Food-derived bioactive peptides in human health: Challenges and opportunities

Nutrients

Volumn 10, Issue 11, 2018, Pages

  Chakrabarti, Subhadeep ^a   Guha, Snigdha ^b   Majumder, Kaustav ^b  

^a Bureau of Nutritional Sciences   (Canada)

^b UNIVERSITY OF NEBRASKA LINCOLN   (United States)

Author keywords

Bioactive peptides; Enzymatic hydrolysis; Fermentation; Functional foods; Oral bioavailability; Peptide absorption

Indexed keywords

BETA LACTOGLOBULIN; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; LACTOGLOBULIN; MILK PROTEIN; NUTRACEUTICAL; PEPTIDE;

AMINO ACID SEQUENCE; BIOAVAILABILITY; BIOLOGICAL ACTIVITY; CLINICAL TRIAL (TOPIC); DIGESTION; FERMENTATION; FOOD; FOOD INTAKE; FOOD PROCESSING; FUNCTIONAL FOOD; GASTROINTESTINAL ABSORPTION; GASTROINTESTINAL TRACT; HUMAN; INFLAMMATORY BOWEL DISEASE; LACTOBACILLUS; LACTOBACILLUS BREVIS; NONHUMAN; NOVEL FOOD; NUTRITIONAL VALUE; PHYSIOLOGY; PROTEIN HYDROLYSIS; PROTEIN PURIFICATION; QUALITY CONTROL; REVIEW; SYNTHESIS; TRADITIONAL FOOD; DIET; DIETARY SUPPLEMENT; DRUG THERAPY; METABOLISM; PROTEIN INTAKE;

AMINO ACID SEQUENCE; BIOLOGICAL AVAILABILITY; DIET; DIETARY PROTEINS; DIETARY SUPPLEMENTS; FUNCTIONAL FOOD; HUMANS; PEPTIDES;

EID: 85056512531     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu10111738     Document Type: Review

References (120)

1. Daliri, E.B.M.; Oh, D.H.; Lee, B.H. Bioactive Peptides. Foods 2017, 6, 32. [CrossRef] [PubMed]
2. Korhonen, H.; Pihlanto, A. Bioactive peptides: Production and functionality. Int. Dairy J. 2006, 16, 945–960. [CrossRef]
3. Kitts, D.D.; Weiler, K. Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr. Pharm. Des. 2003, 9, 1309–1323. [CrossRef] [PubMed]
4. Sánchez, A.; Vázquez, A. Bioactive peptides: A review. FQS 2017, 1, 29–46. [CrossRef]
5. Chakrabarti, S.; Jahandideh, F.; Wu, J. Food-derived bioactive peptides on inflammation and oxidative stress. Biomed. Res. Int. 2014, 608979. [CrossRef] [PubMed]
6. Soory, M. Nutritional antioxidants and their applications in cardiometabolic diseases. Infect. Disord. Drug Targets 2012, 12, 388–401. [CrossRef] [PubMed]
7. Rutherfurd-Markwick, K.J. Food proteins as a source of bioactive peptides with diverse functions. Br. J. Nutr. 2012, 108, S149–S157. [CrossRef] [PubMed]
8. Fields, K.; Falla, T.J.; Rodan, K.; Bush, L. Bioactive peptides: Signaling the future. J. Cosmet. Dermatol. 2009, 8, 8–13. [CrossRef] [PubMed]
9. Moller, N.P.; Scholz-Ahrens, K.E.; Roos, N.; Schrezenmeir, J. Bioactive peptides and proteins from foods: Indication for health effects. Eur. J. Nutr. 2008, 47, 171–182. [CrossRef] [PubMed]
10. Moldes, A.B.; Vecino, X.; Cruz, J.M. Nutraceuticals and Food Additives. In Current Developments in Biotechnology and Bioengineering: Food and Beverages Industry, 1st ed.; Pandey, A., Sanromán, M.A., Du, G., Soccol, C.R., Dussap, C.G., Eds.; Elsevier: Amsterdam, The Netherlands, 2016; pp. 143–164. ISBN 9780444636775.
