Olestra affects serum concentrations of alpha-tocopherol and carotenoids but not vitamin D or vitamin K status in free-living subjects.

Normal, healthy, free-living adults ingested either 18 g/d olestra, with or without 1.1 mg tocopheryl acetate/g olestra, or 18 g/d triglyceride placebo, for 16 wk in a double-blind, placebo-controlled study. Serum concentrations of alpha-tocopherol, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, retinol and cholesterol were measured biweekly. Serum 25-hydroxyvitamin D concentration, prothrombin time, partial thromboplastin time and plasma concentration of functional prothrombin (Simplastin-Ecarin assay) were measured at wk 0, 8 and 16. Relative to the placebo group, serum alpha-tocopherol concentration was reduced 6% for the group given 18 g/d olestra. Addition of tocopheryl acetate to olestra partially offset the effect of olestra. For the group given 18 g/d olestra plus 1.1 mg tocopheryl acetate/g olestra, serum alpha-tocopherol concentration was 4% less than the placebo value. Olestra reduced serum concentration of beta-carotene by 27%; the other carotenoids were similarly affected. Serum cholesterol concentration was reduced approximately 4.5% in the olestra groups, relative to placebo, but the differences were not significant. Serum triglycerides, serum 25-hydroxyvitamin D, prothrombin time, partial thromboplastin time or the plasma concentration of under-gamma-carboxylated prothrombin were unaffected by olestra. Clinical observations and laboratory measures indicated no health-related effects of olestra; mild-to-moderate transient gastrointestinal symptoms such as bloating, cramping, loose stools and diarrhea were reported by all groups.

Effect of dietary fat on length of the follicular phase of the menstrual cycle in a controlled diet setting.

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.

Serum 25-hydroxyvitamin D concentrations of free-living subjects consuming olestra.

The effect of olestra on vitamin D status was assessed in a 6-wk, double-blind, placebo-controlled study involving 202 free-living adults. Subjects consumed a total of 20 g/d of olestra or triglycerides in cookies eaten at each meal. A 20-micrograms ergocalciferol capsule was taken with each morning meal. Serum 25-hydroxyergocalciferol (25-OHD2) concentrations rose from approximately 5.7 to 39.0 and 31.7 nmol/L in the placebo and olestra groups, respectively, at week 6. At week 6, 25-OHD2 contributed 46-54% to total serum 25-OHD concentration compared with 11% at baseline. The 19% decrease in serum 25-OHD2 concentrations produced by olestra in this study is equivalent to a decrease of approximately 1.2 nmol/L under nonsupplemented dietary conditions. Ingesting 20 g olestra/d in the diet is thus not expected to affect vitamin D nutritional status.

Vitamin K status of free-living subjects consuming olestra.

The potential for 20 g olestra/d to affect vitamin K status was assessed in a 6-wk study involving 202 free-living subjects. Functional prothrombin [Simplastin (S)-Ecarin (E) assay] concentrations and classical clotting times were unaffected by olestra. Initial S:E values were 0.80 and 0.79 for the olestra and placebo groups, respectively, compared with a value of 0.92 for normal reference plasma. At week 6 the value was 0.81 for both groups. Mean phylloquinone serum concentrations, expressed as differences from baseline, were not significantly different between groups. Weekly food diaries indicated that the average phylloquinone intake of the subjects was low, approximately 60 micrograms/d. Sensitive measures of vitamin K status were unaffected in a population where any significant decrease in phylloquinone bioavailability should have been reflected in those measures, indicating that 20 g olestra/d in the diet did not affect vitamin K status.

Dietary fat and hormonal influences on lipoprotein fluidity and composition in premenopausal women.

LDL and HDL became more fluid when health, free-living, premenopausal women were fed reduced fat diets with higher proportions of polyunsaturated fatty acids. Lipoproteins were isolated from plasma of 31 female subjects fed one of two sets of diets from typical U.S.A. foods with P/S ratios of 0.3 or 1.0. All subjects were fed high-fat diets (40% of energy) for the duration of four menstrual cycles followed by low-fat diets (20% of energy) for the next four cycles. Blood samples were collected during mid-follicular and mid-luteal phases of the fourth menstrual cycle of each diet period to assess interactive dietary and hormonal control of lipoprotein fluidity. LDL was significantly more fluid, as determined by DPH fluorescence, upon reducing fat consumption from 40 to 20% of energy for subjects eating foods with P/S = 1.0 or 0.3. Generally LDL was more fluid during the follicular phase than the luteal phase of the cycles, thus indicating hormonal influences on LDL fluidity. HDL results were similar but not as pronounced as with LDL. Lipoprotein phospholipid (PL) and cholesteryl ester (CE) fatty acyl compositions were also subject to dietary and hormonal influences. Effects were noted in several fatty acids depending upon diet and hormonal state; however, generally diet fat reduction resulted in reduced linoleate and increased oleate contents. Regression analyses showed that fluidity was more dependent upon the lipoprotein cholesterol content than upon fatty acyl composition.

Influence of dietary fat on fecal mutagenicity in premenopausal women.

A dietary intervention study was conducted on 31 premenopausal women (age: 20-40 years) to investigate the relationship between dietary fat and fecal mutagenicity. After a free-living period (baseline) of one menstrual cycle, the subjects were placed on a high-fat diet (40% calories from fat) for 4 menstrual cycles, followed by a low-fat diet (20% calories from fat) for 4 menstrual cycles. One-half of the subjects were randomly assigned throughout the study to a diet with a P:S ratio of 1.0 while the other half was assigned to one with a P:S ratio of 0.3; body weight by group remained constant. Three-day stool samples were collected at the mid-follicular period during the free-living phase and during the 4th menstrual cycle of each of the 2 controlled diet periods. Mutagenicity was assayed by the SOS chromotest. Reduction of dietary fat was accompanied by a significant decrease in fecal mutagenicity in both P:S groups. Combined values, i.e., both P:S groups, were 20.3 units for high-fat diets vs. 8.78 for low-fat diets.

Dietary fat and menstrual-cycle effects on the erythrocyte ghost insulin receptor in premenopausal women.

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on insulin receptors of erythrocyte ghosts was studied during different phases of the menstrual cycle in 31 healthy premenopausal women. Subjects were divided into two groups and consumed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.30 or 1.00 for four menstrual cycles. They were switched to 19% fat at the same P:S for another four cycles. Fasting blood samples were collected during the follicular and luteal phases. Insulin receptors were measured from right-side-out ghosts. Insulin binding was significantly lower due to fewer receptors when subjects were fed the low-fat, high-carbohydrate diet compared with the high-fat, low-carbohydrate diet. There was no significant effect of level of unsaturation or time of menstrual cycle on insulin binding. Thus, insulin receptors on erythrocytes respond to dietary lipids.

Dietary fat and hormonal effects on erythrocyte membrane fluidity and lipid composition in adult women.

Erythrocyte ghost membrane fluidity and phospholipid linoleate were significantly increased when higher levels of polyunsaturated fats were fed to healthy, free living, premenopausal women. Fluidity was assessed by diphenylhexatriene (DPH) fluorescence polarization measurements with hypotonically lysed red blood cells from 31 female subjects fed one of two sets of diets, which were formulated from typical US foods to contain polyunsaturate to saturate ratios (P/S) of 1.0 or 0.3. Both groups of women were fed diets with 40% of energy as fat for four menstrual cycles followed by low-fat diets having 20% of energy as fat for the next four menstrual cycles. Blood was sampled during the fourth cycle of each dietary period at times estimated to correspond to maximum secretions of estrogen and progesterone to assess interactive hormonal and dietary effects on membrane composition and fluidity. Red blood cell membranes were most fluid following higher levels of linoleate intake, either by higher (40%) total fat or higher P/S levels. Membrane fluidity was directly related to the phospholipid oleate and linoleate contents and inversely related to the molar cholesterol/phospholipid ratio. Hormonal status effects on the membranes were not extensive. Membrane fluidity in cells from women fed P/S = 0.3 diets was higher at 40% than at 20% fat during the luteal phase of the fourth cycle. In contrast, women fed the P/S = 1.0 diets had more fluid red cells at 40% fat during the follicular phase of the cycle. Regression analysis showed a direct linear correlation between membrane fluidity and red cell membrane insulin binding demonstrating a relation between receptor binding and cell membrane fluidity in the human female.

A prospective study of reproductive, familial and socioeconomic risk factors for breast cancer using NHANES I data.

Risk factors for breast cancer in a cohort of women who participated in the first National Health and Nutrition Examination Survey (NHANES) and its followup epidemiologic survey were examined. The analytic cohort consisted of 122 breast cancer cases and 7,304 noncases, with a median followup time of 10 years. We found no appreciable increase in risk among women who reported their onset of menarche as occurring before the age of 13 compared with those reporting onset at ages 13 and older. Breast cancer risk was progressively elevated with increasing age at first live birth (test for trend, P less than 0.007). The number of children born to a woman did not influence risk, but the data suggested an increased risk for nulliparous women. A family history of breast cancer in a first-degree relative was the strongest predictor of risk for this cohort of women, with relative risks of 2.2 and 2.4 associated with a mother or sister affected with breast cancer, compared with women having no family history. The age of natural menopause had little influence on breast cancer risk, and the data suggested a slight protective effect of early surgical menopause. Higher education (compared with less than a high school education) was associated with an increased risk in this cohort of women (relative risk (RR) = 2.1; 95 percent confidence interval (CI) = 0.9-5.1). These results (a) confirm the importance of some well-recognized risk factors for breast cancer in a cohort of women, followed prospectively for 10 years, and perhaps more importantly, (b) uniquely provide risk estimates on a probability sample of women in the United States.

Body iron stores and the risk of cancer.

Because of evidence that increased body iron stores are associated with an increased risk of cancer, we examined iron status and cancer risk in the first National Health and Nutrition Examination Survey, a survey of more than 14,000 adults begun in 1971, with follow-up between 1981 and 1984. Among 242 men in whom cancer developed, the mean total iron-binding capacity was significantly lower (61.4 vs. 62.9 mumol per liter; P = 0.01) and transferrin saturation was significantly higher (33.1 vs. 30.7 percent; P = 0.002) than among 3113 men who remained free of cancer. The risk of cancer in men in each quartile of transferrin-saturation level relative to the lowest quartile was 1.00, 1.01, 1.10, and 1.37 (P = 0.02 for trend). The serum albumin level was significantly lower in men in whom cancer developed than in those who remained cancer-free. Among women, those in whom cancer developed did not have significantly lower total iron-binding capacity or higher transferrin saturation than those who remained cancer-free. However, a post hoc examination of 5367 women (203 with cancer) yielded a relative risk of 1.3 (95 percent confidence interval, 0.9 to 1.9) associated with a very high transferrin saturation (greater than or equal to 36.8 percent, a value in the highest quartile among men); in 5228 women with at least six years of follow-up (149 with cancer), the relative risk associated with transferrin saturation above this level was 1.5 (1.0 to 2.2). These results are consistent with the hypothesis that high body iron stores increase the risk of cancer in men. The possibility that a similar association exists in women requires further study.

Relation of changes in amount and type of dietary fat to fecapentaenes in premenopausal women.

Correlation studies suggest that fecal mutagenicity is increased in groups eating high-fat diets, the same groups who are often found to have high colorectal cancer incidence and mortality. The fecapentaenes are the best characterized class of fecal mutagens, but the relationship of dietary fat intake to the excretion of these potent genotoxins is unknown. We studied the effect of changes in amount and type of dietary fat on fecapentaene levels in 31 premenopausal women 20-40 years of age who participated in a controlled feeding study. After a pre-diet free-living period lasting 1 menstrual cycle, women were placed on a high-fat (40% energy from fat) diet for 4 menstrual cycles and then switched to a low-fat (20% energy from fat) diet for an additional 4 menstrual cycles. One-half the subjects were maintained throughout the study at a ratio of polyunsaturated-to-saturated fatty acids (P/S ratio) of 1.0, the other half at 0.3; body weight was constant. All meals during the controlled diet periods were prepared at the Human Study Facility of the Beltsville Human Nutrition Research Center. Fecapentaene and fecapentaene precursor levels were measured in acetone extracts from 3-day pooled stool samples collected during the study. No differences in fecapentaene or precursor levels were observed between the high- and low-fat diets at either P/S ratio. Fecapentaene and precursor levels were higher while on controlled diets than during the pre-diet free-living period, and levels declined again in the post-diet free-living period. We conclude that dietary fat has no significant effect on fecapentaene or precursor levels in acetone extracts of stool in premenopausal women. The effect of other dietary or non-dietary factors on fecapentaenes remains unknown.

Breast cancer risk assessed by anthropometry in the NHANES I epidemiological follow-up study.

We examined the relation of anthropometric variables and breast cancer risk in the Epidemiological Follow-up Study of the first National Health and Nutrition Examination Survey, a cohort study based on a sample of the United States population. A total of 7149 women, 25 to 74 years of age, who were examined during the period 1971 through 1975 were included in the analysis. Stature, sitting height, elbow width, weight, and subscapular and triceps skinfold measurements were collected during the baseline interview and examination. Breast cancer cases (N = 121) were identified through hospital records or death certificates. The median follow-up period for this cohort was 10 years. Women who developed breast cancer were taller and had greater frame size (elbow width) than women who remained free of breast cancer during the follow-up period. After controlling for the effect of potential confounders, the relative risk of breast cancer was 1.9 (95% confidence interval, 1.1 to 3.1) and 2.2 (95% confidence interval, 1.3 to 3.8) among women in the fourth quartiles of stature and elbow width, respectively. Body size defined by weight, relative weight, or skinfold measurements was not associated with increased risk of breast cancer. The positive association of stature and frame size to risk of breast cancer suggests a potential role of early nutrition in cancer etiology.

Adult stature and risk of cancer.

We examined the relationship between adult stature and cancer incidence using data from the first U.S. National Health and Nutrition Examination Survey and its follow-up study. Among 12,554 participants 25-74 years old, 460 cancers occurred in men and 399 in women after an average follow-up period of approximately 10 years. The age-adjusted relative risk of cancer for the second (Q2) through fourth (Q4) quartiles of stature compared to the first quartile among men were significantly increased: 1.5, 1.4, and 1.4. After adjustment for race, cigarette smoking, income, and body mass index, the all-sites cancer relative risk increased slightly to 1.6, 1.5, and 1.6. For most cancer sites in men, and particularly colorectal cancer (relative risk = 2.1 for Q4), the lowest incidence was observed among those in the shortest quartile of stature. A weaker, positive association was evident among women, restricted primarily to cancer of the breast and colorectum (relative risk in Q4 = 2.1 and 1.6 for the two cancers, respectively). These findings indicate that short stature is associated with reduced risk of cancer, particularly in men, and suggest a role for nutrition early in life in human carcinogenesis.

Cheek cell fatty acids as indicators of dietary lipids in humans.

Analysis of cheek cell lipids has been suggested as a noninvasive method for monitoring the fatty acid composition of diets in humans. In a pilot study conducted to determine the validity of the method, cheek cell samples were collected from subjects consuming a low fat (20% of calories) diet consisting of fatty acids with either a 1.0 or 0.3 P/S ratio. Neither total lipid nor polar lipid fatty acids in cheek cells consistently reflected the P/S ratio of the diets. However, there were trends, particularly in the nonpolar lipids, suggesting that cheek cell fatty acid ratios might be useful for monitoring the fatty acid composition of the diets. The diet with the higher P/S ratio (1.0 vs 0.3) consistently resulted in cheek cell lipids with lower ratios of 18:1/saturated fatty acids and greater 18:2/20:4, 18:2/18:1 and 18:2/18:0 fatty acid ratios.

Menstrual cycle effect on plasma lipids.

In a study of 31 healthy women in which dietary intake and body weight were controlled, a significantly higher mean plasma cholesterol was observed in the follicular phase of the menstrual cycle compared to the luteal phase (mean difference of 8.4% during controlled dietary periods). Higher mean plasma triglycerides (mean difference of 7.4%) and lower HDL-cholesterol (mean difference of 5.8%) were also observed in the follicular phase of the controlled dietary study, although these differences were not consistently significant.

Dietary fiber intake in the US population.

