Figure - available from: Frontiers in Pharmacology
This content is subject to copyright.
Box plots of Δ LDL-C (%) based on quartiles of baseline plasma LDL-C levels in all subjects (n = 80) after 6 months of Bergavit® (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin, and 37% of naringin, daily) supplementation. LDL-C, low-density lipoprotein cholesterol.
Source publication
Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be...
Similar publications
Background: In chronic kidney disease (CKD) patients,measuring carotid artery intima– media thickness (CIMT) canpredict coronary heart disease and stroke, resulting from systemic atherosclerosis.Objective: To find out correlation of carotid artery intima–media thickness and dyslipidemia in chronic kidney disease in a Bangladesh population.Methods:...
Citations
... SdLDL particles, designated as LDL-3 to -7. Particularly, smallest LDL-5 were associated with the change in cIMT in cases of Moderate Hypercholesterolemia. 58 Using a standardized protocol, we performed high resolution B-mode ultrasonography of the common carotid arteries with a linear array probe. We manually measured the IMT using a vernier caliper after taking a picture. ...
Cardiovascular disease (CVD) and atherosclerosis are major causes of mortality worldwide. Early and accurate diagnosis of vascular thickening by predictive markers can help reduce the death rate of these diseases. Low-density lipoprotein (LDL) particles, which are rich in cholesterol, are regarded as key biomarkers for CVD and atherosclerosis. Numerous studies have demonstrated that pattern B (small dense LDL, sdLDL) is more atherogenic than LDL and can serve as a superior quantitative marker for CVD than LDL. Furthermore, several studies have indicated that carotid intima-media thickness (cIMT) is a reliable marker for the early detection of CVD and atherosclerosis in various populations. This review examines the relationship between sdLDL concentration and cIMT. It is concluded that sdLDL concentration has a positive correlation with cIMT, and their combined use can facilitate a more precise assessment of the diseases, especially atherosclerosis.
... The lipid-lowering effects of bergamot flavonoids can be attributed to their multifaceted interaction with lipid metabolism pathways [29]. These flavonoids activate sirtuin-1 and AMPK-α, central regulators of cellular energy homeostasis, which promote fatty acid oxidation through carnitine palmitoyltransferase 1 (CPT1) activation [30][31][32][33], and concurrently reduce very-low-density lipoprotein (VLDL) synthesis by inhibiting hepatocyte nuclear factor 4 (HNF4) [34] and sterol regulatory element-binding protein 1 (SREBP-1) [35]. ...
... This inconsistency can be explained by the methods of extraction, preparation, and standardization that was different from one trial to another. In addition, some trials used an open-label design [38] or a 6-month prospective trial without placebo control [29]. The present study aimed to add an additional piece of information on the efficacy of the bergamot in improving the dyslipidemia in the short and long term in subjects with borderline-high LDL-C levels, while linking it with a standardized and reproducible amount and profile of flavonoids. ...
... The beneficial role of bergamot in lowering LDL-C is well-documented in the literature. Beyond its recognized effects, bergamot flavonoids exert their lipid-lowering action through multifaceted mechanisms, including the modulation of lipid metabolism pathways and enhanced clearance of LDL particles [29]. However, as highlighted in a meta-analysis, these findings are based on studies with relatively small sample sizes, underscoring the need for further research to strengthen the causal relationship between bergamot extract consumption and improvements in lipid profiles [2]. ...
Strategies for controlling cholesterol and lipid metabolism, including the use of food supplements, are part of the non-pharmacological intervention to ameliorate cardiovascular health. To demonstrate the efficacy of a standardized flavonoids (150 mg/day) extract from Citrus bergamia on cholesterol and lipid management, a placebo-controlled clinical trial on 64 subjects with high cholesterol was carried out. The total study duration was 4 months, with intermediate checkpoints at 1-month intervals. Low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) cholesterol, total cholesterol (TC) levels, oxidized low-density lipoprotein (ox-LDL), and paraoxonase activity (PON1) were measured as primary endpoints (efficacy evaluation), while weight, blood pressure, hepatic and renal function blood markers were measured as secondary endpoints (safety evaluation). After 4 months, both TC and LDL-C significantly decreased by 8.8% and 11.5%, respectively, along with a 5.5% increase in HDL-C which was trending towards significance. In addition, ox-LDL was significantly reduced by 2.0%, while PON1 was significantly increased by 6.5%. The secondary endpoints were not changed during the study, demonstrating a good tolerability of the test product. Our findings demonstrate the efficacy of the extract as a natural approach for cholesterol and lipid metabolism management.
