1 Barriers impairing mineral bioaccessibility and

2 bioavailability in plant-based foods and the

3 perspectives for food processing

5 Rousseau, S.1*, Kyomugasho, C.1, Celus, M.1, Hendrickx, M.E.1, Grauwet,

6 T.1**

1
9 Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre

10 (LFoRCe), Department of Microbial and Molecular Systems (M2S), KU Leuven, Kasteelpark

11 Arenberg 22, PB 2457, 3001, Leuven, Belgium

12

13 Author’s email addresses:

14 Rousseau, S.: [email protected]

15 Kyomugasho, C.: [email protected]

16 Celus, M.: [email protected]

17 Hendrickx, M.E.: [email protected]

18 Grauwet, T.: [email protected]

19

20 Journal: Critical Reviews in Food Science and Nutrition

21 Submitted: May 2018

22 Resubmitted: November 2018

1
23 *author whom correspondence should be addressed during submission process:

24 [email protected]

25 +32 16 32 68 29

26

27 ** author whom correspondence should be addressed post-publication:

28 [email protected]

29 +32 16 32 19 47

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30 Abstract

31 Plant-based foods gain more importance since they play a key role in sustainable, low-meat

32 and healthy diets. In developing countries, these food products, especially legumes and cereals,

33 are important staple foods. Nevertheless, the question arises on how efficient they are to deliver

34 minerals and if it is useful to encourage their consumption to reduce the prevalence of mineral

35 deficiencies? This review paper focuses on the discrepancy between the mineral content and

36 the amount of minerals that can be released and absorbed from plant-based foods during human

37 digestion which can be attributed to several inherent factors such as the presence of mineral

38 antinutrients (phytic acid, polyphenols and dietary fiber) and physical barriers (surrounding

39 macronutrients and cell wall). Further, this review paper summarizes the effects of different

40 processing techniques (milling, soaking, dehulling, fermentation, germination and thermal

41 processing) on mineral bioaccessibility and bioavailability of plant-based foods. The positive

42 impact of these techniques mostly relies on the fact that antinutrients levels are reduced due to

43 removal of fractions rich in antinutrients and/or due to their leaching into the processing liquid.

44 Although processing can have a positive effect, it also can induce leaching out of minerals and

45 a reduced mineral bioaccessibility and bioavailability.

46

47 Keywords: Minerals, dietary fiber, phytic acid, polyphenols, physical barriers,

48 processing

49

50 1. Introduction

51 Plant-based foods, including vegetables, fruits, cereals and legumes, are important ingredients

52 in the human diet all over the world (Global Dietary Database 2010). These food products are,

53 for example, becoming increasingly important due to sustainability reasons. Especially in

54 developing countries, plant-based foods represent a high proportion of the dietary intake

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55 (Tontisirin, Nantel and Bhattacharjee 2002). To these populations, plant-based food systems

56 provide not only macronutrients but are also the main source of micronutrients, such as

57 minerals, which are defined as chemical elements required by organisms to perform vital

58 functions (Berdanier, Dwyer and Heber 2013). Minerals are classified as essential nutrients as

59 they cannot be synthesized by the human body, and must be obtained from the diet. This review

60 paper focusses on iron and zinc because of their important physiological role in the human

61 body and because iron and zinc deficiencies have been reported to be prevalent nutritional

62 problems all over the globe (Platel and Srinivasan 2016). Iron participates in a wide variety of

63 metabolic processes, including respiration, energy production, DNA synthesis, and cell

64 proliferation, whereas zinc has been shown to be essential to the structure and function of a

65 large number of macromolecules and for more than 300 enzymatic reactions (Tapiero and Tew

66 2003; Belitz, Grosch and Schieberle 2009; Hentze et al. 2010). The recommended nutrient

67 intake for iron and zinc is on average respectively 13.7 and 14 mg per capita per day for adult

68 males and 29.4 and 10 mg per capita per day for women of reproductive age (FAO and World

69 Health Organization 2004).

70 When food is consumed, the present nutrients can be released from the matrix, followed by

71 conversion into absorbable units which can subsequently be absorbed into the bloodstream and

72 transported to their respective target tissues (Boland, Golding and Singh 2014). The nutrient

73 fraction which is released from the food matrix and available for absorption is referred to as

74 bioaccessible (which can be, for example, determined in vitro), whereas the nutrient fraction

75 which is absorbed and available for utilization in physiologic functions and storage is referred

76 to as bioavailable (examined by in vivo experiments or cell cultures) (Fernández-García,

77 Carvajal-Lérida, and Pérez-Gálvez 2009). In contrast to macronutrients, biochemical

78 conversion during digestion of micronutrients into absorbable units is not needed, since they

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 79 are absorbable as such, with or without a specific carrier (Basu and Donaldson 2003; Jackson

80 and McLaughlin 2009).

81 Absorption of iron and zinc mainly takes place in the small intestine (Sitrin 2014). Although

82 evidence has been found for colonic absorption of other minerals, such as calcium, there is

83 little data to suggest a similar capacity for iron and zinc (Takeuchi et al. 2005, Gopalsamy et

84 al. 2015). In the case of iron, an important distinction should be made between heme iron and

85 non-heme iron. Heme iron, particularly present in animal-based foods, consists of iron

86 complexed with the porphyrin ring from either haemoglobin or myoglobin (Pizarro et al. 2016).

87 Absorption is mediated through heme iron specific receptors on the microvilli of enterocytes.

88 Once absorbed, the iron is split from the complex by heme oxygenase (Fuqua, Vulpe and

89 Anderson 2012). The second type of iron is non-heme iron from plant based-based foods.

90 Within non-heme iron, a distinction must be made between iron in the ferrous state (Fe2+) and

91 the ferric state (Fe3+). The divalent metal transporter 1 (DMT1) transports non-heme iron in the

92 ferrous state together with protons across the mucosal membrane. The non-heme iron in the

93 ferric state must be reduced before it can be absorbed using the same mechanism (Ganong

94 1995; Bohn, Meyer and Rasmussen 2008; Fuqua, Vulpe and Anderson 2012; Sitrin 2014). Zinc

95 is absorbed in the small intestine by a carrier (ZnT-1) -mediated mechanism (Krebs 2000;

96 Roohani et al. 2013).

97 Plant-based foods are expected to become more important in the human diet. As the global

98 population is rising, the pressure will increase on animal-based foods and more sustainable

99 food sources will be needed, e.g. legumes. However, an increase in consumption of plant-based

100 foods could also have consequences for human health. Therefore, this review paper will focus

101 on these plant-based food products. Even though plant-based foods are intrinsically rich in

102 minerals such as iron and zinc (Table 1), it has been reported that their release from the food

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103 matrix during digestion might be limited, thereby reducing the amount available for absorption

104 (Platel and Srinivasan 2016).

105 Among others, the low bioaccessibility and bioavailability of non-heme iron and zinc from

106 plant-based foods can be attributed to several inherent barriers for mineral digestion, of which

107 antinutrients and physical barriers seem to be the most important (Rossander, Sandberg and

108 Sandström 1992; Shahidi 1997; Mishra, Hardcare and Monro 2010; Platel and Srinivasan

109 2016). On the one hand, mineral antinutrients (e.g. dietary fibers, phytic acid and polyphenols)

110 can bind the minerals, potentially inhibiting their release for absorption. The effect of these

111 antinutrients on mineral bioaccessibility depends on the digestibility of the chelate

112 (antinutrient-mineral complex) (Svarc-Gajic 2013; Baye, Guyot and Mouquet-Rivier 2017).

113 Besides binding minerals in the plant-based food systems in situ, antinutrients, originating from

114 other simultaneously ingested food ingredients, are also believed to form complexes with

115 dietary minerals (Kumar et al. 2010). On the other hand, physical barriers (e.g. the cell wall

116 and the digestibility of the surrounding food matrix) for digestion can be present in plant-based

117 foods and thus impede both mineral bioaccessibility and bioavailability (Glahn et al. 2016).

