Think back to high school health class. Do you remember reading about people with bleeding gums, and who bruised easily? Remember the story of 18^th Century British sailors who experienced these problems and were cured with lime juice, hence their nickname, “limeys?” The problem causing these issues was scurvy, the severest form of vitamin C deficiency. In today’s world, with an abundant food supply available all year-round now, you might assume it’s impossible to have suboptimal vitamin C, never mind outright scurvy. And it’s true that these things aren’t extremely common, but they’re not as rare as you might think.

A couple of documented cases of scurvy popped up in 2016 and caused enough of a stir to make it to a national newspaper. The Washington Post reported on a two-and-a-half-year-old boy who was diagnosed with scurvy as a result of extremely picky eating and subsisting on nothing but chocolate milk and graham crackers. In a separate occurrence, in Spain, an 11-month-old baby was identified as having scurvy owing to being fed an almond milk formula and refusing offered pureed fruits and vegetables after displaying an apparent sensitivity to cow milk formula. Vitamin C deficiencies of this magnitude bring devastating consequences, but the good news is, these are easily corrected with inclusion of vitamin C-rich foods in the diet, and/or with supplementation if someone needs higher levels than can be reasonably gotten through diet alone. 

The two children diagnosed with scurvy were eating extremely restrictive diets, so scurvy shouldn’t have been a surprise to the medical professionals on these cases. However, even in people consuming omnivorous diets that contain adequate amounts of fresh vegetables and fruits to provide ample vitamin C, suboptimal vitamin C levels aren’t out of the question. It’s a little-known fact that vitamin C and glucose compete for absorption into cells.¹ For this reason, researchers believe that uptake of vitamin C into cells might be impaired by chronically high blood sugar (hyperglycemia) and/or insulin resistance.² Vitamin C is a critical nutrient for healthy blood vessels, and microscopic damage to blood vessels is one of the hallmarks of poorly managed diabetes. Researchers have speculated that this damage could actually be a result of local vitamin C deficiency.² (However, chronically high blood sugar, by itself, is also damaging to blood vessels.)

Competition between vitamin C and glucose for uptake into cells may be one reason why some studies looking at vitamin C supplementation—especially orally—have shown little or no benefit: these studies did not control for the amount of glucose in subjects’ diets. (Vitamin C administered intravenously can be given at much higher doses and would have a greater chance of overcoming competition from glucose in the blood.) In order to reduce the potential for competition with glucose, it might be prudent to supplement in conjunction with a reduction in dietary carbohydrate for people for whom vitamin C supplementation is indicated.³

Indeed, there’s evidence that very low carbohydrate or ketogenic diets may reduce the requirement for vitamin C. By maintaining generally lower levels of blood glucose, there’s less competition for cellular uptake of vitamin C. Additionally, animal studies show that ketogenic diets increase mitochondrial glutathione levels.⁴ Glutathione is an important antioxidant and helps recycle or “spare” vitamin C, so increased glutathione levels could, in theory, reduce the need for increased vitamin C intake. Ketogenic diets may also increase uric acid levels. Owing to correlations between elevated uric acid levels and occurrence of gout attacks, this is typically seen as a negative thing. But uric acid isn’t always or automatically an enemy. It’s actually a powerful antioxidant in its own right⁵—one that’s been shown to be as powerful as vitamin C itself.⁶ Humans and other higher primates lack the ability to synthesize vitamin C, and we also lack functional uricase, the enzyme that breaks down uric acid. It’s possible these are related, and that uric acid may “make up for” lower vitamin C levels, and perform some of the same antioxidant actions.

Some of this is speculation, but it’s interesting to consider that for as much as is known about the critical effects of vitamin C in the immune system, there’s clearly a lot more to learn about lesser-known properties of this “antiscorbutic” nutrient.

Sources:

1. KC S, Cárcamo JM, Golde DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury.
2. Mann GV, Newton P. The membrane transport of ascorbic acid. Ann N Y Acad Sci. 1975 Sep 30;258:243-52. FASEB J. 2005 Oct;19(12):1657-67.
3. Ottoboni F, Ottoboni A. Ascorbic Acid and the Immune System. Journal of Orthomolecular Medicine 20(3). September 2005.
4. Jarrett SG, Milder JB, Liang LP, Patel M. The ketogenic diet increases mitochondrial glutathione levels. J Neurochem. 2008 Aug;106(3):1044-51.
5. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des. 2005;11(32):4145-51.
6. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858-62.