Nutrient - Vitamin C - Technical Considerations
What's in your vitamin C supplement?
As probably the best known and most talked about vitamin, it is one of the most widely utilised supplements and is available in a number of forms. Here, we take a closer look at vitamin C and its importance in our diet, and discuss what you need to know when making your choice of supplement.
Most vertebrates synthesise vitamin C, or ascorbic acid, in the liver, from glucose; but humans, primates, fruit bats, guinea pigs and some other mammals cannot. Humans lost this capacity, as a result of a defective form of the gene for the enzyme, L-gulonolactone (GULO), which is required for the final step in the synthesis of ascorbate from glucose(1). Experts suggest that these mutations occurred approximately 40 million years ago. Therefore, for non-ascorbic-acid-synthesising mammals, including humans, vitamin C must be consumed through the daily diet(2). Indeed, the human diet contains both vitamin C (ascorbate) and its oxidised form, dehydroascorbic acid (DHA), which is actually the most abundant. DHA is also produced in the lumen of the intestines, due to the presence of oxidants(3), and is generated in oxidative reactions that are associated with normal cellular metabolism.
Ascorbic acid is water-soluble and one of the least stable vitamins, being easily destroyed by cooking, although it can be better retained when foods are steam-cooked. It is easily oxidised in air and is sensitive to both heat and light. Ascorbic acid was first isolated from lemons in 1932, although it was discovered much earlier, when sailors realised it to be a cure for scurvy. Other cultures around the world also discovered excellent sources, such as rosehips, as well as other fruits, because of their rich vitamin C content.
Absorption of ascorbic acid occurs in the duodenum, proximal jejunum and buccal mucous membrane(4), and usually leaves the blood again within three to four hours, hence the need for regular intakes, either within the diet or supplementally, at intervals rather than simultaneously. Transportation into and out of the intestinal cells occurs by facilitated diffusion using the GLUT1 glucose transporter, which is also the transporter of DHA. The reduced form of vitamin C (ascorbic acid) is absorbed by active transport via SVCT1 (a sodium-dependent L-ascorbic acid co-transporter). Once in the cell, the oxidised form is reduced back to ascorbic acid by glutathione or reducing proteins. Which process dominates is yet to be determined. At very high concentrations of ascorbic acid in the gut, the two main processes are likely to reach saturation, with simple diffusion becoming more significant to the total rate of absorption. This will result in a reduction of the overall rate of absorption. Theoretically, therefore, by reducing the concentrations of ascorbic acid in the gut, overall absorption should be heightened, which could be achieved by reducing the rate of movement of vitamin C into the intestine. This effect could also be enhanced by consuming ascorbic acid with food.
Absorption decreases as intake increases. At doses of up to 200mg per day, bioavailability of ascorbic acid is approximately 100% and at 500mg per day absorption can decline to less than 50%. In real terms, ascorbic acid competes for absorption with glucose, due to their structural similarity, which may explain why some studies have not always confirmed the benefits of vitamin C. The studies may not have taken into account dietary carbohydrate competing for ascorbic acid absorption.
Ascorbic acid is probably one of the most controversial and researched vitamins. However, despite sometimes negative press, its role as a powerful antioxidant and immune booster, as well as its role in growth mechanisms of all body tissue; especially in the formation of collagen (an important structural component of bones, teeth, tendons, ligaments blood vessels and skin), L-carnitine (important for the transportation of fat to the mitochondria) and in the conversion of dopamine to noradrenaline (a neurotransmitter playing a number of important roles in brain function and mood)(5); are now well accepted and understood. Vitamin C is a well-known, water-soluble reducing agent (electron donor) and antioxidant that quenches free radicals produced by normal metabolism(6). However, to function as an antioxidant, high levels need to be maintained in the body.
In addition, there has also been much research to support its important role in immunity. In a recent meta-analysis of randomised trials, published over a number of years, researchers concluded that although the evidence was preliminary, it was solid enough to recommend vitamin C supplementation for pneumonia, alongside conventional medicine(7). And, additional meta-analysis of 29 trials involving over 11,000 participants provided evidence that vitamin C has a small but significant effect on reducing the duration and severity of cold symptoms(8).
Ascorbic acid has been shown to stimulate the immune system by enhancing T-cell proliferation in response to infection. It appears that cytokines produced within the immune system stimulate B-cells to synthesise immunoglobulins, in order to control inflammatory reactions. It has been further shown that ascorbic acid protects T-cells and enhances their production(9).
It would seem that mammals who synthesise the vitamin produce more, especially when subject to stress, than the level normally obtained from the diet. It appears that recycling of vitamin C does not occur efficiently in those animals that synthesise the vitamin, which promotes the need to synthesise it in greater quantities. This evidence undermines the rationale for the mega dose approach of its proponents, such as Dr Linus Pauling. The basis for these doses was to try to achieve cellular vitamin C concentrations similar to those achieved by our vitamin C-synthesising counterparts. But these studies did not take DHA into consideration, which may be pointing to lower daily requirements of vitamin C(10).
A recent study suggests that humans may have also evolved a mechanism that enables them to utilise the ascorbic acid in the body efficiently by recycling dehydroascorbate into ascorbic acid, which can then be re-used by the body. The research in Cell(11) suggests a possible physiological adaptation. Humans produce red blood cells in plentiful supply. Human red blood cells strongly favour DHA over glucose and these cells express abundant GLUT1. This GLUT1 transports DHA into the red blood cells, which then enters the mitochondria and is converted to the reduced and antioxidant form we know as ascorbic acid. The red blood cells of other mammals can take up only very little DHA. This further explains the need for mammals that synthesise their own vitamin C to metabolise it in greater quantities. Indeed, it has been calculated that if humans were able to synthesise ascorbic acid, they would do so at the rate of around 2-4g per day under normal conditions and up to 15g per day under stress.
