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Dean Pomerleau posted a topic in CR Science & TheoryAll, Despite low levels of white blood cells, anorexics have been found to be less susceptible to certain viral infections, at least until very advanced stages of the disease [2,3]. Anecdotally, the same has been reported in CR practitioners. While anorexia is far from a perfect model of CR as properly practiced (i.e with less extreme restriction and with adequate nutrition), a lot can be learned from people who severely restrict calories even without adequate nutrition. Thanks to Al Pater for pointing to a new study by our friend Luigi Fontana and his team which investigated the effects of anorexia on the immune system and other blood parameters. The researchers tested the blood of 15 young (15-24) anorexics (avg BMI 15.9) and compared them with age-matched controls. The anorexics had lower IGF-1 and leptin hormone levels, which is also a typical response in CR practitioners. They also had fewer peripheral blood mononuclear cells (PBMCs), which basically comprise several types of the white blood cells responsible for the bodies immune response, including lymphocytes (including natural killer cells), monocytes, and others. This too is commonly observed among CR practitioners. PBMCs from the anorexics that were cultured for two days produced fewer markers of inflammation than controls. The anorexics cells also generated more endogenous antioxidants, and were therefore 24% more stress resistant when exposed to a pro-oxidant (H2O2) than those of controls. They concluded: [O]ur data suggest that excessive CR in AN patients is associated with a reduction in several key immune cell populations, impaired metabolic activity, but preserved immune function. Moreover, our findings suggest that chronic severe CR in young AN patients results in an enhanced anti-oxidant and anti-inflammatory status, which may protect cells from biochemical stress. This study suggests that what may appear like a compromised immune system in CR practitioners (based on numbers like our low WBC count) may actually be a sign of a more efficient and perhaps more robust and effective immune system. It would be nice if someone would do a study in which they directly expose CR practitioners or anorexics (or their immune cells) to an explicit viral challenge to directly test whether our immune systems are more effective at fighting off infections. --Dean --------------  Metabolism. 2015 Mar;64(3):396-405. doi: 10.1016/j.metabol.2014.10.025. Epub 2014 Oct 29. Immune-metabolic profiling of anorexic patients reveals an anti-oxidant and anti-inflammatory phenotype. Omodei D(1), Pucino V(2), Labruna G(3), Procaccini C(4), Galgani M(4), Perna F(5), Pirozzi D(6), De Caprio C(7), Marone G(2), Fontana L(8), Contaldo F(7), Pasanisi F(7), Matarese G(9), Sacchetti L(10). CONTEXT: Anorexia nervosa (AN) is an excessive form of calorie restriction (CR) associated with pathological weight loss and alterations of the immune system. However, AN patients seem to be protected from common viral infections. OBJECTIVES: To investigate the metabolic and molecular adaptations induced by sustained extreme CR in the peripheral blood mononuclear cells (PBMCs) of patients with restrictive alimentary AN. DESIGN: Inflammatory cytokines and adipokines were measured in 15 young (age range, 15-24 years) AN female patients and 20 age-matched healthy controls. Isolated PBMCs were immunophenotyped by flow cytometry, and glycolysis and mitochondrial respiration were determined by measuring the extracellular acidification and oxygen consumption rate. Stress resistance to H2O2 and the antioxidant transcriptional profile of PBMCs and human fibroblasts incubated with sera from AN patients were also determined. RESULTS: Compared with controls, AN patients (BMI, 15.9±0.4 kg/m(2)) had significantly fewer leucocytes, lymphocytes and NK cells, lower serum concentrations of leptin, IGF-1 and sTNFR1, and higher levels of adiponectin, sCD40L and sICAM-1 (p<0.05). IL-1β, TNFα, and IL-6 produced by PBMC cultured with autologous serum for 48 h were significantly lower in AN patients than in controls (p<0.01). Moreover, glycolysis and mitochondrial respiration were lower, and the antioxidant transcriptional profile was higher in the PBMCs of AN patients. Fibroblasts cultured in serum from AN patients showed a 24% increase in resistance to H2O2 damage. CONCLUSIONS: Extreme CR in AN patients is associated with a reduction in several immune cell populations, but with higher antioxidant potential, stress resistance and an anti-inflammatory status. Copyright © 2015 Elsevier Inc. All rights reserved. PMID: 25500208 ------------------  Eur J Clin Nutr. 2002 Aug;56 Suppl 3:S34-7. The adaptive response of the immune system to the particular malnutrition of eating disorders. Nova E(1), Samartín S, Gómez S, Morandé G, Marcos A. Author information: (1)Instituto de Nutrición y Bromatología (CSIC), Edificio Instituto del Frío, Madrid, Spain. Despite the seriously undernourished state of patients with anorexia nervosa (AN) and bulimia nervosa (BN), controversial findings have been published regarding some aspects of the immune system that are otherwise impaired in more typical types of malnutrition, such as protein-energy malnutrition. In general, adaptation processes seem to occur enabling immune function to be preserved during long periods of the illness. However, cell-mediated immunity is usually altered in AN and BN as reflected by lymphocyte subset counts and the response to delayed hypersensitivity tests. Regarding the helper/cytotoxic T cell ratio (CD4:CD8), an immunological marker of the nutritional status, the results of our studies on AN and BN patients showed that the duration of the eating disorder and the time when appropriate treatment is achieved are likely contributors to the alteration of this ratio. Despite these findings, it has been repeatedly pointed out that anorexic patients seem to be free of common viral infections at least until the most advanced stages of debilitation. Some hypotheses that could explain the lack of infection symptoms are reviewed. Cytokines and the altered acute phase response to infection, as well as cortisol and leptin, are considered to be potential factors involved in the adaptation processes occurring in these syndromes. Further progress in the knowledge of the psychoneuroendocrine-immune interactions established in AN and BN will be relevant to the understanding of the aetiology and maintenance mechanisms of these pathologies. PMID: 12142959 -----------------------  Eur J Clin Nutr. 2000 Mar;54 Suppl 1:S61-4. Eating disorders: a situation of malnutrition with peculiar changes in the immune system. Marcos A(1). Author information: (1)Instituto de Nutrición, Facultad de Farmacia, Ciudad Universitaria, Madrid, Spain. email@example.com Eating disorders, such as anorexia nervosa and bulimia nervosa, are significant public health concerns for a great deal of the population, and thus are even considered to be epidemics. These syndromes have a common aim: the pursuit of a desirable and extremely low weight, which is obviously very far from the ideal body weight. Therefore, these patients show abnormal food behavior, leading to a situation of malnutrition. Nutrients play an important role in the development and functionality of the immune system. Thus, the assessment of immunological parameters acquires great interest as a useful tool to evaluate the nutritional status of these patients. In addition, it is very well known that a depleted immune system as a consequence of malnutrition is linked to an increased susceptibility to infections. However, an extensive literature has pointed out that anorexic patients, even though severely malnourished, are relatively free from infectious diseases. As the immune system is altered by distorted food behaviors, such as in case of eating disorders, the awareness of the characteristics of other systems involved in these pathologies, and therefore altered, would be very helpful for the understanding of the mechanisms triggered in these syndromes. In fact, the interactions among the immune system and the remaining systems in eating disorders are beginning to be studied. Finally, the main goal is to limit the evolution of these illnesses through an early diagnosis and appropriate therapy to subsequently get a constant and definitive cure for the patients. PMID: 10805041