Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial
© Gambichler et al; licensee BioMed Central Ltd. 2001
Received: 20 September 2001
Accepted: 20 November 2001
Published: 20 November 2001
Photodegradation of certain vitamins such as riboflavins, carotinoids, tocopherol, and folate has been well-documented. Previous observations suggest that ultraviolet (UV) radiation may cause folate deficiency. This is of great importance since folate deficiency is also known to be linked with the development of neural tube defects. To investigate the influence of UVA radiation on serum folate levels in vivo, we conducted a two-group randomised controlled trial on healthy subjects.
Material and methods
Twenty-four healthy volunteers with skin type II were enrolled into the study. Eight volunteers of the study population were randomly assigned to the control group. UVA irradiation was administered with an air-conditioned sunbed. Blood samples were taken from all volunteers at baseline (T1), 30 min after the first UVA exposure (T2), and at the end of the study 24 h after the sixth UV exposure (T3). The volunteers had two UVA exposures weekly within three weeks (cumulative UVA dose: 96 J/cm2). Volunteers of the control group had no UVA exposures. Serum folate was analysed with an automated immunoassay system.
At all times of blood collection the differences between serum folate levels were insignificant (P > 0.05), except of the non-exposed controls at T2 (P < 0.05). We did not observed significant differences of folate levels between UVA exposed and non-exposed volunteers (P > 0.05).
Our data suggest that both single and serial UVA exposures do not significantly influence serum folate levels of healthy subjects. Therefore, neural tube defects claimed to occur after periconceptual UVA exposure are probably not due to UVA induced folate deficiency.
Folate, the conjugated form of folic acid, is an essential nutrient that is required for nucleotide respective DNA biosynthesis. Apart from macrocytic megaloblastic anemia folate deficiency has also been shown to produce multiple fetal anomalies in nonhuman mammals. Moreover, it has recently been confirmed that there is a connection between defective folate metabolism, neural tube defects (e.g., craniorachischisis, spina bifida), and impaired spermatogenesis in humans [1, 2]. Folate catabolism and simultaneous folate deficiency has been observed in various conditions, such as pregnancy, alcoholism, drug use (e.g., methotrexate), and malnutrition. Photodegradation of certain vitamins such as riboflavins, carotinoids, tocopherol, and folate has been well-documented [3–5]. Photolysis of folate may be significant, especially when serum is exposed in vitro to ultraviolet (UV) radiation. In one study, published in the journal Science, it has been reported that fair-skinned patients undergoing photochemotherapy for dermatological conditions have low serum folate concentrations, suggesting that photolysis may also occur in vivo. Besides, neural tube defects (NTD) have been found associated with sunbed exposures during the first weeks of pregnancy . Nevertheless, phototherapy is generally recommended by dermatologists as safe to use in pregnant women . Since there is a lack of controlled studies in this field, we conducted a two-group randomised controlled trial investigating serum folate levels of healthy fair-skinned subjects undergoing a series of sunbed exposures.
Material and methods
Subjects and setting
Twenty-four healthy volunteers with skin type II  were subsequently recruited. Exclusion criteria included: pregnancy, abnormal diets, drug use, and UV exposure within the last two months prior to the study. All volunteers gave informed consent for participation in the study. Randomised allocation of two groups was performed by asking the volunteers to throw dice without knowing the underlying allocation criteria (nos 1–3: exposed group; nos 4–6: non-exposed group). Thus eight volunteers of the study population were randomly assigned to the control group. The study was conducted in a university dermatological department during winter.
UV source and dosimetry
Blood collection and determination of folate
Blood samples were taken from the volunteers in the morning at baseline (T1), 30 min after the first UV exposure (T2), and at the end of the study 24 h after the sixth UV exposure (T3). Determination of serum folate was performed using the automated immunoassay system AD VIA Centaur® IS (Bayer Diagnostics, Fernwald, Germany). Normal range of serum folate is 3–20 ng/ml with the assay used.
We used the SPSS 10.0 for Windows. Analysis of distribution was made by the Kolmogorov-Smirnov-test. For comparison of paired and independent samples by normal distribution the 2-tailed Student's t-test was used and for comparison of paired samples by non-normal distribution the Wilcoxon test. Differences were considered significant when P < 0.05.
Results and Discussion
Baseline characteristics of the 24 volunteers and means ± SD of serum folate levels (ng/ml) before (T1) and after (T2; T3) UVA exposure
Sex female (f); male (m)
Mean age years
11 f; 5 m
10.1 ± 3.1 (6.3–20)*
10.4 ± 3 (6.1–17)*
5 f; 3 m
11.6 ± 3.5 (7.2–30)*
12.9 ± 3.9 (8.3–32)*
11 ± 3.1 (6.5–20.2)*
The protective role of folate in preventing NTD is well established . Jablonski and Chaplin  recently hypothesized that highly melanised skin protecting against UV induced photolysis of folate is of great importance for individual reproductive success, and that folate photolysis may, especially in fair-skinned women, precipitate a folate deficiency sufficient to cause a neural tube defect during the first weeks of pregnancy. Therefore it has been suggested to avoid periconceptual UV exposure . It has to be stressed, however, that folate deficiency is common in pregnant women and may arise both from inadequate dieatary folate and from increased utilization of the vitamin during pregnancy . In fact, low prevalences of severe folate deficiency and NTD have been observed in native Africans and African Americans [11, 12].
Branda and Eaton  found that exposure of human plasma in vitro to solar-simulated radiation causes 30–50% loss of folate within 60 min. They also conducted an in vivo trial on 10 fair-skinned Scandinavians undergoing photochemotherapy because of various skin diseases which have not been detailed in their paper. However, one may assume that it predominantly concerned psoriasis patients. They were treated with methoxalen and UVA radiation (4.5 to 9.5 J/cm2) once or twice per week. The time of blood collection was after 3 to 13.5 months after starting photochemotherapy. Baseline folate levels were not determined. The authors found that serum folate levels of the patients were significantly lower than those of 64 healthy controls. Nevertheless, the folate levels of the patients were not within the abnormal range. Possible drug interactions (e.g., methoxalen, methotrexate) and disease-associated factors (e.g., psoriasis and alcohol abuse) affecting folate metabolism were not discussed by the authors [6, 13]. Because of the methodology and the restrictive description given in Branda and Eaton's report  definitive conclusions can hardly be drawn from their results.
Lapunzina  observed three patients with NTD whose mothers had sunbed exposures during the first weeks of their pregnancies. All three mothers were young and healthy. Although folate deficiency of the mothers was not proved, the author speculated that sunbed exposure may have caused teratogenesis in these three patients. Based on epidemiological data Van Rootselaar  also suggests that UV radiation may cause NTD in embryos of exposed mothers. Furthermore, Lapunzina  hypothesized that heat respective hyperthermia-related effects could possibly cause NTD. This was also postulated by Milunsky et al. , who found an increased risk for NTD among offspring of women exposed to heat in form of hot tub, sauna, or fever during early pregnancy.
Our data suggest that both single and serial UVA exposures do not significantly influence serum folate levels in vivo. Based on these results, we conclude that NTD claimed to occur after periconceptual UVA exposure are probably not due to UVA induced folate catabolism.
List of abbreviations
neural tube defects
We are very grateful to the Förderverein Sonnenlicht-Systeme e.V. (FVS, Stuttgart, Germany) who provided the sunbed for research works.
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