Nutrition intervention for optimising physical fitness in children. Mario Vaz St. John s Research Institute Bangalore

Nutrition intervention for optimising physical fitness in children Mario Vaz St. John s Research Institute Bangalore

A framework for understanding performance Genetics, Age, Motivation, Training, Body Composition Lung, Cardiovascular Function PERFORMANCE Muscle Function Oxygen carriage Muscle mass Physical activity Micronutrient Status Protein Intake Courtesy: Kurpad AV Micronutrient Intake Energy Intake

Micronutrients and physical performance: Which ones? 1. Iron 2. B vitamins 3. Vitamins A, C and E 4. Other minerals

Micronutrients and physical performance 1. Multiple micronutrient supplementation works best when there is preexisting deficiency 2. Supplementation in replete individuals does not have an effect

Micronutrients and physical performance: how do they work? Ergogenic effect Haemoglobin synthesis / erythropoesis and O2 delivery Anti-oxidant effect

Objectives The primary objective is to determine the within-subject change in endurance [whole body], aerobic capacity, speed and reaction time in 7-11 year old subjects receiving the test product as compared to a control group (provided only the energy equivalent of the test Product) and a no intervention group over a period of 4 months. The secondary objectives are to determine and compare changes over 4 months in: Nutritional status using biochemical markers Muscle strength and endurance in the forearm flexor muscle group

Issues to consider Growth Puberty Normalisation for body size Gender differences Central / Subjective Fatigue (endurance) Less heterogeneity in fitness in healthy children as compared to healthy older adults Repeatability of measurements less well described in children Familiarization / training effects Experimenter-child interaction?size of effect

Study Design Non Intervention Group Intervention Groups No intervention Control Test 50 boys 50 girls 50 boys 50 girls 50 boys 50 girls Pre-intervention Evaluation (Anthropometry, Biochemistry, Diet and Physical activity, Physical Performance Measures) Intervention period (4 months) Mid Point Assessments Post-intervention Evaluation

Inclusion Criteria Ages 7-11 years Z score of height for age and weight for age of > 0 to < -3. Good general health Parental Consent and subject assent Exclusion Criteria Severe anemia (Hb < 8 g%) Cardiovascular disease Respiratory disease Physical disability consuming nutritional supplements and/ or health food drinks on a regular basis Recent history [3mo] of serious infections, injuries and/ or surgeries Participation in any nutritional study in the last 1y likely to move within the study period

Number of schools = 3 Number of children in the eligible age group = 1155 Number of students consented for screening = 379 Number of children excluded from randomisation = 79 Reasons for exclusion Inclusion criteria not met = 68 Z score of height and weight for age > 0 or -3 = 49 Exclusion criteria not met = 11 Consuming supplements or health drinks = 9 Number Randomized = 300 (M=150 / F=150)

Socio-economic status of the final randomised sample (N=300) SE class Lower Upper Lower Lower middle Upper middle Upper Score < 5 5-10 11-15 16-25 26-29 Number 0 236 56 8 0 Based on income, occupation and education Modified Kupuswamy scale, Kumar et al., Indian J Paediatr 2007

Characteristics of the subjects Deficiency % Anaemia 5 Iron 23.2 Vit B2 (riboflavin) 87.7 Vit B6 (pyridoxine) 21.6 Vit B12 (cobalamin) 51 Folate 0.3 Vitamin C 13 > 1 Vitamin deficiency 40.3

The Study Intervention Daily serve: 1sachet (40g in 100mL) ~ 158 Kcal, 3.2g protein, 1.4g fat. fortified with upto 50% RDA of fat-soluble vitamins (A and D), Biotin, Pantothenic acid, Calcium, Magnesium, Zinc and Copper upto 100% RDA of water-soluble vitamins (B1, B2, B6 and B12; Vitamin C), Niacin, Folic acid, Iron and Iodine. Product made available through GlaxoSmithKline Consumer Healthcare

Step test (cardio-respiratory endurance) 20m Shuttle test (endurance) Outcome measures 12 inch step at 22 steps/min for 3 minutes HR manually recorded Started at 4 km/hr and increased by 0.5 km/hr every minute Predicted VO2 max 40m sprint (speed) In groups of 3-5 secs Visual reaction time [computer based] Maximal handgrip (muscle strength) [dynamometer] Sustained isometric contraction of forearm flexors) Best of 3 recordings target visuals randomised for order of appearance Best of three recordings Time taken for reduction to 50% of maximal handgrip manually recorded using a stop watch No of shuttles, Predicted VO2 max msecs Kg force secs

In groups of 3-5 Test stopped: Subjective exhaustion Inability to reach 2 consecutive markers within the beep time

TARGET IMAGES

Reducing the impact of inter-observer bias Test NO Study treatment Arm 111 Study Treatment Arm 145 Study Control Arm 160 Overall Same coder N (%) Same coder N (%) Same coder N (%) Same coder N (%) Handgrip 80 (82.5) 78 (82.1) 76 (79.2) 234 (81.3) Forearm 79 (81.4) 77 (81.1) 78 (81.3) 234 (81.3) Sprint 54 (55.7) 61 (64.2) 61 (63.5) 176 (61.1) Shuttle 84 (86.6) 81 (85.3) 87 (90.6) 252 (87.5) Harvard 87 (89.7) 85 (89.5) 81 (84.4) 253 (87.8) Visual Reaction 60 (61.9) 58 (61.1) 53 (55.2) 171 (59.4)

Were the study arms balanced at baseline?

