Functional Foods and their Impact on Health PDF

J Food Sci Technol https://doi.org/10.1007/s13197-021-05193-3 REVIEW ARTICLE Functional foods and their impact on health Musthafa Mohamed Essa1,2,10 Muhammed Bishir3,4 Abid Bhat3,4 Saravana Babu Chidambaram3,4 Buthaina Al-Balushi1 Hamdan Hamdan5,6 Nagamaniammai Govindarajan7 Robe...

J Food Sci Technol https://doi.org/10.1007/s13197-021-05193-3 REVIEW ARTICLE Functional foods and their impact on health Musthafa Mohamed Essa1,2,10 Muhammed Bishir3,4 Abid Bhat3,4 Saravana Babu Chidambaram3,4 Buthaina Al-Balushi1 Hamdan Hamdan5,6 Nagamaniammai Govindarajan7 Robert P. Freidland8 M. Walid Qoronfleh9 Revised: 23 June 2021 / Accepted: 25 June 2021 Ó Association of Food Scientists & Technologists (India) 2021 Abstract Functional foods play an important role in use in maintaining health. The market for functional food is maintaining a healthy lifestyle and reducing the risk factors keep on expanding, and the global market is projected to of various diseases. Most foods have a functional element reach a value of at least 91 billion USD soon. Over- which is responsible for improving the healthy state. All whelming evidence from preclinical (in vitro and in vivo) food substances such as fruits, vegetables, cereals, meat, and clinical studies have shown that intake of functional fish, dairy contain functional ingredients. A wide range of foods could have an impact on the prevention of chronic naturally occurring substances from plant and animal diseases, especially cancer, cardiovascular diseases, gas- sources having active components which play a role in trointestinal tract disorders and neurological diseases. physiological actions deserve attention for their optimal Extensive research needs to be done to determine the & Musthafa Mohamed Essa 10 College of Agricultural and Marine Sciences, Sultan Qaboos [email protected] University, P.O 34, Al-Khoud, Muscat 123, Sultanate of Oman 1 Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman 2 Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman 3 Dept. of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India 4 Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru, India 5 Department of Physiology, Al Faisal University, Riyadh, Saudi Arabia 6 Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA 7 Department of Food Process Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chengalpettu, Tamil Nadu, India 8 Department of Neurology, University of Louisville School of Medicine, Louisville, KY 40202, USA 9 Q3CG Research Institute (QRI), Research and Policy Division, 7227 Rachel Drive, Ypsilanti, MI 48917, USA 123  J Food Sci Technol potential health benefits for the proper application of these expression and activity of indoleamine 2,3-dioxygenase in foods to improve health state and combat chronic disease human colorectal cancer cells (Ogawa et al. 2012). progression. The aim of this review is to conduct a thor- (Table 1). Food production and eating habits have a pivotal ough literature survey, to understand the various classifi- role in the health, environmental and social life of human cation of functional foods and their health benefits. beings. The aim of this review is to conduct a thorough literature survey, to understand the various classification of Keywords Functional food  Nutraceuticals  Plant food  functional foods and their health benefits. Fruits  Vegetables  Nuts  antioxidants  Probiotics Classification of functional foods Introduction Functional foods are classified into three categories: (1) Functional foods are regarded as foods that have potential conventionally used food, (2) modified food, (3) food beneficial effect on health beyond their basic nutritional ingredients. Conventionally used foods have not undergone value. They promote good health and lower the risk of any modification and appear as a whole such as vegetables, diseases. Functional foods have received widespread pop- fruits, fish, diary, pulses and grains that have potent health ularity across the globe, and they are commonly known as benefits. Modified foods are those foods which have been ‘‘nutraceuticals’’ and ‘‘designer food’’. The concept of enriched or fortified with a specific nutrient in order to functional food was started and regulated by the Ministry promote health benefits. Modified foods include calcium, of Health and Welfare, Japan, in the year 1980s and then anti-oxidants and vitamin fortified beverages, calcium and progressed to North America and other markets (Mellentin folate enriched bread, products enriched with plant fibers, et al. 2014). Amount of biologically active compounds are sterols and omega 3 fatty acids are common examples of very less in the food items and their beneficial effect have modified functional foods (Hasler et al. 2009). been studied in rodent models and clinical studies. Results Fortification is a common term that describes the prac- from epidemiological studies have shown that consumption tice of enhancing the amount of a specific micronutrient in of specific fruits, animal products and vegetables that are a food item. This is a sustainable, cost effective solution to rich in bioactive compounds reduced the risk of various overcome micronutrient deficiencies. Similar to fortifica- metabolic disorders and cancer (Karasawa and Mohan tion another common term used in the food enhancement is 2018) (Fig. 1). fortificants, which are normally found in the raw food, but Natural bioactive molecules such as curcumin, resvera- lost during food processing. In order to overcome this issue trol, quercetin, sulforphane, epigallocatechin, lycopene, techniques have been developed such as biofortification, in and ellagic acid have been studied for their direct and which the nutrient content of the food source had been indirect effects on various molecular pathways. Curcumin increased through genetic engineering and selective is the major bioactive constituent in Curcuma longa and is breeding (Hasler et al. 2009). found in the spice turmeric as well as other sources. It has The third class of functional foods is prebiotics. Gibson