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Other Research Areas

In this section we will look at some of the new Areas of research undertaken on Aquamin by our research partners.


Gut Health

In today’s fast-paced world, highly processed, convenience foods have become a staple in our diets. This increasingly common and unhealthy way of eating has been dubbed “The Western Style Diet”. This diet is high in saturated fats, processed carbohydrates, sugar and is low in fresh fruits and vegetables, whole grains, and seafood. Additionally, the intake of many essential minerals is significantly lower than is recommended for good health. This diet is associat- ed with a range of diseases including: obesity, high blood pressure, high cholesterol, heart disease, type II diabetes, colorectal cancer, liver cancer, and osteoporosis, as well as inflammation and disorders of the digestive system. In the area of gut health Aquamin has been demonstrated to provide:
  • Improvement of the symptoms of colitis
  • Anti-inflammatory activity demonstrated in the GI tract
  • Protection from liver damage while on a high fat Western diet
  • Prevention of polyp formation on a high fat Western diet
  • Maintenance of healthier stomach wall on a high fat Western diet
The Impact of Aquamin (Treated) on 2 markers of active inflammation in Colitis. PMA/I and antiCD3/CD28 represent different subsets of immune cells from the spleen.

Aquamin and Gut Inflammation

For the past decade, Marigot Ltd has worked closely with Professor James Varani and his colleagues at the University of Michigan Medical School, testing the hypothesis that the absence/reduced intake of multi-minerals in a Western style diet, may contribute to diseases with a diet associated factor for exacerbation/ incidence. These investigations began in-vitro, with preliminary observations showing that cultured gut-lining (epithelial) cells showed improved differentiation (non-malignant effect) and proliferation (healthier cells) in the presence of Aquamin (Aslam et al., 2009)1 These initial results demonstrated that the minerals in Aquamin helped maintain a healthy digestive barrier, which is necessary to prevent chronic inflammation in the gut. Follow-up studies investigating the role of Aquamin in the regulation of gastrointestinal inflammation in mice subjected to a mouse version of the Western Style Diet, found a reduction in generalised inflammation in the gut, colonic polyp formation and fatty liver disease (Aslam et al., 2010)2 This finding was further supported in another trial, where mined limestone rock was compared against Aquamin.
Despite each group of mice consuming the same amount of calcium, the mice receiving Aquamin were protected against GI inflammation and resultant polyp formation (Aslam et al, 2012)3 An incidental finding from the study was a significantly reduced liver mass formation in mice on the Western Style Diet and fed Aquamin versus the controls and limestone derived calcium (Aslam et al., 2012)4 Taken together, these results have prompted Marigot Ltd, alongside colleagues from the University of Michigan, to investigate whether these anti-inflammatory effects in-vitro and in the digestive tract of mice can also be observed in humans. This FDA approved and regulated trial is currently underway. The beneficial effects of Aquamin were also seen in a mouse model of colitis. Colitis is one of a number of chronic inflammatory disorders collectively known as inflammatory bowel disease (IBD). Current therapies target the inflammatory pathways with a view to resolving inflammation in the gut. Aquamin supplementation provided a significant reduction in mortality and disease activity along with significant reductions in several markers of inflammation including IL-1β, TNFα and IL-2 (Aviello et. al., 2014)5

Aquamin and Gut Microbial Population

A growing amount of scientific evidence suggests that colon microbiota of Irritable Bowel Syndrome (IBS) patients differ from that of healthy subjects (Kassinen et al., 2007)6 Alterations in several different microbial species, genera or groups have been reported but it is noteworthy that the results of different studies have to some extent been contradictory. An on-going in vitro study assessing the impact of Aquamin on an IBS derived gut microbial population has led to some interesting results. In this study, the levels of gas production and individual short chain fatty acids (SCFAs) were measured in the absence of or with increasing doses of Aquamin. The three most abundant SCFAs are acetic, propionic and butyric acids. In the colon simulation model used in the study, the total acid concentration was used to assess the overall fermentation activity and the relative abundance of individual acids indicated the respective activity of different fermentation pathways. Despite no observed change in overall gas production, a dose-dependent increase in total SCFA production was recorded, ranging from 9% to 17% when compared to the control. Acetate production was stimulated by between 7-9% and propionic acid by 17-44%. Interestingly, there were no significant changes in butyric acid levels at any time point or with any concentration of the dietary supplement. Lactic acid is the strongest of the common SCFAs produced by GI bacteria and its accumulation is considered a negative event for the lower intestinal tract. Inclusion of Aquamin resulted in decreased levels of lactic acid as well as a dose-dependent buffering action on colonic pH in comparison to the control treatment. These results indicate a substantial alteration in bacterial fermentation patterns and a more beneficial phenotype for relieving IBS symptoms which will be further investigated in dietary intervention studies.

