Vitamin C

What Vitamin C actually measures — the analyte, and the assay

The analyte is ascorbate in plasma or serum — and the first question is which ascorbate, because laboratories report either reduced ascorbic acid alone or total vitamin C, the sum of ascorbic acid and its oxidized form dehydroascorbic acid. Those are two different numbers off the same tube.

Measurement is by HPLC, with electrochemical detection as the reference method and ultraviolet detection as the practical one. A head-to-head in 80 consecutive clinical samples found a simplified constant-low-pH UV-HPLC method performed equivalently to the gold-standard electrochemical method Robitaille 2016. The interesting part of that paper is its premise: in-hospital hypovitaminosis C is highly prevalent and almost completely unrecognized, because most hospital laboratories cannot measure plasma vitamin C at all Robitaille 2016. The commonest analytical failure with this marker is that the test is never run.

The sample is fragile in a way trace elements are not. Ascorbate is a reducing agent; it oxidizes in the tube, in light, at room temperature, and fastest of all in the presence of redox-active transition metal ions. A review of why vitamin C research keeps producing contradictory results puts that redox chemistry at the top of the list of design failures Michels 2013. Practically: the tube has to be chilled, protected from light, spun quickly and the plasma acid-stabilized. A low result from a tube that sat on a counter is a laboratory artefact, not a diet.

And the physiology sets a ceiling the assay cannot see past. Uptake runs through a family of saturable sodium-dependent vitamin C transporters, so absorption and elimination are dose-dependent and pharmacokinetics shift from zero-order to first-order as you move from dietary to pharmacological doses Lykkesfeldt 2019. Tissue concentrations at homeostasis run from about 0.2 mM in muscle and heart to about 10 mM in brain and adrenal gland Lykkesfeldt 2019. Plasma is the most dilute compartment in the body and the first one to stop rising.

Vitamin C: what changes the blood, and what only changes the reading

What changes the vitamin C in your body:

1. Intake, dietary and supplemental. Supplement users have a higher mean status and a lower prevalence of deficiency Carr 2020, and a systematic review found supplementation raised measured levels in populations with and without cardiovascular disease Collins 2021.
2. Smoking, which raises requirement through oxidative turnover, and is one of a long list of status determinants that also includes body weight, pregnancy, lactation, genetic variants in the transporters, deprivation, institutionalization and pollution Carr 2020.
3. Acute illness and severe infection, which consume ascorbate quickly — the same review lists severe infection alongside non-communicable disease as a status determinant Carr 2020, and micronutrient status alterations in critical illness are the rule rather than the exception de Man 2024.
4. Cooking and staple foods. Grains contribute negligible vitamin C, and traditional cooking practice destroys much of what is there Carr 2020.

What changes only the reading — and one of these is the reason this marker is misread:

1. The saturation ceiling. Past the point where the transporters saturate, extra intake raises urinary loss rather than plasma concentration Lykkesfeldt 2019. The number stops tracking intake exactly where most people are trying to push it, so a plateau reads as ‘the supplement stopped working’ when it is the transporter doing its job.
2. Sample handling — warmth, light, delay to centrifugation and metal contamination all oxidize ascorbate and lower the result Michels 2013.
3. Which fraction the laboratory reports, ascorbic acid or total vitamin C Robitaille 2016.
4. High-dose vitamin C interfering with other assays. This is the reverse case and it belongs on this page: ascorbate is a strong reducing agent and it can distort other analytes measured by redox chemistry, which is why a high-dose supplement is worth holding before an unrelated panel.

Reference interval or decision threshold — which kind of number Vitamin C is

A deficiency floor dressed as a reference interval. The 0.4–2.0 mg/dL you see printed is the central distribution of whoever the laboratory measured. It has no outcome attached at the top end, and the only well-anchored number is at the bottom: the concentration below which collagen synthesis fails and scurvy follows. Everything above that floor is a description of a population, not a target.

