The Role of Nutraceuticals in Healthcare System as a Nutritional Supplement: A Comprehensive Review

Ankit Kumar^1*, Sushil Singhal¹, Vikrant Kumar¹ and Veenu Choudhary^{2 *}Correspondence: Ankit Kumar, Department of Pharmaceutical Sciences, GRD Institute of Management and Technology, Uttarakhand, India, Email:

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Introduction

Nutraceuticals are defined as “specially designed preparations,” created to meet certain dietary needs and/or provide preventative healthcare. In addition to a supplemental diet, nutraceuticals are the formulation of nutrient(s) that aid in the prevention and treatment of various illnesses (Puri V, et al. , 2022; Santini A and Novellino E, 2018). The terms “nutrition” and “pharmaceutical” were combined to form the phrase “nutraceutical,” which was coined by Dr. Stephen de Felice in 1989. These are foods or portions of foods that have a variety of health advantages, such as the ability to treat and/or prevent disease. From anticipating dietary deficits to focusing on human health and the prevention and treatment of chronic illnesses, nutrition science has advanced to new heights. Following the premise, the terms “nutraceuticals,” “food supplements,” and “dietary supplements” have developed (Lachance PA and Das YT, 2007).

The term “nutraceuticals” is derived from “nutrition” and “pharmaceuticals” and is used for nutrition products that are also used as medicine (Siddiqui RA and Moghadasian MH, 2020; Kalra EK, 2003). “Nutraceuticals” frequently include modified or unmodified whole foods, plant extracts alone or in combination, semi purified or purified phytochemicals, or a variety of phytochemicals (NIH, 2011). On the other hand, nutritional supplements are dietary additives that raise a person’s overall daily consumption in addition to their food (Gosavi S, et al. , 2016; Wansink B, et al. , 2005). Additionally, nutritional supplements may include compounds that are taken alone or in conjunction with vitamins, minerals, other herbal items, zoochemicals (such as creatine, glucosamine, melatonin, and bee pollen), and probiotics (Gupta S, et al. , 2010; Bhowmik D, et al. , 2013; Gupta SK, et al. , 2013).

Contrary to medicines, nutraceuticals are compounds that often do not have patent protection. Although both pharmaceutical and nutraceutical substances may be used to treat or prevent disease, only pharmaceutical substances are approved by the government (Singh R and Geetanjali N, 2013; Nasri H, et al. , 2014; Chauhan B, et al. , 2013). Due to a lack of authoritative oversight, several issues related to the development of nutraceuticals are frequently disregarded. These difficulties include determining the genuine source of the raw materials, compound purity, the existence of additional active compounds, quality, a lack of scientific proof, deceptive advertising, heavy metal contamination, and interactions between supplements and medications. A common plant like “ginseng” has several different variations (van Kleef E, et al. , 2005; Wildman RE, et al. , 2016) such as wild-red ginseng, California ginseng, prickly ginseng, Pacific ginseng, Malaysian ginseng, Indian ginseng, Peruvian ginseng, Southern ginseng, and Brazilian ginseng. While all of them are marketed as ginseng, only the Korean ginseng (P. ginseng ), South China ginseng (P. notoginseng ), and American ginseng (P. quinquefolius ) are really found in the genus Panax. Some star anise variants contain hundreds of times more anisatin, a neurotoxic, than the original star anise (Illicium verum ) does (Halsted CH, 2003; Palthur MP, et al. , 2010; Ahmad MF, et al. , 2011; Chaturvedi S, et al. , 2011).

Literature Review

Nutraceuticals and dietary supplements in various diseases

On the premise of the US “Dietary Supplements Health and Education Act” 1994 (DSHEA), the nutritional additives are those that include fatty acids, fiber, protein, vitamin, amino acid, and mineral, which are referred to as dietary ingredients or dietary supplements (Zeisel SH, 1999).

