March 2021 Issue

CPE Monthly: Understanding Lectins
By Kristin Sementelli, MS, RD, LDN
Today’s Dietitian
Vol. 23, No. 3, P. 46

Suggested CDR Performance Indicators: 8.1.3, 8.3.6, 8.3.7, 8.4.3
CPE Level 2

Take this course and earn 2 CEUs on our Continuing Education Learning Library

Lectins, a type of protein found in most plants, have come under fire in the past several years as the authors of many popular fad diets have suggested they cause negative health effects such as inflammation and digestive issues.

Lectins belong to a family of proteins that have the capacity to bind to specific
carbohydrates, including cellular surfaces. These proteins are found in most plants, including cereal grains, legumes, and fruit, but are present in the highest concentrations in black beans, kidney beans, soybeans, and whole grains. They play a protective role in plants, acting as a defense mechanism against external pathogens such as fungi and other pests and may be useful in plant germination and seed survival.1

In his best-selling book The Plant Paradox, Steven Gundry, MD, famously argued for avoidance of lectins to manage inflammation, obesity, and other chronic health conditions. Gundry goes as far as selling “Lectin Shield” pills on his website to protect against harmful lectins if individuals do choose to “indulge” in nonapproved foods. Proponents of the Paleo, Whole30, and the Bulletproof diets all shun foods containing lectins. As with many debates in nutrition science, there’s evidence both supporting and opposing the inclusion of lectins in the diet, but it’s important to fully understand the entire body of research to develop an informed opinion.

This continuing education course examines lectins’ potential negative effects on the digestive tract and possible role in inflammation, as well as any positive effects their consumption may have. Health benefits of foods containing lectins, specifically legumes and whole grains, are discussed. Practical recommendations for clients and ways to reduce lectins in food sources also will be described.

The Case Against Lectins
Damage to the digestive tract along with the potential to cause inflammation and trigger immune responses in humans have been noted as the primary reasons some individuals avoid consuming foods rich in lectins. Thus far, much of the evidence has been taken from rat studies, with limited research available on human subjects.

Following is a summary of the existing evidence in support of these claims.

Lectins and the Digestive Tract
One of the strongest arguments against the consumption of lectins is that they may cause damage to the digestive tract. A review article by Singh and Sarathi describes a study in which lectins were found in the feces of rats and humans whose diets were rich in dietary sources of lectins. The authors use this study as evidence that some lectins are resistant to breakdown by gut enzymes. They suggest this causes the lectins to bind to and cause damage to the gut lining, contributing to the development of diseases such as colitis, Crohn’s disease, and irritable bowel syndrome.2

Another study further concluded that lectins may decrease gut levels of heat shock proteins—proteins produced in response to stress—which leaves the cell wall less protected to the contents of the lumen. Ovelgönne and colleagues isolated wheat germ agglutination (WGA) as well as phytohaemagglutinin (PHA), a lectin found in red kidney beans. A total of six rats were divided evenly into three groups, each of which was given a good-quality diet mainly consisting of maize starch, potato starch, and glucose. One group acted as a control, while the other two groups had 7% of their diet, equaling 42 mg/day, replaced with either PHA or WGA.3

After 10 days, samples of the jejunum of the rats were examined to measure the response of heat shock proteins. Heat shock proteins are synthesized by the body in times of stress to help cope with damage. Lower levels of heat shock proteins were found in rats fed PHA or WGA compared with the control group. The authors suggest that this decreased response leaves the digestive tract more vulnerable to damage. It should be noted that the small sample size and use of animal models may not provide a full representation of lectin activity in the lumen.3

With the mechanism by which lectins may cause digestive tract damage largely unaddressed by researchers, Miyake and colleagues hypothesized that the presence of lectins may inhibit cell repair. In the study, they removed and mechanically damaged segments of rats’ gastrointestinal (GI) tracts. Repair was measured by monitoring the penetration of dyes across the plasma membrane and the secretion of mucus that accompanies the repair response. They found that the presence of WGA caused damage to the plasma membrane, as evidenced by increased cell permeability and decreased mucus response.4

Other studies examined lectins’ effect on digestive organs. When researchers fed PHA to rats, they observed enlargement of the intestine, liver, and pancreas. Furthermore, they found a decrease in insulin levels, which was linked to the enlargement of the pancreas and may be connected to diabetes development and progression. Atrophy of the thalamus also was found in the PHA-fed rats, a development linked to unusual proliferation of bacteria in the gut.2 While this research suggests lectins may cause damage to the digestive tract and/or digestive organs in humans, it doesn’t specify a safe limit nor provide sufficient evidence in human subjects.

Lectins and Immune Response/Inflammation
Research supports a strong link between inflammation of the gut and inflammation of the joints. A review study by Cordain and colleagues examined this link with the autoimmune disease rheumatoid arthritis.5

Autoimmune diseases occur when the body loses the ability to differentiate between healthy cells in the body and intruder cells, ultimately leading to destruction of tissues by the immune system. Research has shown that increased gut permeability, which can occur after exposure to lectins, allows gut-derived pathogenic antigens into the peripheral tissue, leading to prolonged immunological stimulation and inflammation. Furthermore, the study states that lectins may cause a bacterial overgrowth of E coli and Lactobacillus lactis, which are associated with the expression of rheumatoid arthritis.5

In addition to research on the effects of dietary lectins on rheumatoid arthritis, studies have examined their intake in relationship with other immune responses. A study published in the British Journal of Nutrition compared rats immunized with ovalbumin and later given either a saline solution with those administered WGA intragastrically for five days. The study found that treatment with WGA impaired the allergic response in rats as indicated by increased levels of mast cell protease II, an allergic mediator similar to histamine found in rats.6

Researchers used this finding to suggest that high intake of dietary lectins could trigger food allergies but failed to establish a direct connection. It should be noted that this study involved a small sample size of 18 to 24 rats and administered WGA in doses estimated to be 10 times greater than amounts consumed in a typical vegetarian diet, an eating pattern uncommon in the United States.6

A separate study examined the interleukin-4 (IL-4), interleukin-13 (IL-13), and histamine response to a variety of lectins using blood donations from human subjects. It found that many, but not all, dietary lectins triggered responses from IL-4, IL-13, and/or histamine from human basophils in vitro. Although this study showed evidence of an immune response in humans, its design suffered from a small sample size of nine to 11 subjects.7

This study, along with other similar investigations, have been widely cited as evidence of the inflammatory nature of lectins, but as van Buul and Brouns summarized in their research paper on the topic, the in vitro nature of this and other studies, along with the high levels of WGA used, make them poor models of the human condition.1

Health Benefits of Lectins
While there’s been plenty of focus on the harmful effects of lectin consumption, research has been conducted suggesting their consumption may have antimicrobial, antifungal, and antiviral effects.

Antimicrobial/Antifungal Effects
With antibiotics developing resistance to many strains of bacteria, it’s vital for the medical community to explore alternatives to current medicines. In one study, lectins were extracted from five cultivars of red kidney beans and added to cultures of bacteria and fungus. All five lectin variations demonstrated significant antibacterial activity against three of the bacterial strains studied (Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia) but not with the strand E coli. All lectins also showed antifungal activity against Candida albicans.8

Interestingly, a similar study using lectins isolated from quinoa demonstrated antibacterial activity against P aeruginosa, E coli, and Salmonella enterica, but not against S aureus or K pneumonia, suggesting that different varieties of lectins may protect against different strains of bacteria.9 While these studies are intriguing, more research must be conducted in vivo to conclude benefits. It’s also unclear whether these benefits would transfer to dietary consumption.

