Vitamin C
Sue McGarrigle ND DipION CNHC mBANT
Introduction
This article has been written in response to the many questions about Vitamin C that have cropped up over the years during my time educating and training practitioners, particularly with regard to absorption. It has been one of the most researched vitamins over the years and has also been one of the most controversial. By increasing it in the diet in its most natural state Vitamin C can play a key nutritive role in the health of our clients, particularly in view of just how many foods, whatever form they take whether fruit, vegetable or herbs that contain it, are often found to be missing in many people’s diets today.
Vitamin C
Vitamin C is essential to life; at some point during our evolutionary process we had such an abundance of food rich in vitamin C that our bodies lost the ability to manufacture it. Vitamin C (L-ascorbic acid or ascorbate) is the generic descriptor for compounds having antiscorbutic activity. Vitamin C is a six-carbon compound structurally related to glucose, consisting of two inter-convertible compounds: L-ascorbic acid, (AA) which is a strong reducing agent, and its oxidised derivative, L-dehydroascorbic acid (DHAA). Humans now lack the L-gulonolactone oxidase enzyme that is critical for the last step of vitamin C synthesis1. Most animals are able to synthesise vitamin C from glucose and galactose with the exception of guinea pigs and higher primates who also shared our fate.
To avoid the consequences of not making our own vitamin C, we are now highly dependent on the dietary intake of vitamin C; humans cannot survive without it but for many adults and children with a daily dietary lack of a broad range of fruit and vegetables this essential water soluble nutrient may, through deficiency, prevent the fulfilment of its important roles in the body. Notably, in 2003, Knowles et al demonstrated that vitamin C regulates a key stress-induced transcription factor called Hypoxia Inducible Factor 1α (HIF1α), a protein that, when activated, regulates the expression of hundreds of stress-related genes.2
Specifically, the activation of HIF1α occurs in the absence of adequate oxygen or vitamin C supply. Grano and De Tullio proposed that organisms that have lost vitamin C biosynthesis have an advantage: they can finely regulate HIF1α activation on the basis of the dietary intake of vitamin C3. When vitamin C supply is sufficient, the HIF transcription factor is less active than in conditions of vitamin C deficiency. In other words, the lack of vitamin C biosynthesis allows our bodies to know more about our nutritional status and consequently set the proper baseline of HIF1α expression, which is acting like a sensitive titration system. There is a third yet still unexplored possibility: we know from other studies that pseudogenes are not inert, but can have a significant role in epigenetic control of gene expression4. Could this also apply to the human gulonolactone oxidase pseudogene? Time and research will tell.5
Naturally-occurring vitamin C is found in many fruits and vegetables. Food constituents work synergistically with nutrients in the presence of a number of enzymes, co-enzymes, co-factors and trace minerals. Multiple biochemical interactions take place and the nutritional and biochemical role of vitamin C is enhanced by the associated activity of associated food factors.
Linus Pauling, the Nobel Prize winning scientist recommended using as many food sources as possible to obtain vitamin C with complete nutritive co-factors. Rose hips are a good food example as they contain a high content of vitamin C as well as polyphenols and unsaturated fats, and they are given to guinea pigs to naturally increase their vitamin C levels. Children were encouraged to gather rose hips during the Second World War and were given rose hip syrup as other citrus fruits were not available. Recent clinical research has shown that rose hip powder relieves osteoarthritis in vitro. Scientists believe that rose hip powder provides ‘robust’ anti-inflammatory responses and reduces the catabolic processes as found in osteoarthritis.6
Ascorbate is a major metabolite in plants. It is an antioxidant and, in association with other components of the antioxidant system, it protects plants and their seeds against oxidative damage resulting from aerobic metabolism, photosynthesis and a range of pollutants. Ascorbate occurs in the cell wall where it presents a line of defence against ozone. Gallie and Chen, who helped develop technology to increase vitamin C in plants, showed in a recent study that a boost of the vitamin can help plants defend themselves against the ravages of ozone -- smog's particularly damaging component. They also found that increasing the level of dehydroascorbate reductase (DHAR), a naturally occurring enzyme that recycles vitamin C in plants and animals, increases the level of the vitamin and results in the production of twin and triplet seedlings in a single seed. A question raised by the study is whether vitamin C might have a similar effect in humans.
Deficiency signs of Vitamin C
Typical symptoms of vitamin C deficiency may present as fatigue, bleeding gums, red spots, anaemia, decreased ability to fight infection, poor wound-healing , dry, splitting hair, easy bruising, nose bleeds, possible weight gain because of slowed metabolism, rough, dry, scaly skin, swollen and painful joints, weakened tooth enamel and tooth loss. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which all contain collagen. In severe vitamin C deficiency scurvy may occur and early symptoms of scurvy-like fatigue may result from diminished levels of carnitine, or from decreased synthesis of the neurotransmitter norepinephrine, as vitamin C is required for their synthesis8. In the latest figures from the UK Department of Health, reported cases of scurvy in children increased by 50% from 2004 to 2007 where diet was severely limited.
