Can Dietary Nutrients Prevent Cancer Chemotherapy-Induced Cardiotoxicity? An Evidence Mapping of Human Studies and Animal Models

Abstract

Introduction: Chemotherapy has significantly improved cancer survival rates at the cost of irreversible and frequent cardiovascular toxicity. As the main dose-dependent adverse effect, cardiotoxic effects not only limit the usage of chemotherapeutic agents, but also cause the high risk of severe poor prognoses for cancer survivors. Therefore, it is of great significance to seek more effective cardioprotective strategies. Some nutrients have been reported to diminish cardiac oxidative damage associated with chemotherapy. However, the currently available evidence is unclear, which requires a rigorous summary. As such, we conducted a systematic review of all available evidence and demonstrated whether nutrients derived from food could prevent cardiotoxicity caused by chemotherapy.

Methods: We searched Medline (via PubMed), Embase and the Cochrane Library from inception to Nov 9, 2021 to identify studies reporting dietary nutrients against cancer chemotherapy-related cardiotoxicity. We performed descriptive summaries on the included studies, and used forest plots to demonstrate the effects of various dietary nutrients.

Results: Fifty-seven eligible studies were identified, involving 53 animal studies carried on rats or mice and four human studies in cancer patients. Seven types of dietary nutrients were recognized including polyphenols (mainly extracted from grapes, grape seeds, and tea), allicin (mainly extracted form garlic), lycopene (mainly extracted from tomatoes), polyunsaturated fatty acids, amino acids (mainly referring to glutamine), coenzyme Q10, and trace elements (mainly referring to zinc and selenium). Dietary nutrients ameliorated left ventricular dysfunctions and myocardial oxidative stress at varying degrees, which were caused by chemotherapy. The overall risk of bias of included studies was at moderate to high risk.

Conclusion: The results indicated that dietary nutrients might be a potential strategy to protect cardiovascular system exposed to the chemotherapeutic agents, but more human studies are urged in this field.Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0015/.

Keywords: cardiotoxicity; chemotherapy; diet therapy; heart diseases; oral nutrition; systematic review.

Figure 1

The work flowchart of the study process. Epidemiology, clinical symptoms and current cardioprotective strategies of cancer chemotherapy-induced cardiotoxicity are shown. Our search strategy and main results are also presented. DOX, doxorubicin; FDA, Food and Drug Administration; Top2β, topoisomerase 2β.

Figure 2

The PRISMA flowchart of the literature search and study selection.

Figure 3

The characteristics of the included animal studies. Distribution of countries of included animal studies are shown in the left. The percentages represent the proportion of included studies in each continent, and the numbers are the number of studies in each country. Among them, African and Asian countries account for the largest share with most studies in Egypt (n = 15), India (n = 8), Saudi Arabia (n = 6), Turkey (n = 6), and China (n = 5). Types of dietary nutrients are listed in the right, containing polyphenols, allicin, lycopene, polyunsaturated fatty acids, amino acids, coenzyme Q10, and trace elements.

Figure 4

The risk of bias assessment of the included animal studies.