Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
Chlorthalidone (CTD) may produce various metabolic disturbances, including hypokalemia,
 activation of Renin-Angiotensin- Aldosterone (RAA) system, oxidative stress, dyslipidemia,
 Fibroblast growth factor 23 (FGF23) synthesis, and magnesium depletion. These factors may
 interact with each other to contribute to the development of insulin resistances and
 metabolic syndrome. Smaller studies have suggested that Potassium magnesium Citrate (KMgCit)
 can ameliorate CTD- induced metabolic side effects independent of correction of hypokalemia.
 This study will tests if KMgCit ameliorates CTD induced metabolic effects independent of
 correction of hypokalemia.
CTD- induced metabolic side effects were though to be dependent on hypokalemia, but
 subsequent studies suggested that CTD - induced side effects were independent from
 hypokalemia. On the other hand, magnesium depletion has been linked to increased
 Renin-Angiotensin- Aldosterone (RAA) system, the development of metabolic syndrome and
 insulin resistance with magnesium supplementation ameliorating these effects.

 Participants will participate in a double-blinded, parallel design study. After baseline
 evaluation participants will take Chlorthalidone (CTD) alone for 2-3 weeks. They will then be
 randomized to two equal groups to take KMgCit powder or Potassium Chloride (KCl) powder along
 with CTD for 4 months.

 We speculate that Mg depletion is responsible for hepatic fat deposition, which then produces
 insulin resistance. Co-administration of KMgCit powder would avert magnesium (Mg) depletion,
 block hepatic fat deposition by restoring normal Mg status and direct intestinal binding of
 fat, thereby ameliorating insulin resistance. To test this hypothesis, we shall quantitate
 muscle Mg status and hepatic fat content by magnetic resonance spectroscopy (MRS) before and
 after KMgCit. Change in fasting glucose, insulin resistance, serum potassium, FGF23, and
 aldosterone will be compared between KCL and KMgCit groups after 4 months.
Inclusion Criteria:

 • Treated or untreated stage I hypertension

 Exclusion Criteria:

 -  Diabetes mellitus,

 -  Renal impairment (serum creatinine > 1.4 mg/dL),

 -  Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary
 heart disease,

 -  Chronic regular NSAID use,

 -  Allergy to thiazide diuretics,

 -  Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents
 or antacid more than once a week,

 -  Esophageal-gastric ulcer or history of gastrointestinal bleeding,

 -  Chronic diarrhea, vomiting,

 -  Excessive sweating,

 -  Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),

 -  Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase
 (ALT) above upper limit of normal range),

 -  Subjects on any potassium supplement on a regular basis for any reason, such as
 patients with primary aldosteronism,

 -  Pregnancy,

 -  History of major depression, bipolar disorder, or schizophrenia,

 -  History of substance abuse,

 -  Gout,

 -  Metabolic alkalosis, with serum bicarbonate > 32 meq/L,

 -  Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.

 -  Patient with Claustrophobia will not have MRI but can still participate in the study
 without MRI

 -  Metal implants will not have MRI but can still participate in the study without MRI