118 As a consequence, even when dietary recommendations are met, mineral deficiencies can

119 originate due to impaired mineral absorption. In fact, mineral undernutrition, especially iron

120 and zinc deficiencies, are reported to be prevalent nutritional problems all over the globe (Platel

121 and Srinivasan, 2016). According to the WHO report (2015), iron deficiency is the most

122 common micronutrient deficiency in the world, affecting over 30% of the world’s population,

123 including a large number of children and women in developing countries. Moreover, iron

124 deficiency is believed to be the only micronutrient deficiency that is also significantly prevalent

125 in industrialized countries (World Health Organization 2015). In particular, many women

126 suffer from iron deficiency during pregnancy due to increased iron demand for foetal growth

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127 and development, a condition that is strongly linked to low birth weight, premature delivery,

128 and a multitude of perinatal complications. Alongside being a major factor contributing to the

129 development of anaemia, iron deficiency can cause disturbances in the functioning of both the

130 endocrine and immune systems (Bailey, West and Black 2015). Next to iron, zinc deficiency

131 is also a worldwide health problem with about 33% of the world's population at risk,

132 particularly those in underdeveloped countries. Low zinc blood levels may lead to numerous

133 clinical symptoms, including growth retardation, impaired brain development and cognitive

134 performance, poor wound healing, diarrhoea, infertility and increased risk of infections

135 (Wapnir 2000; Crook 2011).

136 Next to insufficient dietary intake and physiological status of consumers (e.g. malabsorption

137 and illness), the poor bioaccessibility and bioavailability of minerals from plant-based foods

138 could potentially contribute to the high prevalence of mineral deficiencies (Manary et al. 2000).

139 This review paper focuses on the influence of particular mineral antinutrients (cfr.§2) and the

140 physical barriers (cfr.§3) on the bioaccessibility and bioavailability of iron and zinc in plant-

141 based foods. In addition, the perspectives of different processing techniques to modify the

142 bioaccessibility and bioavailability of iron and zinc in plant-based foods are discussed (cfr.§4).

143 2. Antinutrients influencing mineral bioaccessibility and bioavailability

144 “Antinutrients are natural or synthetic compounds that interfere with the absorption of

145 nutrients” (Oxford Dictionary of Biochemistry and Molecular Biology 2006), in this way they

146 reduce the nutrient bioaccessibility and bioavailability from food. Antinutrients are abundantly

147 present in plant-based foods since they play a physiological role in the chemical defence

148 mechanisms against various insects, pests and humans of the plant (part) where they originate

149 from (Svarc-Gajic 2013). Many in vitro (Persson et al. 1991; Olivares et al. 2001; Glahn et al.

150 2002; Bosscher et al. 2003; Lestienne et al. 2005; Andrews et al. 2014; Suliburska and Krejpcio

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151 2014) and in vivo (Drews, Kies and Fox 1979; Larsson et al. 1996; Hurrell et al. 2003;

152 Schlegel, Nys, and Jondreville 2010; Luo and Xie 2012; Miyada, Nakajima and Ebihara 2012)

153 studies have reported the negative consequences of dietary fibers (cfr.§2.1) phytic acid

154 (cfr.§2.2), polyphenols (cfr.§2.3) and on iron or zinc bioavailability. Since these compounds

155 specifically can interfere with the absorption of minerals, they are generally referred to as

156 mineral antinutrients. Although it seems interesting trying to reduce the mineral antinutrient

157 concentration in plant-based foods in order to increase mineral bioaccessibility and

158 bioavailability, it should not be forgotten that these compounds can possess other health-

159 promoting effects as well (cfr. infra).

160 2.1 Dietary fiber

161 Dietary fiber was traditionally defined as the non-digestible components of the plant cell wall

162 (Hipsley 1953). Most recently, dietary fiber is described as “edible carbohydrate monomers

163 (naturally occurring in foods, as well as isolated, modified and synthetic polymers with proven

164 physiologic effects of benefit to health) with ten or more monomeric units, which are not

165 hydrolysed by the endogenous enzymes in the small intestine of human” (Joint FAO/WHO

166 Food Standards Programme Commission 2016). Dietary fibers can be classified into water

167 soluble and water insoluble fibers based on their solubility in water at a defined pH. Water

168 soluble fibers (e.g. pectin, inulin and polydextrose) are fermented in the colon while water

169 insoluble fibers (e.g. cellulose, hemicellulose, lignin and resistant starch) have bulking effects

170 but may only be fermented to a limited extent in the colon. Fruit and vegetables have a

171 significantly higher proportion of soluble dietary fiber while cereals and legumes contain more

172 insoluble dietary fibers (Figuerola et al. 2005; de Almeida Costa et al. 2006). Several

173 components of dietary fiber, such as the free carboxyl group on some sugar residues, uronic

174 acid and the surface hydroxyl group of cellulose are reported to possess the ability to bind

175 minerals (Schneeman 1986). Moreover, dietary fiber may be associated with many other

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176 substances, mostly with proteins, polyphenols and phytic acid, which are believed to also affect

177 its mineral binding capacity (Idouraine et al. 1995; Vitali et al. 2008). Various in vitro studies

178 have shown that the binding of minerals might be affected by the source of fiber, pH and other

179 physicochemical properties of dietary fiber (Thompson and Weber 1979; Camire and

180 Clydesdale 1981; Garcia-Lopez and Lee 1985; Platt and Clydesdale 1987; Persson et al. 1987).

181 Since several dietary fiber components have the ability to bind minerals, these minerals become

182 embedded in an insoluble and/or unabsorbable fiber-mineral complex which cannot be

183 hydrolysed by human digestive enzymes. These minerals can only be released if fermentation

184 of the fiber takes place in the colon, but mineral absorption has generally been accepted to

185 occur mainly in the small intestine (Torre, Rodriguez and Saura-Calixto 1995). Consequently,

186 the extent to which fermentation (breakdown of the fiber-cation complex) in the colon

187 contributes to mineral bioaccessibility and bioavailability is still a point of discussion.

188 Moreover, for some complexes, limited fermentation is hypothesized. Because of this complex

189 formation, by either electrostatic forces or chelation, or due to the anion exchange capacity,

190 dietary fiber can be considered as a mineral antinutrient. The influence on mineral

191 bioaccessibility and bioavailability of fibers depends on specific characteristics of the fiber.

192 For example, the solubility of the fiber plays an important role.

193 Soluble dietary fiber

194 Among the soluble dietary fibers, pectin is abundantly present in the cell wall of plant-based

195 food systems such as fruits, vegetables and legumes (Chan et al. 2017). Pectin is a hetero-

196 polysaccharide, predominantly containing galacturonic acid (GalA) residues, in which varying

197 proportions of the acid groups are present as methoxyl esters, while a certain amount of neutral

198 sugars might be present as side chains (Voragen et al. 2009). The non-methylesterified GalA

199 residues can be ionised (depending on the pH of the system) giving pectin its polyanionic nature

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200 and ability to bind metal-ions. The interaction between pectin and divalent cations is known to

201 generally occur according to the egg-box model (Caffall and Mohnen 2009) and is represented

202 in Figure 1. Changes in the degree of methylesterification (DM) of pectin will influence its

203 polyanionic nature and the mineral binding capacity. In addition, the presence of neutral sugars

204 as well as the degree and nature of branching are reported to influence the cation binding

205 capacity of pectin (Kyomugasho et al. 2017). Besides a reduced degree of esterification, Celus

206 et al. (2018) showed that the pattern of DM (blockwise or randomly), was shown to affect Zn2+

207 or Ca2+ binding capacity of pectin: the more blockwise its pattern of DM, the higher its mineral

208 binding capacity. A schematic representation of structural characteristics of pectin which can

209 influence pectin-mineral binding capacity is shown in Figure 2. Reduced mineral

210 bioavailability, caused by the presence of pectin, has been reported. Bosscher et al. (2003) used

211 an in vitro dialysis model to evaluate the availabilities of calcium, iron, and zinc from infant

212 formulas supplemented with soluble dietary fiber fractions. They found that pectin reduces iron

213 bioaccessibility, which correspond with the in vitro data of Platt and Clydesdale (1987) as well

214 as with the in vivo data of Monnier, Colette and Mirouze (1980). In addition, in vitro studies

215 by Kyomugasho et al. (2015) and Celus et al. (2018), reported that the bioaccessibility of

216 calcium-, zinc- and/or iron-ions decreases with increasing electrostatic pectin-interactions (i.e.

