Obesity has become a global health crisis, with prevalence rates steadily climbing over the past three decades. Conventional methods for managing obesity, such as balanced diets, increased energy expenditure, and lifestyle adjustments, are often supplemented with pharmacological and non-pharmacological interventions. Recently, functional foods and their bioactive components, particularly polyphenols, have gained attention as potential tools in obesity prevention and management.
Polyphenols, naturally occurring phytochemicals found in various plant-based foods, possess biological properties that may modulate physiological and molecular pathways involved in energy metabolism. These compounds have the potential to stimulate β-oxidation, inhibit adipocyte differentiation, and counteract oxidative stress, among other beneficial effects.
This review explores the association between specific polyphenols (resveratrol, quercetin, curcumin, and certain polyphenolic extracts) and obesity, with a focus on human trials. It is important to note that the health effects of polyphenols are influenced by the amount consumed and their bioavailability, and that conflicting results may arise due to variations in study designs, subject characteristics (age, gender, ethnicity), and the chemical forms of dietary polyphenols used.
The Global Obesity Epidemic: A Looming Crisis
Obesity represents a major public health challenge worldwide due to its increasing prevalence in both developed and developing countries and its role as a significant risk factor for various chronic diseases. Obesity, characterized by excessive body fat, can lead to serious health complications, including type 2 diabetes mellitus, fatty liver disease, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnea, and certain cancers. These conditions contribute to a decline in both quality of life and life expectancy.
It is estimated that a substantial proportion of cases of type 2 diabetes, ischemic heart disease, and some cancers are attributable to obesity/overweight. The term "diabesity" highlights the strong association between type 2 diabetes and obesity, with most diabetics being obese or overweight. Projections indicate that the prevalence of obesity-related diabetes is expected to double by 2025, reaching 300 million individuals. If current trends continue, approximately 60% of the world's population will be obese by 2030, leading the World Health Organization (WHO) to recognize obesity as a more severe global health problem than malnutrition.
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The rising obesity rates and their association with other chronic diseases have dramatically increased healthcare costs. Childhood obesity is also a growing concern, with an estimated 108 million children (under 20 years of age) suffering from obesity. Health conditions typically seen in adults, such as type-2 diabetes and cardiovascular disease, are becoming increasingly common among children with obesity.
The marketing of foods and beverages high in sugar, fat, and salt plays a significant role in increasing their consumption by children and adolescents. The WHO has developed recommendations aimed at reducing the impact of such marketing practices.
Obesity is a multifactorial problem influenced by biological, behavioral, and social factors. Genetic factors, sedentary lifestyles, endocrine factors, and certain medications can contribute to weight gain. A recent study has also highlighted a close relationship between obesity and the severity of SARS-CoV-2 disease.
Social and environmental factors also play a significant role in obesity. Obesity prevalence is associated with sex, racial/ethnic identity, and socioeconomic status, creating complex relationships between these characteristics. Food availability, particularly in rural areas and low socioeconomic status communities, is an important factor. The "built environment," including infrastructure, transportation, and neighborhood quality, can also influence the ability to practice healthy behaviors.
Other risk factors for obesity include depression, obesity in earlier age groups, short sleep duration, childhood abuse, and low maternal education. Environments experiencing deprivation, disorder, or high crime are also associated with higher odds of obesity, particularly among individuals of low social status.
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The proliferation of high-calorie, energy-dense food options, combined with reductions in physical activity, contribute to a sustained positive energy balance. The frequency and type of food vendors in a neighborhood also determine the types of foods that residents can purchase, with fast food restaurant density being associated with obesity prevalence.
Strategies for Combating Obesity
The treatment of obesity is inevitably associated with body weight reduction, which can be achieved through various strategies, including lifestyle interventions (diet and exercise), normalization of lipid metabolism, pharmaceutical interventions, or bariatric surgery. Recent studies have shown that some natural dietary factors, particularly polyphenols, can influence body weight and represent a valid strategy for obesity prevention. Dietary interventions using natural bioactive food compounds have emerged as promising therapeutic tools for obesity and metabolic diseases, thanks to their limited side effects. The composition of the diet can affect metabolic and endocrine functions and the global energy balance.
Polyphenols: A Diverse Class of Bioactive Compounds
Polyphenols are a wide group of bioactive compounds naturally occurring in plants as secondary metabolites. They are a natural part of the human diet, and evidence suggests that their consumption is associated with beneficial modulation of a number of health-related variables. There are currently about 8000 different polyphenols; these molecules share a common phenolic structure consisting of hydroxyl groups on an aromatic ring. Although polyphenols are chemically characterized as compounds with phenolic structural features, this group of natural products is highly diverse and contains several sub-groups of phenolic compounds.
