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LONG-TERM EFFECTS OF VARYING CONSUMPTION OF ω 3
FATTY ACIDS IN EAR, NOSE AND THROAT CANCER
PATIENTS: ASSESSMENT 1 YEAR AFTER RADIOTHERAPY.
Journal: International Journal of Food Sciences and Nutrition Manuscript ID: Draft
Manuscript Type: Research Paper Date Submitted by the Author: n/a
Complete List of Authors: Roca-Rodríguez, MM; Virgen de la Victoria Hospital, Endocrinology and Nutrition
García-Almeida, JM; Virgen de la Victoria Hospital, Ruiz-Nava, J; Virgen de la Victoria Hospital, Alcaide, J; Virgen de la Victoria Hospital,
Lupiañez-Pérez, Y; Virgen de la Victoria Hospital, Rico-Pérez, JM; Virgen de la Victoria Hospital, Toledo-Serrano, MD; Virgen de la Victoria Hospital, Cardona, F; Virgen de la Victoria Hospital,
Medina-Carmona, JA; Virgen de la Victoria Hospital, Tinahones, FJ; Virgen de la Victoria Hospital, Keywords: Fatty acids, Nutrition
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LONG-TERM EFFECTS OF VARYING CONSUMPTION OF ω 3 FATTY ACIDS IN EAR, NOSE AND THROAT CANCER PATIENTS: ASSESSMENT 1 YEAR AFTER
RADIOTHERAPY.
Running title: ω 3 fatty acids in ear, nose and throat cancer.
María del Mar Roca-Rodríguez1,2,4, Jose Manuel García-Almeida2, Josefina Ruiz-Nava2, Juan Alcaide1, Yolanda Lupiañez-Pérez3, Jose Manuel Rico-Pérez3, María Dolores Toledo-Serrano3, Fernando Cardona1,4, Jose Antonio Medina-Carmona3, Francisco J. Tinahones1,2,4.
1
Biomedical Research Institute of Malaga (IBIMA),Virgen de la Victoria Hospital, University of Malaga, Spain.
2
Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital, Málaga, Spain.
3
Department of Clinical and Radiotherapeutic Oncology, Virgen de la Victoria Hospital, Málaga, Spain.
4
Biomedical Research Center of Physiopathology of Obesity and Nutrition (CIBER CB06/003), Carlos III Health Institute. Madrid, Spain.
Corresponding authors:
Tinahones Francisco J. and Roca-Rodríguez M. Mar
Biomedical Research Institute of Malaga (IBIMA) and Department of Endocrinology and Nutrition,Virgen de la Victoria Hospital, University of Malaga, 29010 Malaga, Spain. Tel. (+34) 951032648. Fax (+34) 951924651.
E-mail: [email protected], [email protected]
Conflict of interest: The authors report no conflict of interest in this paper.
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ABSTRACTA prospective one-year follow-up study in ear, nose and throat (ENT) cancer patients one year after radiotherapy to assess the effect of varying consumption of ω 3 fatty acid according to whether they consumed more or less than the 50th percentile of ω 3 fatty acids. Clinical, analytical, inflammatory (CRP and IL-6) and oxidative variables (TAC, GPx, GST, and SOD) were evaluated. The study comprised 31 patients (87.1% men), with a mean age of 61.3 ± 9.1 years. Hematological variables showed significant differences in the patients with a lower consumption of ω 3 fatty acids. A lower mortality and longer survival were found in the group with ω 3 fatty acid consumption ≥50th percentile but the differences were not significant. No significant difference was reached in toxicity, inflammation and oxidative stress markers. The group with ω 3 fatty acid consumption <50th percentile significantly experienced more hematological and immune changes.
Keywords: nutritional supplement, cancer, clinical study, metabolic status, survival.
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INTRODUCTIONAbout 40-50% of patients with ear, nose and throat (ENT) cancer suffer from malnutrition (Koom, 2012; Righini, 2013), and malnutrition has been associated with a greater incidence of postoperative
complications, a poor response to treatment and a higher risk of tumor recurrence (Martín-Villares, 2003). This poor nutritional status is more frequent if radiotherapy (RT) is given. RT alters cellular homeostasis, signal transduction pathways and apoptosis (Borek, 2004). RT toxicity is mediated by local inflammatory cytokines (Michalowski, 1994) such as IL-1, IL-6 and TNF-alpha, which are implicated in the cachexia-anorexia syndrome (Peters, 1996). Radiation also generates reactive oxygen species (ROS), damaging lipids, proteins and DNA (Fridlyand, 2005).
Several protective mechanisms exist to prevent or limit oxidative damage. Both enzymatic and non-enzymatic antioxidants exist. Enzymatic antioxidants include superoxide dismutase (SOD), which rapidly dismutates the cellular superoxide anion generated by ionizing radiation to hydrogen peroxide, which is then disposed of by the enzyme glutathione peroxidase (GPx). Additionally, glutathione S-transferase (GST) detoxifies electrophiles by conjugation reactions (Fridlyand, 2005). ROS can also be eliminated or inactivated in vivo by endogenous molecules such as uric acid or albumin, or by different exogenous antioxidants derived from the diet (Baynes, 1991). The sum of endogenous and food-derived antioxidants represents the total antioxidant capacity (TAC).
Many data support the beneficial effect of ω 3 polyunsaturated fatty acids in the prevention and treatment of several chronic diseases, such as cardiovascular disease, inflammatory disease and cancer. These effects are related to apoptosis induction and cell cycle arrest in cancer cells by ω 3 fatty acids (Calviello, 2009; Ruxton, 2007). In addition, ω 3 polyunsaturated fatty acids can also improve quality of life, decrease weight loss in patients with advanced cancer (Fearon, 2013), reduce energy expenditure (Moses, 2004), and exert anti-inflammatory action. However, not all studies agree on these positive effects (Bruera, 2003).
The aim of this study was to assess the changes induced by the varying consumption of ω 3 fatty acids in inflammation, oxidative stress and metabolic status in ENT cancer patients one year after RT.
MATERIALS AND METHODS Study design
This prospective, one-year, follow-up study involved two patterns of ENT cancer patients, according to their total consumption during the first 3 months of the study of ω 3 fatty acids, obtained
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from their diet and from enteral supplements when necessary. The cutoff was the 50th percentile (50thP) of the total consumption of ω 3 fatty acids (0.2 ± 0.84 grams). Consumption of fatty acids (saturated, monounsaturated and polyunsaturated) were quantified by “Diet Source software (1.2)” based on 7-day food record. Respect to polyunsaturated acids, we differentiated between eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. In general population, a consumption of 0.250 grams per day of EPA and DHA acids is recommended (FAO 2010). The study included 31 patients with ENT cancer (TNM stages 3 and 4) who required treatment with RT. The exclusion criteria were: age <18 or >80 years, evidence of acute or chronic inflammatory disease, infectious disease, metastatic disease, prior radiation therapy in the head and neck area, edema and/or ascites, malabsorption, and any psychological or medical disorder that would prevent the signing of informed consent.
The patients were evaluated before RT and chemotherapy and 12 months after starting RT. In addition, the Karnofsky performance status and several analytical variables related to toxicity
(haemogram, ferritin, liver function,...), inflammation (CRP and IL-6) and oxidative stress markers (TAC, GPx, GST, and SOD) were also assessed at 3 and 6 months after RT. Their baseline metabolism, energy intake and body composition were evaluated by SenseWear® PRO 3 armband BodyMedia, Ribefood questionnaire (Martí-Cid, 2007), and BioScan® SPECTRUM multifrequency, respectively, at the start of the study and 12 months later. The patients were monitored for cutaneous, hematologic and mucosal toxicity throughout the follow-up period. The National Cancer Institute (NCI) Common Toxicity Criteria version 4.0 (US National Institute of Health, 2008) was used for grading toxicities. The Karnofsky performance status was also examined.
The study was approved by the Ethics Committee of Virgen de la Victoria Hospital and was conducted in accordance with the Declaration of Helsinki. All the participants gave their signed consent after being fully informed of the goal and characteristics of the study.
