A Review of Anti-Nutritional Factors in Plant Based Foods

Keywords

Anti-Nutritional Factors; Plant-Based Foods And Feeds; Role In Human And Animal Nutrition; Metabolic Products And Biochemical Approaches.

Introduction

Nutrition is well known as one of the most important factors influencing the efficacy, efficiency, and evolution of livestock systems. Despite the fact that the world produces enough food to feed everyone, more than 800 million people go to bed hungry every night [1]. Additionally, malnutrition and hunger-related diseases account for more than 60% of all deaths [2]. One of humanity's most fundamental challenges is eradicating hunger and malnutrition. Furthermore, food sufficiency is not the most important factor; food nutritional quality, as well as the effects of the accepted food portion, are crucial. From this perspective, the topic of the current review, antinutrients, raises important questions about human health and contributes to a better understanding of what people eat and the potential consequences.

Antinutritional factors are compounds or substances of natural or synthetic origin that interfere with nutrient absorption, reducing nutrient intake, digestion, and utilization, as well as producing other negative effects. Antinutrients are naturally synthesized in plants and are frequently associated with plant-based, raw, or vegan diets [3]. Nausea, bloating, headaches, rashes, nutritional deficiencies, and other symptoms can be caused by a large number of antinutrients in the body. On the other hand, when consumed wisely, such chemical compounds can clearly benefit humanity. Plants, in fact, primarily use antinutrients to defend themselves. Despite the fact that people's sensitivity to antinutrients varies greatly, adequate food processing is initially advised to reduce antinutritional factors. Antinutrients cannot be removed from the body once they have been ingested. The correlation between symptoms and effects on human health can be cleared by removing and reintroducing specific foods that contain antinutrients. The biochemical effects of anti-nutritional factors are of particular interest in this regard. The majority of secondary metabolites that act as anti-nutrients cause extremely harmful biological responses, whereas others are widely used in nutrition and as pharmacologically active agents [4].

Antinutrients are most abundant in grains, beans, legumes, and nuts, but they can also be found in the leaves, roots, and fruits of some plant varieties. Phytates, tannins, lectins, oxalates, and other antinutrients found in plant-based foods are the most common. Antinutrients in vegetables, whole grains, legumes, and nuts are only a problem if a person's diet consists entirely of raw plant foods. By binding with calcium, oxalate, for example, prevents calcium from being absorbed in the body. Oxalates are commonly found in raw spinach, kale, broccoli, and soybeans. Excessive tannin consumption, such as that found in tea, wine, some fruits, and chocolate, may inactivate enzymes involved in protein absorption. Phytates can be found in grains, nuts, and seeds, while lectins can be found in peppers, eggplants, and tomatoes. Consumption of phytates can reduce mineral absorption, and lectins can cause a variety of reactions in the body [5]. Saponins, on the other hand, have been linked to the destruction of red blood cells, the inhibition of enzymes, and the intervention of thyroid function [6].

Antinutritional factors can be combated in a variety of ways. Certain allergens and antinutrients in food could be reduced using modern biotechnology techniques. Based on nuclease-based forms of engineering such as the Transcription Activator-Like Effector Nucleases or the Clustered Regularly Interspaced Short Palindromic Repeats/Associated Systems, genome editing biotechnology can create mutations and substitutions in plant and other eukaryotic cells. Antinutrient effects can be influenced positively by increasing prebiotic levels in the body. Thermal treatment of the product, such as extrusion, autoclaving, hydrotechniques, enzymatic and harvest treatments, and so on, is a common method for removing antinutrients [7].

The main challenges nowadays in ruminant production are to reduce feeding cost, improve products quality and diminish the impact of production on environment. The use of unconventional feedstuffs may contribute to decrease feeding cost and environmental impact through reduced methane emissions as well. Not only that, but shrubby plants can be used to combat desertification, mitigating the effect of drought, allowing soil fixation an enhancing the restoration of the vegetation and the rehabilitation of rangelands. In the meantime, browsing tree foliage plays an important role in ruminant feeing systems in many tropical and Mediterranean environments around the world [8]. They are chiefly as good, cheap sources of nitrogen and energy, which may reduce feeding cost and raise sheep productivity in arid and semiarid zone [9]. So, to reach that goal, it must exploit all that is available either unconventional feedstuffs or browse and shrubs. However, the problems of feeding such plants or shrubs (Acacia, Leucaena and Atriplex) that they had different levels of anti-nutritional factors.

Foods and feeds' nutritional value is largely determined by their nutritional and antinutritional composition. The goal of this review was to summarize the availability of antinutrients, explain their effects on the animal and human body, and remember potential ways to disable them.

Methods

This review report was created by searching the literature for Anti-nutritional factors; Plant-based foods and feeds; Role in human and animal nutrition; metabolic products and biochemical approaches utilizing available scientific information and relevant literatures. The logical term operant was used to find objects that matched terms in a search.

Antinutritional Factors

Overview of Antinutritional Factors

Anti-nutritional factors (Anti-nutrients) are substances that, when present in human and animal food and feed or water, reduce the availability of one or more nutrients, either directly or through their metabolic products.

Toxic substances of natural origin can be classified based on their chemical properties and on the basis of their effect on utilization of nutrients. (A) According to their Chemical Properties (Group I: Proteins (Protease inhibitor and Haemagglutinins (Lectins); Group II: Glycosides (Saponins; Cyanogens; Glucosinolates (Goitrogens) or Thioglucosides; Group III: Phenols (Gossypol and Tannins) and Group IV: Miscellaneous or Antimetals and Antivitamins) and (B) On the basis of antinutrients they affect directly or indirectly: 1. Substances depressing digestion or metabolic utilization of proteins: Protease inhibitor (Trypsin and Chymotrypsin inhibitor), Haemagglutinins (Lectins), Saponins, polyphenolic components; 2. Substances reducing solubility or interfering with the utilization of minerals: Phytic acid, Oxalic acid, Glucosinolates (Thioglucosides), Gossypol; 3. Substances increasing the requirements of certain vitamins: Anti-vitamin (A, D, E, K), Anti-vitamin (B1, B6, B12) and nicotinic acid; and 4. Substances with a negative effect on the digestion of carbohydrates: Amylase inhibitors, Phenolic compounds, Flatulence factors). Generally, Anti-nutritional factors are chemical constituents which impair the digestion and absorption of some interesting components (e.g. minerals, proteins, vitamins), or, in some cases, they are simply toxic or cause undesirable physiological side effects (e.g. flatulence). The presence of these antinutritional compounds in plant based foods and feeds is therefore considered one of the limitations to an increased utilization of the grain as food as well as feed sources.

Antinutrients in Plant based foods

Phytates: Phytates can be found in a variety of vegetable products. Phosphorus is stored in the husks of seeds, grains, nuts, and legumes as phytic acid in the form of phytin or phytate salt. Their presence may affect mineral bioavailability, as well as protein and carbohydrate solubility, functionality, and digestion [10]. The bran of grains contains the highest concentration of phytic acid [11]. Phytic acid is found in the cotyledon layer of legumes and can be removed before eating. The digestive enzyme phytase can release phosphorus from phytic acid storage. In the absence of phytase, phytic acid can bind to other minerals like iron, zinc, magnesium, and calcium, preventing them from being absorbed [12].

As a result, highly insoluble salts are produced, which are poorly absorbed by the gastrointestinal tract, resulting in lower mineral bioavailability. Pepsin, trypsin, and amylase are all digestive enzymes that are inhibited by phytates [13].

Lectins: Lectins are non-immune proteins or glycoproteins that are particularly abundant in plants. They have the ability to bind to carbohydrates or glyco-conjugates without modifying them (glycoproteins, glycolipids, polysaccharides). They can successfully recognize animal cell carbohydrates, which is related to the Latin word legere, which means "to choose" [14]. Lectins serve a number of purposes. By breaking down the surface of the small intestine, they can bypass the human defense system and travel all over the body, causing diseases (such as Crohn's disease, Coeliac- Sprue, colitis, and so on). The gut wall develops holes and intestinal permeability when large amounts of lectins are introduced into the body, resulting in leaky gut syndrome.

