Investigating the Potential Positive Impact of the Mediterranean Diet in the Reduction of DNA damage: A Μini Narrative Review

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ACHAIKI IATRIKI | 2025; 44(3):125–130

Review

Ioannis Delimaris

Faculty of Health Sciences, Metropolitan College, Athens, Attica, Greece

Received: 17 Nov 2024; Accepted: 15 Jan 2025

Corresponding author: Delimaris Ioannis, PhD (ClinBiochem), MSc (ClinChem), BSc (BiolSc), PGCE, QTS, Post-Doc (Nutr), Registered College Lecturer (Reg Num 159/2013), Faculty of Health Sciences, Metropolitan College, 42 Akadimias Street, 10672 Athens, Attica, Greece, e-mail: dr.i.delimaris@gmail.com

Keywords: Mediterranean Diet, nutrition, DNA damage, oxidative stress, humans

 

Abstract

The Mediterranean Diet (MD) has garnered attention for its potential health benefits beyond nutritional adequacy, particularly concerning oxidative stress and DNA damage. The aim of the present study is to investigate the potential positive impact of the MD on the reduction of DNA damage through the use of specific biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG) and F2-Isoprostanes. The material of the present study was gathered exclusively from Internet-based sources. The method included a comprehensive electronic literature search for studies published between 2009 and 2024 in the databases PubMed and Google Scholar, conducted from 10 August 2024 to 10 October 2024. The review of the literature revealed that adherence to MD is associated with significant reductions in biomarkers indicative of oxidative stress and DNA damage across various populations. Studies demonstrate increased levels in antioxidant markers and a decrease in DNA damage indicators linked to components of the MD, such as high-quality extra virgin olive oil and green leafy vegetables. The incorporation of coenzyme Q10 and other healthy elements further amplifies the protective effects of the MD, reinforcing its role as a robust dietary strategy for improving overall health outcomes. The findings suggest that the MD serves as an effective dietary intervention to enhance antioxidant defenses, reduce oxidative stress, and mitigate DNA damage, indicating its potential for disease prevention and management across diverse health conditions. Further research is warranted to explore its mechanisms and applications in clinical settings.

Introduction

The Mediterranean Diet (MD) is a dietary pattern traditionally followed in countries bordering the Mediterranean Sea, characterized by high consumption of fruits, vegetables, whole grains, legumes, nuts, and olive oil, moderate intake of fish and poultry, and limited red meat and dairy products [1]. Damigou et al. (2023) [1] evaluated the adherence to MD globally, highlighting trends over time. Findings indicated moderate -though not low- adherence to MD globally. Mediterranean countries in Europe exhibited the highest adherence levels, while geographical and socioeconomic factors were found to significantly influence MD adherence worldwide. This dietary approach via MD has been associated with numerous health benefits, including reduced risks of cardiovascular diseases, type 2 diabetes, and certain cancers. Its protective role can be attributed to its rich nutrient composition, which is high in antioxidants, healthy fats, and anti-inflammatory compounds [1-4]. Biological mechanisms underlying these benefits include the modulation of lipid profiles, improvement in glycemic control, and enhancement of gut microbiota diversity. The anti-inflammatory properties of olive oil and omega-3 fatty acids found in fish contribute to reduced systemic inflammation. Additionally, the abundance of fiber from plant-based foods supports cardiovascular health and metabolic function. Overall, the MD promotes a holistic approach to well-being, emphasizing whole foods that synergistically support vital biological processes essential for preventing chronic diseases and optimizing health [1, 4-6].

Human DNA damage refers to alterations in the DNA structure that can disrupt genetic information.

It represents a significant health concern, as it has been linked to specific diseases, including neurodegeneration (including Alzheimer’s disease and Parkinson’s disease), carcinogenesis, cardiovascular diseases, diabetes, rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, Wilson’s disease, and Huntington’s disease, among others [7]. This damage can be caused by various factors, including environmental stressors like radiation, chemical exposure, and biological agents, as well as internal processes such as oxidative stress from metabolism. The consequences of DNA damage are profound, as they can result in mutations, cell death, or the initiation of oncogenic pathways, ultimately affecting an organism’s overall health. To assess DNA damage, various biological methods are employed [7-9]. The 8-OHdG ELISA test, which measures 8-hydroxy-2-deoxyguanosine levels in human serum or urine, serves as a sensitive biomarker of oxidative DNA damage. Additionally, the comet assay (single-cell gel electrophoresis) analyzes DNA strand breaks in human lymphocytes, providing insights into the extent of DNA damage at the individual cell level. Both techniques highlight the correlation between DNA damage and oxidative stress, making them valuable tools in understanding the impact of environmental and lifestyle factors on human health [7, 10-14].

Some experimental studies suggest the hypothesis that the MD, rich in fruits, vegetables, whole grains, fish, and healthy fats, may reduce human DNA damage due to its high antioxidant content. Antioxidants help combat oxidative stress, a key contributor to DNA damage. Studies have indicated that adherence to this diet correlates with lower levels of oxidative markers and improved genomic stability. Additionally, the anti-inflammatory properties of the diet may further contribute to genomic protection. These findings underscore the diet’s potential role in promoting overall health [15-17].

However, the experimental data on the relationship between the MD and human DNA damage is limited, revealing a gap in international literature. Currently, there is no comprehensive understanding of how this diet may influence DNA damage. Research in this area remains scarce, leaving many aspects of this potential connection unexplored.

Objective

The aim of this study is to investigate the potential positive impact of the MD on reducing DNA damage. This mini narrative review addresses gaps in existing literature and enhances our understanding of this dietary pattern’s role in cellular health and longevity. By analyzing current research, we can better comprehend the mechanisms through which the MD may contribute to DNA repair and protection. The importance of this mini review lies in its potential to inform dietary guidelines and public health initiatives, promoting the MD as a beneficial approach for mitigating DNA damage and improving overall well-being.

Materials and methods

Design

A mini narrative review was performed based on a synthesis of previously published literature. The material of the present study was exclusively Internet-based. A comprehensive electronic literature search in the databases PubMed and Google Scholar was performed (from 10 August 2024 to 10 October 2024) using the following terms/key words: «Mediterranean Diet» AND «DNA damage». In addition, a search in the reference lists was carried out.

Criteria for inclusion of studies were:

  • Literature written in English
  • Literature published from 2009 to 2024 (15 years)
  • Studies that involved original research in volunteers
  • Studies that had keywords in the title and/or abstract

Criteria for exclusion of studies were:

  • Reviews
  • Conference papers
  • Book chapters
  • Books
  • Short surveys
  • Articles and documents written in languages other than English

Selection of studies

All references obtained from the search were organized and duplicates were excluded. The titles and abstracts were screened for content and relevance to the topic with focus on the inclusion criteria. The integral text of selected titles was read, and the reference list of selected articles was consulted in order to find out other relevant publications. Additionally, studies which failed to adequately describe the potential positive impact of the MD on reducing DNA damage were excluded.

Data extraction and analysis

The essential data from each published study was extracted and synthesized. The results are presented in a brief narrative form. Seven (7) research articles were obtained and analyzed.

Results

Urquiaga et al. (2010) [15] assessed the impact of a MD versus an Occidental diet (OD) on oxidative damage in 42 male students (20–27 years) over three months, with additional red wine (240 ml/day) during the second month. The MD enhanced plasma vitamin C, β-carotene, and total antioxidant reactivity (TAR), while OD elevated vitamin E. Wine increased plasma vitamin C, β-carotene, uric acid, TAR, and polyphenols, but reduced vitamin E. The OD group had higher 8-hydroxy-2′-deoxyguanosine (8-OHdG) and plasma nitrotyrosine levels. Overall, the MD provided better antioxidant defenses and reduced oxidative damage compared to OD.

The study of Gutierrez-Mariscal et al. (2012) [16] examined the effects of dietary fat quality on oxidative DNA damage and the role of Coenzyme Q10 (CoQ) supplementation in elderly subjects. In a crossover design with 20 participants, subjects followed three diets: MD, MD with CoQ (Med+CoQ diet), and saturated fatty acids (SFA diet) for four weeks each. The SFA diet resulted in higher postprandial 8-OHdG levels, increased p53 mRNA, and reduced Mdm2 mRNA compared to Med and Med+CoQ diets (p <0.05). The Med+CoQ diet decreased cytoplasmic p53 and nuclear p-p53 (Ser20) (p < 0.05), suggesting it improves oxidative DNA damage.

In the randomized controlled trial of Mitjavila et al. (2013) [17], 110 women aged 55-80 with metabolic syndrome (MetS) were assigned to a low-fat diet or two MD variations (MedDiet + olive oil or nuts). Over one-year, urinary levels of F2-Isoprostane (F2-IP) decreased in all groups, with a borderline significant reduction in MedDiet groups compared to the control. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) also decreased in all groups, with significant reductions in the MedDiet groups (P <0.001). The study concludes that the MedDiet effectively reduces oxidative damage in MetS individuals.

