THE EVALUATION OF VITAMIN C SUPPLEMENTATION ON NUTRITIONAL STATUS OF PATIENTS WITH ACUTE MYELOID LEUKEMIA UNDERGOING CHEMOTHERAPYHTML Full Text
THE EVALUATION OF VITAMIN C SUPPLEMENTATION ON NUTRITIONAL STATUS OF PATIENTS WITH ACUTE MYELOID LEUKEMIA UNDERGOING CHEMOTHERAPY
Atiyeh Hosseini 1, Seyyed Mostafa Jalali 1, Marjan Ajami * 2, Morteza Abdollahi 3, Hossein Ranjbar 4 and Mostafa Badeli 5
Department of Nutrition 1, Department of Food and Nutrition Policy and Planning Research, National Nutrition and Food Technology Research Institute 2, National Nutrition & Food Technology Research Institute, and Social Determinants of Health Research Center 3, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Fellowship of Oncology 4, Tehran University of Medical Sciences, Tehran, Iran.
Department of Nutrition 5, Urmia of Medical Sciences, Urmia, Iran.
ABSTRACT: Background: Leukemia is the seventh common cancer in Iran, and AML is considered as the most common type. Malnutrition is common among patients with cancer. Vitamin C deficiency has a high prevalence among patients with cancer, which may influence a patient's survival chance. This study was aimed to evaluate the effect of vitamin C supplementation on nutritional status and serum albumin in patients with acute myeloid leukemia referred to Shariati Hospital in Tehran. Methods: This study was recruited by a randomized selection of 50 patients with AML, including entrance criteria, into 2 groups including the supplement group and control group. The duration of the study was 1 month. Nutritional status was assessed by the PG-SGA questionnaire, body weight, serum albumin status, and 3 days of food record before and at the end of the study. Results: The results of this study have shown that the nutritional status and body weight in the supplementation group have improved significantly (p-value=0.001 and 0.004, respectively). The serum albumin status has increased significantly in the supplementation group compared to the control group. (P-value=0.002). Conclusion: The results of this study have suggested that vitamin C supplementation in patients with AML under chemotherapy has improved nutritional status and reduced malnutrition due to chemotherapy side effects.
Nutritional status, Vitamin C Supplement, Acute myeloid leukemia, Albumin, Chemotherapy, Appetite
INTRODUCTION: Leukemia is the seventh common cancer in Iran and AML is considered as the most common type of leukemia 1, 2, 3. It is estimated that the incidence of ALM is 3/6 per 10000.
ALM is a condition in which the bone marrow myelocyte cells stop growing at the first stage, which leads to more immature cells and reduction in natural cells count. Fatigue, nausea, and appetite loss are common symptoms of ALM. Patients with ALM are prone to malnutrition and weight loss which may decrease the chance for treatment 1.
Nutritional adequacy is crucial for body mechanisms 2, 4 and immune system optimal health and malnutrition may lead to poor quality of life in these patients 5. Neutropenic diet is a suggested dietary pattern for infection prevention 6 but there are still contradictory results about its efficacy 4-12. The studies have suggested that raw and cooked diet have no effect on the infection incidence 4-16 and patients who adhere from the cooked dietary pattern, the principal of neutropenic diet, have significantly lower vitamin C intake (38.9%). Moreover, the level of vitamin C decreases in blood malignancies 17. Vitamin C is a water-soluble vitamin with antioxidant properties due to its tendency in losing electrons to 8 crucial enzymes involving in neutralizing free radicals 18.
Oxidative stress prevention and increasing in anti-oxidant capacity will affect various health-related and healing processes in the body, including cell aging, inflammation reduction, and cancer-related mechanisms, so human body physiologic mechanisms seem to be a key component in diseases overcoming 18, 19, 20, 21. Studies have suggested that oral intake of vitamin C can reduce CRP and IL-6 18, 22 and even reinforce the immune system. Vitamin C interacts with inflammatory cytokines and protects immune system cells from ROS. Moreover, ascorbic acid derivatives may lead to more antibodies production 23, 24. The aim of this study was to examine the impact of vitamin C supplementation along with a neutropenic diet on nutritional status and serum albumin level in patients with ALM undergoing chemotherapy.