When asked why supplementation should be necessary, one should remember that the traditional hunter/gatherer diet was based on fresh, wild fruits and, therefore, our consumption of vitamin C was naturally much higher than it is today. These foods were likely to have a much higher vitamin C content than modern, commercially farmed foods.
Supplements of vitamin C are available in many forms, including synthetic ascorbic acid, mineral ascorbates, synthetic ascorbic acid with bioflavonoids and vitamin C presented in a fermented product. Interestingly, there appears to be no difference in biological activities or bioavailability between natural and synthetic vitamin C(12). In the ascorbate forms, mineral salts act as a buffer and are, therefore, less acidic than ascorbic acid and may help to reduce the incidence of gastrointestinal disturbances, as well as providing an additional source of minerals, for example, calcium or magnesium.
As we know, nutrients rarely work in isolation and, since vitamin C is frequently found in nature with bioflavonoids in fruits and vegetables, it makes scientific sense to produce supplements that are as near to food ‘as nature intended’. Indeed, Albert Szent-Gyorgyi was awarded the Nobel Prize in 1937 for his work in isolating vitamin C from peppers and he believed that other plant substances protected vitamin C and worked synergistically with it. In addition, Vinson and Bose(13) showed that synthetic ascorbic acid with a natural citrus extract (containing citrus bioflavonoids, proteins and carbohydrates in the citrus extract) was absorbed at a slower rate and was more bioavailable than synthetic ascorbic acid. These flavonoids are found largely in berry and citrus fruits and exhibit potent antioxidant activity. Indeed, researchers at the University of Medical Sciences in Poland(14) recently investigated the effects of citrus flavonoids and found that they strongly inhibited white blood cell ability to generate the superoxide radical. In addition, researchers in Taiwan(15) were able to identify that citrus bioflavonoids have neuroprotective effects against H202 (hydrogen peroxide), even at low concentrations. Other potential benefits of flavonoids include a reduction in the risk of coronary heart disease(16).
Efficacy and absorption are key in any supplement and Higher Nature has developed a vitamin C product that is comparable in antioxidant effect to 1,000mg of vitamin C, while only containing 250mg, as well as other bioflavonoids and food-based nutrients. By adding vitamin C and citrus bioflavonoids to a completed fermentation of the food yeast Saccharomyces cerevisiae, enhanced absorption and bioavailability of all the nutrients is achieved. Fermented yeast is a whole food, in itself, providing a valuable source of vitamins, amino acids and other nutrients, in a form the digestive system recognises, which enhances absorption and bioavailability of all the nutrients present.
Many people are unable to swallow tablets or capsules. Therefore, liquid forms are ideal. The challenge for any supplement manufacturer is to produce a product that is palatable and contains an acceptable daily dose of the nutrient(s). Traditionally, effervescent vitamin C tablets are flavoured and sweetened with unnatural and potentially, harmful synthetic sweeteners and flavourings, in order to get the required taste. Sodium lauryl sulphate is used in numerous hair and personal care products, since it is inexpensive and is also an effective foaming agent, often found in effervescent tablets. However, it has also been found to be potentially carcinogenic, so one should be extremely cautious when looking at effervescent vitamin C products.
As with so much in life, it is not about quantity but quality.
1. Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K. Cloning and chromosomal mapping of the human non-functional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J Biol Chem.1994; 269:13685-8
2. Linster CL, Van Schaftingen E. Vitamin C Biosynthesis, recycling and degradation in mammals. FEBS J 2007; 274; 1-22
3. Kyrtopoulos SA, Pignatelli B, Karkanias G, Golematis B, Esteve J. Studies in gastric carcinogenesis V. The effects of ascorbic acid on N-nitroso compound formation in human gastric juice in vivo and in vitro. Carcinogenesis 1991; 12: 1371-1376
4. Basu T, Donaldson D. Intestinal absorption in health and disease. Micronutrients 2003; 17:957-979.
5. Rebouce CJ. Ascorbic acid and carnitine biosynthesis. Am J Clin Nutr. 1991; 54 Suppl 6:s1147-52
6. Carr A, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am. J. Clin. Nutr 1999; 69:1086-1107.
7. Vitamin C Dietary supplements: An Objective Review of Clinical Evidence. Part III (Volume 3, pages 159-168, 2007, Mark A. Moyad, Seminars in preventative and alternative medicine) (Elsevier)
8. Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews. (4): CD000980
9. Campbell JD, Cole M, Bunditrutavorn B, Vell, AT. Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis. Cell Immunol 1999, 194:1-5
10. Nualart, FJ, Rivas CI, Montecinos VP, Godoy, AS, Guaiquil VH, Golde DW and Vera JC. Recycling of Vitamin C by a Bystander Effect. J Biol. Chem 2003, 278: 10128-10133.
11. Troadec MB, Kaplan J. Some vertebrates go with the GLO. Cell 2008; 132:921-2
12. Gregory JF, 3rd. Ascorbic acid bioavailability in foods and supplements. Nutr Rev. 1993; 51 (10): 301-303
13. Vinson, JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988 Sep; 48(3): 601-4.
14. Zielinska-Przyjemska, M, Ignatowicz, E. Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism. Phytother Res. 2008 Dec; 22 (12): 1557-62
15. Huang, SL, Yen GC. Neuroprotective effects of the citrus flavones against H202-induced cytotoxicity in PC12 cells. J Agric Food Chem. 2008 Feb 13; 56 (3): 859-64. Epub 2008 Jan 12.
16. Geleijnse, JM, Launer LJ, Van der Kuip DA, Hofman, A, Witterman, JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam study. Am J Clin Nutr 2002, 75:880-886