Antiviral Effects
Hepatitis B virus (HBV) is a fairly common viral infection that can lead to more serious health conditions such as chronic hepatitis and cirrhosis of the liver. While a vaccine exists to protect against HBV, it isn’t effective at eliminating chronic HBV infections. Pleurotus ostreatus (POL), a lectin found in mushrooms, was isolated and given to rats infected with a model of HBV. In comparison with controls, POL stimulated helper T cell response and activated toll-like receptor pathways, which are an important early immune response.10

HIV is another virus that presents global health concerns, but an effective vaccine has yet to be discovered. In one study, the lectin actinohivin was examined for its ability to bind to high-mannose type glycans of gp120, a glycoprotein of HIV. While research is new and further studies are needed, early findings suggest that actinohivin shows a strong affinity for gp120 and might be developed as a topical microbicide to prevent HIV infection.11

Anticancer Benefits
Plant lectins already have been in use for several decades as a tool to distinguish between malignant and benign tumors and measure the degree to glycosylation of cancer cells, a marker of tumor progression.12 More recently, lectins have been the focus of scientific research for their potential anticancer activity.

A 2013 article by Liu and colleagues outlined research that has been done on the topic and discussed the role lectins may have in inducing apoptosis, the process of programmed cell death. Numerous studies cited by the authors demonstrate that one particular lectin, concanavalin A (ConA), causes apoptosis in diverse types of cancer cells, including melanoma, glioblastoma, and ovarian cancer.12

ConA, as well as Polygonatum cyrtonema lectin and mistletoe lectins, also have been implicated in the regulation of autophagic cell death in cancer cells.12 A study published in the Journal of Inorganic Biochemistry examined an isolated form of the plant lectin DLasiL, a Brazilian flowering plant found in the seeds of the Dioclea lasiocarpa. DLasiL showed antiproliferative activity against several forms of cancer, including ovarian, lung, breast, and prostate cell lines.13

Digestive cancers are among the most researched forms of cancer in regard to the use of plant lectins for treatment. An article in the International Journal of Molecular Sciences reviewed current research on the activity of plant lectins on various types of digestive cancers. Gastric cancer cells that were exposed to lectins from the Urtica dioica plant, also known as nettle leaf, over 24 hours showed a decrease in cell proliferation and apoptosis compared with controls.14

Similar effects were found using lectins to treat colorectal cancer. In an in vitro study, 65% of cells treated with Korean mistletoe lectins demonstrated apoptosis by inhibiting antiapoptotic proteins. Apoptosis also was demonstrated using leaves of Morus alba (white mulberry trees); Lotus corniculatus, a plant native to North Africa; and tepary beans. On the other hand, some types of lectins, such as peanut agglutinin lectin, have shown mitogenic effects on cancer cells, suggesting more research must be done to identify the associated properties and pathways of lectins and cancer cells.14

The use of lectins as an anticancer agent has been mostly targeted as drug therapy. Beneficial doses for dietary consumption or as a supplement are still unknown, as most of the research has been in vitro.

Health Benefits of Foods Containing Lectins
In the research presented thus far, studies have isolated dietary lectins from food sources to examine their effects on certain health conditions. While it’s important to isolate and study individual components of foods, it’s equally essential to view the health effects of a given food as a whole. It’s been widely demonstrated that foods high in lectins have numerous health benefits. This raises the question of whether eliminating these healthful foods to reduce dietary lectin consumption is worth the trade-off.

While there are many lectin-rich food sources, this section examines the health benefits of legumes, whole grains, and soy, as these are the most widely researched food groups when it comes to lectins.

Legumes
Legumes, also referred to as pulses, include kidney beans, cannellini beans, great Northern beans, navy beans, fava beans, black beans, pinto beans, soybeans, black-eyed peas, chickpeas, and lentils. Each one-half cup serving provides about 8 g each of protein and fiber, and contains many vitamins and minerals, including B vitamins, iron, copper, magnesium, manganese, zinc, and phosphorus.15

Legumes are an integral component of many diets and dietary patterns with well-established health benefits such as the Mediterranean diet, the DASH diet, and vegetarian/vegan diets. Independently, they’ve been credited with the prevention and management of many chronic diseases such as obesity, type 2 diabetes, and CVD.16

Weight management is among the many benefits of legume consumption. Data from the National Health and Nutrition Examination Survey revealed an inverse relationship between legume consumption and body weight.15

