Beta-carotene and lung cancer in
smokers: a meta analysis
Jon Beshara
2020
Tawee Tanyvetyanon MD, Gerold Bepler MD: Beta-carotene
in multivitamins and possible risk of lung cancer among
smokers vs former smokers
CS Journal, 20/06/2008 (https://doi.org/10.1002/cncr.23527)
(https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.23527)
Introduction
A meta analysis and evaluation of national brands
Some studies suggest that beta carotene supplementation may
increase the risk of lung cancer, particularly among
smokers/former smokers. Beta carotene is a pro-vitamin A
available in multivitamins. This study also surveyed the
beta-carotene content in national brand multivitamins.
Each year in the U.S., 200,000+ new cases of lung cancers are
diagnosed and >150,000 people die of it. Preventative measures
have been sought after including chemoprevention by dietary
supplements, but has found little success. However, some studies
have identified beta-carotene as being associated with an
increased risk of lung cancer (esp. amongst smokers/former
smokers)
Introduction & further information
A previous meta analysis containing data from 3 large trials suggested there is a
marginally increased risk of lung cancer associated with beta-carotene supplementation
⅙ Americans regularly consume multivitamins!
It is important to know how much beta-carotene is in national-brand multivitamins.
A smaller proportion of smokers consume multivitamins than nonsmokers (healthier
lifestyles)
Cancer history = more likely to supplement
How was the study conducted?
In the study, we reviewed randomized controlled trials that reported the effect of beta
carotene on the incidence of lung anecr.
For the differential effect of beta carotene in high-risk population who are
current/former smokers - meta analysis was performed on both groups separately.
Studies were excluded if they were in patients with existing lung cancer.
Methods
Randomized control trials compared beta carotene vs placebo using search strategy on
the MEDLINE database.
Quantitative meta-analysis technique was used to pool data regarding the incidence of
lung cancer using the random effects model. Used both the study sample size and
between-study variation when weighing effects.
Summary effect was expressed as the odds ratio.
Trials & participants
Two trials:
Alpha-Tocopherol Beta-Caortene Cancer Prevention Trial (ATBC)
- Age 50-69
- > or = 5 cigarettes/day
Beta-Carotene and Retinol Efficacy Trial (CARET)
- 20 pack year smoking history, stopped 5 years prior or still smoke (* 0.7 non)
- Exposed to asbestos
Conducted exclusively among individuals at high risk for lung cancer.
Two other trials
Physicians Health Study and Women's Health Study
- They were not conducted among high risk individuals exclusively, but reported
lung cancer incidence among high risk participants.
Physicians Health Study: ½ participants smokers/former smokers
Women's Health Study: 49% participants smokers/former smokers
Study results
109,394 participants (54,955 intervention / 54,439 control)
ATBC & CARET reported a significant increase in lung cancer incidence amongst
smokers receiving beta carotene compared to those who did not.
In the ATBC study, after 18 months, an excess cumulative incidence was observed and
kept increasing progressively after. Time-course observation. (not in the other studies)
Study 1 (all participants)
(OR,1.21; 95% confidence interval [95% CI], 1.09–1.34)
Study 2 (current smokers) *OR increased
(OR, 0.73; 95% CI, 0.33–1.59)
Study 3 (former smokers) *OR no significant difference
Study 4 - nonsmokers
In the subgroup of participants who were nonsmokers, there was also no difference
noted with regard to the incidence of lung cancer between participants who received
beta‐carotene and those who did not (OR, 0.73; 95% CI, 0.33–1.59).
Beta carotene & vit. A content in popular multivitamins
24 brands - several formulas. The formula with highest beta carotene was sold to
promote visual health, so multivitamin brands that were sold to promote visual health
were examined
Why beta carotene increases the incidence of cancer
The co carcinogenic effect of beta‐carotene appears to stem from its ability to
exacerbate DNA oxidative damage and modify p53‐related pathways of cell
proliferation and apoptosis, leading to the development of cancer.
However, beta‐carotene does have an efficacy in a dry type of age‐related macular
degeneration (ARMD).
Wait for ophthalmologist recommendation before taking beta carotene.
Discussion & Conclusions
Meta analysis showed that lung cancer risk increased with beta-carotene
supplementation approximately 24% from the baseline risk of current smokers (who
don't take supplementation)
Multivitamins marketed to promote visual health had highest dosage beta-carotene.
50 million Americans consume multivitamins regularly. ~10 million americans current
smokers & consume multivitamins.
NCI - 60/100,000 lung cancer incidence (in general)
Beta carotene + 24% = 74.4/100,000 lung cancer incidence;
Much higher if we consider 22x higher cancer risk in male smokers and 12x female
smokers