... Bergamot, also recognized as Citrus Bergamia, is a well-known plant with high flavonoid contents, including naringenin [107] and shows a beneficial effect on LDL-C. Its possible benefits on cholesterol regulation seem to be these flavonoids inhibiting HMGCR, thereby repressing cholesterol synthesis [108]. ...
Introduction
: Statins are effective in reducing high cholesterol levels; however, due to associated side effects, many patients actively seek alternative medications. This review evaluates the efficacy, side effects, patient adherence, cost-effectiveness, and accessibility of dietary supplements (DS) as a treatment option for hypercholesterolemia.
Methods
This narrative review compares red yeast rice (RYR), flaxseed, artichokes, bergamot, Ayurvedic mixtures (with garlic as a prominent ingredient), and statins for treating hypercholesterolemia. We searched PubMed, Scopus, and Cochrane databases for studies published between 2012 and 2024 using “hypercholesterolemia” in combination with a dietary supplement (red yeast rice, flaxseed, artichokes, garlic, or bergamot). The selected articles were published until 28th January 2024 with no language restrictions.
Results
Study results suggest that alternative treatments using dietary supplements such as flaxseed, bergamot, or red yeast rice may effectively reduce cholesterol levels, with the specific value varying based on the study.
Conclusion
The following natural ingredients - red yeast rice, artichoke extract, bergamot, garlic, and flaxseed - have been specifically selected for their cholesterol-lowering properties. Based on consistent usage, except for aged garlic extract, these ingredients appear to have a beneficial impact on cholesterol levels. (1) It is advisable to conduct a comprehensive cohort study to assess the efficacy of relevant dietary supplements, particularly red yeast rice, bergamot, and flaxseed, in treating hypercholesterolemia. This is important due to the varying effectiveness of alternative treatments. However, there are lingering concerns regarding the lack of supervision and quality control that require attention. (2) Further research into the specific molecular composition and the underlying mechanisms by which it reduces cholesterol levels is warranted.
... GLP-1 RAs, SGLT2is, and dipeptidyl peptidase-4 inhibitors (DPP-4is) have demonstrated positive effects on body weight, lipid profiles, blood pressure, and endothelial function. Incretin-based therapies, such as liraglutide, improve glycemic control and reduce cardiometabolic risk in obese patients with T2DM [6][7][8]. However, the high cost of these medications has sparked interest in alternative treatments, particularly nutritional supplements and medicinal plants. ...
... Nutraceuticals offer a promising alternative for patients at low risk, either as a supplement to existing therapies or as an initial treatment before pharmaceutical intervention in non-high-risk cases [6]. Several plant-based compounds have been explored, including metabolites from Bergamot [7], Pinus pinaster [8], Sophora tonkinensis [9], and Curcuma longa [10]. ...
Background
Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression.
Objective
To assess the efficacy of improving type 2 diabetes (T2DM).
Study design
This randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes.
Methods
All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, β-cell function (homeostasis model assessment [HOMA-β]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention.
Results
After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001.
Conclusions
A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of β-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial.
Trial registration
Thai clinical trials regentrify no.20140303003.
... Another is an increased cholesterol elimination with faeces by lowering its absorption in intestine and increasing the turnover and excretion of bile acids. 12,20,21 There are not many studies regarding the hypolipidemic properties of bergamot extract, although those that are available are promising. 12 Randomized, double-blind, placebo-controlled study conducted on 60 patients by Mollace et al. showed significantly modified cholesterol levels after 30 days in people who was given bergamot polyphenol fraction and bergamot polyphenol fraction phytosomal formulation. ...
