Nutrition and Cancer

ISSN: 0163-5581 (Print) 1532-7914 (Online) Journal homepage: http://www.tandfonline.com/loi/hnuc20

The Effect of Soy Nut Compared to Cowpea Nut on

Body Weight, Blood Cells, Inflammatory Markers
and Chemotherapy Complications in Children with
Acute Lymphoblastic Leukemia: A Randomized
Controlled Clinical Trial

Narges Ramezani, Alireza Moafi, Azadeh Nadjarzadeh, Saeed Yousefian,

Nahid Reisi & Amin Salehi-Abargouei

To cite this article: Narges Ramezani, Alireza Moafi, Azadeh Nadjarzadeh, Saeed Yousefian,
Nahid Reisi & Amin Salehi-Abargouei (2018): The Effect of Soy Nut Compared to Cowpea Nut on
Body Weight, Blood Cells, Inflammatory Markers and Chemotherapy Complications in Children with
Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial, Nutrition and Cancer, DOI:
10.1080/01635581.2018.1495240

To link to this article: https://doi.org/10.1080/01635581.2018.1495240

Published online: 10 Sep 2018.

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NUTRITION AND CANCER
https://doi.org/10.1080/01635581.2018.1495240

The Effect of Soy Nut Compared to Cowpea Nut on Body Weight, Blood
Cells, Inflammatory Markers and Chemotherapy Complications in Children
with Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial
Narges Ramezania,b, Alireza Moafic, Azadeh Nadjarzadeha,b, Saeed Yousefiand, Nahid Reisic, and
Amin Salehi-Abargoueia,b
a
Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; bDepartment of Nutrition,
School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; cDepartment of Pediatric Hematology and
Oncology, Sayed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; dChild Growth and Development Research
Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences,
Isfahan, Iran

ABSTRACT ARTICLE HISTORY

No previous studies were found to examine the effect of soy as a whole food on patients Received 23 December 2017
with leukemia. The present randomized controlled clinical trial studied the effect of soy nut Accepted 24 June 2018
on children with B-cell acute lymphoblastic leukemia (ALL) who were in the maintenance
phase of chemotherapy. The eligible patients were randomized to receive 30 g/day soy or
cowpea nut powder for 12 weeks. Dietary intake, physical activity, anthropometric measure-
ments, complete blood count, serum albumin, serum highly sensitive C-reactive protein
(hs-CRP), and Tumor necrosis factor alpha (TNF-a) as well as chemotherapy side effects were
assessed at the start and the end of the study. In total 29 and 27 children completed the study
(aged 6.34 ± 2.44 and 5.85 ± 2.35 years) in soy and cowpea nut groups, respectively. The total
energy and protein intake, and physical activity as well as body weight, body mass index, num-
ber of red blood cells, hemoglobin and hematocrit levels, and fatigue were significantly
improved in the soy nut group compared to patients who consumed cowpea nut (P < 0.05). Soy
nut intake might improve the nutritional status, anemia, and fatigue in children with ALL.
Studies targeting blood cell fractions and disease recurrence are highly recommended.

Introduction treatment plan and medication (6,7). Low protein and

calorie intake are the common nutritional problems
The acute lymphoblastic leukemia (ALL) is considered
as the most common form of malignancy among chil- among the majority of patients with cancer. Protein
dren and constitutes around 20% of all cancers in and calorie play basic roles in the treatment of ALL
people aged under 20 years of age (1). Anemia, and the resistance to infection (7–9) and a number of
thrombocytopenia, neutropenia, leukopenia, and studies have focused on the impact of malnutrition
leukocytosis are regarded as the common disorders correction on the improvement of chemotherapy com-
found in ALL patients. High levels of serum uric acid plications in children with leukemia and also the need
and lactate dehydrogenase are also observed in these for nutritional guidelines for these patients (10–12).
patients, which are associated with tumor size and the A number of investigations have proposed that soy-
grade of tumor lysis (2,3). Chemotherapy, along with beans might be beneficial in the prevention and treat-
radiation therapy and surgery, which cause several ment of cancer (13,14). For instance, a study indicated
complications in children, are common approaches to that the soy isoflavones might prevent breast cancer
treat patients with ALL (4,5). and also its recurrence (15). Furthermore, it is
Malnutrition is widely common in children with observed that genistein the predominant isoflavone
ALL and might result in significant short-term and found in soybean has anti-tumor and anti-angiogen-
long-term consequences. In addition, malnutrition is esis effects through triggering the NF-kappa B and
regarded as an important factor in deciding on the Akt signaling pathways, which are revealed to