Lectins can cause the pancreas to release insulin or cause cells to act as if they have been stimulated by insulin. By presenting incorrect immune system codes and stimulating the growth of some white blood cells, lectins can also cause autoimmune diseases [15]. This could cause cancer, but lectins have not yet been identified as a cancer-causing agent.

Not all lectins are poisonous or cause damage to the intestine. Wheat, beans, quinoa, peas, and other plant species contain lectins. Birds have been found to be resistant to grains lectins because grains are a common part of their diet [16]. Consumption of lectins has been linked to acne, inflammation, migraines, and joint pains. Because lectins are usually found in the hull, eating white rice reduces your lectin intake. The amount of lectins in plant sources can be significantly reduced by heating them during the cooking process. When compared to sweet potatoes, white potatoes have a higher lectin content [17]. Almonds are also a better source of lectins than peanuts.

Trypsin Inhibitors: Trypsin inhibitors can be found in a variety of foods, including chickpeas, soybeans, red kidney beans, adzuki beans, mung beans, and other Leguminoseae, Solanaceae, and Gramineae members. Grain legumes provide ten percent of the world's dietary protein. The loss of trypsin and chymotrypsin in the gut as a result of trypsin inhibitors prevents protein digestion. The release of cholecystokinin triggered by trypsin inhibitors causes excessive trypsin synthesis and a burden on sulfur containing amino acids in the body's requirements [18].

Alpha-amylase Inhibitors: Inhibition of -amylase is a strategy for treating carbohydrate uptake disorders, as well as dental caries and periodontal diseases, by lowering insulin levels. Amylase inhibitors are chemical compounds that bind to alpha amylases and render them inactive. Alpha-amylase inhibitors have been found to have two functions. Inhibitors have two functions: one is to protect the seed from microorganisms and pests, and the other is to inhibit the endogenous -amylase [19]. However, due to the inhibitor's instability in the gastrointestinal tract and the fact that it's a very heat-sensitive constituent, it can't be used as a starch blocker [20]. It's used to treat type 2 diabetes in humans and has a number of applications in the food industry.

Protease Inhibitors: Proteases are enzymes that regulate cell processes and are found in all cells and tissues. Raw cereals and legumes, particularly soybeans, are high in protease inhibitors. Protease inhibitors bind reversibly or irreversibly to their target proteins. Antinutrient activity of protease inhibitors is linked to growth inhibition, pancreatic hypertrophy [21], and poor food utilization [10]. Exopeptidases cleave peptides within the molecule, whereas endopeptidases remove amino acids from the C- or N-terminus. Grain-eating birds' digestive enzymes have evolved to be resistant to grain protease inhibitors. High levels of protease inhibitors cause the pancreas to secrete more digestive enzymes in human volunteers and animal experiments [22].

Tannins: Plant tannins are a type of antioxidant polyphenol found in foods and beverages that has piqued researchers' interest due to its multiple health benefits. Tannins are flavan-3-ol oligomers and flavan-3, 4-diol oligomers found in the bran fraction of legumes [23]. This water-soluble polyphenol is abundant in grapes and green tea. Tannins have antinutritional properties, preventing the body from absorbing beneficial bioavailable substances and impairing the digestion of various nutrients. Tannins can also bind to proteins and shrink them. Because of the protein substrate and ionisable iron interaction, tannin-protein complexes may cause digestive enzyme inactivation and protein digestibility reduction [24].

Goitrogens: Because the thyroid gland is highly sensitive to stress and environmental stimuli, hypothyroidism is on the rise worldwide [25]. Goitrogens block iodine absorption, affecting thyroid function. Goitrogen-rich foods include vegetables from the genus Brassica, such as broccoli, cabbage, cauliflower, Brussels sprouts, and kale. Triiodothyronine (T3) and thyroxine (T4) levels are affected by cruciferous vegetable consumption, resulting in hypothyroidism [26]. Insufficient water consumption and protein malnutrition can be concomitant factors.

Raffinose Oligosaccharides: Sucrose is used to make raffinose, stachyose, and verbascose, which are all Raffinose Family Oligosaccharides (RFOs). Non-digestible oligosaccharides have a prebiotic effect in the lower intestine by promoting the growth of pathogenic-inhibiting bacteria such as Bifidobacterium and Lactobacillus [27]. Humans are unable to digest RFOs and allow them to pass through the intestinal wall intact due to a lack of appropriate enzyme activity to hydrolyze RFOs (-galactosidase) [28]. A link has been drawn between the consumption of legumes and the likelihood of intestinal discomfort, which manifests as symptoms such as burping, abdominal pain, and bloating [28]. The presence of RFO in one's daily diet can cause problems with nutrient digestion. RFO can reduce the amount of metabolizable energy and protein used.RFO removal has been shown to improve the digestion of all amino acids, thereby increasing the nutritional value of the lupin diet [29].

Saponins: Some saponins (steroid or triterpene glycoside compounds) are edible, but others are poisonous. Saponins with a bitter taste are toxic at high concentrations and can interfere with nutrient absorption by inhibiting enzymes (metabolic and digestive) and binding to nutrients like zinc. Saponins are organic compounds that have a variety of biological effects. Saponins have a strong hypocholesterolemic effect in the presence of cholesterol [30]. They can also cause hypoglycemia [31], as well as impair protein digestion, vitamin and mineral absorption in the gut, and the development of a leaky gut [32].

Exorphins: Gliadins, which are alcohol-soluble proteins (proal imins) found in cereal grains and dairy products, can be further degraded in the gastrointestinal tract to form a collection of opioid-like polypeptides known as exorphins [33]. The bioactivity of food-derived exorphins can affect behavioral traits such as spontaneous behavior, memory, and pain perception. Exorphins can also have an effect on gastric emptying and intestinal transit by lengthening it. Exorphins derived from alpha-casein are produced during milk digestion [34]. According to recent research, milk-derived opiate peptides' epigenetic effects may contribute to gastrointestinal dysfunction and inflammation in sensitive individuals [35].

Contextual Antinutrients: Antinutrient reactions can occur when certain supplements or foods high in certain nutrients are consumed. Calcium-rich foods, for example, can obstruct iron absorption. During the absorption process in/on the intestinal epithelium, zinc and copper have a mutual antagonistic relationship [36]. When added to nonfat foods, phytosterols and phospholipids may reduce cholesterol absorption, according to research. Some foods can make it difficult to absorb medications [37]. Grapefruit and a variety of drugs is the most well-known fooddrug interaction. Drug-metabolizing enzymes are inactivated by bergamottin, which is found in grapefruit juice.

Food interaction warnings are listed on some medical labels for this reason. Resveratrol, found in red wine and peanuts, inhibits platelet aggregation, according to studies, and high doses may increase the risk of bleeding when combined with anticoagulant drugs. Black tea was found to be a more powerful enzyme inhibitor than single-ingredient herbal teas (St. John's Wort, feverfew, cat's claw, and so on) by Canadian researchers [38]. Foods containing tyramine (chocolate, beer, wine, avocados, and so on) and mono-amine oxidase inhibitors (a type of antidepressant) are another well-known food-drug interaction. Vitamin K-rich foods (e.g. broccoli, spinach) and Coumadin, an anticoagulant prescribed to thin the blood and prevent clots, have the most medically significant food-drug interaction [39].

Oxalates: Antinutritional properties can be found in some organic acids. Oxalic acid can be converted to oxalates, which are soluble (potassium and sodium) or insoluble (calcium, magnesium, iron) salts or esters found in plants (e.g. leafy vegetables) or synthesized in the body [40]. Once processed through the digestive system, insoluble salts cannot be processed out of the urinary tract. By forming kidney stones, calcium oxalate can have a negative impact on human nutrition and health. Foods high in oxalates include cruciferous vegetables (kale, radishes, cauliflower, broccoli), chard, spinach, parsley, beets, rhubarb, black pepper, chocolate, nuts, berries (blueberries, blackberries), and beans [41]. Most people can consume normal amounts of oxalate-rich foods, but people with conditions like enteric and primary hyperoxaluria must limit their oxalate intake. Small amounts of oxalates can cause burning in the eyes, ears, mouth, and throat in sensitive people, while large amounts can cause abdominal pain, muscle weakness, nausea, and diarrhea [42]. Some food sources with the typical antinutrients contained in them as well as the amounts variables are mentioned Table 1 below.

