Somogyi JC, Biro Gy, Hitze! Hotzel D (eds): (eds): Nutrition and Cardiovascular Risks. Somogyí JC, Bir Bibl Nutr Dieta. Dieta. Basel, Basel, Karger, 1992, 1992, No No 49, 49, pp pp 59-65 Bibi
and Cardiovascular Cardiovascular Risk: Nutrition and The Biological Biological Markers Markers of Dietary Intake Flaminio Fidanza Istituto di di Scienza Scienza dell'Alimentazione, Università Universita degli Studi, Perugia, Italy
Biomarkers of of Fat Intake epidemiological studies disease were were When the first epidemiological studies on coronary heart disease total serum serum cholesterol cholesterol was considered a reliable marker of total fat started, total [1]. The cholesterol of of middle-aged middle-aged intake [1]. The average average concentration concentration of serum cholesterol of 40% 40% of areas where where the diets were were high in total fats (of (of the order order of men in areas energy), was where the diets total energy), was 25-50% 25-50% greater greater than than the average in areas where were low in total fats (of (of the order order of of 20%, 20%, or less, less, of total energy). energy). And this was not related to race. controlled conditions it was was observed observed that average average serum serum Then under controlled offat in the diet and this change cholesterol responded responded to to aa change in the kind of fat well predicted from the fatty acids and cholesterol composition of was rather well [2]. the exchanged diet [2]. the classical classical Keys equation was derived: From the above experiments the
where S is is the percentage percentage of of total total energy energy from from saturated saturated fatty acids acids and P the percentage percentage of total energy energy from from polyunsaturated fatty acids. Similar results in prospective prospective epidemiological epidemiological studies. have been obtained in With this equation, equation, in in which which some corrections corrections were later made, the small cholesterol has significant proportion of variance by diet to serum total cholesterol but significant recently been explained. effect of The effect of dietary dietary fatty fatty acids on serum cholesterol is actually the sum of modifications induced in the level of the three major lipoprotein lipoprotein classes, classes, of very-low-density lipoprotein (LOL) and very-tow-density lipoprotein (VLOL), (VLDL), low-density low-density lipoprotein lipoprotein (LDL) high-density lipoprotein effects of saturated high-density lipoprotein (HOL). (HDL). While While the the qualitative effects
Downloaded by: Université de Paris 193.51.85.197 - 1/29/2020 1:30:35 AM
dCholesterol 2.7 dS-1.3dP, ∆ Cholesterol == 2.7AS— I .3AΡ,
60
polyunsaturated fatty fatty acids acids are the sum of of those on the three lipoprotein and polyunsaturated classes, the quantitative influence on the individual classes is different: different: in classes, the influence individual classes increase LDL; LDL; oleic oleic acid is as saturated fatty fatty acids acids (except (except C:18) C: 18) increase particular, saturated effective as as polyunsaturated polyunsaturated fatty acids in reducing LDL, LDL, while while concentration concentration seems to remain remain relatively relatively stable; stable; linoleic acid decreases decreases LDL and of HDL seems cholesterol, while eicosapentenoic eicosapentenoic and docosahexenoic docosahexenoic acid dealso HDL cholesterol, triglycerides present in VLDL. crease triglycerides of apo B were used to assess The kinetics of assess dietary dietary influences on the rate of fractionational catabolism catabolism of of LDL, LDL, adapting for epidemioproduction and fractionational logical use measurement of urine/plasma urine/plasma radioactivity logical use the the measurement radioactivity ratio ratio after after an ofaa low dose injection of injection dose of of autologous autologous radiolabeled radiolabeled LDL. LDL. With With this this method, an international collaborative collaborative study metabolic epidemiology epidemiology of plasma plasma international study on metabolic five different different population samples samples [3]. cholesterol was cholesterol was carried carried out in five [3]. In In this population samples samples with high high very interesting study, it was observed that in population fatty acid acid intake, intake, the the high high serum serum cholesterol cholesterol level level is explained in saturated fatty by greater greater rates rates of of LDL LDL production. production. In In population population samples samples with with high high part by exmonounsaturated fatty acid intake the the low low serum serum cholesterol cholesterol level level is exmonounsaturated fatty acid plained in part by by the the high high rates rates of offractional fractional catabolism catabolism of LDL. LDL. In In plained in part samples with population samples with low low fat fat diet diet and and restricted restricted in in saturated and monounsaturatedfatty fatty acids acids the the extremely extremely low low serum serum cholesterol level is explained unsaturated low rates of LDL. by low rates of production and fractional catabolism of alcohol also have some influence on serum lipoproCarbohydrates and alcohol increase VLDL, while influences teins: both increase influences on on HDL HDL are in opposite direcis increased increased by high high alcohol alcohol intake intake and and lowered lowered by by high high tions (HDL (HDL is tions carbohydrate intake). influences on serum cholescholesDietary influences on serum lipoproteins and thereby on serum terol are so varied and complex that they preclude collection of information specific for which is specific for one one single single nutrient. nutrient. Serum lipoproteins average attitude of a Serum lipoproteins might might provide provide an an idea of the average offat population towards fat intake, but they are not indicative of fat intake in the individual subject. Much more can be learned from blood or or adipose adipose tissue tissue analysis. analysis. The Much of adipose tissue can provide an indication of of the fatty fatty acid composition of of the habitual diet over the preceding 2-3 years. To obtain composition of acid composition of the the essential essential omega-6 medium term term intake, intake, particularly particularly of information on medium omega-3 fatty fatty acids, acids, the the determination determination of of fatty fatty acids acids in in erythrocyte erythrocyte and omega-3 of the preceding preceding few used. To assess assess the fatty acid intake of membranes can be used. days, or adherence offatty days, adherence to fat-controlled fat-controlled diet, diet, the determination of fatty acids in recommended. serum triacylglycerols triacylglycerols is is
Downloaded by: Université de Paris 193.51.85.197 - 1/29/2020 1:30:35 AM
Fidanza
Biological Markers Biological Markers of of Dietary Dietary Intake
61
The results of the International Collaborative Study on the Fatty AcidArteriosclerosis were previous Antioxidant Hypothesis Hypothesis of Arteriosclerosis Antioxidant were reported reported in in a previous symposium of this group group [4]. [4]. The The relevant relevant methodology methodology used used will will be be symposium of this considered here in more detail. Adipose tissue composition of body tisAdipose tissue was was selected selected for for fatty fatty acid acid composition sues. Samples Samples were microbiopsy or needle aspiration from from sues. were obtained obtained by by microbiopsy or needle andstored storedatat—40 -40 °C. 0c. anterior abdominal abdominal wall wall under underlocal localanesthesia anesthesiaand the anterior chromatographic determination central laboralaboraGas chromatographic determination was was carried carried out out in in a central [5]. tory [5]. old), by the dietary history history A dietary dietary survey survey of 74 74 men men (40-49 years old), method was carried out concurrently only for the Italian sample from Sapri. method between fatty the corresponding corresponding percenpercenThe correlations between fatty acid intake and the adipose tissue tissue were were weak. weak. In only only 22 cases cases were they tages of fatty acids in adipose energy from from polyunsaturated polyunsaturated statistically significant: significant: percentage statistically percentage of of total total energy 0.26, fatty acids acids versus versus adipose adipose tissue tissue polyunsaturated polyunsaturated fatty fatty acids acids (r(r == 0.26, fatty g1dayof ofmonounsaturated monounsaturated fatty fatty acids acids versus versus monounsaturmonounsaturp < 0.05)and andg/day p
and Cardiovascular Cardiovascular Risk: Nutrition and The Biological Biological Markers Markers of Dietary Intake Flaminio Fidanza Istituto di di Scienza Scienza dell'Alimentazione, Università Universita degli Studi, Perugia, Italy
Biomarkers of of Fat Intake epidemiological studies disease were were When the first epidemiological studies on coronary heart disease total serum serum cholesterol cholesterol was considered a reliable marker of total fat started, total [1]. The cholesterol of of middle-aged middle-aged intake [1]. The average average concentration concentration of serum cholesterol of 40% 40% of areas where where the diets were were high in total fats (of (of the order order of men in areas energy), was where the diets total energy), was 25-50% 25-50% greater greater than than the average in areas where were low in total fats (of (of the order order of of 20%, 20%, or less, less, of total energy). energy). And this was not related to race. controlled conditions it was was observed observed that average average serum serum Then under controlled offat in the diet and this change cholesterol responded responded to to aa change in the kind of fat well predicted from the fatty acids and cholesterol composition of was rather well [2]. the exchanged diet [2]. the classical classical Keys equation was derived: From the above experiments the
where S is is the percentage percentage of of total total energy energy from from saturated saturated fatty acids acids and P the percentage percentage of total energy energy from from polyunsaturated fatty acids. Similar results in prospective prospective epidemiological epidemiological studies. have been obtained in With this equation, equation, in in which which some corrections corrections were later made, the small cholesterol has significant proportion of variance by diet to serum total cholesterol but significant recently been explained. effect of The effect of dietary dietary fatty fatty acids on serum cholesterol is actually the sum of modifications induced in the level of the three major lipoprotein lipoprotein classes, classes, of very-low-density lipoprotein (LOL) and very-tow-density lipoprotein (VLOL), (VLDL), low-density low-density lipoprotein lipoprotein (LDL) high-density lipoprotein effects of saturated high-density lipoprotein (HOL). (HDL). While While the the qualitative effects
Downloaded by: Université de Paris 193.51.85.197 - 1/29/2020 1:30:35 AM
dCholesterol 2.7 dS-1.3dP, ∆ Cholesterol == 2.7AS— I .3AΡ,
60
