Biomarker Reference

What gets measured.
Why it matters.

Standard lab panels were designed to catch disease. BioMarco tests for optimization — the difference between "nothing is wrong" and "everything is working." Select your mode below to see what each marker means for you.

Cardiovascular Metabolic Genomic

Cardiovascular Risk

Atherosclerosis — the slow buildup of plaque in arterial walls — begins decades before a heart attack or stroke. These markers identify the process early, when intervention is most effective, and reveal risk that standard cholesterol numbers routinely miss.

Essential — order on every first visit
ApoB
The true count of harmful cholesterol particles in your blood — more accurate than standard LDL cholesterol.
Direct enumeration of all atherogenic particles (LDL, VLDL, IDL, Lp(a)) via immunoassay. One ApoB per particle — the definitive particle burden metric.
Essential +

Why it matters

Every atherogenic particle carries exactly one ApoB molecule. Measuring ApoB gives you the precise particle count driving plaque formation — something LDL-C cannot do. Two patients can have identical LDL-C with ApoB values differing by 2x, representing completely different cardiovascular risk.

Target ranges

Standard: <130 mg/dL Optimal: <80 mg/dL

High-risk patients (prior cardiovascular event, diabetes, Lp(a) elevation): target <60 mg/dL

Mechanistic depth

ApoB-containing particles enter the arterial intima based on particle number, not cholesterol content. Small dense LDL particles penetrate more readily and are more susceptible to oxidation. ApoB captures this burden regardless of particle size distribution — making it superior to both LDL-C and LDL-P in most metabolic contexts.

Key interactions

  • APOE4 genotype amplifies ApoB-driven risk significantly
  • Insulin resistance elevates ApoB via increased VLDL secretion
  • Statins reduce ApoB ~30-50% — verify with post-treatment retest
  • Dietary saturated fat raises ApoB in most genotypes
Lp(a)
A genetically determined particle that dramatically raises cardiovascular risk — most people have never had it tested.
Lipoprotein(a) — an LDL-like particle with an additional apolipoprotein(a) tail conferring unique thrombogenic and atherogenic properties independent of lifestyle.
Essential +

Why it matters

Lp(a) is 80-90% genetically determined — diet and exercise have minimal impact. Elevated Lp(a) (above 50 mg/dL or 125 nmol/L) roughly doubles cardiovascular risk independent of LDL-C. It needs to be measured once in a lifetime as a baseline risk assessment. Most standard panels don't include it.

Target ranges

Standard: <75 nmol/L Optimal: <30 nmol/L

Note: units vary (mg/dL vs nmol/L). Always confirm units with your lab.

Mechanistic depth

The apolipoprotein(a) tail structurally resembles plasminogen, competitively inhibiting fibrinolysis and promoting thrombosis. Lp(a) also preferentially accumulates in arterial walls, oxidizes phospholipids, promotes macrophage foam cell formation, and stimulates smooth muscle proliferation — multiple parallel mechanisms of harm.

Key interactions

  • PCSK9 inhibitors reduce Lp(a) ~20-30%
  • High-dose niacin reduces Lp(a) but cardiovascular outcome benefit unclear
  • RNA-based therapies (pelacarsen) in late-stage trials — watch this space
  • Elevated Lp(a) changes ApoB target — push lower
hs-CRP
A measure of silent inflammation in your body — elevated levels signal cardiovascular risk even when cholesterol looks normal.
High-sensitivity C-reactive protein — hepatic acute phase reactant reflecting systemic inflammatory tone, independent cardiovascular risk predictor via the JUPITER trial framework.
Essential +

Why it matters

Atherosclerosis is fundamentally an inflammatory disease. CRP reflects the inflammatory environment that allows LDL particles to oxidize and embed in arterial walls. The JUPITER trial showed that people with normal LDL-C but elevated hs-CRP had dramatically reduced cardiovascular events with statin therapy — proving inflammation matters independent of cholesterol.

Target ranges

Standard: <3.0 mg/L Optimal: <1.0 mg/L

Values above 10 mg/L suggest acute infection or injury — retest when resolved.

Mechanistic depth

CRP is produced by the liver in response to IL-6 signaling from adipose tissue, macrophages, and damaged endothelium. It activates complement, promotes LDL uptake by macrophages, and directly stimulates endothelial expression of adhesion molecules. It is both a marker and a mediator of vascular inflammation.

