Abstract
Propolis, a bee product with a rich history spanning millennia, has garnered attention for its potential role in body weight management. Its chemical composition and biological activity, influenced by geographical location, have been extensively studied. Propolis polyphenols can potentially induce thermogenesis in brown and beige fat tissue via the uncoupled protein-1 and creatinine kinase metabolic pathways, potentially raising overall energy expenditure, which might lead to body weight management. This review delves into the structural and biological properties of propolis, providing insights into its promising potential strategies in body weight management.
Introduction: The Buzz About Propolis
Often referred to as "bee glue," propolis has been utilized since ancient times by civilizations such as the Greeks, Romans, and Egyptians. Honey bees produce propolis from various plant parts. It typically consists of approximately 50% resin, 30% beeswax, 10% essential/aromatic oils, 5% pollen, and 5% other components. Propolis varies in color (green, red, or brown) depending on its origin.
The chemical composition of propolis, first explored in the early twentieth century, reveals a complex mixture of over 300 bioactive elements, particularly phenolic compounds. However, the chemical makeup and biological activity of propolis formulations can vary significantly based on geographical region, climate, and plant source. This variation leads to differences in the composition of propolis from different regions, such as Brazilian, Chinese, and Anatolian propolis. For example, the total flavonoid content of Anatolian propolis can range from 16.13 to 199.69 mg/g. Research on propolis from different locations in Turkey has identified phenolic compounds like catechins, caffeic acid, chlorogenic acid, myristine, apigenin, and galangin.
While propolis has gained recognition for its immune-boosting properties, it also exhibits antiviral, anti-inflammatory, and antioxidant activities due to its polyphenol content, including catechins, caffeic acid, Artepillin C, quercetin, and chlorogenic acid. These phenolic components have been linked to energy expenditure and lower body mass index (BMI). Polyphenols may influence body weight management by activating oxidation, inducing satiety, increasing energy expenditure, promoting adipocyte death, and stimulating lipolysis.
The Obesity Epidemic and the Role of Energy Balance
Obesity, resulting from a malfunction in body weight regulation, is a growing public health concern. It arises from various factors and is significant due to its associated comorbidities and increased risk of mortality. The current rise in consumption of high-energy-dense foods and sedentary lifestyles contributes to an imbalance between energy intake and expenditure, leading to a positive energy balance and the development of obesity.
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Energy intake is derived from the oxidation of macronutrients in consumed foods, while the energy consumed during this process is known as the thermic effect. Energy expenditure comprises basal metabolic rate, thermic effect, and physical activity. Maintaining a balance between energy intake and expenditure is crucial for obesity prevention and treatment.
Adipose tissue plays a vital role in maintaining this balance. White adipose tissue stores energy during positive energy balance, while brown adipose tissue transfers energy through uncoupled respiration, mediated by uncoupled protein-1 (UCP1). Browning occurs when white adipose tissue acquires brown adipose tissue characteristics through food consumption and environmental factors like temperature change, physical exercise, and peroxisome proliferator-activated receptor gamma (PPAR-). The increase in UCP-1 mRNA concentrations during white adipose tissue browning triggers thermogenesis in the development of beige adipose tissue, thereby increasing energy expenditure.
In addition to UCP-1, the creatinine kinase pathway has been identified as another mechanism for stimulating thermogenesis in brown and beige adipose tissue. Similar to the UCP-1 pathway, increased creatine kinase enzyme expression in response to various environmental conditions catalyzes the conversion of ATP and creatine to phosphocreatine, dissipating energy as heat. Increased concentrations of brown and beige adipose tissue may enhance energy expenditure, counteracting obesity and its metabolic consequences. Nutrients that promote browning of white adipose tissue may offer potential for obesity prevention and treatment by increasing energy expenditure. Certain nutrients, lipid metabolism, and interaction with adipose tissue can exert anti-obesogenic effects by influencing various enzyme expressions. Propolis, a natural apitherapy product containing these chemicals, emerges as a potential agent.
Metabolic Pathways of Weight Management: How Propolis Might Help
Body weight management is crucial for preventing and treating obesity. This process involves multiple metabolic pathways, with UCP-1 playing a key role.
UCP-1 and Thermogenesis
UCP-1, a mitochondrial membrane protein, is essential for thermogenesis, particularly in brown adipose tissue (BAT). The sympathetic nervous system regulates UCP-1 expression through mechanisms that induce noradrenaline. Noradrenaline binds to the adipocyte plasma membrane's 3-adrenergic receptor (3AR), increasing intracellular cyclic adenosine monophosphate (cAMP) levels, cAMP-dependent protein kinase (PKA), and cAMP-sensitive element-binding protein (CREB) activation. PKA activation increases hormone-sensitive lipase (HSL) production, promoting lipolysis, and the resulting free fatty acids serve as substrates for BAT thermogenesis.