Concerning the RT, the patients were treated with 6 MV photons from a linear accelerator equipped with a secondary multileaf collimator. All the patients underwent computed axial tomography simulation with a thermoplastic mask for immobilization, virtual simulation and application of a three-dimensional calculation algorithm. The volumes and dose specifications were designed according to recommendations of the International Commission on Radiation Units and Measurements (ICRU 50) (Jones, 1999). The patients underwent conventional RT (five fractions of 1.8 to 2 Gy per week) or accelerated schedules with concomitant overlay for 4 weeks.
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Concerning chemotherapy, the patients received 3 cycles of 100 mg/m2 of cisplatin (CDDP). Patients deemed unfit for chemotherapy (23% of the patients) were offered treatment with cetuximab. In these cases, they received 400 mg/m2 of cetuximab (shock dose), after which a 250 mg/m2 dose of cetuximab was administrated concurrently weekly during the course of RT.
Laboratory determinations
Fasting venous blood samples were drawn at baseline before starting RT and chemotherapy and one year after starting RT. The samples were collected in vacutainers with and without
ethylenediaminetetraacetic acid and placed on ice. The samples were centrifuged at 4000 rpm for 15 minutes at 4 Cº. Plasma and serum were aliquotted and stored at -80 Cº until analysis.
Serum biochemical parameters were measured in duplicate. Serum glucose (Randox
Laboratories Ltd., Antrim, UK), uric acid (Dimension autoanalyzer from Dade Behring Inc. Deerfield, IL, USA), albumin, creatinine and urea (Siemens Healthcare Diagnostics Inc., Newark, DE, USA) were measured using standard enzymatic methods. CRP and IL-6 levels were measured using a human CRP Quantikine ELISA Kit from R&D Systems (Abingdon, United Kingdom) and a human IL-6 Quantikine ELISA from R&D Systems (Abingdon, United Kingdom) according to the manufacturer’s instructions, respectively. TAC, GPx, GST, and SOD activities were measured in plasma with commercial kits (Cayman Chemical, Ann Arbor, MI). The intra- and inter-assay coefficients of variation (CV) of TAC were 3.4% and 3.0%, respectively. The intra- and inter-assay CV of GPx were 5.7% and 7.2%, respectively. The intra- and inter-assay CV of GST were 4.1% and 7.9%, respectively. The intra- and inter-assay CV of SOD were 3.2% and 3.7%, respectively. LPO levels were measured in serum using a commercial kit (Cayman Chemical, Ann Arbor, MI).
Statistical analysis
The results are given as the mean ± SD. All clinical parameters are summarized by descriptive statistics. The information at each visit was compared in both groups of consumption of ω 3 fatty acids between baseline and 12 month visits by the U Mann Whitney-test and between the four different visits by the Friedman-test, both for non-parametric variables. Differences between groups in the frequency distribution of qualitative variables were assessed by the Fisher test. The Spearman correlation coefficient was calculated to estimate the linear correlations between variables. In all cases, the rejection level for a null hypothesis was α=0.05 for two tails. The statistical analysis was done with SPSS (Version 15.0 for Windows; SPSS, Chicago, IL).
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RESULTSTable 1 shows the demographic characteristics, the BMI at baseline and survival after the study of the ENT cancer patients according to the consumption of ω 3 fatty acids. There were no significant
differences between the two groups. Nevertheless, a lower mortality and a longer survival were found in the ω 3 fatty acid consumption ≥50thP group, though the differences were not significant (10.5 vs. 25% and 89.5 vs. 75%, respectively).
Table 2 summarizes the differences in body composition and basal metabolism at baseline and after 12 months. No significant differences were seen between the two groups according to the consumption of ω 3 fatty acids.
The energy intake in both groups is expressed in Table 3. After 12 months, the ω 3 fatty acid ≥50thP group had a greater intake of carbohydrates and eicosapentaenoic acid (EPA). During the study, significant differences in the ω 3 fatty acid <50thP group were found between baseline and 12 months, including a lower basal metabolism (p=0.028) and lean mass (p=0.025), and a higher consumption of lipids (p=0.030), monounsaturated fatty acids (p=0.025) and polyunsaturated fatty acids (p=0.035) after 12 months. No significant differences were observed in the ω 3 fatty acid ≥50thP group between baseline and 12 months.
The Karnofsky performance status and several analytical variables were examined at baseline and 3, 6 and 12 months after RT (Table 4). Concerning the hematological variables, both groups experienced a parallel evolution throughout the study, though it should be noted that all the variables, except monocytes, showed significant differences in the patients with a lower consumption of ω 3 fatty acids. On the other hand, the patients with ω 3 fatty acid consumption ≥50thP had significant changes in liver function and levels of lactic dehydrogenase (LDH). No significant differences were observed between the groups according to the ω 3 fatty acid intake in toxicity, inflammation or oxidative stress markers (data not shown, except SOD in Table 4).
Significant positive correlations were observed in all the patients between the total consumption of ω 3 fatty acids at baseline and at 12 months, and the Karnofsky score at baseline (Rs = 0.438, p=0.016 and Rs = 0.435, p=0.023, respectively). In addition, a positive correlation was seen between the total consumption of ω 3 fatty acids at baseline and at 12 months (Rs = 0.435, p=0.023).
Patients with a ω 3 fatty acid intake <50thP showed significant positive correlations between consumption of EPA at baseline and at 12 months, and the Karnofsky score at baseline (Rs = 0.457,
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p=0.011 and Rs = 0.442, p=0.021, respectively), and negative correlations with SOD at baseline and fat mass and total body water at 12 months (Rs = -0.460, p=0.010; Rs-0.406, p=0.032; and Rs = -0.423, p=0.025, respectively). We also observed certain significant correlations concerning the Karnofsky score at 12 months: a negative correlation with basal metabolism at baseline (Rs = -0.464, p=0.013) and a positive correlation with EPA at 12 months (Rs = 0.449, p=0.021).
In the ω 3 fatty acid intake ≥50thP group, the Karnofsky score at baseline correlated negatively with total body water at 12 months (Rs = -0.675, p=0.023) and positively with energy intake,
carbohydrates, polyunsaturated fatty acids and TAC at 12 months (Rs = 0.671, p=0.024; Rs = 0.671, p=0.024; Rs = 0.671, p=0.024; Rs = 0.648, p=0.023; respectively). In addition, the Karnofsky score at 12 months correlated positively with IL-6 at baseline and LDH at 3 months (Rs = 0.998, p=0.044 and Rs = 0.889, p=0.018, respectively).
DISCUSSION
Cancer patients experience anthropometric, metabolic and analytical changes due to the disease and its treatment (Ali, 2011; Somani, 2011). ENT cancer patients often develop difficulties chewing and swallowing food, and thus have a decreased food intake. The final result is a tendency towards
malnutrition, especially in irradiated patients (Chencharick, 1983), which commonly results in the need for a nutritional supplement. The aim of this study was to analyze the effects of the consumption of greater amounts of ω 3 polyunsaturated fatty acids in these patients. Weight loss in cancer patients is frequently ascribed to a combination of a reduced energy intake and hypermetabolism (Moses, 2004). No significant differences regarding weight loss were observed during the study according to the
consumption of ω 3 fatty acids. The group with ω 3 fatty acid consumption ≥50thP showed a greater intake of carbohydrates and EPA. EPA has been shown to inhibit muscle protein catabolism and to increase lean body mass in cancer patients (Moses, 2004).
Cancer and its treatments also involve hematological and immune changes (Ali, 2011). Over the study period, the patients with a lower intake of ω 3 fatty acids experienced more hematological and immune changes. These results are consistent with those of Kemen (Kemen, 1995) et al. and Sorensen et al. (Sorensen, 2009) who reported an increase in T lymphocytes and their subsets in gastrointestinal and head and neck cancer patients after 10 days of nutritional support enhanced with arginine, ω 3 fatty acids and ribonucleic acids.
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No differences in albumin or uric acid levels were observed between the two groups (data not shown), in contrast to previous studies which reported that ω 3 polyunsaturated fatty acids increase serum albumin (Mahdavi, 2007)and reduce levels of uric acid (Reddy, 2002; Sarsilmaz, 2003).
Concerning functional status, we found a higher Karnofsky index at baseline in the patients with ω 3 fatty acid consumption ≥50thP, with no other significant inter-group or intra-group differences throughout the study. Our results are in agreement with others reporting no significant influence on patient function (Bruera, 2003).
Like others (Felekis, 2010), we too found no significant differences according to ω 3 fatty acid intake in inflammation or oxidative stress markers. Inflammatory parameters were increased in both groups of patients during the RT. It is well known that RT initiates a programmed molecular and cellular response to promote tissue repair, which includes the up-regulation of proinflammatory cytokines (Bechoua, 1999). Inflammation is a critical component of tumor progression and nutritional supplements seem to improve inflammatory parameters, with contradictory findings in the literature between specific and standard supplements (Machon, 2012). CRP (Dhankhar, 2011; Chen, 2011; Zeng, 2012; Peter, 2013) and IL-6 (Helzlsouer, 2006; Mojtahedi, 2011; Yadav, 2011; Brailo, 2012) have a prognostic value in head and neck tumors, through direct association with tumor state, tumor progression, metastasis and tumor response to treatment, and therefore disease-free survival and overall survival. Thus, any intervention which decreases levels of IL-6 and/or CRP would have beneficial effects on tumor prognosis (Nibali, 2012). Furthermore, oxidative stress could represent a useful tool for predicting the prognosis of head and neck cancer patients (Ziech, 2011). Again like others (Sharma, 2012), we observed that subjects receiving RT displayed parameters of oxidative stress with no differences according to their ω 3 fatty acid intake. At the end of the study, oxidative stress parameters showed a trend towards normalization. There have been conflicting reports on the effects of ω 3 fatty acid supplementation on oxidant/antioxidant status in humans (Simone, 2009; Park, 2009). Several studies have observed significant associations in head and neck cancer patients between SOD and GPx activity and better disease-specific survival and postoperative RT (Fu, 2011), between manganese SOD and tumor migration and invasion (Liu, 2012), and between the loss of GPx expression and tumor chemoresistance (Chen, 2011), which are significant prognostic factors for survival. Also, a deranged antioxidant defense system due to significantly lower levels of TAC (Korde, 2011) and higher levels of nitric oxide and GST has been found in these cancer patients, with a
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significant increase after RT (Dahiya, 2012). In contrast, we found no significant differences in these parameters.
A meta-analysis by Cerantola et al. (Cerantola, 2011) in patients undergoing major
gastrointestinal cancer surgery concluded that immunonutrition decreased morbidity and hospital stay, but not mortality rates, in contrast to other authors who found no difference in these parameters (Sultan, 2012). A lower mortality and longer survival in the ω 3 fatty acid consumption ≥50thP group were found in our study, but again the differences were not significant.
This study has several limitations, such as the small patient population sample, the contradictory publications evaluating immunonutrition support with which to compare our results, and the
heterogeneous metabolic response to cancer.
CONCLUSIONS
Patients with a lower intake of ω 3 fatty acids experienced more hematological and immune changes. However, no significant differences were observed between the groups according to their ω 3 fatty acid intake in toxicity, inflammation, or oxidative and stress markers. In addition, no significantly lower mortality or longer survival was found in the ω 3 fatty acid ≥50thP group. The absence of significant benefits regarding toxicity, functional status, inflammation, oxidative markers and survival in the ω 3 fatty acid ≥50thP group cannot be considered proof that such benefits do not exit. Survival outcomes of our exploratory study suggest the need for a study where survival was the end point. Finally, further studies with larger population samples and longer follow-up periods could provide additional insights into the effect of greater consumption of ω 3 fatty acids on response, evolution, prognosis and quality of life in ENT cancer patients.
ACKNOWLEDGMENTS
The authors thank the Oncology service and the Oncology nursing staff of the Virgen de la Victoria Hospital, Malaga. The authors also thank Ian Johnstone for English language editing of the text. M. Mar Roca-Rodríguez is supported by a fellowship from the Rio Hortega CM11/00030 Program from the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness.
DECLARATION OF INTEREST
The authors report no conflict of interest in this paper.
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Table 1. Demographic characteristics, BMI at baseline and survival
of ENT cancer patients according to ω 3 fatty acid intake.