Abbreviations NO INTERVENTION GROUP GROUP RECEIVING THE FORTIFIED NUTRITION SUPPLEMENT GROUP RECEIVING ENERGY EQUIVALENT IN SUPPLEMENT NOTRT TRT CNTRL

Baseline Socio-economic status and anthropometry Study Arm NOTRT TRT CNTRL Parameter Age (yr) 8.3 8.3 8.2 SES Score 9.0 8.8 8.8 Height (cm) 122.3 123.2 122.3 Weight (kg) 21.5 21.9 21.2 These parameters were comparable across the groups

Baseline Physical Performance measures Study Arm NOTRT TRT CNTRL Parameter VO2 max from step test (ml/kg/min) 37.0 36.8 37.9 No. of shuttles 52.0 48.2 52.5 * VO2 max from shuttle (ml/kg/min) 32.4 31.6 32.8 One Way ANOVA indicated that No. of shuttles was significantly different (P=0.04)

Baseline Physical Performance measures Study Arm NOTRT TRT CNTRL Parameter Grip strength (ND: kg) Static endurance (time to fatigue, sec) 40 m sprint (sec) Visual reaction time 8.5 8.6 8.6 11.1 12.3 12.4 8.9 9.0 8.9 939 958 932 Comparable across groups

Baseline Haemoglobin and Iron status Study Arm NO TRT TRT CNTRL Parameter Hb (gm/dl) 12.9 12.9 12.9 Serum Ferritin * (ng/ml) 24.5 27.6 20.2 stfr (mg/l) 5.98 5.91 6.2 All medians, * significantly different at baseline

Baseline Vitamins B2, B6 and B12 Study Arm NO TRT TRT CNTRL Parameter Vit B2* 1.57 1.56 1.52 Vit B6 (nmol/l) Vit B12 (pmol/l) 39.3 33.8 34.3 224.0 210.0 213.0 All medians, * significantly different at baseline

Baseline Folate and Vitamin C Study Arm NO TRT TRT CNTRL Parameter Folate (ng/l) 592.8 583.7 585.3 Vitamin C (mg/dl) 0.72 0.69 0.61 All medians, Comparable across groups at baseline

Baseline Dietary Intake Study Arm NOTRT TRT CNTRL Parameter Energy (kcal) 1231 1194 1140 Protein (gm/d) 33.0 33.2 31.2 Fat (gm/d) 31.9 30.4 28.4 Carbohydrate (gm/d) 202.8 197.0 189.8 Comparable across groups

Baseline Physical activity Study Arm NOTRT TRT CNTRL Parameter Total sedentary 1656 1557 1607 Total games 1598 1526 1452 Moderatevigorous activity 1861 1749 1580 All MET-min / week, all medians All comparable across groups

Effect of the Intervention on primary outcomes of physical performance

Compliance to the intervention during the study period Study arm Compliance Planned intervention (Person days) TRT CNTRL 11395.00 11400.00 Actual intervention given (Person days) 10798.40 10776.60 % intervention given 95% 95% % Supervised / Unsupervised 93 / 7% 92/8%

Step Test Change in VO 2 max (ml/kg/min) 2.5 2 1.5 1 0.5 0 NOTRT CNTRL 0.147 0.004

20 m shuttle Change in Number of laps 12 10 8 6 4 2 0 NOTRT 0.005 CNTRL 0.001

20 m shuttle Change in VO 2 max (ml/kg/min) 8 7 6 5 4 3 2 1 0 NOTRT TRT CNTRL 0.003 0.002

Comparison of Manual and Pulse Oximeter Heart Rate at the end of the step test Peak HR post step test-basal N=112 Peak HR post step test-end study N=210 Manual HR HR by pulse oximeter Difference: Man-PO Corr. Between Man-PO 139.8 124.1 + 15.8 *** 0.41*** 134 116 + 18.0 *** 0.37*** The Differences between Manual Vs. PO, at the two time points are significantly different from each other, P = 0.02

40 m sprint Change in timing (sec) 0-0.1-0.2-0.3-0.4-0.5 No TRT CNTRL NS

NS Visual Reaction Time Change in timing (msec) 0-20 -40-60 -80 NOTRT CNTRL

Effect of the Intervention on secondary outcomes of physical performance

NS Maximal Handgrip strength Change in handgrip (kg) 1.5 1.2 0.9 0.6 0.3 0 NOTRT CNTRL

Static Forearm Endurance Change in time to fatigue (sec) 3 2.5 2 1.5 1 0.5 0 NOTRT CNTRL NS

Were the effects of the Intervention confounded by changes in growth, dietary intakes and physical activity?