CONTACT Amin Salehi-Abargouei abargouei@ssu.ac.ir, abargouei@gmail.com Faculty of Health, Department of Nutritional, Shahid Sadoughi
University of Medical Sciences, Yazd 8915173160, Iran.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/r/hnuc.
ß 2018 Taylor & Francis Group, LLC
2 N. RAMEZANI ET AL.

maintain a homeostatic balance between cell survival in this study. Those children, who were in the main-
and apoptosis, targeting the estrogen- and androgen- tenance phase of chemotherapy treatment with no
mediated signaling pathways, antioxidant properties, specific diet or allergy to soybean or black-eyed pea
and also inhibition of angiogenesis and metastasis (cowpea), were included in the study in case of their
(14). An in vitro study revealed that genistein inhibits own and their parents’ consent.
proliferation and induces apoptosis and cell cycle It was planned to exclude participants if children
arrest in ALL, lymphoma and multiple myeloma cells show the disease recurrence in the study period; do
(16). Furthermore, a study showed that soybean isofla- not consume at least half of the selected intervention
vones could be helpful for the treatment of T-cell leu- supplements; show any allergic complications, and
kemia cancer in adults (17). It is also shown that their parents or the child intend to discontinue the
lunasin a novel chemopreventive peptide composed of intervention with any reason.
arginine-glycin-aspartate found in soy might be cyto- Intervention
toxic to leukemia cells (18). We are aware of one The children participating in the study were ran-
study which has been carried out on the effect of soy- domly allocated to receive 30 g soy nut powder or 30 g
bean isoflavone on children with cancer (13). In this cowpea (black-eyed pea) nut powder on a daily basis.
study, Tacyildiz et al. included eight children with Both the Soy and the cowpea were roasted without
cancer, and showed that patients under treatment salt before milling. The participants received soy nut
with soybean isoflavone supplements experienced less and cowpea powders in 30-g sachets, and they were
pain and fewer frequencies of diarrhea (13). Previous recommended to consume one sachet along with their
studies have used soy active compounds particularly food every day for 12 weeks. The sachets were pro-
its isoflavones as a supplement for the intervention; vided for 30 days of consumption and the participants
this is while soybean contains other nutrients in add- were asked to bring back the empty and the remain-
ition to isoflavones, such as protein, omega-3 fatty ing sachets on the monthly visits.
acids, fiber, and riboflavin (19), that might help the The randomization was done using statistical pack-
treatment of children with ALL, which a high percent- age for social sciences software (SPSS). The allocation
age of them experience anorexia, nausea, vomiting, concealment was conducted by keeping the predefined
and malnutrition due to chemotherapy (20). intervention assignments in sealed envelopes; there-
To the best of our knowledge no study is con- fore the person who included the children in the
ducted trying to assess the effect of soy nut on chil- study could not predict the intervention group. We
dren with ALL; therefore, the present randomized tried to blind the participants and personnel, by pro-
controlled clinical trial was conducted to determine viding the soy nut and cowpea powders in similar
the effect of soy nut on the anthropometric indices, sachets and the author who was not involved in the
dietary nutrient intake, serum albumin, complete administrative part of the study coded the sachets.
blood cells count and blast, inflammatory markers, Anthropometric measurements, dietary intake,
and chemotherapy complications in children with B- physical activity, laboratory data, and evaluation of
cell ALL which were in the maintenance phase of chemotherapy complications and the medications
chemotherapy. were recorded at the beginning and the end of the
intervention period. In addition, the rate of adherence
to the intervention was controlled via phone calls and
Materials and methods
counting the returned empty sachets.
The current study was a randomized controlled clin- Anthropometric measurements
ical trial that was conducted in 2016–2017 in Seyed A trained nutritionist performed all anthropometric
Al-Shohada Hospital, Isfahan, Iran. The study was measurements at the beginning and the end of the
confirmed by the ethics committee of Shahid Sadughi study. The weight of the children participating in the
University of Medical Sciences, Yazd, Iran (Ethics study was measured with minimum dressing using a
code: IR.SSU.SPH.REC.1394.103). In addition, this digital scale (OMRON, model number: BF511) with
clinical trial was registered in the Iranian Registry of the precision of 0.1 kg. The height was measured using
Clinical Trials as IRCT2016040212571N4 (http://en. a wall mount stadiometer fixed on a wall with no
irct.ir/trial/12620). dent or bump without shoes. In order to measure the
Participants height, participants stood in such a way that the heel,
It was aimed to include 60 children (aged buttocks, shoulders, and head were in contact with
3–12 years old) with ALL confirmed by an oncologist, the wall, and the head was kept in a horizontal
 NUTRITION AND CANCER 3

