Nutrition as therapy

Role of nutrition in the prevention of disease

  1. Diet and Cancer Prevention: the Fiber First Diet

  2. Calcium and Vitamin D: Their Potential Roles in Colon and Breast Cancer Prevention

  3. Fish Consumption and Cancer Risk

  4. Folate and Cancer Prevention: A New Medical Application of Folate Beyond Hyperhomocysteinemia and Neural Tube Defects

  5. Vegan Proteins May Reduce Risk of Cancer, Obesity, and Cardiovascular Disease by Promoting Increased Glucagon Activity

  6. Influence of Drinking Green Tea on Breast Cancer Malignancy Among Japanese Patients

  7. Legumes and Soybeans: Overview of their Nutritional Profiles and Health Effects

  8. Diet High in Whole and Unrefined Foods Favorably Alters Lipids, Antioxidant Defenses, and Colon Function

  9. Nutrition and Blood Pressure

  10. Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke

  11. Cardiovascular and Renal Benefits of Dry Bean and Soybean Intake

  12. Long-Term Intake of Dietary Fiber and Decreased Risk of Coronary Heart Disease Among Women

  13. Whole-Grain Consumption and Risk of Coronary Heart Disease: Results from the Nurses' Health Study

  14. Pecans Lower Low-Density Lipoprotein Cholesterol in People with Normal Lipid Levels

  15. Nut Consumption, Vegetarian Diets, Ischemic Heart Disease Risk, and All-Cause Mortality: Evidence from Epidemiologic Studies

  16. Frequent Nut Consumption and Risk of Coronary Heart Disease in Women: Prospective Cohort Study

  17. Are Olive Oil Diets Antithrombotic? Diets Enriched with Olive, Rapeseed, or Sunflower Oil Affect Postprandial Factor VII Differently

  18. "The SU.VI.MAX Study": A Primary Prevention Trial Using Nutritional Doses of Antioxidant Vitamins and Minerals in Cardiovascular Diseases and Cancers. SUpplementation en VItamines et Mineraux Antioxidants

  19. Nutritional Strategies in Cardiovascular Disease Control: An Update on Vitamins and Conditionally Essential Nutrients

  20. Serum Vitamins, Carotenoids, and Angina Pectoris: Findings from The National Health and Nutrition Examination Survey III

  21. Dietary Flavonoids as Antioxidants in Vivo: Conjugated Metabolites of (-)-Epicatechin and Quercetin Participate in Antioxidative Defense in Blood Plasma

  22. Toward a New Recommended Dietary Allowance for Vitamin C Based on Antioxidant and Health Effects in Humans

  23. Alzheimer Disease: Protective Factors

  24. Dietary Factors in Relation to Rheumatoid Arthritis: A Role for Olive Oil and Cooked Vegetables?

  25. The Influence of Chronic Yogurt Consumption on Immunity

  26. Tea and Health

  27. Serum Alpha-Tocopherol Status in the United States Population: Findings from the Third National Health and Nutrition Examination Survey.


Diet and Cancer Prevention: the Fiber First Diet

Williams GM, Williams CL, Weisburger JH.
Toxicol Sci. 1999 Dec;52(2 Suppl):72-86.

Diet can play a major role in cancer prevention. The international differences in cancer incidence are largely accounted for by lifestyle practices that include nutrition, exercise, and alcohol and tobacco use. About 50% of cancer incidence and 35% of cancer mortality in the U.S., represented by cancers of the breast, prostate, pancreas, ovary, endometrium, and colon, are associated with Western dietary habits. Cancer of the stomach, currently a major disease in the Far East, relates to distinct, specific nutritional elements such as excessive salt intake. For these cancers, information is available on possible initiating genotoxic factors, promoting elements, and prophylactic agents. In general, the typical diet in the United States contains low levels of the potent carcinogenic agents, heterocyclic amines, formed during the cooking of meats. It provides only about half the potent appropriate fiber intake and is high in calories. About twice as many calories as would be desirable come from fat, certain kinds of which enhance the development of cancers. Other foods with functional properties, such as soy products and tea, can be beneficial. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25-35 g per day for adults. One approach to achieving these goals is the Fiber First Diet, a diet designed around adequate fiber intake from grains, especially cereals, vegetables, legumes, and fruits, which thereby reduces both calorie and fat intake. Such dietary improvements will not only reduce cancer and other chronic disease risks, but will contribute to a healthy life to an advanced age. A corollary benefit is a lower cost of medical care.


Calcium and Vitamin D: Their Potential Roles in Colon and Breast Cancer Prevention

Garland CF, Garland FC, Gorham ED.
Ann N Y Acad Sci. 1999;889:107-119.

The geographic distribution of colon cancer is similar to the historical geographic distribution of rickets. The highest death rates from colon cancer occur in areas that had high prevalence rates of rickets--regions with winter ultraviolet radiation deficiency, generally due to a combination of high or moderately high latitude, high-sulfur content air pollution (acid haze), higher than average stratospheric ozone thickness, and persistently thick winter cloud cover. The geographic distribution of colon cancer mortality rates reveals significantly low death rates at low latitudes in the United States and significantly high rates in the industrialized Northeast. The Northeast has a combination of latitude, climate, and air pollution that prevents any synthesis of vitamin D during a five-month vitamin D winter. Breast cancer death rates in white women also rise with distance from the equator and are highest in areas with long vitamin D winters. Colon cancer incidence rates also have been shown to be inversely proportional to intake of calcium. These findings, which are consistent with laboratory results, indicate that most cases of colon cancer may be prevented with regular intake of calcium in the range of 1,800 mg per day, in a dietary context that includes 800 IU per day (20 micrograms) of vitamin D3. (In women, an intake of approximately 1,000 mg of calcium per 1,000 kcal of energy with 800 IU of vitamin D would be sufficient.) In observational studies, the source of approximately 90% of the calcium intake was vitamin D-fortified milk. Vitamin D may also be obtained from fatty fish. In addition to reduction of incidence and mortality rates from colon cancer, epidemiological data suggest that intake of 800 IU/day of vitamin D may be associated with enhanced survival rates among breast cancer cases. 


Fish Consumption and Cancer Risk

Fernandez E, Chatenoud L, La Vecchia C, Negri E, Franceschi S.
Am J Clin Nutr. 1999 Jul;70(1):85-90.

Background: Although several studies have investigated the relation between fish consumption and the risk of cardiovascular diseases, less attention has been paid to the relation between fish consumption and cancer risk.
Objective: The relation between frequency of consumption of fish and risk of selected neoplasms was analyzed by using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996.
Design: The overall data set included the following incident, histologically confirmed neoplasms: oral cavity and pharynx (n = 181), esophagus (n = 316), stomach (n = 745), colon (n = 828), rectum (n = 498), liver (n = 428), gallbladder (n = 60), pancreas (n = 362), larynx (n = 242), breast (n = 3412), endometrium (n = 750), ovary (n = 971), prostate (n = 127), bladder (n = 431), kidney (n = 190), thyroid (n = 208), Hodgkin disease (n = 80), non-Hodgkin lymphomas (n = 200), and multiple myelomas (n = 120). Control subjects were 7990 patients admitted for acute, nonneoplastic conditions unrelated to long-term modifications of diet. Odds ratios (ORs) were computed for subsequent levels of fish consumption compared with no or occasional consumption (<1 serving/wk) by using multiple logistic regression, including terms for several covariates.
Results: There was a consistent pattern of protection against the risk of digestive tract cancers with fish consumption: oral cavity and pharynx, OR = 0.5 for the highest compared with the lowest level of consumption; esophagus, OR = 0.6; stomach, OR = 0.7; colon, OR = 0.6; rectum, OR = 0.5; and pancreas, OR = 0.7. There were inverse trends in risk of larynx (OR = 0.7), endometrial (OR = 0.8), and ovarian (OR = 0.7) cancers and multiple myeloma (OR = 0.5). No pattern of cancer risk in relation to fish consumption was observed for cancers of the liver, gallbladder, breast, bladder, kidney, or thyroid or for lymphomas.
Conclusion: This study suggests that the consumption of even relatively small amounts of fish is a favorable indicator of the risk of several cancers, especially of the digestive tract.


Folate and Cancer Prevention: A New Medical Application of Folate Beyond Hyperhomocysteinemia and Neural Tube Defects

Kim YI.
Nutr Rev. 1999 Oct;57(10):314-321.

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.


Vegan Proteins May Reduce Risk of Cancer, Obesity, and Cardiovascular Disease by Promoting Increased Glucagon Activity

McCarty MF.
Med Hypotheses. 1999 Dec;53(6):459-485.

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.


Influence of Drinking Green Tea on Breast Cancer Malignancy Among Japanese Patients

Nakachi K, Suemasu K, Suga K, Takeo T, Imai K
Jpn J Cancer Res. 1998 Mar;89(3):254-261.

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow-up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.


Legumes and Soybeans: Overview of their Nutritional Profiles and Health Effects

Messina MJ.
Am J Clin Nutr. 1999 Sep;70(3 Suppl):439S-450S.

Legumes play an important role in the traditional diets of many regions throughout the world. In contrast in Western countries beans tend to play only a minor dietary role despite the fact that they are low in fat and are excellent sources of protein, dietary fiber, and a variety of micronutrients and phytochemicals. Soybeans are unique among the legumes because they are a concentrated source of isoflavones. Isoflavones have weak estrogenic properties and the isoflavone genistein influences signal transduction. Soyfoods and isoflavones have received considerable attention for their potential role in preventing and treating cancer and osteoporosis. The low breast cancer mortality rates in Asian countries and the putative antiestrogenic effects of isoflavones have fueled speculation that soyfood intake reduces breast cancer risk. The available epidemiologic data are limited and only weakly supportive of this hypothesis, however, particularly for postmenopausal breast cancer. The data suggesting that soy or isoflavones may reduce the risk of prostate cancer are more encouraging. The weak estrogenic effects of isoflavones and the similarity in chemical structure between soybean isoflavones and the synthetic isoflavone ipriflavone, which was shown to increase bone mineral density in postmenopausal women, suggest that soy or isoflavones may reduce the risk of osteoporosis. Rodent studies tend to support this hypothesis, as do the limited preliminary data from humans. Given the nutrient profile and phytochemical contribution of beans, nutritionists should make a concerted effort to encourage the public to consume more beans in general and more soyfoods in particular.


Diet High in Whole and Unrefined Foods Favorably Alters Lipids, Antioxidant Defenses, and Colon Function

Bruce B, Spiller GA, Klevay LM, Gallagher SK.
J Am Coll Nutr. 2000 Feb;19(1):61-67.

Objective: Diets rich in whole and unrefined foods, like whole grains, dark green and yellow/orange-fleshed vegetables and fruits, legumes, nuts and seeds, contain high concentrations of antioxidant phenolics, fibers and numerous other phytochemicals that may be protective against chronic diseases. This study compared the effects of a phytochemical-rich diet versus a refined-food diet on lipoproteins, antioxidant defenses and colon function.
Methods: Twelve hyperlipidemic women followed two diets for four weeks starting with a refined-food diet. Subjects then directly crossed over to the phytochemical-rich diet. Duplicate, fasting serum lipids and single, fasting antioxidant enzymes were measured at the end of the four-week refined-food diet period (baseline) and again at the end of the phytochemical-rich diet period.
Results: Total energy and total fat intake were similar during both diet periods, but there was a decrease in saturated fat (SFA) of 61% in the phytochemical-rich diet group. Dietary fiber, vitamin E, vitamin C and carotene intakes were 160%, 145%, 160% and 500% more, respectively, than during the refined-food diet period. The phytochemical-rich diet induced a drop of 13% in total cholesterol (TC) (p < 0.05) and 16% (p < 0.001) in low density lipoprotein-cholesterol (LDL-C). Erythrocyte superoxide dismutase decreased 69% (p < 0.01) and glutathione peroxidase dropped 35% (p < 0.01). Colon function was improved on the phytochemical-rich diet.
Conclusions: A diet abundant in phytochemically-rich foods beneficially affected lipoproteins, decreased need for oxidative defense mechanisms and improved colon function.


Nutrition and Blood Pressure

MacGregor GA.
Nutr Metab Cardiovasc Dis. 1999 Aug;9(4 Suppl):6-15.

Nutrition plays a very important role in regulating blood pressure. If we reverted to our evolutionary diet the problem of high blood pressure would disappear. However, this is unlikely and we, therefore, need to identify the most important factors in our diet that predispose to high blood pressure and, therefore, to vascular disease. Studies clearly demonstrate the very important role of our current intake of salt in our diet as being the major factor in regulating blood pressure in populations. Other dietary factors have also been identified as playing an important role, particularly potassium intake and fruit and vegetable consumption. A more healthy diet,that is a diet with much less salt and increased potassium through an increase in fruit and vegetable consumption, a reduction in fat intake with substitution of saturated by monounsaturated fat, a reduction in meat and dairy products with an increase in fish consumption will have large effects on blood pressure but, at the same time, will decrease other cardiovascular risk factors, particularly cholesterol and glucose intolerance. This healthier diet will reduce cardiovascular disease and is similar to the diet now being advocated for the prevention of some forms of cancer. Diet is by far the most important environmental factor determining our longevity and for those who wish to live longer, a change in diet as early in life as possible will have substantial effects.


Fruit and Vegetable Intake in Relation to Risk of Ischemic Stroke

Joshipura KJ, Ascherio A, Manson JE, et al.
JAMA. 1999 Oct 6;282(13):1233-1239.