217 lower degree of esterification).

218 As mentioned before, the mineral binding capacity of fiber can be influenced by the association

219 of the fiber with other substances. In this context, Persson et al. (1987) investigated the mineral

220 binding capacity of soluble fiber fractions of wheat bran and whole grain wheat bread dough,

221 in which most of the phytic acid was present. They found these fractions interacting strongly

222 with the metal ions, but incubation of these fractions with phytase reduced the complexing

223 ability, indicating the active ligand was phytic acid.

224 Insoluble dietary fiber

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225 In contrast to soluble dietary fibers, which can interact strongly with metal ions, the mineral

226 binding capacity of insoluble dietary fibers is negligible (Persson et al. 1987). Among insoluble

227 fibers, lignin was shown to have more mineral binding capacity than cellulose and

228 hemicelluloses, probably because of its polyphenolic nature (Fernandez and Phillips 1982).

229 The negative influence of dietary fibers on mineral bioavailability is not only due to their ability

230 to bind minerals, but the presence of dietary fibers in the diet can induce a higher digest

231 viscosity which can impede the contact between nutrients and digestive enzymes, and

232 consequently limit the availability of nutrients for absorption (Guillon and Champ 2000).

233 Positive health effects of dietary fiber

234 Although there is evidence that high fiber intake can hinder mineral absorption, the subject is

235 controversial (Idouraine et al. 1995). For instance, in the previously mentioned study, Bosscher

236 et al. (2003) have shown soluble dietary fiber to affect mineral bioavailability not only in a

237 negative way, but also positively, depending on the type of dietary fiber. The fermentation of

238 fibers, such as inulin and fructooligosaccharides (most common dietary source is wheat), in the

239 colon can also enhance mineral absorption. During their fermentation by colonic microbiota,

240 short chain fatty acids are produced. These components can trigger increased proliferation of

241 epithelial cells, which, in turn, increase the absorptive surface area and hence absorption of

242 nutrients (Roberfroid 2007; Baye, Guyot and Mouquet-Rivier 2017). Additionally, short chain

243 fatty acids can decrease luminal pH and thus create an acidic environment, which is more

244 favourable for mineral solubility (Wang et al. 2010). The positive effect of the presence of

245 inulin and fructooligosaccharides on mineral absorption has been shown in several animal

246 studies (Delzenne et al. 1995; Ohta et al. 1995; Younes, Demigné, and Rémésy 1996; Charles

247 Coudray et al. 2003; Lobo et al. 2009) and is partially confirmed in humans (Coudray et al.

248 1997; Ellegard, Andersson and Bosaeus 1997; Van Den Heuvel et al. 1999; Tahiri et al. 2003;

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249 Ducros et al. 2005; Yap et al. 2005) as reviewed by Coudray et al. (2003). The absorption

250 enhancing properties of fibers depends on specific characteristics of the fiber. Improved

251 mineral absorption has been shown for some soluble dietary fibers such as inulin,

252 fructooligosaccharides and pectin while this effect was not observed for insoluble ones (Greger

253 1999; Sakai et al. 2000). In another in vivo study, Kim et al. (1996) demonstrated that pectin

254 structural properties, including both molecular weight and degree of esterification, can

255 influence the mineral binding properties of pectin. They showed that low molecular weight

256 pectins with a high degree of esterification were able to improve the absorption of minerals.

257 However, in high molecular weight pectins with a low degree of esterification these effects

258 were absent.

259 2.2 Phytic acid

260 Phytic acid (Figure 3), known as myo-inositol hexaphosphate (IP6) or phytate when in the salt

261 form, serves as the major phosphor storage form in many plant tissues. According to Oatway,

262 Vasanthan and Helm (2001) and Sandberg (2002), phytic acid is most abundant in plant-based

263 foods such as cereal grains, legumes, nuts and oilseeds comprising 1-5% and it can appear in

264 lower amounts in roots, tubers and vegetables (Gupta, Gangoliya and Singh 2015). Phytic acid

265 is formed during the maturation stage of the plant seed and contains 60-90% of the total

266 phosphor content in dormant seeds, where it is accumulated as mixed salts of several cations,

267 including iron, zinc, magnesium, calcium and potassium (Frossard et al. 2000; Kumar et al.

268 2010). Due to the presence of phytase, phytic acid can be hydrolyzed into lower inositol-

269 phosphates (e.g. inositol penta- (IP5), tetra- (IP4) or triphosphate (IP3)).

270 In this context, phytic acid is a well-known mineral antinutrient that has been intensively

271 investigated throughout the years as reviewed by Harland and Morris (1995), Oatway,

272 Vasanthan and Helm (2001), Schlemmer et al. (2009) and Kumar et al. (2010). This mineral

273 antinutrient exists as a strongly negatively charged ion over a wide pH range (from pH > 2.0)

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274 and it is able to form stable complexes with divalent or trivalent mineral ions such as iron, zinc,

275 calcium and magnesium through electrostatic interactions (Kumar et al. 2010). The complex

276 between phytic acid and minerals can occur either in the plant tissue and/or in the digestive

277 tract. Minerals bind to phytic acid with a strength proportional to their atomic mass and

278 electronegativity. Therefore, zinc and copper have been found to form stronger complexes with

279 phytic acid than lighter atoms, such as iron and calcium (Vohra, Gray and Kratzer 1965;

280 Oberleas and Chan 1997). These complexes, phytates, are not easily digestible by monogastric

281 animals, such as humans, due to the lack of endogenous phytase enzymes (Hurrell and Egli

282 2010). As such, the bioavailability of the bound ions is impaired. According to Sandberg,

283 Carlsson and Svanberg (1989) and Sandström and Sandberg (1992), mainly higher inositol-

284 phosphates (e.g. IP6 and IP5) have a negative effect on mineral bioavailability, given that lower

285 inositol-phosphates (e.g. IP4 and IP3) have a lower capacity to bind minerals and generally

286 form more soluble complexes.

287 In other words, among the essential minerals, zinc has the highest binding strength for phytic

288 acid and as a result thereof, zinc absorption is hypothesized to be more negatively influenced

289 by phytic acid than iron absorption. At marginal dietary zinc supply, the inhibitory effects of

290 phytic acid on zinc bioavailability can be predicted by the molar ratio of phytic acid to zinc in

291 the diet. Davis and Olpin (1979) found that molar ratios exceeding 10:1 (phytic acid:zinc) have

292 a negative influence on zinc absorption. More recently, Ma (2007) reported that when at a

293 molar ratio of 16:1, zinc is no longer bioavailable. The inhibitory effect of phytic acid on zinc

294 bioavailability has been reproduced and confirmed in several studies (Lestienne et al. 2005;

295 Viadel, Barberá and Farré 2006; Schlegel, Nys and Jondreville 2010; Kruger et al. 2013). In

296 addition, high levels of calcium strengthen the inhibitory effect of phytic acid on zinc

297 absorption since zinc coprecipitates with phytic acid and calcium as a zinc-calcium-phytate

298 complex. This complex is even less soluble than phytate complexes formed with either one ion

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299 alone (Lopez and Leenhardt 2002). Since most plant-based foods possess a high calcium

300 amount compared to zinc, this can be of major concern. For example, depending on the legume

301 type, calcium:zinc ratios up to approximately 25:1 have been reported by Eskin and Shahidi

302 (2013). Additionally, gastrointestinal secretions may contain ions as well (Boland, Golding and

303 Singh 2014), which can bind phytic acid in the gastrointestinal tract during digestion.

304 Phytic acid is also capable of complexing with iron in the same way as previously described

305 for zinc. This iron-(calcium-)phytate complex precipitates, withdrawing the iron from the

306 digest and renders it unavailable for absorption. In an in vitro study by Lestienne et al. (2005),

307 it was observed that both iron and zinc bioaccessibility of whole pearl millet flour were

308 significantly improved by phytic acid degradation and removal. However, since

309 dephytinization of the bran fraction had no effect on either iron or zinc bioaccessibility, they

