Novel engineering approaches to obesity, overweight, and energy balance: public health needs and research opportunities.

The obesity epidemic is one of the most rapidly evolving public health problems of our day. At present, 2/3 of American adults and 1/6 of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high and reflects documented increased risk of cardiovascular disease, type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis, and increased mortality from these ailments, especially among the most obese. Innovative engineering technologies are needed to address a large range of problems in energy balance, intake, and expenditure that are associated with the obesity epidemic. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Novel sensors, devices, imaging technologies, nanotechnology, biomaterials, and other approaches need to be developed and evaluated through multidisciplinary collaborations between engineers, physical scientists, and scientists with expertise in obesity and nutrition. The goal is to encourage research to develop useful technologies and tools to facilitate research and eventually to support therapeutic advances and behavioral change. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov).

Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique.

OBJECTIVE: This study examined the accuracy of a multiple-pass, 24-hour dietary recall method for estimating energy intakes of men and women by comparing it with energy intake required for weight maintenance. DESIGN: Three-day, multiple-pass, 24-hour recalls were obtained on randomly selected days during a self-selected diet period when subjects were preparing their own meals and during a controlled diet period when all meals were provided by the study. During the dietary intervention, weight was maintained; body weight and dietary intake were monitored closely, thereby allowing estimation of the energy intake required for weight maintenance. SUBJECTS/SETTING: Seventy-eight men and women (22 to 67 years old) from the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study participated in this study. All 24-hour recalls were collected using a computer-assisted, interactive, multiple-pass telephone interview technique. Energy requirements for each individual were determined by the energy content of the DELTA study foods provided to maintain weight. STATISTICAL ANALYSIS: Paired and independent t tests were conducted to examine differences among study variables. Agreement between recalled energy intake and weight maintenance energy intake was analyzed using the Bland-Altman technique. RESULTS: Compared with weight maintenance energy intake, during the self-selected diet period men and women underestimated energy intake by 11% and 13%, respectively. During the controlled diet period, men underestimated energy intake by 13%, whereas women overestimated energy by 1.3%. APPLICATIONS/CONCLUSIONS: Men had a tendency to under-estimate energy intake irrespective of the recording period. The accuracy of the recalled energy intake of women may be influenced by recording circumstances. Researchers should examine the factors influencing underreporting and overreporting by individuals and their impact on macronutrient and micronutrient intakes. Also, strategies need to be developed to minimize underreporting and overreporting.

Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance.

Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.

Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia.

BACKGROUND: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia. PURPOSE: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian. METHODS: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years. RESULTS: A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. CONCLUSIONS: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus. IMPLICATIONS: Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.

Intake of tapwater and total water by pregnant and lactating women.

BACKGROUND: Despite theoretically higher requirements for water due to physiologic demands of pregnancy and lactation, little is known of actual ranges of intake in pregnant and lactating women. METHODS: Population-based estimates of total water and tapwater intake in women of reproductive age were derived using data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non-pregnant, non-lactating control women. RESULTS: Total water intake (mean +/- SD) was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310 +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to or greater than 3,000 g/day among 7 percent of control women, 11 percent of pregnant women, and 13 percent of lactating women. Tapwater intake was equal to or greater than 2,000 g/day among 10 percent of control women, 15 percent of pregnant women, and 8 percent of lactating women. CONCLUSIONS: These results should be useful in estimating amounts of nutrients and toxic substances that women of reproductive age obtain through the water supply.

Lung cancer among women in north-east China.

A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. Although the amount smoked was low (the cases averaged eight cigarettes per day), the percentage of smokers among women over age 50 in these cities was nearly double the national average. Air pollution from coal burning stoves was implicated, as risks of lung cancer increased in proportion to years of exposure to 'Kang' and other heating devices indigenous to the region. In addition, the number of meals cooked by deep frying and the frequency of smokiness during cooking were associated with risk of lung cancer. More cases than controls reported workplace exposures to coal dust and to smoke from burning fuel. Elevated risks were observed for smelter workers and decreased risks for textile workers. Prior chronic bronchitis/emphysema, pneumonia, and recent tuberculosis contributed significantly to lung cancer risk, as did a history of tuberculosis and lung cancer in family members. Higher intake of carotene-rich vegetables was not protective against lung cancer in this population. The findings were qualitatively similar across the major cell types of lung cancer, except that the associations with smoking and previous lung diseases were stronger for squamous/oat cell cancers than for adenocarcinoma of the lung.

Smoking, air pollution, and the high rates of lung cancer in Shenyang, China.

A case-control study involving interviews with 1,249 patients with lung cancer and 1,345 population-based controls was conducted in Shenyang, an industrial city in northeastern China, where mortality rates are high among men and women. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the lung cancers in males and 37% in females. The attributable risk percentage among females is high compared to elsewhere in China, largely because of a higher prevalence of smoking among women. After adjustment for smoking, there were also significant increases in lung cancer risk associated with several measures of exposure to air pollutants. Risks were twice as high among those who reported smoky outdoor environments, and increased in proportion to years of sleeping on beds heated by coal-burning stoves (kang), and to an overall index of indoor air pollution. Threefold increases in lung cancer risk were found among men who worked in the nonferrous smelting industry, where heavy exposures to inorganic arsenic have been reported. The associations with both smoking and indoor air pollution were stronger for squamous cell and small cell carcinomas than for adenocarcinoma of the lung. Risks due to smoking or air pollution were not greatly altered by adjustment for consumption of fresh vegetables or sources of beta carotene or retinol, prior chronic lung diseases, or education level. The findings suggest that smoking and environmental pollution combine to account for the elevated rates of lung cancer mortality in Shenyang.

Gestational trophoblastic disease: a case-control study from the People's Republic of China.

A case-control study involving 331 patients with complete hydatidiform mole and 662 community controls matched to the cases on age and timing of pregnancy was conducted in Beijing, China. A history of a term birth was associated with reduced risk (odds ratio = 0.6, 95% confidence interval 0.4 to 0.9), with some evidence of further decrease with multiple births. Previous spontaneous abortions were not related to risk, although those with a prior induced abortion were at elevated risk, particularly if two or more abortions were involved (odds ratio = 2.8, 95% confidence interval 1.4 to 5.7). A history of having sought medical advice for infertility was associated with reduced risk (odds ratio = 0.5, 95% confidence interval 0.2 to 0.8), but those who reported use of herbal medicines during a first trimester of a previous pregnancy were at excess risk (odds ratio = 2.2, 95% confidence interval 1.3 to 3.6). In addition, a statistically significant trend in risk was observed with years of oral contraceptive use (odds ratio = 2.6, 95% confidence interval 0.9 to 6.9 for greater than or equal to 4 years of use). Dietary habits and family histories of cancer or trophoblastic disease were not related to risk in this study.

A case-control study of cancer of the esophagus and gastric cardia in Linxian.

A case-control study involving interviews with 1,244 patients (758 males and 486 females) with cancer of the esophagus or gastric cardia and 1,314 population-based controls (789 males, 525 females) was carried out in Linxian, a rural county in North Central China with one of the world's highest mortality rates for these tumors. Cancer risks tended to rise with increasing intake of wheat and corn, but no association was found with adult intake of pickled vegetables, the leading a priori suspect, and risks were not elevated among those consuming low quantities of fresh vegetables or fruits. Few differences in preparation or storage of food or water were detected, although cancer patients reported less fluid intake than controls. Few persons reported drinking alcoholic beverages. Smoking was reported by 61% of the male cases and was a mild risk factor, related more to cancer of the cardia than of the esophagus. The risk was increased by 70% among those whose parents had esophageal or stomach cancer, but only slightly among those whose spouses had such cancers, suggesting that exposure early in life and/or genetic effects may be involved.

Depressed PMNC blastogenic response in patients with cancer of the head and neck: a study of IL-2 production, IL-2 consumption, and IL-2 receptor expression.

Approximately two thirds of patients with head and neck cancer have been shown to have peripheral mononuclear cells that exhibit a lowered blastogenic response to the T-cell mitogens, concanavalin A and phytohemagglutinin. To investigate the possible mechanisms of this phenomenon, we measured the amount of activated T-cell lymphokine interleukin-2 present in the supernatant of concanavalin A- or phytohemagglutinin-stimulated peripheral mononuclear cells taken from patients with squamous cell carcinoma of the upper aerodigestive tract. Concentrations were found that were similar to those of healthy subjects. The rate of interleukin-2 consumption and the degree of interleukin-2 receptor expression also were similar for patients and controls. In the course of these experiments, it was noted that differences in blastogenic response between patients and controls were abolished when, 24 hours after the beginning of either concanavalin A or phytohemagglutinin stimulation, the culture supernatant was removed and replaced by fresh medium, containing recombinant interleukin-2 to further sustain cell growth. This suggests that the lower blastogenic response found in patients with head and neck cancer is not due to global immune unresponsiveness, but instead, is caused by selective cell dysfunction(s), which may include the production of a suppressor factor following concanavalin A or phytohemagglutinin stimulation.

Nutritional status in Linxian, China: effects of season and supplementation.

The ability of a supplement to counteract seasonal alterations in nutritional status for certain vitamins was studied in Linxian, an area in northern China with high rates of esophageal cancer. 150 subjects took one daily pill from April to August (16 weeks), whereas 50 subjects did not take any supplement. Deficiencies of ascorbic acid, riboflavin, folic acid, retinol and tocopherol were prevalent at the outset of the study. The changes in diet occurring between the end of the winter (April) and the start of the autumn vegetable harvest (August) were reflected in greatly improved ascorbic acid status and slightly improved riboflavin status. Plasma retinol, tocopherol, alpha-carotene and beta-carotene were little affected by season, whereas erythrocyte folate levels declined. The ascorbic acid, riboflavin, folate, retinol and tocopherol status of the supplemented subjects was significantly improved. After 16 weeks of supplementation, erythrocyte folate levels of subjects with esophageal dysplasia were improved but remained significantly lower than those of normal supplemented subjects, targeting folic acid as a nutrient of particular interest in this precancerous condition.

Environmental factors and high risk of esophageal cancer among men in coastal South Carolina.

A case-control study involving interviews of 207 men with esophageal cancer and 422 control subjects or their next of kin was conducted to identify reasons for the unusually high rates of esophageal cancer among men in coastal South Carolina. Tobacco and alcohol, including moonshine, were identified as the major determinants of esophageal cancer risk. Increased risk was also associated with low intake of fresh fruits but not with drinking of local herbal teas. The findings suggest that efforts aimed at reducing tobacco and alcohol use will help to lower the elevated rates of esophageal cancer in coastal South Carolina.

Dietary factors in oral and pharyngeal cancer.

A population-based case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on a number of risk factors, including diet. Interviews were obtained from 871 oral cancer patients and 979 controls among whites, frequency matched for age and sex. Consumption frequency of 61 food items was assessed in the questionnaire; attention was given to foods that are sources of vitamins A and C and carotene. The major finding was an inverse relationship between fruit intake and risk of oral and pharyngeal cancer; individuals in the highest quartile of intake had about half the risk of those in the lowest quartile. Vitamin C, carotene, or fiber in fruit did not appear to account completely for this relationship, since these nutrients in vegetables did not provide similar protection. This finding suggests the influence of other constituents in fruits, although it is possible that cooking vegetables may have a nutrient-diminishing effect. Dietary intake of other nutrients, such as the B vitamins, vitamin E, folate, and iron, showed no consistent relationship to risk of oral and pharyngeal cancer. Coffee or other hot beverage consumption did not increase risk; intake of nitrite-containing meats or cooking practices, such as smoking, pickling, or charcoal grilling, also did not increase risk. All analyses were adjusted for the effects of tobacco and alcohol, strong risk factors for oral and pharyngeal cancer. Dietary findings among the few subjects who did not use tobacco or alcohol were similar to those for all subjects.

Diet and high risk of stomach cancer in Shandong, China.

A case-control investigation involving interviews with 564 stomach cancer patients and 1131 population-based controls was conducted to evaluate reasons for the exceptionally high rates of stomach cancer in Linqu, a rural county in Shandong Province in northeast China. Daily consumption of sour pancakes, a fermented indigenous staple, was associated with a 30% increase in risk. Risks of stomach cancer were also increased by 2- to 3-fold among persons with prior chronic gastritis or gastric ulcer, by 80% among those with stomach cancer in a family member, by 50% among men who smoked one or more packs of cigarettes/day, by 40% among those who preferred salty foods, and by 50% among families with moldy grain supplies. In contrast, risks tended to decrease in proportion to increasing consumption of fresh vegetables and fruits. This protective effect was more pronounced for vegetables, with those in the highest quartile of intake at less than one-half the risk of those in the lowest. Stomach cancer risks also declined with increasing dietary intake of carotene, vitamin C, and calcium, but not retinol. These findings provide leads to dietary factors that contribute to the high rates in Linqu, where stomach cancer is the leading cause of cancer and has not yet begun to decline as in other parts of the world.

Effects of heparin on in vitro immune parameters.

The effects of heparin on several in vitro immune functions [blastogenesis, interleukin-2(IL-2) production] were investigated. The addition of heparin to human peripheral mononuclear cells stimulated with phytohemagglutinin or pokeweed mitogen significantly increased the blastogenic response of these cells. Peak IL-2 concentrations in the supernatant of heparin-containing cultures were two- to fourfold higher than in heparin-free cultures. Flow cytometry experiments revealed that Leu-M3-positive cells were the only subset to be significantly affected by heparin, which induced an increase both in number and in fluorescence intensity of Leu-M3-positive cells. In contrast, the expression of DR molecules on monocytes was slightly decreased. It is speculated that the observed antimetastatic effects of heparin may be exerted through local immunomodulation in macrophage-rich tissues.

Sample size and power for case-control studies when exposures are continuous.

In estimating the sample size for a case-control study, epidemiologic texts present formulae that require a binary exposure of interest. Frequently, however, important exposures are continuous and dichotomization may result in a 'not exposed' category that has little practical meaning. In addition, if risks vary monotonically with exposure, then dichotomization will obscure risk effects and require a greater number of subjects to detect differences in the exposure distributions among cases and controls. Starting from the usual score statistic to detect differences in exposure, this paper develops sample size formulae for case-control studies with arbitrary exposure distributions; this includes both continuous and dichotomous exposure measurements as special cases. The score statistic is appropriate for general differentiable models for the relative odds, and, in particular, for the two forms commonly used in prospective disease occurrence models: (1) the odds of disease increase linearly with exposure; or (2) the odds increase exponentially with exposure. Under these two models we illustrate calculation of sample sizes for a hypothetical case-control study of lung cancer among non-smokers who are exposed to radon decay products at home.

Lung cancer among Chinese women.

A case-control study involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smoking was a strong risk factor, but accounted for only about one-fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also reported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

Growth in black and white children with Down syndrome.

Growth in 28 black and 30 white children with Down syndrome was compared at birth, 4 months, 1 year, and 7 years. Weight, length, and head circumference measurements were taken from case records of the U.S. Collaborative Perinatal Project. A multivariate regression model was used to examine simultaneously the effects on these measurements of sex, race, presence of congenital heart disease, maternal smoking during pregnancy, and maternal weight at delivery. Results showed that black and white children with Down syndrome have essentially identical growth rates and that long-term growth of these children may be responsive to external influences, such as maternal smoking and maternal weight at delivery.

A pilot vitamin intervention trial in Linxian, People's Republic of China.

A 24-week pilot study of daily or weekly multiple vitamin supplementation among 852 adults in Linxian, where the rate of esophageal cancer is exceptionally high, demonstrated the feasibility of an intervention trial in this population. Compliance, when judged by pill count, was high for both frequencies of pill use. Only 2% of the subjects refused to take any pills, and, among pill takers, over 95% were reported to be taking most of their pills at the end of the study. Biochemical confirmation of high compliance was demonstrated in urine and blood tests, which showed markedly improved vitamin levels after supplementation. Results of the pilot study indicated that a system in which barefoot doctors were used in pill distribution was effective and that established field operating procedures for a full-scale intervention trial in this area were acceptable.

Nutritional status of the high esophageal cancer risk population in Linxian, People's Republic of China: effects of vitamin supplementation.

Plasma levels of nutrients in 196 individuals were assayed as part of a study of the feasibility of a nutrition intervention trial in Linxian, a county in North Central China with exceptionally high rates of esophageal cancer. High-performance liquid chromatography analyses of samples collected in April 1983 showed low (relative to United States standards) base-line levels for retinol, alpha-tocopherol, and beta- and alpha-carotene. Repeat sampling in August 1983 revealed significantly increased plasma levels of retinol and alpha-tocopherol among those who had in the interim received daily supplementation with multivitamin pills containing the Recommended Dietary Allowance levels of those nutrients but not among those without supplementation. Levels of carotenes, which were not included in the pills, tended to increase regardless of supplementation, consistent with seasonal variations in availability of carotenoid-containing foods. Atomic absorption spectrophotometry analyses showed essentially normal levels of copper and zinc in plasma. Neither was affected by vitamin supplementation (the pills did not contain minerals) nor seasonal variation. The data are generally consistent with prior biochemical surveys in indicating marginal or low status of several nutrients in Linxian and in showing that supplementation with vitamins can effectively raise blood nutrient levels.