The scientific community has also been interested in investigating the purported antiviral and immunomodulatory effects of several dietary supplements and nutraceuticals candidates for the prophylaxis and/or treatment of COVID-19 (Chandra S, et al. , 2022; Lordan R, 2021). These include multivitamins, probiotics, zinc, vitamin C, curcumin, selenium, and melatonin to name a few (Tsoupras A, et al. , 2020; Infusino F, et al. , 2020; Zabetakis I, et al. , 2020). Surprisingly, data from the University of Oxford’s Evidence-Based Medicine Data Lab’s COVID-19 Trials Tracker indicates that traditional medicines are the most common intervention registered for clinical trials against COVID-19, with vitamin D, vitamin C, and probiotics also present on the list amongst the many pharmacological interventions under investigation (Lordan R, et al. , 2021; DeVito N and Inglesby P, 2020; Rando HM, et al. , 2021) (Table 1 ). Different aspects of nutraceuticals as alternatives for pharmaceuticals are used.

Table 1: Nutraceuticals used in various disease conditions

Immune system and nutraceuticals

The immunological function of the human body is heavily impacted by the nutrients and bioactive chemicals found in diets. The anti-disease properties of these bioactive substances have been well researched. Functional foods are consumed in many forms across numerous cultures and provide advantages that go beyond basic nutritional needs. A wide range of nutraceuticals have been demonstrated to have critical roles in immunological state and susceptibility to certain disease situations (Limer JL and Speirs V, 2004). Immunological booster nutraceuticals are beneficial in improving immunological function. Coneflower extracts or plants from the genus Echinacea, such as Echinacea angustfolia, Echinacea pillida, and Echinacea purpurea, are among them (Gupta P, et al. , 2000; Fuller R, 1991). Antioxidants, phytochemicals, fatty acids, amino acids, prebiotics, and probiotics are examples of bioactive derivatives derived from culinary sources found in nutraceuticals. Many of them have anti-inflammatory qualities that might alter the immune system (Ooi SL and Pak SC, 2021). Nutraceuticals can help prevent cancer, neurological illnesses, gastroenterological issues, inflammatory diseases, and infections by boosting the immune system (AlAli M, et al. , 2021; Basak S and Gokhale J, 2022; Medoro A, et al. , 2023; Aarland RC, et al. , 2017).

Cardiovascular Diseases (CVD) and nutraceuticals

Cardiovascular Disease (CVD) is widespread; in fact, the majority of persons over the age of sixty will have some kind of CVD. According to data from 2012 and 2013, CVD is responsible for 17.3 million deaths worldwide each year (Sosnowska B, et al. , 2017). The prevalence of CVD is growing globally, as are research efforts in this field (Ghorbani A, et al. , 2013; Behradmanesh S and Nasri P, 2012; Nasri H, 2012; Asgary S, et al. , 2013; Nasri H, et al. , 2013). CVD refers to heart and blood vessel problems and encompasses coronary heart disease (heart attack), peripheral vascular illnesses, cerebrovascular disease (stroke), hypertension, heart failure, and other conditions. Low diet of vegetables and fruits is thought to be linked to increased CVD mortality (Rafieian KM, 2012). The vast majority of CVDs are avoidable.

Many studies have found that a diet high in vegetables and fruits protects against CVD (Hu FB and Willett WC, 2002; Behradmanesh S and Nasri H, 2013; Amiri M, 2014). Nutraceuticals such as vitamins, minerals, antioxidants, dietary fibers, and omega-3 Polyunsaturated Fatty Acids (n3 PUFAs) are indicated for CVD prevention and therapy, together with physical activity. Polyphenols, for example, are thought to minimize artery disease through altering cellular metabolism and signaling (Shahbazian H, 2013; Asgary S, et al. , 2014).

Flavonoids are abundant in vegetables, onions, endives, cruciferous vegetables, grapefruits, apples, cherries, pomegranate, berries, black grapes, and red wine, and are accessible as flavones, flavanones, and flavonols (Gharipour M, et al. , 2013; Khosravi-Boroujeni H, et al. , 2012; Khosravi-Boroujeni H, et al. , 2013), and play an important role in CVD prevention and treatment. Flavonoids inhibit angiotensin-converting enzymes, cyclooxygenase enzymes that degrade prostaglandins, and platelet aggregation.

They also safeguard the circulatory system, which transports oxygen and nutrients to cells (Nasri H, et al. , 2014; Asgary S, et al. , 2013). Plant foods contain anthocyanin’s, tannins (proanthocyanidins), tetrahydro-carbolines, stilbenes, dietary indoleamines, serotonin, and melatonin, which are thought to provide health advantages (Iriti M and Faoro F, 2006). Orange juice with pulp is high in flavonoids. Hesperidin is a citrus bioflavonoid that is a flavanone glycoside. The richest dietary sources of hesperidin are Citrus sinensis and tangelos. Hesperidin concentrations are higher in the peel and membranous portions of lemons and oranges. Hesperidin is a medication used to treat venous insufficiency and haemorrhoids (Garg A, et al. , 2001). Flavonoid consumption was shown to be significantly inversely related to coronary heart disease mortality and myocardial infarction incidence. Flavonoids included in commonly eaten foods may lessen the risk of mortality from coronary heart disease, particularly in the elderly (Rafieian-Kopaei M, et al. , 2013). Polyphenols may alter glucose homeostasis through a variety of methods, including inhibition of carbohydrate digestion and absorption in the gut, protection of pancreatic-cells, reduction of glucose release from the liver, and activation of insulin receptors and glucose uptake in insulin-sensitive tissues (Hanhineva K, et al. , 2010).

Allergy and nutraceuticals

Allergic illnesses are among the most frequent health problems, impacting around 30% of the world’s population. Mast Cells (MCs) play an important role in allergic responses by secreting proinflammatory mediators such as histamine, lipid mediators, and cytokines/chemokines (Civelek M, et al. , 2022). Allergic rhinitis is a chronic inflammatory illness caused by the immune system’s overreaction to common allergens (Pellow J, et al. , 2020). Allergy is an immune system hypersensitivity condition. When a person’s immune system responds to typically innocuous chemicals, an allergic response ensues. Allergic responses are distinguished by the increased activation of particular white blood cells known as mast cells and basophils by immunoglobulin E. This reaction causes an inflammatory response that can vary from unpleasant to hazardous (Grammatikos AP, 2008). Quercetin protects Low-Density Lipoprotein (LDL-C) against damage, particularly damage to blood arteries. LDL-C is a major cause of heart disease, while quercetin serves as an antioxidant and free radical scavenger. Diabetic people are more vulnerable to oxidative stress-induced blood vessel damage. As a result, quercetin is also useful in these people (Kruger CL, et al. , 2002).

Diabetes and nutraceuticals

Diabetes mellitus type 2 is one of the most common endocrinological illnesses in the general population, particularly among hospitalised patients. The first step towards achieving appropriate glucose control and avoiding diabetes complications is nutritional medical care. Moderate weight reduction (7%), as well as frequent physical exercise (150 minutes per week), are examples of lifestyle modifications. The ideal diet composition is 30% total fat, 10% saturated fats, >15 g/1000 kcal fibre, half soluble, 45%-60% carbs with a modest sugar consumption (50 g/day), and protein intake of 15%- 20% of total calories. Patients should restrict their saturated fat consumption to 7% of their daily calorie intake (Derosa G, et al. , 2014). A broad number of herbal dietary supplements and herbal medications have been scientifically demonstrated to help type 2 diabetes mellitus in preclinical research in recent years (Madiseh MR, et al. , 2014; Rafieian KM and Nasri H, 2013), but few have been proven to do so in adequately planned randomised clinical trials (Tolouian R and Hernandez GT, 2013). Isoflavones are phytoestrogens that have structural and functional properties with human oestrogen. Soy isoflavones have received the greatest attention, and they have been linked to a decreased incidence and death rate of type II diabetes, heart disease, osteoporosis, and some malignancies (Baradaran A, 2012). The effect of L-carnitine on the gene and protein expression of oxidative stress-related proteins Heme Oxygenase-1 (HO-1) and endothelial Nitric Oxide Synthase (ecNOS) in cultured human endothelial cells in the absence and presence of oxidative stress caused by H2O2 (Rajasekar P and Anuradha CV, 2007; Calò LA, et al. , 2006).

Eye disorders and nutraceuticals

One of the key elements driving the pathophysiology of several ocular disorders, including presbyopia, cataracts, Dry Eye Disease (DED), glaucoma, Age-related Macular Degeneration (AMD), and Diabetic Retinopathy (DR), is oxidative stress. Several studies have shown that orally taken nutraceuticals can help with certain conditions (Castro-Castaneda CR, et al. , 2022). A healthy lifestyle that includes foods high in antioxidants including omega-3 fatty acids, lutein, and zeaxanthin appears to be advantageous for Age-related Macular Degeneration (AMD) (Brookmeyer R, et al. , 2007). Nutraceuticals with a high polyphenolic flavonoid concentration have been found to exhibit antioxidant action. Herbs or herbal extracts with antioxidant characteristics, including as green tea, Allium spp., Vitamins C and E, polyphenols, carotenoids (primarily lycopene and -carotene), and coenzyme Q10, are beneficial in AMD (Brouns F, 2002). Astaxanthin is a carotenoid found naturally in marine organisms such as sea bream, salmon, trout, and prawns. It performs a variety of critical biological roles in aquatic species, including protection against oxidation, Ultraviolet (UV) radiation impacts, immunological response, and colouring (Ardalan MR and Rafieian-Kopaei M, 2013). Proinflammatory cytokines, matrix metalloproteinases, and chemokines induce autoreactive T-helper cells, resulting in a vicious cycle of inflammation and damage (Pellegrini M, et al. , 2020; Messmer EM, 2015). Furthermore, tear hyperosmolarity has been demonstrated to contribute to DED development by causing apoptosis of corneal and conjunctival epithelial cells and initiating a concurrent inflammatory cascade that results in goblet cell loss and tearfilm instability (Eghrari AO, et al. , 2015).

Cancer and nutraceuticals

Rhein, a naturally produced anthraquinone found in rhubarb (Rheum rhabarbarum ) leaves and several aloe species, has anti-cancer potential (Baudouin C, et al. , 2013; Henamayee S, et al. , 2020). According to current research, rhein is a multitargeted cytotoxicity molecule. It stimulates apoptosis while inhibiting cell proliferation and angiogenesis via many channels including Mitogen-Activated Protein Kinase (MAPK), Wnt signalling pathway, Nuclear Factor-kappa B (NF-B), and hypoxia inducible factor-1 signalling pathway (Ooi SL, et al. , 2021; Günes-Bayir A, et al. , 2020). Rhein has been shown to have chemopreventive efficacy in vivo or in vitro against a variety of cancers, including breast, cervical, colon, glioma, leukaemia, and liver, lung, nasopharyngeal, ovarian, pancreatic, and oral cancers (Panahipour L, et al. , 2021). In vitro , by amplification of “connexin 43” (Calabrese EJ, 2020; Tripathi YB, et al. , 2005) or flavonoids, which control phase I and II xenobiotic detoxification, or vitamin E, which inhibits protein kinase C, a crucial enzyme in the growth of various cancers (Zheng J, et al. , 2016). Curcumin, Resveratrol (RES), and Berberine (BBR) have been studied in 126, 110, and 35 clinical trials, respectively, and have demonstrated a wide range of activities in human pathologies including cardiovascular disease, colorectal adenoma recurrence, diabetes, defective endothelial function, glucose metabolism/metabolic syndrome, age-related macular degeneration, ageing, Alzheimer’s disease, various types of cancer, and many others (Hiramatsu M and Yoshikawa T, 2005; Aggarwal BB, et al. , 2010; McCubrey JA, et al. , 2017).

Inflammation and nutraceuticals

Clinical studies of dietary supplements have found positive alterations, primarily in inflammatory mediators and adipokines (Kunnumakkara AB, et al. , 2018). In general, the polyphenol content of foods is responsible for their health-promoting benefits, including anti-inflammatory, anti-hypertensive, anti-platelet, and antioxidant properties (Chrysohoou C, et al. , 2004; Montagna MT, et al. , 2019). Polyphenols have become a focus of nutrition study in recent decades due to their favourable health benefits. Polyphenols in green and black tea, grapes, and red wine have been extensively studied, and scientific interest in dark chocolate, another rich source of polyphenols such as theobromine, catechin, procyanidin B2, and epicatechin, has lately developed (Magrone T, et al. , 2017). Researchers discovered that cocoa and chocolate, which are considered nutraceutical foods, had a favourable influence on gastrointestinal motility (Hayek N, 2013; Caponio GR, et al. , 2020). Several in vivo and in vitro investigations demonstrate that anti-inflammatory or anti-oxidative pharmacological drugs may favourably modulate Blood Brain Barrier (BBB) integrity by modulating systemic inflammatory pathways. Some other researchers investigated the effectiveness of several anti-oxidative nutraceuticals, including Garlic Extract-Aged (GEA), Alpha-Lipoic Acid (ALA), niacin, and Nicotinamide (NA), in a well-established dietary-induced model of BBB disruption (Takechi R, et al. , 2013; Kalayci R, et al. , 2005). S-allylcysteine, S-allylmercaptocysteine, diallyl sulphide, and allicin are anti-oxidative phytochemicals found in the GEA that can scavenge reactive oxygen species.

Obesity and nutraceuticals

A variety of nutraceuticals and botanical dietary supplements are used to control body weight (Pallebage-Gamarallage MM, et al. , 2010). Green tea use was observed to enhance the relative abundance of Firmicutes and Actinobacteria while decreasing the concentration of the phylum bacteroidetes in humans using 16S rRNA sequencing (Bertuccioli A, et al. , 2021). Green tea may have antiobesity properties through modifying gut microbiota (Lee HC, et al. , 2006).

Ginseng has a strong potential for weight management via modulating gut flora. A clinical exploratory investigation including 10 obese women aged 40-60 years found that 8 g/day of a chemically characterised P. ginseng extract provided for 8 weeks resulted in weight loss and minor changes in gut microbiota species compared to untreated healthy obese subjects (Sun H, et al. , 2018). Psyllium, inulin, guar gum, Glucans, chitosan, and other fibres are used to manage body weight via modulating gut bacteria.

Infectious pathogens and nutraceuticals

The word nutraceutical is used in the paediatric profession to describe how a proper diet enhanced with biologically active substances allows us to get substantial health advantages in addition to the regular nutritional effects. As a result, functional foods are those that, by natural prerogative or supplementation, may give vitamins, mineral salts, fibres, and fatty acids in sufficient quantities to positively affect various functions or prevent the onset of illnesses. Curcumin has been shown to inhibit SARS-CoV-2 cellular entrance and reproduction, as well as to prevent and repair COVID-19-related damage to pneumocytes, renal cells, cardiomyocytes, and hematopoietic stem cells (Flagg AJ, et al. , 2021; Parisi GF, et al. , 2021). Bromelain is a cysteine protease isolated from the pineapple stem (Ananas comosus ) that has traditionally been utilised in trauma due to its anti-inflammatory and anti-edema characteristics (Soni VK, et al. , 2020). The carboxylation catalysis of vitamin K-dependent proteins (Gla proteins) (Pavan R, et al. , 2012), a post-translational modification of glutamate via which vitamin K is involved in the majority of biological phenomena such as coagulation, calcium homeostasis, bone and vascular mineralization (Berenjian A and Sarabadani Z, 2020).

