Supplemental Calcium in Overweight People
Supplemental Calcium in Overweight People
This study will examine the health effects of calcium supplements in overweight adults.
 Overweight adults often eat a diet low in calcium. Some studies have found low calcium intake
 in people who have some of the medical problems often seen in overweight adults. This study
 will see if extra calcium improves the health of overweight adults.

 Volunteers in general good health 18 years of age or older who are overweight (body mass
 index equal to or greater than 25 kilograms per square meter of body surface) may be eligible
 for this study. Women who are pregnant or breastfeeding may not participate. The study
 includes four visits, described below.

 Visit 1

 Volunteers will be screened for participation in the study with a medical history, physical
 examination, and blood and urine tests. At home, they will collect a 24-hour urine sample;
 fill out questionnaires to assess their average calcium intake; and record their food intake
 for 7 days. Those enrolled in the study will continue with the next 3 visits.

 Visit 2

 Participants will complete a physical activity questionnaire, have their food diary reviewed,
 and meet with a dietitian for nutritional counseling. Triceps fold thickness and waist and
 hip circumferences will be measured three times. Body composition will be analyzed by a DEXA
 study. For this procedure, the subject lies on a flat table while a small dose of X-rays is
 passed through the body.

 Participants will be randomly assigned to take either calcium carbonate (1500 mg/day) or
 placebo capsules twice a day by mouth for 2 years. (The placebo looks like the calcium
 capsules but contains no calcium.) They will receive a 6-month supply of study capsules
 during visit 2 and return to NIH every 6 months for the next supply. They will also be sent
 questionnaires by mail every 3 months to complete information about health problems and how
 often the study capsules are being taken.

 Visits 3 and 4

 Visit 3 is scheduled after participants have taken the study capsules for 1 year; visit 4 is
 scheduled after 2 years (the end of the study). At each of these visits, participants will
 have a DEXA scan, blood and urine tests, blood pressure measurements, and measurements of
 height, weight, waist and hip circumference. They will complete questionnaires about their
 medical history, side effects of the study medications, dietary calcium intake, and physical
 activity, and they will meet with one of the study investigators to talk about any concerns
 regarding the study. At the fourth visit, participants will answer some additional questions
 about their study participation and return the Diet History Questionnaire that was mailed to
 them before the visit.
An estimated 97 million people in the United States are overweight or obese, and therefore
 have an increased risk for a number of other obesity-related co-morbid conditions (such as
 hypertension, dyslipidemia, and Type 2 Diabetes) as well as for all-cause mortality. The
 total cost attributable to obesity amounted to $99.2 billion in the US in 1995 and this
 figure, like the prevalence of increased body mass, is rising at an alarming rate. At the
 same time calcium intake in the US adult population is far below the RDA (recommended daily
 allowance) and much below the daily optimal calcium intake recommended by the 1994 NIH
 consensus conference. An analysis of the NHANES III database suggests a strong inverse
 association between relative risk of obesity and calcium intake. Further, both prospective
 studies in animal models, and retrospective analyses of human studies suggest calcium
 supplementation may play a role in minimizing yearly weight gain, and may possibly induce
 small weight losses.

 In order to test the relationship between calcium intake and body weight, we propose to
 conduct a 2-year, randomized, double-blind, placebo-controlled trial of calcium
 supplementation (1500 mg/day of supplementary calcium vs. placebo) in adults with a BMI
 greater than or equal to 25 kg/m(2). We will study the effects of supplemental calcium on
 body weight, body composition, and obesity-related comorbid conditions, such as insulin
 sensitivity and lipids. The effects of such supplementation on blood pressure will also be
 systematically evaluated. A control group of untreated, healthy, adults will also be enrolled
 for comparisons to study subjects.
-  INCLUSION CRITERIA: (Overweight Subjects)

 Volunteers will qualify if they meet the following criteria:

 1. Good general health. Individuals taking medication for obesity-related co-morbid
 conditions will not be excluded.

 2. Age greater than or equal to 18 years.

 3. Body Mass Index greater than or equal to 25 kg/m(2).

 4. For women with childbearing potential, a negative pregnancy test at the initial
 evaluation.

 5. Normal fasting serum Ca (2.05-2.55 mmol/L) and serum phosphorous levels (2.3 - 4.3
 mg/dl).

 INCLUSION CRITERIA: (Normal Weight Subjects)

 Volunteers will qualify if the meet the following criteria

 1. Good general health.

 2. Age greater than or equal to 18 years.

 3. Body Mass Index 1-24.99 kg/m(2)

 4. For women with childbearing potential, a negative pregnancy test at the initial
 evaluation. Since these subjects have to undergo DXA (dual Energy X-ray
 Absorptiometry) scan screening in their second visit, for safety purposes, pregnant
 women will be excluded from participation in the study.

