Multiple micronutrient supplementation improves vitamin B12 and folate concentrations of HIV infected children in Uganda: a randomized controlled trial

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Abstract

Background

The effect of multiple micronutrient supplementation on vitamin B ₁₂and folate has hither to not been reported in African HIV infected children. This paper describes vitamin B ₁₂and folate status of Ugandan HIV infected children aged 1-5 years and reports the effect of multiple micronutrient supplementation on serum vitamin B ₁₂and folate concentrations.

Methods

Of 847 children who participated in a multiple micronutrient supplementation trial, 214 were assessed for vitamin B ₁₂and folate concentrations pre and post supplementation. One hundred and four children were randomised to two times the recommended dietary allowance (RDA) of a 14 multiple micronutrient supplement (MMS) and 114 to a 'standard of care' supplement of 6 multivitamins (MV). Serum vitamin B ₁₂was measured by an electrochemiluminescence immunoassay and folate by a competitive protein-binding assay using Modular E (Roche) automatic analyzer. Vitamin B ₁₂concentrations were considered low if less than 221picomoles per litre (pmol/L) and folate if < 13.4 nanomoles per litre (nmol/L). The Wilcoxon Signed Ranks test was used to measure the difference between pre and post supplementation concentrations.

Results

Vitamin B ₁₂was low in 60/214 (28%) and folate in 62/214 (29.0%) children. In the MMS group, the median concentration (IQR) of vitamin B ₁₂at 6 months was 401.5 (264.3 - 518.8) pmol/L compared to the baseline of 285.5 (216.5 - 371.8) pmol/L, p < 0.001. The median (IQR) folate concentrations increased from 17.3 (13.5 - 26.6) nmol/L to 27.7 (21.1 - 33.4) nmol/L, p < 0.001. In the 'standard of care' MV supplemented group, the median concentration (IQR) of vitamin B ₁₂at 6 months was 288.5 (198.8 - 391.0) pmol/L compared to the baseline of 280.0 (211.5 - 386.3) pmol/L while the median (IQR) folate concentrations at 6 months were 16.5 (11.7 - 22.1) nmol/L compared to 15.7 (11.9 - 22.1) nmol/L at baseline. There was a significant difference in the MMS group in both vitamin B ₁₂and folate concentrations but no difference in the MV group.

Conclusions

Almost a third of the HIV infected Ugandan children aged 1-5 years had low serum concentrations of vitamin B ₁₂and folate. Multiple micronutrient supplementation compared to the 'standard of care' supplement of 6 multivitamins improved the vitamin B ₁₂and folate status of HIV infected children in Uganda.

Trial registration

http://ClinicalTrials.gov NCT00122941)

Related collections

Most cited references 27

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Kenyan school children have multiple micronutrient deficiencies, but increased plasma vitamin B-12 is the only detectable micronutrient response to meat or milk supplementation.

Jonathan Siekmann, Montague Demment, N Bwibo … (2003)

Animal source foods (ASF) can provide micronutrients in greater amounts and more bioavailable forms compared to plant source foods, but their intake is low in many poor populations. However, the impact of ASF on micronutrient status of undernourished populations has not been assessed. Supplemental meat (60-85 g/d), milk (200-250 mL/d) or energy (isocaloric with the meat and milk, 240-300 kcal/d) were randomly assigned to 555 undernourished school children aged 5-14 y in a rural malaria-endemic area of Kenya, at one school meal daily for one school year. Blood and stool samples were collected at baseline and after 1 y to assess stool parasites, malaria, hemoglobin, serum or plasma C-reactive protein, ferritin, iron, zinc, copper, vitamin B-12, folate and retinol, and erythrocyte riboflavin. At baseline, there was a high prevalence of micronutrient deficiencies (iron, zinc, vitamins A and B-12 and riboflavin), yet plasma ferritin was low in few children, and none had low serum copper. At the end of the year of supplementation, plasma vitamin B-12 concentrations were significantly increased in children fed the Meat or Milk meal; prevalence of severe plus moderate deficiency fell from 80.7% at baseline to 64.1% in the Meat group and from 71.6 to 45.1% in the Milk group, respectively. No significant improvement was observed in the status of other micronutrients compared to the Energy and Control groups, although malaria and other infections may have obscured effects. Supplementation with small amounts of meat or milk reduced the high prevalence of vitamin B-12 deficiency in these children.

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Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking. The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India. Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial. The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001). In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.

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Marc M. Baum, Ashley Fletcher, C Hennekens … (1995)

To determine whether nutritional status affects immunological markers of HIV-1 disease progression. A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

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Author and article information

Journal

Journal ID (nlm-ta): Nutr J

Title: Nutrition Journal

Publisher: BioMed Central

ISSN (Electronic): 1475-2891

Publication date Collection: 2011

Publication date (Electronic): 21 May 2011

Volume: 10

Page: 56

Affiliations

[1 ]Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda

[2 ]Centre for International Health, University of Bergen, Norway

[3 ]Institute of Medicine, University of Bergen, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway

Article

Publisher ID: 1475-2891-10-56

DOI: 10.1186/1475-2891-10-56

PMC ID: 3118332

PubMed ID: 21600005

SO-VID: 8415e491-88a1-47d3-b0d2-2f223ab91733

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.