Adults from all countries/regions of the UK were screened between 2003-2005 in the Low Income Diet and Nutrition Survey to identify low-income/materially deprived households. A valid plasma vitamin C measurement was made in 433 men and 876 women. An estimated 25% of men and 16% of women in the low-income/materially deprived population had plasma vitamin C concentrations indicative of deficiency and a further fifth of the population had levels in the depleted range. This led to the conclusion that health professionals need to be aware that poor vitamin C status is relatively common among adults living on a low income.9
Apart from people on low incomes there are several groups who are at more risk of vitamin C deficiency:
People dependent on drugs and/or alcohol who may not have a healthy, balanced diet.
People who go on fad diets.
People with a medical condition such as Crohn's disease and Ulcerative Colitis that affects the body's ability to digest and absorb food.
Older people who may eat a less varied diet.
Smoking affects the absorption of vitamin C from foods and also vitamin C is used up in the body more quickly in those who smoke.
Increased need due to increased utilisation in pregnant and lactating women, thyrotoxicosis, surgery, and burns.
Anorexia nervosa or anorexia from other diseases such as AIDS or cancer.10,11
Absorption of vitamin C
Vitamin C refers to a number of vitamers that have vitamin C activity in animals, including ascorbic acid (AA) and its salts, and some oxidised forms of the molecule like dehydroascorbic acid (DHAA). Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH.12
Gastrointestinal absorption of vitamin C is efficient and occurs in the small intestine via a saturable active transport mechanism. Absorption efficiency of low oral doses of vitamin C (4 – 64 mg) may be as high as 98%, but decreases with increasing doses of the vitamin13. At the intestine and cells AA is oxidized to DHAA, which is more quickly transported across the cell membrane. Once inside the tissue or intestinal epithelium the vitamin is reduced back to AA. The degree of intestinal absorption decreases as intake of AA increases. Intakes of 1 to 1.5 grams results in 50% absorption, but at intakes over 12 grams only 16% of the vitamin is absorbed. In contrast, an intake of less than 20 mg has a 98% absorption rate. Absorption of vitamin C is greater when several individual doses of vitamin C, in quantities less than one gram, are taken throughout the day rather than one megadose. Eighty to ninety-five per cent of the vitamin C found in foods is absorbed. Metabolites of vitamin C including dehydroascorbate (DHAA), oxalic acid, 2-O-methyl ascorbate, and 2-ketoascorbitol are excreted from the body via the urinary system. The kidneys play a major role in vitamin C excretion and retention. DHAA and AA can be reabsorbed by the kidney tubules as long as body pool levels are equal to or less than 1500 mg. Levels within the body that are 1500 mg or less will result in no urinary excretion of vitamin C.14,15
Vitamin C sites
Vitamin C is widely distributed in all tissues of the body; there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina. Other tissues with intermediate levels of vitamin C include the kidneys, brain, liver, lungs, and thyroid16. The body's pool of vitamin C can be depleted within 1-3 months of severe or total vitamin C deficiency.10
Mechanism of Action
Vitamin C is an electron donor and therefore a reducing agent. A reactive and possibly harmful free radical can interact with ascorbate. The reactive free radical is reduced, and the ascorbyl radical formed in its place is less reactive. Reduction of a reactive free radical with formation of a less reactive compound is sometimes called free radical scavenging or quenching.
Ascorbate is therefore a good free radical scavenger due to its chemical properties17,18.The role of ascorbic acid as a biological reducing agent may be linked to its prevention of degenerative diseases, such as cancer and cardiovascular diseases.19
All known physiological and biochemical actions of vitamin C are due to its action as an electron donor. In humans, vitamin C acts as an electron donor for eight different enzymes. At least for some of the enzymes, ascorbate adds electrons sequentially, with formation of the ascorbyl radical intermediate. Of the eight enzymes, three participate in collagen hydroxylation. These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule, thereby greatly increasing stability of the collagen molecule triple helix structure, an important structural component of blood vessels, tendons, ligaments, and bone. Two other vitamin C dependent enzymes are necessary for synthesis of carnitine. Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation. The remaining three vitamin C dependent enzymes have the following functions: one participates in the biosynthesis of norepinephrine from dopamine, one adds amide groups to peptide hormones, greatly increasing their stability, and one modulates tyrosine metabolism helping the body with its response to stress.20
Functions of vitamin C
It has been claimed that vitamin C protects against the common cold. Beneficial effects on conditions such as cancer, vascular disease, cataracts, diabetes, asthma, arthritis, Parkinson’s disease, autism and depression have also been suggested.13
Vitamin C’s health benefits have been well documented over many years through peer-reviewed research and include its properties as:
Maintenance and integrity of the connective tissue
A major water-soluble antioxidant (against everyday activities exaggerated by stress, disease, sunlight, smoke and pollution). The water-soluble properties of vitamin C allow for the quenching of free radicals before they reach the cellular membrane. Ascorbate is particularly effective in protecting the vascular endothelium, which is especially vulnerable to oxidative stress.
