ADMA

Introduction

As a Nurse Practitioner with autonomous practice in Florida, I frequently evaluate patients for early markers of cardiovascular and metabolic dysfunction. One critical but often overlooked biomarker is Asymmetric Dimethylarginine (ADMA)—a key inhibitor of nitric oxide synthesis and a validated indicator of endothelial health. This article explores ADMA’s physiological role, clinical implications, and its integration in a functional medicine approach to cardiovascular prevention.

What Is ADMA?

ADMA (Asymmetric Dimethylarginine) is an endogenous amino acid derivative formed during protein methylation. It circulates freely in plasma and is known to inhibit nitric oxide synthase, thereby reducing nitric oxide (NO) availability.

Since nitric oxide is essential for vascular tone, endothelial repair, and anti-inflammatory signaling, elevated ADMA levels impair vascular function and are linked to hypertension, atherosclerosis, and cardiovascular events.

The Role of Nitric Oxide and Endothelial Function

The endothelium is the inner lining of blood vessels, regulating vasodilation, inflammation, and thrombosis. Nitric oxide (NO)—produced from L-arginine by nitric oxide synthase—is its primary messenger. NO has:

• Antithrombotic effects
  
• Anti-inflammatory properties
  
• Antioxidant activity
  
• Blood pressure regulation

   

Elevated ADMA disrupts this pathway, serving as a direct contributor to endothelial dysfunction.

Clinical Implications of Elevated ADMA

High ADMA levels are associated with the following:

1. Cardiovascular Disease

• Associated with subclinical atherosclerosis, hypertension, and vascular calcification
  
• A strong predictor of myocardial infarction, stroke, and peripheral artery disease

   

2. Insulin Resistance and Type 2 Diabetes

• ADMA levels are elevated early in insulin resistance, preceding overt diabetes
  
• May reflect impaired glucose metabolism and nitric oxide signaling in diabetics

   

3. Metabolic Syndrome

• Low nitric oxide bioavailability due to ADMA elevation is seen in obesity, hypertension, and dyslipidemia
  
• ADMA integrates with other biomarkers of dysfunction such as C-Reactive Protein and Homocysteine

   

Reference Ranges for ADMA

• Standard Range: 0.00 – 123.00 ng/mL
  
• Optimal Range: 0.00 – 100.00 ng/mL
  
• Elevated Risk: >123.00 ng/mL

   

Elevations may indicate heightened vascular risk, especially when paired with additional cardiometabolic markers.

Factors Affecting ADMA Levels

Lifestyle Factors

• Tobacco use, obesity, high-sugar diet, and inactivity increase ADMA
  
• Weight loss, aerobic training, and a plant-rich diet may reduce levels

   

Drug Associations

• Methylcobalamin and Folate can reduce ADMA levels by enhancing homocysteine clearance
  
• Statins, ACE inhibitors, and L-Arginine may support nitric oxide synthesis

   

Related Biomarkers

To evaluate cardiovascular risk comprehensively, assess ADMA alongside:

• Homocysteine
  
• CRP
  
• Triglyceride:HDL Ratio
  
• Insulin and HOMA2-IR

   

Therapeutic Strategies for Elevated ADMA

Lifestyle Interventions

• Adopt a Mediterranean or DASH-style diet
  
• Increase intake of nitrate-rich vegetables (e.g., beets, arugula)
  
• Engage in 150–300 minutes of aerobic activity weekly
  
• Avoid tobacco and limit processed carbohydrates

   

Supplementation

• L-Arginine or L-Citrulline: Precursors to nitric oxide
  
• Methylated B-vitamins: Methylcobalamin, folate, and B6 may reduce ADMA via homocysteine reduction
  
• Omega-3s and antioxidants for endothelial repair

   

Conclusion

ADMA is a functional biomarker of nitric oxide inhibition and early endothelial dysfunction. Elevated levels signal increased vascular risk and are particularly concerning in the context of diabetes, hypertension, and inflammatory conditions.

In a functional medicine model, ADMA is used as a predictive tool, guiding early lifestyle and nutraceutical interventions that preserve endothelial integrity and support long-term cardiovascular resilience.

References for Further Reading

• Ulusoy, S., et al. (2022). Evaluation of asymmetric dimethylarginine levels in patients with chronic thromboembolic pulmonary hypertension: The effect of pulmonary endarterectomy and prognostic value. Pulmonary Circulation, 12(1), 204589402210740. https://pubmed.ncbi.nlm.nih.gov/34130918/

• Sydow, K., et al. (2014). Asymmetric dimethylarginine (ADMA) and treatment response relationship in male patients with first-episode schizophrenia: A controlled study. Psychiatry Research, 220(1-2), 228-233. https://pubmed.ncbi.nlm.nih.gov/25095755/

• Zoccali, C., et al. (2015). Angiotensin converting enzyme inhibition increases ADMA levels in patients on maintenance hemodialysis. Journal of the American Society of Nephrology, 26(10), 2546-2553. https://pubmed.ncbi.nlm.nih.gov/26494370/

• Schwedhelm, E., & Böger, R. H. (2017). Toxic dimethylarginines: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in human health and disease. Antioxidants & Redox Signaling, 26(10), 339-355. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371847/