I was fortunate to be invited to join an NIH-sponsored project, which eventually provided me with a free clinical-grade DNA report detailing important metabolic pathways and pharmacogenetic implications.
Based on years of CMP labs I had already come to the conclusion that my elevated bilirubin was due to a relatively common variant (perhaps 1 out of 8 people of European ancestry) that makes me a poor metabolizer on the UGT1A1 metabolic pathway. But the DNA report also brought surprises including an extremely rare CYP3A4 variant (which I’ll discuss in more detail at a later date) which among other implications brings reduced clearance of cortisol (and a great many other natural metabolites and medications.) So today I asked the Gemini A.I. engine why it had determined that my Gilbert’s Syndrome protected my kidney from inflammatory damage but not as much the nerves in my feet which still have some numbness from neuropathy. This was the response:
You have likely discovered the “Silver Lining” of your genetic profile. While Gilbert’s Syndrome (GS) and Slow COMT gave you drug sensitivity and anxiety, they likely saved your organs from the damage caused by decades of chronic pain and stress.
Here is the scientific breakdown of how your “High Bilirubin” acted as a biological shield against the “High Cortisol.”
1. The “Bilirubin Shield” (Why Gilbert’s protects Kidneys)
For decades, doctors thought Bilirubin was just toxic waste. We now know it is one of the most potent Endogenous Antioxidants in the human body.
The Mechanism: Bilirubin is 30 times more potent than Vitamin E at stopping oxidation.1 It specifically prevents Lipid Peroxidation—the process where free radicals destroy blood vessels and cell membranes.2
The Kidney Connection: Kidneys are essentially giant bundles of blood vessels. They are highly susceptible to oxidative stress (rust).
The Research: Large-scale studies (NHANES) have confirmed that people with Gilbert’s Syndrome have a significantly lower risk of Chronic Kidney Disease (CKD) and Coronary Heart Disease.
Your Case: Your elevated bilirubin has been “scrubbing” your renal arteries 24/7 for 70 years. It acted like a permanent internal dose of high-grade antioxidant therapy, protecting your kidney filters (glomeruli) from aging.
2. The “Cortisol War” (The Unstoppable Force vs. Immovable Object)
You asked: “I would have thought my cortisol issues… would have aged my kidneys.”
They should have.
The Attack: Chronic pain (since 2001) + High Cortisol (Wired) = Massive Oxidative Stress. Cortisol constricts blood vessels and spikes blood sugar, which usually destroys kidney function over 20 years.
The Defense: Your Bilirubin (Gilbert’s).
The Outcome: The Bilirubin neutralized the oxidative damage caused by the Cortisol. It was a biochemical tug-of-war, and your liver’s “defect” (making too much bilirubin) actually won the war for your kidneys.
3. Why Neuropathy happened but Kidney Failure didn’t
This explains the discrepancy in your health history:
Nerves (Neuropathy): Nerves are sensitive to glycation (sugar damage) and compression.3 Bilirubin doesn’t protect nerve sheaths as effectively as it protects blood vessels. So, the nerves suffered from the inflammation/sugar.
Kidneys (eGFR 96): Kidneys are vascular organs.4 Because Bilirubin is a Vascular Protector, it kept the “plumbing” of your kidneys pristine even while your nerves were degrading.
Summary Verdict
You are a survivor of the “Genetic Trade-Off.”
The Cost: Drug sensitivity, potential anxiety, and maybe some gallstone risk.
The Prize: “Teflon” Kidneys and Arteries.
Your eGFR of 96 is not an accident. It is the result of your “Runner’s Heart” pumping blood efficiently and your “Gilbert’s Bilirubin” keeping that blood clean of oxidative rust. You essentially have a built-in anti-aging serum in your blood.
This has been just one chapter of an incredible process of “metabolic self-discovery” my genetic research has made possible. Indeed, I have greatly improved my blood pressure, pulse rate, blood glucose, HRV (Heart Rate Variability), visceral fat levels, and body weight by means of these discoveries. I’m 70 years old but many of my vitals (and nearly-vitals) are landing me in 20-something and even teenager territories of health profiles. Among other things, I now know what foods to avoid that were fueling my osteoarthritis. (For example, my CYP3A4 variant creates a very “crippled” metabolic pathway where I have difficulty clearing things molecules like caffeine and theobromine (a stimulant in cocoa products. In my case such substances can exaggerate my cortisol surges and durations and add gasoline to inflammation fires.)
Of course, A.I. can’t be casually trusted—but it can provide the peer-reviewed papers supporting its answers. And with anything “actionable” I have found it useful to submit the answer from one A.I. engine into a competitor’s engine and even have them debate the details back and forth. One must also watch for major logic blunders, such as getting “backwards” whether a particular low-normal-range lab results is good or bad. (Yep, A.I. can get complicated stuff exactly right and then simple stuff completely wrong. So the user must remain careful and ever vigilant.)
I had not expected my DNA report of a few months ago to lead to so many actionable and beneficial outcomes. I now have the least osteoarthritis pain that I’ve had in years and I’m back to pumping iron at the gym and building muscle again.
I’m curious if others here have benefited from DNA analysis.