Guest guest Posted August 12, 2005 Report Share Posted August 12, 2005 Hi All, Rodney had me searching for reasons to take monounsaturated fats by one of his posts in this forum. The risks for total mortality related to fats consumed appear to be notably sex-specific, especially for monounsaturated fats. Saturated fats appear to be a lower risk than is generally accepted. The pdf for the below is available. J Intern Med. 2005 Aug;258(2):153-65. Dietary fat intake and early mortality patterns--data from The Malmo Diet and Cancer Study. Leosdottir M, Nilsson PM, Nilsson JA, Mansson H, Berglund G. OBJECTIVES: Most current dietary guidelines encourage limiting relative fat intake to <30% of total daily energy, with saturated and trans fatty acids contributing no more than 10%. We examined whether total fat intake, saturated fat, monounsaturated, or polyunsaturated fat intake are independent risk factors for prospective all-cause, cardiovascular and cancer mortality. DESIGN: Population-based, prospective cohort study. SETTING AND SUBJECTS: The Malmo Diet and Cancer Study was set in the city of Malmo, southern Sweden. A total of 28,098 middle-aged individuals participated in the study 1991-1996. MAIN OUTCOME MEASURES: Subjects were categorized by quartiles of relative fat intake, with the first quartile used as a reference point in estimating multivariate relative risks (RR; 95% CI, 's regression model). Adjustments were made for confounding by age and various lifestyle factors. RESULTS: Women in the fourth quartile of total fat intake had a significantly higher RR of cancer mortality (RR 1.46; CI 1.04-2.04). A significant downwards trend was observed for cardiovascular mortality amongst men from the first to the fourth quartile (P=0.028). No deteriorating effects of high saturated fat intake were observed for either sex for any cause of death. Beneficial effects of a relatively high intake of unsaturated fats were not uniform. CONCLUSIONS: With the exception of cancer mortality for women, individuals receiving more than 30% of their total daily energy from fat and more than 10% from saturated fat, did not have increased mortality. Current dietary guidelines concerning fat intake are thus generally not supported by our observational results. PMID: 16018792 .... Results Tables 1 and 2 show baseline characteristics for subjects, categorized by survival status at the end of follow-up. Till the end of year 2000, over a mean follow-up period of 6.6 years (range 0.19.8 years) a total of 1250 deaths were registered. Mean age at death was 66.2 years (47.377.9) for women and 66.7 years (48.277.8) for men. Cancer was the leading cause of death, responsible for 59% of deaths amongst women (310 of 522) and 43% amongst men (313 of 728). Breast cancer was the most common cancer causing death amongst the women (16%), followed by lung cancer (12%). Amongst men, lung (19%) and prostate (15%) cancers were most common. Ninety-seven of 522 women (19%) and 242 (33%) men died from cardiovascular disease. Of the 28 098 subjects participating in the study, 139 individuals (81 women and 59 men) were lost to follow-up, the main reason being permanent emigration. Table 1 Baseline characteristics for women categorized by survival status at the end of follow-up. Subjects lost to follow-up (n = 81) are not included. Figures are presented as percentages or age-adjusted mean values with range in parentheses ................................................ ------Alive (N = 16 432) Dead (all causes) (N = 522) Dead from CVD (N = 97) Dead from cancer (N = 310) ................................................ Mean age in years (range) 57.3 (4573) 61.8 (4573) 63.8 (4573) 60.9 (4573) Social status Blue collar worker (%) 38.0 43.8 58.3 42.2 White collar worker (%) 54.5 49.0 33.3 52.0 Employer/self-employed (%) 7.6 7.2 8.3 5.9 Smoking habits Never smoked (%) 44.5 35.4 27.8 36.5 Former smoker (%) 27.8 23.8 24.7 22.6 Current smoker (%) 27.6 40.8 47.4 41.0 Marital status Married/co-habiting (%) 60.8 50.3 54.6 48.9 Single/divorced/widowed (%) 39.2 49.7 45.4 51.1 Alcohol consumption (g pure ethanol day1) 7.7 (0.0109.5) 6.8 (0.073.7) 6.3 (0.045.3) 6.8 (0.073.7) Physical activity score 7935 (0316 120) 7490 (039 825) 7184 (033 600) 8011 (039 825) Blood pressure (mmHg) Systolic 139.3 (61230) 140.4 (90210) 147.2 (110210) 138.9 (98200) Diastolic 84.0 (40136) 84.6 (56126) 86.9 (65126) 84.2 (60110) Body mass index (kg m2) 25.4 (14.050.9) 25.3 (15.144.8) 25.6 (15.139.7) 25.4 (16.744.8) Total energy intake (kcal day1) 1999 (5045556) 2015 (7424104) 1923 (7764072) 2063 (7424085) Relative fat intake (% of total energy) 38.4 (9.271.5) 39.0 (13.360.6) 37.9 (9.271.5) 39.5 (13.360.6) Table 2 Baseline characteristics for men categorized by survival status at the end of follow-up. Subjects lost to follow-up (n = 58) are not included. Figures are presented as percentages or age-adjusted mean values with range in parentheses ............................................. ------Alive (N = 10277) Dead (all causes) (N = 728) Dead from CVD (N = 242) Dead from cancer (N = 313) ............................................ Mean age in years (range) 59.1 (4673) 62.7 (4673) 63.3 (4873) 62.8 (4673) Social status Blue collar worker (%) 35.3 42.3 46.7 36.7 White collar worker (%) 47.1 43.6 37.6 47.9 Employer/self-employed (%) 17.6 14.1 15.7 15.4 Smoking habits Never smoked (%) 29.0 17.2 15.3 17.9 Former smoker (%) 43.5 40.0 40.5 39.3 Current smoker (%) 27.5 42.9 44.2 42.8 Marital status Married/co-habiting (%) 73.2 61.8 58.5 68.1 Single/divorced/widowed (%) 26.8 38.2 41.5 31.9 Alcohol consumption (g pure ethanol day1) 15.5 (0.0194.0) 14.3 (0.0161.6) 12.9 (0.092.1) 14.8 (0.095.4) Physical activity score 8386 (0209 556) 7969 (095 200) 7606 (095 200) 8270 (058 790) Blood pressure (mmHg) Systolic 143.9 (90230) 147.3 (90220) 149.2 (92220) 146.3 (108210) Diastolic 87.9 (52136) 89.8 (60128) 91.1 (60128) 88.9 (60115) Body mass index (kg m2) 26.3 (13.950.7) 26.2 (15.243.4) 26.7 (17.443.4) 25.9 (15.638.4) Total energy intake (kcal day1) 2603 (5706789) 2598 (9998304) 2484 (9995229) 2675 (12968304) Relative fat intake (% of total energy) 39.7 (4.768.1) 39.7 (13.060.3) 39.3 (19.158.4) 39.9 (19.260.1) Diet composition Tables 3 and 4 show diet composition and baseline characteristics for women and men, respectively, in the four quartiles of total fat intake. Fat intake in the whole cohort varied from 31% (10th percentile) to 46% (90th percentile) of total energy intake for women and 32% (10th percentile) to 48% (90th percentile) for men. For both sexes, the increase in total fat intake from the first to the fourth quartiles was attributable to increased saturated fat intake (P < 0.001, Tables 3 and 4). Table 3 Diet composition and baseline characteristics within different quartiles of relative fat intake for women. Figures are presented as age-adjusted mean values or percentages ........................................... ------1st 2nd 3rd 4th ........................................... N (n) 4258 (121) 4259 (138) 4259 (112) 4259 (151) % Energy from fat 30.8 36.5 40.3 46.1 % From saturated fats 41.2 42.5 43.4 45.3 % From monounsaturated fats 34.8 34.9 34.7 34.1 % From polyunsaturated fats 16.7 16.0 15.6 14.9 Monounsaturated/saturated fat ratio 0.86 0.84 0.81 0.77 % Energy from carbohydrates 52.0 47.0 43.7 38.7 % Energy from protein 16.6 16.2 15.8 15.2 Fibre intake (g day1) 21.3 19.6 18.3 16.8 Vegetable and fruit intake (g day1) 465 412 369 317 Energy intake (kcal day1) 1832 1964 2039 2163 Age 57.9 57.7 57.3 57.0 Socio-economic status % Blue collar worker 41.3 38.3 37.3 35.7 % White collar worker 51.8 54.1 55.5 55.5 % Self-employed 6.9 7.6 7.3 8.5 % Current smoker 20.9 24.4 29.3 37.6 Prior history of cancer, diabetes, myocardial infarction or stroke (%) 18.6 18.0 17.3 18.3 Use of antihypertensive medication (%) 20.5 17.0 16.4 14.2 BMI (kg m2) 25.5 25.6 25.4 24.9 SBP (mmHg) 141 140 139 138 Alcohol intake (g pure ethanol day1) 5.9 7.3 8.2 9.3 Physical activity score 8407 8075 7682 7537 ........................................... N = number of individuals within each quartile; n = number of deaths from all causes. BMI, body mass index; SBP, systolic blood pressure. Table 4 Diet composition and baseline characteristics within different quartiles of relative fat intake for men. Figures are presented as age-adjusted mean values or percentages ........................................... ------1st 2nd 3rd 4th ........................................... N (n) 