Malnutrition-related polyunsaturated fatty acid changes in plasma lipid fractions of cirrhotic patients

Malnutrition-related polyunsaturated fatty acid changes in plasma lipid fractions of cirrhotic patients

Malnutrition-Related Polyunsaturated Fatty Acid Changes Fractions of Cirrhotic Patients J. Gonzhlez, J.L. Periago, A. Gil, E. Cabrk, A. Abad-Lacruz,...

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Malnutrition-Related

Polyunsaturated Fatty Acid Changes Fractions of Cirrhotic Patients

J. Gonzhlez, J.L. Periago, A. Gil, E. Cabrk, A. Abad-Lacruz,

in Plasma

Lipid

M.A. Gassull, and F. SBnchez de Medina

Cirrhotic patients have both impaired liver function and nutritional derangement. In fact, the prevalence of protein-energy malnutrition (PEM) is very high in these patients. The aim of the present study was to elucidate whether the nutritional status in cirrhosis could be an additional factor that would affect levels of plasma lipids. Plasma lipid phosphorus, cholesterol, and triglycerides (TG), and fatty acid profiles in plasma and plasma fractions were determined in 50 healthy subjects and 92 patients with liver cirrhosis. The cirrhotic patients were prospectively included in three groups according to the result of nutritional assessment: group 1 (n = 38), acceptable nutritional status (including well-nourished and mildly malnourished patients); group 2 (n = 29). moderate PEM; and group 3 (n = 25), severe PEM. The main findings of this study were that the decrease in plasma cholesterol and linoleic, dihomo-y-linolenic, and arachiddnic acid levels of cirrhotic patients was related to the degree of PEM. Cholesteryl esters (CE) appeared to be the most sensitive indicator of lipid changes in cirrhosis. We consider that the role of malnutrition in the changes observed for polyunsaturated fatty acid (PUFA) profiles in plasma lipids of cirrhotic patients may be of major importance, since severe malnourished subjects exhibited the lowest levels of those compounds. Dietary supplementation of both essential fatty acids (EFA) and long-chain PUFA in adequate amounts to the cirrhotic patient might be of importance in the management of the disease. Copyright 0 1992 by W.B. Saunders Company

L

ONG-CHAIN polyunsaturated fatty acids (PUFA) play a key role in membrane structure and in control of cellular function by influencing the activity of some important enzymes and receptors.1-3 In addition, PUFA with 20 carbon atoms, namely, dihomo-y-linolenic [20:3(n-6)], arachidonic [20:4(n-6)], and eicosapentaenoic [20:.5(n-3)] acids are the precursors of prostaglandins and related eicosanoids.4J Long-chain PUFA result from desaturation and elongation of essential fatty acids (EFA). This process requires adequate nutritional status and normal liver functionh Changes in the PUFA profile of plasma and plasma lipid fractions in patients with cirrhosis and hepatitis were described in 1966 by Caren and Corbo.’ They found an increase of palmitate (16:0), palmitoleate [16:l(n-7)], and oleate [18:l(n-9)] and a decrease of linoleate [18:2(n-6)] and 20:4(n-6) levels in all plasma fractions, especially in cholesteryl esthers (CE). The authors suggested that the observed findings were not due to dietary factors or malabsorption, but probably to impairment of liver function. Later on, Gunnlaugsson and Berkowitz8 found similar changes in the individual free fatty acids of plasma from patients with cirrhosis and hepatitis, and suggested that the low level of 20:4(n-6) could be due to hepatic dysfunction. Also, Wilcox et al9 in 1978 described similar changes in all plasma fractions from cirrhotic patients and attributed them both to malabsorption and liver function impairment. More recently, Holman and coworkers*OJ1 have studied the changes in the PUFA profile of plasma fractions in

