## 3 Results
### How Do \(\beta\)CM-7 and the Microbiota Interact in Gut Health and Disease Regulation?
Decreased NO bioavailability is a hallmark of early atherosclerosis and has predictive value for future cardiovascular events [26]. Glutathione, on the other hand, might protect against LDL oxidation. [PERSON] et al. investigated the relationship between A1 casein consumption (comparing A1/A2 milk with A2 milk) and various markers of inflammation. He used ELISA assays to measure IgG1, GSH, and IL-4, as well as hs-CRP, total immunoglobulin G (IgG), and CRP. The study found no significant differences in most of these markers (IgG1, hs-CRP, GSH) between the consumption of milk containing A1/A2 casein and milk containing only A2 casein. The exception was a difference in total IgG between the two groups after two weeks of consumption [50]. In contrast, the effect of removing A1 \(\beta\)-casein on various immune markers (specifically, immuno-globulin [Ig]G, IgG1, IgE, and interleukin-4) was reported by [PERSON] et al. [35] Finally, [PERSON] et al. [45] identified significant differences in TNF-\(\alpha\) and cortisol levels when \(\beta\)-casein A1 was consumed. Scientific evidence demonstrates a well-established relationship between elevated levels of circulating inflammatory and cardiovascular risk. Therefore, the increase in inflammatory markers related to the consumption of A1 \(\beta\)-casein could be reflected in an increased cardiovascular risk in individuals who consume this type of protein. The possible relationship between \(\beta\)-casein A1 consumption and the increased risk of CVD has been explored in two epidemiological studies. [PERSON] et al. hypothesized that \(\beta\)-casein A1 is a specific risk factor for ischemic heart disease (IHD), based on correlations between consumption of this protein and IHD mortality in different countries and regions [48]. [PERSON] and [PERSON] found a positive correlation was found between the per capita supply of A1 \(\beta\)-casein and IHD mortality in 20 countries [49]. On the other hand, dietary trials have offered less conclusive results. [PERSON] et al. investigated whether dietary supplementation with A1 \(\beta\)-casein increased the risk of CVD compared to A2 \(\beta\)-casein. This 24-week study included 15 asymptomatic individuals (six men and nine women) at high risk of CVD, with a mean age of 52 years (several over 60). The results showed no significant differences in vascular function, blood pressure, plasma lipids, or biochemical markers between the two interventions [26]. [PERSON] et al. conducted a randomized crossover trial in New Zealand adults to evaluate the impact of the A1 and A2 \(\beta\)-casein variants on cholesterol levels. After replacing all dairy products in the diet with low-fat milk and cheese containing varying proportions of A1 and A2 \(\beta\)-casein for two 4.5-week periods, no significant differences were found in plasma cholesterol levels [31]. In summary, although some epidemiological studies have reported a positive correlation between the consumption of \(\beta\)-casein A1 and an increased risk of cardiovascular diseases, these findings are based on population-level analyses that do not allow for establishing a direct causal relationship. In contrast, intervention trials conducted in adults at elevated cardiovascular risk have not shown significant differences between the consumption of \(\beta\)-casein A1 and A2 in terms of cardiovascular outcomes. These discrepancies could be explained by confounding factors present in observational studies, such as variations in dietary patterns, genetic background, lifestyle factors, or differences in the characteristics of the studied populations. The previous factors, often not adequately controlled for in epidemiological research, may influence the observed associations. Therefore, the lack of effect in intervention trials suggests that the associations reported in population studies may not be causal, highlighting the need for further investigation into the underlying mechanisms through more rigorous and well-designed studies.