Protective Effects and Benefits of Olive Oil on Women’s Health

Women and men share similar diseases; however, women have unique issues, including gynecologic diseases and diseases related to menstruation, menopause, and post menopause. In recent decades, scientists paid more attention to natural products and their derivatives because of their good tolerability and effectiveness in disease prevention and treatment.

Olive oil is an essential component in the Mediterranean diet, a diet well known for its protective impact on human well-being. Investigation of the active components in olive oil, such as oleuropein and hydroxytyrosol, showed positive effects in various diseases. Their effects have been clarified in many suggested mechanisms and have shown promising results in animal and human studies, especially in breast cancer, ovarian cancer, postmenopausal osteoporosis, and other disorders.

1. Introduction

One of the most prominent parts of the Mediterranean diet (MD) is OO consumption, which is the principal source of fats. Other components of the MD include frequent consumption of various vegetables and fruits, cereals, fish and seafood, moderate alcohol intake, and relatively low meat intake.

Current data on MD suggest that OO and its components have shown preventive effects in cancer [3,4], cardiovascular diseases [3,4], diabetes [3,4], and other diseases [4,5]. Monounsaturated fatty acid (oleic acid) and polyphenol constituents (such as oleuropein, hydroxytyrosol, and tyrosol) were important components that explain the protective role of OO in these diseases [6,7,8]. Among the phenolic components of OO, oleuropein (OLP) is considered the most effective biomolecule [9,10].

Disease prevention and potential treatment therapy research are critical requirements in medical science. In the recent decades, scientists have paid more attention to natural products and their derivatives in order to investigate their effects on disease prevention and treatment. OO and its active components are potential agents with promising research results. Almost all human clinical trials have evaluated the beneficial effects of OO in the context of MD.

2. Structure and Bioactivity

2.2. Bioactivities

OO extracts have shown protective effects against several diseases, such as hypertension, diabetes, sepsis, obesity, osteoporosis, neurodegeneration, and chronic kidney diseases [31,32,33]. OO consumption decreases the risk of all-cause mortality [34]. OO and its active derivatives showed antioxidant and anti-inflammatory effects [35]. Moreover, OO has antibacterial properties [36].

Polyphenols also show anti-cancer effects through various mechanisms related to apoptosis, proliferation, inflammation, angiogenesis, and cell cycle arrest [44]. HT showed a protective effect in the aging process via AMP-activated protein kinase (AMPK) and autophagy [33]. OO consumption decreased the risk of stomach cancer, ovarian cancer, colon cancer, endometrium cancer, particularly breast cancer. These beneficial findings have been reported in several meta-analysis studies [45,46,47]. OO, most likely oleic acid, regulates the HER2 gene associated with cancer [48].

Figure 1. Chemical structure of (a) oleuropein, (b) hydroxytyrosol, and (c) tyrosol.

3. Cancer in Women

Cancer remains a major cause of death in humans. In 2020, the cancer statistics calculated by Ferlay et al. included 19.3 million new cases and almost 10 million cancer-related deaths.

More studies are required to investigate potential low-risk therapies for cancer prevention and treatment to improve the outcome and quality of life of cancer patients. Natural products have recently attracted attention for their anticancer role as potential adjunctive therapies due to their effects and because they are well tolerated. OO extracts and their bioactive components are some of the agents that have been investigated.

3.1. Ovarian Cancer

Ovarian cancer is one of the most common gynecologic cancers in both developed and developing countries, negatively affecting women’s health and fertility. Primary epithelial ovarian cancer is the most common type of ovarian cancer. Risk factors for ovarian cancer include increasing age, infertility, and endometriosis. Approximately 20% of ovarian cancer cases have familial factors.

Ovarian malignancy is diagnosed at an average age of 63. Major therapies for ovarian cancer include surgery and chemotherapy. Ovarian cancer patients with advanced stage disease face a high risk of relapse and poor outcomes [50,51].

In 2021, Benot-Dominguez et al. reported that olive leaf extract (OLE) reduces the cell proliferation cell cycle and increases apoptosis via mitochondrial impairment, which leads to a decrease in tumor growth [52]. Shabani suggested that OLP induces apoptosis, inhibits cell proliferation, and decreases cisplatin resistance by regulating miRNA expression [53].

3.2. Breast Cancer

Breast cancer is the leading cause of cancer-related deaths in women.
The anticancer role of OO extracts and their bioactive components in breast cancer has been evaluated in numerous in vitro, in vivo, and several clinical trials [71,72,73,74,75].

The OO extract contains several types of compounds. OLP has been shown to play the most important role in breast cancer cell toxicity [76,77]. In breast cancer, OLP inhibits cell proliferation, induces apoptosis, and induces cell cycle arrest [78,79,80,81,82].

HT, the main phenolic compound of the olive oil, has also been shown to be effective in breast cancer. It inhibits cell growth and cell cycle arrest by reducing the expression of cyclinD1 by upregulating c-Jun and reducing pin-1 expression [89].
Another bioactive phenolic compound from EVOO purification is S-(-) oleocanthal (OC). OC inhibited triple-negative breast cancer progression and metastasis to the lung in two heterogeneous triple-negative breast cancer animal models, and no considerable toxicity was observed. Additionally, using a microarray gene signature, this study showed that OC treatment protects almost all steps of cancer progression, including cell-to-cell adhesion signaling, interaction, invasion, and migration [93].

3.3. Cervical Cancer

Cervical cancer is the fourth most common cancer in women and is one of the leading causes of death in developing countries [117]. In 2020, 604,000 new cases of cervical cancer and 342,000 deaths were reported worldwide [118]. Human papillomavirus (HPV) infection accounts for 99.7% of cervical cancers [119]. Treatment of cervical cancer includes surgery, chemotherapy, and radiation, which vary with disease stage.

Torics et al. (2020) assessed the effect of the phenolic compounds in EVOO on cervical cancer. They showed that EVOO phenolic extracts inhibit cell growth, although in combination with current cancer therapy such as irinotecan and 5-fluorouracil, the results were not statistical different [120]. OO polyphenols increased GSH levels, the most crucial intracellular antioxidant molecules measured by flow cytometry, but did not alter ROS levels.

HT may have a higher antioxidant effect than tyrosol [121]. A cross-sectional study in Italy by Barchitta et al. suggested that MD might lower the risk of HPV infection and high-grade cervical intraepithelial neoplasia [122]. OLP increases apoptosis by upregulating the JNK/SPAK signaling pathway [123].

Another study showed that a high olive diet enhanced cervical cancer growth and metastasis in a mouse xenograft model. Oleic acid increases cell proliferation, migration, and invasion. Oleic acid induces CD36 via SRC/ERK activation, which contributes to cervical cancer formation and the progression of cervical cancer [124].

Zhang et al. reported that a high olive diet can enhance tumor growth in cervical cancer in vivo. Oleic acid increased the proliferation and migration of cervical cancer cells. This study also showed the different gene expression patterns altered by the olive oil diet and a set of hub genes for further investigation [125].

4. Postmenopausal Disorders

Postmenopausal women suffer from several disorders due to the reduction in estrogen and other hormones, including emotional fluctuations, hot flashes, depression, anxiety, and vaginal dryness from perimenopause to post menopause [135].

The incidence of obesity, metabolic syndrome, cardiovascular diseases, and osteoporosis is associated with menopause [136].

In ovariectomized rats, EVOO reduced IL-6, malonyldialdehyde, and nitrate levels. Thus, OO has antioxidant and anti-inflammatory effects during menopause. This study also evaluated cancer markers, including carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and carbohydrate antigen 19-9 (CA19-9), in two groups of gynecologic cancer patients who had bilateral ovarian and bilateral fallopian excisions and were consuming either 0 or 50 mL of OO every morning. This study showed a significant decrease in the concentrations of CA125, CEA, and AFP in the OO consumption group [137]. OO in combination with vitamin D3, K1, and B6 also showed beneficial effects on platelet function and nitrosative stress prevention in healthy postmenopausal women [138]. Salvini et al. reported that high EVOO consumption, especially HT, prevented oxidative DNA damage in postmenopausal women [139]. Because of the limited number of patients, further studies are required.