ω 3 acids intake
(n)
ω 3 acids < P50
(13)
ω 3 acids ≥ P50
(18)
P
Gender (M/F)
11/2
16/2
0.553
Age (years)
60.8 ± 8.9
61.8 ± 10.0
0.193
BMI (kg/m
2)
BMI < 20
2 (16.7%)
1 (5.3%)
0.578
BMI 20-26
4 (33.3%)
7 (36.8%)
0.587
BMI > 26
6 (50%)
11 (57.9%)
0.438
Survival at study end
Dead
3 (25%)
2 (10.5%)
0.565
Alive with disease
1 (8.3%)
2 (10.5%)
0.574
Alive without disease
8 (66.7%)
15 (79%)
0.343
Values are presented as mean ± SD or numbers (percentages). 2
For Peer Review Only
Table 2. Differences in body composition and basal metabolism at baseline and after 12 months.
Baseline
12 months
ω 3 acids <
50thP
(n=13)
ω 3 acids ≥
50thP
(n=18)
P
ω 3 acids <
50thP
(n=13)
ω 3 acids ≥
50thP
(n=18)
P
Weight (kg)
71.6 ± 10.6
73.9 ± 15.2
0.823
67.0 ± 8.6
70.9 ± 18.0
0.439
BMI (kg/m2)
26.5 ± 4.1
26.9 ± 5.2
0.951
24.9 ± 4.0
24.9 ± 5.9
0.589
Fat mass
15.9 ±6.2
18.0 ± 7.7
0.477
16.5 ± 5.9
20.9 ± 14.3
0.621
Lean mass
55.8 ± 9.3
55.9 ± 10.2
0.897
50.4 ± 7.2
49.9 ± 4.9
0.840
Total body water
40.7 ± 7.3
40.5 ± 8.1
0.863
36.8 ± 5.9
36.0 ± 4.0
0.529
Basal metabolism
(Kcal)
1439.9 ± 188.2
1443.9 ± 239.5
0.931
1342.7 ± 134.9
1426.5 ± 274.8
0.559
Values are presented as mean ± SD or numbers (percentages). BMI: body mass index, Kcal: kilocalories. 2
For Peer Review Only
Table 3. Differences in energy intake at baseline and after 12 months.
Baseline
12months
ω 3 acids <
50thP
(n=13)
ω 3 acids ≥
50thP
(n=18)
P
ω 3 acids <
50thP
(n=13)
ω 3 acids ≥
50thP
(n=18)
P
Energy (Kcal)
1741.9 ± 538.2
2026.3 ± 474.9
0.329
2071.3 ± 540.7
2513.3 ± 499.5
0.051
Carbohydrates
201.7 ± 72.2
232.7 ± 50.0
0.381
215.4 ± 61.2
299.2 ± 81.1
0.010
Lipids
76.3 ± 26.4
93.9 ± 37.0
0.568
99.3 ± 30.2
107.0 ± 32.9
0.760
Proteins
62.2 ± 17.6
72.3 ± 21.2
0.122
76.9 ± 25.5
88.3 ± 18.7
0.249
Saturated fatty
acids
21.3 ± 9.2
27.5 ± 11.7
0.767
25.7 ± 8.1
27.7 ± 13.1
0.869
Monounsaturated
fatty acids
36.2 ± 14.7
41.2 ± 20.1
0.743
49.2 ± 17.9
50.9 ± 19.4
0.814
Polyunsaturated
fatty acids
8.4 ± 5.0
10.2 ± 2.6
0.318
11.9 ± 6.3
14.4 ± 5.3
0.151
Eicosapentaenoic
acid
0.5 ± 0.9
0.9 ± 0.6
0.100
0.1 ± 0.1
1.0 ± 1.35
0.010
Docosahexaenoic
acid
0.09 ± 0.1
0.2 ± 0.3
0.948
0.1 ± 0.1
0.2± 0.2
0.790
Values are presented as mean ± SD or numbers (percentages). BMI: body mass index, Kcal: kilocalories. P Statistically significant differences between both groups according to ω 3 acids intake at baseline and 12 months. Statistically significant differences (p<0.05).
For Peer Review Only
Table 4. Distribution of
Karnofskyperformance and analytical variables during the prospective
study according to the intake of ω 3 acids.
