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,1,12
Institut für Experimentelle Dermatologie, Universität Witten-Herdecke, D-58455 Witten, Germany,
*
Cognis Deutschland GmbH & Co. KG, Nutrition and Health, D-40551 Düsseldorf, Germany and
Institut für Physiologische Chemie I and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, D-40001 Düsseldorf, Germany
2To whom correspondence should be addressed. E-mail: wilhelm.stahl{at}uni-duesseldorf.de
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • sunburn • skin carotenoids • ß-carotene • lycopene • lutein
Supplementation with ß-carotene or the consumption of a carotenoid-rich diet provides moderate protection from UV-induced erythema (1
–5
). In all of the studies showing efficacy, supplementation was for periods longer than 10 wk and the doses ranged from 15 to 180 mg/d.
The protective effects of carotenoids from UV-induced lesions are ascribed to their antioxidant activities including scavenging reactive oxygen species generated in photooxidative processes. However, at higher levels, prooxidant reactions have been observed when carotenoids were applied in vitro (6
–8
). Irradiation of fibroblasts with UV light in the presence of high amounts of ß-carotene increases lipid peroxidation (8
) and stimulates the expression of heme oxygenase-1 and interleukin-6 (9
,10
).
Concerns about the safety of supplementation with higher dosages of ß-carotene has been raised on the basis of the results of two intervention trials in individuals at high risk for lung cancer (11
,12
), in which ß-carotene was applied (20 and 30 mg/d) alone or in combination with 
-tocopherol or retinol for several years. In the -tocopherol, ß-carotene supplementation study (ATBC) (11
) of Finnish long-term heavy smokers (>1 pack/d for 35 y), a slightly higher cumulative incidence of lung cancer was observed in the group that received ß-carotene than in the placebo control. An increased risk for lung cancer was also found in the CARET (ß-Carotene and Retinol Efficacy Trial) study (12
), which included smokers and asbestos workers. No elevated risk was observed in three other intervention trials performed in populations less at risk for lung cancer, supplementing ß-carotene at comparable doses (13
–15
).
ß-Carotene is supplied by a diet rich in fruit and vegetables, which also contains a number of other carotenoids including lycopene, the major carotenoid in the tomato, or xanthophylls like lutein, which is found in green leafy vegetables and in fruit (16
). These carotenoids are also suitable antioxidants, and it has been shown that the consumption of tomato products rich in lycopene protects against UV light–induced erythema (2
). In the present study we investigated whether a high dose of ß-carotene or a mixture of carotenoids provides comparable sun protection.
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SUBJECTS AND METHODS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Thirty-six healthy adults, all of skin type II and between 22 and 55 y old (12 men, 24 women) were randomly assigned to three groups of 12. The "ß-carotene group" ingested 24 mg of ß-carotene per day, the source of which was a natural carotenoid extract from the alga Dunaliella salina (Betatene®, Cognis Australia Pty. Ltd., Melbourne, Australia), provided as a soft gel capsule with soybean oil as the vehicle. In addition to ß-carotene (15.8 mg all-trans ß-carotene, 5.8 mg 9-cis ß-carotene, 2.0 mg other cis isomers), each capsule contained 0.88 mg -carotene, 0.25 mg cryptoxanthin, 0.12 mg zeaxanthin, and 0.12 mg lutein.
The "mixed carotenoid group" was supplemented with a combination of 8 mg ß-carotene (Betatene®; for composition see above), 8 mg lycopene (4% tomato oleoresin, Cognis Australia) and 16 mg lutein esters (from Xangold® Cognis, LaGrange, IL) stoichiometrically equivalent to 8 mg of lutein. A total of 24 mg mixed carotenoids/d was given as a soft gel capsule with soybean oil as the vehicle.
The control group received a soft gel capsule containing only soybean oil.
All participants ingested the carotenoid supplement or placebo once a day for 12 wk. They were advised to ingest the capsule with their main meal. Compliance was monitored by questionnaire and by analysis of serum carotenoid concentration. The diet was not standardized during the study, although the participants were advised not to change their dietary habits. No further supplementation with vitamin or carotenoid supplements was allowed.
Skin type grading was evaluated by coloration of skin, hair and eyes as well as the history of sensitivity to sun exposure (17
). Exclusion criteria were pregnancy, lactation and medication possibly affecting the outcome in any conceivable way. Written informed consent was obtained from each participant, and the study design was approved by the Ethics Committee of the University of Witten-Herdecke, Germany.
Analyses of carotenoids in serum and skin.
Blood was collected at the beginning of the study (wk 0) and after 6 and 12 wk of supplementation. Serum was prepared from the blood samples and stored at -80°C until analysis. The levels of ß-carotene, lutein and lycopene in serum were analyzed by HPLC as described previously (18
). Concentrations of total carotenoids in the skin (palm of the hand) were determined at the beginning of the study (wk 0) and after 6 and 12 wk of treatment by reflection spectroscopy (19
).
Induction of erythema and measurement of skin color.
The MED (minimal erythemal dose) was determined for each subject before the start of the study and after 6 and 12 wk of supplementation. Irradiation with UV light to induce erythema (1.25-fold that of MED) was applied to dorsal skin (back, scapular region) by use of a blue-light solar simulator (Hönle, Munich, Germany). At each time point (wk 0, 6, 12) skin color was measured before and 24 h after irradiation.
Skin color was evaluated by chromametry (Chromameter Minolta CR 200, Ahrensburg, Germany) by use of the three-dimensional color system (L-, a-, b-values). L-values are a parameter for lightness of skin; b-values (blue/yellow axis) are indicative of pigmentation; a-values (red/green-axis) are a measure of erythema formation and were used to quantify skin responses to UV irradiation.
Statistics.