Antinutrients in animal feeds

Protease inhibitor: Soyabean, kidney bean, and mung bean seeds, for example, have the ability to inhibit the proteolytic activity of certain digestive enzymes [57]. Protease inhibitors are concentrated in the cotyledon mass's outer layer. There are two types of protease inhibitors: kunitz inhibitors (which only inhibit trypsin) and Bowman-birk inhibitors (which inhibit all proteases) (inhibits trypsin and Chymotrypsin) [58]. Because the inhibitory substances are mostly heat labile, the protease inhibitors can be inactivated with proper heat treatment [59]. Some nutrients, such as amino acids and vitamins, can be damaged by excessive heat [60]. To assess the adequacy of heat treatment, quality control tests have been developed. Trypsin inhibitor and urease assays are two examples. Soybean trypsin inhibitor reduces the amount of methionine available in raw soybeans. The pancreas of young chickens fed raw soybean developed hypertrophy. Large animal species such as pigs, dogs, and calves do not have pancreatic hypertrophy or hyperplasia [60].

Temperature, heating duration, particle size, and moisture level are all important factors in trypsin inhibitor destruction. The trypsin inhibitory activity of solvent extracted SBM was destroyed by autoclaving under the following conditions or by exposing it to steam for 60 minutes [60]. Duration: 5 psi for 45 minutes, 10 psi for 30 minutes, and 15 psi for 20 minutes [61].

Haemagglutinins (Lections): Soybean Haemagglutinins are found in castor bean (ricin) and other legume seeds. Both plant and animal tissue contain these. These toxic substances can combine with the glycoprotein components of red blood cells (RBC), causing the cells to agglutinate [60]. Ricin is highly toxic, causing severe inflammatory changes in the intestines, kidneys, thyroid gland, and other organs. Lectins are resistant to pancreatic juice digestion and dry heat destruction, but they are destroyed by steam [6].

Saponins: These are bitter-tasting glycosides that form in aqueous solution and in haemolyse RBC. They have the ability to form complexes with sterols, including those found in animal cell plasma membranes. Saponins are less important for monogastric animals in general because their levels are low in most common feed ingredients [60].

Their toxicity is linked to their ability to reduce ruminant surface tension. Lucerne, soybean, and other common forages can cause saponin poisoning in livestock. The saponin content of the leaves is twice that of the stems on average, and the saponin content decreases as the plant ages [60, 62]. Excess feeding of green lucerne or legume forages saponins lower the surface tension of ruminal contents leading to accumulation of gas, condition is known as “bloat” This is also known as tympany/ tympnitis.

The presence of saponins has been cited as one of the factors responsible for the formation of foam in the rumen, which traps gas in the rumen contents, preventing animals from belching it out. As a result of the rumen distension, blood flow is obstructed, and anorexia develops, resulting in respiratory failure. Turpentine and paraffin oil can help with bloat, and ruminants should be fed 1 to 2 kg dry fodder before letting them out on legume pastures or before overfeeding green legume fodders as a preventative measure [60, 61].

Cyanogens: Cyanide can be found in trace amounts in plants, primarily in the form of cyanogenic glycoside. The glucoside is non-toxic in intact tissues of plants. These glycosides can be hydrolyzed into prussic acid or hydrocyanic acid (HCN) by an enzyme found in the same plant or by animals as they digest them. Microbial activity in the rumen can cause this reaction [60]. The HCN is quickly absorbed and some of it is exhaled, but the majority of it is quickly detoxified in the liver by conversion to thiocyanate. Excess cyanide ion can cause anoxia in the central nervous system, deactivating the cytochrome oxidase system and resulting in death in a matter of seconds [60].

Amygdalin (Almonds), Dhurrin (Jowar and other immature grasses), and Linamarin (Pulses, Linseed, and Cassava) are the three distinct glycosides (Glycoside Plant source). Because the enzyme required for the release of HCN is destroyed in horses and pigs by the gastric HCI, ruminants are more susceptible to HCN poisoning than horses and pigs [60].

Sheep are more susceptible than cattle. Jowar, sudan fodder, and linseed: after a period of drought, heavy trampling, or physical damage from frost, etc., new growth may develop toxic levels of HCN. Heavy nitrate fertilization followed by a lot of rain or irrigation could make these crops more susceptible to HCN poisoning.To avoid HCN poisoning, it is best to avoid feeding immature jowar green fodder. Animals that have shown no signs of toxicity may be injected: I/V with 3.0 g sodium nitrate and 15.0 g sodium thiosulphate in 200 ml H2O for cattle; I/V with 1.0 g sodium nitrate and 2.5 g sodium thiosulphate in 50 ml H2O for sheep [60].

Glucosinolates: These substances are found in most cruciferae plants (cabbage, turnips, rutabaga, rapeseed, and mustard green). The pungent flavors found in plants belonging to the genus Brassica are due to these glucosinolates [60]. Their primary biological effect is to suppress thyroid hormone (Thyroxine, T4) and triodothyronine (T3) synthesis, resulting in goiter. Goiter is caused by the hydrolysis products of glucosinolates, not by the glucosinolates themselves.

The glucosinolates are found in the root, stem, leaf, and seed, and they are always accompanied by the enzyme myrosinase (thioglucosidase), which can hydrolyze them into thiocyanates, glucose, acid sulphate, isothiocyanates, or nitriles depending on pH. In the presence of myrosinase, these volatile isothiocyanates cyclize to vinyloxazolidinethione, which is potently goitrogenic [60].

These result in decreased iodine uptake, thyroid gland enlargement, and liver damage. In chicks and pigs, growth depression and enlargement of the liver and kidneys have also been observed. In comparison to pigs and poultry, ruminants appear to be less susceptible to the toxic effects of glucosinolates [60]. This is most likely due to the rumen's glucosinolates being relatively unhydrolyzed. Myrosinase is found not only in the plant and the seed, but also in intestinal bacteria, which have glucosinolate hydrolysis enzyme systems. Inactivation of myrosinase in the seed is not an appropriate way to eliminate the antinutritional effects of glucosinolates due to the presence of myrosinase in the intestine. Rapeseed cultivars with high or low glucosinolate levels are available. In Canada, double-zero cultivars were created [60].

Gossypol: Gossypol is found in the pigment glands of leaves, stems, roots, and seeds of the genus Gossypium. These pigments can be found in two forms: free and as a gossypol-protein complex. Monogastric animals are highly toxic to it. Pigs and rabbits are more sensitive to pesticides than chickens. Horses are resistant, but ruminants are more resistant due to the formation of stable, enzymatically resistant complexes with soluble protein in the rumen [60].

Gossypol forms complexes with metals such as iron, and the toxic effect can be mitigated by taking ferrous sulphate as a supplement [62]. Gossypol is found in whole cotton seeds in amounts ranging from 1.09 to 1.53%, with the free form accounting for 0.19 percent.

The physiological effects of free gossypol are: educed appetite, loss of body weight, accumulation of fluid in the body cavities, cardiac irregularity, and reduced oxygen carrying capacity of the blood (reduced haemoglobin content), adverse effect on certain liver enzymes, Decreased egg size and decreased egg hatchability. Free gossypol content of 0.06% depresses growth in chicks while 0.1% causes severe effect. In laying hens, 0.15% free gossypol reduced egg production [60].

• In laying hens: 0.15% free gossypol reduced egg production. Egg yolk will have an olive green colour. Further higher levels cause yellow brown pigments in liver and spleen due to destructive effect on red blood cells [60].

• In pigs: A dietary level 0.01% reduced growth rate while 0.015% showed toxic symptoms. New varieties of cotton seed: less than 0.01% total gossypol (0.002% in the free form) are available [60]. Commercial production of cottonseed meal: heat treatment: decreases the content of free gossypol. The availability of lysine is reduced because of the interaction of the aldehyde groups of gossypol with the amino group of lysine.

Tannins: There are two types of polyphenolic substances: A. Hydrolysable tannins: These are tannins that can be easily hydrolyzed by water, acids, bases, or enzymes to produce gallotannins and ellagitannins. B. Flavonoids (polymers of flavonol): Condensed tannins are flavonoids (polymers of flavonol). Tannins, both hydrolysable and condensed, are found in abundance in nature [60].

