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  #1   ^
Old Sun, Jul-07-02, 20:06
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Voyajer Voyajer is offline
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Default Harvard Nurses' Health Study

The Nurses' Health Study also called the Harvard or Framingham Nurses' Health Study is an ongoing study of 80,000 or so women that started in 1984. All these women were tracked for daily diet as well as physical activity, weight, and disease. Deaths were recorded and cause of deaths. All this data has been studied, correlated, charted, and analyzed and several reports have been published in several scientific and medical journals. This is an attempt to show the findings.

The well-known Professor Willet, head of the Nutrition Department at Harvard has been in on these studies.

The following reports shows that even while keeping carbohydrate calories high, a change from eating better fats rather than reducing fats was more effective in reducing risk of heart disease. Other findings from this study show that high glycemic carbohydrates increase risk of heart disease and that trans fat increases risk of heart disease. It is also shown that a high-carbohydrate diet typically produces high plasma triglycerides and low HDL-cholesterol concentrations.


New England Journal of Medicine

Volume 337:1491-1499 November 20, 1997 Number 21

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women

Frank B. Hu, M.D., Meir J. Stampfer, M.D., JoAnn E. Manson, M.D., Eric Rimm, Sc.D., Graham A. Colditz, M.D., Bernard A. Rosner, Ph.D., Charles H. Hennekens, M.D., and Walter C. Willett, M.D.

ABSTRACT

Background The relation between dietary intake of specific types of fat, particularly trans unsaturated fat, and the risk of coronary disease remains unclear. We therefore studied this relation in women enrolled in the Nurses' Health Study.

Methods We prospectively studied 80,082 women who were 34 to 59 years of age and had no known coronary disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Information on diet was obtained at base line and updated during follow-up by means of validated questionnaires. During 14 years of follow-up, we documented 939 cases of nonfatal myocardial infarction or death from coronary heart disease. Multivariate analyses included age, smoking status, total energy intake, dietary cholesterol intake, percentages of energy obtained from protein and specific types of fat, and other risk factors.

Results Each increase of 5 percent of energy intake from saturated fat, as compared with equivalent energy intake from carbohydrates, was associated with a 17 percent increase in the risk of coronary disease (relative risk, 1.17; 95 percent confidence interval, 0.97 to 1.41; P = 0.10). As compared with equivalent energy from carbohydrates, the relative risk for a 2 percent increment in energy intake from trans unsaturated fat was 1.93 (95 percent confidence interval, 1.43 to 2.61; P<0.001); that for a 5 percent increment in energy from monounsaturated fat was 0.81 (95 percent confidence interval, 0.65 to 1.00; P = 0.05); and that for a 5 percent increment in energy from polyunsaturated fat was 0.62 (95 percent confidence interval, 0.46 to 0.85; P = 0.003). Total fat intake was not significantly related to the risk of coronary disease (for a 5 percent increase in energy from fat, the relative risk was 1.02; 95 percent confidence interval, 0.97 to 1.07; P = 0.55). We estimated that the replacement of 5 percent of energy from saturated fat with energy from unsaturated fats would reduce risk by 42 percent (95 percent confidence interval, 23 to 56; P<0.001) and that the replacement of 2 percent of energy from trans fat with energy from unhydrogenated, unsaturated fats would reduce risk by 53 percent (95 percent confidence interval, 34 to 67; P<0.001).

Conclusions Our findings suggest that replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.

-------------------------------

American Journal of Clinical Nutrition, Vol. 73, No. 1, 132-133, January 2001
© 2001 American Society for Clinical Nutrition

Letters to the Editor

Reply to DL Katz
Simin Liu, JoAnn E Manson, Frank B Hu and Walter C Willett

Brigham and Women's Hospital, Harvard Medical School, Division of Preventive Medicine, 900 Commonwealth Avenue East, Boston, MA 02215, E-mail: simin.liu~channing.harvard.edu
Department of Nutrition, Harvard School of Public Health, Boston, MA 02215

Dear Sir:

