Voedingssupplementen zouden niets toevoegen aan effect op preventie van kanker. Studie analyse van 14 studies suggereert zelfs dat de levensverwachting erdoor wordt verkort. Maar er is bewust gemanipuleerd met deze studiegegevens

Ervaringen van kankerpatienten met complementaire aanpak kunt u lezen onder uw verhaal - patienten ervaringen. Ervaringen van kankerpatienten met complementaire aanpak op video kunt u bekijken als u hier klikt of op videoknop

20 oktober 2016: in onderstaand artikel de links naar de bronnen van de studies aangebracht.

Hier de bronnen ook bovenaan artikel:

1 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364: 1219-28.
2 Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997; 7: 439-43.
3 Lamberg-Allardt CJ, Outila TA, Karkkainen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Miner Res 2001; 16: 2066-73.
4 Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol 1990; 19: 559-63.
5 Vivekananthan DP, Pen MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular diseases: meta-analysis of randomised trials. Lancet 2003; 361: 2017-23.

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4 oktober 2004: Bron: BBC news.

21 maart 2005: Onder deze inleiding en artikelen staat een discussie over deze studie en een andere studie die dit weerlegt zoals verschenen in The Lancet van februari 2005. Daaruit blijkt eens te meer dat de publiciteit over de eerste studie zwaar overdreven was. Maar lees achtereenvolgens de informatie hierover.

De BBC en vele andere media, zoals ook The Independent alhoewel deze laatste veel kritischer is dan de BBC bv. - beide artikelen plaatsen we hieronder - melden vandaag dat een studieanalyse van 14 studies bewijst dat extra voedingssupplementen in de vorm van capsules niets toevoegt aan de positieve effecten van preventie van kanker. Zelfs suggereert de studie dat de levensverwachting door de voedingssupplementen lager is dan zonder. Een wel heel bijzonder bericht moeten we zeggen. We hebben inmiddels per 11 oktober een antwoord van Patrick Holford, een vooraanstaand wetenschapper erbij gezet wat de publicatie en waarde van de studie nog meer in twijfel brengt.

Een paar kritische aantekeningen van onze kant bij deze publicaties: De kop suggereert dat alle voedingssupplementen bij alle vormen van kanker dit zou uitwijzen. niets is minder waar, er is alleen onderzoek gedaan naar beta-caroteen, vitamines A, C en E en selenium in verschillende combinaties of alleen en dan ook alleen als eventuele preventie van spijsverteringskankersoorten zoals rectaalkanker, darmkanker en maagkanker. Selenium zou overigens wel preventief goed werken bij spijverteringskankersoorten en bij prostaatkanker.
Bovendien valt een ander zinnetje op in het artikel van de BBC: Dr Richard Sullivan of Cancer Research UK said the research could have been biased because many of the people in the study were smokers, who have a higher death risk anyway. Oftewel: wellicht dat de studie beïnvloed is door de deelnemers aan de studie die allemaal rokers waren en deze hebben sowieso een groter risico op vroegtijdig sterven aan kanker.
Nog een opvallende uitspraak van een collega onderzoeker over deze studie: "als deze studie waar zou zijn dan zouden er 9000 mensen per jaar eerder sterven dan statitisch mag worden verwacht", zegt bv. Douglas Altman van het Cancer Research UK aan the Lancet in een editorial.

Al met al een heleboel mediapubliciteit voor een studie, die overigens al dit voorjaar in The Lancet heeft gestaan en nu dus in oktober 2004, uitgeroepen tot borstkankermaand, nog eens extra onder de aandacht wordt gebracht. En het werkt want alle media nemen het klakkeloos over. En daarmee worden alle mensen en dus ook kankerpatienten toch weer aan het twijfelen gebracht of hun aanvullende aanpak wel goed zou zijn. Waarmee we niet willen zeggen dat soms wat minder pillen zeker niet slecht zou zijn maar wie bij ons kijkt onder onderzoek en voeding of onder literatuurlijst van arts-bioloog drs. E. Valstar ziet dat juist meer en meer bewezen wordt dat bepaalde voedingssuppletie vaak significant de kwaliteit van leven vergroot en de levensduur vaak met maanden zo niet jaren verlengt. En ook als preventie bewijzen steeds meer en meer studies dat bepaalde vitamines en mineralentekort vaak de oorzaak is van het ontwikkelen van kanker. Een aanvulling van deze tekorten door een supplement werkt preventief erg goed zoals bv. lycopeen bij prostaatkanker, vitamine D en nog veel andere middelen bij borstkanker, selenium bij prostaatkanker en andere kankersoorten en probiotica bij darmkanker, medicinale paddestoelen met bepaalde stofjes daarin tegen lever en longkanker enz. enz.

Het idee dat juist in de maand oktober, uitgeroepen tot wereldwijd borstkankermaand, de negatieve berichten over natuurlijke middelen als preventie en bij behandelingen van kanker extra aandacht krijgen is o.i. geen toeval. Ook hier het artikel zoals dat bij BBC news verscheen gisteren en een wat kritischer artikel uit The Independent daaronder van 1 oktober 2004. Maar we beginnen bij een analyse van Patrick Holford, een vooraanstaand Amerikaans wetenschapper, die een en ander beter onder woroden brengt dan wij dat zouden kunnen. Zijn titel: Lancet antioxidant artikel toont profijt en geen schade

Lancet Antioxidant Cancer Trial Shows BENEFIT, Not Harm

A study, published in the Lancet currently, on antioxidants and gastrointestinal cancer, is being claimed to indicate that antioxidants don't reduce risk, and may even increase cancer risk. However, experts in nutrition and cancer say the study shows nothing of the sort. In my opinion this is one of the most biased and unsubstantiated reports on antioxidants I've ever read. If you look at the actual results of this supposed comprehensive analysis of research you will see that the only really significant finding in a considerable reduction in gastrointestinal cancer risk with selenium supplementation. Overall, it shows that antioxidant supplements reduce the risk of oesophageal cancer, have little effect on pancreatic or oesophageal cancer, and slightly increase the risk of gastric cancer. Overall, the clear trend is towards protection, not harm. I believe this is an underestimation of the prevention power of antioxidants because this claimed comprehensive analysis of research excludes some very well designed positive studies, such as a trial of 864 people with a history of colorectal adenomas, by the National Cancer Institute (1). The participants were given either 25mg of betacarotene and/or both 100mg of vitamin C and 400mg of vitamin E, versus placebo. While there was approximately a halving of recurrence of colorectal adenomas in those who took either the betacarotene or vitamin C and E or both, there was a modest increase in cancer recurrence among those who only took betacarotene supplements and both smoked and drank alcohol every day. Why was this trial excluded? Perhaps it didn't give the results the researchers wanted. The final table in the Lancet study, which is the only one showing a small negative overall effect on mortality (the difference between 1 in 14 cancer patients on antioxidants, versus 1 in 15 cancer patients), was arrived at by removing any positive studies on the grounds of 'low methodological quality', leaving only 7 studies out of the original 167 studies! Of these studies, one is quoted as showing a massive increased risk. Without this study there is no such effect. However, this study actual showed the exact opposite. The study in question, Correa et al (2), published in the Journal of the National Cancer Institute, gave people with gastric cancer either beta-carotene, vitamin C or anti-Helicobacter Pylori treatment (gastric cancer is increasingly being thought to be initiated by H.Pylori infection, not antioxidant deficiency). All three interventions produced highly significantly improvements, causing substantial regression of gastric cancer. The authors conclude "dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma." (see abstract below). So, how could this study bias the results towards increased mortality? For the simple reason that six people out of 368 treated with antioxidants died, many of whom were smokers, compared to none out of 117 people treated with anti- H.Pylori treatment died! The most logical explanation for this finding is that, by virtue of participating in this trial, these patients were excluded from taking anti- H.Pylori treatment, which is highly recommended for gastric cancer. It is highly unlikely that the antioxidants had anything to do with it. The authors of this study make no reference to the possibility of antioxidants increasing mortality risk, instead concluding that both beta-carotene and vitamin C reduce risk. A review of the Lancet study (also published in the Lancet) by David Forman and Douglas Altman of the Centre for Epidemiology and Biostatistics says "The mortality analysis in this review does not offer convincing proof of hazard." In my opinion this is the most atrocious piece of biased number crunching, and I'm surprised that the Lancet published it. The funding source for this trial should be seriously investigated, just to check it is not as biased as the rhetoric. Drug companies have a lot to gain by discrediting nutritional treatments and I have no doubt that there is an orchestrated campaign under way to do just this. I certainly won't be stopping my daily antioxidant supplement, although I wouldn't advise heavy smokers to supplement beta-carotene on its own. I would advise people wanting to reduce their cancer risk to supplement 50 to 150mcg of selenium, together with other antioxidant nutrients."
Patrick Holford.

