A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Abstract

BackgroundOxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial.MethodsThe study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function.ResultsA significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression.ConclusionThis study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).Trial RegistrationAustralian and New Zealand Clinical Trials Register: ACTRN12605000258651

Effect of Ambrotose AO® on resting and exercise-induced antioxidant capacity and oxidative stress in healthy adults

“…The changes noted in blood antioxidant capacity from pre to post intervention are similar to, albeit slightly less than, those reported in the previous two open-label designs using Ambrotose AO ® [15,16]. Moreover, our increases of approximately 22% in ORAC and 19% in TEAC are similar to other previously published work using either whole foods or antioxidant supplements.…”

Review of existing experimental methods for assessing the outcome of plant food supplementation on immune function

“…The potential studies identified in database searches were screened and ranked based on the plant active ingredient, to identify the plants with the highest number of published reports. The 10 most commonly studied PFS claimed to improve or enhance immune function identified in this study were: Andrographis paniculata (Green Chirayta) (Calabrese et al, 2000;See et al, 2002), Camellia sinensis (Tea) (Myers et al, 2010;Rowe et al, 2007), Corylus avellana (Common Hazel) (Savolainen et al, 2006;Savolainen et al, 2007), Garcinia mangostana (Purple Mangosteen) (Tang et al, 2009), Hibiscus sabdariffa (Roselle) (Beltran-Debon et al, 2010), Lycopersicon esculentum (Tomato) (Briviba et al, 2004;Markovits et al, 2009;Riso et al, 2006;Watzl et al, 1999;Wood et al, 2008), Olea europaea (Olive) (Alvarez-Cuesta et al, 2005), Pleurotus ostreatus (Oyster Mushroom) (Bergendiova et al, 2011;Bobovcak et al, 2010), Sambucus nigra (Elderberry) (Barak et al, 2002), and Vaccinium myrtillus (Bilberry) (Karlsen et al, 2010). The widespread consumption of several PFS obtained from these plants for enhancing immune function is well documented (Cassileth et al, 2009).…”

“…A total of 18 articles were eventually included in the final data extraction set. In order of prevalence 8 of these were based on double-blind randomised controlled trials (Alvarez-Cuesta et al, 2005;Bergendiova, Tibenska, & Majtan, 2011;Bobovcak, Kuniakova, Gabriz, & Majtan, 2010;Briviba et al, 2004;Rowe, Nantz, Bukowski, & Percival, 2007;Savolainen, Jacobsen, & Valovirta, 2006;Savolainen et al, 2007;Tang et al, 2009); 7 trials were conducted without placebo and/or randomisation assignment (Barak, Birkenfeld, Halperin, & Kalickman, 2002;Beltran-Debon et al, 2010;Calabrese et al, 2000;Markovits, Ben Amotz, & Levy, 2009;Myers et al, 2010;See, Mason, & Roshan, 2002;Watzl, Bub, Brandstetter, & Rechkemmer, 1999); and the remainder were based on studies of the following designs: a double-blind randomised controlled cross-over trial (Riso et al, 2006), a randomised controlled trial (Karlsen et al, 2010), and a randomised controlled cross-over trial (Wood, Garg, Powell, & Gibson, 2008). Though the study inclusion criteria was as broad as possible and criteria did not exclude specific trial designs, not all trial designs were encountered in the final 18 selected studies.…”

“…Following pathogen elimination a proportion of lymphocytes persist in the body, retaining immunological memory that can be elicited through a faster secondary immune response to eliminate the same pathogen in the event of subsequent infections (Bonilla & Oettgen, 2010;Parham, 2009). Occasionally, in-borne errors in immune function occur, leading to the development of immune disorders including asthma, Crohn's disease (inflammatory bowel disease), inflammatory arthritis, and autoimmune diseases such as polyglandular syndrome and aspects of diabetes that result from the immune system attacking host cells (Dessein, Chamaillard, & Danese, 2008;Finn & Bigby, 2009;Kim, DeKruyff, & Umetsu, 2010;Mizuno, 2006;Obermayer-Straub, Strassburg, & Manns, 2000;Sly & Holt, 2011;Van Heel, McGovern, & Jewell, 2001). In rare instances severe combined immunodeficiency (SCID) can occur, which represents a group of sometimes fatal congenital disorders characterised by little or no immune response (Pearson, Greiner, & Shultz, 2008).…”

The Mind Body-Wellness in Supportive Housing (Mi-WiSH) study: Design and rationale of a cluster randomized controlled trial of Tai Chi in senior housing

“…Studies have shown that Tai Chi exercise can improve a number of medical conditions relevant to frail elders, including chronic heart failure, [6–9] hypertension, [10–12] hyperlipidemia, [10, 13, 14] coronary artery disease, [15–18] chronic obstructive pulmonary disease, [19–21] cardiorespiratory fitness, [22–24] poor balance, [25–28] reduced musculoskeletal strength and flexibility, [13, 22, 29–31] Parkinson’s disease, [32] rheumatologic conditions, [33–37] cognitive decline, [38, 39] and overall mood. [40] In a previous pilot study, we have shown that Tai Chi can be practiced successfully and without adverse effects by frail seniors living in supportive housing and results in significant improvements in balance, gait, and functional ability after only 12 weeks. [41] However, it remains to be determined whether a longer period of Tai Chi exercise can further improve the health of poor, frail seniors and reduce their health care utilization and costs.…”