The science behind “Everything in moderation”

by Alan Cohen

We’ve all the heard the famous quote “Everything in moderation, including moderation” (attributed variously to Oscar Wilde, Horace Porter, and Petronius), and it probably strikes most of us as good advice. Of course, we can’t apply it too broadly: certain things are better in less than moderation (cyanide and genocide, for example) while others should be taken in more than moderation (walks in the woods and Cirque du Soleil performances come to mind). But is there any real reason to believe the principle is more than an old wives’ tale?

Yes, in fact. Emerging research (including mine, self-congratulatory back pat) is increasingly showing both the evolutionary and physiological bases for this principle, at least in regards to diet and exercise. Let’s look at this from three perspectives:

Modeling moderation

Before we start looking at the biology, let’s consider how we normally conceive of the relationship between quantity and quality. Most of us have a model in our heads that looks something like this:

The reason we think this way is because it’s simple. I’m convinced that our brains are built to find simple patterns in what they observe, and that we need to train them to understand and detect anything more complex. In fact, even this quantitative model is a bit more than our brains like. Ideally it would be simply lots=good, little=bad.

This model provides us with simple general rules to judge things. It can be easily inversed when appropriate: in the case of trans-fats or fuel consumption, lots=bad, little=good. There is also cultural variation in how we see things. Americans tend to view large things and large quantities as good much more than in some other places, notably Japan. Just look at portion sizes, for example… Still, everywhere in the world there is a clear tendency to use simple rules to judge things.

Of course, the real world is sometimes simple and sometimes complex. Most of the time, when there is reason behind a simple rule such as more is better, the rule still has its limits – it is just that our normal experience exposes us just to some of the possibilities. For example, for any healthy food we can imagine, it would presumably be possible to eat so much we die, just as a function of overstressing the capacity of our stomaches to process so much. If you don’t believe me, imagine trying to force down 100 pounds of spinach per day.

In other words, the graph above, when valid, is almost always a close-up of a more general trend, such as these:

All this really means is that an infinite amount of anything would not be infinitely better, and in many cases would actually be worse (as represented by the righthand graph). However, the rule “Everything in moderation” is based on a different scenario, one in which our day-to-day experience offers us the chance to have either too much or too little:

This principle of non-linear dose effects has a fancy name, hormesis, a concept often applied to medications. The fact that we give it a special name indicates that we don’t expect this sort of pattern, though in reality we should. It’s just that it goes against our linear pre-conceptions…

The physiology of moderation

If you go to your doctor and she takes a blood sample, she’s likely to measure things like cholesterol, HDL, sodium, calcium, and so forth. For many of these things, our general rule is more is better (HDL) or less is better (total cholesterol), and there are established medical thresholds for defining risky levels. But for many other things such as sodium and blood cell counts, the thresholds go in both directions. There is a normal range, and you can have too much or too little. Even in most cases where there is a clear direction that is considered bad, this is usually because our lifestyle has changed since we lived like our hunter-gatherer ancestors:

Based on some studies of modern hunter-gatherer populations, it seems that cholesterol levels, for example, are much lower than in developed countries. Cholesterol is essential for metabolism, and it should certainly be possible to have levels that are too low. It’s just that people living in developed countries are unlikely to have those levels, but are very likely to have high levels that would start to cause problems.

In fact, in order for our bodies to function well, there needs to be tight regulation of an entire network of things – hormones, lipids, electrolytes, vitamins, the immune system, and so forth. These things regulate each other in complex, still poorly understood ways. For example, in chickens, eating more vitamin E increases activity of one part of the immune system and decreases another, BUT this relationship is inversed if the chicken also eats more omega-3 fatty acids. For the moment, we don’t know much more than that there is regulation, lots of it, and it is complicated.

For this regulation to function well, it needs to respond to external conditions. When we are stressed, we need to have the fight-or-flight response. When we eat, we need to absorb the nutrition. When we are cold, we need to reduce blood flow to extremities. Most of these responses pass through the regulatory network described above. So the system is not static – it is dynamic. Nonetheless, generally speaking, we can identify a range of normal values for almost any molecule in the network, and in most cases we can define both upper and lower thresholds beyond which things won’t work as well.

The relationship between lifestyle and the levels of these molecules is not always straightforward. For example, it is not clear that eating more cholesterol increases the level of cholesterol in the blood, based on how it is digested. Excess vitamin C is simply excreted, so it’s hard (though not impossible) to overdose. Nonetheless, for most components of our diet, there is a normal range of intake, and deviating too far in either direction could have consequences. Likeswise, our physiology changes when we exercise. It’s probably good to avoid extremely high or low levels of exercise in order to avoid the extreme physiological effects that could result.

