Biological Clocks, Cancer-Stopping Ketones, and How Our Bodies Get Fuel
Welcome back to The Connected, my deep dive into the potential for personalized digital healthcare. This week I’m sharing a couple articles, an update on my tracking dashboard, and foundational research I’ve done over the last week.
Articles
“Aging clocks aim to predict how long you’ll live” - MIT Technology Review
Epigenetic clocks and understanding our true age, not just our laps around the sun. The various tools used to measure age give us the best understanding of our bodies and the effect that various supplements and remedies have on our long term health. I got my ‘biological age’ at a checkup last year and I can’t wait to see how it’s changed since then.
“BHB May Help Prevent Colorectal Cancer” - Cancer Biology Research
Relevant given my research below on Ketosis. BHB (β-hydroxybutyrate) is one of the ketones produced when your body turns to fat for energy and is shown in these studies to reduce cancer in mice by slowing down cell division.
“Ketone bodies are a source of [emergency] energy for the brain. And, based on our study, that same molecule has a second property, which is to shut down everything else that is energy consuming,” he said. “If the body is starving, and you want to keep your brain alive, it would be a waste of energy to [let cells] proliferate. The body can fix things later,”
Tracking Myself
As I mentioned in my last post, I’m building out a dashboard to view the various data I track. This will range from personal health data my Garmin watch records to behavioral info like my fasting times on Zero to potentially more unique data feeds like my screen habits on my computer and phone (although Apple doesn’t make this easy).
The plan is to build a simple web application, something I’ve done before, that will pull in data automatically through API calls and manually uploaded CSVs.
I’m moving steadily along in creating the web app, currently going through a simple tutorial to get the basics in place. I’m close to having my first data (fasting and sleep) uploaded and plan to have something live in the next week.
Regarding APIs, I’ve been intrigued by a company called Terra, which gives users access to many wearable APIs in a standard format. This would ease the development burden on my side. Unfortunately, a license costs $350/month and there is no cheaper price they will give me during development. It’s frustrating because it seems unlikely anyone will pay that price before they’ve started making revenue. I reached out and they explained they don’t want to waste time on users where they won’t be making revenue. I think it’s the right decision for them if they have users willing to pay. It follows the “fire your customers” advice Tim Ferriss gives in the 4 Hour Work Week.
I will still push ahead with API integrations in time. This will mean building a new connector for each service (Strava, Garmin, MyFitnessPal, etc.). Given I’m only using a handful of these services personally, this shouldn’t be an insurmountable hurdle.
How our bodies get fuel: carbs, glucose, fat, and ketones
I’ve been waiting a long time to do this research and get my thoughts down. Sugar has been a boogyman in my life since my first experiment with the Paleo diet in 2010. For the month that I was carb-free, I shed the post-lunch lag. I connected it to the simple carbs I was eating, and those carbs were basically equivalent to even simpler sugar, like candy, in my head. Since then, I’ve looked at all of these sugars, complex carbs, simple carbs, and table sugar, like a sort of drug to be avoided. However, I never really understood their relationships and how they worked their way through my body. What was I actually avoiding by eating salads instead of sandwiches?
For years after, I ate a healthy, carb free breakfast of eggs and greens. This morphed into intermittent fasting several years ago after hearing Tim Ferriss and Peter Attia rave about it. For me, the benefits of IF are mostly twofold. First, I feel much sharper and more energetic before I eat. Even if the meal doesn’t involve carbs, I sustain an energy prior to eating that keeps me productive. Second, having tracked my calorie intake for years through MyFitnessPal, IF shortens my eating window and helps me avoid disastrous days. When it’s 3pm and I still haven’t had a single calorie, it’s hard for me (not impossible) to explode for a 3,500 calorie day. That’s helped me stay fit while binging on unhealthy food at night (ice cream and frozen pizza).
Finally, there’s one research finding I’ve been unable to forget since hearing about it. Metformin, a drug used for diabetes control, has been shown to decrease all-cause mortality in diabetics when compared to all others, both diabetics and non-diabetics.[4] This means that by taking Metformin, diabetics live longer than others, regardless of diabetes. That’s powerful.
I heard this again a couple weeks ago on David Sinclair’s Lifespan podcast and went down the Metformin rabbit. I ended up reading papers about insulin and glycogenesis, and realized I don’t know much about digestion and energy in the body. Before I go buy black market Metformin, it felt appropriate to understand the basics.
The notes below answered a few basic questions.
How do simple carbs and complex carbs differ?