Statistical analysis was performed with Excel 5.0 (Microsoft, Unterschleissheim, Germany). Within groups, the time points were compared through use of the two-sided paired Student’s t test. The pre/post differences were compared among the groups by use of the two-sided, two-sample Student’s t test. Differences were analyzed at each time point. All data are presented as mean ± SD.
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RESULTS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The basal serum ß-carotene, lutein and lycopene concentrations differed somewhat among the groups but all were within the normal ranges for serum carotenoids (Table 1
).
|
In the mixed carotenoid group, the three serum carotenoid concentrations increased significantly after 6 and 12 wk of supplementation. Serum concentrations on wk 12 were somewhat lower than those on wk 6 but the differences were not significant. The levels of lutein were about four times the basal value on wk 6 and wk 12 and ß-carotene and lycopene were approximately doubled. The sum of carotenoids increased from 1.3 µmol/L on wk 0 to 3.5 and 3.0 µmol/L on wk 6 and wk 12, respectively, somewhat less than the increase of total carotenoids in the ß-carotene group, although all three carotenoids cause a rise in serum levels. It is important to note that the ß-carotene levels in the mixed carotenoid group were much lower than those in the ß-carotene group. Serum carotenoid concentrations did not change in the control group during the 12-wk period.
Total carotenoids in skin of the palm of the hand increased similarly (P < 0.001) at both 6 and 12 wk after ingestion of both ß-carotene and the mixture of carotenoids (Fig. 1
upper panel). Total carotenoids in skin were not affected in the control group. Positive chromametry b-values, which are indicative of "yellowing" of the skin and are related to carotenoid levels (20
), increased in both supplemented groups from wk 0 to wk 6 and 12, whereas no changes occurred in the controls (Fig. 1
, lower panel).
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Chromametry a-values were measured on wk 0, 6 and 12 before and 24 h after irradiation of the skin with a solar light simulator (Table 2
). The a-values before irradiation were similar in all groups at all time points. They increased 24 h after irradiation because of erythema formation and are indicative of the redness of the skin and thus reflect the degree of erythema. The a-values 24 h after irradiation did not differ among the three groups at baseline (wk 0).
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Changes in the a-values from wk 0 to wk 6 and wk 0 to wk 12 did not differ between the ß-carotene and the mixed carotenoid groups (P = 0.668 and P = 0.331, respectively). However, changes in both treatment groups differed significantly from those in the controls (P < 0.05 and P < 0.001 for the wk 6 and wk 12 changes, respectively).
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DISCUSSION |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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,4
). Even higher levels of ß-carotene were observed in the long-term intervention studies (>3 y), with means of about 5.7 µmol/L in the ATBC trial and 4.0 µmol/L in CARET (21
).
Administering a carotenoid mixture with less ß-carotene and additional lutein and lycopene increased serum levels of all three carotenoids. However, maximal levels of ß-carotene were 1.7 and 1.3 µmol/L on wk 6 and 12, respectively (i.e., much lower than in the group receiving ß-carotene alone). Similar levels were measured in the Linxian study, somewhat above the 5th percentile to the 95th percentile of the U.S. population, which is 0.09–0.9 µmol ß-carotene/L. Serum levels of lutein and lycopene rose to about 0.7 and 1.0 µmol/L, respectively, which is consistent with earlier reports (2
,22
). After the intake of 10 mg lutein/d (from lutein esters) for 12 wk, increases in plasma levels from 0.2 to 0.9 µmol/L were reported (22
). Daily consumption of tomato paste providing 16 mg lycopene increased lycopene levels from 0.4 µmol/L on d 0 to 0.7 µmol/L by wk 10 (2
). With a balanced supplementation supplying a variety of carotenoids, excessive serum levels of a single compound can be avoided.
Total carotenoids in the skin on the palm of the hand increased during the study. After 12 wk of supplementation, a total of 1.2 nmol carotenoids/g tissue was detected in the ß-carotene group and 1.4 nmol carotenoids/g tissue in the mixed carotenoid group. Although carotenoids were not analyzed individually, it is likely that increases in skin levels of the ß-carotene group result from increases only in ß-carotene, whereas levels of total carotenoids in the mixed carotenoid group result from increases in all three carotenoids. In a similar supplementation study with ß-carotene, 1.0 nmol total carotenoids/g tissue was reported for palm of the hand (19
).
"Yellowing" of the skin can be quantified by positive chromametry b-values. Previously, it was shown that b-values are related to carotenoid levels in the skin (20
). In the present study we found that they increased in both supplemented groups, whereas no change occurred in controls, confirming earlier findings.
Lowered chromametry a-values 24 h after irradiation result from the preventive effects of treatment with either ß-carotene or a mixture of carotenoids, which provides further evidence that endogenous sun protection may be achieved by use of micronutrients; the extent of prevention is comparable to that of previous studies (1
,2
). After 6 and 12 wk, balanced supplementation with three different carotenoids is as effective as supplementation with ß-carotene alone. For people with a high risk for lung cancer, supplementation with high doses of ß-carotene has been questioned and safety issues have been addressed with regard to long-term intake of ß-carotene (11
,12
,21
,23
). The use of a carotenoid mixture with lower doses of individual carotenoids instead of a higher dose of a single carotenoid (ß-carotene) may be an alternative for sun protection.
The extent of protection with ingested carotenoids is not comparable to the use of a sunscreen with a high sun protection factor. However, increasing the basal protection systemically contributes to the permanent defense against UV light–mediated skin damage.
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FOOTNOTES |
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Manuscript received 27 August 2002. Initial review completed 13 September 2002. Revision accepted 10 October 2002.
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LITERATURE CITED |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Stahl, W., Heinrich, U., Jungmann, H., Sies, H. & Tronnier, H. (2000) Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am. J. Clin. Nutr. 71:795-798.
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