science and metabolic cleansing

Excess weight and body fat is linked to increased risk of Insulin Resistance and Diabetes Type 2. It is also linked to other well known health disorders such as Osteoarthritis and inflammatory auto-immune diseases such as Rheumatoid Arthritis. Furthermore, the net result of excess weight, insulin resistance and inflammation are conditions that prevent weight loss and lead to worsening health. Here is a scientific understanding of how this both occurs and why Metabolic Cleansing is needed.

It should be noted that genetic factors (such as family history) predispose an individual to the cascade that leads to onset of Insulin Resistance as well as Inflammatory disorders (such as Arthritis).

Inflammatory cytokines and intermediary messengers in Insulin Resistance

Adipocytes, the cells that compose adipose tissue and store fat can release inflammatory cytokines and chemokines. The major source of those proinflammatory cytokines are adipose tissue macrophages (ATMs). These macrophages are recruited and activated by mediary factors such as tumor necrosis factor α (TNFα) and proinflammatory free fatty acids due to changes in adipocyte metabolism and gene expression resulting from excess adipose tissue.

The net effect is that these ATMs are activated into an MI state, whereby they release proinflammatory mediators, namely TNFα, IL-6 and IL-1β that act on adipocytes to induce an insulin-resistant state. In addition a positive feedback loop is established, whereby more and more macrophages are recruited, a loop that further amplifies inflammation and insulin resistance.

Cellular insulin resistance is caused by Jun N-terminal kinase (JNK) upon being activated by TNFα, IL-6, IL-1β, and other cytokines and macrophage-secreted factors. Jun N-terminal kinase (JNK) further activates pro-inflammatory transcription factor nuclear factor-κB (NF-κB), the activator of inflammation. Both JNK and NF-κB are activated by Reactive Oxygen Species (ROS). In addition, NF-κB is activated by Advanced Glycation End products (AGEs). Prolonged hypergycemia, the lead cause of excess AGE production, will lead to NF-κB activation.

Inflammatory cytokines and intermediary messengers in Rheumatoid Arthritis (RA)

RA is an inflammatory disorder that results from the antibody attack of body (namely joint) tissue which results in cartilage damage and degradation. This results in the key characteristics of RA – the swelling and degradation of joints and cartilage with associated pain and restricted movement. RA begins with the presentation of an antigenic protein that could be viral or endogenous. The end result of this presentation is the production of key cytokines which are instrumental to the inflammatory process in RA. Those cytokines are: Interleukin-1 (IL-1), interleukin-6 (IL-6), and TNF-alpha (TNF-α). IL-1 and TNF-α are noted for stimulating neutrophil activity, and neutrophils are noted for releasing enzymes that damage and degrade the proteoglycans in cartilage tissue.

Inflammation – an increasing spiral

In both Insulin Resistance and inflammatory disorders such as RA, the same cytokines (TNFα, IL-6, IL-1β ) are being produced locally in the body. However, the risk of those same cytokines leaking into general circulation (and causing pro-inflammatory and insulin resistance in other cells) is also occurring. The net effect is that either or both disorders can trigger, contribute to and augment the incidence of the other. In addition, elevated TH1 lymphocytes (due to bacterial or viral infection) promote inflammatory M1 activated ATMs that further increase insulin resistance. And ROS activity resulting from immune mediated activity such as inflammation, allergy response and auto-immune response, results in increased MI activation by ATMs. The overall result of this is the creation of a spiral or conditions that support and complement each other in a synergistic pattern to augment inflammation and cellular insulin resistance.

Mediating factors in this spiral are the use of energy at a cellular level (namely in muscular exertion) and blood sugar levels. The net effect of blood sugar being elevated due to inadequate carbohydrate intake (above cellular use) is that the blood sugar causes increasing arterial damage and formation of AGEs, as well as inflammation and inflammatory compound activation (such as NF-κB).

