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Is There Such a Thing as "Anti-Nutrients"? A Narrative Review of Perceived Problematic Plant Compounds



Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to promote antioxidant defense and reduce inflammation. While recommendations encourage the intake of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase plant-food consumption, there have been some concerns raised about whether they are beneficial because of the various 'anti-nutrient' compounds they contain. Some of these anti-nutrients that have been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins. As a result, there may be select individuals with specific health conditions who elect to decrease their plant food intake despite potential benefits. The purpose of this narrative review is to examine the science of these 'anti-nutrients' and weigh the evidence of whether these compounds pose an actual health threat.
Is There Such a Thing as “Anti-Nutrients”?
A Narrative Review of Perceived Problematic
Plant Compounds
Weston Petroski and Deanna M. Minich *
Human Nutrition and Functional Medicine Graduate Program, University of Western States,
2900 NE 132nd Ave, Portland, OR 97230, USA;
Received: 2 August 2020; Accepted: 22 September 2020; Published: 24 September 2020
Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases.
The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to
promote antioxidant defense and reduce inflammation. While recommendations encourage the intake
of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase
plant-food consumption, there have been some concerns raised about whether they are beneficial
because of the various ‘anti-nutrient’ compounds they contain. Some of these anti-nutrients that have
been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins.
As a result, there may be select individuals with specific health conditions who elect to decrease their
plant food intake despite potential benefits. The purpose of this narrative review is to examine the
science of these ‘anti-nutrients’ and weigh the evidence of whether these compounds pose an actual
health threat.
anti-nutrient; goitrogens; oxalates; phytates; phytoestrogens; plant-based diet;
phytonutrients; tannins
1. Introduction
Longstanding evidence suggests that consuming a diet rich in plant-based foods plays a significant
role in prevention and reduction of chronic diseases, such as cardiovascular disease, cancer, stroke,
dementia, diabetes, cataracts, and others [
]. Well-researched dietary patterns including the
Mediterranean, Dietary Approaches to Stop Hypertension (DASH), vegan and vegetarian, as well as
the hunter-gatherer (Paleolithic) diet, all provide ample amounts of whole foods in some capacity,
including fruits, vegetables, nuts, legumes, and/or whole grains. Though specific aspects of these
eating patterns may dier, they all encourage a variety of nutrient-dense, unprocessed plant foods,
and reduced consumption of processed grains, added sugars and salt [37].
Similarly, the 2015–2020 Dietary Guidelines for Americans recommends eating a variety of
nutrient-dense foods, particularly dark green vegetables, red and orange vegetables, and legumes [
Despite continuing educational eorts by the USDA, total fruit and vegetable intake remains exceedingly
low, with less than 10% of Americans meeting recommended vegetable and fruit guidelines of
2.5 servings/day and two servings/day, respectively [
]. On the other hand, daily intakes of energy-dense
refined grains are significantly higher than recommended values. Consuming a wide spectrum
of plant foods ensures that individuals meet nutritional needs while staying within suggested
energy requirements.
Plant-based foods, beyond micro- and macronutrients, contain significant concentrations of
bioactive plant compounds. Research demonstrates that the reduction in chronic disease risk
Nutrients 2020,12, 2929; doi:10.3390/nu12102929
Nutrients 2020,12, 2929 2 of 32
may be attributed to the synergistic eects of these anti-inflammatory phytochemicals, including
an endless array of polyphenols, alkaloids, carotenoids, organosulfur compounds, terpenoids,
and phytosterols [1,2]
. Due to the diverse and complex interactions of vitamins, minerals and
phytochemicals in a single food, health eects of a whole food, or combination of foods, will likely
be significantly dierent than that of isolated compounds [
]. To complicate research even further,
interaction of phytochemicals and microbiota within the intestinal environment could alter both
bioavailability and biological eects [
]. For these reasons, elucidating the physiological eects of
individual plant components obtained through dietary sources, composed of thousands of dierent
compounds, is an implausible task.
More recently, various research has questioned the healthfulness of plant-foods because of the
presence of certain compounds, termed ‘anti-nutrients’. These purported antinutrients, which include
lectins, oxalates, phytates, phytoestrogens, and tannins, are thought to restrict bioavailability of key
nutrients, while other studies conclude they may have health promoting eects [
] (Table 1).
The purpose of this narrative review article is to provide an objective, scientific literature review
of antinutrient compounds to assess whether they impose any significant health risk, and, further,
whether they incur clinical implications.
Table 1. Plant Compounds, Food Sources, and Their Suggested Clinical Implications.
‘Anti-nutrient’ Food Sources Suggested Clinical Implications
Lectins Legumes, cereal grains, seeds,
nuts, fruits, vegetables Altered gut function; inflammation
Spinach, Swiss chard, sorrel,
beet greens, beet root, rhubarb,
nuts, legumes, cereal grains,
sweet potatoes, potatoes
May inhibit calcium absorption;
May increase calcium kidney
stone formation
Phytate (IP6)
Legumes, cereal grains,
pseudocereals (amaranth,
quinoa, millet), nuts, seeds
May inhibit absorption of iron, zinc
and calcium; Acts as an antioxidant;
Antineoplastic eects
Brassica vegetables (kale,
Brussels sprouts, cabbage, turnip
greens, Chinese cabbage,
broccoli), millet, cassava
Hypothyroidism and/or goiter;
Inhibit iodine uptake
Soy and soy products, flaxseeds,
nuts (negligible amounts), fruits
and vegetables
(negligible amounts)
Endocrine disruption; Increased risk
of estrogen-sensitive cancers
Tea, cocoa, grapes, berries,
apples, stone fruits, nuts, beans,
whole grains
Inhibit iron absorption; Negatively
impact iron stores
2. Lectins
2.1. Definition
Lectins, or hemagglutinins, are a diverse family of carbohydrate-binding proteins found in almost
all organisms, including plants, animals, and microorganisms [
]. These proteins/glycoproteins
possess the unique capability to reversibly bind to specific carbohydrate moieties on cells, resulting
in erythrocyte agglutination. The carbohydrate specificity of lectins allows them to function in cell
recognition, tissue development, host defense and tumor metastasis in both plants and animals [
Over 500 lectins have been isolated and identified from plants, who produce them primarily as defense
mechanisms against insects, molds, fungi and diseases [14].
Nutrients 2020,12, 2929 3 of 32
2.2. Background
Plant lectins are widely distributed throughout the plant kingdom, available from many dietary
sources including legumes, seeds, nuts, fruits, and vegetables [
]. Insignificant amounts of lectins are
consumed from unprocessed fruits and vegetables, while raw legumes and whole grains are far more
concentrated sources of dietary lectins. Due to their high culinary use around the globe and potential
for toxicity, Phaseolus vulgaris (common bean) lectins (PHA), and wheat germ agglutinin (WGA) derived
from wheat, have arguably received the most attention by researchers [
]. Common beans include
dark and light red kidney beans, pinto beans, black beans, and white beans. An analysis of raw Canadian
legumes measured hemagglutinating activity against rat erythrocytes and found that soybeans showed
the highest activity (692.8 HU/mg), followed by common beans (Phaseolus vulgaris) (87.69–88.59 HU/mg),
lentils (10.91–11.07 HU/mg), peas (5.53–5.68 HU/mg), fava beans (5.52–5.55 HU/mg), and chickpeas
(2.73–2.74 HU/mg), respectively [19].
Lectin content may vary with regards to cultivar, cultivation area, and disease susceptibility.
Spanish cultivars of chickpeas and fava beans contained greater amounts of lectins, but lesser amounts
in soybeans and kidney beans as compared to Canadian pulses [
]. Sun et al. found significant
variations in PHA levels among fresh kidney bean cultivars, ranging from less than 200 ug/g to more
than 51,200 ug/g. PHA levels appeared to decrease with bean maturity, as concentrations are highest
during the growth period for protection [
]. Disease susceptibility and genetic resistance may also
play a role in lectin content [21,22].
2.3. Eects of Cooking/Processing
Although lectins are fairly resistant to enzymatic digestion in the gastrointestinal tract, they can
be removed from foods by various processes (Table 2). For example, soaking, autoclaving, and boiling
causes irreversible lectin denaturation. Boiling legumes for one hour at 95
C reduced hemagglutinating
activity by 93.77–99.81% [
]. Adeparusi et al. found that autoclaving lima beans for 20 min eliminated
all anti-nutrients except tannins [
]. Boiling of red and white kidney beans, notoriously rich in
phytohemoggluttinin (PHA), also resulted in complete elimination of lectins [
]. Microwave ovens on
the other hand, are not an eective method for lectin deactivation. Though microwaving destroyed
hemagglutinins in most legume seeds, it did not significantly aect lectins in common beans [
Additionally, fermentation over 72 h has been demonstrated to destroy almost all lectins in lentils
(Lens culinaris) [26].
Table 2. Preparation tips for reducing ‘anti-nutrients’.