11. Haque, E.; Chand, R.; Kapila, S. Biofunctional properties of bioactive peptides of milk origin. Food Rev. Int. 2009, 25, 28–43. [CrossRef]
12. Fu, Y.; Therkildsen, M.; Aluko, R.E.; Lametsch, R. Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: Successes and challenges. Crit. Rev. Food Sci. Nutr. 2018, 1–17. [CrossRef] [PubMed]
13. Przybylski, R.; Firdaous, L.; Châtaigné, G.; Dhulster, P.; Nedjar, N. Production of an antimicrobial peptide derived from slaughterhouse by-product and its potential application on meat as preservative. Food Chem. 2016. [CrossRef] [PubMed]
14. Gu, Y.; Majumder, K.; Wu, J. QSAR-aided in silico approach in evaluation of food proteins as precursors of ACE inhibitory peptides. Food Res. Int. 2011, 44, 2465–2474. [CrossRef]
15. Perez Espitia, P.J.; de Fátima Ferreira Soares, N.; dos Reis Coimbra, J.S.; de Andrade, N.J.; Souza Cruz, R.; Alves Medeiros, E.A. Bioactive Peptides: Synthesis, Properties, and Applications in the Packaging and Preservation of Food. Compr. Rev. Food Sci. Food Saf. 2012, 11, 187–204. [CrossRef]
16. Gobbetti, M.; Ferranti, P.; Smacchi, E.; Goffredi, F.; Addeo, F. Production of Angiotensin-I-Converting-Enzyme-Inhibitory Peptides in Fermented Milks Started by Lactobacillus delbrueckii subsp. bulgaricus SS1 and Lactococcus lactis subsp. cremoris FT4. Appl. Environ. Microbiol. 2000, 66, 3898–3904. [CrossRef] [PubMed]
17. El-Fattah, A.M.A.; Sakr, S.S.; El-Dieb, S.M.; Elkashef, H.A.S. Bioactive peptides with ACE-I and antioxidant activity produced from milk proteolysis. Int. J. Food Prop. 2017, 20, 3033–3042. [CrossRef]
18. Ferri, M.; Graen-Heedfeld, J.; Bretz, K.; Guillon, F.; Michelini, E.; Calabretta, M.M.; Lamborghini, M.; Gruarin, N.; Roda, A.; Kraft, A.; et al. Peptide fractions obtained from rice by-products by means of an environment-friendly process show in vitro health-related bioactivities. PLoS ONE 2017, 12, e0170954. [CrossRef] [PubMed]
19. Fu, Y.; Liu, J.; Hansen, E.T.; Bredie, W.L.P.; Lametsch, R. Structural characteristics of low bitter and high umami protein hydrolysates prepared from bovine muscle and porcine plasma. Food Chem. 2018, 257, 163–171. [CrossRef] [PubMed]
20. Mora, L.; Bolumar, T.; Heres, A.; Toldrá, F. Effect of cooking and simulated gastrointestinal digestion on the activity of generated bioactive peptides in aged beef meat. Food Funct. 2017, 8, 4347–4355. [CrossRef] [PubMed]
21. Aspri, M.; Leni, G.; Galaverna, G.; Papademas, P. Bioactive properties of fermented donkey milk, before and after in vitro simulated gastrointestinal digestion. Food Chem. 2018, 268, 476–484. [CrossRef] [PubMed]
22. Vieira, E.F.; das Neves, J.; Vitorino, R.; Dias da Silva, D.; Carmo, H.; Ferreira, I.M. Impact of in vitro Gastrointestinal Digestion and Transepithelial Transport on Antioxidant and ACE-Inhibitory Activities of Brewer’s Spent Yeast Autolysate. J. Agric. Food Chem. 2016, 64, 7335–7341. [CrossRef] [PubMed]
23. Picariello, G.; Miralles, B.; Mamone, G.; Sánchez-Rivera, L.; Recio, I.; Addeo, F.; Ferranti, P. Role of intestinal brush border peptidases in the simulated digestion of milk proteins. Mol. Nutr. Food Res. 2015, 59, 948–956. [CrossRef] [PubMed]