2765 (186) 2766 (183) 2766 (155) 2766 (204) % Energy from fat 31.7 37.8 41.7 47.7 % From saturated fats 40.1 41.6 42.4 44.6 % From monounsaturated fats 35.4 35.4 35.4 34.7 % From polyunsaturated fats 17.4 16.5 16.0 15.0 Monounsaturated/saturated fat ratio 0.90 0.87 0.85 0.80 % Energy from carbohydrates 51.7 46.2 42.9 37.6 % Energy from protein 16.0 15.8 15.4 14.8 Fibre intake (g day1) 24.8 22.1 20.7 18.7 Vegetable and fruit intake (g day1) 416 357 326 284 Energy intake (kcal day1) 2408 2543 2658 2798 Age 59.4 59.5 59.2 60.0 Socio-economic status % Blue collar worker 37.0 36.5 34.9 34.8 % White collar worker 48.1 46.5 47.2 45.8 % Self-employed 15.0 17.1 17.9 19.5 % Current smoker 20.9 24.7 28.1 40.6 Prior history of cancer, diabetes, myocardial infarction or stroke (%) 16.7 13.7 11.6 11.1 Use of antihypertensive medication (%) 24.7 21.3 20.5 18.6 BMI (kg m2) 26.3 26.4 26.3 26.1 SBP (mmHg) 144 144 144 144 Alcohol intake (g pure ethanol day1) 12.6 14.1 16.7 18.5 Physical activity score 9028 8489 8111 7798 N = number of individuals within each quartile; n = number of deaths from all causes. BMI, body mass index; SBP, systolic blood pressure. The average intake of each type of fat in different quartiles can be seen in Tables 5-7. Intakes of unsaturated fats were more or less in line with Nordic dietary guidelines, which recommend 1015% of total daily energy intake coming from cis monounsaturated fats and 510% from polyunsaturated fats [22]. Note that trans fatty acids were not recorded as a separate variable in our study and are thus incorporated into the monounsaturated, and to some extent, polyunsaturated variables. Fibre intake as well as fruit and vegetable intake decreased significantly from the first to the fourth quartiles of total fat, saturated fat, monounsaturated- and polyunsaturated fat for both sexes (P < 0.001 for both sexes, all types of fat). By including fibre intake as a continuous variable in our multivariate analyses, it was significantly negatively correlated to all-cause mortality and cardiovascular mortality for all types of fat for men (P < 0.05) but not for women. No significant effects of fibre intake were observed on cancer mortality for either sex in the multivariate analyses. Total mortality Relative risks for total mortality for different quartiles of fat intake for men and women can be seen in Table 5. Women in the fourth quartile of total fat intake had somewhat higher RR of total mortality (RR 1.22; CI 0.941.58) even though not statistically significant. This risk increase was mostly applicable to a high RR for the same quartile for cancer mortality (RR 1.46; CI 1.042.04, P = 0.029). Women in the fourth quartile of monounsaturated fat intake had higher total mortality (RR 1.44; CI 1.002.08, P = 0.049). The second and third quartiles also had RR >1.00, even though not significant (Table 5). No significant difference in RR was observed between quartiles of saturated fat intake, polyunsaturated fat intake, or the ratio between mono- or polyunsaturated fat and saturated fat intake for women. Table 5 Relative risks (95% CI) for total mortality by quartiles of relative fat intake for women and men. Adjusted for age, alcohol consumption, smoking, social class, marital status, physical activity, BMI and fibre intake. Saturated, monounsaturated and polyunsaturated fats were included simultaneously in the multivariate analysis. Adjustments were made for total fat intake for the ratio between unsaturated and saturated fats. Also shown is the percentage of daily energy intake (EI) that the relevant fat contributes ....................................... -------Quartiles---P for trend -----1 2 3 4--- ....................................... Women Total fat RR (95% CI) 1.00 (ref) 1.08 (0.841.40) 0.93 (0.711.22) 1.22 (0.941.58) 0.26 % of EI 30.8 36.5 40.3 46.1 Saturated fat RR (95% CI) 1.00 (ref) 0.96 (0.731.26) 0.82 (0.601.10) 0.89 (0.641.23) 0.39 % of EI 12.2 15.2 17.5 21.8 Monounsaturated fat RR (95% CI) 1.00 (ref) 1.17 (0.881.56) 1.28 (0.921.76) 1.44 (1.002.08)a 0.06 % of EI 10.6 12.6 14.0 16.0 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.80 (0.621.03) 0.77 (0.591.01) 0.85 (0.641.13) 0.22 % of EI 4.3 5.4 6.3 8.1 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.94 (0.741.21) 0.82 (0.631.07) 0.99 (0.771.27) 0.39 Ratio 1.00 0.86 0.77 0.65 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.93 (0.721.20) 0.93 (0.721.20) 0.93 (0.721.20) 0.35 Ratio 0.56 0.41 0.33 0.23 Men Total fat RR (95% CI) 1.00 (ref) 0.92 (0.751.13) 0.77 (0.620.95)b 0.89 (0.721.10) 0.14 % of EI 31.7 37.8 41.7 47.7 Saturated fat RR (95% CI) 1.00 (ref) 0.85 (0.671.07) 1.04 (0.811.32) 0.91 (0.691.19) 0.72 % of EI 12.3 15.3 17.6 22.3 Monounsaturated fat RR (95% CI) 1.00 (ref) 0.82 (0.651.04) 0.76 (0.590.99)c 0.88 (0.651.19) 0.37 % of EI 11.0 13.3 14.7 16.9 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.88 (0.711.09) 1.02 (0.821.27) 0.85 (0.661.09) 0.44 % of EI 4.5 5.7 6.7 8.6 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.95 (0.771.17) 1.00 (0.811.24) 1.11 (0.901.37) 0.51 Ratio 1.00 0.90 0.80 0.67 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.94 (0.761.16) 0.93 (0.751.15) 1.11 (0.901.38) 0.58 Ratio 0.59 0.43 0.35 0.24 ................................... aP = 0.049. bP = 0.017. cP = 0.046. For men, a significantly lower RR of total mortality was observed in the third quartile of total fat intake (RR 0.77; CI 0.620.95, P = 0.017), with RR for the second and fourth quartiles also <1.00 (Table 5). No trend towards higher mortality was observed for saturated fat intake. For unsaturated fats, men in the third quartile for monounsaturated fats had significantly lower total mortality (RR 0.76; CI 0.590.99, P = 0.046). No significant difference or trend was observed between quartiles of polyunsaturated fat or the unsaturated/saturated fat ratios. After excluding individuals with <1 year follow-up, prior history of myocardial infarction, stroke, cancer or diabetes (3101 women and 1510 men) significance did not hold for any of the results. These exclusions involved 16.5% of the cohort, thus decreasing the power of the calculations considerably. However, the observed trends in mortality did not change. Cardiovascular mortality Relative risks of cardiovascular mortality for quartiles of all types of fat can be seen in Table 6. For women, no significant difference was observed between quartiles of total fat or saturated fat intake. For men, a significant trend towards lower cardiovascular mortality in upper quartiles of total fat intake was observed (P = 0.028) with the RR for men in the fourth quartile being 0.65 (CI 0.450.94, P = 0.023) (Fig. 1). No difference was observed between quartiles of saturated fat intake for men. When looking at unsaturated fats, women in the third quartile of polyunsaturated fat had lower RR (0.46; CI 0.240.89, P = 0.021), as did men in the second quartile of monounsaturated fat intake (0.63; CI 0.420.95, P = 0.027). Having relatively high intakes of monounsaturated or polyunsaturated fats compared with saturated fats did not show benefit for either sex. Table 6 Relative risks (95% CI) for cardiovascular mortality by quartiles of relative fat intake for women and men. Adjusted for age, alcohol consumption, smoking, social class, marital status, physical activity, BMI and fibre intake. Saturated, monounsaturated and polyunsaturated fats were included simultaneously in the multivariate analysis. Adjustments were made for total fat intake for the ratio between unsaturated and saturated fats. Also shown is the percentage of daily energy intake (EI) that the relevant fat contributes ........................................ ---------Quartiles---P for trend ------1 2 3 4--- ....................................... Women Total fat RR (95% CI) 1.00 (ref) 0.99 (0.571.72) 0.80 (0.451.43) 0.74 (0.401.36) 0.25 % of EI 30.8 36.5 40.3 46.1 Saturated fat RR (95% CI) 1.00 (ref) 0.89 (0.491.62) 0.76 (0.391.45) 0.55 (0.261.17) 0.16 % of EI 12.2 15.2 17.5 21.8 Monounsaturated fat RR (95% CI) 1.00 (ref) 1.66 (0.883.15) 1.91 (0.923.94) 1.53 (0.653.64) 0.34 % of EI 10.6 12.6 14.0 16.0 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.82 (0.471.42) 0.46 (0.240.89)a 0.63 (0.331.22) 0.10 % of EI 4.3 5.4 6.3 8.1 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 1.04 (0.611.78) 0.81 (0.451.46) 0.84 (0.461.53) 0.39 Ratio 1.00 0.86 0.77 0.65 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 1.03 (0.601.76) 0.81 (0.451.46) 0.84 (0.461.54) 0.82 