‘Anti-nutrient’ Food Preparation that Reduces Food Preparation that Increase
Lectins Soaking, boiling, autoclaving,
germination, fermentation Roasting, baking
Soaking, boiling, steaming, pairing
with high calcium foods
Roasting, grilling, baking,
low-calcium diet
Phytates Soaking, boiling, germination,
fermentation n/a
Tannins Cooking, peeling skins of fruits
and nuts n/a
Phytoestrogens n/aBoiling, steaming, fermenting
(increases aglycone content)
Goitrogens Steaming, boiling
2.4. Safety
The safety and overall health eects of dietary lectins has long been a topic of concern among
researchers, with some suggesting that they are harmful to health, hence the term ‘anti-nutrients’ [
Nutrients 2020,12, 2929 4 of 32
Cases of food poisoning involving raw or inadequately cooked legumes are well documented [
For example, in the UK between 1976 and 1989, 50 cases of food poisoning were suspected to be caused
by inadequately prepared kidney beans [
]. PHA toxicity, caused by consumption of fresh kidney
beans, is also common in China, and aected over 7000 individuals between 2004 and 2013 [
]. In all
cases, beans were either consumed raw, soaked, or cooked using temperatures inadequate to destroy
PHA. Nonetheless, PHA toxin appears to be eliminated by 10 min of boiling [
]. Mechanistically,
lectins and hemagglutinins are resistant to digestion by both host enzymes and bacteria, and therefore
pass through the gastrointestinal tract functionally and immunologically intact. Upon arrival into the
small intestine, lectins can bind to glycan receptors and glycoconjugates on the luminal surface of the
enterocytes [30,31].
In animal models, high doses of isolated legume lectins and raw legume flours have been shown
to impair the integrity of the intestinal mucosa by inducing intestinal hyperplasia, altering villus
architecture, reducing disaccharidase activity, increasing intestinal permeability and activating the
immune system (Table 1) [
]. This change in intestinal integrity resulted in compromised nutrient
absorption (protein, lipid and vitamin B12) and reduced growth of experimental animals [
Nciri and colleagues demonstrated that administration of 300 mg of a raw Beldia bean (white kidney
bean) flour for 10 days caused intestinal alterations, distorted jejunum morphology of the microvilli,
and reduced
enzyme activity in mice [
]. Another proposed mechanism of PHA toxicity is intestinal
dysbiosis secondary to PHA-induced intestinal damage [
]. Clinical human trials using whole
(cooked) beans, on the other hand, do not exhibit the same eects as
in vitro
in vivo
animal models
that use isolated lectins and raw bean flours [24].
2.5. Human Studies
Clinical human trials of lectin administration are limited. Though lectins from raw legume flours
demonstrate adverse eects when administered in isolation in animal models, cooking/autoclaving
beans resulted in complete amelioration of PHA and associated erythrocyte agglutination in humans [
Contradictory findings may be due to studies which employ animal models, cell cultures, and use
isolated lectins. This does not simulate real world scenarios, where lectins are consumed in relatively
small amounts with combinations of other foods and bioactive components [40].
In contrast to the anti-nutritional characteristics of lectins initially proposed by many researchers,
some evidence suggests that lectins may have therapeutic benefits and could be used as functional
foods and nutraceutical agents. Because of lectins’ strong anity and specificity to glycans, interest
lies in their potential as both cancer diagnostic and treatment tools [
]. Current approaches to cancer
treatment are often accompanied by harmful side eects due to their poor target specificity, but lectins
can identify cancer cells by their secretion of unusual glycan structures. Therefore, lectins are being
researched as adjuvants, alongside conventional chemotherapy agents [
]. Legume lectins isolated
from lentils, chickpeas, jack beans, peas and common beans all show anti-proliferative activity against
various cancer cell lines, however, human clinical trials are still needed before any conclusions can be
made [14].
2.6. Conclusions
Overall, research does demonstrate that lectin-rich foods, if not prepared properly, can lead
to food poisoning. However, traditional processes such as soaking, sprouting, fermenting, boiling,
and autoclaving are all methods that can significantly reduce lectin content. In the case of particularly
high-lectin legumes, such as soybeans and kidney beans, boiling or autoclaving is required to eliminate
lectins, as reduced cooking temperatures do not significantly aect lectin content. In their whole
and cooked form, there is currently no strong evidence from human trials to support the claim that
lectin-rich foods consistently cause inflammation, intestinal permeability, or nutrient absorption issues
in the general population. Vojdani et al. tested 500 individuals for anti-lectin antibodies and found
a range of immunoreactivity between 7.8% and 18% against dierent lectins, therefore, there may
Nutrients 2020,12, 2929 5 of 32
be some individuals who respond to undigested lectins [
]. Of note, legumes and other lectin-rich
plant foods are excellent sources of essential amino acids, prebiotic fibers, vitamins, minerals as
well as powerful antioxidant and anti-inflammatory compounds [
]. Diets rich in legumes and
whole grains are associated with reduced inflammatory biomarkers in both animal and human
trials [
]. Until further human clinical trials demonstrate otherwise, the health-promoting eects
of lectin-containing foods would seem to far outweigh any possible negative eects of lectins.
3. Oxalates
3.1. Definition
Oxalate, or oxalic acid, is a substance that can form insoluble salts with minerals, including
sodium, potassium, calcium, iron, and magnesium. These compounds are produced in small amounts
in both plants, and mammals. All major groups of photosynthetic organisms produce oxalate. It is
suggested that plants manufacture oxalate for a variety of functions including calcium regulation,
plant protection, and detoxification of heavy metals [
]. In mammals, endogenous oxalate is a
metabolite of ascorbate, glyoxylate, hydroxyproline and glycine. Urinary oxalate mostly consists of
endogenous oxalate, as opposed to exogenous dietary oxalate. Plant-derived oxalate is available in
several dierent forms; as either water-soluble oxalate (oxalic acid, potassium, sodium and ammonium
oxalates) or insoluble oxalate salts (primarily as calcium oxalate) [
]. Soluble (unbound) oxalates can
chelate minerals, reducing absorption, or are absorbed through the intestines and colon. Absorbed
dietary oxalates are believed to contribute to calcium oxalate kidney stone formation [
]. Insoluble
oxalates, on the other hand, are excreted in the feces [
]. Due to their eects on nutrient absorption
and possible role in kidney stone formation, oxalates are considered by some to be ‘antinutrients’.
Although events of toxicity have occurred in livestock chiefly grazing on oxalate-rich plants [
a balanced human diet typically contains only small amounts of oxalates [53].
3.2. Background
Oxalates are present in many commonly consumed plant foods. Plant foods with the highest
oxalate content include spinach, swiss chard, amaranth, taro, sweet potatoes, beets, rhubarb,
and sorrel
Raw legumes, whole grains, nuts, baking cocoa and tea also contain oxalate, though in smaller amounts.
Distribution of oxalate within a plant can vary. Leaves (spinach, beet greens) are reported to have far
greater oxalate content than stalks (rhubarb) or roots (beets, carrots). A distinction should be made
between total oxalate, soluble and insoluble oxalate, as excess soluble oxalate has more of an eect on
bioavailability and kidney stone formation [
]. Chai and Liebman reported fresh spinach to contain an
average of 1145 mg/100 g fresh weight (FW) total oxalate, 803 mg being in the soluble form, and 343 mg
being insoluble oxalate [
]. Another group found spinach to contain 978 mg/100 g FW of total oxalate,
543 mg of that being soluble oxalate [
]. Nuts are also reported to be rich in oxalates, ranging from
42 mg/100 g in raw macadamia nuts, to 140, 262, and 469 mg/100 g in roasted peanuts, cashews
and almonds, respectively. Soluble content in peanuts and almonds were found to be 108 mg and
153 mg/100 g [
]. Wheat bran contains a somewhat higher amount of soluble oxalate (113 mg/100 g
dry weight (DW)), while whole grain products contain much less (13.8 mg in oats, 44 mg/100 g in
whole wheat flour) [57].
Rawlegumesvarywidelyin oxalatecontent.Soybeanscontainthegreatestamount(
370 mg/100 g DW
followed by lentils and peas (168–293 mg/100 g DW), chickpeas (192 mg/100 g DW), and common
beans (98–117 mg/100 g DW) [
]. Soluble oxalate in raw chickpeas and lentils is only a fraction of total
oxalate [
]. Beet root, another vegetable known for its oxalate content, averages 65 mg/100 g FW of
oxalate, with 47 mg being soluble oxalate [
]. Dierences in total oxalate content is variable among
cultivars, season, and growing conditions. For example, among 310 dierent cultivars of spinach,
oxalate concentration ranged from 647.2 to 1286.9 mg/100 g FW, with an average of 984 mg/100 g [
Savage et al., on the other hand, found only 266.2 mg/100 g FW in New Zealand grown spinach [
Nutrients 2020,12, 2929 6 of 32
Horner and colleagues found over a two-fold dierence in oxalate values among 116 cultivars of
soy, ranging from 82 to 285 mg/100 g dry weight [
]. Time of harvest can have additional impacts
on oxalate concentrations [
]. Research has not demonstrated any dierences in oxalate between
organic and conventional cultivars [
]. Oxalate values in raw food items are not representative of
actual content consumed, as items like legumes and greens are typically cooked prior to consumption.
Traditional preparation methods have demonstrated ecacy in significantly reducing oxalate content.
3.3. Eects of Cooking/Processing
Like lectins, the cooking, preparation, and processing of food can impact the oxalate content
and, therefore, mineral availability of food items (Table 2). Due to oxalate’s solubility in water,
wet processing methods such as boiling, and steaming seem to be the most ecient solutions to
decreasing oxalate content. Chai and Liebman reported significant reductions of soluble oxalate in
vegetables by boiling for 12 min, ranging from 30 to 87% [
]. Spinach and Swiss chard experienced the
largest losses (87 and 85%, respectively). Steaming has a lesser impact, though still resulted in losses
of 46% and 42% in green Swiss chard and spinach, respectively [
]. Vegetables with lesser exposed
surface area and relatively small amounts of oxalate, such as beets, carrots and Brussels sprouts, did not
experience similar reductions in soluble oxalate [
]. These results are in agreement with a previous
analysis on New Zealand vegetables [53].
Traditional and industrial cooking methods such as soaking overnight and boiling or autoclaving,
significantly reduces total and soluble oxalate content in legumes. Cooking lentils on a hot plate for
just fifteen minutes reduced soluble oxalate content by 42.6%, and in chickpeas (60 min) by 19.5% [
Common beans (cooked for 45 min) experienced a 59.61% loss in oxalate. Even further reductions of
85.7–92.9% were observed in canning (autoclaving) and microwaving of legumes [
]. It has also been
found that an overnight soak, followed by a 2-h boil reduced soluble oxalate in red beans by 40.5% [
In contrast, there was a 76.9% loss of soluble oxalate in white beans [
]. These dierences may be
due to variations in genetics, growing conditions, cooking times and exact cooking temperatures.
Roasting of peanuts, cashews and almonds did not have any significant impact on oxalate content [
In most
cases, cooking techniques significantly reduces soluble oxalate, and should therefore enhance
mineral availability. Aside from cooking, pairing high-oxalate foods with calcium-rich foods may
oset soluble oxalate absorption. A normal calcium diet (800–1,000 mg/day) should be able to oset
potential inhibitory eects from dietary oxalates [63].
3.4. Safety
Despite evidence of relatively low soluble oxalate concentration in most ‘problematic foods’,
dietary oxalate is thought to play a role in hyperoxaluria, a risk factor in the formation of calcium
oxalate kidney stones (Table 1). Total dietary oxalate intake is only in the range of 50–200 mg, though
in some individuals could be as high as 1000 mg [
]. It has been suggested that dietary oxalate may
contribute up to 50% of total urinary oxalate excretion, and that one-third of stone formers hyper-absorb
oxalate at a rate of more than 10% total oxalate consumed [65].
3.5. Human Studies
A study of 20 healthy men and women found that an oxalate-rich diet (600 mg/day from rhubarb
juice) significantly increased urinary excretion from 0.354 to 0.542 mmol/24 h [
]. However, oxalate is
not typically consumed every day in such a concentrated form as rhubarb juice, but is, instead, a small
fragment in an intricate web of dietary factors. Observing dietary patterns, a prospective analysis from
the Nurses’ Health Study (NHS) found only a modest association between dietary oxalate and kidney
stone formation after multivariate adjustment [
]. Participants in the highest quintile as compared to
the lowest quintile of dietary oxalate, experienced a relative risk of 1.22 for men and 1.21 for older
women. Even more significant, in men with lower calcium intake (<755 mg/day), the risk in the highest
quintile of dietary oxalate jumped to 1.46. Conversely, in men with calcium intake at or above the
Nutrients 2020,12, 2929 7 of 32
median, the multivariate risk dropped to 0.83. Overall, authors concluded that dietary oxalate is not a
major risk factor for stone formation [
]. In a more recent NHS I and NHS II analysis, authors again
concluded that dietary oxalate had little impact on kidney stone formation, while dietary calcium
intake was inversely associated with kidney stone formation [67].
Additionally, dietary potassium, magnesium, and phytate all decrease kidney stone formation
through an array of mechanisms [
]. Despite significantly more dietary oxalates (254 mg/day) and
oxalate-containing foods such as nuts, vegetables, and whole grains, participants with higher DASH
scores have a 40–50% decreased risk of kidney stones [
]. This is perhaps attributed to the protective
and synergistic eects of phytate, potassium, calcium, and other phytochemicals all abundant in the
DASH dietary pattern. Similar findings regarding the protective role of vegetables on urolithiasis risk
were reported by Zhuo et al. [
]. While animal protein consumption was associated with higher kidney
stone risk, vegetable and tea consumption were associated with a decreased risk of stone formation.
Tea is a rich source of oxalate, yet it is believed that polyphenols and other antioxidant phytochemicals
may contribute to the prevention of stone formation [
]. Although there is a connection between
calcium oxalate excretion, exogenous (dietary) oxalate, and stone risk, the association may be more
complex than once believed.
Gastrointestinal health may also play a role in oxalate absorption and associated health risks.
Those with digestive disorders such as inflammatory bowel disease (IBD) have been shown to
be at higher risk for calcium-oxalate kidney stones, assumed to be partially caused by oxalate
hyperabsorption [
]. Patients with bowel disorders often experience deranged intestinal barrier
function, characterized by increased intestinal permeability [
]. Fat malabsorption, secondary to
epithelial damage, may also contribute to excess calcium-fatty acid salts, in turn increasing the
availability of soluble oxalate [
]. The combination of these factors is theorized to increase oxalate
absorption, however, the association between intestinal permeability and oxalate hyperabsorption
has yet to be proven. Interestingly, children with autism have demonstrated increased plasma
and urinary oxalate levels, but not increased risks of kidney stone formation [
]. This result
may be partially explained by increased intestinal permeability and additional dysbiosis found in
those with autism spectrum disorders, though is yet to be completely elucidated [
]. The gut
microbiome, or oxalobiome, may also play a role in reducing dietary oxalates, as bacterial species
like Oxalobacter formigenes possess oxalate-degrading genes [
]. Nonetheless, human trials using
oxalate-degrading probiotics have been mixed, and for the most part, unsuccessful [76,77].
3.6. Conclusions
Despite the demonization of oxalate and promotion of a low-oxalate diet in kidney stone patients,
more recent observational studies of dietary patterns may prompt a reevaluation of current guidelines.
Certain segments of the population do seem to be at greater risk of increased oxalate excretion,
and consuming oxalate-rich foods may play a possible role in kidney stone formation, but other factors
such as food preparation techniques, calcium intake, endogenous oxalate production, and intestinal
health may play a larger role than once thought. Cooking oxalate-rich foods, as well as consuming
adequate amounts of calcium and potassium demonstrate eciency in significantly minimizing
available soluble oxalate from dietary sources. Furthermore, oxalate containing foods possess an array
of protective, beneficial compounds which may outweigh any possible negative eects of oxalate.
4. Goitrogens
4.1. Definition
Plant-derived goitrogens are another set of compounds which have received attention among
nutrition researchers and health professionals. The term ‘goitrogen’ broadly refers to agents that interfere
with thyroid function, thus increase the risk of goiter and other thyroid diseases [
]. Sources of these
compounds include medications, environmental toxins, as well as certain foods [
]. Glucosinolates,
Nutrients 2020,12, 2929 8 of 32
a diverse class of over 120 compounds, are dietary goitrogens found primarily in the Brassica family,
as well as other plant foods [
]. Upon mastication and ingestion, the enzyme myrosinase (activated in
damaged plant tissue and produced by human microflora) converts glucosinolates to a variety of other
compounds, including thiocyanates, nitriles, isothiocyanates and sulforaphane [
]. Much research
surrounding glucosinolates and associated analogues have focused on their potential to prevent cancer,
induce phase II detoxification enzymes, induce apoptosis, regulate redox reactions, and inhibit Phase I
detoxification enzymes [
]. Despite the potential beneficial eects of glucosinolates, some evidence
suggests that goitrin, produced from the glucosinolate precursor, progoitrin, as well as thiocyanate
(an indole glucosinolate degradation product), may have adverse eects on the thyroid (Table 1).
Early animal and cell models demonstrated goitrin and thiocyanate ions to inhibit the thyroid’s
utilization and uptake of iodine [80,88,89].
4.2. Background
Vegetables in the Brassica genus are the most well-known goitrogen containing foods, although there
is an enormous variation of these compounds between species, and even varietals [
]. Kale (Brassica
oleracea acephala and B. napus) and Brussels sprout (B. oleracea gemmifera) varietals have been shown
to contain the largest amounts of indole glucosinolates and progoitrin, 840
mol/100 g FW total,
and 400.33
mol/100 g FW total, respectively [
]. However, other studies have found kale to
contain very little concentrations of indole glucosinolates and progoitrin [
]. Red Russian kale
(B. napus) and Siberian kale (B. napus ssp pabularia) were reported to contain 365.9
mol/100 g,
and 148.1
mol/100 g FW of progoitrin, respectively. Kale (B. oleracea acephala) also contained
higher concentrations of glucoraphanin (sulforaphane precursor) than Russian or Siberian species
(B. napus ssp) [80].
Glucoraphanin is metabolized to sulforaphane and is found to be a potent inducer of Phase II
enzymes [
]. Broccoli, often accused of being high in goitrogens, was actually reported to contain
low levels of progoitrin and indole glucosinolates, while being rich in beneficial glucoraphanin [
Broccoli sprouts may be an even richer source of glucoraphanin than mature plants, while still containing
only negligible amounts of progoitrin [
]. In addition to glucosinolates, resveratrol, isoflavones,
and flavonoids may also have goitrogenic eects, though much of the research is based on
in vitro
in vivo
animal models [
]. Isoflavones (genistein and daidzein) are found almost exclusively
in soy, while resveratrol and other flavonoids are widespread throughout the plant kingdom [
Millet also contains goitrogenic compounds called C-glycosylflavones, which have been shown in
in-vitro models to inhibit thyroid peroxidase (TPO) [97,98].
4.3. Eects of Cooking/Processing
Factors such as soil conditions, weather, growing location, use of plant growth regulators or
pesticides, pathogen challenges, plant stressors, as well as date of harvest and storage time all can
impact glucosinolate content [
]. The processing of foods, such as cooking, and fermenting,
may lower total glucosinolate concentration (Table 2). However, cooking will also remove beneficial
glucosinolates. One study found that steaming broccoli for just 5 min reduced glucoraphanin and total
glucosinolate content by 57%, and 51%, respectively [
]. Therefore, it is important to evaluate the
current evidence of dietary goitrogens on thyroid and human health, before eliminating or modifying
phytonutrient rich plant foods from the diet.
