Saturday, October 15, 2022

Why are we getting fatter?

[This is a transcript of the video embedded below. Some of the explanations may not make sense without the animations in the video.]

Today I want to talk about personal energy storage. I don’t mean that drawer we all have that’s full of batteries in the wrong size, I mean our expanding waistlines that store energy in form of fat. What are the main causes of obesity, how much of a problem is it, and what are you to make of the recent claims that obesity is caused by plastic? That’s what we’ll talk about today.

Obesity is common and becoming more common, so common in fact that the World Health Organization says “the issue has grown to epidemic proportions.” The proportions of the issue are, I guess, approaching that of a sphere, and the word “epidemic” just means it’s a widely spread health problem. Though, interestingly enough, obesity is in some sense infectious. Not because it’s spread by a virus, but because eating habits spread in social networks. If your friends are obese, you’re more likely to be obese too.

In the past decades, the fraction of people who are obese has steadily increased everywhere. In the United States, more than a third of adults are now obese. Canada, the UK, and Germany are not far behind. The United States by the way are not world-leaders in obesity, that title goes to a pacific island by name Nauru where 60 percent of adults are obese. I have no idea what is going on there, but I want to move there when I retire.

Jokes aside, the economic burden of obesity is staggering. According to an estimate from the Milken Institute for the United States alone, obesity and overweight account for direct health care costs of at least four-hundred eighty billion dollars per year. The indirect costs due to lost economic productivity are even higher, about 1 point two four trillion dollars per year. Together that’s more than 9 percent of the entire American GDP.

But what, exactly, is obesity? The World Health Organization defines obesity as an “abnormal or excessive fat accumulation that may impair health”. I believe that an “excessive fat accumulation” does not mean stuffing your fridge with so much cheese that it hits you in the face when you open the door. They probably mean an accumulation of fat in the human body. This is why obesity is most commonly measured with the body mass index, BMI for short, that’s your weight in kilogram divided by the square of your height in meters. For adults, a BMI over 25 kilogram per square meter is overweight, and over 30 it’s obese.

The BMI is widely used because it’s easy to measure, but it has several shortcomings. The biggest issue is that it doesn’t take into account how much of your body weight is fat. You can put on muscle rather than fat and your BMI goes up. A more reliable measure is the amount of body fat.

There are no accepted definitions for obesity based on the percent of body fat, because academia wouldn’t be academia if people could just agree on definitions and move on. But a commonly used indicator for overweight is more than 25 percent fat for men and more than 35 percent for women. Turns out that about 12 percent of men who have a BMI about 25 have a normal amount of body fat, so probably just a lot of muscles. And on the flip side, about 15 percent of women with a BMI below 25 have an abnormally high percentage of body fat.

But using body fat as a measure for obesity is also overly simplistic because the problem isn’t actually the fat, it’s where you store it.

You see, the body removes fat from the blood and then tries to store it in fat cells. But in adults the number of fat cells doesn’t increase, it’s just the size of the cells that increases. And there’s only so much fat that a single cell can store. The problem begins when all the fat cells are full. Because then the body has to store the fat in places where it doesn’t belong and it does that notably around the liver and in muscle tissue. That’s right, the fat isn’t the problem, it’s the lack of fat cells that’s the problem. I would like to add that for the same reason books aren’t the problem, it’s the lack of bookshelves that’s the problem.

The out-of-place storage of fat seems to be the major reason for most of the health problems associated with obesity. Among others, that’s an increased risk for heart attacks and strokes, type 2 diabetes, breathing problems, knee, hip, and back problems, and an increased risk for certain types of cancer. But since there are individual differences in how much fat the body can store in the available fat cells, the onset of disease doesn’t happen at any particular amount of fat. About 20 percent of people with a BMI above thirty appear to be metabolically healthy.

This is why researchers have tried to figure out specifically where too much fat is a problem. But it’s not as easy as saying, if your waist circumference is more than so-and-so then that’s too much. To begin with, as you have undoubtably noticed, men and women store fat in different places. Men store it mostly at the belly, women store it primarily at the breasts, thighs (!th), and bottom, which is why you never get to see my bottom. It doesn’t fit on the screen. So, if you use a measure like waist circumference, at the very least you have to use a different one for men and women. To make matters more complicated, the onset of metabolic disease with waist circumference seems to depend on the ethnic group.

To return to the definition from the WHO, we see that it’s not all that easy to figure out when “an accumulation of fat impairs health”. It’s clearly not just the number on your scale that matters and it’s true that some obese people are healthy. Still, after all is said and done, the BMI is very strongly correlated with the ill effects of obesity.

So what are the possible causes of this obesity epidemic? Yes, the universe also expands, but it’s the space between galaxies that expands, not planets, or people on planets. So I’m afraid we can’t blame Einstein for this one. But if not Einstein, then what?

The first possible cause of obesity is too much food. Bet you didn’t think of this one.

Food has become more easily accessible to almost everyone on the planet, but especially in the developed world. It doesn’t help that food companies have an incentive to make you want to eat more. In a familiar pattern, the sugar industry has tried to play down evidence that sugar contributes to coronary heart disease for decades, though the evidence is now so overwhelming that they’ve given up denying it.

But just saying obesity is caused by easy access to food is a poor explanation because not everyone who has food in abundance also gets fat. Let’s therefore look at the second possible cause, the wrong type of food.

Modern food is nothing like the food our ancestors ate. A lot of the stuff we eat today is highly processed, which means for example that meat is shredded to small pieces, mixed with saturated fats and preservatives, and then formed to shapes. Processed food also often lacks fiber and protein and is instead rich in salt, sugar and fat, possibly with chemical compositions that don’t occur in nature.

The issue with processed food is that we may say we’re “burning energy” but, I mean I’m just a physicist, but I believe the human body doesn’t literally burn food. It’s rather that we have to take apart the molecules to extract energy from them. And taking apart the food requires energy, so the net turnout depends on how easy the food is to digest. Processed food is easy to digest, so we get more energy out of it, and put on weight faster.

The correlation between processed food and overweight is well-established. For example, in 2020 a a study looked at a sample of about 6000 adults from the UK. They found that the highest consumption of processed food was associated with 90 percent higher odds for being obese. Another paper from a just a few weeks ago analyzed data from adolescents who had participated in a Health and Nutrition Survey in the United States. They too found that the highest consumption of ultra-processed food was associated with up to 60 percent higher odds of being obese.

A particular problem are trans fats, that are fats which don’t identify with the hydrogen bonds they were assigned at birth. Trans fats are chemically modified so that they can be produced in solid or semi-solid form which makes them handy for the food industry. The consumption of trans fats is positively correlated not only with obesity but also with cardiovascular diseases, disorders of the nervous system, and certain types of cancer, among others. Forty countries have banned or are in the process of banning trans fats. I’m not a doctor but I guess that means they really aren’t healthy.

Let’s then look at the third possible cause, lack of exercise. Just last year, a group of European researchers published a review of reviews on the topic, so I guess that’s a meta-meta-review. They found that exercise led to a significant weight loss in obese people. But when they say “significant” they mean statistically significant not that it’s a lot of weight. If you look at the numbers they are referring to fat loss of about 2 kilogram on average, a difference that most obese people would hardly notice. Part of the reason may be that exercise has a rebound effect. If people start exercising, they also eat more.

Don’t get me wrong, exercise has a lot of health benefits in and by itself, so it’s a good thing to do, but it seems that its impact on reducing obesity is limited.

The next cause we’ll look at are your genes. Obesity has a strong genetic component. Twin, family, and adoption studies show that the chance that obesity is passed down the family line lies between 40 and 70 percent.

The genetic influence on obesity comes in two types, monogenic and polygenic. The monogenic type is caused by only one of a number of genes that affect the regulation of food intake. Monogenic obesity is rare and affects fewer than 5 percent of obese people. Those who are affected usually gain weight excessively already as infants.

Polygenic obesity has contributions from many different genes, though some of them stand out. For example, the so-called FTO gene affects the production of a hormone called ghrelin. Ghrelin is often called the “hunger hormone” because it regulates appetite. The ghrelin level is high if you’re hungry and decreases after you’ve eaten. A study in 2013 found that people with the obesity variant of the FTO gene showed less reduction of ghrelin levels after they’d eaten. So they’ll stay hungry longer, and you don’t need to be Einstein to see how this can lead to weight gain.

How many obese people are obese because of their genes? No one really knows. For one, not all genes that contribute to obesity are known, not all people who carry those genes are obese, and the prevalence of certain genes depends strongly on the population you look at. For example, the variation of the FTO gene that’s correlated with an increase of BMI is present in about 42 of people with European ancestry, but only 12 percent of those with African ancestry. So, it’s complicated, but that’s why you’re here, so let’s make things more complicated and look at the next possible cause of obesity, the microbiome.

The microbiome, that’s all those bacteria, viruses, and fungi that live in your gut. They strongly affect what you can digest and how well. Several studies have shown that obese people tend to have a somewhat different microbiome. However, some other studies seem to contradict that, and it’s also again unclear whether this is a cause or an effect of obesity. So my conclusion on this one is basically, more work is needed. The next suspect is your circadian rhythm.

Your inner clock regulates metabolic processes, that includes digestion. If you mess with it and eat or sleep at the wrong time, you might extract more or less energy from food. A 2018 review paper reported strong evidence that disrupted sleep and circadian misalignment, such a working night shifts, contributes to obesity.

However, while the correlation is again statistically significant, the effect isn’t particularly large. A survey by the American Cancer Society found that in women, missing out on sleep is associated with a BMI that’s greater by 1.39 kilogram per square meter, while in men it’s a difference of up to 0 point 57 kilogram per square meter. That typically converts to one or two kilogram in weight.

