- Email: [email protected]
Trans fatty acids and dieting
1093
Sp02 was 95-97%. Blood gas measurements showed a p02 12 kPa a pC02 15 kPa. Endotracheal intubation and mechanical
and
ventilation were performed, and the patient then required tracheostomy. The third case was a 69-year-old man in the anaesthetic recovery after anterior cervical spinal fusion to relieve spinal cord compression. He was receiving oxygen via a Hudson mask, with Sp02 96%. The nurses were concerned when he became sleepy and called for medical assistance. The patient was found to be deeply unconscious, with no gag reflex and little ventilatory effort. Endotracheal intubation was done under general anaesthesia and mechanical ventilation was started. Naloxone administration roused the patient, but he was quadriplegic; he was electively sedated and ventilated. Blood gas measurements were not done until the patient was settled in the intensive care unit but there was clinical evidence of hypoventilation before intubation. Power had returned to normal after 12 h of mechanical ventilation. Nunn’ showed that only small increments in inspired oxygen concentration are required to correct hypoxaemia resulting from hypoventilation, by contrast with that resulting from ventilationperfusion mismatch. With the alveolar minute ventilation reduced to 1 L/min, alveolar pC02 may rise to about 20 kPa, while the administration of 40% oxygen can return alveolar p02 to normal. As a result, no conclusion should be made from Sp02 values about the adequacy of ventilation during supplemental oxygen administration. Staff need to understand that pulse oximetry can be used as an assessment of oxygenation and circulation but not as an alternative to clinical observation of ventilation or blood gas analysis. Department of Anaesthetics, R. E. JOHN Royal Hallamshire Hospital, Sheffield S10 2RX, UK J. E. PEACOCK area
1. Eichhom JH, Cooper JB, Cullen DJ, Maier WR, Philip JH, Seeman RG. Standards for patient monitoring during anaesthesia at Harvard Medical School. JAMA 1986; 256: 1017-20. 2. Sykes MK. Essential monitoring. Br J Anaesth 1987; 59: 901-12. 3. Aorab JSM. Who needs pulse oximetry? BMJ 1988; 296: 658-59. 4. Tremper KK, Barker SJ. Pulse oximetry. Anesthesiology 1989; 70: 98-108. 5. Kidd JF, Vickers MD. Pulse oximeters: essential monitors with limitations. Br J Anaesth 1989; 62: 355-57. 6. Editorial. The trust in pulse oximeters. Lancet 1990; 335: 1130-31. 7. Nunn JF. Applied respiratory physiology. 3rd ed. London: Butterworth, 1987: 389.
Trans fatty acids and
dieting
SIR,-Professor Willett and colleagues (March 6, p 581) show that there is a very good correlation between consumption of the trans fatty acids produced by partial hydrogenation of polyunsaturated vegetable oils and the occurrence of coronary heart disease (CHD). Scientists in essential fatty acid (EFA) research have long been aware of the negative effects of trans fatty acids on EFA metabolism,l,2 and more recently attention has been drawn to deleterious effects in adults3 and in infants.4 Warnings about health hazards of trans fatty acids have hitherto gone unheeded. That situation may now change, and the public should become aware that the partially hydrogenated domestic oils are, in fact, greater health hazards than dairy products and natural saturated fats. Trans fatty acids disturb the balance between synthesis of eicosanoids of the PGl’ PG2, and PG3 families by inhibiting the enzyme delta-6-desaturase, which is responsible for the initial further desaturation of the parent fatty acids of both omega-6 and omega-3 families, linoleic acid (LA), and ct-linolenic acid (ALA). Thus availability of the immediate precursors for eicosanoids of the PG1 and PG3 families, dihomo-gamma-linolenic acid (DGLA), and eicosapentanoic acid (EPA), respectively, is reduced. Where vegetable oils are the sole source of EFAs, the availability of arachidonic acid (AA), precursor for eicosanoids of the PGfamily, would also be reduced, but since the conventional human diet contains substantial amounts of meat, a considerable proportion of the AA used for prostaglandin synthesis is dietary and not endogenous in origin. It is also noteworthy that the presence of stearidonic acid (an omega-3 EFA from the action of delta-6desaturase on ALA) in the substrate pool competitively inhibits delta-5-desaturase, the enzyme responsible for converting DGLA to AA, and this is believed to be part of the regulatory mechanism for ensuring balance in prostaglandin synthesis.