4.4. Safety
The evidence published thus far investigating the impacts of dietary goitrogens is mixed and
may be more complex than initially thought. “Cabbage goiter” was first observed in rabbits fed a diet
consisting almost entirely of cabbage [
]. Later, researchers also observed ‘antinutritional’ eects in
rats that were fed high-glucosinolate rapeseed meal and purified rapeseed progoitrin for 30 days [
An early human study assessed radioactive iodine uptake following goitrin administration and found
Nutrients 2020,12, 2929 9 of 32
that 25 mg (194
mol) of recrystallized goitrin decreased iodine uptake, though 10 mg (70
resulted in no inhibition [
]. These results, however, cannot be extrapolated for human health, as they
are not representative of a balanced human diet.
Due to the potential inhibitory eects of goitrogens on iodine uptake, populations with underlying
iodine deficiency that consume large amounts of goitrogenic foods, may be more at risk than healthy
individuals. In rats consuming an iodine-deficient diet containing pure thiocyanate, they experienced
significant reductions in thyroxine (T4) levels, as well as reductions in certain proteins and nucleic acids.
Adding iodine back to their diet restored levels of thyroxine, reversing the eects of thiocyanate [
In contrast, progoitrin-rich rutabaga sprouts had no impact on thyroid function in healthy rats. Adverse
eects of iodine deficiency were only pronounced in rats with preexisting hypothyroidism [104].
4.5. Human Studies
Human studies investigating the eects of dietary goitrogens in healthy individuals are relatively
sparse. Some epidemiological evidence supports an association between goitrogen-containing foods
and thyroid dysfunction, though mostly only in the presence of low iodine intake. A study on children
found only modest associations between genistein levels and increased thyroglobulin autoantibodies
and decreased thyroid volume [
]. In Ethiopian children with iodine deficiency, there was a positive
association with consumption of goitrogenic foods (such as taro root, cabbage, Abyssinian cabbage and
banana), low levels of iodine in the diet, and lower urinary iodine levels [
]. In a study on pregnant
Thai women, higher levels of thyroid stimulating hormone (TSH) were associated with thiocyanate
exposure, but only in those with low urinary iodine levels [
]. No associations were found between
thiocyanate exposure and thyroid function in mildly iodine-deficient pregnant women [
]. Moreover,
consumption of cruciferous vegetables, in combination with low iodine intake, was associated with
increased risk of thyroid cancer in women from New Caledonia [
]. A 1.5-fold higher risk of
thyroid cancer was observed in a Polish sample who frequently consumed cruciferous vegetables [
Other epidemiological studies in the United States have demonstrated an inverse relationship between
cruciferous vegetable intake and risk of thyroid cancer [110].
While a small handful of epidemiological studies demonstrate potential concern regarding dietary
goitrogens in combination with low iodine, other human studies show no correlations. In a three-year
trial of genistein, considered an isoflavone goitrogen, no impacts on thyroid function or health
were observed [
]. A review on soy isoflavones arrived at similar conclusions, but still advised
soy-consuming individuals taking thyroid medication to increase their dosage of thyroid medication,
due to the possibility of decreased drug absorption [
]. Vegans are found to contain slightly higher
levels of urinary thiocyanates and lower iodine levels than vegetarians, however no association could
be made with thyroid function, based on TSH and T4 levels [112].
Foods exist as complex matrix of compounds, which often have synergistic eects, that have
yet to be discovered. In this regard, foods considered to be ‘goitrogenic’ also contain thousands of
other bioactive compounds that may be protective against thyroid cancer. According to a case-control
study in French Polynesia, a traditional Polynesian diet, rich in cassava and cabbage, was significantly
associated with a decreased risk of thyroid cancer when compared to a Western style diet [
Zhang et al. found similar negative associations between urinary thiocyanate and thyroid cancer [
At the same time, several case-control studies and meta-analysis found no relationship between
cruciferous vegetable consumption and thyroid cancer risk [115117].
4.6. Conclusions
Overall, most human studies investigating the eects of goitrogenic foods on thyroid health
display neutral eects, although some conflicting results are still present. Evidence seems to suggest
that suboptimal iodine status may potentiate any negative impacts of dietary goitrogens on thyroid
health. Furthermore, progoitrin content amongst the Brassica genus varies significantly. Items such
as broccoli, Chinese cabbages, bok choi, broccoli sprouts, and some kale varietals generally contain
Nutrients 2020,12, 2929 10 of 32
progoitrin and thiocyanate-generating glucosinolates at concentrations far below those likely to cause a
physiological eect. In fact, consuming these foods as part of a varied, colorful, plant-based diet should
not pose significant risks in healthy individuals, and, conversely, may be of great benefit. In addition
to beneficial glucosinolates, cruciferous vegetables provide a plethora of other health-promoting
phytochemicals, fiber, and essential vitamins and minerals. For those with thyroid disease, or at higher
risk of thyroid disease, long-term daily intake of progoitrin-rich items, like Russian kale, broccoli rabe
or collard greens may decrease iodine uptake, and should be cooked with iodized salt to avoid reduced
iodine uptake.
5. Phytoestrogens
5.1. Definition
Phytoestrogens are plant-derived polyphenolic dietary compounds with structural similarities to
-estradiol (E2), the primary sex hormone in females [
]. Due to their similarity to 17-
these bioactive compounds can bind to estrogen receptors (ER), in turn, modulating estrogenic
activity. Many tend to have higher anities for ER-beta than ER-alpha and have a weaker bond than
E2 [
]. Phytoestrogens are classified into four phenolic compounds: isoflavones, lignans, stilbenes,
and coumestrol [120]
. Isoflavones and lignans have received much of the attention, as they are the
most relevant with respect to the human diet. Isoflavones are flavonoids found primarily in soybeans,
and consist of genistein, daidzein, glycitein, and biochanin A. Lignan phytoestrogens, mostly associated
with flaxseeds and other cereals, exist as the glycosides secoisolariciresinol and matairesinol but also
include pinoresinol, lariciresinol and syringaresinol [
]. Intestinal microflora are responsible for the
conversion to the “mammalian lignans,” enterodiol and enterolactone [
]. Similarly, the microbiome
hydrolyzes isoflavone glycosides to their physiologically active aglycone metabolites.
5.2. Background
More than 20 isoflavone metabolites have been identified, the most well-studied of which is
equol [
]. Equol production varies between populations. It has been found that of Western
populations, only about 25–30% are able to convert isoflavones to equol, compared to 50–60% of Asian
populations and vegetarians [
]. It is hypothesized that regular consumption of isoflavone-rich
foods provides substrates for equol producing bacteria to thrive, if present [
]. There are many
suggested health benefits of phytoestrogens, including reduced menopausal symptoms, reduced risk of
cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes, cognitive disorders,
and various
forms of cancer [
]. Nonetheless, concerns are frequently raised that soy isoflavones and
other phytoestrogens may act as endocrine disruptors and stimulate the growth of estrogen-sensitive
cancers [
]. Thus, much debate exists among consumers and clinicians alike, on whether
phytoestrogen-rich foods should be included in those with a history or family history of breast cancer.
Phytoestrogens are widespread throughout the plant kingdom, and consumption can vary greatly
depending on cultural food preferences. Traditional Asian diets, for example, are estimated to contain
15–50 mg/day of isoflavones, whereas consumption in Western countries is estimated to be only
around 2.5 mg/day [
]. This dierence can be attributed to the long history of soy products in Asian
cuisine. Soy products are one of the richest sources of dietary isoflavones. Whole soybeans contain
103.6 mg/100 g of isoflavones, followed by soy nuts (68.6 mg/100 g), tofu (27.2 mg/100 g), tempeh
(18.3 mg/100 g), soymilk (2.9 mg/100 g) and miso soup (1.5 mg/100 g) [
]. Fruits, vegetables, nuts,
and other legumes also contain isoflavones, though in significantly lesser amounts [
]. Lignans
are the second leading source of dietary phytoestrogens, and are ubiquitous throughout plants, though
in generally small amounts. Flaxseeds and sesame seeds are reported to contain the greatest amount
of lignans, with 379.4 mg and 8.00 mg/100 g respectively [
]. Nuts were found to contain between
0.025 mg and 0.198 mg/100 g [
]. Lignans, in general, were found to be negligible in legumes, fruits,
Nutrients 2020,12, 2929 11 of 32
vegetables and cereals (<0.01 mg/100 g). Exceptions were noted for garlic, olive oil, winter squash,
dried apricots, dried dates, dried prunes and multigrain bread [134].
5.3. Eects of Cooking/Processing
As previously stated, dietary phytoestrogen glycosides must first be transformed to aglycones
by glucosidases before they can be utilized by humans [
]. Glycosides can be hydrolyzed
via intestinal glucosides, intestinal bacterial glucosides, as well as through various processing
methods [123,139141]
. Boiling and steaming led to significant increases in beta-glucosides and
aglycones, though pressure steaming resulted in the greatest amounts (Table 1) [
]. Fermentation by
Lactobacillus and Bifidobacteria also results in increased aglycone content [
]. Bau et al. found that
by fermenting soymilk for 30 h with kefir culture, glycitin and daidzin were completely hydrolyzed
into aglycones, while 89% of genistin was bioconverted [
]. Consuming traditionally fermented
soy products, such as Korean cheonggukjang, Japanese natto, and Thai Thua, may further enhance
isoflavone bioavailability, though more human trials are necessary [122].
