|Year : 2015 | Volume
| Issue : 1 | Page : 1-5
Vitamin C supplementation in pregnancy: A review of current literature
Emmanuel Ajuluchukwu Ugwa
Department of Obstetrics/Gynaecology, Federal Medical Centre, Birnin Kudu, Jigawa, Nigeria
|Date of Web Publication||8-May-2015|
Emmanuel Ajuluchukwu Ugwa
Department of Obstetrics/Gynaecology, Federal Medical Centre, Birnin Kudu
Source of Support: None, Conflict of Interest: None
Vitamin C deficiency is a prevalent problem among pregnant women in developing countries. This review is undertaken to evaluate current literature on effect of vitamin C supplementation on the course and outcomes of pregnancy so as to recommend its supplementation or otherwise. Electronic search of Medline, PubMed, Health Internetwork access to Research Initiative (HINARI), and Google Scholar databases was conducted for articles from 1 st January, 1993 to 30 th November, 2014 using keywords such as "micronutrients", "vitamin C", "ascorbic acid", "vitamin supplementation", and "nutrition in pregnancy". Current evidence from developing countries where vitamin C is deficient among pregnant women has shown that vitamin C may reduce the incidence of some complications of pregnancy and therefore encourage their supplementation in pregnancy. Additional studies, however, are needed in different geographic regions to identify whether vitamin C supplementation in pregnancy results in functional and measurable outcomes for maternal and foetal health. These studies would enable the appropriate intervention strategies to be developed, implemented, and evaluated. Such efforts will require the collaboration and commitment of government agencies, health care providers, nutritionists, research institutions, and the community.
Keywords: Pregnancy, supplementation, Vitamin c
|How to cite this article:|
Ugwa EA. Vitamin C supplementation in pregnancy: A review of current literature. Niger J Basic Clin Sci 2015;12:1-5
| Introduction|| |
Vitamin C or ascorbic acid is an essential water-soluble micronutrient, involved in the synthesis of collagen, an essential component of connective tissue.
Deficiencies in micronutrients such as folate, iron, zinc, and vitamins A, B6, B12, C, E and riboflavin are highly prevalent and may occur concurrently among pregnant women.  Nutrient deficiencies are generally found in low socio-economic populations, where they are more likely to involve multiple rather than single deficiencies. 
Vitamin C, like other vitamins is an organic substance, which is required by the body in small amounts to maintain life and health and acts as a catalyst in the formation of hormones, enzymes, blood cells, neurotransmitters, and genetic material.  It is also essential to complete the metabolism of carbohydrates, proteins, and fats. The body's need for vitamin C is met by diet, especially fruits. Vitamin C has antioxidant properties and as such either blocks the initiation of free radical formation or inactivates (scavenge) free radicals. 
Humans, unlike most animals, are unable to synthesise vitamin C endogenously, so it is an essential dietary component. The sources of vitamin C are fresh citrus fruits, pineapple, guava, water melon, tomatoes, cabbage, and green pepper. Fruits and vegetables are the best sources of vitamin C.  Vitamin C is one of the important vitamins and few studies have linked various obstetric problems with its deficiency during pregnancy, especially in the third trimester. 
Supplements typically contain vitamin C in the form of ascorbic acid, which has equivalent bioavailability to that of naturally occurring ascorbic acid in foods, such as orange juice and broccoli. ,
In addition to the numerous benefits of this vitamin in human metabolism and health, Vitamin C supplementation could help to prevent the development of such complications of pregnancy like gestational hypertension, intra-uterine growth retardation, and gestational diabetes, conditions all known to be associated with high levels of oxidative stress. 
Data on vitamin C status among pregnant women as well as other water-soluble vitamins are very few and are mainly from developed countries. Many of the studies and literature reviews dealing with maternal nutrition and birth outcomes have approached the issue by investigating multiple nutrients. There is considerable debate on the potential adverse effects of providing multiple micronutrient supplements during pregnancy. There is a concern about an increase in neonatal mortality in less developed health systems that have suboptimal maternal care. , Examination of a single nutrient supplementation such as vitamin C supplementation is necessary for an in-depth study of the complex issues involved.
The effects of maternal vitamin C supplementation on perinatal mortality and other pregnancy outcomes can differ depending on study characteristics and study population. An updated review is essential to provide the basis for future research and for a discussion of policy implications.