Fruits, vegetables, whole grains, and other types of foods and beverages, such as tea, chocolate, and wine, are rich sources of polyphenols. The diversity and wide distribution of polyphenols in plants have led to different ways of categorizing these naturally occurring compounds, including by their source of origin, biological function, and chemical structure. Chemically, polyphenols are a large heterogeneous group of compounds characterized by hydroxylated phenyl moieties.
Flavonoids form a major heterogeneous subgroup comprising a variety of phenolic compounds with a common diphenyl-propane skeleton. Flavonoids are built from a basic structure made up of an oxygenated heterocycle and 2 phenolic rings. They are distinguished by the oxidation state of the heterocyclic pyran ring, forming several groups (e.g., flavonols, flavanols, and anthocyanins). Over 4000 flavonoids have been described in plants, and this number is constantly expanding due to multiple ways by which primary substituents are replaced, yielding more complex structures. Moreover, flavan-3-ols are also found in oligomer and polymer forms, known as proanthocyanidins. The nonflavonoids include phenolic acids (benzoic and hydroxycinnamic acids) and stilbenes. Further nonflavonoids that may be found in nature are gallotannins, ellagitannins, stilbene oligomers, and lignans.
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Studies of food diaries suggest a wide variability in the consumption of polyphenols. In the United States, Spain, and Australia, it is estimated as a consumption of about 190, 313, and 454 mg/day of flavonoids, respectively. The consumption of flavonoids in the diet is generally compensated by simpler phenols, as, for example, in Finland, where there is an average consumption of 222 mg/day of flavonoids and 640 mg/day of phenolic acids.
Polyphenols possess a wide range of beneficial effects against atherosclerosis, brain dysfunction, stroke, cardiovascular diseases, and cancer. Evidence suggests that polyphenols can modulate/regulate or inhibit many cell signaling pathways in the human body. Although deficiencies in polyphenol intake do not result in specific deficiency diseases, adequate intake of polyphenols could confer health benefits, especially with regard to chronic diseases.
Tea, cocoa, fruits, and berries, as well as vegetables, are rich in polyphenols. Flavan-3-ols from cocoa have been found to be associated with a reduced risk of stroke, myocardial infarction, and diabetes, as well as improvements in lipids, endothelial-dependent blood flow and blood pressure, insulin resistance, and systemic inflammation. In recent decades, particular attention has been paid to the antioxidant or antiproliferative role of polyphenols in the human diet, with evidence to support their contribution in the prevention of degenerative diseases.
Although oxidative stress has been observed during aging, under certain pathological conditions, or contractile activity, a number of studies have revealed that it is also related to the development of obesity. Oxidative stress also suppresses the endocrine functions of adipose tissue by interrupting the secretion of adipokins, such as adiponectin. Obesity is associated with low-grade chronic systemic inflammation in the adipose tissue, a condition influenced by the activation of the innate immune system in the adipose tissue that promotes the pro-inflammatory state and oxidation stress, triggering a systemic acute-phase response.
Adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low-grade inflammation with permanently increased oxidative stress. Therefore, increasing the intake of antioxidants in the diet could have positive effects in obese patients. In addition, increased intake of polyphenols can therefore help to reduce body weight in elderly people at high cardiovascular risk.
Human Studies on Polyphenols and Obesity
A number of in vitro studies have provided basic information for understanding the beneficial effects of polyphenols. In addition, many animal scientific research studies have shown that dietary supplementation with a polyphenolic extract is a potentially viable nutritional strategy for the prevention of obesity. In recent years, research has also focused on human experimentation, studying the action of single polyphenols and polyphenolic mixtures.
Curcumin
Curcumin is the most bioactive polyphenol in Curcuma longa, a plant usually consumed as a spice in India and other Asian states. It has been used for thousands of years in Ayurveda medicine. Curcumin exerts several biological functions, including antioxidation, anti-inflammation, and antiangiogenesis, in different organs, including adipose tissue.
Unlike the studies on the effects of curcumin in cells or animals, studies on obese subjects are limited. The first clinical trial using curcumin for obesity treatment was conducted by Mohammadi et al. In this study, obese subjects were treated with a commercial formulation of curcumin (1 g/day) supplemented with a bioavailability enhancer, piperine, for a month. Although there were no changes in weight, BMI, or body fat, serum triglyceride levels were significantly decreased after curcumin treatment, indicating the improvement of insulin actions. In another randomized study, Ganjali and Sahebkar showed that 30-day treatment of curcumin (500 mg/day) reduced serum levels of inflammatory cytokines IL-1β and IL-4 of obese individuals, indicating the anti-inflammatory activity of curcumin in obesity therapy. Moreover, oral curcumin supplementation (1 g/day for 30 days) was effective in reducing oxidative stress.
