Throughout my life I never paid too much attention to health, exercise, diet or nutrition. I knew that you’re supposed to get some exercise and eat vegetables or something, but it stopped at that (“mom said”-) level of abstraction. I also knew that I can probably get away with some ignorance while I am young, but at some point I was messing with my health-adjusted life expectancy. So about halfway through 2019 I resolved to spend some time studying these topics in greater detail and dip my toes into some biohacking. And now… it’s been a year!

Now, I won’t lie, things got a bit out of hand over the last year with ketogenic diets, (continuous) blood glucose / beta-hydroxybutyrate tests, intermittent fasting, extended water fasting, various supplements, blood tests, heart rate monitors, dexa scans, sleep trackers, sleep studies, cardio equipments, resistance training routines etc., all of which I won’t go into full details of because it lets a bit too much of the mad scientist crazy out. But as someone who has taken plenty of physics, some chemistry but basically zero biology during my high school / undergrad years, undergoing some of these experiments was incredibly fun and a great excuse to study a number of textbooks on biochemistry (I liked “Molecular Biology of the Cell”), biology (I liked Campbell’s Biology), human nutrition (I liked “Advanced Nutrition and Human Metabolism”), etc.

For this post I wanted to focus on some of my experiments around weight loss because 1) weight is very easy to measure and 2) the biochemistry of it is interesting. In particular, in June 2019 I was around 200lb and I decided I was going to lose at least 25lb to bring myself to ~175lb, which according to a few publications is the weight associated with the lowest all cause mortality for my gender, age, and height. Obviously, a target weight is an exceedingly blunt instrument and is by itself just barely associated with health and general well-being. I also understand that weight loss is a sensitive, complicated topic and much has been discussed on the subject from a large number of perspectives. The goal of this post is to nerd out over biochemistry and energy metabolism in the animal kingdom, and potentially inspire others on their own biohacking lite adventure.

What weight is lost anyway? So it turns out that, roughly speaking, we weigh more because our batteries are very full. A human body is like an iPhone with a battery pack that can grow nearly indefinitely, and with the abundance of food around us we scarcely unplug from the charging outlet. In this case, the batteries are primarily the adipose tissue and triglycerides (fat) stored within, which are eagerly stockpiled (or sometimes also synthesized!) by your body to be burned for energy in case food becomes scarce. This was all very clever and dandy when our hunter gatherer ancestors downed a mammoth once in a while during an ice age, but not so much today with weaponized truffle double chocolate fudge cheesecakes masquerading on dessert menus.

Body’s batteries. To be precise, the body has roughly 4 batteries available to it, each varying in its total capacity and the latency/throughput with which it can be mobilized. The biochemical implementation details of each storage medium vary but, remarkably, in every case your body discharges the batteries for a single, unique purpose: to synthesize adenosine triphosphate, or ATP from ADP (alright technically/aside some also goes to the “redox power” of NADH/NADPH). The synthesis itself is relatively straightforward, taking one molecule of adenosine diphosphate (ADP), and literally snapping on a 3rd phosphate group to its end. Doing this is kind of like a molecular equivalent of squeezing and loading a spring:

This is completely not obvious and remarkable – a single molecule (ATP) functions as a universal $1 bill that energetically “pays for” much of the work done by your protein machinery. Even better, this system turns out to have an ancient origin and is common to all life on Earth. Need to (active) transport some molecule across the cell membrane? ATP binding to the transmembrane protein provides the needed “umph”. Need to temporarily untie the DNA against its hydrogen bonds? ATP binds to the protein complex to power the unzipping. Need to move myosin down an actin filament to contract a muscle? ATP to the rescue! Need to shuttle proteins around the cell’s cytoskeleton? ATP powers the tiny molecular motor (kinesin). Need to attach an amino acid to tRNA to prepare it for protein synthesis in the ribosome? ATP required. You get the idea.

Now, the body only maintains a very small amount ATP molecules “in supply” at any time. The ATP is quickly hydrolyzed, chopping off the third phosphate group, releasing energy for work, and leaving behind ADP. As mentioned, we have roughly 4 batteries that can all be “discharged” into re-generating ATP from ADP:

1. super short term battery. This would be the Phosphocreatine system that buffers phosphate groups attached to creatine so ADP can be very quickly and locally recycled to ATP, barely worth mentioning for our purposes since its capacity is so minute. A large number of athletes take Creatine supplements to increase this buffer.
2. short term battery. Glycogen, a branching polysaccharide of glucose found in your liver and skeletal muscle. The liver can store about 120 grams and the skeletal muscle about 400 grams. About 4 grams of glucose also circulates in your blood. Your body derives approximately ~4 kcal/g from full oxidation of glucose (adding up glycolysis and oxidative phosphorylation), so if you do the math your glycogen battery stores about 2,000 kcal. This also happens to be roughly the base metabolic rate of an average adult, i.e. the energy just to “keep the lights on” for 24 hours. Now, glycogen is not an amazing energy storage medium – not only is it not very energy dense in grams/kcal, but it is also a sponge that binds too much water with it (~3g of water per 1g of glycogen), which finally brings us to:
3. long term battery. Adipose tissue (fat) is by far your primary super high density super high capacity battery pack. For example, as of June 2019, ~40lb of my 200lb weight was fat. Since fat is significantly more energy dense than carbohydrates (9 kcal/g instead of just 4 kcal/g), my fat was storing 40lb = 18kg = 18,000g x 9kcal/g = 162,000 kcal. This is a staggering amount of energy. If energy was the sole constraint, my body could run on this alone for 162,000/2,000 = 81 days. Since 1 stick of dynamite is about 1MJ of energy (239 kcal), we’re talking 678 sticks of dynamite. Or since a 100KWh Tesla battery pack stores 360MJ, if it came with a hand-crank I could in principle charge it almost twice! Hah.
4. lean body mass :(. When sufficiently fasted and forced to, your body’s biochemistry will resort to burning lean body mass (primarily muscle) for fuel to power your body. This is your body’s “last resort” battery.

All four of these batteries are charged/discharged at all times to different amounts. If you just ate a cookie, your cookie will promptly be chopped down to glucose, which will circulate in your bloodstream. If there is too much glucose around (in the case of cookies there would be), your anabolic pathways will promptly store it as glycogen in the liver and skeletal muscle, or (more rarely, if in vast abundance) convert it to fat. On the catabolic side, if you start jogging you’ll primarily use (1) for the first ~3 seconds, (2) for the next 8-10 seconds anaerobically, and then (2, 3) will ramp up aerobically (a higher latency, higher throughput pathway) once your body kicks into a higher gear by increasing the heart rate, breathing rate, and oxygen transport. (4) comes into play mostly if you starve yourself or deprive your body of carbohydrates in your diet.

Since I am a com

Read More