5.4. Safety
Phytoestrogens have received a large amount of attention over the past few decades, particularly
because of their potential estrogenic eects (Table 1). For this reason, much research has examined
possible benefits of phytoestrogens on menopause symptoms, although results have been mixed [
A recent systematic review and meta-analysis concluded that phytoestrogen supplementation resulted
in significantly greater reductions in hot flashes as compared to placebo, but did not significantly
impact the Kupperman Index, an index which included 11 symptoms of menopause [
]. Another
meta-analysis found similar benefits in the ability of soy isoflavones to improve hot flashes, as well
as vaginal dryness score [
]. Chen and colleagues concluded in a recent literature review that
isoflavones reduced hot flashes, attenuated bone mineral density (BMD) loss in the lumbar spine and
may have potential benefits on blood pressure and glycemic control [144].
Nonetheless, a recent Cochrane review was unable to conclusively state that phytoestrogens
are eective for reducing menopausal symptoms due to the heterogeneity of studies, and individual
variability in metabolism and absorption of isoflavones [
]. An exception was noted for genistein
supplementation of 30–60 mg/day, which reliably demonstrated a benefit for hot flash frequency [
The heterogeneity in results may be partially explained by equol. An observational study of
365 peri- and post-menopausal women, found that equol producers in the highest quartile of
daidzein intake were 76% less likely to report vasomotor symptoms than those in the lowest intake
quartile. No associations were found between daidzein intake and vasomotor symptoms in equol
nonproducers [
]. Equol supplementation may also be of benefit to non-producers. A 12-week
double-blind RCT found that equol supplementation (10 mg/day) improved mood-related symptoms,
even in non-producers. Those that received 10 mg three times daily demonstrated significantly better
outcomes in all measures [
]. A meta-analysis of equol supplementation also revealed significant
improvement in hot flash severity, both in equol producers and non-producers [148].
Another primary concern regarding phytoestrogens is due to their possible endocrine-disrupting
eects [129]. Due to the rising rates of soy-based infant formulas, developing babies and infants may
be most at risk. Serum genistein concentrations are 10–50-fold higher in soy-formula fed infants than
in Asian adults, and 100–700-fold higher than US adults [
]. Nonetheless, the biological significance
of increased phytoestrogen exposure in infants is yet to be determined [
]. Collective findings in
adults have not identified conclusive evidence that soy food or isoflavones adversely aect thyroid
function in euthyroid or iodine-replete individuals [94].
The other common concern surrounding soy and phytoestrogen intake is increased risk of
estrogen-sensitive breast and uterine cancer [
]. Thus far, no evidence has demonstrated a link between
phytoestrogen-rich diets and estrogen-sensitive malignant growths. In contrast, soy consumption may
actually be associated with reduced risk of breast cancer incidence, recurrence and mortality [
Nutrients 2020,12, 2929 12 of 32
5.5. Human Studies
Studies investigating the specific potential impact on female reproductive health are mixed.
A systematic
review and meta-analysis concluded that isoflavones have no eect on endometrial
thickness or breast density [
]. Another meta-analysis of pre- and postmenopausal women
found isoflavones to have only a weak eect on the hypothalamic-pituitary-gonadal axis [
In premenopausal women, soy isoflavone consumption had no eect on circulating estradiol, estrone
or sex hormone binding globulin (SHBG). Follicle stimulating hormone (FSH) and luteinizing hormone
(LH) concentrations were significantly reduced, and menstrual length increased by 1.05 days. However,
once bias was accounted for, changes were no longer significant [
]. In postmenopausal women,
no statistically significant eects were noted for circulating total estradiol, estrone, SHBG, FSH, LH or
TSH, though soy increased total circulating estradiol non-significantly [
]. Women that were fed
soy-formula as an infant reported slightly longer menstrual bleeding times (0.37 days), and greater
discomfort during menstruation than cow milk fed infants [
]. Another study conducted on Korean
girls with central precocious puberty (CPP) found a positive association between elevated serum
isoflavones and risk of CPP [
]. As soy-based formulas are also known to contain pesticide and
glyphosate residues, eects of soy cannot be attributed to phytoestrogens alone [157].
Despite concerns over estrogen’s endocrine disrupting eects, estrogen is (E2) is proposed to
play a role in protection against cardiovascular disease (CVD), and the ensuing increased risk of
CVD post-menopause once E2 levels decline [
]. Due to the structural similarities to E2,
phytoestrogens have also been investigated for possible cardiovascular benefits. Epidemiological
evidence suggests potential protective eects of phytoestrogens, particularly in Asian populations
with high isoflavone intake from soy products [
]. A positive relationship has been found between
isoflavone intake, endothelial function and reduced lower carotid atherosclerotic burden [
]. Ferreira
and colleagues also found that higher isoflavone intake was independently associated with lower
risk for subclinical CVD in menopausal women [
]. Results from experimental studies using
phytoestrogens for CVD prevention and treatment have been mixed, but generally positive. In one
study, soy isoflavones in combination with probiotic resistant starch or probiotics (L. acidophilus,
B. bifidus and LGG), was shown to significantly decrease total and LDL cholesterol, independent of
isoflavone bioavailability [
]. Another study using 15 g of soy protein with 66 mg isoflavone daily for
6 months resulted in significant reductions in systolic blood pressure (SBP). The reductions in SBP led
to a 27% reduction in 10-year coronary heart disease risk, a 37% reduction in myocardial infarction risk,
a 24% reduction in cardiovascular disease and 42% reduction in CVD death risk [
]. A meta-analysis
of 17 RCTs suggested that isoflavone-containing soy products can modestly, but significantly improve
endothelial function, as measured by flow mediated dilation (FMD) [
]. Finally, several studies have
suggested that genistein significantly improves FMD, reduces endothelin-1 levels, and induces nitric
oxide-dependent vasodilation to a similar extent of estrogen [166168].
Soy-based and phytoestrogen-rich products have also been proposed for the prevention of certain
cancers, including breast, prostate, endometrial, and colorectal cancer [
]. Some studies,
however, have suggested that soy isoflavone intake is associated with significantly reduced breast cancer
risk only in Asian populations, but not in Western populations [
]. Ingestion of phytoestrogens
and soy may also oer significant protection against prostate cancer. A recent meta-analysis from the
University of Illinois found that total soy food, genistein, daidzein, and unfermented soy food to be
significantly associated with reduced advanced prostate cancer risk [
]. In another meta-analysis,
soy isoflavone supplementation led to a significant reduction in prostate cancer diagnosis in those
with an identified risk [177]. No reductions in PSA levels or steroid endpoints were observed.
The benefits of phytoestrogens may be due to their anti-inflammatory and antioxidant
properties [
]. Data from the 1999–2010 NHANES revealed an inverse associated with urinary
phytoestrogens and serum C-reactive protein (CRP), a marker of inflammation [
]. These results
should be interpreted with caution however, as an increased intake of phytoestrogens in Western
Nutrients 2020,12, 2929 13 of 32
cultures may be evidence of an overall healthy diet, rich in a variety of other nutrients and bioactive
compounds that reduce CRP levels [179].
5.6. Conclusions
Overall, the evidence surrounding phytoestrogens within the currently published literature is
still mixed, with a large amount of heterogeneity between studies. The microbial makeup of the gut,
bio-individuality, and the phytoestrogen source all play a significant role in the decision to include
phytoestrogen-rich foods in one’s diet. Supplementation using isolated isoflavones may be beneficial
for some populations but may pose increased risk for others. Babies and infants are at higher risk of
the endocrine-disrupting potential because of their small size and underdeveloped digestive tract.
With that said, epidemiological and observational data suggests that including phytoestrogen-rich
foods as part of a varied, plant-based diet should not be of concern, but may be beneficial. Additionally,
phytoestrogen-containing foods such as legumes, grains, seeds, nuts, fruits, and vegetables, are rich
sources of essential vitamins, minerals, fiber and other health-promoting phytochemicals.
6. Phytates
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 [
]. Phytate
is produced during seed development and can account for 60–90% of total phosphorus content in cereal
grains, nuts, seeds, and legumes [
]. 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+[
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 [
]. Low-income,
developing countries that rely predominantly on grains and legumes as dietary staples are of special
concern for zinc deficiency and/or insuciency [
]. The chelating properties of phytate also allow it
to act as an antioxidant, lending possible protective traits [
]. Ensuring an appropriate phytate to
mineral ratio minimizes the negative eects 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 [
]. In cereals, phytate is mainly found in the
outermost layer, and in legumes is found within the endosperm and cotyledons [
]. 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 [
]. Growing methods,
seasons, and cultivars can have a significant impact on phytate content [
Shi et al.
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 [
]. 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 [
]. Split varieties of lentils and peas contain more phytate,
since much of the hull is lost during processing [
]. 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 [
]. Upon processing,
phytate content can be significantly reduced in many grains, seeds, and legumes.