310 concluded that even if phytates are involved in reducing iron and zinc bioaccessibility in pearl

311 millet flour, fibers and tannins may also play an important role by chelating a high proportion

312 of iron and zinc in grain hulls. Next to in vitro studies, in vivo studies reported the negative

313 effect of phytic acid on iron absorption. The negative effect of phytic acid on iron absorption

314 has, for instance, been shown by performing a cell culture study using model systems (Andrews

315 et al. 2014). Caco-2 cells were incubated with iron for 24 h and subsequently challenged with

316 phytic acid, pectin or tannic acid for another 24 h. Finally, iron uptake was determined. The

317 results were as expected: phytic acid, pectin or tannic acid each decreased the iron uptake and

318 addition of calcium to phytic acid strengthened its inhibitory effect. Hallberg, Brune and

319 Rossander (1989) showed the inhibitory effect of sodium phytate on iron absorption in man by

320 serving wheat rolls containing no phytates and rolls to which various amounts were added just

321 before serving. In this study, the negative effect of phytic acid has also been shown to be dose

322 dependent. They showed that 10 mg/100 g, 20 mg/100 g and 100 mg/100 g phytic acid reduced

323 iron absorption by 20%, 40% and 60%, respectively. These results were confirmed by Petry et

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324 al. (2010) who served dephytinized and nondephytinized red bean porridge to young women.

325 In addition, Saha, Weaver and Mason (1994) showed that iron absorption in rats decreased

326 significantly when the molar ratios of phytic acid to iron were above 14:1. For example, 100 g

327 beans (phaseolus vulgaris) can contain up to 2.38 g phytic acid and up to 14 mg iron (dry

328 weight), this means that in realistic cases the ratio exceeds 14:1 (Schlemmer et al. 2009; Hayat

329 et al. 2014).

330 Besides its role in mineral bioavailability, phytic acid can also influence protein digestibility.

331 This complex formation with proteins alters the protein structure, which make the proteins less

332 soluble, and affects the enzymatic degradation and peptic digestion (Kumar et al. 2010).

333 Positive health effects of phytic acid

334 Although the presence of phytic acid in the human diet can have a negative impact on mineral

335 bioavailability and protein digestibility, phytic acid has been shown to be protective to a variety

336 of cancers (Jenab and Thompson 2001). It has been suggested that phytic acid is a potent

337 inhibitor of the iron-mediated generation of the hazardous oxidant, hydroxyl radical (as

338 described in section 2.3). Graf and Eaton (1985) have proposed that inhibition of intracolonic

339 hydroxyl radical generation, for example via the chelation of iron ions by phytic acid, may help

340 to explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by

341 diets rich in phytic acid.

342 2.3 Polyphenols

343 Polyphenols are an integral part of the human diet since they are omnipresent in plant tissues,

344 where they serve as protective substances against harmful external influences (e.g. ultraviolet

345 radiation and aggression by pathogens) (Pandey and Rizvi 2009). Phenolic compounds are

346 composed of an aromatic ring with at least one hydroxyl group in their structure. In plants, the

347 majority of polyphenols are conjugated to one or two sugar moieties. Other compositions, for

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348 instance with amines, lipids and organic or carboxylic acids make up the remaining part (Bravo

349 1998). Polyphenolic compounds can be classified based on the number of phenol rings and

350 their linkages. In plants, the majority of polyphenolics are represented by flavonoids (low

351 molecular weight phenolic compounds, including anthocyanins) and tannins (intermediate to

352 high molecular weight phenolic compounds, also referred to as polymeric flavonoids). The

353 common structure of flavonoids is a diphenylpropane (C6-C3-C6) and consists of two aromatic

354 rings linked through three carbons that usually form an oxygenated heterocycle (Figure 4). The

355 best known tannin is tannic acid that consists of a hepta- to octa-galloyl-β-d-glucose in which,

356 on average, two to three additional galloyl groups are esterified to a preexisting β-1,2,3,4,6-

357 pentagalloyl-d-glucose core (Figure 5) (Haslam 1992; Liu et al. 2005). The occurrence and

358 amount of polyphenols may vary from plant to plant (mainly depending on genetic factors and

359 environmental conditions), however, they are generally concentrated in the seed coat of plant-

360 based food products. Tea (75-105 mg/100 ml), coffee (130-350 mg/100 ml), fruit juices (0.2-

361 710 mg/100 ml) and red wine (100-650 mg/ 100 ml) are the most abundant dietary sources,

362 while vegetables (e.g. leek: 20-40 mg/100 g dm), cereals (e.g. wheat: 22-40 mg/100 g dm) and

363 legumes (e.g. chickpeas: 78-230 mg/100 g dm) also contribute to the total polyphenol intake

364 (Bravo 1998; Belitz, Grosch and Schieberle 2009; Quideau et al. 2011).

365 Depending on the type of flavonoid structure, polyphenols can exhibit metal chelating

366 properties. If polyphenols and metal cations are present together in the food matrix and/or the

367 digestive tract, the metal cations can interact with hydroxyphenyl and carboxyl groups of the

368 polyphenols. A general iron-polyphenol complex is illustrated in Figure 6. Intestinal absorption

369 of these complexes is influenced by their molecular weight, degree of glycosylation and

370 esterification. In the case these complexes are absorbed, most polyphenols are quickly

371 eliminated in urine and bile without release of the bound minerals during the polyphenol

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372 metabolism (Scalbert et al. 2002). In other words, polyphenolic compounds can reduce mineral

373 bioaccessibility and bioavailability and are therefore considered as antinutrients (Bravo 1998).

374 The mineral chelating capacity of polyphenols has mainly been explored in relation to iron.

375 Several in vitro studies have reported the high iron chelating capacity of both flavonoids (Mira

376 et al. 2002; Ryan and Hynes 2007; Mladěnka et al. 2011) and tannins (Yoneda and Nakatsubo

377 1998; Iffat, Maqsood and Fatima 2005; Karamać 2009). Due to this iron chelating capacity

378 (principally taking place in the gastrointestinal lumen during human digestion), flavonoids and

379 tannins have been associated with a reduced absorption of iron from the human diet (Disler et

380 al. 1975; Brune, Rossander and Hallberg 1989; Hurrell, Reddy and Cook 1999; Layrisse et al.

381 2000; Petry et al. 2010).

382 Zinc, as compared to iron, has a lower affinity for polyphenols, particularly at neutral and acidic

383 pH (Santos-Buelga and Scalbert 2000). Only few in vivo studies examined the effect of

384 polyphenol-rich foods (e.g. tea and red wine) on zinc absorption. For example, Ganji and Kies

385 (1994), showed that tea consumption has a small but not statistically significant adverse effect

386 on zinc bioavailability in humans. However, Coudray et al. (1998) reported that phenolic

387 compounds may decrease intestinal absorption of zinc in rats. In a subsequent study, Coudray

388 et al. (2000) showed that the short- or long-term consumption of red wine did not have a

389 negative effect on intestinal absorption or tissue levels of zinc in rats. The absence of an effect

390 of red wine on zinc absorption may be due to the antagonist actions of polyphenols and ethanol.

391 More research should be performed to investigate the effect of polyphenol-rich foods on zinc

392 absorption.

393 Beyond their mineral binding capacity, polyphenols can form insoluble complexes with dietary

394 proteins, starch and other carbohydrates, reducing the digestibility of these nutrients. In

17
395 particular, the presence of tannins in food has been considered as an antinutritional aspect due

396 to their well-known capacity to bind and precipitate proteins (Svarc-Gajic et al. 2013).

397

398 Positive health effects of polyphenols

399 Although the metal chelating activity of polyphenols can have a negative impact on mineral

400 bioavailability, this action can be beneficial in certain circumstances. Iron can be the initiator

401 of hydroxyl radical production by the Fenton and Haber-Weiss reactions (Figure 7).