What does insulin do?
How does eating carbs make someone fat?
What happens when I stop eating carbs?
What happens when I stop eating altogether?
How does ketosis work?
I don’t envision The Connected as a research newsletter, but with all the tracking that I’m doing it felt necessary to build a solid foundation. There are a few important topics I still want to research, namely Metformin and autophagy, the 2016 Nobel Prize winning internal process that cleans cells and is sped up through multiday fasts (which I plan to do), and I’ll likely cover those in the newsletter in time.
I hope these notes are informative. Please get in touch if you have any thoughts, feedback, or just want to say 👋.
Fueling the Body
How sugar and insulin work
Digestion begins in the mouth then onto the stomach, where minimal carbohydrate digestion occurs. Most digestion happens in the small intestine, where pancreatic and other enzymes break down food.[5]
Simple carbs - small chains of sugar molecules, absorbed quickly.
Monosaccharides (1 molecule) are absorbed immediately, disaccharides (2 molecules) are quickly broken down into single molecules and absorbed.
Complex carbs - long chains of sugar molecules with 3 or more molecules.
Also likely to contain vitamins, minerals, and fibers, causing longer digestion time.
This raises blood sugar levels, which causes the pancreas to produce insulin.
Insulin aids the absorption of glucose into cells. This is the default state for energy entering cells.
Type 1 Diabetes: not enough insulin is produced so it must be supplemented.
Type 2 Diabetes: insulin which is produced becomes ineffective at aiding absorption of glucose into the cells.
Excess sugar
Glycogenesis: Creation of glycogen to store extra energy.
When sugar and insulin are at high levels, insulin tells the liver and muscles to store glucose as glycogen (8-12 glucose molecules) through the enzyme glycogen synthase.[2]
Lipgenesis: creation of fatty acids and triglycerides from glucose.[9]
When the liver cannot hold more glycogen, the glucose in your blood is stored as triglycerides in fat cells.[7]
Three fatty acid molecules and one glycerol molecule undergo esterification to form one triglyceride molecule.[10]
Not enough sugar
Glycogenolysis: glycogen to glucose
When blood sugar is low, glycogenolysis occurs which breaks down glycogen into glucose.[7,8]
Roughly 2000 calories can be stored as glycogen. This can be broken down and last 6-24 hours if no other calories are consumed.[8]
Lipolysis: fat to fatty acids and glycerol to ketones and glucose
When glycogen is depleted, lipolysis breaks down fat into fatty acid and glycerol.[8]
Ketogenesis: fatty acids to ketones.
Ketogenesis breaks down fatty acids into ketones: acetoacetate which is further broken down into beta-hydroxybutyrate (BHB) and acetone.[8]
Acetoacetate and BHB can both be used for energy and are 70% more efficient as fuel for cells than glucose.[8]
BHB is especially useful for brain cells.
Acetone makes your breath smell and its production reduces over time, while your body still creates BHB.[8]
Gluconeogenesis: glycerol (and protein and lactate) to glucose.
Some cells require glucose, not ketones, for energy. This comes first from glycerol which is a product of lipolysis[8]
Body can also turn proteins and lactate from the muscles into sugar.
Eating more protein raises insulin, which slows down ketogenesis and increases gluconeogenesis to produce more sugar for fuel.
Fasting to get into ketogenesis is a balance to avoid too much protein which is used in gluconeogenesis and enough protein to avoid breaking down muscle tissue for the body’s required glucose demands.
Additional benefits of Ketosis:
Mitochondria production increases when cells use ketones for fuel, especially in the brain.
Nervous system protection and regeneration happens from ketones.
Ketones act as an antioxidant because using glucose as fuel leads to free oxygens, which doesn’t happen with ketones as fuel.
Cancer reduction may occur because some cancers cannot use ketones for fuel.
Improved brain activity from ketones as fuel rather than glucose.
Summary
Sugars provide energy to cells, helped in absorption by insulin. Type 1 diabetes is low insulin production. Type 2 diabetes is ineffective insulin.
Blood sugar gets high, sugar stored as glycogen.
When glycogen stores are full, stored as fatty acids and triglycerides in fat.
When blood sugar is low, glycogenesis turns glycogen into glucose for energy.
When glycogen is depleted, body turns to fatty acid and glycerol from fat cells.
Fat breakdown leads to production of ketones and glucose for energy. Ketones are better for some cells than glucose, but glucose is needed for other cells.
Not enough protein intake leads to protein from muscles used for glucose production.
Sources