Other studies have demonstrated promising outcomes pertaining to diabetes. A recent study showed that consumption of 3.4 servings of legumes per week over four years decreased the risk of type 2 diabetes by 35% compared with lower consumption (1.5 servings weekly).17

As cited by Jayalath and colleagues in a 2014 meta-analysis, a study by Jenkins and colleagues compared HbA1c levels in participants before and after a three-month intervention period during which they consumed one cup of legumes per day. A significant reduction of 0.5% in HbA1c levels was found among 56 participants.18,19

Many studies have shown legumes to be helpful in managing components of heart health, the leading cause of death in the United States.20 One meta-analysis of 10 randomized controlled trials revealed that eating legumes for a minimum of three weeks lowered total cholesterol by 11.8 mg/dL and LDL cholesterol by 8 mg/dL compared with controls.15

The Jayalath meta-analysis of randomized controlled trials, which encompassed a total of 554 participants, showed that the inclusion of legumes led to a significant decrease in systolic blood pressure but a nonsignificant decrease in diastolic blood pressure.18 The study by Jenkins and colleagues discussed previously, however, showed a significant decrease in both systolic and diastolic blood pressure.19 The researchers indicated that the high fiber and potassium content of legumes likely contribute to their blood pressure–lowering effects. They note that replacing animal sources of protein, which are high in saturated fat, with vegetarian protein sources likely is a contributing factor in some cases.

Whole Grains
Whole grains, including sources such as quinoa, barley, brown rice, millet, oatmeal, rye, and many others, provide important nutrients, including complex carbohydrates, fiber, B vitamins, a variety of phytonutrients, and minerals such as iron, magnesium, and selenium.21 As with legumes, they’ve been extensively researched and promoted for their ability to improve weight, diabetes, and cardiovascular health. In addition, positive effects on the GI tract also have been demonstrated.

A review study by Jonnalagadda and colleagues summarized research on whole grain consumption and weight gain. Of the 14 cross-sectional studies conducted at the time of publication, the researchers observed an inverse relationship between whole grain intake and BMI, with an average of 1-unit difference in BMI found between the highest and lowest quartiles of whole grain intake. A fairly modest intake of three servings of whole grains per day may yield this effect. The authors suggest that the fiber content of whole grains is responsible for this effect, as it promotes satiety by increasing food volume, regulating glycemic response, and slowing gastric emptying.21

Several studies have shown that whole grain consumption may be useful in the prevention of type 2 diabetes. One prospective cohort study found a 38% reduction in relative risk of developing type 2 diabetes when comparing the highest quartiles of whole grain intake compared with the lowest.21 A meta-analysis found a 21% risk reduction with a two-serving per day increase in whole grains.22 It’s been suggested that the rate of digestion of whole grains compared with that of refined grains, due to the fiber content, as well as the presence of antioxidants in whole grains, may contribute to this benefit.21

CVD risk appears to be lowered when individuals include dietary whole grains. Data from the Atherosclerosis Risk in Communities study, Iowa Women’s Health Study, and Nurses’ Health Study show a 28%, 30%, and 49% reduction in heart disease, respectively, when comparing high whole grain consumption (equivalent to three servings per day as described in one study) with low consumption. A meta-analysis of seven prospective cohort studies showed similar results, finding a 21% risk reduction in CVD events with consumption of 2.5 servings of whole grains compared with 0.2 servings/day. The heart-protective benefits of whole grains have been attributed to fiber, which is known to reduce cholesterol by causing fecal excretion of cholesterol from bile acids as well as inhibiting cholesterol synthesis through gut fermentation into short-chain fatty acids.21

The fiber found in whole grains also is thought to have beneficial effects on the GI tract by increasing fecal weight and transit time, efficiently removing carcinogenic compounds and lowering colonic pH. A 2005 study used dietary assessment to determine whole grain intake for 61,433 women aged 40 to 76. After a mean follow-up of 14.8 years, women in the highest quintile of whole grain consumption (five servings per day) had a 24% lower risk of colorectal cancer than did those in the lowest quintile (1.1 servings per day).23 A similar study in 489,611 men and women aged 50 to 71 defined high intake of whole grains as 1.3 servings and low intake as 0.2 servings per 1,000 kcal, yet found a similar risk reduction of 21% with the highest group compared with the lowest.24