24. Rizzello, C.G.; Lorusso, A.; Russo, V.; Pinto, D.; Marzani, B.; Gobbetti, M. Improving the antioxidant properties of quinoa flour through fermentation with selected autochthonous lactic acid bacteria. Int. J. Food Microbiol. 2017, 241, 252–261. [CrossRef] [PubMed]
25. Aguilar-Toalá, J.E.; Santiago-López, L.; Peres, C.M.; Peres, C.; Garcia, H.S.; Vallejo-Cordoba, B.; González-Córdova, A.F.; Hernández-Mendoza, A. Assessment of multifunctional activity of bioactive peptides derived from fermented milk by specific Lactobacillus plantarum strains. J. Dairy Sci. 2017, 100, 65–75. [CrossRef] [PubMed]
26. Ahn, J.E.; Park, S.Y.; Atwal, A.; Gibbs, B.F.; Lee, B.H. Angiotensin I-Converting Enzyme (Ace) Inhibitory Peptides From Whey Fermented By Lactobacillus Species. J. Food Biochem. 2009, 33, 587–602. [CrossRef]
27. Sanjukta, S.; Rai, A.K.; Muhammed, A.; Jeyaram, K.; Talukdar, N.C. Enhancement of antioxidant properties of two soybean varieties of Sikkim Himalayan region by proteolytic Bacillus subtilis fermentation. J. Funct. Foods 2015, 14, 650–658. [CrossRef]
28. Chaudhury, A.; Duvoor, C.; Reddy Dendi, V.S.; Kraleti, S.; Chada, A.; Ravilla, R.; Marco, A.; Shekhawat, N.S.; Montales, M.T.; Kuriakose, K.; et al. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front. Endocrinol. 2017, 8, 6. [CrossRef] [PubMed]
29. Li-Chan, E.C.Y. Bioactive peptides and protein hydrolysates: Research trends and challenges for application as nutraceuticals and functional food ingredients. Curr. Opin. Food Sci. 2015, 1, 28–37. [CrossRef]
30. Hanke, A.T.; Ottens, M. Purifying biopharmaceuticals: Knowledge-based chromatographic process development. Trends Biotechnol. 2014, 32, 210–220. [CrossRef] [PubMed]
31. Cheung, I.W.Y.; Li-Chan, E.C.Y. Angiotensin-I-converting enzyme inhibitory activity and bitterness of enzymatically-produced hydrolysates of shrimp (Pandalopsis dispar) processing byproducts investigated by Taguchi design. Food Chem. 2010, 122, 1003–1012. [CrossRef]
32. Kopf-Bolanz, K.A.; Schwander, F.; Gijs, M.; Vergères, G.; Portmann, R.; Egger, L. Impact of milk processing on the generation of peptides during digestion. Int. Dairy J. 2014, 35, 130–138. [CrossRef]
33. Kamdem, J.P.; Tsopmo, A. Reactivity of peptides within the food matrix. J. Food Biochem. 2017, e12489. [CrossRef]
34. Jakubczyk, A.; Baraniak, B. Angiotensin I Converting Enzyme Inhibitory Peptides Obtained after in vitro Hydrolysis of Pea (Pisum sativum var. Bajka) Globulins. Biomed. Res. Int. 2014, 438459. [CrossRef]
35. Yousr, M.; Howell, N. Antioxidant and ACE Inhibitory Bioactive Peptides Purified from Egg Yolk Proteins. Int. J. Mol Sci. 2015, 16, 29161–29178. [CrossRef] [PubMed]
36. Holton, T.A.; Vijayakumar, V.; Khaldi, N. Bioinformatics: Current perspectives and future directions for food and nutritional research facilitated by a Food-Wiki database. Trends Food Sci. Technol. 2013, 34, 5–17. [CrossRef]
37. Minkiewicz, P.; Dziuba, J.; Iwaniak, A.; Dziuba, M.; Darewicz, M. BIOPEP database and other programs for processing bioactive peptide sequences. J. AOAC Int. 2008, 91, 965–980. [PubMed]
38. Rawlings, N.D.; Barrett, A.J.; Finn, R. MEROPS:the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 2016, 44, D343–D350. [CrossRef] [PubMed]
39. Zelazko, M.; Chrzanowska, J.; Polanowski, A. Pancreatic proteinases—Species diversity and the appending feeding and biotechnological implications. Biotechnologia 2007, 76, 107–120.
