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Annals of Vitamin and Metabolism
Summary
The German, Austrian, and Swiss diet societies are the editors of the ‘reference values for nutrient consumption’. They’ve revised the reference values for the consumption of vitamin C and revealed them in February 2015. The typical vitamin C requirement in wholesome adults is taken into account to be the vitamin C quantity that compensates for the metabolic losses of vitamin C, and ensures a fasting ascorbate plasma stage of fifty µmol/l. Primarily based on the current knowledge from research with non-smoking males, metabolic losses of fifty mg/day are assumed, in addition to an absorption fee of 80% and an urinary excretion of 25% of the vitamin C consumption. Taking this into consideration, the calculated common requirement in males is 91 mg/day. Contemplating a coefficient of variation of 10%, a reference worth (advisable consumption) of 110 mg/day for males is derived. The vitamin C requirement in ladies in addition to in kids and adolescents is extrapolated from the requirement in males and in relation to their physique weight. This ends in a advisable consumption of about 95 mg/day for grownup ladies. As a result of the requirement in pregnant and lactating ladies is elevated, greater advisable intakes are derived for them, 105 mg/day for pregnant ladies from the fourth month on and 125 mg/day for lactating ladies, respectively. For girls and boys on the age of 1 to below 15 years, there are growing advisable consumption values from 20 to 85 mg/day. For female and male adolescents, on the age of 15 to below 19 years, the advisable consumption is 105 and 90 mg, respectively. As people who smoke have greater metabolic losses and decrease plasma ranges of vitamin C than non-smokers (turnover is 40% greater), the reference worth for vitamin C consumption is about to 135 mg/day for feminine people who smoke and 155 mg/day for male people who smoke. For infants of their first yr of life, the reference worth (estimated worth) is about to twenty mg vitamin C/ day, primarily based upon the bottom noticed vitamin C consumption for infants in the UK and the US, that clearly meets the requirement in infants and that’s 3 instances greater than the quantity needed to stop scurvy (7 mg/day).
© 2015 S. Karger AG, Basel
Introduction
The D-A-CH ‘reference values for nutrient consumption’ [1] are collectively issued by the diet societies of Germany, Austria and Switzerland (the abbreviation D-A-CH arises from the preliminary letters of the frequent nation identification for the nations Germany (D), Austria (A) and Switzerland (CH)). At present, the ‘reference values for nutrient consumption’ are being revised. Following the revised reference values for vitamin D [2], calcium [3] and folate [4], the revised reference values for vitamin C (desk 1) have been revealed in February 2015.
Desk 1Reference values for vitamin C consumption (advisable consumption) [1]
Vitamin C (ascorbic acid) is a extremely efficient lowering agent in lots of intra- and extracellular reactions. Vitamin C is a cofactor of copper- and iron-dependent enzymes. Additionally it is concerned within the synthesis of collagen, L-carnitine, and catecholamines, in addition to in tyrosine formation and the peptide amidations which can be needed for the exercise of hormones like oxytocin [5,6]. Vitamin C is a robust antioxidant that scavenges free radicals and different reactive oxygen and nitrogen species comparable to superoxide, hydroxyl radicals and hypochlorous acid. Thus, it protects biomolecules like lipids and presumably additionally the DNA in opposition to oxidative harm [6,7,8].
Standards for the Evaluation of Vitamin C Provide
Plasma Ascorbate Focus
Vitamin C is transported because the free anion ascorbate in plasma. The plasma ascorbate focus is an acceptable indicator of the vitamin C standing. It’s a biomarker for present vitamin C consumption, and the fasting plasma ascorbate focus is a biomarker for the whole physique pool and long-term consumption of vitamin C.
When the vitamin C consumption will increase, the plasma ascorbate focus will increase in line with a sigmoidal (S-shaped) curve [9,10,11,12,13]. The plasma ascorbate focus is characterised by a steep rise, as much as about 50 μmol/l, when vitamin C consumption is between 60 and 100 mg/day. At greater consumption ranges, it reaches a plateau at about 70-80 µmol/l resulting from decreased absorption charges and elevated excretion. Ladies attain this plateau at decrease vitamin C consumption ranges than males [14,15,16].
The plasma ascorbate focus is proscribed by the utmost fee of renal tubular reabsorption (reabsorption capability), which is about 1.5 mg/100 ml [17]. Throughout deficiency, the renal tubular reabsorption fee is elevated, indicating a sure adaption to the vitamin C physique pool [18].
