Greg Fredericks ND NMD ©2024
If stress was a commodity there is no doubt it would be a safe investment for the future. We often hear that stress is the cause of someone’s demise but unfortunately it leaves us with a vague explanation of the cause of death. With deeper investigations into the leading cause of death, namely cardiovascular disorders, key components arise as determining factors. Recently evidence of a stress hormone known as aldosterone that is not widely known has been implicated in a variety of disorders such as cardiovascular disease, kidney disease, Meniere’s disease, metabolic syndrome, palsy, tinnitus, sleep apnoea and strokes.
Meta-analysis studies have shown that people with primary aldosteronism (PA) have a 77% higher risk of coronary heart disease and a 2.5 fold higher risk of stroke compared to patients with regular hypertension (Monticone et al. 2018). It is thought and taught in medical schools that PA is relatively rare affecting only 5% of people with hypertension. However, new evidence suggests that the percentage needs to be revised to 30%. PA may be more prevalent than previously thought and has been found in women suffering with PTSD (Nishimi et al. 2021).
When examining the main cause of high blood pressure (hypertension) most cardiac specialists focus on the endothelial glycocalyx which is the inner structures of veins and arteries. When these structures are not in a relaxed state constrictive blood flow plays a role in hypertension.
Nitric oxide levels have been found to be an important factor for widening of the vascular system for proper blood flow (vasodilation). Nitric oxide is also important for achieving normal oxygen levels throughout the body and maintaining peripheral circulation to the micro vascular system controlled by capillaries (Francis et al. 2010). The micro capillaries are found especially in the eyes and brain as well as in the extremities such as the hands and feet. Nitric oxide has a significant influence on circulation disorders however it pales in
comparison to the effects of the stress related steroid hormone aldosterone in chronic vascular related diseases.
Today there are an ever increasing number of people subjected to stressors from many different areas in their lives including work, relationships, financial and environmental. This article will examine how to understand and deal with one of the most profound and complex silent killer’s afflicting stressed individuals that is seldom discussed.
Aldosterone Affects Hypertension and more
Aldosterone is a silent killer of individuals who experience cardiovascular ischemic disorders related to blood pressure. Aldosterone is a steroid hormone that primarily acts through activation of the mineralocorticoid receptor (MR), a nuclear receptor responsible for downstream genomic regulation. Aldosterone helps regulate magnesium and potassium levels in your blood and has a significant effect on acidosis. Aldosterone also manages the balance of salts and water in the kidneys by holding on to sodium and releasing potassium.
The activation of the MR across a wide distribution of tissue types has been implicated in multiple adverse consequences for cardiovascular, cerebrovascular, renal and metabolic disease independent of blood pressure alone (Brown et al. 2024).
Elevated aldosterone levels can also contribute to fluid retention, overall weakness in the body and in rare cases periodic paralysis. Aldosterone secretion contributes to the development of metabolic alkalosis as salt retention by the kidneys is linked to increased bicarbonate reabsorption and acid excretion.
Aldosterone and the MR have been linked not only to cardiac tissue changes and heart failure (HF) but also to the development of atherosclerosis and atherosclerotic cardiovascular disease events independent of the effects of hypertension alone. In preclinical models aldosterone and MR activation have been implicated in the development of atherosclerosis through multiple pathologic mechanisms including inflammatory cell activation, differentiation, migration, reactive oxygen species formation and plaque composition (Van Der Heijden et al. 2018). Aldosterone has been demonstrated to cause coronary inflammation 2 and arterial stiffening of resistance vessels without a change in blood pressure (Leibovitz et al. 2009).
Effects on Atrial Fibrillation and Obstructive Sleep Apnoea
Atrial fibrillation (AF) has been identified as a prevalent consequence of aldosterone–MR activation. Studies have found that elevated aldosterone together with renin suppression (a marker of MR activation) increases blood pressure volumes to the left ventricle of the heart causing hypertrophy and increasing the risk of atrial fibrillation (Brown et al. 2022). It is also worth noting that obstructive sleep apnoea, a common risk factor in both hypertension and AF, has also been associated with a high prevalence of underlying primary aldosteronism (Di Murro et al. 2010).
A Main Cause of Chronic Kidney Disease (CKD)
Evidence of a direct pathogenic role of aldosterone and MR activation on the development and progression of CKD has been elucidated in studies. In preclinical models aldosterone and MR activation have been implicated in activation of inflammatory cell activation and profibrotic pathways in renal cells beyond the tubular epithelium (Barrera‐Chimal et al. 2019). Further studies in Germany on the population found a compromise in urine flow by renal glomerular filtration rate (eGFR) being affected by an inverse association between
the aldosterone‐to‐renin ratio and eGFR (Hannemann et al. 2015).
Metabolic Syndrome Associated
Metabolic syndrome which is the inherited traits of both cardiovascular disease and insulin resistance has been found to be clinically associated with primary aldosteronism (PR) independent of BP elevation (Hanslik et al. 2015). In a meta‐analysis comparing patients with PA to controls with essential hypertension, PA was associated with a 33% higher risk of diabetes (95% CI, 1.01–1.74) and a 53% higher risk of metabolic syndrome (95% CI, 1.22–1.91) (Monticone et al. 2018). However the impact of glycemic control in PA is not well
established and difficult to disentangle from the effects of changing renal function.
Stress and Aldosterone
Early studies have demonstrated that stress induces aldosterone independent of non aldosterone induced blood pressure (Markou et al. 2015). A recent study has shown that PTSD is associated with stress-related hormones including dysregulated glucocorticoid activity such as cortisol. Further dysregulation of aldosterone activated by psychological stress and implicated in cardiovascular damage may be a relevant pathway linking PTSD and cardiovascular risk in both men and women (Nishima et al. 2021).
Angiotensin II is the main cause of the release of aldosterone while also triggering the pituitary gland to secrete the antidiuretic hormone vasopressin. Angiotensin II is produced systemically and locally in the kidneys. Angiotensin II not only causes vasoconstriction which increases blood pressure but also causes the sensation of thirst and cravings for salt often resulting in fluid retention. Angiotensin II and aldosterone cause the kidneys to excrete vital potassium into the urine. This can cause fluid retention and muscle cramps of which magnesium will have little to no effect. Vasopressin also significantly reduces sodium excretion and urine flow. Angiotensinogen is synthesized by the liver and released into the bloodstream where it is cleaved to form the inactive peptide angiotensin I by renin secreted from the kidney. ACE catalyzes the formation of the vasoconstrictor angiotensin II from angiotensin I.
The Lung-Kidney Connection
Traditional Chinese Medicine (TCM) has the principal that the lung affects the kidneys and the kidneys affect the knees. The interlinking of these organs affecting each other is demonstrated with the angiotensin converting enzyme (ACE).
Angiotensin-converting enzyme (ACE) plays a central role in generating angiotensin II from angiotensin I and capillary blood vessels in the lungs are one of the major sites of ACE expression and angiotensin II production in the human body. Angiotensin II triggers your adrenal glands to release aldosterone and your pituitary gland to release antidiuretic hormone (ADH, or vasopressin). Together aldosterone and ADH cause your kidneys to retain sodium. This is often reflected in the form of fluid retention and knee problems.
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The Importance of ACE Inhibitors
In orthodox pharmacology angiotensin-converting enzyme (ACE) inhibitors are medicines that help relax the veins and arteries to lower blood pressure. ACE inhibitors prevent an enzyme in the body from making angiotensin II, the substance that narrows blood vessels.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are both first-choice groups of medications for treating high blood pressure.
It is important to note that according to the Eighth Joint National Committee (JNC8) an advisory panel for the prevention, detection, evaluation, and treatment of high blood pressure, it is recommended that for the general population pharmacologic treatment be started at a systolic blood pressure (SBP) of 150 mmHg or diastolic blood pressure (DBP) of 90 mmHg. However, for patients with Chronic Kidney Disease treatment shall begin when the values of SBP and DBP reach 140 or 90 mmHg or higher, respectively (James et al. 2014).
Natural Medicine ACE and ARB Treatments
ACE inhibitors are pharmaceutical go-to medications for managing high blood pressure and heart failure. In these conditions they can protect the kidneys however, as ACE inhibitors are cleared through the kidneys they also carry a risk of causing kidney injury.
In herbal medicine Mother Nature has provided natural ACE inhibitors such as; Garlic (Allium sativum), Indian Gooseberry (Emblica officinalis), Grape seed extract (Vitis vinifera), Ashwagandha (Withania somnifera), Roselle (Hibiscus sabdriffa), Ginkgo (Ginkgo Biloba), Hawthorne (Crataegus monogyna) and the Ayurvedic herb Arjuna (Terminalia Arjuna).
While these above herbs help address the ACE receptive issue the complexity of aldosterone also requires attention to the neuroendocrine stress response affecting the adrenal glands.