Change in Height (cm) 2.5 2 1.5 1 0.5 0 No TRT CNTRL Height increase of about 2 cm, comparable across groups

Change in Weight (kg) 2 1.5 1 0.5 0 NOTRT CNTRL Weight increase less than 1 kg, comparable across groups

Changes in diet (Final-baseline) Study arm No TRT TRT CNTRL Parameter Energy (kcal) -165-226 -88.4 Protein (g) -4.4-5.4-3.0 Fat (g) -7.3-6.5-3.4 Carbohydrate (g) -18.8-3.4-14.1 Energy intakes and macro-nutrient intake decreased with intervention But with no differences between groups

Study arm Parameter Changes in physical activity: (Final-baseline) NO TRT TRT CNTRL Sedentary -48-78 -21 Games -390-259 -207 Moderate- Vigorous activity -351-388 -382 All MET-min per week, all Medians Physical activity decreased with the intervention but changes were comparable across groups

Effect of the Intervention on biochemical status of micronutrients

Change in Iron status Study Arm Parameter Serum Ferritin * (ng/ml) NO TRT TRT CNTRL 0.17 1.94 stfr (mg/l) * -0.02-0.24

Change in Iron status Study Arm Parameter Serum Ferritin * (ng/ml) NO TRT TRT CNTRL 0.17 9.36 (33.9%) stfr (mg/l) * -0.02-0.33 (5.6%) 1.94-0.24 All medians, TRT group is significantly different from NO TRT and CNTRL % is change in relation to baseline value

Change in status of Vitamins B2, B6 and B12 Study Arm NO TRT TRT CNTRL Parameter Vit B2 (ratio)* 0-0.04 Vit B6 * (nmol/l) Vit B12 * (pmol/l) 2.52 4.72-10.1 5.3

Change in status of Vitamins B2, B6 and B12 Study Arm Parameter NO TRT TRT CNTRL Vit B2 (ratio)* 0-0.32 (20.5%) Vit B6 * (nmol/l) Vit B12 * (pmol/l) 2.52 23.96 (71.1%) -10.1 210.8 (100%) -0.04 4.72 5.3 All medians, TRT group is significantly different from NO TRT and CNTRL % is change in relation to baseline value

Change in status of Folate and Vitamin C Study Arm NO TRT TST CNTRL Parameter Folate (ng/l) -9.6-13.0 Vitamin C (mg/dl) 0.09 0.13 All medians, TRT group is significantly different from NO TRT and CNTRL % is change in relation to baseline value

Change in status of Folate and Vitamin C Study Arm NO TRT TST CNTRL Parameter Folate (ng/l) -9.6 397 (68%) -13.0 Vitamin C (mg/dl) 0.09 0.83 (120%) 0.13 All medians, TRT group is significantly different from NO TRT and CNTRL % is change in relation to baseline value

% Low serum ferritin (< 15ng/ml) 35 30 25 20 15 10 5 0 NOTRT TRT CNTRL P= 0.042 P < 0.001

% High soluble transferrin receptor (> 7.6mg/L) 25 20 15 10 5 0 NOTRT TRT CNTRL NS P = 0.026

% Low Vitamin B2 (ratio > 1.4) 100 90 80 70 60 50 40 30 20 10 0 NOTRT TRT CNTRL P < 0.001 P < 0.001

% Low Vitamin B6 (< 20nmol/L) 25 20 15 10 5 0 NOTRT TRT CNTRL P = 0.005 P = 0.06

% Low Vitamin B12 (< 150pmol/L) 25 20 15 10 5 0 NOTRT TRT CNTRL P < 0.001 P < 0.001

Conclusions

the fortified nutritional supplement in apparently healthy children between 7 to 11 years with z-scores of height for age and weight for age of between 0 to -3, resulted in: a significant increase in aerobic capacity and whole body endurance a significant improvement in the status of a range of micronutrients (iron status, vitamins B2, B6, B12, folate) contained in the fortified supplement in the test group no significant effect on speed, visual reaction time, muscle strength and forearm endurance

The current study cannot determine the relative contributions of the different micronutrients to enhanced physical performance While the study has high internal validity, the external validity of the study must be interpreted in terms of the subject characteristics studied Methods / Strategies to enhance the micronutrient intake of children need to be developed and implemented