Aldosterone in treatment of obesity is an emerging area of research exploring whether targeting this hormone might offer metabolic benefits. Aldosterone, a mineralocorticoid hormone produced by the adrenal glands, primarily regulates sodium balance and blood pressure. However, recent studies suggest it may also influence fat metabolism, insulin sensitivity, and inflammation—factors relevant to obesity. Whilst mineralocorticoid receptor antagonists (MRAs) such as spironolactone are licensed in the UK for heart failure and hypertension, they are not approved for obesity treatment. Current evidence shows only modest metabolic effects, and significant safety concerns limit their use outside approved indications.

Understanding Aldosterone and Its Role in Weight Regulation

Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex, primarily known for its role in regulating sodium and potassium balance, blood pressure, and fluid homeostasis. Secreted in response to the renin-angiotensin-aldosterone system (RAAS), aldosterone acts on the distal tubules and collecting ducts of the kidneys to promote sodium reabsorption and potassium excretion. This fundamental physiological function has traditionally positioned aldosterone as a key player in cardiovascular and renal health rather than metabolic regulation.

However, emerging research over the past two decades has revealed that aldosterone may have broader metabolic effects beyond its classical renal actions. Laboratory and observational studies suggest that aldosterone may influence adipocyte function, insulin sensitivity, and inflammatory pathways—all of which are relevant to obesity and metabolic syndrome. The hormone appears to be associated with adipogenesis (fat cell formation) and may contribute to insulin resistance through various mechanisms, including oxidative stress and endothelial dysfunction, though the precise causal relationships remain under investigation.

Key physiological actions of aldosterone include:

• Sodium retention and potassium excretion in the kidneys

• Regulation of blood volume and blood pressure

• Modulation of inflammatory responses in various tissues

• Potential effects on adipose tissue metabolism and insulin signalling

Whilst aldosterone is not primarily considered an obesity hormone like leptin or insulin, its dysregulation in conditions such as primary aldosteronism (Conn's syndrome) has been observed alongside increased visceral adiposity and metabolic disturbances in some studies. Understanding these associations has prompted investigation into whether targeting aldosterone pathways might offer therapeutic benefits for obesity management, though this remains an area of active research rather than established clinical practice.

When to suspect primary aldosteronism:

Clinicians may consider investigating for primary aldosteronism in patients with resistant hypertension (blood pressure uncontrolled on three or more antihypertensive drugs), spontaneous or diuretic-induced hypokalaemia, hypertension with an adrenal incidentaloma, or hypertension at a young age (under 40 years). NICE guideline NG136 (Hypertension in adults: diagnosis and management) and the British and Irish Hypertension Society provide UK pathways for case detection and management of secondary causes of hypertension, including primary aldosteronism.

How Aldosterone Affects Obesity and Metabolic Health

The relationship between aldosterone and obesity appears to be bidirectional and complex. Observational studies have demonstrated that individuals with obesity often exhibit elevated aldosterone levels, even in the absence of primary aldosteronism. Adipose tissue itself may contribute to this elevation, as fat cells produce factors that stimulate aldosterone secretion, creating a potential feedback loop. However, confounding factors such as RAAS activation in obesity, dietary salt intake, and comorbid hypertension make it difficult to establish direct causality.

Aldosterone may influence metabolic health through several proposed mechanisms. The hormone promotes inflammation in adipose tissue by activating mineralocorticoid receptors, which are present not only in the kidneys but also in fat cells, vascular endothelium, and other tissues. This activation triggers oxidative stress and inflammatory cascades that may impair insulin signalling, potentially contributing to the development of type 2 diabetes. Additionally, aldosterone-mediated sodium retention may increase blood pressure, a common comorbidity in obesity that further compounds cardiovascular risk.

Observed associations with elevated aldosterone include:

• Increased visceral fat accumulation

• Impaired glucose metabolism and insulin resistance

• Enhanced inflammatory markers (such as C-reactive protein)

• Endothelial dysfunction affecting vascular health

• Increased risk of metabolic syndrome components

Research has also identified that aldosterone may interfere with adiponectin, a beneficial hormone secreted by fat tissue that normally improves insulin sensitivity and has anti-inflammatory properties. Lower adiponectin levels in the context of elevated aldosterone could represent another pathway linking this hormone to adverse metabolic outcomes. However, it is important to note that whilst these associations exist in observational data, establishing causality remains challenging, and there is no confirmed evidence that aldosterone directly causes obesity in individuals without underlying endocrine disorders. These associations may reflect complex interactions between hormonal systems, lifestyle factors, and genetic predisposition.

Clinical Evidence for Aldosterone-Targeted Treatments

The concept of targeting aldosterone for obesity treatment has emerged primarily from studies using mineralocorticoid receptor antagonists (MRAs), medications traditionally prescribed for heart failure and hypertension. Spironolactone and eplerenone are the two main MRAs available in the UK, both licensed by the MHRA for cardiovascular indications. According to the British National Formulary (BNF) and UK Summaries of Product Characteristics (SmPCs), spironolactone is licensed for heart failure, resistant hypertension, and primary aldosteronism, whilst eplerenone (Inspra) is licensed for heart failure post-myocardial infarction and chronic heart failure. Neither is licensed for obesity treatment.

Several small-scale clinical trials and observational studies have explored whether MRAs might offer metabolic benefits in obesity. Some research has suggested modest improvements in insulin sensitivity, reductions in inflammatory markers, and small decreases in body weight or fat mass (typically 1–2 kg) in patients treated with these agents. However, these studies were not primarily designed to assess weight loss as an outcome, often enrolled patients with comorbidities such as hypertension or heart failure, and the observed effects have generally been modest and inconsistent.

Current evidence limitations include:

• Most studies are small, short-term, or observational in nature

• Weight loss effects, when observed, are typically minimal (1–2 kg)

• Research has focused on patients with comorbidities rather than obesity alone

• No large-scale randomised controlled trials specifically for obesity treatment

• Mechanisms remain incompletely understood

It is crucial to emphasise that MRAs are not licensed or recommended for obesity treatment in the UK. NICE guidance does not include aldosterone antagonism as a strategy for weight management. The existing evidence, whilst intriguing from a research perspective, does not support the use of these medications solely for obesity. Any off-label use would require careful clinical justification, documented informed consent, and rigorous monitoring in accordance with UK Good Clinical Practice and local governance frameworks. The potential benefits must be weighed against known risks and side effects, which are significant.

Safety Considerations and Side Effects

Mineralocorticoid receptor antagonists carry significant safety considerations that limit their use outside approved indications. The most serious risk associated with MRAs is hyperkalaemia (elevated potassium levels), which can be life-threatening if severe. Because aldosterone normally promotes potassium excretion, blocking its action leads to potassium retention. This risk is particularly elevated in patients with chronic kidney disease, those taking other medications that raise potassium, or individuals with reduced renal function—factors that may be present in some people with obesity.

Spironolactone, the more commonly prescribed MRA in the UK, has additional side effects related to its non-selective action on other steroid hormone receptors. These include gynaecomastia (breast tissue development in men), breast tenderness, menstrual irregularities in women, and reduced libido. Eplerenone is more selective for the mineralocorticoid receptor and causes fewer hormonal side effects, but it is more expensive and still carries the hyperkalaemia risk.

Important safety considerations include:

• Regular monitoring of serum potassium and renal function is essential (baseline urea and electrolytes; check potassium and eGFR at approximately 1 week, then monthly for the first 3 months, then periodically; dose adjustment or withholding if potassium rises)

• Contraindicated in patients with severe renal impairment (typically eGFR < 30 mL/min/1.73 m²), pre-existing hyperkalaemia, or Addison's disease

• Eplerenone is contraindicated with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, clarithromycin)

• High-risk drug interactions include trimethoprim/co-trimoxazole, potassium-sparing diuretics, potassium supplements or salt substitutes, ACE inhibitors, ARBs, NSAIDs, heparin/LMWH, and aliskiren (dual RAAS blockade)

