Lectins

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 [14]. 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 [15,16]. Over 500 lectins have been isolated and identified from plants, who produce them primarily as defense mechanisms against insects, molds, fungi and diseases [14]. 

2.2. Background 

Plant lectins are widely distributed throughout the plant kingdom, available from many dietary sources including legumes, seeds, nuts, fruits, and vegetables [17]. 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 [16,18]. 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 [19]. 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 [20]. Disease susceptibility and genetic resistance may also play a role in lectin content [21,22]. 

2.3. Effects 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% [19]. Adeparusi et al. found that autoclaving lima beans for 20 min eliminated all anti-nutrients except tannins [23]. Boiling of red and white kidney beans, notoriously rich in phytohemoggluttinin (PHA), also resulted in complete elimination of lectins [24]. Microwave ovens on the other hand, are not an effective method for lectin deactivation. Though microwaving destroyed hemagglutinins in most legume seeds, it did not significantly affect lectins in common beans [25]. Additionally, fermentation over 72 h has been demonstrated to destroy almost all lectins in lentils (Lens culinaris) [26].

2.4. Safety 

The safety and overall health effects 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’ [27]. Nutrients 2020, 12, 2929 4 of 32 Cases of food poisoning involving raw or inadequately cooked legumes are well documented [28]. For example, in the UK between 1976 and 1989, 50 cases of food poisoning were suspected to be caused by inadequately prepared kidney beans [28]. PHA toxicity, caused by consumption of fresh kidney beans, is also common in China, and affected over 7000 individuals between 2004 and 2013 [20]. 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 [29]. 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) [32,33]. This change in intestinal integrity resulted in compromised nutrient absorption (protein, lipid and vitamin B12) and reduced growth of experimental animals [34–37]. 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 [29,38]. Another proposed mechanism of PHA toxicity is intestinal dysbiosis secondary to PHA-induced intestinal damage [37,39]. Clinical human trials using whole (cooked) beans, on the other hand, do not exhibit the same effects as in vitro or 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 effects when administered in isolation in animal models, cooking/autoclaving beans resulted in complete amelioration of PHA and associated erythrocyte agglutination in humans [24]. 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 affinity and specificity to glycans, interest lies in their potential as both cancer diagnostic and treatment tools [41]. Current approaches to cancer treatment are often accompanied by harmful side effects 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 [42–44]. 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 affect 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 different lectins, therefore, there may be some individuals who respond to undigested lectins [45]. 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 [46]. Diets rich in legumes and whole grains are associated with reduced inflammatory biomarkers in both animal and human trials [47–50]. Until further human clinical trials demonstrate otherwise, the health-promoting effects of lectin-containing foods would seem to far outweigh any possible negative effects of lectins.