The German, Austrian, and Swiss nutrition societies are the editors of the ‘reference values for nutrient intake'. They have revised the reference values for the intake of vitamin C and published them in February 2015. The average vitamin C requirement in healthy adults is considered to be the vitamin C amount that compensates for the metabolic losses of vitamin C, and ensures a fasting ascorbate plasma level of 50 µmol/l. Based on the present data from studies with non-smoking men, metabolic losses of 50 mg/day are assumed, as well as an absorption rate of 80% and an urinary excretion of 25% of the vitamin C intake. Taking this into account, the calculated average requirement in men is 91 mg/day. Considering a coefficient of variation of 10%, a reference value (recommended intake) of 110 mg/day for men is derived. The vitamin C requirement in women as well as in children and adolescents is extrapolated from the requirement in men and in relation to their body weight. This results in a recommended intake of about 95 mg/day for adult women. Because the requirement in pregnant and lactating women is increased, higher recommended intakes are derived for them, 105 mg/day for pregnant women from the fourth month on and 125 mg/day for lactating women, respectively. For boys and girls at the age of 1 to under 15 years, there are increasing recommended intake values from 20 to 85 mg/day. For male and female adolescents, at the age of 15 to under 19 years, the recommended intake is 105 and 90 mg, respectively. As smokers have higher metabolic losses and lower plasma levels of vitamin C than non-smokers (turnover is 40% higher), the reference value for vitamin C intake is set to 135 mg/day for female smokers and 155 mg/day for male smokers. For infants in their first year of life, the reference value (estimated value) is set to 20 mg vitamin C/ day, based upon the lowest observed vitamin C intake for infants in the United Kingdom and the United States, that obviously meets the requirement in infants and that is 3 times higher than the amount necessary to prevent scurvy (7 mg/day).
The D-A-CH ‘reference values for nutrient intake'  are jointly issued by the nutrition societies of Germany, Austria and Switzerland (the abbreviation D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)). Currently, the ‘reference values for nutrient intake' are being revised. Following the revised reference values for vitamin D , calcium  and folate , the revised reference values for vitamin C (table 1) were published in February 2015.
Vitamin C (ascorbic acid) is a highly effective reducing agent in many intra- and extracellular reactions. Vitamin C is a cofactor of copper- and iron-dependent enzymes. It is also involved in the synthesis of collagen, L-carnitine, and catecholamines, as well as in tyrosine formation and the peptide amidations that are necessary for the activity of hormones like oxytocin [5,6]. Vitamin C is a strong antioxidant that scavenges free radicals and other reactive oxygen and nitrogen species such as superoxide, hydroxyl radicals and hypochlorous acid. Thus, it protects biomolecules like lipids and possibly also the DNA against oxidative damage [6,7,8].
Criteria for the Assessment of Vitamin C Supply
Plasma Ascorbate Concentration
Vitamin C is transported as the free anion ascorbate in plasma. The plasma ascorbate concentration is a suitable indicator of the vitamin C status. It is a biomarker for current vitamin C intake, and the fasting plasma ascorbate concentration is a biomarker for the total body pool and long-term intake of vitamin C.
When the vitamin C intake increases, the plasma ascorbate concentration increases according to a sigmoidal (S-shaped) curve [9,10,11,12,13]. The plasma ascorbate concentration is characterised by a steep rise, up to about 50 μmol/l, when vitamin C intake is between 60 and 100 mg/day. At higher intake levels, it reaches a plateau at about 70-80 µmol/l due to decreased absorption rates and increased excretion. Women reach this plateau at lower vitamin C intake levels than men [14,15,16].
The plasma ascorbate concentration is limited by the maximum rate of renal tubular reabsorption (reabsorption capacity), which is about 1.5 mg/100 ml . During deficiency, the renal tubular reabsorption rate is increased, indicating a certain adaption to the vitamin C body pool .