40. Agyei, D.; Danquah, M.K. Industrial-scale manufacturing of pharmaceutical-grade bioactive peptides. Biotechnol. Adv. 2011, 29, 272–277. [CrossRef] [PubMed]
41. Erdmann, K.; Cheung, B.W.; Schröder, H. The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J. Nutr. Biochem. 2008, 19, 643–654. [CrossRef] [PubMed]
42. Meyerhof, W. Elucidation of mammalian bitter taste. Rev. Physiol. Biochem. Pharmacol. 2005, 154, 37–72. [CrossRef] [PubMed]
43. Bumberger, E.; Belitz, H.D. Bitter taste of enzymic hydrolysates of casein—I. Isolation, structural and sensorial analysis of peptides from tryptic hydrolysates of β-casein. Z. Lebensm. Unters. Forsch. 1993, 197, 14–19. [CrossRef] [PubMed]
44. Maehashi, K.; Huang, L. Bitter peptides and bitter taste receptors. Cell. Mol. Life Sci. 2009, 66, 1661–1671. [CrossRef] [PubMed]
45. Kim, H.-O.; Li-Chan, E.C.Y. Quantitative Structure−Activity Relationship Study of Bitter Peptides. J. Agric. Food Chem. 2006, 54, 10102–10111. [CrossRef] [PubMed]
46. Li, L.; Yang, Z.Y.; Yang, X.Q.; Zhang, G.H.; Tang, S.Z.; Chen, F. Debittering effect of Actinomucor elegans peptidases on soybean protein hydrolysates. J. Ind. Microbiol. Biotechnol. 2008, 35, 41–47. [CrossRef] [PubMed]
47. Huang, W.Q.; Zhong, L.F.; Meng, Z.Z.; You, Z.J.; Li, J.Z.; Luo, X.C. The Structure and Enzyme Characteristics of a Recombinant Leucine Aminopeptidase rLap1 from Aspergillus sojae and Its Application in Debittering. Appl. Biochem. Biotechnol. 2015, 177, 190–206. [CrossRef] [PubMed]
48. Fu, J.; Li, L.; Yang, X.Q. Specificity of carboxypeptidases from actinomucor elegans and their debittering effect on soybean protein hydrolysates. Appl. Biochem. Biotechnol. 2011, 165, 1201–1210. [CrossRef] [PubMed]
49. Saha, B.C.; Hayashi, K. Debittering of protein hydrolyzates. Biotechnol. Adv. 2001, 19, 355–370. [CrossRef]
50. Leksrisompong, P.; Gerard, P.; Lopetcharat, K.; Drake, M. Bitter Taste Inhibiting Agents for Whey Protein Hydrolysate and Whey Protein Hydrolysate Beverages. J. Food Sci. 2012, 77, S282–S287. [CrossRef] [PubMed]
51. Liu, B.Y.; Zhu, K.X.; Guo, X.N.; Peng, W.; Zhou, H.M. Effect of deamidation-induced modification on umami and bitter taste of wheat gluten hydrolysates. J. Sci. Food Agric. 2017, 97, 3181–3188. [CrossRef] [PubMed]
52. Zhang, C.; Alashi, A.M.; Singh, N.; Liu, K.; Chelikani, P.; Aluko, R.E. Beef Protein-Derived Peptides as Bitter Taste Receptor T2R4 Blockers. J. Agric. Food Chem. 2018, 66, 4902–4912. [CrossRef] [PubMed]
53. Hartmann, R.; Meisel, H. Food-derived peptides with biological activity: From research to food applications. Curr. Opin. Biotechnol. 2007, 18, 163–169. [CrossRef] [PubMed]
54. Majumder, K.; Wu, J. Purification and characterisation of angiotensin i converting enzyme (ACE) inhibitory peptides derived from enzymatic hydrolysate of ovotransferrin. Food Chem. 2011, 126, 1614–1619. [CrossRef] [PubMed]
55. Fujita, H.; Yoshikawa, M. LKPNM: A prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology 1999, 44, 123–127. [CrossRef]
56. Offengenden, M.; Chakrabarti, S.; Wu, J. Chicken Collagen Hydrolysates Differentially Mediate Anti-inflammatory Activity and Type I Collagen Synthesis on Human Dermal Fibroblasts. Food Sci. Hum. Wellness 2018, 7, 138–147. [CrossRef]