Context: Few studies have evaluated the relationship between fruit and vegetable intake and cardiovascular disease.
Objective: To examine the associations between fruit and vegetable intake and ischemic stroke.
Design, Setting, and Subjects: Prospective cohort studies, including 75 596 women aged 34 to 59 years in the Nurses' Health Study with 14 years of follow-up (1980-1994), and 38683 men aged 40 to 75 years in the Health Professionals' Follow-up Study with 8 years of follow-up (1986-1994). All individuals were free of cardiovascular disease, cancer, and diabetes at baseline.
Main Outcome Measure: Incidence of ischemic stroke by quintile of fruit and vegetable intake.
Results: A total of 366 women and 204 men had an ischemic stroke. After controlling for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake (median of 5.1 servings per day among men and 5.8 servings per day among women) had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.52-0.92) compared with those in the lowest quintile. An increment of 1 serving per day of fruits or vegetables was associated with a 6% lower risk of ischemic stroke (RR, 0.94; 95 % CI, 0.90-0.99; P =.01, test for trend). Cruciferous vegetables (RR, 0.68 for an increment of 1 serving per day; 95% CI, 0.49-0.94), green leafy vegetables (RR, 0.79; 95% CI, 0.62-0.99), citrus fruit including juice (RR, 0.81; 95% CI, 0.68-0.96), and citrus fruit juice (RR, 0.75; 95% CI, 0.61-0.93) contributed most to the apparent protective effect of total fruits and vegetables. Legumes or potatoes were not associated with lower ischemic stroke risk. The multivariate pooled RR for total stroke was 0.96 (95% CI, 0.93-1.00) for each increment of 2 servings per day.
Conclusions: These data support a protective relationship between consumption of fruit and vegetables-particularly cruciferous and green leafy vegetables and citrus fruit and juice-and ischemic stroke risk.


Cardiovascular and Renal Benefits of Dry Bean and Soybean Intake

Anderson JW, Smith BM, Washnock CS.
Am J Clin Nutr. 1999 Sep;70(3 Suppl):464S-474S.

Dry beans and soybeans are nutrient-dense, fiber-rich, and are high-quality sources of protein. Protective and therapeutic effects of both dry bean and soybean intake have been documented. Studies show that dry bean intake has the potential to decrease serum cholesterol concentrations, improve many aspects of the diabetic state, and provide metabolic benefits that aid in weight control. Soybeans are a unique source of the isoflavones genistein and diadzein, which have numerous biological functions. Soybeans and soyfoods potentially have multifaceted health-promoting effects, including cholesterol reduction, improved vascular health, preserved bone mineral density, and reduction of menopausal symptoms. Soy appears to have salutary effects on renal function, although these effects are not well understood. Whereas populations consuming high intakes of soy have lower prevalences of certain cancers, definitive experimental data are insufficient to clarify a protective role of soy. The availability of legume products and resources is increasing, incorporating dry beans and soyfoods into the diet can be practical and enjoyable. With the shift toward a more plant-based diet, dry beans and soy will be potent tools in the treatment and prevention of chronic disease.


Long-Term Intake of Dietary Fiber and Decreased Risk of Coronary Heart Disease Among Women

Wolk A, Manson JE, Stampfer MJ, et al.
JAMA. 1999 Jun 2;281(21):1998-2004.

Context: Epidemiological studies of men suggest that dietary fiber intake protects against coronary heart disease (CHD), but data on this association in women are sparse.
Objective: To examine the association between long-term intake of total dietary fiber as well as fiber from different sources and risk of CHD in women.
Design and Setting: The Nurses' Health Study, a large, prospective cohort study of US women followed up for 10 years from 1984. Dietary data were collected in 1984, 1986, and 1990, using a validated semiquantitative food frequency questionnaire.
Participants: A total of 68782 women aged 37 to 64 years without previously diagnosed angina, myocardial infarction (MI), stroke, cancer, hypercholesterolemia, or diabetes at baseline.
Main Outcome Measure: Incidence of acute MI or death due to CHD by amount of fiber intake.
Results: Response rate averaged 80% to 90% during the 10-year follow-up. We documented 591 major CHD events (429 nonfatal MIs and 162 CHD deaths). The age-adjusted relative risk (RR) for major CHD events was 0.53 (95% confidence interval [CI], 0.40-0.69) for women in the highest quintile of total dietary fiber intake (median, 22.9 g/d) compared with women in the lowest quintile (median, 11.5 g/d). After controlling for age, cardiovascular risk factors, dietary factors, and multivitamin supplement use, the RR was 0.77 (95% CI, 0.57-1.04). For a 10-g/d increase in total fiber intake (the difference between the lowest and highest quintiles), the multivariate RR of total CHD events was 0.81 (95% CI, 0.66-0.99). Among different sources of dietary fiber (eg, cereal, vegetables, fruit), only cereal fiber was strongly associated with a reduced risk of CHD (multivariate RR, 0.63; 95% CI, 0.49-0.81 for each 5-g/d increase in cereal fiber).
Conclusions: Our findings in women support the hypothesis that higher fiber intake, particularly from cereal sources, reduces the risk of CHD.


Whole-Grain Consumption and Risk of Coronary Heart Disease: Results from the Nurses' Health Study

Liu S, Stampfer MJ, Hu FB, et al.
Am J Clin Nutr. 1999 Sep;70(3):412-419.