When, at high intake levels, the plasma concentration ranges in the flattening part of the sigmoidal curve (>50 µmol/l), the plasma concentration is of limited value as a biomarker . The biomarker is also affected by smoking, pregnancy, age, gender and presence of infections, with usually lower plasma ascorbate levels in smokers [20,21,22], men, pregnant women [23,24], elderly people (e.g. due to reduced intake, chronic disease; there is no effect of aging itself ) and people with infections [19,26,27]. The plasma ascorbate concentration is also influenced by the genotype (polymorphism). Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Some limited data exist on the influence of genetic changes in manganese superoxide dismutase (SOD2) and glucose transport proteins (SLC2) on ascorbate levels in humans .
A plasma ascorbate concentration of 50 µmol/l or higher is considered to represent an adequate status (see ‘fulfillment of the functions of vitamin C, saturation of body pools and renal reabsorption capacity'). Plasma ascorbate concentrations between 10 and 50 µmol/l indicate a suboptimal status with an increased risk of deficiency . Plasma ascorbate concentrations below 20 μmol/l are often associated with subclinical symptoms . The subclinical signs of an insufficient vitamin C supply are non-specific; the earliest sign is general fatigue. Additionally, muscle weakness, lethargy and anaemia occur .
The concentration in blood cells (neutrophils, monocytes, thrombocytes, lymphocytes) is also associated with the intake of vitamin C. In non-smoking women and men, the intracellular ascorbate concentration reaches saturation at intake levels from about 100 mg vitamin C/day (neutrophils about 1.3 mmol/l, monocytes about 3 mmol/l, thrombocytes about 3.5 mmol/l in women, lymphocytes about 3.5-4 mmol/l) [14,15].
Body Pool and Losses
Vitamin C is accumulated by almost all human tissues. Higher concentrations (per 100 g wet tissue) are found in the pituitary glands (40-50 mg), the adrenal glands (30-40 mg), the eye lens (25-31 mg) and the brain (13-15 mg) than in the plasma (up to 1 mg), saliva (0.07-0.09 mg), kidney (5-15 mg) and skeletal muscle tissue (up to 4 mg) [31,32]. The total body pool of vitamin C varies depending on the intake and can reach 1.5-2.0 g in adult men [10,33].
Maximum metabolic vitamin C losses are about 40-50 mg/day (approx. 3% of the body pool) as observed from studies with non-smoking men. This refers to a plasma ascorbate concentration of about 45-50 µmol/l with a total body pool of about 1.5 g [10,34,35,36]. Absolute values for metabolic losses in women are not available. At the same vitamin C intake, smokers have greater metabolic losses than non-smokers due to increased oxidative stress [10,25,26,37].
Vitamin C that is not absorbed by the intestine is partially metabolised to organic acids and carbon dioxide by the microbiota  and excreted via faeces . Ascorbic acid and its metabolites like oxalic acid, L-threonic acid and L-xylose are mainly excreted in the urine. Renal excretion rises with increasing plasma concentrations or vitamin C intake levels, respectively, due to saturation of renal tubular reabsorption [14,15,18,40]. At a vitamin C intake of 100 mg/day, about 25% of the vitamin C intake is excreted in the urine [14,26]. Excretion is strongly increased if the plasma concentration is between 45 and 60 µmol/l [10,36,37,41,42]; therefore, proximate saturation of body pools is assumed at a concentration from about 50 µmol/l onwards .
Urinary Ascorbic Acid
Urinary ascorbic acid concentration reflects recent intakes of vitamin C [15,43,44]. In subjects on a vitamin C-deficient diet, urinary excretion declines rapidly to undetectable values [34,45]. As mentioned before (see ‘Body Pool and Losses'), urinary excretion rises with rising plasma ascorbate concentration or vitamin C intake, respectively [14,15,18,40], with ascorbic acid excreted in urine even at low, not yet deficient, plasma ascorbate concentrations and there is an abrupt rise in excretion at plasma concentrations near saturation [10,36,37,41,42]. However, the measurement of urinary ascorbic acid is of limited value as a marker for vitamin C status. As stated by others [19,46,47], urinary ascorbic acid is insensitive and unreliable due to extremely small differences in urinary concentrations found in individuals with either inadequate or normal intakes.
