Betacarotene and Cancer Risk. It is time to accept the facts.

Jacob Schor, ND

September 19, 2007

 

 

An article I wrote on vitamin D appeared in the Naturopathic Doctor News and Review a few months back. In the article, as an example of surprising research revelations, I mentioned the studies that say supplemental betacarotene increases the risk for smokers to develop lung cancer. [1] [2] [i] [ii]

[NDNR article: Sunscreen and skin cancer]

Unsurprisingly, I received a number of emails explaining why those betacarotene studies were in error. The most often used rationale is that this prospective study supplied smokers with betacarotene in pill form and the actual vitamin pills used synthetic carotenes. Thus, the argument is that if they had used natural betacarotene, the smokers would have gotten protection from betacarotene's antioxidant capacity. Smokers in this study had a 30% increased risk of lung cancer if they took betacarotene.

 

 

Last evening's reading was a 2004 article in the American Journal of Clinical Nutrition that tracked dietary intake of carotenoids and essential fatty acids and the risk of breast cancer. [3] [iii] This was a population based case control study that looked at 414 cases of breast cancer. Dietary intake was estimated with questionnaires and interviews. Supplements were not used.

 

No significant association was seen between dietary carotenoids and the risk of breast cancer. Yet in premenopausal women who ever smoked, there was an increased risk when the upper and lower quartiles of intake were compared. Premenopausal women who had ever smoked and who were in the upper 25% of gamma-carotene intake had a relative risk of 2.40 compared to those in the lower 25% of intake. On the other hand there was a reduced risk (0.57) related to beta-carotene in women who never had used hormone therapy.

 

In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (1.92) and inversely associated in those with a high docosahexanoic acid (DHA) intake (0.52)

 

There are a few lessons one could learn from this. First, drop the excuses to explain those older smoking studies. Betacarotene and smoking do not mix. It is not just vitamins, even dietary carotenoids increases risk. Smokers should not drink carrot juice, period. Carotenoids also increase risk of cancer in people who consume high levels of arachidonic acid. People who eat a lot of red meat should also avoid carrot juice. What does work though is fish and fish oil, which increase DHA intake. In combination, these two appear to cut breast cancer risk in half.

 

Driving to work this morning, I debated with myself whether to mention a particular multi-level-marketing company by name and have decided not to. There is a company, not to be named that promotes its line of supplements using a special meter that they claim measures antioxidant status in the body. It works by shining light on the skin and measuring the wavelengths reflected back. As far as I understand this meter measures carotene content of the skin. As anyone who has ever drank carrot juice regularly will tell you, high carotene levels are visible as a yellowing of the skin. We call this condition carrot jaundice. The company, that won't be named, uses their special meter to measure carotenoids in their potential customers, and then sells them supplements containing high levels of carotenoids. These supplements prove effective on follow up testing at increasing the purchasers ‘antioxidant' reading on the meter. Given what we know about carotenoids and cancer, this promotional practice is troubling. If combined with high doses of fish oil, it might lower cancer risk. These supplements given alone, without DHA supplementation to smokers could double their cancer risk.

 

 

 

Am J Clin Nutr. 2004 May;79(5):857-64. Click here to read

Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal , Canada .

Nkondjock A , Ghadirian P .

Epidemiology Research Unit, Research Centre, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, Pavillon Masson, 3850 Saint Urbain Street, Montreal, Quebec, Canada H2W 1T7.

BACKGROUND: Evidence from previous investigations into the possible role of dietary and serum carotenoid concentrations in the etiology of breast cancer is inconsistent. No study has examined the combined effect of carotenoids and essential fatty acids on the risk of breast cancer. OBJECTIVE: The objective was to assess the possible association between specific and total carotenoids and breast cancer risk and to evaluate the effect modification by diet-related fatty acids and lifestyle factors in the development of breast cancer. DESIGN: A population-based case-control study involving 414 incident cases and 429 controls was conducted in French Canadians in Montreal . Dietary intake was estimated with the use of a validated food-frequency questionnaire in face-to-face interviews. RESULTS: No significant association was apparent between any of the individual or total carotenoids and the risk of breast cancer after adjustment for major underlying determinants of breast cancer. In premenopausal women who ever smoked, an increased risk was related to alpha-carotene [odds ratio (OR) for the upper relative to the lowest quartiles of intake: 2.40; 95% CI: 0.90, 6.41; P for trend = 0.046]. Conversely, a reduced risk was related to beta-carotene (OR: 0.57; 95% CI: 0.26, 1.24; P for trend = 0.05) in women who never used hormone replacement therapy. In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (OR: 1.92; 95% CI: 0.93, 3.94; P = 0.028 for trend) and inversely associated in those with a high docosahexaenoic acid intake (OR: 0.52; 95% CI: 0.25, 1.07; P for trend = 0.054). CONCLUSION: These findings suggest that the combined high intake of total carotenoids and docosahexaenoic acid may reduce the risk of breast cancer.