Aquamin Polyp Formation and Gut Malignancy

The level of colon polyp prevention seen with Aquamin is clearly greater than previously evidenced for calcium alone, which leads to the strong argument that these minerals work more effectively when found together in their natural forms. Other minerals present in the marine algae, including copper, chromium, manganese, molybdenum, selenium and zinc, have all been shown to reduce tumour forma- tions or suppress other types of tissue injury in gastro-intestinal tracts. It is also thought that each of these elements may exert some level of protection against polyp formation by itself or they may well function synergistically with one another or with calcium. Marigot Ltd’s digestive health studies prove that the minerals present in Aquamin, are able to reduce colon polyp formation in high-fat and low-fat diets. Calcium alone cannot explain the protective effects of the multi-mineral complex, and the many other additional minerals present are likely to contribute to colon health.
(A) and (B) Inhibition of growth of 2 human colon cancer cell lines by Aquamin. (C) and (D) Induction of Calcium receptor CaSR in 2 colon cancer cell lines which leads to a reduction in cell proliferation. (E) and (F) Western blot of CaSR expression in 2 colon cancer cell lines. Beta-actin used as standard.
(Dame et al, 2011)7 showed that treatment of human colon tissue in organ culture with Aquamin is sufficient to see immunohistochemical changes reflective of improved differentiation and appears to enhance growth control properties of calcium. In vitro work carried out using malignant cell lines focused on determining a potential mode of action involved in the reduction of malignant phenotypes. The calci- um sensing receptor (CaSR) is a robust promoter of differentiation in colonic epithelial cells and functions as a tumor suppressor. Cancer cells that do not express CaSR (termed CaSR null) are highly malignant while acquisition of CaSR expression in these cells circumvents the malignant phenotype (Singh et. al., 2015)8. CBS and HCT116 human colon carcinoma cell lines and the corresponding CaSR null cells isolated from these lines were used in this study to evaluate the effect of Aquamin versus calcium and vitamin D. All three components induced CaSR mRNA and protein expression and inhibited cellular proliferation in the parental and CaSR null cells. However, Aquamin was found to be the most potent in this regard. This study provides a rationale for the use of a multi-mineral approach for a healthy gut.

References:

[1] Aslam MN, Bhagavathula N, Paruchuri T, Hu X, Chakrabarty S, Varani J. Cancer Letters.(2009) Oct 8;283(2):186-92. Growth-inhibitory effects of Aquamin, a mineralized extract from the red algae, Lithothamnion calcareum, on Ca2+-sensitive and Ca2+-resistant human colon carcinoma cells. [2] Aslam MN, Paruchuri T, Bhagavathula N, Varani J., Integr Cancer Ther (2010) 9:93. A Mineral-Rich Red Algae Extract Inhibits Polyp Formation and Inflammation in the Gastrointestinal Tract of Mice on a High-Fat Diet. [3] Aslam MN,, Bergin I, Naik M, Paruchuri T, Hampton A, Rehman M, Dame MK, Rush H, Varani J. Nutrition and Cancer,(2012) 64 (7): 1020-8. A Multimineral Natural Product from Red Marine Algae Reduces Colon Polyp Formation in C57BL/6 Mice. [4] Aslam MN, Bergin I, Naik M, et al. A multi-mineral natural product inhibits liver tumor formation in C57BL/6 mice. Biol Trace Elem Res. 2012;147(1-3):267-74. [5] Aviello G, Amu S, Saunders SP, Fallon PG. A mineral extract from red algae ameliorates chronic sponta- neous colitis in IL-10 deficient mice in a mouse strain dependent manner. Phytotherapy research : PTR. 2014;28(2):300-4. [6] Kassinen, A., et al., The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology, 2007. 133(1): p. 24-33. [7] Dame MK, Veerapaneni I, Bhagavathula N, et al. Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation. In Vitro Cell Dev Biol Anim. 2011;47(1):32-8. [8] Singh N, Aslam MN, Varani J, Chakrabarty S. Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype. Mol Carcinog. 2015;54(7):543-53.