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UCP-1 is primarily generated in BAT through the activation or overexpression of biomolecules like 3AR, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1), and PPAR-γ. UCP-1 expression has also been observed in white adipose tissue of rats in response to various stimuli and in beige adipocytes produced in white adipose tissue (WAT). When environmental factors such as cold or food components activate UCP1, ATP phosphorylation is halted, enhancing respiratory chain activity and generating heat, which is dispersed throughout the body via circulation. Thus, UCP-1 expression helps limit body fat storage by increasing energy expenditure. Nutritional components can aid in body weight management by increasing thermogenesis and total energy expenditure through UCP-1 activation and/or contributing to browning in adipocytes.
The amount of brown adipose tissue expressing UCP-1 decreases with age. Emerging research suggests that specific dietary interventions may promote the development of beige adipocytes within white adipose tissue, offering potential avenues for addressing obesity. Studies have indicated a correlation between certain dietary components and increased formation of beige adipocytes.
The Creatinine Cycle
In addition to the UCP-1 pathway, the creatinine cycle exists in brown and beige adipocytes to release chemical energy as heat without mechanical or chemical activity, increasing energy expenditure through thermogenesis. Creatine kinases catalyze the reversible transfer of a phosphoryl group from ATP to creatine. Encoded by four different genes with tissue-specific expression and variable subcellular localization, creatine kinases located near ATPs created by selective oxidative phosphorylation release energy through thermogenesis by forming phosphocreatine with phosphorus acquired from ATP, particularly in brown and beige adipose tissue mitochondria. The phosphatase enzyme also degrades phosphocreatine and transforms it into creatinine to produce new ADPs. While this transformation occurs in many tissues, the ratio of mitochondrial creatinine kinase to the total cellular creatinine kinase pool is higher in brown adipocytes, and intracellular activation of the creatine kinase enzyme in these tissues can be regulated by a single isoenzyme. Therefore, the creatinine cycle in brown and beige tissue is critical for thermogenesis and energy expenditure.
Other Pathways
Besides UCP-1 and cretin kinase pathways, lipolysis induction, lipogenesis, and adipogenesis inhibition processes contribute to weight management. Lipolysis is induced by increased cAMP levels and HSL activity. Reduced fatty acid synthetase and acetyl-CoA carboxylase gene expression levels inhibit lipogenesis, while decreasing PPAR-γ and CCAAT/enhancing binding protein (C/EBP) gene expression levels inhibit adipogenesis.
Propolis Polyphenols and Their Anti-Obesogenic Potential
Propolis contains various polyphenols that may contribute to its potential anti-obesogenic effects.
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Artepillin C (ArtC)
Artepillin C (ArtC), a cinnamic acid derivative, is a key component of propolis due to its high phenolic content. ArtC, particularly in Brazilian propolis, possesses antioxidant, anti-inflammatory, anti-diabetic, neuroprotective, gastroprotective, anticancer, and immunomodulatory properties. It has also been shown to enhance beige adipose tissue and thermogenesis. ArtC induces beige adipocytes in murine C3H10T1/2 cells and primary inguinal WAT (iWAT) adipocytes. Oral administration of ArtC at 10 mg/kg for 4 weeks promotes beige adipocyte generation in mouse iWAT through increased UCP-1 expression. Artepillin C has been shown to stimulate thermogenesis by acting as a PPAR-agonist, as well as enhancing UCP-1 expression and creatinine metabolism. In vivo investigations have revealed that propolis possesses anti-obesogenic properties. Brazilian propolis consumption (100 mg/kg for 12 weeks) has been demonstrated to diminish visceral adipose tissue mass in obese mice. Propolis interventions at various doses and times (50 mg/kg-10 days; 20 mg/kg-12 weeks) have dramatically reduced body weight gain and accumulation of body fat in mice fed a high-fat diet. These findings suggest that several phenols present in propolis may induce BAT thermogenesis, sympathetic nervous system stimulation, browning in WAT, AMPK activation, and mitochondrial biogenesis.
Quercetin
Quercetin, one of the most abundant dietary polyphenols, stimulates AMP-activated protein kinase (AMPK), promotes UCP-1, and enhances energy expenditure. Quercetin use (100 mg/day for 12 weeks) has reduced total body fat and BMI values in overweight/obese individuals. Another study found that quercetin (150 mg/day) significantly reduced waist circumference in obese people. The decrease in body weight and body fat percentages of obese patients following onion extract consumption was associated with quercetin. The anti-obesogenic activity of quercetin is linked to BAT thermogenesis, browning in WAT, and mitochondrial biogenesis pathways.
