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Glycyrrhetinic Acid + Aminophylline

Recent advancements in the area of fat loss and improving body composition have led to the development of non-invasive treatment options that help reduce stubborn fat in different body areas. One of these non-surgical options is topical fat burners or fat burning creams that are directly applied to fatty areas. Once applied, they function to boost metabolism and stimulate fat loss.

Glycyrrhetinic acid and aminophylline are the most common ingredients found in fat loss creams. They work through a variety of complex mechanisms that help burn stored fat so that they can be used as energy. There’s a good deal of evidence demonstrating that application of these fat loss creams are safe and effective in reducing body fat percentage, body mass index (BMI), waist size, and overall weight. Therefore, fat loss creams containing both glycyrrhetinic acid and aminophylline can produce greater efficacy.

Overall Health Benefits of Glycyrrhetinic Acid + Aminophylline

  • Promotes Weight Loss [1-7]
  • Controls Blood Sugar Levels [8-12]
  • Fights Infection [14-29]
  • Fights Cancer [31-52]
  • Protects the Liver [53-63]
  • Combats Inflammatory Conditions [64-75]
  • Treats Lung Diseases/Injuries [76-94]
  • Improves Kidney Function [100-110]
  • Improves Cardiovascular Health [111-119]
  • Improves Cognitive Function [120-122]
  • Improves Sleep Quality [123-125]

Glycyrrhetinic Acid

Glycyrrhetinic acid, also known as glycyrrhizic acid, is one of the main bioactive compounds of licorice that is widely used in various foods as a natural sweetener. It’s also used to impart a flavor in a wide array of cosmetic and personal care products. As a therapeutic agent, glycyrrhetinic acid is also the main ingredient in various health formulations because of its anti-inflammatory, anti-ulcer, anti-allergic, anti-tumor, anti-diabetic, antioxidant, and liver-protective properties.

How does Glycyrrhetinic Acid Works?

Glycyrrhetinic acid is available in the alpha and beta forms. The alpha form is present in highest amounts in the stomach and liver, and it is thought that the dominance of glycyrrhetinic acid in these areas can produce anti-inflammatory effect. On the other hand, beta glycyrrhetinic acid exerts its beneficial effects by reducing lipid peroxidation and increasing antioxidant activity. Glycyrrhetinic acid also works to lower inflammatory substances and free radical levels in the body. Moreover, Glycyrrhetinic acid increases the levels of substances that stimulate gastric acid and mucus secretion in the digestive system.

Proven Health Benefits of Glycyrrhetinic Acid

The medical use of glycyrrhetinic acid dates back to ancient Egyptian times where they used licorice root as a cure-all concoction. This herb also became an important treatment strategy in Chinese medicine. Interestingly, modern clinical trials found that the glycyrrhetinic acid in licorice exerts potent therapeutic effect in a wide array of medical conditions.

Promotes Weight Loss

Glycyrrhetinic acid may benefit people who are overweight or obese. Studies show that this powerful compound has the ability to promote fat loss:

  • Cell studies found that glycyrrhetinic acid promotes fat breakdown and inhibits the production fat cells (adipocytes). [1]
  • In normal-weight subjects, glycyrrhetinic acid administration at 3.5 grams a day for 2 months reduced body fat mass. [2]
  • In healthy women (age range 20-33 years) with normal body mass index (BMI), application of a cream containing 2.5% glycyrrhetinic acid reduced the thickness of subcutaneous thigh fat. [3]
  • In obese animal models, glycyrrhetinic acid supplementation significantly lowered body weight, fat weight, and plasma lipids levels. [4]
  • In diet-induced obese rats, glycyrrhetinic acid supplementation decreased the weight of abdominal adipose tissue by regulating enzymatic activity involved in deposition and breakdown of fats. [5]
  • Glycyrrhetinic acid administration in obese rats promoted weight loss by reducing the levels of SREBP-1, a protein which stimulates fat production. [6]
  • In moderately overweight men and women, glycyrrhetinic acid administration at 900 mg/day for 8 weeks significantly decreased visceral fat area, body weight, and BMI. [7]

Controls Blood Sugar Levels

There is also increasing evidence that supports the anti-diabetic effect of glycyrrhetinic acid:

  • In mice, supplementation of an extract containing glycyrrhetinic acid improved glucose tolerance. [8]
  • In streptozotocin-diabetic rats, administration of 18beta-glycyrrhetinic acid was able to reduce hyperglycemia (high blood sugar levels). [9]
  • In adult male rats, 18beta-glycyrrhetinic acid administration was associated with increased antioxidants status and decreased lipid peroxidation, which reflects protective effect against diabetes risk. [10]
  • A cell study found that glycyrrhetinic acid has protective effects against high blood sugar levels and oxidative stress. [11]
  • In noninsulin-dependent diabetes mouse model, glycyrrhetinic acid supplementation improved tolerance to oral glucose loading 9 weeks after the beginning of test feeding. [12]
  • In rats with streptozotocin-induced diabetes, glycyrrhetinic acid treated hyperglycemia, hyperlipidemia and associated oxidative stress, suggesting that it may be a potential therapeutic agent for diabetes treatment. [13]

