The media occasionally warn against the consumption of fortified drinks or dietary supplements containing isolated beta-carotene. The following article section provides background on the safety of beta-carotene and factually supports the discussion with facts and figures.
The facts in brief
Starting point of the discussion in the 1990s: The ATBC and CARET studies
According to the results of two intervention studies published in the mid-1990s, in which beta-carotene was supplemented in high doses (20-30 mg) over several years, asbestos workers and longtime heavy smokers (mind. 20 cigarettes/day for more than 30 years) an increased risk of lung cancer. Non-smokers and former smokers
For nonsmokers and former smokers, no increased risk of lung cancer has been demonstrated to date in intervention studies involving a total of several 10,000 participants at high beta-carotene doses (WHS, HPS, AREDS, REACT, PHS, Su.VI.MAX), nor for cardiovascular disease (PHS). This applies equally to the combined intake of beta-carotene, vitamin C and E ( ACE). Self-restraint of the economy organized in the BLL
In light of the findings from ATBC and CARET, industry committed to self-restraint in 2001: In beverages, it does not use more than 2 mg of isolated beta-carotene per 100 ml. Dietary supplements with consumption recommendations above 4.8 mg of isolated beta-carotene are either labeled with a statement that this product is not suitable for heavy smokers or a statement is included that the use should be limited in time. Self-commitment: No risk for consumers, not even for smokers
There is no risk to any consumer group if the upper limits for isolated beta-carotene are adhered to as part of the industry's voluntary commitment, this is shown by a model calculation based on consumption data from the GfK trade and household panel. Beta-carotene is the safe source of vitamin A
Beta-carotene is the safe source of vitamin A at doses specified in the voluntary commitment, because beta-carotene is converted by the body into vitamin A as needed.
Starting point of the discussion in the 1990s: The results of the ATBC and CARET studies
In 1994 the result of the ATBC study on nearly 30,000 long-term heavy habitual smokers published. Study participants who received 20 mg of beta-carotene daily for 5-8 years had increased lung cancer incidence and mortality compared to placebo – but this only affected those who smoked at least 20 cigarettes daily [ATBC study group, 1994; Albanes et al., 1996]. In 1996, the results of CARET published. In CARET received approx. 18 300 smokers and/or asbestos workers over 5 years daily placebo or 30 mg beta-carotene plus 7.5 mg vitamin A. Lung cancer incidence and mortality were increased in active habitual smokers and asbestos workers, but not in former smokers [Omenn et al., 1996]. Discussions in professional circles. In the popular media. The focus was on the question of how these studies should be evaluated and the results explained; what significance the results have for the general population, as well as whether and if so. which regulatory projects are necessary.
1996: No risk of lung cancer in non-smokers and former smokers from beta-carotene intake
With regard to the question of the influence of beta-carotene for non-smokers and former smokers gave already in 1996 the results of the Physicians' Health Study (PHS) Evidence: It showed that there was no increased risk of lung cancer for these groups of people. At the PHS participated ca. 22. 000 people participated – including smokers, non-smokers as well as former smokers. After 12 years of taking 50 mg of beta-carotene every other day, the risk of lung cancer was not increased for nonsmokers, former smokers, or active smokers [Hennekens et al, 1996]. PHS and CARET thus showed that in non-smokers resp. in former smokers, consumption of beta-carotene is not associated with an increased risk of lung cancer.
Findings over the past 10 years confirm: Beta-carotene is safe for non-smokers
Since the publications of ATBC, CARET and PHS in the 1990's a large number of studies on beta-carotene were carried out and evaluated. They show that beta-carotene is safe for non-smokers:
In the Women's Health Study (WHS) no increased risk of cancer or death was observed in the study period of 2.1 years and in 2 years of follow-up. Lung cancer risk observed. This study involved 40 000 women, including 13% smokers. They received 50 mg of beta-carotene every other day [Lee et al., 1999].