Nutrients 2020,12, 2929 14 of 32
6.3. Eects 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 [
]. 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 [
]. 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 [
]. 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 [
]. 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 [
]. 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 [
]. 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 [
]. The exact mechanism is unknown
but may be due to an increase in ferric iron [
]. 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 [
]. High-phytate foods such as beans are rich in fermentable
fibers, which have a beneficial eect on cecal pH by increasing SCFA production [
]. This eect
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 [
]. The ideal molar ratio of phytate to iron is ~0.4, with an
inhibitory eect 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 [
however a study on young children, aged 8–50 months, found phytates to not have a discernable eect
on zinc absorption [
]. 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 [
]. 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,
Nutrients 2020,12, 2929 15 of 32
no improvement in iron bioavailability was observed [
]. Removing fiber was found to have a more
significant impact on iron absorption, demonstrating an independent eect 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 [
]. 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 [
]. The addition of complementary foods high in ascorbic acid
(vitamin C) may allow consumers enjoy the benefits of phytate-rich foods, while osetting phytate’s
inhibitory eect 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 [
]. Fenton reactions are oxidative reactions involving iron and hydrogen peroxide,
producing hydroxyl radicals and other reactive oxygen species (ROS) [
]. 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 [
]. Since only a small amount
of heme is absorbed in the small intestine, up to 90% may reach the colon [
]. 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 [
]. However, human trials validating phytate’s elucidated antioxidant eects 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 [
]. Considering the deleterious eects 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 eects, 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 [
IP6 has also been shown to decrease kidney stone risk [
], dental calculi [
], osteoporosis
risk [
], and help prevent age-related cardiovascular calcification [
]. Furthermore, adequate
consumption of phytate-rich foods was found to prevent abdominal aortic calcification in patients
with chronic kidney disease [
]. 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.
7. Tannins
7.1. Definition
Tannins are a broad class of polyphenol compounds of high molecular weight (
500–3000 Daltons
ubiquitously present in commonly consumed plant foods and are responsible for the astringent taste
of many fruits and beverages [
]. They can be chemically classified into two groups: hydrolysable
tannins and condensed tannins (also known as catechin tannins, flavanols, or proanthocyanidins).
Hydrolysable tannins, including gallotannins and ellagitannins, are selectively found in the
Nutrients 2020,12, 2929 16 of 32
diet. Condensed tannins, or proanthocyanidins, on the other hand, are the most abundant
plant-derived polyphenols in the diet and include catechin, epicatechin (EC), epigallocatechin (EGC),
epicatechin-3-gallate, and (-)-epigallocatechin-3-gallate (EGCG) [224].
Due to their phenolic nature, tannins are chemically reactive, forming intra- and inter-molecular
hydrogen bonds with macromolecules like proteins and carbohydrates. This lends to their role in
plant defense, as well as to their antioxidant, anticarcinogenic, immunomodulatory, detoxifying,
and cardioprotective activities [
]. Tannins may act as antioxidants by scavenging free radicals,
although their ability to act as chelators have also been reported to inhibit the absorption of dietary
minerals such as iron, copper, and zinc [
]. The elucidated ‘anti-nutritional’ eects of dietary
tannins have been suggested as a contributor to iron-deficiency anemia, particularly in developing
and low-income countries who rely on tannin-rich foods [
]. Other studies suggest that iron status
and absorption is not significantly aected by dietary tannin intake and is found to be highly variable
between individuals [227,232].
7.2. Background
Tannins, specifically proanthocyanidins or catechins, are one of the most abundant secondary plant
metabolites, found in cocoa beans, tea, wines, fruits, juices, nuts, seeds, legumes and cereal grains [
Dark and baking chocolate contains the highest amounts of proanthocyanidins (828–1332 mg/100 g) [
A Danish study found fruits with the richest concentrations of catechins included black grapes
(203.9 mg/kg FW), apples (71.1–115.4 mg/kg FW), apricots (110 mg/kg), plums (61.9 mg/kg), cherries
117.1 mg/kg
), all edible berries (11.1–187.4 mg/kg), pears (30.6–85 mg/kg), cranberries (42 mg/kg),
and peaches (23.3 mg/kg) [
]. Nuts (almonds, walnuts, pecans, and pistachios), common beans and
some cereals, such as sorghum, also contain notable amounts of catechins [
]. Darker beans, such as
dark red kidney beans, have been shown to contain more catechins than lighter beans [233].
Tea and wine are rich sources of catechins. Arts et al. found that of the red wines tested,
catechin values were between 27.3 and 95.5 mg/L [
], though others have cited values as high
as 300 mg/L [
]. Content in tea has been found to be between 100 and 800 mg/L in green tea,
and 60–500 mg/L in black tea [
]. Tea is the predominant source of epigallocatechin gallate (EGCG),
a powerful and well-studied antioxidant [
]. Ceylon has been reported to contain the most
EGCG (128–229 mg/L) [
]. Ellagitannins, a class of hydrolysable tannins, are found in a limited
number of fruits and nuts, including walnuts, pecans, berries and pomegranates [225].
7.3. Eects of Cooking/Processing
Cooking and processing may decrease total catechin content in some foods (Table 2). Arts et al.
reported reductions in rhubarb, broad beans and pears by 28, 58 and 26%, respectively [
], although
a majority of catechin-rich foods, like fruits, are consumed raw. Removing the skins from nuts may
reduce phenolic content by up to 90% [
]. Catechin content in tea increases with the amount of
tea used and with increased infusion time, however catechin concentrations and antiradical activity
seem to peak at 4–5 min of brew time [
]. Tannin content in foods and tea can be influenced by
region, variety, processing methods, and storage time [
]. Polyphenols were found to vary
significantly between agricultural methods, though not as much as between cultivars [239241].
7.4. Safety
Despite their ubiquitous nature in many nutritionally dense plant foods, some researchers and
clinicians have deemed tannins as antinutritional factors due to their potential to reduce iron absorption
(Table 1) [
]. Early animal studies reported tannins to cause depressed growth and egg
production in poultry, when fed at levels of 0.5–2% of feed [
]. In weaning pigs, consumption of 125,
250, 500, or 1000 mg tannic acid/kg in feed resulted in a significant drop in hemoglobin, and depletion
of serum iron concentrations. However, erythrocyte counts, hemoglobin and hematocrit decreased
similarly in the control group to that of the 125, 250, and 500 mg/kg diet groups [
]. Other animal
Nutrients 2020,12, 2929 17 of 32
studies using condensed tannins (more commonly found in the human diet) have not found any
significant impacts on iron status [244].
7.5. Human Studies
The aforementioned concentrations are far greater than regularly consumed through a diverse
diet. Delimont and colleagues found that 4-weeks of condensed tannin supplementation (1.5, 0.35 and
0.03 g 3 times/day) had no impact on iron bioavailability or status in premenopausal women [
Tea, one of the richest sources of dietary tannins, may inhibit iron absorption when consumed directly
with a nonheme iron-rich meal. In a study of healthy adults, iron absorption was decreased by 37%
when tea was consumed with an iron-fortified porridge, however, was not aected when tea was
consumed an hour after the meal [
]. Other factors, such as gender and baseline iron status, may also
influence the impact of tannins on iron parameters. In a study investigating the eects of green and
black tea on iron status of omnivores and vegetarians, 1 L of black tea/day for four-weeks (with meals)
resulted in significantly lower ferritin levels only in omnivorous females, but no eects were observed
in omnivorous males [
]. Green tea had no influence on ferritin levels in omnivorous and vegetarian
females. In females with low baseline ferritin (<25
g/L), both green and black tea significantly reduced
ferritin levels [247].
Tannins are not consumed alone, but in combination with thousands of other bioactives, including
ascorbic acid. Potential inhibitory eects of tannins may be oset by the inclusion of 30 mg of ascorbic
acid [
]. This may explain why human epidemiological studies investigating iron deficiency
anemia are unable to demonstrate any correlations between dietary tannin intake and iron-deficiency
anemia. Of 2593 French subjects, serum-ferritin concentrations were not related to tea consumption,
independent of strength, infusion time or time of tea drinking [
]. A cross-sectional analysis of
1605 healthy adults also found that tea consumption did not significantly increase risk for iron deficiency
or iron-deficiency anemia [
]. Similar findings were also shown by Root et al. in adults from rural
China [
]. A systematic review by Speer et al. concluded that total polyphenol intake did not
interfere with iron status but did improve inflammatory biomarkers in participants [
]. The review
included a limited number of studies, but it speaks to the numerous demonstrated health benefits of
tannins and tannin-rich plant foods.
Although the ‘anti-nutritional’ eects of tannins are debatable and highly variable, evidence
supporting the many health benefits of tannins are widespread [
]. Dietary intake of
polyphenols is associated with a decreased risk of T2DM, metabolic syndrome, risk of ischemic stroke,
non-fatal cardiovascular events risk, and risk of atherosclerotic vascular disease [
The Takayama
study, consisting of over 29,000 Japanese individuals, found significantly lower CVD mortality in
subjects with the highest polyphenol intake, as compared to those in the lowest quartile [
]. Inverse
associations also existed for mortality from digestive diseases. Polyphenols in this population
were mainly derived from beverages such as green tea and coee [
]. Consumption of
proanthocyanidin-rich foods has been shown to reduce the risk of chronic kidney insuciency
and renal disease [
]. Proanthocyanidins are believed to exert their renal and cardioprotective eects
by reducing oxidative stress and improving endothelial function [
]. A randomized crossover
study found that drinking 3 cups black tea resulted in immediate improvement in brachial artery FMD
in healthy subjects [261].
Tea catechins and ellagitannins may lower CVD risk by upregulating Nrf2 [nuclear factor erythroid
2 (NF-E2) p45-related factor 2] [
]. Nrf2 is a key transcription factor responsible for the body’s
detoxification and antioxidant defense systems [
]. Ellagic acids, present in raspberries, strawberries,
pomegranates, and nuts have demonstrated anticarcinogenic eects
in vivo
. Animal models suggest
that ellagic acid may modulate phase I and phase II enzymes by lowering or inhibiting cytochrome
P450 enzymes, and inducing glutathione-s-transferase, UDP and NAD(P)H-quinone reductase
; however, human clinical data indicating similar eects has not been demonstrated.
