Obesity and genes: the skinny of it

The predictable response to blaming obesity on genes is that genes take a long time to change, whereas obesity by comparison is a relatively modern problem. But genes play an inescapable role in explaining individual phenotypic variation when environment is held constant. That is, why do some people get much fatter than others when everyone has access to the same food? Why do some people lose or gain weight more easily than others? We cannot just dismiss genes altogether.

Many obese individuals likely have slow metabolisms, too much ghrelin, insufficient leptin, etc. and either are too hungry all the time, or do not get full despite eating large quantities of food, or burn too few of calories consumed (the rest stored as fat, but hunger does not subside). This is all to some extent determined by genes. Although evolution is gradual, the 20th century introduction of hyper-palatable, calorie-dense foods makes such genes maladaptive in our present environment of abundance.

One problem is obese people’s bodies simply do not burn many calories relative to body weight, like being as big as a Suburban but having the mileage of a Prius. This is backed by studies showing that obese people tend to be more efficient, even after losing weight. The difference can be quite large:

In a previous study, Dr. Indelicato and his colleagues found that obese people had an average MF of 8.3 calories per pound, compared to 10.6 for overweight people and 12.8 for normal-weight individuals This means that an obese person needs just eight calories per pound to maintain his or her body weight, while a normal-weight person burns 12 calories per pound while at rest—50% more.

So although obese people do tend to eat more compared to non-obese people, they still tend to be more efficient relative to body weight (which is probably how they became obese to begin with), which is counterintuitive and makes dieting hard. To people who say that the difference of a few hundreds calories a day is not that much–not quite so. Metabolic adaptation likely means more calories need to be cut than predicted.

Same for ‘thrifty’ vs. ‘spendthrift’ metabolisms:

Researchers at the Phoenix Epidemiology and Clinical Research Branch (PECRB), part of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, studied 12 men and women with obesity in the facility’s metabolic unit. Using a whole-room indirect calorimeter – which allows energy expenditure to be calculated based on air samples – researchers took baseline measurements of the participants’ energy expenditure in response to a day of fasting, followed by a six-week inpatient phase of 50 percent calorie reduction. After accounting for age, sex, race and baseline weight, the researchers found that the people who lost the least weight during the calorie-reduced period were those whose metabolism decreased the most during fasting. Those people have what the researchers call a “thrifty” metabolism, compared to a “spendthrift” metabolism in those who lost the most weight and whose metabolism decreased the least.

Such ‘metabolic phenotypes’ is also suggested by overfeeding experiments, in more detail here. ‘Thrifty’ people gain more weight during overfeeding and lose less weight during restriction. That is not to say this explains why obesity has increased worldwide, but it could explain individual variation of weight relative to environment, or success rates for dieting. It’s evident that not everyone converts or partitions the same amount of calories into equal proportions of stored fat vs. spent energy.

Al Sharpton, for example, who was famously rotund back in the 80s and 90s, in order to maintain his present BMI of 18 ( 130 at 5’10”) must restrict his daily intake to 1,000 calories, which is 40 percent of the predicted calorie intake according to calculators for a man of his height, activity level, age, and weight–or about how much a petite sedentary woman or a toddler would be expected eat. That is terrible genetics. Such people are almost condemned to being fat, short of voluntary starvation. Their bodies are too good at turning food into fat, or need very little energy to run.

A Reddit thread of former or presently obese people who describe their daily habits while obese, many of them were not eating obscene amounts of food. 3-4k calories/day, which is equal to a large meal, a small (or two medium-sized meals), and some snacks, is enough to ‘blow up’ to 270-300 lbs or more if your genetics are bad.

For example, Quora user “Todd Elliot” despite only eating two meals day and physical activity, at 5’11” and 220lbs (130+90, going by the information supplied) has a BMI of 30.7, which is technically obese. Yet he’s not eating that much and hikes a lot, at least by his own admission (self-reported calorie counts are notoriously inaccurate though, and people tend to underestimate how much they report eating).

Someone with average or good genetics is able autoregulate his or her metabolism to adjust to caloric surpluses, without blowing up.

Personally in 2007-2020 I was eating well above predicted TDEE , and never got above 190lbs or so. I remember weighing 190 in 2008 and then in 2018 being scared and disappointed that I still weighed the same. I thought I must have been sick or something, cause my diet was awful and I was doing no exercise and I was certain I should have weighed more (I actually wanted to be bigger). In the ‘aughts’ I was eating a Jack in the Box sausage meal for breakfast, king-sized candy as a mid-afternoon snack, Panda Express for lunch, more snacks, and then steak and mac and cheese for dinner, and lots of soda. Around 2013, I remember having a habit of going to a dollar store and buying those huge 2-litre off-brand orange sodas to maximize my intake relative to how much I spent, in addition to ‎Mc Donald’s Big Breakfast® with Hotcakes, Taco Bell, and the usual steak dinners. Or in 2014-2018 buying four or more packs of candy, 400 calories each, and eating it all during evening, and then more candy in the morning too (addicted to junk food, and still am despite having lost significant weight ), in addition to full meals and lots of soda. But the unluckiest individuals in the above Reddit thread were eating less than me and still became obese, some morbidly so (such as over 300lbs at 5’9″ ).

Above some threshold of bodyweight, for myself 190 lbs, the extra calories are burned off, not stored as fat. However, I was still well in the overweight BMI category, and attempts at weight loss below 160 or so resulted in a significant reduction of metabolism than predicted by bodyweight, weight, height, and activity level alone, hence indicative of mediocre genetics at best on my part. Trying to get thin long-term (below 148 or so) is probably not in the cards for me, because the caloric reduction and discomfort is too great.

People with good genetics for weight loss can stay slim without having to reduce calories much. Someone with superior genetics may have a resting metabolic rate (RMR) of around 2,400 calories/day, and to lose significant weight (going from ‘normal weight’ to underweight) such an individual would maybe only need to cut by perhaps 400 calories/day, which is much more doable than someone whose genetics are worse and has a RMR of only 1,800 calories/day and needs to cut by 700 calories/day (such as an obese person whose RMR is only 1,800 calories/day but is consuming 3,000 calories/day, so to become ‘normal weight’ would need to cut to 1,100 calories/day, which sounds horrible). Of course, in times of famine the first individual is at a major disadvantage. But in our era of abundance, it’s reversed.

Now that we’ve covered bad genetics in detail, what does good genetics look like? Here’s one example of such an individual, Michael Rae, who has top-tier genetics. He is part of a NYC dieting social circle of sorts inspired by the longevity and life-extension gurus Ray Kurzweil and Aubrey de Grey, who hope to live longer through calorie restriction (or denoted as proper noun, Calorie Restriction, which is the name of the clique). Out of everyone he stands out as especially noteworthy as being both exceptionally thin and consuming a relatively normal amount of food, but not having any pathologies that could account for such remarkable thinness:

Michael’s regimen of 1,913 calories a day is exactly that: 1,913 calories every single day, 30 percent of them derived from fat, 30 percent from protein, and 40 percent from carbohydrates. Cooking for him is the same elaborate exercise in dietary Sudoku it is for all CR die-hards, only more so.

A 1,900 TDE while basically voluntarily starving oneself (at 6’0″ and 115lbs, a skeleton-thin BMI of 15.6), is jaw-dropping. Although most people wouldn’t even think that there is anything unusual about this, consider that even Minnesota starvation experiment subjects had to eat 1,500 calories/day or less in order to achieve a similar weight loss. Bodybuilders not uncommonly eat fewer calories when cutting, and they have steroids and lots muscle helping too. It shows how important genes are for weight loss, even intentional weight loss. Having a really fast metabolism and minimal metabolic adaptation will make it easier because you can eat more food and those calories get burned off, not stored as fat.

Someone like Michael with top genes has the ability to voluntarily induce a cachectic state, minus the cancer. It’s possible fashion models are blessed with such genes (although eating disorders and drug use is common too). People with cancer can effortlessly lose significant weight despite only eating slightly less or even the same amount of food, without the sensation of hunger that comes with dieting. Before diagnosis, such weight loss is often erroneously attributed to diet and exercise. The accelerated calorie burning process occurs after the food has left the stomach, so there is no feeling of hunger, unlike dieting (although cachexia by definition means significant muscle wasting too). Diets fail because being hungry all the time is just not a sustainable ‘state of being’ for most people.

As much as we like to think that we have choice or free will, genes to large extent control or determine our ultimate fate, or at least how much of a difference lifestyle modification makes. People with better genes will get more mileage for their efforts, like how smart kids tend to pick up concepts faster in school and score higher on standardized tests. Such is life. Trying to fix the obesity problem in America means having to come to terms that obesity is not just a lifestyle problem but also a biological one, and must be treated as such like any other disease.