In several studies beta-carotene was not given alone, but together with vitamin E and/or vitamin C. Also in these studies – the Heart Protection Study (HPS, 20.000 participants, 20 mg beta-carotene) and the Age-Related Eye Disease Study (AREDS, 3.640 patients, 15 mg beta-carotene) – had shown no evidence of increased risk of lung cancer [Heart Protection Study Collaborative Group, 2002; Age-Related Eye Disease Study Research Group, 2001]. In the Heart Protection Study, one study group received 20 mg beta-carotene plus 600 mg vitamin E plus 250 mg vitamin C daily, a second group received 40 mg simvastatin, a third group received antioxidants plus simvastatin, and finally a fourth placebo. The duration of the intervention was five years. In AREDS, placebo or a combination of 15 mg beta-carotene, 400 I.E. Vitamin E, 500 mg vitamin C, 80 mg zinc, and 2 mg copper given. In AREDS, positive effects of supplementation on the actual parameter studied, in this case age-related macular degeneration, were observed over the study duration of 6.3 years on average.
About 13.000 participants, including 16% smokers, supplemented their diet in the French Su.VI.MAX study over 7.5 years with 6 mg beta-carotene and other antioxidant vitamins and minerals. In males, the risk of cancer was reduced by as much as 31% compared to placebo, this was mainly respiratory and digestive tract tumors [Hercberg et al., 2004].
A study with high-dose beta-carotene (50 mg/d) consumed over several years (median 50 months) found an antioxidant effect even in smokers, while prooxidant effects could not be detected [Mayne et al., 2004].
In ATBC and CARET the study participants continued to be observed after the end of the actual intervention phase (Follow up). In ATBC, there was no longer a difference in lung cancer risk six years after the end of the intervention between the groups receiving placebo or. had received beta-carotene [ATBC study group, 2003]. In CARET, it was still elevated after six years of follow-up as well; however, the difference compared with placebo was no longer statistically significant [Goodman et al., 2004].
The Mechanisms, underlying the increased risk of lung cancer in high-risk groups such as heavy smokers were conducted primarily at Tufts University in Boston, USA, in a suitable Animal model (ferret) examined. Accordingly, so-called "smoking" ferrets develop increased lung cancer when given beta-carotene in supraphysiological dosages (corresponding to 30 mg beta-carotene/day in humans with 70 kg body weight) precursors to lung cancer via a cascade of cellular processes. These are initiated by high tie concentrations of beta-carotene in conjunction with the oxidative and inflammatory processes in the lung caused by smoking [Lui et al., 2000]. This would explain the results of ATBC and CARET. Similar – but less marked – changes were also observed with supraphysiological doses of beta-carotene in the absence of cigarette smoke [Lui et al., 2000]. In humans, however, no corresponding effects have been demonstrated, as the results of the Physicians' Health Study and the Women's Health Study in particular show. Physiological doses (corresponding to 6 mg/day in humans [Liu et al., 2000]), just as the administration of beta-carotene in combination with vitamin E and vitamin C [Kim et al., 2006], on the other hand, protect animals from the development of such precancerous lesions or. Lung tumors. The "ACE" combinations used correspond to 30 or. 12 mg beta-carotene, 100 I.E. vitamin E, and 210 mg vitamin C/day in a 70 kg body weight individual [Kim et al., 2006]. Relevant are these findings v. a. against the background that in fortified foods and dietary supplements beta-carotene is usually not used alone, but in combination with vitamins E and C.
Smokers have an increased risk of cardiovascular disease – regardless of beta-carotene intake
The Federal Institute for Risk Assessment (BfR) published a press release in no. 5 pointed out in 2001 that the intake of 20 mg beta-carotene can also cause health damage in people with cardiovascular diseases [BfR, 2001]. Various media had picked up on this link. However, this relationship is not tenable for the general population. It is correct – as the BfR states in the same report – that "in the case of heavy smokers under the administration of isolated beta-carotene both an increase in the lung cancer rate and an increase in the number of deaths from pre-existing cardiovascular diseases were observed" [BgVV, 2001, emphasis not in original]. An association between the intake of beta-carotene in nonsmokers with cardiovascular disease. health hazards cannot be established from the available studies.
In this context, it should be noted that a meta-analysis by Egger et al., 1998. While this mentions that beta-carotene supplementation is associated with an increased risk of cardiovascular deaths. However, the focus of this publication is on methodological aspects of meta-analyses in general. As an example, the aforementioned meta-analysis on the relationship between beta-carotene. cardiovascular diseases conducted. The intervention studies ATBC, CARET, PHS and the Skin Cancer Prevention Study by Greenberg et al., 1996. Overall, in the meta-analysis of these four studies, 60% active smokers and 23% former smokers summarized. However, this analysis does not take into account that smokers per se have an increased risk of cardiovascular disease. A statistical analysis for the confounding factors (here "smoking"), has not been done. It is reasonable to ame that the result of the meta-analysis is dominated by smokers and therefore not relevant for nonsmokers. This assessment is confirmed by the PHS mentioned on page 2: Here, the risk of cardiovascular disease was calculated separately for smokers and nonsmokers – the risk for nonsmokers was not increased even with beta-carotene intake [Hennekens et al, 1996].
