Last year I got my annual physical. Doctor said my bloodwork looked "perfect." Total cholesterol 195, fasting glucose 94, liver enzymes normal. He shook my hand and told me to keep doing what I was doing.

Three weeks later, I ran my own panel through a direct-to-consumer lab. My ApoB was 118 mg/dL — firmly in the range that Peter Attia would call unacceptable cardiovascular risk. My fasting insulin was 11.2 µIU/mL, more than double what longevity physicians consider optimal. My homocysteine was elevated. My vitamin D was 28 ng/mL, which my doctor would have called "normal" but which the Endocrine Society considers insufficient.

Everything was "fine." Nothing was optimal.

And the gap between those two words might be the most dangerous thing in modern preventive medicine.

The Problem With "Normal"

Here is what your doctor does not tell you — and what, frankly, most of them do not know.

The reference ranges on your lab results are not health targets. They are statistical distributions derived from the population that uses that lab. The lab takes a sample of people who get blood drawn at that facility, calculates the 2.5th to 97.5th percentile, and calls that the "normal" range. If the average American is overweight, pre-diabetic, and inflamed — and roughly 88% of American adults are metabolically unhealthy according to a 2022 study from the University of North Carolina published in the Journal of the American College of Cardiology — then "normal" just means you look like everyone else.

It does not mean you are healthy. It means you are average.

And average, in this country, is quietly dying.

A fasting glucose of 99 mg/dL is "normal." It is also one point below the pre-diabetic threshold. Your doctor will not flag it. A total cholesterol of 200 is "borderline." But total cholesterol is such a crude metric that roughly half of all heart attacks occur in people with "normal" cholesterol levels. The Framingham Heart Study demonstrated this decades ago, and yet total cholesterol remains the centerpiece of standard lipid panels.

This is the core problem. Standard bloodwork was designed to detect disease after it arrives, not to prevent it.

Longevity medicine flips that model entirely. It asks a different question: what do the earliest measurable signals of metabolic decline look like, and can we intervene years or decades before a diagnosis? Peter Attia calls this "Medicine 3.0" — shifting from reactive sick care to proactive health optimization. The tools already exist. The markers are available. Your doctor just is not ordering them.

The 15 Markers That Actually Matter

I am going to walk through these in the order I think about them, which is roughly the order of how badly standard medicine undervalues them.

ApoB is, in my opinion, the single most important blood marker most people have never heard of. Apolipoprotein B is the structural protein on every atherogenic lipoprotein particle — every LDL, VLDL, IDL, and Lp(a) particle carries exactly one ApoB molecule. That means ApoB gives you a direct particle count of every lipoprotein capable of driving atherosclerosis. Standard LDL cholesterol measures the cholesterol content inside those particles, which is an indirect and often misleading proxy.

Two people can have identical LDL-C numbers and wildly different ApoB levels — and it is the ApoB that predicts cardiovascular events. A 2021 meta-analysis in JAMA Cardiology by Sniderman et al. confirmed that ApoB is superior to LDL-C for predicting cardiovascular risk across every subgroup studied. Your lab's "normal" range is below 130 mg/dL. Peter Attia targets below 60 mg/dL for his patients.

That is not a small gap. That is a canyon.

Lp(a) — lipoprotein(a) — is the marker I wish someone had told me about ten years earlier. It is almost entirely genetically determined, it is an independent and causal risk factor for cardiovascular disease, and roughly 20% of the global population has elevated levels. A 2022 consensus statement from the European Atherosclerosis Society called Lp(a) a "major inherited risk factor for atherosclerotic cardiovascular disease."

The kicker: most doctors never order it, and there is no approved drug to lower it yet (though Novartis's pelacarsen is in Phase 3 trials). You only need to test it once in your life. If it is high, it changes your entire risk calculus and makes aggressive ApoB reduction even more critical.

Fasting insulin might be the most underappreciated marker in all of metabolic health. Your doctor checks fasting glucose. Maybe HbA1c if you are lucky. But fasting insulin rises years — sometimes a full decade — before glucose goes out of range. By the time your fasting glucose hits 100, your pancreas has been overproducing insulin to compensate for insulin resistance that has been building silently.