Obtaining optimal levels of lipoproteins and total cholesterol is one of the main goals for reducing cardiovascular risk. Many patients insist on changing their statin treatment to a nutraceutical such as Bergamot extract or red yeast rice extract, due to statin intolerance affecting some of them and increasing disinformation on statin side effects. This is why, interest in lipid-lowering ability of available nutraceuticals, is growing. In our work, we tried to summarise what is known about nutraceuticals such as red yeast rice and bergamot extract and how they can be used in clinical practise. We searched two databases such us Pubmed and Medline byusing the terms “bergamot”, ”red yeast rice”, “dyslipidaemia” and “hypercholesterolaemia” Products containing red yeast rice and bergamot extract are dietary supplements which are sold over the counter. There is possibility that they can be seen as natural substances which significantly reduce cholesterol levels, however, they have weaker effect than strong statins. They cannot be replacement for them. Red yeast rice is the leading substance. It can be used in patients with moderate hypercholesterolemia or can be combined with ezetimibe if statins are badly tolerated. There is no clear opinion of experts on bergamot due to lack of larger and longer studies. As our article show it is crucial to conduct more scientific research on nutraceuticals especially Bergamot extract.
... These data are also available in rats with a dosage of 50 mg/kg/day. Furthermore, this study highlighted that an oral dose of 150 mg/day of bergamot polyphenolic extract for 6 months [71] or an oral dose of BPF from 500 to 1000 mg/day for 30/60 days [43,[72][73][74] leads to a reduction in body weight or a decrease in total cholesterol, triglycerides, LDL, and an increase in HDL. The effects of bergamot on the skin have been evaluated in only two studies, but more research is needed [70]. ...
Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects.
... Referring to this scientific work [16] Nauman et al. (2019) collated research papers that tested the correlation between bergamot and lipid metabolism. The paper collected studies [17] [18] [19][20] [21] whose results claimed, to a greater or lesser extent, that polyphenols were able to raise HDL-C levels and lower triglycerides. It should be noted that the results of the studies are not consistent across the board. ...
Introduction and purpose: Citrus bergamia, commonly known as bergamot, is a unique plant native to the Calabria region in Italy, prized for its fragrant fruits and versatile applications. Historically utilized for extracting essential oil, bergamot has garnered attention for its therapeutic properties, particularly its Bergamot-derived Polyphenolic Fraction (BPF), which exhibits lipid-lowering, antioxidant, and anti-inflammatory effects. This paper aims to provide a comprehensive summary of existing research on the therapeutic potential of BPF in humans.Brief description of the state of knowledge: BPF has shown promise in supporting wound healing, alleviating neuropathic pain, and exhibiting antimicrobial properties. Research highlights BPF's role in modulating lipid metabolism, particularly in reducing LDL cholesterol and triglycerides while increasing HDL cholesterol levels. Additionally, BPF demonstrates anti-inflammatory effects, accelerating the recovery process in conditions such as non-alcoholic steatohepatitis (NASH) and potentially influencing pathways involved in cancer cell proliferation and apoptosis. Further studies explore BPF's impact on bone metabolism, erectile dysfunction, and its potential in dermatological applications, particularly in counteracting photoaging.Conclusions: While existing studies underscore the promising therapeutic effects of BPF in various medical domains, further research is warranted to establish its efficacy and safety for broader clinical use. Continued investigation on a larger scale holds the potential to develop BPF as a valuable physiotherapeutic strategy across diverse medical fields.
... Also, ginseng that aid in lowering the choles- terol and LDL-C by inhibition of -hydroxy--methylglutaryl-CoA reductase ( Sotaniemi et al., 1995 ). Bergamot juice has significant effects on metabolic markers, as atherogenic lipoproteins, subclinical atherosclerosis, and plasma lipids ( Toth et al., 2016 ). Mulberry leaf extract has impact on MetS by decreasing postprandial glucose, triglycerides, LDL-C and increasing HDL-C ( Kojima et al., 2010 ). ...
