The Three Pillars Behind Almost Every Modern Illness

Only around 1 out of 8 American adults is metabolically healthy.

Your blood pressure, blood sugar, lipids, and waist circumference have to all fall within normal ranges for you to be considered as such. A majority of the adult population has warning signs on their internal organs without realizing it.

When you read a medical publication nowadays, it can be easy to think of these conditions as siloed problems. If your heart is failing, see a cardiologist. Having issues with blood sugar means you visit an endocrinologist. Memory loss is a neurologist's specialty — and so on. It's easy to forget that research increasingly shows a variety of illnesses have common denominators that, if addressed, could have downstream benefits for all of them.

These common denominators take the form of three interrelated issues: chronic inflammation, insulin resistance, and dysfunctional mitochondria.

This newsletter is about those three pillars of health and disease. It's about what we know and what we don't know. You'll never find advice here on the latest unproven miracle substance or procedure. Instead, you'll always find what has been proven to help, for better or for worse.

Pillar one: chronic, low-level inflammation

Inflammation is the body's natural response to tissue damage and it plays a critical role in healing.

If you cut your hand on a piece of glass, your inflammatory response sends signals to your brain that cause pain and lead to the typical swelling you associate with injury. This serves two purposes: it prevents you from using that hand so you avoid causing further damage, and it tells the body to send white blood cells to the site to begin repair. Inflammation serves a useful and necessary function.

But imagine if that inflammation never went away. Imagine if there were trucks outside your house and sirens wailing for years, for decades. You would eventually stop noticing the noise.

It turns out this is exactly what happens, in a process called inflammaging. Inflammation related to aging has been found to contribute to cardiovascular disease, diabetes, autoimmune conditions like rheumatoid arthritis, several cancers, and cognitive decline including Alzheimer's disease.

Inflammation is a risk factor for nearly every age-related illness.

Pillar two: insulin resistance

Insulin resistance is another condition in which the body becomes desensitized to a hormone and its effects.

Insulin is a messenger hormone your pancreas releases after you eat. It knocks on the door of your cells and causes them to absorb blood sugar, which they use for energy. When you eat something sweet, your blood sugar rises and insulin is released to bring it back down.

Now imagine ringing the doorbell of your cells a couple hundred times a day, for years at a time. If you eat snacks, drink soda, eat bread, or eat chips throughout the day, your cells start to ignore the signal. This leads to chronically high blood sugar, since the cells are no longer responding. Your body tries to compensate by making more insulin to force a response.

Your body can maintain normal blood sugar levels for a long period — 10 to 15 years on average — and hide the underlying dysfunction the whole time.

That's why type 2 diabetes, metabolic syndrome, and much of cardiovascular disease occur. Some researchers think Alzheimer's is partly the brain becoming insulin resistant; they've nicknamed it type 3 diabetes.

But this is still largely theoretical. If you buy into a supplement or drug to treat Alzheimer's based on this theory, you should understand you're getting ahead of the science.

Pillar three: mitochondrial dysfunction

Mitochondrial dysfunction occurs when the power plants of the cell stop producing as much energy as they used to.

There are organelles inside your cells called mitochondria, and they convert the food you eat and the oxygen you breathe into energy. They power your entire body. When they're working properly, energy is plentiful for your muscles, your heart, your brain — everything. When these power plants start to fail, your cells can't make enough energy to keep up.

The parts of your body that need the most energy suffer first. You may find yourself constantly lethargic — a fatigue much more intense than regular tiredness, and one that can't be fixed by sleeping more.

Researchers believe mitochondrial dysfunction may be a core hallmark of aging.

The hidden connection

What I haven't said yet is that these pillars aren't separate issues.

Inflammation causes cellular insulin resistance, which wreaks havoc on your mitochondria, which in turn causes more inflammation. It's a self-reinforcing loop that leads to a collection of conditions rather than one specific disease. That combination of problems is what we think of as aging.

Even though the interconnectedness is disappointing from a treatment standpoint, it has an upside. There are lifestyle interventions and medications that address all of these at once. You don't need a separate treatment for each symptom, since they share common mechanisms.

The boring stuff that actually works

When it comes to healthspan, I'm not a fan of miracle cures. The things with the most robust and consistent evidence behind them are rarely interesting or exciting. They're also usually non-negotiable.

Getting real sleep — not just time spent in bed. Developing muscle mass. Moving in a way that doesn't destroy your joints. Avoiding foods that spike your insulin. All have strong scientific backing.

Not smoking has downstream effects on all three pillars, since it increases inflammation while also impairing mitochondrial function and insulin sensitivity.

If you want to maximize your healthspan, you can't cut corners on these fundamentals.

Anything that promises to help you accomplish these things faster or with less effort than you think is likely preying on your ignorance of the science. That doesn't mean the flashy solutions have no value, but they're almost always significantly overrated, especially measured against the risks.

We'll explore many of those flashy treatments here. In fact, that's the point. This is a health and longevity newsletter, after all. But every single one will be measured against the same evidence. What does the research say? Are these treatments safe? Do they actually work? Is there any downside?

You get this information from me in an easily digestible format. You won't find fear-mongering or snake oil sales pitches. I'll give you the facts, both good and bad, about everything from peptides to surgeries to everyday supplements.

Next time we'll dig into the first pillar — chronic inflammation — in more detail, and look at the lifestyle changes you can implement to reduce it.