References
1 Baron, J et al., 'Neoplastic and antineoplastic effects of beta-carotene on volorectal adenoma', J Natl Cancer Inst. 95, 10, pp. 717-22 (2003). 2 Correa P et al., 'Chemoprevention of gastric dysplasia:randomised trial of antioxidant supplements and anti-helicobacter pylori therapapy', J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8.

ABSTRACT OF THE CRITICAL STUDY
J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy.
Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G, Realpe JL, Malcom GT, Li D, Johnson WD, Mera R.Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, LA 70112-1393, USA. BACKGROUND: Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Narino, Colombia, in the Andes Mountains.

METHODS: A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti- Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided.

RESULTS:
All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0- 9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia). CONCLUSIONS: In the very high- risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma

1. Baron, J et al., 'Neoplastic and antineoplastic effects of beta-carotene on volorectal adenoma', Journal of the National Cancer Institute 95, 10, pp. 717-22 (2003).

Hier het artikel zoals gepubliceerd in the Lancet.

Vitamins pills do not stop cancer

Popping pills may not be the answer Vitamin supplements do nothing to prevent gut cancers and may shorten life expectancy, research suggests. A review of 14 trials involving more than 170,000 people found antioxidant vitamins, like vitamin E, offered no protection against these cancers. People taking some supplements died prematurely, the European researchers said in the Lancet. Cancer Research UK cautioned the findings were preliminary and did not offer convincing proof of hazard. The study authors themselves emphasised that they had only studied the effect of certain antioxidant supplements.
"The results should not be translated to the potential effects of vegetables and fruit, which are rich in antioxidants and other substances," they said.
Antioxidants are thought to stop cancer by preventing or slowing damage caused by certain oxygen compounds. Dr Goran Bjelakovic and his colleagues, working at the Copenhagen Trial Unit in Denmark, looked at the supplements beta-carotene, vitamins A, C and E and selenium as different combinations or separately. They compared the rate of gastrointestinal cancers, such as stomach, liver or bowel cancer, among people taking the antioxidant supplements and people taking fake tablets with no active ingredient. Other than selenium, regular use of antioxidant supplements did not prevent gastrointestinal (GI) cancers.
In half of the 14 trials reviewed, vitamin tablets appeared to shorten life expectancy. Food better than pills The combination of beta-carotene and vitamin A or vitamin E increased risk of premature death by 30% and 10%, respectively. Dr Bjelakovic said: "We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers. "On the contrary, they seem to increase overall mortality." He said the potential merits of taking selenium to prevent GI cancers should be further investigated. Dr Richard Sullivan of Cancer Research UK said the research could have been biased because many of the people in the study were smokers, who have a higher death risk anyway. "There are no shortcuts to prevent bowel cancer. If you're taking vitamins to protect yourself against the disease, you're wasting your money. "The best way to lower the risk is to eat a healthy diet and not smoke." He said the study added to the evidence that trials into the benefits of selenium are warranted.