Gastroenterological disorders and nutraceuticals

The actual practice of relieving stomach discomfort with various types of food has long recognized the dietary influence on gut health, and recently the association between specific diets and reduced occurrences of numerous gastrointestinal disorders has been found (Janssen R, et al. , 2021). Curcumin is the main natural curcuminoid (a kind of phenol) found in the plant Curcuma longa , and it is extensively used as a spice, food preservative, and food colouring agent. Its anti-inflammatory mechanism works primarily by suppressing the Nuclear Factor kappa-light-chain-enhancer of activated B cells (Gao X, et al. , 2020) (NF-B)-related inflammatory pathway, followed by inhibition of TNF-, IL-12, and IL-2, thereby modulating the immune response and representing a safe and promising agent for the treatment of Inflammatory Bowel Disease (IBD) (Mosele JI, et al. , 2015; Brumatti LV, et al. , 2014). Another indication of how nutrition is linked to disease activity is the fact that Exclusive Enteral Nutrition (EEN) can induce clinical and endoscopic remission in paediatric patients (Larussa T, et al. , 2017).

Antioxidants and nutraceuticals

Oxidative stress is an imbalanced redox state generated by a high concentration of reactive species in the body and a correspondingly low number of endogenous antioxidants. When oxidative stress becomes established, it can affect cell structure and protein conformation, as well as destroy genetic elements (Corsello A, et al. , 2020). Nutraceuticals aid in the restoration of appropriate digestion and absorption of minerals and vitamins to avoid deficiencies, cleanse cells, block undesirable biochemical processes, promote the establishment of good microbiota, and eliminate waste (Anand S and Bharadvaja N, 2022). Nutraceuticals have antioxidant, anti-aging, and anti-cancer effects, as well as the ability to improve biochemical processes and structures. They also cause immunomodulatory effects, boost immunological response, boost phagocytosis, inhibit hypersensitivity, and lower auto-immune reaction (Zhou W, et al. , 2020; Carr AC and Maggini S, 2021). Nutraceuticals can aid in the prevention and treatment of heart disease, neurodegeneration, oxidative stress-related conditions, and modern lifestyle disorders such as diabetes, hypertension, and cancer (Das L, et al. , 2012; Sachdeva V, et al. , 2020).

Miscellaneous complications and nutraceuticals

Angiogenesis is an enzymatic process that is normally suppressed in healthy people. Because antiangiogenic chemicals are selective towards newly created blood vessels while protecting existing ones, they may not cause negative effects even after lengthy periods of exposure. Antiangiogenic substances may help to avoid degenerative illnesses such multiple sclerosis, arthritis, osteoporosis, diabetes, cancer, Alzheimer’s, and Parkinson’s. Curcumin, flavins, isoflavones, and catechins, resveratrol, proanthocyanidins, flavonoids, saponins, terpenes, chitin, chitosan, vitamins B3 (Ronis MJ, et al. , 2018) and D3, fatty acids, peptides, and amino acids are examples of bioactive chemicals that may be efficient angiogenic agents (Baradaran A, et al. , 2013).

Moringa oleifera Lam is an excellent source of different amino acids and phenolics, protein, vitamins, -sitosterol, caffeoylquinic acid, kaempferol, and -carotene with great nutritional and therapeutic properties. This plant’s leaves, seed, bark, fruit, roots, flowers, and immature pods have antitumor, antipyretic, antiepileptic, anti-inflammatory, diuretic, antihypertensive, antidiabetic, cholesterol-lowering, antiulcer, antispasmodic, antioxidant, hepatoprotective, antibacterial, and antifungal properties (Ateyyat MA, et al. , 2009).

Discussion and Conclusion

The basis of the world is good healthcare. Nutrition is a person’s most basic requirement. Most of us fail to consume a well-balanced diet on a regular basis, but some nutrients are necessary in larger levels at various times and for specific people (infants, pregnant women, chronic patients, and adults) than their diets can offer. Many people experience an overall sense of well-being when they take their daily multivitamins. Each vitamin and mineral in a proper daily multivitamin dosage provides the advantage of the individual elements as well as the combined synergistic effects of all ingredients working together. In this review paper, the fastest expanding sector in human health and illness prevention is nutraceuticals. In recent years, the market for natural goods in nutraceuticals has expanded. Another key factor in the market for natural goods in nutraceuticals is technical advancement. The bioavailability of nutraceuticals is boosted by using natural or synthetic polymers to improve the physicochemical features.

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