Negative Effects of Oral Fatty Acid Supplementation on Sweat Chloride in Cystic Fibrosis

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50 PEDIATRICS Vol. 64 No. 1 July 1979

Negative

Effects

of Oral

Fatty

Acid

Supplementation

on Sweat

Chloride

in

Cystic

Fibrosis

John D. Lloyd-Still, MD, Stuart H. Simon, MD, Hans U. Wessel, MD,

and Lewis E. Gibson, MD

From the Department of Pediatrics, Northwestern University, and Department of Pediatrics, Loyola University, Chicago

ABSTRACT. Essential fatty acid supplementation with

oral safflower oil (1 gm/kg/day) to 1 1 cystic fibrosis

patients (aged 6 months to 14 years) for one year

pro-duced no significant change in sweat chloride

concentra-tion (mEq/liter) or sweat rate (gm/min/m2). Addition of vitamin E (10 mg/kg/day) to the safflower oil had no

effect on sweat chloride concentration or rate compared

to placebo. No clinical improvement could be detected compared to a control group. These results do not support

previous reports of the effects of fatty acid

supplementa-tion on sweat electrolyte concentrations in cystic fibrosis. Pediatrics 64:50-52, 1979; cystic fibrosis, fatty acids, sweat tests.

Several investigators’ have reported a reduction in sweat sodium concentration in children with cystic fibrosis after intravenous lipid infusion. Ro-sentund et al4 gave oral corn oil (1 gm/kg/day) and vitamin E (10 mg/kg/day) to 13 children with cystic

fibrosis and noted a significant reduction (P < .01)

in mean sweat sodium concentration after one year of fatty acid supplementation. We have performed

a trial of oral safflower oil supplementation (1 gm/

kg/day) with either added vitamin E (10 mg/kg/

day) or placebo for one year in 1 1 children with

cystic fibrosis.

METHODS

In the Cystic Fibrosis Clinic of the Children’s Memorial Hospital 16 children were initially eval-uated for inclusion in the trial. Eleven children

Received for publication Sept 8, 1978; accepted Nov 7, 1978.

Presented in part at the 19th Annual Meeting Cystic Fibrosis

Club, New York, April 25, 1978.

Reprint requests to (J.D.L.), Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, Illinois 60614.

completed one year of safflower oil supplementa-tion. The safflower oil was administered three times each day with meals and the code as to whether vitamin E or placebo was added was broken at the end of one year. The patients’ ages ranged from 6 months to 14 years. Five patients were less than 3 years of age and two had had meconium ileus. The average Shwachman score5 was 75 with a range of

60-86. Studies performed at the onset of the trial

included complete blood counts, protein electropho-resis, immunoglobutins, liver function tests, fatty acid profiles, prostaglandins E and F, 72-hour fecal fat, vitamins A and E, glucose tolerance tests with insulin levels, and pulmonary function tests when

possible.

Sweat tests were performed by the method of Gibson and Cooke and three consecutive collec-tions were made for 5, 10, and 15 minutes. Sweat

tests were performed in duplicate on both arms, so

a total of six individual readings for sweat chlorides

(mEq/liter) were obtained each time. Average sweat rates (gm/mm/sq m) were estimated for each collection. At the end of the year the identical procedure was performed and six sweat chloride concentrations (mEq/liter) were again obtained. The same technician performed all 132 individual sweat chloride determinations. Results were ana-lyzed by paired comparison and significance deter-mined by Student’s t test.

Age-matched controls were selected from the

same Cystic Fibrosis Clinic population for

compar-ison of clinical scores.5

RESULTS

All patients had documented pancreatic insuffi-ciency. The mean fecal fat was 27.3 gm/day, mean

vitamin A level 38.8 ig/dl (normal values are >30

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TABLE. Sweat Chloride Concentrations and Sweat Rates Before and After One Year of Safflower Oil Supplementation*

Before safflower oil

R

0-5 mm 6-16 mm 17-32 mm

L R L R L

Sweat rate 5.5 ± 1.8 5.8 ± 2.2 5.4 ± 1.6 5.5 ± 1.7 4.0 ± 1.5 4.0 ± 1.1

(gm/mm/sq m)

Sweat chloride 118.0 ± 15.0 118.0 ± 14.0 114.0 ± 11.0 117.0 ± 11.0 109.0 ± 17.0 113.0 ± 15.0

(mEq/liter) After safflower oil

Sweat rate 4.8 ± 1.7 5.0 ± 1.8 5.4 ± 1.8 5.8 ± 2.1 4.0 ± 1.3 4.2 ± 1.4

(gm/mm/sq m)

Sweat chloride 120.0 ± 12.0 120.0 ± 11.0 120.0 ± 7.0 120.0 ± 7.0 118.0 ± 10.0 119.0 ± 10.0

(mEq/liter)

* Eleven children with cystic fibrosis were studied. In each individual study three consecutive collections of sweat were

made at 0-5, 6-16, and 17-32 minutes. R, right arm; L, left arm; data represent means ±1 SD of the mean of the 11

patients.

ARTICLES 51

ig/d1) and mean vitamin E 0.38 mg/dl (normal

values are >0.5 mg/dl).

There was no significant reduction in sweat

chlo-ride in any of the 1 1 patients in either the 5-, 10-, or

15-minute collections (Table). All 132 individual

sweat chloride determinations were within the

cys-tic fibrosis range. The lowest individual sweat chlo-ride was 76 mEq/liter prior to fatty acid supple-mentation. The maximum range in sweat chloride in any individual patient in six collections was 27

mEq/liter. No significant change in sweat rate (gm/ mm/sq m of body surface area) was detected be-tween the 5-, 10-, or 15-minute samples (Table).

No significant improvement in clinical status

could be detected compared with an age-matched control group. The average Shwachman score at the completion of the trial was 76, an increase of 1 point. The control group increased their clinical score from 69 to 74 during the same time period.

DISCUSSION

No significant reduction in sweat chloride

con-centration or sweat rate could be detected in 11

cystic fibrosis patients supplemented with oral

saf-flower oil for one year. Previous reports of changes

in sweat salt concentrations are not entirely

con-vincing. In order to duplicate Elliott’s work2 as

closely as possible we also used the fractional

col-lection method suggested by Schwartz and

Thay-sen. Whereas we report the actual concentrations

and rates found during each collection period, El-liott reports the mean sodium concentrations and the mean rates. The details of the calculations are not given nor is there any explanation of the

tend-ency for the mean rates to drop during the course

of the study. Although the patients of Roselund et al’ did appear to have a significant drop in sodium

concentration, the finding of sweat sodium above

200 mEq/liter initially in some patients is unusual. Theoretically such high values are very difficult to explain, and in our laboratory such a high value would be taken as an indication of evaporation and would necessitate a repeat sweat test. The correla-tion between sweat sodium and chloride in cystic fibrosis is very close with the mean chloride values higher than the sodium at all ages.” There was no significant improvement in clinical status compared to an age-matched control group. These results do not support previous observations on the effects of essential fatty acid supplementation in cystic

fibro-sis.’4

All of our patients had documented pancreatic insufficiency and their fatty acid profiles9 prior to the study were similar to those previously reported in cystic fibrosis.’#{176} Six of the 11 patients had sig-nificantly reduced levels of linoleic acid at the onset of the trial. Safflower oil contains 74% linoteic acid. Elliott2 postulated that intravenous supplementa-tion with fatty acids in cystic fibrosis may partially correct an error of metabolism of prostaglandins present in this disease. Deficiencies of linoleic and arachidonic acid, the precursors of the

prostaglan-dins, could result in impaired prostaglandin

produc-tion in cystic fibrosis.2 However, none of the pub-lished data on levels of prostaglandins in cystic fibrosis lend support to this hypothesis. Plasma and red blood cell prostagtandin levels in cystic fibrosis indicate that prostagtandin F2 a levels are usually increased.’ ‘-‘3 Our own data (L. M. Demers and J.

D. Lloyd-Stilt, unpublished data) on 39 patients

with cystic fibrosis showed the mean levels of pros-taglandin E and prostaglandin F were in the normal range, but there was a very wide distribution of values. No significant correlation could be detected between the age of the patients, levels of prosta-glandins E and F, or clinical status, thus confirming the data of Lemen et al.’2 Newer methods for

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52 ORAL FATTY ACID SUPPLEMENTATION

tection of the stable metabolic end products of prostaglandin synthesis may clarify some of these conflicting results.

REFERENCES

1. Elliott RB, Robinson PG: An unusual clinical course

in a child with cystic fibrosis treated with fat

emul-sion. Arch Dis Child 50:76, 1975

2. Elliott RB: A therapeutic trial of fatty acid

supple-mentation in cystic fibrosis. Pediatrics 57:474, 1976

3. Beveridge J: Intralipid and cystic fibrosis. Pediatrics

58:465, 1976

4. Rosenlund ML, Selekman JA, Kim HK, et al: Dietary

essential fatty acids in cystic fibrosis. Pediatrics 59: 428, 1977

5. Shwachman H, Kulczycki LL: Long-term study of

105 patients with cystic fibrosis. Am J Dis Child 96:

6, 1958

6. Gibson LE, Cooke RE: A test for concentration of

electrolytes in sweat in cystic fibrosis of the pancreas

utilizing pilocarpine by iontophoresis. Pediatrics 23: 545, 1959

7. Schwartz IL, Thaysen JH: Excretion of sodium and potassium in human sweat. J Clin Invest 35: 1 14, 1956

8. Shwachman H, Mahmoodian A: Pilocarpine

ionto-phoresis sweat testing: Results of seven years

expe-rience. Mod Probl Paediatr 10: 158, 1967

9. Holman RT: Function and metabolism of essential

fatty acids. Proceedings of the 5th Western

Hemi-sphere Nutrition Congress, Quebec, August 1977

10. Hubbard VS, Dunn GD, DiSant’Agnese PA:

Abnor-mal fatty acid composition of plasma lipids in cystic

fibrosis. Lancet 2:1302, 1977

1 1. Dubois RS, Selley ML, Smith I, et al: Plasma pros-taglandin levels in cystic fibrosis. Gastroenterology

72:1052, 1977

12. Lemen RJ, Gates AJ, Mathe AA, et al: Relationships

among digital clubbing, disease severity and serum prostaglandins F2 alpha and E concentrations in cys-tic fibrosis patients. Am Ret’ Respir Dis 1 17:639, 1978

13. Chase HP, Dupont J: Fatty acids and prostaglandins

in children with cystic fibrosis. Pediatr Res 12:431, 1978

14. Hyman AL, Spannhake EW, Kadowitz PJ:

Prosta-glandins and the lung. Am Ret’ Respir Dis 117:111,

1978

UNCLASSIFIED MENTAL RETARDATION

A disturbing number of cases of microcephaly with mental retardation seem unrelated either to obstetric history or to any recognized pediatric syndrome

. . . the pathogenesis of such microcephaly may be related more to the timing of

an insult in relation to the normal timing of neurogenesis in the brain, than to the specific nature of the insult; and that the vulnerable period for at least some microcephaly may therefore be during the multiplication of neuroblasts, which in human brain happens in the first half of the second trimester (about 12-20 weeks’ gestation) . Except for microneurons in certain recognised regions, neu-roblast multiplication ceases at about mid-gestation when they differentiate into mature neurons.

The best evidence for this suggestion inevitably derives largely from experi-ments with animals, but there is also a body of circumstantial evidence from clinical observation in human beings ...

A paper by Ounsted and her colleagues reports a reduced head circumference,

at birth, of babies whose mothers received methyldopa during pregnancy as treatment for hypertension. Amongst several interesting findings, it was only when treatment began in the period from 16 to 20 weeks of gestation that the newborn head circumference was reduced. Treatment beginning before 16 and later than 20 weeks produced no detectable effect, nor was the amount of methyldopa prescribed related in any detectable way to the degree of reduction of head circumference.

From Lancet: February 3, 1979.

Submitted by Student

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1979;64;50

Pediatrics

John D. Lloyd-Still, Stuart H. Simon, Hans U. Wessel and Lewis E. Gibson

Fibrosis