rs33972313 — SLC23A1 Val264Met

Primary intestinal and renal vitamin C transporter — variant reduces ascorbate absorption and reabsorption efficiency

See your personal result for SLC23A1

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

SLC23A1 Val264Met — Your Vitamin C Transporter

Vitamin C cannot be made by the human body. Every microgram of ascorbate11 ascorbate
The biologically active, ionized form of ascorbic acid at physiological pH in your blood got there by being eaten and then actively transported across your intestinal lining and conserved by your kidneys. The gene SLC23A1 encodes SVCT122 SVCT1
Sodium-dependent Vitamin C Transporter 1 — a 12-transmembrane-domain protein expressed on the apical surface of intestinal and kidney epithelial cells, the transporter protein responsible for both of these steps. A single nucleotide change at position 264 swaps valine for methionine in the transporter, reducing its efficiency and measurably lowering circulating vitamin C levels.

The Mechanism

SVCT1 is an apical membrane33 apical membrane
The cell surface facing the intestinal lumen or kidney tubule, where nutrients are absorbed from transporter that uses the sodium gradient to drive ascorbic acid into intestinal epithelial cells and kidney tubule cells. In the intestine it mediates dietary vitamin C absorption; in the kidney it reclaims filtered ascorbate before it can be lost in urine. The Val264Met substitution occurs in the protein's core transmembrane region, likely altering the conformational changes needed for the transport cycle. In vitro studies show the variant transporter moves ascorbate at roughly 40-50% reduced capacity44 40-50% reduced capacity
Eck P et al. Genomic and functional analysis of the sodium-dependent vitamin C transporter SLC23A1-SVCT1. Genes Nutr, 2007 compared to the wild-type protein.

Knockout mouse studies55 Knockout mouse studies
Corpe CP et al. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J Clin Invest, 2010 dramatically illustrate SVCT1's importance: mice completely lacking Slc23a1 excrete 18 times more ascorbate in their urine, and 45% of pups die perinatally from vitamin C depletion. Humans carrying Val264Met have a far milder effect — they still absorb and reabsorb vitamin C, just less efficiently.

The Evidence

The definitive human study is a meta-analysis of five independent UK cohorts66 meta-analysis of five independent UK cohorts
Timpson NJ et al. Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with >15,000 participants. Am J Clin Nutr, 2010 totaling 15,087 participants. Each copy of the T allele was associated with a 5.98 umol/L reduction in plasma vitamin C (95% CI: -8.23 to -3.73; P = 2.0 x 10-7). Heterozygotes had roughly 24% lower plasma vitamin C than homozygous normal individuals. The effect was consistent across all five cohorts, ranging from -4.15 umol/L in the discovery cohort to -8.31 umol/L in the EPIC-Norfolk study.

For context, adequate plasma vitamin C is generally considered to be above 28 umol/L, with levels below 11 umol/L indicating deficiency. A reduction of ~6 umol/L per allele is clinically meaningful in people whose dietary intake is already marginal — it can push borderline-adequate levels into the insufficient range.

The variant has also been used as a genetic instrument in Mendelian randomization studies77 Mendelian randomization studies
Wade KH et al. Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid. Am J Clin Nutr, 2015 to test whether vitamin C causally protects against cardiovascular disease. Despite strong observational correlations between higher vitamin C and better cardiometabolic profiles, the genetic evidence showed no causal relationship — the observational associations are likely due to confounding (people who eat more fruit and vegetables tend to be healthier overall). A similar Mendelian randomization in 106,147 individuals88 106,147 individuals
Kobylecki CJ et al. Genetically high plasma vitamin C and urate: a Mendelian randomization study. Rheumatology, 2018 found no causal link between genetically determined vitamin C levels and plasma urate or gout risk.

Practical Implications

The Val264Met variant is relatively rare — only about 3-4% of Europeans carry one copy, and homozygotes are extremely uncommon (<0.5%). Among people of African descent the T allele is somewhat more common (~6%), while it is rarer in East Asian (~1.2%) and South Asian (~1.5%) populations.