Another possible cause of obesity is stress. For example, a 2019 paper looked a group of about 3000 adult Americans and their exposure to a wide range of psychosocial stressors, such as financial strain, relationship trouble, people who believe in the many worlds interpretation of quantum mechanics, etc. They found that stress increased the risk of obesity by 15 to 25 percent.

But correlation doesn’t mean causation. For one thing, stressed people don’t sleep well, which we’ve seen also makes obesity more likely. Or maybe they are stressed because they’re obese to begin with?

Yet another possible cause of obesity that researchers have looked at are vitamin and mineral deficiencies. These are indeed common among overweight and obese individuals. That’s been shown by a number of independent studies. But in this case, too, the direction of causation remains unclear because excess body weight alters how well those nutrients are absorbed and distributed.

Another option to explain why you’re fat is to blame your mother. Indeed, there’s quite convincing evidence that if your mother smoked while pregnant, you’re more likely to be obese. For example, a 2016 meta-review from a group in the UK found that children born to smoking mothers had a 55 percent increased risk of being obese. A similar meta-analysis from 2020 came to a similar conclusion. However, these meta-reviews are difficult to interpret because there are many factors that have to be controlled for. Maybe your mother smoked because she’s stressed and that’s why you didn’t get enough sleep and now you’re fat. This is all getting very confusing, so let’s talk about the two newest ideas that scientists have come up with to explain the obesity epidemic, viruses and plastic.

Did I say obesity is not caused by a virus, oops!

Turns out that a number of viruses are known to cause obesity in chickens, mice, and rats. And it’s not just animals. A meta-analysis from 2013 showed that a previous Adenovirus 36 infection is correlated with an increased risk of obesity of about 60 percent. A few other viruses are suspect, too, but this Adenovirus 36 seems to be the biggest offender. An infection with adenovirus 36 has the symptoms of a common cold but can also lead to eye infections.

A review published in 2021 in the International Journal of Obesity found that 31 out of 37 studies. reported a positive correlation between Adenovirus 36 antibodies and weight gain, obesity, or metabolic changes. However, this virus is incredibly common. About every second person has antibodies against it, not all of them are obese, and not all obese people have had an infection. So this might play a role for some people but it’s unclear at the moment how relevant it is. In any case, face masks also protect from obesity, just don’t take them off.

This finally brings us to the headlines you may have seen some weeks ago claiming that plastic makes us fat. These headlines were triggered by three review papers that appeared simultaneously in the same journal about the role of obesogens in the obesity epidemic.

“Obesogen” is a term coined in 2006 by two researchers from UC Irvine. They are a type of “endocrine disrupting chemicals” that resemble natural hormones and can interfere with normal bodily functions. About a thousand chemicals are currently known to have, or are suspected to have endocrine disrupting effects. About 50 of those are believed to be obesogens that affect the metabolic rate, the composition of the microbiome, or the hormones that influence eating behavior.

Obesogens are in cosmetics, preservatives, sun lotion, furniture, electronics, plastics, and the list goes on. From there they drift into the environment. They have been found also in dust, water, and even in medication and processed foods.

The review papers report fairly convincing evidence that obesogens affect the development of fat and muscle cells in a petri dish, not to be confused with a peach tree disk. There is also some evidence that obesogens affect the development of mice and other animals. However, the evidence that they play a significant role for obesity is not quite as convincing.

The majority of studies on the topic show a positive correlation between obesogen exposure and an elevated BMI, especially when exposure occurs during pregnancy or in childhood. However, as we saw earlier, just because a correlation is statistically significant doesn’t mean the effect is large. How large the effect may be is at present guess work. In a recent interview with The Guardian the lead author of one of the reviews, Robert Lustig, said “If I had to guess, based on all the work and reading I’ve done, I would say obesogens will account for about 15 to 20 percent of the obesity epidemic. But that’s a lot.”

Maybe. If it was correct. But maybe asking the lead author isn’t the most objective way to judge the relevance of a study. There are also some studies which didn’t find correlations between obesogen exposure and obesity risk and again, the results are difficult to interpret, because exposure to certain chemicals depends on living conditions that are correlated with all kinds of demographic factors.

Despite that, the researchers claim that “epidemiological studies substantiate a causal link between obesogen exposure and human obesity”. They don’t stop there but put forward a new hypothesis for the cause of obesity.

In their own words: “This alternative hypothesis states that obesity is a growth disorder, in effect, caused by hormonal/enzymatic defects triggered by exposures to environmental chemicals and specific foods in our diet.” You can see how this would make big headlines. It’s such a convenient explanation, all those damned chemicals are making us fat. However, until there’s data on how big the effect is, I will remain skeptical of this hypothesis.

So, let’s wrap up. The best evidence for factors that make obesity more likely are genetics and the consumption of processed food. Factors that may make the situation worse, are stress, lack of sleep, exercise, or essential vitamins and minerals, and an abnormal microbiome, but in all those cases it’s difficult to tell apart cause and effect. When it comes to viruses and exposure to certain chemicals, the headlines are bigger than the evidence.

If you’re interested in a video on possible treatment options for obesity, let us know in the comments.

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