Soy
Soy has long been a staple of high-quality protein in vegetarian diets—their potential for chronic disease prevention has been a hot topic in research over the past couple of decades. It has demonstrated cardioprotective benefits such as lowering LDL cholesterol, especially in individuals with hypercholesterolemia. Studies also have suggested that soy consumption can lead to a reduction in triglyceride levels by up to 5%. Meta-analyses have shown a more modest reduction in both systolic and diastolic blood pressure with soy consumption, by 2.5 and 1.5 mm Hg, respectively.25

At least three large prospective epidemiologic studies have found soymilk consumption to be protective against the development of osteoporosis and fracture in women. Several others have shown that isoflavones, a phytonutrient prevalent in soybeans, increase bone turnover, bone calcium, and/or bone mineral density.25

There has been conflicting information in the public and media regarding the relationship between soy and cancer risk. Some of the misunderstanding seems to come from findings in rat studies wherein giving rodents high doses of isoflavones was associated with an increased risk of breast cancer. This was thought to be from the isoflavones acting like estrogen in the body. The vast majority of human studies, however, have shown soy to either have no effect or a protective effect in the development of breast cancer.26

Despite the vast amount of research on the benefits of soy consumption, most has been done in Asian populations, a culture that tends to include many more soy products than the average American diet. Going forward, more research must be done in American populations to discern whether a protective effect is possible with lower soy consumption.

How to Reduce Lectin Content in Foods
With concern about the lectin content of food, clients can take steps to reduce the amount in their foods while still reaping the health benefits of those foods containing lectins.

Lectins have a globular tertiary structure, meaning they’re three-dimensional and approximately spherical in shape. Due to their structure, lectins in their raw form aren’t effectively broken down by digestive enzymes and have been found in significant concentrations in the blood and feces after ingestion. At high concentrations, it’s clear that lectins exhibit adverse health effects. However, the amount of lectins typically consumed per sitting as well as how foods are processed greatly influence lectin concentration and activity. For example, a recent thesis explained that WGA wasn’t detected in plasma samples taken after consumption of 50 g of wheat germ. Considering wheat germ represents only a tiny portion of the whole kernel, this amount would be equivalent to more than 80 slices of bread.1

Heat has been demonstrated to greatly affect the biological activity of lectins. One study showed that cooking pasta for 10 minutes at 149˚ F, a time and temperature authors concluded was representative of typical cooking methods, effectively inactivates WGA.1 Beans, which are essentially inedible in their raw form and need to be boiled to be consumed, are another example of how traditional food preparation methods limit lectin consumption. Pressure cooking winged beans for 10 minutes at 250˚ F essentially eliminated lectin content in one study.26

Vaz and colleagues examined the effect of food irradiation—a food processing technique that improves the shelf life of foods—on WGA activity. In one animal study, mice were assigned either as controls or treated with irradiated or nonirradiated WGA in amounts equivalent to the average American vegetarian. The results showed that irradiation made WGA significantly less active. Furthermore, mice fed irradiated WGA showed fewer immunological and allergic reactions than mice given nonirradiated WGA. While research on food irradiation and lectin activity is limited, this study shows that certain processing methods may reduce lectin levels in foods.27

Putting It Into Practice
Taking into account the research as a whole, the benefits of consuming foods containing lectins appear to outweigh any potential negative effects of their consumption for most of the population. Legumes, whole grains, and soy are important components of many well-researched dietary patterns, including the DASH, Mediterranean, and vegetarian/vegan diets. Health benefits of these plant foods range from providing fiber, vitamins, and minerals to preventing obesity, type 2 diabetes, and CVD.

