Technical Journal of Engineering and Applied Sciences
Available online at www.tjeas.com
©2013 TJEAS Journal-2013-3-17/1958-1962
ISSN 2051-0853 ©2013 TJEAS
Changes of weight, BMI and waist circumference
following fish oil supplementation in patients with
persistant and permanent atrial fibrillation
Elnaz Khorrami1, Mohammadjavad Hosseinzadeh-Attar1, 2*, Mostafa Hosseini3, Zahra
Emkanjoo4, Roya Kolahdoz Mohammadi2, Sina Moradmand5
1. International Campus, Tehran University of Medical Sciences
2. Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical
Sciences
3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical
Sciences
4. Department of cardiology, Iran University of Medical Sciences
5. Department of cardiology, Tehran University of Medical Sciences
Corresponding Author: Mohammadjavad Hosseinzadeh-Attar
ABSTRACT: Some studies have reported positive effects of fish oil supplementation on atrial fibrillation
(AF) which its mechanism is unknown. Fish oil supplementation could also improve endothelial function.
An association between AF and endothelial dysfunction was shown in previous studies. In this study we
investigated whether fish oil supplementation alters weight, body mass index (BMI) and waist
2
circumference in patients with chronic AF. Eighty chronic AF subjects with BMI>25kg/m , and age
between 50-85 years, were randomized to receive 2g/day fish oil or placebo for 8 weeks. Anthropometric
indices, including height, weight and waist circumference were measured and BMI was calculated before
and after the intervention. The intake of energy, macronutrients and n-3 PUFAs did not change
significantly in intervention period. Weight (72.58±13.26 vs. 73.74±12.13, P=0.02), BMI (28.61±4.81 vs.
29.15±4.27, P=0.02) and waist circumference (99.85±16.23 vs. 100.21±8.78, p<0.001) were significantly
decreased in fish oil group. Our findings demonstrated fish oil supplementation could improve endothelial
function through decreasing weight, BMI and waist circumference in patients with chronic AF that leads to
lower risk of stroke in these patients.
Keywords: Atrial fibrillation, Fish oil, Body mass index (BMI), Waist circumference
INTRODUCTION
Atrial fibrillation is the most common form of arrhythmia (AF) (Go et al, 2001) which increases the risk of
stroke and thromboembolism events (Wolf et al, 1978). Since risk of AF is increased with advancing age (Krahn et
al, 1995) the prevalence of AF is going to increase in most population. According to ATRIA study in United States
2.3 million are affected from AF and in 2050 the prevalence will be increased to 5.6 million (Go et al, 2001).
Inflammation is a main part of obesity and excess adiposity is accompanied with endothelial dysfunction.
The development of AF is more likely in obese subjects than normal individuals. Four percent increase of AF has
been shown with increases of 1 unit BMI (Wang et al, 2004). Moreover, in some studies it was shown there is an
association between endothelial dysfunction and AF (Freestone et al, 2007; Freestone et al, 2008; Akar et al,
2008). On the other hand patients with AF may be at increased risk for mortality mostly through stroke and other
embolic events (Benjamin et al, 1998). Obesity independently increases risk of thromboembolism.
Adipocytes produce adipocytokines including inflammatory cytokines. These molecules may increase
inflammation and oxidative stress in obese people. An association between inflammation and AF has been
reported in many studies. Independent increased C-reactive protein has been shown with increased AF risk
(Maycock et al, 2003). Elevated C-reactive protein, 174G/C IL-6 promotor gene, IL-6 serum levels, and WBC count
are positively correlated with incidence of post-surgery AF (Bruins et al, 1997; Gaudino et al, 2003; Abdelhadi et al,
Tech J Engin & App Sci., 3 (17): 1958-1962, 2013
2004). Moreover, the risk of thrombogenesis is increasing with inflammation. The independent relation between
inflammatory markers (C-reactive protein and IL-6) and indices of the prothrombotic state in individuals with AF has
been reported in Conway et al study (Conway et al., 2004). Adiponectin (Kourliouros et al., 2011), apelin (Ellinor et
al., 2006), resistin (Gungor et al, 2011) and recently asymmetric dimethylarginine (ADMA) (Xia et al, 2008) known
adipocytokines are associated with AF. Moreover these biomarkers related to endothelial function. Therefore,
reduction of fat mass may reduce risk of AF via changing serum adipocytokines and inflammatory cytokines.
An association between high intake of omega 3 and lower incidence of AF was reported in previous studies
(Virtanen et al, 2009). Moreover in some studies it was shown fish oil supplementation could reduce incidence of
post CABG AF (Calò et al, 2005) and AF recurrence after pulmonary vein antrum isolation (Patel et al, 2009). But
the exact mechanism of these effects is unclear. Fish oil could also improve endothelial function (López et al, 2004;
Hill et al, 2007). There are some evidences showing intervention with fish oil may reduce weight and percentage
body fat. In the present study alteration of weight, BMI and waist circumference following fish oil supplementation
were investigated in patients with chronic AF in an Iranian population.
METHODS AND SUBJECTS
Forty three postmenopausal women and 37 men with chronic AF were recruited from the Shahid Rajaei
2
Heart Center, Tehran, Iran. Including criteria were age ≥50 years and BMI ≥25 kg/m . Hyperthyroidism, valvular
heart disease, coronary artery bypass surgery in the preceding three months, class III and IV cardiac failure, a
history of drug or alcohol abuse, acute illnesses and/or infectious diseases and, serum triglyceride >4 mmol/L were
excluded. The study protocol was approved by Ethical Committee of Tehran University of Medical Science and all
patients signed out consent forms. Eight week supplementation with 2g/day (two 1000mg capsules) fish oil
including 300mg EPA and 200mg DHA in each capsule, or 2g/day olive oil as placebo (Dana Company-Iran) was
given to the subjects. Subjects in each group and stratum of diabetic and non-diabetic were randomly assigned to
fish oil and placebo using permuted random blocks method.
Seca Instruments were used to measuring anthropometric indexes including height, weight, and waist
circumference before and after intervention. Height and weight were measured without shoes and with light clothes
after a 12 hours fasting respectively. Waist circumference was also measured with an unelasticated tape between
the lowest rib margin and the iliac crest. A 24-hour questionnaire was used to assessing the daily intake of energy,
macronutrients and n-3 PUFAs for three times in each group before and after supplementation. Dietary and lifestyle
habits were asked to monitor any change.
SPSS (18.0) was used to analyze the data. All quantitative data have been presented as mean± standard
deviation (Table 1). As the distributions of the studied factors were not normal for either fish oil or placebo group a
Mann-Whitney U test was used to compare groups as the baseline. Then, analysis of covariance (ANCOVA) was
performed for final group comparison adjusting for the baseline measurements. The Spearman coefficients of
correlation were computed between the variables. The Significant level was set as P values ˂ 0.05.
RESULTS
Clinical characteristics of the subjects in fish oil and placebo groups are shown in Table 1.
Table 1. Clinical Characteristics of the Patients with Atrial Fibrillation.
Factor
Male, n (%)
Diabetics, n (%)
Hypercholesterolemia, n (%)
Age, y
Weight, kg
Height, cm
BMI, kg/m2
Waist circumference, cm
Fish oil group
(n=40)
18 (45%)
(27.5%)
(55%)
68.57±8.33
73.57±13.29
159.29±7.46
29.01±4.94
102.7±15.96
Placebo group
(n=40)
19 (47.5%)
(27.5%)
(55%)
69.72±7.67
73.8±12.91
158.82±9.53
29.18±4.24
100.31±8.89
P value
0.82
1
1
0.52
0.93
0.8
0.87
0.5
Data are mean±SD or frequency counts, as appropriate.
No significant differences were observed in sex and age between fish oil and placebo group before
intervention (table 1). Prevalence of Hypercholesterolemia in each group was 55%. Moreover 27.5% of patients in
each group were diabetic. There were no significant changes in the intake of energy, macronutrients and n-3
PUFAs in each group and also between two groups before and after intervention.
1959
Tech J Engin & App Sci., 3 (17): 1958-1962, 2013
There was no significant differences between fish oil and placebo groups in weight, BMI and waist
circumference before intervention. Weight (p value=0.02), BMI (p value=0.02) and waist circumference (p
value<0.001) were decreased after fish oil supplementation (table2).