HiPhenolic: A Polyphenol-Rich Supplement
HiPhenolic is a high-concentration, highly purified polyphenolic blend that has been scientifically demonstrated to make positive shifts in functional metabolic targets. It provides multidimensional support to maintain blood pressure levels already within the normal range, manage weight, and increase satiety and appetite control. Maintaining healthy blood pressure levels has become a primary concern for many in the United States and across the globe. Blood pressure fluctuations cause a variety of cardiovascular challenges, and this is one of the most common cardiometabolic challenges experienced.
There is abundant evidence that dietary factors play a significant role in determining cardiovascular risk driven by several potential mechanisms. Plant-derived foods are high in fiber and phytochemicals proven to be antioxidant powerhouses. Polyphenols are a large group of plant metabolites that exert a variety of key biological activities including increasing satiety hormones (like GLP-1 [glucagon-like peptide-1]) and decreasing hunger hormones (like ghrelin), activating mechanism for human metabolism. Metabolaid (Hibiscus and Lemon Verbena Extract) Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional formulations in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese formulations in the manner of a tea to help maintain normal blood pressure levels and normal inflammatory balance.
Metabolaid: A Synergistic Blend of Hibiscus and Lemon Verbena
Metabolaid® is a combination of the plant polyphenols in lemon verbena (Lippia citriodora) and hibiscus flower (Hibiscus sabdariffa L.) extracts. These extracts have been shown to work synergistically on the activation of AMPK and promote optimal metabolic efficiency through the modulation of fat metabolism.
In a 2018 double-blind, placebo-controlled and randomized trial in 56 subjects with weight management challenges, participants were given 500 mg of a combination of polyphenolic extracts from Lippia citriodora L. and Hibiscus sabdarifa L. for two months and showed significant improvement in body weight, abdominal circumference, and body fat percentage. of blood pressure within the normal range, and improved heart rate. In addition, they experienced positive perception of overall health status. This polyphenolic combination has been shown to significantly increase metabolic function and support healthy weight by decreasing appetite biomarkers.
Green Coffee Bean Extract: Harnessing the Power of Chlorogenic Acid
Coffee is one of the most consumed drinks in the world. Green coffee beans are the beans from the Coffea fruit which have not yet been roasted. Coffee beans are naturally high in chlorogenic acid, and roasting them reduces the chlorogenic acid content. Chlorogenic acid, a polyphenol, is what holds the antioxidant properties and increases the overall health benefits of coffee,7 therefore, the effects and benefits of coffee are maximized in its natural and unroasted state. In addition, the green coffee bean extract in HiPhenolic has had the caffeine removed, so the benefits of the polyphenols can be maximized.
In another systemic review and meta-analysis study consisting of 637 participants, it was shown that green coffee bean extract consumption can help maintain optimal lipid markers, decrease body weight, and improve metabolism and glucose disposal. Finally, in a randomized clinical trial, 43 subjects consumed GCBE for eight weeks. After supplementation, all indices of cardiovascular health showed benefits.
Magnesium: An Essential Cofactor for Metabolic Processes
Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium is required for energy creation, which involves oxidative phosphorylation and glycolysis. It contributes to the development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm. The role of magnesium as an enzyme cofactor for activities that generate adenosine triphosphate (ATP) highlight its significance for maintaining energy levels and metabolic efficiency.
HiPhenolic: A Natural Alternative for Weight Management and Cardiovascular Health
Orthomolecular has recently presented a new supplement called HiPhenolic, designed to support weight management and cardiovascular health. It is a very pure, high concentration blend of polyphenols. HiPhenolic has scientifically demonstrated favorable shifts in metabolic targets such as maintaining blood pressure levels, improving satiation (i.e., fullness), and controlling appetite. HiPhenolic contains an extract blend of lemon verbena, hibiscus flower, green coffee bean, and magnesium.
In two, double-blind, placebo-controlled, and randomized studies, hibiscus and lemon verbena extracts have been shown to work synergistically on the activation of the energy sensor AMPK and promote optimal metabolic efficiency through the modulation of fat metabolism. In both studies, there were improvements in weight, body fat percentage, waist circumference, and maintenance of blood pressure and heart rate in normal ranges.
HiPhenolic offers these benefits in a concentrated, easy-to-take form, making it an excellent choice for those looking to achieve and maintain a healthy weight.
Scientific Insights on Polyphenols and Weight Loss
Research underscores the role of polyphenols in weight management. Key findings include:
- Fat oxidation: Polyphenols help the body use fat as an energy source.
- Appetite suppression: They may influence hormones like leptin and ghrelin, which regulate hunger and fullness.
- Blood sugar control: Stabilizing blood glucose levels helps reduce fat storage and prevents energy crashes.
- Gut health optimization: A healthy gut microbiome, supported by polyphenols, is linked to reduced fat accumulation and improved digestion.
HiPhenolic’s blend of polyphenols is carefully selected to maximize these weight loss benefits while promoting overall health.
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