MATERIALS AND METHODS: This randomized controlled clinical trial was conducted for a period of one month. 50 Patients diagnosed with ALM referring to Shariati Hospital Oncology Department in Tehran were selected for this study according to the formula below and then divided into “study” and “control” groups randomly.
µ1 - µ2 = 4
s1= s2= 5
α = 0/05
Z1- α/2 =1/96
Z1-β = 0/84
Inclusion Criteria for the Study:
- Willingness to participation.
- Age older than 18 years.
- AML diagnosis approved by hematologist,
- A maximum of one month from the onset of a person's illness,
- Simultaneous chemotherapy protocol,
- Affected by any type of AML except type 3.
Exclusion Criteria for the Study:
- Any vitamin-mineral supplement consumption,
- BMI<18/5 before entering the study,
- History of chemotherapy drugs consumption,
- bone marrow transplant,
- Pregnant and lactating women.
Energy Calculation and Dietary Suggestions: The total required energy was calculated by Mifflin formula according to body weight and height, appropriate stress factor and physical activity (1.36 according to previous studies). The diet pattern included 50-55% of carbohydrate, 15-20% protein, and 30% fat.
The nutritional suggestions were given as brochures and included: the consumption of cooked vegetables, raw banana and pilled orange, fruit compote and juices, well-cooked egg and meat, pasteurized dairy products and boiled water. All patients were advised to avoid consuming raw vegetables 7, 10. Each patient was given 28 fizzy tablets containing 500 mg vitamin C for the duration of 4 weeks produced by Vita Fiz company approved by the FDA.
Anthropometric Measurements: The patient’s body weight and height were measured by seca scale and height gauge with the precise of 100 grams and 0.5 centimeters, respectively. The body mass index was calculated using weight and height.
Vitamin C Assessment and Calorie Intake: For energy and vitamin C intake assessment, 3 days food records were taken before and at the end of the study via interview and the data were analyzed by nutritionist 4 software.
Malnutrition Severity Assessment: The severity of malnutrition was assessed by PG-SGA malnutrition evaluation questionnaire which included weight loss, any changes in food intake, and any complaints related to nutrition, physical activity status and physical examination for patients with cancer undergoing chemotherapy. The percentage of weight loss was calculated according to questionnaire manual, past and current body weight in the past first and 6 months. After submitting the data from the clinical examination, the scores were ranked in each part. For nutritional complaint and adipose tissue examination, >6 was severe, 3-6 was moderate and <3 was low. For weight loss during the past 6 months, the ranking was >20%, 10-20%. 5-10% and<5% and for muscular adipose tissue loss were >6 for severe, 4-6 for moderate and <3 for low which was explained according to required intervention for questionnaire and malnutrition severity including level A (appropriate nutrition), B (at risk of malnutrition) and C (severe malnutrition).
Serum Albumin Assessment: Blood samples were collected before and after the chemotherapy and serum albumin was measured after centrifuging and serum separation in -80°C with coloring method using Zell bio Germany kit with the accuracy of 0.2 gr/dl.
Statistical Analysis: All of the data was analyzed by SPSS software version 21. The means of the two groups were compared using paired t-test in the case of normal distribution.
RESULTS: Of the 58 subjects recruited in the study, two subjects dropped out and six subject was excluded because of a lack of consumption supplement. There was no significant difference in gender, age, and height at the first of the study between the two groups Table 1. The average age was 40.80 ± 12.77 and 38.36 ± 13.75 for supplementation and control group, respectively. There was no significant difference between energy, carbohydrate, protein, fat, vitamin E and vitamin C intake at the beginning and the end of the study in each group. As shown in the table, the average of energy, protein, fat, vitamin C and E intake between the two groups showed a significant difference at the end of the study Table 2.
TABLE 1: INTERVENTION AND CONTROL GROUPS PARTICIPANT’S GENERAL INFORMATION
|Variable||Intervention group||Control group||P-value**|
Age and height are reported as standard deviation average,**t-test
TABLE 2: CALORIE AND SOME OF THE NUTRIENTS INTAKE IN PARTICIPANTS
|Variable||Baseline||At the end||P value**|
*variable are reported as average ± standard deviation, *** paired t-test, *** t-test
The results have suggested that there were no significant differences in serum albumin level between the two groups at the beginning of the study. The serum albumin level increased in the intervention group (from 3.45 ± 0.63 to 3.59 ± 0.57). But it was not significant. Serum albumin decreased significantly in control group (from 3.51 ± 0.79 to 3.09 ± 0.5) at the end of the study (p-value= 0.03) Table 3. There was no significant difference between body weight, body mass index at the beginning and the end of the study between the two groups Table 4. The nutritional status was not significantly different at the first bud has shown a significant difference at the end of the study between the two groups (p-value=0.001) Table 4.
TABLE 3: PARTICIPANT’S SERUM ALBUMIN LEVEL COMPARISON AT THE BEGINNING AND THE END OF THE STUDY
|Variable||Baseline||At the end||P-value**|
*variable are reported as average ± standard deviation, *** paired t-test, ***t-test
TABLE 4: PARTICIPANT’S BODY WEIGHT, BODY MASS INDEX AND NUTRITIONAL STATUS AT THE BEGINNING OF THE STUDY COMPARED TO THE END OF THE STUDY*
|Variable||Baseline||At the end||P-value**|
|Body mass index|
|Prone to malnutrition||12||6|
|Prone to malnutrition||10||6|
*variable are reported as average ± standard deviation, **paired t-test, ***t-test, ****Chi Square
DISCUSSION: Vitamin C deficiency is common among patients with cancer and it is estimated that 30% of patients with advanced cancer are vitamin C deficient which may affect their chance for survival and even cause some clinical problem such as fatigue, anorexia, and depression. This deficiency may be as a result of nausea and vomiting as a side effect of cancer and may increase the risk of unbalanced diets. The studies have indicated that there is a significant association between vitamin C status and serum albumin level. Moreover, malnutrition as a cause of chemotherapy, may lead to malnutrition and increase the risk of vitamin C deficiency in patients with cancer 1, 2, 25.
On the other hand, infection is another common problem in patients with AML and patients with cancer undergoing chemotherapy, which may be caused by disease or treatment processes.
So interventions for decreasing the risk of infections, such as neutropenic diets are usually used in order to decrease the exposure to infectious agents. Karen Moody and et al have suggested that neutropenia is a clinical side effect of chemotherapy in patients with cancer and the decrease in the number of neutrophils may increase the risk of infections 26, 27.
In this study, vitamin C supplementation combined with neutropenic diet were given to AML patients for the first time in Iran. As mentioned before, neutropenic diet is a common diet among patients with leukemia under chemotherapy including cooked foods and vegetables, raw banana and pilled orange, fruit compote and juice, well-cooked meat and egg, pasteurized dairy products, boiled water and avoiding from salad and raw vegetables consumption, which includes safety points in preparation of the foods, also 14, 18, 25, 28-32.
Vitamin C loss during cooking is approved by the previous studies. This study was aimed to assess the effect of neutropenic diet on nutritional status, serum albumin level and anthropometric factors in AML patients under chemotherapy. The results have suggested that vitamin C supplementation has improved nutritional status in these patients. The rate of patients prone to malnutrition and severe malnutrition has decreased by 48%. In a study on 63 patients with leukemia in 3 hospitals of Tehran, 19.4% of patients were malnourished before the chemotherapy and after that, 76.1% had moderate malnourished and 6.3% were severely malnourished. Khoshnevis and et al., have suggested that 53.1% of their study subjects were malnourished. Among these patients, 29.1% were moderately malnourished and 24% were severed malnourished 29. So the results suggest that malnutrition is common among patients with cancer under chemotherapy which is compatible with our results.
The analysis of 3 days food records have suggested that the average of energy, protein, and fat intake in the intervention group were significantly different compared to the control group at the end of the study. There was no significant difference between vitamin E and C intake in the two groups at first, but there was a significant difference in the intervention group compared to the control group at the end of the study. At the end of the study, the intake of macronutrients (carbohydrate. Protein and fat) and micronutrients (Vitamin C and E) have significant differences in the intervention group compared to the control group.
There were no significant differences between body weight and body mass index in the two groups. Albumin is an indicator for malnutrition which has significantly increased in the intervention group at the end of the study. Fumeron and et al., aimed to evaluate the effect of vitamin C supplement on inflammatory factors and oxidative stress in hemodialysis patients and have suggested that the serum albumin level has increased in the patients under hemodialysis but was not significant compared to the control group 18, 19, 28. Quan Jun Yang and et al., have suggested that cancer cachexia is characterized by weight loss, adipose tissue wasting, muscle atrophy and loss of appetite. Serum albumin levels and some other factors such as IGF-1 are considered as cachexia side effects during cancer which may be due to low carnosine depeptidase-1 level in patients with gastrointestinal cancer 33, 34, 35, 36, 37.
Daniel W. Nixon et al., also realized that the serum vitamin C, vitamin A, and folate are lower in 20-45% of patients in the second phase of their study and have concluded that protein and energy undernutrition in common in patients with cancer and is combined with the loss of adipose tissue and visceral protein. Furthermore, they have assessed the degree of malnutrition with creatinine to height ratio and serum albumin level. The results have suggested that the lower serum albumin level (lower than 3.5 g/dl) is significantly related to survival incidence 25.
CONCLUSION: According to the results, it can be concluded that vitamin C supplementation in a patient undergoing chemotherapy significantly improves nutritional status. Also, food intake and serum albumin are improved by vitamin C supplementation. Further studies are needed to approve the results of the present study.
ACKNOWLEDGEMENT: Kindly thanks and regards to all participants, A and B Shariati Hospital Oncology Department.
COMPLIANCE WITH ETHICS GUIDELINE: Study protocol was approved by the Nutrition Research Institute ethical committee. All participants gave their written informed consent before they participated in the study.
COMPETING INTEREST: The authors declare that they have no competing interests.
- Ferreira IB, Marinho Eda C, Custodio ID, Gontijo CA, Paiva CE, Crispim CA and Maia YC: Food intake and the nutritional status of women undergoing chemotherapy. Ciencia & Saude Coletiva 2016; 21: 2209-18.
- Custodio ID, Marinho Eda C, Gontijo CA, Pereira TS, Paiva CE and Maia YC: Impact of chemotherapy on diet and nutritional status of women with breast cancer: A prospective study. PloS One 2016; 11: e0157113.
- Zeinab Fazeli1 MAP, Vahedi M, Abadi A, Sadat F and Fazeli Bavand-Pour ARB: Leukemia cancer mortality trend in Iran, from 1995 to 20042013.
- Esfahani A, Ghoreishi Z, Abedi Miran M, Sanaat Z, Ostadrahimi A, Eivazi Ziaei J, Ghayour Nahand M, Asghari Jafarabadi M, Sorusheh Y and Esmaili H: Nutritional assessment of patients with acute leukemia during induction chemotherapy: association with hospital outcomes. Leukemia & Lymphoma 2014; 55: 1743-50.
- Carr SE and Halliday V: Investigating the use of the neutropenic diet: a survey of UK dietitians. J Hum Nutr Diet 2015; 28: 510-5.
- Sonbol MB, Firwana B, Diab M, Zarzour A and Witzig TE: The Effect of a neutropenic diet on infection and mortality rates in cancer patients: A meta-analysis. Nutrition and Cancer 2015: 1-9.
- Lassiter M and Schneider SM: A pilot study comparing the neutropenic diet to a non-neutropenic diet in the allogeneic hematopoietic stem cell transplantation population. Clin J Oncol Nurs 2015; 19: 273-8.
