Ascorbic Acid

The Basics On Ascorbic Acid

What is Ascorbic Acid?

Form of vitamin C that has antioxidant properties.

What are other names for Ascorbic Acid?

L-ASCORBIC ACID, ASCORBIC ACID, ASCORBIC ACID (VITAMIN C), and VITAMIN C

What is Ascorbic Acid used for?

Ascorbic acid, another name for Vitamin C, is a water-soluble, unstable vitamin that is the main antioxidant compound for our skin. It is a vital component of our skin structure and function.

How Ascorbic Acid is classified

Antioxidants, Vitamins

Recommendations for using Ascorbic Acid during pregnancy and breastfeeding

Limited data suggests no known risk

 

Ascorbic Acid During Pregnancy

What we know about using Ascorbic Acid while pregnant or breastfeeding

Limited information available.

In Vivo Ascorbic acid Frohberg et al. (1973) administered daily oral doses of 150, 250, 500, or 1000 mg/kg Ascorbic Acid to pregnant rats in a first trial from day 6 to day 15 of pregnancy and in a second trial from day 0, preconception, to day 21 postpartum. Also, mice received daily oral doses of 250, 500, or 1000 mg/kg Ascorbic Acid from 80 COSMETIC INGREDIENT REVIEW TABLE 16 Effect of Ascorbic Acid on metal toxicity Metal Species Effects of Ascorbic Acid Reference Copper Pig Reduced iron deficiency induced by copper Gipp et al. (1974) Rubidium Rat Ascorbic Acid supplementation afforded some protection against the alterations of certain liver enzymes as well as in regard to the histological changes of either liver and kidney effects caused by Rb Chatterjee et al. (1979) Lead (Pb) Human Ameliorated toxicity Federation of American Societies for Experimental Biology (1979) Pb Guinea pig Variable toxicity Pb Human No effect on toxicity Evans et al. (1943) Pb Rat 1% Ascorbic Acid prevented growth depression, reduction of food consumption, anemia, and decreased the accumulation of lead in tissues (long-term) Suzuki and Yoshida (1979) Selenium Rat Marginal benefit from toxicity Levander and Morris (1970) Vandium Chick Ameliorated toxicity Berg and Lawrence (1971) Chromate (CrO4) pigments (Na, Ca, Zn, and basic Pb chromates) Cell culture media Increased production of reactive oxygen species (ROS) Lefebvre and Pezerat (1994) CrO4 Rat CrO4 and Ascorbic Acid administered concomitantly completely prevented proteinuria by enhancement of extracellular reduction of chromate IV to III Appenroth et al. (1994) Aluminum Rat Aluminum concentrations in the bone, kidney, liver, and spleen were significantly increased, as was the overall cumulative urinary excretion of Al due to the gastric intubation of Ascorbic Acid Domingo et al. (1994) day 6 to day 15 of pregnancy. There were no indications of maternal toxicity, terata, or fetal toxicity. There was no effect on the embryonic and postpartum development of the young or on breeding behavior, pregnancy, parturition, or lactation capacity of the mother animals. Nandi et al. (1973) fed Charles Foster albino rats a fortified wheat diet consisting of whole grain wheat flour, 63 g; sucrose, 10 g; caesin, 15 g; groundnut oil, 5 g; shark liver oil, 5 g; USP XVII salt mixture, 4 g; and AOAC (Association of Official Agricultural Chemists) vitamin mixture, 1 g. Ascorbic Acid (0.5 mg to 250 mg in 0.75 ml water) was administered orally to individual male and female rats (100 mg/100g bw day−1) for 2 weeks before, and then during mating. Females were separated from males after becoming pregnant. Ascorbic Acid feeding was continued during the period of gestation and lactation. Control animals received no Ascorbic Acid supplementation. The average body weight of male rats receiving 100 mg Ascorbic Acid was not significantly different from controls. The administration of large doses of Ascorbic Acid had no influence on pregnancy or growth of the litters. The average number of pups born per litter and body weight of the pups from Ascorbic Acid-fed parents were similar to those from the control litters (Nandi et al. 1973). FDRL (1975a) reported that the administration of 520 mg/kg bw of Ascorbic Acid to pregnant mice for 10 consecutive days had no clear effect on nidation or on maternal or fetal survival. The number of abnormalities observed in either soft or skeletal tissues of the treated group did not differ from those observed in the negative control group. The administration of 550 mg/kg bw of Ascorbic Acid to pregnant rats for 10 consecutive days had no clear effect on nidation or on maternal or fetal survival. The number of abnormalities ASCORBIC ACID, ASCORBYL PHOSPHATES, AND ASCORBATES 81 observed in either soft or skeletal tissues of the treated group did not differ from those observed in the negative-control group (FDRL 1975b). Alleva et al. (1976) exposed guinea pigs, rats, and hamsters to large daily doses of Ascorbic Acid during pregnancy. Guinea pigs received twice daily subcutaneous injections of Sodium Ascorbate (400 mg/kg/day) after being housed 6 days with a male. The control group received only saline injections. After pregnancy was established, the treated guinea pigs received daily oral treatments of Ascorbic Acid. Control animals received water. Female Holtzman rats were exposed to males and those with vaginal sperm the following morning were given a single oral dose of 0, 50, 150, or 450 mg of Ascorbic Acid daily from days 1 to 19 of pregnancy. Lakeview hamsters with fresh vaginal sperm were given Ascorbic Acid in the same daily doses given to the rats, from day 1 to day 15 of pregnancy. No increases in abortion or mortality of offspring were observed in guinea pigs, rats, or hamsters given daily doses of Ascorbic Acid as described. A slight increase in pup weight was observed in treated guinea pigs and hamsters. In a study described earlier in “Absorption, Distribution, Metabolism, and Excretion,” Norkus and Rosso (1981) fed guinea pigs a control (0.04% Ascorbic Acid) diet from day 3 of gestation. At day 31 the animals were divided into control, 0.56% Ascorbic Acid, and 0.82% Ascorbic Acid diets. There were no differences found in litter size, mean birth weight, and body weight among offspring from all groups at either 5 or 10 days after birth. In a study by Seidenberg et al. (1986), a group of 30 adult ICR/SIM mice received 3200 mg/kg/day of Ascorbic Acid in water by oral intubation on days 8 through 12 of gestation. The mice were allowed to deliver and the neonates were examined, counted, and weighed. Two of the pregnant mice died and their average weight gain was 6.6 ± 2.6 g. Twenty-five litters were born and there was no resorption. The survival rate of the neonates was 99%. The average neonatal weight on day 1 and day 3 was 1.7 ± 0.09 and 2.3 ± 0.2 g, respectively. Ascorbic Acid was considered non-teratogenic in this study. Basu (1985) examined the influence of prolonged exposure of guinea pigs to excessive Ascorbic Acid on the outcome of pregnancy, as well as the adaptive effect of the vitamin either during preweanling life or following. Duncan-Hartley guinea pigs were maintained on a stock pellet diet containing 70 mg Ascorbic Acid/100 g, and water was given ad libitum containing either 1 mg or 0.1 mg Ascorbic Acid/ml. The total intake of Ascorbic Acid per animal was not recorded. Females in two groups (test and control) were mated. The test groups received extra dietary Ascorbic Acid in their drinking water each day for two weeks before mating. In treated groups, the pregnant females continued to receive extra Ascorbic Acid. Following birththree pups were put with onelactating mother, and at 21 days of age, the offspring were separated from their mothers and the females were put back with males for further mating. These weanlings were divided into two groups: group A was maintained on 1 mg Ascorbic Acid/ml drinking water, while group B was reduced to 0.1 mg/ml during the first 31 days of postweanling life. At 31 days these animals were killed. The control animals were also mated and the offspring were separated from their mothers at 21 days. For four weeks, the offspring were maintained on 1 mg/ml Ascorbic Acid in the drinking water. The animals were then divided into two groups: group 1 continued on 1 mg/ml Ascorbic Acid for the next 4 weeks, while group 2 received 0.1 mg/ml. At the end of 4 weeks, the animals were killed. All animals became pregnant; no significant difference was observed between the groups, neither in terms of the number of offspring per pregnancy, nor in their weights at birth. Continuous dietary administration of 0.1 mg/ml Ascorbic Acid from intrauterine life resulted in a significantly higher body weight gain at all periods studied compared to normal intake. However, change in the Ascorbic Acid treatment from high to normal amounts resulted in a marked loss in body weight by 31 days. This reduction also led to the development of scurvylike signs, which were characterized by deep elevations on the paws and legs, swollen knee joints, enlarged epiphyses of ribs, andimpairedjoint movement. The plasma,leucocyte, and adrenal concentrations of Ascorbic Acid were measured in all groups of animals at the end of 31 days. Concentrations were significantly higher in animals in the high-supplementation group compared to those who received 0.1 mg/ml Ascorbic Acid. However the offspring of guinea pigs given high supplementation throughout pregnancy and lactation, followed by normal Ascorbic Acid had significantly lower Ascorbic Acid concentrations in their plasma, leucocyte, and adrenals than did controls (Basu 1985). In a study by Pillans et al. (1990) pregnant C3H mice were exposed to 3.43 or 6.68 g Ascorbic Acid/kg bw on the 11th day postcopulation, and to coadministration of a teratogenic dose of cyclophosphamide (CP; 15 mg/kg bw). Sixteen hours after drug administration, embryonal cephalic DNA strand breaks were assessed. The mice were killed on day 18 after copulation and the fetal weights, gross morphological abnormalities, and fetal deaths were recorded. The administration of 3.43 g/kg Ascorbic Acid was not associated with demonstrable toxic effects, but with 6.68 g/kg Ascorbic Acid there was a 46% incidence of fetal deaths. When Ascorbic Acid (3.34 g/kg) was coadministered with CP the incidence of DNA strand breaks was unchanged. CP-treated mice had 59% cephalic double-stranded DNA and controls had 81%. All fetuses treated with Ascorbic Acid and CP were morphologically normal and there was no reduction in fetal weight. These findings demonstrate that the administration of 6.68 g/kg Ascorbic Acid was toxic to the mouse embryo, but the lower dose was not and had a protective effect against the toxic manifestations of CP (Pillans et al. 1990). Colomina et al. (1994) dosed three groups of pregnant Swiss mice daily with aluminum hydroxide, Ascorbic Acid (85 mg/kg), or aluminum hydroxide (300 mg/kg) concurrent with Ascorbic 82 COSMETIC INGREDIENT REVIEW Acid (85 mg/kg) on gestational days 6 to 15 by gavage. A fourth group of pregnant females received distilled water and served as the control group. Aluminum levels were determined in fetuses and in maternal organs and tissues. The authors concluded that the reproductive data did not suggest embryotoxic or fetotoxic effects in any group. No gross, internal, or skeletal malformations or variations related to the different treatments were found. There were no differences between control and treated groups on the aluminum levels in maternal liver and bone as well as in whole body fetuses, whereas aluminum concentrations were significantly higher in placenta and kidney of dams receiving aluminum hydroxide and aluminum hydroxide plus Ascorbic Acid. No signs of maternal or developmental toxicity were observed when aluminum hydroxide was given alone or concurrently with Ascorbic Acid (Colomina et al. 1994). Sodium Ascorbate Siman and Eriksson (1997) fed normal and streptozotocin diabetic rats either a standard diet or a diet enriched with 0.9%, 1.8%, or 4% Sodium Ascorbate throughout pregnancy. On gestational day 20, the litters of normal and diabetic rats without Sodium Ascorbate supplement contained 9% and 12% resorptions, 2% and 17% late resorptions, and 1% and 27% malformations, respectively. Sodium Ascorbate treatment reduced the rates of late resorptions and malformations in the diabetic groups in proportion to the dose administered. In the diabetic group with 4% ascorbate treatment, unchanged numbers of early resorptions, 7% late resorptions, and 8% malformations were observed. Maternal diabetes did not alter tissue levels of Ascorbic Acid in the fetuses at term but Sodium Ascorbate supplementation caused an accumulation of Ascorbic Acid in the placenta and maternal and fetal liver. Cohen et al. (1998) evaluated the effects of Sodium Ascorbate in a two-generation bioassay that involved feeding male and female F344 rats 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (28 days old) male F1 generation rats for the remainder of their lifetime (up to 128 weeks). Dietary levels of 1%, 5%, and 7% Sodium Ascorbate were tested. Ammonium Chloride (NH4Cl) was administered in two groups at 2.04% and 2.78% with Sodium Ascorbate. Control animals received no added chemicals to their diet. No abnormalities were noted in the F0 generation during feeding of the respective diets before conception and during lactation, nor was there evidence of increased morbidity or mortality. F1 males coadministered NH4Cl showed significantly lower weights than the other groups. Rats fed 7% Sodium Ascorbate at week 0 and 5% Sodium Ascorbate at week 24 weighed significantly less than controls. Mortality in F1 rats was increased only in the high Sodium Ascorbate/high NH4Cl group. The most common cause of death in all groups was leukemia, with a grossly enlarged spleen and usually diffuse infiltrates of leukemic cells in other tissues, especially in the lungs and liver. At 5% and 7% Sodium Ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-response increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% Sodium Ascorbate. The group fed 5% Sodium Ascorbate and 2.04% NH4Cl showed complete inhibition of the urothelial effects of Sodium Ascorbate and significant inhibition of its renal effects (Cohen et al. 1998). In Vitro Ascorbic Acid Mummery et al. (1984) screened Ascorbic Acid for induction of differentiation in mouse N1E-115 neuroblastoma cells. These investigators reported Ascorbic Acid as a non-teratogen. The toxic dose and no effect dose of Ascorbic Acid were reported as 1 × 10−3 M and 1 × 10−7 M, respectively. According to Pratt and Willis (1985), Ascorbic Acid was screened for growth inhibition of human embryonic palatal mesenchymal cells. The IC50 (inhibitory concentration of 50% of the culture) for Ascorbic Acid was 300 μg/ml. Ascorbic Acid was considered a non-teratogen that was not inhibitory in vitro. Uphill et al. (1990) assessed Ascorbic Acid for its teratogenic potential in the in vitro micromass assay (single cell suspensions of midbrain [CNS] and limb-buds [LB] from 13-day rat embryos). Concentrations of Ascorbic Acid were assessed for effects on inhibition of cell differentiation and cell survival by 50% compared to control values (IC50). The IC50 values for the CNS cells based on differentiation and survival were 120 and 100 μg/ml, respectively; the IC50 values for the LB cells based on differentiation and survival were 335 and 370 μg/ml, respectively. Ascorbic Acid was considered a non-teratogen. DeYoung et al. (1991) evaluated the developmental toxicity of Ascorbic Acid with the frog embryo teratogenesis assay: Xenopus (FETAX). Small cell Xenopus laevis blastulae were exposed to Ascorbic Acid for 96 h. The most common malformations induced by Ascorbic Acid was failure of the gut to coil (10 mg/ml). At 13 mg/ml, facial, eye, and brain malformations were noted. Growth was stunted and severe malformations of the gut, musculoskeletal system, face, eye, and heart occurred at 19 mg/ml. According to the authors, the FETAX protocol compares TI values, embryo growth, and the type and severity of induced malformations, and, in general, TI values <1.5 indicate low teratogenic potential (Ascorbic Acid averaged 1.633 in three tests). Nonetheless, these authors stated that Ascorbic Acid tested negative in FETAX. The results are given in Table 17. Anderson and Francis (1993) measured the malformations and growth reductions in whole rat embryo cultures after treatment with the oxygen radical generating system of xanthine/ xanthine oxidase and/or L-Ascorbic Acid. Treatment with xanthine/xanthine oxidase caused a significant linear trend towards ASCORBIC ACID, ASCORBYL PHOSPHATES, AND ASCORBATES 83 TABLE 17 Developmental toxicity of Ascorbic Acid with in vitro FETAX assay (DeYoung et al. 1991) Test no. LC50a EC50 b TIc MCIGd MCIGe 1 19.2 11.6 1.7 10.0 52 2 20.3 12.8 1.6 10.0 49 3 19.6 12.0 1.6 10.0 51 aMedian lethal concentration (mg/ml). bConcentration inducing malformations in 50% of the surviving embryos (mg/ml). cTeratogenic index TI = LC50/EC50. dMinimum concentration to inhibit growth (mg/L). eMinimum to inhibit growth as a percent of LC50. increasingly severe abnormalities when compared to controls (xanthine only). Low concentrations of Ascorbic Acid (10 or 100 μm) added to cultures containing xanthine/xanthine oxidase did not abolish this trend. These cultures were not significantly different from cultures without Ascorbic Acid. However xanthine/xanthine oxidase plus 1000 μm Ascorbic Acid caused a significant linear trend toward decreasingly severe abnormalities when compared with xanthine/xanthine oxidase. Ascorbic Acid (10, 100, or 1000 μm) added to xanthine control cultures did not differ significantly from the control cultures. No biologically significant effects on growth parameters of the embryos treated with L-Ascorbic Acid were observed. Germ cell detachment was also measured in mixed cultures of Sertoli and germ cells treated with xanthine/xanthine oxidase and/or L-Ascorbic Acid. Treatment with xanthine/xanthine oxidase in studies significantly increased germ cell detachment when compared to controls. Detachment was also significant with Ascorbic Acid doses of 1 mM and 2 mM. With the highest dose of Ascorbic Acid with the xanthine/xanthine oxidase system there was a significant decrease in detachment. Ascorbic Acid treatment alone had no effect on the system.

General safety info about Ascorbic Acid from CIR

This report reviews the safety of Ascorbic Acid (L-form [CAS no. 50-81-7]), commonly known as Vitamin C, Calcium Ascorbate (CAS No. 5743-27-1), Magnesium Ascorbate, Magnesium Ascorbyl Phosphate (CAS No. 114040-31-2), Sodium Ascorbate (CAS No. 134-03-2), and Sodium Ascorbyl Phosphate (CAS No. 66170-10-3) in cosmetic formulations. These ingredients function primarily as antioxidants in cosmetics. Related ingredients, Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate, have been previously reviewed and were found “to be safe for use as cosmetic ingredients in the present practices of good use” (Cosmetic Ingredient Review [CIR] 1997). In a review article, Bates (1997) describes Ascorbic Acid as an acidic molecule with strong reducing activity, derived from hexose sugars, and essential to most living tissue. D-Isoascorbic acid is a structural analogue but with only 5% of the antioxidant activity of L-Ascorbic Acid in vivo. The enantiomer D-ascorbic acid has no vitamin activity. This author also notes that many living species are able to synthesize Vitamin C from hexose sugars such as glucose. The final enzyme used in this pathway is L-glucuronolactone oxidase. This enzyme is missing in species not able to synthesize Vitamin C. Such species, including humans, higher primates, guinea pigs, and birds require a dietary source. Without the required dietary Vitamin C, the body stores become depleted and the fatal deficiency disease, scurvy, manifests. Clinical scurvy is characterized by failure of wound healing, bleeding gums, bone and joint lesions, and other signs of connective tissue failure culminating in death. Although contending that there are many functions of Ascorbic Acid yet to be defined, this author states that the Ascorbic Acid reducing potential and conversion to AFR (ascorbate free radical) are key to its biological activity, including its free radical scavenging and its relationship to the oxidation of transition metals such as iron and copper at enzyme active sites and in food (Bates 1997).

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Products where you might find Ascorbic Acid

Paula’s Choice 10% Azelaic Acid Booster, Lancer Skincare The Method: Body Nourish with Hylaplex and Glycolic Acid 10%, Paula’s Choice RESIST Daily Smoothing Treatment with 5% Alpha Hydroxy Acid; The Ordinary Ascorbic Acid 8% + Alpha Arbutin 2%, The Ordinary Ethylated Ascorbic Acid 15% Solution, Drunk Elephant C-Firma Vitamin C Day Serum