Key interactions

  • Visceral fat is the primary driver in metabolic syndrome
  • Omega-3 supplementation consistently reduces hs-CRP
  • Sleep deprivation acutely elevates CRP
  • Periodontal disease is a significant underappreciated source
Homocysteine
An amino acid that damages artery walls when elevated — directly linked to your B vitamin status and genetic methylation variants.
Sulfur-containing amino acid at the intersection of the methionine cycle and transsulfuration pathway — elevated levels reflect methylation insufficiency and independently predict cardiovascular and cognitive risk.
Essential +

Why it matters

Elevated homocysteine directly damages endothelial cells, promotes oxidative stress, impairs nitric oxide production, and increases thrombotic risk. It bridges cardiovascular and methylation health — a single marker telling you about vascular risk AND whether your B12, folate, and B6 pathways are functioning. Often elevated silently for years.

Target ranges

Standard: <15 µmol/L Optimal: 6–9 µmol/L

Levels above 12 µmol/L warrant B12, folate, B6 investigation and MTHFR genotyping.

Mechanistic depth

Homocysteine accumulates when the methionine cycle stalls — either from B12/folate deficiency impairing remethylation, or B6 deficiency impairing transsulfuration to cysteine. MTHFR variants (especially C677T homozygous) reduce 5-MTHF availability, slowing remethylation. The result is SAH accumulation which product-inhibits all methyltransferase reactions.

Key interactions

  • MTHFR C677T homozygous raises homocysteine ~25%
  • Metformin depletes B12, raising homocysteine over time
  • 5-MTHF (not folic acid) is the correct supplementation for MTHFR variants
  • Trimethylglycine (TMG) provides an alternative remethylation route via BHMT
Advanced — high yield add-ons
Oxidized LDL
The damaged form of LDL that directly triggers plaque buildup — more dangerous than regular LDL cholesterol.
ox-LDL — LDL particles modified by reactive oxygen species, recognized by scavenger receptors on macrophages initiating foam cell formation and atherogenesis.
Advanced +

Why it matters

Not all LDL is equally dangerous. LDL only becomes atherogenic after oxidation. Oxidized LDL is taken up by macrophages uncontrollably, forming foam cells — the core of arterial plaque. Someone with moderate ApoB but high ox-LDL is in a more pro-atherogenic environment than someone with high ApoB but low oxidative stress.

Target ranges

Optimal: <60 U/L

Reference ranges vary by lab. Trend over time matters as much as absolute value.

Mechanistic depth

Small dense LDL particles are preferentially oxidized due to lower antioxidant content and longer plasma residence time. Myeloperoxidase from activated neutrophils is a primary oxidizing agent in the arterial wall. Elevated ox-LDL predicts cardiovascular events independently of LDL-C and is a direct readout of oxidative stress burden in the vascular compartment.

Key interactions

  • Vitamin E, CoQ10, polyphenols reduce LDL oxidation
  • Smoking dramatically increases ox-LDL
  • Omega-3 index inversely correlates with ox-LDL
  • High fructose intake increases ox-LDL via uric acid and ROS generation
ApoA1
The protein that makes HDL work — measures your protective cholesterol capacity more accurately than HDL-C alone.
Primary structural apolipoprotein of HDL particles — activates LCAT, facilitates ABCA1-mediated cholesterol efflux from macrophages, enabling reverse cholesterol transport.
Advanced +

Why it matters

HDL-C measures cholesterol cargo inside HDL particles. ApoA1 counts the functional particles doing the protective work. The ApoB:ApoA1 ratio captures both sides of the atherogenic equation simultaneously — particle burden vs. protective capacity. Insulin resistance typically suppresses ApoA1 while raising ApoB, creating a doubly dangerous divergence.

Target ranges

Standard: >120 mg/dL (women) >110 mg/dL (men) ApoB:ApoA1 ratio <0.7

Mechanistic depth

ApoA1 activates LCAT which esterifies free cholesterol within HDL, loading the particle for hepatic delivery. It binds ABCA1 on macrophage surfaces to initiate cholesterol efflux from foam cells. HDL particle functionality — not just cholesterol content — determines atheroprotective capacity. ApoA1 is the functional proxy for that capacity.

