What Your Blood Work Isn’t Telling You

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Issue #22: December 8, 2025

🩸 Why Your “Normal” Blood Test Isn’t the Whole Story

Every year, millions of people walk out of their annual physical relieved.
Your doctor scans the results, says “Everything looks normal,” and the appointment is basically over.

But there’s an important piece of context most people never hear:

“Normal” lab ranges are based on the average U.S. population — and the average U.S. population is not very healthy.
High rates of insulin resistance, metabolic dysfunction, inflammation, and poor lipid profiles all get baked directly into those reference ranges.

So when something falls into the “normal” bucket, it often just means “not worse than the average American.”
That’s a very low bar — and it’s not the same as optimal.

And none of this is your doctor’s fault. The entire medical system — from insurance reimbursements to clinical guidelines to diagnostic cutoffs — is built around identifying disease, not optimizing health.

If your goal is prevention, longevity, performance, or simply understanding where your health is headed, the routine panel leaves major blind spots.

Let’s walk through the biggest ones.

🫀 1. Cardiovascular Risk: LDL Alone Doesn’t Tell the Full Story

LDL-C is the number everyone knows — but LDL-C only measures the cholesterol content of LDL particles. It doesn’t tell you how many LDL particles are circulating.

As I covered in my recent cholesterol issue, that distinction matters. The number of particles is what drives plaque formation. This is why ApoB is a far stronger predictor of cardiovascular risk than LDL-C.

Standard panels also miss:

• Lp(a) — genetically driven and highly atherogenic

• LDL-P — particle count

• Particle size & pattern — small dense LDL is more atherogenic

• Remnant cholesterol — a major driver of metabolic dysfunction

Two people can have identical LDL-C but drastically different risk profiles when ApoB, Lp(a), and particle size are considered. A standard panel doesn’t capture any of this nuance.

And because this topic goes even deeper — LDL particle size shifts, discordance between LDL-C and ApoB, triglyceride-driven pattern changes — I’ll be breaking down advanced lipid testing in its own upcoming issue.

🍩 2. Metabolic Health: Glucose is the Last Thing to Change

Most people — and most doctors — look at fasting glucose or A1C (3-month glucose average) to gauge metabolic health.

But glucose is a lagging indicator. It’s one of the last things to move.

The earliest sign of metabolic dysfunction is fasting insulin.

Here’s why that matters:

Insulin’s job is to escort glucose out of your bloodstream and into your cells. When everything is working well, insulin stays low because your cells respond efficiently. Your body only needs a small amount to maintain stable blood sugar.

But when your cells become less responsive — a process called insulin resistance — your pancreas has to pump out more insulin to get the same job done. So insulin rises long before glucose does.

That means you can have:

• a perfect fasting glucose

• a normal A1C

• and still have elevated insulin

…which indicates your metabolism is already under strain even though your standard labs appear normal.

This matters because insulin resistance sits at the center of so many modern conditions:

• stubborn weight gain

• fatigue and energy swings

• fatty liver

• PCOS

• increased cardiovascular risk

• type 2 diabetes

• high triglycerides

• low HDL

• high blood pressure

It’s one of the most important early markers of long-term health — yet it’s almost never included in routine testing.

Fasting insulin gives you a first glimpse into how your metabolism is functioning today, not years from now when glucose finally rises and the problem becomes obvious.

🔥 3. Inflammation: The First Domino in Modern Disease

Chronic inflammation is a major driver of almost every chronic illness.
Yet the standard panel barely looks at it.

Meaningful inflammation markers include:

• hs-CRP

• Homocysteine

• Ferritin (when elevated)

• Uric acid

• Fibrinogen

• ESR

These reveal low-grade inflammation long before symptoms appear — and long before your doctor would have any reason to test for it.

🦋 4. Thyroid & Hormones: More Nuanced Than TSH Alone

Most thyroid screening begins and ends with TSH.
People assume “normal TSH” means “normal thyroid function.”

But TSH is only one hormone in a very complex system.

What’s missing:

• Free T3

• Reverse T3

• TPO antibodies

• Thyroglobulin antibodies

Someone can have a “normal” TSH and still have impaired conversion, low circulating T3, or early autoimmune thyroid activity. None of that shows up on a basic panel.

