Does Potassium Bicarbonate Improve the Effect of Dietary Protein on Bone and Muscle?

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine whether adding the basic salt potassium bicarbonate to the diet will have a positive effect on how dietary protein affects your bone and muscle.

Detailed Description
-----------------
The balance between the amount of protein in the diet (anabolic component) and the net acid load of the diet (catabolic component) in part determines whether the diet as a whole has a net anabolic or catabolic effect on bone and muscle. This study will investigate whether the addition of an alkaline salt of potassium, potassium bicarbonate, will allow dietary protein to have a more favorable net impact on intermediary indices of bone and muscle conservation than is observed with protein in the usual acidic environment. Men and postmenopausal women, age 50 and older, will be enrolled in this 42-day study in order to have 20 completers. Subjects may continue in the study for up to an additional two weeks should this be necessary for reasons related to intercurrent illness (unrelated to the research) or scheduling circumstances. Over the first 15 days, subjects will be placed on gradually increasing doses, up to a maximum of 90 mmol/d of potassium bicarbonate or placebo. They will remain on this dose for the rest of the study. Subjects will then have two 10-day metabolic diet cycles each, in random order, as follows: Group 1 - low protein diet (0.5 g/kg/d) then high protein diet (1.5 g/kg/d) Group 2 - high protein diet (1.5 g/kg/d) then low protein diet (0.5 g/kg/d) There will be a 5-day period between the two metabolic diets in which subjects consume their usual diets but continue to take the study pills.

Official Title
-----------------
Does Potassium Bicarbonate Improve the Effect of Dietary Protein on Bone and Muscle?

Conditions
-----------------
Osteoporosis, Sarcopenia

Intervention / Treatment
-----------------
* Dietary Supplement: potassium bicarbonate
* Dietary Supplement: Placebo (microcrystalline cellulose)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: This study will be conducted in subjects with body mass index < 38 kg/m2. Women must be at least 6 months since last menses. Subjects must be willing to maintain their usual exercise level and agree not to attempt to gain or lose weight or change their diets substantially during the study. Subjects will not be allowed to take their own calcium or vitamin D supplements from one week before their screening visit through the end of the study. They must also agree not to ingest bicarbonate- or potassium-rich products such as selected antacids and salt substitutes during the study. They must also agree not to consume alcohol during the study. Exclusion Criteria: Medications Oral glucocorticoid use for > 10 days in the last 3 months Estrogen, raloxifene, or calcitonin use in the last 6 months, bisphosphonate or teriparatide use in the last 2 years Current use of diuretics Regular use of NSAIDS (> 3 times per wk) or anabolic drugs (steroids or other). Note that subjects may use acetominophen for joint or other discomforts during the study. Conditions/Diseases Renal disease including kidney stones in the past 5 years or creatinine clearance < 50 ml/min/1.73 X m2 of body surface area Cirrhosis GERD requiring treatment with alkali-containing antacids (use of Lowsium okay) Hyperparathyroidism Untreated thyroid disease Significant immune disorder such as rheumatoid arthritis, SLE Current unstable heart disease Active malignancy or cancer therapy in the last year 24-hr urine calcium > 300 mg/d after 1 wk off of calcium supplements Subjects with arrythmias (surgically treated arrythmias acceptable), or myocardial infarction in last 12 months Total hip T score of < -3.0 Abnormal serum calcium; alkaline phosphatase >10% above the upper end of the reference range Adrenal insufficiency, primary aldosteronism, Bartter's syndrome Diabetes mellitus (fasting blood sugar > 130) Alcohol use exceeding 2 drinks/day Peptic ulcers or esophageal stricture Screening serum 25(OH)D levels below 16 ng/ml Vegetarians Other abnormalities in screening labs, at discretion of the study physician (principal investigator)

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Participants receive potassium bicarbonate in dosage of 90 mmol/d. This compound has no other name. | Dietary Supplement: potassium bicarbonate<br>* 90 mmol/d given as 4 tablets after each meal, with a full glass of water<br>|
| Placebo Comparator: 2<br>Participants receive placebo as microcrystalline cellulose. This compound has no other name. | Dietary Supplement: Placebo (microcrystalline cellulose)<br>* Given as 4 tablets after each meal, with a full glass of water<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the impact of administration of an alkalinizing salt on urinary nitrogen excretion in older men and women. |  | before and after low and high protein diet cycles | 
| To determine the impact of administration of an alkalinizing salt on urinary calcium excretion in the same population. |  | before and after low and high protein diet cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether the administration of an alkalinizing salt of potassium alters the effect of protein on biochemical markers of bone turnover in the same population. |  | before and after low and high protein diet cycles | 
| To determine whether the administration of an alkalinizing salt of potassium alters the effect of protein on calcium absorption in the same population. |  | before and after low and high protein diet cycles | 
| To determine whether the administration of an alkalinizing salt of potassium alters the effect of protein on serum IGF-1 in the same population. |  | before and after low and high protein diet cycles | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
acid-base, potassium, acidosis, osteoporosis, sarcopenia, calcium absorption, dietary protein