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lycopene; hypolipidemic agents; hypercholesterolemia; tomato; olive oil
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Del Castillo Vidal G, Lozada-Urbano M, Miranda D et al. Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.12688/f1000research.133905.1)
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Research Article
Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients
[version 1; peer review: 2 not approved]
PUBLISHED 11 Oct 2023
OPEN PEER REVIEW
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Abstract
Corresponding authors:
Michelle Lozada-Urbano, Oriana Rivera-Lozada, Jaime Yáñez
Competing interests:
Portions of this work were previously published by G.D.C.V. as a thesis for a second specialty in clinical nutrition with a mention in oncological nutrition. The authors declare no conflict of interest.
Grant information:
Universidad Peruana de Ciencias Aplicadas, UPC-EXPOST-2023-2
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:
© 2023 Del Castillo Vidal G et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Del Castillo Vidal G, Lozada-Urbano M, Miranda D et al. Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.12688/f1000research.133905.1)
First published: 11 Oct 2023, 12:1315 (https://doi.org/10.12688/f1000research.133905.1)
Latest published: 11 Oct 2023, 12:1315 (https://doi.org/10.12688/f1000research.133905.1)
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Introduction
The ideal cardiovascular health is determined by the absence of tobacco, body mass index <25 kg/m2, physical activity and, according to current guidelines, untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg and fasting blood glucose <100 mg/dL.1 The American Heart Association recommends maintaining total cholesterol values at no more than 200 mg/dL, while values higher than 240 mg/dL are considered high. The optimal high-density lipoprotein (HDL) and LDL levels are considered to be at least 60 mg/dL and not more than 100 mg/dL, respectively.2
The use of lycopene has been reported to reduce blood cholesterol in the range of 30 to 60 mg/dL (a 25 to 30% reduction) in patients with initial levels of 250 to 300 mg/dL.3 Lycopene is a strong antioxidant, which prevents oxidative stress of LDL cholesterol molecules, and helps prevent atherosclerosis and benefits cardiovascular health.4,5 The antioxidant function of lycopene has been reported to be twice as active as β-carotene’s.6 Lycopene acts synergistically with other components7–12 and is transported by lipoproteins in the plasma and then distributed to different organs.13 In humans, lycopene has been reported to have a bioavailability of 10-30%, which is influenced by biological and other lifestyle factors such as age, gender, hormonal status, body composition, blood triglyceride levels, smoking, and alcohol consumption.5
Pharmacological treatment through statins has been reported to be effective in reducing low-density lipoprotein (LDL) cholesterol by up to 60%, but can lead to adverse events such as muscle complications and an increased risk of diabetes.14 Statins have been reported to improve the lipid profile in both genders, but higher improvements observed in women older than 70 years old.15 An advantage of consuming lycopene through tomatoes is that it shows no adverse effects over statins, and has been reported to lower blood pressure.16 These results strengthen the practice of including tomatoes in individualized and nutritional strategies for treating cardiovascular diseases.17,18 There is not a universally established dose of lycopene that is considered healthy, but it has been reported that including at least one tomato per day in our diet decreases the risk of cardiovascular disease due to its antioxidant effect.15 In the terms of servings of tomato, it has been reported that one serving is equivalent to half a cup of tomato sauce for spaghetti, a quarter cup of tomato paste or puree, or a medium tomato.19 Tomatoes are rich in antioxidants20 such as lycopene21–24 and other bioactive compounds such as flavonols, flavanones and hydroxycinnamic acids,4,8–12,25–28 and a preparation rich in antioxidants has been reported to contribute for the prevention of cancer and other noncommunicable diseases.29–37 Longitudinal studies in men have shown that those who consumed ten servings per week of cooked tomato products had one-third less risk than men who ate less than two servings per week.38 Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect has been proposed to be related to inhibition of cholesterol synthesis.39 Furthermore, tomato lycopene has been used as adjuvant treatment for arterial circulation disorders including angina pectoris and myocardial infarction.3 Other studies suggest that lycopene may influence the reduction of the risk of other cancers, including colon, rectum, and breast cancer.19 The effects of tomato products and lycopene supplementation have shown positive effects on blood lipids, blood pressure, and endothelial function.18
The combination of olive oil and tomato lycopene has been reported to decrease the risk of coronary heart disease by improving the serum lipid profile compared to a diet rich in carbohydrates, low in fat and rich in lycopene.40 Also, the consumption of tomato products with olive oil has been reported to improve the antioxidant activity of plasma.41 The antioxidant and hypocholesterolemic activity of the phenolic extracts of virgin and extra virgin olive oil has been reported while protecting HepG2 liver cells from hydrogen peroxide induced oxidative stress by reducing intracellular reactive oxygen species (ROS) and lipid peroxidation levels.42 Olive oil has also been reported to modulate the low-density lipoprotein receptor (LDLR) pathway causing a reduction in plasma levels of LDL cholesterol and the oxidation of these lipoproteins.42 Therefore, diets rich in monounsaturated fatty acids promote the formation of compounds with antiaggregating and vasodilating action.43–45
In developing countries such as Peru there is limited access to adequate and timely access to pharmaceutical treatment for cardiovascular diseases.46 The incidence of cardiovascular risk in Peru surpasses an average of 41% in people older than 15 years, being higher (43.5%) in urban areas but lowed in rural areas (31.2%).47 The prevalence of hypercholesterolemia in Peru is 19.6% in adults over 20 years of age and the population having high levels of triglycerides and LDL is approximately 15% and 13%, respectively.48,49
Furthermore, Peru has a considerable consumption of medicinal plants35 and it is easier in some instances to implement nutritional and lifestyle intervention or recommend the adjuvant treatment with a fruit, vegetable or medicinal plant.50–53 The use of tomato lycopene alone and in combination with olive oil offers a plausible acceptable adjuvant treatment to reduce cholesterol levels in the Peruvian population. Therefore, we designed an intervention study to determine the effect in cholesterol levels after at least 9 days of consumption of tomato juice alone and in combination with olive oil accompanied with usual diet in comparison with a low-calorie diet (1000 calories) in 50 70 patients in a hospital in Lima, Peru.
Methods
Type and level of research
Analytical study with a longitudinal and prospective design, quantitative type. Figure 1 shows the three treatments the study patients received, (1) tomato juice + olive oil and usual diet; (2) tomato juice (3) low calorie diet (1000 kcal).
Figure 1. Treatment schedule of study patients.
Population and sampling
A total of 70 patients were recruited; however, a total of 50 patients finished the study protocol. Patients with the diagnosis of hypercholesterolemia who were treated in the Nutrition service at a Department of Nutrition of Sanidad de la Policia del Perú (hospital based in Lima, Peru). Convenience sampling was used to allow representative samples to be obtained from the population of patients in medical consultation from June to November 2018 and who met the inclusion criteria.
Inclusion and exclusion criteria
The inclusion criteria were patients older than 18 years old with a diagnosis of hypercholesterolemia of both genders in a hospital in Lima that were not receiving pharmacological treatment. The patients were previously diagnosed with hypercholesterolemia based on their medical history. The patients that accepted to be part of the study were referred to a nutritionist appointment and a confirmatory cholesterol measurement was performed. The hospital (Sanidad de la Policia del Perú) uses the definition of the American Heart Association for high cholesterol when the total cholesterol levels are above 240 mg/dL.54
The exclusion criteria were the use of pharmacological treatment for hypercholesterolemia or any pharmacological treatment, which may produce synergistic or antagonistic effects with cholesterol. Another exclusion criteria were history of food allergy to some of the components of the interventions.
Assignment and variables
Patients were randomized into the three intervention groups at the time of their initial clinic visit. The patients that met the inclusion criteria were explained about the study and the objectives and were requested to sign the informed consent. Then, the patients were requested to return the following day for baseline measurement of total cholesterol in blood and for anthropometric measurements (weight, height, BMI and waist circumference). Total cholesterol was measured using a colorimetric enzymatic method, as previously described.55
Preparation of tomato juice; tomato juice + olive oil and low-calorie diet
The tomato juice and olive oil were prepared with approximately 420 grams of peeled ripe tomatoes, whose pulp with seeds was liquefied and with the addition of approximately 18 mL of extra virgin olive oil. It was mixed for one more minute until obtaining a homogeneous mixture. This was macerated for eight hours at room temperature. This preparation was made by the nutritionist in charge of patient care and was consumed in the office.
The tomato juice was prepared with approximately 420 grams of fresh and ripe tomatoes, from which the skin was removed, the pulp along with the seeds were blended without any additives. It was stored at room temperature for eight hours before being consumed in the office. This preparation was made by the nutritionist in charge of patient care.
The type of food preparation was selected because it has been previously reported that the use of olive oil can generate a biocompatible microemulsion containing lycopene that exhibit good solubility in aqueous and non-polar media and can enhance the health promoting properties of both lycopene and olive oil.56 The tomato variety utilized in our study was organic Milano Perseo, which has been reported to contain 219.95 ± 1.76 μg lycopene per gram of tomato57; therefore, the tomato juice preparations averaged approximately 92.38 ± 0.74 mg of lycopene.
A plan of one thousand calories was provided by the nutritionist in charge of patient care. A list of food exchanges for the day was given to the patients based on the World Health Organization (WHO) energy and protein requirements.58 The low-calorie diet was consumed by the patients in their homes without supervision.
Procedure for consumption of tomato juice+ olive oil and low-calorie diet
The first group of patients consumed tomato juice + olive oil, which was prepared by the nutritionist the day before (eight hours before) and was delivered to the patients in the hospital in the morning while fasting. This was performed for nine consecutive days.
To the second group, the nutritionist gave tomato juice without olive oil, which was also prepared the day before and consumed in the hospital in the morning while fasting. This was performed for nine consecutive days.
The third group of patients did not drink tomato juice or tomato juice + olive oil, they consumed a detailed plan of 1000 calories that was prepared by themselves at home.
The duration of the study treatment for nine days was based on previous studies that have evaluated similar tomato treatments and their effect in cholesterol levels and endothelial function for periods of time between seven days and 14 days. For instance, Stangl et al. evaluated the effect of tomato products on endothelial function after administration of 70 g of tomatoes containing 46.2 mg of lycopene for 7 days to healthy non-smoking postmenopausal women.59 Another study delivered 70 g tomato paste containing 33.3 mg of lycopene for 14 days to evaluate endothelial dynamics and plasma total oxidative status in healthy subjects.60
Protocol adherence and follow-up
To control protocol adherence, the patients who consumed the hypocaloric diet were called by telephone by the nutritionist in charge of patient care to follow-up if they prepared the proposed nutritional plan.
There was no control diet, the reason is because the patients were referred from the doctor’s care with a reference sheet to be attended by the nutritionist. At that moment they entered a list to be randomized and they were assigned to one of the three treatment groups. Because of their hypercholesterolemia diagnosis, the patients needed a nutritional plan that required changes in the usual diet. Therefore, having a control diet based on their usual diet was not appropriate because of the need of proper timely care.
Data processing and statistical analysis
Descriptive statistics (central tendency and dispersion measures) were used. The variables were described according to the type of preparation or diet received. Because cholesterol is a quantitative variable, the normality test was performed, and Shapiro Wilk was used since the population was less than 50 patients. The test for homogeneity of variances was observed to see if the results adjust or not to a normal model. It was proposed to apply a contrast of equality of means for two independent samples with the Student’s T test. Statistical significance was determined with p-values < 0.05. The results were analyzed in the statistical package SPSS, version 23.
Ethical aspects
Participants received an explanation about the study objectives and procedures. It was explained that their identity and the results obtained from the laboratory were protected at all times, and that if they decided to leave the study, they could do so at any time they chose. Once they voluntarily accepted to participate, they signed the informed consent form. The study protocol was approved by the institutional ethics committee for health research of the Universidad Norbert Wiener (# 0014-2018).
Results
A total of 70 patients were recruited; however, a total of 50 patients finished the study protocol. Out of these, 21 received tomato juice with olive oil (TOO) and their regular diet; 14 patients received only tomato juice (TJ) and regular diet; and 15 had only nutritional counseling regarding the 1,000-calorie diet (LCD). The average age in the first (TOO) group was 53.48, in the second (TJ) group 54.13, and in the third (LCD) group, it was 52.60 years.
The initial body mass index (BMI) for two of the TOO and TJ groups showed the level of overweight (BMI ± SD) (29.53 ± 3.15 kg/m2 and 29.26 ± 4.73 kg/m2 respectively); and for group LCD (30.59 ± 3.46 kg/m2), it had a value corresponding to obesity. Furthermore, there were no statistically significant differences in the initial cholesterol measurements nor the anthropometric measurements (weight, height, BMI and abdominal circumference) between the treatment groups.
The BMI on Day 9 exhibited a slight increase in all the treatment groups, which correlated to a slightly higher body weight even though the abdominal circumference measurements in all the treatment groups were lower; however, all these differences were not statistically significant.
The baseline cholesterol levels in the three groups were in the range of 219.90 and 264.04 mg/dL, which were considered elevated. However, the cholesterol levels on Day 9 were reduced to values lower than 200 mg/dL that were considered normal (Table 1).
Table 1. Clinical, biochemical and anthropometric characteristics of patients treated at a hospital in Lima in 2018 by intervention.
It was determined that the cholesterol values at baseline (CHOL1) and at the end of the study (CHOL2) do not have a normal distribution, therefore, the medians were compared using non-parametric tests: Kruskal Wallis and Wilcoxon. In Table 2, the differences of the CHOL2-CHOL1 level were analyzed to verify if the cholesterol levels were reduced with the diet, effectively. It was determined that there were significant differences (p< 0.05) in cholesterol levels within each type of intervention.
Table 2. Wilcoxon Signed Ranks Test of related samples.
The CHOL 1 value at the start of the intervention was checked with the Kruskal Wallis test to verify whether the cholesterol values were the same in all groups. It was determined that at baseline patients had similar cholesterol level (p>0.05). Then, the CHOL 2 level at the end of the intervention was analyzed and it was found that there were no significant differences (p>0.05) between the type of diet (see Table 3).
Table 3. Kruskal Wallis Test of independent samples differences.
| Type of preparation | Independent samples differences* | p-value | |||
|---|---|---|---|---|---|
| Mean | SD | Median | |||
| CHOL1 | Tomato juice and olive oil | 264.04 | 98.60 | 230.00 | 0.409 |
| Tomato juice | 228.22 | 91.21 | 210.00 | ||
| Low-calorie diet | 219.90 | 79.72 | 216.50 | ||
| CHOL2 | Tomato juice and olive oil | 145.56 | 80.67 | 124.00 | 0.331 |
| Tomato juice | 118.35 | 36.69 | 112.00 | ||
| Low-calorie diet | 139.00 | 52.49 | 119.50 | ||
Discussion
The patients who consumed tomato juice and olive oil were 53.48 years old on average and had a BMI of 29.53 (overweight) and final cholesterol of 145.56 md/dL. Patients who consumed tomato juice were 54.13 years old on average and had a BMI of 29.26 (overweight) and final cholesterol of 118.35 md/dL, and patients who consumed only their diet were 52.60 years old on average and had a BMI of 30.59 (obesity) and final cholesterol of 139.00 md/dL. The distribution of cholesterol before and after the intervention in the three groups: tomato juice and olive oil (TOO), tomato juice (TJ) and low-calorie diet (LCD), shows the same distribution among the categories and there were no statistical differences.
The benefits of diets rich in tomatoes for the cardiovascular system have been linked to plasma carotenoid concentrations. It has been reported that all lycopene isomers significantly increased in subjects consuming tomato juice (TJ) with oil, reaching maximum concentration at 24 h. LDL and total cholesterol decreased significantly six h after TJ consumption with oil, which was significantly correlated with an increase in trans-lycopene and 5-cis-lycopene, respectively.61 Lycopene has been reported to be a potentially useful compound to prevent and treat cardiovascular diseases and cancers because of its antioxidant capacity.62 Salazar Lugo showed that the consumption of tomato juice for six weeks decreased total cholesterol and LDL cholesterol, being more effective in patients with hyperlipidemia,63 which correlates with our results.
The consumption of diets containing olive oil and rich in lycopene for 9 days have been reported to decrease the cholesterol levels by improving the lipid profile compared to diets rich in carbohydrates, low in fat and rich in lycopene.61,64 The consumption of tomatoes with olive oil improves the antioxidant capacity of plasma.41 Although the measurement of antioxidant activity was not the objective of this study, it was observed that the serum lipid profile measured by cholesterol did change. The results show that a significant difference was found between the first and second measurements in the tomato juice and olive oil (TOO) preparation, while no difference was observed for the tomato juice (TJ) preparation. The low-calorie diet (LCD) showed differences between the first and second cholesterol measurements, but no differences between groups were observed.
