What is the best method to assess ascorbic acid (Vitamin C) levels?

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From the Guidelines

The best method to assess ascorbic acid (Vitamin C) levels is through plasma vitamin C analysis, which is the preferred option for status assessment. This is because intracellular leukocyte vitamin C level analysis, although supposed to be more indicative of tissue vitamin C stores, requires more sample volume and preanalytical steps than plasma and has some caveats related to variability of vitamin C in different cell types 1.

When assessing plasma vitamin C levels, it is crucial to follow strict sample collection and pre-analytical procedures, including immediate separation of plasma samples after blood drawing and storage at ultra-low-temperature (-70 and -80 °C), as well as protection against light exposure 1. The determination of plasma ascorbic acid necessitates considerable logistical and analytical effort due to the high susceptibility of vitamin C to degradation related to temperature, light, pH, dissolved oxygen, and the presence of oxidizing/reducing agents 1.

Some key considerations for plasma vitamin C analysis include:

  • Using lithium heparin when total vitamin C (sum of AA and DHAA) is determined 1
  • Employing efficient analytical methods such as HPLC with ultraviolet (UV), fluorescence or electrochemical detection 1
  • Including a typical sample stabilization preanalytic step before HPLC, such as acidification followed by immediate cold storage at ultra-low temperature 1
  • Using a reducing agent such as dithiothreitol (DTT) or dithioerythritol (DTE) to convert DHAA into AA for total vitamin C analysis 1

Alternatively, a recently developed point-of-care device that measures the blood static oxidation-reduction potential (sORP) can be used to estimate plasma ascorbic acid levels, which is strongly related to the plasma vitamin C concentration and can be measured in non-acidified, non-reduced plasma within 20 min, directly after centrifugation 1.

From the Research

Assessment Methods for Ascorbic Acid (Vitamin C) Levels

  • Biochemical measurements are considered the most objective approach to determining vitamin C nutritional status 2
  • The measurement of serum levels of ascorbic acid is the most commonly used and practical procedure for determining vitamin C nutritional status in individuals or population groups 2
  • Leukocyte ascorbate levels provide information concerning the body stores of the vitamin, but the measurement is technically more difficult to perform 2, 3
  • Newer analytical techniques, such as high-performance liquid chromatography (HPLC), allow for the determination of reduced (ascorbic acid), oxidized (dehydroascorbic acid), or total amounts of vitamin C in biological specimens or foods 3, 4, 5

Blood Components for Assessing Vitamin C Status

  • Platelets, PMN leukocytes, and MN leukocytes concentrate ascorbic acid, suggesting an important role in their physiological functions 4
  • The ascorbic acid content of PMNs and platelets correlates positively with plasma concentration and supplementation with vitamin C 4
  • MN leukocytes maintain the highest levels of ascorbic acid and play a very important function in immunocompetence 4

Analytical Techniques for Measuring Ascorbic Acid

  • Automated or manual colorimetric and fluorometric procedures can be used to measure ascorbic acid in biological samples 2
  • HPLC with monolithic column and UV-detection is a high-throughput method for assessing plasma ascorbic acid and total ascorbic acid 5
  • Reversed-phase HPLC method for ascorbic acid can be used in conjunction with cellular differential centrifugation technique for the determination of ascorbic acid in relatively pure blood cell fractions 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Human requirements and needs. Vitamin C status: methods and findings.

Annals of the New York Academy of Sciences, 1975

Research

Assessment of human vitamin C status.

The Journal of nutrition, 1990

Research

High-throughput analysis of vitamin C in human plasma with the use of HPLC with monolithic column and UV-detection.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2005

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.

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