• Hormonal side effects may affect quality of life and treatment adherence

• Risk of hypotension, particularly when combined with other blood pressure medications

• Spironolactone has anti-androgenic effects and should be avoided in pregnancy and breastfeeding; women of childbearing potential should discuss contraception with their healthcare provider

Patients should never use MRAs for weight management without medical supervision. Anyone prescribed these medications for approved indications should have baseline blood tests and regular monitoring as recommended by their GP or specialist, in line with UK SmPC guidance and BNF recommendations. If experiencing symptoms such as muscle weakness, irregular heartbeat, palpitations, severe dizziness, syncope, chest pain, or unusual fatigue—which may indicate electrolyte disturbances or other serious adverse effects—patients should contact their healthcare provider promptly. In an emergency (e.g., severe palpitations, chest pain, collapse), dial 999; for urgent advice, contact NHS 111.

Patients and healthcare professionals are encouraged to report suspected adverse drug reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

Current NHS Guidelines on Hormonal Approaches to Obesity

NICE guideline CG189 (Obesity: identification, assessment and management) and quality standard QS127 provide comprehensive recommendations for obesity assessment and treatment but do not include aldosterone-targeted therapies. The NHS approach to obesity emphasises lifestyle interventions as first-line treatment, including dietary modification, increased physical activity, and behavioural support. When pharmacological intervention is appropriate, NICE recommends specific licensed medications. Orlistat (a lipase inhibitor) may be considered in primary care for eligible patients. More recently, NICE technology appraisals have recommended GLP-1 receptor agonists for weight management in specialist services: liraglutide 3 mg (TA664) and semaglutide 2.4 mg (TA875) are available for managing overweight and obesity in adults meeting specific criteria, typically within Tier 3 specialist weight management services. Access and eligibility criteria may vary by Integrated Care Board.

Hormonal approaches to obesity within NHS practice are limited to addressing identified endocrine disorders that contribute to weight gain. These include hypothyroidism, Cushing's syndrome, and polycystic ovary syndrome (PCOS), where treating the underlying hormonal imbalance may facilitate weight management. Primary aldosteronism, when diagnosed, is treated with MRAs or surgery, and patients may experience some weight reduction as a secondary benefit, but this is not the primary therapeutic goal. Routine aldosterone testing is not part of standard obesity assessment and should only be undertaken when clinical features suggest secondary hypertension or primary aldosteronism (as outlined in NICE NG136).

NHS-recommended obesity management pathway:

• Initial assessment including BMI calculation (with ethnicity-adjusted thresholds where appropriate: lower BMI thresholds apply for adults of South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean family origin), comorbidity screening, and identification of underlying causes

• Tier 1–2 interventions: lifestyle advice, dietary counselling, and physical activity programmes delivered in primary care or community settings

• Tier 3 services: specialist multidisciplinary weight management programmes for patients with complex needs or significant comorbidities

• Pharmacotherapy: only licensed medications (orlistat in primary care; liraglutide 3 mg or semaglutide 2.4 mg in specialist services for eligible patients)

• Bariatric surgery (Tier 4): for patients meeting strict eligibility criteria, typically BMI ≥ 40 kg/m², or BMI 35–39.9 kg/m² with significant obesity-related comorbidities (lower thresholds may apply for some ethnic groups and specific conditions such as type 2 diabetes, as per CG189)

Patients interested in hormonal aspects of weight regulation should discuss concerns with their GP, who can arrange appropriate investigations if an underlying endocrine disorder is suspected. Blood tests may include thyroid function, cortisol assessment, and in specific circumstances (e.g., resistant hypertension, spontaneous hypokalaemia), aldosterone and renin levels. However, treatment with MRAs for weight management alone would not be supported by current evidence-based guidelines. The focus remains on proven interventions with established safety profiles and demonstrated efficacy for long-term weight management and health improvement. Further information on NHS weight management services is available at nhs.uk/live-well/healthy-weight.

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