Tocopherol and glutathione also rely on AA for regeneration back to their active isoforms. The relationship between AA and glutathione is unique. Vitamin C reduces glutathione back to the active form. Once reduced, glutathione will regenerate vitamin C from its DHAA or oxidized state.
Evidence for in vivo antioxidant functions of ascorbate include the scavenging of reactive oxidants in activated leukocytes, lung, and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion21. As a highly effective antioxidant, even in small amounts, vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA), from damage by free radicals.22
Anti-atherogenic against heart disease and stroke.23,24
For eye health particularly in the lens and aqueous humour, studies have shown a decreased level of vitamin C in the aqueous humour as well as the overall body when cataracts are forming.28
As a support to the immune system.
A supporting role in respiratory function particularly in strenuous exercise and the effects of cold climate.30,31
Other fundamental benefits are listed below:
Research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids, which may have implications for blood cholesterol levels and the incidence of gallstones.32
Vitamin C regulates iron distribution and storage through its regulation of the ratio of ferritin to hemosiderin.33
It helps convert tryptophan to 5-hydroxytryptophan (5HTP).
Vitamin C enhances the antioxidant activity of vitamin E, a fat-soluble free radical scavenger.34
It also possesses anti-histamine activity and may help reduce some inflammatory reactions.35-37
Vitamin C also acts as a chelating agent and aids in the detoxification of toxic metals such as lead.38
Side effects
Vitamin C is a very safe vitamin, especially in a non-acidic form. Vitamin C absorption can be impaired by a number of factors. A single large dose saturates the enzyme kinetics for vitamin C, leading to excess AA in the intestinal lumen, which may cause numerous gastrointestinal problems. Pectin and zinc also inhibit AA absorption, but this mechanism is not well understood. A high iron concentration in the gastrointestinal tract may cause oxidative destruction and in turn impair uptake.14
Pro-oxidant activity
Under certain conditions, some anti-oxidants can also exhibit a pro-oxidant mechanism of action. Vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide39. Ascorbic acid has been shown to reduce transition metals, such as cupric ions (Cu2+), to cuprous (Cu1+), and ferric ions (Fe3+) to ferrous (Fe2+) during conversion from ascorbate to dehydroascorbate in vitro40. This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper are bound to diverse proteins41.
Oxidation reactions are crucial for life, but they can also be damaging; Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage42. Vitamin C is used in isolate form at high doses particularly in cancer therapy, however this is not usage for nutritional value but as a therapeutic adjunct with a drug-like action. Ascorbate at pharmacologic concentrations was found to be a pro-oxidant, generating hydrogen peroxide dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells43. A study completed in late 2011 in Germany compared breast cancer patients receiving IV vitamin C and standard therapy together, versus standard therapy alone. Those receiving IV vitamin C experienced a marked reduction (nearly 50%) in unpleasant symptoms and chemo/radiotherapy side effects such as loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis44. Research is ongoing into the effects of vitamin C as a pro-oxidant.
Guidance levels
The Department of Health Expert Group on vitamins and minerals (EVM) suggested vitamin C to be of low toxicity, though adverse effects, in particular on the gastrointestinal system, may occur in subjects consuming quantities of vitamin C greater than 1000 mg/day. The precise dose at which such effects occur is variable. These effects may be a serious problem for individuals with disordered gastrointestinal function. A limited study by Cameron and Campbell45 suggests a lowest observed adverse effect level (LOAEL) for gastrointestinal effects in humans of 3000-4000 mg/day. For guidance purposes, based on a LOAEL of 3000 mg/day, and applying an uncertainty factor (UF) of 3 for LOAEL to no observed adverse effect level (NOAEL) extrapolation, a supplemental dose of 1000 mg/day supplement would not be expected to have any significant adverse effects. The dose is equivalent to 17 mg/kg body weight per day in a 60 kg adult. A guidance level for total vitamin C intake has not been estimated since adverse effects appear to follow supplemental, bolus doses rather than intake of vitamin C in food. It should be noted that higher levels of vitamin C may be without adverse effects in many individuals.A number of potentially vulnerable groups have been identified; these include individuals who are heterozygous for haemochromatosis and thalassaemia, or those with a pre-disposition to urinary or renal stones. Data on the possible adverse effects of vitamin C on these individuals are also conflicting, but appear to occur at intakes above 1 g/day.46
New research
Tuberculosis
According to new research, vitamin C can kill ‘superbug’ varieties of tuberculosis (TB) bacteria that have grown immune to every available drug, giving hope to millions of people who are infected every year. The vitamin appears to kill multi-drug-resistant TB bacteria, which affects 650,000 worldwide every year, and is responsible for most of the annual 1.4 million deaths the disease causes. The bacteria are resistant to every drug, including isoniazid, the first-line treatment.
Researchers at Yeshiva University made the discovery by accident. The team suspected that cysteine was helping to kill TB bacteria by acting as a reducing agent that triggers the production of reactive oxygen species, which can damage DNA. "We predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture— something totally unexpected." Dr William Jacobs stated. “To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent— vitamin C,” said Dr. Jacobs. “The combination of isoniazid and vitamin C sterilized the M. tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible TB, but also sterilized MDR-TB and XDR-TB strains”.47
Pregnancy
University of Copenhagen scientists have found that maternal vitamin C deficiency can have significant effects on a baby's brain development, which cannot be corrected with after birth vitamin C supplementation. This new research brings further evidence that the mother's diet is crucial in shaping the health of her offspring.48
Bone density
A study team found that mice not receiving vitamin C supplementation had a much lower bone mineral density (BMD) as compared to the control groups. Supplemented animals retained normal BMD, suggesting vitamin C prevented BMD loss in this group. The researchers also commented that vitamin C could provide a natural method to maintain bone health without the use of pharmaceuticals in many ageing adults at risk for osteoporosis.49
Diabetes
The American Journal of Physiology: Endocrinology and Metabolism published a medical study in January 2011 showing the positive effects that rose hips have on diabetic mice. Rose hip powder was fed to diabetic mice, along with a high fat diet. Lean mice were fed this diet for twenty weeks, while obese mice were fed this diet for ten weeks. Rose hip powder was shown to be able to not only prevent a weight increase in the mice, the obese mice also lost weight. Glucose tolerance tests showed the mice on a diet which included rose hip powder tolerated glucose better than the control mice. There was also a reduction in fat cells (lipids) in the liver.
In addition to these benefits, the total blood cholesterol in the mice that ate rose hip powder was lowered. The ratio between LDL and HDL cholesterol levels was also improved. The study concluded that rose hips prevented a diabetic state and lowered the lipid profile in mice.50
Summary
Around 90% of vitamin C in the diet comes from fruit and vegetables. Cooking reduces vitamin C content by 30-40%.
The recommended daily intake of vitamin C in the diet depends on age and sex.
In October 2009 the recommended daily amount within the European Union was increased from 60mg to 80mg daily51
Recommended nutrient intakes increase in pregnancy to 50 mg/day in the last trimester of pregnancy and, during lactation, to 70 mg/day.52
The content of vitamin C in fruits and vegetables can be influenced by various factors such as:
Genotypic differences
Preharvest climatic conditions and cultural practices
Vitamin C content in plant tissues is affected by the intensity of light during the growing season
Nitrogen fertilizers at high levels tend to decrease the vitamin C content in many fruits and vegetables
Maturity and harvesting methods and postharvest handling procedures: temperature management after harvest is the most important factor to maintain vitamin C content of fruits and vegetables; losses are accelerated at higher temperatures and with longer storage durations
Conditions favourable to water loss after harvest result in a rapid loss of vitamin C especially in leafy vegetables.
The retention of vitamin C is also lowered by bruising, and other mechanical injuries, and by excessive trimming.53
Given our reliance on mass production of fruit and vegetables and the increasing tendency to transport such products long distances from farm to table, it is important to ensure that our clients’ vitamin C levels are appropriate for their personal lifestyle and health requirements.
About the Author
Sue McGarrigle is a clinical nutritionist and naturopath and has practised as a clinical Nutritionist since graduating from ION in 2001. As Technical Manager at Biounutri, Sue has helped to launch a range of innovative products for practitioner use since joining the company in 2008. As a lecturer to college and university students to masters level, Sue has trained hundreds of healthcare and medical practitioners in many aspects of nutritional therapy and continues to advise practitioners about products, clinical protocols and drug/nutrients interactions. Sue has written specialist nutrition articles for magazines and newspapers and made contributes to several books as well as speaking at national conferences.
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