Background: Although current dietary guidelines for Americans recommend increased intake of grain products to prevent coronary heart disease (CHD), epidemiologic data relating whole-grain intake to the risk of CHD are sparse.
Objective: Our objective was to evaluate whether high whole-grain intake reduces risk of CHD in women.
Design: In 1984, 75521 women aged 38-63 y with no previous history of cardiovascular disease or diabetes completed a detailed, semiquantitative food-frequency questionnaire (SFFQ) and were followed for 10 y, completing SFFQs in 1986 and 1990. We used pooled logistic regression with 2-y intervals to model the incidence of CHD in relation to the cumulative average diet from all 3 cycles of SFFQs.
Results: During 729472 person-years of follow-up, we documented 761 cases of CHD (208 of fatal CHD and 553 of nonfatal myocardial infarction). After adjustment for age and smoking, increased whole-grain intake was associated with decreased risk of CHD. For increasing quintiles of intake, the corresponding relative risks (RRs) were 1.0 (reference), 0.86, 0.82, 0.72, and 0.67 (95% CI comparing 2 extreme quintiles: 0.54, 0.84; P for trend < 0.001). After additional adjustment for body mass index, postmenopausal hormone use, alcohol intake, multivitamin use, vitamin E supplement use, aspirin use, physical activity, and types of fat intake, these RRs were 1.0, 0.92, 0.93, 0.83, and 0.75 (95% CI: 0.59, 0.95; P for trend = 0.01). The inverse relation between whole-grain intake and CHD risk was even stronger in the subgroup of never smokers (RR = 0. 49 for extreme quintiles; 95% CI: 0.30, 0.79; P for trend = 0.003). The lower risk associated with higher whole-grain intake was not fully explained by its contribution to intakes of dietary fiber, folate, vitamin B-6, and vitamin E.
Conclusions: Increased intake of whole grains may protect against CHD.


Pecans Lower Low-Density Lipoprotein Cholesterol in People with Normal Lipid Levels

Morgan WA, Clayshulte BJ.
J Am Diet Assoc. 2000 Mar;100(3):312-318.

Objective: To compare serum lipid profiles and dietary intakes of people with normal lipid levels who consumed pecans and those who did not consume nuts.
Design: Eight-week, randomized, controlled study of pecan treatment group vs control group. SUBJECT: Nineteen people with normal lipid levels completed the study; 10 had been randomly assigned to the pecan treatment group (7 women, 3 men, mean age = 45 +/- 10 years) and 9 to the control group (8 women, 1 man, mean age = 37 +/- 12 years).
Intervention: The pecan treatment group consumed 68 g pecans per day for 8 weeks plus self-selected diets. The pecans contributed 459 kcal and 44 g fat daily. The control group avoided nuts and consumed self-selected diets.
Main Outcome Measures: Total serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total triglyceride levels were measured at the time of entrance to the study (baseline), week 4, and week 8. Computer analyses were done on five 3-day food records.
Statistical Analysis: Comparisons were made using analysis of variance or paired t test.
Results: LDL-C was lowered in the pecan treatment group from 2.61 +/- 0.49 mmol/L at baseline to 2.35 +/- 0.49 at week 4 (P < .05) and to 2.46 +/- 0.59 at week 8 (P < .05). At week 8, total cholesterol and HDL-C in the pecan treatment group were significantly lower (P < .05) than in the control group (total cholesterol: 4.22 +/- 0.83 vs 5.02 +/- 0.54 mmol/L; HDL-C: 1.37 +/- 0.23 vs 1.47 +/- 0.34 mmol/L). Dietary fat, monounsaturated fat, polyunsaturated fat, insoluble fiber, magnesium, and energy were significantly higher in the pecan treatment group than in the control group. Body mass indexes and body weights were unchanged in both groups.
Applications: Pecans can be included in a healthful diet when energy intake and potential weight gain are addressed.


Nut Consumption, Vegetarian Diets, Ischemic Heart Disease Risk, and All-Cause Mortality: Evidence from Epidemiologic Studies

Sabate J.
Am J Clin Nutr. 1999 Sep;70(3 Suppl):500S-503S.

Perhaps one of the most unexpected and novel findings in nutritional epidemiology in the past 5 y has been that nut consumption seems to protect against ischemic heart disease (IHD). Frequency and quantity of nut consumption have been documented to be higher in vegetarian than in nonvegetarian populations. Nuts also constitute an important part of other plant-based diets, such as Mediterranean and Asian diets. In a large, prospective epidemiologic study of Seventh-day Adventists in California, we found that frequency of nut consumption had a substantial and highly significant inverse association with risk of myocardial infarction and death from IHD. The Iowa Women's Health Study also documented an association between nut consumption and decreased risk of IHD. The protective effect of nuts on IHD has been found in men and women and in the elderly. Importantly, nuts have similar associations in both vegetarians and nonvegetarians. The protective effect of nut consumption on IHD is not offset by increased mortality from other causes. Moreover, frequency of nut consumption has been found to be inversely related to all-cause mortality in several population groups such as whites, blacks, and the elderly. Thus, nut consumption may not only offer protection against IHD, but also increase longevity.


Frequent Nut Consumption and Risk of Coronary Heart Disease in Women: Prospective Cohort Study

Hu FB, Stampfer MJ, Manson JE, et al.
J Nutr.1999 Jun;129(6):1135-1139.

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.


Are Olive Oil Diets Antithrombotic? Diets Enriched with Olive, Rapeseed, or Sunflower Oil Affect Postprandial Factor VII Differently

Larsen LF, Jespersen J, Marckmann P.
Am J Clin Nutr. 1999 Dec;70(6):976-982.

Background: The incidence of ischemic heart disease (IHD) in Crete was lower than expected on the basis of blood lipid concentrations of participants in the Seven Countries Study. A favorable effect of a high intake of olive oil on thrombogenesis may have contributed to this finding.
Objective: We compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis.
Design: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive oil, sunflower oil, or rapeseed oil for periods of 3 wk. On the final day of each period, participants consumed standardized high-fat meals (42% of energy as fat). Fasting and nonfasting blood samples were collected after each period.
Results: Mean (+/-SEM) nonfasting peak concentrations of activated FVII (FVIIa) were 11.3 +/- 5.1 U/L lower after olive oil than after sunflower oil, an 18% reduction (P < 0.05). Olive oil also tended to cause lower FVIIa peak concentrations than did rapeseed oil (mean difference: 8.6 U/L, a 15% reduction; P = 0.09). There were no significant differences between diets with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI.
Conclusion: A background diet rich in olive oil may attenuate the acute procoagulant effects of fatty meals, which might contribute to the low incidence of IHD in Mediterranean areas.


"The SU.VI.MAX Study": A Primary Prevention Trial Using Nutritional Doses of Antioxidant Vitamins and Minerals in Cardiovascular Diseases and Cancers. SUpplementation en VItamines et Mineraux AntioXydants

Hercberg S, Preziosi P, Galan P, et al.
Food Chem Toxicol. 1999 Sep-Oct;37(9-10):925-930.

The "SUpplementation en VItamines et Mineraux AntioXydants" (SU.VI.MAX) Study is a randomized double-blind, placebo-controlled, primary-prevention trial which started in 1994 in France. This epidemiologic study is designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg, vitamin E, 30 mg, and beta-carotene, 6 mg) and minerals (selenium, 100 microg, and zinc, 20 mg) at nutritional doses, in reducing the main causes of premature death (cancers and cardiovascular diseases); 12,735 eligible subjects (women aged 35 to 60 years, and men aged 45 to 60 years) were included in 1994 and will be followed up for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. After 2 years of supplementation, biochemical indicators of vitamin and trace element status reach reasonable level without reaching concentrations as high as those observed in intervention studies, which tested relatively high doses of antioxidants, and ended up with higher risk of pathology.


Nutritional Strategies in Cardiovascular Disease Control: An Update on Vitamins and Conditionally Essential Nutrients

Kendler BS.
Prog Cardiovasc Nurs. 1999 Autumn;14(4):124-129.

Several nutritional interventions for cardiovascular disease (CVD) prevention and therapy have recently appeared in the biomedical literature. These include appropriate use of several vitamins (E, C, B6, folate) and conditionally essential nutrients (CoQ10, L-arginine, propionyl L-carnitine). Possible undesirable consequences of long term nutritional supplementation with vitamin E and of adverse drug-nutrient interactions between the statins and CoQ10 are also considered. Although additional intervention studies are needed, current scientific evidence generally supports nutritional supplementation with these nutrients as an effective adjunctive strategy for CVD control.


Serum Vitamins, Carotenoids, and Angina Pectoris: Findings from The National Health and Nutrition Examination Survey III

Ford ES, Giles WH.
Ann Epidemiol. 2000 Feb;10(2):106-116.