57. Chang, C.; Lahti, T.; Tanaka, T.; Nickerson, M.T. Egg proteins: Fractionation, bioactive peptides and allergenicity. J. Sci. Food Agric. 2018, 98, 5547–5558. [CrossRef] [PubMed]
58. Nongonierma, A.B.; FitzGerald, R.J. Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins. Anal. Bioanal. Chem. 2018, 410, 3407–3423. [CrossRef] [PubMed]
59. Jahandideh, F.; Majumder, K.; Chakrabarti, S.; Morton, J.S.; Panahi, S.; Kaufman, S.; Davidge, S.T.; Wu, J. Beneficial Effects of Simulated Gastro-Intestinal Digests of Fried Egg and Its Fractions on Blood Pressure, Plasma Lipids and Oxidative Stress in Spontaneously Hypertensive Rats. PLoS ONE 2014, 9, e115006. [CrossRef] [PubMed]
60. Wada, Y.; Lönnerdal, B. Bioactive peptides released by in vitro digestion of standard and hydrolyzed infant formulas. Peptides 2015, 73, 101–105. [CrossRef] [PubMed]
61. Ng, D.H.C.; Embleton, N.D.; McGuire, W. Hydrolyzed formula compared with standard formula for preterm infants. JAMA 2018, 319, 1717–1718. [CrossRef] [PubMed]
62. Muheem, A.; Shakeel, F.; Jahangir, M.A.; Anwar, M.; Mallick, N.; Jain, G.K.; Warsi, M.H.; Ahmad, F.J. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm. J. 2016, 24, 413–428. [CrossRef] [PubMed]
63. Lundquist, P.; Artursson, P. Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues. Adv. Drug Deliv. Rev. 2016, 106, 256–276. [CrossRef] [PubMed]
64. Artursson, P.; Knight, S.D. Breaking the intestinal barrier to deliver drugs. Science 2015, 347, 716–717. [CrossRef] [PubMed]
65. Lindmark, T.; Kimura, Y.; Artursson, P. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J. Pharmacol. Exp. Ther. 1998, 284, 362–369. [PubMed]
66. Lindmark, T.; Schipper, N.; Lazorová, L.; De Boer, A.G.; Artursson, P. Absorption enhancement in intestinal epithelial Caco-2 monolayers by sodium caprate: Assessment of molecular weight dependence and demonstration of transport routes. J. Drug Target. 1998, 5, 215–223. [CrossRef] [PubMed]
67. Maher, S.; Kennelly, R.; Bzik, V.A.; Baird, A.W.; Wang, X.; Winter, D.; Brayden, D.J. Evaluation of intestinal absorption enhancement and local mucosal toxicity of two promoters. I. Studies in isolated rat and human colonic mucosae. Eur. J. Pharm. Sci. 2009, 38, 291–300. [CrossRef] [PubMed]
68. Jin, Y.; Blikslager, A.T. Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury. Am. J. Physiol. Cell Physiol. 2016, 311, C996–C1004. [CrossRef] [PubMed]
69. Murthy, K.S.; Zhou, H.; Grider, J.R.; Brautigan, D.L.; Eto, M.; Makhlouf, G.M. Differential signalling by muscarinic receptors in smooth muscle: m2-mediated inactivation of myosin light chain kinase via Gi3, Cdc42/Rac1 and p21-activated kinase 1 pathway, and m3-mediated MLC20 (20 kDa regulatory light chain of myosin II) phosphorylat. Biochem. J. 2003, 374, 145. [CrossRef] [PubMed]
70. Pooga, M.; Langel, Ü. Classes of cell-penetrating peptides. In Cell-Penetrating Peptides: Methods and Protocols; Humana Press: New York, NY, USA, 2015; Volume 1324, pp. 3–28, ISBN 9781493928064.
71. Dupont, E.; Prochiantz, A.; Joliot, A. Penetratin story: An overview. In Cell-Penetrating Peptides: Methods and Protocols; Humana Press: New York, NY, USA, 2015; Volume 1324, pp. 29–37, ISBN 9781493928064.
