The biggest losers: Metabolic damage or constrained energy?

A lot of viral infections impact cortisol in humans. Infection tends to ramp up cortisol levels, but prolonged or chronic infection can both deplete cortisol (so called adrenal fatigue) and/or make the body more resistant to the effects of cortisol. This is seen in the extreme in the case of HIV. I assume cortisol resistance is analogous to insulin resistance in prediabetics. Apparently chronic stress can have similar effects. And chronic stress may be associated with chronic viral reactivation. [1]

Great comment! Interestingly, depleted cortisol levels from chronic stress may be associated with the development of long covid. [2] I wonder if down the road we will see that people who have had long covid are at increased risk of developing or exacerbating obesity.

[1] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470332/

[2] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519365/

CICO works quite well at the extremes. It's effectiveness varies, but it is directionally correct.

If someone is sitting at a 35+ BMI, then their caloric intake is so out of whack, that CICO helps ground them. Similarly, an anorexic who starves gets a clear directive for increasing weight by increasing calories.

CICO also promotes calorie general calorie comparison. It helps you understand that a milkshake has the same weight impact as an average Mediterranean lunch bowl.

Now the absolute impact on both foods will vary from person to person. But comparatively, it helps ground the unhealthiness of foods like sugar rich shakes and icecream.

Why would the body touch anything else when it has a preferential energy storage?

no, Rae is truly exceptional. Other calorie-restrictors eat far less and weigh more ,even controlling for height

https://www.webmd.com/diet/features/restrict-calories-revive...

"I eat the same thing twice a day, seven days a week, 365 days a year," says Pomerleau, of his diet of 1,200 calories a day. "It's a lot of veggies with olive oil-based salad dressing, a lot of mixed fruits, almonds and hazelnuts, and flaxseed oil for omega-3 fatty acids."

https://archive.is/e345S#selection-4235.216-4239.443

.Bob Cavanaugh, a 54-year-old landscaper from Morehead, N.C., has trimmed his intake to two meals a day, totaling 1,500 calories. Breakfast consists of one cup of quick oats, two tablespoons of toasted wheat germ, one cup of skim milk and blueberries. For dinner, he eats vegetables, fruit and a small portion of fish. "I'm hoping to see my great, great grandchildren," he says. Mr. Cavanaugh's diet may sound extreme, particularly since at 5-feet 9-inches tall and 158 pounds, he isn't overweight. But over the next several years, if the monkey results hold up, they could represent a major shift in how we view food and nutrition. The U.S. Department of Agriculture says the average sedentary woman should eat 1,600 calories a day and the average man 2,200 -- benchmarks already significantly overshot by most Americans.

and a third guy https://pbs.twimg.com/media/EW8oScgXsAAVqeg.jpg

A bmi of 21, nowhere close to 16 despite eating fewer calories (1700)

Thanks for asking. I'll first explain the process (because I want to highlight why IF matters), and then I'll answer your question directly. It's going to take a little bit to properly elaborate, but I believe it's worth your time to read.

We first need to choose which of the following macronutrients contribute most to weight gain: protein, fat, or carbohydrates. Proteins (or, rather, amino acids) are not known for contributing to body fat in any significant manner. Fat was once thought to be the main contributor when calories--not carbohydrates--became accepted as fattening. However, modern science shows fat has little significant contribution to body fat and that the real contributor to body fat are carbohydrates. The discovery of leptin about 30 years ago finally shows why.

Carbs are sugars. Sugars, such as glucose, are the main source of fuel in the body, as they are eventually synthesized into ATP. Blood glucose levels are regulated by the hormone insulin. Elevated blood glucose levels increases insulin production, whereas low blood glucose decreases insulin production (with glucagon helping stabilize blood glucose levels). High insulin levels promotes anabolism, whereas low insulin levels promotes catabolism. Creating body fat is an anabolic process, whereas burning body fat is a catabolic process. Putting it all together, eating carbs inhibits the essential catabolic processes for burning fat.

While entirely cutting out carbs should be the answer, it's not. Many obese people report failure to lose weight on ketogenic diets. Why? The hormone leptin. See, leptin levels increase with insulin levels. Leptin signals the availability of energy reserves in the body. Adipose tissue (that is, body fat) is the primary producer of leptin. Importantly, leptin levels vary exponentially with body fat. The obese individual's body is so oversaturated with leptin, the body becomes resistant to leptin.

Decreased leptin levels will cause body fat to be burned. On a ketogenic diet, catabolic processes initially cause a reduction in body fat, which then decreases leptin production. Because the obese body has leptin resistance, the leptin production decrease is interpreted by the brain as a severe drop in available energy reserves, causing total energy expenditure to be immediately reduced and placing the body in "starvation mode." At this point, eliminating body fat actually becomes more difficult, as excess carbs become anabolized into body fat due to decreased energy expenditures.

So, to finally get to your question, how do carbs matter with respect to leptin? To lose weight over months and years, an obese person needs to eat carbs to (1) keep their leptin levels stable over the course of each week to prevent the body from entering starvation mode while (2) maximizing the efficacy of catabolic processes. As the body gradually recovers from its leptin resistance (which will likely take time), the body will shed fat without triggering the energy-minimization mode.

In this paradigm, your total energy expenditure determines how fast fat will be burned. According to the book "The Obesity Code", "total energy expenditure is the sum of basal metabolic rate, thermogenic effect of food, nonexercise activity thermogenesis, excess post-exercise oxygen consumption [(EPOC),] and exercise". Of these five factors, EPOC is mostly likely underutilized. A simple 10-minute HIIT routine every other day will regularly drive EPOC, which causes ATP synthesis. When an person isn't eating carbs, the body dips into fat stores to acquire the necessary glucose for ATP synthesis. Note that with this approach, exercise isn't strictly necessary but becomes extremely beneficial to maximize the efficacy of catabolic processes.

Intermittent fasting should work as long as the specific protocol doesn't decrease leptin levels such that the obese body enters starvation mode. In my opinion, the most workable approach for people is to try their best to completely eliminate carbs Monday-Friday, eat all the carbs they want on the weekends, and do the bare minimum of a 10-minutes HIIT routine every other day.