What is the 5R program?

The 5R program is a functional medicine framework supporting GI health and restoration. It consists of the following five phases: 

• Remove: Identify and remove food triggers that may prompt or exacerbate GI dysbiosis or inflammation; this phase often consists of an elimination diet. 
• Replace: Support digestion by including nutrients that promote GI healing, such as vitamins and minerals, enzymes, and hydrochloric acid.
• Replenish: Support healthy GI microbiome by introducing probiotics, prebiotics, synbiotics, post-biotics, or short-chain fatty acids.
• Revive: Support normal inflammatory responses, GI barrier integrity, and cellular health by adding back healthy nutrients, such as broths, collagen, and L-glutamine. 
• Rebalance: Mitigate occasional stress and promote resilience by implementing positive lifestyle modifications, such as adequate sleep, exercise, mindfulness, relaxation techniques, and self-care. 

What is serum-derived bovine immunoglobulin?

Immunoglobulins, also known as antibodies, are glycoproteins produced by plasma cells as part of the body’s immune system. They circulate in the bloodstream and bind to antigens, facilitating their elimination. SBI is derived from bovine plasma in which the immunoglobulin content has been increased from about 13% of the protein in liquid plasma to a formulation where immunoglobulin G makes up more than 50% of the total protein content. SBI is a dairy-free alternative to colostrum, which may be more suitable for people with lactose intolerance. In addition, SBI provides clinically relevant amounts of immunoglobulins and may contain lower levels of potential endotoxin contamination as compared to colostrum. 

How does SBI fit in the 5R program? It can be used in two phases!

Given that immunoglobulin supplementation may help mitigate the absorption of antigens into systemic circulation and promote normal immune responses and GI barrier integrity, SBI may be supportive in the Remove and Revive phases of the 5R program.

The goal of the Remove phase is to attenuate the sources of inflammation in the GI tract, such as pathogens, toxins, and inflammatory foods. By having the potential to bind to these antigens and facilitate their evacuation, SBI may support the Remove phase and promote immune health and normal inflammatory responses. 

The goal of the Revive phase of the 5R program is to promote GI integrity by supporting the gut barrier and the mucosal function. GI dysbiosis and bacterial antigens may contribute to inflammatory cascades leading to compromised intestinal barrier function, increased epithelial permeability, and mucosal inflammation. By binding to bacterial antigens in the intestinal lumen, SBI may support a healthy GI barrier function, normal digestion and nutrient absorption, and a healthy GI microbial environment. 

SBI Clinical Evidence

Clinical studies have demonstrated that SBI supplementation may be supportive for GI health, nutritional status, and healthy inflammatory responses. In a single-center, retrospective, chart review study (n = 45), patients supplemented with 5 g/day of SBI were 2.8 times more likely to report clinical improvements in GI symptom scores. The percentage of patients reporting a positive response to the SBI supplementation increased from 49% during the first week to 76% after 12 weeks.

A study performed at the University of North Texas (n = 19) suggests that SBI serving sizes as low as 1 g/day may be clinically relevant. The goal of the study was to determine if supplementing with SBI could decrease markers for dietary endotoxemia, characterized by elevated serum levels of lipopolysaccharides (LPS), which are immunostimulatory endotoxins produced by gram-negative bacteria. In the presence of GI dysbiosis and a compromised intestinal barrier function, LPS and other bacterial products may enter systemic circulation, which in turn may induce chronic inflammation. At baseline, after a high-fat, high-calorie meal, participants displayed increased levels in serum LPS when measured at three and five hours after the meal, indicating inflammatory responses. Following 45 days of SBI supplementation with 1 g or 2 g per day, participants showed lower serum LPS levels after the same meal, suggesting that low-dose SBI supplementation may improve dietary endotoxemia (p<0.05 for the 1 g/day group).

SBI may be especially supportive in inflammatory GI conditions accompanied by diarrhea and abdominal pain.

• One randomized, double-blind, placebo-controlled study (n = 66) evaluated the impact of SBI supplementation on GI symptom scores in subjects with diarrhea-predominant irritable bowel syndrome. The authors found that individuals supplemented with SBI at 10 g/day showed reductions in abdominal pain, loose stools, bloating, flatulence, and urgency. Individuals supplemented with SBI at 5 g/day showed reductions in days with flatulence and days with incomplete evacuation.
• In a survey-based study (n = 595), patients with irritable bowel syndrome or inflammatory bowel disease responded to questions related to how SBI supplementation may have impacted their GI function and quality of life. The number of respondents with IBS reporting normal stool frequency increased from 35% prior to supplementing with SBI to 91% while using SBI. The mean daily stool numbers decreased for respondents with IBS and IBD from 6.5±4.3 before SBI supplementation to 2.6±1.9 following SBI use. In terms of quality of life, 67% of respondents agreed strongly or very strongly that SBI helped them manage their condition and 59% of respondents indicated that it helped them return to the activities they enjoyed. 
• A randomized, double-blind study (n = 30) found that patients with IBS-D supplemented with 5 g or 10 g of SBI per day for six weeks reported improved GI symptom scores and a reduction in the number of days with flatulence or incomplete evacuation. 

The applicability of SBI in GI health is gaining increasing interest. Further randomized controlled trials are warranted, especially at lower doses; however, current research suggests that SBI may play an important role in mitigating antigen inflammation and supporting healthy GI function.

Learn more about immunoglobulins and gut health: 

Serum-derived Bovine Immunoglobulins and Gut Barrier Function

The Connection Between Autoimmune Diseases and Intestinal Permeability

Potential Benefits for Bovine Colostrum in Pediatric Health

By Antonia Toupet, PhD