Beef as a Functional Food for Improving Human Nutrition and Health

Beef is an abundant source of all proteinogenic amino acids (AAs;in both adequate amounts and balanced ratios) and physiologically essential nonproteinogenic AAs (taurine and β-alanine). The content and bioavailabilities of proteinogenic AAs in beef are greater than those in plant-sourced foods. Taurine (a potent anti-oxidant) is essential for the integrity and functions of tissues, including eyes, heart, and skeletal muscle, whereas β-alanine is required for the production of antioxidative and neuromodulatory dipeptides. Furthermore, beef contains a large amount of creatine (essential for energy metabolism in tissues, particularly brain and skeletal muscle), anti-oxidative dipeptides (carnosine and anserine), and 4-hydroxyproline (an anti-inflammatory nutrient that maintains intestinal integrity and inhibits colitis). There are myths that plants provide all nutrients that are available in animal-sourced foods. However, taurine, vitamin B12, creatine, carnosine, and anserine are absent from plants, whereas β-alanine and 4-hydroxyproline are low or negligible in plants. Like other animal-sourced foods, beef plays an important role in the optimum growth of children and the prevention of anemia in humans, as well as maintaining muscle mass, delaying ageing, and mitigating sarcopenia in adults, while meeting the high demands of exercising individuals for high-quality protein. Some epidemiological studies raised concern that the consumption of red meat might increase risks for chronic diseases in humans, including obesity, type 2 diabetes mellitus, cardiovascular disease, kidney disease, and cancers. However, findings from many epidemiological and clinical studies do not support these claims. Beef-derived AAs and other nutrients enhance the metabolism (e.g., nitric-oxide and glutathione syntheses) and the functions of monocytes, macrophages, lymphocytes, and other cells of the immune system, thereby helping the human host to kill pathogenic bacteria, fungi, parasites, and viruses. The latter include severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 (COVID-19). Therefore, beef is a functional food for optimizing human growth, development, and health.

Important roles of amino acids in immune responses.

This commentary highlighted the background, take-home messages, and impacts of our 2007 British Journal of Nutrition paper entitled "Amino acids and immune function". In 2003-2004, there was an outbreak of severe acute respiratory syndrome (SARS) caused by SARS coronavirus-1 (CoV-1) in Asian countries. By the mid-2000's, clinical and experimental evidence indicated important roles for amino acids (AA) in improving innate and adaptive immunities in humans and animals. Based on our long-standing interest in AA metabolism and nutritional immunology, we decided to critically analyze advances in this nutritional field. Furthermore, we proposed a unified mechanism responsible for beneficial effects of AA and their products (including nitric oxide, glutathione, antibodies, and cytokines) on immune responses. We hoped that such integrated knowledge would be helpful for designing AA-based nutritional methods (e.g., supplementation with glutathione, arginine and glutamine) to prevent and treat SARS-like infectious diseases in the future. Our paper laid a framework for subsequent studies to quantify AA metabolism in intestinal bacteria, determine the effects of functional AA on cell-mediated and humoral immunities, and establish a much-needed database of AA composition in foodstuffs. Unexpectedly, COVID-19 (caused by SARS-CoV-2) emerged in December 2019 and has become one of the deadliest pandemics in history. Notably, glutathione, arginine and glutamine have now been exploited to effectively relieve severe respiratory symptoms of COVID-19 in affected patients. Functional AA (e.g., arginine, cysteine, glutamate, glutamine, glycine, taurine and tryptophan) and glutathione, which are all abundant in animal-sourced foodstuffs, are crucial for optimum immunity and health in humans and animals.

Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans.

As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular mechanistic target of rapamycin (MTOR) and focal adhesion kinase cell signaling pathways in mammals, thereby stimulating protein synthesis, inhibiting autophagy and proteolysis, enhancing cell migration and wound healing, promoting spermatogenesis and sperm quality, improving conceptus survival and growth, and augmenting the production of milk proteins. Although Arg is formed de novo from glutamine/glutamate and proline in humans, these synthetic pathways do not provide sufficient Arg in infants or adults. Thus, humans and other animals do have dietary needs of Arg for optimal growth, development, lactation, and fertility. Much evidence shows that oral administration of Arg within the physiological range can confer health benefits to both men and women by increasing NO synthesis and thus blood flow in tissues (e.g., skeletal muscle and the corpora cavernosa of the penis). NO is a vasodilator, a neurotransmitter, a regulator of nutrient metabolism, and a killer of bacteria, fungi, parasites, and viruses [including coronaviruses, such as SARS-CoV and SARS-CoV-2 (the virus causing COVID-19). Thus, Arg supplementation can enhance immunity, anti-infectious, and anti-oxidative responses, fertility, wound healing, ammonia detoxification, nutrient digestion and absorption, lean tissue mass, and brown adipose tissue development; ameliorate metabolic syndromes (including dyslipidemia, obesity, diabetes, and hypertension); and treat individuals with erectile dysfunction, sickle cell disease, muscular dystrophy, and pre-eclampsia.

Epithelial Dysfunction in Lung Diseases: Effects of Amino Acids and Potential Mechanisms.

Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.