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Table 30Oral multivit and mineral vs. standard care

Bibliographic referenceStudy TypeEvidence levelNo. of patientsPatients characteristicsInterventionComparisonLength of follow upOutcome measuresEffect sizeComments (including source of funding)
Allsup et al 20048RCT1+164 patients randomised

46 withdrew

Total number of patients analysed: n=118

Multivit/min: n=81 (20 withdrew)

Placebo: n= 83 (26 withdrew)
People living in nursing and residential homes (31 homes) in the city of Liverpool.

Inclusion/exclusion criteria: Eligibility depended on participants being able to give informed consent (abbreviated mental score>7), not having neoplastic disease, and not prescribed immunosuppressant medication at the time of recruitment.

Individuals taking multivit supplements, vitamin C, or vitamin B and those with a previous adverse reaction to influenza vaccine were also excluded.

Median (IQR) age:
Multivit/min: 83.1 (6.6)
Control: 82.6 (8.8)

Gender-Male, n(%)
Multivit/min: 25 (41.0)
Placebo: 18 (31.6)

Barthel score, median (IQR):
Multivit/min: 75 (55)
Placebo: 60 (50)

BMI (Kg/m2), median (IQR):
Multivit/min: 25.8 (8.3)
Placebo: 25.6 (7.6)

Albumin (g/L), mean +/− SD
Multivit/min: 36.4 +/− 3.3
Placebo: 35.4 +/− 3.6

Prescribed vit B12 replacement therapy, n (%):
Multivit/min: 0
Placebo: 2 (3.5)

Prescribed Iron therapy, n (%)
Multivit/min: 6 (9.8)
Placebo: 4 (7.0)

Prescribed vit D supplements, n (%)
Multivit/min: 4 (6.6)
Placebo: 5 (8.8)

Influenza Immunization in 1999/2000, n (%)
Multivit/min: 51 (83.6)
Placebo: 50 (87.7)
Multivit/min supplement.

One tablet twice a day for 8 weeks (starting on week -4).

Content: Vit A 2,666 IU, Vit D3 400 IU, Vit E 60 mg, Vit B1 1.2 mg, Vit B2 1.4 mg, Vit B6 3.0 mg, nicotinamide 14 mg, folic acid 0.6 mg, vit B12 200 μg, biotin 30μg, calcium 240 μg, and magnesium 100 mg.

All participants were administered split- virus inactivated influenza vaccine in week 0. The vaccine contained three antigens: H1N1, H3N2 and B.

Blood samples were taken from participants on three occasions: at the start of the study (week -4), immediately before vaccination (week 0), and 4 weeks after vaccination (week +4).
Placebo tablet

One tablet twice a day for 8 weeks (starting on week -4).

All participants were administered split- virus inactivated influenza vaccine in week 0. The vaccine contained three antigens: H1N1, H3N2 and B.

Blood samples were taken from participants on three occasions: at the start of the study (week -4), immediately before vaccination (week 0), and 4 weeks after vaccination (week +4).
8 weeksMultivit/min: n=61
Control: n=57

Antibody response assessed separately for each of the three antigens.

MFI (mean fold increase):

H1N1:
Multivit/min: 4.3
Control: 2.7

MFI ratio multivit/min/control (95% CI):

1.6 (1.1–2.4)

H3N2:
Multivit/min: 4.8
Control: 3.8

MFI ratio multivit/min/control (95% CI):
1.3 (0.8–2.1)

B:
Multivit/min: 3.0
Control: 3.4

MFI ratio multivit/min/control (95% CI): 0.9 (0.6–1.4)

Responders-n (%)(proportion of subjects having a fourfold or greater rise between week 0 and week +4, with a rise in titre from less than 1:10 to 1:20 or greater, also considered a fourfold or greater increase)

H1N1:
Multivit/min: 28 (49)
Control: 25 (41)

Difference in percentage response (Control – Multivit/min) (95% CI): −8 (−25 to 10) [p=0.374]

H3N2:
Multivit/min: 33 (58)
Control: 30 (49)

Difference in percentage response (Control –Multivit/min) (95% CI):
−9 (−26 to 9) [p=0.343]

B:
Multivit/min: 23 (40)
Control: 25 (41)
Difference in percentage response (Control –Multivit/min) (95% CI): 1 (−17 to 18) [p=0.944]

Plasma levels of vitamins and minerals at week −4, 0 and week +4
There was a high drop out rate (27%). Short length of follow up.
Girodon et al 1997126 and Girodon et al 1997a124

(Two papers, same study. Different outcomes reported. Presented together)
RCT1+81 patients

Four arms:

Placebo group n=20
Mineral group n=20
Vitamin group n=20
Mineral and vitamin group n=21

9 died after 1 year

16 died during the second year
Long-term institutionalised subjects. They had only age-related diseases.

Age (y) (mean +/− SD)

Placebo group= 84 +/−8
Mineral group= 84 +/− 8
Vitamin group= 84 +/−8
Mineral and vitamin group= 83 +/− 8
NS

Gender (W/M)

Placebo= 14/6

Mineral= 15/5
Vitamin= 17/3
Mineral and vitamin= 15/6

BMI (kg/m2)

Placebo= 25.64 +/− 10.21
Mineral= 21.07 +/− 4.20
Vitamin= 22.83 +/− 4.02
Mineral and vitamin= 21.35 +/− 3.51
NS

Exclusion criteria:
history of cancer, GI, liver and kidney disease, medication that might interfere with nutritional status and immunocompetence, or vit. And/or mineral supplements
Four arms. Patients received one capsule per day.

Mineral group: Zinc sulfate and selenite (20 mg zinc and 100 μgrams selenium)

Vitamin group: ascorbic acid (120 mg), betacarotene (6 mg= 1000 retinol equivalent), and alfa-tocopherol (15 mg)

Mineral and vitamin group: both of the above mineral and vitamin supplements

Placebo group: (calcium phosphate and cellulose)
Mineral effect
Mineral + (Mineral and vitamin) v
Placebo + Vitamin

Vitamin effect
Vitamin+ (Mineral and Vitamin) v
Placebo+ Mineral
Two yearsOutcome measures reported in Girodon 1997aThis study appears to be a subsample of a larger scale study (see below Girodon 1999).

The population of this institution had previously participated in nutritional surveys.

Blood samples of apparently healthy volunteers were utilised as the reference young controls for the free radical-initiated haemolysis test.

Funding: Societe des Produits Roche (France) and Laboratories Labcatal (France). Partly supported by the Institut National de la Sante et de la Recherche Medicale (INSERM), the Conseil Rgional de Bourgogne and the Universite de Bourgogne.
Biochemical assessment of plasma vitamin and mineral levels at baseline, after 6 months, 1 year and 2 years of supplementation.Mean plasma levels of alfa-tocopherol/cholesterol, beta carotene and vit C increased significantly after 6 months of supplementation in the vitamin and (mineral and vitamin) groups.

Mean plasma levels of alfa-tocopherol/cholesterol and betacarotene decreased between day 365 and day 730 in the vitamin and (mineral and vitamin) groups.
Indicators of oxidative stress and antioxidant enzymes

Free radical-initiated haemolysis test (blood samples of apparently healthy normal volunteers were utilised as the reference young controls 11 men and 7 women)

Outcome measures reported in Girodon 1997
There was a significant increase in GPx (selenium-dependent gluthathione peroxidase) (antioxidant) in groups receiving minerals (alone or with vitamins) at 6 months
Infections (only respiratory and symptomatic urogenital infections were reported)Placebo group (n=20):
1st year= 16
2nd year= 19
Total= 35
Mean= 1.75
SD= 1.48

Mineral group (n=20):
1st year= 7
2nd year=5
Total= 12
Mean=0.60
SD= 0.99

Vitamin group (n=20):
1st year= 10

2nd year=14
Total= 24
Mean= 1.20
SD= 1.43

Vitamin and mineral group (n=21):

1st year=14
2nd year= 9
Total= 23

Mean = 1.09
SD= 1.09

Subjects who received minerals alone or with vitamins had significantly fewer respiratory and urogenital infections [p<0.01] than those who had no trace elements supplementation.
MortalityNumber of deaths after two years:

Placebo group= 7 (2 died because of infection)
Mineral group=6
Vitamin group= 5
Vitamin and mineral group= 7 (1 died because of infection)

No beneficial effect of supplementation upon survival was noted.
Girodon et al 1999125RCT1+?725 patients from 25 nursing homes.

There are four arms in this study:

Trace element group (T) n= 182 (withdrawn: 4)

Vitamin group (V) n= 180 (Withdrawn 3)

Trace element and Vitamin group (TV) n= 181 (withdrawn 3)

Placebo n= 182 (withdrawn 4)

Total withdrawn 14
Long-term institutionalised elderly patients with no acute illness >= 65 years old.

Age (mean +/− SD)

Placebo = 83.7 +/− 7.4

Trace element group = 83.6 +/− 7.6

Vitamin group = 83.8 +/− 7.9

Vitamin and trace element group = 83.4 +/− 7.5

Gender (M/W)

Placebo= 46/136

Trace element group= 49/133

Vitamin group= 46/134

Vitamin and trace element group= 44/137

BMI (Kg/m2)

Placebo= 24.5 +/− 5.8

Trace element group= 23 +/− 5.7

Vitamin group= 24.5 +/− 6.7

Vitamin and trace element group= 24 +/− 5.7

Exclusion criteria:
patients with a history of cancer or those taking medication that might interfere with nutritional status, immunocompetence, or vitamin or mineral supplements.
Four arms: Patients received 1 capsule daily, with their breakfast:

Trace element-Zinc sulfate and selenium (providing 20 mg of zinc and 100 μgr of selenium)

Vitamin-Ascorbic acid (120 mg), beta carotene (6 mg= 1000 retinol equivalents), alfa-tocopherol (15 mg)

Vitamin and trace element-Trace elements and vitamin supplements

Placebo: calcium phosphate and microcrystalline cellulose
Vitamin effect Vitamin + (Vitamin and trace element ) v Placebo + Trace element

Trace elements effect

Trace element+ (Vitamin and trace element) v Placebo + Vitamin
Two yearsSerum levels of alfa- tocopherol, beta carotene, vitamin C, Zinc and Selenium. Base levels and after 6, 12 and 24 months of supplementationPatients were not treated equally during the study. A subsample of patients (n=173) had an hypersensitivity test and another subsample (n=140) underwent humoral response to influenza vaccine test.

Fourteen patients were withdrawn from the study after transfer to other hospital.

There are some limitations in this study. A subsample of 140 patients received influenza vaccine.
Infections are reported in total and not extracted for this group of patients.

Funding: Produits Roche SA (Paris, France) and Labcatal (Montrougue, France)
Delayed-type hypersensitivity skin test responses to 7 antigensAssessed in a subsample n=173 at baseline and after 6 and 12 months of supplementation
Humoral response to influenza vaccine.Tested in a subsample n=140 patients.
Vaccine was injected after 15 to 17 months of supplementation.
Seroprotected patients after influenza vaccine %:
Day 28
Placebo: 27.7
Trace element: 44.1
Vitamin: 12.1
Vitamin and trace element: 30.0
Trace element effect: T + TV [p<0.05]

Day 90:
Placebo: 31.4
Trace element: 43.2
Vitamin: 11.7
Vitamin and trace element: 33.3
Trace element effect: T + TV [p<0.05]

Day 180:
Placebo: 25.7
Trace element: 36.1
Vitamin: 8.8

Vitamin and trace element: 16.1 [NS]

Day 270:
Placebo: 21.8
Trace element: 29.4
Vitamin: 6.0
Vitamin and trace element: 6.4 [NS]
Infectious morbidity (only respiratory tract and urogenital infections were recorded)The overall proportion of patients who remained free from respiratory infections was higher in those with mineral supplementation than in those without [p=.06]. When classifying into numbers of infectious events, there was NS difference between groups.
Mortality n (%)Placebo group= 51
Trace element group= 55
Vitamin group= 45
Vitamin and trace element group= 55 [p>.10]
Mortality after two yearsSurvival analysis of the 2 years did not show any difference between the groups.
Jiamton et al
2003169
RCT481 patients randomised

Multivit/min: n=242 (8 died, 41 lost follow up)

Placebo: n=239 (3 died, 12 lost to follow-up)
HIV-infected patients.

Patients were eligible for the trial if they were over 18 years old, had not been taking micronutrients or antiretrovirals in the last 30 days and had a CD4 cell count between 50 x 106 and 550 x 106/l. A few patients attending hospital for routine testing for sexually transmitted infections also volunteered.

Age (mean-range)
Multivit/min: 32 (18,63)
Placebo: 32 (20,60)

Gender (men-%):
Multivit/min: 95 (39)
Placebo: 94 (39)

Body mass index (kg/m2) (mean-SD):
Multivit/min: 21.2 (2.7)
Placebo: 21.6 (3.3)
One tablet twice daily after food.

Tablet content: vit A 3000 μg, betacarotene 6 mg, vitamin D3 20 μg, vit E 80 mg, vit K 180 μg, vit C 400 mg, vit B1 24 mg, vit B2 15 mg, vit B6 40 mg, vit B12 30 μg, folacin 100 μg, panthothenic acid 40 mg, iron 10 mg, magnesium 200 mg, manganese 8 mg, zinc 30 mg, iodine 300 μg, copper 3 mg, selenium 400 μg, chromium 150 μg anc cystine 66 mg.
Placebo tablet. One tablet twice a day after food.48 weeksMinor adverse effects (n)Multivit/min: 64
Placebo: 73
Funding: Supported by Nestle Foundation. S. J. is supported by a strategic grant in Epidemiology from the Medical Research council, UK. The micronutrients were supplied by Vitabiotics Ltd, London. The sponsors of the trial had no role in the study design, data collection, data analysis, data interpretation or the writing of the report
Patients reporting discoloration of urineMultivit/min: 23
Placebo: 0 [p<0.0001]
Plasma levels of vitamin E and seleniumData not extracted
Deaths [n/n (%)]Multivit/min: 8/242
Placebo: 15/239

Mortality hazard ratio (95% CI)
0.53 (0.22–1.25) [p= 0.1]
- Death in patients with CD4 cell counts <200 (x 106/l)Multivit/min: 5/96
Placebo: 12/92

Mortality hazard ratio (95% CI)
0.37 (0.13–1.06) [p= 0.052]
- Death in patients with CD4 cell count <100 (x 106/l)Multivit: 3/40
Placebo: 10/41

Mortality hazard ratio (95% CI)
0.26 (0.07–0.97) [p= 0.03]
Admissions to hospitalThe rate of first admissions did not differ significantly between the two groups either overall or when stratified by baseline CD4 cell count
Median CD4 cell count at the final follow-up and mean fall in CD4 cell count from baselineThere were no significant differences between the groups overall and among those with baseline
CD4 cell < 200 x 106/l or >= 200 x 106/l ([p>0.3] in each case)
Plasma viral loadDid not differ significantly between the groups

From: Appendix Four, Evidence Tables

Cover of Nutrition Support for Adults
Nutrition Support for Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition.
NICE Clinical Guidelines, No. 32.
National Collaborating Centre for Acute Care (UK).
Copyright © 2006, National Collaborating Centre for Acute Care.

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