402 By chelating this mineral, the production of reactive oxygen species (ROS) can be prevented,

403 consequently chelation of iron is one of the ways polyphenols exert their antioxidant capacity

404 (Bravo, 1998). Additionally, polyphenolic antioxidants (PPH) can interfere with the oxidation

405 of lipids and other molecules by rapid donation of a hydrogen atom to radicals (ROO• and

406 RO•):

407 ROO • +PPH → ROOH + PP •

408 RO • +PPH → ROH + PP •

409 The formed phenoxy radical intermediates (PP•) are relatively stable and therefore a new chain

410 reaction is not easily initiated. The phenoxy radical intermediates also act as terminators of the

411 propagation route by reacting with other free radicals:

412 ROO • +PP • → ROOPP

413 RO • +PP • → ROPP

414 Concludingly, by preventing the formation of ROS and/or scavenging ROS, polyphenols can

415 slow down lipid oxidation and non-enzymatic browning during food storage on the one hand,

416 and on the other hand oxidative stress-related chronic diseases and age-related disorders such

417 as cardiovascular diseases (e.g. atherosclerosis), carcinogenesis, neurodegeneration (e.g.

18
418 Alzheimer’s disease), as well as skin deterioration can be prevented or reduced if polyphenols

419 are consumed. Polyphenols are proven to be the most abundant antioxidants in the human diet

420 (Brune, Rossander and Hallberg 1989; Bravo 1998; Mira et al. 2002; Mennen et al. 2005;

421 Svarc-Gajic et al. 2013).

422 Although the antioxidant capacity of polyphenols is their most discussed characteristic, it

423 should also been mentions that polyphenolic compounds have been proven to be beneficial for

424 human health through other mechanisms. For instance, because of their particular structural

425 and conformational characteristics, polyphenols interact with specific biological targets (e.g.

426 enzymes, transcription factors and receptors) (Fraga et al. 2010).

427 3. Physical barriers influencing mineral bioaccessibility and bioavailability

428 3.1 Cell wall

429 In the above sections this paper, we have been discussing factors at the sub-cellular and

430 molecular level that may affect mineral bioaccessibility and bioavailability. At the (multi-)

431 cellular level, the plant cell wall has to be taken into account since many sources of food

432 nutrients are swallowed in the form of intact plant tissue fragments (Boland, Golding and Singh

433 2014). Tissues of plant-based food systems are made up of cells which are surrounded by a cell

434 wall. This cell wall provides the cell both structural support and protection. Within the plant

435 cell, the cell wall structure is continuously modified, depending on the developmental stage

436 and the environmental conditions. The plant cell wall can consist of three structural entities,

437 namely the middle lamella, the primary cell wall and the secondary cell wall, but in plant-based

438 food systems (fruits, vegetables, cereals and legumes) there rarely is a secondary cell wall

439 present. The middle lamella in fruits, vegetables and legumes is rich in pectin and cements the

440 cell walls of two neighbouring plant cells together. The primary cell wall is located next to the

19
441 middle lamella and mainly consists of pectin, cellulose and hemicellulose (Cafall and Mohnen

442 2009; Burton, Gidley and Fincher 2010; Burton and Fincher 2014).

443 The plant tissue structure has been known to influence the bioaccessibility and bioavailability

444 of carbohydrates and other macronutrients as the cell wall may act as (partial) barrier to both

445 digestive enzyme penetration into, and nutrient diffusion out of the fragment or particle

446 (Mishra, Hardcare and Monro 2010; Pallares et al., 2019). Consequently, it can be questioned

447 if the cell wall can be considered as a physical barrier for mineral bioaccessibility and

448 bioavailability as well. During mechanical disruption of intact plant tissues (for example by

449 chewing), the tissue may disintegrate by two possible tissue failure characteristics: cell

450 breakage and/or cell separation (Figure 8) (Van Buggenhout et al., 2009). Depending on the

451 composition and characteristics of the cell wall polymers, one of the tissue failure

452 characteristics will be more prevalent. In the case of cell breakage, cell content is released and

453 believed to be physically more available for digestive enzyme action or absorption in the

454 digestive tract. However, if cell walls are not disrupted and the cell wall stays intact,

455 nutrient/metabolite release kinetics might be influenced and nutrient availability might be

456 reduced as such. Only recently this hypothesis for minerals has been investigated by Glahn et

457 al. (2016), more specifically for iron in common beans. The cell wall of legumes, particularly

458 of beans, has been shown to be microstructurally resistant to cooking and the digestion

459 conditions and enzymes of the human intestinal tract. Therefore, Glahn et al. (2016) used

460 relatively high intracellular pressure (>4000 psi) to initiate cell wall rupture but, surprisingly,

461 this cell lysis did not result in a consistent or strong enhancement of bioavailable iron. They

462 suggest that the liberated intracellular starch and protein influenced the iron bioavailability by

463 creating a matrix that inhibited the exchange of iron with the cell transport mechanism.

464 However, it should be noted that these results can also indicate that minerals which are bound

20
465 to cell wall material, are not being released due to cell lysis. These observations should be

466 further investigated and for example confirmed by in vivo experiments.

467 3.2 Digestibility of the surrounding macronutrients

468 If macronutrients form a food matrix in which minerals are embedded remain undigested, it is

469 hypothesized that they can form a physical barrier for mineral transfer to the absorption site in

470 the small intestine (Glahn et al. 2016). Research has to be done to further examine this

471 hypothesis.

472 4. Perspectives of food processing to impact mineral bioaccessibility

473 Food processing can increase food safety and stability, it can create desired process-induced

474 flavours and can result in palatability improvement. Although there are many benefits,

475 processing can also be detrimental, for example, by causing undesirable changes such as loss

476 of colour, flavour, texture and smell (Considine et al. 2008). In addition, processing can affect

477 the nutritional quality of foods. The nutritional quality of minerals in foods depends on their

478 quantity as well as their bioaccessibility and bioavailability (Reddy and Love 1999).

479 In contrast to vitamins, minerals cannot be destroyed by light, heat, humidity, oxidizing or

480 reducing agents and acids or bases (Miller 1996; Singh et al. 2007). However, on the one hand,

481 food processing can affect the mineral content. Minerals can either be removed from foods

482 during processing (leaching, physical separation) or processing can be responsible for mineral

483 enrichment by addition or by transfer of minerals from other ingredients, machinery or packing

484 material (Alegria et al. 2015). On the other hand, food processing can have an impact on

485 mineral release from the food matrix.

486 The mineral concentration and the bioaccessibility and bioavailability of minerals from plant-

487 based foods can, for example, be affected by milling (cfr.§4.1), soaking (cfr.§4.2), dehulling

21
488 (cfr.§4.3), fermentation (cfr.§4.4), germination (cfr.§4.5) and thermal processing (cfr.§4.6).

489 These processes particularly affect the mineral concentration and by altering, degrading or

490 removing antinutrients, the mineral bioaccessibility and bioavailability can be altered. In

491 addition, several of these techniques are also believed to influence physical barriers.

492 4.1 Milling

493 Milling, a processing method commonly applied on raw cereal grains, has the objective to crush

494 the grain into flour, whether or not combined with a (complete) separation of bran and germ

495 from the endosperm (Belderok, Mesdag and Donner 2000).

496 Milling leads into tissue disruption whereby cell structures can be opened as well. On the one

497 hand, this can enable the different components (e.g. minerals, antinutrients and enzymes) to

498 come in more close contact, affecting mineral bioaccessibility and bioavailability (Raes et

499 al.,2014). On the other hand, by disrupting the cell wall, it has been hypothesised this physical

500 barrier for mineral bioaccessibility and bioavailability can be eliminated (Glahn et al. 2016).

501 Cell wall breakage during mechanical disintegration can depend on previous processing steps.

502 For example, mechanical disintegration of pulse seeds after cooking, may lead rather to cell

503 separation than cell disruption, due to pectin solubilisation in the middle lamella (Dhital et al.

504 2016; Pallares et al. 2018). The intactness of cell wall structures, after cell separation, has been

505 hypothesized to be a barrier for mineral bioaccessibility and bioavailability as discussed before

506 (cfr.§3.1).

507 The effect of separation of bran and germ from the endosperm in cereal grains during milling

508 can also influence the mineral concentration and mineral bioaccessibility and bioavailability.

