Not All Vitamin C is Created Equal: AA-2βG, a Powerful Vitamin C Analogue From Goji Berries Outperforms Its Cousin L-Ascorbic Acid and Teaches Scientists "Nature Still Knows Best!"

Vitamin C, also known as L-ascorbic acid probably is the best known of all anti-oxidants; and the marketing  departments of the food companies know that and how to make use of its popularity with slogans like "Extra rich in vitamin C", "Extra Vitamin C", etc. Back in the days, when food was still exclusively nourishing and nobody expected it to heal the ailments it, or other food was causing, ascorbic acid was mostly added to products to extend their shelf-life (this is still common practice, btw.). Today, however, the highly processed foodstuff the unhealthy majority of the fast food society, we have become, is consuming on a daily basis contains vitamin C to... well, I guess to be more marketable. After all, scientific evidence for the purported beneficial effects of vitamin C in isolation, i.e. outside of the natural nutrient mix of real food (vegetables, fruits, meat, eggs, etc.) is scarce and a recent study (Zhang. 2011) from the College of Life Science at the Ningxia University in Yinchuan, Ningxia, China, suggest that structural and compositional differences between vitamin C as we know it, i.e. l-ascorbic acid, and the naturally occurring mix of ascorbic acids and its structural analogues may be the actual reason for the lack of effect all the added ascorbic acid in our foodstuff has on the health of its consumers.

Image 1: Dried Goji or Wulfberries, a
natural source of powerful VitaminS(!) C.
1 gram of the dried fruit contains about
5mg of the power-antioxidant AA-2βG
(data from Toyoda-Ono. 2004)

The paper (Zhang. 2011), which appeared in the May issue of the Archives of Pharmacological Research, reports the results of in-vitro and in-vivo analyses of the anti-oxidant activities of AA-2βG, a natural vitamin C analogue from Goji berries (Lycium barbarum L.). From a molecular perspective, 2-O-β-D-Glucopyranosyl-L-ascorbic acid (AA-2βG) is nothing but plain ascorbic acid (AA) with an added D-glucose moiety and a β-glucoside linkage at the C2 position of the AA molecule. While the fact that this "extension" should (see below) reduce the count of hydrogen radicals or electrons the molecule can donate to scavenge NO2- molecules from two (AA) to one (AA-2βG), it adds to the stability of the molecule, which in its original form (ascorbic acid) cannot "is poorly stored in the body [which] makes it difficult to sustain high concentrations of AA within the body for therapeutic interventions". So, other than science, nature, in her infinite wisdom ;-), obviously knew about the storage problem with vitamin C all along and hid the solution in a fruit that, despite having being used in traditional Chinese medicine for hundreds of years, appeared on the screen of western medical science (and in a huge amount of commercial supplements) only very recently: Goji berries, lat. Lycium barbarum L., the dry fruit of L. barbarum (cf. image 1).

For the alpha- variety, AA-2αG (also known as AA-2G), which has a D-glucose moiety and an α-glucoside linkage at the C2 position, studies similar to the one performed by Zhang et al. had already found that despite the reduced amount of donable hydrogen radicals or electrons (see above), compared to normal ascorbic acid, the AA-2G radical that formed in the process of a first DPPH  [2,2-diphenyl-1-picrylhydrazyl is a dark-colored crystalline powder composed of stable free-radical molecules used to test the in-vitro anti-oxidant capacities of various chemicals compounds] scavenging was "able to react with another DPPH molecule to form a covalent adduct", this covalent adduct from the second reaction was then capable of "slowly quenching a third DPPH radical molecule to generate an unidentified product", so that one molecule of this vitamin C analogue, despite ostensible structural inferiorities, scavenges one additional DPPH radical compared to plain L-ascorbic acid. And while the 2-O substituted AA derivative does lack the ability to to scavange O2−radicals in vitro,

[...] it was more efficient at scavenging H2O2 and OH- than AA (p < 0.01 and p < 0.05, respectively) (Figs. 2B, 3A). This implied that the AA-2βG and AA [ascorbic acid] antioxidant mechanisms differ such that the antioxidant activities of AA-2βG are efficient at scavenging H2O2 and OH- instead of directly scavenging O2−radicals.

With different mechanisms of action, however, the radical scavenging effects of L-ascorbic acid and its derivative(s) add up. This makes the naturally occuring mix of vitamins C an even more potent weapon in the nutritional, supplemental and pharmacological war against oxidative stress reduction and the prevention of lipid peroxidation and cell damage (e.g. erythrocyte hemolysis; cf. figure 1).

Figure 1: Percentage of hemolytic red blood cells in a solution with 500µM H2O2 at various concentrations of Ascorbic Acid (AA) and AA-2βG cells vs. control (0µM) without added anti-oxidants (data adapted from Zhang. 2011)

If you bear in mind that even in the absence of H2O2 roughly 9% of the erythrocytes are damaged by oxidation, the level (~13%) at which the protective effects of AA-2βG saturate (cf. figure 1) indicates that the vitamin C analogon blocks H2O2 induced hemolysis almost completely.

Figure 2: Liver-protective effect of different doses of AA-2βG(dose in mg/kg) in CCl4-induced mouse injury
model; ALT, AST on primary, MDA on secondary axes (data adapted from Zhang. 2011)

Similarly astonishing are the liver protective effects of AA-2βG, of which Zhang et al. found in experiments with CCl4 intoxicated rodents that, in contrast to untreated animals,

[...] serum ALT and AST levels in animals pretreated with AA-2βG were reduced significantly compared to those in the untreated group (Table III) [and] AA-2βG exhibited dose-dependent protection against liver injury, as serum ALT and AST activities in mice given a high AA-2βG dose (300 mg/kg) decreased dramatically to levels similar to those in untreated animals.

So, after all, this seems to be another instance, where nature knew best. Even with all the bioflavonoids, esters, minerals or whatever else supplement producers keep adding to plain L-ascorbic acid to justify the exorbitant prices of their products, the natural vitamin C mix in a bunch of fresh Goji or Wulfberries still outperforms the fanciest supplement.