position (horizontal plane). The height of the partici- and the Kolmogorov-Smirnov test. Independent sam-
pants was recorded with the precision of 0.5 cm. The ples t test and Chi-square test were used for compar-
upper right side of the iliac bone was marked for the ing qualitative and quantitative variables between the
measurement of the waist, and it was recorded by the two study groups. Paired samples t test was used for
precision of 0.5 cm. intra-group comparison of quantitative variables
Biochemical evaluation between baseline and after the intervention period.
Blood samples (5 ml) were taken from children in The independent samples student t test was also used
the fasting state from the internal Cubital vein. An to compare the mean changes between the interven-
automated cell counter was used in order to evaluate tion and the comparison group. In addition, the ana-
the number of white blood cells, red blood cells, plate- lysis of covariance (ANCOVA) with Bonferroni
lets, hematocrit and hemoglobin (ADIVA 360 hema- correction was applied to compare change values after
tology system, Germany). Serum albumin was assessed adjusting for age and sex for variables which were sig-
using conventional agarose gel electrophoresis. In add- nificantly different between the intervention groups in
ition, serum hs-CRP level was evaluated using an the crude analyses. The normal distribution of resid-
enzyme-linked immunosorbent assay (ELISA) kit uals was checked by visually evaluating the histograms
(Diagnostic Biochemistry, Canada) and the tumor and Kolmogrov-Smirnov test. We also checked the
necrosis factor-alpha (TNF-a) was examined using an outliers for the change values and in case of their
ELISA kit prepared by East Biopharm company. The presence the analyses were replicated after removing
within and between assay coefficient of variation for the outliers. Within and between group comparisons
the hs-CRP kit was <11 and 10%, respectively. In for chemotherapy symptoms were done using non-
addition, for the TNF-a kit, the values were <10 and parametric tests including Wilcoxon signed rank test
12%, respectively. and Mann–Whitney U test, respectively; because their
Dietary intake and physical activity evaluations data were not normally distributed. Quantitative val-
In the current study, the parents of the participants ues are reported as the mean ± standard deviation
were asked to keep the children’s normal diet and (SD) unless indicated. SPSS software version 20 was
physical activity during the study and avoid any severe used for data analysis and P values less than 0.05 were
changes. For evaluation of dietary intake (including considered as statistically significant.
daily calorie, protein, fats, carbohydrates, vitamins,
and minerals intake), 3-day dietary records, including
Results
two workdays and a weekend day, were used, which
were completed by mothers at the beginning and the In total, 63 participants were evaluated to be included in
end of the study. The daily intake of macro- and the present study. Two parents did not give the
micronutrients were calculated using the Nutritionist informed consent, and another participant was excluded
IV Software (version 3.5.2, Axxya Systems, Redmond, because of father’s perception of the allergenic nature of
Washington, USA). The daily physical activity of chil- soy nut. Finally, 60 children were randomly allocated to
dren was recorded at the beginning and the end of the two groups receiving soy or cowpea nuts. One child
study using 3-day record forms, which was filled by from the soy nut intervention group did not complete
parents. Data related to children’s physical activity the study because of following the treatment in another
was calculated based on the type, duration, and meta- city, and three children were excluded from the cowpea
bolic equivalent of task (MET) values and the physical group because of the following reasons: One child expe-
activity was reported as MET-h/day (16). rienced the recurrence of the disease; one child was
Evaluation of chemotherapy complications referred for bone marrow transplantation and the
Nine common symptoms in patients with cancer parents of another child decided not to continue the
were recorded at the beginning and the end of the study. Finally, 29 children in the soybean group and 27
study using The Edmonton Symptom Assessment children in the cowpea group completed the study and
System (ESAS), which includes pain, fatigue, nausea, were included in the final analysis. The study flowchart
depression, anxiety, and drowsiness, lack of appetite, is represented in Fig. 1.
well-being, and dyspnea. These symptoms are scaled There were 12 (41.4%) and 8 (29.6%) girls in the
as 0–10 (17). soybean and cowpea groups, respectively and there
Statistical analysis was no significant statistical difference in terms of sex
The normal distribution of the quantitative data between the intervention groups (P ¼ 0.412).
was evaluated by looking at the distribution diagram Participants were aged 6.34 ± 2.44 in the soybean and
4 N. RAMEZANI ET AL.

Figure 1. Study flow diagram.

5.85 ± 2.35 in the cowpea group (P ¼ 0.445). The chil- Table 2 summarizes the effects of interventions on
dren were also identical in terms of pharmacological the anthropometric measurements and the blood bio-
regimen related to chemotherapy. chemical parameters. Anthropometric measures were
As revealed in Table 1, there was no statistically not significantly different between the two groups at
significant difference between the intervention and the beginning of the study (P > 0.05). According to
control group regarding the energy, carbohydrate, the results, the mean weight, height, and BMI showed
fat, protein, calcium, sodium, potassium, iron, zinc, a statistically significant increase in the soy nut group
vitamin B1, vitamin B2, vitamin B6, and vitamin C (P < 0.05). However, these anthropometric markers
intake and also physical activity level at baseline. did not significantly change in the cowpea group
Moreover, none of these parameters showed signifi- (P > 0.05). The waist circumference significantly
cant change before and after intervention in the cow- increased both in the intervention and the control
pea group. The mean energy, calcium, iron, vitamin groups (P < 0.05). The comparison of mean change
B1, vitamin B2 and protein intake and physical activ- from baseline in the anthropometric measures
ity significantly increased in the soy nut group between the two groups showed that weight and BMI
(P < 0.05). In addition, there was a significant differ- significantly increased in the soy nut group when
ence in the mean change of energy, calcium, and compared to the cowpea nut group (P < 0.5).
protein intake and physical activity of participants There was not any significant difference between
between the soy nut and the cowpea the two groups at the beginning of the study in terms
groups (P < 0.05). of blood biochemical markers. However, according to
 NUTRITION AND CANCER 5

Table 1. Dietary intake of macro and micro-nutrients and physical activity based on intervention groups.
Soy group (n ¼ 29) Cowpea group (n ¼ 27)
Before After Before After
intervention intervention Change P valuea intervention intervention Change P valueb P valuec P valued
Energy 1345.6± 175.9 1419.8 ± 182.1 74.1 ± 138.6 0.008 1282.8 ± 175.8 1270.4 ± 173.8 12.3 ± 140.6 0.652 0.187 0.024
(Kcal/day)
Carbohydrate 198.8 ± 37.6 211.6 ± 37.9 12.7 ± 34.2 0.054 194.9 ± 30.1 193.2 ± 39.5 1.6 ± 28.4 0.764 0.666 0.093
(g/day)
Fat (g/day) 42.6 ± 11.2 40.7 ± 8.3 1.9 ± 0.85 0.092 37.1 ± 11.4 36.5 ± 10.3 0.6 ± 7.4 0.653 0.079 0.485
Protein (g/day) 35.6 ± 8.9 46.6 ± 9.6 11.0 ± 6.8 >0.001 38.7 ± 7.0 37.3 ± 8.6 1.4 ± 7.27 0.320 0.164 >0.001
Calcium (mg/day) 387.6 ± 264.8 500.7 ± 253.0 113.0 ± 209.2 0.007 397.2 ± 238.2 375.1 ± 197.3 22.1 ± 131.7 0.391 0.888 0.006
Sodium (mg/day) 295.6 ± 212.5 301.1 ± 189.8 5.4 ± 176.4 0.869 301.6 ± 186.9 321.4 ± 210.7 19.7 ± 141.5 0.475 0.912 0.740
Potasium (mg/day) 2332.3 ± 614.2 2405.6 ± 607.8 73.2 ± 765.2 0.610 2449.0 ± 541.9 2248.4 ± 554.6 200.5 ± 811.1 0.210 0.456 0.199
Iron (mg/day) 8.4 ± 2.1 9.5 ± 2.1 1.0 ± 2.7 0.045 8.2 ± 1.5 8.1 ± 2.0 0.04 ± 2.7 0.934 0.615 0.135
Zinc (mg/day) 5.6 ± 1.7 5.9 ± 1.8 0.3 ± 2.3 0.436 5.8 ± 1.7 6.2 ± 1.6 0.4 ± 2.2 0.359 0.706 0.906
Vitamin B1 1.0 ± 0.5 1.4 ± 0.5 0.3 ± 0.8 0.040 1.0 ± 0.4 1.0 ± 0.4 0.01 ± 0.7 0.915 0.813 0.094
(mg/day)
Vitamin B2 1.3 ± 0.6 1.6 ± 0.6 0.3 ± 0.8 0.036 1.2 ± 0.6 1.2 ± 0.6 0.02 ± 0.9 0.886 0.841 0.954
(mg/day)
Vitamine B6 1.1 ± 0.4 1.0 ± 0.3 0.07 ± 0.6 0.505 1.1 ± 0.4 1.0 ± 0.4 0.08 ± 0.5 0.467 0.657 0.954
(mg/day)
Vitamine C 156.8 ± 91.6 169.4 ± 94.6 12.5 ± 123.9 0.591 169.6 ± 86.2 178.7 ± 82.8 9.0 ± 137.4 0.736 0.593 0.921
(mg/day)
Physical activity 34.7 ± 8.5 38.4 ± 7.8 3.6 ± 6.5 0.005 34.9 ± 8.3 34.3 ± 6.6 0.5 ± 4.2 0.489 0.954 0.039
(MET-h/day)
a
Comparison of mean values before and after intervention in the intervention with soy nut (statistical analysis was done using paired t test).
b
Comparison of mean values before and after intervention in intervention with cowpea nut (statistical analysis was done using paired t test).
c
Comparison of mean values before intervention period between soy nut and cowpea nut groups (statistical analysis was done using independent sam-
ples t test).
d
Comparison of mean change values between the soy nut and the cowpea nut groups (statistical analysis was done using independent samples t test).