Tannin content of various feedstuffs: 20 to 10% sorghum, 9.0 to 12 percent salseed meal, 5.0 to 7% mangoseed cake, 2.5 to 3.5 percent mustard oil cake, and 0.1 to 3.0% lucerne meal Tannins are astringent, which makes them unpalatable [60]. They cause a dry mouth sensation by reducing the lubricant action of the glycoproteins in the saliva.

Tannin bind the proteins and are thus inhibitors of proteolytic enzymes. High tannin content also depresses cellulose activity and thus affects digestion of crude fibre. So tannins reduce the digestibility of protein and dry matter. Sorghum contains high levels of condensed tannins. Most of the tannins are locate in seed coats. Decortication of seeds will reduce the tannin content. Germination of legumes also result a decrease in the tannin content [60].

Tannins: in some tree leaves: form complexes with plant proteins: increasing the amount of plant protein bypassing the rumen. When the tannin-protein complexes are dissociated in the low pH of the abomasums, an additional source of protein is made available, but in some cases, the tannins protect the proteins from digestion even in the small intestine [60].

Tannins: protein availability: - beneficial effect (increasing by pass protein), detrimental effect (depressing palatability, decreasing rumen ammonia, decreasing postruminal protein absorption) Tannins suppress:methanogenesis by reducing methanhogenic populations in the rumen:- either directly or by reducing the protozoal population thereby reducing methanogens symbiotically associated with the protozoal population [60].

Tannin sources containing both hydrolysable tannins and condensed tannins are more potent in suppressing methanogenesis than those containing only hydrolysable tannins. Phytic acid: The 6 alcoholic groups of inositol are combined with 6 molecules of hexaphosphonc acid to form phytic acid. As a result, it's known as inositol hexaphosphoric acid. It can form simple salts or mixed salts, as well as metabolic or protein complexes, due to the large number of phosphoric acid radicals present [60].

Salts of sodium and potassium are soluble. Even at pH 3-4, calcium, iron, magnesium, copper, zinc, and lead salts (phytates) are insoluble [60].

Phytate phosphorus is a poor phosphorus source. Phytic acid is abundant in cereal seeds, dried legumes, oilseeds, and nuts. The rind (pericarp + aleurone layer) and the embryo have higher phytic concentrations than the core (endosperm). Phytin P accounts for about 67 percent or more of the P in cereal grains; non-ruminant availability of P from plant feeds is less than 33 percent. More than 80% of the P comes from inorganic mineral supplements and animal sources. Because phytin is incompletely broken down in the digestive tract of poultry, pigs, and horses, PP is less effective than the inorganic form. Breakdown of PP by dietary phytase and microbial phytase.

Addition of the enzyme phytase to the ingredients of vegetable origin can increase phosphorus digestibility. Phytase produced by rumen microorganisms makes phytin phosphorus available to ruminants. Phytic acid depresses the utilization of several mineral elements such as Ca, Mg, Fe, Zn, etc. It forms insoluble compounds which are eliminated in the faeces [60].

Oxalic acid: Oxalic acid is abundant in plant foods. Animalbased foods contain a small amount of oxalic acid. Oxalic acid is a dicarboxylic acid (COOH)2 that exists in both free and salt form. Plants contain the majority of oxalic acid in the form of soluble oxalates (potassium, sodium and ammonium oxalates) [60].

Within the cells, 10-20 percent oxalic acid appears as insoluble calcium and magnesium oxalate. The leaves are more nutrient-dense than the rest of the plant. Young leaves, on average, contain fewer nutrients than mature leaves. An increase in the proportion of calcium oxalate is associated with the aging and overripening of vegetables. Cattle fed paddy straw and napier, bajra, and grasses (2 percent oxalate) develop a calcium deficit [60]. Many soluble oxalic acid and, to a lesser extent, its calcium salts are decomposed by rumen microflora (Pseudomonas, Streptomyces, etc.).When dietary amount exceeds: normal degradation (by microbes) is interrupted and the excess oxalates combine with feed calcium to form insoluble calcium oxalate and thus calcium becomes unavailable for absorption or excess oxalate (20-30mg per cent) may be absorbed from the rumen into the blood stream where it can combine with calcium: produce hypocalcaemia. The insoluble calcium oxalate may then crystalise in various tissues, specially kidneys and rumen wall [60].

Antivitamins: These are organic compounds which either destroy certain vitamins or combine and form unobservable complexes or interfere with digestive and /or metabolic functions. Antivitamin A: Raw soybean contains enzyme lipoxygenase which can be destroyed by heating 5min with steam at atmospheric pressure. Lipoxygenase catalyses oxidation of carotene the precursor of vitamin A[60].

Antivitamin E: Diets with raw kidney beans produced muscular dystrophy in chicks and lambs by reducing plasma vitamin E. Autoclaving destroys the factor.

Antivitamin K: Eating sweet clover cause fatal haemorrhagic condition in cattle. This is known as “Sweet clover disease” Dicoumarol present in sweet clover is responsible.Dicoumarol reduce prothrombin levels in blood and affects blood clotting Antivitamin D: Rachitogenic activity of isolated soya protein (unheated) has been found with chicks and pigs. Autoclaving eliminates this rechitogenic activity [60].

Antipyridoxine: 1-amino-D-proline has been identified as a pyridoxine antagonist from linseed. Linatine is a peptide that occurs naturally when glutamic acid is combined with it. After water treatment and autoclaving, the nutritional value of linseed meal for chicks can be significantly improved [60].

Antiniacin: An antagonist of niacin, niacytin is found in maize wheat bran etc. which cause perosis and growth depression [60]. Antithiamine: Enzyme thiaminase present in bracken fern act as antithiamine factor [60].

Alkaloids: Alkaloids are basic compounds with a heterocyclic nitrogen ring. Alkaloids are found in 15-20% of all vascular plants [60]. The majority of alkaloids are created by plants from amino acids. Decarboxylation of amino acids produces amines, which are then converted to aldehyde by amine oxides [63]. The heterocyclic ring is formed by condensation of the aldehyde and amine groups. Atropine, Deadly nightshade; Cocaine, Coca plant leaves; Morphine, opium poppy dried latex; Nicotine, Tobacco; Quinine, Cinchona bark; Solanine, Unripe potatoes; and Strychnine, Nuxvomic seeds.

Health Aspect of Antinutrients

Anti-nutrients and human health: While antinutrients can be harmful, some of them may also be beneficial to your health. Consumers should be aware of any potential effects, both positive and negative. Furthermore, concentration-dependent effects must be taken into account. Data can be manipulated to provide health-related benefits, making chronic disease management possible [18].

Antinutrients are beneficial active ingredients found in foods and beverages. Phytic acid, lectins, and phenolic compounds, as well as enzyme inhibitors and saponins, have all been shown to lower blood glucose and/or plasma cholesterol and triacylglycerols when used at low doses. Saponins have also been shown to be effective in maintaining liver function, preventing steoporosis, and preventing platelet agglutination [64].

As a result of the foregoing, antinutrients may prove to be useful tools in the treatment of a variety of diseases. Even if they have no nutritional value, they may not always be harmful.Meanwhile, phytoestrogens, plant-derived phenolic compounds, phytic acid, protease inhibitors, saponins, lignans, and phytoestrogens have all been shown to reduce cancer risk. Antiviral, antibacterial, and antiparasitic properties have been discovered in anti-nutrient compounds like tannins.In humans, phytoestrogens and lignans, for example, have been linked to infertility induction. As a result, investigating all aspects of food antinutrients, including their potential health benefits and analysis methods [18], is a good idea.

The most important factor is to concentrate on dosage intake in order to strike a balance between the beneficial and harmful effects of plant bioactives and antinutrients, as well as the chemical structure, exposure time, and interactions with other dietary components. Their activity is influenced by a variety of factors. They can be classified as either antinutritive factors with negative health consequences or nonnutritive compounds with beneficial health consequences. Consumer education is critical, particularly when abnormal health conditions are discovered.

Anti-nutrients and animal health: Anti-nutritional factors are substances that, when present in animal feed or water, reduce the availability of one or more nutrients, either directly or through their metabolic products. Starch polysaccharides and no-starch polysaccharides are found in plants, and some of them are antinutritional. Plants contain a mixture of water-soluble and insoluble no starch polysaccharides, and the ratio varies depending on the plant type and maturity stage. Cellulose is a fiber that is insoluble in water. The viscosity of most no-starch polysaccharides has a negative impact on animal digestion.