For carriers, the key takeaway is straightforward: your body is less efficient at absorbing and retaining vitamin C, so you may need to be more intentional about intake. This does not mean megadosing — vitamin C absorption has a saturation ceiling regardless of genotype. It means ensuring you consistently get enough through diet (citrus, berries, bell peppers, broccoli, kiwi) or a modest daily supplement (200-500 mg ascorbic acid), and being aware that your baseline plasma levels will run lower than someone with the same diet but normal SVCT1 function.

Smokers and people with high oxidative stress should pay particular attention, since smoking independently lowers vitamin C levels. If you carry this variant and smoke, or have a diet low in fruits and vegetables, your plasma ascorbate may dip into the deficiency range.

Interactions

SLC23A1 works alongside SLC23A299 SLC23A2
Encodes SVCT2, a vitamin C transporter expressed in metabolically active tissues (brain, adrenals, eyes). Unlike SVCT1, which controls whole-body homeostasis, SVCT2 handles local tissue-level vitamin C delivery, which encodes the tissue-level vitamin C transporter SVCT2. Variants in both transporters could theoretically compound the effect on vitamin C status, though this specific interaction has not been well studied. In the EPIC cohort, both rs33972313 (SLC23A1) and SLC23A2 variants (rs6053005, rs6133175) independently predicted plasma vitamin C levels, suggesting additive effects on vitamin C homeostasis.

Nutrient Interactions

vitamin C reduced_absorption

Genotype Interpretations

What each possible genotype means for this variant.

CC Normal Transporter Normal

Normal vitamin C transport — SVCT1 functions at full capacity

With two normal copies of the SLC23A1 gene, your SVCT1 transporter has its full complement of valine residues at position 264 in the transmembrane domain. This means the transporter undergoes its normal conformational cycle to shuttle ascorbate across intestinal and renal epithelial cell membranes.

In the Timpson et al. 2010 meta-analysis, CC homozygotes had the highest mean plasma vitamin C levels across all five cohorts. Your vitamin C status is effectively "what you eat is what you get" — standard dietary recommendations (75 mg/day for women, 90 mg/day for men, with smokers needing an extra 35 mg) apply without genetic adjustment.

CT Reduced Transporter Reduced

One reduced-function copy — lower plasma vitamin C by ~6 umol/L

With one functional and one reduced-function copy of SVCT1, your intestinal vitamin C absorption and renal reabsorption operate at intermediate efficiency. In the Timpson et al. meta-analysis of 15,087 participants, heterozygotes had roughly 24% lower mean plasma vitamin C than CC homozygotes.

The 5.98 umol/L average reduction per allele may seem modest, but plasma vitamin C exists in a relatively narrow functional range. Adequate status is above 28 umol/L, and deficiency (scurvy risk) occurs below 11 umol/L. If your baseline dietary intake yields plasma levels of 35-40 umol/L, a 6 umol/L genetic penalty brings you closer to the margin where suboptimal vitamin C status begins to affect collagen synthesis, immune function, and antioxidant capacity.

TT Significantly Reduced Transporter Deficient

Two reduced-function copies — substantially lower vitamin C absorption and retention

With two copies of the Val264Met variant, both of your SVCT1 transporters carry the methionine substitution in the transmembrane domain. Based on the per-allele effect of -5.98 umol/L from the Timpson et al. meta-analysis, homozygous carriers can expect plasma vitamin C levels approximately 12 umol/L lower than CC individuals on equivalent dietary intake. This brings you uncomfortably close to the deficiency threshold of 11 umol/L if your diet is not rich in vitamin C.

The in vitro data showing 40-50% reduced transport capacity per variant allele suggests that homozygotes may have substantially compromised both intestinal absorption and renal conservation of ascorbate. While this is not equivalent to the devastating effects seen in complete Slc23a1 knockout mice (45% perinatal mortality), it is the most significant common genetic effect on vitamin C homeostasis identified to date.