Key interactions

  • Exercise is the most consistent ApoA1 raiser
  • Insulin resistance suppresses hepatic ApoA1 synthesis
  • Alcohol raises HDL-C but not necessarily ApoA1 functionality
  • PPARα agonists (fibrates) upregulate ApoA1 transcription

Metabolic Optimization

Metabolic dysfunction is upstream of nearly every major chronic disease — cardiovascular disease, type 2 diabetes, Alzheimer's, certain cancers, and more. These markers identify inefficiencies in how your body handles energy, fuel, and cellular regulation long before disease manifests.

Essential — order on every first visit
Fasting Insulin
The single most important metabolic marker most doctors never order — reveals insulin resistance years before blood sugar becomes abnormal.
Fasting serum insulin — the earliest quantifiable signal of insulin resistance, detecting beta-cell compensation before glucose dysregulation becomes apparent on standard panels.
Essential +

Why it matters

Insulin resistance can be present for 10-15 years before fasting glucose rises. During that window the pancreas compensates by producing more insulin to overcome resistance — glucose stays normal, but insulin is elevated. Measuring fasting insulin catches this compensatory state. It's the difference between detecting a problem at year 2 versus year 12.

Target ranges

Standard: <25 µIU/mL Optimal: <6 µIU/mL

Combine with fasting glucose to calculate HOMA-IR for a complete picture.

Mechanistic depth

Insulin resistance begins in skeletal muscle (reduced GLUT4 translocation), progresses to hepatic insulin resistance (failure to suppress gluconeogenesis), and finally manifests as beta-cell exhaustion and glucose elevation. Fasting insulin captures the early muscle/liver resistance phase. Chronically elevated insulin drives VLDL overproduction, suppresses lipolysis, promotes fat storage, and activates mTOR — accelerating aging pathways.

Key interactions

  • HOMA-IR = (fasting glucose × fasting insulin) / 405 — target <1.5
  • Triglyceride:HDL ratio >2.0 is a surrogate when insulin not available
  • Time-restricted eating consistently reduces fasting insulin
  • Resistance training improves insulin sensitivity within 2 weeks
Uric Acid
Far more than a gout marker — elevated uric acid predicts insulin resistance, high blood pressure, and cardiovascular risk, often linked to fructose intake.
End product of purine catabolism via xanthine oxidase — a metabolic readout of fructose load, ATP depletion, and oxidative stress with direct mechanistic links to insulin resistance and endothelial dysfunction.
Essential +

Why it matters

Uric acid above 5.5 mg/dL inhibits endothelial nitric oxide synthase, directly impairing vascular function. It promotes insulin resistance independently, drives hepatic fat accumulation, and is a direct readout of how much fructose the liver is processing. The old gout framing badly undersells this marker's metabolic significance.

Target ranges

Standard: <7.0 mg/dL (men) Optimal: 3.5–5.0 mg/dL

Standard ranges were set to prevent gout — not to optimize metabolic health.

Mechanistic depth

Fructose phosphorylation by fructokinase depletes intracellular ATP unregulated, generating AMP which is catabolized to uric acid. Intracellular uric acid is pro-oxidant and activates a fat-storage switch via ChREBP and lipogenic enzymes. Simultaneously uric acid inhibits eNOS by competing with arginine for tetrahydrobiopterin, reducing NO and raising blood pressure. Richard Johnson's research group has detailed this pathway extensively.

Key interactions

  • Fructose (including fruit juice, HFCS, honey, agave) is primary driver
  • Thiazide diuretics raise uric acid — clinically important for pharmacists
  • Losartan uniquely lowers uric acid among ARBs
  • Low-dose aspirin raises uric acid via competing renal tubular secretion
  • Allopurinol being studied for cardiovascular benefit beyond gout
GGT
A liver enzyme that rises before conventional liver tests — an early warning signal for oxidative stress, detox strain, and metabolic dysfunction.
Gamma-glutamyl transferase — membrane-bound enzyme reflecting hepatic oxidative stress, glutathione turnover, and Phase II detoxification capacity. Rises before ALT in many metabolic conditions.
Essential +

Why it matters

GGT is the most sensitive early marker of hepatic metabolic stress — it rises before ALT or AST in NAFLD, insulin resistance, and environmental toxin burden. Elevated GGT also independently predicts cardiovascular mortality, type 2 diabetes, and all-cause mortality. Most clinicians ignore it until it's dramatically elevated. In precision health it's an early warning system.

Target ranges

Standard: <55 U/L (men) Optimal: <25 U/L

Even within normal range, higher GGT tracks with increasing metabolic risk.