Lectin consumption does appear to have some effect on the integrity of the digestive tract and to negatively affect those with rheumatoid arthritis. More research should be focused in these areas to more accurately assess the risks and determine appropriate recommendations. Clients with digestive disorders such as colitis, Crohn’s disease, and irritable bowel syndrome, as well as those with rheumatoid arthritis, should seek help from an RD in determining whether lectin consumption may be contributing to their symptoms. Those in the above-mentioned groups or otherwise looking to reduce lectins in their diet should be advised to thoroughly cook their foods before consuming them.

— Kristin Sementelli, MS, RD, LDN, is a clinical dietitian based in Chicago.

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Discuss what lectins are and which foods are sources.
2. Counsel clients on the potential negative effects of consuming lectins.
3. Distinguish the health benefits of consuming foods rich in lectins.
4. Provide practical recommendations about lectin consumption to consumers.

CPE Monthly Examination

1. Which type of lectin(s) can be found in red kidney beans?
a. Wheat germ agglutinin
b. Phytohaemagglutinin
c. Aleuria aurantia lectin
d. Vitamin C and magnesium

2. How have lectins been used to identify and diagnose cancer?
a. They’re a marker for cell death.
b. They’ve been found naturally in cancerous cells that have been biopsied.
c. They’ve been found as part of imaging tests.
d. They’re used to measure the degree to glycosylation of cancer cells.

3. Which book has greatly influenced the public’s perception of dietary lectins?
a. Forks Over Knives
b. Intuitive Eating
c. The Plant Paradox
d. The Omnivore’s Dilemma

4. The relationship between soy consumption and breast cancer risk has been most widely studied in which population?
a. Males
b. Eastern Europeans
c. Americans aged 40 and older
d. Asian populations

5. All five variations of lectins extracted from red kidney beans demonstrated antibacterial activity against all of the following bacterial strains, except which?
a. E coli
b. Staphylococcus aureus
c. Pseudomonas aeruginosa
d. Klebsiella pneumonia

6. Some studies have shown that lectins may cause an overgrowth of which two strains of bacteria that are associated with the expression of rheumatoid arthritis?
a. E coli and Lactobacillus lactis
b. Bacillus subtilis and Haemophilus influenzae
c. Clostridium perfringens and Bacillus subtilis
d. E coli and Haemophilus influenzae

7. Which of the following factors has not been proposed as a reason why lectins cause damage to the digestive tract?
a. Resistance to breakdown by gut enzymes
b. Decreased levels of stress proteins in the gut
c. Inhibition of cell repair
d. Decreased transit time in the gut

8. Legumes are an integral part of all of the following diets except which?
a. Mediterranean diet
b. Paleo diet
c. DASH diet
d. Vegetarian diet

9. Whole grains are a rich source of what nutrient, which has been shown to decrease the risk of colon cancer?
a. Folate
b. Vitamin B12
c. Fiber
d. Protein

10. Which cooking method has been shown to reduce lectin content in foods?
a. Heating
b. Freezing
c. Puréeing
d. Pasteurizing

References
1. van Buul VJ, Brouns FJPH. Health effects of wheat lectins: a review. J Cereal Sci. 2014;59(2):1-6.

2. Singh H, Sarathi S. Insight of lectins-a review. Int J Sci Eng Res. 2012;3(4)813-821.

3. Ovelgönne JH, Koninkx JF, Pusztai A, et al. Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins. Gut. 2000;46(5):679-687.

4. Miyake K, Tanaka T, McNeil PL. Lectin-based food poisoning: a new mechanism of protein toxicity. PLoS One. 2007;2(8):e687.

5. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000;83(3):207-217.

6. Watzl B, Neudecker C, Hänsch GM, Rechkemmer G, Pool-Zobel BL. Dietary wheat germ agglutinin modulates ovalbumin-induced immune responses in Brown Norway rats. Br J Nutr. 2001;85(4):483-490.

7. Haas H, Falcone FH, Schramm G, et al. Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. Eur J Immunol. 1999;29(3):918-927.

