Vitamin C is nothing more than ascorbic acid, or more precisely L-ascorbic acid. No expert in the world can say otherwise. This L-ascorbic acid is produced by all living organisms except humans, primates and a few other species (more on the reasons for this later). Polyphenols (flavonoids) are not produced by animals, so the suggestion that those are vitamins C or even necessary for vitamin C to work is strange... Since 2000, only L-ascorbic acid has been produced worldwide, no other raw material exists, so the distinction between natural and artificial vitamin C is meaningless, although it did make sense before, because then synthetically produced ascorbic acid still often contained the D-isomer, i.e. it was DL-ascorbic acid, not L-ascorbic acid. Vitamin C is present in all living things and is found exclusively in the form of L-ascorbic acid. Polyphenols (bioflavonoids, etc.) all have very good effects, but they have nothing to do with vitamin C, even though they can help (and hinder) its action. For example, the effect of copper is also enhanced by zinc, or the effect of D3 by magnesium, but D3 is not Mg, just as zinc is not copper, and zinc will not make up for a copper deficiency, nor will D3 make up for a Mg deficiency.

Supplementation with the artificial but natural form of vitamin C, L-ascorbic acid, has the same effect and benefits as if ingested from natural plant sources, as has been shown in dozens of animal and human studies. Moreover, vitamin C extracted from plants is no more than pure l-ascorbic acid, because it is not a case of vitamin C being obtained by ingesting a plant source with its other vitamins, minerals/trace elements and active substances, but in most cases only a plant extract standardised to ascorbic acid. That is, only vitamin C is extracted from it, with no or unknown amounts of other ingredients. At best, such an extract is standardised to polyphenols, but even then it is no more than adding polyphenol extracts to L-ascorbic acid or taking vitamin C with a few bites of fruits or vegetables... So my main statement is the same as what the current literature claims: Neither ascorbyl palmitate nor vitamin C from plant extracts has been considered any better than ascorbic acid since 2000, wizh regard to the fact that only the natural L-form is produced since 2000, and vitamin C from plant extracts is the same as L-ascorbic acid, but at 10-100x the price. In addition, the best, most effective and most cost-efficient way to supplement vitamin C is to take it as plain ascorbic acid on an empty stomach (at least 2 hours after a meal), when the SVCT1 transport system delivers any dose of ascorbic acid from the stomach into the bloodstream with almost 100% utilisation – but it is only true to ascorbic acid! (Flavonoids inhibit this efficient absorption mechanism). Taken on an empty stomach, plain ascorbic acid rivals the benefits of intravenously administered vitamin C, and actually doubles the maximum blood level, according to a human clinical trial published in 2020! This can only be achieved with plain, cheap, simple ascorbic acid! In addition, only ascorbic acid is certain to have all the effects of vitamin C, ascorbate salts and ascorbyl palmitate are presumed not to, so the name vitamin C is certainly only for the ascorbic acid form, there is no other form in nature anyway.

Vitamin C in an evolutionary context

Let's start at the very beginning, 61 million years ago, or even earlier... I'll briefly present a great paper by Doris Loh:[1]

Ascorbic acid is essential for the functioning of all living things, it is the best (and perhaps the only dose-independent) redox regulator molecule in our bodies, which is important because free radicals are also important regulators of these processes. Too much and too little free radicals are also a problem. Ascorbic acid is essential for keeping these levels at an optimum. Because of this, almost all living things can produce it for themselves, but it is also essential for those that can't. So why did humans and other primates, as well as a few other species have lost the ability to synthesise vitamin C (ascorbic acid)? What advantage could could it pose for them, that is, for us?

