Vitamins are organic compounds which have to be obtained from the diet or synthesis. We cannot synthesize vitamin C even though it plays important roles in our body. Vitamin C is a water-soluble compound with anti-oxidant properties and it is also essential for collagen, neurotransmitters and carnitine synthesis. This makes vitamin C an essential component of the human diet. Despite these vital properties of vitamin C, why did humans lose this ability? Wouldn’t it be better if we retain this trait?

Each individual is subjected to a process of natural selection. Positive natural selection, or the tendency of beneficial traits to increase in frequency in a population, is the driving force behind adaptive evolution. For a trait to undergo positive selection the trait must be beneficial; in other words, it must increase the organism’s probability of surviving and reproducing. Conversely, the negative selection also called purifying selection, it means that selection is purging changes that cause deleterious impacts on the fitness of the host. In some cases, negative selection pressure isn’t strong enough and mildly disadvantageous traits continue to persist in the population. While in other some cases the trait may have a trade-off which essentially makes no changes to the overall fitness.

How did humans lose the ability of vitamin c synthesis?

Humans cannot produce Vitamin C due to several mutations in the GULO ( L-gulonolactone oxidase) gene, which located at 8p21 chromosome in human. GULO codes an enzyme that catalyzes the final step of the vitamin c biosynthesis. These mutations are likely to have accumulated since the cessation of transcription, as there is no selection pressure against ineffective mutations.

vitamin c biosynthesis
vitamin C biosynthesis pathways

Loss of GULO activity in the primate order occurred about 63 million years ago, at about the time it split into the suborders Haplorhini (which lost the enzyme activity) and Strepsirrhini (which retained it). The haplorhines (“simple-nosed”) primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys, and humans). The strepsirrhines (bent or wet-nosed) primates, which are still able to make vitamin C enzymatically, include lorises, galagos, pottos and to some extent, lemurs.

Taxonomy of the primates
Taxonomy of the primates

The paradox of Vitamin C

At first glance, this trait may look as harmful even deleterious. But this is just the tip of the iceberg. Scientists have been suggested several advantages to the loss of Vitamin C synthesis in human.

Grano and De Tullio proposed that organisms that have lost ascorbic acid biosynthesis have an advantage in that they can finely regulate HIF1α activation on the basis of the dietary intake of vitamin C. When vitamin C supply is sufficient, the HIF transcription factor is less active than in conditions of vitamin C deficiency. In other words, the lack of ascorbic acid biosynthesis may allow our bodies to know more about our nutritional status and consequently set the proper baseline of HIF1α expression. It is like a sensitive titration system.

Millar J. proposed that loss of this biosynthetic ability has allowed vitamin C to act as a ‘fertility factor’ in primate societies. It is argued that the requirement for vitamin C increases with age, and so in times of food shortages the older members of society suffer higher mortality than the younger. This reduces the median age of the population towards the younger and most fertile members, and so enables the population to regrow rapidly when food resources are restored.

Johnson et al. have hypothesized that the mutation of the GULOP (pseudogene that produces L-gulonolactone oxidase) so that it stopped producing GULO may have been of benefit to early primates by increasing uric acid levels and enhancing fructose effects on weight gain and fat accumulation. With a shortage of food supplies, this gave a mutants survival advantage.

Scientists also suggested that this trait may provide protection against the hemolytic effects of Glucose-6-phosphate dehydrogenase deficiency or enhanced sensitivity to ascorbic acid induced hemolysis. Therefore this trait may be selected for in malarial belts. It is interesting to note that H2O2 is produced during the synthesis of ascorbic acid. It is interesting also that an inverse relationship across different phyla has been reported for SOD and GLO activities.

Consequences of loss

In response to that, we developed an ascorbic acid recycling system in our red blood cells, that can re-reduce oxidized ascorbic acid back to its useable form. This mechanism helps us to minimize our daily intake of Vitamin C requirement.

RBC ascorbate recyling
DHA: Dehydroascorbic acid , Ascorbate(Vitamin C)

Obtaining ascorbic acid exclusively from exogenous sources may lead us to tend towards endogenous antioxidants, such as uric acid. Uric acid is a potent antioxidant and waste product of purine metabolism. Therefore, it doesn’t need a specific effort to produce. Fortunately, our urate oxidase gene which converts uric acid into allantoin also mutated. This mutation provides to increasing our uric acid levels. This is like partial replacement of one antioxidant by another and this mutation favored by the positive selection.

Uric acid metabolism
Uricase(urate oxidase)


The abundance of vitamin C rich foods in nature, mechanisms which we developed against deficiency of ascorbate and advantages of this trait may outweigh ill effects of this mutation. And may contribute to the fitness of primates.

Sources and further reading

Drouin G, Godin JR, Pagé B. The genetics of vitamin C loss in vertebrates. Curr Genomics. 2011;12(5):371-8.

 Pollock JI, Mullin RJ (May 1987). “Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius”. Am. J. Phys. Anthropol. 73 (1): 65–70. 

Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N (March 2008). “Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C”. Cell132 (6): 1039–48. 

Grano A, De Tullio MC (2007). “Ascorbic acid as a sensor of oxidative stress and a regulator of gene expression: the Yin and Yang of vitamin C”. Med. Hypotheses69 (4): 953–4.

Millar J. Vitamin C–the primate fertility factor? Med Hypotheses. 1992Aug;38(4):292-5.

Nandi A, Mukhopadhyay CK, Ghosh MK, Chattopadhyay DJ, Chatterjee IB.Evolutionary significance of vitamin C biosynthesis in terrestrial vertebrates.Free Radic Biol Med. 1997;22(6):1047-54.

Bánhegyi G, Braun L, Csala M, Puskás F, Mandl J. Ascorbate metabolism and its regulation in animals. Free Radic Biol Med. 1997;23(5):793-803. Review.

Johnson RJ, Andrews P, Benner SA, Oliver W (2010). “Theodore E. Woodward award. The evolution of obesity; insight from the mid-Miocene” Trans. Am. Clin. Climatol. Assoc121: 295–305, discussion 305–8

Benzie IF. Evolution of antioxidant defense mechanisms. Eur J Nutr. 2000 Apr;39(2):53-61.

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