been studied for its antioxidant and anti-inflammatory and Roberfroid were the first to define prebiotics, they properties (Sneharani 2019). Resveratrol (3,5,4-trihydrox- defined it as ‘‘food components which nurture the growth ystilbene) is found in grapes and pomegranates and studies and activity of a single and/or a specific group of have shown its benefits on vascular function, immunity and microorganisms residing in the gastrointestinal tract, the gut microbiota (Chaplin et al. 2018). Apples are thereby improving the health condition of host’’.The most abundant in quercetin, which has shown potent neuropro- common form of prebiotics is inulin and oligofructose. tective properties in neurodegenerative diseases (Elumalai They selectively upregulate the useful gut microorganisms and Lakshmi 2016). Cruciferous vegetables such as broc- such as bacteria and fungi. The concept of prebiotics was coli, cabbage and kale are abundant in sulforphane, which first introduced in 1995 by Glenn Gibson and Marcel is a. potent activator of the Nrf2-ARE pathway and pro- Roberfroid. Oligofructose such as fructo-oligosaccharides moter of redox, thereby protecting from oxidative stress. In (FOS), galacto-oligosaccharides (GOS), and trans-galacto- addition, sulforphane modulates Phase I and II xenobiotic- oligosaccharides (TOS) are the most common prebiotics. metabolizing enzymes and directly inhibits binding of Gut microbiota ferments these oligofructose to produce the carcinogens to DNA, preventing DNA adduct formation short chain fatty acids (SCFAs) butyric acid, acetic acid (Juengel et al. 2017). Epigallocatechins are a group of and propionic acid which have potential health benefits. compounds found in in tea leaves which have been shown The major health benefits include improve cognition, to have widespread pharmacological properties. Recent immunity, Ca2? absorption and decrease in the prevalence studies have determined that epigallocatechins inhibits the of irritable bowel syndrome (IBS) and colorectal cancer. 123 J Food Sci Technol Fig. 1 Health benefits of functional foods The bacteria that aerobically ferment dietary fiber produce deleterious effects on the body. Natural antioxidants are the short chain fatty acids which enhance the integrity of widely distributed in food and medicinal plants. Polyphe- the colonic epithelium intestinal epithelium improving the nols are a key bioactive ingredient responsible for antiox- gut blood barrier. Short chain fatty acids also readily enter idant properties. Moreover, they are proven to have anti- the bloodstream and pass the blood brain barrier producing allergic, anti-carcinogenic, anti-mutagenicity (Alshatwi satiety. They also epigenetically improve the production of et al. 2010) and neuroprotective properties (Yu et al. 2017). regulatory lymphocytes that are actively anti-inflammatory In this review, we discus some of the plant derived foods (Blaak et al. 2020). that are rich in polyphenols and other bioactive compounds. Functional food of plant origin Tomato Plants are the rich source of natural oxidants and help to Tomatoes are the fruits of Lycopersicon esculentum and strengthen innate immunity and protects from the toxic they originated in Mexico. They are regarded as vegeta- effects of oxidants. Many molecules in living cells are bles and one of the highly consumed food products across prone to oxidation and antioxidant molecules which are the globe. The Lycopersicon esculentum has a deep red present in the body and which are obtained from plant color which is associated with the carotenoid pigment sources help to fight against the oxidants and their synthesized during fruit ripening. Majority of the fruits and 123  J Food Sci Technol Table 1 Chemical structures of some bioactive constituents Bioactive Structure Properties constituent Lycopene Prevents DNA mutation (Lindshield et al. 2007), Improves lipid profile (Ibrahim et al. 2008), inhibits tumor growth (Tang et al. 2005) Neoxanthin Potent anti-oxidant properties (Lindshield et al. 2007) Carotenoids Potent anti-oxidant properties (Lindshield et al. 2007) Isorhamnetin Inhibits tumerogenesis (Damon et al. 2005) S-methyl Prevents DNA strand breakage. Inhibition of carcinogen activation by cysteine cytochrome P450 (H.Wiseman 2005) sulphoxide peptide LPYPR Reduces total cholesterol and LDL cholesterol (Yoshikawa et al. 2000) Flavanoids Potent antioxidant properties Ellagic acid Potent antioxidant and antiinflammatory properties (Akbar et al. 2015) Punicalagin Helps in reducing hypertension, arthritis, cancer, hyperglycaemia, oxidative stress and maintaining cholesterol levels (Zarfeshany et al. 2014) vegetables contain which phenolic molecules belongs to cryptoxanthin, b-carotene, c-carotene, f-carotene, a-car- the flavonoid family. Tomato contains a plethora of otene, phytoene, phytofluene, cyclo-lycopene-neu- bioactive compounds such as lycopene, neoxanthin, vio- rosporene, and b-carotene 5, 6-epoxide (Burns et al. 2003). laxanthin, a-cryptoxanthin, zeaxanthin, lutein, b- 123 J Food Sci Technol Lycopene is the prominent bioactive compound in studies focused on the concentration of prostate specific tomatoes and it has been widely studied over the past antigen (PSA), which determines the risk of prostate can- decade. Approximately 100 g of tomato contains 12 mg of cer. A study from Chen et al. (2001), 32 prostate cancer lycopene. Chemically lycopene is acyclic carotene with 11 patients where supplemented with tomato sauce for conjugated double bonds, these double bonds are contin- 21 days (30 mg lycopene/day). They found that tomato gent to isomerism and their isomers are reported to be sauce consumption decreased the PSA level by 20%. found in blood plasma. The human body by itself is unable Moreover, biochemical estimation of the prostate tissue to synthesize carotenoids so the body is completely revealed a decrease in the ratio of 8-hydroxy-20 -deox- dependent on dietary sources. Studies have been reported yguanosine (8-OHdG) (oxidative stress marker associated that 85% of the lycopene in the human diet is obtained with