We appreciate Katz's interest in our article. He suggested that because women who had coronary heart disease (CHD), angina, or overt CHD risk factors may have changed their diet to a high-carbohydrate one, the positive association between dietary glycemic load and CHD risk observed in our study may be spurious because of confounding by these high-risk conditions. This concern, although theoretically possible, was not supported by findings in the Nurses' Health Study. First, higher intake of dietary carbohydrate, total starch, or total grain was not significantly associated with higher CHD risk (1, 2); neither was intake of total fat (3). However, higher intake of trans fat (3) as well as lower intakes of polyunsaturated and monounsaturated fats (3), whole grains (1), and fruit and vegetables (4) were significantly associated with higher CHD risk. Second, nurses who had CHD, angina, or diabetes at baseline were excluded from the main analyses and higher dietary glycemic load was not associated with a less favorable CHD risk profile (Table 1 in reference 2). Third, the positive association between dietary glycemic load [i.e. carbohydrate glycemic load] and CHD [coronary heart disease] risk became even stronger after adjustment for conventional risk factors, arguing against the possibility of residual confounding.

Our findings that the types of carbohydrate as measured by the glycemic indexes are important for predicting CHD risk are consistent with an inverse relation between dietary fiber intake and CHD risk that we (5) and others (6) reported previously. Incorporating the concept of glycemic index in our assessment of the physiologic effect of carbohydrates enabled us to measure both the total amount of carbohydrate and the quality of carbohydrate intake. As shown in our article, the positive association between dietary glycemic load and CHD risk was independent of dietary fiber intake and was particularly strong in overweight women. This finding is supported by metabolic data showing that the adverse metabolic effects of high carbohydrate intake on blood HDL-cholesterol and triacylglycerol concentrations depend directly on the degree of insulin resistance, which is largely determined by excess body fat (7).

Although a prevalent nutritional recommendation has been that a low-fat, high-carbohydrate diet can prevent heart disease, few empirical data support such a recommendation (6). Results from the Nurses' Health Study add to the growing body of evidence suggesting that neither total fat nor total carbohydrate in the range typically eaten is related to CHD risk and that a more complex picture exists relating to different types of fats and carbohydrates. As in any field of scientific pursuit, new data often generate new hypotheses to be tested. Future investigations are thus needed to confirm our findings in high-quality prospective studies of different populations in whom the range and nature of carbohydrate intake and the degree of insulin resistance may be different. We do not advocate that dietary recommendations be based on epidemiologic data alone but do note that our findings are consistent with results from metabolic studies, including those cited by Katz. Additional basic and experimental studies are also warranted to achieve an understanding of how different types of carbohydrates may affect CHD risk. For example, why does a high-carbohydrate diet typically produce high plasma triacylglycerol and low HDL-cholesterol concentrations characteristic of the insulin resistance syndrome? How do different types of carbohydrates affect insulin and other hormonal responses, particularly in individuals who are already prone to insulin resistance? What other hemodynamic or inflammatory markers may also be related to such a diet?

-------------------------------

American Journal of Clinical Nutrition, Vol. 71, No. 6, 1455-1461, June 2000
© 2000 American Society for Clinical Nutrition

--------------------------------------------------------------------------------

Original Research Communications

A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women1,2,3

Simin Liu, Walter C Willett, Meir J Stampfer, Frank B Hu, Mary Franz, Laura Sampson, Charles H Hennekens and JoAnn E Manson

1 From the Departments of Epidemiology and Nutrition, the Harvard School of Public Health; the Channing Laboratory; and the Division of Preventive Medicine, the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston.

2 Supported by CA40356, the main Nurses' Health Study Grant, and Nutrition Training Grant T32DK07703 from the US National Institutes of Health.


Background: Little is known about the effects of the amount and type of carbohydrates on risk of coronary heart disease (CHD).

Objective: The objective of this study was to prospectively evaluate the relations of the amount and type of carbohydrates with risk of CHD.