The amount of material in the digestive tract affects the ability of the digestive enzymes to do their job, which leads to a reduction in feed efficiency. Meanwhile, the presence of anti-nutritional factors limits the use of leaves, pods, and edible twigs of shrubs and trees as animal feed.

Anti-nutritional factors are classified according to their effects on the nutritional value of feedstuffs as well as the animal's biological response to them. The anti-nutritional factors were divided into groups by Huisman and Tolman [65]: Factors with a depressive effect on protein digestion and on the utilization of protein, such as protease inhibitors, tannins and saponins; Factors that affect mineral utilization, which include phytates; Factors that stimulate the immune system and may cause a damaging hypersensitivity reaction, such as antigenic proteins; Carbohydrate digestion-inhib iting substances, such as amylase inhibitors, phenolic compounds, and flatulence factors.

It can also appear as: Non-protein Amino Acids (Mimosine), as found in Leucaena; Glycosides (Saponins), which are found in Acacia; Polyphenolic compounds (tannins and lignins), which are found in all vascular plants; Alkoaois, which is found in Acacia, and Oxalate, which is also found in Acacia.

Mimosine's mechanism of action is unknown, but it could act as an amino acid, disrupt catalytic trans-aminases, or form a complex with a metal such as zinc [66]. To address the minomsine issue when feeding Leucaena, limit green forage to 30% for cattle and buffalo, and 50% for goats [67]. Saponins are a diverse group of naturally occurring steroidal glycosides that produce foam and are found in a wide range of plants.

Kidney bean, lentil, pea, chickpea, alfalfa, soybean, groundnut, and sunflower are examples of oilseeds. Through intralumenal physicochemical interaction, they reduce the uptake of certain nutrients such as glucose and cholesterol in the gut. As a result, hypocholesterolemic effects have been reported. Meanwhile, they cause bloat, hemolysis, and inhibit microbial fermentation and synthesis in the rumen, and they have distinct foaming characteristics with white clover and alfalfa [68]. However, due to structural differences in their sapogenin fractions, it has a wide range of biological effects.

Tannins are phenolic compounds that are water soluble and are found in forage legumes, trees, and shrubs [69]. Proteins can be precipitated from aqueous solution by them. The two types of tannins (hydrolysable and condensed Tannins are found in tree and shrub leaves.

Tannins have more effect in reducing digestibility than hydrolysable tannins. However, tannins' mechanism effect stemmed from their ability to form strong H bonds with nutrients, which resulted in inhibitions of digestive enzymes and rumen microbial activity [70], and this effect can be amplified as the molecular weight of tannins increases. Because of increased bypass, concentrations of 2-4 percent of dry mater increase N utilization; concentrations of >7% usually reduce nutrient utilization.

Tannins are present in the NDF and ADF of the tree leaves, which are bound to the cell wall & cell protein and can resulted in decreasing digestibility [71], they also cause decreased palatability, feed intake, reduced growth rate [72] or loss in weight, poor utilization and decrease iron absorption. But, on the other hand, tannins have some advantages due to their efficiency on animal health, as it had other properties such as, anti-diarrhea, antibacterial, antioxidant, free-radical, scavenging ant proliferative activity in liver cells. Not only that but it can work as protein protection during ensilage.

Alkaloids cause gastrointestinal and neurological disorders. The glycoalkaloids, solanine and chaconine present in potato and Solanum spp. are toxic to fungi and humans [73]. Some plant alkaloids are reported to cause infertility [74]. Anti vitamin factors there are some antivitamin factors in some plants, especially leguminous plants. Anti-vitamin E has also been noted in isolated soya protein, which is suspected to be tocopherol oxidase. Anti-metals Phytates bind minerals like calcium, iron, magnesium and zinc and make them unavailable. Anemia and other mineral deficiency disorders are common in regions where the diet is primarily a vegetarian [75]. Oxalate is considered an anti-nutrient because it inhibits calcium absorption and can increase the risk of developing kidney stones [76].

Methods of reducingor disabling the deleterious effect of Antinutrients

Disabling antinutrients in Plant based food: It is critical to remove undesirable food components in order to improve the quality of the product. Soaking, cooking, fermentation, radiation, germination, and chemical treatment are some of the techniques that can be used for antinutritional disabling [77]. Combining several of the above-mentioned methods may be more effective than using a single technique in removing anti-nutrients.

Heating: Antinutrients like phytic acid, tannins, and oxalic acid can be reduced by cooking whole grains, beans, and vegetables. Because of their protein nature, protease inhibitors are easily denatured by heat. Controlled heating at a temperature less than boiling for at least 15 minutes has been shown to reduce antinutrient levels [78]. Tannins, phytic acid, hydrogen cyanide, trypsin inhibitors, and oligosaccharides can all be significantly reduced by autoclaving. Cooking sweet potato leaves in lemon juice reduced polyphenols by 56% and lowered oxalate levels. The raffinose content of bambara groundnut seeds is significantly reduced and their protein digestibility is improved after 60 minutes of boiling [79].

Fermentation: The reduction of phytic acid and polyphenol content was achieved by fermenting assorted grain flour with L. acidophilus at 37°C for 24 hours. For a day of fermentation, recent research has shown a noticeable reduction in the entire antinutrient properties of soybean [80]. Ojokoh et al. [81] investigated the effect of fermentation on the antinutritional composition of breadfruit and cowpea flours, finding that hydrogen cyanide, oxalate, and phytate content were significantly reduced. Fermentation has been shown to increase the protein content of chickpeas by 13% while lowering the phytic acid content by 45% [82]. Adeyemo et al. [83] investigated the effects of sorghum fermentation on trypsin inhibitor, protease inhibitor, phytate, and tannin at 0, 72, and 120 hours.With L. plantarum as the starter culture, a significant reduction in trypsin inhibitor (69%), protease inhibitor (30%), phytate (60%), and tannin (72%) was observed after 120 hours. At 120 hours, however, L. brevis as a starter appeared to be effective, with a 58 percent reduction in trypsin inhibitor, a 40 percent reduction in protease inhibitor, a 70 percent reduction in phytate, and a 56 percent reduction in tannin.

Soaking: Soaking is one of the most straightforward physical processes for removing soluble antinutritional factors. Total phenols, ortho-dihydroxyphenols, tannins, and phytates were reduced by 33, 41, 35, and 21 percent, respectively, after soaking in distilled water, 1 percent NaHCO3, and mixed salt solutions [84]. Soaking soybean flour reduced total protein, soluble sugar, and tannins [85]. Enzyme inhibitors can be deactivated by soaking and sprouting grains, nuts, seeds, and beans. This method of deactivation, however, has no effect on lectin.

Sprouting (Germination): Germination is one of the most effective methods for lowering anti-nutritive compounds, such as phytate levels. With sprouting, the trypsin inhibitory activity, amylase inhibitory activity, and phytate content of the MACS-13 soy bean variety decreased [86]. According to Kanensi et al. [87], germi-nated amaranth seeds have a lower antinutrient level. Tannins and phytate levels were insignificant. Kajla et al. [88] used the germination process in flax seeds to overcome the antinutritional levels. Other authors [89] confirm that germination increases nutritional content while decreasing anti-nutrient content in plantbased foods.

Genomic technology: Although genomic resources can be used to interfere with RNA and remove antinutrient factors, this technology has yet to be tested in vivo. Because corn contains high levels of phosphorus stored in the form of phytic acid, Shukla et al. [90] designed zinc-finger nucleases constructs to mutate the IPK1 gene in maze, one of the phytic acid biosynthesis genes. Although genome editing technology can improve crop quality, there is still a debate about the safety of genetically modified organisms [91].

Gamma radiation: Gamma radiation appeared to be an effective method for reducing trypsin inhibitor, phytic acid, and oligosaccharides in broad bean by 5 to 10%. Hassan et al. [92], on the other hand, found that a 2 kGy dose had no effect on the tannin content of two maize cultivars. El-Niely [93] and Fombang et al. [94] both made similar observations. Antinutritional factors such as tannin and phytic acid were significantly reduced in Faba bean seeds after low doses of gamma irradiation (0.5 and 1.0 kGy). To reduce antinutrients in millet grains, gamma radiation can be used as a safe postharvest method [95].