Ascorbic acid is produced from glucose and in the process of production, 1 piece of ascorbic acid is produced along with 1 piece of hydrogen peroxide, i.e. free radical molecule. The brain is an inherently highly energy-intensive organ, with the production of a lot of free radicalsduring energy production, so a larger brain or increased brain function requires more antioxidant activity to maintain an optimal redox balance. If there is a sufficient external source of ascorbic acid, then a mutation that eliminates the function/production of the enzyme that synthesizes vitamin C becomes advantageous, since we can obtain it from an external source, so that the glutathione produced in our body does not have to neutralize the hydrogen peroxide free radicals that are a by-product of vitamin C synthesis in our body. This may have resulted in better antioxidant capacity in species that were able to ensure high vitamin C intake and increased brain activity. (Doris in this paper does not link improved antioxidant systems as a prerequisite for increased brain function, this parallel is just my own opinion). Even today, fruits are still the food group with the highest ascorbic acid content, and this was especially true before they were bred, as the vitamin C content of fruits is decreasing due to breeding...[4] I wonder, what was the vitamin C content of fruits millions of years ago? Animals that live on fruit have access to lots of vitamin C, and fruit mainly grows on trees. 61million years ago, man's ancestor (which must have been some kind of shrew-like tree-hopping fruit-eating creature back then) lost the ability to synthesise vitamin C. This coincides with the period of global warming, when everything from the North Pole to the South Pole began to be covered in dense jungle. There was plenty of fruit, so the mutation leading to the loss of the ability to synthesise vitamin C was beneficial. Then, some 10 million years later, there was another global cooling, which caused fruits to shrink, and the reduced ability to break down/secrete uric acid proved to be a useful mutation, as it allowed higher levels of uric acid to be produced, which also has antioxidant effects. In contrast to ascorbic acid, uric acid only has an antioxidant effect outside the cell (extracellularly), whereas it has a specific oxidative effect inside the cell (intracellularly) (ascorbic acid can have both an antioxidant effect inside and outside the cell and eliminates the oxidative effect of uric acid inside the cell). Because of the food shortages that accompanied the global cooling, this high uric acid level proved beneficial in creating insulin resistance and helping fat accumulation in order to survive. But with proper levels of ascorbic acid, the effect of uric acid is not bad (in fact, together they're about like Batman and Robin, at least in one mouse study, where mice were modified to have both uric acid and ascorbic acid levels elevated, they lived significantly longer than normal mice, whereas if you just increased uric acid level but not vitamin C level, they didn't.) In any case, the reduced excretion of uric acid was retained, similarly to the inability to produce vitamin C in modern humans. This is probably because humans had enough vitamin C until they started to breed the fruit and so our elevated uric acid levels compared to other animals remained beneficial, and in no way detrimental. Vitamin C is known to be good for problems correlated with high uric acid levels.

Now let's return to the present day…

I have explained all the above mainly because it is interesting, and because I would like more people to get to know Doris Loh's writings. On the other hand, I hope this will help to clarify that vitamin C is ascorbic acid. Animals do not produce polyphenols, nor do humans. Of course, in plant sources of ascorbic acid there are polyphenols and fibres and minerals and all sorts of things, but it's nonsense to confuse them with ascorbic acid. Bioflavonoids are called P vitamins. I don't really understand where the idea comes from, that polyphenols (and bioflavonoids within them) are also vitamins C. And why vitamins C? In the plural? Vitamin C! There is only one vitamin C, and that is ascorbic acid. To claim otherwise is completely unprofessional (artificially created ascorbate salts also break down into ascorbic acid, which makes them a source of vitamin C). Polyphenols have many good effects, as do many other things and everything works together in unity. One member of the antioxidant system helps another member of the antioxidant system, naturally. In this sense, you could say that all antioxidants are vitamin C. In this sense, vitamins C would also include vitamin E, polyphenols, Q10 and everything... Well, not a very sophisticated approach...

It is also worth considering that fruits are mainly bred for sweetness, flavour and colour, and to be more resistant to insects, pests and environmental conditions. What does it mean? That their polyphenol/flavonoid content may even have increased, since polyphenolic compounds give plants their colour and in many cases polyphenolic compounds help plants tolerate environmental conditions, as well as being produced to repel pests. In addition, by far the richest sources of polyphenols/flavonoids are coffee, red wine, chocolate, tea and onions. Because of their consumption, the polyphenol/flavonoid intake of modern humans is probably significantly higher than at any time in our evolution. Our intake of vitamin C (ascorbic acid), which is very much reduced, because the breeding for flavour mentioned above also meant a reduction of the sour flavour, and ascorbic acid is very sour... I might add that flavonoids like quercetin can also hinder the utilisation of vitamin C.[5] Sugar content has increased, and vitamin C content has decreased a lot in today's fruits. (One source suggests that the vitamin C content of apples, for example, may have fallen by as much as a hundredfold in the last century or so.)[4] Polyphenol content may not have changed much, but it may even have increased. The state we have evolved to is therefore best achieved by supplementing ascorbic acid (unless our intake of coffee, chocolate, onions, fruit, etc. is low, in which case it is also worth supplementing polyphenols).

Studies on vitamin C supplementation

Well, enough for now of speculation and explication, let's see what opinion can be found in literature. Does it prove that other forms have no advantage to ascorbic acid? May it even be beneficial to just supplement with pure ascorbic acid?

Quite a number of human clinical trials have been conducted, in addition to numerous pre-clinical studies, to determine whether there is any difference in the utilisation and effects of naturally occurring (L-) but synthesised ascorbic acid and vitamin C from the consumption of various fruits, vegetables, herbs or extracts of these plants. As it turns out, there is none.[5]

There is only one review study published on this topic,[5] which also includes all studies published to date, as no new studies have been published on this topic since 2013 and this review study is from 2013. Many different studies have compared the utilisation/effects of consuming plain ascorbic acid compared to consuming kiwi, orange, orange juice, cooked broccoli, raw broccoli, raw cabbage, raw cabbage, tomato juice, papaya juice, guava juice, raspberries, potatoes, etc. containing the same amount of ascorbic acid – and there is no difference. (There were sometimes small differences in favour of one or the other, but these insignificant differences may have been due to the difficulty of standardising vitamin C intake in the diet, and the vitamin C content of fruit etc. consumed is more difficult to measure and dose accurately than ascorbic acid, so it may have been measured slightly above or below. This source of error and possible cause of slight discrepancies was also mentioned in the study.)

Of course, vegetables and fruits contain many useful ingredients, fibres, minerals, polyphenols, etc., so obviously vitamin C supplementation is not a substitute for them, but it is a perfect substitute for the vitamin C taken out of today's fruits and vegetables, as well as for the vitamin C intake needed to give us the advantage of our ability to synthesise vitamin C that we have lost during our evolution. (Today, actually there are no vitamin C-rich fruits). Quercetin, for example, one of the most abundant polyphenols (more specifically flavonoids) in fruits and vegetables, specifically inhibits vitamin C uptake and utilisation in cells through several mechanisms.[5] This may be the result of the slightly higher serum ascorbic acid levels and slower urinary excretion measured when quercetin and other flavonoids are consumed with vitamin C.[5] If this was caused because less was getting into the cells, then this is more of a disadvantage than a benefit... higher blood levels could also be due to the antioxidant effect of polyphenols, not to the improvement in the utilisation of ascorbic acid itself, as it is known that the intake of one antioxidant often increases the blood levels of another antioxidant without taking it, due to a sparing effect. However, a large number of studies have shown that there is no correlation between the origin and utilisation of ascorbic acid, and that nature-identical pure L-ascorbic acid is also the perfect, i.e. the cheapest, form. There is no other vitamin C, in fact only ascorbic acid alone has all the vitamin C effects for sure, ascorbate salts such as Na/Mg/Ca-ascorbate or ascorbyl palmitate do not, so only ascorbic acid is definitely a full-fledged vitamin C, nothing else. [2,3,6] This is not to say that other forms are not good, just that there are contexts in which they are less good. Now let's look at why, and also what the benefits are in terms of utilisation, increase in blood levels and entry into/uptake by cells as well as in regeneration when nothing else but pure ascorbic acid is used on an empty stomach... (or titrating it at 200mg, which is not very practical).

