In 2013, a study, Immunomodulatory Effects of ResistAid™: A Randomized, Double-Blind, Placebo-Controlled, Multidose Study, evaluated the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid™, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge of tetanus and influenza vaccines in a dose-dependent manner compared to placebo. The study showed that at a dose of 1.5 g/day, the proprietary arabinogalactan extract significantly increased the IgG antibody response to tetanus vaccine compared to placebo. As it is flu season, Today’s Practitioner is revisiting the study and the subject with an interview with Bryan Rodriguez, Global Products Manager, of Lonza, makers of Resist Aid. Download the full study at the end of this article.
The adaptive immune system (also called the acquired immune system) is composed of specialized cells and actions that are involved in the elimination or prevention of pathogenic challenges. The adaptive immune response provides the immune system with the ability to recognize and remember specific pathogens and to mount a stronger response each time a pathogen is encountered. Adaptive immunity is triggered in humans when a pathogen invades the innate immune system and generates a threshold level of antigen. The adaptive immune response has been exploited by modern medicine through the use of vaccines. By using live (attenuated) or inactivated pathogens or part of pathogens, vaccines trigger an immune response and development of vaccine-specific antibodies. The measurement of this response is frequently used as a way to measure the immunomodulatory effect of certain drug and dietary interventions.
Arabinogalactins and Immune Response
Arabinogalactans are high-molecular-weight, highly branched, water-soluble polysaccharides that contain units of D-galactose and L-arabinose. Dietary intake of arabinoglactans comes from plant food sources such as carrots, radishes, tomatoes, pears, and wheat. Gum arabic, a commonly used food additive, is composed of highly branched arabinogalactan. The mean estimated intake of arabinogalactan from the diet is approximately 10.474 g. The most common commercial source of arabinogalactans is from the wood of the larch tree (Larix spp.). Larch arabinogalactan consists of galactose and arabinose in a 6:1 ratio. It is a long, densely branched nonstarch polysaccharide with a galactan backbone with side chains of galactose and arabinose.
The human clinical study was designed to test the hypothesis that the ingestion of ResistAid, a proprietary arabinogalactan extracted from larch (Larix laricina), would selectively enhance the antibody response to the tetanus and influenza vaccines in a dose-related manner compared to placebo. The selected doses were 1.5 and 4.5 g, both of which had demonstrated effects in previous clinical studies.
All 3 groups demonstrated an expected rise in influenza A IgG following the vaccine, which peaked at day 45 for the 4.5 g/day and placebo groups and at day 60 for the 1.5 g/day group. The placebo group was significantly lower than the 4.5 g/day at baseline (p = 0.029); however, there were no significant differences between IgG levels in any of the 3 groups at day 45 or 60. The following within-group changes were statistically significant: (1) placebo group at day 45 (p = 0.002) and day 60 (p = 0.0001); (2) 1.5 g/day group at day 45 (p = 0.006); and (3) 4.5 g/day group at day 45 (p = 0.001) and day 60 (p = 0.007).
All 3 groups demonstrated an expected rise in influenza B IgG after the vaccine with a peak at day 45 for the 4.5 g/day group and day 60 for the 1.5 g/day group and placebo group (see Table 5). There were no significant differences between the values in any of the 3 groups at any time point. The within-group changes were statistically significant for all 3 groups at day 45 and day 60.
Daily ResistAid supplementation at a dose of 1.5 g/day for 30 days before the administration of the tetanus vaccine significantly increased the tetanus IgG antibody response compared to placebo. The 4.5 g/day dose of ResistAid also increased the IgG antibody response to the tetanus vaccine and this increase continued to rise by day 60; however, these values did not reach statistical significance. Neither group demonstrated any significant elevations in IgM or IgG antibody response to the influenza vaccine. The results suggest that ResistAid induces an elevated response to bacterial antigens (in the form of vaccine), but not viral antigens.
Interview with Bryan Rodriguez, Lonza
Q: What are larch arabinogalactans?
It is composed of galactose and arabinose, which have the ability to strengthen both the innate and adaptive arms of the immune system. Galactose and arabinose are common structural components of cell walls of environmental invaders such as bacteria. Therefore, the immune cells directly recognize the components and bind to ResistAid. It acts as a biological response modifier, via receptor sites on immune cells.
Lonza’s ResistAid, composed of larch arabinogalactan, is a prebiotic dietary fiber. This prebiotic helps aid the digestive tract, where 70 percent of the immune system is located. Prebiotics are noted to have immunomodulating activity, in part by increasing lactic acid bacteria and increasing production of short-chain fatty acids in the GI tract. As a secondary or indirect means, ResistAid has the ability to enhance and support the beneficial microflora populations within the large intestine as a fermentable substrate. Due to fermentation, the beneficial microflora proliferate and interact with the immune system in a beneficial way. Specifically, the flora population has the ability to produce substances that provide localized protection against pathogenic bacteria, as well as their ability to influence other parameters of the immune system. ResistAid contains polyphenolic flavonoids that have antioxidant capacity and represent the third pathway of the triple-action immune support benefits of ResistAid.
Q: For at-risk and elderly patients who may need additional immune support, what are the benefits to ResistAid arabinogalactans?
Instead of speaking to general immune support, Lonza has used its science to educate customers and consumers of ResistAid’s ability to function as an immune modulation ingredient, as opposed to an immune booster. According to the research, ResistAid provides an immunomodulatory effect, meaning it can enhance the appropriate response to an antigen, as opposed to indiscriminately enhancing other arms of the immune system that would not be expected to respond. Therefore, it can selectively call upon both the non-specific, cellular response, as well as the adaptive immune response in healthy adults.
Q: What is the biological mechanism for the immunomodulating activity?
The immune system is a highly complex and interrelated system that has two pathways to address foreign substances. The innate arm of the immune system is non-specific and targets anything that is viewed as foreign to the body, whereas the adaptive system targets specific foreign substances.
According to research, ResistAid provides the ability to selectively call upon both the non-specific, cellular response, as well as the adaptive immune response in healthy adults. It also provides an immunomodulatory effect, meaning it can enhance the appropriate response to an antigen, as opposed to indiscriminately enhancing other arms of the immune system that would not be expected to respond.