Disabling anti-nutrients in animal nutrition: To combat the negative effects of such anti-nutritional factors, a variety of methods have been tried, with tannins coming out on top. Making hay, silage with inoculants, using polyethylene glycol [96]; urea [97] or biological treatment with fungi [98] can all be used to either eliminate or reduce anti-nutritional factor concentrations.

It is will know that alkali treatment includes polyethylene glycol, which a tannins-binding agent, [99] was shown to be a powerful tool for isolating the effect of tannins on various digestive function [100]. But it may not be economic. Although the incorporation of polyethylene glycol, which binds with and inactivates tannins, is quite effective, success of its adoption depends on the cost: benefit ratio [101]. Russsell & Olley suggest feed animals with 1% urea. In that system, urea not only provides extra N but also deactivates the leaf tannins [83]. Conclusion for increasing the utilization of dietary nutrients, reducing environmental contamination and decrease feeding cost, the optimum use of unconventional feedstuffs as well as any local sources (shrubs, browsing tree) has big potential. Each region can select what is reasonable and suitable for his case to optimize all feed resources in order to reach its goal.

×

Table 1:

Close

Table 1. Anti-nutritional factors in different foods [43, 44-56].

Perspectives

Different authors across the world have reported on the nutritional value of plant based foods and feeds in human and animal nutrition. However, in most cases of our country, the breeding and variety selection programs are going on without taking the nutritive data into criteria. This is because, if a crop and forages are found to be disease resistant, high yielding and good performing in general and not good in its nutrient compositions or high in antinutritional factors, this is not a good package to take to the production. This may led to lack of such important information in breeding packages or programs. In this regard, it is better if included in criterion for varietal selection for either breeding programs or production. So, much work will be expected with respect to nutritional value of these plant based feed and foods. Moreover, Optimization of different processing methods for nutrient retention and antinutrient reduction is an important point. Hence, many of the antinutritional factors are toxic, unpalatable or indigestible, they are needed to be eliminated from the feed and food staff either by selection of plant genotypes or through post-harvest processing (germination, boiling, leaching, fermentation, extraction), and polyethylene glycol and biological treatment before consumption. It is also important to research on different product development,particularly blending potent plant based foods, to overcome the problem of malnutrition in proteinenergy and micronutrient nutrient.

Conclusion

Antinutritional factors are common food compounds that are particularly difficult to avoid for those who follow a predominantly plant-based diet, such as vegans and vegetarians. Antinutrients can have beneficial health effects in small doses or cause nutrient deficiencies in large doses. When the latter is not readily available, uninformed consumers may encounter some misleading information. When antinutrients are consumed in excess of their upper limit, they can cause negative side effects. Ant nutritional breakdown products can also cause negative effects. When the consumer is presented with little knowledge about the environmental influence on the human organism's detoxification capacity, the presence of lectins, tannins, alkaloids, and saponins, goitrogens, inhibitors, and other substances in foods may cause a variety of reactions. Antinutritional removal tools can be used in both traditional and modern agricultural biotechnological programs. Health risks, on the other hand, can be avoided by introducing a daily sustainable diet based on sound scientific evidence.

The optimal use of unconventional feedstuffs as well as any local sources (shrubs, browsing tree) has a lot of potential for increasing dietary nutrient utilization, reducing environmental contamination, and lowering feeding costs. Each region can choose what is reasonable and appropriate for his situation in order to maximize all feed resources and achieve its goal.