🥦 5. Nutrient Status: Quiet Deficiences With Real Consequences

This is one of the most overlooked — and easiest to improve — areas of bloodwork.

A few examples:

• Vitamin D: Low levels affect immunity, mood, and bone health. Optimal is often 40–60 ng/mL.

• Omega-3 Index: Below ~4% raises cardiovascular risk; above 8% is protective. Most diets don’t reach this without fatty fish or supplementation.

• B12 with MMA: Standard B12 can look normal while the body is still deficient. MMA shows true cellular status.

• RBC magnesium: More accurate than serum magnesium. Low levels affect sleep, muscle function, and insulin sensitivity.

• Iron status: Ferritin + iron saturation reveal both deficiency and overload.

These are foundational markers — yet they’re absent from almost every annual panel.

📊 What Comprehensive Testing Actually Changes

The benefit of deeper testing isn’t about collecting more numbers.
It’s about getting ahead of problems rather than reacting to them.

With more complete data, you can:

• adjust diet and training before insulin resistance develops

• lower inflammation long before it becomes disease

• confirm whether your habits are improving your biomarkers

• identify genetic cardiovascular risks like high Lp(a)

• optimize recovery, energy, and performance

• catch thyroid or nutrient issues often mislabeled as “stress” or “fatigue”

Standard labs tell you if you’ve crossed a diagnostic boundary.
Comprehensive labs tell you how close you are — and what to do next.

🧠 What You Can Do (Practical, Realistic Options)

1. Ask your doctor for targeted add-ons

Often covered with clinical justification (family history, symptoms, borderline labs):

• ApoB

• Lp(a)

• Fasting insulin

• hs-CRP

• Homocysteine

• Free T3 + TPO antibodies

If insurance denies them, many can be ordered individually for $50–$150 through direct labs.

2. Work with an integrative or functional practitioner

They tend to order deeper labs and interpret results through a prevention lens.

3. Use direct-to-consumer labs (optional)

Comprehensive panels from Function Health cost ~$365 and are best done once or twice per year.

Not required — just an option for full visibility.

💸 If Cost is a Barrier: Focus on the Highest-Yield Markers

You don’t need everything at once. Prioritize:

• Family history of heart disease: ApoB, Lp(a)

• Low energy or weight issues: Fasting insulin, HOMA-IR, hs-CRP

• Thyroid symptoms: Free T3, TPO antibodies

• Fatigue or brain fog: Vitamin D, B12/MMA

Most cost ~$30–$80 individually.
You can build a meaningful panel over time without a huge financial hit.

📌 Big Picture

Your annual blood test is helpful, but it’s not designed for optimization.
It misses insulin, ApoB, inflammation markers, thyroid antibodies, nutrient levels, and more — all of which shape long-term health.

You don’t need hundreds of biomarkers.
You just need the right ones.

When you measure smarter, you act sooner — and you understand where your health is heading, not just where it is today.

Until next week. Stay vital.

-Jordan Slotopolsky

📚 Sources

• Sniderman AD, et al. Apolipoprotein B vs LDL-C as Predictors of Cardiovascular Risk. Journal of the American College of Cardiology.

• Ference BA, et al. Clinical Impact of ApoB, LDL Particle Number, and Lp(a) on Atherosclerotic Disease. European Heart Journal.

• Tsimikas S. Lipoprotein(a): Biology, Pathobiology, and Clinical Implications. Circulation.

• Shulman GI. Mechanisms of Insulin Resistance in Humans. Cell.

• Samuel VT & Shulman GI. The Pathogenesis of Insulin Resistance: Integrating Signaling Pathways and Metabolism. Nature.

• Calder PC. Omega-3 Fatty Acids and Cardiovascular Disease. Prostaglandins, Leukotrienes & Essential Fatty Acids.

• Holick MF. Vitamin D Deficiency and Its Health Consequences. The New England Journal of Medicine.

• Pearce EN. Update in Lipid Management and Thyroid Function. Journal of Clinical Endocrinology & Metabolism.

• Ridker PM. C-Reactive Protein and Cardiovascular Risk. Circulation.

• O’Keefe JH, et al. Insulin Resistance and Systemic Inflammation as Early Predictors of Cardiometabolic Disease. Mayo Clinic Proceedings.