Two things make this more than a technicality. First, a scoping review of 107 studies across 31 countries concluded that the prevalence of deficiency in high-income countries is likely between 0% and 15%, and — more pointedly — that current reference ranges underestimate inadequacy for optimal health by roughly 33.6% Carter 2025. That is a reference interval being used as though it were a decision threshold, and the review says so explicitly, recommending intake recommendations be aligned to optimal health outcomes rather than to the mere prevention of deficiency.

Second, the same review found that only 31 countries have measured community serum vitamin C in the last twenty years, with nationally representative data missing for most age groups Carter 2025. The reference population behind your printed range is thinner than the confidence with which it is printed.

So: a floor, yes. An optimum, no — and this site will not manufacture one, because the pharmacokinetics say a plasma optimum is not a coherent object above saturation Lykkesfeldt 2019.

How you would know your Vitamin C was wrong — and when to redraw

Four to six weeks, and the reason is the transporter, not a store. Plasma ascorbate responds to a change in intake within days and reaches its new steady state in weeks, because the pool is small and renal handling is saturable Lykkesfeldt 2019. This is the fastest marker in the micronutrient set — the opposite of the red-cell measures, which take four months. Waiting twelve weeks does not make the value more informative; it just delays it.

Conditions that must match: same laboratory and same fraction (ascorbate or total), sample chilled and protected from light, spun promptly, and supplements taken on the same schedule relative to the draw — a dose two hours before the needle measures the dose, not your status.

How you would know your vitamin C was wrong. Draw hs-CRP on the same sample. Ascorbate falls in acute illness and inflammation independently of intake, and a low value drawn during an infection is a consumption signal rather than a dietary one Carr 2020 de Man 2024. The interpretable result is a rise in ascorbate with hs-CRP unchanged. If the reason you are supplementing is iron absorption, then ferritin and the iron panel carry the falsifiable prediction: non-heme iron absorption is the best-evidenced downstream effect vitamin C has on another number, and if those do not move over two or three months, the ascorbate went somewhere that did not matter. And if a supplement produces no rise at all, the answer is usually the ceiling rather than the product Lykkesfeldt 2019.

What Vitamin C cannot tell you

It cannot tell you tissue status. Brain and adrenal sit near 10 mM while plasma sits three orders of magnitude lower Lykkesfeldt 2019, and the gradient is maintained by transporters rather than by concentration. A plasma value is the compartment vitamin C is passing through, not the compartment it works in.

It cannot be pushed usefully upward. Above saturation, extra intake raises urinary loss, so a higher plasma number is not evidence of a better-supplied body Lykkesfeldt 2019.

It cannot be trusted from a badly handled tube. Ascorbate oxidation in transit is a documented source of spurious low results and one of the reasons this literature contradicts itself Michels 2013.

It cannot tell you that vitamin C did anything. The randomized evidence base is compromised by exactly the design faults the artefacts review catalogs — wrong dose ranges, replete populations, unappreciated redox chemistry Michels 2013. A number moving is not an outcome changing.

The wrong inference here is the mirror image of the one on most pages: a mid-range plasma ascorbate read as ‘optimized’ and then chased upward with grams a day — which raises urinary oxalate rather than tissue vitamin C, and in a susceptible person raises stone risk for nothing.

Sources read for these sections

• Lykkesfeldt J, et al. The Pharmacokinetics of Vitamin C. Nutrients 2019 · PMID 31601028
• Robitaille L, et al. A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use. Nutrition Journal 2016 · PMID 27102999
• Carter DM, et al. The Community Prevalence of Vitamin C Deficiency and Inadequacy - How Does Australia Compare With Other Nations? A Scoping Review. Health Science Reports 2025 · PMID 40642565
• Carr AC, et al. Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective. Nutrients 2020 · PMID 32630245
• Michels AJ, et al. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Nutrients 2013 · PMID 24352093
• Collins BJ, et al. Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review. Nutrients 2021 · PMID 34371840
• de Man AME, et al. What do we know about micronutrients in critically ill patients? A narrative review. JPEN Journal of Parenteral and Enteral Nutrition 2024 · PMID 39555865