When so-called normal food intake includes dietary sources of both trans fatty acids and AA, prostaglandin synthesis is not only quantitatively diminished, but also distorted into an unnatural equilibrium, since eicosanoids of the PG2 family will continue to be formed, but producton of the eicosanoids from the other families is reduced. Theoretically, this reduction can have considerable consequences for homoeostasis. For example, the production of thromboxane A2 could continue as normal, but in the absence of counterparts from the PG1 and PG3 families, the resultant imbalance could increase the risk of thrombosis. The practical verification of this prediction has been reported by Lands,s who noted that feeding AA to volunteers in fairly small amounts increased thrombogenic potential such that the study had to be abandoned. Patients on energy-restricted diets, if they have previously been consuming a normal western diet, will have stores of both AA and trans fatty acids in their adipose tissue; thus, when they are obliged to mobilise and eliminate these fat reserves in a weight reduction programme, free trans fatty acids and AA will be released into the circulation. Considerable increases in blood AA concentrations occur on low calorie diets,6,7 and patients on such diets may have increased EFA requirements.8 Conversion of the primary EFAs into the immediate precursors of the eicosanoids is therefore probably reduced in such patients. Recent findings9 indicate that the gall bladder contracts significantly less frequently in the dieting than in the non-dieting patient, and that the bile in patients on low-calorie diets contains increased amounts ofAA, which increases synthesis of the glycoprotein that stimulates cholesterol nucleation;’O and these are both prostaglandin-dependent factors in gallstone formation. Thus whether or not the dieting patient continues to consume foods containing AA and trans fatty acids, they remain exposed to the risk. In practice, most commercial diet programmes promote the use of light margarines and lean red meat, which aggravates the situation, and some diet programmes condone use of partially hydrogenated domestic oils, condemning use of other, more natural, alternatives. Banatrix International, Lachine, Quebec, Canada H8T 3J9
DENNIS
JONES
Fats and Oils in Human Nutrition; report of an expert consultation. Rome: Food and Agriculture Organization of the United Nations, 1980. 2. Hill EG, Johnson SB, Lawson LD, Mahfouz MM, Holman RT. Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil. Proc Natl Acad Sci 1982; 79: 953-57. 3. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density lipoprotein cholesterol levels in healthy subjects. N Engl J Med 1990; 323: 439-45. 4. Koletzko B. Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. Acta Paediatr Int J Paediatr 1992; 81: 302-06. 5. Lands WEM. Renewed questions about essential fatty acids. Nutr Rev 1986; 44: 189-95. 6. Rossner S, Walldius G, Bjorvell H. Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. Int J Obesity 1989; 13: 603-12. 7. Phinney SD, Davis PG, Johnson SB, Holman RT. Obesity and weight loss alter serum polyunsaturated lipids in humans. Am J Clin Nutr 1991; 53: 831-38. 8. Jones D. Neglected nutrients in dietary weight reduction programmes: the essential fatty acids! The Bariatrician Am J Bar Med 1990 (fall); 11-15. 9. Marzio L, Capone F, Neri M, Mezzetti A, De Angelis K, Cuccurullo F. Gallbladder kinetics in obese patients. Effect ofa regular meal and low-calorie meal. Dig Dis Sci 1988; 33: 4-9. 10. Marks JW, Bonorris GG, Albers G, Schoenfield LJ. The sequence of biliary events preceding the formation of gallstones in humans. Gastroenterology 1992; 103: 566-67.
