To better understand how and why the loss of vitamin C occurred, we need to understand the benefits of it. Scurvy is a deadly disease that occurs in vertebrates that are unable to synthesize vitamin C when their diet does not include fresh fruit and vegetables, rich sources of the vitamin. Historically, this disease killed many sailors, who did not have such perishable foods available during their long voyages at sea. Scurvy takes some time to develop in a human with a vitamin-C-free diet, and when it does it can show a range of symptoms. These include lassitude, neurological dysfunction, and, more commonly, dramatic defects in blood vessel and bone integrity. These latter symptoms are the most easily recognized because they cause skin spots, bleeding of gums, and loose teeth, as well as bone and cartilage fragility.

In the late 1950s, the new tools of biological chemistry allowed the identification of another essential role for vitamin C that helped explain these fundamentally disabling symptoms. In 1962, through analysis of the radioactivity incorporated into collagen using a tritiated version of the amino acid proline, Stone and Meister discovered that vitamin C is used as a co-substrate by peptidyl-prolyl hydroxylase, an enzyme that catalyzes the selective modification of proline to hydroxyproline. This modification is essential for proper collagen folding. Consequently, the lack of vitamin C results in the formation of non-functional collagen in blood vessels and bones, which accounts for most of the severe bone and blood vessel related symptoms. The variety of scurvy symptoms beyond those stemming from collagen defects occur because vitamin C is also a co-substrate for multiple enzymes involved in biosynthesis, including the synthesis of dopamine, an important neurotransmitter, and carnitine which helps mitochondria keep in pace with the demand for energy production. Lack of these two compounds helps explain the neurological dysfunction and lassitude symptoms of scurvy.

Nowadays, scurvy is not as widespread as it used to be, although cases still occur among people with unhealthy eating habits. However, vitamin C became quite popular in the 20th century, not for its role in the prevention of scurvy, but for its potent "antioxidant" function. The identification of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide ions, as molecules that are potentially harmful for biological membranes and other cell components, has intensified interest in things that are anti-ROS, known as antioxidants. These compounds are able to react with dangerous oxidants and keep cells and tissues healthy. Indeed, vitamin C is one of the best physiological non-toxic antioxidants because it is so efficient: it reacts with many different kinds of ROS. There is a common misconception that antioxidants are always beneficial, when rather they are complex molecules that are part of intricate systems ensuring proper cell function. Regardless, because of the integral role that vitamin C plays inside a cell, be it antioxidant or co-substrate, preserving its biosynthesis should have been a selective advantage. Why did humans lose this ability?