Chlorogenic Acid
Chlorogenic acid, a polyphenol derived from the esterification of caffeic acid with quinic acid, has also demonstrated potential benefits. In an in vivo study, chlorogenic acid administration (0.21 mg/day decaffeinated phenol-chlorogenic acid, 2.3 g/day chromium dinicocysteinate, and 0.1 mg/day caffeine) resulted in body weight loss with increased energy expenditure in obese mice. Another in vivo investigation showed that chlorogenic acid (100 mg/kg/day for 8 weeks) reduced visceral fat accumulation, abdominal circumference, and body weight in rats fed a high-fat high-carbohydrate diet (16 weeks). A clinical investigation found that consuming beverages containing chlorogenic acid (600 mg/day chlorogenic acid-5 days) improved fatty acid oxidation in individuals with normal body weight. Another study showed that oxygen consumption, fat use, and anaerobic threshold during exercise increased as a result of consumption of chlorogenic acid-containing beverages (359 mg/day chlorogenic acid-7 days) in individuals with normal body weight. A case (369 mg/day) control (35 mg/day) study conducted on overweight individuals and examining the effects of 12 weeks of chlorogenic acid given with coffee, it was found that body weight, abdominal fat area, visceral fat area, and waist circumference were significantly reduced in the intervention group compared to the control group. Another study applying the same dose (369 mg/day for 7 days) found that it increased post-prandial fat utilization and energy expenditure. These findings may be related to a decrease in the expression of enzymes involved in fatty acid synthesis and the production of malonyl CoA.
Caveats and Considerations
While the research suggests potential benefits of propolis for weight management, it's important to acknowledge certain caveats and considerations.
Limited Human Studies
Many of the studies investigating the effects of propolis and its components on weight management have been conducted in animals or in vitro. Further research, particularly well-designed human clinical trials, is needed to confirm these findings and determine the optimal dosage and duration of propolis supplementation for weight loss.
Variability in Propolis Composition
The chemical composition of propolis varies significantly depending on its geographical origin, plant source, and bee species. This variability can affect the efficacy and safety of propolis products. It's crucial to choose propolis supplements from reputable manufacturers that provide detailed information about the composition and standardization of their products.
Potential Side Effects and Interactions
Propolis may cause allergic reactions in some individuals, especially those with bee or pollen allergies. It can also interact with certain medications, such as blood thinners and CYP450 substrates. Pregnant or breastfeeding women should avoid using propolis due to a lack of safety data. It's essential to consult with a healthcare professional before taking propolis supplements, especially if you have any underlying health conditions or are taking medications.
Not a Magic Bullet
Propolis should not be considered a magic bullet for weight loss. It's most likely to be effective when combined with a healthy diet, regular exercise, and other lifestyle modifications. A holistic approach to weight management is essential for achieving sustainable results.
Propolis: More Than Just Bee Glue?
Beyond its potential weight management benefits, propolis has been traditionally used for various purposes due to its purported antibacterial, antifungal, and anti-inflammatory properties.
Traditional Uses
Historically, propolis has been used to:
- Heal wounds
- Prevent infections
- Ease symptoms of cancer treatments
However, modern science doesn't fully support all of these claims, and further research is needed to validate these traditional uses.
Potential Benefits
Some studies suggest that propolis may have potential benefits for:
- Managing diabetes: Propolis could have a positive effect on people with Type 2 diabetes, potentially reducing hemoglobin A1C and fasting blood sugar levels. However, other evidence-based treatments are available for diabetes management.
- Healing cold sores: Propolis may speed up the healing of cold sores caused by oral herpes (HSV-1). However, stronger antiviral medications are available for this purpose.
- Relieving oral mucositis: Propolis may help lessen the effects of oral mucositis, a common and painful side effect of chemotherapy.
Risks and Side Effects
Despite its potential benefits, propolis is not risk-free. It can cause allergic reactions, especially in people with bee or pollen allergies. It can also interact with certain medications and may not be safe for people with certain health conditions.
Who Should Avoid Propolis?
Propolis poses an increased risk to people with these conditions:
- Bee allergies: Because propolis is made by bees, it’s not safe for people who are allergic to bees or bee byproducts. In some cases, taking propolis has led to life-threatening allergic reactions.
- Pollen allergies: If you have allergic rhinitis (hay fever) driven by an allergy to pollen or other forms of pollen, propolis may increase your risk for allergic reactions.
- Asthma: Allergic reactions from propolis can trigger your asthma.
- Eczema: Propolis may cause allergic reactions to the skin, especially in people with eczema.
- Bleeding disorders: Propolis can slow down the blood clotting process, which can increase your risk of bleeding.
- Pregnancy: There’s not enough information to show where propolis is safe during pregnancy, so it’s best to avoid it.
Potential Interactions with Medications
Like other vitamins and supplements, propolis can negatively interact with other medications that you take, making them less effective and even raising your risk for certain conditions.
- Blood thinners: Because propolis can slow the blood clotting process, it may interfere with anticoagulants (including warfarin) that you take to prevent and treat blood clots.
- CYP450 substrates: Propolis can affect your liver’s ability to break down certain medications, including many types of statins, immunosuppressants, antidepressants and beta-blockers.
- Other supplements: Taking propolis with other supplements that slow blood clotting, like garlic, ginger and ginkgo, can further raise your risk of bleeding.
Because propolis can make it harder for your blood to clot, it’s not safe to take before surgery.
Regulation and Quality Control
The Food and Drug Administration (FDA) does not regulate supplements, including propolis, in the same way as medications. This means there's no guarantee of the purity, potency, or safety of propolis products. Contamination with heavy metals, insect fragments, mites, and rodent hair has been reported in some propolis samples.