Recent studies have reported that patients supplemented with tomato were associated with significant reductions in LDL cholesterol, IL-6, and flow-mediated dilation.20,61,64 Tomato consumption also had positive effects on blood pressure and endothelial function, while lycopene intake has been classified as a preventive and non-pharmacological therapeutic measure for different types of diseases.65 The dose of lycopene needed to obtain health benefits has not yet been agreed upon, and most epidemiological studies have shown the consumption of seven to ten servings per week of lycopene source foods, equivalent to five to ten mg/day of lycopene, seem to have positive effect.66 It is important to note that based on previous lycopene quantification (219.95 ± 1.76 μg lycopene per gram of tomato),57 our tomato juice preparations could average approximately 92.38 ± 0.74 mg of lycopene. Tomato juice preparations, rich in lycopene, combined other synergistic foods such as olive oil have been reported. For instance, tomato juice made with 420 g of tomatoes and macerated for more than 8 hours with the 18 mL of extra virgin olive oil, have been reported to increase the content of relevant phytochemicals such as lycopene, chlorogenic acid, caffeic acid and ferulic acid, lutein and zeaxanthin67 and vitamin C. Tomato also contains various flavonoids such as quercetin, rutin, naringenin that possess antioxidant effects and health related benefits.68,69 Likewise, the consumption of olive oil improves the absorption of lycopene from tomato preparations,70,71 and extra virgin olive oil provides an excellent amount of vitamin E,72 which is scarce in food and has a high anti-oxidant capacity.73 Extra virgin olive oil consumption has been reported to provide a cardioprotective effect by reducing total cholesterol and LDL, because of its high monounsaturated fat content.74
Limitations
The main limitation is that the sample size was small, and it can only be considered as a pilot study. There was no evaluation of tomato maturity, phytochemical content nor physicochemical and organoleptic evaluation of the tomatoes and extra virgin olive oil used. Only total cholesterol was quantified, and no information was obtained from the HDL or LDL cholesterol or any other cardiovascular relevant biochemical parameter. Future research should be performed with a better and more detailed characterization of the food preparations and for longer periods of administration.
Conclusions
There was an effect on the measurement of cholesterol with the preparation of tomato juice and olive oil as well as the low-calorie diet. These recommendations would support patients with cardiovascular disease and dyslipidemia. The found information would support the creation of individualized nutritional strategies involving lycopene-rich products such as tomatoes in patients with cardiovascular disease and dyslipidemia.
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how to cite this article
Del Castillo Vidal G, Lozada-Urbano M, Miranda D et al. Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.12688/f1000research.133905.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Version 1
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PUBLISHED 11 Oct 2023
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How to cite this report:
Valls-Belles V. Reviewer Report For: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.5256/f1000research.146920.r217460)
The direct URL for this report is:
https://f1000research.com/articles/12-1315/v1#referee-response-217460
https://f1000research.com/articles/12-1315/v1#referee-response-217460
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 11 May 2024
Victoria Valls-Belles,
Universidad Jaume I, Castellón, Spain
Not Approved
VIEWS 4
Introduction:
- Does not mention the clinical practice guidelines for cardiovascular risk (ATP II and ATP III).
- The bibliography is not very current (2 articles from 2021; 3 from 2022 and 1 from 2023, when there are ... Continue reading
- Does not mention the clinical practice guidelines for cardiovascular risk (ATP II and ATP III).
- The bibliography is not very current (2 articles from 2021; 3 from 2022 and 1 from 2023, when there are ... Continue reading
CITE
HOW TO CITE THIS REPORT
Valls-Belles V. Reviewer Report For: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.5256/f1000research.146920.r217460)
The direct URL for this report is:
https://f1000research.com/articles/12-1315/v1#referee-response-217460
https://f1000research.com/articles/12-1315/v1#referee-response-217460
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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How to cite this report:
Sittiprapaporn P. Reviewer Report For: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.5256/f1000research.146920.r230745)
The direct URL for this report is:
https://f1000research.com/articles/12-1315/v1#referee-response-230745
https://f1000research.com/articles/12-1315/v1#referee-response-230745
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 15 Feb 2024
Not Approved
VIEWS 12
Review Results
Manuscript entitled: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil.
I am really appreciative of this study and enjoy reading this manuscript. However, ... Continue reading
Manuscript entitled: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil.
I am really appreciative of this study and enjoy reading this manuscript. However, ... Continue reading
CITE
HOW TO CITE THIS REPORT
Sittiprapaporn P. Reviewer Report For: Total cholesterol effect after consumption of tomato juice alone and in combination with extra virgin olive oil. A nine-day pilot study in hypercholesterolemic patients [version 1; peer review: 2 not approved]. F1000Research 2023, 12:1315 (https://doi.org/10.5256/f1000research.146920.r230745)
The direct URL for this report is:
https://f1000research.com/articles/12-1315/v1#referee-response-230745
https://f1000research.com/articles/12-1315/v1#referee-response-230745
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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