cancer) to 20 -deoxyguanosine (a marker of oxidative from tomato and tomato-based food products. Moreover, DNA damage) in patients supplemented with tomato sauce lycopene is a key intermediate in the biosynthesis of other as compared to normal control patients. Similar results essential carotenoids like b-carotene, and xanthophylls were found in the study from Grainger et al. (2008), they (Ruiz-Sola and Rodrı́guez-Concepción 2012). found that consumption of tomato products daily (lycopene It has been reported that consumption of foods that are 25 mg/day) for 56 days reduced the PSA levels in 34% of rich in vitamins, carotenoids and tannins protect the body the patients. Phase 2 clinical trial of Lyc-o-MatoÒ from oxidative damage. Lycopene is a potent antioxidant, 15 mg/day lycopene has also shown decrease in the PSA and can protect DNA from free radicals and thereby pre- levels (Vaishampayan et al. 2007). vent mutations that lead to cancer (Lindshield et al. 2007). The protective effects of Lycopene are well studied in In addition, higher lycopene (20 mg lycopene/kg diet) from cardiovascular diseases. Potent free radical quenching tomato sauce and ketchup was reported to improve the lipid properties of lycopene protects endothelial cells. Oxidative profiles of the hyperlipidemic rats (Ibrahim et al. 2008). stress leads to endothelial damage due to decline in nitric This result suggest that increase consumption of tomatoes oxide (NO) levels causing damage to endothelial cells. is beneficial in hyperlipidemic patients. Lycopene is also Lycopene reduces oxidative stress, enhances the avail- noted to be a potent anti- carcinogen. A study from ability of NO, promotes endothelial vasodilation, and Alshatwi et al. (2010) had shown that lycopene can protect alleviates DNA, lipids, and mitochondrial damage (Abdel- cells from chromosomal aberration. Lycopene traps the Daim et al. 2018). Hung et al. 2008 showed the beneficial singlet oxygen, impairs the free radical formation and role of lycopene in atherosclerosis and other inflammation thereby protect DNA from oxidative damage. In addition, it induced cardiovascular events. They found that lycopene improves gene functioning, carcinogen metabolizing can inhibit Tumor Necrosis Factor (TNF-a) induced acti- enzymes, apoptotic pathways and immune function. Clin- vation of Nuclear Factor Kappa B (NF-jB) and the ical research suggests that lycopene is beneficial in prostate expression of other molecules such as intracellular adhe- cancer. Most of the in vivo and in vitro studies have con- sion molecule-1 (ICAM-1). In addition, lycopene also centrated on prostate gland cancer models. Studies from inhibits the interaction between monocytes and endothelial Tang et al. analyzed the effect of Lycopene on the growth cells, which may explain the beneficial role of lycopene in rate of DU145 prostate gland cell lines in BALB/c nude cardiovascular disease (Hung et al. 2008). mice. They had found that lycopene at 100 and 300 mg/kg Some clinical studies have also reported the relationship inhibited the tumor growth by 56% and 76% respectively between lycopene consumption and cardiovascular dis- (Tang et al. 2005). eases. A randomized crossover study from Agarwal and Dietary intake of tomato prevents the development of Rao (1998) has reported significant decrease in the serum high fat diet induced hepatocellular carcinoma in BCO1/ lipid peroxidation and LDL oxidation. The lipoprotein BCO2 double knockout mice by decreasing the mRNA oxidation lag period, which is a measure of protection expression of proinflammatory mediators, increased against oxidative stress was increased in healthy subjects NAD? production by upregulating the expression of sirtuin consumed tomato soup for 15 days. Another clinical trial 1 and nicotinamide phosphoribosyltransferase. This action from Shen et al. (2007) treated 24 subjects with various is mediated by increased microbial richness and diversity tomato formulation (all the formulation delivering 40 mg and reducing the Clostridium and Mucispirillum abun- lycopene/day) for 42 days, they found decrease in the dance. Tomato seeds have also been found to reduce Fir- triglyceride and LDL cholesterol levels and an increase in micutes/Bacteroidetes ratio, Rikenella, Enterorhabdus and the High Density Lipoprotein levels. increases abundance of Lactobacillusin mice (Xia et al. Lycopene have been extensively studied in neurode- 2018). generative diseases both in preclinical and clinical stages. Several clinical trials have been conducted to evaluate Lycopene reduces oxidative stress, restores mitochondrial the anti-cancer properties of the lycopene. Majority of the membrane potential and inhibited early apoptotic pathway 123  J Food Sci Technol activation in rat cortical neurons exposed to amyloid b. Broccoli Lycopene administration in Tau Transgenic Mice increased the memory consolidation by reducing tau phosphoryla- Broccoli are the flowers of Brassica oleracea var. italica. tion, malonaldehyde (MDA) concentrations and increased Its flowering head, leaves and stalk are consumed as veg- Glutathione peroxidase (GSH-Px) activities (Yu et al. etables across the globe. Broccoli originated in the Roman 2017). Lycopene reduces neuronal damage and increased empire by the primitive cultivators and then became pop- the expression of BDNF in hippocampus region of AD rats. ular in the Italian Peninsula and Sicily. Broccoli is com- Lycopene also inhibits depletion of dopamine in substantia monly regarded as the ‘‘Crown Jewel of Nutrition’’ nigra and striatum and prevents neuronal damage in rodent because, it is immensely rich in variety of nutrients such as model of Parkinson’s disease. In addition, lycopene have vitamins, minerals, fibres and secondary metabolites. 100 g also been reported to have beneficial effects in Hunting- of broccoli contains: calories (31 g), protein (2.5 g), car- ton’s disease, depression, cerebral ischemia by reducing bohydrate (6 g), sugar (1.5 g), Fiber (2.4 g) and fat (0.4 g). oxidative stress and inhibiting proinflammatory release Broccoli is rich in sulphur containing compounds and their (Chen et al. 2019) (Fig. 2). biometabolic products glucosinolates, isothiocyanates have been reported to have potent anti-cancer properties. Moreover, broccoli is also rich in polyphenols such as isorhamnetin, sinapic acid, quercetin and rutin. In addition, it is rich in Vitamin K, B1, B2 (Damon et al. 2005) and Fig. 2 Lycopene present in tomato is a potent antioxidant which provides several health benefits 123 J Food Sci Technol minerals like Na, K, Ca, Mg, Cl, P and S. Dietary con- Soya bean sumption of cruciferous vegetables is highly beneficial in preventing stomach, colon, thyroid, skin and prostate Soya beans (Glycine max) are a legume species originated cancers. Anti—cancer property of broccoli is associated in Southeast Asia and it was first grown by Chinese farmers with sulforaphane, indoles, polyphenols, vitamins and around 1100 BC. Soya beans consist of protein (35–40%), minerals. It has been reported that sulforaphane prevents lipids (20%), and fiber (9%). The major bioactive fractions carcinogen induced tumorogenesis. It reduced incidence, of soya beans include peptides, isoflavones, saponins, and multiplication and growth of breast cancer in dimethyl- protease inhibitors. The prominent protein fractions of soya benzanthracene (DMBA)-treated rats. Moreover, sul- beans are b-conglycinin (bCG, 7S) and glycinin (11S) foraphane or 4-methylsulfinylbutyl isothiocyanate induces which constitute around 80–90% of the whole proteins in phase 2 detoxification enzymes such as glutathione trans- the soya bean. Moreover, soya beans are also rich in iso- ferases, epoxide hydrolase, NAD(P)H: quinone reductase, flavones which have potent estrogenic and anti-estrogenic and glucuronosyltransferases through inhibiting Nrf2-Keap properties and saponins which are proven to have signifi- 1 interactions and MAP Kinase activation (Bai Y et al. cant anti-inflammatory, anti-carcinogenic and cardiopro- 2015)). In a clinical study where subjects consumed 250 tective properties (Guang et al. 2014). gm/day (9 oz/day) of broccoli, it was found that broccoli The majority of the scientific studies have been focused consumption increased the urinary excretion of a potential on the hypolipidemic properties of soya beans. Yoshikawa carcinogen—2- amino-1-methyl-6-phenylimidazo [4, 5-b] et al. in 2000 have discovered the bioactive peptide LPYPR pyridine (PhIP), which is commonly found in meat (Wal- from the glycine fraction of soya beans. They found that ters et al. 2004). Broccoli has also been reported to alter gut administration of LPYPR (50 mg/kg) significantly reduced microbiome in humans. the total cholesterol and LDL cholesterol levels in rats Several studies have reported the cardioprotective (Yoshikawa et al. 2000). Further studies revealed that properties of broccoli. Broccoli sprouts are rich in gluco- LPYP functions by inhibiting 3-hydroxy-3-methylglutaryl raphanin which is a metabolic product of sulforaphane. It CoA reductase (HMGR) enzyme, which is the prominent has been reported that glucoraphanin can induce phase II rate limiting enzyme in cholesterol biosynthesis. In addi- proteins which in turn decreases oxidative stress and tion, other glycine derived peptides like IAVPGEVA and inflammation in both kidneys and the cardiovascular sys- IAVPTGVA had shown potent inhibitory effects on tem. Thus, it lowers the risk of hypertension and HMGR enzyme, thus promoting hypolipidemic activity. atherosclerosis in spontaneously hypertensive stroke prone Moreover, peptides derived from bCG like KNPQLR, rats (Wu et al. 2004). In a clinical study where the subjects EITPEKNPQLR, and RKQEEDEDEEQQRE had found to consumed broccoli sprouts (100 gm/day) for a week it was effective in inhibiting fatty acid synthase activity and found that total cholesterol levels and escalated HDL thereby decreased serum triglyceride levels in rodents cholesterol levels declined (Murashima et al. 2004). (Singh et al. 2014). Broccoli reduces mRNA and protein levels of thioredoxin Bioactive peptides that are available in food products super family members which are commonly found fol- are well studied for their anti-hypertensive properties lowing ischemic reperfusion injury, thus broccoli improves (Singh et al. 2014). The bioactive peptides isolated include: the cardiac function, reduces the risk of myocardial valyl-prolyl-proline (Val-Pro-Pro), isoleucyl- prolyl-pro- infraction, and cardiomyocyte apoptosis (Mukherjee et al. line (Ile-Pro-Pro) and (Tyr-Pro). These peptides elicit their 2008). action by inhibiting angiotensin-converting enzyme (ACE), Sulforaphane, bioactive compound of broccoli has been which is a key enzyme in the regulation the blood pressure found to be beneficial in neurodegenerative diseases. (Cam and de Mejia 2012). The marketed fermented soya Broccoli inhibits glial cell activation and improves the bean food products like soya sauce, natto and tempeh are expression of GABA, AMPA, and NMDA receptors in abundant in ACE inhibitory peptides (Hernández-Ledesma hippocampus region of rats. Broccoli consumption inhibits et al. 2004). Fermented Korean soya bean contain anti- NF-jB signaling cascade and proinflammatory cytokines hypertensive peptide HHL, also soya bean fermented with which are responsible for neuroinflammation. Broccoli also Bacillus natto or Bacillus subtilis contains two anti-hy- upregulates the expression of Nrf2 pathway, inhibits neu- pertensive peptides VAHINVGZK and YVWK (Singh ronal apoptosis and enhances memory consolidation in et al. 2014). mice (Subedi et al. 2019). Broccoli protects from Ab-in- Soybean supplementation improve cholinergic trans- duced neurotoxicity in cell line model by mediating mission by increasing the levels of acetylcholine in cortex mitochondrial functioning, increased Hsp70 mRNA levels and hippocampus region of rats (Pan et al. 1999). Soybeans and improving the expression of Nrf2-ARE signalling also promote the release of neurotrophic factors which (Masci et al. 2015). have a critical role in brain development and functioning. 123  J Food Sci Technol Soyabean upregulates the expression of brain derived nitrate content, this can affect arterial stiffness as well as neurotrophic factor in cortical region of rats, nerve growth central and peripheral blood pressure. The patients were factor in cortex and hippocampus of rats (Pan et al. 1999) supplemented with spinach (845 mg nitrate/day). They and improve memory performance in mice which is cor- found postprandial reduction in augmentation index and roborated to decrease in high blood lipid levels and concluded that spinach consumption contributes to hemo- increased activity of neurotransmitters in mice. Clinical dynamic properties, decreased arterial stiffness and central studies have also found that intake of soya improves both blood pressure. short term and long-term memory. Soybeans have also been found to improve the motor functions in Parkinson’s Brown rice disease by inhibiting the levodopa metabolism in humans (Liu et al. 2007). Brown rice is a whole grain rice with the outer inedible husk removed. Green revolution in 1960’s and 1970’s has Spinach improved the crop yield and economy of the Asian coun- tries like Japan and Korea. Since then, these countries Spinach (Spinacia oleracea) is a leafy green vegetable be- focused on improving the taste, appearance and the texture longing to the family Amaranthaceae and originated from of rice. A meta-analysis study from (Itani et al. 2002) has Persia in the 7thcentury. Spinach is consumed in both raw shown that increased consumption of sugar rich rice such and cooked form. Primarily the major chemical con- as processed rice and sedentary life style raised the inci- stituents are water (91.4), carbohydrates (3.6%), proteins dence of type 2 diabetes. This happened due to rice milling, (2.9%) and fat (0.4%). The lipid fraction mainly consists of which discards the micronutrients, proteins and fiber rich poly unsaturated fatty acids (PUFA) (Park 1966). In addi- outer aleurone layer. Brown rice possesses prominent tion, spinach is an abundant source of the carotenoid leutin, health benefits when compared to white rice. One cup of which is highly beneficial for patients with macular boiled brown rice has 216.4 cal of energy, monosaturated degeneration and cataracts (Olmedilla et al. 2003). Com- and polysaturated fat (0.64 g and 0.63 g respectively), pared to other leafy vegetables spinach is rich in flavonoids 44.8 g of carbohydrates and 5.3 g of proteins. In addition, which includes patuletin, spinacetin, spinatoside, jaceidin, brown rice is also a rich source of fiber (3.5 g), thiamine and flavone (Koh et al. 2012). These compounds are (12%), riboflavin (15%), nicotinic acid, zinc (8%), iron responsible for the potent antioxidant and anti-inflamma- (5%), magnesium (21%), phospherous (16%) and pan- tory properties of spinach. tothenic acid (6%). The vitamin E component of brown Antioxidant properties of spinach are well established. rice consists of eight lipid homologues a, b, c and d Studies have reported that spinach scavenges 2,2’-Azino- tocopherol or tocotrienol these are having potent lipid per- bis(3-ethylbenzothiazoline-6-sulfonic acid; ABTS) radical, oxy radical scavenging properties thus preventing cellular superoxide anion (O2-), Fe2?, peroxyl radical, hydroxyl ageing (Kim et al. 2015). radical, and peroxynitrite thereby protecting cells from Lee et al., conducted a randomized 12-week clinical oxidative damages (Jaiswal et al. 2011). A water-soluble study where the type 2 diabetes patients were assigned to natural antioxidant (NAO) mixture extracted from spinach follow brown rice-based vegan diet. They found that brown contains polyphenols and flavonoids. NAO was found to be rice-based vegan diet is more effective for glycaemic effective in preventing malonaldehyde (MDA) formation control in type 2 diabetic patients than conventional diet. In (Bergman et al. 2001). The ant-inflammatory properties of addition, they also found a reduction in the HbA1C levels spinach are also well established. Animals treated with among the vegan diet followed patients (Lee et al. 2016). spinach derived NAO and then challenged with Kozuka et al., have elucidated the underlying mechanism lipopolysaccharide have shown reduced severity of lesions on how brown rice improves the glucose intolerance and and alleviated the COX2 mediated inflammation (Bergman impede the onset of diabetes. They investigated the effect et al. 2001). In addition, leutin has potential free radical of c-oryzanol (orz) which is a major chemical constituent scavenging property and thereby decreased the levels of of brown rice on the feeding behavior and glucose home- PGE2, TNF-a, and IL-1b in the LPS induced inflammatory ostasis. They found that orz significantly improved the model. Spinach intake reduces infarct volume, lowers glucose intolerance and this was achieved by attenuating caspase activity in cerebral cortex and increased locomotor endoplasmic reticulum stress in mice fed with high fat diet. activity in focal ischemic rat brain (Lingappan 2018). Using HEK293 cell line the revealed that orz prominently Clinical studies have also proven the potential cardio- inhibits the transcriptional activity in the endoplasmic protective properties of spinach. In a A Randomized, reticulum stress responsive element. In addition, they also Controlled Trial Jovanovski et al. (2015) had hypothesized found that orz significantly down-regulated the gene that short term consumption of spinach, which is high expression of endoplasmic reticulum stress related 123 J Food Sci Technol molecules in fetal mouse brain derived neuronal cells. Several clinical studies have also shown potential health Moreover, orz also has shown to improve glucolipotoxicity benefits of BW. He et al. (1995) has shown that daily intake induced pancreatic islets disruption via enhancing glucose- of 100 g of lowered both total and LDL cholesterol in 850 stimulated insulin secretion and inhibiting excessive people of ethnic minority in china. In a doube blind secretion of glucan (Kozuka et al. 2015). crossover study from Wieslander et al. (2011) samples were supplemented with normal BW (16.5 mg