This article is not intended to be medical or healthcare advice. Before starting on any health related regimen, seek the care of your primary care physician.
Over Expression of Angiotensin II Can Lead To Potassium Excretion and Water Retention
There are a number of genes in the Renin Angiotensin Aldosterone system, the key ones being:
AGT - encodes for angiotensinogen, catalyzed by renin into angiotensin I. The direct physiological activity of Ang I has been debated, Ang I is further catalyzed by angiotensin-converting enzyme (ACE) to angiotensin II: a vasoconstrictive and inflammatory agent. Angiotensin is a hormone in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure. To increase blood pressure, angiotensin II causes the blood vessels to constrict, thus upping the pressure.
AGTR1 - Angiotensin 1 - AGTR1 encodes for angiotensin II (Ang II) receptor type 1 (AT1), a primarily receptor for angiotensin II. Binding of Ang II to AT1 results in the production of aldosterone from the kidneys, and signals for the body to retain water and sodium, and the release of potassium. Activation of AT1 has shown to activate Nf-kB, and NADPH oxidase (NOX). Angiotensin I is a precursor hormone that is converted into angiotensin II by the ACE enzyme. Stopping the conversion of angiotensin I into II by blocking the ACE enzyme decreases blood pressure. ACE inhibitors are a commonly used type of blood pressure medication. Genetic variants in AGTR1 increase the expression of the angiotensin II receptor 1 — increasing blood pressure. Angiotensin receptor blockers (ARBs), a class of blood pressure medication, act on AGTR1. RX: losartan and valsartan. Natural Angiotensin Blockers: Coq10, Resveratrol, Taurine, B-6, and Garlic [6]. In addition to blood vessels, the angiotensin II receptor is found in the kidneys and lungs. AGTR1 affects the way your kidneys respond to sodium and affects the changes that occur in kidney disease due to diabetes. AGTR1 genetic variants are also tied to cancer risk and endometriosis.
ACE - Angiotensin Converting Enzyme - Angiotensin-converting enzyme, encoded by ACE, has the critical role in the conversion of angiotensin I to its active form angiotensin II. Angiotensin II has vasoconstrictive and inflammatory properties and stimulates aldosterone secretion from the adrenal gland. Aldosterone has a major role in electrolyte homeostasis and thus blood pressure. Research suggests both angiotensin II and aldosterone may stimulate NADPH oxidase (NOX), and IL-6. The angiotensin-converting enzyme (ACE) plays a role in maintaining blood pressure at a normal level. It works within the body’s blood pressure regulation system, converting angiotensin I into angiotensin II. Too much Angiotensin II will cause blood vessels to constrict and a subsequent increase in blood pressure. A common genetic variant in the ACE gene that impacts levels of angiotensin-converting enzyme. For people with the ACE deletion/deletion genotype, 6-weeks on high-fat diet doubled their risk for diabetes
ACE2 - Angiotensin-converting enzyme 2, encoded by ACE2, catalyzes the vasoconstrictive angiotensin I and angiotensin II into the vasodialative and anti-inflammatory angiotensin 1-9, and 1-7, respectively. ACE2 also appears to have a role in the degradation of des-Arg9 bradykinin into inactive metabolites. ACE2 may be inhibited by glutamate.
AGTR2 - Angiotensin II - AGTR2 encodes for angiotensin II (Ang II) receptor type 1 (AT2), a receptor for angiotensin II. Research suggest AGTR2 may have an important role in developmental biology; however, this gene has also been suggested to have an important role in infection-induced inflammatory reaction. For angiotensin II to constrict blood vessels (and increase blood pressure), it must bind to its receptor, logically called the angiotensin II receptor type-1.
Renin - REN encodes for renin, which is a hormone. Renin catalyzes the conversion of angiotensinogen to angiotensin I via the activation of ATP6AP2, also known as the renin receptor.
Angiotensin I-7 - Angiotensin-(1-7) is a vasoactive peptide of the renin–angiotensin system (RAS), which is generated mainly by angiotensin-converting enzyme 2 (ACE2) and exerts its actions via activation of its receptor Mas. The Ang-(1-7)/ACE2/Mas axis is nowadays considered to be a main mechanism, which counterbalances the vasoconstrictive actions of classical RAS, which includes renin, ACE, ANG II, and its receptors AT1 and AT2. Whereas the classical RAS has been known for more than 100 years, the protective arm of the RAS was relatively recently discovered. Both Mas and Ang-(1-7) were first described almost 30 years ago; however, it took an additional 15 years until the interaction of these components was revealed.[10]
Low Potassium (Too Much Aldosterone) Leaves You Vulnerable to B-12 Supplementation Side Effects
B-12 supplementation will draw serum potassium into the red cell and can cause potassium deficiency side effects, and in some cases this can be quite dangerous if potassium is quite low. It seems establishing a good baseline of potassium sufficiency and or status prior to embarking on b-12 supplementation is wise.
"Hypokalemia (resulting in death) has occurred during vitamin B12 therapy as a result of increased red blood cell requirements during hematopoiesis. Clinical monitoring and correction of potassium levels prior to and during vitamin B12 therapy is necessary."[7]
"A case of megaloblastic anemia probably caused by malabsorption is analyzed. Blood potassium levels were monitored before and during treatment with vitamin B12. It is concluded that low potassium levels in chronically hypoxic patients may be dangerous and that blood potassium should be monitored constantly during the treatment of this type of anemia."[8]
"In patients with megaloblastic anemia serum-potassium levels fell during treatment, in some cases to levels low enough to warrant replacement therapy; at the same time red-blood-cell potassium concentrations rose. It is suggested that low serum-potassium levels in a chronically hypoxic patient could be serious, and that serum-potassium should be monitored in patients with megaloblastic anemias."[9]
Low levels of potassium has all sorts of symptomatic side effects, and can be serious. If you have the classic symptomology and your genetics match with issues related to Angiotensin and Aldosterone, establishing potassium sufficiency may prove beneficial.
If you would like to examine your genetics in more detail around this topic, please reach out to me to schedule an appointment. I also encourage you to review the references listed below for more details.
References
Hypertension: Is It Time to Replace Drugs With Nutrition and Nutraceuticals?
Association between AGTR1Â A1166C polymorphism and the susceptibility to diabetic nephropathy. Yan Zhuang, PhD,a Fukun NiuMedicine (Baltimore). 2018 Oct; 97(41): e07689.
Involvement of angiotensin II receptor type 1/NF-κB signaling in the development of endometriosis. Zhimin Zhang,1,* Yi YuanExp Ther Med. 2020 Oct; 20(4): 3269–3277.
AGTR1 Is Overexpressed in Neuroendocrine Neoplasms, Regulates Secretion and May Potentially Serve as a Target for Molecular Imaging and Therapy
Dietary Fat Intake Modulates Effects of a Frequent ACE Gene Variant on Glucose Tolerance with association to Type 2 Diabetes. Rita Schüler,1,2 Martin A. Osterhoff Sci Rep. 2017; 7: 9234. Published online 2017 Aug 23. doi: 10.1038/s41598-017-08300-7
Hypertension: Is It Time to Replace Drugs With Nutrition and Nutraceuticals?
https://www.drugs.com/disease-interactions/cyanocobalamin,vitamin-b12.html
Hypopotassemia and megaloblastic anemia. Presentation of a case. E Omboni, M Checchini, F Longoni. PMID: 3627537Minerva Med. . 1987 Aug 31;78(16):1255-7.
HYPOKALÆMIA IN MEGALOBLASTIC ANÆMIAS. D.H. Lawson, J.L.W. Parker, R.M. Murray, G. HayVolume 296, Issue 7673, 19 September 1970, Pages 588-590.
Angiotensin-(1-7) and Mas, The Protective Arm of the Renin Angiotensin System (RAS). Natalia Alenina, and Robson Augusto Souza dos Santos2015 : 155–159. Published online 2015 Apr 24. doi: 10.1016/B978-0-12-801364-9.00021-3