ADMA & SDMA
Naturally occurring inhibitors of nitric oxide synthase. ADMA blocks nitric oxide production, impairing blood vessel dilation; SDMA is primarily a kidney function marker.
A direct window into endothelial function — how well your blood vessels dilate. Relevant to blood pressure, erectile function and early cardiovascular disease, often before structural damage appears.
The assay disagrees with itself, and that is the whole answer. Pooled across 42 HPLC studies the healthy mean was 0.71 µmol/L (range 0.34–1.10); across 24 ELISA studies it was 0.57 µmol/L (0.25–0.92). Heterogeneity was I² = 99.96%, and the authors conclude the methods can result in almost incomparable results. Until a reference measurement procedure exists, an ADMA number means something only against other results from the same laboratory and the same method — which is exactly what an 'optimal range' is supposed to free you from. Ask which method your lab used; if the report does not say, the number is not interpretable.
Check a ADMA & SDMA result against this range →
What ADMA & SDMA actually measures — the analyte, and the assay
ADMA and SDMA are structural isomers with identical mass, and telling them apart is the entire analytical task. Asymmetric dimethylarginine carries both methyl groups on one guanidino nitrogen and inhibits nitric oxide synthase; symmetric dimethylarginine carries one on each and does not. They have the same molecular formula, so mass alone cannot separate them — only chromatography can El-Khoury 2012.
That is why the ELISA and the mass-spectrometry literature disagree so completely. Comparison of an HPLC method with a commercial ELISA for ADMA in human serum found the two do not agree Valtonen 2005, and the analytical approaches available were reviewed specifically because of the divergence Schwedhelm 2005. In chronic kidney disease — where SDMA accumulates because it is cleared renally — UPLC-MS/MS and ELISA were compared directly, and the exchange that followed in the literature is itself the citation Boelaert 2016.
The reference method is stable-isotope-dilution LC-MS/MS with chromatographic resolution of the two isomers, ideally without derivatization, and its reference ranges were established as part of the method rather than borrowed El-Khoury 2012.
Concentrations are in the region of 0.4–0.7 µmol/L for ADMA, which is roughly a hundredth of free arginine on the same sample — another reason the chromatography has to work.
ADMA & SDMA: what changes the blood, and what only changes the reading
What changes the dimethylarginines in you:
- Protein turnover. ADMA and SDMA are not synthesized as free amino acids: arginine residues are methylated while inside proteins by protein arginine methyltransferases, and the dimethylarginines are released only when those proteins are degraded. Circulating ADMA is therefore a read-out on proteolysis.
- Kidney function, but differently for the two. SDMA is cleared almost entirely by the kidney and rises steeply as eGFR falls; ADMA is mostly metabolized by dimethylarginine dimethylaminohydrolase in liver and kidney tissue and rises far less Boelaert 2016. A panel reporting both is reporting two different physiologies.
- Oxidative stress, which inhibits that metabolizing enzyme and raises ADMA.
- Liver disease, through the same enzyme.
- Insulin resistance, hyperhomocysteinemia and smoking, each modestly and by overlapping routes.
What changes only the reading:
- ELISA versus chromatography. This is the dominant artifact and it is not small Valtonen 2005 Boelaert 2016.
- Failure to resolve SDMA from ADMA, which inflates the ADMA result in exactly the population — reduced kidney function — where the marker is most often ordered El-Khoury 2012.
- Hemolysis, since red cells contain arginine methyltransferase activity and their contents enter the plasma Koseoglu 2011.
- Sample storage, over which free dimethylarginines can be released by continued proteolysis.
- Which reference range the laboratory printed. A systematic review and meta-analysis was written on precisely this: the issue of the plasma ADMA reference range, because published ranges differ enough to change whether a person is called abnormal Nemeth 2017.
Reference interval or decision threshold — which kind of number ADMA & SDMA is
The reference range is contested, and there is a paper whose title says so. A systematic review and meta-analysis of plasma ADMA reference ranges found the published intervals inconsistent enough that the concept of a single reference range is questionable Nemeth 2017. Almost no other marker on this site has that written about it explicitly.
The inconsistency is mostly methodological, not biological. Ranges derived on ELISA and on mass spectrometry differ systematically, so pooling them produces a range wider than either Valtonen 2005 Schwedhelm 2005.
There is no decision threshold anywhere. No guideline acts on an ADMA value, no drug is titrated to it, and no trial has randomized anyone by it. Every published association is a cohort finding.
The SDMA-to-ADMA ratio and the arginine-to-ADMA ratio are computed, not measured, and inherit the imprecision of both parents Knight 2020.
How you would know your ADMA & SDMA was wrong — and when to redraw
Three months, because the pool turns over with body protein. Free ADMA has a short plasma residence, but the flux into it is set by the rate at which methylated proteins are degraded, which is a whole-body process measured in weeks.
Fasting, and on the same platform. The single most useful condition is that both samples were run by the same method, because the method difference exceeds most real changes Valtonen 2005.
Conditions that must match: the same laboratory and method; a non-hemolyzed sample Koseoglu 2011; stable kidney function; and the same fasting state.
What would have to change for the second number to mean something:
- ADMA high? Before anything else, check creatinine and eGFR inside the CMP, and read the SDMA on the same report. If SDMA is high and ADMA only slightly so, the finding is renal Boelaert 2016.
- Both high with normal kidney function? Ask which method was used. An ELISA result that cannot be reproduced by chromatography is the expected outcome, not a puzzle Valtonen 2005.
- Looking for endothelial function itself? Flow-mediated dilation measures it directly, and no plasma concentration substitutes for it.
- Chasing vascular risk? ApoB and Lp(a) have thresholds, treatments and outcome trials behind them. ADMA has none.
- Homocysteine also raised? The two travel together through shared methylation and oxidative-stress pathways, and homocysteine is the better-characterized of the pair.
What ADMA & SDMA cannot tell you
It cannot measure nitric oxide availability. ADMA competes with arginine at nitric oxide synthase, but intracellular concentrations at the enzyme are not plasma concentrations, and the intracellular arginine pool is far larger than plasma suggests.
It cannot be compared across methods, and the method is frequently absent from the report Schwedhelm 2005 Nemeth 2017.
ADMA cannot be interpreted without kidney function, and SDMA essentially cannot be interpreted as anything else Boelaert 2016.
It cannot be lowered by any established intervention. There is no drug, supplement or diet with a demonstrated ADMA-lowering effect that has then been shown to change an outcome.
The wrong inference readers actually draw is that ADMA is a measurable endothelial health score. It is a research analyte with a disputed reference range, no threshold, no treatment and a between-method disagreement larger than the differences people try to interpret Nemeth 2017 Valtonen 2005.
Sources read for these sections
- Nemeth B, et al. The issue of plasma asymmetric dimethylarginine reference range - A systematic review and meta-analysis. PLoS One 2017 · PMID 28494019
- Valtonen P, et al. Comparison of HPLC method and commercial ELISA assay for asymmetric dimethylarginine (ADMA) determination in human serum. Journal of Chromatography B 2005 · PMID 16214427
- Schwedhelm E. Quantification of ADMA: analytical approaches. Vascular Medicine 2005 · PMID 16444874
- El-Khoury JM, et al. A simple and fast liquid chromatography-tandem mass spectrometry method for measurement of underivatized L-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Analytical and Bioanalytical Chemistry 2012 · PMID 22124751
- Boelaert J, et al. Response to Tsikas et al. Comments on Boelaert et al. Determination of Asymmetric and Symmetric Dimethylarginine in Serum from Patients with Chronic Kidney Disease: UPLC-MS/MS versus ELISA. Toxins 2016, 8, 149. Toxins 2016 · PMID 27801792
- Knight V, et al. Variability in the Laboratory Measurement of Cytokines. Archives of Pathology and Laboratory Medicine 2020 · PMID 32401053
Where to start with ADMA & SDMA
In this order. Start at the supplement and you learn nothing, because you never established the number was real.
You have the range, where it came from and the first two moves. Inside is the rest of the five-pathway protocol — supplements, hormones, peptides — the order to run them in, and what to change when the number will not move.
Get the full protocol — $10/mo →📚 Böger RH, J Nutr 2004 — ADMA as a cardiovascular risk marker.
🩸 Test your ADMA & SDMA
Order directly through Marek Diagnostics — no doctor's visit needed, drawn at any Quest location in the US. Code CAMERON applies 10% off automatically.
Order this test — 10% off → Browse all 103 markers →What ADMA & SDMA is usually tested alongside
One marker is a data point. These panels add the markers that make ADMA & SDMA interpretable, name why each is on the list, and load the set into your cart at 10% off.
includes this + 8 more markers — Family history of clots, stroke or early heart attack; on testosterone or estrogen; long-haul travel; or a standard lipid panel that looked fine and you don't believe it.
What people use ADMA & SDMA to decide
Nobody orders a test for its own sake. ADMA & SDMA is on the test list for these pathways — each one links to what the pathway claims, and what its test list is read for before you spend anything on it.
ADMA inhibits nitric oxide synthase directly, so it is the most specific endothelial marker available. Dysfunction here precedes visible plaque by decades.
The highest-yield test on this whole page. Ferritin under 30 impairs endurance well before hemoglobin drops, so the full blood count reads normal while performance falls off a cliff — and it is disproportionately common in women and plant-based athletes.
Erectile dysfunction is an early cardiovascular symptom — the penile arteries are narrower than the coronaries and narrow first, typically three to five years ahead. Treat this as a heart finding, because it is one.
Would you feel it? Symptoms ADMA & SDMA helps explain
People search for how they feel, not for a marker. These are the complaints where this one is worth checking, and whether it is first-line or a follow-up.
Why your ADMA & SDMA might be wrong
Most abnormal results are interference, not disease. Check these before you change anything. Each says whether the number is wrong (repeat it), badly timed (redraw it), or real with a cause.
Rises after eating, so a non-fasted draw measures your breakfast rather than your baseline.
Draw fasted, 10–12 hours, water only.
ADMA is cleared renally, so impaired kidney function raises it substantially without any additional endothelial problem.
Read against cystatin C eGFR.
What ADMA & SDMA means in combination
One marker tells you a little; combinations tell you the story. These are the named patterns this one takes part in.
Two mechanisms a standard lipid panel cannot see. ADMA inhibits nitric oxide synthase and marks endothelial dysfunction, which precedes plaque by years. TMAO is produced by gut bacteria from choline and carnitine and links the microbiome to arterial risk.
Read ADMA against kidney function — it is renally cleared and rises with impairment. For TMAO, standardize diet for 48 hours and avoid fish for 24, because fish raises it sharply without the same implication.
What to test next
These put ADMA & SDMA in context — each with its own full breakdown.
Frequently asked questions
ADMA 0.4–0.75 µmol/L; SDMA 0.3–0.7 µmol/L. Ranges vary by laboratory and assay — always compare to the range printed on your own report.
No reference range exists. HPLC and ELISA methods disagree enough that results are close to incomparable, so lower-is-better is a direction, not a target. Systematic review and meta-analysis of ADMA reference ranges, PLOS One 2017.
Impaired endothelial function — associated with hypertension, ED and cardiovascular events. High SDMA specifically suggests declining kidney function.
Favorable — healthy nitric oxide signaling.
You can order ADMA & SDMA directly through Marek Diagnostics without a doctor's visit — drawn at any Quest Diagnostics location in the US. Code CAMERON applies 10% off automatically.
Where this goes next
The pages here are the frameworks. The protocols — the dosing, the order to correct things in, the week-by-week schedule and what to retest — are inside Skool.