rutin/day) Buckwheat and tartary BW cookies (359.7 mg rutin/day) for two weeks. They found that tartary BW cookies consumption Buckwheat (BW) is a gluten free commonly eaten func- reduced the serum myeloperoxidase, total serum choles- tional food belonging to family Polygonaceae genus terol and HDL-cholesterol. Moreover, they also found that Fagopyrum. It is considered as a food of high nutritional tartary BW consumption improved the lung vital capacity. value due to the presence of protein, lipid, dietary fiber, Hence, consumption of BW reduces the inflammatory minerals, phenolic compounds, and sterols. Buckwheat markers and cardiovascular events in human beings. contains flavonoids such as rutin and polyphenolic com- pounds like hyperin, quercitrin, and studies showed that quercetin could be responsible for the beneficial effects. Fruits as a source of functional food BW is also rich in amino acid lysine, arginine and vitamins (Giménez-Bastida and Zieliński 2015). Recently it has Fruits are a rich source of fiber, vitamins and polyphenolic been found that buckwheat also contains c-aminobutyric and anthocyanin compounds. These compounds have many acid (GABA) and 200 -hydroxynicotianamine. BW has physiological functions and delays the onset of ageing shown to possess strong antioxidant activity and prevents related changes, helps in fighting infections and chronic the DNA damage induced by oxidative stress (Zhou et al. diseases, impedes cancer, osteoporosis and neurological 2012). Phenolic compunds and flavonoids present in BW disease progression. Some of the fruits which act as func- exert anti-inflammatory effect by reducing the expression tional food discussed below. of IL-6, IL-1b, and TNF-a and inhibit NF-jB (Hole et al. 2009). BW consumption reduces body fat, low density Blueberries lipids (LDL) and increases the content of high density lipids (HDL) and lowers cholesterol and triglycerides (TG) Blueberries were known as ‘super fruit’ because of their in rats (Kayashita et al. 1996), thus inhibiting the devel- strong antioxidant activity and rich content of polyphenolic opment and progression of cardiovascular diseases. BW compounds. Blueberries contain flavonoid and non- intake also affects the mRNA expression of enzymes flavonoid. Anthocyanins (60%) are the major components. responsible for lipid metabolism. BW decreases the Malvidin 3-galactoside, delphinidin 3-galactoside, del- expression of glucose-6-phosphate dehydrogenase and phinidin 3-arabinoside, petunidin 3-galactoside, petunidin fatty acid synthase and downregulates expression of PPAR 3-arabinoside, malvidin 3-arabino-side, cyanidin 3-glu- -c, peroxisome proliferator activated receptor-c, CCAAT/ coside, cyanidin 3-galactoside, cyanidin 3-arabinoside and enhancer-binding protein-a, sterol regulatory element- delphinidin 3-glucoside are the major anthocyanins present binding protein 1c, and carbohydrate responsive element- in blueberries. Proanthocyanidins, flavonols and chloro- binding protein and of lipogenic genes acetyl-coenzyme a genic acid are also present in blueberries. The commer- carboxylase 1 or 2 (ACC1 and 2), stearyl-coenzyme A cially available blueberries species are Vaccinium oxidase, and FA synthase (Choi et al. 2007). Preclinical corymbosum L., V. virgatum Aiton, V. angustifolium, V. studies have shown that BW reduces the blood glucose myrtillus L. The association between the higher intake of levels in diabetic rats (Yao et al. 2008), inhibited a-amy- anthocyanin and health benefits have been well studied. lase and a-glucosidase activity (Lee et al., 2015) and also Higher intake of anthocyanin was associated with a modulates satiety, improve insulin sensitivity and glucose decrease in hypertension risk in women, improved vascular tolerance in hyperglycaemia patients (Qiu et al. 2016). function and helps in weight maintenance (Bertoia et al. Polyphenols present in buckwheat exert neuroprotection 2016).Blueberries are also found to be beneficial in dia- because of its free radical scavenging activity. Buckwheat betes. Higher intake of anthocyanins improved insulin has shown to improve spatial memory by inhibiting glu- sensitivity, reduced inflammation and oxidative stress in tamate release and inhibiting production of nitric oxide in diabetic patients (Li et al. 2015). Anthocyanin intake also cerebral ischemia induced rat (Giménez-Bastida and Zie- reduced the risk of Alzheimer’s disease, dementia and PD liński 2015). Buckwheat also improved the memory in (Gao et al. 2012). In vitro studies have shown that antho- in vivo model of AD by reducing oxidative stress in mice cyanins improved viability and differentiation of human (Choi et al. 2007) (Fig. 3). corneal epithelial cells (Song et al. 2010) and improve 123  J Food Sci Technol Fig. 3 Mechanism by which buckwheat intake provides benefits in different disease conditions retinal photoreceptor sensitivity. Blueberries have been anthocyanins (pelargonidin 3-glucoside, cyanidine 3-glu- shown to reduce cancer progression by inhibiting produc- coside, delphinidin 3-glucoside, pelargonidin 3,5-diglu- tion of pro-inflammatory molecules, oxidative stress and coside, cyanidine 3,5-diglucoside and delphinidin 3,5- products of oxidative stress such as DNA damage, inhibi- diglucoside), ellagitannins and hydrolysable tannins. Invi- tion of cancer cell proliferation and increased apoptosis tro data has shown decreased cell viability in A549 fol- (Johnson and Arjmandi 2013). lowing PFE administration. They found that PFE upregulates the cell cycle regulatory molecules like WAF1/ Pomegranate p21 and KIP1/p27. WAF1/p21 and KIP1/p27 are regarded as the universal molecules of inhibitor of cyclin–cdk Pomegranate (Punica granatum L) fruits are rich source of complexes. PFE administration has also significantly phytochemical such as polyphenols, anthocyanins, tannins, downregulated the cyclin–cdk associated molecules. In flavonoids, lignans, terpenoids, and sterols. Ellagitannin addition, the PFE administration declined progression of which is broken down to ellagic acid is the main active A549 human lung carcinoma cells