Mechanistic depth

GGT catalyzes the transfer of glutamyl groups from glutathione to peptides and amino acids — a critical step in glutathione recycling and cysteine supply for new GSH synthesis. When oxidative load is high, GGT is upregulated to meet demand, making it a proxy for total oxidative burden. It also reflects CYP450 enzyme induction, tracking xenobiotic detoxification activity in the liver.

Key interactions

  • Alcohol is the most potent GGT inducer — even moderate intake elevates it
  • NAC supplementation supports glutathione and may reduce GGT
  • Environmental toxin exposure (pesticides, heavy metals) raises GGT
  • Elevated GGT + normal ALT often = early NAFLD or metabolic syndrome
Vitamin D (25-OH)
More hormone than vitamin — deficiency is linked to cardiovascular disease, insulin resistance, immune dysfunction, and mood disorders. Nearly universal in northern climates.
25-hydroxyvitamin D — the stable circulating storage form reflecting total body vitamin D status, precursor to the active 1,25(OH)2D3 hormone binding nuclear VDR receptors in virtually every tissue.
Essential +

Why it matters

Vitamin D receptors exist in over 35 tissues. Deficiency impairs insulin secretion, raises parathyroid hormone, increases cardiovascular risk, suppresses immune regulation, and reduces muscle strength. In northern latitudes like New Brunswick deficiency is nearly universal from October through April. Standard labs flag deficiency at <50 nmol/L — optimal for health is considerably higher.

Target ranges

Standard: >50 nmol/L Optimal: 100–150 nmol/L

Supplement with D3 + K2 (MK-7). Retest after 3 months to calibrate dose.

Mechanistic depth

VDR variants (Bsm1, Fok1, Taq1, Cdx2 polymorphisms) significantly affect vitamin D receptor sensitivity — two people with identical serum 25-OH D3 can have dramatically different tissue responses. VDR genotyping explains why some patients need 5000 IU/day to maintain 125 nmol/L while others maintain that on 1000 IU. This is where genomics directly personalizes dosing.

Key interactions

  • VDR variants determine individual dose requirements
  • Magnesium is required for vitamin D activation — deficiency blunts response
  • K2 (MK-7) directs calcium to bone rather than soft tissue
  • Obesity sequesters vitamin D in adipose — higher doses needed
Advanced — deeper metabolic picture
Magnesium (RBC)
Serum magnesium is nearly useless — RBC magnesium measures what's actually inside your cells, where magnesium does its work.
Erythrocyte magnesium — intracellular Mg²⁺ status reflecting true tissue availability. Cofactor in 300+ enzymatic reactions including ATP synthesis, DNA repair, and methylation cycle activity.
Advanced +

Why it matters

Magnesium is a cofactor in over 300 enzymatic reactions — including every ATP-generating reaction, DNA and RNA synthesis, glutathione production, and multiple methylation cycle steps. Serum magnesium is tightly regulated and stays normal until depletion is severe. RBC magnesium reveals the true intracellular status. Deficiency is estimated to affect 50-60% of the population.

Target ranges

Standard: 4.0–6.4 mg/dL (RBC) Optimal: 5.5–6.5 mg/dL (RBC)

Magnesium glycinate or malate preferred for absorption over oxide forms.

Mechanistic depth

ATP exists biologically as Mg-ATP — magnesium chelation is required for ATP stability and recognition by kinases. Mg²⁺ is a cofactor for COMT (catecholamine metabolism), methionine adenosyltransferase (SAM synthesis), and DNA methyltransferases. Low intracellular magnesium impairs methylation capacity independent of B vitamin status — an underappreciated connection.

Key interactions

  • PPIs reduce magnesium absorption — clinically significant on long-term use
  • High-dose vitamin D increases magnesium demand for activation
  • Stress hormones (cortisol, adrenaline) deplete intracellular magnesium
  • COMT variants increase magnesium demand for catecholamine clearance
Omega-3 Index
Measures EPA and DHA in your red blood cells — a direct readout of your cardiovascular and inflammatory protection status from omega-3 fats.
RBC EPA + DHA as % of total fatty acids — a stable 3-month integrated measure of omega-3 tissue status with strong epidemiological links to cardiovascular, cognitive, and inflammatory outcomes.
Advanced +

Why it matters

The omega-3 index predicts sudden cardiac death risk with similar power to LDL-C — yet almost no standard panels include it. A low index (<4%) roughly doubles cardiovascular risk. Target above 8%. Most North Americans sit at 4-5%. It's also the correct way to monitor fish oil supplementation — serum omega-3 fluctuates daily, RBC levels reflect actual tissue incorporation over months.

Target ranges

Average North American: 4–5% Optimal: >8%

Typically requires 2–4g EPA+DHA daily to reach target in most people.

Mechanistic depth

EPA and DHA incorporate into cell membrane phospholipids altering fluidity, receptor function, and eicosanoid production. EPA competes with arachidonic acid for COX and LOX enzymes, shifting the balance from pro-inflammatory prostaglandins and leukotrienes toward resolvins and protectins — specialized pro-resolving mediators that actively terminate inflammation rather than just suppressing it.

Key interactions

  • FADS1/FADS2 variants reduce ALA to EPA/DHA conversion — direct supplementation essential
  • High omega-6 intake competes with omega-3 incorporation
  • Triglyceride form (fish oil) vs ethyl ester affects absorption — triglyceride form superior
  • Vitamin E protects EPA/DHA from peroxidation during supplementation

Genomic Personalization

Genetics doesn't determine destiny — but it does determine your personal biochemical terrain. These variants explain why two people with identical lifestyles can have completely different metabolic and cardiovascular outcomes, and why supplement and dietary strategies must be individualized.

Key variants — interpret with whole genome or SNP data
MTHFR
The most discussed gene in functional health — variants here affect how your body processes folate, impacting methylation, homocysteine, and cardiovascular risk.
Methylenetetrahydrofolate reductase — catalyzes conversion of 5,10-MTHF to 5-MTHF, the primary methyl donor for homocysteine remethylation. C677T and A1298C variants reduce enzyme activity 30-70%.
Genomic +

Why it matters

MTHFR variants are present in roughly 40% of the population in some form. C677T homozygous (TT genotype) reduces enzyme activity by ~70%, impairing the conversion of dietary folate to the active 5-MTHF form. This raises homocysteine, impairs DNA methylation, reduces SAM availability, and changes the correct form of folate supplementation entirely — folic acid can be counterproductive in these patients.

Clinical action

  • C677T heterozygous (CT): moderate impact, monitor homocysteine
  • C677T homozygous (TT): significant — use 5-MTHF not folic acid
  • A1298C: affects BH4 synthesis, impacts neurotransmitters
  • Check homocysteine, B12, RBC folate alongside genotype

Mechanistic depth

5-MTHF is the methyl donor for the MTHFR-driven remethylation of homocysteine to methionine via methionine synthase (MTR). Reduced 5-MTHF availability impairs this reaction, accumulating homocysteine and depleting SAM — the universal methyl donor. SAM depletion impairs DNMT activity (epigenetic methylation), COMT (catecholamine clearance), PNMT (adrenaline synthesis), and dozens of other methyltransferases simultaneously.

Supplement implications

  • Use L-5-MTHF (methylfolate) not folic acid for TT genotype
  • Introduce methylfolate slowly — overstimulation common in COMT variants
  • TMG provides BHMT-pathway backup for homocysteine remethylation
  • Riboflavin (B2) is MTHFR cofactor — often deficient alongside
APOE
The single most important cardiovascular and Alzheimer's risk gene — APOE4 carriers need fundamentally different dietary and lipid targets than everyone else.
Apolipoprotein E — determines lipid particle clearance efficiency via hepatic LDL receptor binding. ε2/ε3/ε4 alleles confer dramatically different cardiovascular and neurodegenerative risk profiles.
Genomic +

Why it matters

APOE4 carriers (roughly 25% of the population) have impaired clearance of ApoB-containing lipid particles and dramatically elevated Alzheimer's risk — APOE4 homozygotes have 8-12x elevated Alzheimer's risk vs APOE3. Dietary saturated fat raises LDL far more in APOE4 carriers. Statin targets should be pushed lower. This single gene changes clinical management more than almost any other variant.

Clinical action by genotype

  • ε3/ε3 (most common): standard targets apply
  • ε3/ε4: lower ApoB target (<70), limit saturated fat
  • ε4/ε4: aggressive ApoB target (<60), Mediterranean diet, omega-3 priority
  • ε2/ε3: lowest cardiovascular risk, but watch for dysbetalipoproteinemia

Mechanistic depth

APOE protein mediates hepatic uptake of IDL and chylomicron remnants via LDL receptor and LRP1 binding. APOE4 has reduced receptor binding affinity relative to APOE3, impairing remnant clearance and prolonging atherogenic particle plasma residence time. In the brain APOE4 impairs amyloid-β clearance, promotes tau phosphorylation, and disrupts synaptic lipid transport — explaining its neurodegenerative effects.

Supplement and diet implications

  • APOE4: reduce saturated fat, prioritize olive oil and omega-3
  • APOE4: DHA prioritization for brain protection (high-dose fish oil)
  • APOE4: berberine may improve LDL receptor upregulation
  • APOE2: paradoxically may need different lipid monitoring — watch triglycerides
COMT
Controls how quickly your body clears stress hormones and estrogen — variants here directly affect your response to methylated supplements and your stress tolerance.
Catechol-O-methyltransferase — degrades catecholamines (dopamine, norepinephrine, epinephrine) and catechol estrogens via SAM-dependent methylation. Val158Met variant reduces enzyme activity ~40%.
Genomic +

Why it matters

COMT is directly relevant to supplement strategy — slow COMT variants (Met/Met) are highly sensitive to methylated supplements. Too much methylfolate or methylcobalamin can flood the methylation system, raise SAM, overstimulate COMT, and produce symptoms of catecholamine excess (anxiety, insomnia, irritability). This is precisely why some patients feel terrible on standard methylation supplements.

Clinical action

  • Val/Val (fast COMT): tolerates methyl donors well, may need more
  • Val/Met (intermediate): start low with methyl donors, titrate slowly
  • Met/Met (slow COMT): high sensitivity — micro-dose methylfolate only
  • Magnesium is COMT cofactor — address deficiency first

Mechanistic depth

COMT transfers a methyl group from SAM to catechol hydroxyl groups, producing methoxylated metabolites for urinary excretion. Val158Met substitution reduces thermostability and Vmax by ~40%. Slow COMT means catecholamines clear more slowly — higher prefrontal dopamine tone (better working memory, but anxiety-prone under stress), slower estrogen detoxification (raising 4-OH estrogen quinone risk), and greater sensitivity to SAM fluctuations from supplementation.

Supplement implications

  • Met/Met: start methylfolate at 100-200 mcg not 1mg+ doses
  • Hydroxocobalamin or adenosylcobalamin preferred over methylcobalamin
  • Phosphatidylcholine provides methylation support without methyl donor load
  • EGCG (green tea) inhibits COMT — caution in Met/Met genotype
VDR
Your vitamin D receptor gene — determines how well your body actually responds to vitamin D, explaining why standard doses work for some and not others.
Vitamin D receptor — nuclear receptor mediating genomic effects of 1,25(OH)2D3 across 35+ tissues. Bsm1, Fok1, Taq1, and Cdx2 polymorphisms alter receptor expression and ligand sensitivity.
Genomic +

Why it matters

Two patients can have identical serum 25-OH vitamin D levels but completely different tissue responses based on VDR genotype. VDR variants explain why some people maintain optimal levels on 1000 IU daily while others need 5000+ IU to see the same response. It personalizes vitamin D dosing from a guess to a targeted strategy — which matters particularly in northern latitudes where baseline deficiency is nearly universal.

Clinical action

  • Fok1 ff genotype: reduced receptor efficiency — higher doses often needed
  • Bsm1 bb: associated with lower bone density response to D3
  • Test serum 25-OH D3 alongside VDR to calibrate individual dose
  • Always pair D3 with K2 (MK-7) and magnesium regardless of genotype

Mechanistic depth

VDR forms a heterodimer with RXR upon 1,25(OH)2D3 binding, translocating to the nucleus and binding vitamin D response elements (VDREs) in promoter regions of target genes. Fok1 polymorphism affects the translation start site, producing a receptor 3 amino acids longer with reduced transcriptional efficiency. Bsm1 affects mRNA stability. These functional differences alter the serum-to-tissue response ratio, making genotyping essential for precise supplementation.

Supplement implications

  • VDR Fok1 ff: target higher serum 25-OH D3 (125-150 nmol/L)
  • Magnesium deficiency blunts VDR signaling independently of genotype
  • K2 MK-7 (not MK-4) preferred for carboxylation of osteocalcin and MGP
  • Retest 25-OH D3 every 6 months to confirm dose adequacy