The Truth About Vitamin C (3)

Summary of This Issue:

Vitamin C (ascorbic acid) is an important antioxidant that we all need.
Various foods are rich in Vitamin C, but its dietary sources are mainlyplant-based foods.
Humans have lost the ability to synthesize Vitamin C, which may bring other advantages.

This article has 2667 words, writing time: 5 hours, recommended reading time: 4 minutes.

Vitamin C: Miracle Drug or Philosopher’s Stone?

In the previous two issues, I discussed the scientific discovery process of Vitamin C.From this issue onward, I will introduce why it is important for human health.

The True Identity of Vitamin C

First, let’s unveil the mystery of Vitamin C and get to know this shy molecule.As summarized in the figure below, Vitamin C is primarily considered a reducing agent (also known as an antioxidant), which is oxidized to dehydroascorbic acid while providing two active hydrogen atoms to reduce other oxidizing chemical molecules.The main molecular function of Vitamin C is to provide reducing power through this reaction, and the other substances it reduces mainly include some biochemical metabolic enzymes, which I will detail later.

Oxidized Vitamin C is not excreted as metabolic waste; instead, it is regenerated back to Vitamin C through a “Vitamin C regeneration reduction reaction” using the “glutathione reduction regeneration system” for recycling (as shown in the figure above – in the “Milk” series written by Peichuan, the glutathione reduction system was briefly introduced, please refer tothe content from September 12, 2017).

Although human cells and intestinal flora cannot synthesize Vitamin C, they can maintain a very high utilization efficiency.Multiple modern studies have shown that normal humans only need to supplement 10 mg of Vitamin C daily through diet to maintain health, which is roughly equivalent to the Vitamin C content of two small florets (10 grams) of raw broccoli, two medium-sized citrus fruits, or two medium-sized strawberries.

Moreover, even if Vitamin C cannot be ingested in the short term, scurvy symptoms will not appear immediately.According to several early studies on scurvy, after stopping Vitamin C intake, symptoms typically appear after a month (British study) or more than six months (American study);thus, the unhealthy British dietary habits once again become a highlight.It is worth mentioning that these early studies used Vitamin C skeptics (British study) and incarcerated individuals (American study), and due to scientific ethics and the level of knowledge dissemination, it is no longer possible to replicate such studies.

Although some studies suggest a daily intake of over 100 mg, according to current nutritional standards, it is believed that 60 mg of Vitamin C per day is sufficient to ensure health.Our body reserves about 1500 mg of Vitamin C, mainly stored in the liver and muscles, thus can maintain several weeks’ worth of supply.Moreover, due to storage capacity limitations, excessive intake of Vitamin C will not increase body reserves but will be excreted through the kidneys into urine.It is noteworthy that once the body experiences various discomforts, the demand for Vitamin C will increase exponentially.For example, our immune cells contain a large amount of Vitamin C, and when an infection occurs, the consumption of Vitamin C will also surge.Therefore, maintaining a stable and sufficient daily intake of Vitamin C is an important guarantee for maintaining a healthy body.

The Biosynthesis of Vitamin C

I mentioned in the last issue that Vitamin C is an essential organic molecule for all eukaryotic cells, and most organisms in nature have the ability to synthesize it, including all plants and most animals.In the biosynthesis pathway of Vitamin C, the raw material comes from glucose (in animals) or similar hexose sugars (in plants), which is abundant, and the steps are summarized as follows.

In plants and certain protists, mannose (Man) and galactose (Gal) are the raw materials for synthesizing Vitamin C.Various parts of the plant can synthesize Vitamin C, with particularly high concentrations in certain cellular locations.For example, leaves contain many chloroplasts, where the Vitamin C concentration can reach 20 mM (millimoles, equivalent to 3.4 grams per liter).This is because chloroplasts require Vitamin C as an antioxidant to effectively inhibit and alleviate excessive oxidative free radicals generated during the process of photosynthesis.

In various dietary habits, plant-based foods can be eaten raw, especially fruits, thus avoiding high-temperature cooking that destroys Vitamin C.Therefore, in various cultures, plant-based foods are the primary dietary source of Vitamin C.The table below lists some common plant foods rich in Vitamin C and their content (source:Wikipedia).

Plant-Based Food	Vitamin C Content per 100g (mg)
Sea Buckthorn	695
Green Chili	244
Guava	228
Red Bell Pepper	190
Red Chili	144
Celery	130
Kiwi	90
Broccoli	90
Brussels Sprouts	80
Goji Berries	73
Lychee	70
Fresh Persimmon	66
Papaya	60
Strawberry	60
Citrus and Lemon	53

In animals, the raw material for Vitamin C synthesis is glucose, with the synthesis occurring mainly in the liver (in mammals) or kidneys (in reptiles and birds).Therefore, animal foods rich in Vitamin C are various livers, but their levels cannot compare with the same amounts of plant foods, and modern dietary habits generally do not consume liver raw, so animal foods are not the main source of Vitamin C, and I will not list them here.

Humans and Vitamin C: The Loss of Synthesis

We now know that humans and a few other animal species cannot synthesize Vitamin C.Interestingly, modern molecular biology research has discovered that all these animals lacking the ability to synthesize Vitamin C lack a gene called “gulonolactone oxidase” (L-GulO) (see the annotation in the Vitamin C synthesis diagram above).More precisely, the L-GulO gene in these animals does not have the ability to produce active proteases, which are known as “pseudogenes,” so the cells of these animals cannot complete the final step of Vitamin C synthesis and cannot convert gulonolactone into the end product Vitamin C.

On the evolutionary tree, humans clearly appeared later, and other species that cannot synthesize Vitamin C are merely individual exceptions of their respective genera.This indicates that humans lost the ability to synthesize Vitamin C during evolution.

Since Vitamin C is so important, why did our bodies lose the ability to synthesize it?

There are some explanations in the scientific community, mainly based on the “gulonolactone oxidase“.Let’s first look at the chemical reaction catalyzed by this enzyme.

Do you see the clue?

This chemical reaction converts gulonolactone through an oxidation reaction into Vitamin C, while simultaneously adding the reaction products (two active hydrogen atoms) to an oxygen molecule, generating hydrogen peroxide (H2O2).

Hydrogen peroxide, commonly known as “bleach” in aqueous solution, is a common oxidative free radical that can indiscriminately attack and oxidize other chemical molecules, such as proteins and DNA, causing biological function disruption and gene mutations.

Imagine if every time a Vitamin C is synthesized, a hydrogen peroxide molecule is also produced, then the oxidative free radicals in our bodies would also become a significant burden, requiring extra energy to alleviate, such as using the glutathione regeneration reduction system.Therefore, eliminating this burden is evolutionarily advantageous.

This viewpoint can also be supported by evolutionary evidence: animal species that cannot synthesize Vitamin C in other evolutionary branches also possess the same ineffective gulonolactone oxidase gene.This may explain that the loss of the active gulonolactone oxidase gene can provide survival advantages across many different evolutionary pathways.

More intriguingly, these organisms that lost the ability to synthesize Vitamin C “coincidentally” also lost the ability to degrade uric acid.In animals that can degrade uric acid, such as crabs, the nitrogen released after uric acid degradation can be recycled and re-involved in amino acid synthesis.Therefore, these organisms can survive in extremely nitrogen-poor conditions.

After humans lost the ability to degrade uric acid, they have no choice but to excrete it through the kidneys, resulting in much higher uric acid levels in the blood compared to other organisms.High blood uric acid can lead many people to develop gout, which can severely affect their health and ability to enjoy high-protein foods.

No one knows for sure why this is the case.However, uric acid is also an antioxidant, similar to Vitamin C, and has the ability to scavenge free radicals.The loss of the ability to degrade uric acid gives humans additional chemical antioxidant capacity, allowing them to tolerate greater intensity of aerobic metabolic activities (the main source of oxidative free radicals) and gain other advantages in evolution.For example, human long-distance running endurance is unparalleled in nature.To some extent, this new type of antioxidant capacity also provides operational space for humans to lose the ability to synthesize Vitamin C.

There is a biological link between Vitamin C and uric acid.For example:

In clinical studies, it was found that taking 500 mg of Vitamin C daily can significantly reduce uric acid levels in the blood.
However, some studies have found that using the same dose of Vitamin C can lower blood uric acid, but the extent is not sufficient to alleviate gout symptoms.
Other studies reported that in patients undergoing kidney dialysis, the higher the uric acid level in the blood, the lower the amount of oxidized Vitamin C.

References:

https://www.ncbi.nlm.nih.gov/pubmed/21671418

http://www.wiley.com/WileyCDA/PressRelease/pressReleaseId-108712.html

https://www.ncbi.nlm.nih.gov/pubmed/11239034

This seems to indicate that the relationship between the two should be to jointly maintain the chemical environment of redox potential in the body.The specific mechanism remains to be further studied.However, for gout patients, increasing Vitamin C intake in the diet may indeed lower blood uric acid levels and at least will not worsen the condition.

How does Vitamin C affect human health at the molecular level?We will continue to introduce this in the next issue.

Scientific Editor: Peichuan Executive Editor: Yang Ming