Twenty-four hour recall data from adults interviewed in the Second National Health and Nutrition Examination Survey, NHANES II, were used as the basis to estimate total dietary fiber intake in the United States. Food fiber values were calculated for the 2500 foods in NHANES II in two ways: 1) using fiber values compiled from the literature by NCI and 2) values based on the Southgate methodology. Mean dietary fiber intake in the US adult population (greater than 19 y of age) is 11.1 g/d using the first set of values and 13.3 g/d according to Southgate values. On a per 1000 kcal basis, women consume more dietary fiber (6.5 g/1000 kcal) than men (5.5 g/1000 kcal) at every age. Fiber intake by geographic region, age, race, and sex is discussed. Our study indicates that dietary fiber intake in the United States is considerably lower than that previously reported.

Influence of dietary fat on menstrual cycle and menses length.

Menstrual cycle and menses lengths were determined in 31 healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40 per cent energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20 per cent energy from fat). There was a significant increase of 1.3 d (P = 0.02) in the average menstrual cycle length and 0.5 d (P = 0.01) in menses length on the low fat diet. Although no significant differences were evident between the P/S groups, the effect of low fat on menstrual cycle and menses length was most pronounced in the P/S = 1.0 group.

Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

The relationship between dietary fat intake and breast cancer incidence was examined in the National Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is derived from adults (greater than or equal to 25 yr) examined in the NHANES I (1970-75) cross-sectional survey of the U.S. population and provides a mean follow-up time of 10 years. An analytic sample of 5,485 women, including 99 breast cancer cases (34 premenopausal and 65 postmenopausal at NHANES I baseline), was examined for associations with dietary intake of fat, percent energy from fat, total energy, saturated fat, polyunsaturated fat, monounsaturated fat, and cholesterol on the basis of a 24-hour recall administered at the baseline NHANES I examination. No significant differences in dietary fat intake between cases and noncases were evident when mean intakes for each group were compared. For total fat (g) and saturated fat (g), a significant inverse association was indicated in proportional hazards analyses. Adjustment of fat for total energy intake resulted in a smaller effect that was no longer statistically significant. Adjustment for accepted breast cancer risk factors did not change these findings. This prospective study of a sample from the U.S. population does not support the hypothesis that high dietary fat intake increases breast cancer risk. Indeed, some lower risk associated with high fat intake may be indicated, although this result may be influenced by methodologic problems with the dietary assessment.

Influence of caloric contribution and saturation of dietary fat on plasma lipids in premenopausal women.

Total cholesterol, HDL cholesterol, and triglycerides were measured in 31 premenopausal women randomized into one of two diet groups: one diet with a P:S ratio of 1.0 and one diet with a P:S ratio of 0.3. Both groups were fed a high-fat diet (40% of energy from fat) for four menstrual cycles per subject followed by a similar interval on a low-fat diet (20% of energy from fat). Changing from the high-fat to the low-fat diet resulted in a nonsignificant mean decrease of 7% in total cholesterol. HDL-cholesterol response to the low-fat regimen was influenced by the P:S ratio. Women in the high P:S group showed no change; mean HDL cholesterol in women in the low P:S group decreased 12%. Plasma triglycerides increased in both groups on the low-fat diet although the increase was greatest in the low P:S group.

Alcohol consumption and breast cancer in the epidemiologic follow-up study of the first National Health and Nutrition Examination Survey.

We investigated the relation between alcohol consumption and breast cancer in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey, a cohort study based on sample of the U.S. population. A total of 7188 women 25 to 74 years of age who were examined during the period 1971 through 1975 were included in the analysis. Information about alcohol consumption was obtained during the base-line interview. The median follow-up period for this cohort was 10 years. One hundred twenty-one cases of breast cancer that developed after the baseline examination were identified through hospital records or death certificates. The relative-risk estimate for any amount of drinking relative to no drinking was 1.5 (95 percent confidence interval, 1.1 to 2.2). The estimates for three levels of consumption, from the lowest to the highest, were 1.4 (confidence interval, 0.9 to 2.3), 1.5 (0.9 to 2.6), and 1.6 (1.0 to 2.7), in comparison to no drinking at all. These relative-risk estimates were not materially affected by adjustment for known risk factors for breast cancer or for several dietary factors. The results of this study, consistent with those of two other cohort studies and a number of case-control studies, suggest that moderate alcohol consumption is associated with an elevation in the risk of breast cancer of 50 to 100 percent.