EAL

HTN: Vitamins (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the effects of long term supplementation with Mg and Zn, vitamin E and C and a combination of these micronutrients on blood pressure levels in type 2 diabetic patients.

Inclusion Criteria:

Type 2 diabetes for at least one year
Normotensive or mildly hypertensive
Not taking vitamin or mineral supplements, thyroid hormones, estrogens, progesterone, diuretics or beta blockers
Normal renal and hepatic function
No history of mocardial infarction
Not pregnant.

Exclusion Criteria:

Subjects who did not use more than 10% of capsules given during study were excluded from the statistical analysis.

Description of Study Protocol:

Recruitment

No information provided.

Design

Randomized double-blind, placebo-controlled clinical trial with subjects stratified by gender and randomly assigned to one of four treatment groups using block randomization procedure
All subjects were interviewed at baseline regarding dietary habits, BMI, medical history, smoking addiction, medication and dietary supplements
Compliance with study protocol was monitored by capsule count at Weeks Six and 12 and confirmation of serum or urine changes
Additionally, individual counseling sessions occured at Weeks Six and 12 with phone contacts between counseling sessions to encourage compliance
Blood and urine samples were collected at baseline and at the end of the three-month trial. They were analyzed for plasma ascorbic acid, alpha-tocopherol, Zn and Mg in urine and serum, serum and urinary excreion of sodium and potassium, urine creatinine and serum malondialdehyde
Systolic and diastolic blood pressure was measured at baseline and after three months, twice each time with a mean of the two readings used
Mean arterial pressure (MAP) was calculated using the formula (SBP +2 DBP)/3
Nutrient intake was estimated from two 24-hour recall questionnaires at the beginning and end of the trial
Subjects were asked not to change usual diets and physical activity during the study and to avoid changes in medication.

Blinding Used

Double-blinded with placebo used for control group.

Intervention

Subjects were randomized to one of four groups listed below:

Group M: Received 30mg zinc as zinc sulfite and 200mg magnesium as magnesium oxide for three months
Group V: Received 200mg Vitamin C and 150mg Vitamin E for three months
Group MV: Received both of the vitamin and mineral supplements described above for three months
Group P: Received lactose as a placebo for three months.

Statistical Analysis

Values are expressed as mean±SD.
Differences between the four groups were determined by one-way ANOVA for continuous data. Chi-square test was used to determine differences for group data. A value of P<0.05 was used for significance.

Data Collection Summary:

Timing of Measurements

At baseline and at the end of the three-month trial.

Dependent Variables

Variable One: Systolic blood pressue (five minutes' seated rest, used mean of two readings)
Variable Two: Diastolic blood pressure (five minutes' seated rest, used mean of two readings)
Variable Three: Mean arterial pressure (MAP), calcuated using the following formula: (SBP + DBP)/3.

Independent Variables

Variable One: 30mg zinx and 200mg magnesium
Variable Two: 200mg Vitamin C and 150mg Vitamin E
Variable Three: 30mg zinc, 200mg magnesium, 200mg Vitamin C and 150mg Vitamin E.

Control Variables

Variable One: Lactose as a placebo
Variable Two: Nutrients intakes estimated from two 24-hour dietary recalls
Variable Three: Serum or urine measurements of zinc, magnesium, vitamin C and vitamin E.

Description of Actual Data Sample:

Initial N: 76 type 2 diabetics
Attrition (final N): 69 (33 males, 36 females); divided equally among four groups.

Age

30 to 69 years old; per group mean±SD

Group P: 49.6±9.2 years
Group M: 51.5±7.5
Group V: 49.9±9.2
Group MV: 50.6±9.7.

Ethnicity

Not given.

Other Relevant Demographics

Groups were similar with respect to age, gender, duration of diabetes, BMI, smoking and daily intake of vitamin C and E, magnesium and zinc.

Anthropometrics

Mean±SD BMI per group

Group P: 27.6±3.6
Group M: 28.0±4.7
Group V: 27.5±4.7
Group MV: 28.8±3.9.

Groups were not different.

Location

Tehran, Iran.

Summary of Results:

No statistical difference between groups for systolic blood pressue (SBP), diastolic blood pressure (DBP) or MAP at baseline (see table below).

Baseline Levels of Systolic, Diastolic and Mean Blood Pressure in Type 2 Diabetic Patients

	Group P (N=18)	Group M (N=16)	Group V (N=18)	Group MV (N=17)
SBP (mm Hg)	127±16	122 +15	125+15	130±19
DBP (mm Hg)	82±9	78±12	81±9	83±11
MAP (mm Hg)	97±9	93±3	95±10	99±13

Decreases in systolic, diastolic and mean blood pressure following three months of intervention with zinc, magnesium, Vitamin C and Vitamin E (Group MV) occurred (see table below)
These changes were also significant when compared to Group P (placebo)
There were no significant chages in the other three groups.

	Value	Change	P
SBP (mm Hg)	122±16	-8	<0.05
DBP (mm Hg)	77±9	-6	<0.05
MAP (mm Hg)	92±9	-7	<0.05

Other Results

There was a significant (P<0.05) effect of vitamin and mineral supplementation to increase serum potassium and to decrease serum sodium-potassium ratio
A positive correlation betwee the decrease in serum sodium and the reduction in SBP was shown in group MV (R=0.734, P=0.001)
Vitamin and mineral supplementation produced a significant reduction in serum malondialdehide in group MV (P<0.05).

Author Conclusion:

In type 2 diabetic patients, a combination of vitamins and minerals rather than vitamin C and E, or magnesium and zinc, might decrease blood pressure.

Funding Source:

University/Hospital:

Tehran University of Medical Sciences (Iran)

Reviewer Comments:

Manual blood pressure measurement was discussed as a limitation as opposed to conducting 24-hour ambulatory blood pressure measurements. These results should be confirmed in hypertensive diabetic individuals, since these subjects were normotensive or mildly hypertensive
Ethnicity was not described, however the study took place in Iran
Physical activity was not measured, however subjects were asked not to alter usual diet and activity patterns
Exclusion criteria was not particularly stringent, meaning that subjects could have not used up to 89% of supplements and their data was still used
Authors suggest that the minerals and vitamins may be acting synergistically.

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?	???
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?	Yes
	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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.)	Yes
	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?	Yes
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	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?	Yes
	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)?	N/A
	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?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
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