Bioavailability of Vitamin C
The bioavailability (absorption rate) of vitamin C is 80% or higher at intake levels from 15 to 100 mg/day [14,36,48]. The higher the vitamin C intake, the lower the absorption rate [10,14,18,49,50]; at an intake level of 1,250 mg/day or more, it is less than 50% [13,14,36,51]. The European Food Safety Authority (EFSA) takes a bioavailability of about 80% at an intake of 100 mg vitamin C/day as a basis for deriving the reference values for vitamin C intake .
Criteria for Derivation of the Reference Values for Vitamin C Intake
The maintenance of the body pools and of plasma and cellular vitamin C concentrations are considered a criterion for establishing the requirement for vitamin C, assuming that proximate saturation of body pools and plasma concentrations is associated with fulfilling the coenzymatic and antioxidant functions of vitamin C [26,29].
Biomarkers of the functions of vitamin C, like markers of collagen metabolism, carnitine concentrations in blood or urine, markers of oxidative damage such as lipid peroxidation as well as markers of the function of the immune system are not considered to be suitable criteria for deriving the requirement for vitamin C [25,26]. Present data on the effect of genotype on plasma ascorbate concentration are insufficient to determine the requirements for vitamin C according to genotype variants [26,28]. Data from studies on the association between vitamin C intake or plasma ascorbate concentrations, respectively, and endpoints as the concentration of blood lipids, blood pressure, risk, severity and duration of common colds and the occurrence of chronic diseases are also no suitable criteria for deriving the requirement for vitamin C  (see ‘Reference Values for Vitamin C Intake').
Reference Values for Vitamin C Intake
Adults Under 65 Years of Age
In line with the EFSA , the average vitamin C requirement in healthy adults is considered to be the vitamin C amount that compensates for the metabolic losses of vitamin C and ensures a fasting ascorbate plasma level of 50 µmol/l.
Based on the present data from studies with non-smoking men, metabolic losses of 50 mg/day are assumed as well as an absorption rate of 80% and an urinary excretion of 25% of the vitamin C intake. Taking this into account, the calculated average requirement in men is 91 mg/day. Considering a coefficient of variation of 10% (addition of 20%), a recommended intake of about 110 mg/day for men is derived (table 2).
As data on metabolic losses in women are not available, the vitamin C requirement in women is extrapolated from the requirement in men and in relation to their body weight, because body weight is considered to be an essential factor for gender-related differences in the pharmacokinetics of vitamin C. Taking into account their reference body weight, the average requirement in women is 77 mg/day. Assuming a coefficient of variation of 10% (addition of 20%), the recommended intake for women is about 95 mg/day (table 2).
With intake levels according to the recommended intake for adults, the desirable plasma concentration of >50 μmol/l and saturation of immunocompetent cells is achieved .
Adults Above 65 Years of Age
So far, pharmacokinetic studies with elderly people or persons with infection, inflammation or other diseases have not been conducted. There are no significant data on deriving other reference values for older adults in comparison with younger adults.
At medium vitamin C intake, no differences regarding the absorption or the metabolism of older compared with younger adults are known. Lower blood concentrations of vitamin C in elderly people may, for example, be due to insufficient intake, chronic diseases or other factors like permanent medication, but not to an effect of aging itself .
Thus, the reference values for younger adults are applied to adults above 65 years - 110 mg/day for men and 95 mg/day for women (table 1).
As described earlier, smokers have higher metabolic losses and lower plasma levels of vitamin C than non-smokers. If smokers stop smoking, the vitamin C plasma concentration increases .
