Longevity Blood Test: the 8 Biomarkers That Actually Matter, and Why 'Normal' Is Not 'Optimal'

Eight markers cover most of what you can get out of a 'longevity blood test': HOMA-IR and fasting insulin, hs-CRP, homocysteine, HbA1c, the Omega-3 Index, ferritin and vitamin D (25-OH-D). Each one has an official lab reference range and a tighter, literature-cited 'optimal' window. The two most causal lipid markers, ApoB and Lp(a), we deliberately do not go deep on here; they get their own guide.

Here is the spine of this guide: 'normal' is not the same as 'optimal'. A lab reference range is defined statistically, as the central 95% of a reference population. It tells you whether you fall into the middle of the distribution, not whether your value carries the lowest risk of disease and death. Those two things often come apart.

Timing matters: glucose, fasting insulin and therefore HOMA-IR need a fast (usually at least 8 hours), because HOMA-IR is explicitly computed from fasting glucose and fasting insulin. ^[1] HbA1c, hs-CRP, homocysteine, the Omega-3 Index, ferritin and 25-OH-D do not. Homocysteine is reported as a fasting value in most reference studies, but a non-fasting sample is acceptable for screening. ^[6]

One point where a lot of results flip: hs-CRP and ferritin are so-called acute-phase reactants, markers that spike with any inflammation. Do not test them within about two to three weeks of an infection, injury, surgery or vaccination, or the result is uninterpretable for its intended purpose. Retest when you are well again. ^[2][12]

And the honest money question up front: we sell neither lab tests nor supplements and earn no commission on panels. The 'optimal' targets below come from guidelines and peer-reviewed research, not from a lab's upsell page. Which of these markers your insurer already covers with an indication, and what you pay out of pocket, we cover in the guide on statutory cover vs. self-pay and in the self-pay longevity guide.

HOMA-IR is a simple calculation from fasting insulin and fasting glucose that estimates how insulin-resistant your metabolism is, meaning how poorly your cells still respond to the hormone insulin. The catch: insulin and HOMA-IR often rise years before fasting glucose or HbA1c move at all. That is the entire point of measuring early. ^[1]

The formula comes from the original HOMA paper by Matthews et al. 1985: HOMA-IR = fasting insulin (micro-units per mL) times fasting glucose (mg/dL) divided by 405. The SI variant is insulin times glucose (mmol/L) divided by 22.5. ^[1]

There is no single globally valid cutoff; the thresholds depend on population, ethnicity, age and lab assay. They usually land somewhere between 2.0 and 2.9. Instead of importing a US or Asian value, use the German data: the population-based Gutenberg Health Study reported a median HOMA-IR of 1.09 (IQR 0.85 to 1.42) in a stringently healthy reference group (n=1,065), with a 97.5th percentile of 2.35. So the statistical upper limit of 'normal' in healthy Germans is around 2.35. ^[3]

The optimal longevity window is best read from the median: a healthy median near 1.0 (German data: 1.09) supports the often-cited 'optimal around below 1.0 to 1.5'. Be honest here: 'below 1.0' is a wellness target, not a clinical cutoff validated against hard endpoints. ^[3] What still makes HOMA-IR serious: in a meta-analysis of non-diabetic adults, a higher HOMA-IR carried a 34% higher all-cause mortality (RR 1.34, 95% CI 1.11 to 1.62) and a roughly 2.1-fold higher cardiovascular mortality (RR 2.11, 95% CI 1.01 to 4.41), highest versus lowest category. ^[4]

Now an important caveat about fasting insulin on its own: the usual lab reference range of about 2.6 to 24.9 micro-units per mL is very wide, and metabolic-health literature cites an optimal window of roughly 2 to 6. But that '2 to 6' is wellness consensus with no backing from outcome trials at all. The meta-analysis above concludes that the mortality association holds for HOMA-IR, not for fasting insulin in isolation. So read '2 to 6' as an aspirational metabolic target, not a proven value. ^[4] Conversion: 1 micro-unit per mL is about 6.0 pmol/L, so 2 to 6 lands at roughly 12 to 36 pmol/L.

HbA1c and HOMA-IR are the metabolic pair you read together: HOMA-IR flags early insulin resistance, while HbA1c shows whether blood sugar has already caught up.