A 2005 paper by Reaven in the Annual Review of Nutrition laid this out clearly: hyperinsulinemia precedes and predicts type 2 diabetes, cardiovascular disease, and all-cause mortality. Optimal fasting insulin is below 5 µIU/mL. The lab range goes up to 25. Think about that.

HOMA-IR is a calculated ratio using your fasting insulin and fasting glucose — it quantifies insulin resistance with more precision than either number alone. The formula is simple: (fasting insulin x fasting glucose) / 405. Optimal is below 1.0. Most longevity physicians get nervous above 1.5. The standard lab will not calculate this for you, but it takes ten seconds with a calculator once you have both numbers.

HbA1c measures your average blood sugar over roughly 90 days by looking at the percentage of hemoglobin molecules that have glucose attached to them. Standard "normal" is below 5.7%. The American Diabetes Association considers 5.7-6.4% "pre-diabetic." But longevity physicians like Attia aim for below 5.0%, because a 2019 study in the BMJ found that cardiovascular risk begins increasing at HbA1c levels well below the diabetic threshold.

The disease is a continuum. The cutoffs are arbitrary.

High-sensitivity C-reactive protein — hsCRP — measures systemic inflammation, and chronic low-grade inflammation is arguably the connective tissue linking every major age-related disease. Cancer, cardiovascular disease, Alzheimer's, type 2 diabetes — all have inflammation as a core driver.

The CANTOS trial in 2017, published in the New England Journal of Medicine, proved this definitively by showing that reducing inflammation with canakinumab (an IL-1beta inhibitor) reduced cardiovascular events independent of lipid levels. Optimal hsCRP is below 0.5 mg/L. The standard "normal" cutoff is below 3.0 mg/L. That is a six-fold difference between what your doctor accepts and what the science suggests you should target.

Homocysteine is an amino acid intermediate in the methylation cycle, and elevated levels are associated with cardiovascular disease, cognitive decline, and increased fracture risk. A 2002 meta-analysis in JAMA by the Homocysteine Studies Collaboration found that a 25% reduction in homocysteine levels was associated with an 11% lower risk of ischemic heart disease and a 19% lower risk of stroke.

Optimal is below 7 µmol/L. Most labs flag it only above 15. The fix is often straightforward — methylated B vitamins (methylfolate, methylcobalamin, P5P) address it in most people.

Ferritin is a tricky one. It is a marker of iron storage, but it is also an acute-phase reactant that rises with inflammation. Low ferritin (below 30 ng/mL in women, below 50 in men) suggests iron deficiency and is shockingly common — a 2022 Lancet Haematology paper estimated that iron deficiency affects nearly 30% of the global population.

But high ferritin is equally concerning. Levels above 200-300 ng/mL in men can indicate iron overload, which drives oxidative stress. The sweet spot is 40-100 ng/mL for most people, and you need to interpret it alongside inflammation markers.

Vitamin D — specifically 25-hydroxyvitamin D — is tested more often than most markers on this list, and still most people are insufficient. The lab "normal" starts at 30 ng/mL. The Endocrine Society's 2024 updated guidelines recommend 40-60 ng/mL for optimal function, and some longevity physicians push for 50-70 ng/mL.

A 2023 umbrella review in the BMJ covering 74 meta-analyses found that vitamin D sufficiency was associated with reduced all-cause mortality, reduced cancer mortality, and improved immune function. I keep mine between 55 and 65. My wife thinks I am unreasonably obsessed with this number, and she might be right, but the data supports the obsession.

The omega-3 index measures the percentage of EPA and DHA in your red blood cell membranes. If you read Issue #1, you know I think this is foundational. An index below 4% is associated with a significantly higher risk of sudden cardiac death. The target is 8-12%. The Harris and Von Schacky 2004 paper in Preventive Medicine proposed the omega-3 index as a novel risk factor for death from coronary heart disease, and subsequent research has validated it repeatedly.

Most Americans sit around 4-5%. That number alone should tell you something about the state of our food supply. You can check yours at home with an OmegaQuant test kit available on Amazon — it is the same lab used in most of the research studies.

Your thyroid panel — and I mean the full panel, not just TSH — is another area where standard medicine falls short. Most doctors order TSH alone. If it is between 0.5 and 4.5 mIU/L, they say you are fine. But TSH is a pituitary hormone, not a thyroid hormone. You need free T3, free T4, reverse T3, and thyroid antibodies (TPO and thyroglobulin) to understand what is actually happening at the tissue level.

Subclinical hypothyroidism — where TSH is "normal-high" but free T3 is suboptimal — is rampant and causes fatigue, weight gain, brain fog, and depression that gets treated with SSRIs instead of thyroid optimization.

Optimal TSH is 1.0-2.0 mIU/L. That is very different from the 0.5-4.5 reference range.

Testosterone and estradiol matter for both men and women, not just for vitality and body composition, but for cardiovascular health, bone density, and cognitive function. The Endocrine Society defines low testosterone in men as below 300 ng/dL, but symptoms often begin at levels well above that cutoff. Optimal total testosterone for men is typically 600-900 ng/dL with free testosterone in the upper quartile of the reference range.

Estradiol in men is often ignored but matters — too low increases cardiovascular and bone risk, too high drives symptoms and potentially prostate issues. Women should track estradiol, progesterone, and testosterone across their cycle, especially as they approach perimenopause.

DHEA-S — dehydroepiandrosterone sulfate — is the most abundant circulating steroid hormone and a precursor to both testosterone and estrogen. It peaks in your mid-20s and declines steadily with age. Low DHEA-S is associated with increased all-cause mortality, cardiovascular disease, and cognitive decline in multiple prospective studies, including a 2010 analysis in the Journal of the American Geriatrics Society.

Optimal levels are mid-range for your age group, and tracking the trend over time matters more than any single reading.

IGF-1 — insulin-like growth factor 1 — is one of the more nuanced markers on this list. It is a key mediator of growth hormone's effects, and it sits at an uncomfortable intersection: higher levels support muscle growth, tissue repair, and recovery, but chronically elevated IGF-1 is associated with increased cancer risk in multiple epidemiological studies.

The 2012 meta-analysis by Renehan et al. in The Lancet Oncology found positive associations between IGF-1 and colorectal, prostate, and premenopausal breast cancer.

The goal is not to maximize IGF-1 — it is to keep it in a moderate range appropriate for your age, activity level, and family cancer history. This is one marker where context matters enormously, and where the longevity community itself is still debating the optimal target.

Finally, the ALT/AST ratio — your liver enzymes. Standard panels check these and flag them only when they are elevated above 40-50 U/L. But emerging research, including a 2021 study in Hepatology Communications, suggests that ALT above 25 U/L in men and 22 U/L in women may already indicate hepatic insulin resistance and early non-alcoholic fatty liver disease.

Your doctor sees 38 and says "normal." A longevity physician sees 38 and starts investigating.

The AST/ALT ratio also matters — when AST exceeds ALT, it can suggest alcohol-related liver damage, muscle damage, or more advanced liver fibrosis. Ideal ALT is below 20-25 U/L. Given that non-alcoholic fatty liver disease now affects roughly 25% of the global population and is tightly linked to insulin resistance, this is not a minor marker. It is a metabolic early warning system hiding in plain sight on the panel your doctor already orders.

How to Actually Get These Tests

Your primary care doctor will order some of these if you ask. Others — ApoB, fasting insulin, Lp(a), a full thyroid panel, DHEA-S, the omega-3 index — you may have to push for, or you may need to go direct-to-consumer. Companies like Marek Health, InsideTracker, and Owens offer comprehensive panels that cover most of this list. Quest and Labcorp both allow self-ordering in most states.

Expect to pay $200-500 out of pocket for a comprehensive longevity panel. That sounds expensive until you compare it to the cost of a cardiac catheterization ($30,000+), a lifetime of metformin, or the immeasurable cost of a preventable heart attack at 55.

How often should you test? If you are establishing a baseline or actively optimizing, quarterly. If you are in maintenance mode and your numbers are where you want them, every six months to annually. Lp(a) only needs to be checked once. Everything else benefits from trend data — a single snapshot tells you far less than the trajectory over time.

My Stance

I think the standard annual physical blood panel is borderline negligent for anyone who cares about longevity.

Not because doctors are bad at their jobs — most are doing exactly what they were trained to do. But the system they operate in was designed to manage acute disease, not optimize healthspan. Insurance reimburses for treating heart disease. It does not reimburse for preventing it twenty years early. The reference ranges were built to catch pathology, not to prevent it. And the markers they choose to check are a relic of 1990s medicine that has not kept pace with the last two decades of cardiovascular and metabolic research.

If there is one thing I want you to take from this issue, it is this: get your ApoB tested. Tomorrow. It is cheap, it is available, and it is the single best predictor of your cardiovascular future that most people have never measured. If your doctor will not order it, order it yourself. This is not a "nice to have" marker — Sniderman, Thanassoulis, and dozens of other researchers have argued for years that ApoB should replace LDL-C as the primary lipid metric. The evidence is overwhelming.

And while you are at it, add fasting insulin. Because a fasting glucose of 95 with a fasting insulin of 15 is not "normal" — it is a pancreas screaming that insulin resistance is already underway, and your glucose is only being held in range because your body is compensating. Hard.

That compensation fails eventually.

Always.

For those of you who are ready to track these markers and want a solid foundation of third-party tested supplements to address common deficiencies — D3, omega-3, B vitamins, magnesium — Thorne is what I personally use. NSF Certified for Sport, no proprietary blends, published COAs. I have tried a lot of brands. They are consistently the ones I come back to.

So here is my question for you: when was the last time you actually looked at your bloodwork — not just the "normal/abnormal" flags, but the actual numbers? And did your doctor check a single marker on this list that was not glucose, cholesterol, or a basic metabolic panel?

I would bet most of you already know the answer. And that is exactly the problem.

Disclosure: Product links above may be affiliate links. I only recommend products I would personally use and would recommend regardless of compensation.

References

1. Araújo J, Cai J, Stevens J. "Prevalence of Optimal Metabolic Health in American Adults." Journal of the American College of Cardiology. 2022. 2. Sniderman AD, et al. "Apolipoprotein B vs Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol as the Primary Measure of Apolipoprotein B Lipoprotein-Related Risk." JAMA Cardiology. 2021;6(12):1422-1430. 3. Kronenberg F, et al. "Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement." European Heart Journal. 2022;43(39):3925-3946. 4. Reaven GM. "The insulin resistance syndrome: definition and dietary approaches to treatment." Annual Review of Nutrition. 2005;25:391-406. 5. Selvin E, et al. "Glycated hemoglobin and the risk of cardiovascular disease and death." BMJ. 2019. 6. Ridker PM, et al. "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS)." New England Journal of Medicine. 2017;377(12):1119-1131. 7. Homocysteine Studies Collaboration. "Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis." JAMA. 2002;288(16):2015-2022. 8. Pasricha SR, et al. "Iron deficiency." The Lancet Haematology. 2022. 9. Autier P, et al. "Vitamin D supplementation and health outcomes: umbrella review of systematic reviews and meta-analyses." BMJ. 2023. 10. Harris WS, Von Schacky C. "The Omega-3 Index: a new risk factor for death from coronary heart disease?" Preventive Medicine. 2004;39(1):212-220. 11. Cappola AR, et al. "Hormones and Aging: An Endocrine Society Scientific Statement." Journal of the American Geriatrics Society. 2010. 12. Renehan AG, et al. "Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk." The Lancet Oncology. 2012. 13. Kwo PY, Cohen SM, Lim JK. "ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries." Hepatology Communications. 2021.