Ratio 0.56 0.41 0.33 0.23 Men Total fat RR (95% CI) 1.00 (ref) 0.76 (0.531.09) 0.74 (0.521.07) 0.65 (0.450.94)b 0.03 % of EI 31.7 37.8 41.7 47.7 Saturated fat RR (95% CI) 1.00 (ref) 1.03 (0.691.53) 1.24 (0.821.89) 0.94 (0.581.53) 0.98 % of EI 12.3 15.3 17.6 22.3 Monounsaturated fat RR (95% CI) 1.00 (ref) 0.63 (0.420.95)c 0.72 (0.471.12) 0.61 (0.361.03) 0.11 % of EI 11.0 13.3 14.7 16.9 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.81 (0.561.19) 1.08 (0.741.58) 0.99 (0.651.53) 0.64 % of EI 4.5 5.7 6.7 8.6 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.93 (0.651.34) 0.89 (0.621.30) 1.11 (0.771.59) 0.59 Ratio 1.00 0.90 0.80 0.67 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.80 (0.551.16) 0.82 (0.571.19) 1.03 (0.721.48) 0.77 Ratio 0.59 0.43 0.35 0.24 ............................................ aP = 0.021. bP = 0.023. cP = 0.027. As with total mortality, significance did not hold after excluding subjects with short follow-up, prior history of myocardial infarction, stroke, cancer or diabetes. Cancer mortality Relative risks of cancer mortality for quartiles of all types of fat can be seen in Table 7. Women in the fourth quartile of total fat intake (46.1% of daily energy from fat) had a significantly higher RR of dying from cancer (RR 1.46; CI 1.042.04, P = 0.029) (Fig. 2). This was mostly attributable to a high RR for women in the fourth quartile of monounsaturated fat intake (RR 1.47; CI 0.922.34, P = NS). RR for women in the second quartile of polyunsaturated fat intake was significantly lower, with an RR of 0.70 (CI 0.500.98, P = 0.038). Saturated fat intake, and the ratio between monounsaturated or polyunsaturated fat and saturated fat, did not show any significant effect on cancer mortality for women. For men, significant differences in cancer mortality between quartiles were not revealed for any type of fat. Table 7 Relative risks (95% CI) for cancer mortality by quartiles of relative fat intake for women and men. Adjusted for age, alcohol consumption, smoking, social class, marital status, physical activity, BMI, and fibre intake. Saturated, monounsaturated and polyunsaturated fats were included simultaneously in the multivariate analysis. Adjustments were made for total fat intake for the ratio between unsaturated and saturated fats. Also shown is the percentage of daily energy intake (EI) that the relevant fat contributes ............................................ ---------Quartiles---p for trend ------1 2 3 4--- ............................................ Women Total fat RR (95% CI) 1.00 (ref) 1.08 (0.771.53) 1.06 (0.751.50) 1.46 (1.042.04)a 0.03 % of EI 30.8 36.5 40.3 46.1 Saturated fat RR (95% CI) 1.00 (ref) 1.21 (0.841.75) 1.04 (0.701.57) 1.15 (0.921.79) 0.78 % of EI 12.2 15.2 17.5 21.8 Monounsaturated fat RR (95% CI) 1.00 (ref) 1.00 (0.681.46) 1.12 (0.731.70) 1.47 (0.922.34) 0.08 % of EI 10.6 12.6 14.0 16.0 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.70 (0.500.98)b 0.80 (0.571.13) 0.77 (0.531.12) 0.28 % of EI 4.3 5.4 6.3 8.1 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 1.07 (0.771.48) 0.91 (0.651.28) 1.10 (0.791.53) 0.86 Ratio 1.00 0.86 0.77 0.65 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.81 (0.581.13) 0.99 (0.721.37) 0.90 (0.651.25) 0.51 Ratio 0.56 0.41 0.33 0.23 Men Total fat RR (95% CI) 1.00 (ref) 1.08 (0.791.47) 0.74 (0.531.05) 1.00 (0.721.39) 0.56 % of EI 31.7 37.8 41.7 47.7 Saturated fat RR (95% CI) 1.00 (ref) 0.89 (0.631.25) 0.92 (0.631.35) 0.98 (0.641.48) 0.82 % of EI 12.3% 15.3% 17.6% 22.3% Monounsaturated fat RR (95% CI) 1.00 (ref) 0.86 (0.611.21) 0.67 (0.441.01) 0.92 (0.581.44) 0.55 % of EI 11.0 13.3 14.7 16.9 Polyunsaturated fat RR (95% CI) 1.00 (ref) 0.97 (0.701.33) 0.99 (0.711.39) 0.84 (0.581.23) 0.40 % of EI 4.5 5.7 6.7 8.6 Monounsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.93 (0.671.28) 0.90 (0.651.25) 1.13 (0.821.55) 0.84 Ratio 1.00 0.90 0.80 0.67 Polyunsaturated/saturated fat RR (95% CI) 1.00 (ref) 0.98 (0.711.35) 0.93 (0.671.28) 1.03 (0.741.42) 0.70 Ratio 0.59 0.43 0.35 0.24 ......................................... aP = 0.029. bP = 0.038. The observed trends in mortality were unchanged after excluding individuals with <1 year follow-up, prior history of myocardial infarction, stroke, cancer