several human diseases, including liver cirrhosis. They found a generalized decrease of long-chain PUFA greater than 18 carbon atoms in plasma phospholipids (PL) of cirrhotic patients without any significant decrease of 18:2(n6), suggesting that liver damage was affecting PUFA metabolism. Long-chain PUFA decreases have also been described in a range of malnourished subjects, such as elderly patients treated by gastric tube feeding,i2 patients with operable upper-gastrointestinal malignancies,‘-’ and elderly institutionalized populations.‘4 Changes in PUFA profiles in liver disease have also been described for plasma lipoproteins,*5~16 platelets.” and erythrocytes,is demonstrating the high probability of a decrease of 20:4(n-6) in other body membranes. This could be of particular importance for the kidney, due to the key role of arachidonate-derived prostaglandins in the maintenance of renal hemodynamic function in liver cirrhosis.]” Patients with cirrhosis have both impaired liver function and nutritional derangement. In fact, the prevalence of PEM is very high in these patients.20-Z3 The aim of the present study was to elucidate the importance of malnutrition in the establishment of PUFA deficiency. We have previously published a preliminary report demonstrating a relationship between the severity of PEM and changes in plasma PUFA profiles. 24In this report, the results obtained from the study of plasma and plasma lipid fraction fatty acid patterns of a total of 92 cirrhotic patients and their relationship to the degree of malnutrition are reported. MATERIALS

AND METHODS

Subjects From the Department of Biochemistry and Molecular Bioloa, University of Granada; the Research Department of UNIASA, Granada; and the Service of Digestive Disease, Hospital Trias i Pujol, Badalona, Barcelona, Spain. Address reprint requests to F. Sanchez de Medina, Depanment of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Granada, Granada, 18001, Spain. Copyright Q I992 by W B. Saunders Company 00260495/92/4109-0005$03.0010 954

A total of 142 subjects were included in the study. Ninety-two patients (59 men and 33 women, aged 63.0 ? 17.3 years [range, 34 to 761) were studied. Seventy had an alcoholic etiology, 16 had suffered viral hepatitis and six developed cryptogenetic cirrhosis. Forty patients had ingested more than 80 g/d of alcohol during the last 30 days. The diagnosis of liver cirrhosis was biopsy proven or based on unequivocal clinical, biochemical, scintigraphic, and ultrasonographic findings. Patients with liver cancer were excluded from the study. Fifty (28 men and 22 women, aged 51.3 2 14.8 Metabolism, Vol41, No 9 (September).

1992: pp 954-960

PLASMA FATTY ACIDS IN CIRRHOTIC PATIENTS

years [range, 32 to 761) healthy, well-nourished individuals were used as controls. Cirrhotic patients were classified into three groups according to their degree of malnutrition. All patients were also classified according to the severity of liver disease by the Child-Pugh prognostic indexz3; only severely affected patients were hospitalized, whereas mildly and moderately affected patients were ambulatory. The study protocol was approved by the Ethical Committee of the hospital. Informed written consent was obtained from each patient. Nutritional Assessment For nutritional assessment in all cases, three simple parameters were used: triceps skinfold (TSF), mid-arm muscle circumference (MAMC), and serum albumin concentration (SA), as representative of body fat, muscle protein, and visceral protein, respectively. A patient was considered to be malnourished when at least one of these parameters was below the fifth percentile of the standards from the age- and sex-matched healthy population living in the area served by the hospital, as previously described.2s Four possible degrees for each of the mentioned parameters were established before beginning the study: 0 (normal, above the fifth percentile), I (mild, 90% to 100% of the fifth percentile value), II (moderate, 80% to 90% of the fifth percentile value), and III (severe, < 80% of the fifth percentile value). A detailed description of these classification criteria has been previously reported.23 The cirrhotic patients were prospectively included in three groups according to the result of nutritional assessment (Table 1): group 1, acceptable nutritional status (including well-nourished and mildly malnourished patients not assigned to the following groups); group 2, moderate proteinenergy malnutrition (PEM), which includes patients with severe effects on SA and mild or moderate effects on either MAMC or TSF, or moderate effects on two parameters and mild effects on the third one; and group 3, severe PEM, includes patients with severe effects on SA and one or two of the other parameters, and those having moderate effects on the three parameters. This nutritional classification has proved to be of prognostic value in cirrhosis.z3 Sampling In all patients and healthy controls, a 5-mL venous blood sample for plasma lipid determination was drawn after a 14-hour overnight fast at the same time that nutritional assessment was performed. Plasma was separated by centrifugation at 3,000 x g for 5 minutes and immediately frozen and stored at -50°C under nitrogen atmosphere. Analytical Methods Two OS-mL aliquots of plasma were used in fatty acid analysis. A solution of heptadecanoic acid (17:0) (10 mg/mL) in chloroform was added as an internal standard to one aliquot to obtain a final Table 1. Nutritional Parameters of Three Groups of Cirrhotics

