Anorexia of Illness

What is anorexia of illness?

During sickness it is very common to lose one’s appetite and reduce energy intake. This anorexia of illness is one of a group of symptoms collectively known as sickness behaviors. Whether anorexia and other sickness behaviors are adaptive is uncertain and the optimal amount of nutrition to provide during illness is an unanswered question in medicine. However, various authors have speculated that anorexia of illness might be beneficial by assisting host defense during infection or by changing energy provisioning for various parts of the body.  If true, it is possible that providing fewer than normal nutrients during illness might speed recovery and improve survival. On the other hand, malnutrition or starvation has been associated with mortality in infection.

What are the possible benefits of illness anorexia?

Exton (1997) postulated that anorexia may be beneficial by limiting the availability to pathogens of essential trace metals, notably iron; and he presented evidence that dietary restriction can enhance certain immune functions.

Straub et al. (2010) proposed an “energy appeal reaction” model that sees the catabolic state of the APR as an attempt to redirect nutrient energy toward meeting the high metabolic costs of fighting infection.

Anorexia also promotes cell apoptosis and might aid in pathogen clearance (LeGrand 2000). Anorexia may also be a gamble on the part of the host that the host can better withstand the nutritional stress better than the invading organism.

Because the host has stored energy reserves, anorexia may disproportionately affect gut pathogens and make infected intestinal epithelial cells more susceptible to apoptosis (LeGrand and Alcock 2012).

Anorexia may occur as a means of preventing pathogenic gut microbes from gaining access to growth limiting nutrients (LeGrand and Alcock 2012).

The idea of permissive underfeeding in critical illness was proposed by Zaloga and Roberts (1994). They hypothesized that maximizing nutrition “may adversely affect the host response to injury, especially when given in excess of energy and protein needs.” Recent evidence suggests that calorie restriction during illness might be protective:

Is there evidence from animal experiments?

Adamo et al. (2007), working on the assumption that anorexia during infection is beneficial, found that force-feeding bacterially infected caterpillars with a high lipid diet increased mortality.

Murray et al. (1978) force-fed Listeria-infected mice back to their preinfection food intake levels and found that these mice with “good/normal nutrition” had lower survival than did the infected sham force-fed mice.

Is there evidence from human trials?

More recently, human trials have shown similar results:

Observational trials:

Patients with higher illness severity were found to have longer stays in the ICU when feeding was initiated early, versus late (Huang et al 2012). Arabi and colleagues showed that achieving target nutrition (e.g. higher calories) is associated with worse outcomes in the ICU (2010) in keeping with previously reported work (Krishnan et al. 2003). This idea remains controversial, and other observational studies have reported better outcomes with higher calorie delivery (Heyland Cahill and Day 2011; Elke et al.  2013).

Randomized controlled trials:

Arabi and colleagues (2011) randomized patients to underfeeding (60%) vs. normal (100%) replacement of calorie needs in critical illness. This group found decreased deaths in the underfeeding group.
Writing Assignment

You are called to do a nutrition consultation for a patient in the ICU. The question is should we feed this patient less calories, more calories, or the same calories as the patient needed before they got sick?

Reading 1: Self-Medication as Adaptive Plasticity: Increased Ingestion of Plant Toxins by Parasitized Caterpillars (for discussion)

Reading 2 Schetz artificial nutrition (for writing assignment)

Reading 3 (mandatory; emailed to you, contact me if you did not receive it)

Optional (but recommended for the writing assignment) reading 4:

Kenra et al Infection and Anorexia

More references:

Krishnan JA, Parce PB, Martinez A, Diette GB, Brower RG. Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes. Chest 2003, 124: 297-305.


Microbial Manipulation

For an introduction, read this Berkeley Science Review.

And: How Pernicious Parasites Turn Victims into Zombies.

And Carl Zimmer’s article in the New York Times Science section.

The human gut microbiota has been described as a “forgotten organ” that is essential to human health and happiness. Evidence suggests that commensal microbes are protective against allergy, nutrient deficiency, and certain infections. However, not all interactions between vertebrates and their microbes are friendly. Competition for nutrients and other resources can cause conflicts of interest in the metagenome, the combination of human and microbial genes. Metagenomic conflicts of interests might drive some unhealthy eating behaviors, since nutrient energy is shared between the host and microbiota. This hypothesis has implications for food cravings and the obesity epidemic.

1. Required Reading Alcock-aktipis-maley-puppetmaster

2. Optional extra: Lyte 2014 Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior.

Writing assignment (1 page max): Do you think it is likely that our food cravings are driven by the evolutionary interests of our gut microbiota? Why or why not? What are the other explanations for why we crave fatty, sugary, and salty foods? (remember that you do not need to agree with the argument in the paper.)

The Hygiene Hypothesis

The prevalence of allergic diseases has dramatically increased in recent decades, and these diseases currently affect one in five people in the US. Allergic and autoimmune diseases also reduce quality of life and they are expensive, costing approximately $15 billion annually. The massive increase in allergy has occurred along with many social changes, such as altered infant feeding practices, antibiotic use, urban living, and reduced family size. All these lifestyle changes can result in reduced microbial exposure. How important could it be to have a diverse microbiota in early life?  More generally, how does exposure to microorganisms affect chronic inflammation and allergic diseases? Is exposure to a diverse microbial environment a good or bad thing for human? Should physicians treat diseases by manipulating gut bacteria?

Bach 2002

Bach 2002 NEJM 347:12

Writing assignment:

How does exposure to microorganisms affect chronic inflammation and allergic diseases?  Is exposure to a diverse microbial environment a good or bad thing for humans?



2) 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis 2010. Rook G. Clinical and Experimental Immunology. 160: 70–79. (optional)

3) Missing Microbes

(If you have time, listen to the interview and read the excerpt in the link above.)

4) Bach Hygiene Hypothesis

Optional extras:

Highly recommended Radiolab program on hygiene and hookworm:

Radiolab hookworm story

Excellent NPR piece on microbiota diversity:


The Paleo Diet – Good Idea or Paleofantasy?

What is the Paleo diet? Should we eat like our stone age ancestors? How did our ancestors eat, exactly? How far back should we go to identify humans’ healthiest diet? Can modern hunter-gatherers be a stand-in for our ancestral hominins in terms of diet?

Hadza and honey

1) Quickly skim this recent piece in the Huffington Post

2) Next read Eaton (2006)-Ancestral human diet

3) Most importantly, read this review:

Paleofantasy by Marlene Zuk

4) Then read about artificial sweeteners here

5) Optional extra. Paleo microbiota

Writing Assignment:

For Tuesday: Pima Indians (Tohono O’odham) of Arizona have the highest rates of diabetes in the world. They eat processed foods and refined carbohydrates like other Arizonans (the typical American diet).  Their Pima relatives who farm in the Sierrra Madre of Mexico eat a more traditional diet and have much less diabetes and obesity. In light of the Paleo diet hypothesis and the backlash it has generated, how would you explain the differences in diabetes between the two closely related groups

Optional Extra credit Writing Assignment:

Several papers have been written about balancing selection, evolution and Factor V Leiden (FVL) mutation since the Lindqvist paper was published 6 years ago. Skim these and see if you can find any evidence to back up the hypothesis that FVL helps women survive bleeding in childbirth (or if another idea makes more sense).

Citing Articles are here

Read the van Mens article

Weiler Favor V Leiden in sepsis

Basque Polymorphisms

Factor V Metaanalysis

Saccharin causes pre-diabetic changes via the microbiota

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Sweet ‘N Low contains saccharin, an ingredient that was the subject of a recent study in the Journal Nature: “Artificial sweeteners induce glucose intolerance by altering the gut microbiota.” Click below to read the article, which describes changes in microbiota that are responsible for the adverse effects of saccharin and other artificial sweeteners. This study suggests that non-caloric sweeteners interact with gut microbes to cause metabolic changes, like those seen in diabetes and obesity.

I just posted a summary of this article on the Evolution and Medicine Review. Read more here.