A study of Erdrich et al. (2015) [18], involving 20 men with diagnozed prostate cancer who followed a modified MD for three months showed significant reductions in DNA damage compared to baseline (p = 0.013). Notable improvements were linked to increased intake of folate (p = 0.023), vitamin C (p = 0.007), legumes (p = 0.004), and green tea (p = 0.002). Conversely, higher red meat and dairy intakes were inversely associated with DNA damage (p = 0.003 and p = 0.008).

In the study of Luisi et al. (2019) [19], the MD, enriched with 40 g/d HQ-Extra Virgin Olive Oil (HQ-EVOO), was tested on 18 overweight/obese (BMI ≥25 kg/m²) and 18 normal-weight controls (BMI 18.5–24.9 kg/m²) over three months. Results showed significant reductions in myeloperoxidase and 8-hydroxy-2-deoxyguanosine, markers of inflammation and oxidative stress, across both groups. In cases, pro-inflammatory cytokines decreased, while IL-10 and adiponectin levels increased.

Frugé et al. (2021) [20] in a 12-week randomized controlled crossover trial evaluated the effects of green leafy vegetables (GLV) on colonic DNA damage and colorectal cancer risk in adults (BMI > 30 kg/m²) with high red meat intake. Twenty-six participants were in the immediate intervention group (IG) and 24 in the delayed intervention group (DG). During the four-week intervention, daily GLV consumption resulted in increased plasma Vitamin K1 (p < 0.001) and decreases in circulating 8OHdG (p< 0.001), fecal 8OHdG (p< 0.001), and TNFá (p < 0.001).

The study of Acevedo-León et al. (2022) [21] investigated the association between adherence to the MD and oxidative stress (OS) markers in 80 colorectal cancer (CRC) patients. Using the 14-item Mediterranean Diet Adherence Screener (MEDAS), 51.2% of patients exhibited high MD adherence. These patients showed decreased 8-oxodG levels, increased glutathione peroxidase (GPX) and HDL–cholesterol, and a trend towards a lower GSSG/GSH ratio. High MD adherence correlated with a lower tumor histological grade and reduced synchronous adenomas. The findings suggest that adherence to the MD is protective against metabolic and oxidative DNA damage in CRC patients.

Discussion

Synthesis of the studies

Several studies highlight the protective effects of the MD against oxidative stress and DNA damage across different populations. Urquiaga et al. (2010) [15] demonstrated that the MD enhances antioxidant markers such as vitamin C and total antioxidant reactivity, effectively reducing oxidative damage compared to an Occidental diet. Gutierrez-Mariscal et al. (2012) [16] found that MD combined with Coenzyme Q10 supplementation significantly decreased DNA damage indicators in elderly subjects, while Mitjavila et al. (2013) [17] reported significant reductions in oxidative markers among metabolic syndrome patients following MD, outperforming a low-fat diet. In a pilot study by Erdrich et al. (2015) [18], men with prostate cancer benefited from changes linked to a modified MD, marked by decreased DNA damage. Similarly, Luisi et al. (2019) [19] revealed that an MD enriched with high-quality extra virgin olive oil reduced inflammation and oxidative stress in both obese and normal-weight adults. Frugé et al. (2021) [20] emphasized the benefits of green leafy vegetables in lowering oxidative DNA damage in adults at risk for colorectal cancer. Finally, Acevedo-León et al. (2022) [21] reported that adherence to the MD correlated with lower oxidative DNA damage markers and improved metabolic profiles in colorectal cancer patients. Collectively, these findings reinforce the MD’s role as a robust dietary strategy for enhancing antioxidant defenses and mitigating oxidative damage across diverse populations and health conditions (Figure 1) [15-21].

Figure 1. The positive impact of MD in the reduction of DNA damage according to the literature [15-21].

The studies reviewed share a common theme of investigating the protective effects of the MD against oxidative damage, particularly in relation to DNA integrity, inflammation, and overall health outcomes in diverse populations. Across various age groups and health conditions, ranging from young volunteers to elderly subjects and colorectal cancer patients, these studies consistently demonstrate that adherence to the MD is associated with significant reductions in biomarkers indicative of oxidative stress and DNA damage, such as 8-hydroxy-2’-deoxyguanosine (8-OHdG) and F2-Isoprostanes. The incorporation of additional healthful components, such as red wine and coenzyme Q10, enhances the protective benefits of the MD, further mitigating oxidative stress [15-21]. Moreover, the studies highlight that specific dietary elements, including high-quality extra virgin olive oil and green leafy vegetables, contribute to these positive outcomes by improving antioxidant defenses and inflammatory responses. The findings reinforce the MD’s role as a beneficial dietary pattern for promoting antioxidant capacity, reducing systemic inflammation, and providing a protective effect against chronic diseases and oxidative damage. Collectively, these studies underscore the potential of dietary interventions rooted in the MD to improve health outcomes through the modulation of oxidative stress pathways and support further research in dietary strategies for disease prevention and management [15-21].