Table 2. Comparison of anthropometric and blood biochemical parameters at baseline, after the intervention and their change
between the soy nut and the cowpea nut groups.
Soy group (n ¼ 29) Cowpea group (n ¼ 27)
Before After Before After
intervention intervention Change P valuea intervention intervention Change P valueb P valuec P valued
Weight (kg) 21.2 ± 6.8 22.4 ± 7.0 1.2 ± 1.1 <0.001 18.7 ± 6.5 18.8 ± 6.4 0.07 ± 0.2 0.074 0.169 <0.001
Height (cm) 114.8 ± 15.2 115.3 ± 15.3 0.4 ± 0.5 <0.001 109.2 ± 16.3 109.7 ± 16.1 0.4 ± 0.5 <0.001 0.187 0.187
Body mass 15.7 ± 1.9 16.5 ± 2.0 0.8 ± 0.8 <0.001 15.3 ± 1.8 15.2 ± 1.8 0.06 ± 0.2 0.179 0.431 <0.001
index (kg/m2)
Waist 56.8 ± 5.2 57.1 ± 5.2 0.2 ± 0.4 0.006 55.3 ± 4.7 55.5 ± 4.7 0.1 ± 0.3 0.022 0.259 0.616
circumference (cm)
White blood 4.1 ± 3.0 4.7 ± 3.1 0.5 ± 3.6 0.403 3.5 ± 3.0 4.3 ± 2.8 0.7 ± 2.8 0.163 0.488 0.821
cells (mm3)
Red blood 3.9 ± 0.5 4.2 ± 0.7 0.3 ± 0.5 0.004 4.0 ± 0.7 3.8 ± 0.7 0.2 ± 0.5 0.060 0.499 0.001
cells (mm3)
Hemoglobin 10.7 ± 1.8 11.4 ± 1.6 0.6 ± 0.4 >0.001 10.6 ± 1.7 10.4 ± 1.6 0.1 ± 0.6 0.137 0.836 0.001
(Hb; g/dl)
Hematocrit (HCT; %) 32.3 ± 5.6 38.2 ± 4.7 5.9 ± 3.5 >0.001 33.1 ± 6.0 32.9 ± 5.2 0.2 ± 2.6 0.616 0.590 <0.001
Platelet (PLT; mm3) 257.4 ± 225.8 290.9 ± 216.2 33.5 ± 224.6 0.428 183.4 ± 151.6 239.5 ± 124.4 56.0 ± 184.5 0.126 0.159 0.624
Neutrophil (mm3) 2.4 ± 2.4 2.8 ± 2.7 0.3 ± 3.0 0.516 1.9 ± 52.5 2.4 ± 2.3 0.5 ± 2.3 0.249 0.450 0.826
Lymphocyte (mm3) 1.1 ± 0.9 1.3 ± 0.8 0.2 ± 1.2 0.365 1.2 ± 0.9 1.3 ± 0.9 0.1 ± 1.3 0.497 0.859 0.925
Monocyte (mm3) 0.3 ± 0.2 0.3 ± 0.2 0.009 ± 0.3 0.864 0.2 ± 0.2 0.2 ± 0.2 0.05 ± 0.2 0.294 0.173 0.576
Eosinophil (mm3) 0.09 ± 0.08 0.1 ± 0.09 0.01 ± 0.13 0.629 0.07 ± 0.1 0.08 ± 0.09 0.01 ± 0.15 0.677 0.509 0.998
hs-CRP (mm3) 7.1 ± 8.1 8.5 ± 6.5 1.3 ± 4.9 0.139 8.5 ± 8.6 8.9 ± 7.7 0.4 ± 6.9 0.748 0.544 0.553
TNF-a (Pgr/ml) 19.2 ± 13.2 20.0 ± 8.8 0.8 ± 13.4 0.749 20.6 ± 11.9 19.8 ± 9.9 0.8 ± 13.5 0.760 0.679 0.657
Serum 5.8 ± 3.0 5.6 ± 3.0 0.2 ± 3.6 0.773 6.1 ± 3.0 6.3 ± 2.8 0.1 ± 3.2 0.780 0.732 0.688
albumin (g/dl)
a
Comparison of mean values before and after intervention in the intervention with soy nut (statistical analysis was done using paired t test).
b
Comparison of mean values before and after intervention in intervention with cowpea nut (statistical analysis was done using paired t test).
c
Comparison of mean values before intervention period between soy nut and cowpea nut groups (statistical analysis was done using independent sam-
ples t test).
d
Comparison of mean change values between the soy nut and the cowpea nut groups (statistical analysis was done using independent samples t test).

the results, red blood cells (RBCs), hemoglobin, and in these blood factors were statistically significant
hematocrit levels significantly increased in the soy nut between the two groups (P < 0.05). The intervention
group (P < 0.05); this is while these changes were not did not significantly change other biochemical markers
significant in the cowpea group. In addition, changes (Table 2). All of the children who completed the study
6 N. RAMEZANI ET AL.

Table 3. Comparison of the changes in blood and anthropometric parameters in the two intervention
groups after adjustment for age and gender.
Soy nut (n ¼ 29) Cowpea nut (n ¼ 27) Standardized mean difference P value
Mean ± SE Mean ± SE (Cohen’s d±SE)
Weight (kg)
Crude 1.25 ± 0.15 0.08 ± 0.16 1.37 ± 0.30 <0.001
Adjusted modela 1.25 ± 0.16 0.07 ± 0.16 1.38 ± 0.30 <0.001
Body mass index (kg/m2)
Crude 0.82 ± 0.12 0.07 ± 0.12 1.40 ± 0.30 <0.001
Adjusted modela 0.84 ± 0.12 0.08 ± 0.12 1.45 ± 0.30 <0.001
Red blood cells (mm3)
Crude 0.34 ± 0.10 0.21 ± 0.11 0.99 ± 0.28 0.001
Adjusted modela 0.34 ± 0.11 0.21 ± 0.11 0.94 ± 0.28 0.001
Hemoglobin (g/dl)
Crude 0.64 ± 0.10 0.18 ± 0.11 1.48 ± 0.30 <0.001
Adjusted modela 0.65 ± 0.10 0.20 ± 0.11 1.53 ± 0.30 <0.001
Hematocrit (%)
Crude 5.94 ± 0.58 0.26 ± 0.60 1.82 ± 0.32 <0.001
Adjusted modela 5.93 ± 0.59 0.25 ± 0.61 1.95 ± 0.32 <0.001
a
Comparison of mean change values between intervention groups after adjustment for age and gender (statistical analysis was
done using the analysis of covariance).