Up until 2020, vitamin C utilisation appeared to be close to 100% up to an amount of 200 mg, but above that, utilisation starts to decline and excretion increases [6] (although even with 1000 mg taken at a time, utilisation is still around 50%). Blood concentrations above 220 micromoles per litre cannot be achieved with oral vitamin C, [7] only by intravenous administration,[7] or by dissolution with liposomal and other nanocolloid systems by ingesting 10-30 g of vitamin C (which is equivalent to ingesting about 50-150 ml of oily emulsion or "sludge") [[8,9,10]

New discovery made in 2020

In 2020, however, a major discovery was made in a human clinical trial:[2, 11] Vitamin C levels in the blood were measured minute by minute after ingestion (this can be done with a simple blood glucose meter at home). Subjects were given different doses of vitamin C and vitamin C forms on an empty stomach for different periods of time, and then the change was measured continuously minute-by-minute in their blood glucose difference, which shows their blood vitamin C levels. (In previous studies, blood levels of vitamin C were only measured every half hour or so) 3 particularly interesting observations were made in this study:

In one study, 10 g of ascorbic acid taken orally on an empty stomach was compared with 11.3 g of Na-ascorbate given intravenously (this is because it is equivalent to 10 g of ascorbic acid. However, ascorbic acid cannot be administered intravenously, only sodium (Na) ascorbate, because of the pH of the blood...). The result was a surprise: Taking 10 g of ascorbic acid at a time raised vitamin C level in the blood twice as high as 10 g of vitamin C taken intravenously! More interesting is how: it was this high for a short time in the 3rd minute after the intake, then a few minutes later it dropped back to the initial level, then a few minutes later it increased again to extremely high but less high than before, then dropped again, then increased again but in a rate less and less than before. That is to say, for about half an hour it was fluctuating. (The reason for this fluctuation is presumably that when the level drops, it docks into the receptors in the cells, during which time it disappears from the blood, then regenerates in the cells and is released back into the blood, again and again... And the fact that it appears in the bloodstream within 3 minutes of ingestion is because vitamin C can be absorbed directly from the stomach if it is in the form of ascorbic acid, in a high enough concentration and if the stomach is acidic enough. The stomach is home to the SVCT1 transporter, which can release unlimited amounts of ascorbic acid and possibly other weak acids into the bloodstream with apparently incredible efficiency, if the stomach is acidic enough. [2,11] Fortunately, humans produce the same amount of stomach acid as scavengers, so once you have min. 2-3 hours without food, the pH of a healthy person's stomach is around 1, which is 10-100 times more acidic than, for example, that of predators.[12]

Image source: reference 11.

The other interesting thing was that 10 g of Na-ascorbate taken orally, like ascorbic acid, did not raise blood levels anywhere near that and the uptake was only a fraction of that! One reason is that Na-ascorbate may have raised the pH of the stomach. [2,11]

Image source: reference 11.

The third interesting point was that no fluctuations in Na-ascorbate levels have been observed with any dosage of Na-ascorbate, suggesting that for some reason it cannot "dock" into a particular receptor in cells to regenerate and therefore does not rise again and again. [2,3,11]

The implication is that ascorbate salts presumably do not have all the effects of ascorbic acid, although this may only be due to their poor utilisation at high doses. In the end, it's pretty much all the same. Certainly only ascorbic acid can be said to have all the effects of vitamin C, [2,3] which is why it is the best choice, not just because it can achieve the highest blood levels and perfect absorption at high doses, and because it is the cheapest and most economical. The combination of these facts is also very positive from a user/customer perspective.