Strengths of the studies

The studies collectively demonstrate robust methodological strengths, particularly in their focus on the MD and its relationship with oxidative damage. Most of the research employed controlled designs, including randomized controlled trials and crossover approaches, enhancing the reliability of results by minimizing confounding variables. A diverse range of participant demographics, including young adults, the elderly, women with metabolic syndrome, and colorectal cancer patients, allows for broader applicability of findings across different populations. The use of well-defined dietary patterns and supplementation (such as coenzyme Q10 and high-quality extra virgin olive oil) helps isolate the specific effects of these interventions on oxidative damage. Measurement of various biomarkers, such as 8-OHdG and estradiol, provides a comprehensive picture of oxidative stress and its implications for health. Additionally, some studies incorporate complementary assessments, such as gut microbiota analysis, which enriches the understanding of the MD’s multifaceted benefits. Overall, the methodological rigor and diverse approaches utilized in these studies underscore the potential health advantages of the MD in mitigating oxidative damage and promoting better health outcomes across various populations [15-21].

Limitations of the studies

The studies reviewed exhibit several limitations. Firstly, sample sizes varied, with some studies including as few as 20 participants (Erdrich et al., 2015), potentially limiting the generalizability of results [18]. The demographic homogeneity (e.g., age, gender, health status) of certain studies, such as Urquiaga et al. (2010), raises concerns about the applicability of findings to broader populations. Additionally, the short duration of interventions, typically ranging from 3 to 12 weeks, may not capture long-term effects or adaptations to dietary changes [15]. Temporal factors, such as seasonal variations in food availability, were not consistently controlled across studies, which could influence dietary composition and oxidative stress markers. Some studies relied on self-reported dietary intake, which is susceptible to recall bias (Acevedo-León et al., 2022) [21]. Additionally, cross-sectional and observational designs, like those seen in some studies (e.g., Mitjavila et al., 2013), limit causal inferences [17]. Variability in methods for measuring biomarkers of oxidative stress further complicates comparisons across studies. Lastly, the influence of confounding variables (such as lifestyle factors, physical activity, and concurrent medications) was not always accounted for, which may skew results related to dietary impacts on oxidative damage [15-21].

Future directions

Future studies should focus on several key directions to deepen our understanding of the MD and its protective effects against oxidative damage. First, larger, multicenter randomized controlled trials are needed to establish the long-term impact of MD and its variations, such as those enriched with Coenzyme Q10 or high-quality olive oil, on diverse populations, including various age groups and individuals with different metabolic conditions. Second, investigations into the mechanisms underlying the effects of MD components, such as polyphenols, omega-3 fatty acids, and antioxidants, on DNA repair pathways and oxidative stress responses will provide insights into the biological processes involved. Additionally, exploring the interactions between diet and the gut microbiome will be crucial, as emerging evidence suggests that these factors may modulate inflammation and oxidative stress. Finally, research should examine the effects of dietary interventions in patients with specific conditions, such as cancer or metabolic syndrome, to tailor dietary recommendations that optimize health outcomes and reduce disease risk. These investigations will collectively enhance our understanding of the MD’s role in promoting health and preventing chronic diseases through oxidative stress modulation [15-21].

Conclusions

In conclusion, the body of research evaluating the MD highlights its significant protective effects against oxidative stress and DNA damage across diverse populations. Consistent findings from various studies demonstrate that adherence to MD correlates with reduced oxidative biomarkers, such as 8-OHdG and F2-Isoprostanes, indicating improved DNA integrity and lower inflammation levels. The inclusion of health-promoting components, such as extra virgin olive oil, green leafy vegetables, and coenzyme Q10, enhances these protective effects, further substantiating the MD’s role in mitigating oxidative damage. Given the association between oxidative stress and numerous chronic diseases, these studies emphasize the MD as a beneficial dietary approach that promotes antioxidant capacity and supports overall health. The evidence advocates for dietary interventions grounded in the principles of the MD as viable strategies for disease prevention and health improvement. Future research should continue to explore the biological mechanisms underlying these protective effects and seek to establish practical guidelines for the implementation of the MD in various at-risk populations. Overall, MD emerges as a powerful tool for enhancing health outcomes, particularly in the context of oxidative stress and chronic disease management.

Conflict of interest disclosure

None to declare.

Declaration of funding sources

None to declare.

Author contributions

ID was responsible for the conception, research, writing and the final draft of this review.

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