Nutrients 2020,12, 2929 18 of 32
Furthermore, flavanol-rich foods, such as fruits, vegetables, and cocoa demonstrate positive
eects on cognition, executive function, and even mood, although exact mechanisms are yet to be
elucidated [
]. Neshatdoust et al. observed significant improvements in cognitive performance
and increases in brain-derived neurotropic factor (BDNF) levels after an 18-week intervention of
high-flavonoid fruits and vegetables (>15 mg/100g) [
]. Another intervention utilizing a high-flavanol
cocoa beverage (494 mg total flavanols) resulted in significantly higher brain-derived neurotropic
factor (BDNF) levels in older individuals, when compared to the low-flavanol cocoa drink (23 mg total
flavanols) group [
]. The CoCoA study, an 8-week supplementation with a high-flavanol cocoa drink
(993 mg flavanol), reduced measures of age-related cognitive dysfunction. Significant improvements
in insulin resistance, blood pressure and lipid peroxidation were also observed in the high flavanol
(993 mg) and intermediate flavanol group (520 mg), suggesting insulin modulation as a possible
mechanism [
]. Grassi et al. found that consumption of high-flavanol dark chocolate ameliorated
vascular impairment after sleep deprivation and improved working memory performance [
indicating that cognitive improvements may be due to eects of flavanols on blood pressure and
peripheral and central blood flow.
Flavanols may additionally act as prebiotics, positively influencing the gut microbiota, in turn
alleviating neuroinflammation and balancing serotonin metabolism [
]. Ingestion of a high-cocoa
flavanol drink (494 mg cocoa flavanols) significantly increased Bifidobacteria and Lactobacilli populations,
while at the same time significantly decreasing Clostridia counts, when compared to the low-cocoa
flavanol (23 mg) drink [
]. Significant reductions in plasma triacylglycerol and C-reactive protein
concentrations were also linked to the changes in microbial counts [
]. Being that many polyphenols
are metabolized by gut microbiota [
], individual microbial composition and dietary habits may
influence both the bioavailability and physiological eects of flavanol-containing foods.
7.6. Conclusions
Tannins are highly bioactive compounds which are widely found in plant foods and beverages,
including berries, apples, stone fruit, cocoa, legumes, whole grains, tea as well as many others.
Although some studies have found that tannins may interfere with iron absorption when consumed in
isolation, other studies investigating whole diets demonstrate otherwise. Harmful (and even beneficial)
eects of an individual, isolated compound or phytochemical are often quite dierent than when the
same compound is within the complex food matrix. For this reason, epidemiological evidence has not
demonstrated any correlation between iron status and flavanol intake. Ascorbic acid, present in many
tannin-rich foods, may further enhance the absorption of non-heme iron. Nonetheless, some studies
still advise that those with low iron stores, especially females, consume tannin-rich beverages, such as
tea, after or in-between meals to avoid potential eects on iron absorption. Overall, evidence suggests
that the many health benefits of consuming a diverse, plant-based diet, rich in polyphenol and bioactive
containing foods and beverages, far outweighs the potential impact of tannins on iron status.
8. Limitations
There are limitations to this narrative review that should be noted. First, human clinical trial
research investigating the eects of antinutritional compounds in whole food form are limited, and in
some cases do not always arrive at clear-cut conclusions. In place of clinical trials, epidemiological
and observational studies must be used, though are typically limited in their applicability due to
uncontrolled variables. Second, much of the research on antinutritional components are performed
using isolated compounds in animal models, which are not representative of a balanced diet. Research
limitations are further compounded by the often synergistic nature of food, eects of cooking and
processing, as well as the bio-individuality of study participants. More research which takes these
variables into consideration are needed before definitive conclusions can be made regarding the
ill-eects of these compounds in their whole food form.
Nutrients 2020,12, 2929 19 of 32
9. Overall Conclusions
The purpose of this review was to assess whether there is considerable clinical data to warrant
certain compounds in plants to be positioned as ‘anti-nutrients’ in the sense that they block the
absorption or assimilation of essential nutrients or, in some way, interfere with physiological function
of an organ. The summary of our findings would suggest the following:
Of the compounds reviewed, there are indications that when given in the diet in what would be
considered moderate to high quantities, or when administered in isolation, they may exert eects
that would be detrimental or impair the body’s reserves or function in some way. There may be
some individuals who are more susceptible to these eects for various reasons.
These compounds are rarely ingested in their isolated format as we know from how these foods
are traditionally consumed. Plant-based diets which contain these compounds also contain
thousands of other compounds in the food matrix, many of which counteract the potential eects
of the ‘anti-nutrients’. Therefore, it remains questionable as to whether these compounds are as
potentially harmful as they might seem to be in isolation, as they may act dierently when taken
in within whole foods that are properly prepared. Cooking and application of heat seems to be
essential for the activation of some of these compounds.
In some cases, what has been referred to as ‘anti-nutrients,’ may, in fact, be therapeutic agents for
various conditions. More exploration and research are required to know for certain.
Author Contributions:
Conceptualization, D.M.M.; writing–original draft preparation, W.P.; writing–review and
editing, D.M.M.; supervision, D.M.M., funding acquisition, D.M.M. All authors have read and agreed to the
published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest:
Deanna Minich is a health educator, consultant, and author in the wellness area. Weston
Petroski is a community health educator in the field of nutrition.
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... Beberapa senyawa anti gizi yang di duga menurunkan bioavaibilitas nutrisi yaitu lektin, oksalat, goitrogen, fitoestrogen, fitat dan tannin (Petroski and Minich, 2020). Selain itu masih banyak senyawa yang bersifat anti gizi, di antaranya saponin, alkaloid, protease inhibitor, sianogen, dan letogen (Sinha and Khare, 2017). ...
... Tabel 11.5 di bawah ini menunjukkan efek positif zat anti gizi bagi kesehatan. Sumber: (Petroski and Minich, 2020) 1. Lektin Lektin atau hemaglutinin merupakan kelompok protein pengikat karbohidrat yang hampIr ditemukan di semua organisme termasuk tumbuhan, hewan dan mikroorganisme (Mishra et al., 2019). Lektin mampu mengikat secara reversibel pada bagian karbohidrat khusus pada sel dan menghasilkan aglutina eritrosit. ...
... Dan oksalat berkontribusi terhadap pembentukan batu ginjal berupa kalsium oksalat. Karena efek oksalat pada penyerapan nutrisi dan kemungkinan berperan dalam pembentukan batu ginjal, maka oksalat dianggap oleh beberapa orang sebagai anti gizi (Petroski and Minich, 2020). ...
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Setiap orang memiliki kebutuhan pangan berbeda-beda tergantung kebutuhan dan pertimbangan aktivitas. Bahan pangan yang tersedia sebagai sumber gizi yang bermanfaat bagi kesehatan manusia. Dalam konsep pangan, pangan dikonsumsi karena memiliki gizi baik makro maupun mikro. Kebutuhan tersebut harus dicukupi baik dari segi kualitas maupun kuantitas. Ketimpangan asupan zat gizi akan menyebabkan terganggunya kesehatan manusia. Berbagai upaya baik perbaikan proses maupun penambahan zat gizi dilakukan untuk mencegah terjadinya kekurangan gizi yang terjadi. Dalam buku ini diharapkan akan menambah pengetahuan pembaca tentang peran penting pangan dan gizi dalam kehidupan manusia. Beberapa topik yang akan dibahas di antaranya: Bab 1 Pengantar Pangan dan Gizi Bab 2 Kandungan dan Fungsi Zat Gizi Bab 3 Metabolisme Zat Gizi Bab 4 Nilai Gizi Bahan Pangan Bab 5 Pola Konsumsi Pangan Bab 6 Kebutuhan Zat Gizi Bab 7 Upaya Perbaikan Gizi Bab 8 Kecukupan Zat Gizi Bab 9 Status Gizi Bab 10 Malnutrisi Bab 11 Fortifikasi dan Anti Gizi Bab 12 Keamanan Pangan dan Gizi Bab 13 Sistem Kewaspadaan Pangan dan Gizi (SKPG)
... Additionally, despite the fact that grain legumes are a rich source of minerals, several Anti-nutritional elements or factors, including as phytic acids (phytate or PA), oxalates, and tannins, chelate the minerals and reduce their bioavailability by limiting their absorption in our dietary system, thus numerous health issues occur. Several studies demonstrated the presence of phytic acids (Urbano et al., 2000;Shi et al., 2018;Pramitha et al., 2021), RFOs (Zhawar et al., 2011;Roorkiwal et al., 2021), oxalates (Noonan and Savage, 1999;Shi et al., 2018) and tannins (Arts et al., 2000;Petroski and Minich, 2020) in legumes and their Anti-nutritional properties. ...
... Therefore phytase treatment may be advantageous in plant-based foods where high phytic acid levels may prevent proper protein digestion. Processing techniques such as soaking, fermentation, sprouting, germinating, and cooking procedures can drastically change the phytate content of grains in legumes, allowing improved mineral bioavailability (Petroski and Minich, 2020). For example, cooking legumes for 1 h at 95°C resulted in phytate reduction up to 23% in yellow split peas, 20%-80% in lentils, and 11% in chickpeas. ...