in athymic mice. The constituent of pomegranate which is responsible for its potent anti-oxidant property aid to the chemoprotective strong antioxidant activity (Akbar et al. 2015). Punicalagin nature of PFE. and punicalin are the two other ellagitannins having Studies have showed the role of pomegranate juice in antioxidant and anti-inflammatory activity (Vučić et al. preventing hypertension and congestive heart disease (Es- 2019). Numerous studies have claimed health benefits of maillzadeh et al. 2006). Pomegranate juice also promotes pomegranates in preventing chronic diseases such as the expression of transcription factors such as CREB, and hypertension, arthritis, cancer, hyperglycaemia, reducing BDNF which play a critical role in brain development. oxidative stress and maintaining cholesterol levels (Zarfe- Pomegranate juice reduces cerebral amyloid beta deposits shany et al. 2014). by increasing the expression of CREB and synaptic pro- Khan et al. (2007) has revealed that pomegranate juice teins which were also found to be involved in the cleavage inhibits cell growth, induces pro-apoptotic proteins and of amyloid precursor protein in transgenic mice model of downregulates anti-apoptotic proteins and suppresses the Alzheimer’s disease (Braidy et al. 2016). Decreased progression of prostate cancer and breast cancer as well as expression of amyloid beta in hippocampus due to pome- lung and colon cancer (Khan et al. 2007). The pomegranate granate intake improves cognitive functions in mice. fruit extract (PFE) used in this study was rich in six Pomegranate juice also enhances neuronal survival, 123 J Food Sci Technol protects from oxidative stress, reduces a-synuclein aggre- in almonds improve memory consolidation in rodent gation and could be able to increase mitochondrial activity models of amnesia (Batool et al. 2016). in rotenone model of Parkinson’s disease. Pomegranate administration also reduces the neuroinflammation and Walnut improved motor functions in mice (Kujawska et al. 2019). Walnuts are one of the most nutritive nuts belonging to Mango family Juglandaceae. They are rich in proteins, fats, vita- mins, minerals, and polyphenols. The major triacylglyc- Mango (Mangifera indica L.) is rich in polyphenols and erols; free fatty acids found in the walnut kernel are oleic, other micronutrients which exert several health benefits. linoleic, linolenic acids (Poulose et al. 2014). They also Mangiferin, gallic acid, gallotannins, quercetin, iso- contain high quantity of omega-3 fat [alpha-linolenic acid] quercetin, ellagic acid, and b-glucogallin are the polyphe- which has been linked with numerous health benefits. nols present in mango. Mango parts have been used in Walnuts also contain amino acids such as lysine and traditional system in the management of various diseases. arginine which are converted to nitric oxide, which acts as Mango extracts counteract the oxidative damage induced a potent vasodilator, inhibiting platelet adhesion and by the excessive production of free radicals and exert anti- aggregation, and reducing the progression of atheroscle- inflammatory activity in mice model of colitis by reducing rosis. Ellagic acid present in the walnut reduces the risk of the expression of inflammatory mediators via IGF1R/AKT/ congestive heart disease and suppresses cancer progres- mTOR pathway (Kim et al. 2016). Mango extract has sion. Melatonin present in walnut is a powerful antioxidant beneficial effects in hypoglycaemia by inhibiting a-amy- and regulates circadian rhythm. Dietary supplement of lase and a-glucosidase activities (Gondi and Prasada Rao walnut improves memory consolidation and has been 2015). Bioactive compounds of mango have also shown to reported to delay the progression of neurological disorders. possess anticancer activity which is mediated by down- Moreover, walnut supplementation provided neuroprotec- regulating the anti-apoptotic factor Bcl-2 and activating tion and improved motor functions in rodent model of caspase proteases. Mango intake reduces the risk of obesity Parkinson’s disease (Choi et al. 2016). Taken together, and promotes endothelial function. Phytochemicals present evidences suggest that integration of nuts in a healthy diet in mango improve the lipid profile and reduced blood could be an effective measure to maintain a health state and pressure surge in hypertensive rats (Liu et al. 2003). Mango delay the onset of diseases. intake also reduces the development of neurological dis- eases such as Alzheimer’s disease. In vitro and in vivo studies have confirmed that magniferin protects the neu- Functional foods of animal origin rons by scavenges the ROS and restores mitochondrial membrane potential and improved cognitive performance Fish (Bhatia et al. 2008). The chief bioactive component present in fish products are polyunsaturated fatty acids. Eicosapentaenoic acid and Nuts as a source of functional food docosahexaenoic acid (DHA) form the major components of polyunsaturated fatty acids. DHA forms an essential Almond component of cellular membranes in brain and retina. DHA is critical for normal functioning and development of Almonds are the most popular nut consumed by humans. organs in children. Preclinical and clinical studies have They have a high nutritional value and are rich in shown the beneficial effects of fatty acids in inflammatory poylphenols, vitamins, carbohydrates and polyphenols. diseases such as arthritis, psoriasis, Crohn’s disease, and Almonds are also rich in monounsaturated fatty acids such chronic diseases such as cancer and cardiovascular dis- as oleic, linoleic and palmitic acids. Intake of almonds eases. DHA have also been found to provide protective reduce chronic disease such as diabetes, hypertension and effect in neurological diseases (Wergeland et al. 2012). help in weight maintenance. Invitro and animal studies have reported that almonds reduce oxidative stress and Probiotics DNA damage. Epidemiological studies have shown that higher intake of almonds in Mediterranean countries con- Probiotics are the viable microorganisms that improve the