatitis.[34,35] Among many other acute and chronic diseases, cancer is a paradigm of DRM, and most patients with cancer (30%–90%) experience malnutrition because of both disease progression and treatment consequences.[36–38] Malnutrition is associated with numerous clinically relevant adverse effects, and approximately 40% of patients with cancer die of malnutrition.[39] Despite clinical heterogeneity and some discrepancies in available studies, strong evidence indicates relevant benefits of nutritional treatment on cancer patient outcomes. Bargetzi et al reported that calorie and protein supplementation improve QoL indicators, functional status, and survival.[40] Timing of treatment also seems important, as another study reported that early nutritional treatment was associated with prolonged survival in miscellaneous advanced cancer patients compare to later intervention.[41] Khosravi et al found that nutrition care alone and second-line chemotherapy had equivalent protective roles on progression-free survival and overall survival in patients with advanced non–small-cell lung cancer who had failed first-line chemotherapy.[42] Lu et al also reported that nutrition care reduces risk of death by 32% and prolonged survival by 2.9 months in patients with advanced esophageal cancer and gastric cancer.[43] In patients undergoing non-surgical treatment, nutrition care may significantly improve chemoradiotherapy tolerance, reduce toxic side effects, improve QoL, and prolong survival time.[44] In general, substantial evidence in recent years has confirmed that pre-rehabilitation and nutritional therapy starting before the time of anti-cancer treatments (approximately 2 weeks in advance), including both surgery and chemoradiotherapy, is more beneficial in improving outcomes and prolonging survival time than nutritional care concurrent with anti-tumor treatments. Perioperative nutritional therapy including ONS and immunomodulatory formulas, included within the enhanced recovery after surgery (ERAS) protocol,[45] has proven to be a main element and a critical step to achieve better surgical results, including reductions in complications, the need for the intensive care unit (ICU), and hospital stay, costs, and mortality.[46] Based on the above considerations and findings, several guidelines provide evidence-based recommendations that patients with cancer as well as several other chronic and acute conditions undergo regular nutritional screening and evaluation, and be managed accordingly through all stages of disease treatment.[37,44,45,47] Prevention of chronic NCDs and chronic disease progression In the context of NCDs, hypertension, diabetes, and cardiovascular and cerebrovascular diseases, which are mostly, although not exclusively related to over-nutrition and unhealthy dietary habits,[48] have become the most important threats to the health of the world’s population.[49] Indeed, strong scientific evidence indicates an increase in NCDs also in low-income and middle-income countries since 2000, as previously seen in high-income settings.[50] NCDs share a number of causal behavioral risk factors,[51,52] including high-energy/fat diet,[53,54] high intake of ultra-processed foods,[55] high salt intake,[56] low fresh fruit and vegetable diet, obesity,[57] physical inactivity,[58] tobacco smoking, and alcohol excess.[58] Unhealthy lifestyle (eg, high salt, energy, fat and cholesterol intake, low vegetable intake, and physical inactivity) may lead to metabolic derangements with chronic systemic inflammation, oxidative stress injury, and insulin resistance,[59] that significantly increase the risk of NCDs and related mortality.[60] As mentioned above, NCDs may further enhance similar metabolic abnormalities leading to synergistic derangements that further lead to altered nutritional state and DRM. Appropriate nutrition care (eg, nutrition and health consultation and education through TV media, public service advertisements, popular science articles, family follow-up, and other ways) help patients and community population to adhere to a healthy diet and lifestyle, including limiting alcohol consumption, use of low-fat dairy products, consuming diets low in saturated fat and cholesterol, reducing the intake of red and processed meat, increasing the intake of whole grains, fruits, vegetables, nuts, seeds, and legumes, and attaining balanced energy intake and body weight, can prevent NCDs, reverse early conditions, delay disease progression in patients with moderate or severe NCDs, and ultimately reduce the risk of death and improve survival.[61–63] In the context of cardiometabolic disease prevention, randomized controlled trials have confirmed that a low intake of dietary saturated fat and replacement with polyunsaturated vegetable oil reduced cardiovascular disease (CVD) by ≈30%, similar to reductions achieved by statin treatment.[64] A balanced Mediterranean diet (adequate levels of fruits and vegetables and moderate levels of fish, meat, olive oil, and red wine),[65] and potentially vegetarian diet have been shown to limit the incidence of various NCDs, including cardiovascular disease, diabetes, and some cancers,[66] while improving disease treatment and prolonging survival.[67,68] The DASH dietary pattern, which is widely recommended by international diabetes and heart association guidelines, is associated with decreased incidence of cardiovascular disease[69] and kidney disease.[70] In China, most patients with hypertension have type H hypertension (hypertension with hyperhomocysteinemia) with folate deficiency and high homocysteine levels.[71] Folate supplementation could reduce homocysteine levels and the risk of high blood pressure and its complications, including stroke. Antihypertensive drug treatment with folate supplementations accordingly significantly reduced the incidence of stroke and the corresponding medical and financial burden in China.[72,73] Appropriate diet, exercise, and other behavioral therapies for lifestyle interventions could prevent the progression or worsening of metabolic syndrome, including insulin resistance, with resulting beta-cell failure, diabetes mellitus, polycystic ovary syndrome (PCOS), hyperinsulinemia, and reactive hypoglycemia.[74] In one study, a dietary pattern low in staple foods and high in dairy milk was associated with a lower risk of type 2 diabetes in Chinese individuals.[75] Cancer represents another paradigm also for nutritional prevention. The World Cancer Research Foundation (WCRF) and American Society for Cancer Research (AICR) have proposed multiple versions of cancer prevention dietary guidelines (eg, recommending increased intake of vegetables, fruits, cereals, and legumes [over 2/3]; weight control, maintaining body mass index (BMI) between 20 and 23 kg/m2; increased physical exercise; eating less red meat or processed meat, consuming less refined sugar and alcohol) aimed at preventing cancer through diet and lifestyle. Changes in the cancer spectrum in the Chinese population suggest that it is urgent to improve dietary intake at population level for primary and secondary cancer prevention.[76] Also highlighting the key role of diet in cancer development, data from the National Cancer Center of China showed that in the past 30 years, the incidence of tumors associated with exposure to toxic carcinogens (eg, pickled, smoked, and moldy food), such as gastric, esophageal, and liver cancer, has significantly decreased, while the incidence of cancers associated with the prevalence of Western lifestyle (high-energy/high-fat diet, low physical activity) and obesity, such as colorectal, thyroid, prostate, and breast cancer, has increased 2- to 3-fold.[77] Dietary interventions combined with cancer drugs could also potentially be considered. Although the risk of malnutrition should be always considered, some preliminary and pre-clinical studies have suggested that limited nutrient restriction can potentiate the efficacy of, or alleviate resistance to cancer drugs.[78] Further studies are needed for clinical implementation of this hypothesis. Among other diseases, premature ovarian insufficiency (POI) ranks among the top reproductive disorders that may impair multiple functioning systems. Symptoms can be partially alleviated by hormone replacement therapy. The therapeutic effect of functional nutrition, such as proliferative, anti-inflammatory, antioxidant, and mitochondria-protective potential, during the course of menopause on POI is driving increasing attention.[79] In the context of disease control and treatment, diet should be a of effective treatment for multiple chronic diseases. 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