The value of bovine colostrum as a biologic in medicine is documented in clinical trials and supported by relatively large databases containing case reports and anecdotal findings. The main actions include an antibacterial effect and modulation of the immune response. The ability of bovine colostrum concentrates (BCC are polyvalent bovine colostrum concentrates produced from the colostrums of several 100 cows) to neutralize lipopolysaccharides, i.e. endotoxins arising from Gram-negative bacterial pathogens and to inhibit enterogenic endotoxemia in animal models as shown in the last review to have its counterpart in patient therapy. Clinical trials with BCC provide evidence that oral application reduces the influx of LPS from the gut and this appears to be a major mechanism underlying its therapeutic effect in patients at risk for Gram-negative septic shock; data from two well-controlled clinical studies with a total of 100 surgical patients have shown that the inhibition of intestinal LPS absorption measured after the application of BCC not only reduced the LPS levels in the peripheral blood but also inflammatory parameters like IL-6 and CRP were found to be diminished. The usual daily dose of the commercially available BCC preparation, LactobinA (LC1) is 10 â 20 g daily, but higher doses can be used in the majority of patients because of the low incidence of intolerance problems. In chronic diarrhea involving severe forms of secondary immunodeficiencies, patients receiving LC1 were disease-free for about 4 weeks but the response may be lower in patients with AIDS. BCC is effective in infants with hemorrhagic diarrhea caused by infections with enterohemorrhagic E. coli and reduces the likelihood of the disease progressing to a hemolytic uremic syndrome. The safety of newer BCC products obtained from BSE-free regions seems now beyond contention. In the case of LC1, which was used as a commercial dietary foodstuff in Germany until 1992 and tested in three Phase 1 and 5 clinical studies (two trials in patients with secondary immunodeficiencies, one in surgical patients with gastrointestinal disorders, one in patients undergoing open heart surgery and one in pediatric patients with EHEC infections), there were no cases of BSE-associated disease such as the new variant of Creutzfeldt-Jakob disease. Side effects of clinical relevance are limited to possible intolerance to lactose and sensitivity to milk proteins as these are also present in many commonly used foodstuffs. Important synergistic actions with conventional drug therapies have been observed with BCC including a reduction in LPS plasma levels in patients with Gram-negative bacterial infections treated with bactericidal antibiotics. In healthy persons there are only small concentrations of LPS detectable in peripheral blood (normal values: 3 â 10 pg/ ml plasma, i.e. approximately 0.1 EU/ml). In contrast, elevated systemic levels with concentrations > 300 pg/ml are common in patients with severe Gram-negative sepsis and septic shock. Raised LPS levels occur mainly in patients with Gram-negative bacterial infections who have been treated with bacteriocidal antibiotics. The LPS-lowering effects of BCC are probably due to the numerous active components present in BCC which have their origin in the innate humoral and adaptive immune system of their biologic source, the cow.