8. Hamid R, Masood A. Dietary lectins as disease causing toxicants. Pakistan J Nutr. 2009;8(3):293-303.

9. Pompeu DG, Mattioli MA, Ribeiro RIMD, et al. Purification, partial characterization and antimicrobial activity of lectin from Chenopodium quinoa seeds. Food Sci Technol (Campinas). 2015;35(4):696-703.

10. He M, Su D, Liu Q, Gao W, Kang Y. Mushroom lectin overcomes hepatitis B virus tolerance via TLR6 signaling. Sci Rep. 2017;7:5814.

11. Tanaka H, Chiba H, Inokoshi J, et al. Mechanism by which the lectin actinohivin blocks HIV infection of target cells. Proc Natl Acad Sci U S A. 2009;106(37):15633-15638.

12. Liu Z, Luo Y, Zhou TT, Zhang WZ. Could plant lectins become promising anti-tumour drugs for causing autophagic cell death? Cell Prolif. 2013;46(5):509-515.

13. Gondim ACS, Romero-Canelón I, Sousa EHS, et al. The potent anti-cancer activity of Dioclea lasiocarpa lectin. J Inorg Biochem. 2017;175:179-189.

14. Estrada-Martínez LE, Moreno-Celis U, Cervantes-Jiménez R, Ferriz-Martínez RA, Blanco-Labra A, García-Gasca T. Plant lectins as medical tools against digestive
system cancers. Int J Mol Sci. 2017;18(7):1403.

15. Polak R, Phillips EM, Campbell A. Legumes: health benefits and culinary approaches to increase intake. Clin Diabetes. 2015;33(4):198-205.

16. Melina V, Craig W, Levin S. Position of the Academy of Nutrition and Dietetics: vegetarian diets. J Acad Nutr Diet. 2016;116(12):1970-1980.

17. Becerra-Tomás N, Díaz-López A, Rosique-Esteban N, et al. Legume consumption is inversely associated with type 2 diabetes incidence in adults: a prospective assessment from the PREDIMED study. Clin Nutr. 2018;37(3):906-913.

18. Jayalath V, de Souza RJ, Sievenpiper JL, et al. Effect of dietary pulses on blood pressure: a systematic review and meta-analysis of controlled feeding trials. Am J Hypertens. 2014;27(1):56-64.

19. Jenkins DJA, Kendall CWC, Augustin LSA, et al. Effect of legumes as part of a low glycemic index diet on glycemic control and cardiovascular risk factors in type 2 diabetes mellitus: a randomized controlled trial. Arch Intern Med. 2012;172(21):1653-1660.

20. Heart disease. Centers for Disease Control and Prevention website. https://www.cdc.gov/heartdisease/index.htm. Updated June 23, 2020. Accessed October 23, 2020.

21. Jonnalagadda S, Harnack L, Liu RH, et al. Putting the whole grain puzzle together: health benefits associated with whole grains—summary of American Society for Nutrition 2010 Satellite Symposium. J Nutr. 2011;141(5):1011S-1022S.

22. de Munter JSL, Hu FB, Spiegelman D, Franz M, van Dam RM. Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med. 2007;4(8):e261.

23. Larsson SC, Giovannucci E, Bergkvist L, Wolk A. Whole grain consumption and risk of colorectal cancer: a population-based cohort of 60,000 women. Br J Cancer. 2005;92(9):1803-1807.

24. Yang L, Allred CD, Awika JM. Emerging evidence on the role of estrogenic sorghum flavonoids in colon cancer prevention. Cereal Foods World. 2014;59(5):244-251.

25. Messina M. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients. 2016;8(12):754.

26. Srivastava S, Khokhar S. Effects of processing on the reduction of β‐ODAP (β‐N‐oxalyl‐L‐2,3‐diaminopropionic acid) and Anti‐Nutrients of khesari dhal, Lathyrus sativus. J Sci Food Agric. 1996;71(1):50-58.

27. Vaz AFM, Souza MP, Carneiro-da-Cunha MG, et al. Molecular fragmentation of wheat-germ agglutinin induced by food irradiation reduces its allergenicity in sensitised mice. Food Chem. 2012;132(2):1033-1039.