All of this is to say, based on relatively simple knowledge of how our bodies work, that it makes sense in most cases to consider moderation as a guiding principle.

The evolutionary basis for moderation

The physiology I just described is fairly basic, but it makes sense to ask why our bodies function in this particular way. Why not build bodies that just work better the more good stuff we eat? Why not build bodies that are fine no matter what our intake of different things, or no matter how much we exercise? Evolutionary theory provides some answers to these questions.

One popular misconception of evolution is that it is always building the best possible (i.e. optimal) organism for each environment. If this were true, humans would have wings like angels – it would be better, right? In fact, evolution works slowly over long periods of time making (mostly) small modifications to existing forms, and this creates a fair amount of inertia. It’s not easy to make the jump from four limbs to six limbs (I believe I’m correct in saying that it hasn’t even happened once in the last 500 million years), and it’s not easy, when you use testosterone and estrogen to regulate sexual development and breeding cycles, to find new hormones to take their place.

So the starting point for any organism is that it has a network of molecules that regulate each other and maintain it in homeostasis. In order for this regulation to work, and in order for the system to respond to changing conditions, there need to be physiological consequences to changing the levels of different molecules. And this means that some levels must be better than others, at least in certain situations.

It is possible – and indeed often observed – for the normal levels of different molecules to change across species. For example, unlike most mammals, humans do not synthesize vitamin C in their livers, meaning they have to get it from the diet. As a result, circulating levels of vitamin C are much lower in humans – presumably we have evolved to be perfectly healthy with much lower levels than are needed in other species. There are many such examples. At the same time, natural selection favors individuals who can tolerate a wide range of environments. Our ancestors lived in a wide range of environments and ate diverse diets. Some ate mostly meat, others ate huge quantities of shellfish, and others still large quantities of grain. Conditions could change from year to year or century to century, and so flexibility in nutritional and exercise needs must have been a good thing.

But in evolution, as elsewhere, everything has its price. Evolutionary biologists call these trade-offs: you can’t have your cake and eat it too, and you can’t (if you’re a diving bird) build a body that is light enough to fly well and heavy enough to dive well. It appears that there are trade-offs operating on flexibility too. Many evolutionary biologists think that it is often possible to build bodies that tolerate a wide range of conditions, but that doing so makes them function less perfectly in any of the conditions. For example, birds that migrate or need to survive a cold northern winter are often shorter lived than birds that stay in the tropics year-round.

What does all this mean for moderation? It means that over time, as environments change, organisms will change their physiology in response. The optimal level of cholesterol, or protein, or vitamin E, will change so that it corresponds to what the animal is likely to and able to take in. There will be some tolerance for straying a bit from this optimum – not many organisms could survive if a slight deviation was fatal – but there will not be infinite tolerance. And so, in the end, organisms will be healthiest if they live lives not too different from those of their ancestors. Their physiology is optimized for it.

This general principle, easy to see for diet, should apply to many things. We are accustomed to thinking of marathon running as a healthy hobby, and of people who do it as extremely fit. It is true that marathon runners are able to train their bodies amazingly, and have stamina beyond most of us – it is this fact that makes us admire them. But for exactly the same reason – that it requires so much effort above and beyond what seems the typical task of our bodies – that we should doubt if it is really good for our health in the long run. Evolution surely gave us bodies that could, as necessary, adapt to the physical hardship of different environments (such as marathon training), but that does not mean we are better off in those environments, or that we pay no price for these adjustments. If marathons are a reasonable approximation of the physiological exertion our ancestors faced, they are probably healthy to train for, but if they exceed that, they are probably unhealthy.

Of course, it is hard to know exactly what kind of life our ancestors led. Modern hunter-gatherers may or may not be similar to our ancestors, and even they are quite diverse for just about every aspect of their lives we study. Still, many aspects of our modern lives are clearly far from what our bodies are built for, and to the extent that this is true we are probably hurting our health and accelerating the aging process.

Caveat: I am NOT arguing that we need to replicate our ancestors lives in every way. Getting attacked by jaguars, suffering from malaria, and starving once in a while are hardly desirable. We just need to recognize that our bodies were designed to make the most possible out of that world, not the one we live in. Give us 100,000 years of modern life and we’ll probably have changed that…

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