or diabetes, although significance did not hold. Discussion With the exception of cancer mortality for women in the highest quartile of relative fat intake, individuals receiving more than 30% of their total daily energy from fat did not have increased mortality. Men in the fourth quartile of total fat intake, receiving almost 50% of their total energy intake from fat, had the lowest cardiovascular mortality. Receiving more than 10% of total energy intake from saturated fat did not have a significant effect on all-cause, cardiovascular or cancer mortality for men or women. Beneficial effects of relatively high intakes of unsaturated fats were not uniform, and having a high index of unsaturated fat compared with saturated fat intake did not have any detectable effect on mortality. When looking at cardiovascular mortality, the first large-scale prospective observational study on the dietary fatcardiovascular disease relationship was the ecological Seven Countries study [2]. In the 15-year follow-up publication, a strong correlation was observed between all-cause mortality, cancer mortality and cardiovascular mortality, and the ratio between monounsaturated and saturated fat in the diet [26]. A somewhat weaker association was observed between mortality and saturated fat intake, but total fat intake did not have any effect. Prospective cohort studies, published at a similar time and over the next decade, showed weak or no correlation between total fat and saturated fat and cardiovascular mortality and/or disease [2731]. However, dietary assessment methods used in these studies and confounding for which adjustments were made varied considerably. Adjustments for other types of fat, especially trans fatty acids, were not uniform. Also, adjustments for fibre intake were generally not made in these studies. It has been shown that high-fat Western diets tend to be poor in fibre [32, 33]. Fibre intake has been shown to protect against cardiovascular disease and to a less extent some types of cancer [34, 35]. Thus, not adjusting for fibre intake when evaluating the effect of fat on disease incidence and mortality, especially cardiovascular disease, produces an important confounding effect. In more recent epidemiological studies, where adjustments for fibre intake were made, total fat intake and cardiovascular disease and/or mortality were as in our study not positively correlated, and saturated fat intake showed no or borderline significant correlation [36, 37]. One of those, the Health Professionals Follow-up Study (HPFS), underlined the important effect fibre intake has on the fatcardiovascular disease relationship, with RR for the upper quintiles of fat intake dropping by approximately 20% when additional adjustments were made for fibre intake [37]. In the Nurses Health Study (NHS), a prospective cohort study of over 80 000 women, no statistically significant effects of high intakes of total or saturated fats were noticed, even though fibre intake was not adjusted for in their multivariate analysis [38]. Studies on the effect of dietary fats on cerebrovascular disease are much sparser. The two most recent large-scale cohort studies have shown no effect or even beneficial effects of increased total and saturated fat intake on stroke incidence [39, 40]. Several reviews on prospective cohort studies examining the effects of unsaturated fats on cardiovascular disease have been published [4, 8, 40]. Most conclude that high intakes of polyunsaturated fats protect against cardiovascular disease. However, in the more than 20 studies reviewed, results are not unanimous, with some studies showing null or negative findings [4, 8, 3638, 41]. Monounsaturated fats seem to provide little if any protective effects [36, 38, 41]. In the two before-mentioned studies on cerebrovascular disease, polyunsaturated fats did not give beneficial effects, with monounsaturated fats providing no or slight benefit [39, 40]. In our study, women in the third quartile of polyunsaturated fat intake had the lowest cardiovascular mortality, but high polyunsaturated fat intake did not show any benefit for men. Monounsaturated fat intake however showed some protecting effects for men, with the second quartile having the lowest RR and the third and fourth quartiles having RR <1.00, even though not statistically significant. The opposite was observed for women, with RR in the second to fourth quartiles over 1.00. However, the number of cardiovascular cases amongst women was few, thus giving poor statistical power to the calculations with wide CI. A separate analysis within the same cohort, evaluating the effect of dietary fat on fatal and nonfatal cardiovascular events, with more than 2000 registered endpoints, awaits publication. The fact that trans fatty acids are included in the unsaturated fat variables in our study, could have confounded the results considerably. Also, the limited variation in unsaturated fat intake in our study population, with mean intakes for the first as well as the fourth quartiles lying approximately within recommended intakes, diminishes the likelihood of revealing significant effects [22]. Unlike the ecological Seven Countries Study's results, the ratio between mono- or polyunsaturated fats and saturated fats did not show any beneficial effects for either sex in our study. In prospective cohort studies, the NHS and the HPFS, a similar ratio, the Keys score (incorporating polyunsaturated fat, saturated fat and cholesterol intake, with higher scores indicating relatively lower intakes of polyunsaturated fats as opposed to saturated fats and cholesterol), was evaluated [37, 38]. The Keys score was positively correlated to coronary heart disease in the NHS, but not in the HPFS. When evaluating the effect on fatal coronary disease in HPFS, significance was lost after adjustment for fibre intake [37]. When looking at cancer mortality, our results showed significantly higher RR for women in the fourth quartile of total fat intake. Monounsaturated fat intake seemed to be the largest contributor to this effect. For men, total fat, subtypes of fat, and the unsaturated/saturated fat ratio had no effect on cancer mortality. This gender difference might thus be attributable to female cancers such as breast, ovarian, and endometrial tumours, which jointly accounted for 38% of cancer deaths amongst women. Evidence from multiple large prospective cohort studies has confirmed that total fat intake probably has no effect on breast cancer risk [9, 42, 43]. In non-Mediterranean Western countries, where monounsaturated fats in the diet mostly come from meat and dairy products and not from olive oil, no significant effects of diets rich in monounsaturated fat on breast cancer incidence have been observed [9, 42, 43]. Previous publications from the EPIC study (European Prospective Investigation into Cancer and Nutrition), to which the MDC cohort contributes, have indeed shown that the main source of monounsaturated fats in this population was margarines and animal products [44]. Some facts have to be taken into account when interpreting our findings. First, it has been shown in this cohort that fat-rich diets tended to be poor in vegetables and fruit [33]. Inverse associations between vegetable and fruit intake and breast cancer have been reported repeatedly [43]. Secondly, the fact that trans fatty acids were not recorded separately in our study might have confounded our observed effect of monounsaturated fat intake. Some studies on trans fatty acids and breast cancer have shown increased breast cancer risk with higher levels of trans fatty acids in adipose tissue [45]. However, studies on the effect of trans fatty acids on breast cancer are sparse, and results have not been unanimous [45, 46]. Limitations The participation rate in the MDC Study was quite low (approximately 40%). Hence, the risk of selection bias must be considered when interpreting our results. The diet in MDC was only evaluated at one point in time, and the number of people changing their diet during the follow-up period is unknown. Confounding effects from dietary factors not adjusted for in this study, for example diet composition and nutritional value, cannot be ruled out. The follow-up time in our study was relatively short, with mean age at death being 66.5 years and thus only early mortality being observed. Other factors might be of greater importance for death later in life. Pooling all cancer deaths together