Table 2. Fasting serum Adiponectin, ADMA, lipids and FBS in patients before and after 8-week fish oil supplementation and
placebo
Parameters
weight (kg)
BMI (kg/m2)
waist circumference (cm)
Time
Baseline
Endpoint
Baseline
Endpoint
Baseline
Endpoint
Fish oil (n=40)
Mean±SD
73.57±2.21
72.58±2.09
29.01±0.78
28.61±0.76
102.27±2.52
99.85±2.56
Placebo (n=40)
Mean±SD
73.8±2.04
73.74±2.06
29.18±0.67
29.15±0.67
100.31±1.4
100.21±1.38
p value
intervention
0.02*
0.02*
<0.001**
Mean±SD was significantly different from baseline: (ANCOVA analysis)
DISCUSSION
In many studies it was shown that secretion of adipocytokines was altered following adiposity. Since the
association of AF with these biomarkers was reported in previous studies, importance and necessity of weigh
reduction in these patients could be mentioned. Interestingly, we found the effect of fish oil on decreasing weight,
BMI and waist circumference. A few probable mechanisms were mentioned in some studies with combination use
of fish oil with exercise, such as increased gene expression of key enzymes in β-oxidation and transportation of
fatty acids including lipoprotein lipase, acetyl-CoA carboxylase-2 (Buettner et al, 2008), FA translocase, carnitine
palmitoyl transferase 1 (Murata et al, 2000; Wang et al, 1999; Tunstall et al, 2002), and mitochondrial uncoupling
protein 3 (Baillie et al, 1999). Also adipocyte differentiation may be affected by n-3 polyunsaturated fatty acids
through targeting key regulatory transcription factors that involved in adipogenesis (Madsen et al, 2005). Leptin
could inhibit white adipose tissue (WAT) lipogenesis independent of signal transducer and activator of transcription3 (STAT3) signaling (Buettner et al, 2008). Leptin could also decrease fatty acid synthase expression, increases
the enzymes of free fatty acid (FFA) oxidation, and stimulates a form of lipolysis in which glycerol is released
without a proportional release of FFA (Wang et al, 1999). Up-regulation of leptin gene expression and increase of
its secretion through a hexosamine biosynthetic pathway in 3T3-L1 adipocytes by EPA was reported (Murata et al,
2000). However size of human adipocytes could be related to n-3 fatty acids (Garaulet et al, 2006). Therefore,
weight reduction following fish oil consumption could be in result of decreasing fat mass. Preterm infants who have
been fed with DHA-enriched formula for 12 months accumulated less fat mass than their age-matched controls
(Groh-Wargo et al, 2005). Kabir et al also have reported decreases of total fat mass and subcutaneous adipocyte
diameter following fish oil supplementation in women with type 2 diabetes in spite of unchanged total body weight
(Kabir et al, 2007). Our findings is in agreement with some (Thorsdottir et al, 2007) but not all studies (Mori et al,
1999). Although percentage body fat has not been determined in the present study, reduction of waist
circumference may be due to reduced abdominal fat in these patients. Moreover, fish oil as part of an energyrestricted diet decreased body weight and waist circumference in Thorsdottir et al study (Thorsdottir et al, 2007).
Furthermore an inverse correlation between BMI, waist circumference and hip circumference in one hand and
plasma n-3 PUFA was reported in Michelle et al study (Micallef et al, 2009). Although body weight, waist
circumference and waist-to-hip ratio did not significantly change in Chan et al study (Chan et al, 2002). The small
sample size of subjects with insulin-resistance and dyslipidemia may cause different results.
CONCLUSION
In the present study, fish oil supplementation decreased weight, BMI and waist circumference significantly
in patients with chronic AF. Obesity is a risk factor for endothelial dysfunction and AF. Moreover Obesity could
increases thromboembolism events independently. Since the association between endothelial dysfunction and AF
could independently raise risk of stroke and other embolic events, therefore weight reduction following fish oil
consumption could improve endothelial function which leads to lower risk of thromboembolism in patients with
chronic AF.
1960
Tech J Engin & App Sci., 3 (17): 1958-1962, 2013
ACKNOWLEDGMENT
This study was a piece of research dealing with MSc dissertation supported by Tehran University of
Medical Sciences. Dana Company (Iran) provided the supplements and placebos.
We also thank Dr Soraya Shahrzad for her support, Dr Kambiz Mozaffari and Mohammad Sepasi
(Laboratory, Shahid Rajaei Heart Center) for their technical assistance.
REFRENCES
Abdelhadi RH, Gurmhs, Van Wagoner DR, Chung MK. 2004. Relation of an exaggerated rise in white blood cells after coronary bypass or
cardiac valve surgery to development of atrial fibrillation postoperatively. The American journal of cardiology 93(9): 1176-1178.
Akar JG, Jeske W, Wilber DJ. 2008. Acute onset human atrial fibrillation is associated with local cardiac platelet activation and endothelial
dysfunction. Journal of the American College of Cardiology 51(18): 1790-1793.
Baillie R, Takada R, Nakamura M, Clarkes. 1999. Coordinate induction of peroxisomal acyl-CoA oxidase and UCP-3 by dietary fish oil: a
mechanism for decreased body fat deposition. Prostaglandins, leukotrienes and essential fatty acids 60(5): 351-356.
Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. 1998. Impact of atrial fibrillation on the risk of death: the Framingham
Heart Study. Circulation 98(10): 946-952.
Bruins P, te Velthuish, Yazdanbakhsh AP, Jansen PGM, Van Hardevelt FWJ, de Beaumont EMFH, Wildevuur CRH, Eijsman L, Trouwborst A,
Hack CE. 1997. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves
C-reactive protein and is associated with postoperative arrhythmia. Circulation, 96(10): 3542-3548.
Buettner C, Muse ED, Cheng A, Chen L, Scherer T, Pocai A, Su K, Cheng B, Li X, Harvey-White J. 2008. Leptin controls adipose tissue
lipogenesis via central, STAT3–independent mechanisms. Nature medicine: 14(6): 667-675.
Calo L, Bianconi L, Colivicchi F, Lamberti F, Loricchio ML, de Ruvo E, Meo A, Pandozi C, Staibano M, Santini M. 2005. N-3 Fatty acids for the
prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. Journal of the American College of
Cardiology, 45(10): 1723-1728.
Chan DC, Watts GF, Barrett PHR, Beilin LJ, Redgrave TG, Mori TA. 2002. Regulatory effects of HMG CoA reductase inhibitor and fish oils on
apolipoprotein B-100 kinetics in insulin-resistant obese male subjects with dyslipidemia. Diabetes, 51(8): 2377-2386.
Conway DSG, Buggins P, Hughes E, Lip GYH. 2004. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic
atrial fibrillation. Journal of the American College of Cardiology 43(11): 2075-2082.
Ellinor PT, Low AF, Macrae CA. 2006. Reduced apelin levels in lone atrial fibrillation. European heart journal 27(2): 222-226.
Freestone B, Chong A Y, Nuttall S, Blann AD, Lip GYH. 2007. Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body
nitrate/nitrite product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation. CHEST
Journal, 132(4): 1253-1258.
Freestone B, Chong AY, Nuttall S, Lip G. 2008. Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial
fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels. Thromb Res 122(1): 85-90.
Garaulet M, Hernandez-Morante J, Lujan J, Tebar F, Zamora S. 2006. Relationship between fat cell size and number and fatty acid composition
in adipose tissue from different fat depots in overweight/obese humans. International journal of obesity 30(6): 899-905.
Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A. 2003. The−
174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial
Fibrillation an Inflammatory Complication? Circulation, 108(10): II-195-II-199.
Go AS, Hylek EM, Phillips KA, Chang YC, Henault LE, Selby JV, Singer DE. 2001. Prevalence of diagnosed atrial fibrillation in adults. JAMA:
the journal of the American Medical Association 285(18): 2370-2375.
Groh-Wargo S, Jacobs J, Auestad N, O'Connor DL, Moore JJ, Lerner E. 2005. Body composition in preterm infants who are fed long-chain
polyunsaturated fatty acids: a prospective, randomized, controlled trial. Pediatric research 57: 712-718.
Gungor H, Ayik MF, Kirilmaz B, Ertugay S, Guli, Yildiz BS, Nalbantgil S, Zoghi M. 2011. Serum resistin level: as a predictor of atrial fibrillation
after coronary artery bypass graft surgery. Coronary Artery Disease 22(7): 484-490.
Hill AM, Buckley JD, Murphy KJ, Howe PR. 2007. Combining fish-oil supplements with regular aerobic exercise improves body composition and
cardiovascular disease risk factors. The American journal of clinical nutrition 85(5): 1267-1274.
Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, Quignard-Boulange A, Vidal H, Slama G, Clement K. 2007. Treatment for 2 mo
with n− 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women
with type 2 diabetes: a randomized controlled study. The American journal of clinical nutrition, 86(6): 1670-1679.
