How Does Ascorbic Acid Interfere with Blood Biomarkers?

Ascorbic acid (vitamin C) can affect or interfere with specific lab results, especially those using hydrogen peroxide or peroxidase, e.g., the Trinder method.

Consumption of peroxide appears to be the predominant mechanism of interference, either inhibiting chromophore production or creating a lag phase in which color does not develop, an effect dependent on the amount of ascorbic acid present. Interference may be minimized by incorporating ascorbic acid inhibiting agents into the test sample or restricting ascorbic acid intake before testing (Martinello 2006).

Besides the ascorbate reduction of hydrogen peroxide or competition with a chromogen, other potential interference mechanisms include electrode interference and cross-reaction with chemicals such as picrate (Meng 2005).

Ascorbic acid interference may cause an increase or decrease in biomarker values, depending on lab methodology and concentration of ascorbic acid. Some changes are not seen until ascorbic acid reaches very high concentrations that may not be seen under ordinary circumstances.

Food Sources of Select Nutrients, including Vitamin C

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Research utilizing Beckman Synchron LX20® equipment demonstrated significant interference with specific biomarkers when evaluated with ascorbic acid exceeding 14 mg/dL ( 800 umol/L, 0.8 mmol/L), with some biomarkers becoming non-detectable with ascorbic acid levels of 211 mg/dL (12000 umol/L, 12 mmol/L. Changes at the highest level of ascorbic acid (211 mg/dL), which is excessively high, included (Meng 2005):

• Sodium, potassium, calcium, and creatinine increased by 43%, 58%, 103% and
  26%, respectively
• Chloride, total bilirubin, and uric acid values decreased by 33%, 62%, and 83%, respectively were undetectable for total cholesterol, triglyceride, ammonia, and lactate
• No interference or level change was observed for total CO2, urea, glucose, phosphate, total protein, albumin,
  amylase, creatine kinase, CK-MB, AST, ALT, alkaline phosphatase, total iron, unbound iron-binding capacity, or magnesium
• Ascorbic acid does not interfere with assays involving
  colorimetric and non-redox enzymatic reactions

Source: Meng, Qing H et al. “Interference of ascorbic acid with chemical analytes.” Annals of clinical biochemistry vol. 42,Pt 6 (2005): 475-7. doi:10.1258/000456305774538274 Convert mmol/L to umol/L https://www.convertunits.com/from/mmol/l/to/umol/l Convert umol/L to mg/dL https://unitslab.com/node/223

Very high ascorbic acid levels may be achieved with intravenous use, including use as an adjuvant to chemotherapy or radiation, where serum levels may reach as high as 17–88 mg/dL (1000–5000 umol/L, 1-5 mmol/L). A significantly falsely elevated glucose result can be observed when checking capillary glucose with glucose oxidase-based strips. Researchers note that serum ascorbic acid levels seen with regular oral use have not been shown to interfere with capillary glucose monitoring, e.g., 1.55-3.1 mg/dL (88-176 umol/L, 0.88-0.176 mmol/L) (Vasudevan 2014).

Optimal Takeaways

• Ascorbic acid interference with biomarker results is most likely to occur at high levels of ascorbic acid intake or elevated levels in the blood
• Vitamin C intake from foods is less likely to interfere with testing unless serum levels become elevated above optimal
• Consider limiting ascorbic acid supplementation before testing biomarkers associated with ascorbic acid interference

References

Katzman, Brooke M et al. “Unintended Consequence of High-Dose Vitamin C Therapy for an Oncology Patient: Evaluation of Ascorbic Acid Interference With Three Hospital-Use Glucose Meters.” Journal of diabetes science and technology vol. 15,4 (2021): 897-900. doi:10.1177/1932296820932186

Martinello, Flávia, and Edson Luiz da Silva. “Mechanism of ascorbic acid interference in biochemical tests that use peroxide and peroxidase to generate chromophore.” Clinica chimica acta; international journal of clinical chemistry vol. 373,1-2 (2006): 108-16. doi:10.1016/j.cca.2006.05.012

Meng, Qing H et al. “Interference of ascorbic acid with chemical analytes.” Annals of clinical biochemistry vol. 42,Pt 6 (2005): 475-7. doi:10.1258/000456305774538274

Nagel, Dietmar et al. “Investigations of ascorbic acid interference in urine test strips.” Clinical laboratory vol. 52,3-4 (2006): 149-53.

Nah, Hyunjin et al. “Ascorbate Oxidase Minimizes Interference by High-Concentration Ascorbic Acid in Total Cholesterol Assays.” Annals of laboratory medicine vol. 36,2 (2016): 188-90. doi:10.3343/alm.2016.36.2.188

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.

Vasudevan, Sumangala, and Irl B Hirsch. “Interference of intravenous vitamin C with blood glucose testing.” Diabetes care vol. 37,5 (2014): e93-4. doi:10.2337/dc13-2452