72. Vives, E. Present and future of cell-penetrating peptide mediated delivery systems: “Is the Trojan horse too wild to go only to Troy?”. J. Control. Release 2005, 109, 77–85. [CrossRef] [PubMed]
73. Koren, E.; Torchilin, V.P. Cell-penetrating peptides: Breaking through to the other side. Trends Mol. Med. 2012, 18, 385–393. [CrossRef] [PubMed]
74. Thuenauer, R.; Müller, S.K.; Römer, W. Pathways of protein and lipid receptor-mediated transcytosis in drug delivery. Expert Opin. Drug Deliv. 2017, 14, 341–351. [CrossRef] [PubMed]
75. Kohli, N.; Westerveld, D.R.; Ayache, A.C.; Verma, A.; Shil, P.; Prasad, T.; Zhu, P.; Chan, S.L.; Li, Q.; Daniell, H. Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers. Mol. Ther. 2014, 22, 535–546. [CrossRef] [PubMed]
76. Chen, J.; Liu, C.; Shan, W.; Xiao, Z.; Guo, H.; Huang, Y. Enhanced stability of oral insulin in targeted peptide ligand trimethyl chitosan nanoparticles against trypsin. J. Microencapsul. 2015, 32, 632–641. [CrossRef] [PubMed]
77. Pridgen, E.M.; Alexis, F.; Kuo, T.T.; Levy-Nissenbaum, E.; Karnik, R.; Blumberg, R.S.; Langer, R.; Farokhzad, O.C. Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci. Transl. Med. 2013, 5, 213ra167. [CrossRef] [PubMed]
78. Harokopakis, E.; Hajishengallis, G.; Michalek, S.M. Effectiveness of liposomes possessing surface-linked recombinant B subunit of cholera toxin as an oral antigen delivery system. Infect. Immun. 1998, 66, 4299–4304. [PubMed]
79. Geissler, S.; Zwarg, M.; Knütter, I.; Markwardt, F.; Brandsch, M. The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters. FEBS J. 2010, 277, 790–795. [CrossRef] [PubMed]
80. Satake, M.; Enjoh, M.; Nakamura, Y.; Takano, T.; Kawamura, Y.; Arai, S.; Shimizu, M. Transepithelial Transport of the Bioactive Tripeptide, Val-Pro-Pro, in Human Intestinal Caco-2 Cell Monolayers. Biosci. Biotechnol. Biochem. 2002, 66, 378–384. [CrossRef] [PubMed]
81. Bejjani, S.; Wu, J. Transport of IRW, an Ovotransferrin Derived Antihypertensive Peptide, in Human Intestinal Epithelial Caco-2 cells. J. Agric. Food Chem. 2013, 61, 1487–1492. [CrossRef] [PubMed]
82. Miner-Williams, W.M.; Stevens, B.R.; Moughan, P.J. Are intact peptides absorbed from the healthy gut in the adult human? Nutr. Res. Rev. 2014, 27, 308–329. [CrossRef] [PubMed]
83. Santiago-Lopez, L.; F. Gonzalez-Cordova, A.; Hernandez-Mendoza, A.; Vallejo-Cordoba, B. Potential Use of Food Protein-Derived Peptides in the Treatment of Inflammatory Diseases. Protein Pept. Lett. 2017, 24, 137–145. [CrossRef] [PubMed]
84. Wang, C.Y.; Liu, S.; Xie, X.-N.; Tan, Z.R. Regulation profile of the intestinal peptide transporter 1 (PepT1). Drug Des. Dev. Ther. 2017, 11, 3511–3517. [CrossRef] [PubMed]
85. Zhang, H.; Hu, C.-A.A.; Kovacs-Nolan, J.; Mine, Y. Bioactive dietary peptides and amino acids in inflammatory bowel disease. Amino Acids 2015, 47, 2127–2141. [CrossRef] [PubMed]
86. De Medina, F.S.; Daddaoua, A.; Requena, P.; Capitán-Cañadas, F.; Zarzuelo, A.; Dolores Suárez, M.; Martínez-Augustin, O. New insights into the immunological effects of food bioactive peptides in animal models of intestinal inflammation. Proc. Nutr. Soc. 2010, 69, 454–462. [CrossRef] [PubMed]
87. Mandigers, P.J.J.; Biourge, V.; German, A.J. Efficacy of a commercial hydrolysate diet in eight cats suffering from inflammatory bowel disease or adverse reaction to food. Tijdschr. Diergeneeskd. 2010, 135, 668–672. [PubMed]
88. Shi, Y.; Rupa, P.; Jiang, B.; Mine, Y. Hydrolysate from eggshell membrane ameliorates intestinal inflammation in mice. Int. J. Mol. Sci. 2014, 15, 22728–22742. [CrossRef] [PubMed]
89. Epstein, J.; Seitz, R.; Dhingra, N.; Ganz, P.R.; Gharehbaghian, A.; Spindel, R.; Teo, D.; Reddy, R. Role of regulatory agencies. Biol. J. Int. Assoc. Biol. Stand. 2009, 37, 94–102. [CrossRef] [PubMed]
90. L’abbé, M.R.; Dumais, L.; Chao, E.; Junkins, B. Health claims on foods in Canada. J. Nutr. 2008, 138, 1221S–1227S. [CrossRef] [PubMed]
91. Ellwood, K.C.; Trumbo, P.R.; Kavanaugh, C.J. How the US Food and Drug Administration evaluates the scientific evidence for health claims. Nutr. Rev. 2010, 68, 114–121. [CrossRef] [PubMed]
92. Tapsell, L.C. Evidence for health claims: A perspective from the Australia-New Zealand region. J. Nutr. 2008, 138, 1206S–1209S. [CrossRef] [PubMed]
93. Government of Canada. Food and Drugs Act (R.S.c., 1985, c. F-27). Available online: http://laws-lois.justice. gc.ca/eng/acts/F-27/FullText.html (accessed on 9 August 2018).
94. Coppens, P.; da Silva, M.F.; Pettman, S. European regulations on nutraceuticals, dietary supplements and functional foods: A framework based on safety. Toxicology 2006, 221, 59–74. [CrossRef] [PubMed]
95. Leroy, F.; De Vuyst, L. Fermented food in the context of a healthy diet: How to produce novel functional foods? Curr. Opin. Clin. Nutr. Metab. Care 2014, 17, 574–581. [CrossRef] [PubMed]
96. Frias, J.; Martinez-Villaluenga, C.; Peñas, E. Fermented Foods in Health and Disease Prevention, 1st ed.; Frias, J., Martinez-Villaluenga, C., Peñas, E., Eds.; Academic Press: Cambridge, MA, USA, 2017; ISBN 9780128023099.
97. Government of Canada. Justice Laws Website. Food and Drug Regulations (CRC C.870). Available online: http://laws-lois.justice.gc.ca/eng/regulations/C.R.C.%2C_c._870/page-102.html#h-142 (accessed on 9 August 2018).
98. Paul, R.H.; Frestedt, J.; Magurany, K. GRAS from the ground up: Review of the Interim Pilot Program for GRAS notification. Food Chem. Toxicol. 2017, 105, 140–150. [CrossRef] [PubMed]
99. U.S. Food & Drug Administration. Food. Generally Recognized as Safe (GRAS). Available online: https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/default.htm (accessed on 9 August 2018).
100. Hunter, P.M.; Hegele, R.A. Functional foods and dietary supplements for the management of dyslipidaemia. Nat. Rev. Endocrinol. 2017, 13, 278–288. [CrossRef] [PubMed]
101. Matos, J.; Cardoso, C.; Bandarra, N.M.; Afonso, C. Microalgae as healthy ingredients for functional food: A review. Food Funct. 2017, 8, 2672–2685. [CrossRef] [PubMed]
102. Hobbs, J.E.; Malla, S.; Sogah, E.K. Regulatory Frameworks for Functional Food and Supplements. Can. J. Agric. Econ. 2014, 62, 569–594. [CrossRef]
103. Patel, D.; Dufour, Y.; Domigan, N. Functional food and nutraceutical registration processes in Japan and China: A diffusion of innovation perspective. J. Pharm. Pharm. Sci. 2008, 11, 1–11. [CrossRef] [PubMed]
104. Govt of Japan Ministry of Health, Labour and Welfare: Food with Health Claims, Food for Special Dietary Uses, and Nutrition Labeling. Available online: https://www.mhlw.go.jp/english/topics/foodsafety/fhc/02.html (accessed on 9 August 2018).
