Research paper
Hypolipidemic effect of Lactuca sativa seed extract, an adjunctive treatment, in patients with hyperlipidemia: a randomized double-blind placebo-controlled pilot trial

https://doi.org/10.1016/j.hermed.2020.100373Get rights and content

Abstract

Purpose

: Lettuce has demonstrated antidiabetic, antioxidant and anti-inflammatory activities. In the present work the hypolipidemic effect of administration of aqueous-ethanolic extract of lettuce (Lactuca sativa) seed was investigated. Hyperlipidemic patients meeting the inclusion criteria were randomly assigned into the treatment and placebo groups.

Methods

: All patients received atorvastatin (20 mg/day) as the main drug. The patients in treatment group took lettuce seed capsule (1000 mg, once per day); whereas the patients in placebo group took placebo capsule (once per day) for 12 weeks. The lipid profile, blood pressure, body mass index and liver enzymes of the patients were evaluated at baseline, and after 6 and 12 weeks of the clinical trial.

Result and conclusion

: The results indicated that lettuce seed extract significantly (P < 0.05) improved triglyceride, cholesterol, Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) compared to the placebo group. It had no effect on systolic or diastolic blood pressure and the effect on BMI reduction was not significant (P > 0.05) compared to placebo. The lettuce seed extract showed an inhibitory effect on atorvastatin-induced elevation of hepatic enzymes and possible liver toxicity. No serious side effect was reported for lettuce seed extract administration. Therefore, lettuce seed extract could be considered as a supplement for treatment of dyslipidemia.

Introduction

In recent years, with socioeconomic development, changes in lifestyle, diet and the aging of the population, the incidence of hyperlipidemia has increased (Ambrosetti and Faggiano, 2014).It is one of the most important public health problems and threats to human health worldwide and is associated with excessive medical expenses (Bechsgaard et al., 2015). Hyperlipidemia is an asymptomatic chronic condition commonly characterized by an excess of lipid profiles in the bloodstream, and it can silently harm the blood vessels, heart, brain, and kidneys (de Winter and Evenhuis, 2014; Jose et al., 2015). Thus, these patients have a significant and recognized risk factor of progression of atherosclerosis, cardiovascular and cerebrovascular diseases (Wu et al., 2013; Ye and Zhang, 2013). Cholesterol is a fatty substance which circulates in the blood and has an essential role in the body as protection for the vascular walls, linings of body organs, digestive function and a component in forming cell membranes and some hormones (Shen et al., 2014). But, it can also be a problem, if too much is taken in through the diet and not metabolized or used. High levels of cholesterol have been shown to destroy vascular function and structure and lead to accumulation of fatty plaques on vessel walls, narrowing veins and arteries and decreasing blood flow to the heart muscle, brain, and other organs or leading to emboli (Verma and Shaikh, 2015). In addition, high cholesterol causes oxidative change, which has an augmentative role in the formation of atheroma plaques in vessel walls (Hillebrand et al., 2016; Jose et al., 2015; Toodeji et al., 2015). Generally, hyperlipidemia is diagnosed by blood cholesterol levels of >200 mg/dl or blood triglyceride levels of >180 mg/dl (Chahal et al., 2014). Controlling hyperlipidemia also has a vital role in the prevention of hypertension, myocardial infarction, risk of stroke, coronary deaths, and overall mortality. Although a healthy lifestyle, weight loss, and decreased dietary cholesterol have been shown to lower the risk of developing hyperlipidemia (Ahmed et al., 2017). If these interventions are not efficient, drug therapy will be necessary in decreasing hyperlipidemia (Lehtovirta et al., 2016). Many anticholinergic adverse effects such as weight gain or weight loss, nausea, constipation, sedation, cardiac toxicity, orthostatic hypotension, arrhythmias, sexual dysfunction and many drug interactions may occur with antihyperlipidemic medicine (Lampela et al., 2015; Nishtala and Salahudeen, 2016; O’Dwyer et al., 2016). At the present time, the interest for herbal remedies as an important factor for treatment and maintenance of health is increasingly emphasized (Ghorani-Azam et al., 2018a; Moghadam et al., 2013; Sepahi et al., 2014); however, some studies have shown that children taking medicinal herbs should be more cautious (Ghorani-Azam et al., 2018b). The use of herbal remedies has become wide spread in the world due to their low expense, availability, less side effects and drug interactions compared to the chemical drugs (Tashakori-Sabzevar et al., 2013).