Kourliouros A, Karastergiou K, Nowell J, Gukop P, Hosseini MT, Valencia O, Ali VM, Jahangiri M. 2011. Protective effect of epicardial
adiponectin on atrial fibrillation following cardiac surgery. European Journal of Cardio-Thoracic Surgery 39(2): 228-232.
Krahn AD, Manfreda J, Tate RB, Mathewson F, Cuddy TE. 1995. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in
the Manitoba Follow-Up Study. The American journal of medicine 98(5): 476.
Lopez D, Orta X, Casos K, Saiz MP, Puig-Parellada P, Farriol M, Mitjavila MT. 2004. Upregulation of endothelial nitric oxide synthase in rat
aorta after ingestion of fish oil-rich diet. American Journal of Physiology-Heart and Circulatory Physiology 287(2): H567-H572.
Madsen L, Petersen RK, Kristiansen K. 2005. Regulation of adipocyte differentiation and function by polyunsaturated fatty acids. Biochimica et
Biophysica Acta (BBA)-Molecular Basis of Disease 1740(2): 266-286.
Maycock CAA, Lappe dl, Crandall BG, Muhlestein JB, Horne BD, Bair TL, Li Q, Reyna SP, Renlund DG, Anderson JL. 2003. Is atrial fibrillation
an inflammatory disease reflected by elevated C-reactive protein? Journal of the American College of Cardiology 41(6): 99-99.
Micallef M, Munro I, Phang M, Garg M. 2009. Plasma n-3 polyunsaturated fatty acids are negatively associated with obesity. British Journal of
Nutrition 102(9): 1370.
Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ. 1999. Dietary fish as a major component of a weight-loss diet: effect on serum
lipids, glucose, and insulin metabolism in overweight hypertensive subjects. The American journal of clinical nutrition 70(5): 817-825.
Murata M, Kaji H, Takahashi Y, Iida K, Mizuno I, Okimura Y, Abe H Chihara K. 2000. Stimulation by Eicosapentaenoic Acids of Leptin mRNA
Expression and Its Secretion in Mouse 3T3-L1 Adipocytes< i> in Vitro</i>. Biochemical and biophysical research communications
270(2): 343-348.
1961
Tech J Engin & App Sci., 3 (17): 1958-1962, 2013
Patel D, Shaheen M, Venkatraman P, Armaganijan L, Sanchez JE, Horton RP, DI Biase L, Mohanty P, Canby R, Bailey SM. 2009. Omega-3
polyunsaturated fatty acid supplementation reduced atrial fibrillation recurrence after pulmonary vein antrum isolation. Indian pacing and
electrophysiology journal 9(6): 292.
Thorsdottir I, Tomasson H, Gunnarsdottir I, Gisladottir E, Kiely M, Parra M, Bandarra N, Schaafsma G, Marninez J. 2007. Randomized trial of
weight-loss-diets for young adults varying in fish and fish oil content. International journal of obesity 31(10): 1560-1566.
Tunstall RJ, Mehan KA, Wadley GD, Collier GR, Bonen A, Hargreaves M, Cameron-Smith D. 2002. Exercise training increases lipid metabolism
gene expression in human skeletal muscle. American Journal of Physiology-Endocrinology And Metabolism 283(1): E66-E72.
Virtanen JK, Mursu J, Voutilainen S, Tuomainen TP. 2009. Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of
atrial fibrillation in men. Circulation 120(23): 2315-2321.
Wang MY, Lee Y, Unger RH. 1999. Novel form of lipolysis induced by leptin. Journal of Biological Chemistry 274(25): 17541-17544.
Wang TJ, Parise H, Levy D, D’Agostino SR RB, Wolf PA, Vasan RS, Benjamin EJ. 2004. Obesity and the risk of new-onset atrial fibrillation.
JAMA: the journal of the American Medical Association 292(20): 2471-2477.
Wolf PA, Dawber TR, Thomas JR HE, Kannel WB. 1978. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke The
fiamingham Study. Neurology 28(10): 973-973.
Xia W, Qu X, Yu Y, Zhang X, Feng W, Song Y. 2008. Asymmetric dimethylarginine concentration and early recurrence of atrial fibrillation after
electrical cardioversion. Pacing and clinical electrophysiology 31(8): 1036-1040.
1962