Design: A cohort of 75521 women aged 38–63 y with no previous diagnosis of diabetes mellitus, myocardial infarction, angina, stroke, or other cardiovascular diseases in 1984 was followed for 10 y. Each participant's dietary glycemic load was calculated as a function of glycemic index, carbohydrate content, and frequency of intake of individual foods reported on a validated food-frequency questionnaire at baseline. All dietary variables were updated in 1986 and 1990.

Results: During 10 y of follow-up (729472 person-years), 761 cases of CHD (208 fatal and 553 nonfatal) were documented. Dietary glycemic load was directly associated with risk of CHD after adjustment for age, smoking status, total energy intake, and other coronary disease risk factors. The relative risks from the lowest to highest quintiles of glycemic load were 1.00, 1.01, 1.25, 1.51, and 1.98 (95% CI: 1.41, 2.77 for the highest quintile; P for trend < 0.0001). Carbohydrate classified by glycemic index, as opposed to its traditional classification as either simple or complex, was a better predictor of CHD risk. The association between dietary glycemic load and CHD risk was most evident among women with body weights above average [ie, body mass index (in kg/m2) 23].

Conclusion: These epidemiologic data suggest that a high dietary glycemic load from refined carbohydrates increases the risk of CHD, independent of known coronary disease risk factors.

-----------------------

More articles on results from the Nurses' Study will be posted later.
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  #2   ^
Old Sun, Jul-07-02, 20:11
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Voyajer Voyajer is offline
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American Journal of Clinical Nutrition, Vol. 73, No. 1, 130-131, January 2001
© 2001 American Society for Clinical Nutrition

--------------------------------------------------------------------------------

Letters to the Editor

Reply to BO Schneeman
Simin Liu, JoAnn E Manson, Frank B Hu and Walter C Willett
Brigham and Women's Hospital, Harvard Medical School, Division of Preventive Medicine, 900 Commonwealth Avenue East, Boston, MA 02215-1204

Dear Sir:

We appreciate Schneeman's comments regarding our article. As noted, women with high dietary glycemic loads tended to be a health-conscious group (1). However, eating large amounts of low-quality carbohydrate, as reflected by a high dietary glycemic load, appeared to increase the risk of coronary heart disease (CHD) in these women, independent of healthy choices such as smoking less and consuming more dietary fiber and vitamins.

Any carbohydrate-containing food can induce plasma glucose responses, and dietary glycemic load (the amount of carbohydrate multiplied by its glycemic index) represents the quality and quantity of carbohydrate and the interaction between the 2. The interaction implies that carbohydrate quality, represented by glycemic index, should have a greater biological effect when the amount of carbohydrate consumed is large than when the amount is small. Also, because a common standard referent food—white bread—was used to standardize all carbohydrate-containing foods, we essentially compared the relative associations of different glycemic responses from these foods with CHD risk. Because a higher intake of dietary fiber, vitamin E, or folate was each independently associated with a lower risk of CHD (2), it is important to evaluate the association with glycemic load or glycemic index with adjustment for these other dietary factors. In relation to glycemic index, the Spearman correlation coefficients were –0.20 for dietary fiber, -0.23 for dietary folate, and –0.32 for vitamin E, indicating that the overall glycemic index was inversely associated with the intakes of these micronutrients that are thought to be protective against CHD. Thus, in a multivariate model that included dietary fiber, folate, and vitamin E, the independent association between glycemic load and CHD risk was even stronger (Table 2 of our article).

Cooking methods can have some influence on glycemic index; thus, we used average values for the ways that foods are usually consumed (eg, potatoes are eaten cooked and apples are eaten raw). Meal patterns may affect the absolute glycemic response but do not affect the relative differences between foods (3–5). Metabolic studies using standardized methods indicated that the correlation between the glycemic index of mixed meals and the average glycemic indexes of individual component foods ranges from 0.84 to 0.99 (5–7). Even though the total quantity of the glycemic and insulinemic effects of foods may not be fully captured by dietary glycemic load, these measurement errors were likely to have been modest and unrelated to CHD because diets were assessed before disease occurred. Recently, in a random sample of 185 postmenopausal women in the Nurses' Health Study who provided fasting blood samples, we found a strong positive relation between dietary glycemic load assessed by a food-frequency questionnaire and fasting triacylglycerol concentrations (8), a well-established relation from metabolic studies (9).

Metabolic experiments suggested that the adverse metabolic responses to a high dietary glycemic load, including hyperinsulinemia, hypertriglyceridemia, and low HDL-cholesterol concentrations, are strongly related to an individual's underlying degree of insulin resistance (10). Thus, our observation of a stronger positive association between dietary glycemic load and CHD risk in overweight women highlights the importance of considering the physiologic effects of carbohydrate quality in the context of other metabolic variables. Judged by its abilities to predict physiologic responses as well as clinical endpoints, glycemic index appears to represent a more informative means than the conventional simple versus complex approach in classifying carbohydrates.
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  #3   ^
Old Sun, Jul-07-02, 20:21
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American Journal of Clinical Nutrition, Vol. 73, No. 6, 1019-1026, June 2001
© 2001 American Society for Clinical Nutrition

--------------------------------------------------------------------------------

Original Research Communication

Dietary fat intake and risk of type 2 diabetes in women1 ,2,3

Jorge Salmerón, Frank B Hu, JoAnn E Manson, Meir J Stampfer, Graham A Colditz, Eric B Rimm and Walter C Willett


Background: The long-term relations between specific types of dietary fat and risk of type 2 diabetes remain unclear.

Objective: Our objective was to examine the relations between dietary fat intakes and the risk of type 2 diabetes.

Design: We prospectively followed 84204 women aged 34–59 y with no diabetes, cardiovascular disease, or cancer in 1980. Detailed dietary information was assessed at baseline and updated in 1984, 1986, and 1990 by using validated questionnaires. Relative risks of type 2 diabetes were obtained from pooled logistic models adjusted for nondietary and dietary covariates.

Results: During 14 y of follow-up, 2507 incident cases of type 2 diabetes were documented. Total fat intake, compared with equivalent energy intake from carbohydrates, was not associated with risk of type 2 diabetes; for a 5% increase in total energy from fat, the relative risk (RR) was 0.98 (95% CI: 0.94, 1.02). Intakes of saturated or monounsaturated fatty acids were also not significantly associated with the risk of diabetes. However, for a 5% increase in energy from polyunsaturated fat, the RR was 0.63 (0.53, 0.76; P < 0.0001) and for a 2% increase in energy from trans fatty acids the RR was 1.39 (1.15, 1.67; P = 0.0006). We estimated that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk (RR: 0.60; 95% CI: 0.48, 0.75).

Conclusions: These data suggest that total fat and saturated and monounsaturated fatty acid intakes are not associated with risk of type 2 diabetes in women, but that trans fatty acids increase and polyunsaturated fatty acids reduce risk. Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially.
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  #4   ^
Old Mon, Jul-08-02, 09:36
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Hey Voyajer,

Thanks for posting these, plus the other articles you've posted. It's also cool that you've <b>bolded the English </b> for those times when my brain is too mushy to draw my own conclusions.
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  #5   ^
Old Tue, Jul-23-02, 08:34
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Voyajer Voyajer is offline
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My pleasure Kristine.

JAMA 1999 Apr 21;281(15):1387-94

A prospective study of egg consumption and risk of cardiovascular disease in men and women.

Hu FB, Stampfer MJ, Rimm EB, Manson JE, Ascherio A, Colditz GA, Rosner BA, Spiegelman D, Speizer FE, Sacks FM, Hennekens CH, Willett WC.

Department of Nutrition, Harvard School of Public Health, Boston, Mass 02115, USA. Frank.hu~channing.harvard.edu

CONTEXT: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. OBJECTIVE: To examine the association between egg consumption and risk of CHD and stroke in men and women. DESIGN AND SETTING: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). PARTICIPANTS: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. RESULTS: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]). CONCLUSIONS: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.