Baseline 3months 6months 12months P
ω 3 acids < 50thP
Karnofsky 91.7 ± 9.2 89.2 ± 9 91.3 ± 11.3 88.4 ± 10.7 0.186
Hematocrit (%) 39.7 ± 4.1 36 ± 3.3 38.4 ± 4.3 38.5 ± 4 0.002
Erythrocytes (x 106/µL) 4.3 ± 0.5 3.8 ± 0.4 4.2 ± 0.5 4.2 ± 0.5 <0.001
Hemoglobin (gr/dL) 13.1 ± 1.5 11.9 ± 1.1 12.6 ± 1.4 12.8 ± 1.2 0.006
Leukocytes (x 103/µL) 7.3 ± 2.4 5.9 ± 2.3 5.9 ± 2.2 6.5 ± 3 0.020
Lymphocytes (x 103/µL) 1.6 ± 0.7 0.9 ± 0.3 0.9 ± 0.4 1.2 ± 0.5 <0.001
Monocytes (x 103/µL) 0.6 ± 0.3 0.4 ± 0.2 0.5 ± 0.2 0.4 ± 0.2 0.338
Ferritin (ng/mL) 255 ± 201.2 254.2 ± 176.2 204.1 ± 158.7 153.4 ± 132.2 0.037
B12 Vitamin (pg/mL) 785.1 ± 183.5 709.7 ± 504 631.6 ± 272.6 656.3 ± 333.6 0.137
Total-Chol (mg/dL) 208 ± 39.9 223.9 ± 37.2 211.8 ± 36.2 217 ± 46.1 0.053
GGT (UI/L) 35.9 ± 17.5 44.8 ± 33.3 31.8 ± 2 37.5 ± 39.6 0.098
GPT (UI/L) 44.6 ± 16.7 35 ± 6 34.1 ± 7.5 35.3 ± 10.3 0.160
LDH (UI/L) 142.3 ± 26 124.8 ± 35.5 124.5 ± 29 155.2 ± 36.5 0.392
SOD (U/ml) 2.3 ± 1.1 3.3 ± 1.6 3.2 ± 2 1.9 ± 1.4 0.052
ω 3 acids ≥ 50thP
Karnofsky 98.3 ± 3.9 83.3 ± 5.8 85 ± 7.1 93 ± 8.2 0.163
Hematocrit (%) 40.8 ± 5.6 39.3 ± 5.2 40.1 ± 4.1 39.9 ± 4.4 0.562
Erythrocytes (x 106/µL) 4.4 ± 0.6 4.1 ± 0.6 4.3 ± 0.5 4.2 ± 0.5 0.498
Hemoglobin (gr/dL) 13.7 ± 1.9 13.2 ± 1.8 13.5 ± 1.2 13.4 ± 1.4 0.288
Leukocytes (x 103/µL) 7.4 ± 2.5 6.7 ± 3.3 5.9 ± 1.7 6.2 ± 1.4 0.468
Lymphocytes (x 103/µL) 1.5 ± 0.6 1 ± 0.4 1.1 ± 0.6 1.2 ± 0.4 0.018
Monocytes (x 103/µL) 0.6 ± 0.3 0.5 ± 0.2 0.4 ± 0.2 0.4 ± 0.2 0.043
Ferritin (ng/mL) 417.4 ± 437 334.3 ± 222.9 266.6 ± 200.8 151.2 ± 107 0.088
B12 Vitamin (pg/mL) 557 ± 248.2 569.6 ± 196.3 640.6 ± 182.4 455.5 ± 140.2 0.069
Total-Chol (mg/dL) 200 ± 55 225.8 ± 39.2 184.4 ± 26.3 178.6 ± 25.5 0.214
GGT (UI/L) 59.9 ± 32.9 80.4 ± 68.2 47 ± 22.1 42.7 ± 15.8 0.026
GPT (UI/L) 59.8 ± 13.4 52.5 ± 21.4 43.2 ± 11.2 42.9 ± 19.1 0.029
LDH (UI/L) 156.2 ± 26.8 140 ± 25.6 178.7 ± 30.4 212.9 ± 85 0.022
SOD (U/ml) 1.6 ± 1.1 3.7 ± 0.7 3.3 ± 0.1 1.8 ± 0.8 0.615
Data expressed as means ± SD. GGT: gamma glutamyl transferase, GPT: glutamic pyruvic transaminase, LDH: lactic dehydrogenase, SOD: superoxide dismutase. P value was based on the Friedman test.