509 Cereal grains generally contain high levels of minerals in the bran and germ fractions (Ozturk

510 et al. 2006; Eagling et al. 2014). By removing these fractions, endosperm with low mineral

511 content leaves behind. For example, conversion of whole wheat to white flour can result in up

22
512 to 86% loss of iron, zinc, copper, magnesium and selenium (Miller 1996; Fardet 2010).

513 However, not only minerals are removed since antinutrients like phytic acid, dietary fiber and

514 tannins, are mainly found in the bran and germ fraction (Rendleman 1982; Dykes and Rooney

515 2007; Suma and Urooj 2014). For example, when milling is used to remove the bran and/or

516 germ from cereal, up to 90% of the phytic acid content can be discarded (Gibson et al. 2010).

517 Due to partial separation of the bran fraction of pearl millet, semi refined flour was low in

518 antinutrients which improved the mineral bioaccessibility (Suma and Urooj 2014). Milling of

519 cereals grains and separation of bran and germ from the endosperm in cereal grains during

520 milling has been shown to enhance mineral bioaccessibility and bioavailability, although the

521 content of minerals of milled cereals can be simultaneously reduced (Gibson et al. 2006;

522 Oghbaei and Prakash 2013).

523 4.2 Soaking

524 Soaking of pulses and cereal grains is a widely applied technique at both household and

525 industrial scales to soften their texture, to reduce the cooking time as well as to influence their

526 nutritional value (Xu and Chang 2008). The technique consists of hydration of the seeds and

527 grains in a soaking medium (mostly water), usually until they reach maximum weight. The

528 nutritional value of these food products, in the context of mineral concentration and mineral

529 bioaccessibility and bioavailability, is influenced by soaking in following ways: removal of

530 antinutrients and minerals (leaking into the soaking medium), pH changes and hydrolysis of

531 phytic acid (by activation of endogenous phytases). First, soaking has the potential to remove

532 some antinutrients, which can be eliminated with the discarded soaking medium. However, the

533 amount of removed antinutrients depends on the antinutrient type, pH and length and

534 conditions of soaking (Gibson et al. 2006). Although it has been observed that soaking has the

535 advantage of decreasing phytic acid and polyphenol levels of for example brown rice (Liang et

536 al. 2008; Albarracín et al. 2013), sorghum (Mahgoub and Elhag 1998) and pulses

23
537 (Vijayakumari et al. 1998; Lestienne et al. 2005; Xu and Chang 2008; Khandelwal, Udipi and

538 Ghugre 2010), simultaneously, it can also cause undesirable losses of minerals such as iron and

539 zinc. Reduced levels up to 60 and 30% for iron and zinc respectively are reported after soaking

540 for sorghum and pearl millet (Lestienne et al. 2005; Afify et al. 2011; Albarracín et al. 2013).

541 It is therefore important to balance both positive and negative aspects of soaking treatments

542 (Liang et al. 2008). Additionally, during soaking, pH changes may occur as well (Raes et al.

543 2014). Lowering the pH may reduce the complexation of bivalent minerals to pectin (Debon

544 and Tester 2001; Kyomugasho et al. 2017), and in this way the amount of free iron and zinc

545 can be increased. Further, due to the activation of phytase during soaking, phytic acid can be

546 hydrolyzed into lower inositol-phosphates (e.g. IP4 and IP3), which have a lower capacity to

547 bind minerals (Sandström and Sandberg 1992). It was reported that soaking cereals such as

548 pearl millet with endogenous or exogenous phytase enzymes, at optimum conditions,

549 significantly improved the in vitro bioaccessibility of iron and zinc by 2–23% (Lestienne et al.

550 2005). Additionally, Hurrell et al. (1992), showed that iron absorption from soy-protein isolates

551 in humans increased four- to fivefold after an exogenous phytase treatment of the isolates.

552 4.3 Dehulling

553 When considering processing of pulses, dehulling, next to soaking, is commonly seen as one

554 of the most applied processing techniques (Wang 2005). Pulse seeds are commonly composed

555 of cotyledons and a seed coat. Upon dehulling, the seed coat of soaked pulses is removed and,

556 in most cases, discarded (Black, Singh and Meares 1998). By discarding this fraction, both

557 minerals and antinutrients can be removed. For example, it has been observed that the seed

558 coat of different common bean varieties in general can contain over 85% of total calcium while

559 cotyledons can contain over 75% of total potassium (Moraghan and Grafton 2002; Ribeiro et

560 al. 2012). However, for minerals such as iron, zinc and copper, the accumulation can vary

561 widely between seed coat and cotyledon fraction depending on the common bean variety

24
562 (Ribeiro et al. 2012). Concerning antinutrients, discarding the seed coat in pulse seeds does not

563 necessarily lead to a decrease in phytic acid content, since it is mainly present in the cotyledons

564 (Gibson et al. 2010). Contrarily, dietary fibers and tannins are primarily located in the seed coat

565 and therefore their concentration in pulse seeds will decrease by removal of this fraction

566 (Troszynska et al. 1997; Diaz, Caldas and Blair 2010; Shahidi et al. 2001; Sreerama et al. 2010;

567 Eashwarage et al. 2017). Moreover, pectin in the seed coat of common beans has been shown

568 to have structural characteristics important for binding minerals (cfr.§2.1) (Chigwedere et al.

569 2018). Because this physical separation technique is often combined with other processing

570 methods, information on the effect of dehulling of pulses on the improvement of their mineral

571 bioavailability is scarce (Ghavidel and Prakash 2007). In addition, the interplay between the

572 removal of both minerals and antinutrients (e.g. dietary fibers and tannin but in many cases not

573 of phytic acid) gives extra complexity to this manner. In this context, Luo, Xie and Cui (2010)

574 reported that although faba beans were dehulled, they did not show significant increased iron

575 and zinc bioavailabilities indicating that the reduction of the mineral content, by removing the

576 seed coat, is an important factor.

577 4.4 Fermentation

578 Fermentation, initially applied as a preservation technique, depends on the biological activity

579 of microorganisms for production of a range of metabolites which can suppress the growth and

580 survival of undesirable microflora in food products (Ross, Morgan and Hill 2002). Nowadays,

581 fermented foods are consumed both in developing and industrialised countries, not only for the

582 benefit of preservation and safety, but also for their sensory characteristics (e.g. flavour, aroma

583 and texture) (Holzapfel 2002). During non-spontaneous fermentation, raw, soaked and/or

584 heated pulse seeds or cereal grains, in a moist solid state, are inoculated with (various)

585 microorganisms (Holzapfel 2002). There are three main kinds of microorganisms used in the

586 fermentation of pulses and cereals: lactic acid bacteria, bacteria of the genus Bacillus,

25
587 Aspergillus fungi and yeasts (Raes et al. 2014). Some microorganisms associated with

588 fermented foods, are capable of producing enzymes (e.g. phytase and polyphenol oxidase)

589 which can degrade antinutrients such as phytic acid and polyphenols. Additionally, lactic

590 fermentation leads to lowering of pH as a consequence of production of organic acids, mainly

591 lactic acid, which is favourable for endogenous phytase and polyphenol oxidase activity

592 (optimal pH ranges from 4.5 to 6.0) (Konietzny and Greiner 2002; Sandberg 2002; Towo,

593 Matuschek and Svanberg 2006). Moreover, a pH change can affect the complexation of

594 antinutrients with minerals, as mentioned in §4.2, and an acidic environment may result in

595 abstraction of hydride ions and rearrangement of phenolic structures (Towo, Matuschek and

596 Svanberg 2006). Incorporation of these organisms into starter cultures may, therefore, improve

597 mineral bioaccessibility and bioavailability (Gibson and Hotz 2001; Duhan, Khetrapaul and

598 Bishnoi 2004). Besides degrading phytic acid and polyphenol content, fermentation could also

599 improve mineral bioavailability by virtue of the formation of organic acids, which can form

600 soluble and absorbable ligands with the minerals, thereby preventing the formation of insoluble

601 complexes with for example phytic acid (Sandberg 2002; Hemalatha, Platel and Srinivasan

602 2007; Sokrab, Ahmed and Babiker 2014).