tributes to lower incidences of coronary heart disease, intestine functions in the host organisms. Probiotics are reduce inflammatory diseases and improve endothelial known for their anti-carcinogenic, hypocholesterolemic functions (Kamil and Chen 2012). Dietary elements present and antagonistic action against enteric pathogen in the 123  J Food Sci Technol intestines. Dairy products are the best source of calcium. The most significant change in the food regulation was Probiotics have been incorporated in milk products, may- implemented by Dietary Supplement Health and Education onnaise, edible spreads (Begum et al. 2017). Probiotics Act of 1994 (DSHEA). This act considered the food constitute around 65% of functional food market. Probi- additives as vitamins, minerals, amino acids used by man otics inhibit pathogen growth by synthesizing biochemical to improve the health conditions. They introduced ‘‘sig- compounds which possess antimicrobial activity, altering nificant Scientific agreement’’ which includes the reports of the pH, receptor binding of pathogens, and initiating the safety and efficacy of these compounds in living sys- immune response. Probiotics have also been found to be tem. This includes the role of the bioactive compound that useful in the management of neurological disorders. affects the functioning of living systems and the mecha- Alteration in gut microbiome have been reported in autistic nism by which the compound induces pharmacological children. Lower levels of Bifidobacterium have been found effect. In addition, if the compound claims to treat any in autism. Similarly, fecal matter of autistic children has conventional nutrient deficiency diseases then the preva- higher levels of Clostridium spp. In case of Alzheimer’s lence of the disease in the United States should be pro- disease Oscillospira were found to be reduced while as duced. Manufacturers who are using structural and Enterobacter, Shigella and Roseburia increased. Various functional claims on the label should notify the FDA within clinical and animal studies have confirmed the beneficial 30 days of marketing and the following statement should effects of probiotics in autism. The key mechanism by be kept as a disclaimer (‘‘Dietary Supplement Health and which probiotics have an impact on the gut microbiome are Education Act of 1994,’’ n.d.). by competing for dietary ingredients production of end products having inhibitory property increased innate immunity reduced inflammatory response. Some of the Conclusion commonly used microorganisms in probiotics are Lacto- bacillus rhamnosus, Lactobacillus reuteri, Bifidobacteria, Functional foods have been receiving considerable global Lactobacillus casei Lactobacillus acidophilus, Bacillus attention because of their nutritional value and the presence coagulans, Escherichia coli, Saccharomyces boulardii. of constituents which are critical in regulation of physio- Probiotics may contain a single strain or mixture of these logical processes. Functional foods have all the ingredients microorganisms. necessary for a healthy diet and have been found to possess health benefits. Recommendation of functional foods is evolving and will be an essential strategy for maintenance FDA perspective on functional foods of healthy sate and delaying or preventing the onset of diseases. The Federal Food Drug and Cosmetic Act (FFDCA) does not provide a specific definition for the functional food. Acknowledgements The authors wish to thank their institutions for continued support. The language and technical editing support pro- Hence, FDA does not have an established regulation for the vided by The Editing Refinery, MD, USA is highly acknowledged. functional foods. Therefore, marketing functional foods The financial support in the form of internal grant from SQU Oman to come under the existing regulatory options. There is a MME is highly acknowledged. The project was also supported by rising concern to develop regulations to document the Alfaisal university by INTERNAL RESEARCH GRANTS IRG20314. safety of the dietary ingredients and dietary supplements. Nutrition Labeling and Education Act which was devel- Author contributions MB, and AB performed literature research, oped (NLEA) in 1990 introduced food labels, this explains gathered and analyzed information, and generated short preliminary the relationship between food or a food component with write-ups. SBC, BB, HH and NG provided research insight, content disease or health conditions. These potential health benefit examination and supported wide ranging aspects of the manuscript development process. MME, RPF and MWQ conceptual work, claims should be approved by FDA before marketing. In framework, final draft write-up, critical reading and editing. All 1997, the FDA Modernization Act (FDAMA) had been authors read and approved the final manuscript. implemented. This act smoothened the FDA preapproval process by implementing the ‘‘authoritative statements’’ on Funding MME highly acknowledge the funding support provided by food labels as health claims. These statements should be SQU, Oman in the form of Internal Grant. The support provided to HH by Al-Faisal university, KSA as INTERNAL RESEARCH published by US government bodies which are responsible GRANTS IRG20314 is highly acknowledged. for the public health like National Institute of Health (NIH). Manufacturers who intend to use the authoritative Availability of data and materials All data generated or analyzed statement should notify the FDA 120 days prior to the during this study are included in this published article. marketing (Affairs 2019 p. 1). 123 J Food Sci Technol Declarations Chaplin A, Carpéné C, Mercader J (2018) Resveratrol, metabolic syndrome, and gut microbiota. Nutrients. https://doi.org/10. Conflict of interest Authors declare no conflict of interest. 3390/nu10111651 Chen D, Huang C, Chen Z (2019) A review for the pharmacological effect of lycopene in central nervous system disorders. Biomed Pharmacother 111:791–801. https://doi.org/10.1016/j.biopha. 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