Table 4. Median (95% confidence interval) for chemotherapy complications in soy nut and cowpea nut groups before and after
interventiona.
Soy group (n ¼ 29) Cowpea group (n ¼ 27)
Before After Before After
intervention intervention Change P valueb intervention intervention Change P valuec P valued P valuee
Pain 6 (2.5, 8.5) 6 (2.0, 8.5) 0 (3.0, 1.5) 0.012 7 (3.4, 8.6) 6 (4.0, 8.0) 0 (2.0 , 3.6) 0.221 0.202 0.065
Fatigue 6 (3.5, 8.5) 5 (3.5, 7.5) 1 (4.0, 1.5) <0.001 6 (3.4  9.0) 6 (3.4, 8.0) 0 (2.6, 3.0) 0.167 0.874 0.041
Nausea 4 (0.5, 7.5) 3 (1.0, 6.0) 1 (5.0, 2.5) 0.192 3 (1.4, 8.2) 3 (1.4, 7.6) 0 (1.0, 1.6) 0.564 0.920 0.267
Depression 3 (0.0, 7.5) 3 (0.0, 7.0) 0 (4.0, 2.0) 0.330 3(0.0, 7.0) 4 (0.0, 6.0) 0 (2.0, 3.6) 0.429 0.954 0.220
Anxiety 6 (1.0, 9) 5 (3.0, 7.5) 1 (4.0, 2.0) 0.006 4 (3.0, 8.6) 5 (1.8, 7.0) 0 (2.6, 2.2) 0.060 0.236 0.800
Drowsiness 6 (3.0, 8.0) 5 (3.0, 7.0) 0 (2.0, 1.5) 0.036 6 (3.0, 8.6) 5 (3.4, 8.0) 0 (2.6, 2.0) 0.132 0.425 0.319
Appetite 3 (1.0, 5.0) 4 (2.0, 5.5) 1 (1.5, 3.5) 0.006 3 (1.0, 5.0) 4 (2.0, 6.2) 0 (2.2, 2.0) 0.107 0.447 0.535
Well being 4 (3.0, 5.5) 5 (2.0, 5.5) 0 (1.5, 2.0) 0.031 4 (3.0, 6.0) 5 (3.0, 6.0) 0 (1.0, 1.0) 0.366 0.262 0.509
Dyspnea 0 (0.0, 3.0) 0 (0.0, 1.5) 0 (1.5, 0.5) 0.021 0 (0.0, 3.0) 0 (0.0, 1.6) 0 (1.6, 0.6) 0.035 0.879 0.817
a
Values are represented as median (95% confidence interval)
b
Comparison of values before and after intervention in the intervention with soy nut (statistical analysis was done using Wilcoxon signed rank test).
c
Comparison of values before and after intervention in intervention with cowpea nut (statistical analysis was done using Wilcoxon signed rank test).
d
Comparison of values before intervention period between soy nut and cowpea nut groups (statistical analysis was done using Mann–Whitney U test).
e
Comparison of change values between the soy nut and the cowpea nut groups (statistical analysis was done using Mann–Whitney U test).

had the blast number of 5 both in the intervention the soy nut group vs. 0.08 ± 0.08 for the cowpea nut
and control groups, before and after the intervention. group, P < 0.001).
The differences found in weight, BMI, RBCs, Given the fact that chemotherapy complications’
hemoglobin, and Hematocrit changes between the two data lacked normal distribution, non-parametric tests
intervention groups remained significant after adjust- were used for within and between group comparisons.
ing the comparison for age and gender using According to the results, at the beginning of the inter-
ANCOVA (P < 0.05). The residuals were normally vention, there was no significant difference in chemo-
distributed in each intervention group in all therapy complications between the study groups;
ANCOVA analyses. The crude and age and sex however, the analysis showed a significant decrease in
adjusted change values as well as standardized differ- pain, drowsiness, anxiety, fatigue, and dyspnea and a
ences in change values between the soy nut and the significant increase in appetite and well-being in the
cowpea nut groups are represented in Table 3. We soy nut group (P < 0.05). The changes in chemother-
observed two outliers for the weight change in the soy apy complications were significant only for dyspnea in
nut group; therefore we replicated the analysis after the cowpea group (P < 0.05). Evaluation of difference
removing the outliers and conducting the ANCOVA. in the change values showed that only the decrease in
The analysis revealed that the weight change is still fatigue level was significantly higher in soy nut group
significantly higher in the soy nut group in the crude compared to the cowpea group, and there was no dif-
model (0.98 ± 0.08 for the soy nut group vs. ference in the change of other chemotherapy compli-
0.08 ± 0.08 for the cowpea nut group, P < 0.001) and cations between the soy nut and the cowpea nut
after adjustment for age and gender (0.98 ± 0.08 for groups (P < 0.05) (Table 4).
 NUTRITION AND CANCER 7

Discussion showed that soy supplementation might improve the

quality of life in men with prostate cancer (26).
The current randomized controlled clinical trial
In terms of anthropometric parameters, this study
revealed that daily consumption of 30 g soy nut pow-
indicated that consumption of soy nut supplement
der along with foods might significantly improve the
significantly increased weight and BMI in children
body weight, BMI, red blood cell count, hemoglobin,
with ALL, but it had no significant impact on waist
and hematocrit levels compared to equivalent amount
circumference when compared to the control group.
of cowpea nut in children with ALL. In addition, cur-
Increasing daily calorie and protein intake in children
rent study indicated that soy nut might not signifi-
might be the reason for this result. This impact is
cantly affect inflammatory markers, albumin, and
noticeable and significant, because den Hoed et al.
white blood cell. To the best of our knowledge, this
showed that underweight children with ALL are more
study was the first randomized clinical trial study in
this regard. likely to experience the recurrence of the diseases
ALL is the most prevalent form of leukemia among compared to normal and overweight children (27). In
children (5). It is proposed that soy nut is one of the addition, children who had a reduction in BMI during
foods that might help in prevention and treatment of ALL treatment had a lower survival rate due to the
different types of cancer (21,22). However, the previ- risk of recurrence compared to other children (27).
ous studies published in this regard, have used isofla- Linga et al. also found that children with blood malig-
vones extracted from soybean (23,24). nancies would experience a higher rate of chemother-
According to the results of the present study, sup- apy if they had malnutrition (28). Improvement in the
plementation of soy nut increases daily energy and status of malnutrition in children with ALL might
protein intake in children. As the children with ALL also improve many chemotherapy complications. They
are suffering from malnutrition due to complications also found that children with hematologic malignan-
of chemotherapy, it seems that consuming a daily cies had increased mortality rates if they were mal-
dose of 30-g soybean powder in children with ALL nourished (28).
significantly improves appetite and eating habits, so The present study also indicated that the use of
that the total daily calorie intake was significantly soy nut improves the markers of anemia such as
higher than that of the control group. According to hemoglobin and hematocrit levels, and the red blood
the results of the current study, the highest increase in cell count in the children with ALL. This effect may
daily calorie intake is due to the increase in protein be due to improved daily intake of protein and the
intake, which is due to the protein found in soybean iron and the ferritin content of soybean. It has also
(19). In a study Linga et al. found that children with been shown that the polysaccharides in soy contribute
hematologic malignancies commonly suffer from mal- to more iron absorption (29). On the other hand, it
nutrition (79% lacked calorie intake and 74% lacked seems that the reason for anemia in children with
protein intake) which might lead to poor treatment cancer is the suppression of blood cell production in
and mortality rates (3). According to this study, use the bone marrow by infiltration of blast cells (30,31).
of soy nut regularly for a 3-month period can improve Studies have shown that the soy isoflavones such as
the calorie and protein intake of children with ALL, genistein might have anti-cancer effects in several
and thus it might improve the prognosis of pathways (32). In addition, studies indicate that
the disease. anemia in children may be due to chemotherapy in
In addition, this study showed that the daily phys- children with cancer (33). In a study in Turkey, a
ical activity level significantly increased in the soy nut reduction in chemotherapy complications using soy
supplemented group compared to the control group. isoflavone was shown (13). Tacyildiz et al. studied
In the current study, children with ALL also reported eight children under chemotherapy and showed that
lower fatigue levels after consumption of the soy nut consumption of pills containing soybean isoflavones
supplement. Also daily calorie intake was significantly was effective in reducing side effects of chemotherapy
increased. These factors might be the reason for and radiotherapy in leukemia, so that the children
increasing physical activity. In line with our results, a experienced lower bone marrow suppression (shorter
study done by Nomura et al. revealed that soy food neutropenics), less inflammation, less infections
consumption was related with less treatment related (shorter antibiotic use), decreased diarrhea (a com-
menopausal symptoms and also fatigue in breast can- mon complication in abdominal radiotherapy), and
cer survivors (25). A recent systematic review also less blood transfusion (13).
8 N. RAMEZANI ET AL.

In the current study, soy nut had no significant Disclosure statement

impact on inflammatory factors including hs-CRP and Authors declare that they have no conflict of interest
TNF-a compared to cowpea in children with ALL. In regarding the publication of the manuscript.
line with our results, Mazidi et al. showed that con-
sumption of soy protein had no statistically significant
impact on inflammatory factors (11). Funding
Although a number of studies have tried to assess The present clinical trial was financially supported by the
the effect of soy isoflavones on the treatment of can- chancellery for research, Shahid Sadoughi University of
cer, based on our knowledge, none of the previous Medical Sciences, Yazd, Iran.
studies investigated anti-cancer effect of soy nut on
ALL. The only similar study was done by Tacyildiz Authors’ contribution
et al. (11) which included only eight children, and
ASA, NR, and AN conceived the study. NR, SY, AM, and
supplemented the soybean isoflavones. In a previous NR recruited the participants and followed them. ASA and
study, Farina et al. sowed that the soybean isoflavone NR conducted the statistical analyses. Data interpretation
consumption causes a reduction in angiogenesis in was done by ASA, NR, and AM. All authors contributed to
tumor cells (12). Therefore, genistein of soybean has the study conception, design and drafting of the manuscript.
anti-tumor and anti-angiogenesis properties. Raynal
et al. also found that soybean genistein had anti- ORCID
inflammatory and anti-cancer effects on people with
lymphoblastic leukemia and myelogenous leukemia Amin Salehi-Abargouei http://orcid.org/0000-0002-
7580-6717
(34). Similar results were obtained in mice with leuke-
mia (4).
The current study had some limitations that should
be taken into account when interpreting the results. References
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