603 4.5 Germination

604 This process, whereby dry pulses and cereal grains are soaked in water, drained of water and

605 allowed to germinate in humid and warm (20-30°C) environments, results in the start of a

606 sequence of biochemical reactions. For example, germination leads to an increase in phytase

607 activity through de novo synthesis and/or activation of endogenous phytase. Phytase activity

608 during germination is needed to mobilize phosphorus from phytic acid, as it is required for the

609 growth of the new seed. Relative to the soaking process, an increase in phytate degradation of

610 4-50% is observed in sorghum and millet, depending on the type of pulse or cereal grain studied

611 (Eyzaguirre et al. 2006; Afify et al. 2011). In addition, Hemalatha, Platel and Srinivasan (2007)

26
612 and Kayodé et al. (2013) observed a decrease in tannin content in several pulses and cereal

613 grains after germination. The loss of phenolic compounds during germination could be due to

614 enzymatic activity (polyphenol oxidase), conversion into other phenolics, leaching, and

615 complex formation with proteins. Hemalatha, Platel and Srinivasan (2007) reported that

616 germination of food grains had contrasting effects on the bioaccessibility of zinc and iron. Zinc

617 bioaccessibility of chickpea was not affected while it was significantly decreased in the case of

618 finger millet (up to 38%) and green gram (up to 44%). Iron bioaccessibility increased by 62%

619 in green gram, by 39% in chickpea and by 20% in finger millet after germination. Platel,

620 Eipeson and Srinivasan (2010) observed as well that in general the impact of germination on

621 zinc bioaccessibility is much lower (or even negative) compared to the one observed for iron.

622 4.6 Thermal processing

623 The previously described processing techniques are mainly applied on pulses and cereal grains.

624 Heat treatments, such as cooking, pasteurization, sterilization, microwave heating and roasting,

625 are more widely used. These techniques all differ in temperature-time profiles obtained during

626 the process, as well as by the use of dry or wet heating technologies (Wang and Sun 2016).

627 Since minerals are heat-stable, they will not be destroyed during the treatment, but they can

628 leach out if wet heating is performed (Schroeder 1971). In addition, in the case of wet heat

629 treatments, heat-stable antinutrients such as phytic acid and polyphenols (predominant in seed

630 coats and outer layers) can leach out as well (Wang et al. 2010). Rehman and Shah (2005)

631 reported for pulses a reduction of about 21-27% tannin and 24-35% phytic acid contents upon

632 cooking. The reduction of phytic acid and tannin has been shown to increase mineral

633 bioaccessibility and bioavailability (Disler et al. 1975; Brune, Rossander and Hallberg 1989;

634 Hurrell, Reddy and Cook 1999; Layrisse et al. 2000; Petry et al. 2010; Gupta, Gangoliya and

635 Singh 2015). Dietary fiber has shown to be effected by thermal processing (Dhingra et al.

636 2012). In general, heat treatments can change the ratio between insoluble and soluble fibers as

27
637 well as the total dietary fiber content (Elleuch et al. 2011). However, no clear statement upon

638 fiber increase or decrease during thermal treatment can be made due to conflicting results in

639 current literature. On the one hand, Rehman and Shah (2004) reported, for example, a decrease

640 of insoluble dietary fiber components (e.g. cellulose and hemicellulose) after cooking pre-

641 soaked pulses. Reduction of these components could be attributed to partial degradation of

642 cellulose and hemicellulose into simple carbohydrates (e.g. glucose, arabinose, xylose and

643 galactose) since an increased temperature has been reported to split glycoside linkages in

644 dietary fiber polysaccharides (Nyman and Asp 1987). On the other hand, cooking significantly

645 increased the insoluble dietary fiber fraction for all pulses studied by Wang et al. (2010). This

646 increase may be due to formation of protein-fiber complexes after Maillard reactions, induced

647 by the cooking process, in which carbohydrates and proteins condense to form insoluble

648 polymers (e.g. lignin) (Van Soest and Robertson 1979). Changes in soluble dietary fiber

649 content, as a consequence of thermal treatment, can be due to leaching in the cooking media

650 (causing a decrease) and formation of resistant starch and Maillard reaction products (causing

651 an increase) (Van Soest and Roberson 1979; Osorio-Diaz et al. 2003; Dhingra et al. 2012).

652 Moreover, more soluble fiber is expected to leach out after thermally induced depolymerization

653 of the fiber. Upon depolymerization, caused by heat processing of plant-based foods, soluble

654 dietary fiber shows a shift towards a lower molecular weight (Sila et al. 2009). When pectin is

655 depolymerized, it is believed that the mineral binding capacity will be reduced (Kyomugasho

656 et al. 2018). Because of these contradictory phenomena, studies reported decreasing, increasing

657 and non-changing soluble dietary fiber fractions in plant-based foods after thermal treatment.

658 In legumes and cereals, both decrease and increase of soluble dietary fiber has been reported.

659 For example, Kutos et al. (2003) studied the modifications that happen during the thermal

660 processing of kidney beans and reported that total fibre content was reduced mainly due to loss

661 of soluble fibre. However, Puna and Paruchuri (2004) did not see a significant change on the

28
662 total, soluble and insoluble dietary fiber contents in green leafy vegetables upon cooking.

663 Mainly a changing soluble dietary fiber content is believed to affect the mineral bioaccessibility

664 and bioavailability of plant-based foods since the mineral binding capacity of insoluble dietary

665 fibers is negligible (Persson et al. 1987). However, an effect on mineral bioaccessibility caused

666 by changes in soluble and insoluble dietary fiber content (due to thermal processing) still

667 should be confirmed by research.

668 Thermal processing has also the potential to enhance mineral bioaccessibility and

669 bioavailability by releasing them from entrapment in the plant matrix, by influencing several

670 physical barriers in plant-based foods. On the one hand, food processing by heat can generally

671 alter bioaccessibility and bioavailability of macronutrients (Hemalatha, Platel and Srinivasan

672 2007). Depending on starch type and type of heat treatment, gelatinization may occur (Ma et

673 al. 2011). Since gelatinized starch is more susceptible to α-amylase, this form of starch is more

674 easily digestible (Batey 1982). Besides, protein denaturation, which enhances protein

675 digestibility, can occur during thermal processing (Davis and Williams, 1998). This implies

676 that thermal processing can have a positive influence on mineral bioaccessibility and

677 bioavailability if, as mentioned in §3.2, it is hypothesized that undigested macronutrients,

678 surrounding minerals, can form a physical barrier for mineral transfer to the absorption site in

679 the small intestine. Moreover, since protein digestibility increases when food is heated, protein-

680 bound elements can be released which can improve the absorption of these micro-elements

681 (Oliveira et al. 2018). On the other hand, heat processing can also alter the plant cell wall

682 structure, cell wall softening and disruption. This effect can mainly be attributed to

683 solubilization and depolymerization of pectin in the middle lamella (Sila et al. 2009; Njoroge

684 et al. 2016). As a consequence, the adhesion between surrounding cells is reduced which

685 facilitates the release of intact cells upon mechanical stress (e.g. grinding or chewing) (Dhital

686 et al. 2016; Pallares et al. 2018). If during mechanical stress cells are separated instead of

29
687 broken down, the cell content cannot be released and the cell wall can remain a physical barrier

688 for mineral release and absorption. However, if during processing the cell wall becomes

689 permeable (as pectin is solubilized), it is expected that small molecules and compounds can

690 still be released. Because of this phenomena, the sequence of processing techniques can be of

691 relevance. For example, if pulse seeds are grinded before thermal processing, the cell wall as a

692 physical barrier will be eliminated and cell content will be released. However, if pulse seeds

693 are first thermally processed, grinding will lead to cell separation and the (more permeable)

694 cell wall can nevertheless still remain a physical barrier.

695 In addition, depending on the heat treatment, enzymes will be inactivated in most cases. As a

696 consequence, phytase for example, will no longer contribute to the enhancement of mineral

697 bioaccessibility and bioavailability (Raes et al. 2014).

698 In general, thermal processing can influence mineral bioaccessibility and bioavailability in

699 several ways. The interplay between these factors makes investigating the effect of thermal

700 processing a complex matter, therefore further research is needed.