might confound our results, as dietary fats have been shown to effect different types of cancers in different ways [9]. The same might be applicable to cardiovascular mortality, as dietary fats do not seem to effect cerebrovascular disease incidence in the same way as cardiovascular disease and mortality [4, 8, 3641]. Factors such as vitality, biological ageing and subclinical disease can affect appetite, energy intake, palatability and dietary habits, as well as disease development and mortality. As such, they can produce confounding effects in large-scale epidemiological studies like the current study. These limitations have to be taken into account when interpreting the results. Underreporting of total energy and fat intake when using self-reported dietary assessment methods is considerable [47, 48]. Mattisson et al. [49] showed in a subsample of the MDC cohort that 41.6% of the subjects would be classified as under-reporters. Various adjustment models, which take biomarker measurements such as doubly labelled water and urinary nitrogen into account, have been created to try and further elucidate the effect of misreporting [47, 50]. Even though such models were not directly applied in the MDC Study, the dietary assessment instruments used in MDC were validated against weighed food records and urinary nitrogen measurements, showing correlation with r-values in the range of 0.500.60 for total energy intake and energy-adjusted fat and protein intake, which is comparable with the highest observations in similar validation studies [20]. Also, by stratifying analysis by sex and adjusting for confounding by body mass index, smoking, physical activity, and socio-economic factors, we partly compensate for differences between individuals in factors with impact on diet reporting, thus further limiting the biasing effect on our results. Future implications For the last 50 years, internationally used dietary guidelines recommending low-fat diets, have had great impact on both the lives of ordinary healthy free-living people and the food industry as a whole [68]. Whilst total energy intake over the last decades has increased to some extent in the Western world, the percentage of total daily energy coming from total fat and saturated fats especially has decreased, with intake of carbohydrates, mostly from refined sugars, increasing [4, 51]. Life expectancy has increased steadily during the same time, with incidence and death rates from heart disease and stroke diminishing dramatically [6, 52]. The changing nutritional- and lifestyle habits have, however, bred new problems with an overwhelming rise in the incidence of obesity and diabetes [53]. In the light of these changing trends, recent dietary and lifestyle advice from health authorities and professionals have, on the individual and population-based level, increasingly stressed a balanced energy intake and regular physical activity to avoid obesity, and to eat a diet rich in fruits, vegetables and fibre, including calories from all energy sources [54]. Our results support this trend, and not the change towards low-fat diets. However, studies with long-term follow-up and hard endpoints are still needed for further understanding the effect of diet on disease development and prevention. We also need a better understanding of the biological mechanisms behind our food choices, with the subjects' vitality possibly being an important determinant of high energy and high fat intake [23]. Conclusions With the exception of cancer mortality for women in the highest quartile of relative fat intake, individuals receiving more than 30% of their total daily energy from fat and more than 10% from saturated fat, did not have increased mortality. Beneficial effects of relatively high intakes of unsaturated fats were not uniform. With our results added to the pool of evidence from large-scale prospective cohort studies on dietary fat, disease and mortality, traditional dietary guidelines concerning fat intake are thus generally not strongly supported. Al Pater, PhD; email: old542000@... __________________________________________________ Quote Link to comment Share on other sites More sharing options...
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