Reference should also be made to another meta-analysis by Vivekananthan et al. Relationship between antioxidant vitamins. The risk for cardiovascular disease has been studied. Eight large intervention studies were included in the evaluation on beta-carotene (ATBC, CARET, PHS, AREDS, HPS, WHS, the Skin Cancer Prevention Study, and The Nambour Skin Cancer Prevention Trial by Green et al, 1999). The association between beta-carotene supplementation and overall mortality, cardiovascular deaths, and cerebrovascular events (z. B. stroke). Overall, the risk of general mortality and cardiovascular death was slightly (but not significantly) increased in the beta-carotene groups, but not the risk of stroke. Even in the analysis of Vivekananthan, however, no attention was paid to confounding factors (such as z.B. smoking) analyzed. As in Egger et al. Here, too, the results for general mortality and cardiovascular deaths are very probably due to the large number of smokers in the studies included and are therefore not readily transferable to non-smokers.
Protecting heavy smokers: Action on the Regulatory Side – A Review
Beta-carotene: Voluntary self-restraint of the economy (2001)
Statement on supplementation with beta-carotene with voluntary self-restriction by the industry
In response to ATBC and CARET, the former recommended Federal Institute for Consumer Health Protection and Veterinary Medicine (BgVV) in January 1998 smokers to avoid beta-carotene-containing preparations [BgVV, 1998]. In October 2000, although the former Scientific Committee on Food of the European Commission (SCF) revoked its ADI (Acceptable daily intakeii) of 5 mg/kg body weight, it also stated that there was no evidence that the current intake in Europe of 1-2 mg of isolated beta-carotene from additives was harmful [SCF, 2000a]. He did not establish a new UL (Tolerable Upper Intake Leveliii) because of insufficient data on the dose-response relationship [SCF 2000b]. In January 2001, the former BgVV called on food manufacturers to refrain from using isolated beta-carotene in vitaminized foods [BgVV, 2001]. In June 2001, the members of the Bund fur Lebensmittelrecht und Lebensmittelkunde (BLL) on a voluntary self-restriction for beta-carotene [BLL, 2001]:
In June 2002, the Federal Ministry of Consumer Protection, Food and Agriculture (BMVEL) a draft ordinance amending the ordinance on vitaminized foods: No more than 2 mg of beta-carotene in isolated form in 100 g or 100 ml of the food shall be added to food for nutritional purposes. Foods that are recommended for consumption (z.B. one capsule daily, 1 glass of juice/day) should not exceed 2 mg in relation to the recommended daily dose. In this context, industry has contributed data on intakes of isolated beta-carotene. The proceedings have not been concluded for the time being in this case. For drugs that contain beta-carotene, the Federal Institute for Drugs and Medical Devices (BfArM) initiated a step-by-step plan procedure in June 2003, which was completed in January 2006 [BfArM, 2003; BfArM 2006]: if the recommended maximum daily intake exceeds 20 mg of beta-carotene for medicinal products, heavy smokers (d.h. Persons who smoke more than 20 or more cigarettes per day) refrain from taking the drug ("contraindication"). For medicinal products containing between 2 and 20 mg beta-carotene/recommended daily dose, add to the package insert in the section "Warnings and precautions for use" that the medicinal product should not be taken regularly over a long period of time by heavy smokers with a consumption of 20 or more cigarettes/day).
Maximum levels for beta-carotene are now expected throughout Europe in the course of setting maximum and minimum levels for food supplements and fortified foods. Discussions on this subject began with the publication of a discussion paper by the European Commission in June 2006 [European Commission, 2006].
How much isolated beta-carotene consumers in Germany take in from fortified foods?
By far the most significant foods for beta-carotene fortification are beverages. Against this background, the Association of the German Fruit Juice Industry e. V. (VdF), the Association of German Mineral Springs e. V. (VDM), the German Trade Association of Non-Alcoholic Beverages e.V. (wafg) and some raw material producers evaluated data based on the GfK retail panel and the household panel with regard to this question in 2004.
