USE OF CORTISOL 30 IN MANAGING THE CONDITIONS ASSOCIATED WITH METABOLIC SYNDROME

Homeopathic drug CORTISOL 30 contains Molecular imprints of the hormone cortisol. CORTISOL 30 is a great remedy for many ailments that are associated with Metabolic Syndrome.

Cortisol, also known as “stress hormone”, is a very important hormone produced mainly by the zona fasciculata of the adrenal cortex in the adrenal gland. It is produced in other tissues also in smaller quantities. It is released with a diurnal cycle and its release is increased in response to stress and low blood-glucose concentration. It functions to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It also decreases bone formation.

In general, cortisol stimulates the synthesis of ‘new’ glucose from non-carbohydrate sources. This is known as gluconeogenesis, mainly in the liver, and also in the kidneys and small intestine under certain circumstances. The net effect of cortisol is an increase in the concentration of glucose in the blood, further complemented by a decrease in the sensitivity of peripheral tissue to insulin, thus preventing this tissue from taking the glucose from the blood. Moreover, cortisol has a permissive effect on the actions of hormones that increase glucose production, such as glucagon and adrenaline.

Cortisol also plays an important, but indirect, role in liver and muscle glycogenolysis, the breaking down of glycogen to glucose.

Elevated levels of cortisol, if prolonged, can lead to proteolysis or breakdown of proteins, and muscle wasting. The reason for proteolysis is to provide the relevant tissue with ‘building blocks’ for gluconeogenesis. The effects of cortisol on lipid metabolism are more complicated since lipogenesis is observed in patients with chronic, raised circulating cortisol levels, although an acute increase in circulating cortisol promotes lipolysis. The usual explanation to account for this apparent discrepancy is that the raised blood glucose concentration through the action of cortisol will stimulate insulin release. Insulin stimulates lipogenesis, so this is an indirect consequence of the raised cortisol concentration in the blood but it will only occur over a longer time scale.

Metabolic syndrome or MetS is a cluster of common abnormalities arising from persistent high levels of cortisol in the blood. This Syndrome includes hyperglycemia, abdominal obesity, reduced high-density lipoprotein cholesterol levels, and elevated triglyceride and blood pressure. The common characteristics of MetS and hypercortisolemic conditions such as Cushing’s syndrome suggest that the pathogenesis of MetS and central obesity might involve prolonged and excessive exposure to cortisol.

Metabolic Syndrome was originally described as “insulin resistance syndrome”. The components of Metabolic Syndrome are associated with endothelial dysfunction and atherosclerosis and increase the risk for type 2 diabetes mellitus as well as vascular morbidity and mortality. It is estimated that about one fourth of the world’s adult population has Metabolic Syndrome.

Despite the increasing prevalence of MetS worldwide, there is still a lack of uniformly accepted diagnostic criteria, and there is controversy regarding the pathogenesis of MetS. Different organizations have provided their own definitions of MetS. MetS is diagnosed when three or more of the following parameters are present: waist circumference greater than 102 cm in men and greater than 88 cm in women, TG of at least 150 mg/dl (≥1.7 mmol/liter), HDL-C less than 40 mg/dl (<1.04 mmol/liter) in men and less than 50 mg/dl (<1.29 mmol/liter) in women, BP of at least 130/85 mm Hg, and fasting glucose of at least 110 mg/dl (≥6.1 mmol/liter).

It is unclear whether a single primary abnormality triggers a cascade of diverse events that lead to the manifestation of the components of MetS. Because the diagnostic features of MetS are shared by Cushing’s syndrome (CS), which results from endogenous or exogenous hypercortisolism, it was proposed that cortisol contributes to the pathogenesis of both states although only mild hypercortisolism occurs in MetS in contrast with CS. It was also suggested that inhibiting cortisol action could provide a novel therapeutic approach for MetS. Indeed, preliminary data suggest that circulating cortisol concentrations are higher in patients with MetS compared with healthy subjects, both in basal conditions and during dynamic stimulation. This difference is more evident in patients with MetS and hypertension or impaired glucose tolerance. Furthermore, weight loss normalizes cortisol levels and improves insulin resistance. Despite the fact that cortisol levels are within the normal range, there is evidence of increased activity of cortisol in the periphery and dysregulation of the hypothalamic-pituitary-adrenal axis. Differences between CS and MetS also need to be emphasized; in CS, once the tumor is removed, symptoms improve; in the MetS, weight loss reverses both hypercortisolism and phenotypic abnormalities.

Cortisol appears to play a role in adiposity in Metabolic Syndrome. Elevated serum uric acid levels are shared by MetS and CS Syndome. Increased exposure to cortisol contributes to increased fat accumulation in visceral deposits of fat. Increased cortisol serum overnight levels are also associated with insulin resistance.

Some studies showed elevated cortisol levels in situations such as work stress and unemployment. Others reported that chronic life stress results in subtle hyperactivity of HPA axis leading to intraabdominal adiposity and development of Metabolic Syndrome. Patients with Metabolic Syndrome appear to have higher urinary excretion of cortisol metabolites compared with healthy subjects. In vitro, cortisol appears to increase lipoprotein lipase or fat-storing enzyme levels in adipose tissue and particularly in visceral fat.

Experimental studies with cortisol inhibitors further support the role cortisol in the pathogenesis of Metabolic Syndrome, and might provide novel therapeutic approaches in patients with metabolic syndrome or obesity.