-------------

Note: This study showed that those who ate one egg or more per day were not any different than those who ate less than one egg per week , but the researchers have to make sure they keep the cholesterol myth going so they say in conclusion only to have up to one egg per day when their own data just showed that eating more doesn't matter!
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  #6   ^
Old Tue, Jul-23-02, 08:44
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Voyajer Voyajer is offline
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Default Eat your eggs and Eat your nuts

People avoid nuts because they are high in fat. UGH!!

BMJ 1998 Nov 14;317(7169):1341-5

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study.

Hu FB, Stampfer MJ, Manson JE, Rimm EB, Colditz GA, Rosner BA, Speizer FE, Hennekens CH, Willett WC.

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. Frank.Hu~channing.harvard.edu

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.
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Old Tue, Jul-23-02, 09:03
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Voyajer Voyajer is offline
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Am J Clin Nutr 1999 Aug;70(2):221-7

Dietary protein and risk of ischemic heart disease in women.

Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Speizer FE, Hennekens CH, Willett WC.

Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA. frank.hu~channing.harvard.edu

BACKGROUND: Ingestion of animal protein raises serum cholesterol in some experimental models but not in others, and ecologic studies have suggested a positive association between animal protein intake and risk of ischemic heart disease. Prospective data on the relation of protein intake to risk of ischemic heart disease are sparse. OBJECTIVE: The objective was to examine the relation between protein intake and risk of ischemic heart disease. DESIGN: The study was a prospective cohort study. RESULTS: We examined the association between dietary protein intake and incidence of ischemic heart disease in a cohort of 80082 women aged 34-59 y and without a previous diagnosis of ischemic heart disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Intakes of protein and other nutrients were assessed with validated dietary questionnaires. We documented 939 major instances of ischemic heart disease during 14 y of follow-up. After age, smoking, total energy intake, percentages of energy from specific types of fat, and other ischemic heart disease risk factors were controlled for, high protein intakes were associated with a low risk of ischemic heart disease; when extreme quintiles of total protein intake were compared, the relative risk was 0.74 (95% CI: 0.59, 0.94). Both animal and vegetable proteins contributed to the lower risk. This inverse association was similar in women with low- or high-fat diets. CONCLUSIONS: Our data do not support the hypothesis that a high protein intake increases the risk of ischemic heart disease. In contrast, our findings suggest that replacing carbohydrates with protein may be associated with a lower risk of ischemic heart disease. Because a high dietary protein intake is often accompanied by increases in saturated fat and cholesterol intakes, application of these findings to public dietary advice should be cautious.
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  #8   ^
Old Tue, Jul-23-02, 10:08
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Default Someone had a problem with Willet recommending protein. Willet replies:

American Journal of Clinical Nutrition, Vol. 71, No. 3, 850-851, March 2000
© 2000 American Society for Clinical Nutrition

--------------------------------------------------------------------------------

Letters to the Editor

Reply to TC Campbell
Frank B Hu and Walter Willett
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, E-mail: frank.hu~channing.harvard.edu

Dear Sir:

Although dietary protein has been the focus of controversy regarding several popular diets, scientific data on the effects of protein intake on the development of chronic disease are limited. International studies suggest a positive correlation between animal protein intake and ischemic heart disease rates across countries (1). Therefore, we tested this hypothesis directly in the Nurses' Health Study (2). By analyzing repeated measures of dietary data over 14 y of follow-up, we firmly rejected the hypothesis that high protein intakes increase the risk of ischemic heart disease. In contrast, our data suggest a modest inverse association for both animal and vegetable protein intake. This finding is compatible with results of metabolic studies indicating improved blood lipid profiles when protein replaces carbohydrates (3). In the conclusion, we cautioned the application of these findings to public dietary advice because a high dietary protein intake is often accompanied by high saturated fat and cholesterol intakes.