This review was undertaken to evaluate current literatures on the effect of vitamin C supplementation on the course and outcomes of pregnancy so as to recommend its supplementation or otherwise [Figure 1].
Ascorbic acid is derived from glucose via the uronic acid pathway.  The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates, making ascorbic acid required in the diet. The active form of vitamin C is ascorbic acid itself. The main function of ascorbate is as a reducing agent in a number of different reactions. Ascorbate is the cofactor for Cu + -dependent mono-oxygenases and Fe 2+ -dependent dioxygenases. Ascorbate has the potential to reduce cytochromes a and c of the respiratory chain as well as molecular oxygen. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodelling. Vitamin C is also necessary for bone remodelling due to the presence of collagen in the organic matrix of bones. Ascorbic acid also serves as a reducing agent and an antioxidant. When functioning as an antioxidant, ascorbic acid itself becomes oxidised to semidehydroascorbate and then dehydroascorbate. Semidehydroascorbate is reconverted to ascorbate in the cytosol by cytochrome b 5 reductase and thioredoxinreductase in reactions involving NADH and NADPH, respectively. Dehydroascorbate, the fully oxidised form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH.
Several other metabolic reactions require vitamin C as a cofactor. These include the catabolism of tyrosine and the synthesis of epinephrine from tyrosine and the synthesis of the bile acids. It is also believed that vitamin C is involved in the process of steroidogenesis since the adrenal cortex contains high levels of vitamin C, which are depleted upon stimulation of the gland by adrenocorticotropic hormone (ACTH).
| Functions of ascorbic acid|| |
Due to the role of vitamin in the post-translational modification of collagens, deficiency of vitamin C leads to the disease, scurvy. Scurvy is characterised by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing, haemorrhage, osteoporosis, and anaemia. Vitamin C is readily absorbed and so the primary cause of vitamin C deficiency is poor diet and/or an increased requirement. The primary physiological state leading to an increased requirement for vitamin C is severe stress (or trauma). This is due to a rapid depletion in the adrenal stores of the vitamin. The reason for the decrease in adrenal vitamin C levels is unclear but may be due to either redistribution of the vitamin to areas that need it or an overall increased utilisation.
Inefficient intake of vitamin C has also been associated with a number of conditions, such as high blood pressure, gallbladder disease, stroke, some cancers, and atherosclerosis (plaque in blood vessels that can lead to heart attack and stroke). Sufficient vitamin C in the diet may help reduce the risk of developing some of these conditions; however, the evidence that taking vitamin C supplements will help or prevent any of these conditions is still lacking.
The amount of vitamin C that is recommended for consumption each day (the RDA) depends upon the age and sex of the individual. Infants less than 1 year old should get 50 milligrams (mg) per day. Children 1-3 years old need 15 mg, 4-8 years old need 25 mg, and 9-13 years old need 45 mg. Adolescent girls should get 65 mg per day and adolescent boys should get 75 mg per day. Adult males need 90 mg per day and adult women should get 75 mg per day. Women who are breastfeeding should increase their intake to at least 120 mg per day. Individuals who smoke should increase their daily intake by at least 35 mg since smoking depletes vitamin C levels. The recommended daily intake of vitamin C to prevent conditions such as the cardiovascular disorders indicated above is reported to be between 500 mg and 1000 mg.
Fruits and vegetables are excellent sources of vitamin C. These include oranges, watermelon, paw-paw, grapefruit, strawberries, raspberries, blueberries, cranberries, pineapple, mango, green peppers, broccoli, turnip greens, spinach, red and green peppers, canned and fresh tomatoes, potatoes, Brussels sprouts, cauliflower, and cabbage. Citrus juices or juices fortified with vitamin C are also excellent sources of the vitamin.
Vitamin C is sensitive to light, air, and heat, so the most vitamin C is available in fruits and vegetables that are eaten raw or lightly cooked. Natural or synthetic vitamin C can be found in a variety of forms. Tablets, capsules, and chewables are probably the most popular forms, but vitamin C also comes in powdered crystalline, effervescent, and liquid forms. An esterified form of vitamin C is also available, which may be easier on the stomach for those who are prone to heartburn. The best way to take vitamin C supplements is 2-3 times per day, with meals, depending on the dosage.
| Methods|| |
Electronic search of Medline, PubMed, Health Internetwork Access to Research Initiative (HINARI), and Google Scholar databases up to November, 2014 was conducted for studies that analysed the effects of supplying vitamin C on the course of pregnancy and pregnancy outcomes.
Search was done in keywords like pregnancy, micronutrient, supplement, vitamin C, clinical trials. A function extracting related articles as well as reference lists from research, reviews, and editorials were used during the search process. The full version of the English-language analysed articles and abstracts of most found papers were available during the selection process except for PubMed search.
Literature involving observational studies, quasi-randomised trials, and prospective randomised controlled trials (RCTs) evaluating vitamin C and multiple micronutrient supplementation in women during pregnancy, published in English language, were included.
| Results|| |
Studies done in Nigeria have shown low serum vitamin C levels among cohorts of pregnant women [Table 1]. Some studies done in developed countries where vitamin C deficiency among pregnant women is uncommon did not support vitamin C supplementation in pregnancy [Table 2].
| Discussion|| |
Decision as to which micronutrients are of greatest concern in developing countries requires a more systematic and comprehensive approach. This will result in a consensus on the objectives of prophylactic supplementation of vitamin C and probably other micronutrients, the criteria for identifying and setting concentrations, and the outcomes to be measured. It will require careful review of the dietary intakes of both non-pregnant, non-lactating women and pregnant women; the vitamin C status of non-pregnant, non-lactating women; and the cost-effectiveness of ongoing interventions in developing countries including Nigeria.
Studies have found significant reduction in serum vitamin C in pregnant Nigerians. ,,,, Plasma vitamin C decline during pregnancy follow a linear trend with time in some studies , while in others it did not.  Vitamin deficiency may be accounted partly by the physiological haemodilution of pregnancy, inadequate intake and the use of vitamin C to combat the oxidative stress of pregnancy.  These Nigerian studies are however few, small samples and mostly cross-sectional. Majority of the studies are from developed economies where vitamin C deficiency is uncommon. , Although these studies were of high quality and of large samples, they did not exclude women with normal vitamin C status. Therefore, these studies did not favour the supplementation of vitamin C to pregnant women. ,,
Studies from less-developed economies where vitamin C deficiency among pregnant mothers is prevalent showed significant benefit of vitamin C supplementation during pregnancy in reducing low birth weight and small for gestational age births. ,, Vitamin C may be protective against development of pre-eclampsia. , Supplementation with vitamin C and E reduces oxidative stress and endothelial dysfunction  and pre-eclampsia.  It has also been shown that supplementation with vitamins C and E after preterm premature rupture of membranes (PPROM) is associated with statistically significant increase in difference in the number of days before delivery. ,, However, another study was of the contrary and does not support vitamin C use for management or prevention of PPROM. 
Vitamin C has been reported to play an important role in embryogenesis and foetal growth as well as in the progression of pregnancy and delivery.  Indeed, it has been reported that maternal vitamins A and C status tends to affect the foetal size.  Ascorbic acid protects against lipopolysaccharide-induced intra-uterine foetal death and intra-uterine growth retardation in mice.  These studies proposed that the use of exogenous antioxidant supplement during pregnancy to mitigate against this oxidative stress may be necessary to prevent pregnancy complications. , However conflicting report ,, means that further research especially in resource restrained settings are needed.
| Conclusion and recommendations|| |
The need for vitamin C supplementation in pregnancy in developing countries is likely to be great because of widespread maternal malnutrition. Public health resources, however, are limited and it is inevitable that priority will be given to interventions that are both efficacious and effective. Current evidence from developing countries where vitamin C is deficient among pregnant women has shown that vitamin C may reduce the incidence of some complications of pregnancy and therefore encourage their supplementation in pregnancy. Additional studies, however, are needed in different geographic regions to identify whether vitamin C supplementation in pregnancy results in functional and measurable outcomes for maternal and foetal health. These studies would enable the appropriate intervention strategies to be developed, implemented, and evaluated. Such efforts will require the collaboration and commitment of government agencies, health care providers, nutritionists, research institutions, and the community.
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[Table 1], [Table 2]