Fights Infection

Studies show that glycyrrhetinic acid also has immune-boosting properties that can help fight infection:

  • The antiviral activity of glycyrrhetinic acid can fight a wide array of virus such as vesicular stomatitis virus, influenza virus, herpes simplex virus, Newcastle disease virus, and vaccinia virus. [14-16]
  • Glycyrrhetinic acid exerts its antiviral activity by inhibiting the replication of viruses. [17]
  • In murine models of skin and soft tissue infection, 18β-Glycyrrhetinic acid inhibited the survival of Methicillin-resistant Staphylococcus aureus (MRSA). [18-19]
  • In rodents, 18β-Glycyrrhetinic acid significantly attenuated H. pylori-infected gastritis. [20]
  • In cell culture-produced hepatitis C virus, glycyrrhetinic acid reduced viral replication. [21-25]
  • Glycyrrhetinic acid also decreased hepatic and splenic parasite burden in mice infected with protozoa. [26]
  • A cell study also found that glycyrrhetinic acid has significant antiviral activity against rotavirus replication. [27]
  • In mice with burn injuries, glycyrrhetinic acid improved resistance to Pseudomonas aeruginosa wound infection. [28]
  • Glycyrrhetinic acid improved the resistance of mice to opportunistic infection of Candida albicans through modulation of T cell responses. [29]

Fights Cancer

Numerous studies also show that glycyrrhetinic acid has potent anti-cancer properties:

  • A study found that glycyrrhetinic acid has cytotoxic and anti-tumor properties. [30]
  • Glycyrrhetinic acid may help prevent breast cancer by inducing programmed cell death (apoptosis) of malignant cells. [31]
  • In human skin cancer cells exposed to ultraviolet radiation, glycyrrhetinic acid inhibited cell replication. [32]
  • 18 β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer by inhibiting proliferation and migration of malignant cells. [33]
  • In nine human cancer cell lines, glycyrrhetinic acid prevented cell replication through apoptosis. [34]
  • In human gastric cancer cells, 18β-glycyrrhetinic acid inhibited migration and invasion of malignant cells. [35]
  • In colon cancer cells, glycyrrhetinic acid induced apoptosis by activating caveolin-1 and Kruppel-like factor-4 proteins. [36]
  • In liver cancer cells, treatment with glycyrrhetinic acid induced apoptosis. [37]
  • Glycyrrhetinic acid exerts its anticancer effects by inhibiting the PTEN/PI3K/Akt signalling pathway. [38]
  • Glycyrrhetinic acid hydrogel treatment significantly inhibited liver tumor cell growth. [39]
  • Glycyrrhetinic acid exerts its anti-cancer effect by selectively targeting liver cancer cells. [40-41]
  • In hamsters, oral administration of glycyrrhetinic acid at a dose of 45 mg/kg body weight resulted in complete prevention of oral tumor formation and restoration of detoxification enzymes. [42]
  • Administration of glycyrrhetinic acid in tumor-bearing mice recovered body weight and rescued damage of liver and kidney. [43]
  • In human ovarian cancer cells, glycyrrhetinic acid caused cell death by inducing apoptosis. [44]
  • In a mouse model of gastric cell cancer, glycyrrhetinic acid inhibited gastric tumorigenesis through TLR2-accelerated energy metabolism. [45]
  • In leukemia cell line, treatment with glycyrrhetinic acid alone resulted in significant induction of apoptosis and loss of cell viability. [46-47]
  • In prostate cancer cell line, treatment with glycyrrhetinic acid reduced the rate of cell proliferation and production of prostate‐specific antigen (marker of prostate cancer). [48-49]
  • In non-small cell lung cancer, 18β-Glycyrrhetinic acid treatment suppressed cell proliferation. [50]
  • In mice bearing Krebs-2 carcinoma, glycyrrhetinic acid inhibited tumor growth and reduced tumor cell count. [51]
  • In mice with liver cancer, glycyrrhetinic acid treatment resulted in inhibition of tumor growth, reduction of tumor microvascular density, reduction of inflammatory markers, and improvement in the production of immune system cells. [52]

Protects the Liver

Evidence suggests that glycyrrhetinic acid has a protective effect on liver injury through its anti-inflammatory activity:

  • A study found that glycyrrhetinic acid could prevent drug-induced liver injury and disruption of bile acid metabolism in humans. [53]
  • Pretreatment of liver cells with glycyrrhetinic acid protects against aflatoxin-induced oxidative stress. [54]
  • In mice with liver injury caused by Propionibacterium acnes, glycyrrhetinic acid treatment inhibited the activation and proliferation of liver-infiltrating CD4(+) T cells and reduced the production of inflammatory substances such as interferon-gamma and tumor necrosis factor-alpha. [55]
  • In rats, low-dose glycyrrhetinic acid (50 mg/kg) exhibited a protective effect against Triptolide-induced liver injury through its anti-inflammatory, antioxidant, and antiapoptotic properties. [56-57]
  • In mice, ingestion of glycyrrhetinic acid prevented accumulation of fats in the liver by protecting mitochondria against oxidative stress. [58]
  • In rats, glycyrrhetinic acid treatment reduced endotoxin-induced acute liver injury after partial hepatectomy (surgical removal of a part of the liver). [59]
  • In rats, glycyrrhetinic acid treatment prevented liver injury by inhibiting the production of proteins involved in liver scarring. [60-62]
  • In mice, glycyrrhetinic acid attenuated acetaminophen-induced liver injury. [63]

Combats Inflammatory Conditions

Numerous studies suggest that the potent anti-inflammatory properties of glycyrrhetinic acid allow it to treat a multitude of inflammatory conditions:

  • A study found that glycyrrhetinic acid contains substances that are very effective in suppressing inflammatory markers such as nuclear factor-κB (NF-κB) and 12-O-tetradecanoylphorbol-13-acetate. [64]
  • In healthy volunteers and in patients with chronic moderate/severe blepharitis (eyelid inflammation), administration of glycyrrhetinic acid ophthalmic solution showed good clinical anti-inflammatory activity. [65]
  • In mice with arthritis, glycyrrhetinic acid treatment reduced symptoms. [66]
  • In mice with heart muscle inflammation (myocarditis), glycyrrhetinic acid treatment reduced the degree of swelling. [67]
  • In contact hypersensitivity model mice, glycyrrhetinic acid administration resulted in an anti-allergic effect as evidenced by reduced skin inflammation. [68]
  • In mice with spinal cord compression injury, glycyrrhetinic acid administration reduced secondary inflammatory process. [69-70]
  • In mice with allergic rhinitis, glycyrrhetinic acid treatment was associated with enhanced antioxidant status and improved immunity activities in the blood and nasal mucosa. [71]
  • In mice with nerve inflammation, glycyrrhetinic acid treatment inhibited pro-inflammatory mediators in the brain tissue. [72]
  • Glycyrrhetinic acid treatment also alleviated asthmatic features in mice. [73-74]
  • In rats, glycyrrhetinic acid treatment ameliorated intestinal inflammation. [75]

Aminophylline

Aminophylline is known as a potent bronchodilator medicine. This means that it opens the airways of the lungs by relaxing the smooth muscles. Because of this effect, aminophylline is prescribed for the treatment of wheezing, breathing difficulties, asthma, emphysema, chronic bronchitis, acute bronchospasm, and other respiratory disorders.

How Aminophylline Works

Aminophylline achieves its therapeutic effect through the following mechanisms:

  • It relaxes the smooth muscles of the lungs to allow more air in.
  • It reduces inflammation by decreasing the sensitivity of the lungs to allergens.
  • It draws more air into the lungs by increasing the contractions of the diaphragm.

Proven Health Benefits of Aminophylline

An overwhelming body of clinical studies found that this potent bronchodilator can help improve pulmonary, cardiovascular, renal, and cognitive health without any adverse side effects.

Treats Lung Diseases/Injuries

Aminophylline is often prescribed for a multitude of lung conditions. There’s robust evidence supporting the benefits of this drug on pulmonary health:

  • In adults hospitalized for acute asthma, treatment with aminophylline was associated with fewer nebulizations of albuterol and lower rate of exacerbations. [76-77]
  • In patients with acute severe asthma, aminophylline infusions improved lung function and symptoms. [78]
  • In patients with respiratory fatigue, aminophylline administration reduced the risk of intubation. [79]
  • In patients with partially reversible severe airway obstruction, intravenous injections of aminophylline (250 mg) was associated with consistent improvement in the mean forced expiratory volume, a measure of how much air a person can exhale during a forced breath. [80]
  • In patients with acute exacerbation of asthma or chronic obstructive pulmonary disease, aminophylline infusion decreased hospital admissions. [81]
  • In patients with chronic obstructive pulmonary disease (COPD), aminophylline administration improved symptoms by reducing the levels of inflammatory markers. [82]
  • In patients with COPD, oral administration of aminophylline (400 mg) increased mean forced expiratory volume and forced vital capacity. [83-84]
  • In patients with COPD, low dose aminophylline increased the efficacy of inhaled corticosteroids by reducing the incidence of exacerbations. [85-86]
  • In patients undergoing valve replacement, aminophylline administration had anti-inflammatory effect and improved pulmonary oxygenation. [87]
  • Prolonged use of maintenance aminophylline therapy in COPD patients increased diaphragmatic contractility and endurance and improved several aspects of mucociliary function (defense mechanism of the lung). [88]
  • Administration of long-acting 225-mg aminophylline compounds twice daily for 8 weeks improved peak expiratory flow rate in younger COPD patients and relieved symptoms of chest tightness in older COPD patients. [89]
  • Aminophylline administration in COPD patients enhanced the anti-inflammatory effect of corticosteroids. [90]
  • In patients with chronic bronchitis and moderate to severe chronic obstruction to airflow, aminophylline administration at 800 mg daily led to an improvement in peripheral ventilation. [91]
  • In normal young adults, aminophylline prevented alterations in breathing pattern. [92]
  • In patients with mild asthma, low-dose aminophylline led to a significant reduction in mean sputum eosinophils (a measure of allergic reaction). [93]
  • In patients with atopic asthma, aminophylline administration at 200 mg every 12 hours reduced airway inflammatory response to allergen inhalation. [94]