Parameter TSF MAMC SA (g/L)

Group 1 (n = 38)

Group 2

Group 3

(n = 29)

(n = 25)

75.4 + 5.0

60.9 2 6.8*

30.3 + 1.6*t

104.1 + 1.9

96.8 k 2.4’

32.7 k 0.8

24.3 k 0.9*

92.2 + 3.9’ 24.6 k 0.8*

NOTE. Results are expressed as means k SEM. Cirrhotic patients: group 1, acceptable nutritional status; group 2, moderate PEM; group 3, severe

PEM. TSF and MAMC

are expressed

as percentage

standards from age- and sex-matched healthy population. ‘P

< .Ol

versus

group 1.

tP < .Ol versus group 2.

of

concentration of 0.2 mg/mL. This fatty acid was added to plasma to allow plasma fatty acid concentrations to be determined as absolute values and not only as relative percentages. The other aliquot was used to determine the relative fatty acid composition of plasma lipid fractions. Plasma lipids were extracted with chloroform/ methanol (2/l, vol/vol) containing the antioxidant, 2,6-di-tert-butylp-cresol ([BHT] 50 mg/L).26 Plasma lipid fractions were separated by thin-layer chromatography (TLC) on silica gel G 60, using hexaneiethyl ether/acetic acid (80/20/l, vol/vol/vol).z7 Total PL, triglycerides (TG), and CE were immediately scrapped and analyzed for their fatty acid composition. Methylation of total fatty acids and fatty acids from each lipid fraction was performed according to the Morrison and Smith procedure.Z Fatty acid methyl esters were stored at -30°C under nitrogen until analyzed. Fatty acid analysis was performed by gas-liquid chromatography (GLC) using a Hewlett-Packard 5890A gas chromatograph (Avondale, PA) equipped with a 30-m, wide-bore column, 0.75-mm internal diameter impregnated with SP 2330 as stationary phase (Supelco, Bellefonte, PA), and a flame ionization detector. The identification and quantitation of fatty acid methyl esters was made possible by the use of an external standard supplied by Sigma Chemical (St Louis, MO). Individual response factors were calculated for each fatty acid. Plasma cholesterol and TG levels were determined using commercial kits purchased from Boehringer (Boehringer Mannheim, Barcelona, Spain) and Biotrol (Biotrol, Paris, France), respectively. Lipid phosphorus was measured by spectrometry according to the Fiske and Subarrow method as modified by Bartlett2” StatisticalAnalysis Comparisons between mean values for nutritional parameters, plasma lipids, and fatty acids and related indexes were made by one-way ANOVA followed by a Scheffe test30 RESULTS

According to their nutritional status, 38 (41%), 29 (32%), and 25 (27%) patients were included in groups 1, 2, and 3, respectively. Within group 1, six were classified as ChildPugh grade A, 20 as grade B, and 12 as grade C. Group 2 included six patients of grade B and 23 of grade C. Group 3 included two patients of grade B and 23 of grade C. Seventy patients had ascites, 22 developed acute encephalopathy, and noone had chronic encephalopathy. Table 1 shows the mean values of the nutritional parameters studied. TSF was related to the degree of malnutrition; significant differences were found among the three cirrhotic groups. MAMC and SA, which estimate the body protein compartment, were significantly reduced in those patients with mild and severe PEM, as compared with those with acceptabIe nutritional status. Table 2 shows the results obtained for plasma lipid phosphorus, cholesterol, and TG. The patients with cirrhosis had low concentrations of plasma lipid phosphorus and total cholesterol. The latter was most affected in those patients with severe PEM; no significant differences for total cholesterol were found between groups 1 and 2, although there was a trend for it to be lower in the last one. Free cholesterol and plasma TG levels were fairly similar in all cirrhotic groups, and no differences were detected in relation to the controls.

