You all know something about glands. It is a simple idea. The thyroid gland makes thyroid hormone that regulates metabolism like the idle setting in a car. You also know that the pancreas makes insulin which regulates the sugar level in cells and the blood. Abdominal fat is the largest gland in the body. The more abdominal fat you have, the more hormones you make, and one of the things they do is interfere with your ability to lose weight.
One of the most important of these hormones from belly fat is aldosterone. It is equally as important as thyroid hormone or insulin, and it has several normal functions. If you are in a hot dry place and you become dehydrated, your aldosterone level will increase even if you are thin. That is a normal response. Increased aldosterone helps you retain salt and water so that you can survive longer and that is good. But as with thyroid and insulin, too much aldosterone can make you sick.
The more abdominal fat you have, the more aldosterone you make, even if you are healthy- but you won’t stay healthy as long because high aldosterone levels make you older and sicker faster. Normal, healthy people with too much belly fat are already insulin resistant and that is directly related to the high aldosterone levels. Insulin resistance is the first step on the way to type 2 diabetes. High aldosterone levels are present with increased abdominal fat, and they are already causing trouble in apparently healthy people. High aldosterone levels increase inflammation, scar formation in vital organs, and the death of functional cells in the heart, kidney, and other vital organs. In healthy people, if there is loss of kidney or liver tissue, the remaining organ can grow and compensate. After a couple of decades of extra belly fat and high aldosterone levels, the functional kidney and liver cells die and regenerate repeatedly while scar tissue continues to grow. The end result is a shrunken organ mostly made of scar tissue that can’t regenerate.
The first abnormality we recognize from high aldosterone is high blood pressure. Up to 80% of all cases of high blood pressure are related to high aldosterone. High blood pressure is hard to control. If you have another risk factor like diabetes or arterial disease, your blood pressure should be under 130/80 and fewer that half of the people with hypertension even have control below 140/90. Blocking the effects of aldosterone has a major effect to improve those control rates. If the blood pressure is not controlled by losartan plus hydrochlorothiazide and amlodipine, that person has resistant hypertension. Adding just 25 mg of spironolactone at that point drops the top number on the blood pressure by 25 points. No other medication does that. Eplerenone does the same thing every more precisely. Compared to other anti hypertensive drugs, spironolactone was superior for treating obese patients with resistant high blood pressure who were already on 3 blood pressure medications including drugs like losartan or lisinopril.
Aldosterone produces its effects by something like a lock and key mechanism. There is a receptor in the wall of the cell that is like a lock. Aldosterone fits precisely in that receptor like a key to activate it. Eplerenone is like a key broken off in the lock to very narrowly block only the effects of aldosterone and related molecules like the steroid hormone cortisol. It blocks the effect of aldosterone elevation without other detrimental effects.
The extremely damaging impact of aldosterone does not stop with blood pressure elevation. High aldosterone also leads directly to resistance to the effects of insulin, high triglycerides, a lower good cholesterol, higher bad cholesterol, and reduced insulin production.
Increased levels of aldosterone due to excess abdominal fat also lead to the production of increased oxidants. You have also learned that oxidants make you age faster and get sick sooner. Some of you took vitamin E as an antioxidant to help you stay healthy longer. That did not work, but blocking aldosterone effects is an antioxidant that does work to keep you healthy longer. The effects of aldosterone that we have discussed damage the arteries, the heart, and the kidney to contribute to the development of atherosclerosis, heart attacks, heart failure, and chronic kidney disease.
High aldosterone levels lead to the development of senescent cells in vascular smooth muscle. Senescent is another term for old. Senescent cells no longer function normally and they accumulate with the increasing antioxidant imbalance in older people. Spironolactone or eplerenone block the formation of senescent cells which secrete multiple inflammatory mediators which are part of the inflammation related to obesity and aging. They may also secrete growth factors. The inflammation and growth factors together promote the development of cardiovascular disease and cancer.
High aldosterone levels from abdominal fat occur in healthy younger people. These increases lead to increased risk factor levels, then diabetes, heart attack, and stroke and later still contribute to the development of chronic kidney disease and heart failure. High aldosterone also leads to the development of senescent cells at a younger age. Senescent cells also accumulate as a natural part of the aging process. They stop functioning as normal cells and make molecules themselves that make us age faster and become ill sooner. It is a vicious cycle. This is a predictable progression that we can block with spironolactone or eplerenone in small doses. Taken together, these multiple processes switch on many genes that remain switched on. The best thing is to stay slender and avoid developing higher aldosterone levels. It makes sense to block the effects of aldosterone earlier and to continue low dose spironolactone or eplerenone even after weight loss when the blood pressure and sugar come down. Aldosterone excess plays a key role in aging and chronic illness development and we can block it precisely.
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