Herman Pontzer and colleagues published a landmark study of energy expenditure in people from a very physically active hunter-gatherer group, the Hadza of Tanzania. These important findings have been central to how I think about diet and obesity. Here is what they found: Hadza hunter gatherers spend about the same amount of energy daily than do North Americans, or Europeans, or Russians, even though industrialized populations get a whole heck of a lot less exercise per day. In fact, Ponzter concludes that all humans burn about the same amount of energy a day, after correcting for body mass. This feature of human biology is shaped by evolutionary imperatives that conserve energy when it is spent at increasing rates. As Pontzer describes in his book Burn, not all groups are exactly equivalent – the Tsimane of lowland Bolivia may have a very slightly higher energy expenditure owing to frequent infections – but as a general rule, we are all about the same. Further, the body defends energy intake and spend set points. This explains why contestants in the reality TV show The Biggest Loser mostly gained weight back after their dramatic weight loss induced by an extreme calorie restricted diet paired with an extreme physical workout routine. After losing about the mass of an average human ~ 70 kilograms, their metabolisms went into starvation mode, reducing energy expenditure while hunger increase. No wonder the weight of these folks later rebounded.

The lesson here is that energy set points are defended by the human organism to the detriment of those aiming for exercise induced weight loss, or starvation dieting. Exercise in particular has a poor track record as a weight loss method; long term exercisers often gain weight, though some of that is muscle mass. Appetite increases after exercise, in a way that compensates for the increase in calories burned.

The implication of these findings is that no matter how much energy you spend in voluntary physical activity, the body will attempt to maintain a constant energy balance, and usually weight is stably maintained. It also turns out that adult weight fluctuates very little for most adults living a traditional hunter gatherer or hunter horticulturalist lifestyle, unlike most of us industrialized folk.

The other implication is that when we get sick, our metabolic needs skyrocket. When suffering a systemic bacterial infection, we spend energy as if we are running while we are standing still. In light of humans having a constrained energy limit, it makes sense then, that we move less when we get sick. How does that happen?

Lassitude, lethargy, and profound fatigue are just some of the symptoms associated with infection. These so-called sickness symptoms have the effect of reducing voluntary physical activity. These are also sometimes caused sickness behaviors, because fatigue, plus headache, muscle and joint pains, profoundly de-motivate physical activity. Pain plays a large role in this reduction of physical activity when sick. Several studies have shown that people suffering from pain move less, as measured by wearable accelerometers. The symptoms of being sick, then, may have evolved in part to make us move around less.

Less movement doesn’t just make sense in a constrained energy expenditure model, it is absolutely necessary to conserve energy when we face grave infectious threats.

We have left out one of the most paradoxical sickness symptoms. This is the puzzling feature of sickness – loss of appetite and interest in food, sometimes along with nausea and vomiting. Since energy spend is constrained, and physical activity diminishes when sick to compensate, why wouldn’t appetite also increase to compensate? LeGrand and I speculate that sickness anorexia (loss of appetite) happens because we are in a life and death contest with invading pathogens over energy. We eat less in because starving pathogens is a host defense; it unfortunately has the by product of starving ourselves too. We also speculated that this is particularly true for threats coming from the microbiome – since we feed our microbiomes at the same time that we feed ourselves. If this notion is true, we would expect greater weight loss and more profound illness anorexia when we have a GI infection versus a non GI infection. That makes sense intuitively and it is supported by the evidence.

When we are confronted with a life-threatening infection, the increased energetic needs of activated immune cells, combined with reduced calorie intake from illness anorexia, make energy conservation a crucial priority of the organism. These are modulated by sickness behaviors – lassitude and lethargy and increased sleep – and reinforced by sickness symptoms that lead to reduced activity – headache, nausea and body pain. Even if we wanted to work out when we were sick, the body alters energy traffic in a way that makes burning more energy from voluntary physical activity almost impossible – we engage insulin resistance. I speculated about the adaptive benefit of insulin resistance, which makes glucose uptake by muscles more difficult, in my paper with Henry Lin in 2014:

‘Modulation of metabolism by fats and microbiota may be adaptive in fueling the increased energy needs of immune cells activated by dysbiosis. By blocking glucose uptake, IR {insulin resistance} reduces energy utilization by tissues dependent on GLUT4 glucose uptake (predominantly skeletal muscle and fat) and diverts energy access to tissues not reliant on insulin-stimulated GLUT4. Phagocytes (for example, macrophages) and intestinal epithelial cells do not rely on GLUT4. As a result, glucose energy is expected to be preferentially delivered to activated innate immune cells in the gut during the IR state.‘

Being sick, then, necessitates a variety of energetic shifts – in behavior, nutrition, gut activity, muscle metabolism, and immunity – that make sense from an evolutionary perspective. Because these events are dictated by evolutionary adaptations that mostly benefit the host, some pathogens could be expected to fight back, which we will get into in future posts. But as a teaser, it is worth mentioning that Salmonella typhmurium, blocks the decrease in appetite that usually accompanies sickness; this effect increases the transmission of the bacterium. So too, SARS-CoV-2 might inhibit sickness behavior and sickness symptoms, in a way that increase social interaction by infected hosts, thereby increasing its transmission. Read more about that possibility here.

Copyright © Joe Alcock MD

Categories: Uncategorized

Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine