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Assessment of the effects of supplementation with vitamin E on health and production of feedlot cattle using meta-analysis
Preventive Veterinary Medicine 88 (2009) 229–246
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Review
Assessment of the effects of supplementation with vitamin E on health and production of feedlot cattle using meta-analysis Paul Cusack a,*, Neil McMeniman b, Ahmad Rabiee c, Ian Lean c a
Australian Livestock Production Services, 102 Darling St., Cowra, NSW 2794, Australia School of Veterinary Science, University of Queensland, St. Lucia, Qld 4067, Australia c Strategic Bovine Services, P.O. Box 660, Camden, NSW 2570, Australia b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 October 2007 Received in revised form 12 September 2008 Accepted 11 December 2008
Delivery of supplemental antioxidant vitamins to cattle placed in feedlots might be expected to improve health and performance outcomes by reducing the effects of oxidative stress to which these cattle are presumably exposed. Meta-analytic procedures were used in this study to assess published experiments on the effects of vitamin E supplementation in feedlot cattle. The health outcome of morbidity, and the production outcomes of average daily gain (ADG) and gain to feed ratio (G:F), were analysed. The currently available data do not support the use of supplemental vitamin E administered as an injection (morbidity risk ratio = 1.17; P = 0.17). The authors conclude that supplemental dietary vitamin E should be fed within the [NRC, 1996. National Research Council. Nutrient Requirements of Beef Cattle, 7th ed. Natl. Acad. Press, Washington, DC] recommended range. ß 2009 Elsevier B.V. All rights reserved.
Keywords: Systematic review Dietary supplement Injection
Contents 1. 2.
3.
4.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Literature search and methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Dietary vitamin E with or without additional selenium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Effects of dietary vitamin E on morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Effects of dietary vitamin E on production—dry matter intake, average daily gain and gain:feed . . . . . . . . . . . . . . . 3.4. Vitamin E and selenium injection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
229 234 234 241 242 242 242 244 244 245 245
1. Introduction
* Corresponding author. Tel.: +61 2 6341 3113; fax: +61 2 6342 1795. E-mail address: [email protected] (P. Cusack). 0167-5877/$ – see front matter ß 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.prevetmed.2008.12.002
Cattle newly arrived at a feedlot are usually exposed to oxidative challenges arising from transport and handling (Sconberg et al., 1993), fasting (Nockels et al., 1996), and possibly, dietary polyunsaturated fatty acids (MacPherson, 1994) and bovine respiratory disease (Breazile, 1988). Some
230
Table 1 Vitamin E and selenium studies with pen as the unit of interest and vitamin E/selenium administered as a dietary supplement. Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean SEc (where SE provided)
P value
Carter et al. (2005)
Split plot randomised complete block (blocked by load, sorted by BW) 4 time levels of supplementation (0, 7, 14 or 28 d)
Vitamin E 20.3 IU/animal/d (d 0–7) 90.3 IU/animal/d (d 8–14)
7 pens of 174– 183 animals
Feed supplement 1259 IU vitamin E/animal/d (Roche vitamins, nutley, NJ) = 6.71 IU/kg BW/d
DMI
E0 = 4.33 0.25
0.31
G:F
E7 = 4.38 0.25 E14 = 4.53 0.25 E28 = 4.49 0.25 E0 = 0.20 0.14 E7 = 0.20 0.14 E14 = 0.19 0.14 E28 = 0.20 0.14
0.87
DMI
E0 = 6.6 0.1
>0.10
G:F
E375 = 6.6 0.1 E0 = 0.22 0.01 E375 = 0.22 0.01
>0.10
E0 = 8.1 0.3
>0.10
Arnold et al. 2 3 factorial (2 (1992) Exp. 1 treatment levels 3 designated slaughter weights) 3 initial weight blocks with random treatment allocation within blocks
Arnold et al. Presumably randomised – (1992) Exp. 2 not stated
Vitamin E: 9 IU/kg diet DM = 9 pens of 6 animals 74 IU/animal/d = 0.20 IU/kg BW Se: 0.08 mg/kg diet DM
Vitamin E: 126 IU/animal/d = 0.29 IU/kg BW Se: 0.1 mg/kg diet DM
4 animals in 1 pen
Feed supplement 375 IU/animal/d (Rovimix E-40% dispersable liquid concentrate, Roche vitamins, Nutley, NJ) = 1.65 IU vitamin E/kg BW
DMI Feed supplement 1266 IU/animal/d (Rovimix E-40% dispersable liquid concentrate, Roche Vitamins, Nutley, NJ) = 2.90 IU vitamin E/kg BW
E1266 = 8.0 0.3 G:F
>0.10 E0 = 0.17 0.01 E1266 = 0.18 0.01
Arnold et al. Presumably randomised – (1992) Exp. 3 not stated
Garber et al. (1996) Exp. 1 (beef)
Blocked by BW and randomly allocated to 5 treatment levels
Vitamin E: 113 IU/animal/d = 0.18 IU/kg BW Se: 0.1 mg/kg diet DM
Vitamin E: 167 IU/animal/d = 0.46 IU/kg BWd
5 animals in 1 pen
15 animals (no. of pens not stated)
Feed supplement 1317 IU/animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.12 IU vitamin E/kg BW
Feed supplement 333 IU/animal/d (source not stated) = 0.92 IU/kg BWd or 632 IU/animal/d = 1.75 IU/kg BWd or 1139 IU/ animal/d =3.16 IU/kg BWd or 1920 IU/animal/d = 5.32 IU/kg BWd
DMI
E0 = 8.1 0.4
G:F
E1317 = 7.8 0.4 E0 = 0.15 0.02 >0.10 E1317 = 0.17 0.02
DMI
E0 = 11.8 0.4
>0.10
>0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Reference
G:F (SE expressed for feed/gain = 0.5)
E333 = 10.9 0.4 E632 = 11.2 0.4 E1139 = 12.4 0.4 E1920 = 11.8 0.4 E0 = 0.12 E333 = 0.12
>0.10
E632 = 0.12 E1139 = 0.12 E1920 = 0.12 Garber et al. (1996) Exp. 2 (dairy)
Blocked by BW and randomly Vitamin E: 167 IU/animal/d allocated to 4 treatment levels = 0.46 IU/kg BWd
15 animals (no. of pens Feed supplement 632 IU/animal/d not stated) (source not stated) = 1.73 IU/kg BWd or 1139 IU/animal/d = 3.11 IU/kg BWd or 1920 IU/animal/d = 5.25 IU/kg BWd
DMI
E632 = 12.5 0.5 E1139 = 12.5 0.5 E1920 = 12.6 0.5 E0 = 0.09 E632 = 0.10
>0.10
>0.10
E1139 = 0.10 E1920 = 0.10 Hays et al. (1997)
Random allocation to pens for dietary supplement. Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry
Vitamin E: not measured
2 pens of 32 animals for Feed supplement (source not stated) 400 IU vitamin E/lb diet = 880 IU/kg feed supplement & 65 diet = 6324 IU/animal/d = 26 IU/kg animals for injection BWd injection of 3000 IU/animal (product not stated) = 12.3 IU/kg BW
Feed supplement (over 28 d)
SE’s not stated
DMI (vitamin E increased)
E0 = 6.93
<0.01
E6324 = 7.19 E0 = 0.11 E6324 = 0.15
NSDe
DMI (d 0–14)
E217 = 2.29 0.15
>0.10
DMI (d 14–28)
E380 = 2.00 0.15 E787 = 2.07 0.15 E217 = 4.82 0.33 E380 = 4.32 0.33 E787 = 4.65 0.33
>0.10
G:F
Rivera et al. Random allocation to pen (2002) Exp. 1 with 3 levels of supplementation.
Pen was used as the experimental unit for the analysis of all performance data.
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 217 IU/animal/d = 1.25 IU/kg BWd 380 IU/animal/d = 2.20 IU/kg BWd 787 IU/animal/d = 4.55 IU/kg BWd
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
G:F (SE expressed for feed/gain = 0.7)
E0 = 12.4 0.5
Receiving period
231
232
Table 1 (Continued ) Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean SEc (where SE provided)
P value
DMI (d 0–28)
E217 = 3.45 0.22 E380 = 2.98 0.22 E787 = 3.27 0.22 E217 = 1.10 1.20 E380 = 0.75 1.20 E787 = 0.90 1.20 E217 = 1.34 0.20 E380 = 1.13 0.20 E787 = 1.31 0.20 E217 = 1.22 0.10 E380 = 0.95 0.10 E787 = 1.11 0.10 E217 = 0.47 0.05 E380 = 0.39 0.05 E787 = 0.43 0.05 E217 = 0.47 0.05 E380 = 0.39 0.05 E787 = 0.43 0.05 E217 = 0.35 0.01 E380 = 0.33 0.01 E787 = 0.34 0.01 E217 = 0.84 0.14 E380 = 0.81 0.14 E787 = 0.80 0.14
>0.10
ADG (d 0–14)
ADG (d 14–28)
ADG (d 0–28)
G:F (d 14–28)
G:F (d 0–28)
ADG (d 0–164)
Rivera et al., 2002
Random allocation to pen with 3 levels of supplementation.
Exp. 1
Pen was used as the experimental unit for the analysis of all performance data.
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 285 IU/animal/d = 0.75 IU/kg BWd 570 IU/ animal/d = 1.51 IU/kg BWd 1140 IU/animal/d = 3.05 IU/kg BWd
Finishing period (98 d) E285 = 2.00 0.05
>0.10
>0.10
>0.10
>0.10
>0.10
>0.10
0.07
ADG (quadratic effect – E570 = 2.15 0.05 570 IU/animal/d highest)
E1140 = 2.03 0.05 DMI (quadratic effect – E285 = 9.88 0.14 0.04 570 IU/animal/d highest) E570 = 10.28 0.14 E1140 = 9.88 0.14 G:F E285 = 0.20 0.01 >0.10 E570 = 0.21 0.01 E1140 = 0.20 0.01 Rivera et al. Random allocation to (2002) Exp. 2 pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13 to 15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/ animal/d = 5.63 IU/kg BWd
Receiving Period DMI (d 0–14)
E335 = 3.52 0.13
E640 = 3.37 0.13
>0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
G:F (d 0–14)
>0.10
DMI (d 14–28)
DMI (d 0–28)
ADG (d 0–14 – linear increase with vitamin E)
Rivera et al. Random allocation to (2002) Exp. 2 pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13–15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/animal/d = 5.63 IU/kg BWd
E640 = 1.07 0.14 E1148 = 1.27 0.14 E335 = 1.81 0.11 0.06
ADG (d 0–28)
E640 = 1.85 0.11 E1148 = 1.55 0.11 E335 = 1.39 0.06 >0.10 E640 = 1.46 0.06 E1148 = 1.40 0.06
Receiving period
E335 = 0.20 0.54
G:F (d 0–14)
E640 = 0.26 0.54 E1148 = 0.37 0.54 E335 = 0.32 0.03 <0.05
G:F (d 14–28 decrease with higher vitamin E)
G:F (d 0–28 – decrease with higher vitamin E)
ADG (d 0–164)
Finishing period (91 d) ADG DMI
G:F
>0.10
E640 = 0.33 0.03 E1148 = 0.23 0.03 E335 = 0.31 0.01 >0.05 E640 = 0.31 0.01 E1148 = 0.29 0.01 E335 = 0.58 0.01 >0.10 E640 = 0.59 0.01 E1148 = 0.57 0.01 E335 = 1.88 0.04 >0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
ADG (d 14–28 – linear decrease with vitamin E)
E1148 = 3.81 0.13 E335 = 5.90 0.17 >0.10 E640 = 5.75 0.17 E1148 = 6.15 0.17 E335 = 4.71 0.12 >0.10 E640 = 4.56 0.12 E1148 = 4.98 0.12 E335 = 0.93 0.14 0.10
E640 = 1.85 0.04 E1148 = 1.86 0.04 E335 = 9.62 0.24 >0.10 E640 = 9.36 0.24 E1148 = 9.37 0.24 E335 = 0.20 0.08 >0.10 E640 = 0.19 0.08 E1148 = 0.20 0.08
233
0.30 Data not stated. G:F
Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate), or a dietary concentration of 15–60 IU/kg DM (NRC, 1996). b DMI: dry matter intake, kg; G:F: kg of BW gain: kg of DMI; F:G: kg of DMI: kg of BW gain; ADG: average daily BW gain, kg. c The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. d Based on BW at Exp. commencement. e NSD: no significant difference.
a
Data not stated. DMI Feed supplement (source not stated) control = 200 IU/animal/d = 0.63 IU/kg BWd and 1500 IU/animal/d = 4.74 IU/kg BWd 12 pens of 8 animals Vitamin E: not measured Loneragan et al. 2 2 factorial, random (2002) Exp. 2 allocation with 6 weight blocks and 4 levels of supplementation (control, vitamin E, aspirin and vitamin E + aspirin)
Mean SEc (where SE provided) Outcome measuredb Dose or exp. duration Sample size per treatment Basal intakea Study design Reference
Table 1 (Continued )
0.30
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246 P value
234
studies on the effects of antioxidant vitamins in cattle found positive effects on humoral immunity for vitamin E (Reddy et al., 1986, 1987). However, few published experiments examined responses to vitamin E in feedlot cattle. While in vitro studies are important in understanding mechanisms of action, white blood cell responses and antibody responses are not necessarily reflected in improvements in health and production (Droke and Loerch, 1989). The results from experiments measuring health and production outcomes in response to supplemental vitamin E have been variable and therefore difficult to interpret in their entirety. Nevertheless, the perception that increasing vitamin E has the potential to improve health and production in feedlot cattle appears to be common in the feedlot industries of Australia and North America. Statistically liberal interpretations of selected individual experiments can be used to promote supplemental vitamin E. Meta-analysis is a statistical tool that evaluates effects of an intervention for all relevant randomised controlled experiments. Support for the existing NRC (1996) dietary vitamin E recommendations is well documented. The aim of this quantitative evaluation of published studies is to determine if supplementing vitamin E in concentrations that exceed NRC (1996) recommendations, or as an injection at feedlot entry, improve the health and production of feedlot cattle. The effect of selenium supplementation is considered in conjunction with that of vitamin E due to interactions between the selenium containing enzyme, glutathione peroxidase, and vitamin E. 2. Materials and methods 2.1. Literature search and methodology English-language papers published between 1950 and 2006 that investigated the effects of supplemental vitamin E and selenium on feedlot cattle health and production were identified by a computerised literature search (Commonwealth Agricultural Bureau, Agricola, and Biological Abstracts), use of the Hoffmann-LaRoche abstracting service (to 2002), library searches of relevant journals and through citations in review papers. Keywords for computerised searching included vitamin E, feedlot, and, beef cattle. Abstracts and unpublished reports were not accepted. Experiments listed in Tables 1–3 were evaluated for their potential to be included in meta-analysis. There were four evaluators, all of whom were veterinarians with research doctorates, and two had previously published meta-analyses (Morgan and Lean, 1993; Burton and Lean, 1995; Beckett and Lean, 1997; Rabiee et al., 2004, 2005; Duffield et al., 2008a,b). The evaluators assessed the papers for inclusion without reference to the authors or journal. The criteria used for inclusion were a completely randomised design with appropriate controls, the use of supplemental vitamin E and duration of treatment, number of animals, and definition of a common outcome with associated measures of variability. Data extracted from each trial included the number of cattle enrolled, the number of cattle in treatment and control groups, dry matter intake (DMI), average daily gain (ADG), gain:feed ratio (G:F), morbidity, presence or absence of negative (no treatment) or positive (treatment with other medication)
Table 2 Vitamin E and selenium studies with animal as the unit of interest and vitamin E/selenium administered as a dietary supplement. Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Carter et al. (2005)
Split plot randomised complete block (blocked by load, sorted by BW) 4 time levels of supplementation (0, 7, 14 or 28 d)
Vitamin E
E0; 183
Feed supplement
ADG (kg/hd/d)
E0 = 0.95 0.05
0.56
20.3 IU/animal/d (d 0–7) 90.3 IU/animal/d (d 8–14)
E7; 180 E14; 178
1259 IU vitamin E/animal/d (Roche Vitamins, Nutley, NJ) = 6.71 IU/kg BW/d
E7 = 0.99 0.05 E14 = 0.98 0.05 E28 = 1.00 0.05
E28; 174 Morbidity (%)
E0 = 67.8 0.07 E7 = 68.3 0.07 E14 = 61.8 0.07 E28 = 60.3 0.07 Treatments/animal E0 = 0.92 0.80 E7 = 0.84 0.80 E14 = 0.78 0.80 E28 = 0.76 0.80 Treatment cost ($/animal; E0 = 6.29 0.70 tended to decrease with increased d of vitamin E supplement) E7 = 5.67 0.70 E14 = 5.18 0.70 E28 = 4.88 0.70
0.22
>0.10
Arnold et al. (1992) Exp. 1
2 3 factorial (2 treatment levels 3 designated slaughter weights) 3 initial weight blocks with random treatment allocation within blocks
Vitamin E: 9 IU/kg diet DM = 74 IU/animal/d = 0.20 IU/kg BW Se: 0.08 mg/kg diet DM
9 pens of 6 animals
Feed supplement 375 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 1.65 IU vitamin E/kg BW
ADG
E0 = 1.4 0.1
Arnold et al. (1992) Exp. 2
Presumably randomised – not stated
Vitamin E: 126 IU/animal/d = 0.29 IU/kg BW Se: 0.1 mg/kg diet DM
4 animals
Feed supplement 1266 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.90 IU vitamin E/kg BW
ADG
E0 = 1.4 0.1
Arnold et al. (1992) Exp. 3
Presumably randomised – not stated
Vitamin E: 113 IU/animal/d = 0.18 IU/kg BW Se: 0.1 mg/kg diet DM
5 animals
Feed supplement 1317 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.12 IU vitamin E/kg BW
ADG
E0 = 1.2 0.2
0.14
0.08
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Reference
E375 = 1.4 0.1 >0.10
E1266 = 1.4 0.1
235
E1317 = 1.2 0.2
>0.10
236
Table 2 (Continued ) Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Garber et al. (1996) Exp. 1 (beef)
Blocked by BW and randomly allocated to 5 treatment levels
Vitamin E: 167 IU/animal/d = 0.46 IU/kg BWd
15 animals
Feed supplement 333 IU/ animal/d (source not stated) = 0.92 IU/kg BWd or 632 IU/ animal/d = 1.75 IU/kg BWd or 1139 IU/animal/d = 3.16 IU/kg BWd or1920 IU/animal/d = 5.32 IU/kg BWd
ADG
E0 = 1.76 011
>0.10
Garber et al. (1996) Exp. 2 (dairy)
Blocked by BW and randomly allocated to 4 treatment levels
Vitamin E: 167 IU/animal/d
15 animals
Feed supplement 632 IU/ animal/d (source not stated) = 1.73 IU/kg BWd or 1139 IU/ animal/d = 3.11 IU/kg BWd or 1920 IU/animal/d = 5.25 IU/kg BWd
ADG
= 0.46 IU/kg BWd
E0 = 1.41 0.06
>0.10
E632 = 1.45 0.06 E1139 = 1.57 0.06 E1920 = 1.46 0.06
Pehrson et al. (1991) Exp. 1
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
19 animals in 5 pens (first 5 mo)
Feed supplement 200 IU/ animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
ADG first 5 months
Control = 1.15 0.05 >0.05
Pehrson et al. (1991) Exp. 2
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
13 animals in 2 pens (last 4 months)
Feed supplement 200 IU/animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
ADG last 4 mo (animals with higher vitamin E intake grew faster)
Control = 1.13 0.13 <0.05
+E = 1.20 0.08
+E = 1.24 0.12 Pehrson et al. (1991) Exps. 1 and 2
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
19 animals in 5 pens (first 5 months) 13 animals in 2 pens (last 4 months)
Feed supplement 200 IU/animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
Morbidity (%)
Control = 70
E+ = 85
NSDe
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
E333 = 1.64 0.11 E632 = 1.72 0.11 E1139 = 1.88 0.11 E1920 = 1.78 0.11
Carter et al. (2002)
Blocked on weight (2 l evels) and randomly allocated to treatment pens with 4 time levels of supplementation (0, 7, 14, 28 d)
Vitamin E: not measured
E0 = 98
Feed supplement 2000 IU/animal/d (source not stated) = 10.1 IU/kg BWd
ADG
E7 = 98 E14 = 97 E28 = 94 Morbidity (%) (SE not stated)
Mortality (%) (SE not stated)
E7 = 1.06 0.38 E14 = 1.05 0.31 E28 = 1.05 0.36 E0 = 65.3 E7 = 61.2 E14 = 54.6 E28 = 51.1 E0 = 2.0 E7 = 0.0 E14 = 0.0 E28 = 0.0 E0 = 9.23 5.87
>0.05
>0.05
>0.05
0.02
E7 = 8.64 5.27 E14 = 8.08 4.13 E28 = 7.44 3.19 Hays et al. (1997)
Vitamin E: not measured Random allocation to pens for dietary supplement. Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry (Table 3).
2 pens per treatment
Feed supplement (source not stated) 400 IU vitamin E/lb diet = 880 IU/kg diet = 6324 IU/animal/d = 26 IU/kg BWd
Feed supplement (over 28 d)
SE’s not stated
ADG (vitamin E increased)
E0 = 0.75
No. sick days Morbidity (%) (vitamin E decreased)
Rivera et al. (2002) Exp. 1
Random allocation to pen with 3 levels of supplementation
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 217 IU/animal/d = 1.25 IU/kg BWd 380 IU/animal/d = 2.20 IU/kg BWd 787 IU/animal/d = 4.55 IU/kg BWd
E6324 = 1.03 E0 = 4.73 E6324 = 3.62 E0 = 78.1
<0.001
<0.07 <0.05
E6324 = 61.4 E0 = 2.3 E6324 = 0
NSDe
Morbidity (%)
E217 = 53.9
>0.10
(SE not stated)
E380 = 58.3 E787 = 56.4 E217 = 15.4 E380 = 27.8 E787 = 10.3
>0.10 237
Mortality (%)
Retreatment (%) (SE not stated)
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Treatment cost (28 d vitaminE < controls – v. hi. SD’s with overlap)
E0 = 1.02 0.62
238
Table 2 (Continued ) Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Rivera et al. (2002) Exp. 2
Random allocation to pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13 to 15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/animal/d = 5.63 IU/kg BWd
Morbidity (%)
E335 = 53.9
>0.10
(SE not stated)
E640 = 58.3 E1148 = 56.4 E335 = 15.4 E640 = 27.8 E1148 = 10.3
>0.10
Retreatment (%) (SE not stated)
Vitamin E: not measured 32 animals Feed supplement (source not stated) Lung lesions at Data not stated. 2 2 factorial - random control 200 IU/animal/d = = 0.63 IU/kg slaughter allocation with 2 weight d BW and 1500 IU/animal/d blocks and 4 levels of supplementation (control, = 4.75 IU/kg BWd vitamin E, aspirin and vitamin E + aspirin) a Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate), or a dietary concentration of 15–60 IU/kg DM (NRC. 1996. NRC (1996). b ADG = Average daily BW gain, kg. c The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. d Based on BW at Exp. commencement. e NSD = No significant difference.
Loneragan et al. (2002) Exp. 1
NSDe
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Reference
Table 3 Studies with vitamin E/selenium administered as an injection. Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where S.E. provided)
P value
Droke and Loerch (1989) Exp. 1
Completely randomized 2 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
13 animals (individual pens)
Injection of 25 mg Se + 340 IU vitamin E (source not stated) = 0.09 mg Se/kg BWd + 1.27 IU vitamin E/kg BWd
ADG
S.E.’s not stated
>0.05
DMI G:F
Randomised complete block (blocked by 2 sources) 4 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
35 animals except for DMI and G:F with 3 pens
Injection of 25 mg Se &/or 340 IU vitamin E (Source not stated) = 0.12 mg Se/kg BWd + 1.67 IU vitamin E/kg BWd
ADG
DMI
G:F
No. sick days
Morbidity (%)
Droke and Loerch (1989) Exp. 3
Completely randomized 4 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
26 animals except for DMI and G:F with 3 pens
Injection of 25 mg Se &/or 340 IU vitamin E (source not stated) = 0.12 mg Se/kg BWd + 1.61 IU vitamin E/kg BWd
ADG
DMI
>0.05 >0.05
SE’s not stated
E0 = 0.84 +Se = 0.84 E340 = 0.75 E+Se = 0.81 E0 = 3.71 +Se = 3.61 E340 = 3.69 E+Se = 3.69 E0 = 0.23 +Se = 0.23 E340 = 0.20 E+Se = 0.22 E0 = 0.88 +Se = 1.08 E340 = 0.72 E+Se = 0.60 E0 = 54.8 +Se = 55.6 E340 = 46.2 E+Se = 43.0
>0.05
>0.05
>0.05
>0.05
>0.05
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Droke and Loerch, 1989 Exp. 2
E0 = 0.47 E+Se = 0.21 E0 = 4.11 E+Se = 3.98 E0 = 0.11 E+Se = 0.06
SE’s not stated
>0.05
>0.05 239
E0 = 0.88 +Se = 0.95 E340 = 0.94 E+Se = 0.95 E0 = 4.30 +Se = 4.48 E340 = 4.36
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
G:F
No. sick days
Morbidity (%)
Completely randomized 3 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
16 animals per treatment (individual pens)
Injection of 25 mg Se + 340 IU vitamin E day 14 or repeat injection d 0 (source not stated) = 0.10 mg Se/kg BWd + 1.37 IU vitaminE/kg BWd
ADG
DMI
G:F
No. sick days
Droke and Loerch (1989) Exp. 5
Completely randomized 3 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
35 animals except for DMI and G:F with 4 pens
Injection of 25 mg Se + 340 IU vitamin E (source not stated) = 0.12 mg Se/kg BWd + 1.66 IU vitamin E/kg BWd or 50 mg Se + 680 IU vitamin E = 0.24 mg Se/kg BWd + 3.32 IU vitamin E/kg BWd
ADG
DMI
G:F
No. sick days
Morbidity %
E+Se = 4.38 E0 = 0.20 +Se = 0.21 E340 = 0.22 E+Se = 0.22 E0 = 0.64 +Se = 0.59 E340 = 0.67 E+Se = 0.52 E0 = 35.6 +Se = 33.3 E340 = 40.7 E+Se = 44.4
P value
>0.05
>0.05
>0.05
SE’s not stated
Control = 0.83 ESe-14 = 0.87 ESe-14.0 = 0.84 Control = 4.65 ESe-14 = 4.71 ESe-14.0 = 4.67 Control = 0.17 ESe-14 = 0.18 ESe-14.0 = 0.18 Control = 0.06 ESe-14 = 0.31 ESe-14.0 = 0.13
>0.05
>0.05
>0.05
>0.05
SE’s not stated
E0 = 0.84 E340Se25 = 0.48 E680Se50 = 0.71 E0 = 3.94 E340Se25 = 3.34 E680Se50 = 3.74 E0 = 0.22 E340Se25 = 0.14 E680Se50 = 0.18 E0 = 0.86 E340Se25 = 1.89 E680Se50 = 1.16 E0 = 46.2
>0.05
>0.05
>0.05
>0.05
>0.05
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Droke and Loerch (1989) Exp. 4
Mean S.E.c (where S.E. provided)
240
Table 3 (Continued ) Reference
NSDe
e
d
c
b
Mortality %
Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate; NRC (1996). ADG: average daily BW gain, kg; DMI: dry matter intake, kg; G:F = kg of BW gain: kg of dry matter intake. The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. Based on BW at Exp. commencement. NSD: no significant difference.
Morbidity %
241
controls. The details of the treatment protocol including the dose and route of administration of vitamin E were also extracted from the eligible papers. Thirty-five of 70 experiments or specified periods within experiments were eligible for meta-analysis. The unit of interest for dietary vitamin E was the pen, and the unit of interest for injectable vitamin E was the animal.
a
NSDe
<0.06 No. sick days (vitamin E increased)
E0 = 0.91 E3000 = 0.87 E0 = 3.60 E3000 = 4.75 E0 = 65.6 E3000 = 73.9 No mortalities ADG
SE’s not stated Injection (over 28 d) Injection of 3000 IU/animal (product not stated) = 12.3 IU/kg BWd 65 animals Vitamin E: not measured Random allocation to pens for dietary supplement (Table 2). Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry Hays et al. (1997)
E340Se25 = 73.3 E680Se50 = 60.6
NSD
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2.2. Statistical analysis The effects of vitamin E on DMI, ADG, and G:F were evaluated using the standardised mean difference or effect size methods (Cohen, 1988). Reported standard errors and number of animals for the treatment and control groups were used to calculate standard deviations. The effect size is the difference between the standardized treatment and control groups, expressed as DMI, ADG or G:F, divided by the standard deviations, that is, a Z score for the treatment group mean in the control group population (Cohen, 1988). A negative effect size indicates that cattle supplemented with additional vitamin E had lower DMI, ADG or G:F compared with controls. Morbidity and mortality risk data were analysed as risk ratios. Risk ratio estimates on data pooled across experiments were obtained with a fixed effects model (Mantel and Haenszel, 1959). Forest plots were used to present the effect size and risk ratio data. Each experiment is represented by a black square and a horizontal line, showing the point estimate and the 95% confidence interval of the individual experiment-level effect size and risk ratio. Variation in experiment level risk ratios was assessed with a x2-test for heterogeneity. The null hypothesis was that the effect of supplemental vitamin E was the same across k trials and this was rejected if the heterogeneity test statistic was greater than a critical value that separated the upper 10% of a x2 distribution with (k 1) degrees of freedom. An a level of 0.10 was used because of the relatively poor power of the x2-test to detect heterogeneity among small numbers of experiments (Egger and Smith, 2001). Heterogeneity of results among trials was quantified using the I2 statistic (Higgins et al., 2003). The I2 statistic describes the percentage of total variation across studies that is due to heterogeneity rather than chance. Where Q is the x2 heterogeneity statistic and k is the number of trials, I2 was calculated as I2 ¼
Q ðk 1Þ 100 Q
Uncertainty intervals for I2 (dependent on Q and k) were calculated using the method described by Higgins and Thompson (2002). Negative values of I2 were put equal to 0, consequently I2 lay between 0 and 100%. A value greater than 50% indicates substantial heterogeneity in the data. With heterogeneous data, a random effects model was used to estimate effect size or risk ratio (Der Simonian and Laird, 1986). A meta-regression analysis was used in this study to explore the source of heterogeneity of response, using the individual effect size for each trial as the outcome and the associated standard error as the measure of variance. Meta-regression can formally test whether there is evidence of different effects in different subgroups of
242
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trials. It examines the relationship between one or more study-level characteristics and the sizes of effect observed in the studies. Meta-regression extends a random effects meta-analysis to estimate the extent to which one or more covariates, with values defined for each study in the analysis, explain heterogeneity in the treatment effects. The presence of publication bias was investigated using funnel plots (Light and Pillemer, 1984). Funnel plots display a measure of study size on the horizontal axis against intervention or treatment effect on the vertical axis. The precision of the estimation of the intervention or treatment effect increases as the size of component studies increases. Results from smaller studies therefore scatter more widely, with the spread narrowing among larger studies. In the absence of bias, the plot resembles a symmetrical funnel on its side. If there is bias, for example, because smaller studies showing no statistically significant effects remain unpublished, the plot will be asymmetrical. In these situations, the effect calculated in the metaanalysis may have been overestimated. However, funnel plot asymmetry may reflect other types of bias, or even result from the true intervention or treatment effect differing between small and large studies. The small number of experiments eligible for meta-analysis in this study made interpretation of funnel plots difficult and the results are therefore not reported. Publication bias was also investigated statistically using both Begg’s test (Begg and Manumdar, 1994), and Egger’s test (Egger et al., 1997). However, because these tests have low power and there is some debate regarding their statistical properties, potentials and limitations, these were not reported. 3. Results and discussion 3.1. Dietary vitamin E with or without additional selenium Selenium was supplemented in the diet at concentrations from 0.08 to 0.1 mg/kg dry matter (DM) as reported
in five of the experiments listed in Tables 1 and 2. No significant effects of selenium, either solely, or as a result of interactions with vitamin E were identified. The selenium concentrations supplemented in the diets reported all exceeded the recommendation in the Feeding Standards for Australian Livestock (1990) of 0.05 mg/kg DM. The low number of studies reporting selenium treatments and confounding with vitamin E treatment prevented further statistical evaluation. Of 67 study outcomes listed in Tables 1 and 2, only two studies found significant effects of vitamin E on DMI (2 of 11; Rivera et al., 2002, Exp. 1; Hays et al., 1997), two on ADG (2 of 12; Hays et al., 1997; Pehrson et al., 1991), two on G:F (2 of 11; Rivera et al., 2002, Exp. 2), one on morbidity (1 of 6; Hays et al., 1997) and one on treatment cost (1 of 2; Carter et al., 2002). However, supplemental dietary vitamin E was associated with a negative effect on G:F over the first 28 days in the feedlot (Rivera et al., 2002, Exp. 2). Further, the positive effects Hays et al. (1997) found on DMI, ADG and morbidity were compared to cattle that received no supplemental vitamin E and the positive effect found by Carter et al. (2002) on mean treatment cost, occurred with cattle fed 2000 IU vitamin E animal1 d1 for 28 days compared with cattle not supplemented. Therefore, the experiments of Hays et al. (1997) and Carter et al. (2002) did not show positive effects for supplementing vitamin E at concentrations that exceeded the NRC recommendation, only that supplementing cattle with dietary vitamin E could improve health and production compared with cattle not supplemented with dietary vitamin E. 3.2. Effects of dietary vitamin E on morbidity The risk ratios derived from studies examining the effects of dietary vitamin E on morbidity in Fig. 1 shows a trend (P = 0.09) towards a reduction in morbidity with supplemental vitamin E. However, the only study with a
Fig. 1. Risk ratios, 95% confidence intervals and percentage weight for individual studies on dietary vitamin E and morbidity. Only studies of at least 28 days duration are included (heterogeneity x2 = 8.93 (d.f. = 7), P = 0.26; overall risk ratio = 0.92, z = 1.69, P = 0.09).
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243
Fig. 2. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of dry matter intake (heterogeneity x2 = 4.3 (d.f. = 5), P = 0.51; overall effect size =0.04, z = 0.17, P = 0.86).
statistically significant improvement in morbidity in response to dietary vitamin E (Hays et al., 1997; P < 0.05) was a comparison between cattle supplemented with very high dietary concentrations of vitamin E and cattle provided with no additional vitamin E. Further, meta-regression of studies measuring the effects of dietary vitamin E on morbidity from Table 2 showed that within
the range of vitamin E doses reported, dose/animal and dose/kg BW were not significant (P = 0.61 for both). Conversely, longer duration of feeding dietary vitamin E was associated with a reduction in morbidity (P < 0.01). These findings indicate that prolonged exposure, rather than increased dietary concentrations, might be beneficial to cattle health.
Fig. 3. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of average daily gain (heterogeneity x2 = 8.97 (d.f. = 14); P = 0.83; overall effect size = 0.06, z = 1.13, P = 0.26).
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244
Fig. 4. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of gain:feed ratio (kg of BW gain: kg of dry matter intake). (Heterogeneity x2 = 0.44 (d.f. = 5), P = 0.99; overall effect size = 0.05, z = 0.20, P = 0.84).
3.3. Effects of dietary vitamin E on production—dry matter intake, average daily gain and gain:feed The forest plots of effect size of dietary vitamin E on DMI (Fig. 2), ADG (Fig. 3), and G:F (Fig. 4), show no significant effects resulting from vitamin E supplementation of diets (all P > 0.26). While a small number of studies were assessed, it appears that production responses to increased dietary vitamin E, above NRC (1996) recommended concentrations, are unlikely. There were insufficient studies to interpret the results of influence analysis with DMI and G:F, and insufficient studies to interpret funnel plots to detect publication bias with DMI, G:F and ADG. No studies significantly influenced the pooled estimates of effect size with ADG. The effect on DMI of supplemental dietary vitamin E found by Rivera et al. (2002, Exp. 1, finishing period) was identified for a 98 days finishing period. Responses in this study can be considered in terms of the NRC dietary vitamin E concentration recommendation of 15– 60 IU/kg of diet DM (NRC, 1996). The estimated dietary vitamin E concentration (Rivera et al., 2002) associated with the greatest (P = 0.04) DMI was 55.4 IU/kg DM, compared with 28.8 IU/kg DM and 115.4 IU/kg DM. The
55.4 IU/kg concentration falls within the upper limit of the NRC recommendation. A similar positive effect was found by Rivera et al. (2002, Exp. 1, finishing period) for ADG, but the result was not significant (P = 0.07). Pehrson et al. (1991, Exp. 2, finishing period) also found a significant effect of supplemental dietary vitamin E on ADG during a 4-month finishing period. In this experiment, a calculated supplemental dietary vitamin E concentration of 66.1 IU/kg DM was associated with greater (P < 0.05) ADG than a concentration of 15.1 IU/kg DM. The positive effects of these individual experiments on DMI and ADG indicate that there are potential benefits from feeding diets that have vitamin E concentrations close to the upper limit of the NRC (1996) recommendation. 3.4. Vitamin E and selenium injection Table 3 lists five experiments where selenium was injected in combination with vitamin E. There were no significant effects on health or production associated with selenium either solely or in combination with vitamin E (Table 3) and insufficient data for meta-analysis. Injecting vitamin E at doses from 340 to 3000 IU (1.27– 12.3 IU/kg BW) resulted in no significant positive effects on
Table 4 Summary of pooled effect size for dry matter intake, average daily gain, and gain:feed ratio, and pooled risk ratios for morbidity with cattle supplemented or injected with vitamin E. Outcome
ES/RRa (95% CI)
Dry matter intake Average daily gain Gain:feed ratio
0.04 (0.44, 0.53) 0.06 (0.04, 0.16) 0.05 (0.40, 0.50)
Morbidity (Dietary vitamin E) (Vitamin E injection)
0.92 (0.84, 1.01) 1.17 (0.94, 1.45)
a
ES = effect size/RR = risk ratio.
n
P value
I2
Heterogeneity 2
Q
d.f.
P value
6 15 6
0.86 0.26 0.84
4.3 9.0 0.44
5 14 5
0.51 0.83 0.99
0 0 0
5 5
0.09 0.17
8.9 8.6
7 4
0.26 0.07
22 53
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Fig. 5. Risk ratios, 95% confidence intervals and percentage weights for individual studies on vitamin E injection and morbidity. The studies are of at least 28 days duration (heterogeneity x2 = 8.57 (d.f. = 4), P = 0.07; overall risk ratio = 1.17, z = 1.39, P = 0.17).
health or production (Table 3). Similarly, Cusack et al. (2008) found no significant effects on health or production of feedlot cattle when injected with vitamin E at feedlot entry at concentrations from 250 to 5000 IU (0.74–14.7 IU/ kg BW), except that incidence of anorexia was greater (P = 0.02) in the cattle given the highest vitamin E dose. The data from studies that examined the effect of vitamin E injection on morbidity was heterogeneous (x2 = 8.57, P = 0.07, I2 > 50%; Table 4), so a random effects model was used to estimate a pooled risk ratio (Fig. 5). This metaanalysis shows vitamin E injection did not have a significant effect on morbidity (P = 0.17). Table 4 summarises the results presented in Figs. 1–5, and indicates whether or not the data for each outcome is heterogeneous with the I2 statistic. In keeping with the effect size plots and the x2 heterogeneity tests, only morbidity responses to vitamin E injection varied across experiments greater than expected by chance (I2 > 50%). One of these experiments (Droke and Loerch, 1989; Exp. 2) found reduced morbidity while all others found an increase. Vitamin E and selenium were both administered in this experiment, without a treatment group using vitamin E alone. However, similar doses of selenium were used in the other experiments in this series of studies, and no significant effects on health were observed from injection with selenium alone. The heterogeneity in this data set might reflect the difficulty of consistently measuring the outcome of morbidity rather than genuine differences in experimental outcomes. 4. Conclusions This meta-analysis indicates that feeding vitamin E at concentrations greater than the NRC recommendation (1996), or the administration of vitamin E as an injection, does not improve ADG, G:F or morbidity in feedlot cattle.
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Contents lists available at ScienceDirect
Preventive Veterinary Medicine journal homepage: www.elsevier.com/locate/prevetmed
Review
Assessment of the effects of supplementation with vitamin E on health and production of feedlot cattle using meta-analysis Paul Cusack a,*, Neil McMeniman b, Ahmad Rabiee c, Ian Lean c a
Australian Livestock Production Services, 102 Darling St., Cowra, NSW 2794, Australia School of Veterinary Science, University of Queensland, St. Lucia, Qld 4067, Australia c Strategic Bovine Services, P.O. Box 660, Camden, NSW 2570, Australia b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 October 2007 Received in revised form 12 September 2008 Accepted 11 December 2008
Delivery of supplemental antioxidant vitamins to cattle placed in feedlots might be expected to improve health and performance outcomes by reducing the effects of oxidative stress to which these cattle are presumably exposed. Meta-analytic procedures were used in this study to assess published experiments on the effects of vitamin E supplementation in feedlot cattle. The health outcome of morbidity, and the production outcomes of average daily gain (ADG) and gain to feed ratio (G:F), were analysed. The currently available data do not support the use of supplemental vitamin E administered as an injection (morbidity risk ratio = 1.17; P = 0.17). The authors conclude that supplemental dietary vitamin E should be fed within the [NRC, 1996. National Research Council. Nutrient Requirements of Beef Cattle, 7th ed. Natl. Acad. Press, Washington, DC] recommended range. ß 2009 Elsevier B.V. All rights reserved.
Keywords: Systematic review Dietary supplement Injection
Contents 1. 2.
3.
4.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Literature search and methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Dietary vitamin E with or without additional selenium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Effects of dietary vitamin E on morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Effects of dietary vitamin E on production—dry matter intake, average daily gain and gain:feed . . . . . . . . . . . . . . . 3.4. Vitamin E and selenium injection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
229 234 234 241 242 242 242 244 244 245 245
1. Introduction
* Corresponding author. Tel.: +61 2 6341 3113; fax: +61 2 6342 1795. E-mail address: [email protected] (P. Cusack). 0167-5877/$ – see front matter ß 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.prevetmed.2008.12.002
Cattle newly arrived at a feedlot are usually exposed to oxidative challenges arising from transport and handling (Sconberg et al., 1993), fasting (Nockels et al., 1996), and possibly, dietary polyunsaturated fatty acids (MacPherson, 1994) and bovine respiratory disease (Breazile, 1988). Some
230
Table 1 Vitamin E and selenium studies with pen as the unit of interest and vitamin E/selenium administered as a dietary supplement. Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean SEc (where SE provided)
P value
Carter et al. (2005)
Split plot randomised complete block (blocked by load, sorted by BW) 4 time levels of supplementation (0, 7, 14 or 28 d)
Vitamin E 20.3 IU/animal/d (d 0–7) 90.3 IU/animal/d (d 8–14)
7 pens of 174– 183 animals
Feed supplement 1259 IU vitamin E/animal/d (Roche vitamins, nutley, NJ) = 6.71 IU/kg BW/d
DMI
E0 = 4.33 0.25
0.31
G:F
E7 = 4.38 0.25 E14 = 4.53 0.25 E28 = 4.49 0.25 E0 = 0.20 0.14 E7 = 0.20 0.14 E14 = 0.19 0.14 E28 = 0.20 0.14
0.87
DMI
E0 = 6.6 0.1
>0.10
G:F
E375 = 6.6 0.1 E0 = 0.22 0.01 E375 = 0.22 0.01
>0.10
E0 = 8.1 0.3
>0.10
Arnold et al. 2 3 factorial (2 (1992) Exp. 1 treatment levels 3 designated slaughter weights) 3 initial weight blocks with random treatment allocation within blocks
Arnold et al. Presumably randomised – (1992) Exp. 2 not stated
Vitamin E: 9 IU/kg diet DM = 9 pens of 6 animals 74 IU/animal/d = 0.20 IU/kg BW Se: 0.08 mg/kg diet DM
Vitamin E: 126 IU/animal/d = 0.29 IU/kg BW Se: 0.1 mg/kg diet DM
4 animals in 1 pen
Feed supplement 375 IU/animal/d (Rovimix E-40% dispersable liquid concentrate, Roche vitamins, Nutley, NJ) = 1.65 IU vitamin E/kg BW
DMI Feed supplement 1266 IU/animal/d (Rovimix E-40% dispersable liquid concentrate, Roche Vitamins, Nutley, NJ) = 2.90 IU vitamin E/kg BW
E1266 = 8.0 0.3 G:F
>0.10 E0 = 0.17 0.01 E1266 = 0.18 0.01
Arnold et al. Presumably randomised – (1992) Exp. 3 not stated
Garber et al. (1996) Exp. 1 (beef)
Blocked by BW and randomly allocated to 5 treatment levels
Vitamin E: 113 IU/animal/d = 0.18 IU/kg BW Se: 0.1 mg/kg diet DM
Vitamin E: 167 IU/animal/d = 0.46 IU/kg BWd
5 animals in 1 pen
15 animals (no. of pens not stated)
Feed supplement 1317 IU/animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.12 IU vitamin E/kg BW
Feed supplement 333 IU/animal/d (source not stated) = 0.92 IU/kg BWd or 632 IU/animal/d = 1.75 IU/kg BWd or 1139 IU/ animal/d =3.16 IU/kg BWd or 1920 IU/animal/d = 5.32 IU/kg BWd
DMI
E0 = 8.1 0.4
G:F
E1317 = 7.8 0.4 E0 = 0.15 0.02 >0.10 E1317 = 0.17 0.02
DMI
E0 = 11.8 0.4
>0.10
>0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Reference
G:F (SE expressed for feed/gain = 0.5)
E333 = 10.9 0.4 E632 = 11.2 0.4 E1139 = 12.4 0.4 E1920 = 11.8 0.4 E0 = 0.12 E333 = 0.12
>0.10
E632 = 0.12 E1139 = 0.12 E1920 = 0.12 Garber et al. (1996) Exp. 2 (dairy)
Blocked by BW and randomly Vitamin E: 167 IU/animal/d allocated to 4 treatment levels = 0.46 IU/kg BWd
15 animals (no. of pens Feed supplement 632 IU/animal/d not stated) (source not stated) = 1.73 IU/kg BWd or 1139 IU/animal/d = 3.11 IU/kg BWd or 1920 IU/animal/d = 5.25 IU/kg BWd
DMI
E632 = 12.5 0.5 E1139 = 12.5 0.5 E1920 = 12.6 0.5 E0 = 0.09 E632 = 0.10
>0.10
>0.10
E1139 = 0.10 E1920 = 0.10 Hays et al. (1997)
Random allocation to pens for dietary supplement. Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry
Vitamin E: not measured
2 pens of 32 animals for Feed supplement (source not stated) 400 IU vitamin E/lb diet = 880 IU/kg feed supplement & 65 diet = 6324 IU/animal/d = 26 IU/kg animals for injection BWd injection of 3000 IU/animal (product not stated) = 12.3 IU/kg BW
Feed supplement (over 28 d)
SE’s not stated
DMI (vitamin E increased)
E0 = 6.93
<0.01
E6324 = 7.19 E0 = 0.11 E6324 = 0.15
NSDe
DMI (d 0–14)
E217 = 2.29 0.15
>0.10
DMI (d 14–28)
E380 = 2.00 0.15 E787 = 2.07 0.15 E217 = 4.82 0.33 E380 = 4.32 0.33 E787 = 4.65 0.33
>0.10
G:F
Rivera et al. Random allocation to pen (2002) Exp. 1 with 3 levels of supplementation.
Pen was used as the experimental unit for the analysis of all performance data.
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 217 IU/animal/d = 1.25 IU/kg BWd 380 IU/animal/d = 2.20 IU/kg BWd 787 IU/animal/d = 4.55 IU/kg BWd
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
G:F (SE expressed for feed/gain = 0.7)
E0 = 12.4 0.5
Receiving period
231
232
Table 1 (Continued ) Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean SEc (where SE provided)
P value
DMI (d 0–28)
E217 = 3.45 0.22 E380 = 2.98 0.22 E787 = 3.27 0.22 E217 = 1.10 1.20 E380 = 0.75 1.20 E787 = 0.90 1.20 E217 = 1.34 0.20 E380 = 1.13 0.20 E787 = 1.31 0.20 E217 = 1.22 0.10 E380 = 0.95 0.10 E787 = 1.11 0.10 E217 = 0.47 0.05 E380 = 0.39 0.05 E787 = 0.43 0.05 E217 = 0.47 0.05 E380 = 0.39 0.05 E787 = 0.43 0.05 E217 = 0.35 0.01 E380 = 0.33 0.01 E787 = 0.34 0.01 E217 = 0.84 0.14 E380 = 0.81 0.14 E787 = 0.80 0.14
>0.10
ADG (d 0–14)
ADG (d 14–28)
ADG (d 0–28)
G:F (d 14–28)
G:F (d 0–28)
ADG (d 0–164)
Rivera et al., 2002
Random allocation to pen with 3 levels of supplementation.
Exp. 1
Pen was used as the experimental unit for the analysis of all performance data.
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 285 IU/animal/d = 0.75 IU/kg BWd 570 IU/ animal/d = 1.51 IU/kg BWd 1140 IU/animal/d = 3.05 IU/kg BWd
Finishing period (98 d) E285 = 2.00 0.05
>0.10
>0.10
>0.10
>0.10
>0.10
>0.10
0.07
ADG (quadratic effect – E570 = 2.15 0.05 570 IU/animal/d highest)
E1140 = 2.03 0.05 DMI (quadratic effect – E285 = 9.88 0.14 0.04 570 IU/animal/d highest) E570 = 10.28 0.14 E1140 = 9.88 0.14 G:F E285 = 0.20 0.01 >0.10 E570 = 0.21 0.01 E1140 = 0.20 0.01 Rivera et al. Random allocation to (2002) Exp. 2 pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13 to 15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/ animal/d = 5.63 IU/kg BWd
Receiving Period DMI (d 0–14)
E335 = 3.52 0.13
E640 = 3.37 0.13
>0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
G:F (d 0–14)
>0.10
DMI (d 14–28)
DMI (d 0–28)
ADG (d 0–14 – linear increase with vitamin E)
Rivera et al. Random allocation to (2002) Exp. 2 pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13–15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/animal/d = 5.63 IU/kg BWd
E640 = 1.07 0.14 E1148 = 1.27 0.14 E335 = 1.81 0.11 0.06
ADG (d 0–28)
E640 = 1.85 0.11 E1148 = 1.55 0.11 E335 = 1.39 0.06 >0.10 E640 = 1.46 0.06 E1148 = 1.40 0.06
Receiving period
E335 = 0.20 0.54
G:F (d 0–14)
E640 = 0.26 0.54 E1148 = 0.37 0.54 E335 = 0.32 0.03 <0.05
G:F (d 14–28 decrease with higher vitamin E)
G:F (d 0–28 – decrease with higher vitamin E)
ADG (d 0–164)
Finishing period (91 d) ADG DMI
G:F
>0.10
E640 = 0.33 0.03 E1148 = 0.23 0.03 E335 = 0.31 0.01 >0.05 E640 = 0.31 0.01 E1148 = 0.29 0.01 E335 = 0.58 0.01 >0.10 E640 = 0.59 0.01 E1148 = 0.57 0.01 E335 = 1.88 0.04 >0.10
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
ADG (d 14–28 – linear decrease with vitamin E)
E1148 = 3.81 0.13 E335 = 5.90 0.17 >0.10 E640 = 5.75 0.17 E1148 = 6.15 0.17 E335 = 4.71 0.12 >0.10 E640 = 4.56 0.12 E1148 = 4.98 0.12 E335 = 0.93 0.14 0.10
E640 = 1.85 0.04 E1148 = 1.86 0.04 E335 = 9.62 0.24 >0.10 E640 = 9.36 0.24 E1148 = 9.37 0.24 E335 = 0.20 0.08 >0.10 E640 = 0.19 0.08 E1148 = 0.20 0.08
233
0.30 Data not stated. G:F
Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate), or a dietary concentration of 15–60 IU/kg DM (NRC, 1996). b DMI: dry matter intake, kg; G:F: kg of BW gain: kg of DMI; F:G: kg of DMI: kg of BW gain; ADG: average daily BW gain, kg. c The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. d Based on BW at Exp. commencement. e NSD: no significant difference.
a
Data not stated. DMI Feed supplement (source not stated) control = 200 IU/animal/d = 0.63 IU/kg BWd and 1500 IU/animal/d = 4.74 IU/kg BWd 12 pens of 8 animals Vitamin E: not measured Loneragan et al. 2 2 factorial, random (2002) Exp. 2 allocation with 6 weight blocks and 4 levels of supplementation (control, vitamin E, aspirin and vitamin E + aspirin)
Mean SEc (where SE provided) Outcome measuredb Dose or exp. duration Sample size per treatment Basal intakea Study design Reference
Table 1 (Continued )
0.30
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246 P value
234
studies on the effects of antioxidant vitamins in cattle found positive effects on humoral immunity for vitamin E (Reddy et al., 1986, 1987). However, few published experiments examined responses to vitamin E in feedlot cattle. While in vitro studies are important in understanding mechanisms of action, white blood cell responses and antibody responses are not necessarily reflected in improvements in health and production (Droke and Loerch, 1989). The results from experiments measuring health and production outcomes in response to supplemental vitamin E have been variable and therefore difficult to interpret in their entirety. Nevertheless, the perception that increasing vitamin E has the potential to improve health and production in feedlot cattle appears to be common in the feedlot industries of Australia and North America. Statistically liberal interpretations of selected individual experiments can be used to promote supplemental vitamin E. Meta-analysis is a statistical tool that evaluates effects of an intervention for all relevant randomised controlled experiments. Support for the existing NRC (1996) dietary vitamin E recommendations is well documented. The aim of this quantitative evaluation of published studies is to determine if supplementing vitamin E in concentrations that exceed NRC (1996) recommendations, or as an injection at feedlot entry, improve the health and production of feedlot cattle. The effect of selenium supplementation is considered in conjunction with that of vitamin E due to interactions between the selenium containing enzyme, glutathione peroxidase, and vitamin E. 2. Materials and methods 2.1. Literature search and methodology English-language papers published between 1950 and 2006 that investigated the effects of supplemental vitamin E and selenium on feedlot cattle health and production were identified by a computerised literature search (Commonwealth Agricultural Bureau, Agricola, and Biological Abstracts), use of the Hoffmann-LaRoche abstracting service (to 2002), library searches of relevant journals and through citations in review papers. Keywords for computerised searching included vitamin E, feedlot, and, beef cattle. Abstracts and unpublished reports were not accepted. Experiments listed in Tables 1–3 were evaluated for their potential to be included in meta-analysis. There were four evaluators, all of whom were veterinarians with research doctorates, and two had previously published meta-analyses (Morgan and Lean, 1993; Burton and Lean, 1995; Beckett and Lean, 1997; Rabiee et al., 2004, 2005; Duffield et al., 2008a,b). The evaluators assessed the papers for inclusion without reference to the authors or journal. The criteria used for inclusion were a completely randomised design with appropriate controls, the use of supplemental vitamin E and duration of treatment, number of animals, and definition of a common outcome with associated measures of variability. Data extracted from each trial included the number of cattle enrolled, the number of cattle in treatment and control groups, dry matter intake (DMI), average daily gain (ADG), gain:feed ratio (G:F), morbidity, presence or absence of negative (no treatment) or positive (treatment with other medication)
Table 2 Vitamin E and selenium studies with animal as the unit of interest and vitamin E/selenium administered as a dietary supplement. Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Carter et al. (2005)
Split plot randomised complete block (blocked by load, sorted by BW) 4 time levels of supplementation (0, 7, 14 or 28 d)
Vitamin E
E0; 183
Feed supplement
ADG (kg/hd/d)
E0 = 0.95 0.05
0.56
20.3 IU/animal/d (d 0–7) 90.3 IU/animal/d (d 8–14)
E7; 180 E14; 178
1259 IU vitamin E/animal/d (Roche Vitamins, Nutley, NJ) = 6.71 IU/kg BW/d
E7 = 0.99 0.05 E14 = 0.98 0.05 E28 = 1.00 0.05
E28; 174 Morbidity (%)
E0 = 67.8 0.07 E7 = 68.3 0.07 E14 = 61.8 0.07 E28 = 60.3 0.07 Treatments/animal E0 = 0.92 0.80 E7 = 0.84 0.80 E14 = 0.78 0.80 E28 = 0.76 0.80 Treatment cost ($/animal; E0 = 6.29 0.70 tended to decrease with increased d of vitamin E supplement) E7 = 5.67 0.70 E14 = 5.18 0.70 E28 = 4.88 0.70
0.22
>0.10
Arnold et al. (1992) Exp. 1
2 3 factorial (2 treatment levels 3 designated slaughter weights) 3 initial weight blocks with random treatment allocation within blocks
Vitamin E: 9 IU/kg diet DM = 74 IU/animal/d = 0.20 IU/kg BW Se: 0.08 mg/kg diet DM
9 pens of 6 animals
Feed supplement 375 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 1.65 IU vitamin E/kg BW
ADG
E0 = 1.4 0.1
Arnold et al. (1992) Exp. 2
Presumably randomised – not stated
Vitamin E: 126 IU/animal/d = 0.29 IU/kg BW Se: 0.1 mg/kg diet DM
4 animals
Feed supplement 1266 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.90 IU vitamin E/kg BW
ADG
E0 = 1.4 0.1
Arnold et al. (1992) Exp. 3
Presumably randomised – not stated
Vitamin E: 113 IU/animal/d = 0.18 IU/kg BW Se: 0.1 mg/kg diet DM
5 animals
Feed supplement 1317 IU/ animal/d (Rovimix E-40% Dispersable Liquid Concentrate, Roche Vitamins, Nutley, NJ) = 2.12 IU vitamin E/kg BW
ADG
E0 = 1.2 0.2
0.14
0.08
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Reference
E375 = 1.4 0.1 >0.10
E1266 = 1.4 0.1
235
E1317 = 1.2 0.2
>0.10
236
Table 2 (Continued ) Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Garber et al. (1996) Exp. 1 (beef)
Blocked by BW and randomly allocated to 5 treatment levels
Vitamin E: 167 IU/animal/d = 0.46 IU/kg BWd
15 animals
Feed supplement 333 IU/ animal/d (source not stated) = 0.92 IU/kg BWd or 632 IU/ animal/d = 1.75 IU/kg BWd or 1139 IU/animal/d = 3.16 IU/kg BWd or1920 IU/animal/d = 5.32 IU/kg BWd
ADG
E0 = 1.76 011
>0.10
Garber et al. (1996) Exp. 2 (dairy)
Blocked by BW and randomly allocated to 4 treatment levels
Vitamin E: 167 IU/animal/d
15 animals
Feed supplement 632 IU/ animal/d (source not stated) = 1.73 IU/kg BWd or 1139 IU/ animal/d = 3.11 IU/kg BWd or 1920 IU/animal/d = 5.25 IU/kg BWd
ADG
= 0.46 IU/kg BWd
E0 = 1.41 0.06
>0.10
E632 = 1.45 0.06 E1139 = 1.57 0.06 E1920 = 1.46 0.06
Pehrson et al. (1991) Exp. 1
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
19 animals in 5 pens (first 5 mo)
Feed supplement 200 IU/ animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
ADG first 5 months
Control = 1.15 0.05 >0.05
Pehrson et al. (1991) Exp. 2
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
13 animals in 2 pens (last 4 months)
Feed supplement 200 IU/animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
ADG last 4 mo (animals with higher vitamin E intake grew faster)
Control = 1.13 0.13 <0.05
+E = 1.20 0.08
+E = 1.24 0.12 Pehrson et al. (1991) Exps. 1 and 2
Systematic allocation to achieve similar distributions of BW and breeds
Vitamin E (control intake): 50 IU/animal/d (first 2 months) 100 IU/animal/d (next 2 months) 150 IU/ animal/d (remainder of period)
19 animals in 5 pens (first 5 months) 13 animals in 2 pens (last 4 months)
Feed supplement 200 IU/animal/d (source not stated) (first 2 months) 400 IU/animal/d (next 2 months) 600 IU/animal/d (remainder of period) = approx. 2 IU/kg BW
Morbidity (%)
Control = 70
E+ = 85
NSDe
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
E333 = 1.64 0.11 E632 = 1.72 0.11 E1139 = 1.88 0.11 E1920 = 1.78 0.11
Carter et al. (2002)
Blocked on weight (2 l evels) and randomly allocated to treatment pens with 4 time levels of supplementation (0, 7, 14, 28 d)
Vitamin E: not measured
E0 = 98
Feed supplement 2000 IU/animal/d (source not stated) = 10.1 IU/kg BWd
ADG
E7 = 98 E14 = 97 E28 = 94 Morbidity (%) (SE not stated)
Mortality (%) (SE not stated)
E7 = 1.06 0.38 E14 = 1.05 0.31 E28 = 1.05 0.36 E0 = 65.3 E7 = 61.2 E14 = 54.6 E28 = 51.1 E0 = 2.0 E7 = 0.0 E14 = 0.0 E28 = 0.0 E0 = 9.23 5.87
>0.05
>0.05
>0.05
0.02
E7 = 8.64 5.27 E14 = 8.08 4.13 E28 = 7.44 3.19 Hays et al. (1997)
Vitamin E: not measured Random allocation to pens for dietary supplement. Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry (Table 3).
2 pens per treatment
Feed supplement (source not stated) 400 IU vitamin E/lb diet = 880 IU/kg diet = 6324 IU/animal/d = 26 IU/kg BWd
Feed supplement (over 28 d)
SE’s not stated
ADG (vitamin E increased)
E0 = 0.75
No. sick days Morbidity (%) (vitamin E decreased)
Rivera et al. (2002) Exp. 1
Random allocation to pen with 3 levels of supplementation
Vitamin E: not measured
4 pens of 10 animals
Feed supplement (source not stated) 217 IU/animal/d = 1.25 IU/kg BWd 380 IU/animal/d = 2.20 IU/kg BWd 787 IU/animal/d = 4.55 IU/kg BWd
E6324 = 1.03 E0 = 4.73 E6324 = 3.62 E0 = 78.1
<0.001
<0.07 <0.05
E6324 = 61.4 E0 = 2.3 E6324 = 0
NSDe
Morbidity (%)
E217 = 53.9
>0.10
(SE not stated)
E380 = 58.3 E787 = 56.4 E217 = 15.4 E380 = 27.8 E787 = 10.3
>0.10 237
Mortality (%)
Retreatment (%) (SE not stated)
P. Cusack et al. / Preventive Veterinary Medicine 88 (2009) 229–246
Treatment cost (28 d vitaminE < controls – v. hi. SD’s with overlap)
E0 = 1.02 0.62
238
Table 2 (Continued ) Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where SE provided)
P value
Rivera et al. (2002) Exp. 2
Random allocation to pen with 3 levels of supplementation
Vitamin E: not measured
5 pens of 13 to 15 animals
Feed supplement 335 IU/animal/d = 1.64 IU/kg BWd 640 IU/animal/d = 3.14 IU/kg BWd 1148 IU/animal/d = 5.63 IU/kg BWd
Morbidity (%)
E335 = 53.9
>0.10
(SE not stated)
E640 = 58.3 E1148 = 56.4 E335 = 15.4 E640 = 27.8 E1148 = 10.3
>0.10
Retreatment (%) (SE not stated)
Vitamin E: not measured 32 animals Feed supplement (source not stated) Lung lesions at Data not stated. 2 2 factorial - random control 200 IU/animal/d = = 0.63 IU/kg slaughter allocation with 2 weight d BW and 1500 IU/animal/d blocks and 4 levels of supplementation (control, = 4.75 IU/kg BWd vitamin E, aspirin and vitamin E + aspirin) a Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate), or a dietary concentration of 15–60 IU/kg DM (NRC. 1996. NRC (1996). b ADG = Average daily BW gain, kg. c The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. d Based on BW at Exp. commencement. e NSD = No significant difference.
Loneragan et al. (2002) Exp. 1
NSDe
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Reference
Table 3 Studies with vitamin E/selenium administered as an injection. Reference
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
Mean S.E.c (where S.E. provided)
P value
Droke and Loerch (1989) Exp. 1
Completely randomized 2 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
13 animals (individual pens)
Injection of 25 mg Se + 340 IU vitamin E (source not stated) = 0.09 mg Se/kg BWd + 1.27 IU vitamin E/kg BWd
ADG
S.E.’s not stated
>0.05
DMI G:F
Randomised complete block (blocked by 2 sources) 4 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
35 animals except for DMI and G:F with 3 pens
Injection of 25 mg Se &/or 340 IU vitamin E (Source not stated) = 0.12 mg Se/kg BWd + 1.67 IU vitamin E/kg BWd
ADG
DMI
G:F
No. sick days
Morbidity (%)
Droke and Loerch (1989) Exp. 3
Completely randomized 4 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
26 animals except for DMI and G:F with 3 pens
Injection of 25 mg Se &/or 340 IU vitamin E (source not stated) = 0.12 mg Se/kg BWd + 1.61 IU vitamin E/kg BWd
ADG
DMI
>0.05 >0.05
SE’s not stated
E0 = 0.84 +Se = 0.84 E340 = 0.75 E+Se = 0.81 E0 = 3.71 +Se = 3.61 E340 = 3.69 E+Se = 3.69 E0 = 0.23 +Se = 0.23 E340 = 0.20 E+Se = 0.22 E0 = 0.88 +Se = 1.08 E340 = 0.72 E+Se = 0.60 E0 = 54.8 +Se = 55.6 E340 = 46.2 E+Se = 43.0
>0.05
>0.05
>0.05
>0.05
>0.05
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Droke and Loerch, 1989 Exp. 2
E0 = 0.47 E+Se = 0.21 E0 = 4.11 E+Se = 3.98 E0 = 0.11 E+Se = 0.06
SE’s not stated
>0.05
>0.05 239
E0 = 0.88 +Se = 0.95 E340 = 0.94 E+Se = 0.95 E0 = 4.30 +Se = 4.48 E340 = 4.36
Study design
Basal intakea
Sample size per treatment
Dose or exp. duration
Outcome measuredb
G:F
No. sick days
Morbidity (%)
Completely randomized 3 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
16 animals per treatment (individual pens)
Injection of 25 mg Se + 340 IU vitamin E day 14 or repeat injection d 0 (source not stated) = 0.10 mg Se/kg BWd + 1.37 IU vitaminE/kg BWd
ADG
DMI
G:F
No. sick days
Droke and Loerch (1989) Exp. 5
Completely randomized 3 treatment levels
Vitamin E: not measured. Se: 0.033–0.076 mg/kg diet DM
35 animals except for DMI and G:F with 4 pens
Injection of 25 mg Se + 340 IU vitamin E (source not stated) = 0.12 mg Se/kg BWd + 1.66 IU vitamin E/kg BWd or 50 mg Se + 680 IU vitamin E = 0.24 mg Se/kg BWd + 3.32 IU vitamin E/kg BWd
ADG
DMI
G:F
No. sick days
Morbidity %
E+Se = 4.38 E0 = 0.20 +Se = 0.21 E340 = 0.22 E+Se = 0.22 E0 = 0.64 +Se = 0.59 E340 = 0.67 E+Se = 0.52 E0 = 35.6 +Se = 33.3 E340 = 40.7 E+Se = 44.4
P value
>0.05
>0.05
>0.05
SE’s not stated
Control = 0.83 ESe-14 = 0.87 ESe-14.0 = 0.84 Control = 4.65 ESe-14 = 4.71 ESe-14.0 = 4.67 Control = 0.17 ESe-14 = 0.18 ESe-14.0 = 0.18 Control = 0.06 ESe-14 = 0.31 ESe-14.0 = 0.13
>0.05
>0.05
>0.05
>0.05
SE’s not stated
E0 = 0.84 E340Se25 = 0.48 E680Se50 = 0.71 E0 = 3.94 E340Se25 = 3.34 E680Se50 = 3.74 E0 = 0.22 E340Se25 = 0.14 E680Se50 = 0.18 E0 = 0.86 E340Se25 = 1.89 E680Se50 = 1.16 E0 = 46.2
>0.05
>0.05
>0.05
>0.05
>0.05
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Droke and Loerch (1989) Exp. 4
Mean S.E.c (where S.E. provided)
240
Table 3 (Continued ) Reference
NSDe
e
d
c
b
Mortality %
Current National Research Council recommendation for cattle newly arrived at the feedlot is 400–500 IU vitamin E/animal/d (1 IU = 1 mg a-tocopherol acetate; NRC (1996). ADG: average daily BW gain, kg; DMI: dry matter intake, kg; G:F = kg of BW gain: kg of dry matter intake. The doses of vitamin E are shown as EX for each level, where X denotes the dose of vitamin E or the period of vitamin E exposure, as noted in the study design. Based on BW at Exp. commencement. NSD: no significant difference.
Morbidity %
241
controls. The details of the treatment protocol including the dose and route of administration of vitamin E were also extracted from the eligible papers. Thirty-five of 70 experiments or specified periods within experiments were eligible for meta-analysis. The unit of interest for dietary vitamin E was the pen, and the unit of interest for injectable vitamin E was the animal.
a
NSDe
<0.06 No. sick days (vitamin E increased)
E0 = 0.91 E3000 = 0.87 E0 = 3.60 E3000 = 4.75 E0 = 65.6 E3000 = 73.9 No mortalities ADG
SE’s not stated Injection (over 28 d) Injection of 3000 IU/animal (product not stated) = 12.3 IU/kg BWd 65 animals Vitamin E: not measured Random allocation to pens for dietary supplement (Table 2). Systematic allocation of vitamin E injection (odd numbered ear-tags). Half of the cattle in the control pens and half of the cattle in the supplemented pens were given vitamin E injection at feedlot entry Hays et al. (1997)
E340Se25 = 73.3 E680Se50 = 60.6
NSD
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2.2. Statistical analysis The effects of vitamin E on DMI, ADG, and G:F were evaluated using the standardised mean difference or effect size methods (Cohen, 1988). Reported standard errors and number of animals for the treatment and control groups were used to calculate standard deviations. The effect size is the difference between the standardized treatment and control groups, expressed as DMI, ADG or G:F, divided by the standard deviations, that is, a Z score for the treatment group mean in the control group population (Cohen, 1988). A negative effect size indicates that cattle supplemented with additional vitamin E had lower DMI, ADG or G:F compared with controls. Morbidity and mortality risk data were analysed as risk ratios. Risk ratio estimates on data pooled across experiments were obtained with a fixed effects model (Mantel and Haenszel, 1959). Forest plots were used to present the effect size and risk ratio data. Each experiment is represented by a black square and a horizontal line, showing the point estimate and the 95% confidence interval of the individual experiment-level effect size and risk ratio. Variation in experiment level risk ratios was assessed with a x2-test for heterogeneity. The null hypothesis was that the effect of supplemental vitamin E was the same across k trials and this was rejected if the heterogeneity test statistic was greater than a critical value that separated the upper 10% of a x2 distribution with (k 1) degrees of freedom. An a level of 0.10 was used because of the relatively poor power of the x2-test to detect heterogeneity among small numbers of experiments (Egger and Smith, 2001). Heterogeneity of results among trials was quantified using the I2 statistic (Higgins et al., 2003). The I2 statistic describes the percentage of total variation across studies that is due to heterogeneity rather than chance. Where Q is the x2 heterogeneity statistic and k is the number of trials, I2 was calculated as I2 ¼
Q ðk 1Þ 100 Q
Uncertainty intervals for I2 (dependent on Q and k) were calculated using the method described by Higgins and Thompson (2002). Negative values of I2 were put equal to 0, consequently I2 lay between 0 and 100%. A value greater than 50% indicates substantial heterogeneity in the data. With heterogeneous data, a random effects model was used to estimate effect size or risk ratio (Der Simonian and Laird, 1986). A meta-regression analysis was used in this study to explore the source of heterogeneity of response, using the individual effect size for each trial as the outcome and the associated standard error as the measure of variance. Meta-regression can formally test whether there is evidence of different effects in different subgroups of
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trials. It examines the relationship between one or more study-level characteristics and the sizes of effect observed in the studies. Meta-regression extends a random effects meta-analysis to estimate the extent to which one or more covariates, with values defined for each study in the analysis, explain heterogeneity in the treatment effects. The presence of publication bias was investigated using funnel plots (Light and Pillemer, 1984). Funnel plots display a measure of study size on the horizontal axis against intervention or treatment effect on the vertical axis. The precision of the estimation of the intervention or treatment effect increases as the size of component studies increases. Results from smaller studies therefore scatter more widely, with the spread narrowing among larger studies. In the absence of bias, the plot resembles a symmetrical funnel on its side. If there is bias, for example, because smaller studies showing no statistically significant effects remain unpublished, the plot will be asymmetrical. In these situations, the effect calculated in the metaanalysis may have been overestimated. However, funnel plot asymmetry may reflect other types of bias, or even result from the true intervention or treatment effect differing between small and large studies. The small number of experiments eligible for meta-analysis in this study made interpretation of funnel plots difficult and the results are therefore not reported. Publication bias was also investigated statistically using both Begg’s test (Begg and Manumdar, 1994), and Egger’s test (Egger et al., 1997). However, because these tests have low power and there is some debate regarding their statistical properties, potentials and limitations, these were not reported. 3. Results and discussion 3.1. Dietary vitamin E with or without additional selenium Selenium was supplemented in the diet at concentrations from 0.08 to 0.1 mg/kg dry matter (DM) as reported
in five of the experiments listed in Tables 1 and 2. No significant effects of selenium, either solely, or as a result of interactions with vitamin E were identified. The selenium concentrations supplemented in the diets reported all exceeded the recommendation in the Feeding Standards for Australian Livestock (1990) of 0.05 mg/kg DM. The low number of studies reporting selenium treatments and confounding with vitamin E treatment prevented further statistical evaluation. Of 67 study outcomes listed in Tables 1 and 2, only two studies found significant effects of vitamin E on DMI (2 of 11; Rivera et al., 2002, Exp. 1; Hays et al., 1997), two on ADG (2 of 12; Hays et al., 1997; Pehrson et al., 1991), two on G:F (2 of 11; Rivera et al., 2002, Exp. 2), one on morbidity (1 of 6; Hays et al., 1997) and one on treatment cost (1 of 2; Carter et al., 2002). However, supplemental dietary vitamin E was associated with a negative effect on G:F over the first 28 days in the feedlot (Rivera et al., 2002, Exp. 2). Further, the positive effects Hays et al. (1997) found on DMI, ADG and morbidity were compared to cattle that received no supplemental vitamin E and the positive effect found by Carter et al. (2002) on mean treatment cost, occurred with cattle fed 2000 IU vitamin E animal1 d1 for 28 days compared with cattle not supplemented. Therefore, the experiments of Hays et al. (1997) and Carter et al. (2002) did not show positive effects for supplementing vitamin E at concentrations that exceeded the NRC recommendation, only that supplementing cattle with dietary vitamin E could improve health and production compared with cattle not supplemented with dietary vitamin E. 3.2. Effects of dietary vitamin E on morbidity The risk ratios derived from studies examining the effects of dietary vitamin E on morbidity in Fig. 1 shows a trend (P = 0.09) towards a reduction in morbidity with supplemental vitamin E. However, the only study with a
Fig. 1. Risk ratios, 95% confidence intervals and percentage weight for individual studies on dietary vitamin E and morbidity. Only studies of at least 28 days duration are included (heterogeneity x2 = 8.93 (d.f. = 7), P = 0.26; overall risk ratio = 0.92, z = 1.69, P = 0.09).
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243
Fig. 2. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of dry matter intake (heterogeneity x2 = 4.3 (d.f. = 5), P = 0.51; overall effect size =0.04, z = 0.17, P = 0.86).
statistically significant improvement in morbidity in response to dietary vitamin E (Hays et al., 1997; P < 0.05) was a comparison between cattle supplemented with very high dietary concentrations of vitamin E and cattle provided with no additional vitamin E. Further, meta-regression of studies measuring the effects of dietary vitamin E on morbidity from Table 2 showed that within
the range of vitamin E doses reported, dose/animal and dose/kg BW were not significant (P = 0.61 for both). Conversely, longer duration of feeding dietary vitamin E was associated with a reduction in morbidity (P < 0.01). These findings indicate that prolonged exposure, rather than increased dietary concentrations, might be beneficial to cattle health.
Fig. 3. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of average daily gain (heterogeneity x2 = 8.97 (d.f. = 14); P = 0.83; overall effect size = 0.06, z = 1.13, P = 0.26).
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Fig. 4. Effect size plot of experiments with supplemental dietary vitamin E measuring the outcome of gain:feed ratio (kg of BW gain: kg of dry matter intake). (Heterogeneity x2 = 0.44 (d.f. = 5), P = 0.99; overall effect size = 0.05, z = 0.20, P = 0.84).
3.3. Effects of dietary vitamin E on production—dry matter intake, average daily gain and gain:feed The forest plots of effect size of dietary vitamin E on DMI (Fig. 2), ADG (Fig. 3), and G:F (Fig. 4), show no significant effects resulting from vitamin E supplementation of diets (all P > 0.26). While a small number of studies were assessed, it appears that production responses to increased dietary vitamin E, above NRC (1996) recommended concentrations, are unlikely. There were insufficient studies to interpret the results of influence analysis with DMI and G:F, and insufficient studies to interpret funnel plots to detect publication bias with DMI, G:F and ADG. No studies significantly influenced the pooled estimates of effect size with ADG. The effect on DMI of supplemental dietary vitamin E found by Rivera et al. (2002, Exp. 1, finishing period) was identified for a 98 days finishing period. Responses in this study can be considered in terms of the NRC dietary vitamin E concentration recommendation of 15– 60 IU/kg of diet DM (NRC, 1996). The estimated dietary vitamin E concentration (Rivera et al., 2002) associated with the greatest (P = 0.04) DMI was 55.4 IU/kg DM, compared with 28.8 IU/kg DM and 115.4 IU/kg DM. The
55.4 IU/kg concentration falls within the upper limit of the NRC recommendation. A similar positive effect was found by Rivera et al. (2002, Exp. 1, finishing period) for ADG, but the result was not significant (P = 0.07). Pehrson et al. (1991, Exp. 2, finishing period) also found a significant effect of supplemental dietary vitamin E on ADG during a 4-month finishing period. In this experiment, a calculated supplemental dietary vitamin E concentration of 66.1 IU/kg DM was associated with greater (P < 0.05) ADG than a concentration of 15.1 IU/kg DM. The positive effects of these individual experiments on DMI and ADG indicate that there are potential benefits from feeding diets that have vitamin E concentrations close to the upper limit of the NRC (1996) recommendation. 3.4. Vitamin E and selenium injection Table 3 lists five experiments where selenium was injected in combination with vitamin E. There were no significant effects on health or production associated with selenium either solely or in combination with vitamin E (Table 3) and insufficient data for meta-analysis. Injecting vitamin E at doses from 340 to 3000 IU (1.27– 12.3 IU/kg BW) resulted in no significant positive effects on
Table 4 Summary of pooled effect size for dry matter intake, average daily gain, and gain:feed ratio, and pooled risk ratios for morbidity with cattle supplemented or injected with vitamin E. Outcome
ES/RRa (95% CI)
Dry matter intake Average daily gain Gain:feed ratio
0.04 (0.44, 0.53) 0.06 (0.04, 0.16) 0.05 (0.40, 0.50)
Morbidity (Dietary vitamin E) (Vitamin E injection)
0.92 (0.84, 1.01) 1.17 (0.94, 1.45)
a
ES = effect size/RR = risk ratio.
n
P value
I2
Heterogeneity 2
Q
d.f.
P value
6 15 6
0.86 0.26 0.84
4.3 9.0 0.44
5 14 5
0.51 0.83 0.99
0 0 0
5 5
0.09 0.17
8.9 8.6
7 4
0.26 0.07
22 53
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Fig. 5. Risk ratios, 95% confidence intervals and percentage weights for individual studies on vitamin E injection and morbidity. The studies are of at least 28 days duration (heterogeneity x2 = 8.57 (d.f. = 4), P = 0.07; overall risk ratio = 1.17, z = 1.39, P = 0.17).
health or production (Table 3). Similarly, Cusack et al. (2008) found no significant effects on health or production of feedlot cattle when injected with vitamin E at feedlot entry at concentrations from 250 to 5000 IU (0.74–14.7 IU/ kg BW), except that incidence of anorexia was greater (P = 0.02) in the cattle given the highest vitamin E dose. The data from studies that examined the effect of vitamin E injection on morbidity was heterogeneous (x2 = 8.57, P = 0.07, I2 > 50%; Table 4), so a random effects model was used to estimate a pooled risk ratio (Fig. 5). This metaanalysis shows vitamin E injection did not have a significant effect on morbidity (P = 0.17). Table 4 summarises the results presented in Figs. 1–5, and indicates whether or not the data for each outcome is heterogeneous with the I2 statistic. In keeping with the effect size plots and the x2 heterogeneity tests, only morbidity responses to vitamin E injection varied across experiments greater than expected by chance (I2 > 50%). One of these experiments (Droke and Loerch, 1989; Exp. 2) found reduced morbidity while all others found an increase. Vitamin E and selenium were both administered in this experiment, without a treatment group using vitamin E alone. However, similar doses of selenium were used in the other experiments in this series of studies, and no significant effects on health were observed from injection with selenium alone. The heterogeneity in this data set might reflect the difficulty of consistently measuring the outcome of morbidity rather than genuine differences in experimental outcomes. 4. Conclusions This meta-analysis indicates that feeding vitamin E at concentrations greater than the NRC recommendation (1996), or the administration of vitamin E as an injection, does not improve ADG, G:F or morbidity in feedlot cattle.
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