Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities
2
Randomized Trial of Intake of Fat, Fiber, and Beta Carotene to Prevent Colorectal Adenomas
3
Chemoprevention of Gastric Dysplasia: Randomized Trial of Antioxidant Supplements and Anti-Helicobacter pylori Therapy
4
Acute Adverse Effects of Radiation Therapy and Local Recurrence in Relation to Dietary and Plasma Beta Carotene and Alpha Tocopherol in Head and Neck Cancer Patients
5
Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: A randomized trial among head and neck cancer patients
6
Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients
7
Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: A randomized controlled trial
8
Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral Premalignancy
9
p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia
10
Comparison of low-dose isotretinion with beta-carotene to prevent oral carcinogenesis
11
Effects of α-Carotene and α-Tocopherol on Bleomycin-induced Chromosomal Damage
141 women with colposcopically confirmed cervical intraepithelial neoplasia (CIN) I or minor squamous atypia
β-carotene 30 mg/day, vitamin C 500 mg/day, both, or placebo
Median 23 months
Regression and progression rates of cervical lesions
Non-significant increase in regression with β-carotene and decrease with vitamin C. Slightly increased progression with the dose of both beta-carotene and vitamin C.
High doses of β-carotene and vitamin C are unlikely to increase regression or decrease progression of minor cervical abnormalities.
A combination of Low fat diet (reducing dietary fat to 25% of total calories), 25 g/day wheat bran, 20 mg/day beta carotene
2 years
New adenoma recurrence
No statistically significant prevention of total new adenomas with any intervention except in patients on low fat and added wheat bran who had zero large adenomas at 24 and 48 months
Low fat and high fiber may reduce progression of adenomas. Beta-carotene had no effect.
https://pubmed.ncbi.nlm.nih.gov/11106679/
Gastric precancerous lesions
Potentially beneficial
Randomized controlled trial
852 subjects from Colombia with confirmed diagnosis of multifocal nonmetaplastic atrophy and/or intestinal metaplasia
Anti-H. pylori triple therapy for 14 days; β-carotene 30 mg/day and Ascorbic acid 1 g twice a day; or placebo
6 years
Histologic progression, regression or no change of gastric lesions
All treatments increased regression rates; H. pylori eradication especially increased regression
These treatments may interfere with precancerous process (especially H. pylori eradication) mostly by increasing the rate of regression of cancer precursor lesions
https://pubmed.ncbi.nlm.nih.gov/17927499/
Head and neck
Potentially beneficial
Prospective cohort study
540 patients with head and neck cancer treated with radiation therapy
Usual dietary intake measured by a food frequency questionnaire and plasma levels measured at baseline
Median follow-up 51 months
Severe acute adverse effects of radiation therapy and local recurrence of head and neck cancer
Higher dietary beta carotene was associated with fewer severe acute adverse effects. Higher plasma beta carotene was associated with significantly lower local recurrence.
Higher dietary beta carotene may reduce acute adverse effects of radiation therapy and decrease local recurrence.
https://pubmed.ncbi.nlm.nih.gov/18059031/
Head and neck
Not significant in nonsmokers
Randomized controlled trial
540 patients with head and neck cancer undergoing radiation therapy
α-tocopherol (400 IU/day) and β-carotene (30 mg/day)
During and for 3 years after radiation therapy
HNC recurrence, overall mortality, HNC mortality
Among smokers, increased risk of adverse outcomes with antioxidant supplements; no effect in nonsmokers.
Antioxidants may reduce efficacy of radiation therapy when combined with smoking, however there was no effect of the antioxidants witnessed in non-smokers.
https://pubmed.ncbi.nlm.nih.gov/16841333/
Head and neck
Potentially harmful
Randomized controlled trial
540 patients with head and neck cancer undergoing radiation therapy
α-tocopherol (400 IU/day), β-carotene (30 mg/day), together or placbeo
During raditation (43 days) and for 3 years after radiation therapy
All-cause and cause-specific mortality
Overal survival was consistently lower in participants randomized to the supplementation arms. Higher all cause mortality rates were observed in particiapnts in the alpha-tocopherol arm and the beta-carotene + alpha-tocopherol arm
High-dose vitamin E may have prooxidant effects and displace other antioxidants therefore increase vulnerability to oxidative damage.
https://pubmed.ncbi.nlm.nih.gov/25156040/
Oral leukoplakia
Not significant
Randomized, double-blind controlled trial
46 Japanese patients with oral leukoplakia, median age 65 years
10 mg/day beta-carotene and 500 mg/day vitamin C (experimental) or 50 mg/day vitamin C (control)
1 year
Clinical remission at 1 year; malignant transformation over 5 years
17.4% response rate in experimental arm vs 4.3% in control arm (p=0.346); No difference in malignant transformation
Low-dose beta-carotene and vitamin C were not significantly effective for clinical remission or prevention of oral cancer
13-cis RA had a higher response rate but adverse effects were more common in this group than the others.
Overall, BC+RP and RP alone did not demonstrate equivalent activity to 13-cis RA. However, none of these treatments are recommended for chemoprevention currently
https://pubmed.ncbi.nlm.nih.gov/27605086/
Oral leukoplakia
Not significant
Randomized controlled trial
46 patients with oral leukoplakia, never or ex-smokers, 23 in experimental arm who completed 1 year trial
Beta-carotene 10 mg/day, Vitamin C 500 mg/day (experimental); Vitamin C 50 mg/day (control)
1 year
To determine if baseline expression of p53 and Ki67 demonstrated differences between those responding and not. Relationship between clinical response and dietary factors.
p53 LI higher in non-responders; ki67 no significant difference. There was no significant relationship between the presence of epithelial dysplasia and over expression of p53 or ki67.
Overall, p53 was inversely related to clinical response of the supplements. Aberrant p53 expression indicates resistance to chemoprevention. This could elucidate a potential mechanism for beta-carotene and vitamin C chemoprevention.
https://pubmed.ncbi.nlm.nih.gov/8416267/
Oral
Well-tolerated
Clinical trial
first phase: 70 patients with leukoplakia
second phase: patients with responses or stable lesions were randomly assigned to maintenance therapy
first phase: 1.5mg per kg of body weight of isotretinon
second phase: beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 per kg/day)
first phase: 3 months
second phase: 9 months
isotretinion toxicity, response to therapy (lesion size)
The overal rate of disease progression of 55% in the beta-carotene group was significantly higher than the rate of 8% in the low-dose isotretinoin group (p<0.001).
Therefore, these results show that beta-carotene is not an effective maintenance agent in leukoplakia. Maintence therapy with beta-carotene was well-tolerated and caused less toxicity compared to treatment with low-dose isotrentin, but was not effective.
https://pubmed.ncbi.nlm.nih.gov/9488585/
DNA damage
Not significant
Randomized crossover trial
22 healthy volunteers
15 mg β-carotene, 400 IU α-tocopherol vs placebo
6 weeks
Bleomycin-induced chromatid breaks
The average number of chromatid breaks per cell was similar among participants in the placebo and supplemention groups
These results suggest that mutagen sensitivity was not affected by beta-carotene or α-tocopherol supplementation