701 5. Conclusions and future outlook

702 The reduced iron and zinc bioaccessibility and bioavailability from plant-based foods can be

703 attributed to several inherent factors such as the presence of mineral antinutrients and physical

704 barriers. Insoluble and non-absorbable mineral chelates, formed with dietary fiber, phytic acid,

705 and some polyphenols in the plant-based food system or in the digestive tract cannot be broken

706 down during human digestion and consequently, they cannot be absorbed in the small intestine.

707 In addition, minerals which are bound to absorbable polyphenols are generally not released

708 during the polyphenol metabolism. Among dietary fibers, mostly soluble dietary fiber (such as

709 pectin) negatively influences iron and zinc absorption. The binding strength of minerals for

710 phytic acid is proportional to their atomic mass and electronegativity. Therefore, zinc has been

30
711 shown to form stronger complexes with phytic acid than lighter atoms, such as iron. As a result,

712 phytic acid negatively impacts zinc absorption at lower concentrations compared to iron

713 absorption. In the case of polyphenols, mainly iron absorption is inhibited.

714 The quest of why mineral bioaccessibility and bioavailability is reduced in plant-based food

715 systems is an intricate matter. In reality, the reduced mineral bioaccessibility and

716 bioavailability can never be attributed to a single factor only, for example, there is always

717 competition at several levels inside a plant-based food system. Minerals are involved in mutual

718 competition to bind antinutrients, while antinutrients compete each other to bind minerals.

719 Moreover, as mentioned before, an antinutrient can be bound to another antinutrient (e.g. phytic

720 acid and polyphenols to dietary fiber) which should be kept in mind when investigating reduced

721 mineral bioaccessibility and bioavailability in plant-based food systems. Furthermore, mineral

722 antinutrients can also form insoluble complexes with dietary proteins, starch and other

723 carbohydrates, reducing their digestibility as well. It becomes even more complicated since

724 minerals and the mineral chelates are embedded in a food matrix, surrounded by macronutrients

725 and a cell wall, forming physical barriers. Overall, the interplay between antinutrients, minerals

726 and other factors creates a very complex system, playing an essential part in the understanding

727 of mineral bioaccessibility and bioavailability in real food systems.

728 The positive effect of different processing techniques on mineral bioaccessibility and

729 bioavailability of plant-based foods, mostly relies on the fact that the amount of antinutrients

730 is reduced due to the removal of fractions rich in antinutrients and/or due to their leaching into

731 the processing liquid. In addition, activation of enzymes (e.g. phytase) can enhance mineral

732 bioaccessibility and bioavailability. Although processing can have a positive effect, it also can

733 induce a reduced mineral concentration and mineral bioaccessibility and bioavailability (e.g.

734 leaching out minerals, cell wall intactness when grinding is applied after cooking, phytase

735 inactivation during thermal processing).

31
736 Breeding programs to grow new varieties with lower antinutrient levels can also be a solution,

737 besides reducing antinutrient content through processing. However, the function that mineral

738 antinutrients have in plants, should not be forgotten. In addition, it should be taken into account

739 that mineral antinutrients can possess other health-promoting effects as well.

740 Challenges in investigating mineral bioaccessibility and bioavailability in plant-based foods

741 and how this can be influenced by food processing, not only include the complexity of the

742 interplay between all the possible barriers but also include strategic choices that need to be

743 taken in the context of the relevant experimental set up for the investigation of this problem.

744 Nowadays, mineral bioaccessibility is mainly evaluated by in vitro methods. They offer a

745 standardized, high-throughput screening method that may predict mineral bioaccessibility. By

746 expanding these methods with, for example, relevant cell lines, an idea on nutrient

747 bioavailability can be given. Nevertheless, estimating nutrient bioavailability in foods ideally

748 should be determined by in vivo studies, taking into account the whole range of nutritional,

749 physiological and ecological factors that can influence absorption (Guéguen & Pointillart,

750 2000). Therefore, in vitro methods should be seen as good screening methods, but validation

751 by in vivo methods is necessary. However, nowadays it is still difficult to examine long term

752 and between- and inter-person variations effects by in vivo methods. In addition, there is a need

753 to investigate the specific role of the gut microflora on mineral release and to what extend

754 minerals are functionalised in the colon. Furthermore, researchers should not only focus on

755 pulses and cereal for investigating this matter (which mainly has been done now), but should

756 also include more often other plant-based foods such as fruit and vegetables, which might not

757 be best plant-based sources for minerals but might be rich in relevant antinutrients as well.

32
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1280 Wang, Y., Zeng, T., Wang, S.E., Wang, W., Wang, Q. and Yu, H.X. (2010). Fructo-
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1298 increases absorption of calcium and magnesium in the large intestine of the rat. Brit. J.
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1300 Zhou, J. R., Fordyce, E.J., Raboy, V., Dickinson, D. B., Wong, M. S., Burns, R. A. and
1301 Erdman Jr., J.W. (1992). Reduction of phytic acid in soybean products improves zinc
1302 bioavailability in rats. J. Nutr. 122: 2466-2473.

1303

47
1304 Table 1. Amounts of iron and zinc (mg) in plant-based foods (average per 100 mg) (Belitz, Grosch and Schieberle. 2009;

1305 Bielsalski 2013; Hayat et al. 2014; Saini, Nile and Keum 2016; Gregory et al. 2016).

Vegetables Fruits Cereals Legumes

Iron (mg 100 g-1) 0.3-13.9 0.2-2.8 1.5-7.6 6.2-15.7
Zinc (mg 100 g-1) 3.1-38.7 0.5 1.1-7.6 1.0-10.9
1306

1307

48
1308
1309 Figure 1. The egg-box model of calcium crosslinking in pectic polysaccharides. Reprinted, with permission, from

1310 Caffall and Mohnen (2009). The structure, function, and biosynthesis of plant cell wall pectic polysaccharides.

1311 Carbohydrate research, 14: 1879-1900. Copyright (2018).

1312

49
1313
1314 Figure 2. Schematic representation of structural characteristics of pectin which can influence pectin-mineral binding capacity. For each characteristic: above, a possible

1315 schematic presentation of a single pectin molecule is shown; below, a possible simplified scheme of pectin-mineral crosslinkings between pectin molecules is shown. This is a

1316 simplified representation, combination between different characteristics is possible. GalA: Galacturonic acid residue; 6-O Me GaIA: Galacturonic acid residues with

1317 methylesterification at O-6 position; Gal: D-galactose; Rha: L- rhamnose; Ara: D- arabinose.

1318

50
1319

1320
1321 Figure 3. Basic chemical structure of phytic acid. Reprinted, with permission, from Kumar et al. (2010). Dietary

1322 roles of phytate and phytase in human nutrition: A review. Food Chemistry, 120: 945–959. Copyright (2018).

51
1323

1324 Figure 4. Basic chemical structure and numbering system of flavonoids. Reprinted, with permission, from

1325 Prochazkova, Bousova and Wilhelmova (2011). Antioxidant and prooxidant properties of flavonoids. Fitoterapia,

1326 82:513–523. Copyright (2018).

1327

52
1328

1329 Figure 5. Chemical structure of tannic acid. Reprinted, with permission, from Xu, Han and Wang (2019). Effect

1330 of tannic acid on corrosion behavior of carbon steel in NaCl solution. Journal of Materials Science & Technology,

1331 1:64–75. Copyright (2018).

53
1332

1333 Figure 6. Expected octahedral coordination geometry of general iron-polyphenol complexes. Gallols, R=0H;

1334 catechols, R=H. Reprinted, with permission, from Perron and Brumaghim (2009). A review of the antioxidant

1335 mechanisms of polyphenol compounds related to iron binding. Cell Biochemistry and Biophysics, 53: 75-100.

1336

54
1337

1338 Figure 7. Fenton and Haber-Weiss reactions.

1339

55
1340

1341 Figure 8. Schematic representation of possible plant tissue disintegration after mechanical disruption. During

1342 mechanical disruption two characteristic tissue failure modes may occur: cell separation and/or cell breakage. In

1343 the case of cell breakage, the cell wall is ruptured and cell content (e.g. starch, protein and minerals) is released.

56