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 [223]. 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 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 [225–229]. 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 [230]. The elucidated ‘anti-nutritional’ effects 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 [231]. Other studies suggest that iron status and absorption is not significantly affected 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 [225]. Dark and baking chocolate contains the highest amounts of proanthocyanidins (828–1332 mg/100 g) [225]. 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) [233]. Nuts (almonds, walnuts, pecans, and pistachios), common beans and some cereals, such as sorghum, also contain notable amounts of catechins [233]. 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 [234], though others have cited values as high as 300 mg/L [225]. 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 [225]. Tea is the predominant source of epigallocatechin gallate (EGCG), a powerful and well-studied antioxidant [235,236]. Ceylon has been reported to contain the most EGCG (128–229 mg/L) [234]. 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. Effects 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 [233], 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% [230,233]. 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 [234,237]. Tannin content in foods and tea can be influenced by region, variety, processing methods, and storage time [233,234,238]. Polyphenols were found to vary significantly between agricultural methods, though not as much as between cultivars [239–241]. 

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) [230,231,242]. Early animal studies reported tannins to cause depressed growth and egg production in poultry, when fed at levels of 0.5–2% of feed [242]. 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 [243]. Other animal 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 [245]. 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 affected when tea was consumed an hour after the meal [246]. Other factors, such as gender and baseline iron status, may also influence the impact of tannins on iron parameters. In a study investigating the effects 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 effects were observed in omnivorous males [247]. Green tea had no influence on ferritin levels in omnivorous and vegetarian females. In females with low baseline ferritin (<25 µg/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 effects of tannins may be offset by the inclusion of 30 mg of ascorbic acid [248–250]. 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 [251]. 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 [252]. Similar findings were also shown by Root et al. in adults from rural China [232]. 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 [253]. 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’ effects of tannins are debatable and highly variable, evidence supporting the many health benefits of tannins are widespread [225,228,254]. 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 [254]. 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 [255]. Inverse associations also existed for mortality from digestive diseases. Polyphenols in this population were mainly derived from beverages such as green tea and coffee [255,256]. Consumption of proanthocyanidin-rich foods has been shown to reduce the risk of chronic kidney insufficiency and renal disease [257]. Proanthocyanidins are believed to exert their renal and cardioprotective effects by reducing oxidative stress and improving endothelial function [258–260]. 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] [262,263]. Nrf2 is a key transcription factor responsible for the body’s detoxification and antioxidant defense systems [229]. Ellagic acids, present in raspberries, strawberries, pomegranates, and nuts have demonstrated anticarcinogenic effects 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 activity [264–266]; however, human clinical data indicating similar effects has not been demonstrated.

 Furthermore, flavanol-rich foods, such as fruits, vegetables, and cocoa demonstrate positive effects on cognition, executive function, and even mood, although exact mechanisms are yet to be elucidated [267–270]. 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) [267]. 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 [267]. 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 [268]. Grassi et al. found that consumption of high-flavanol dark chocolate ameliorated vascular impairment after sleep deprivation and improved working memory performance [271], indicating that cognitive improvements may be due to effects 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 [256]. 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 [272]. Significant reductions in plasma triacylglycerol and C-reactive protein concentrations were also linked to the changes in microbial counts [272]. Being that many polyphenols are metabolized by gut microbiota [256], individual microbial composition and dietary habits may influence both the bioavailability and physiological effects 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) effects of an individual, isolated compound or phytochemical are often quite different 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 effects 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.