 5. Normal fasting serum Ca (2.05-2.55 mmol/L) and serum phosphorus levels (2.3-4.3
 mg/dl).

 EXCLUSION CRITERIA: (overweight subjects)

 Volunteers will be excluded (and referred to non-experimental treatment programs as
 needed) for the following reasons:

 1. A presence of major illnesses: renal, hepatic (other than obesity-related
 steatosis), gastrointestinal, most endocrinologic (e.g., Cushing syndrome, hyper-
 or hypothyroidism), hematological problems or pulmonary disorders (other than
 asthma not requiring continuous medication or sleep-apnea related disorders);

 2. Women who are pregnant, or who are currently nursing an infant; or who are having
 unprotected intercourse;

 3. Individuals who have a current substance abuse or a psychiatric disorder or other
 condition that in the opinion of the investigators would impede competence or
 compliance or possibly hinder completion of the study;

 4. Subjects who regularly use prescription medications unrelated to the
 complications of obesity {e.g., calcium channel blockers, diuretics (including
 thiazide diuretics), beta-blockers etc}. Oral contraceptive use will be
 permitted, provided the contraceptive has been used for at least two months
 before starting study medication. The use of over-the-counter medications will be
 reviewed on a case-by -case basis;

 5. Subjects who have a total calcium intake of more than 3.5 g/day on the screening
 calcium intake questionnaire (SCQ) or more than 3 g/day of total calcium intake
 on review of their 7-day food diaries;

 6. Subjects who take supplement calcium in excess of 300 mg/day or vitamin D
 supplements in excess of 400 IU/day;

 7. Recent (3 months) use of anorexiant medications;

 8. History of renal stones;

 9. Intentional weight change of more than 3% of body weight in the past two months.

 10. Post-menopausal women who are medically advised to take calcium supplementation.

 11. Subjects with iPTH greater than 75 pg/ml (Normal range: 10-75 pg/ml) when
 associated with a serum calcium level greater than 2.5 mmol/L. (normal range 2.05
 to 2.55 mmol/L)

 12. Subjects with a serum 25-(OH)-D level less than 10 ng/ml (Normal range: 10-68
 ng/ml) when associated with a serum 1-225-(OH)(2)-D level of less than 22 pg/ml
 (Normal Range: 22-67 pg/ml.

 13. Subjects with a consistently (2 weeks apart) elevated systolic blood pressure of
 greater than 160 mm Hg and/or a diastolic blood pressure greater than 95 mm Hg.

 EXCLUSION CRITERIA: (Normal Weight Subjects)

 Volunteers will be excluded (and referred to non-experimental treatment programs as
 needed) for the following reasons:

 1. Presence of major illnesses: renal (serum creatinine greater than 1.6), hepatic
 (AST/ALT greater than 3 times upper limit of normal range used in Clinical Center
 assays), gastrointestinal, most endocrinologic (e.g. Cushing syndrome, hyper- or
 hyothyroidism), hematological problems or pulmonary disorders (other than asthma
 not requiring continuous medication or sleep-apnea related disorders);

 2. Women who are pregnant, or who are currently nursing an infant;

 3. Individuals who have current substance abuse of a psychiatric disorder or other
 condition that in the opinion of the investigators would impede competence or
 compliance or possibly hinder completion of the study;

 4. Subjects who regularly use prescription medications. Oral contraceptive use will
 be permitted, provided the contraceptive has been used for at least two months
 before starting study medication. Individuals taking medications for most
 conditions will be excluded, but medication use will be considered on a
 case-by-case basis.

 5. Subjects who take supplemental calcium in excess of 300 mg/day or vitamin D
 supplements in excess of 400 IU/day.

 6. Recent (3 months) use of anorexiant medications;

 7. Intentional weight change of more than 3% of body weight