The components of Metabolic Syndrome are associated with endothelial dysfunction and atherosclerosis, and increase the risk for type 2 diabetes mellitus as well as vascular morbidity and mortality.

It was also suggested that inhibiting cortisol action could provide a novel therapeutic approach for Metabolic Syndrome. Indeed, preliminary data suggest that circulating cortisol concentrations are higher in patients with Metabolic Syndrome compared with healthy subjects, both in basal conditions and during dynamic stimulation. It was also proved that
reduction of body weight normalizes cortisol levels and improves insulin resistance.

Emerging data suggest that patients with MetS show hyperactivity of the hypothalamic-pituitary-adrenal axis, which leads to a state of “functional hypercortisolism.” The cause for this activation of the HPA axis remains uncertain but may be associated with chronic stress, which is associated with increased circulating cortisol levels and greater responsiveness of the HPA axis. Increased exposure to cortisol contributes to increased fat accumulation in visceral depots. Increased enzyme activity in adipose tissue and liver might contribute to the development of several features of the MetS.

Central abdominal obesity is one of the main components of the MetS. Cortisol appears to play a role in adiposity in MetS. Increased urinary cortisone/cortisol ratio in women with increased abdominal fat compared with those with peripheral fat distribution was observed by researchers, suggesting an increase in the peripheral metabolism of cortisol. Interestingly, cortisol clearance seems to be inversely correlated with insulin sensitivity, and this correlation is independent of body fat. It is also well documented that glucocorticoids promote the differentiation and proliferation of human adipocytes and that their receptors are more abundant in visceral than in subcutaneous adipose tissue. They also redistribute adiposity from peripheral to central depots, increase the size and number of fat cells, and activate lipolysis and the release of free fatty acids into the circulation.

Increased cortisol levels are also associated with insulin resistance. Higher cortisol concentrations were related to a reduced insulin secretion.

Hypertension is one of the most distinguishing features of Metabolic Syndrome as well as hypercortisolism. Many studies reported an association between cortisol and systolic and diastolic BP levels. This correlation might be attributed to the effect of stress, which is associated with the activation of the HPA axis and sympathetic nervous system. Indeed, patients with Metabolic Syndrome and hypertension appear to have higher urine levels of both cortisol and catecholamine metabolites than healthy individuals. A possible mechanism by which cortisol elevate BP seems to be an increased responsiveness to vasoconstrictors along with a decreased vasodilator production.

Obesity , a common finding in both CS and MetS, is also associated with hypertension. The possible underlying mechanisms include volume expansion, increased cardiac output and systemic vascular resistance, increased sodium reabsorption, increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, high leptin levels and concurrent leptin resistance.

Patients with Metabolic Syndrome as well as hypercortisolism frequently have elevated blood glucose levels. In patients with MetS, serum cortisol levels are significantly associated with fasting glucose concentration. The relationship between fasting hyperglycemia and cortisol is due to the glucocorticoid effects on hepatic gluconeogenesis and insulin secretion.

Metabolic Syndrome is associated with endothelial dysfunction that significantly predisposes to an increased risk for cardiovascular diseases. Endothelial dysfunction is also observed in patients with hypercortisolism. Hypercoagulability of blood is also present in MetS. Indeed, elevated fibrinogen and homocysteine concentrations have been observed in MetS patients compared with healthy controls. Hyperfibrinogenemia and homocysteinemia seem to be independent risk factors for cardiovascular diseases and venous thrombosis.

Elevated serum uric acid levels are seen both in Metabolic Syndrome and Hypercortisolism. High uric acid levels are regarded as a predictor of cardiac and overall mortality in patients with cardiovascular diseases or stroke. Elevated uric acid is also associated with higher risk of stroke in patients with or without cardiovascular disease. It was demonstrated that statin atorvastatin therapy is associated with a reduction in uric acid levels, along with an increase in estimated glomerular filtration rate in CKD patients with MetS. This effect on renal function is perhaps due to an amelioration of endothelial function and renal blood flow. On the other hand, patients with CS may have higher SUA and urinary uric acid excretion than healthy subjects.

Adipose tissue is recognized as an important endocrine organ that secretes a variety of bioactive peptides, termed adipokines. These adipokines exert multiple effects and play a key role in glucose and lipid metabolism, insulin sensitivity, BP, and angiogenesis. The major components of this family of adipokines are adiponectin and leptin, which are mainly produced by adipose tissue. Both these proteins exert an insulin-sensitizing effect through fatty-acid oxidation and, in addition, adiponectin is associated with antiatherogenic, antidiabetic, and antiinflammatory properties. In obesity, insulin resistance has been linked to leptin resistance, elevated leptin, and low adiponectin levels, which are associated with higher cardiovascular risk. Resistin is expressed in abdominal fat and is also associated with increased risk of central obesity-related diabetes. However, resistin may not be an “adipokine” because in humans it is mainly produced by monocytes, and its link with central obesity is debated. Excess adiposity leads to dysregulation of adipokine production, which in turn promotes a state of low-level systemic chronic inflammation predisposing to atherosclerosis.

Since molecular imprints of cortisol contained in cortisol 30 can act as artificial binding pockets for cortisol, it can antidote the adverse biological effects of excess cortisol circulated in the body. As such, cortisol 30 will be a powerful ingredient of Homeopathic Prescriptions in the management of all complaints associated with Metabolic Syndrome.

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