Promotes Weight Loss

A good deal of evidence also suggests that aminophylline can improve body composition by reducing body fat percentage and promoting lean muscle mass:

  • In overweight men and women, application of 0.5% aminophylline cream to the waist twice a day was associated with significant reduction in waist circumference. [95]
  • In participants with fat deposits on their thighs, application of aminophylline lotion significantly reduced thigh circumference, thigh skinfold thickness, and thigh fat mass. [96]
  • Twelve weeks of 0.5% aminophylline cream administration significantly decreased waist-to-hip ratios in overweight female participants compared to male participants. [97]
  • A study found that aminophylline promotes fat loss by inducing breakdown of fat cells. [98]
  • In women with lower body fat distribution, application of aminophylline cream significantly reduced thigh fat. [99]

Improves Kidney Function

Numerous studies also support the beneficial effects of aminophylline on kidney function and related diseases:

  • In patients with acute kidney injury, aminophylline therapy significantly improved renal excretory function as evidenced by increased urine output. [100]
  • In neonates and children, a single dose of aminophylline prevented acute kidney injury and severe renal dysfunction. [101]
  • In patients with renal colic, a type of pain associated with kidney stones, administration of 375 mg of aminophylline reduced pain by 24% to 39%. [102]
  • Aminophylline administration also reduced the prevalence of acute kidney injury after cardiac surgery in pediatric patients. [103]
  • In patients with acute renal failure, aminophylline administration was associated with an improvement in renal function indices. [104]
  • In premature infants, aminophylline improved kidney function by enhancing urinary calcium and uric acid excretion. [105]
  • Intravenous aminophylline administration in human subjects was associated with a 52% reduction in the risk of contrast-induced acute kidney injury. [106-107]
  • In intensive care unit patients with acute kidney injury, aminophylline infusion at 5 mg/kg increased urine output. [108]
  • In patients admitted to a general intensive care unit following major surgery, aminophylline administration increased blood flow to the kidneys and improved glomerular filtration rate (filtering ability of the kidneys). [109]
  • In patients undergoing chemotherapy, aminophylline administration prevented the deterioration of glomerular filtration rate. [110]

Improves Cardiovascular Health

There’s also increasing evidence showing that aminophylline can help improve heart health:

  • A study found that aminophylline has the ability to restore normal heart rhythm, thus reducing one’s risk for heart failure and other fatal heart conditions. [111]
  • In COPD patients, oral and intravenous administration of aminophylline enhanced both right and left heart systolic pump function. [112-113]
  • In human subjects, aminophylline administration increased heart rate and cardiac output via stimulation of the sympathetic nervous system. [114-115]
  • In COPD patients, aminophylline administration improved global cardiac function and reduced dyspnea. [116-117]
  • In animal models, aminophylline improved left ventricular contractility and heart rate variability (interval between heartbeats). [118-119]

Improves Cognitive Function

Studies also support that aminophylline has cognitive-boosting properties:

  • Administration of escalating doses of aminophylline in patients who received sevoflurane anesthesia accelerated postoperative cognitive recovery. [120]
  • In school-aged patients, aminophylline administration led to greater improvement on all tests of memory and concentration. [121]
  • In patients with brain damage, aminophylline administration improved cognitive function by increasing oxygen levels within the brain. [122]

Improves Sleep Quality

Aminophylline administration can also help treat sleeping difficulties associated with various medical conditions:

  • In healthy male volunteers, aminophylline administration normalized high-altitude sleep-disordered breathing. [123]
  • In patients with obstructive sleep apnea syndrome, aminophylline improved impaired breathing and increased NREM (non-rapid eye movement) sleep or dreamless sleep. [124]
  • In patients with sleeping difficulties related to acute mountain sickness, aminophylline administration improved sleep efficiency without any adverse effects. [125]

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