105. Joint Food & Agriculture Organization (FAO)/World Health Organization (WHO). Codex Alimentarius Commission. CODEX STAN 72-1981 Standard for Infant Formula and Formulas for Special Medical Purposes Intended for Infants Sections A&B Revision 2007. Amended 2016. Available online: http://www.fao.org/fao-who-codexalimentarius/sh-proxy/fr/?lnk=1&url=https%253A%252F%252Fworkspace. fao.org%252Fsites%252Fcodex%252FStandards%252FCODEX%2BSTAN%2B72-1981%252FCXS_072e.pdf (accessed on 9 August 2018).
106. Institute of Medicine (US) Committee on the Evaluation of the Addition of Ingredients New to Infant Formula. Infant Formula: Evaluating the Safety of New Ingredients; National Academies Press: Washington, DC, USA, 2004; ISBN 978-0-309-09150-3.
107. Vandenplas, Y. Prevention and Management of Cow’s Milk Allergy in Non-Exclusively Breastfed Infants. Nutrients 2017, 9, 731. [CrossRef] [PubMed]
108. von Berg, A. Modified proteins in allergy prevention. Nestle Nutr. Workshop Ser. Pediatr. Program 2009, 64, 239–247, discussion 247–257. [CrossRef] [PubMed]
109. Salvatore, S.; Vandenplas, Y. Hydrolyzed Proteins in Allergy. Nestle Nutr. Workshop Ser. Pediatr. Program 2016, 86, 11–27. [CrossRef]
110. Government of Canada. Category Specific Guidance for Temporary Marketing Authorization: Supplemented Food. Available online: https://www.canada.ca/en/health-canada/services/food-nutrition/legislation-guidelines/guidance-documents/category-specific-guidance-temporary-marketing-authorization-supplemented-food.html (accessed on 9 August 2018).
111. Gilani, G.S.; Xiao, C.; Lee, N. Need for accurate and standardized determination of amino acids and bioactive peptides for evaluating protein quality and potential health effects of foods and dietary supplements. J. AOAC Int. 2008, 91, 894–900. [PubMed]
112. Santini, A.; Cammarata, S.M.; Capone, G.; Ianaro, A.; Tenore, G.C.; Pani, L.; Novellino, E. Nutraceuticals: Opening the debate for a regulatory framework. Br. J. Clin. Pharmacol. 2018, 84, 659–672. [CrossRef] [PubMed]
113. Aronson, J.K. Defining “nutraceuticals”: Neither nutritious nor pharmaceutical. Br. J. Clin. Pharmacol. 2017, 83, 8–19. [CrossRef] [PubMed]
114. U.S. Food & Drug Administration. Dietary Supplements. Available online: https://www.fda.gov/Food/DietarySupplements/(accessed on 9 August 2018).
115. Health Canada, Natural Health Products Ingredients Database. Available online: http://webprod.hc-sc.gc. ca/nhpid-bdipsn/search-rechercheReq.do (accessed on 9 August 2018).
116. U.S. Food & Drug Administration. New Dietary Ingredients Notification Process—Submitted 75-Day Premarket Notifications for New Dietary Ingredients. Available online: https://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/ucm534510.htm (accessed on 9 August 2018).
117. Government of Canada. Natural Health Products Regulations. Available online: http://laws-lois.justice.gc. ca/eng/regulations/SOR-2003-196/page-1.html (accessed on 9 August 2018).
118. Parveen, A.; Parveen, B.; Parveen, R.; Ahmad, S. Challenges and guidelines for clinical trial of herbal drugs. J. Pharm. Bioallied Sci. 2015, 7, 329–333. [CrossRef] [PubMed]
119. Paller, C.J.; Denmeade, S.R.; Carducci, M.A. Challenges of conducting clinical trials of natural products to combat cancer. Clin. Adv. Hematol. Oncol. 2016, 14, 447–455. [PubMed]
120. Dwyer, J.T.; Coates, P.M.; Smith, M.J. Dietary Supplements: Regulatory Challenges and Research Resources. Nutrients 2018, 10, 41. [CrossRef] [PubMed]