1. FAO/WHO, Dietary
SiR,—There seem to be three possible explanations for Professor Willet and colleagues findings. First, trans fatty acids, as previously shown, result in an increase in total or low-density-lipoprotein cholesterol, or possibly, a small decrease in high-densitylipoprotein (HDL) cholesterol similar to saturated fatty acids;’ second, they have an independent effect on the risk of cardiovascular disease; and third, trans fatty acid intake is a marker for other nutrients or behavioural characteristics that are associated with the risk of coronary heart disease. The Nurses Study provides no independent measurements of blood lipoprotein concentrations, blood pressure, or other risk factors. Thus, the relation between the trans fatty acids and risk factors related to cardiovascular disease could not be measured.
1094
We have analysed the relation between reported margarine intake and risk factors among 540 premenopausal women at baseline in the Healthy Women Study.2 Dietary information was obtained from food frequency and 24 h recall. Frequent users were defined as having margarine four or more times per week (n=259, 48%). Frequent users weighed about 23kg more (p=0-05) than infrequent users; they had significantly lower HDL2 cholesterol (0-53 vs 0-59 mmol/L) and lower total HDL cholesterol concentrations. They also had higher total cholesterol (484 vs 4-71
mmol/L; p=0-07), higher triglyceride (0-99 vs 0-90 mmol/L; p 004), and higher apo B (1 -75 vs 1-66 umol/L; p 0-04), and the =
=
log of 0-28
2 h blood insulin after
glucose load was also higher (031
vs
nmol/L). Despite the fact that margarine consumers weighed
2 kg more than infrequent consumers, they reported roughly the same caloric intake (1700 calories) and similar levels of physical activity. The Nurses Study had previously reported only 12001400 calorie intakes for similarly aged women 3 The food frequency questionnaire, as used in the Nurses and other studies, provides a poor estimate of individual dietary intake of fat and specific fats or caloric intake. There is a substantial underestimation of caloric intake4 compared with body size.s The Nurses Study previously noted that the mean fat intake (75 g) was the same for nurses with body mass index (BMI) of 21 or more and for those with BMI of 29 or more. It is highly unlikely that this difference is attributable to exercise. We suspect that most of the missing calories are fat calories. It is obviouis that women who consume more margarine, baked goods, and cookies, are eating more fat, have higher saturated fat calories, are probably fatter, and, obviously, are consuming more trans fatty acids. Without better dietary data and risk factor measurements, it cannot be determined in the Nurses Study whether there is causal link between trans fatty acids and cardiovascular risk factors. Second, because there are no measurements of the other cardiovascular risk factors, whether the trans fatty acids have an independent effect on cardiovascular disease cannot be established. Third, because of the weakness of the instrument in measuring dietary intake, it is impossible to determine whether the results are related to trans fatty acids or some other measures of dietary intake.
over
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
LEWIS H. KULLER
1. Troisi R, Willett WC, Weiss ST. Trans-fatty acid intake in relation to serum lipid concentrations in adult men. Am J Clin Nutr 1992; 56: 1019-24. 2. Matthews KA, Meilahn EN, Kuller LH, et al. Menopause and coronary heart disease risk factors. N Engl J Med 1989; 231: 641-46. 3. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985; 122: 51-65. 4. Marmot M, Elliott P, eds. Coronary heart disease epidemiology: from aetiology to public health. New York: Oxford University Press, 1992. 5. Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990; 322: 882-89.