'Scary speculation'

"There is currently a study of the protective effects of selenium in prostate cancer in the US, but further research is needed into the wider role of selenium." Selenium is found in nuts, white fish, liver and kidney, shellfish, cereals, bread and dairy products. Douglas Altman from Cancer Research UK told the Lancet in an editorial: "If their findings are correct, 9,000 out of every million users would die prematurely as a result." He said this was a "scary speculation" given the vast quantities of vitamin supplements used. He said more research was needed and described the study as "work in progress" that offered no convincing proof of hazard. Martin Ledwick from CancerBACUP said: "Further investigation is needed into the effects of vitamin supplements.
"In the meantime, it's probably sensible to avoid taking very large doses of vitamin supplements and to try to get the necessary vitamins from eating five or more portions of fruit and vegetables every day." Hier zoals The Independent erover schreef:

Vitamin boosts may increase death rate of users, report says
By Jeremy Laurance, Health Editor
01 October 2004

Thousands of people could be dying prematurely from vitamin supplements, researchers report today, stating that the pills increase the death rate of those who take them by 6 per cent.

One in three women and one in four men in the UK is estimated to take dietary supplements for health reasons. But a review of 14 trials of vitamin pills taken by 170,000 people found they increased the death rate by 6 per cent. While they offered no explanation as to what caused the deaths, they discovered that the supplements offered no protection against cancers of the gut.

The researchers, writing in The Lancet, estimate that for every one million people taking the supplements, 9,000 would die prematurely as a result. The figure takes account of the background level of premature death in the population.

Dr Goran Bjelakovic, of the University of Nis in Serbia, who led the review, said: "We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers. On the contrary, they seem to increase overall mortality."

Two UK experts described the findings as "somewhat chilling". Professor David Forman of the University of Leeds and Douglas Altman of Cancer Research UK says in The Lancet: "The prospect that vitamin pills may not only do no good but also kill their consumers is a scary speculation given the vast quantities that are used in certain communities."

The Lancet has printed the quote in large type on the cover of its current issue.

Professor Forman said yesterday that supplements could be useful for people such as pregnant women and the elderly, who might be unable to get adequate vitamins from their diet. But they did not offer a short cut to better health. For the majority of the population who ate a balanced diet, there were no grounds for taking vitamin supplements, he said. "If someone has a good reason for taking these supplements other than to prevent cancer, then they should continue to do so. But I remain sceptical of their overall value."

The Lancet study is the latest to cast doubt on the value of dietary supplements.

A huge trial of betacarotene (the pre-cursor of vitamin A) and vitamin E in male smokers in 2000 found it increased the lung cancer rate by 18 per cent and the death rate by 8 per cent. Smokers are now advised against taking these vitamins pills.

A second trial of multivitamin supplements in people at high risk of heart disease published in 2002, also in The Lancet, found that after five years they had no protective effect against the risk of heart attacks, strokes, cancer or other serious health problems.

Vitamins are organic nutrients essential for normal metabolism and good health. But specialists say there is a difference between the life-long physiological effects of small amounts ingested in the diet from childhood and pharmacological doses of the same micronutrients taken over a few years by middle-aged adults.

For the latest study, the researchers examined the role of vitamins A, C, E and betacarotene (which is converted into vitamin A in the body) and the mineral selenium, taken either singly or in combination. They investigated their effect against cancers of the oesophagus (gullet), stomach, bowel, pancreas and liver. The results showed that a combination of betacarotene and vitamin A increased the death rate by 30 per cent and betacarotene combined with vitamin E increased it by 10 per cent. Selenium was associated with a lower risk of cancer, but the authors say this could be due to bias.

A possible explanation for the findings is that people may vary in their need for antioxidants (vitamins) according to the circulating levels of substances known as free radicals in the blood. Those with high levels of free radicals need extra vitamins to neutralise them but in those with low levels, extra vitamins may paradoxically protect cancer cells and have carcinogenic effects. The researchers acknowledge they did not look at all trials of vitamin supplements in preventing death and their results are preliminary. The Lancet commentary says that the study is a "work in progress" and "does not provide convincing proof of hazard".

It adds: "In the event that a hazard is established from a complete review, these researchers will need to identify which specific interventions are associated with any risk. It is unlikely that all supplements will exert a similar effect and it will be vital to establish the safety profile for those with demonstrated benefits."

The Health Supplements Information Service, said in a statement yesterday that The Lancet findings were of "borderline statistical significance" and involved some vitamin doses above recommended safe levels. It added: "What is important to take away from this piece of research is that these results are preliminary and further investigations into the role of vitamins in cancer are needed."

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and are used up by the body very slowly.

The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly and excess amounts are eliminated through the kidneys. Taking large doses of vitamin C or B, beyond what the body can immediately absorb, only creates expensive urine.

THE PROS AND CONS OF VITAMINS

Vitamin A

Essential for growth, bone development, night vision and healthy skin.
Found in liver, dairy products and eggs. Also in dark red, green and yellow vegetables. Deficiency causes skin disorders, eye damage and may increase the risk of cancer.
Toxic in overdose, causing dizziness, nausea, vomiting and can cause damage to the bones, blood, skin and nervous system.

Betacarotene
Found in many yellow fruits and vegetables.
Converted into vitamin A in the body (see above).

Vitamin C
Essential for the production of collagen, the basic protein in bones, cartilage, tendons and ligaments. May help boost the immune system.
Found in citrus fruits, tomatoes, potatoes, cauliflowers and Brussels sprouts.
Deficiency causes tiredness, weight loss, irritability, bleeding gums, rough skin and wasting away of muscles. In extreme cases, scurvy.
High doses, above 2gms a day, may cause headaches and diarrhoea. Long-term high doses may increase risk for kidney stones.

Vitamin E
Helps prevent cell membrane damage. May prevent blood clots and the formation of fatty plaques in the arteries.
Found in vegetable oil, avocados, nuts and soya beans. Also produced by bacteria in the intestines.
Deficiency may result in easy bruising and bleeding. May increase the risk of hip fractures in women.
Large doses may cause bleeding problems, rashes and itching.
Hieronder de discussie zoals die in The Lancet plaatsvond over bovenstaande studies.