Although the evidence is relatively limited, OO and its components have a positive impact on other aspects of women’s health, such as menstruation and sex. This study showed a similar effect of EVOO and ibuprofen in relieving the symptoms of primary dysmenorrhea, including pain scores and pain durations [140]. Sexual disorders are a common disorder in breast cancer survivors. Juraskova et al. showed that OO, during intercourse is one of the factors of OVERcome therapy, and like OO, vaginal exercise, and moisturizer, improved dyspareunia and sexual disorders in breast cancer patients [141].

5. Osteoporosis

Osteoporosis is a common chronic disease that affects most elderly persons, with women accounting for two-thirds of cases. The risk of osteoporosis increases dramatically in the postmenopausal period. Osteoporosis is a complication that leads to an increase in mortality in patients with osteoporosis [142].

Olive and olive polyphenols have been shown to increase bone mineral density and protect bone health [143]. Liu et al. reported that EVOO increased bone mineral density (BMD) in rats in an artificial menopause state due to ovariectomy [137].

Hagiwara et al. also reported the suppression of bone loss in ovariectomized mice when they used OLP and HT orally at 3-day intervals [144]. Puel et al. in several studies showed the effect of OO and its components in bone loss prevention in animal models [145,146,147,148]. Saleh et al. also showed similar results in osteoporosis models in rats [149].

Several studies have suggested that olive polyphenols protect bone health via oxidative stress reduction and anti-inflammatory effects. Olive polyphenols enhance the growth and differentiation of pre-osteoblasts and decrease osteoclast formation [143,144,150,151]. Gamma-linolenic acid originating from OO inhibits bone resorption and increases calcium levels in bone [152].

Filip et al. showed that polyphenol extract from OO increases osteocalcin concentration, a bone formation marker, and may help maintain lumbar BMD [153]. In contrast, Keiler et al. showed that using the total polyphenolic fraction of EVOO did not attenuate bone loss due to ovariectomy in rat models [154].

6. Cardiovascular Diseases and Type 2 Diabetes

OO positively impacts cardiovascular diseases. The available data demonstrated its protective role on vascular endothelial functions, lowering triglyceride levels, LDL-cholesterol reduction, pro-thrombotic reduction, and anti-atherogenic effects [155,156,157,158,159,160].

EVOO also improved dyslipidemia in postmenopausal women [161]. Jimenez-Morales showed that EVOO interacted with the NOS3 Glu298Asp polymorphism to reduce endothelial dysfunction in patients with metabolic syndrome [160].

The protective effect of OO was observed in a meta-analysis, and OO consumption can reduce the risk of coronary heart disease and stroke [162]. OO also has anti-inflammatory and antioxidant effects [163,164]. The beneficial effects of OO were observed in young women with mild hypertension. Additionally, OO enhanced endothelial function in this group [165].

Moreover, OO showed beneficial effects on anti-inflammatory markers related to cardiovascular diseases, such as C-reactive protein and interleukin-6 [166]. Lockyer et al. supported that OLE protects vascular function and that OLE also significantly decreases the concentration of the cytokine IL-8. This study used a digital volume pulse to measure vascular function in a randomized, double-blind, placebo-controlled, crossover, acute intervention trial in humans [167]. Filip et al. documented that polyphenol extract (Bonolive®) from olives decreased the total and LDL-cholesterol levels in postmenopausal women [153].

OO consumption also reduced the risk of type 2 diabetes in a meta-analysis study [168]. OLP also showed a potential effect in preventing hypoglycemia and oxidative stress-related complications in diabetic rabbits via a positive impact on enzymatic and non-enzymatic antioxidants [164].

7. Conclusions and Future Directions

The collected evidence showed the beneficial effects of OO on women’s health, especially in breast cancer, ovarian cancer, postmenopausal osteoporosis, cardiovascular disease, type 2 diabetes, and other disorders, along with the potential action mechanisms. Two groups of OO constituents were investigated: monounsaturated fatty acids (oleic acid) and the phenolic components. However, the bioactivities of the two groups might have contrasting effects, for instance, in cervical cancer. Almost all human studies have evaluated the effect of OO in the context of MD, so interpreting these studies might be challenging. However, evidence for gynecologic malignancy is limited, and the results remain inconsistent. Therefore, further studies are required to clarify the role of OO in this disease group, especially the active components, and to investigate the underlying mechanisms.

The roles of OO in various aspects of women’s health are summarized in Table 1.

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