Antimicrobial peptides are essential components of the innate immune system and are the first line of defense against invading pathogens. Human beta-defensin 1 (hBD-1) is the most important antimicrobial peptide in human epithelia, its expression is constitutive in most tissues, and it is not induced in instances of infection or inflammation. In addition to its antibacterial activity, hBD-1 has an immunomodulatory activity by recruiting immune cells. Our objective was to determine whether immune-enhancing ingredients, such as arginine, isoleucine, and polyunsaturated fatty acids (PUFA), which are added to immune-enhancing formulas, mediate their beneficial activity by bolstering the immune system through hBD-1 induction. Real-time PCR analysis of hBD-1 in human colon cells, HCT-116, revealed upregulation after treatment with arginine, isoleucine, and bovine serum albumin (BSA). BSA increased transcription as well as secretion of hBD-1. hBD-1 upregulation in response to BSA treatment was concomitant with c-myc over-expression, suggesting that hBD-1 may be regulated via a non-inflammatory pathway involving c-myc. Assuming similar control in vivo, our results may imply that nutrients found in immune-enhancing formulas upregulate hBD-1 expression, which, in turn, recruits the adaptive immune system. This sequence of events bolsters of the immune system, which may lead to fewer infectious complications, less antibiotics usage, and a shorter hospital stay, as indeed has been shown in patients fed immune-enhancing formulas.