Kallner et al.  compared the effect of vitamin C supplementation in 17 healthy smokers (men at the age of 21-69 years, >20 cigarettes/day) with the effect in non-smokers . The results showed that for smokers, a daily intake of at least 140 mg is necessary to achieve adequate plasma concentrations and body pools, while non-smokers achieve this with 100 mg.
Taking into account the by 40% higher turnover, the reference intake values for male and female smokers are set to 155 mg/day for men and to 135 mg/day for women (table 1).
In infants, there are no systematic investigations regarding the intake of vitamin C and the resulting vitamin C supply.
Breast milk is considered to be the optimal diet for infants [53,54]. Vitamin C intake from breast milk in breastfed infants is probably higher than the requirement in infants. The vitamin C concentration in breast milk depends on the mother's vitamin C supply, so it rather reflects the mother's intake than the requirement in the infant [55,56]. Thus, the concentration in breast milk is not considered to be a suitable parameter for deriving the reference value for infants.
Foods consumed by infants in the second half year of life are often fortified with vitamin C; therefore, current data on the intake are considered to be no appropriate basis for deriving reference values for vitamin C intake .
Following the procedure adopted by the Scientific Committee on Food  and the EFSA [26,57], for infants in their first year of life, the reference value (estimated value) is set to 20 mg vitamin C/day, based upon the lowest observed vitamin C intake of infants in the United Kingdom and the United States (23 mg/day) that obviously meets the requirement in infants, and that is three times higher than the amount necessary to prevent scurvy (7 mg/day; table 1).
Children and Adolescents
Regarding children and adolescents, no data for deriving the average requirement are available. Following the procedure adopted by the EFSA  and the IOM , the vitamin C requirement in this age group is extrapolated from the vitamin C requirement in adults, taking into account the differences regarding reference body weight. Recommended intakes are set assuming a coefficient of variation of 10% (addition of 20% to the average requirement; table 3). When using the age groups and reference body weights the D-A-CH reference values are based upon the recommended intake for 1- to under 4-year-olds 20 mg, for 4- to under 7-year-olds 30 mg, for 7- to under 10-year-olds 45 mg, for 10- to under 13-year-olds 65 mg and for 13- to under 15-year-olds 85 mg/day. The recommended intake at the age of 15 to under 19 years is 105 mg/day for male adolescents and 90 mg/day for female adolescents (table 1).
In pregnant women, haemodilution (higher percentage increase of plasma volume than of erythrocyte volume)  and transfer of vitamin C to the foetus  lead to a decreased plasma ascorbate concentration and a higher requirement for vitamin C. However, convincing data on the quantitative determination of the requirement in pregnant women or the amount transferred to the foetus are not available.
Irwin and Hutchins  summarised six publications from the 1930s to the 1950s that indicate that 67-100 mg up to 200 mg/day is an adequate intake in pregnant women. Olson and Hodges  concluded from estimates that for compensation of maternal losses during pregnancy, intake should be increased during the second and third trimesters of pregnancy by 5 and 10 mg/day, respectively. Using these estimates and due to the vitamin C amount of about 7 mg/day that is necessary to prevent scurvy in the infant [60,61,62,63], from the fourth month of pregnancy onwards, a 10 mg higher recommended intake in comparison to the requirement in non-pregnant women is derived. Assuming a coefficient of variation of 10% (addition of 20% to the average requirement), the reference value for the intake of pregnant women from the fourth month on is set to 105 mg/day (table 1).
The reference value for the intake of vitamin C for lactating women is derived on the basis of the estimated value for infants (20 mg vitamin C/day). At an absorption rate of 80%, about 25 mg vitamin C/day are sufficient to compensate for the amount that is transferred with breast milk when feeding the infant. Therefore, the average requirement in lactating women is 25 mg/day higher than that in non-lactating women. Assuming a coefficient of variation of 10% (addition of 20%), this results in a reference value for the intake that is about 30 mg/day higher than in non-lactating women. Therefore, the recommended intake of vitamin C for lactating women is 125 mg/day (table 1). Considering the estimated vitamin C amount secreted with breast milk while deriving reference values would lead to higher values than probably needed (see ‘Infants').
Ensuring a Sufficient Vitamin C Supply
It is possible to achieve a sufficient vitamin C supply by consuming foods that naturally contain the vitamin. A diet rich in vegetables and fruits, according to the food-related recommendations for a wholesome diet [64,] provides plenty of vitamin C.
Vegetables and fruits and products made from them such as juices and smoothies are the best sources of vitamin C. For example, foods with particularly high content of vitamin C, containing more than 100 mg/100 g, are buckthorn berries and juice made therefrom, sweet pepper, black current and parsley. However, citrus fruits, potatoes, cabbage, spinach and tomatoes are relevant for the supply of vitamin C due to their high vitamin C content and the quantity that is consumed .
Vitamin C is an additive (antioxidant, E300 to E304, E315 and E316) in many processed foods such as meat and sausage products, and so these foods also contribute to the vitamin C supply. Foods that are fortified with vitamin C are commercially available as well. Fortified foods and nutritional supplements are not necessary to ensure a sufficient vitamin C supply.
Oxidative damage to cells and molecules is associated with the development of a number of degenerative chronic diseases. The antioxidative efficacy of vitamin C in the body leads to the hypothesis that vitamin C can affect the occurrence, course and mortality of such diseases. It is also being discussed whether vitamin C strengthens the immune system. In the following, the current available data on vitamin C in association with health-related aspects are outlined using existing meta-analyses or systematic reviews.
In the past, data from observational studies led to the conclusion that a diet rich in vitamin C (plenty of vegetables and fruits) may contribute to the prevention of cardiovascular diseases and some kinds of cancer. However, results from randomised controlled intervention studies (vitamin C supplementation) could not confirm this [25,26], which suggests that the benefit of a diet rich in vegetables and fruits is not solely caused by the associated intake of a single nutrient such as vitamin C [66,67].
Regarding cancer and mortality, comprehensive data are available. There is no association with intake or vitamin C supply, respectively [26,68,69,70,71,72,73].
There are also many studies available on the relationship between vitamin C intake or supply, respectively, and eye diseases, but they are not consistent or not sufficiently specific . Cochrane reviews of randomised controlled studies on supplementation of vitamin C alone or in combination with other antioxidants conclude that there are no effects on the prevention or course of eye diseases [74,75,76].
On the basis of a comprehensive review of the literature published between 1991 and 2011 , the EFSA  has described inconsistent associations between vitamin C intake and/or plasma ascorbate concentrations and bone density as well as the risk of diabetes, Parkinson's disease, Alzheimer's disease, dementia, preterm delivery, breathing difficulties and eczema in the first 2 years of life, medulloblastoma during childhood, hearing loss, periodontal disease and multiple sclerosis. Due to the low number of available studies regarding these endpoints, it is not possible to draw conclusions on the supposed role of vitamin C in the pathogenesis of these diseases .
Supplementation of vitamin C during pregnancy for the prevention of pregnancy complications or promotion of the mother's and the child's health is not justified on the basis of the available scientific data [78,79,80].
In total, intervention studies on the effect of preventive vitamin C supplementation with ≥200 mg/day showed no effect on the incidence of common colds in the general public. However, in a subgroup including marathon runners, skiers and soldiers under subarctic conditions, the risk was reduced by about 50%. When vitamin C was taken prophylactically, the duration of common colds was reduced by 8% in adults and by 14% in children. The severity of the cold was reduced too. The lack of effect of vitamin C supplementation on the incidence of common cold in the general public suggests that routine high-dose prophylaxis is not justified. However, it may be justified for persons under extreme physical strain or in a very cold environment . The EFSA notes about this Cochrane review that common colds were self-diagnosed by the subjects in most of the respective trials, and that no clear criteria were specified to assess either the severity or the duration of a common cold episode .
The current data indicate that no preventive effects are to be expected from supplementation of vitamin C in the general public.