Results from two randomised clinical trials show that beta carotene doubles the risk from lung cancer for former smokers, whereas there was no statistically significant increase in participants assigned lutein/zeaxanthin.
The long-term epidemiologic follow-up trial examined the findings from the Age-Related Eye Diseases Study (AREDS) Research Group to assess the effectiveness of specific therapeutics, including lutein/zeaxanthin, on AMD progressions and various cancer outcomes.
The study demonstrates that antioxidant vitamins (C and E) and zinc with copper in reduced AMD by 25% over five years but concludes that beta carotene was a significant risk factor for lung cancer.
Secondary trials identified lutein/zeaxanthin as a safer option in terms of lung cancer risk and suggest supplementation may provide incremental increases in prevention of progression of late AMD, the authors say.
“We found a persistent long-term beneficial association of lutein/zeaxanthin with progression to late AMD in both the primary analyses of the four separate treatment groups and the main outcome analyses of the entire cohort.”
A total of 4,203 participants were recruited for the AREDS research with an average baseline age of 72. Initial trials examined the connection between beta carotene and cancer and cardiovascular disease prevention.
Findings reveal that 39 (2.1%) participants in the beta carotene group developed lung cancer, compared to 11 (0.9%) in the no beta carotene group. In follow-up, a further 78 participants in the intervention group had confirmed lung cancer.
“Those who were current smokers and former smokers had higher rates of development of lung cancer than non-smokers. The odds ratio (OR) for the risk of developing lung cancer in former smoker’s vs non-smokers was 1.84.”
In light of these results, further trials were carried out to corroborate or challenge the findings and investigate further options for AMD treatment.
Researchers examined the effects of replacing beta carotene with lutein/zeaxanthin and/or docosahexaenoic acid (DHA/EPA) fatty acids in formulas for subjects presenting with bilateral large drusen or unilateral large drusen with late AMD.
Disease progress was compared in four treatment groups: lutein/zeaxanthin only, docosahexaenoic acid (DHA/EPA) only, both treatments or the placebo.
Figures showed the probability of late AMD progression over 10 years with lutein/zeaxanthin only supplementation was 47.9%, as opposed to 49% with no supplementation. Across all groups, 48% of participants developed late AMD.
Data demonstrated an association between beta carotene and reductions in HR progression in late AMD in subjects randomly assigned to this group, however, further analysis revealed a stronger protective association of lutein/zeaxanthin with progression to late AMD, when compared directly with beta carotene.
Study authors discovered that both hazard rates (HR) and progression probability were lowest when lutein/zeaxanthin was consumed on its own.
No significant increased risk of lung cancer was associated with lutein/zeaxanthin, whereas results confirmed that beta carotene doubles the risk of lung cancer.
“The totality of information, both clinical (lung cancer and AMD outcomes) and laboratory, provides evidence for using lutein/zeaxanthin rather than beta carotene in a supplement designed to slow the progression of AMD in patients with intermediate AMD or late AMD in one eye,” they write.
The authors maintain that beta carotene should not be included in AREDS formulations, given the present evidence and clinical benefits of lutein/zeaxanthin.
“Potentially, there may be an additional absolute 2.7% beneficial effect or additional relative 10% to 20% additional beneficial effect of lutein/zeaxanthin.
“Even a modest increase in the treatment effect to prevent late AMD would be clinically important because of the exceedingly large number (288 million) of patients anticipated to be affected globally in 2040.”
Source: JAMA Opthalmology
Published online: doi:10.1001/jamaophthalmol.2022.1640
‘Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression AREDS2 Report 28’
Emily Chew et al.