Angiotensin receptor blockers (ARBs), also known as angiotensin II receptor antagonists, are used to treat high blood pressure and heart failure. When angiotensin II is chronically elevated it promotes excessive vasoconstriction, hypertension, inflammation, oxidative stress, vascular immune dysfunction and thrombosis. ARB’s are also used for chronic kidney disease and prescribed following a heart attack. They include pharmaceutical drugs; Irbesartan, Valsartan, Losartan and Candesartan. Natural ARB’s include Omega 3’s and
Vitamin E.
Calcium-channel blockers (CCBs) or beta blockers, diuretics, central alpha agonists or alpha blockers are sometimes recommended by GP’s and cardiologists “But if you change the lifestyle and give it some time, eventually you probably can get [patients] off many of the drugs.” – Mark Houston, MD triple board certified hypertension specialist.
Spironolactone the Primary Treatment for Aldosterone
Spironolactone is a molecule that acts as an aldosterone receptor antangonist and is used in orthodox medicine as a treatment for PA. Spironolactone is a potassium-sparing diuretic. Diuretics cause water loss and are used to treat a variety of conditions including high blood pressure, heart failure and diseases of the kidneys and liver. Spironolactone is available as a single agent and in a combination drug product.
In natural Herbology the herbs that contain spironolactone are; Buchu (Agathosma betulina), Cleavers (Galium aparine), Dandelion (Taraxacum officinale), Gravel Root (Eutrochium purpureum), Horsetail (Equisetum arvense), Juniper (Juniperus communis) and Bearberry (Arctostaphylos uva ursi). While herbs offer diuretic activity for deterring fluid retention as we have seen PA is a complex illness that requires more complex treatment.
Diet and Lifestyle Attenuation of Aldosterone
Looking after one’s adrenal health is a top priority for avoiding elevated aldosterone. Maintaining good sleep patterns with between 7-9 hours of sleep is essential. A regular exercise routine is also important as well as Magnesium and Vitamin D. Maintaining a healthy diet consisting of nutrient rich salmon, mackerel, free range chicken, avocado, cruciferous vegetables such as brussel sprouts, broccoli and cauliflower. Nuts such as almonds, walnuts and chia, flax, and pumpkin seeds and olive oil are valuable contributors
to good adrenal health. The most recommended diet is essentially a Mediterranean diet with some modification: a lot of vegetables, some fruit, minimal to no carbohydrates, high-quality organic protein and the right types of fats (primarily Omega-3 fatty acids, monounsaturated fats, limited saturated fats and no trans fats). According to a recent Harvard Medical study Omega 3’s containing the rare ‘DPA’ found in Atlantic Menhaden is ten times more powerful than EPA/DHA and lowers the risk of heart attack by 28% and
survival of cardiac infraction by 50%.
A salt restricted diet which is often recommended by dieticians has been shown to unexpectedly increase aldosterone. These findings were demonstrated in patients after 6 months of salt free consumption. The study revealed that Body Mass Index (BMI) remained constant while plasma renin and serum aldosterone decreased following salt repletion. Adequate salt consumption attenuates mineralocorticoid receptor antagonist (MRA) -induced hyperkalemia in relatively salt-restricted PA patients without affecting blood
pressure (BP) or body mass index (BMI) (Fountoulakis et al. 2020).
Other Nutritional considerations
Adrenal stress support:
B5, B6, glandular adrenal cortex supplement.
Central alpha agonists:
Taurine and vitamin B 6 followed by potassium.
Diuretics:
that contain Spironolactone as mentioned above.
Vasodilators:
Omega-3 fatty acids including docosapentaenoic acid (DPA) magnesium and co-enzyme Q10 (CoQ10) Vit. K, beetroot and blackcurrent juice.
CCBs (Calcium Channel Blockers):
Among those with optimal activity are alpha-lipoic acid, magnesium and omega-3s (eicosapentaenoic acid and docosahexaenoic acid).
ACEIs (angiotensin-converting enzyme inhibitors}: Among the best natural compounds that have been studied is dried bonito fish which are part of the tuna/mackerel family.
Pycnogenol, omega-3s, and hydrolysed whey protein (which can also help with glutathione levels) are also effective.
DASH 2 Diet:
Consisting of fruits and vegetables, low sodium, high potassium, high magnesium, high fiber.
https://ww w.freepik.com/free-photos-vectors/mediterranean-diet
Dr Mark Houston from the American Board of Internal Medicine says “In hypertension beta
blockers are less effective in reducing central blood pressure, coronary heart disease, MI, and
overall cardiovascular mortality compared to ACE inhibitors, ARBs, CCBs, or these in
combination—and they really make you feel bad,”. CCBs are very good for reducing blood
pressure and for reducing strokes at the same blood pressure level compared to any other
class (by 10% more (Alexander et al. 2024).
https://pixabay.com/images/search/blood%20pressure/
Caffeine and the Aldosterone Response
It is well documented that overconsumption of caffeinated beverages is known to cause various medical complications such as anxiety, palpitations, tremors, jaw clenching and electrolyte imbalance such as abnormally low potassium in the blood (hypokalemia) and low electrolytes in the form of phosphate (hypophosphatemia). Caffeine is associated with renin-angiotensin-aldosterone system activation (Kamijo et al. 2018). This condition is characterized with generalized muscle weakness, fatigue and development of numbness
and low serum renin which is one of the main hallmarks of aldosterone induced hypertension. Long term caffeine consumption is also linked to fatty liver, insulin resistance, Meniere’s disease and diabetes.
Other Herbal Remedies and Strategies for Primary Aldosteronism
While there are studies demonstrating herbs used to reduce stress responses there are no specific studies dealing with aldosterone. While some herbs may raise serotonin and reduce cortisol they may not be specifically appropriate to attenuate aldosterone. Ashwagandha or Withania somnifera has shown effects of lowering circulating glucocorticoids cortisol and corticosterone through alteration of the Hypothalamic-pituitary-adrenal (HPA) axis, ameliorating stress symptoms (Speers et al. 2021).
In traditional Chinese medicine (TCM) the herb Rehmannia glutinosa has a long history for treating CKD and calming the adrenal glands. The mushroom Wolfiporia cocos known as the medicine of immortality has also been used in TCM for over two thousand years for draining dampness reducing insomnia and regulating electrolytes. The herb Bupleurum is also useful for its calming liver cooling characteristics and for regulating stress responses.
Salvia miltiorrhiza known as Dan Shen has shown to reduce urine protein levels, improve kidney function and attenuate CKD without significant side effects. The combination of Tanshinone IIA (TIIA) from the herb Dan Shen and angiotensin receptor blocker (ARBs) were shown to be more effective than ARB monotherapy in modulating hypertensive nephropathy (Xu, et al. 2019). This was indicated by improved eGFR (kidney function) and reduced urinary protein, serum creatinine, cystatin-C and better control in systolic blood
pressure (SBP) and diastolic blood pressure (DBP) in group combined with STS plus ARBs than in ARBs alone group. From this study one can see a combination of treatments is more effective in dealing with complex hypertension especially where aldosterone is involved.
Elevated aldosterone is treated by general practitioners and cardiologists who prescribe anti hypertensive drugs and Spironolactone based pharmaceuticals. In fact aldosterone is much more complex as it is also an immune stimulant which finds its self fitting within the realm of neuroimmunoendocrinology even though most of its effects are cardiovascular. Within this perspective it is relatively new territory for Naturopaths and Herbalists to treat such a complex disorder but with research and education protocols can be developed. Nutrition,
nutraceutical supplements, antioxidants, weight loss, Mediterranean diet, exercise, meditation and sleep patterns must all be considered.
The Mindset and Stress Response
Changing ones mindset by starting with making changes in habits, routines and thought patterns may have a positive impact on lowering aldosterone. Deprogramming habitual subconscious patterns can go a long way to changes in one’s biochemistry. Accessing the pharmacy within is always the ultimate goal often through meditation and altering ones brain waves from beta to alpha and then to theta and delta.
https://www.istockphoto.com/search/2/image-film?phrase=human+brain+waves
Biofeedback using an electroencephalogram (EEG) has demonstrated that the temporomandibular joint is a key area for manifesting beta brain waves that reflect stress responses. By relaxing an otherwise clenched jaw one can change their brainwaves from beta to alpha in minutes. A clenched jaw is often attributed to adrenal stress the source of aldosterone production. The practice of relaxing the jaw is an ideal state for avoiding beta waves. It not only helps one attain a good night’s sleep it is also be helpful for achieving a
meditative state.
As one can see there are many variables involved in avoiding an elevated aldosterone level. Most medical doctors believe it can only be regulated through antihypertensive drugs. The author hopes the information presented in this article will inspire more rigorous evidence based research that is currently needed on this stress induced mineralocorticoid.
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