Antioxidant supplements for prevention of gastrointestinal cancers

Goran Bjelakovic and colleagues (Oct 2, p 1219)1 quoted our chemoprevention trial2 of gastric precancerous lesions in their meta-analysis as showing an increased risk of gastrointestinal cancer and general mortality in individuals who receive antioxidant dietary supplements. We do not think our data support this conclusion. Our trial was specifically designed to address changes in the progression or regression of the gastric precancerous lesions, and needed a sample size much smaller than that necessary to assess endpoints of gastrointestinal cancer and general mortality. We take issue with the conclusions of the Cochrane Group that antioxidants could kill, based on the application of the fixed-effects model. That model assumes that all trials are similar in some key aspects of their design and of the populations studied. In view of the pronounced differences of the trials grouped in the meta-analysis, we believe the appropriate model for their assessment is the random-effects model. Therefore, the absence of an association between antioxidants and mortality should be the conclusion of the meta-analysis. We declare that we have no conflict of interest. *Pelayo Correa, Elizabeth Fontham, Luis E Bravo, Robertino Mera correa@lsuhsc.edu *LSU Health Science Center, 1901 Perdido Street, Box P5-1, New Orleans, LA 70112, USA (PC, EF, RM); and Universidad del Valle, Depto de Patologia, Cali, Colombia (LEB) 1 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364: 1219-28. 2 Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst 2000; 92: 1881-88. Goran Bjelakovic and colleagues1 conclude that antioxidant supplementation does not prevent gastrointestinal cancers and even seems to increase overall mortality. We believe, however, their data should be interpreted with caution. Their conclusion was drawn after exclusion of two trials of low quality; however, the test for heterogeneity was still significant when analyses were done on the seven remaining trials. Furthermore, trials included in the meta-analysis were mainly done in high-risk populations--eg, heavy smokers, individuals exposed to carcinogens through their work, or patients with coronary disease, other occlusive arterial disease, diabetes, or gastric or skin precancerous lesions--rather than in groups representative of the general population. Most of these studies were not designed for the specific purpose of testing the effect of antioxidants on gastrointestinal cancers. Additionally, the doses tested in some of the selected trials were not nutritional but pharmacological doses. Finally, Bjelakovic and colleagues' analyses did not take into consideration baseline antioxidant concentrations across populations and sex. Results of the SU.VI.MAX study--a randomised double-blind primary prevention trial done on a population not selected for specific risk factors--indicate that a combination of antioxidant nutrients (betacarotene, vitamins C and E, zinc, and selenium) given for 7·5 years at nutritional doses (reachable with a balanced diet) lower total cancer incidence and all-cause mortality in men, but not in women.2 The efficiency of supplementation in men only could be due to a lower nutritional intake and thus lower baseline concentrations of betacarotene and vitamin C in men than in women. The effect of antioxidant supplementation on cancer could, hence, depend on baseline antioxidant status (different between men and women and dependent on nutritional status) and health status. Antioxidant supplementation might have a beneficial effect on cancer incidence only in healthy individuals not exposed to cancer risk, and with a particularly low baseline status.3 Sex could affect the outcome of supplementation because of differences in metabolism, resulting from a hormone-sensitive effect. Finally, antioxidants and free radicals seem to be ambiguous nutrients with a wide range of benefits and toxicity. High doses of antioxidant supplements could be deleterious in high-risk individuals without any clinical symptoms in whom the initial phase of cancer development has already started. Even if Bjelakovic and colleagues were to emphasise the fact that their results should not be translated to the potential protective effects of fruits and vegetables (rich in antioxidants), we believe their conclusions might mislead readers of The Lancet, in terms of public-health prevention of cancers through nutrition. The main conclusion of this meta-analysis is that regular use of high doses of antioxidant supplements, especially in individuals at high risk of cancer, should be cautious. This advice is not new, and the general guideline of a diverse diet of foods rich in antioxidant nutrients is still important. We declare that we have no conflict of interest. *S Czernichow, P Galan, S Hercberg sebastien.czernichow@htd.aphp.fr Nutritional Epidemiology Unit, French Institute of Health and Medical Research (INSERM), Unit 557, UMR (INSERM/INRA/CNAM), 5 rue Vertbois, 75003 Paris, France 1 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364: 1219-28. 2 Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX study: a randomised, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 2004; 164: 1-8. 