... According to Shi et al. (2018), soybeans had the highest concentration of oxalates (370 mg/100 g dry weight (DW)), followed by lentils and peas (168-293 mg/100 g DW), chickpeas (192 mg/100 g DW), and common beans (98-117 mg/100 g DW). However, studies have shown that cooking can effectively reduce the amount of soluble oxalate that is present in the diet (Petroski and Minich, 2020). ...
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Global food security, both in terms of quantity and quality remains as a challenge with the increasing population. In parallel, micronutrient deficiency in the human diet leads to malnutrition and several health-related problems collectively known as “hidden hunger” more prominent in developing countries around the globe. Biofortification is a potential tool to fortify grain legumes with micronutrients to mitigate the food and nutritional security of the ever-increasing population. Anti-nutritional factors like phytates, raffinose (RFO’s), oxalates, tannin, etc. have adverse effects on human health upon consumption. Reduction of the anti-nutritional factors or preventing their accumulation offers opportunity for enhancing the intake of legumes in diet besides increasing the bioavailability of micronutrients. Integrated breeding methods are routinely being used to exploit the available genetic variability for micronutrients through modern “omic” technologies such as genomics, transcriptomics, ionomics, and metabolomics for developing biofortified grain legumes. Molecular mechanism of Fe/Zn uptake, phytate, and raffinose family oligosaccharides (RFOs) biosynthesis pathways have been elucidated. Transgenic, microRNAs and genome editing tools hold great promise for designing nutrient-dense and anti-nutrient-free grain legumes. In this review, we present the recent efforts toward manipulation of genes/QTLs regulating biofortification and Anti-nutrient accumulation in legumes using genetics-, genomics-, microRNA-, and genome editing-based approaches. We also discuss the success stories in legumes enrichment and recent advances in development of low Anti-nutrient lines. We hope that these emerging tools and techniques will expedite the efforts to develop micronutrient dense legume crop varieties devoid of Anti-nutritional factors that will serve to address the challenges like malnutrition and hidden hunger.
... Depending on the type of goi-trogen, this results in a suppression of thyroid gland function, reduction of production of thyroid hormones, inability of the thyroid to properly uptake and process I, leading to lower I excretion into the milk, or all of these. (Petroski and Minich, 2020;Bertinato, 2021). ...
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Given the lack of research regarding the effect of microalgal supplementation in dairy cows on milk mineral concentrations, this study investigated the effect of feeding different protein supplements in dairy cow diets on milk, feces, and blood plasma mineral concentrations , associated milk and blood plasma transfer efficiencies, and apparent digestibility. Lactating Finn-ish Ayrshire cows (n = 8) were allocated at the start of the trial to 4 diets used in a replicated 4 × 4 Latin square design experiment: (1) control diet (CON), (2) a pelleted rapeseed supplement (RSS; 2,550 g/d), (3) a mixture of rapeseed and Spirulina platensis (RSAL; 1,280 g of RSS + 570 g of S. platensis per day), and (4) S. platensis (ALG; 1,130 g of S. platensis per day). In each of the 4 experimental periods, a 2-wk adaptation to the experimental diets was followed by a 7-d sampling and measurement period. Feed samples were composited per measurement period, milk, and feed samples (4 consecutive days; d 17-20), and blood plasma samples (d 21) were composited for each cow period (n = 32). Data were statistically analyzed using a linear mixed effects model with diet, period within square, square and their interaction as fixed factors, and cow within square as a random factor. Cows fed ALG were not significantly different in their milk or blood plasma mineral concentrations compared with CON, although feeding ALG increased fecal concentrations of macrominerals (Ca and Mg) and trace elements (Co, Cu, Fe, I, Mn, and Zn), and reduced their apparent digestibility, compared with CON. When compared with CON and ALG, milk from cows fed RSAL and RSS had lower milk I concentrations (−69.6 and −102.7 μg/kg of milk, respectively), but total plasma I concentrations were not affected significantly. Feeding S. platensis to dairy cows did not affect mineral concentrations in cows' blood or milk, but care should be taken when rapeseed is fed to avoid reducing milk I concentrations which may in turn reduce consumers' I intake from milk and dairy products.
... These are abundant in beans (2.4%-5% of the total protein) and lentils while are low in lupin and garden pea (Campos-Vega et al., 2010). Lectins are deactivated by the traditional soaking of seeds for several hours and the cooking process (Adamcová et al., 2021;Petroski and Minich, 2020). The accidental ingestion of lectin containing foods can alter the gut function, causing nausea, vomiting, stomach upset, and diarrhea. ...
Sustainable sources of dietary proteins are making their way into the market to reduce the impact of food production on the environment. Considerations from several standpoints are to be made when supporting the dietary shift toward these alternative sources, particularly regarding their nutritional and safety quality. Research is making enormous steps forwards by producing highly valuable proteins with little environmental impact or by turning by-products and wastes into sources of valuable proteins. The chapter will summarize the environmental, nutritional, and safety aspects related to novel foods, including microalgae, plants, insects, microbial, and synthetic-based ingredients. Consumer acceptability is taken into central consideration throughout the chapter being the final user of the novel food ingredients.
... Hydrolysable tannins posess antinutritional properties, due to their potential to complex iron ions and reduce their absorption (Petry et al., 2010). However, those effect may be offset by the development of formulations with modified release of extract or by the inclusion in diet of other bioactives, such as ascorbic acid, which prevents the inhibitory effect of polyphenols on iron absorption (Petroski and Minich, 2020). The acute complications of advanced stages of colorectal cancers includes a number of complications, such as bleeding, perforation and/or obstruction (Yang and Pan, 2014). ...
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Cinquefoils have been widely used in local folk medicine in Europe and Asia to manage various gastrointestinal inflammations and/or infections, certain forms of cancer, thyroid gland disorders, and wound healing. In the present paper, acetone extracts from aerial parts of selected Potentilla species, namely P. alba (PAL7), P. argentea (PAR7), P. grandiflora (PGR7), P. norvegica (PN7), P. recta (PRE7), and the closely related Drymocalis rupestris (syn. P. rupestris) (PRU7), were analysed for their cytotoxicity and antiproliferative activities against human colon adenocarcinoma cell line LS180 and human colon epithelial cell line CCD841 CoN. Moreover, quantitative assessments of the total polyphenolic (TPC), total tannin (TTC), total proanthocyanidins (TPrC), total flavonoid (TFC), and total phenolic acid (TPAC) were conducted. The analysis of secondary metabolite composition was carried out by LC-PDA-HRMS. The highest TPC and TTC were found in PAR7 (339.72 and 246.92 mg gallic acid equivalents (GAE)/g extract, respectively) and PN7 (332.11 and 252.3 mg GAE/g extract, respectively). The highest TPrC, TFC, and TPAC levels were found for PAL7 (21.28 mg catechin equivalents (CAT)/g extract, 71.85 mg rutin equivalents (RE)/g extract, and 124.18 mg caffeic acid equivalents (CAE)/g extract, respectively). LC-PDA-HRMS analysis revealed the presence of 83 compounds, including brevifolincarboxylic acid, ellagic acid, pedunculagin, agrimoniin, chlorogenic acid, astragalin, and tiliroside. Moreover, the presence of tri-coumaroyl spermidine was demonstrated for the first time in the genus Potentilla. Results of the MTT assay revealed that all tested extracts decreased the viability of both cell lines; however, a markedly stronger effect was observed in the colon cancer cells. The highest selectivity was demonstrated by PAR7, which effectively inhibited the metabolic activity of LS180 cells (IC50 = 38 µg/mL), while at the same time causing the lowest unwanted effects in CCD841 CoN cells (IC50 = 1134 µg/mL). BrdU assay revealed a significant decrease in DNA synthesis in both examined cell lines in response to all investigated extracts. It should be emphasized that the tested extracts had a stronger effect on colon cancer cells than normal colon cells, and the most significant antiproliferative properties were observed in the case of PAR7 (IC50 LS180 = 174 µg/mL) and PN7 (IC50 LS180 = 169 µg/mL). The results of LDH assay revealed that all tested extracts were not cytotoxic against normal colon epithelial cells, whereas in the cancer cells, all compounds significantly damaged cell membranes, and the observed effect was dose-dependent. The highest cytotoxicity was observed in LS180 cells in response to PAR7, which, in concentrations ranging from 25 to 250 µg/mL, increased LDH release by 110% to 1062%, respectively. Performed studies have revealed that all Potentilla species may be useful sources for anti-colorectal cancer agents; however, additional research is required to prove this definitively.
... Soybeans (legumes) and almonds (nuts) are among the foods that are known to contain high content of oxalate. The reported amounts of oxalate in soybeans and almonds per 100 g in the literature varies greatly; in soybeans the range is from 82 to 285 mg oxalate and in almonds the range is from 192 to 469 mg oxalate (Ellis and Lieb, 2015;Petroski and Minich, 2020). The discrepancy in the oxalate concentrations of plant foods can be related to growing conditions (e.g., light exposure, soil quality, level of maturity), harvest time, variety and different analytical methods used for oxalate extraction and determination (Siener et al., 2017). ...
Background: Plant-based milk alternatives have become increasingly popular over the years and numerous commercial products are already available. The aim of this study was to investigate the use of additives in plant-based milk alternatives. In addition, the percentage of contribution of soymilk and almond milk towards the Recommended Daily (RDI) Intake of oxalate was also estimated. Methods: The ingredient labels in 81 plant-based milk alternatives were used to identify the type and frequency of use of additives. Moreover, the mean plant material content was also extracted from the ingredient labels and was used to estimate the percentage of contribution of plant-based milks (for soymilk and almond milk) towards the RDI of oxalate. Result: More than half of 81 plant-based milk alternatives cont