1. McGuire S. FAO, IFAD, and WFP. The State of Food Insecurity in the World 2015: Meeting the 2015 International Hunger Targets: Taking Stock of Uneven Progress. Rome: FAO, 2015. AdvNutr. 2015 Sep;6(5):623-4. PubMed PMID: 27352453.
2. UNICEF. The State of the World’s Children.Women and Children the Double Dividend of Gender Equality.New York: UN. 2007.
3. Gemede HF, Ratta N. Antinutritional factors in plant foods: potential health benefits and adverse effects. Int J Nutr Food Sci. 2014;3(4):284-9.
4. Soetan KO. Pharmacological and other beneficial effects of antinutriional factors in plants - A review.Afr J Biotechnol. 2008;7(25):4713-21.
5. Gupta RK, Gangoliya SS, Singh NK.Reduction of phytic acid and enhancement of bioavailable micronutrients in food grains. J Food Sci Technol. 2015 Feb;52(2):676-84. PubMed PMID: 25694676.
6. Fan Y, Guo DY, Song Q, Li T. Effect of total saponin of aralia taibaiensis on proliferation of leukemia cells. Zhong Yao Cai. 2013 Apr;36(4):604-7. Chinese.PubMed PMID: 24134011.
7. Muzquiz M, Hill GD, Cuadrado C, Pedrosa MM, Burbano C. Recent advances of research in antinutritional factors in legume seeds and oilseeds. Proceedings of the fourth international workshop on antinutritional factors in legume seeds and oilseeds. Toledo, Spain. 2004.
8. Mahipala MK, Krebs GL, McCafferty P, Gunaratne LH. Chemical composition, biological effects of tannin and in vitro nutritive value of selected browse species grown in the West Australian Mediterranean environment. Animal Feed Sci Technol. 2009 Sep 24;153(3-4):203-15.
9. FAO. Fodder trees & Shrubs in range and Feeding System in North Africa. Rome: Food Agricultural Organization (FAO); 1987.
10. Salunkhe DK, Chavan JK, Kaden SS. Dietary tannins: Consequences and remedies. Boca Roton, FL: CRC Press; 1990. pp. 67-75.
11. Wcislo G, Szarlej-Wcislo K. Colorectal cancer prevention by wheat consumption: A three-valued logic - true, false, or otherwise? In: Wheat and Rice in Disease Prevention and Health. 2014; pp. 91-111.
12. MasumAkond ASMG, Crawford H, Berthold J, Talukder ZI, Hossain K. Minerals (Zn, Fe, Ca and Mg) and Antinutrient (Phytic Acid) Constituents in Common Bean. Am J Food Technol. 2011;6(3):235-243. PubMed PMID: 29861700.
13. Kumar V, Sinha AK, Makkar HP, Becker K. Dietary roles of phytate and phytase in human nutrition: A review. Food Chem. 2010 Jun 15;120(4):945- 59.
14. Boyd WC, Shapleigh E. Specific Precipitating Activity of Plant Agglutinins (Lectins). Science. 1954 Mar 26;119(3091):419. PubMed PMID: 17842730.
15. Fahmi N, Sharma N, Pandey A. Interactions of lectins in the red blood cells of oral squamous cell carcinoma patients: A comparative study. Int J CurrAdv Res. 2017;6(7):4753-7.
16. Losvik A, Beste L, Mehrabi S, Jonsson L. The Protease Inhibitor CI2c Gene Induced by Bird Cherry-Oat Aphid in Barley Inhibits Green Peach Aphid Fecundity in Transgenic Arabidopsis. Int J Mol Sci. 2017 Jun 20;18(6):1317. PubMed PMID: 28632160.
17. Zubcevic N, Damir S, Focak M, Rukavina D. Effects of plant lectins on human erythrocyte agglutination. Serb J ExpClin Res. 2016;17(3):207-14.
18. Shahidi F. ACS Symposium Series. 1-9.
19. Henry RJ, McKinnon GE, Haak IC, Brennan PS. Use of alpha-amylase inhibitors to control sprouting. Pre-Harvest Sprouting in Cereals 1992.1993 Jan 1:232-5.
20. Tysoe C, Williams LK, Keyzers R, Nguyen NT, Tarling C, Wicki J, et al. Potent Human α-Amylase Inhibition by the β-Defensin-like Protein Helianthamide. ACS Cent Sci. 2016 Mar 23;2(3):154-161. PubMed PMID: 27066537.
21. Adeyemo SM, Onilude AA. Enzymatic reduction of anti-nutritional factors in fermenting soybeans by Lactobacillus plantarum isolates from fermenting cereals. Niger Food J. 2013 Jan 1;31(2):84-90.
22. Logsdon CD, Ji B. The role of protein synthesis and digestive enzymes in acinar cell injury.Nat Rev GastroenterolHepatol. 2013 Jun;10(6):362-70. PubMed PMID: 23507798.
23. Ngozi OO, Nkiru OA. Evaluation of tannin, phytate and mineral composition of different indigenous dishes based on pumpkin (Cucurbita pepo).Int J Nutr Food Sci. 2014;3(6):493-6.
24. Salunkhe DK, Chavan JK, Kadam SS. Dietary tannins: Consequences and remedies. Boca Raton, Florida: CRC Press 1990; pp. 150-73.
25. Vijayalakshmi A, Kumar YK. Evaluation of goitrogenic and antithyroidal effect of the fern Adiantumcapillus-veneris.Brazilian J Pharmacogn. 2013 Sep 1;23(5):802-10.
26. Abdul-Aziz A, Kadhim KK. Efficacy of the cruciferous vegetable on the thyroid gland and the gonads in rabbits. Adv. Anim. Vet. Sci. 2015;3(3):183- 91.
27. Berrios JD, Morales P, Cámara M, Sánchez-Mata MC. Carbohydrate composition of raw and extruded pulse flours. Food Res Int. 2010 Mar 1;43(2):531-6.
28. Reddy NR, Pierson MD, Sathe SK, Salunkhe DK. Chemical, nutritional and physiological aspects of dry bean carbohydrates - A review. Food Chem. 1984 Jan 1;13(1):25-68.
29. Glencross BD, Boujard T, Kaushik SJ. Influence of oligosaccharides on the digestibility of lupin meals when fed to rainbow trout, Oncorhynchus mykiss. Aquaculture. 2003 Apr 2;219(1-4):703-13.
30. Ikewuchi CC. Hypocholesterolemic effect of an aqueous extract of the leaves of Sansevieriasenegambica Baker on plasma lipid profile and atherogenic indices of rats fed egg yolk supplemented diet. EXCLI J. 2012 Jun 22;11:346-56. PubMed PMID: 27418909.
31. El Barky AR, Hussein SA, Alm-Eldeen AE, Hafez YA, Mohamed TM. Saponins and their potential role in diabetes mellitus.Diabetes Manag. 2017 Jan 1;7(1):148-58.
32. Johnson IT, Gee JM, Price K, Curl C, Fenwick GR. Influence of saponins on gut permeability and active nutrient transport in vitro. J Nutr. 1986 Nov;116(11):2270-7. PubMed PMID: 3794833.
33. Tatham AS, Shewry PR. Allergens to wheat and related cereals. ClinExp Allergy. 2008 Nov;38(11):1712-26. PubMed PMID: 18823308.
34. Loukas S, Varoucha D, Zioudrou C, Streaty RA, Klee WA. Opioid activities and structures of alpha-casein-derived exorphins.Biochemistry. 1983 Sep 13;22(19):4567-73. PubMed PMID: 6313043.
35. Trivedi MS, Hodgson NW, Walker SJ, Trooskens G, Nair V, Deth RC. Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells. NutrMetab (Lond). 2015 Dec 9;12:54. PubMed PMID: 26664459.
36. Van Campen DR. Copper interference with the intestinal absorption of zinc-65 by rats.J Nutr. 1969 Jan;97(1):104-8. PubMed PMID: 5763434.
37. Genser D. Food and drug interaction: consequences for the nutrition/health status. Ann NutrMetab. 2008;52Suppl 1:29-32. PubMed PMID: 18382075.
38. Foster BC, Vandenhoek S, Hana J, Krantis A, Akhtar MH, Bryan M, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products.Phytomedicine. 2003 May;10(4):334- 42. PubMed PMID: 12809364.
39. 2017.https://patienteducation.osumc.edu/Documents/diet-ant.pdf
40. Akwaowo EU, Ndon BA, Etuk EU. Minerals and antinutrients in fluted pumpkin (Telfairiaoccidentalis Hook f.). Food Chem. 2000 Aug 1;70(2):235- 40.
41. Mamboleo TF. Nutrients and antinutritional factors at different maturity stages of selected indigenous African green leafy vegetables. 2015.
42. Natesh HN, Abbey L, Asiedu SK. An overview of nutritional and antinutritional factors in green leafy vegetables.HorticInt Journal. 2017;1(2):58-65.
43. Kumari S. The effect of soaking almonds and hazelnuts on Phytate and mineral concentrations (Doctoral dissertation, University of Otago).
44. Khokhar S, Chauhan BM. Antinutritional factors in moth bean (Vignaaconitifolia): varietal differences and effects of methods of domestic processing and cooking. J Food Sci. 1986 May;51(3):591-4.
45. Ndidi US, Ndidi CU, Olagunju A, Muhammad A, Billy FG, Okpe O. Proximate, Antinutrients and Mineral Composition of Raw and Processed (Boiled and Roasted) Sphenostylisstenocarpa Seeds from Southern Kaduna, Northwest Nigeria. ISRN Nutr. 2014 Mar 16;2014:280837. PubMed PMID: 24967265.
46. Margier M, Georgé S, Hafnaoui N, Remond D, Nowicki M, Du Chaffaut L, et al. Nutritional Composition and Bioactive Content of Legumes: Characterization of Pulses Frequently Consumed in France and Effect of the Cooking Method. Nutrients. 2018 Nov 4;10(11):1668. PubMed PMID: 30400385.
47. Sinha K, Khare V. Review on: Antinutritional factors in vegetable crops. Pharma Innov J. 2017 Nov;6(12):353-8.
48. Chai W, Liebman M. Oxalate content of legumes, nuts, and grain-based flours. J Food Compos Anal. 2005 Nov 1;18(7):723-9.
49. Harland BF, Smikle-Williams S, Oberleas D. High performance liquid chromatography analysis of phytate (IP6) in selected foods. J Food Compos Anal. 2004 Apr 1;17(2):227-33.
50. Ahmed E. Peanut and soybean lectin determination. Peanut Sci. 1986;13:7- 10.
51. Kasim AB, Edwards HMJ. The analysis of inositolphosphate forms in feed ingredients. Sci Food Agric. 1998;76:1-9.