What about ascorbyl palmitate?

In this regard, human studies have found no or only slight differences in utilization compared to ascorbic acid. Ascorbyl palmitate showed slightly higher blood levels and slower excretion in one study and no difference in another.[13] It's hard to evaluate these old studies knowing that blood levels were not measured every minute, but only every half hour at best, and half an hour later the majority of the surge in ascorbic acid had long subsided (it was highest in the first 15 minutes, especially the first few minutes after the 3rd minute). So unfortunately no pre-2020 test can give an actual picture, because they missed the point of it all by measuring blood levels only half an hour later, by which time ascorbic acid has already been docked into the cells many times... Anyway, ascorbyl palmitate is absorbed from the small intestine, where it is first broken down into ascorbic acid and palmitic acid.[13] If it does pass through the intestinal wall in its unaltered form (in the case of large intakes), it is taken to the liver and broken down into ascorbic acid and palmitic acid before entering the bloodstream.[13] That is, it too is eventually broken down into “only” ascorbic acid before it gets into our blood.  It can provide more uniform absorption, and in this respect it is actually a good question whether it is a disadvantage or an advantage... It is actually much more expensive, much less natural (it does not occur at all in nature, nor in living organisms, so the ascorbyl palmitate molecule can be called unnatural, although this is not a problem, as it is completely broken down into ascorbic acid and palmitic acid before absorption, which are already natural molecules). I'm sure it's very good in external uses, for preserving cosmetics, but I don't see any other benefit.

Summary

Expensive vitamin C produced from plant extracts has no advantage over plain, cheap, naturally-derived synthetic vitamin C (L-ascorbic acid). Surprisingly, they can have a drawback, although only at high doses. Of course, eating the plants themselves can have various benefits, but not in the context of their vitamin C content, but simply because they may have other benefits than vitamin C. Our evolutionary intake of vitamin C can practically only be met by supplementing with ascorbic acid. The best way to do this is with plain ascorbic acid, which certainly has all the effects of vitamin C, whereas ascorbate salts have recently been strongly suspected of not having all the positive effects of vitamin C. In addition, ascorbate salts not only lack the natural "blood level surge" or regeneration in cells and the back-and-forth between the cells and the blood, which is characteristic of vitamin C, i.e. their metabolism differs from the natural form of vitamin C, but also have a fractional utilisation compared to plain ascorbic acid when used in high doses. The best way to get the best benefit is to take it on an empty stomach (min. 3 hours after a meal or in the morning on an empty stomach. A little plain salt or betaine HCl, a stomach acid booster, will also help perfect absorption if there is a stomach acid deficiency). Thus, blood levels equivalent to intravenous dosing can be achieved when taking high doses. In principle, just a few grams of any vitamin C a day will provide high enough blood and tissue levels, but it seems important to provide a significant proportion or even all the amount in the form of ascorbic acid rather than ascorbate salt. I would definitely recommend supplementing with at least 500mg of ascorbic acid per day, but preferably a few grams, about 1g every 4 hours on an empty stomach, to ensure a high enough "evolutionary" level of vitamin C. There is no point in taking any form other than plain ascorbic acid, unless you want to replace intravenous vitamin C treatment, in which case extreme doses of liposomal or other nanocolloid-integrated vitamin C may make sense, although this is a little uncertain (if someone does take liposomal or any vitamin C for this reason, I suggest they check their blood glucose levels with a blood glucose meter to see if they are going above about 250 micromoles/l (0.25mmol/l) significantly, because if not, it will have the opposite effect.. This value is considered to be the cut-off point above which hydrogen peroxide production is increased, which is the main purpose of intravenous high-dose vitamin C treatments. This 0.25mmol/l as a cut-off is also quite uncertain, so I would set 0.5mmol/l as a minimum, and if it is not reached, I think it is a waste to be tried for IV-C replacement).