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EICOSAPENTAENOIC ACID IN FAT
1202 ERYTHROCYTE FATTY ACID
EICOSAPENTAENOIC ACID IN FAT
SiR,-Professor Katan and Mr van de Bovenkamp (April 11, 862) found eicosapentaenoic acid (EPA; C20: [5n-3]) in adipose tissue of three healthy volunteers. This fatty acid belongs to one of the two families of essential fatty acids. Field et aP in a study of diet and of fatty acids in triglycerides (stored fat) and in phospholipids (membrane fat) of adipose tissue from 20 healthy volunteers, found a mean EPA of 0-20% (SD 0-02) in adipose tissue. 8 years ago one of us (H. S.) ate an eskimo diet (seal, fish and other marine animals, and water) for 100 days. Linoleic acid (C18 :[2n6]), a member of the other family of essential fatty acids, decreased from 29-1% of fatty acids in adipose tissue before the diet to 20-7% after 23 days, and was 23.6% at the end of the diet; 40 days later, the level had increased to 29-2%. But, after 74 days on the diet, we found only 0-5 % EPA and, at the end of the diet, only a trace; no EPA was found before the diet or 40 days afterwards. Yet H. S. was ingesting about 14 g EPA daily. The speed with which changes occur in the fatty acid composition of adipose tissue depends on the amount of such tissue, on the dietary pattern of fatty acids and of carbohydrate, and on the quantity of fatty acids in the diet over the past weeks or months. More rapid changes in fatty acids occur in the phospholipids of erythrocytes and of platelets. We found that EPA in erythrocytes was 2-3% before the diet, 8-2% after 10 days, and 12.8% at the end of the diet. Manku et al2 found a mean of 0-65% (SD 0-03) in erythrocytes of 50 normal volunteers. We also found large changes
LEVELS*
p
in the phospholipids of platelets, in the lipid components of different lipoproteins, and in skeletal muscle. In a multicentre trial of a fish-oil supplement in patients with multiple sclerosis (chairman Professor R. H. S. Thompson), we analysed the fatty acids in adipose tissue from those taking the fish oil (1-8g EPA daily) and from controls. In the Belfast arm of the trial, after about 36 months, all 28 patients had EPA (mean 0-51 %) but 28 controls did not; in the Newcastle arm, 17 of 18 patients had EPA (mean 0-47 %) but again no controls had EPA. Levels of linoleic acid were high (about 20%) although the patients were probably all taking sunflower-seed oil. Thus these patients, who were taking an eighth or less of the amount of EPA ingested by H. S. on the eskimo diet, had on average about the same amount of EPA in adipose tissue as the highest amount found on the eskimo diet. We need to know more about the factors that affect the composition of adipose tissue. Analyses of adipose tissue are useful for indicating the dietary level of linoleic acid in past months, but analysis of erythrocyte ghosts is more useful for EPA, which does not reflect so usefully past dietary intake, as our eskimo diet experiment showed. If present, EPA must almost certainly have been ingested in fish because the conversion of dietary linolenic acid to EPA is slow. Large amounts of EPA can be ingested without this fatty acid appearing in adipose tissue. International Institute of Human Nutrition, Sutton Courtenay, Abingdon OX14 4AW
HUGH SINCLAIR MARY GALE
1. Field CJ, Angel A, Clandinin MT. Relationship of diet to the fatty add composition of
human adipose tissue structural and stored lipids. Am J Clin Nutr 1985; 42: 1206-20. 2. Manku MS, Horrobin DF, Huang YS, Morse N. Fatty acids in plasma and red cell membranes in normal humans. Lipids 1983; 18: 906-08.
FATTY ACID PATTERN AND ISCHAEMIC HEART DISEASE
SIR,-We have compared the fatty acid composition of total erythrocyte lipids in 20 men presenting with acute myocardial infarction (MI) with that of ’the same number of healthy male controls. MI patients had significantly lower linoleic acid levels and significantly higher oleic acid levels (table). Because the erythrocyte fatty acids are slow to reflect dietary fat modification3 and are unlikely to alter directly after MI, we suggest that total erythrocyte fatty acid composition indicates pre-infarct fatty acid status. Our results support the conclusion of Dr Wood and colleagues (Jan 24, p 177), who studied fatty acid levels in adipose tissue and platelets directly after MI, that these patients probably had a lower long-term dietary intake of linoleic acid. We
*Expressed as mean (SD) percentage of total fatty acids. Erythrocyte lipids were extracted according to Broekhuyse,’ transesterifieC112 and fatty acid methyl esters were analysed by a Perkin Elmer 3920 gas chromatograph with a 3 mm outside diameter x 3 m column packed with 10% SP2330 (Supelco Inc, Bellefonte, Pennsylvania). tp < 0002. $p < 0 005.
do not agree with Dr Bang and Dr Dyerberg (March 14, p 633) that the data of Wood and colleagues are inconsistent with the plasma fatty acid pattern of patients who, eight months previously, had had an acute MI. It should be realised that there can be no stronger motivation for an individual to change to and remain on a new diet than suffering a coronary incident. Because plasma fatty acids indicate short-term dietary fat intake,s Bang and colleagues’ observations might be explained in terms of changed dietary habits of the MI patients. Comparison of these two sets of data is invalid. Department of Chemical Pathology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa
C. H. RAPLEY J. B. UBBINK L. S. DE VILLIERS
Broekhuyse RM. Quantitative two-dimensional thin-layer chromatography of blood phospholipids. Clin Chim Acta 1969; 23: 457-61. 2. Christie WW. The preparation of derivatives of lipids. In: Lipid analysis: Isolation, separation, identification and structural analysis of lipids, 2nd ed. Oxford: Pergamon Press, 1979: 51-61. 3. Faquhar JW, Ahrens EH. Effects of dietary fats on human erythrocyte fatty add patterns. J Clin Invest 1963; 42: 675-85. 4. Simpson HCR, Barker K, Carter RD, Cassels E, Mann JI. Low dietary intake of linoleic acid predisposes to myocardial infarction. Br Med J 1982; 285: 683-84. 5. Moore RA, Oppert S, Eaton P, Mann JI. Triglyceride fatty adds confirm a change in dietary fat. Clin Endocrinol 1977; 7: 143-49. 1.
TRISOMY 21 MOSAICISM AND MATERNAL AGE EFFECT
SIR,-Stein and colleagues1 have suggested that the incidence of trisomy 21 increases with maternal age because of the progressive failure of a post-fertilisation screening mechanism. Under this "elimination" hypothesis (EH) one copy of the trisomic autosome is usually eliminated. The ratio of maternally to paternally derived extra chromosomes does not increase with maternal age,2 and the constancy of this ratio conflicts with predictions based on the conventional "generative" hypothesis (GH) whereby a differential rate of origin, through increased meiotic error, is responsible for the increased incidence in older mothers.3 Predictions implicit in EH can be tested on published cases where aneuploid, disomic gametes are generated at an abnormally high but constant rate. Under GH, these should produce a high, constant rate of trisomy while age-dependent, post-fertilisation removal of extra chromosomes will preferentially reduce the incidence in younger mothers and increase mean maternal age where screening fails. On EH the incidence of trisomy at the oldest maternal ages can be used to calculate the proportion of trisomic zygotes which are "corrected" in younger mothers. The induction rate of trisomy is taken1 as 1 % of conceptions, and the attrition rate will reflect the efficiency of prerecognition maternal screening. At young ages the process would seem to be highly efficient: the frequency of trisomy in normal mothers is such that efficiency must be 90% or more for ages below 35 but almost zero at ages over 40.1 A high frequency of gametic disomy is expected in individuals with constitutional aneuploidy, but such individuals are rare and usually do not reproduce. However, individuals with trisomy 21 mosaicism can produce trisomy 21 offspring at significant rates, and the underlying incidence of disomic gametes will usually be much higher than 1 %. On EH both mosaic and normal mothers of
EICOSAPENTAENOIC ACID IN FAT
SiR,-Professor Katan and Mr van de Bovenkamp (April 11, 862) found eicosapentaenoic acid (EPA; C20: [5n-3]) in adipose tissue of three healthy volunteers. This fatty acid belongs to one of the two families of essential fatty acids. Field et aP in a study of diet and of fatty acids in triglycerides (stored fat) and in phospholipids (membrane fat) of adipose tissue from 20 healthy volunteers, found a mean EPA of 0-20% (SD 0-02) in adipose tissue. 8 years ago one of us (H. S.) ate an eskimo diet (seal, fish and other marine animals, and water) for 100 days. Linoleic acid (C18 :[2n6]), a member of the other family of essential fatty acids, decreased from 29-1% of fatty acids in adipose tissue before the diet to 20-7% after 23 days, and was 23.6% at the end of the diet; 40 days later, the level had increased to 29-2%. But, after 74 days on the diet, we found only 0-5 % EPA and, at the end of the diet, only a trace; no EPA was found before the diet or 40 days afterwards. Yet H. S. was ingesting about 14 g EPA daily. The speed with which changes occur in the fatty acid composition of adipose tissue depends on the amount of such tissue, on the dietary pattern of fatty acids and of carbohydrate, and on the quantity of fatty acids in the diet over the past weeks or months. More rapid changes in fatty acids occur in the phospholipids of erythrocytes and of platelets. We found that EPA in erythrocytes was 2-3% before the diet, 8-2% after 10 days, and 12.8% at the end of the diet. Manku et al2 found a mean of 0-65% (SD 0-03) in erythrocytes of 50 normal volunteers. We also found large changes
LEVELS*
p
in the phospholipids of platelets, in the lipid components of different lipoproteins, and in skeletal muscle. In a multicentre trial of a fish-oil supplement in patients with multiple sclerosis (chairman Professor R. H. S. Thompson), we analysed the fatty acids in adipose tissue from those taking the fish oil (1-8g EPA daily) and from controls. In the Belfast arm of the trial, after about 36 months, all 28 patients had EPA (mean 0-51 %) but 28 controls did not; in the Newcastle arm, 17 of 18 patients had EPA (mean 0-47 %) but again no controls had EPA. Levels of linoleic acid were high (about 20%) although the patients were probably all taking sunflower-seed oil. Thus these patients, who were taking an eighth or less of the amount of EPA ingested by H. S. on the eskimo diet, had on average about the same amount of EPA in adipose tissue as the highest amount found on the eskimo diet. We need to know more about the factors that affect the composition of adipose tissue. Analyses of adipose tissue are useful for indicating the dietary level of linoleic acid in past months, but analysis of erythrocyte ghosts is more useful for EPA, which does not reflect so usefully past dietary intake, as our eskimo diet experiment showed. If present, EPA must almost certainly have been ingested in fish because the conversion of dietary linolenic acid to EPA is slow. Large amounts of EPA can be ingested without this fatty acid appearing in adipose tissue. International Institute of Human Nutrition, Sutton Courtenay, Abingdon OX14 4AW
HUGH SINCLAIR MARY GALE
1. Field CJ, Angel A, Clandinin MT. Relationship of diet to the fatty add composition of
human adipose tissue structural and stored lipids. Am J Clin Nutr 1985; 42: 1206-20. 2. Manku MS, Horrobin DF, Huang YS, Morse N. Fatty acids in plasma and red cell membranes in normal humans. Lipids 1983; 18: 906-08.
FATTY ACID PATTERN AND ISCHAEMIC HEART DISEASE
SIR,-We have compared the fatty acid composition of total erythrocyte lipids in 20 men presenting with acute myocardial infarction (MI) with that of ’the same number of healthy male controls. MI patients had significantly lower linoleic acid levels and significantly higher oleic acid levels (table). Because the erythrocyte fatty acids are slow to reflect dietary fat modification3 and are unlikely to alter directly after MI, we suggest that total erythrocyte fatty acid composition indicates pre-infarct fatty acid status. Our results support the conclusion of Dr Wood and colleagues (Jan 24, p 177), who studied fatty acid levels in adipose tissue and platelets directly after MI, that these patients probably had a lower long-term dietary intake of linoleic acid. We
*Expressed as mean (SD) percentage of total fatty acids. Erythrocyte lipids were extracted according to Broekhuyse,’ transesterifieC112 and fatty acid methyl esters were analysed by a Perkin Elmer 3920 gas chromatograph with a 3 mm outside diameter x 3 m column packed with 10% SP2330 (Supelco Inc, Bellefonte, Pennsylvania). tp < 0002. $p < 0 005.
do not agree with Dr Bang and Dr Dyerberg (March 14, p 633) that the data of Wood and colleagues are inconsistent with the plasma fatty acid pattern of patients who, eight months previously, had had an acute MI. It should be realised that there can be no stronger motivation for an individual to change to and remain on a new diet than suffering a coronary incident. Because plasma fatty acids indicate short-term dietary fat intake,s Bang and colleagues’ observations might be explained in terms of changed dietary habits of the MI patients. Comparison of these two sets of data is invalid. Department of Chemical Pathology, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa
C. H. RAPLEY J. B. UBBINK L. S. DE VILLIERS
Broekhuyse RM. Quantitative two-dimensional thin-layer chromatography of blood phospholipids. Clin Chim Acta 1969; 23: 457-61. 2. Christie WW. The preparation of derivatives of lipids. In: Lipid analysis: Isolation, separation, identification and structural analysis of lipids, 2nd ed. Oxford: Pergamon Press, 1979: 51-61. 3. Faquhar JW, Ahrens EH. Effects of dietary fats on human erythrocyte fatty add patterns. J Clin Invest 1963; 42: 675-85. 4. Simpson HCR, Barker K, Carter RD, Cassels E, Mann JI. Low dietary intake of linoleic acid predisposes to myocardial infarction. Br Med J 1982; 285: 683-84. 5. Moore RA, Oppert S, Eaton P, Mann JI. Triglyceride fatty adds confirm a change in dietary fat. Clin Endocrinol 1977; 7: 143-49. 1.
TRISOMY 21 MOSAICISM AND MATERNAL AGE EFFECT
SIR,-Stein and colleagues1 have suggested that the incidence of trisomy 21 increases with maternal age because of the progressive failure of a post-fertilisation screening mechanism. Under this "elimination" hypothesis (EH) one copy of the trisomic autosome is usually eliminated. The ratio of maternally to paternally derived extra chromosomes does not increase with maternal age,2 and the constancy of this ratio conflicts with predictions based on the conventional "generative" hypothesis (GH) whereby a differential rate of origin, through increased meiotic error, is responsible for the increased incidence in older mothers.3 Predictions implicit in EH can be tested on published cases where aneuploid, disomic gametes are generated at an abnormally high but constant rate. Under GH, these should produce a high, constant rate of trisomy while age-dependent, post-fertilisation removal of extra chromosomes will preferentially reduce the incidence in younger mothers and increase mean maternal age where screening fails. On EH the incidence of trisomy at the oldest maternal ages can be used to calculate the proportion of trisomic zygotes which are "corrected" in younger mothers. The induction rate of trisomy is taken1 as 1 % of conceptions, and the attrition rate will reflect the efficiency of prerecognition maternal screening. At young ages the process would seem to be highly efficient: the frequency of trisomy in normal mothers is such that efficiency must be 90% or more for ages below 35 but almost zero at ages over 40.1 A high frequency of gametic disomy is expected in individuals with constitutional aneuploidy, but such individuals are rare and usually do not reproduce. However, individuals with trisomy 21 mosaicism can produce trisomy 21 offspring at significant rates, and the underlying incidence of disomic gametes will usually be much higher than 1 %. On EH both mosaic and normal mothers of