52. Shah BS, Sartaj L, Ali F, Shah AS, Khan TM. Plant extracts are the potential inhibitors of α-amylase: a review. MOJ BioequivAvailab. 2018;5(5):270-3.
53. Haque MR, Bradbury JH. Total cyanide determination of plants and foods using the picrate and acid hydrolysis methods. Food Chem. 2002 May 1;77(1):107-14.
54. Popoola OE, Doherty VF, Odusami JO, Durowoju OS. Oxalate content of some Nigerian tubers using titrimetric and UV-spectrophotometric methods. Acad J Agric Res. 2014;2(2):54-7.
55. Akalu ZK, Geleta SH. Antinutritional levels of tubers of Colocasiaesculenta, L. Schott (Taro) and Dioscoreaalata (Yam) cultivated in Ethiopia. J Nutr Food Sci. 2017;7(2):585.
56. Akubugwo IE, Obasi AN, Ginika SC. Nutritional potential of the leaves and seeds of black nightshade-Solanum nigrum L. Varvirginicum from Afikpo-Nigeria. Pak J Nutr. 2007;6(4):323-6.
57. Singh U, Praharaj CS, Singh SS, Singh NP, editors. Biofortification of food crops. New Delhi: Springer; 2016 Jan 22.
58. Sessa DJ, Bietz JA. Toasted soybean flour components with trypsin inhibitor activity.Journal of the American Oil Chemists' Society. 1986 Jun;63(6):784- 8.
59. Siddique KH, Brinsmead RB, Knight R, Knights EJ, Paull JG, Rose IA. Linking Research and Marketing Opportunities for Pulses in the 21st Century. SpringerScience and Business Media LLC; 2000.
60. ndvsu.org [Internet]. Harmful Natural Constituents Present in Livestock Feedstuffs.Available from: https://www.ndvsu.org/images/StudyMaterials/ Nutrition/Antinutritional-factors.pdf.
61. de.slideshare.net
62. www.actascientific.com
63. https://beta.garj.org/
64. Kao TH, Huang SC, Inbaraj BS, Chen BH. Determination of flavonoids and saponins in Gynostemmapentaphyllum (Thunb.)Makino by liquid chromatography- mass spectrometry.Anal ChimActa. 2008 Sep 26;626(2):200- 11. PubMed PMID: 18790122.
65. Huisman J, Tolman GH. Antinutritional factors in the plant proteins of diets for non ruminants. Recent developments in pig nutrition. Netherlands; 2001;3:261-322.
66. Hegarty MP. Toxic amino acids of plant origin.In: Effect of poisonous plants on livestock. 1987.
67. Hiremath NB. Kubabul (Leucaenaleucocephala)--a wonder plant.Indian dairyman. 1981;33:351-356.
68. Lu CD, Jorgensen NA. Alfalfa saponins affect site and extent of nutrient digestion in ruminants. J Nutr. 1987 May;117(5):919-27. PubMed PMID: 3585546.
69. Min BR, Barry TN, Attwood GT, McNabb WC. The effect of condensed tannins on the nutrition and health of ruminants fed fresh temperate forages: a review. Anim Feed Sci Technol. 2003 Apr 21;106(1-4):3-19.
70. Kumar R, Singh M. Tannins: their adverse role in ruminant nutrition. J Agric Food Chem. 1984 May;32(3):447-53.
71. Reed JD, Soller H, Woodward A. Fodder tree and straw diets for sheep: intake, growth, digestibility and the effects of phenolics on nitrogen utilisation. Anim Feed Sci Technol. 1990 Jul 1;30(1-2):39-50.
72. Roeder E. Medicinal plants in China containing pyrrolizidine alkaloids. Pharmazie. 1995 Feb 1;50:83-98.
73. Aletor VA. Anti-nutritional factors in some Nigerian feedstuffs, herbage byproducts, crop residues and browse plants. A monograph prepared for the Presidential task force on alternative formulation of livestock feeds. Product Development, Quality Evaluation and Health Implications.1991.
74. Olayemi FO. A review on some causes of male infertility.AJBT. 2010;9(20):2834-3842.
75. Erdman JW. Oilseed phytates: nutritional implications. J Am Oil Chern Soc. 1979 Aug;56(8):736-41.
76. Holmes RP, Goodman HO, Assimos DG. Contribution of dietary oxalate to urinary oxalate excretion. Kidney Int. 2001 Jan;59(1):270-6. PubMed PMID: 11135080.
77. Gupta V, Nagar R. Minerals and antinutrients profile of rabadi after different traditional preparation methods. J Food Sci Technol. 2014 Aug;51(8):1617- 21. PubMed PMID: 25114357.
78. Udousoro II, Akpan EB. Changes in anti-nutrients contents of edible vegetables under varied temperature and heating time.Curr Res Nutr Food Sci. 2014 Dec 30;2(3):146-52.
79. Adeleke OR, Adiamo OQ, Fawale OS, Olamiti G. Effect of processing methods on antinutrients and oligosaccharides contents and protein digestibility of the flours of two newly developed bambara groundnut cultivars. Int Food Res J. 2017 Oct 1;24(5):1948-1955.
80. Babalola RO, Giwa OE. Effect of fermentation on nutritional and antinutritional properties of fermenting Soy beans and the antagonistic effect of the fermenting organism on selected pathogens. Int Res J Microbiol. 2012;3(10):333-8.
81. Ojokoh AO, Daramola MK, Oluoti OJ. Effect of fermentation on nutrient and anti-nutrient composition of breadfruit (Treculiaafricana) and cowpea (Vignaunguiculata) blend flours.Afr J Agric Res. 2013 Jul 18;8(27):3566-70.
82. Valdez-González FJ, Gutiérrez-Dorado R, García-Ulloa M, Cuevas-Rodríguez BL, Rodríguez-González H. Effect of fermented, hardened, and dehulled of chickpea (Cicer arietinum) meals in digestibility and antinutrients in diets for tilapia (Oreochromisniloticus). Span J Agric Res. 2018 Apr 26;16(1):e0605.
83. Adeyemo SM, Onilude AA, Olugbogi DO. Reduction of Anti-nutritional factors of sorghum by lactic acid bacteria isolated from Abacha-an African fermented staple. Front Sci. 2016;6(1):25-30.
84. Devi R, Chaudhary C, Jain V, Saxena AK, Chawla S. Effect of soaking on anti-nutritional factors in the sun-dried seeds of hybrid pigeon pea to enhance their nutrients bioavailability. JPP. 2018;7(2):675-80.
85. Agume AS, Njintang NY, Mbofung CM. Effect of Soaking and Roasting on the Physicochemical and Pasting Properties of Soybean Flour. Foods. 2017 Feb 10;6(2):12. PuMed PMID: 28231091.
86. Dikshit M, Ghadle M. Effect of sprouting on nutrients, antinutrients and in vitro digestibility of the MACS-13 soybean variety. Plant Foods Hum Nutr. 2003 Sep;58:1-11.
87. Kanensi OJ, Ochola S, Gikonyo NK, Makokha A. Optimization of the period of steeping and germination for amaranth grain. J Agric Food Tech. 2011;1(6):101-5.
88. Kajla P, Sharma A, Sood DR. Effect of germination on proximate principles, minerals and anti nutrients of flaxseeds. Asian J Dairy Food Res. 2017;36(1):52-7.
89. Chauhan ES. Effects of processing (germination and popping) on the nutritional and anti-nutritional properties of finger millet (Eleusinecoracana). Curr Res Nutr Food Sci. 2018 Aug 25;6(2):566-72.
90. Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, et al. Precise genome modification in the crop species Zea mays using zincfinger nucleases. Nature. 2009 May 21;459(7245):437-41. PubMed PMID: 19404259.
91. Kim H, Kim ST, Kim SG, Kim JS. Targeted genome editing for crop improvement. Plant Breed Biotechnol.2015;3(4):283-90.
92. Hassan AB, Osman GA, Rushdi MA, Eltayeb MM, Diab EE. Effect of gamma irradiation on the nutritional quality of maize cultivars (Zea mays) and sorghum (Sorghum bicolor) grains. Pak J Nutr. 2009;8(2):167-71.
93. El-Niely HF. Effect of radiation processing on antinutrients, in-vitro protein digestibility and protein efficiency ratio bioassay of legume seeds. Radiat Phys Chem. 2007 Jun 1;76(6):1050-7.
94. Fombang EN, Taylor JR, Mbofung CM, Minnaar A. Use of γ-irradiation to alleviate the poor protein digestibility of sorghum porridge. Food Chem. 2005 Aug 1;91(4):695-703.
95. Mahmoud NS, Awad SH, Madani RM, Osman FA, Elmamoun K, Hassan AB. Effect of γ radiation processing on fungal growth and quality characteristcs of millet grains. Food SciNutr. 2015 Oct 17;4(3):342-7. PubMed PMID: 27247763.
96. Ben Salem H, Ben Saem L, Tisser JL. Deactivation of condensent tannins in Acacia cyanophyllalinddl. Foilage by PEG infee blocks effect on feed intake, diet digestibility, nitrogen balance, microbial synthesis and growth by sheep. Livest Prod Sci. 2000;64:51-60.
97. Russell RW, Lolley JR. Deactivation of tannin in high tannin milo by treatment with urea. J Dairy Sci. 1989 Sep;72(9):2427-30. PubMed PMID: 2592654.
98. Hassan AA, Shwerab AM, Khale MS, Yacout MH. Influence of acacia condensed tannins on protein degradability of alfalfa silage and lamb performance. In12th Scientific Conference on Animal Nutrition, Sharim El- Sheikh Cituy, Egypt 2009.
99. Jones WT, Mangan JL. Complexes of the CT of ainfon (onobrycliviciae folia scoap) with fraction leaf protein and with sub maxillary mucoprotein and their reversal by PEG and pH.J Sci Food Agric. 1977;28:26-136.
100. Kumar R, Vaithiyanathan S. Occurrence, nutritional significance and effect on animal productivity of tannins in tree leaves.Anim Feed Sci Technol. 1990 Jul 1;30(1-2):21-38.
101. . Makkar HPS. Effects and Fate Tannins in Ruminant Animals, Adaptation to Tannins, and Strategies to Overcome Detrimental Effects of Feeding Tannin-Rich Feeds. Small Rumin Res. 2003 Sep 1;49(3):241-256.