Is a normal anion gap concerning?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Article Review Status
Submitted
Under Review
Approved

Last updated: May 23, 2025 • View editorial policy

From the Guidelines

A low anion gap is concerning and warrants further evaluation to determine the underlying cause, as it may indicate serious medical conditions such as hypoalbuminemia, multiple myeloma, or medication toxicity. The normal anion gap range is typically considered to be 8-12 mEq/L, with values below 8 mEq/L considered low. Although the provided study 1 focuses on the treatment of ethylene glycol poisoning and recommends extracorporeal treatment for high anion gap values (> 27 mmol/L), it does not directly address the concern of a low anion gap. However, it is essential to note that a low anion gap can be associated with various conditions, including laboratory error, hypoalbuminemia, multiple myeloma, lithium toxicity, bromide ingestion, and severe hypernatremia.

  • Common causes of a low anion gap include: + Laboratory error + Hypoalbuminemia (low albumin levels) + Multiple myeloma + Lithium toxicity + Bromide ingestion + Severe hypernatremia
  • Management of a low anion gap focuses on treating the underlying condition rather than the low anion gap itself. For example, if hypoalbuminemia is the cause, addressing the reason for low albumin levels (such as malnutrition or liver disease) would be the appropriate approach, as for every 1 g/dL decrease in albumin, the anion gap decreases by approximately 2.5 mEq/L 1. While a low anion gap is less frequently associated with immediately life-threatening conditions compared to a high anion gap, it should not be ignored as it may be the first indication of serious disorders.

From the Research

Low Anion Gap Concerns

  • A low anion gap can be a useful diagnostic tool, but its clinical significance is often unrecognized 2.
  • It may be a handy clinical clue for the diagnosis of life-threatening intoxications or occult neoplasms, such as multiple myeloma 2.
  • The baseline low anion gap may mask the identification of a high gap metabolic acidosis in certain patients 2.
  • Interpretation of a low anion gap can provide valuable clinical information 2.
  • A low anion gap is often overlooked in teaching and practice, resulting in missed opportunities to diagnose acute or chronic disorders requiring treatment 3.

Diagnostic Approach

  • A stepwise approach to diagnostic testing can be used to evaluate a low anion gap 3.
  • The constituents of the anion gap should be reviewed, and a differential diagnosis for a low anion gap should be built using case examples 3.

Relation to Other Conditions

  • Lactic acidosis, which can be associated with a low anion gap, is a relatively rare complication in patients with diabetes 4.
  • Alcohol abuse and metformin treatment are potential causes of lactic acidosis in diabetic patients 4, 5.
  • Lactic acidosis can be a serious acute complication of diabetes, and its incidence, morbidity, and mortality are decreasing, but still remain significant 5.
  • Current treatments for lactic acidosis, such as eliminating the triggering conditions and administering sodium bicarbonate, have limitations, and future research into new therapies, such as selective NHE1 inhibitors, is warranted 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Low anion gap.

Southern medical journal, 1998

Research

Evaluating a low anion gap: A practical approach.

Cleveland Clinic journal of medicine, 2023

Research

Lactic acidosis in patients with diabetes.

Polskie Archiwum Medycyny Wewnetrznej, 2013

Research

Lactic Acidosis: Current Treatments and Future Directions.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.