PLASMA

FAll-Y

957

ACIDS IN CIRRHOTIC PATIENTS

DISCUSSION Plasma

•l Control

n

Group 1

q Group

2

m Group 3

PL

18:2(n-6)

PWA(n-6)>18C

Fig 1. Levels of linoleic acid and (n-6) PUFA greater than 16 carbon atoms [PUFA (n-6) > 16C] in plasma, plasma PL, and plasma CE of cirrhotic patients with different nutritional status. Resutts are expressed as means f SEM. Groups 1.2. and 3 as in Table 1. OP < .05, A/J c .Ol, AP c .Wl versus healthy controls. lP < .05, AP < .Ol, OP < 401 versus group 1.

fractions. No differences were found between groups 2 and 3. Compound 18:2(n-6) levels were significantly lower in CE from cirrhotic patients, whereas only a slight decrease for this fatty acid was observed in PL from severely malnourished subjects. PUFA of the (n-6) series decreased in both fractions (Fig 1). Compounds 20:3(n-6) and 20: 4(n-6) in PL and 20:4(n-6) in CE were the responsible fatty acids for this decrease. No major differences for 20:4(n-6) were seen among the three groups of patients. The UNID of plasma PL and CE was severely diminished in cirrhotic patients for both fractions. Those with either moderate or severe malnutrition showed the lowest values. TG did not exhibit major changes in their fatty acid composition as related to cirrhosis and degree of malnutrition. Only 18:2(n-6) was relatively decreased in groups 2 and 3, and 16:l(n-7) was increased in all groups of patients as compared with healthy controls.

A number of diseases, particularly those affecting the gastrointestinal tract, lead to a decrease in the PUFA levels in plasma and tissue membranes. It has been reported that arachidonic acid is significantly decreased in essential fatty acid deficiency, cystic fibrosis, chronic malnutrition, achrodermatitis enteropathica, cirrhosis, alcoholism, and hepatic encephalopathy.7-*8 PEM in hospitalized patients with liver cirrhosis may adversely affect hepatic function, perpetuate liver injury, and ultimately affect prognosis.23 Malnutrition in cirrhotic patients is a clinical condition often forgotten when the therapeutic strategies are designed. Indeed, this study was designed to ascertain whether nutritional status in cirrhosis could be an additional factor that would enhance the decrease in levels of plasma PUFA. We have found that the intensity in the decrease of total plasma cholesterol was associated with the degree of malnutrition in cirrhotic patients. Free cholesterol levels were maintained fairly constant. Thus, the decrease in total cholesterol appears to be due to an impaired synthesis of CE. Wilcox et alp have documented low levels of CE in cirrhotic patients; the lower concentrations were found in those subjects with the most severe illness, although no attempt was made to classify them according to their nutritional status. The decrease in CE in some liver diseases has been attributed to either a low activity or a low synthesis of lecithin-cholesterol-acyl-transferase (LCAT).*6,32j33Malnutrition could also affect the rate of synthesis of LCAT, given that this situation is a well known cause for the decrease in plasma protein synthesis.34J5 Plasma PL levels were also found to be lower in cirrhotic patients as compared with healthy subjects, and the decrease was not affected by the severity of malnutrition. However, the degree of severity of cirrhosis has been related to the intensity of the decrease in the plasma PL fraction9 The main findings of this study have been that PUFA, namely 20:3(n-6) and 20:4(n-6) were decreased in total plasma lipids and in PL and CE, and the decrease was related to the degree of PEM. The parent EFA, 18:2(n-6), also decreased with advancing malnutrition, especially in plasma and CE. As expected, the results of this study showed a similar fatty acid profile in plasma fractions to that obtained in plasma from a reduced number of patients, as previously reported.24 The lower levels of 18:2(n-6) found in those patients with a higher degree of malnutrition could be either due to a poor dietary intake or to an impaired fat absorption related to decreased levels of bile salts and to lymphangiectasia, frequently observed in cirrhosis.31 In addition to a low accretion of EFA, the relatively low concentrations of long-chain PUFA, mainly of the n-6 series, may be due to a decrease in the activities of the liver desaturases. These enzymes have been demonstrated to have a low activity in rats fed a low-protein diet,36 and it has been suggested to be diminished in malnourished infants.37 The hypothesis of a low desaturase activity in liver cirrhosis is supported in this study by the increase in the

958

GONZALEZ ET AL

Table 4. Fatty Acid Composition of Plasma PL in Cirrhotic Patients With Different Nutritional Status HealthyControls (n = 50)

FattyAcid

CirrhoticPatients Group 1

(n =

38)

Group 2 In = 291

Group 3 (n = 25)

16:0

26.6 r 0.3

27.9 k 0.9

28.7 -c 0.6t

30.8 + 0.7$§#

18:0

14.3 f 0.2

12.3 + 0.3$

11.5 + 0.4*

11.5?

22:o

0.4 k 0.1

0.5 2 0.2

0.9 + 0.2*

24:0

<0.2

<0.2

16:l (n-7)

1 .o s 0.3

1.6 k 0.2*

0.5*

0.5 + 0.2

<0.2

c 0.2

2.1 i 0.2t

2.3 f 0.3*§

18:l (n-9)

13.9 f 0.4

17.5 2 0.5*

24:l (n-9)

< 0.2

<0.2

<0.2

co.2

18:2 (n-6)

22.0 k 0.6

22.2 + 0.7

21.2 + 0.9

19.7 2 0.7’5

18:3 (n-6)

<0.2

20.4 k 0.7$11

< 0.2

< 0.2

19.5 t 0.7$§

-:0.2

20:2 (n-6)

0.7 t 0.1

0.3 + 0.1*

0.3 + 0.1*

20:3 (n-6)

3.7 It 0.1

3.3 -t 0.2*

2.6 k O.lSI/

2.4 k 0.2*/l

0.2*

20:4 (n-6)

13.2 ? 0.4

10.5 k 0.4*

9.2 + 0.4*9

9.7 k 0.4*

22:4 (n-6)

<0.2

< 0.2

<0.2

< 0.2

22:5 (n-6)

<0.2

< 0.2

< 0.2

< 0.2

18:3 (n-3)

<0.2

< 0.2

< 0.2

20:5 (n-3)

0.6 + 0.1

0.3 2 o.o*

22:5 (n-3)

0.4 t 0.0

0.3 2 0.0

22:6 (n-3) SAT MONO UNID 18:2 (n-6)/20:4

(n-6)

2.7 k 0.2

2.8 2 0.2

41.5 2 0.3

40.7 k 0.8

0.3 + 0.11
0.3 -t 0.1 < 0.2* <0.2$/j 2.2 2 0.3 43.0 -t 0.71

15.0 2 0.6

19.2 -c 0.6$

22.7 +- 0.9$//

21.9 + 0.8$§

146.7 k 1.9

137.3 + 3.2*

126.1 k 3.5$§

124.2 + 2.8$11

1.7 i 0.1

2.2 2 0.1*

2.4 k 0.2$

2.1 t 0.1*

NOTE. Results are m ean percentages 2 SEM of total fatty acid methyl esters. Cirrhotic patients: group 1, acceptable nutritional status; group 2. moderate PEM; group 3, severe PEM. Abbreviations: SAT, total saturated fatty acids; MONO, total monounsaturated

fatty acids; UNID, unsaturation index (calculated as ?:fatty acid x

number of double bonds). *P < .05, tP < .Ol, SP < ,001 versus healthy controls. §P < .05, IIP < .Ol, llP < ,001 versus group 1. #P < .05 versus group 2.

Table 5. Fatty Acid Composition of Plasma CE in Cirrhotic Patients With Different Nutritional Status HealthyControls (n = 50)

FattyAcid 16:0

12.3 t 0.3

18:0

2.4 + 0.3

22:o

<0.2

CirrhoticPatients Group 1

tn =

381

Group 2 In = 29)

Group 3 (n = 251

14.7 ?I 0.6$

18.0 2 0.9$11

17.8 + l.O$§

2.1 + 0.3

4.9 + l.lf§

3.2 r 0.7

< 0.2

1.8 + 0.7’5

0.7 k 0.2’

16:l (n-7)

2.7 + 0.1

6.1 -c 0.5$

8.9 t 0.6*7

18:l (n-9)

22.7 -t 0.4

27.2 + 0.8$

28.7 i 1.6%

29.8 k 1.8.t

8.3 t 0.8%§

41.0 + 1.2*

32.1 + 2.5*11

33.3 k 2.3$1/

18:2 (n-6)

50.0 + 0.9

18:3 (n-6)

0.8 + 0.3

0.8 + 0.1

0.6 + 0.2

20:3 (n-6)

0.5 + 0.1

0.5 +- 0.1

i 0.2t1/

20:4 (n-6)

7.6 + 0.2

5.8 + 0.4$

4.3 i 0.4*1/

5.0 i- 0.6s

0.7 2 0.1*

0.3 k 0.1

0.6 + 0.3

0.4 + 0.2

< 0.2

<0.2*

18:3 (n-3)

<0.2

20:5 (n-3)

0.3 t- 0.1

22:6 (n-3)

0.3 L 0.1

<0.2

14.8 f 0.5

17.1 ? 0.8*

SAT MONO UNID 18:2 (n-6)/

20:4 (n-6)

<0.2 24.6 2 2.1$/l

0.8 t 0.3 < 0.2*11

co.2 21.6 k 1.6tf

25.4 k 0.5

33.4 * 0.9*

37.6 ? 1.5*/l

38.2 k 1.9*§

163.7 k 1.7

148.0 + 2.7*

124.1 + 5.3tll

130.7 + 4.7*//

7.8 + 0.8

7.0 t 0.9

6.9 + 0.3

7.5 + 0.6

NOTE. Results are mean percentages k SEM of total fatty acid methyl esters. Cirrhotic patients: group 1, acceptable nutritional status; group 2. moderate PEM; group 3, severe PEM. Abbreviations: SAT, total saturated fatty acids; MONO, total monounsaturated fatty acids; UNID, unsaturation index (calculated as ?. fatty acid x number of double bonds). *P < .05, tP < .Ol, SP i

.OOl, versus healthy controls.

§P i .05,1IP < .Ol, llP < ,001 versus group 1.

PLASMA

959

FATTY ACIDS IN CIRRHOTIC PATIENTS

Table 6. Fatty Acid Composition of Plasma TG in Cirrhotic Patients With Different Nutritional Status CirrhoticPatients HealthControls (n = 50)

FattyAcid

Group 1 (n = 38) 24.7 + 0.5

Group 2 (n = 29) 24.8 2 0.6

Group 3 (n = 25) 25.1 + 0.6

16:0

23.8 IT 0.4

18:0

5.7 k 0.3

4.4 + 0.3t

5.5 k 0.6

5.8 + 0.65

22:o

0.4 * 0.2

0.8 k 0.3

1.1 ? 0.4

0.4 + 0.1

7.2 + 0.4$§

6.1 i 0.5t

4.4 I 0.2

6.2 + 0.3*

18:l (n-9)

46.9 + 0.9

47.1 -c 1.0

47.5 2 1.2

47.7 + 1.4

18:2 (n-6)

16.9 + 0.9

14.5 + 0.9

12.2 2 l.O$

12.4?

18:3 (n-6)

<0.2

<0.2

<0.2

10.2t

<0.2*

<0.2*

<0.2

<0.2

<0.2

16:l(n-7)

0.5 + 0.1

20:2 (n-6)

<0.2

20:3 (n-6)

1.2t

<0.2

20:4 (n-6)

0.7 + 0.1

1.0 k 0.1

0.9 + 0.2

1.2 f 0.2

18:3 (n-3)

< 0.2

0.3 + 0.1

<0.2§

0.7 2 0.3

< 0.2

22:6 (n-3)

29.9 2 0.7

SAT

0.6 k 0.4 30.0 z 0.6

<0.2

10.2

31.4 2 0.8

31.2 + 1.1

MONO

51.3 2 0.9

53.3 k 1.0

54.7 2 1.2s

53.9 5 1.7

UNID

90.9 2 1.7

91.8 % 3.0

85.8 2 1.7*

87.7 2 2.2

7.1 * 1.3

8.9 + 1.4

4.6 + l.O§

5.5 k 1.0

18:2 (n-6)/20:4

(n-6)

NOTE. Results are mean percentages + SEM of total fatty acid methyl esters. Cirrhotic patients: group 1, acceptable nutritional status; group 2, moderate PEM; group 3, severe PEM. Abbreviations: SAT, total saturated fatty acids; MONO, total monounsaturated

fatty acids; UNID, unsaturation index (calculated as P fatty acid x

number of double bonds). *P < .05, tP < .Ol, SP §P

< .05, llP

< ,001

< .Ol, IIP < ,001

versus healthy controls. versus group 1.

18:2(n-6)/20:4(n-6) ratio in total plasma fatty acids and in PL. A6 Desaturase, the key enzyme in the synthesis of PUFA, could be the most affected one. In fact, Bereziat et a13* have reported that dietary supplementation with oenothera oil, which is particularly rich in y-linolenic acid [18:3(n-6)], leads to an increase of 20:3(n-6) and 20:4(n-6) in PL and CE from cirrhotic patients, suggesting that the activity of 18-20 elongase and A5 desaturase activities are preserved in this situation. We consider that the role of malnutrition in the changes observed for PUFA profiles in plasma lipids of cirrhotic patients may be of major importance, since severely malnourished subjects exhibited the lowest levels of those compounds. Compound 18:2(n-6) was always decreased in plasma and CE, paralleling their nutritional status. PL was the only fraction in which there were not appreciable

changes for this fatty acid. Holman and Johnsonlo have attributed the decrease of 20:4(n-6) in PL of cirrhotics to liver damage, since there were no significant changes for 18:2(n-6) percentages in this fraction. However, our results demonstrate a decrease in plasma 18:2(n-6) levels and its derived PUFA when they are quantitatively measured. Also, CE shows a remarkable decrease in the relative percentages of 18:2(n-6). CE thus appears to be the most sensitive indicator of PUFA changes in cirrhosis, as previously suggested by Caren and Corbo.’ Dietary treatment in cirrhosis is mainly based on carbohydrate-rich and lipidpoor foods, which may contribute to the low levels of body PUFA storage. Dietary supplementation of 18:2(n-6) and n-6 long-chain PUFA in adequate amounts to the cirrhotic patient might be of importance in the management of this disease.

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7. Caren R, Corbo L: Plasma fatty acids in pancreatic cystic fibrosis and liver disease. J Clin Endocrinol26:470-477, 1966 8. Gunnlaugsson 0, Berkowitz D: Individual free fatty acids in patients with liver disease. Am J Dig Dis 22~10051009,1977 9. Wilcox HG, Dunn GD, Schenker S: Plasma long chain fatty acids and esterified lipids in cirrhosis and hepatic encephalopathy. Am J Med Sci 276:293-303, 1978 10. Holman RT, Johnson S: Changes in essential fatty acid profile of serum phospholipids in human disease. Prog Lipid Res 20:67-73, 1981 11. Johnson SB, Gordon E, McClain C, et al: Abnormal polyunsaturated fatty acid patterns of serum lipids in alcoholism and cirrhosis: Arachidonic acid deficiency in cirrhosis. Proc Nat1 Acad Sci USA 82:1815-1818, 1985 12. Bjerve KS, Mostad IL, Thorensen L: Alpha-linolenic acid deficiency in patients on long-term gastric-tube feeding: Estima-

GONZALEZ

tion of linolenic acid and long-chain unsaturated n-3 fatty requirement in man. Am J Clin Nutr 45:66-77, 1987

acid

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