When, at excessive consumption ranges, the plasma focus ranges within the flattening a part of the sigmoidal curve (>50 µmol/l), the plasma focus is of restricted worth as a biomarker [19]. The biomarker can be affected by smoking, being pregnant, age, gender and presence of infections, with often decrease plasma ascorbate ranges in people who smoke [20,21,22], males, pregnant ladies [23,24], aged individuals (e.g. resulting from decreased consumption, continual illness; there isn’t a impact of getting old itself [25]) and other people with infections [19,26,27]. The plasma ascorbate focus can be influenced by the genotype (polymorphism). Polymorphisms within the genes encoding sodium-dependent vitamin C transport proteins are strongly related to plasma ascorbate ranges and sure influence tissue mobile vitamin C standing. Some restricted knowledge exist on the affect of genetic adjustments in manganese superoxide dismutase (SOD2) and glucose transport proteins (SLC2) on ascorbate ranges in people [28].
A plasma ascorbate focus of fifty µmol/l or greater is taken into account to characterize an sufficient standing (see ‘success of the capabilities of vitamin C, saturation of physique swimming pools and renal reabsorption capability’). Plasma ascorbate concentrations between 10 and 50 µmol/l point out a suboptimal standing with an elevated threat of deficiency [26]. Plasma ascorbate concentrations beneath 20 μmol/l are sometimes related to subclinical signs [29]. The subclinical indicators of an inadequate vitamin C provide are non-specific; the earliest signal is common fatigue. Moreover, muscle weak point, lethargy and anaemia happen [30].
Immunocompetent Cells
The focus in blood cells (neutrophils, monocytes, thrombocytes, lymphocytes) can be related to the consumption of vitamin C. In non-smoking ladies and men, the intracellular ascorbate focus reaches saturation at consumption ranges 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 ladies, lymphocytes about 3.5-4 mmol/l) [14,15].
Physique Pool and Losses
Vitamin C is gathered by nearly all human tissues. Increased concentrations (per 100 g moist tissue) are discovered within the pituitary glands (40-50 mg), the adrenal glands (30-40 mg), the attention lens (25-31 mg) and the mind (13-15 mg) than within the plasma (as much as 1 mg), saliva (0.07-0.09 mg), kidney (5-15 mg) and skeletal muscle tissue (as much as 4 mg) [31,32]. The full physique pool of vitamin C varies relying on the consumption and may attain 1.5-2.0 g in grownup males [10,33].
Most metabolic vitamin C losses are about 40-50 mg/day (approx. 3% of the physique pool) as noticed from research with non-smoking males. This refers to a plasma ascorbate focus of about 45-50 µmol/l with a complete physique pool of about 1.5 g [10,34,35,36]. Absolute values for metabolic losses in ladies should not obtainable. On the identical vitamin C consumption, people who smoke have larger metabolic losses than non-smokers resulting from elevated oxidative stress [10,25,26,37].
Vitamin C that isn’t absorbed by the gut is partially metabolised to natural acids and carbon dioxide by the microbiota [38] and excreted through faeces [39]. Ascorbic acid and its metabolites like oxalic acid, L-threonic acid and L-xylose are primarily excreted within the urine. Renal excretion rises with growing plasma concentrations or vitamin C consumption ranges, respectively, resulting from saturation of renal tubular reabsorption [14,15,18,40]. At a vitamin C consumption of 100 mg/day, about 25% of the vitamin C consumption is excreted within the urine [14,26]. Excretion is strongly elevated if the plasma focus is between 45 and 60 µmol/l [10,36,37,41,42]; due to this fact, proximate saturation of physique swimming pools is assumed at a focus from about 50 µmol/l onwards [26].
Urinary Ascorbic Acid
Urinary ascorbic acid focus displays current intakes of vitamin C [15,43,44]. In topics on a vitamin C-deficient weight-reduction plan, urinary excretion declines quickly to undetectable values [34,45]. As talked about earlier than (see ‘Physique Pool and Losses’), urinary excretion rises with rising plasma ascorbate focus or vitamin C consumption, respectively [14,15,18,40], with ascorbic acid excreted in urine even at low, not but poor, plasma ascorbate concentrations and there’s an abrupt rise in excretion at plasma concentrations close to saturation [10,36,37,41,42]. Nonetheless, the measurement of urinary ascorbic acid is of restricted worth as a marker for vitamin C standing. As said by others [19,46,47], urinary ascorbic acid is insensitive and unreliable resulting from extraordinarily small variations in urinary concentrations present in people with both insufficient or regular intakes.
Bioavailability of Vitamin C – “vitamin c 25mg”
The bioavailability (absorption fee) of vitamin C is 80% or greater at consumption ranges from 15 to 100 mg/day [14,36,48]. The upper the vitamin C consumption, the decrease the absorption fee [10,14,18,49,50]; at an consumption stage of 1,250 mg/day or extra, it’s lower than 50% [13,14,36,51]. The European Meals Security Authority (EFSA) takes a bioavailability of about 80% at an consumption of 100 mg vitamin C/day as a foundation for deriving the reference values for vitamin C consumption [26].
Standards for Derivation of the Reference Values for Vitamin C Consumption
The upkeep of the physique swimming pools and of plasma and mobile vitamin C concentrations are thought-about a criterion for establishing the requirement for vitamin C, assuming that proximate saturation of physique swimming pools and plasma concentrations is related to fulfilling the coenzymatic and antioxidant capabilities of vitamin C [26,29].
Biomarkers of the capabilities of vitamin C, like markers of collagen metabolism, carnitine concentrations in blood or urine, markers of oxidative harm comparable to lipid peroxidation in addition to markers of the operate of the immune system should not thought-about to be appropriate standards for deriving the requirement for vitamin C [25,26]. Current knowledge on the impact of genotype on plasma ascorbate focus are inadequate to find out the necessities for vitamin C in line with genotype variants [26,28]. Information from research on the affiliation between vitamin C consumption or plasma ascorbate concentrations, respectively, and endpoints because the focus of blood lipids, blood strain, threat, severity and length of frequent colds and the prevalence of continual illnesses are additionally no appropriate standards for deriving the requirement for vitamin C [26] (see ‘Reference Values for Vitamin C Consumption’).
Reference Values for Vitamin C Consumption
Adults Below 65 Years of Age
In step with the EFSA [26], the common vitamin C requirement in wholesome adults is taken into account to be the vitamin C quantity that compensates for the metabolic losses of vitamin C and ensures a fasting ascorbate plasma stage of fifty µmol/l.
Primarily based on the current knowledge from research with non-smoking males, metabolic losses of fifty mg/day are assumed in addition to an absorption fee of 80% and an urinary excretion of 25% of the vitamin C consumption. Taking this into consideration, the calculated common requirement in males is 91 mg/day. Contemplating a coefficient of variation of 10% (addition of 20%), a advisable consumption of about 110 mg/day for males is derived (desk 2).
Desk 2Calculation of the advisable consumption of vitamin C for adults
As knowledge on metabolic losses in ladies should not obtainable, the vitamin C requirement in ladies is extrapolated from the requirement in males and in relation to their physique weight, as a result of physique weight is taken into account to be a necessary issue for gender-related variations within the pharmacokinetics of vitamin C. Bearing in mind their reference physique weight, the common requirement in ladies is 77 mg/day. Assuming a coefficient of variation of 10% (addition of 20%), the advisable consumption for girls is about 95 mg/day (desk 2).
With consumption ranges in line with the advisable consumption for adults, the fascinating plasma focus of >50 μmol/l and saturation of immunocompetent cells is achieved [14].
Adults Above 65 Years of Age
To date, pharmacokinetic research with aged individuals or individuals with an infection, irritation or different illnesses haven’t been carried out. There are not any important knowledge on deriving different reference values for older adults compared with youthful adults.
At medium vitamin C consumption, no variations concerning the absorption or the metabolism of older in contrast with youthful adults are recognized. Decrease blood concentrations of vitamin C in aged individuals could, for instance, be resulting from inadequate consumption, continual illnesses or different elements like everlasting treatment, however to not an impact of getting old itself [25].
Thus, the reference values for youthful adults are utilized to adults above 65 years – 110 mg/day for males and 95 mg/day for girls (desk 1).
People who smoke
As described earlier, people who smoke have greater metabolic losses and decrease plasma ranges of vitamin C than non-smokers. If people who smoke quit smoking, the vitamin C plasma focus will increase [52].
Kallner et al. [37] in contrast the impact of vitamin C supplementation in 17 wholesome people who smoke (males on the age of 21-69 years, >20 cigarettes/day) with the impact in non-smokers [10]. The outcomes confirmed that for people who smoke, a every day consumption of a minimum of 140 mg is important to realize sufficient plasma concentrations and physique swimming pools, whereas non-smokers obtain this with 100 mg.
Bearing in mind the by 40% greater turnover, the reference consumption values for female and male people who smoke are set to 155 mg/day for males and to 135 mg/day for girls (desk 1).
Infants
In infants, there are not any systematic investigations concerning the consumption of vitamin C and the ensuing vitamin C provide.
Breast milk is taken into account to be the optimum weight-reduction plan for infants [53,54]. Vitamin C consumption from breast milk in breastfed infants might be greater than the requirement in infants. The vitamin C focus in breast milk is dependent upon the mom’s vitamin C provide, so it relatively displays the mom’s consumption than the requirement within the toddler [55,56]. Thus, the focus in breast milk isn’t thought-about to be an acceptable parameter for deriving the reference worth for infants.
Meals consumed by infants within the second half yr of life are sometimes fortified with vitamin C; due to this fact, present knowledge on the consumption are thought-about to be no applicable foundation for deriving reference values for vitamin C consumption [26].
Following the process adopted by the Scientific Committee on Meals [56] and the EFSA [26,57], for infants of their first yr of life, the reference worth (estimated worth) is about to twenty mg vitamin C/day, primarily based upon the bottom noticed vitamin C consumption of infants in the UK and the US (23 mg/day) that clearly meets the requirement in infants, and that’s 3 times greater than the quantity needed to stop scurvy (7 mg/day; desk 1).
Kids and Adolescents
Relating to kids and adolescents, no knowledge for deriving the common requirement can be found. Following the process adopted by the EFSA [26] and the IOM [25], the vitamin C requirement on this age group is extrapolated from the vitamin C requirement in adults, making an allowance for the variations concerning reference physique weight. Advisable intakes are set assuming a coefficient of variation of 10% (addition of 20% to the common requirement; desk 3). When utilizing the age teams and reference physique weights the D-A-CH reference values are primarily based upon the advisable consumption for 1- to below 4-year-olds 20 mg, for 4- to below 7-year-olds 30 mg, for 7- to below 10-year-olds 45 mg, for 10- to below 13-year-olds 65 mg and for 13- to below 15-year-olds 85 mg/day. The advisable consumption on the age of 15 to below 19 years is 105 mg/day for male adolescents and 90 mg/day for feminine adolescents (desk 1).
Desk 3Calculation of the advisable consumption of vitamin C for youngsters and adolescents
Being pregnant
In pregnant ladies, haemodilution (greater proportion improve of plasma quantity than of erythrocyte quantity) [23] and switch of vitamin C to the foetus [58] result in a decreased plasma ascorbate focus and a better requirement for vitamin C. Nonetheless, convincing knowledge on the quantitative willpower of the requirement in pregnant ladies or the quantity transferred to the foetus should not obtainable.
Irwin and Hutchins [11] summarised six publications from the Thirties to the Nineteen Fifties that point out that 67-100 mg as much as 200 mg/day is an sufficient consumption in pregnant ladies. Olson and Hodges [59] concluded from estimates that for compensation of maternal losses throughout being pregnant, consumption must be elevated in the course of the second and third trimesters of being pregnant by 5 and 10 mg/day, respectively. Utilizing these estimates and because of the vitamin C quantity of about 7 mg/day that’s needed to stop scurvy within the toddler [60,61,62,63], from the fourth month of being pregnant onwards, a ten mg greater advisable consumption compared to the requirement in non-pregnant ladies is derived. Assuming a coefficient of variation of 10% (addition of 20% to the common requirement), the reference worth for the consumption of pregnant ladies from the fourth month on is about to 105 mg/day (desk 1).
Lactation
The reference worth for the consumption of vitamin C for lactating ladies is derived on the premise of the estimated worth for infants (20 mg vitamin C/day). At an absorption fee of 80%, about 25 mg vitamin C/day are ample to compensate for the quantity that’s transferred with breast milk when feeding the toddler. Due to this fact, the common requirement in lactating ladies is 25 mg/day greater than that in non-lactating ladies. Assuming a coefficient of variation of 10% (addition of 20%), this ends in a reference worth for the consumption that’s about 30 mg/day greater than in non-lactating ladies. Due to this fact, the advisable consumption of vitamin C for lactating ladies is 125 mg/day (desk 1). Contemplating the estimated vitamin C quantity secreted with breast milk whereas deriving reference values would result in greater values than most likely wanted (see ‘Infants’).
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