Lactuca sativa, commonly known as lettuce, is a plant species belonging to the family Asteraceae. It is most often grown as a leaf vegetable and sometimes for its stem and seeds. It is a very popular herb for salad and food (Brouwer et al., 2012). In recent pharmacological studies, lettuce has demonstrated antidiabetic, narcotic, antioxidant and anti-inflammatory activities (Kalinova et al., 2014; Li et al., 2015; Yamazaki et al., 2012). Phenolic acids, flavonoids, anthocyanins, and vitamins A and C are the major active compounds in lettuce. Some well-designed clinical trials have indicated the efficacy of lettuce in sleep disorder, anxiety and diabetes (Bernatoniene et al., 2009; Hou et al., 2016; Wang et al., 2015). In this study, the hypolipidemic effect of chronic administration of aqueous ethanolic extract of lettuce seed in a 12-week double-blind, placebo-controlled and randomized clinical trial was investigated. The data suggested that lettuce extract has hypolipidemic properties and should be further investigated as a potential intervention for hyperlipidemia treatment in patients.

Section snippets

Preparation of lettuce extract

Lettuce seeds were obtained from Imam Pharmacy (Mashhad, Iran) and approved by the herbarium of the school of pharmacy. The lettuce seeds were rinsed with clean water and then dried in the shade at room temperature. The dried seeds were ground into a fine powder by a laboratory grinder. The dry powder (50 g) was soaked in 250 ml solvent [aqueous-ethanolic (20/80, v/v)] and concentrated using a rotary evaporator at room temperature. The samples were centrifuged (4000 rpm for 10 min) and the

Characteristics of the participants

The baseline demographic data of each participant in the treatment group and placebo group were similar (Table 1). A total of 150 patients were included into the study but ten patients (6 females and 4 males, mean age 43 years) could not complete the study and finally 140 patients successfully finished the trial. At baseline, there were no significant difference (Pvalue >0.05) between demographic characters like age, gender, BMI and level of education of the patients in two groups (Table 1).

Efficacy measures

Discussion

Atherosclerosis is assumed to be a main factor of mortality in recent years; it is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This disease is caused by hardening and narrowing of artery walls and consequently the reduction of elasticity which blocks arteries and finally putting blood flow at risk in the major organ such as brain and heart.

To the authors knowledge, this is the first published study of the effect of L. sativa seed extract on

Conclusion

In this work, addition of lettuce seed extract capsules (1000 mg/day); augmented the effects of atorvastatin in treatment of hyperlipidemic patients. Also, due to the absence of considerable side effects, lettuce seed was shown to be a particularly effective therapeutic adjuvant. Improvements in lipid profile were the clinical relevance of the hypolipidemic effect of lettuce seed. As evident from mentioned results, the hypolipidemic effect of lettuce seed could be related to lactucin,

AUTHORS’ CONTRIBUTIONS

Maryam Hassanpour Moghadam, Samaneh Sepahi, Raheleh Rahbarian, Hooman Mosannen Mozaffari and Seyed Ahmad Mohajeri contributed in study concept, design, and critical revision of the manuscript. Maryam Hassanpour Moghadam and Zohreh Ghasemi participated in the experimental analysis and drafting of the manuscript. Seyed Ahmad Mohajeri contributed in revision and final approval of the manuscript.

Declaration of Competing Interest

None

Acknowledgement

The authors gratefully acknowledge the Vice Chancellor of Research, Mashhad University of Medical Sciences for financial support through grant number 940704. The authors have declared there is no conflict of interest.

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