Metabolic syndrome (MetS) is a bunch of metabolic defects comprising hypertension, insulin resistance, visceral obesity, fatty liver, and atherogenic cardiovascular diseases. Lifestyle modification is the first step for controlling the MetS progression. If left untreated, MetS is significantly related to a high danger of evolving type 2 diabetes and atherogenic cardiovascular diseases. Thus, MetS is a prominent cause of morbidity and mortality internationally and has been become very important to investigate novel therapies in this context to decrease the heavy burden of the disease. Though, there is no single treatment for MetS and the currently available pharmacother-apy and related comorbidities demand the continued use of multiple drugs that is challenging for patients as the polypharmacy and reduced accordance. There is increasing concern in the use of nutraceuticals in the management of MetS. This review follows MetS with an emphasis on the risk factors and how to control it, epidemiology, pathogenesis, pathophysiology, diagnosis, and treatments. Moreover, the review recaps on the health benefits of natural products in the management of the MetS to give a complete guide to other researchers for new natural products investigation. Novelty Statement MetS is significantly related to develop type 2 diabetes and car-diovascular diseases as well as MetS is considered a prominent reason of morbidity and mortality worldwide. Thus, it is critical to explore new treatments in this circumstance. However, there is no single treatment for MetS and the existing pharmacotherapy require the continuous use of numerous drugs that is challenging for patients as the polypharmacy and diminished accordance. There is rising interest in the utilization of nutraceuticals in the management of MetS. Also, the investigation of an efficient approach to manage those complications not studied well, where the authors highlighted this point in our manuscript. We presented in this review a wide information concerning the risk factors, patho
... 44 Phytochemicals, such as flavonoids has been shown to decrease lower serum lipids levels by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme and up-regulating peroxisome proliferators-alpha and gamma expressions in the liver. 45 Flavanoids prevent the oxidation of low-density lipoprotein, lowers the blood lipid levels thereby reducing the risk for the development of atherosclerosis. It has been suggested that consumption of tannin containing food and beverages, can prevent a variety of ailments such as heart related diseases. ...
Grewia mollis Juss (Malvaceae) commonly described as “Dargaza” is a shrub, popularly used in folk medicine to treat obesity, diarrhoea and to ease childbirth. However, there are no established reports on its antiobesity activity in literature, hence, the aim of the study was to evaluate the antihyperlipidemic and antiobesity effects of Grewia mollis (GM) in rodents. Hyperlipidemia was induced by 200 mg/kg of triton WR-1339 and the rats were orally pre-treated with extract (150-600 mg/kg) and atorvastatin (25 mg/kg) for 3 days. Obesity was induced with dietary cholesterol (600 mg/kg) for 10 weeks and rats were orally treated with extract (150-600 mg/kg). The effects of the extract on body weight, total food consumption, relative organ weight, Lee index, lipid profile, atherogenic index, coronary risk index and histopathological indices were evaluated. Preliminary phytochemical screening showed presence tannins, saponins, alkaloids, flavonoids and steroidal nucleus. The extract significantly (p<0.05) decreased total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL), non-high-density lipoprotein cholesterol, atherogenic index, coronary risk index in hyperlipidemic rats. In the obese rat, there was significant (p<0.05) decrease in relative liver weight, body weight, Lee index, triglycerides, VLDL. Atherosclerotic changes in the coronary artery and aorta were ameliorated by the extract. The reduction in lipid profile and amelioration of atherosclerotic lesions indicate a possible anti-atherogenic property. These effects appear to be mediated via inhibition de novo triglyceride and cholesterol biosynthesis. The extract shows therapeutic promise in the management of obesity, hyperlipidemia and in the prevention of atherosclerosis.
... Bergamot has been used in numerous clinical trials and has consistently been shown to be well tolerated in studies lasting from 30 days to 12 weeks. For example, a randomized double-blind placebo-controlled study by Toth et al. [151] assessed the hypolipidemic effects of a bergamot polyphenol fraction. The bergamot polyphenol fraction decreased total cholesterol from 262 to 196, LDL cholesterol from 175 to 116, and triglycerides from 252 to 170. ...
... Polyphenols have been found to modulate over 100 miRNAs, which play a role in regulating various cellular processes such as inflammation and apoptosis. Some of the polyphenols that have been reported to exert their effects through microRNAs include naringenin, apigenin, kaempferol, hesperidin, ellagic acid, and oleuropein [150,151]. The majority of the research on this subject has been conducted in vitro using various cell lines, particularly cancer cell lines. ...
Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases.