Phytic Acid

6.1. Definition 

Phytate, also known as phytic acid or myo-inositol hexaphosphate (IP6), is another commonly considered “anti-nutrient” widely distributed in amongst the plant kingdom. It primarily serves as storage for plant phosphate, as an energy source, and antioxidant for germinating seeds [180]. Phytate is produced during seed development and can account for 60–90% of total phosphorus content in cereal grains, nuts, seeds, and legumes [181]. Structurally, phytate (IP6) is made up of six phosphate groups, attached to an inositol ring, with the ability to bind up to 12 protons total. These phosphate groups act as strong chelators, readily binding to mineral cations, particularly Cu2+, Ca2+, Zn2+, and Fe3+ [182]. These complexes are insoluble at neutral pH values (6–7), and cannot be digested by human enzymes, thus could decrease mineral bioavailability in high-phytate, homogenous diets [12]. Low-income, developing countries that rely predominantly on grains and legumes as dietary staples are of special concern for zinc deficiency and/or insufficiency [183]. The chelating properties of phytate also allow it to act as an antioxidant, lending possible protective traits [180]. Ensuring an appropriate phytate to mineral ratio minimizes the negative effects of phytate on mineral absorption in vulnerable populations. 

6.2. Background 

Phytate is found in a wide array of plant foods, with the highest concentrations occurring in cereals, legumes, nuts, seeds and pseudocereals [182]. In cereals, phytate is mainly found in the outermost layer, and in legumes is found within the endosperm and cotyledons [180]. Reported daily intake of phytate for vegetarians and other rural inhabitants in developing countries is estimated to be 2000–2600 mg, while mixed diets may contain as low as 650 mg of phytate [184]. Growing methods, seasons, and cultivars can have a significant impact on phytate content [185–187]. Shi et al. reported phytate content in Canadian grown peas, lentils, fava beans, chickpeas, and common beans to be 9.93–12.40 mg/g, 8.56–17.1 mg/g, 19.65–22.85 mg/g, 11.33–14 mg/g and 15.64–18.82 mg/g, respectively. Soybeans contained the highest amount, at 22.91 mg/g [19]. However, Wang and colleagues reported Canadian lentil, chickpea and bean cultivar values to be much less, containing 7.2–11 mg/g, 9.6–10.6 mg/g and 9.9–13.8 mg/g, respectively [188,189]. Split varieties of lentils and peas contain more phytate, since much of the hull is lost during processing [19]. Unprocessed cereals generally have similar phytate value to that of legumes, though processed cereals contain significantly less. For instance, wild rice contains between 12.7 and 21.6 mg/g, but polished rice, only 1.2–3.7 mg/g [184]. Upon processing, phytate content can be significantly reduced in many grains, seeds, and legumes. 

6.3. Effects of Cooking/Processing 

Processing techniques such as soaking, fermentation, sprouting, germinating, and cooking can significantly alter phytate content in grains and legumes, allowing for increased mineral availability (Table 2). Cooking of legumes for 1 h at 95 ◦C resulted in up to a 23% loss in yellow split peas, 20–80% loss in lentils, and 11% loss in chickpeas. Only a marginal reduction of 0.29% was noted in black beans [19]. Utilizing the natural phytases present in cereals and legumes has proven to be a valuable tool in reducing phytate. Phytases are enzymes capable of hydrolyzing phytate. Soaking seeds in fresh water, a traditional preparation method, reduced phytate values in millet, maize, rice, and soybean by 28, 21, 17, and 23%, respectively [190]. No IP6 was found in the soaking water, implying that the phytate was hydrolyzed by endogenous cereal phytases. Although soaking reduced phytate, it also resulted in significant losses of iron and zinc in the soaking water. For this reason, soaking did not lower the phytate/iron ratio, and only had minor impacts on the phytate/zinc ratio [190]. Mineral loss could be partially mitigated by cooking rice in the soaking water, as the seeds will ‘recover’ the leached minerals. Germination of foods can further reduce phytate, as endogenous phytases are activated to free the phosphate from phytate to be used for energy. Germinating chickpeas and pigeon peas reduced phytate concentrations by over 60%, while still preserving mineral content [191,192]. Fermentation, such as the natural leavening of bread, has also been found to significantly reduce phytate. It is elucidated that along with activity of bacterial phytases, lactic acid bacteria activate endogenous cereal phytates by lowering the pH of the dough to ~4–5. Slight acidification with lactic acid produces similar results [193]. Additional research by Castro-Alba et al. demonstrated that inoculation of quinoa, amaranth, and canihua with L. plantarum 299v reduced phytate concentrations by 47–51%, 12–14%, and 25–27%, respectively. Accessibility of iron, zinc and calcium was also increased in the fermented flours [194]. Furthermore, L. plantarum species from supplements (L. plantarum 299v), or from fermented vegetables (L. plantarum spp.), have been found to improve iron bioavailability from high phytate meals [195,196]. In a study performed by Scheers et al., iron absorption increased from 13.6 to 23.6% in the low phytate meal, and 5.2 to 10.4% in the high phytate meal, when eaten alongside fermented vegetables. Zinc absorption changed minimally [195]. The exact mechanism is unknown but may be due to an increase in ferric iron [195,197]. Supporting microbiome health through the consumption of fermentable fibers and other prebiotics also lowers cecal pH values, allowing for an increased solubility of zinc and iron [198–200]. High-phytate foods such as beans are rich in fermentable fibers, which have a beneficial effect on cecal pH by increasing SCFA production [201,202]. This effect may lend insight into the phenomenon of phytate adaption, in which non-heme iron absorption can be partially negated by the consumption of a high-phytate diet [203]. 

6.4. Safety 

As discussed, phytate is viewed as an ‘anti-nutrient’ because it can chelate iron, calcium, and zinc, limiting absorption of these minerals (Table 1). Chelation, however, is dependent on the proportion of phytate to metal ions, as well as pH [204]. The ideal molar ratio of phytate to iron is ~0.4, with an inhibitory effect in ratios above 1. For zinc, ratios higher than 15 may inhibit absorption rates, with optimal ratio of below 5. Calcium absorption has been shown to be impeded by molar ratios above 0.17 [182]. 

6.5. Human Studies 

Many studies support the hypothesis that phytate negatively impacts zinc bioavailability [205,206], however a study on young children, aged 8–50 months, found phytates to not have a discernable effect on zinc absorption [207]. An increase of 500 mg/day of dietary phytate led to less than a 0.04 mg/day reduction in zinc absorption. The largest variance in absorption rates occurred based on age, height and weight [207]. The relationship between dietary phytate and iron bioavailability may be more complex than that of zinc. Even after removal of 90% of IP6 in sorghum flour through phytase treatment, no improvement in iron bioavailability was observed [208]. Removing fiber was found to have a more significant impact on iron absorption, demonstrating an independent effect of fiber in phytate-rich foods. Also, despite higher phytate concentration, animal models have found whole-wheat flour to result in greater iron absorption than refined white flour [209]. Nonetheless, due to phytate’s overall impact on zinc and iron absorption, it is recommended that DRIs be increased for these minerals to account for bioavailability values [210,211]. The addition of complementary foods high in ascorbic acid (vitamin C) may allow consumers enjoy the benefits of phytate-rich foods, while offsetting phytate’s inhibitory effect on mineral absorption [212]. Although phytates are viewed by many in a negative light, they may actually act as beneficial antioxidants by their ability to chelate excess iron, thereby preventing damaging Fenton reactions from taking place [204]. Fenton reactions are oxidative reactions involving iron and hydrogen peroxide, producing hydroxyl radicals and other reactive oxygen species (ROS) [213]. Not only can excess iron contribute to ROS through the Fenton reaction, but research has linked heme-iron to microbial dysbiosis, hyperproliferation of colon cells and altered intestinal barrier function [214]. Since only a small amount of heme is absorbed in the small intestine, up to 90% may reach the colon [214]. When eaten alongside heme-rich foods, phytate acts as ‘nature’s iron regulator’, attenuating possible heme-induced damage. Animal studies have demonstrated a protective role of IP6 against iron-induced lipid peroxidation in the colon [215]. However, human trials validating phytate’s elucidated antioxidant effects are limited. In one randomized cross over trial, Sanchis et al. reported significant reductions (~25%) of advanced glycation end-products (AGEs) in patients with type 2 diabetes mellitus supplemented with 1 g of IP6 [216]. Considering the deleterious effects AGEs have on microvascular and macrovascular function in type 2 diabetes (T2DM), dietary phytates could be promising tools in the treatment of T2DM. Phytate may also possess other beneficial effects, yet much of this research is still in its infancy. The mechanisms of action of IP6 include enhanced immunity, inhibition of inflammatory, cytokines, caspase modification, regulation of phase I and II enzymes, and decreased cell proliferation [180,215]. IP6 has also been shown to decrease kidney stone risk [217], dental calculi [218], osteoporosis risk [219], and help prevent age-related cardiovascular calcification [220,221]. Furthermore, adequate consumption of phytate-rich foods was found to prevent abdominal aortic calcification in patients with chronic kidney disease [180,222]. Future research is needed to identify the exact physiological mechanisms behind phytate, but research thus far supports the inclusion of phytate-rich foods into a balanced diet. 

6.6. Conclusions 

Since its discovery, the role of phytate in human nutrition has been a controversial topic. On one hand, phytate may decrease the bioavailability of essential minerals, while on the other hand, acts as a potent antioxidant. Phytates should not significantly impair mineral status when included as part of a diverse and balanced diet, especially if using traditional processing methods such as soaking, germinating, fermenting, and cooking. Consuming complementary foods rich in ascorbic acid and certain probiotic bacteria could also have beneficial impacts on mineral absorption from high-phytate meals. Overall, by consuming a colorful, plant-based diet, the benefits of phytate containing foods to human health exceed the impacts on mineral absorption.