rs33972313 — SLC23A1 Val264Met

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.