Conclusion

The inflammatory compounds TNFα, IL-6, IL-1 and NFkB play key pivotal roles in inflammatory disorders and also in Insulin Resistance. IL-6 itself is noted for increasing inflammatory disorders and it is produced during long term stress response. In addition, TNFα, IL-6, IL-1 and NFkB play pivotal roles in Gastro Intestinal disorders.

The danger therefore is that once inflammatory compounds are being produced in various parts of the body (by adipocytes and ATMs as well as joints with Arthritis), those compounds may be freed into general circulation and promote inflammation and damage to Gastro Intestinal tissues. The net effect of this would be the beginning of Tight Junction (TJ) permeability of the gut mucosal layer by both bacteria and large food particles. The effect of this would be enhanced possibility of the translocation of those bacteria to sites within the body (which will promote an immune response causing inflammation). Added, nutritional absorption would be adversely affected whilst the immune system defends the body from what is leaked across the gut mucosal boundary (ie Leaky Gut Syndrome) and anti-body reactions to food could furthermore result. In sum, the net effect of enhanced inflammation throughout the body is the possibility of food sensitivity and allergy, with continuing problems such as anti-body mistaking a body part (such as the Thyroid gland) as an antigen due to its similarity in surface proteins with food allergens (such as wheat gluten).

These dangers do not stop there. For attempts to lose weight, if successful, could release toxins from where they are most often stored under conditions of toxic overload. During toxic overload, the body stores exogenous or endogenous toxins that it is unable to rid itself of in fatty tissue. In weight loss, these toxins are released. The net effect of this release is that immune and liver resources are diverted for eliminating these toxins, with consequential weakening of immune and liver resources to deal with other micro-organisms, endotoxins or xenobiotics. Thus weight loss, to deal with insulin resistance caused by excess fat and weight, bears a risk of overtaxing the immune and liver system as a result.

In sum, a program to deal with these concerns and successfully afford safe weight loss, insulin sensitivity and lowered arthritic inflammation should be graded in stages. And this program moreover should be graded towards cleansing of both the immune and liver systems: simplifying their load and supporting their function with sufficient nutrients. Overall, a lifestyle approach should be adopted, whereby you gradually adopt practices (and eliminates possible toxins, allergens and avoids exposure to them) that become lifelong habits. This dietary and lifestyle approach, which would also entail stress reduction and management, is Metabolic Cleansing.

Adapted from:

Jerrold M. Olefsky and Christopher K. Glass. (2010). Macrophages, Inflammation, and Insulin Resistance. Annual Review of Physiology, 72 (pp. 219-246). DOI: 10.1146/annurev-physiol-021909-135846. Retrieved from: http://www.annualreviews.org.ncc1701.libprox.jfku.edu:8080/doi/full/10.1146/annurev-physiol-021909-135846

Steven E. Shoelson, Jongsoon Lee and Allison B. Goldfine (2006). Inflammation and insulin resistance. The Journal of Clinical Investigation, 116 (7). doi:10.1172/JCI29069. Retrieved from: http://www.jci.org/articles/view/29069

Ernest H S Choy, & Gabriel S Panayi. (2001). Cytokine pathways and joint inflammation in rheumatoid arthritis. The New England Journal of Medicine, 344(12), 907-16. Retrieved May 18, 2012, from ProQuest Health and Medical Complete. (Document ID: 69894911).

Simopoulos, A.P. (2002). Omega-3 Fatty Acids in Inflammation and Autoimmune Disease. Journal of the American College of Nutrition, 21 (6). Retrieved from: http://www.jacn.org.ncc1701.libprox.jfku.edu:8080/content/21/6/495.full

Kiecolt-Glaser, J.K., Preacher, K.J., MacCallum, R.C., Atkinson, C.A., Malarkey, W.B., Glaser, R. (2003). Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the national academy of sciences, 100 (15).

Vojdani, A. and Lambert, J. (2011). The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy, Part II. Evidence-Based Complementary and Alternative Medicine. Article ID 984965. doi:10.1093/ecam/nep063

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