Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression

Abstract

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06–1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08–1.35) and non-medics (RR = 1.18, 95% CI = 1.07–1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.

Investigating Causal Associations of Circulating Micronutrients Concentrations with the Risk of Lung Cancer: A Mendelian Randomization Study

“…In the subsequent gender stratification analysis, researchers found that this effect is mainly reflected in men. However, a recent meta-analysis involving 167,141 participants yielded inconsistent results [ 18 ]. The meta-regression showed no relationship between the supplemental dose of beta-carotene and the size of the negative effect of lung cancer.…”

“…We obtained the initial catalogue by searching Pubmed ( (accessed on 1 August 2022)) for published observational studies or meta-analyses of micronutrients related to LC. The preliminary catalogue includes 20 nutrients: beta carotene, calcium, copper, folate, iron, lycopene, magnesium, potassium, phosphorus, retinol, sodium, selenium, zinc, and vitamins B1, B2, B6, B12, C, D, and E [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. We exclude iron and vitamins C, D, E, and B12 because the causal relationship between these circulating nutrient concentrations and LC risk has been thoroughly analyzed [ 30 , 31 , 32 , 33 , 34 ].…”

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy

“…Furthermore, beta-carotene has been proven to synergistically enhance the anticancer effect of 5-fluorouracil in esophageal squamous cell carcinoma both in vivo and in vitro [ 179 ]. However, a recent meta-analysis indicated that supplementation with beta-carotene had a negative effect on the lung cancer risk in smokers and asbestos industry workers [ 180 ].…”

Mechanisms of Action of Polyacetylenes’ Anti-Inflammatory Function and Their Potential in Cancer Chemoprevention and Treatment

“…β -carotene was initially believed to be protective against multiple chronic diseases, particularly cardiovascular disease, and cancer of the lung; gastrointestinal tract; and pancreas, in addition to cataracts and age-related macular degeneration [12][13][14]. However, meta-analyses of subsequent intervention studies ruled out a role of β -carotene in suppressing lung cancer development, since dietary supplementation with purified beta-carotene failed to reduce lung cancer incidence and even increased the risk of lung cancer [15]. Thus, other bioactive substances such as polyacetylenes (FaOH and FaDOH) could be responsible for the health benefits of carrot [16] with evidence supporting that polyacetylene compounds improve human health by stimulating anti-cancer and anti-inflammatory mechanisms [3].…”