"More than food but less than pharmaceuticals"
As simple as Hippocrates once stated, “Let thy food be thy medicine and thy medicine be thy food”. This concept highlights the importance of nutrition in the prevention and treatment of diseases since ancient times. However, nowadays this principle has emerged as a stronger trend in a nutraceutical notion. Nutraceuticals come from natural sources such as plants or food and contribute with a high concentration of a particular substance that will exert its effects in pro of human or animal health. The aim is to prevent diseases by reducing risk factors and to improve chronic disease treatment by enhancing physiological functions [1, 2]. The term nutraceutical was first coined in 1989 by Stephen DeFelice. Unfortunately, these products have been difficult to categorize, because they can’t be legally considered either as food or as drugs. Instead, they fall into the grey area between the two, that is to say, in limbo [1,2]. Some examples of nutraceuticals are Vitamins and minerals, terpenoids, polyphenols, probiotics, and prebiotics, among others . Some studies have shown that nutraceutical products such as probiotics have an important role in the prevention and therapy of important skin diseases, such as Atopic Dermatitis  and Acne vulgaris , and other cardiometabolic diseases . Additionally, some flavonoids are considered to be potential candidates to prevent neuroinflammation due to their capability to cross the blood-brain barrier, increasing angiogenesis and improving the cognitive process during aging . Unlike pharmaceutical products, nutraceuticals are fine noble products in every respect. They can be “purchased over the counter”, as well as come recommended by doctors or nutritionists without prescriptions and the necessity to be patented [1,2]
Figure 1. Comparison of nutraceuticals and pharmaceuticals .
Since for a nutraceutical manufacturer it is not mandatory to follow the strict pharmaceutical guidelines, there is an inherent health risk due to the lack of awareness on their consumption and increased uptake of nutraceutical products by consumers and their combination with pharmaceutical products, new ingredients, or formulations . From a global perspective, it is required to submit a notification or registration form to market new products, as they pose a low safety risk. Unlike the compulsory pre-market approval approach needed for drugs in most countries. However, there should be guidance on the minimum validation requirements based on industry practice and available regulations on this topic, as well as established lists for permitted ingredients, to help conduct their evaluations .
Figure 2. Global notification or registration for foods/supplements in a few countries .
Harmonizing food and supplement rules among all nations of the world: Codex was created in 1962 comprising more than 150 countries and international organizations with the purpose to encourage fair international trade in food, exchange of information and ideas related to safety issues . Thanks to this common effort, the nutraceutical industry has been steadily growing over the past 10 years. According to the Global Nutraceutical Market Growth Analysis Report, the global nutraceutical market size was valued at USD 382.51 billion in 2019 and is expected to reach USD 722.5 billion by 2027. Among the International Leaders of the Nutraceutical Industry stand out: Cargill; Incorporated; Archer Daniels Midland Company; DuPont; Nestle S.A; Danone; General Mills; Innophos; WR Grace; Amway Corporation .
Figure 3. Global nutraceuticals market share .
A better understanding of the effect of nutraceutical products on the body’s molecular machine can lead to the obtention of safer products. Nutraceuticals are trusted products by the consumers, even if they lack strict regulation like pharmaceuticals. However, nutraceutical industries are responsible for ensuring the safety of their products and it is indispensable to improve control over their processes. Although clinical trials have shown effectiveness and general safety, it is essential to improve credibility, since scientific validation is the top priority. As imagined, these products cannot be considered completely harmless since some of them may have unpredictable behavior. However, we must be conscious of the consumption of any product claiming a health benefit and aware of its possible side effects. Whatever your attitude towards nutraceutical is, remember that natural doesn’t always mean safety, does it?
 What are nutraceuticals and how do they work? (2020, February 17). Global News. https://globalnews.ca/content/6522962/what-are-nutraceuticals-and-how-do-they-work/  Sauer, S., & Plauth, A. (2017). Health-beneficial nutraceuticals—myth or reality? Applied Microbiology and Biotechnology, 101(3), 951–961. https://doi.org/10.1007/s00253-016-8068-5  Özdemir, Ö. (2012). The Role of Probiotics in Atopic Dermatitis (Eczema) and Skin Allergy Reactions: Prevention and Therapy. Bioactive Dietary Factors and Plant Extracts in Dermatology, E1. https://doi.org/10.1007/978-1-62703-167-7_49  Amer, S. S., Nasr, M., Abdel-Aziz, R. T. A., Moftah, N. H., El Shaer, A., Polycarpou, E., Mamdouh, W., & Sammour, O. (2020). Cosm-nutraceutical nanovesicles for acne treatment: Physicochemical characterization and exploratory clinical experimentation. International Journal of Pharmaceutics, 577, 119092. https://doi.org/10.1016/j.ijpharm.2020.119092  Sampaio, K. B., do Nascimento, Y. M., Tavares, J. F., Cavalcanti, M. T., de Brito Alves, J. L., Garcia, E. F., & de Souza, E. L. (2021). Development and in vitro evaluation of novel nutraceutical formulations composed of Limosilactobacillus fermentum, quercetin and/or resveratrol. Food Chemistry, 342, 128264. https://doi.org/10.1016/j.foodchem.2020.128264  Singh, P., Sivanandam, T. M., Konar, A., & Thakur, M. K. (2021). Role of nutraceuticals in cognition during aging and related disorders. Neurochemistry International, 143, 104928. https://doi.org/10.1016/j.neuint.2020.104928  Bagchi, D. (2019). Nutraceutical and Functional Food Regulations in the United States and around the World (3rd ed.). Academic Press.  Global Nutraceutical Market Growth Analysis Report, 2020-2027. (2020, April). Grand View Research. https://www.grandviewresearch.com/industry-analysis/nutraceuticals-market To find more information about Nutraceuticals:  Professional Supplement Center. (2015, July 6). What Is A Nutraceutical? Pharmaceuticals Containing Bioactive Compounds Obtained from Food. YouTube. https://www.youtube.com/watch?v=dwQLnU-Fpac