Purpose: Whether various vitamins and carotenoids can protect against ischemic heart disease remains an unsettled question.
Methods: We performed a cross-sectional analysis of data from National Health and Nutrition Examination Survey III (1988-1994) and examined the associations between serum vitamins A, C, E, and B12, serum folate, red blood cell folate, serum carotenoids, and angina pectoris in a representative population-based sample of 11,327 men and women aged 35->90 years.
Results: After adjusting for age, sex, race or ethnicity, education, smoking status, systolic blood pressure, serum cholesterol, high-density lipoprotein cholesterol, history of diabetes mellitus, body mass index, and physical activity with multiple logistic regression analysis, no significant associations were present for any of the serum vitamin concentrations and angina pectoris. Significant linear trends were observed for serum concentrations of alpha-carotene (p < 0.001), beta-carotene (p = 0.026), and beta-cryptoxanthin (p = 0.003). Compared with participants with carotenoid concentrations in the lowest quartile, participants with concentrations in the highest quartile had odds ratios for angina pectoris of 0.45 (95% confidence interval (CI) 0.31-0.65), 0.57 (95% CI 0.38-0.86), and 0.57 (95% CI 0.38-0.84) for alpha-carotene, beta-carotene, and beta-cryptoxanthin, respectively.
Conclusions: These results provide little support for a cross-sectional association between angina pectoris and serum and red blood cell folate concentrations or concentrations of vitamins A, C, E, and B12. Several serum carotenoid concentrations were associated with a reduced risk for angina pectoris, however.


Dietary Flavonoids as Antioxidants in Vivo: Conjugated Metabolites of (-)-Epicatechin and Quercetin Participate in Antioxidative Defense in Blood Plasma

Terao J.
J Med Invest. 1999 Aug;46(3-4):159-168.

Flavonoids are present in mainly plant foods and have attracted much attention in relation to disease prevention. Their antioxidant activity at least partly accounts for their potential health effect, because oxidative stress leads to a variety of pathophysiological events. It is essential to know the bioavailability of flavonoids involving intestinal absorption, metabolic conversion and urinary excretion, in order to evaluate their in vivo antioxidant activity after intake. Here (-)-epicatechin and quercetin were selected as typical flavanol- and flavonol-flavonoids present in vegetables, fruits and tea. Our rat study suggests that their metabolic conversion begins in the intestinal mucosa where the activity of uridine-5'-diphosphoglucuronosyltransferase (UGT) is at its highest. Both flavonoids accumulated mostly as glucuronide and sulfate conjugates in blood plasma after oral administration. No intact quercetin was found in the circulation. However, on the oral administration of these flavonoids, the antioxidative ability of rat plasma was enhanced indicating that conjugated metabolites participate in the antioxidant defense in blood plasma. Therefore, the intake of vegetables, fruits and tea rich in flavonoids may help to prevent oxidative damages in the blood.


Toward a New Recommended Dietary Allowance for Vitamin C Based on Antioxidant and Health Effects in Humans

Carr AC, Frei B.
Am J Clin Nutr. 1999 Jun;69(6):1086-1087.

The current recommended dietary allowance (RDA) for vitamin C for adult nonsmoking men and women is 60 mg/d, which is based on a mean requirement of 46 mg/d to prevent the deficiency disease scurvy. However, recent scientific evidence indicates that an increased intake of vitamin C is associated with a reduced risk of chronic diseases such as cancer, cardiovascular disease, and cataract, probably through antioxidant mechanisms. It is likely that the amount of vitamin C required to prevent scurvy is not sufficient to optimally protect against these diseases. Because the RDA is defined as "the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all healthy individuals in a group," it is appropriate to reevaluate the RDA for vitamin C. Therefore, we reviewed the biochemical, clinical, and epidemiologic evidence to date for a role of vitamin C in chronic disease prevention. The totality of the reviewed data suggests that an intake of 90-100 mg vitamin C/d is required for optimum reduction of chronic disease risk in nonsmoking men and women. This amount is about twice the amount on which the current RDA for vitamin C is based, suggesting a new RDA of 120 mg vitamin C/d.


Alzheimer Disease: Protective Factors

Nourhashemi F, Gillette-Guyonnet S, Andrieu S, et al.
Am J Clin Nutr. 2000 Feb;71(2):643S-649S.

Approximately 6-8% of all persons aged >65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. The objective of this article was to review recent studies in this field.


Dietary Factors in Relation to Rheumatoid Arthritis: A Role for Olive Oil and Cooked Vegetables?

Linos A, Kaklamani VG, Kaklamani E, et al.
Am J Clin Nutr. 1999 Dec;70(6):1077-1082.

Background: Although several studies showed that risk of rheumatoid arthritis (RA) is inversely associated with consumption of n-3 fatty acids, the one study showing that olive oil may have a protective role has not yet been confirmed.
Objective: We examined the relation between dietary factors and risk of RA in persons from southern Greece.
Design: We studied 145 RA patients and 188 control subjects who provided information on demographic and socioeconomic variables, prior medical and family history, and present disease status. Subjects responded to an interviewer-administered, validated, food-frequency questionnaire that assessed the consumption of >100 food items. We calculated chi-square statistics for linear trend and odds ratios (ORs) for the development of RA in relation to the consumption of olive oil, fish, vegetables, and a series of food groups classified in quartiles.
Results: Risk of developing RA was inversely and significantly associated only with cooked vegetables (OR: 0.39) and olive oil (OR: 0.39) by univariate analysis. A significant trend was observed with increasing olive oil (chi-square: 4.28; P = 0.03) and cooked vegetable (chi-square: 10. 48; P = 0.001) consumption. Multiple logistic regression analysis models confirmed the independent and inverse association between olive oil or cooked vegetable consumption and risk of RA (OR: 0.38 and 0.24, respectively).
Conclusions: Consumption of both cooked vegetables and olive oil was inversely and independently associated with risk of RA in this population. Further research is needed to elucidate the underlying mechanisms of this finding, which may include the antioxidant properties or the high n-9 fatty acid content of the olive oil.