Campbell questioned the validity of our findings because they contradict the results of international correlation studies on animal product consumption and disease rates. However, international correlations such as those cited by Campbell are intractably confounded by other dietary and lifestyle factors associated with economic affluence in different countries; differences in physical activity, body fat, and smoking are particularly important. Also, the food disappearance data used in most of the calculations may be more indicative of food wastage within a country than actual consumption. Correlational studies conducted within a country can usually provide more credible data than international comparisons because of relatively homogeneous populations and the possibility of collecting data on potential confounding variables at individual levels. A survey of 65 counties in rural China, however, did not find a clear association between animal product consumption and risk of heart disease or major cancers (4).

Prospective cohort studies of individuals, in which diet is assessed before the occurrence of disease, are typically considered to be the strongest nonrandomized design because it is possible to control for other known risk factors. One common misperception is that the dietary experience of a single population in a typical prospective cohort study is too homogeneous to detect associations with disease risk. In the Nurses' Health Study, however, we identified several important dietary factors for risk of ischemic heart disease, including trans fatty acids (5), the ratio of polyunsaturated to saturated fat (5), -linolenic acid (6), cereal fiber (7), nuts (8), whole-grain products (9), and fruit and vegetables (Kumudi unpublished observations, 2000).

Because high protein intakes are associated with other dietary variables and lifestyle factors, we conducted careful statistical analyses to adjust for these variables. However, the multivariate relative risks were similar to the age-adjusted ones, suggesting that confounding by other dietary variables and lifestyle factors was likely to be minor. Also, in stratified analyses according to levels of smoking and exercise and intakes of dietary fat and fiber, the modest inverse association with dietary protein persisted. Campbell suggests that the independent effects of various nutrients cannot be teased out because of their high correlations. This assertion is not substantiated by our analyses showing opposite associations with risk of coronary heart disease for different types of dietary fat that are intercorrelated (5). The large sample size, the long follow-up, and the multiple dietary measurements made in the Nurses' Health Study provide high power to examine independent effects of many individual nutrients. Although we agree that overall dietary patterns are also important in determining disease risk (10), we believe that identification of associations with individual nutrients should be the first step because it is the specific compounds or groups of compounds that are fundamentally related to the pathophysiology of the disease. Specific components of diet can be modified, and individuals and the food industry are actively doing so. Understanding the health effects of specific dietary changes, which Campbell refers to as "reductionism," is therefore an important undertaking.

REFERENCES


Connor WE, Cerqueira MT, Connor RW, Wallace RB, Malinow MR, Casdorph HR. The plasma lipids, lipoproteins, and diet of the Tarahumara Indians of Mexico. Am J Clin Nutr 1978;31:1131–42.[Medline]
Hu FB, Stampfer MJ, Manson JE, et al. Dietary protein and risk of ischemic heart disease in women. Am J Clin Nutr 1999;70:221–7.[Abstract/Full Text]
Wolfe BM. Potential role of raising dietary protein intake for reducing risk of atherosclerosis. Can J Cardiol 1995;11(suppl):127G–31G.[Medline]
Chen J, Campbell TC, Tunyao L, et al. Diet, lifestyle and mortality in China: a study of the characteristics of 65 Chinese counties. Oxford, United Kingdom: Oxford University Press, 1990.
Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and risk of coronary heart disease in women. N Engl J Med 1997;337:1491–9.[Abstract/Full Text]
Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of -linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 1999;69:890–7.[Abstract/Full Text]
Wolk AM, Manson JE, Stampfer MJ, et al. Long-term intake of dietary fiber and decreased risk of coronary heart disease among women. JAMA 1999;281:1998–2004.[Medline]
Hu FB, Stampfer MJ, Manson JE, et al. Frequent nut consumption and risk of coronary heart disease: prospective cohort study. BMJ 1998;317:1341–5.[Abstract/Full Text]
Liu S, Stampfer MJ, Hu FB, et al. Whole-grain consumption and risk of coronary heart disease: results from the Nurses' Health Study. Am J Clin Nutr 1999;70:412–9.[Abstract/Full Text]
Hu FB, Rimm E, Smith-Warner SA, et al. Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. Am J Clin Nutr 1999;69:243–9.[Abstract/Full Text]
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