EAL

H/A: Monitoring of Food Intake (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The objectives of the present article are to report dietary intake and serum values of vitamin B₁₂ in a cohort of HIV-positive subjects and to evaluate the influence of protease inhibitors (PIs) on changes in serum B₁₂ levels.

Inclusion Criteria:

Participants in The Nutrition for Healthy Living (NFHL) cohort study
HIV-positive adults (age 18 years and older) living in the greater Boston area or in Rhode Island
Special efforts to recruit women and non-white minorities.

Exclusion Criteria:

Presence of any of the following conditions at enrollment: pregnancy, thyroid disease or malignancies other than Kaposi sarcoma
Not fluent in English.

Description of Study Protocol:

Recruitment

NFHL cohort study, a longitudinal study of HIV-positive subjects (age ≥18 years) at different stages of disease living in the greater Boston area or in Rhode Island.

Design

Cohort study.

Blinding used

Analyses of blood samples done in clinical labs.

Intervention

No intervention; some data was categorized by source of vitamin B₁₂ intake (food and/or supplements)

Statistical Analysis

Data for analysis included only data from individuals who had at least two consecutive visits spaced within four months to eight months of each other (mean six months)
The unit of analysis was person-intervals rather than individuals. Each participant could contribute one to four intervals to the analysis.
Regression models, including restricted cubic spline function, were used to assess the linearity of the association between B₁₂ intake and any change in serum B₁₂ over the entire range of B₁₂ intake levels
Multivariate linear regression models using generalized estimating equations were used to correct SEs for the use of multiple intervals per participant.

Data Collection Summary:

Timing of Measurements

Participants were seen in the clinic every six months.

Dependent Variables

Serum vitamin B₁₂ levels.

Independent Variables

Dietary intake
Use or no use of protease inhibitors.

Control Variables

Sex, race, baseline CD4 cell counts, viral load, neutrophil counts and hemoglobin levels for each interval were evaluated as potential confounders and effect modifiers
Did not adjust for virus loads or CD4 cell counts because they are part of the mechanistic pathway of the interaction of PIs and HIV on B₁₂ absorption and metabolism.

Description of Actual Data Sample:

Initial N: 686 participants in NFHL study

Attrition (final N): 412 participants had intervals with mean B₁₂ intakes less than 150mcg per day; contributed 1,073 intervals for the analysis

Age: 40.3 years±7.7 years

Ethnicity: 62% white, approximately 25% black and 8% Hispanic

Anthropometrics: Body mass index (BMI) within normal range for men (24.8) and slightly above normal for women (26.9)

Location: Greater Boston area or Rhode Island.

Summary of Results:

Variables

All Intervals

Intervals with PI Use

Intervals without PI Use

Statistical Significance of Group Difference

Dietary B₁₂ intake

No. of intervals

Median mcg/day (IQR)

1,073

9.67 (5.4 - 19.68)

615

11.9 (6.0 - 22.6)

454

7.6 (4.6 - 15.0)

P=0.0002

Interval baseline

values

serum B₁₂

No. of intervals

median pg per ml (IQR)

1,073

479 (376-40

615

491 (383-667)

454

462 (369-617)

P=0.0077

CD4 cell count

No. of intervals

Median cells/mm³

1,055

346 (191-533)

607

308 (177-491)

444

408 (229-574)

P=0.5761

HIV load

No. of intervals

Median log10 copies per ml (IQR)

1,013

3.47 (2.30-4.38)

584

3.07 (2.30-4.26)

426

3.8 (2.85-4.47)

P<0.0001

Other Findings

Median serum values were 546pg per ml in supplement users vs. 420pg per ml in non-supplement users (P<0.0001).
Approximately 30% non-supplement users had serum values less than 350pg per ml
15% of supplement users had serum values less than 350pg per ml
“Although the standard normal range for serum B₁₂ is 200 to 1,250 pg/mL, some researchers consider values less than 350 pg/mL to be deficient (ref 25)…”
Median B₁₂ intake (food and supplements was 8.1mcg per day (DRI=2.4mcg per day).
NHANES III reported a median intake of 3mcg to 5mcg per day.
The upper quartile was taking B₁₂ supplements at levels more than6.0mcg per day , which is more than in a standard one-a-day pill.
Median intake from food alone was 5.3mcg per day
Malabsorption (D-xylose levels less than 20mg per L) not associated with changes in serum B₁₂ nor the association between intake and changes in serum levels.
Intervals during which participants reported PI use had, on average, higher B₁₂ intakes and higher serum B₁₂ levels at the baseline for each interval.
21.8% of intervals with no PI use had serum values less than 350pg per ml, whereas 17.4% of those intervals with PI use had serum values less than 350pg per ml.
Association of total B₁₂ intake and change in serum B₁₂ depended on PI use
B₁₂ intake levels as high as four times the DRI were associated with negative changes in serum B₁₂ levels during intervals in which the participants were not receiving the PIs.
As B₁₂ intake increased, changes in serum B₁₂ levels became positive during the interval. The authors gave examples indicating not a clinically important increase during a six-month time period.

Author Conclusion:

The effect of vitamin B₁₂ intake on changes in serum B₁₂ levels was dependent on PI therapy.

The incidence of subjects and intervals in which serum B₁₂ values were less than 350pg per ml was approximately 20%, regardless of whether a person was taking a PI. These levels can result in neurological changes that have been described in the HIV population; therefore, the authors recommended yearly determinations of serum B₁₂.

The authors also recommended B₁₂ injections if serum levels were less than 350pg per ml because dietary supplementation may not be effective, especially in those receiving PIs.

This study does address the question and indicates that dietary intervention may not be enough; injections may be needed to maintain B₁₂ levels.

Funding Source:

Government:	NIDDK, NIH, National Institute on Drug Abuse
University/Hospital:	Lifespan/Tufts/Brown Center for AIDS Research

Reviewer Comments:

Unsure why authors automatically excluded individuals who were not fluent in English.

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)	N/A
	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.)	N/A
	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?	N/A
	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?	N/A
	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?	N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	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?	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