For cardiovascular risk the AHA/CDC consensus says: below 1 mg/L is low risk, 1 to 3 mg/L is average risk and above 3 mg/L is high risk. hs-CRP (high-sensitivity C-reactive protein, an inflammation marker in the blood) measures the same low-grade background inflammation that tracks with atherosclerosis, the slow build-up of plaque in your arteries. ^[2]

hs-CRP measures the same molecule as standard CRP, just with a high-sensitivity assay that can resolve the low range below 10 mg/L, which is exactly the window that matters for heart risk. ^[2]

The longevity-optimal target is below 1 mg/L, which is directly the AHA/CDC 'low risk' band. Some practitioners aim for below 0.5 mg/L. Be precise: below 1 is guideline-backed, below 0.5 is a tighter wellness threshold that is not in the AHA/CDC statement. ^[2]

A value above 10 mg/L almost always means an acute phase, a running infection or inflammation. For heart risk it is then worthless; the consensus advises discarding it and retesting when you are well again. If the value stays high, it is worth searching for a non-cardiac source of inflammation. ^[2]

What else skews hs-CRP: infection, recent injury or surgery, vaccination and active inflammatory disease push it up for days to weeks. Obesity and smoking also raise the baseline, so interpret with care. ^[2]

hs-CRP and ferritin are the acute-phase pair you always read together: if both are high at the same time, inflammation is often behind it rather than the value you actually set out to measure.

The honest answer first: B vitamins reliably lower homocysteine by around 25%, but five large randomized trials and a meta-analysis of 37,485 people show that this lowering did not reliably cut heart attacks. Treat homocysteine as a risk marker and a clue to your B-vitamin status, not as a proven drug target. ^[7][8][11]

Homocysteine is an amino acid that climbs when folate, vitamin B12 or B6 run low or methylation (a central metabolic pathway) stalls. The usual upper lab limit is about 15 micromol per liter (often around 13 for women, 15 for men). Hyperhomocysteinemia is classically defined above 15. ^[6] As a practical optimum, below 7 to 10 is often cited; risk appears to rise continuously from about 6 to 7 upward, well below the lab limit. Here too: 'below 10' is a practitioner target, not a hard guideline cutoff, and the exact value depends on method and population. ^[6]

That B vitamins work is not in dispute: folate, B12 and B6 typically lower homocysteine by about 25%. ^[7][8][11] The honest part is that this lowering did not reliably reduce cardiovascular events. Here are the trials that show it:

• The HOPE-2 trial (NEJM 2006) gave 5,522 high-risk patients folic acid 2.5 mg plus B6 50 mg plus B12 1 mg. Homocysteine fell, but the primary composite of cardiovascular death, heart attack and stroke did not (RR 0.95, 95% CI 0.84 to 1.07). Only stroke showed a modest signal (RR 0.75, 95% CI 0.59 to 0.97). ^[7]
• The NORVIT trial (NEJM 2006) treated 3,749 patients after a heart attack. No benefit (primary RR 1.08, not significant), and the triple-combination arm even trended toward harm (RR 1.22, P=0.05). The authors advised against routine use after a heart attack. ^[8]
• The VITATOPS trial (Lancet Neurol 2010) gave 8,164 patients after stroke or TIA B vitamins. Homocysteine fell, but major vascular events did not drop significantly (RR 0.91, P=0.05, not significant). ^[9]
• The B-PROOF trial (Am J Clin Nutr 2014) gave older people with elevated homocysteine folic acid 400 micrograms plus B12 500 micrograms. No significant effect on fractures, and an unexpected rise in cancer incidence in the treatment arm, a harm signal. The authors could not recommend it. ^[10]
• The Clarke et al. 2010 meta-analysis pooled 8 randomized trials with 37,485 people. Despite a roughly 25% homocysteine reduction, no significant effect on major vascular events (RR 1.01), coronary events (1.03), stroke (0.96), cancer or all-cause mortality (1.02). All null. ^[11]

The reading: the only residual signal is a small, inconsistent stroke effect (and even VITATOPS was not significant here, at P=0.05). Everything else is null, with two harm signals (the NORVIT combination, the B-PROOF cancer signal). Elevated homocysteine is a clue to check your B-vitamin and methylation status, not a promise that 'lowering it' prevents heart attacks. What you actually do is best discussed with your GP.

By the ADA 2024 cutoffs, an HbA1c below 5.7% (below 39 mmol/mol) is normal, 5.7 to 6.4% (39 to 47 mmol/mol) is prediabetes and at or above 6.5% (at or above 48 mmol/mol) counts as diabetes, confirmed on a second test. ^[5] HbA1c (your long-term blood sugar, the share of sugar-coated red blood cells over about three months) is the counterpart to HOMA-IR: it shows whether blood sugar has already caught up.

The WHO confirmed the same diagnostic threshold of 6.5% (48 mmol/mol) for diabetes in 2011, but notes that a value below 6.5 does not rule out diabetes diagnosed via glucose. ^[14] The German DDG/DGKL practice recommendation (2022 update) uses the same anchors: HbA1c at or above 48 mmol/mol (6.5%) and fasting glucose at or above 126 mg/dL (7.0 mmol/L). ^[15]

A quick word on the two units that get muddled in German lab reports: the master formula is NGSP (%) = 0.915 times IFCC + 2.15. That makes 5.7% about 39, 6.0% about 42 and 6.5% about 48 mmol/mol. ^[16]

What is optimal? Values in the lower-normal band carry the lowest risk of progressing to diabetes and the lowest all-cause mortality, which is why below 5.4 to 5.6% is often named as the optimum. That sits below the prediabetes line of 5.7. Be exact: the '5.4' is a wellness optimum; the guideline-defined ceiling of 'normal' is 5.6% (below 5.7). ^[5]

And now the most important trap: HbA1c is distorted by your red-cell turnover. Iron deficiency (with or without anemia) falsely raises the measured HbA1c without any rise in your actual blood sugar. Conversely, non-iron-deficiency anemia, hemolysis (breakdown of red cells), recent blood loss and many hemoglobinopathies lower it. The systematic review by English et al. 2015 (Diabetologia) confirms the direction: iron deficiency upward, non-iron-deficiency anemia downward. So read a borderline-high HbA1c in someone with low ferritin with caution, it may be an artefact. Always read HbA1c alongside ferritin and a blood count. ^[13]

The Omega-3 Index is the share of EPA and DHA (the two marine omega-3 fatty acids) in the membrane of your red blood cells, expressed as a percentage. It is a status marker and reflects about 120 days of intake, a stable weeks-to-months average, unlike the swinging plasma fatty acids. You do not need to fast for it. ^[17]

The original paper by Harris and von Schacky 2004 (Prev Med) proposed the index as a graded, continuous risk factor for death from coronary heart disease: at or above 8% the greatest protection (the desirable target), at 4% or below the least protection (high risk). The often-quoted 'intermediate' band of 4 to 8% is a derived, graded reading of the same curve. So read the index as a continuum, not three rigid boxes. ^[17] As an optimal range, 8 to 12% is usually cited, with below 4% counting as high risk. ^[17][18]

Now the honest nuance on supplementation: the trial evidence for omega-3 capsules is mixed. The REDUCE-IT trial (NEJM 2019) found that high-dose, purified EPA (icosapent ethyl, 4 g per day) cut major cardiovascular events by around 25% (HR 0.75, 95% CI 0.68 to 0.83) in statin-treated patients with high triglycerides. But the mineral-oil placebo raised LDL and hs-CRP, which makes the benefit contested. ^[19] The STRENGTH trial (JAMA 2020) with an EPA-plus-DHA formulation found no cardiovascular benefit at all (HR 0.99) and was stopped early for futility. ^[20] The VITAL trial (NEJM 2019) found that 1 g of marine omega-3 per day did not lower the primary cardiovascular and cancer endpoints in a general, largely-replete population. ^[21]

The consequence: the index measures your status cleanly, but raising it with capsules has not consistently led to fewer events. The first lever is diet, meaning oily sea fish. For how to make the effect of a fish-rich meal on your own metabolism visible, the glucose and blood sugar guide shows the idea using glucose.

Ferritin reflects your iron stores, but it is also an acute-phase reactant: an infection or inflammation falsely raises it, independent of your actual iron status. So always read ferritin alongside hs-CRP. ^[12]

The WHO 2020 thresholds for apparently healthy people: iron deficiency from a ferritin below 12 micrograms per liter (children under 5) and below 15 (people 5 and older, including non-pregnant women and adults). ^[12] If an infection or inflammation is present at the same time, the higher cutoffs apply: below 30 (children under 5) and below 70 (people 5 and older). ^[12] Clinically, many use below 30 micrograms per liter as the practical deficiency cutoff in adults, which is more sensitive than below 15. Below 15 is highly specific but insensitive. (Note: ng/mL and micrograms per liter are numerically identical for ferritin, 1 ng/mL = 1 microgram per liter.) ^[12]

This is exactly where the headline example of 'normal is not optimal' sits: functional complaints like fatigue, restless legs and hair loss can occur at 'low-normal' ferritin (about 15 to 50 micrograms per liter), even without anemia, in the middle of the lab normal range. ^[12] But be honest about the numbers: the specific symptom thresholds (such as the often-cited below 50 to 75 for restless legs) come from practitioner literature, not from a guideline. Treat them as a clue, not a settled cutoff.

And more is not better: ferritin above 150 (women) or above 200 (men) in apparently healthy people, or above 500 in non-healthy individuals, can flag iron overload or disease. ^[12] Whether a low or a high value needs to be worked up in your case belongs in the hands of your GP.

By the standard Endocrine Society 2011 thresholds, a 25-OH-D (the storage form of vitamin D in the blood) below 20 ng/mL (below 50 nmol/L) means deficiency, 20 to below 30 ng/mL (50 to below 75 nmol/L) means insufficiency and at or above 30 ng/mL (at or above 75 nmol/L) is sufficient. The US Institute of Medicine, by contrast, considered 20 ng/mL (50 nmol/L) already enough for bone health. ^[22]

The German line from RKI and DGE: below 30 nmol/L (below 12 ng/mL) is deficient, 30 to below 50 nmol/L (12 to below 20 ng/mL) is suboptimal and at or above 50 nmol/L (at or above 20 ng/mL) is adequate for bone health. About 60% of German adults sit below 50 nmol/L. The RKI explicitly aligns with the IOM bone-health target of 50 nmol/L, not with higher 'optimum' claims. ^[24] Many longevity practitioners aim for 30 to 50 ng/mL (75 to 125 nmol/L). Be clear: that is a higher target than the population-level bone adequacy of 20 ng/mL and is not a longevity value validated against endpoints. ^[22]

And now the most important honesty: the VITAL trial (NEJM 2019) gave 25,871 largely-replete US adults vitamin D3 at 2000 IU per day for about five years. It lowered neither cancer (HR 0.96) nor major cardiovascular events (HR 0.97) versus placebo. ^[21] Consequently the 2024 Endocrine Society guideline recommends against routine 25-OH-D screening in healthy adults and frames supplementation for select groups (such as 75 and older, pregnancy, prediabetes, under-18s) as empiric, meaning without prior testing. ^[23]

The reading: correct a genuine deficiency (bone, fall risk), but do not sell vitamin D as a heart or cancer prevention drug for people who are already replete. And more is not better here either: a 25-OH-D above 150 ng/mL (above 375 nmol/L) is the hallmark of vitamin D intoxication with hypercalcemia, and the Endocrine Society set the safety upper limit at around 100 ng/mL. ^[25] If you want to supplement vitamin D, discuss dose and monitoring with your doctor. For how epigenetic age tests differ from single biomarkers like these, see the guide on epigenetic age tests.

Here is everything in one table: on the left the standard lab reference range (in conventional and SI units), in the middle the tighter 'optimal' longevity window cited in the literature, on the right the sources. Read the optimal column as aspirational, not as a diagnosis: several of these tighter targets are practitioner or wellness goals, not guideline cutoffs validated against hard endpoints.

Marker	Standard / lab reference (conventional and SI)	Optimal longevity target	Sources
HOMA-IR	healthy 97.5th pct up to 2.35 (unitless); IR cutoffs ~2.0 to 2.9 (population-dependent)	~below 1.0 to 1.5 (healthy median ~1.09)	[1][3][4]
Fasting insulin	~2.6 to 24.9 micro-U/mL; ~16 to 150 pmol/L	~2 to 6 micro-U/mL; ~12 to 36 pmol/L (wellness target, NO outcome-trial backing, the mortality signal is for HOMA-IR)	wellness consensus
hs-CRP	below 1 low / 1 to 3 average / above 3 high mg/L; above 10 = acute	below 1 mg/L (guideline); some aim for below 0.5 (not guideline)	[2]
Homocysteine	upper limit ~15 micromol/L (~13 women / 15 men)	below 7 to 10 micromol/L (practitioner target; lowering NOT proven as heart protection)	[6][7][11]
HbA1c	normal below 5.7% (below 39 mmol/mol); preDM 5.7 to 6.4 (39 to 47); DM at or above 6.5 (at or above 48)	below 5.4 to 5.6% (below 5.4 is a wellness target)	[5][14][16]
Omega-3 Index	below 4% high risk / 4 to 8% intermediate / at or above 8% desirable (continuum)	8 to 12% (RBC EPA+DHA)	[17][18]
Ferritin	deficiency below 15 micrograms/L (5 and older, healthy); below 30/70 with inflammation; overload above 150 women / 200 men	~30 to ~150 micrograms/L comfort window (symptoms possible below 50, practitioner level); 1 ng/mL = 1 microgram/L	[12]
Vitamin D (25-OH-D)	deficient below 20 ng/mL (below 50 nmol/L); insufficient 20 to 30 (50 to 75); sufficient at or above 30 (ES) / at or above 20 (IOM/RKI)	30 to 50 ng/mL; 75 to 125 nmol/L (practitioner; toxicity above 150 ng/mL)	[22][23][24][25]
ApoB / Lp(a)	in the sister lipid guide	see cross-link	(sibling)

Two things to take away. First: the two most causal lipid markers are missing here on purpose. ApoB and Lp(a) we cover in the sister guide, because they deserve their own depth. Second: 'normal' is the start, not the goal, but do not overclaim the optimum. Where the evidence is thin (fasting insulin, hs-CRP below 0.5, HbA1c below 5.4, ferritin symptom thresholds), we flagged it openly above. And we still sell neither tests nor supplements: these targets come from the literature, not from a product catalogue.