Rate of Decline of Vitamin A Levels in Serum
Serum vitamin A (retinol) levels are homeostatically controlled and remain stable until liver reserves fall below critical levels, at which point serum levels begin to decline.
Vitamin A Storage and Metabolism
Vitamin A is primarily stored in the liver, which contains approximately 90% of the body's total vitamin A reserves 1. The serum contains only about 1% of total body vitamin A 1. This storage pattern has important implications for how quickly serum levels change:
- Vitamin A is released from the liver bound to retinol-binding protein (RBP) and coupled to transthyretin 2
- Serum retinol levels are homeostatically controlled over the physiologic range of liver vitamin A concentrations (20-300 μg/g liver) 1
- Serum levels only begin to decline when liver reserves fall below approximately 20 μg/g 1
Factors Affecting Serum Vitamin A Levels
Several factors can influence serum vitamin A levels and the rate at which they change:
Physiological Factors
- Inflammation: Retinol binding protein (RBP) is a negative acute phase protein, leading to decreased serum retinol during inflammation 2
- Acute infections: Serum retinol levels should not be assessed during acute infections as they temporarily decrease 3
- Liver function: Patients with liver disease show more rapid depletion of vitamin A stores 3
Clinical Conditions Associated with Faster Vitamin A Depletion
- Infection (sepsis, HIV)
- Burns
- Mechanical ventilation
- Steroid use
- Hepatobiliary dysfunction
- Renal failure
- Trauma
- Intestinal dysfunction
- Protein-energy malnutrition
- Zinc deficiency
- Cystic fibrosis 2
Interpreting Serum Vitamin A Levels
Serum vitamin A levels must be interpreted carefully:
- Normal range (adults and children >6 months): 300-800 μg/L (1.05-2.8 μmol/L) 2
- Deficiency (premature infants): <200 μg/L (0.7 μmol/L) 2
- Severe deficiency (depleted liver stores): <100 μg/L (0.35 μmol/L) 2
Assessment Methods for Vitamin A Status
Since serum levels don't accurately reflect vitamin A status except in cases of deficiency or excess, other methods may be used:
- Relative dose response (RDR) tests: Measure response to a small dose of vitamin A 4
- RBP/transthyretin ratio: More reliable during inflammation 2
- Isotope dilution techniques: More accurate for assessing total body reserves 4
Important Clinical Considerations
- Serum vitamin A levels are not good indicators of vitamin A status except in cases of deficiency or excess 1
- When liver reserves exceed 300 μg/g, plasma values tend to increase, potentially leading to toxicity 1
- At very high intakes, plasma vitamin A values can exceed 300 μg/dL, mostly in the form of retinyl ester 1
Practical Implications
When monitoring patients at risk for vitamin A deficiency:
- Regular assessment is needed in patients with conditions that increase vitamin A utilization or decrease absorption
- Consider measuring inflammation biomarkers (CRP, AGP) when interpreting vitamin A levels 3
- Be aware that serum levels may remain normal until liver reserves are significantly depleted
- In patients with suspected deficiency, functional tests like dark adaptation may be more sensitive than serum levels 5