- Foster M: Reevaluating the neutropenic diet: time to change. Clin J Oncol Nurs 2014; 18: 239-41.
- Braun LE, Chen H and Frangoul H: Significant inconsistency among pediatric oncologists in the use of the neutropenic diet. Pediatr Blood Cancer 2014; 61: 1806-10.
- Garofolo A: Neutropenic diet and quality of food: a critical analysis. Revista Brasileira de Hematologia e Hemoterapia 2013; 35: 79-80.
- Galati PC, Lataro RC, Souza VM, de Martinis EC and Chiarello PG: Microbiological profile and nutritional quality of raw foods for neutropenic patients under hospital care. Revista Brasileira de Hematologia e Hemoterapia 2013; 35: 94-8.
- Trifilio S, Helenowski I, Giel M, Gobel B, Pi J, Greenberg D and Mehta J: Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation. Biology of blood and marrow transplantation. Journal of the American Society for Blood and Marrow Transplantation 2012; 18: 1385-90.
- Mutel T, Foegle J, Belotti L, Sery V, Bourneton O, Hernandez C, Lutz P and Lavigne T: Diet of neutropenic patients in pediatric oncology service; the experience of the University Hospital of Strasbourg (HUS). Pathol Biol (Paris) 2012; 60: 340-6.
- Fox N and Freifeld AG: The neutropenic diet reviewed: moving toward a safe food handling approach. Oncology (Williston Park) 2012; 26: 572-5, 80, 82 passim.
- Boeckh M: Neutropenic diet-good practice or myth? Biology of blood and marrow transplantation, Journal of the American Society for Blood and Marrow Transplantation 2012; 18: 1318-9.
- Aftandilian CC, Milotich C and Sakamoto KM: The neutropenic diet. still ageless? Oncology (Williston Park) 2012; 26: 586, 8-9.
- Huijskens MJ, Wodzig WK, Walczak M, Germeraad WT and Bos GM: Ascorbic acid serum levels are reduced in patients with hematological malignancies. Results in Immunology 2016; 6: 8-10.
- Schoenfeld JD, Alexander MS, Waldron TJ, Sibenaller ZA, Spitz DR, Buettner GR, Allen BG and Cullen JJ: Pharmacological ascorbate as a means of sensitizing cancer cells to radio-chemotherapy while protecting normal tissue. Seminars in Radia Oncol 2019; 29: 25-32.
- Ryszawy D, Pudelek M, Catapano J, Ciarach M, Setkowicz Z, Konduracka E, Madeja Z and Czyz J: High doses of sodium ascorbate interfere with the expansion of glioblastoma multiforme cells in-vitro and in-vivo. Life Sciences 2019: 116657.
- Li MC, Chiu YH, Gaskins AJ, Minguez-Alarcon L, Nassan FL, Williams PL, Petrozza J, Hauser R and Chavarro JE: Men's Intake of Vitamin C and beta-Carotene Is Positively Related to Fertilization Rate but Not to Live Birth Rate in Couples Undergoing Infertility Treatment. The Journal of Nutrition 2019.
- Gao X, Wei K, Hu B, Xu K and Tang B: Ascorbic acid induced HepG2 cells' apoptosis via intracellular reductive stress. Theranostics 2019; 9: 4233-40.
- Takahashi H, Mizuno H and Yanagisawa A: High-dose intravenous vitamin C improves quality of life in cancer patients. Personalized Medicine Universe 2012; 1: 49-53.
- Qiu M, Zhou YX, Jin Y, Wang ZX, Wei XL, Han HY, Ye WF, Zhou ZW, Zhang DS, Wang FH, Li YH, Yang DJ and Xu RH: Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy. Support Care Cancer 2015; 23: 1933-9.
- Panunzio MF, Caporizzi R, Antoniciello A, Cela EP, Ferguson LR and D'Ambrosio P: Randomized, controlled nutrition education trial promotes a Mediterranean diet and improves anthropometric, dietary, and metabolic parameters in adults. Ann Ig 2011; 23: 13-25.
- O'Leary BR, Houwen FK, Johnson CL, Allen BG, Mezhir JJ, Berg DJ, Cullen JJ and Spitz DR: Pharmacological ascorbate as an adjuvant for enhancing radiation-chemotherapy responses in gastric adenocarcinoma. Radiation Research 2018; 189: 456-65.
- Moody K, Finlay J, Mancuso C and Charlson M: Feasibility and safety of a pilot randomized trial of infection rate: neutropenic diet versus standard food safety guidelines. J Pediatr Hematol Oncol 2006; 28: 126-33.
- Moody K, Charlson ME and Finlay J: The neutropenic diet: what's the evidence? J Pediatr Hematol Oncol 2002; 24: 717-21.
- Vineetha RC, Archana V, Binu P, Arathi P and Nair RH: L-Ascorbic acid and alpha-tocopherol reduce hepatotoxicity associated with arsenic trioxide chemotherapy by modulating Nrf2 and Bcl2 transcription factors in chang liver cells. Nutrition and Cancer 2018; 70: 684-96.
- Khoshnevis N, Ahmadizar F, Alizadeh M and Akbari ME: Nutritional assessment of cancer patients in Tehran, Iran. Asian Pacific Journal of Cancer Prevention: APJCP 2012; 13: 1621-6.
- Restau J and Clark AP: The neutropenic diet: does the evidence support this intervention? Clin Nurse Spec 2008; 22: 208-11.
- Iversen PO, Ukrainchenko E, Afanasyev B, Hulbekkmo K, Choukah A, Gulbrandsen N, Wisloff F and Tangen JM: Impaired nutritional status during intensive chemotherapy in Russian and Norwegian cohorts with acute myeloid leukemia. Leukemia & Lymphoma 2008; 49: 1916-24.
- Gardner A, Mattiuzzi G, Faderl S, Borthakur G, Garcia-Manero G, Pierce S, Brandt M and Estey E: Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. Journal of clinical oncology: Official Journal of the American Society of Clinical Oncology 2008; 26: 5684-8.
- Chanphai P and Tajmir-Riahi HA. Conjugation of vitamin C with serum proteins: A potential application for vitamin delivery. International Journal of Biological Macromolecules 2019; 137: 966-72.
- Higashiyama Y, Kojima C, Kubota M, Nagai A, Watanabe K, Adachi S and Usami I: Longitudinal nutritional assessment in acute lymphoblastic leukemia during treatment. Pediatr Int 2014; 56: 541-6.
- Fei B, Pan J, Wu H, Gao Q, Han W, Du J and Jin L: [Application of preoperative nutritional risk screening in perioperative nutrition support for colorectal cancer patients]. Zhonghua Wei Chang Wai Ke Za Zhi 2014; 17: 582-5.
- Miyata H, Yano M, Yasuda T, Hamano R, Yamasaki M, Hou E, Motoori M, Shiraishi O, Tanaka K, Mori M and Doki Y: Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Clin Nutr 2012; 31: 330-6.
- Liao Q, Zhao YP, Wang WB, Dai MH, Hu Y, Liu ZW and Zhu Y. [Perioperative nutrition support of the patients with pancreatic head cancer]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2005; 27: 579-82.
How to cite this article:
Hosseini A, Jalali SM, Ajami M, Abdollahi M, Ranjbar H and Badeli M: The evaluation of vitamin C supplementation on nutritional status of patients with acute myeloid leukemia undergoing chemotherapy. Int J Pharm Sci & Res 2020; 11(1): 489-95. doi: 10.13040/ IJPSR.0975-8232.11(1).489-95.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
A. Hosseini, S. M. Jalali, M. Ajami *, M. Abdollahi, H. Ranjbar and M. Badeli
Department of Food and Nutrition Policy and Planning Research, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
08 October 2018
27 July 2019
13 August 2019
01 January 2020