New Fontana Paper on the Immune System of Anorexics

[Dean Pomerleau]

All,

 

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

 

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[1] 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 

 

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[2] 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

 

-----------------------

[3] 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. amarcos@eucmax.sim.ucm.es

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

[nicholson]

For what it is worth, my (with no qualifications in the subject matter!) understanding is that *blood* WBCs are a poor (useless?) measure of immune function.

 

Rather, low WBC data imply low levels of infection and inflammation.   Naturally that implies excellent health.

 

High blood WBCs imply that WBCs are being transported to where it is perceived they are needed to solve one or more problems.  Clearly, implying less excellent health.

 

What matters is how effectively the *stores* of WBCs *in bone marrow* can be deployed when the body detects infection or inflammation.

 

So, yes, a test checking on effectiveness of response to a relevant challenge would be helpful.

 

Rodney.

 

"The unverified conventional wisdom is almost invariably mistaken."

[kpfleger]

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.

 

Why hasn't anyone done this in rodents, where it would presumably be much easier?

[kpfleger]

 

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.

 

Why hasn't anyone done this in rodents, where it would presumably be much easier?

 

Ah, I see that Dean himself subsequently reported on several experiments on immunity in the face of CR in rodents over in another thread:

CR, immunity and under-nutrition, and Rhesus LS

The combined evidence from those pointers gives me the impression that low WBC should be a concern, rather than something to take as a sign of an efficient immune system as suggested in the first post of this thread (and despite the anecdotal or at least small-n survey self-reports of fewer viruses among CR folk who participate in on-line communities here and on Facebook, which obviously suffer from some selection bias). But for more details see that more recent thread......

[Matt]

Viral and bacterial challenge to CR mice has already been done and the results are mixed, depending on the type of infection. One of the issues is that the body weight of the mice goes too low, and they don't have enough reserves anymore to fight off an infection. 

 

Since I've started CR, I've gone through periods of excellent immunity from bugs, getting no viral infections for years, to getting 2-3 colds in one year. Having 7 nephews and nieces coming here almost daily helps ensure that I am exposed to plenty of viruses. :) One thing I've noticed when coming down with a virus, usually a cold, is I didn't sleep well in the night(s) before. Actually, this is almost always the case.

My white blood count hasn't been consistent over the years, although it has dropped down to the lower end of normal at various points. My last one was fairly high, primarily because of a high neutrophil count, and I'm not entirely sure of the reason. I know neutrophils can rise rapidly. I wrote about it on my blog, but forgot that I had a deep filling replaced (precedes CR) a few days prior to blood being drawn.. but have no idea if this could be the reason.

[Sthira]

I feel like Greg Fahy's thymus regeneration efforts should be emerging (soon?) in the next few years? Fingers and toes crossed. Meanwhile, maybe keeping T cells lower due to eating less food and avoiding snotty nosed people will help preserve the thymus until that therapy brings back some immune strength of youth.