This was based on a "worst case scenario": firstly, it was amed that the beverages purchased were too 100% also themselves – and not by other household members – were drunk. Second, it was amed that the highest conceivable 5.2% of the soft drink market would be actually was fortified with beta-carotene and, third, that the maximum value of 2 mg/100 ml at the each Drink exhausted was.
Result was: 98.4% of the population ingested less than 2mg isolated beta-carotene/day from beverages, 1.37% (1.13 million.) between 2mg – 3.5 mg. The highest mean intake of isolated beta-carotene from beverages in the "heavy user" household group is 3.5 mg/day – in each case aming the "worst case scenario" applies.
This model calculation based on market data shows that the calculated intake levels would not be relevant to health even for heavy smokers. Therefore, the industry's voluntary commitment is sufficient to protect even the at-risk group of heavy smokers from high intakes of excessive amounts of beta-carotene [AFG-V, 2004].
What is the intake of beta-carotene from dietary supplements?
Representative data on the intake of nutrients from dietary supplements were collected as part of the Federal Health Survey conducted by the Robert Koch Institute in 1998. In this nationwide study, about one in ten people took a supplement daily/almost daily – this corresponded to 484 people in the sample. 45 persons of these – i.e. 1.1% of the respondents – consumed a daily supplement that also contained beta-carotene. The median intake resulting in this group of persons from dietary supplements (and possibly also recorded over-the-counter drugs) was 1.6 mg beta-carotene/day; the 10. percentile was 0.2 mg, which was 90. percentile 15 mg/day [Beitz et al., 2004]. Whether the small proportion of respondents who consumed higher amounts were smokers was not estimated in the publication. It should be noted, however, that o. g. Industry's 2001 voluntary commitment to label dietary supplements containing more than 4.8 mg with a statement for smokers.
The o. g. Publication further explored the question of whether the ie of multiple intakes was relevant. With respect to beta-carotene, it was found that 4 individuals in the sample, d.h. 0.06% of the population consumes several supplements daily, all of which contain beta-carotene. However, the amounts ingested from these are safe – even for smokers (median: 3.4 mg; 10th. percentile: 2.2 mg; 90. Percentile: 3.4 mg) [Beitz et al, 2004]. The publication shows, moreover, that the importance of multiple intakes of nutrients from dietary supplements is overestimated.
If the amount reported in the nutrition declaration refers only to isolated beta-carotene?
In the case of fortified foods that advertise beta-carotene, lt. Nutrition Labelling Regulation, the total content of beta-carotene contained (irrespective of the source) shall be indicated. If, for example, beta-carotene is added to an orange-carrot juice for nutritional purposes, the naturally contained beta-carotene content and the amount added for nutritional purposes must be added together and indicated on the label. If this value exceeds 2mg/100 ml, this does not necessarily mean a violation of the self-restriction of the industry: Because this refers – like also the regulation proposal of the BMVEL – only to the added isolated beta Carotin.
How consumers should behave?
Adverse effects of high-dose beta-carotene supplementation have been reported only in longtime heavy smokers (min. 20 cigarettes/day for more than 30 years) and asbestos workers proven. An increased risk of lung cancer has not been proven for non-smokers and former smokers, nor has it been proven for cardiovascular diseases. This applies both to the administration of high doses of beta-carotene and to the combined administration of beta-carotene, vitamin E and C at high doses. In the treatment of a hereditary disease ("erythropoietic protoporphyria"), which is associated with painful hypersensitivity of the skin to sunlight, beta-carotene has been used for decades in doses of up to 180 mg/day without any side effects being reported – apart from a yellowish discoloration of the skin, which disappears after beta-carotene is discontinued.
Heavy smokers should pay attention to the dosage of dietary supplements and avoid high-dose preparations, or. do not use it every day for a long period of time.
In children and adults, care should be taken to ensure that the intake of beta-carotene and vitamin A is in line with requirements. Especially for pregnant and breastfeeding women who avoid animal-based foods, beta-carotene from dietary supplements or. fortified foods provide a valuable source of vitamin A: Beta-carotene is converted by the body into vitamin A as needed. This can prevent the harmful effects of excessive doses of vitamin A (e.g., vitamin E). B. from liver) can be prevented. These do not occur with isolated beta-carotene, even at high doses, because the conversion of beta-carotene to vitamin A in the body is tightly controlled.