The Influence of Chronic Yogurt Consumption on Immunity

Van de Water J, Keen CL, Gershwin ME.
J Nutr. 1999 Jul;129(7 Suppl):1492S-1495S.

There has been increased interest in the study of nutrition and immunity. This is especially true with respect to the hypothesis that consumption of specific foods may reduce an individual's susceptibility to the establishment and/or progression of immunologic disease. Although an increased intake of a specific food may improve health status in select cases, chronic consumption of large amounts of one specific food may in fact be detrimental. The studies described here examined the long-term effect of yogurt consumption on two different age populations, young adults (20-40 y) and senior adults (55-70 y). There were three study groups per age group, live-culture yogurt, pasteurized yogurt and control (no yogurt), given 200 g/d of yogurt for 1 y. The subjects completed a questionnaire detailing health parameters on a weekly basis and a 4-d food record was taken monthly. Blood was taken every 3 mo and complete blood chemistry, blood count, total and specific immunoglobulin (Ig)E, and interferon-gamma (IFN-gamma) production measured.Yogurt consumption, especially for the live-culture groups, was associated with a decrease in allergic symptoms in both age groups. Seniors in the control group experienced an increase in both total and LDL cholesterol, whereas those in the yogurt groups remained stable during the course of the study. There was little effect on IFN-gamma and IgE production, although seniors in the yogurt group had lower levels of total IgE throughout the year.

Published erratum appears in J Nutr. 1999 Oct;129(10):1932.


Tea and Health

Yang CS.
Nutrition. 1999 Nov-Dec;15(11-12):946-949.

The possible beneficial effects of tea consumption in the prevention of cancer and cardiovascular diseases have been demonstrated in animal models and suggested by studies in vitro. Similar beneficial effects, however, have not been convincingly demonstrated in humans: beneficial effects have been demonstrated in some studies but not in others. If such beneficial effects do exist in humans, they are likely to be mild, depending on many other lifestyle-related factors, and could be masked by confounding factors in certain populations. Another concern is that the amounts of tea consumed by humans are lower than the doses required for demonstrating the disease-prevention effects in animal models. Caution should be applied, however, in the use of high concentrations of tea for disease prevention. Ingestion of large amounts of tea may cause nutritional and other problems because of the caffeine content and the strong binding activities of tea polyphenols, although there are no solid data on the harmful effects of tea consumption. More research is needed to elucidate the biologic activities of green and black tea and to determine the optimal amount of tea consumption for possible health-beneficial effects.


Serum Alpha-Tocopherol Status in the United States Population: Findings from the Third National Health and Nutrition Examination Survey.

Ford ES, Sowell A.
Am J Epidemiol. 1999 Aug 1;150(3):290-300.

Despite the role vitamin E may have in protecting against various chronic conditions, little is known about vitamin E status in the US population. Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the distribution and correlates of serum alpha-tocopherol among 16,295 US adults aged 18 or more years. The mean concentration of alpha-tocopherol was 26.8 micromol/liter (geometric mean, 25.0 micromol/liter). The 25th, 50th, and 75th percentiles were 19.6, 24.1, and 30.4 micromol/liter, respectively.The mean alpha-tocopherol/cholesterol ratio was 5.1 (geometric mean, 4.9); the 25th, 50th, and 75th percentiles were 4.1, 4.7, and 5.5 (10(-3)), respectively. About 27% of the US population had a low alpha-tocopherol concentration (<20 micromol/liter). After age standardization, 29% of the men, 28% of the women, 26% of the whites (men, 27%, and women, 26%), 41% of the African Americans (men, 42%, and women, 40%), 28% of the Mexican Americans (men, 29%, and women, 27%), and 32% of the other participants (men, 36%, and women, 29%) had this low concentration. For all participants, age, educational attainment, serum cholesterol, and several serum vitamins and carotenoids were directly related to and high density lipoprotein cholesterol was inversely related to serum alpha-tocopherol concentration in multiple linear regression analysis. Men had a higher concentration than did women, and African Americans had the lowest concentration of any racial or ethnic group. These results show that important proportions of US adults have a low serum alpha-tocopherol concentration, which may increase their risk for chronic diseases in which low dietary intake or blood concentration of alpha-tocopherol have been implicated.


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