PMID: 15113726 [PubMed - indexed for MEDLINE]

 

 

 

 

 

[1] Albanes D. “Beta-carotene and Lung Cancer: A case study.” Am J Clin Nutr 1999;69(suppl):1345S-1350S

[2] Lee I-M, “Antioxidant Vitamins in the Prevention of Cancer” Proc Assoc Am Physicians 1999:111(1):10-15.

[3] Nkondjock and Ghadirian. Intake of specific carotenoid and essential fatty acids and breast risk in Montreal , Canada . Am J Clin Nutr 2004;79:857-64

[i] J Natl Cancer Inst. 1996 Nov 6;88(21):1550-9. Click here to read

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

Omenn GS , Goodman GE , Thornquist MD , Balmes J , Cullen MR , Glass A , Keogh JP , Meyskens FL Jr , Valanis B , Williams JH Jr , Barnhart S , Cherniack MG , Brodkin CA , Hammar S .

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center , Seattle , WA 98104 , USA .

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996 , announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland .

 

[ii] Am J Clin Nutr. 1999 Jun;69(6):1345S-1350S. Click here to read

Beta-carotene and lung cancer: a case study.

Albanes D .

Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda , MD 20892-7058 , USA . daa@nih.gov

The conflicting evidence of the relation between beta-carotene and lung cancer in humans serves as a poignant case study with respect to what types of evidence are sufficient to support or change a nutrition recommendation. This article is a review of the available evidence of the relation between beta-carotene and lung cancer, including data regarding beta-carotene intake (from diet and supplements), beta-carotene biochemical status, and vegetable and fruit consumption, and a discussion of the role of this evidence in making nutrition recommendations. More than 30 case-control and cohort studies were conducted over many years in various populations and indicated that people who eat more vegetables and fruit, foods rich in carotenoids, and carotenoids (beta-carotene in particular), as well as those with higher blood beta-carotene concentrations, have a lower risk of lung cancer than those who eat fewer such foods or have lower beta-carotene concentrations. In contrast, the intervention results from large, controlled trials of beta-carotene supplementation do not support the observed beneficial associations or a role for supplemental beta-carotene in lung cancer prevention; instead, they provide striking evidence for adverse effects (ie, excess lung cancer incidence and overall mortality) in smokers. The findings require that caution be exercised in recommending supplemental beta-carotene, particularly for smokers, and argue against changing the vegetable-fruit recommendations in the direction of greater nutrient specificity. This case study of beta-carotene and lung cancer stresses the importance of having results from at least one, and preferably more, large, randomized intervention trial before public health recommendations concerning micronutrient supplementation are considered.

PMID: 10359235 [PubMed - indexed for MEDLINE]

 

[iii] Am J Clin Nutr. 2004 May;79(5):857-64. Click here to read

Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal , Canada .

Nkondjock A , Ghadirian P .

Epidemiology Research Unit, Research Centre, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, Pavillon Masson, 3850 Saint Urbain Street, Montreal, Quebec, Canada H2W 1T7.

BACKGROUND: Evidence from previous investigations into the possible role of dietary and serum carotenoid concentrations in the etiology of breast cancer is inconsistent. No study has examined the combined effect of carotenoids and essential fatty acids on the risk of breast cancer. OBJECTIVE: The objective was to assess the possible association between specific and total carotenoids and breast cancer risk and to evaluate the effect modification by diet-related fatty acids and lifestyle factors in the development of breast cancer. DESIGN: A population-based case-control study involving 414 incident cases and 429 controls was conducted in French Canadians in Montreal . Dietary intake was estimated with the use of a validated food-frequency questionnaire in face-to-face interviews. RESULTS: No significant association was apparent between any of the individual or total carotenoids and the risk of breast cancer after adjustment for major underlying determinants of breast cancer. In premenopausal women who ever smoked, an increased risk was related to alpha-carotene [odds ratio (OR) for the upper relative to the lowest quartiles of intake: 2.40; 95% CI: 0.90, 6.41; P for trend = 0.046]. Conversely, a reduced risk was related to beta-carotene (OR: 0.57; 95% CI: 0.26, 1.24; P for trend = 0.05) in women who never used hormone replacement therapy. In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (OR: 1.92; 95% CI: 0.93, 3.94; P = 0.028 for trend) and inversely associated in those with a high docosahexaenoic acid intake (OR: 0.52; 95% CI: 0.25, 1.07; P for trend = 0.054). CONCLUSION: These findings suggest that the combined high intake of total carotenoids and docosahexaenoic acid may reduce the risk of breast cancer.

PMID: 15113726 [PubMed - indexed for MEDLINE]