Laboratory Tests to Confirm Vitamin A Deficiency
Serum retinol measured by high-pressure liquid chromatography (HPLC) is the primary laboratory test to confirm vitamin A deficiency, with levels below 0.7 mmol/L (200 μg/L) indicating deficiency in adults and children over 6 months. 1
Primary Diagnostic Tests
Serum Retinol (First-Line Test)
- Normal range: 1.05–2.8 mmol/L (300–800 μg/L) for children >6 months and adults 1
- Deficiency thresholds:
- Measured by HPLC with ultraviolet detection 1
- Critical limitation: Serum retinol remains homeostatically controlled until liver stores are severely depleted (<20 μg/g liver tissue), making it insensitive for detecting early deficiency 1, 2
Retinol-Binding Protein (RBP)
- RBP <0.48 mmol/L is associated with severe vitamin A deficiency 1
- RBP correlates strongly with serum retinol and is simpler and less expensive to measure 3
- Under stress or inflammatory conditions, use the RBP/transthyretin ratio instead of serum retinol alone, as inflammation reduces RBP release from the liver 1
Functional Assessment Tests
Relative Dose Response (RDR) Test
- Administer 450–1000 μg retinyl palmitate orally, then measure serum retinol at baseline (A0) and 5 hours post-dose (A5) 1, 4, 5
- Calculate RDR = [(A5 - A0)/A5] × 100 4
- RDR ≥14–20% indicates deficiency and depleted liver stores 1, 4, 5
- This test is considered valid for determining inadequate vitamin A status as it indirectly measures hepatic retinol stores 1
- Important caveat: In chronic liver disease, the RDR test is unreliable because reduced RBP synthesis interferes with mobilization of endogenous vitamin A 6
Modified Relative Dose Response Test
Special Considerations for Inflammation
Adjustment for Inflammatory States
- Serum retinol and RBP concentrations decrease with increasing inflammation, independent of true vitamin A status 1
- During inflammation, RBP release from the liver is reduced and the prealbumin-RBP complex redistributes from plasma 1
- Measure C-reactive protein (CRP) and/or alpha-1-acid glycoprotein (AGP) simultaneously to adjust for inflammation 1
- The BRINDA adjustment equation can be used to correct retinol and RBP values for inflammation 1
High-Risk Populations Requiring Testing
Check vitamin A levels in patients with: 1, 7, 8
- Night blindness, xerophthalmia, Bitot spots, or other ocular symptoms 1, 7, 8
- Chronic liver disease (62.4% prevalence of deficiency; 69.8% in transplant candidates) 8, 6
- Malabsorptive procedures (BPD/DS, RYGB): Check every 3 months until stable, then annually 1
- Steatorrhea or protein malnutrition 1
- Chronic conditions: cystic fibrosis, celiac disease, short bowel syndrome, chronic diarrhea 1, 8
- Chronic kidney disease (requires regular monitoring as levels fluctuate unpredictably) 1, 8
- Infections (sepsis, HIV), burns, mechanical ventilation, steroid use 1
Monitoring Frequency
- Initial assessment: 3,6, and 12 months post-bariatric surgery or in high-risk conditions 1
- Ongoing: At least annually thereafter 1
- After malabsorptive procedures (BPD/DS): Every 3 months until stable, then annually 1
Important Pitfalls
- Serum retinol can remain falsely normal despite depleted liver stores, particularly in chronic alcohol consumption 8, 6, 2
- Zinc and protein deficiencies can confound serum retinol measurements 1
- Retinoids are susceptible to photo-degradation and oxidation; samples require antioxidants, light protection, and proper temperature handling 1
- In chronic liver disease, low RBP availability relative to retinol concentration (50% of patients) makes interpretation challenging 6
- Retinyl esters >250 nmol/L in serum suggest hypervitaminosis A, not deficiency 1