SIR,-Professor Willett and colleagues’ report will undoubtedly result in the margarine industry considering avoidance of the potentially hazardous trans fatty acids in their products. For the general public, however, the main message of the study is in table i: coronary heart disease (CHD) risk was lower among individuals who exercised most and ate the least fat and most vegetables (carotene and dietary fibre). Unfortunately, this is not the message that was picked up by the Danish public. Willett’s statements that "partially hydrogenated vegetable oils may contribute to occurrence of CHD", whereas "butter... was not significantly associated with risk of CHD" have prompted the Danish media to claim that margarine is no better and may be even worse than butter. As a consequence, the Danes may now choose to eat more of their beloved butter, and to reduce their margarine consumption. These reported observations do not justify such conclusions. Firstly, it is essential to emphasise that Willett and colleagues’ study population was American nurses with a very low CHD mortality rate (about 16 deaths per 100 000 person-years). The results are therefore not necessarily relevant for individuals at high coronary risk, such as Danish middle-aged men (about 350 CHD deaths per 100 000 person-years). Secondly, the cholesterol-raising trans fatty
acids of
margarines, notably the soft table-margarines, are accompanied by considerable amounts of polyunsaturated fatty efficiently counteract an increase in blood cholesterol. Therefore, a net increase in blood cholesterol concentrations would be expected if butter was used in preference to margarines. In this acids that
context, it would be most valuable if Willett and co-workers could provide the blood cholesterol concentrations of each quintile of women according to their trans fatty acid consumption adjusted for age and total energy intake. Since physical activity varies between quintiles, it would also be of interest to know the trans fatty acid intake unadjusted for total dietary energy of the individual quintiles. Department of Human Nutrition, Royal Veterinary and Agricultural University, DK 1958 Frederiksberg C, Copenhagen, Denmark Research
Q fever with cutaneous and involvement
PETER MARCKMANN
encephalitic
SIR,-A 23-year-old man was in Togo for 6 months, and on chloroquine-proguanil prophylaxis. He presented with hallucinations and agitated delirium and was repatriated to our hospital with suspected psychiatric disease. He was confused without nuchal rigidity. Rectal temperature was 37-5°C and he had erythematous macules suggestive of vasculitis on the thorax, legs, and feet. Leucocyte and platelet counts, haemoglobin, and serum and renal chemical values were normal. Aspartate aminotransferase was 99 U/L (normal <40) and alanine aminotransferase was 69 fluid ( < 40). (CSF) was normal and sterile, as Cerebrospinal U/L were blood and urine. Serological tests for Borrelia burgdorferi, syphilis, brucella, HIV, arboviruses, cytomegalovirus, and EpsteinBarr virus were negative. Repeated blood smears were negative for Plasmodium falciparum. Initial chest radiographs and electroencephalogram on day 6 were normal. Computed tomography (CT) of the head showed limited lateral ventricular dilation. Nuclear magnetic resonance imaging was normal. Specific antibodies for Coxiella burnetii in the indirect fluorescence antibody method were positive for phase II IgG and IgM in serum (table). Skin biopsy confirmed the vasculitis. C burnetii was demonstrated with specific fluorescence antibody. The patient was treated intravenously with doxycycline 200 mg per day for 5 days and rapidly improved. Oral treatment was continued for 15 days. Erythematous macules with a white outline lasted 2 weeks. He was discharged on day 21. A month later he had gained 8 kg. Other tests were normal; 2 months later, ventricular dilation had disappeared on CT. Human infection with C burnetii occurs after inhalation of the organism.1 Diagnosis is usually serological. During acute disease, antibody titre to phase II antigens increases; in chronic Q fever, antiphase I antibodies titre equals or exceeds that of antiphase II antibodies. By contrast with the other rickettsial infections, cutaneous involvement is rare in Q fever.2-4 Involvement of the central nervous system is also rare. In the acute illness, this involvement appears as menigoencephalitis. In the chronic form, the neurological manifestations are secondary to endocarditis.1,s The mechanisms by which C burnetii may cause central nervous system symptoms are unknown. C burnetii has been isolated from CSF in 1 patient with Q fever meningoencephalitis.6 Secondary vasculitis may also be responsible. Q fever has been associated with immunological manifestations such as immune complex glomerulonephritis, positive latex-test
results, vasculitis, false-positive syphilis-test results, haemolytic anaemia, positive Coomb’s test, smooth muscle antibodies, and cold SEROLOGICAL TEST FOR CRt7/?/Vfn/ )N SERUM AT TIME OF DIAGNOSIS
Phase
11 IgG titre greater than 200 with IgM titre of 50
is
considered positive.
Sp02 was 95-97%. Blood gas measurements showed a p02 12 kPa a pC02 15 kPa. Endotracheal intubation and mechanical
and
ventilation were performed, and the patient then required tracheostomy. The third case was a 69-year-old man in the anaesthetic recovery after anterior cervical spinal fusion to relieve spinal cord compression. He was receiving oxygen via a Hudson mask, with Sp02 96%. The nurses were concerned when he became sleepy and called for medical assistance. The patient was found to be deeply unconscious, with no gag reflex and little ventilatory effort. Endotracheal intubation was done under general anaesthesia and mechanical ventilation was started. Naloxone administration roused the patient, but he was quadriplegic; he was electively sedated and ventilated. Blood gas measurements were not done until the patient was settled in the intensive care unit but there was clinical evidence of hypoventilation before intubation. Power had returned to normal after 12 h of mechanical ventilation. Nunn’ showed that only small increments in inspired oxygen concentration are required to correct hypoxaemia resulting from hypoventilation, by contrast with that resulting from ventilationperfusion mismatch. With the alveolar minute ventilation reduced to 1 L/min, alveolar pC02 may rise to about 20 kPa, while the administration of 40% oxygen can return alveolar p02 to normal. As a result, no conclusion should be made from Sp02 values about the adequacy of ventilation during supplemental oxygen administration. Staff need to understand that pulse oximetry can be used as an assessment of oxygenation and circulation but not as an alternative to clinical observation of ventilation or blood gas analysis. Department of Anaesthetics, R. E. JOHN Royal Hallamshire Hospital, Sheffield S10 2RX, UK J. E. PEACOCK area
1. Eichhom JH, Cooper JB, Cullen DJ, Maier WR, Philip JH, Seeman RG. Standards for patient monitoring during anaesthesia at Harvard Medical School. JAMA 1986; 256: 1017-20. 2. Sykes MK. Essential monitoring. Br J Anaesth 1987; 59: 901-12. 3. Aorab JSM. Who needs pulse oximetry? BMJ 1988; 296: 658-59. 4. Tremper KK, Barker SJ. Pulse oximetry. Anesthesiology 1989; 70: 98-108. 5. Kidd JF, Vickers MD. Pulse oximeters: essential monitors with limitations. Br J Anaesth 1989; 62: 355-57. 6. Editorial. The trust in pulse oximeters. Lancet 1990; 335: 1130-31. 7. Nunn JF. Applied respiratory physiology. 3rd ed. London: Butterworth, 1987: 389.
Trans fatty acids and
dieting
SIR,-Professor Willett and colleagues (March 6, p 581) show that there is a very good correlation between consumption of the trans fatty acids produced by partial hydrogenation of polyunsaturated vegetable oils and the occurrence of coronary heart disease (CHD). Scientists in essential fatty acid (EFA) research have long been aware of the negative effects of trans fatty acids on EFA metabolism,l,2 and more recently attention has been drawn to deleterious effects in adults3 and in infants.4 Warnings about health hazards of trans fatty acids have hitherto gone unheeded. That situation may now change, and the public should become aware that the partially hydrogenated domestic oils are, in fact, greater health hazards than dairy products and natural saturated fats. Trans fatty acids disturb the balance between synthesis of eicosanoids of the PGl’ PG2, and PG3 families by inhibiting the enzyme delta-6-desaturase, which is responsible for the initial further desaturation of the parent fatty acids of both omega-6 and omega-3 families, linoleic acid (LA), and ct-linolenic acid (ALA). Thus availability of the immediate precursors for eicosanoids of the PG1 and PG3 families, dihomo-gamma-linolenic acid (DGLA), and eicosapentanoic acid (EPA), respectively, is reduced. Where vegetable oils are the sole source of EFAs, the availability of arachidonic acid (AA), precursor for eicosanoids of the PGfamily, would also be reduced, but since the conventional human diet contains substantial amounts of meat, a considerable proportion of the AA used for prostaglandin synthesis is dietary and not endogenous in origin. It is also noteworthy that the presence of stearidonic acid (an omega-3 EFA from the action of delta-6desaturase on ALA) in the substrate pool competitively inhibits delta-5-desaturase, the enzyme responsible for converting DGLA to AA, and this is believed to be part of the regulatory mechanism for ensuring balance in prostaglandin synthesis.
When so-called normal food intake includes dietary sources of both trans fatty acids and AA, prostaglandin synthesis is not only quantitatively diminished, but also distorted into an unnatural equilibrium, since eicosanoids of the PG2 family will continue to be formed, but producton of the eicosanoids from the other families is reduced. Theoretically, this reduction can have considerable consequences for homoeostasis. For example, the production of thromboxane A2 could continue as normal, but in the absence of counterparts from the PG1 and PG3 families, the resultant imbalance could increase the risk of thrombosis. The practical verification of this prediction has been reported by Lands,s who noted that feeding AA to volunteers in fairly small amounts increased thrombogenic potential such that the study had to be abandoned. Patients on energy-restricted diets, if they have previously been consuming a normal western diet, will have stores of both AA and trans fatty acids in their adipose tissue; thus, when they are obliged to mobilise and eliminate these fat reserves in a weight reduction programme, free trans fatty acids and AA will be released into the circulation. Considerable increases in blood AA concentrations occur on low calorie diets,6,7 and patients on such diets may have increased EFA requirements.8 Conversion of the primary EFAs into the immediate precursors of the eicosanoids is therefore probably reduced in such patients. Recent findings9 indicate that the gall bladder contracts significantly less frequently in the dieting than in the non-dieting patient, and that the bile in patients on low-calorie diets contains increased amounts ofAA, which increases synthesis of the glycoprotein that stimulates cholesterol nucleation;’O and these are both prostaglandin-dependent factors in gallstone formation. Thus whether or not the dieting patient continues to consume foods containing AA and trans fatty acids, they remain exposed to the risk. In practice, most commercial diet programmes promote the use of light margarines and lean red meat, which aggravates the situation, and some diet programmes condone use of partially hydrogenated domestic oils, condemning use of other, more natural, alternatives. Banatrix International, Lachine, Quebec, Canada H8T 3J9
DENNIS
JONES
Fats and Oils in Human Nutrition; report of an expert consultation. Rome: Food and Agriculture Organization of the United Nations, 1980. 2. Hill EG, Johnson SB, Lawson LD, Mahfouz MM, Holman RT. Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil. Proc Natl Acad Sci 1982; 79: 953-57. 3. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density lipoprotein cholesterol levels in healthy subjects. N Engl J Med 1990; 323: 439-45. 4. Koletzko B. Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. Acta Paediatr Int J Paediatr 1992; 81: 302-06. 5. Lands WEM. Renewed questions about essential fatty acids. Nutr Rev 1986; 44: 189-95. 6. Rossner S, Walldius G, Bjorvell H. Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. Int J Obesity 1989; 13: 603-12. 7. Phinney SD, Davis PG, Johnson SB, Holman RT. Obesity and weight loss alter serum polyunsaturated lipids in humans. Am J Clin Nutr 1991; 53: 831-38. 8. Jones D. Neglected nutrients in dietary weight reduction programmes: the essential fatty acids! The Bariatrician Am J Bar Med 1990 (fall); 11-15. 9. Marzio L, Capone F, Neri M, Mezzetti A, De Angelis K, Cuccurullo F. Gallbladder kinetics in obese patients. Effect ofa regular meal and low-calorie meal. Dig Dis Sci 1988; 33: 4-9. 10. Marks JW, Bonorris GG, Albers G, Schoenfield LJ. The sequence of biliary events preceding the formation of gallstones in humans. Gastroenterology 1992; 103: 566-67.
1. FAO/WHO, Dietary
SiR,—There seem to be three possible explanations for Professor Willet and colleagues findings. First, trans fatty acids, as previously shown, result in an increase in total or low-density-lipoprotein cholesterol, or possibly, a small decrease in high-densitylipoprotein (HDL) cholesterol similar to saturated fatty acids;’ second, they have an independent effect on the risk of cardiovascular disease; and third, trans fatty acid intake is a marker for other nutrients or behavioural characteristics that are associated with the risk of coronary heart disease. The Nurses Study provides no independent measurements of blood lipoprotein concentrations, blood pressure, or other risk factors. Thus, the relation between the trans fatty acids and risk factors related to cardiovascular disease could not be measured.
1094
We have analysed the relation between reported margarine intake and risk factors among 540 premenopausal women at baseline in the Healthy Women Study.2 Dietary information was obtained from food frequency and 24 h recall. Frequent users were defined as having margarine four or more times per week (n=259, 48%). Frequent users weighed about 23kg more (p=0-05) than infrequent users; they had significantly lower HDL2 cholesterol (0-53 vs 0-59 mmol/L) and lower total HDL cholesterol concentrations. They also had higher total cholesterol (484 vs 4-71
mmol/L; p=0-07), higher triglyceride (0-99 vs 0-90 mmol/L; p 004), and higher apo B (1 -75 vs 1-66 umol/L; p 0-04), and the =
=
log of 0-28
2 h blood insulin after
glucose load was also higher (031
vs
nmol/L). Despite the fact that margarine consumers weighed
2 kg more than infrequent consumers, they reported roughly the same caloric intake (1700 calories) and similar levels of physical activity. The Nurses Study had previously reported only 12001400 calorie intakes for similarly aged women 3 The food frequency questionnaire, as used in the Nurses and other studies, provides a poor estimate of individual dietary intake of fat and specific fats or caloric intake. There is a substantial underestimation of caloric intake4 compared with body size.s The Nurses Study previously noted that the mean fat intake (75 g) was the same for nurses with body mass index (BMI) of 21 or more and for those with BMI of 29 or more. It is highly unlikely that this difference is attributable to exercise. We suspect that most of the missing calories are fat calories. It is obviouis that women who consume more margarine, baked goods, and cookies, are eating more fat, have higher saturated fat calories, are probably fatter, and, obviously, are consuming more trans fatty acids. Without better dietary data and risk factor measurements, it cannot be determined in the Nurses Study whether there is causal link between trans fatty acids and cardiovascular risk factors. Second, because there are no measurements of the other cardiovascular risk factors, whether the trans fatty acids have an independent effect on cardiovascular disease cannot be established. Third, because of the weakness of the instrument in measuring dietary intake, it is impossible to determine whether the results are related to trans fatty acids or some other measures of dietary intake.
over
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
LEWIS H. KULLER
1. Troisi R, Willett WC, Weiss ST. Trans-fatty acid intake in relation to serum lipid concentrations in adult men. Am J Clin Nutr 1992; 56: 1019-24. 2. Matthews KA, Meilahn EN, Kuller LH, et al. Menopause and coronary heart disease risk factors. N Engl J Med 1989; 231: 641-46. 3. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985; 122: 51-65. 4. Marmot M, Elliott P, eds. Coronary heart disease epidemiology: from aetiology to public health. New York: Oxford University Press, 1992. 5. Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990; 322: 882-89.
SIR,-Professor Willett and colleagues’ report will undoubtedly result in the margarine industry considering avoidance of the potentially hazardous trans fatty acids in their products. For the general public, however, the main message of the study is in table i: coronary heart disease (CHD) risk was lower among individuals who exercised most and ate the least fat and most vegetables (carotene and dietary fibre). Unfortunately, this is not the message that was picked up by the Danish public. Willett’s statements that "partially hydrogenated vegetable oils may contribute to occurrence of CHD", whereas "butter... was not significantly associated with risk of CHD" have prompted the Danish media to claim that margarine is no better and may be even worse than butter. As a consequence, the Danes may now choose to eat more of their beloved butter, and to reduce their margarine consumption. These reported observations do not justify such conclusions. Firstly, it is essential to emphasise that Willett and colleagues’ study population was American nurses with a very low CHD mortality rate (about 16 deaths per 100 000 person-years). The results are therefore not necessarily relevant for individuals at high coronary risk, such as Danish middle-aged men (about 350 CHD deaths per 100 000 person-years). Secondly, the cholesterol-raising trans fatty
acids of
margarines, notably the soft table-margarines, are accompanied by considerable amounts of polyunsaturated fatty efficiently counteract an increase in blood cholesterol. Therefore, a net increase in blood cholesterol concentrations would be expected if butter was used in preference to margarines. In this acids that
context, it would be most valuable if Willett and co-workers could provide the blood cholesterol concentrations of each quintile of women according to their trans fatty acid consumption adjusted for age and total energy intake. Since physical activity varies between quintiles, it would also be of interest to know the trans fatty acid intake unadjusted for total dietary energy of the individual quintiles. Department of Human Nutrition, Royal Veterinary and Agricultural University, DK 1958 Frederiksberg C, Copenhagen, Denmark Research
Q fever with cutaneous and involvement
PETER MARCKMANN
encephalitic
SIR,-A 23-year-old man was in Togo for 6 months, and on chloroquine-proguanil prophylaxis. He presented with hallucinations and agitated delirium and was repatriated to our hospital with suspected psychiatric disease. He was confused without nuchal rigidity. Rectal temperature was 37-5°C and he had erythematous macules suggestive of vasculitis on the thorax, legs, and feet. Leucocyte and platelet counts, haemoglobin, and serum and renal chemical values were normal. Aspartate aminotransferase was 99 U/L (normal <40) and alanine aminotransferase was 69 fluid ( < 40). (CSF) was normal and sterile, as Cerebrospinal U/L were blood and urine. Serological tests for Borrelia burgdorferi, syphilis, brucella, HIV, arboviruses, cytomegalovirus, and EpsteinBarr virus were negative. Repeated blood smears were negative for Plasmodium falciparum. Initial chest radiographs and electroencephalogram on day 6 were normal. Computed tomography (CT) of the head showed limited lateral ventricular dilation. Nuclear magnetic resonance imaging was normal. Specific antibodies for Coxiella burnetii in the indirect fluorescence antibody method were positive for phase II IgG and IgM in serum (table). Skin biopsy confirmed the vasculitis. C burnetii was demonstrated with specific fluorescence antibody. The patient was treated intravenously with doxycycline 200 mg per day for 5 days and rapidly improved. Oral treatment was continued for 15 days. Erythematous macules with a white outline lasted 2 weeks. He was discharged on day 21. A month later he had gained 8 kg. Other tests were normal; 2 months later, ventricular dilation had disappeared on CT. Human infection with C burnetii occurs after inhalation of the organism.1 Diagnosis is usually serological. During acute disease, antibody titre to phase II antigens increases; in chronic Q fever, antiphase I antibodies titre equals or exceeds that of antiphase II antibodies. By contrast with the other rickettsial infections, cutaneous involvement is rare in Q fever.2-4 Involvement of the central nervous system is also rare. In the acute illness, this involvement appears as menigoencephalitis. In the chronic form, the neurological manifestations are secondary to endocarditis.1,s The mechanisms by which C burnetii may cause central nervous system symptoms are unknown. C burnetii has been isolated from CSF in 1 patient with Q fever meningoencephalitis.6 Secondary vasculitis may also be responsible. Q fever has been associated with immunological manifestations such as immune complex glomerulonephritis, positive latex-test
results, vasculitis, false-positive syphilis-test results, haemolytic anaemia, positive Coomb’s test, smooth muscle antibodies, and cold SEROLOGICAL TEST FOR CRt7/?/Vfn/ )N SERUM AT TIME OF DIAGNOSIS
Phase
11 IgG titre greater than 200 with IgM titre of 50
is
considered positive.