3 Hercberg S, Galan P, Preziosi P, et al. Background and rationale behind the SU.VI.MAX study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. Int J Vitam Nutr Res 1998; 68: 3-20. Authors' reply Pelayo Correa and colleagues might have misinterpreted our main conclusions. We did not see an increased risk of gastrointestinal cancer in the participants of placebo-controlled randomised trials who received antioxidant supplements (betacarotene, vitamin A, vitamin C, vitamin E, or selenium).1 Furthermore, we did not find convincing evidence that antioxidant supplements had either a beneficial or a harmful effect on the incidence of gastrointestinal cancers. Selenium might have a beneficial effect, but this effect has yet to be proven.1 We did note that antioxidant supplements led to a significantly increased all-cause mortality.1 We obtained this finding from a fixed-effect model analysis that considered all randomised trials to report mortality, and from fixed-effect model analyses that included trials with high methodological quality, with or without the inclusion of the smallest trial assessing selenium. The mineral selenium could have different effects from those of the antioxidant vitamins. Correa and colleagues were possibly misled by the fact that the findings of our random-effects model analysis showed significantly higher mortality in the antioxidant group when only high-quality trials, excluding the selenium trial, were considered (relative risk 1·08, 95% CI 1·01-1·17, p=0·04).1 Such high-quality trials allow unbiased assessment of intervention effects.2 Correa and colleagues suggest that data for gastrointestinal cancer or mortality cannot be used if a trial has been designed to look at precancerous lesions. On the contrary, we believe that mortality is so relevant an outcome measure that it should always receive consideration in studies of medical interventions. Furthermore, the results of our meta-analyses remain the same after exclusion of the Correa trial: incidence of gastrointestinal cancers relative risk 0·96, 95% CI 0·88-1·04, p=0·31; mortality with fixed-effect model meta-analysis 1·05, 1·01-1·08, p=0·02; mortality with random-effects model meta-analysis after exclusion of low-quality trials and the selenium trial 1·08, 1·00-1·17, p=0·04. The results of a new meta-analysis3 indicate a dose-dependent increase in mortality in participants taking vitamin E supplements. We think the time has come to reassess the recommended daily allowances and the recommended tolerable upper daily concentrations of antioxidant supplements. We agree with Sebastien Czernichow and colleagues that population and dose of antioxidants might be important determinants of the effect of antioxidants on cancer and mortality. The effect of antioxidant supplements could also depend on baseline antioxidant status. Antioxidant supplements could influence the balance between oxidative stress and apoptosis in human cells, resulting in undesirable health consequences. We discussed this issue at length in our review. The SU.VI.MAX results4 are interesting and may not in fact contradict our findings (different population, different doses of antioxidants, and differential use of selenium). However, the positive SU.VI.MAX results originate from subgroup analyses, which must be interpreted with caution.5 Finally, results of recent and ongoing randomised clinical trials, when incorporated into our meta-analysis, will provide more precise, evidence-based facts about the potential influence of antioxidant supplements on our health. We declare that we have no conflict of interest. *Goran Bjelakovic, Dimitrinka Nikolova, Rosa G Simonetti, Christian Gluud goranb@junis.ni.ac.yu Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 1 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers (Cochrane Review). Cochrane Database Syst Rev 2004; 4: CD004183. 2 Kjærgard LL, Villumsen J, Gluud C. Reported methodological quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135: 982-89. 3 Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37-46. 4 Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX study: a randomised, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med 2004; 164: 2335-42. 5 Oxman AD, Guyatt GH. A consumer's guide to subgroup analyses. Ann Intern Med 1992; 116: 78-84. The prospect raised by Goran Bjelakovic and colleagues1 that vitamins might not only do no good but also kill their consumers is a scary one. We agree with their careful interpretation of the study's results. However, reporting by the media of a lack of effect of most vitamins is unfortunate, since insufficient dietary intake of micronutrients, including vitamins, is still a common health problem worldwide. Data consistently show that vitamin D deficiency is frequent in Europe among healthy adults. The optimum values for serum vitamin D concentrations are about 80 nmol/L.2 However, epidemiological studies in Europe indicate that 75% of healthy adults in France have vitamin D serum concentrations less than 78 nmol/L and 14% have values below 30 nmol/L.2 In Finland, 86% of women age 31-43 years had serum values of vitamin D less than 80 nmol/L.3 Little is being done to tackle this problem, and the public and even health professionals seem unaware of the situation. Widespread vitamin D deficiency could have a serious effect on public health. There is a well-established link between vitamin D and bone health and cardiovascular disease.4 The public should be informed about the importance of vitamin D and those deficient for the nutrient identified and provided with supplements or advised about appropriate food groups. The design and the nutritional status of the study populations of trials that have not detected a positive effect of antioxidants on cancer or cardiovascular disease prevention1,5 should be examined carefully, since in most of these studies supplements were given to individuals without evidence of deficiency for vitamins or antioxidants. The probability of observing a clinical benefit is, therefore, low and the likelihood of an adverse effect high. Supplementation with vitamin A, for example, is unlikely to result in a clinical benefit in countries where low vitamin A intake is uncommon, but in low-income countries where inadequate vitamin A intake is frequent, this clinical benefit is obvious. We declare that we have no conflict of interest. *Rodrigo Moreno-Reyes, Marleen Boelaert, Sylvain Meuris rmorenor@ulb.ac.be *Department of Nuclear Medicine, Erasme Hospital (RM-R) and Laboratory of Experimental Hormonology (SM), Université Libre de Bruxelles, Route de Lennik 808, B-1070 Brussel Belgium; and Institute of Tropical Medicine, Antwerp, Belgium (MB)