polyunsaturated fatty fatty acids acids are the sum of of those on the three lipoprotein and polyunsaturated classes, the quantitative influence on the individual classes is different: different: in classes, the influence individual classes increase LDL; LDL; oleic oleic acid is as saturated fatty fatty acids acids (except (except C:18) C: 18) increase particular, saturated effective as as polyunsaturated polyunsaturated fatty acids in reducing LDL, LDL, while while concentration concentration seems to remain remain relatively relatively stable; stable; linoleic acid decreases decreases LDL and of HDL seems cholesterol, while eicosapentenoic eicosapentenoic and docosahexenoic docosahexenoic acid dealso HDL cholesterol, triglycerides present in VLDL. crease triglycerides of apo B were used to assess The kinetics of assess dietary dietary influences on the rate of fractionational catabolism catabolism of of LDL, LDL, adapting for epidemioproduction and fractionational logical use measurement of urine/plasma urine/plasma radioactivity logical use the the measurement radioactivity ratio ratio after after an ofaa low dose injection of injection dose of of autologous autologous radiolabeled radiolabeled LDL. LDL. With With this this method, an international collaborative collaborative study metabolic epidemiology epidemiology of plasma plasma international study on metabolic five different different population samples samples [3]. cholesterol was cholesterol was carried carried out in five [3]. In In this population samples samples with high high very interesting study, it was observed that in population fatty acid acid intake, intake, the the high high serum serum cholesterol cholesterol level level is explained in saturated fatty by greater greater rates rates of of LDL LDL production. production. In In population population samples samples with with high high part by exmonounsaturated fatty acid intake the the low low serum serum cholesterol cholesterol level level is exmonounsaturated fatty acid plained in part by by the the high high rates rates of offractional fractional catabolism catabolism of LDL. LDL. In In plained in part samples with population samples with low low fat fat diet diet and and restricted restricted in in saturated and monounsaturatedfatty fatty acids acids the the extremely extremely low low serum serum cholesterol level is explained unsaturated low rates of LDL. by low rates of production and fractional catabolism of alcohol also have some influence on serum lipoproCarbohydrates and alcohol increase VLDL, while influences teins: both increase influences on on HDL HDL are in opposite direcis increased increased by high high alcohol alcohol intake intake and and lowered lowered by by high high tions (HDL (HDL is tions carbohydrate intake). influences on serum cholescholesDietary influences on serum lipoproteins and thereby on serum terol are so varied and complex that they preclude collection of information specific for which is specific for one one single single nutrient. nutrient. Serum lipoproteins average attitude of a Serum lipoproteins might might provide provide an an idea of the average offat population towards fat intake, but they are not indicative of fat intake in the individual subject. Much more can be learned from blood or or adipose adipose tissue tissue analysis. analysis. The Much of adipose tissue can provide an indication of of the fatty fatty acid composition of of the habitual diet over the preceding 2-3 years. To obtain composition of acid composition of the the essential essential omega-6 medium term term intake, intake, particularly particularly of information on medium omega-3 fatty fatty acids, acids, the the determination determination of of fatty fatty acids acids in in erythrocyte erythrocyte and omega-3 of the preceding preceding few used. To assess assess the fatty acid intake of membranes can be used. days, or adherence offatty days, adherence to fat-controlled fat-controlled diet, diet, the determination of fatty acids in recommended. serum triacylglycerols triacylglycerols is is
Downloaded by: Université de Paris 193.51.85.197 - 1/29/2020 1:30:35 AM
Fidanza
Biological Markers Biological Markers of of Dietary Dietary Intake
61
The results of the International Collaborative Study on the Fatty AcidArteriosclerosis were previous Antioxidant Hypothesis Hypothesis of Arteriosclerosis Antioxidant were reported reported in in a previous symposium of this group group [4]. [4]. The The relevant relevant methodology methodology used used will will be be symposium of this considered here in more detail. Adipose tissue composition of body tisAdipose tissue was was selected selected for for fatty fatty acid acid composition sues. Samples Samples were microbiopsy or needle aspiration from from sues. were obtained obtained by by microbiopsy or needle andstored storedatat—40 -40 °C. 0c. anterior abdominal abdominal wall wall under underlocal localanesthesia anesthesiaand the anterior chromatographic determination central laboralaboraGas chromatographic determination was was carried carried out out in in a central [5]. tory [5]. old), by the dietary history history A dietary dietary survey survey of 74 74 men men (40-49 years old), method was carried out concurrently only for the Italian sample from Sapri. method between fatty the corresponding corresponding percenpercenThe correlations between fatty acid intake and the adipose tissue tissue were were weak. weak. In only only 22 cases cases were they tages of fatty acids in adipose energy from from polyunsaturated polyunsaturated statistically significant: significant: percentage statistically percentage of of total total energy 0.26, fatty acids acids versus versus adipose adipose tissue tissue polyunsaturated polyunsaturated fatty fatty acids acids (r(r == 0.26, fatty g1dayof ofmonounsaturated monounsaturated fatty fatty acids acids versus versus monounsaturmonounsaturp < 0.05)and andg/day p
