EAL

NSUP: Vitamin D (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test whether a high-protein nutritional supplement enriched with calcium, vitamin D, vitamin K and phytoestrogens had an effect on bone mineral density and markers of bone metabolism in elderly, healthy Chilean people.

Inclusion Criteria:

70 years or more
Living in the community of Santiago, Chile
Presence of femoral neck osteoporosis
Passed a Mini-Mental State Examination
Mini-Nutritional Assessment score of over 17.

Exclusion Criteria:

Taking medications that interfere with bone metabolism
Suffered a fracture in the preceding six months
Chronic or debilitating disease such as cancer, renal or functional capacity II-III cardiac failure, the presence of chronic infections such as tuberculosis, connective tissue diseases or diabetes mellitus.

Description of Study Protocol:

Recruitment: Healthy, elderly men and women aged 70 years and above living in the community of Santiago, Chile
Design: 100 subjects randomized into two groups of 50; one group taking a special nutritional supplement (SS) and the other group taking the standard nutritional supplement (MS) provided by the Chilean Ministry of Health to all elderly subjects aged 70 or more
Intervention: The special nutritional supplement which contains per serving more protein (15.7g vs. 7.6g), vitamin D (200IU vs. 35IU), vitamin K (30ug vs. zero), calcium (400mg vs. 234mg) and isoflavones (45 vs. zero).

Statistical Analysis

Correlations calculated using the Pearson correlation coefficient
The effects of the SS on outcomes were evaluated with repeated measures two-way ANOVA, correcting data for covariables such as sex and age (for variables with a normal distribution)
Mann-Whitney U-test used for variables with a non-normal distribution
Results expressed as means±SD with normal distribution.

Data Collection Summary:

Timing of Measurements:

Baseline, six months and 12 monthly follow-ups after 12 months

Body composition (fat-free mass and fat mass)
Bone mineral density (femoral neck and spine).

Fasting blood chemistry

Serum OH vitamin D
Intact parathyroid hormone (iPTH)
Osteocalcin
Decarboxylated osteocalcin
Urinary aminoterminal telopeptide of type I collagen (NTX)
Deoxypyridoline cross links
Equol
Glucose
Creatinine
Urea nitrogen
Calcium
Phosphorous
Total and HDL cholesterol
Triglycerides.

Monthly for 12 months: Urinary daidzein (Dpd).

Dependent Variables

Body composition
Bone mineral density.

Independent Variables

Nutritional supplement amounts of:

Protein
Vitamin K
Vitamin D
Calcium
Phytoestrogens.

Description of Actual Data Sample:

Initial N

N=100
SS Group: 50
MS Group: 50.

Attrition (Final N)

84
SS Group: One due to death; two due to severe adverse event; one moved out of town; one was hospitalized
MS Group: Three due to traumatic fractures; one moved out of town; one due to death; one was hospitalized; one for use of unauthorized medication; four lost from follow-up.

Age

SS Group; 76.6±5.1
MS Group: 76.4±5.4.

Ethnicity

Chilean.

Anthropometrics

Initial	SS Group	MS Group
Weight (kg)	55.3±9.6	60.6±9.5
Waist Circumference (cm)	93.8±10.6	97.6±10.7
Body Mass Index (kg/m²)	26.1±4.8	27.4±4.7

Location

Santiago, Chile.

Summary of Results:

12 Months		SS N=45	MS N=39	ANOVA SS vs. MS
Body Composition	Fat-Free Mass	33.5±5.1	35.6±4.2	0.03
Body Composition	Fat Mass	19.7±8.3	22.3±8.7	0.16
Bone Mineral Density	Femoral Neck	0.67±0.06	0.66±0.05	0.48
Bone Mineral Density	Spine	0.84±0.15	0.89±0.15	0.11

Compliance with supplement use: SS, 82.8±11.7%; MS, 71%
SS use improved several markers of bone formation and resorption [osteocalcin, serum 25(OH)D, iPTH over 12 months]
For both SS and MS groups, no change in body composition or differences between groups for evolution of bone mineral density in the spine.

Other Findings

Serum vitamin D levels increased significantly in subjects receiving the SS
Undercarboxylated osteocalcin decreased significantly in subjects receiving the SS
The iPTH remained constant in subjects receiving the SS, but increased in those receiving the MS.

Author Conclusion:

The special nutritionally enhanced supplement improved markers of bone turnover such as improved serum vitamin D, reduced serum iPTH and undercarboxylated osteocalcin levels but did not affect bone mineral density in elderly Chileans with femoral osteoporosis.

Funding Source:

University/Hospital:

University of Chili

Reviewer Comments:

Study limitations included the lack of a control group with no supplementation provided. Quoting the author, "bone turnover markers are good predictors for long term changes in bone mineral density and risk of fractures."

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	No
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	???
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	No
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes