Knowledge that certain nutraceuticals can modulate the immune system is not new. These naturally occurring compounds are known as immunoceuticals, which is a novel term that refers to products and systems that naturally improve an individual’s immuno-competence. Examples of immunoceuticals include vitamin D3, mushroom glycans, flavonols, quercetin, omega-3 fatty acids, carotenoids, and micronutrients (e.g., zinc and selenium), to name a few. The immune system is a complex and highly intricate system comprising molecules, cells, tissues, and organs that are regulated by many different genetic and environmental factors. There are instances, such as pathological conditions, in which a normal immune response is suboptimal or inappropriate and thus augmentation or tuning of the immune response by immunoceuticals may be desired. With infectious diseases, cancers, autoimmune disorders, inflammatory conditions, and allergies on the rise in both humans and animals, the importance of the use of immunoceuticals to prevent, treat, or augment the treatment of these conditions is becoming more evident as a natural and often economical approach to support wellness. The global nutraceuticals market, which includes immunoceuticals, is a multi-billion-dollar industry, with a market size value of USD 454.55 billion in 2021, which is expected to reach USD 991.09 billion by 2030. This review will provide an overview of the immune system, the importance of immunomodulation, and defining and testing for immunocompetence, followed by a discussion of several key immunoceuticals with clinically proven and evidence-based immunomodulatory properties.

Despite the increasing interest and use of NAC over the decades, there remains much debate surrounding NAC’s mechanisms of action. It was widely believed that NAC exerts its antioxidant and cytoprotective properties through its ability to act as a scavenger of reactive oxygen species, a precursor for glutathione biosynthesis, and a disulfide reductant. However, these three major narratives are only applicable under specific circumstances and cannot explain NAC’s actions in a more general context.  A newly emerging alternative mechanism of action of NAC involving hydrogen sulfide and sulfane sulfur species may serve to provide an explanation of NAC’s effects in a more generalized context. Part II of this review will provide an overview of NAC’s mechanisms of molecular action.

N-acetylcysteine (NAC), an acetylated derivative of the amino acid L-cysteine has been widely used as a mucolytic agent and antidote for acetaminophen overdose since the 1960s and the 1980s respectively. NAC possesses antioxidant, cytoprotective, anti-inflammatory, antimicrobial and mucolytic properties, making it a promising therapeutic agent for a wide range of diseases in both humans and livestock in which oxidative stress and inflammation plays a major role in the onset and progression of the disease. NAC’s primary role is to replenish glutathione (GSH) stores; the master antioxidant in all tissues, however it can also reduce levels of pro-inflammatory tumor necrosis factor-alpha (TNF-) and interleukins (IL-6 and IL-1), inhibit formation of microbial biofilm, destroy biofilms, and break down disulfide bonds between mucin molecules. Many experimental studies have been conducted on the use of NAC in addressing a wide range of pathological conditions, however, its effectiveness in addressing different pathological conditions in clinical trials remains limited and studies often have conflicting results. The purpose of this review is to provide a concise overview of promising NAC usages for treatment of different human and livestock disorders.