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Mediterranean diet: the past and the present.

Mortality statistics from the World Health Organization have provided early evidence that diet in the Mediterranean countries has been affecting the health of the respective populations and, in particular, their coronary health. Keys (1) has taken the lead arguing that the traditional Mediterranean diet has beneficial effects on health. Recent studies, capturing the evidence accumulated over the last three decades, have documented that the traditional Mediterranean diet meets several important criteria for a healthy diet. An attempt to conceptualize the proper diet and to make it able to function has been reported and a score has been developed and evaluated. Studies among the elderly in Greece, Denmark, Australia, Spain and China have shown that the overall Mediterranean dietary pattern was more important for longevity than single nutrients. These findings suggest, therefore, that a Mediterranean diet is associated with longer survival. Two additional questions should be addressed at this time: Is the Mediterranean diet an integral entity, or the sum of identifiable components that can and should be separately considered in the development of guidelines? Is the Mediterranean diet or its major components transferable to populations living far from the Mediterranean area? Answers to these questions would be important for scientific and policy reasons. The dietary patterns that prevail in the Mediterranean area have many common characteristics, most of which stem from the fact that olive oil plays an important role in all of them. Thus, although different regions in the Mediterranean basin have their own diets, it is legitimate to consider them as variants of a single entity, the Mediterranean diet. The Mediterranean diet can be described as the dietary pattern found in the olive growing areas of the Mediterranean region, in the late '50s and early '60s, when the consequences of World War II were overcome, but the fast-food culture had not reached the area yet (2). Olive oil is important both because of its several beneficial properties and because it allows the consumption of large quantities of vegetables and legumes in the form of salads and of cooked foods. Other essential components of the Mediterranean diet are wheat, grapes, and their derived products. Total lipid consumption may be high, around 40% of total energy intake as in Greece, or moderate, around 30% of total energy intake as in Italy. In all instances, however, the ratio of monounsaturated to saturated dietary lipids is much higher than in other places of the world, including northern Europe and North America (3).

Cardiovascular Diseases↗

Mediterranean diet and longevity.

While several investigations have focused on the association between individual foods and nutrients upon the development of chronic diseases, few have examined the role that entire dietary patterns may play in health and disease. A dietary pattern generally considered to have beneficial health effects is that of the Mediterranean diet. In this paper, five cohort studies exploring the association of Mediterranean diet with overall mortality and hence longevity are reviewed. A number of conclusions can be drawn. First, there appears to exist sufficient evidence that diet does indeed influence longevity. Secondly, an optimal diet for the prevention of both coronary heart disease and cancer is likely to extensively overlap with the traditional Mediterranean diet. It is not yet clear which components in the Mediterranean diet are more important for its apparent health effects, but olive oil, plant foods and moderate wine consumption are likely candidates.

Cohort Studies↗

Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.

BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.

Aged↗

Patterns of dietary intake and serum lipids interact with proteinuria as risk factors for progression of chronic renal failure.

UNLABELLED: This prospective study assessed the interactions between patterns of nutrient intake and serum lipids with other risk factors for progression of chronic renal failure. The study cohort consisted of 52 individuals with documented chronic renal failure, 18 women and 34 men, with a mean age of 65 +/- 11 years at the time of recruitment. The dependent variable was the rate of progression of chronic renal failure, which was determined by the slope of the curve generated from five or more values of the reciprocal of serum creatinine (SCr-1) and divided by time (in months of follow-up) for each patient, and recorded in dung/month. The independent variables included dietary factors (phosphorus, protein); serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides); proteinuria; serum phosphorus; serum albumin; serum glucose; and blood pressure. Serum creatinine was drawn in a fasting state and determined using the picric acid technique on five or more occasions for each patient. The mean monthly rate of decline in dL/mg/month was calculated for each patient. The cohort was followed for 1.5 years. Descriptive statistics were determined for all variables. Analysis of principal components was used to generate variables representing patterns of nutrient intake and serum lipids. The outcome variable was modeled using stepwise linear regression which included principal components representing dietary and serum lipid patterns. The Student's t test and the F test were used for hypothesis testing. All tests were significant at p < 0.05. RESULTS AND CONCLUSIONS: Multicolinearity prevented the inclusion of more than one individual dietary or serum lipid variable into the multiple linear regression model of rate of decline in kidney function. Principal components representing patterns of dietary intake and serum lipids, contributed to the prediction of rate of decline in renal function together with proteinuria.

Adolescent↗

Setting dietary guidance: the Canadian experience.

This article outlines processes underlying recent dietary guidance in Canada. In 1977, Nutrition Recommendations for Canadians were adapted from the Report of the Committee on Diet and Cardiovascular Disease. In the late 1980s, as science revealed new relationships between dietary patterns and chronic disease, the unified front of consistent dietary guidelines began to crumble when researchers and health organizations began to provide "unique" dietary advice. Evolution in health promotion concepts during this time, combined with the need for updated dietary guidance, influenced Health Canada to appoint two advisory committees in 1987. The Scientific Review Committee was charged with describing the dietary pattern that would supply recommended levels of essential nutrients while reducing risk of chronic disease, resulting in updated Nutrition Recommendations. The Communications and Implementation Committee translated the scientific recommendations into dietary advice for the public, leading to Canada's Guidelines to Healthy Eating. From this process, Canada's Food Guide to Healthy Eating emerged. The development of the Dietary Reference Intakes has resulted in updated nutrient requirement values and better tools for dietary assessment and planning. Health Canada recognizes the need to ensure alignment with this updated science through continuing leadership in defining and communicating accurate dietary guidance for Canada.

Canada↗

Effect of health lifestyle pattern on dietary change.

PURPOSE: To examine the effect of lifestyle on the effectiveness of a low-intensity dietary intervention. DESIGN: A secondary data analysis was performed using data from the Eating Patterns Study, a randomized controlled trial that found that self-help materials with physician advice was effective in changing dietary intake and behavior. SETTING: Primary care clinics in a large health maintenance organization. SUBJECTS: A total of 2111 patients with a routine scheduled appointment with their primary care physicians. MEASURES: Participants were grouped into one of six health lifestyle patterns based on similarities in baseline measures of alcohol intake, smoking, diet quality, and exercise. Within each lifestyle pattern, changes from baseline in usual fat and fiber intake (based on a food frequency) and a fat and fiber behavior score were compared at 3 months and 12 months for intervention vs. control participants. INTERVENTION: Self-help materials delivered by a physician with advice to change diet. RESULTS: Intervention participants in the fitness lifestyle group made the largest changes relative to controls for each dietary outcome at 3 and 12 months. For intervention participants defined by their alcohol intake or current smoking, either no changes in diet were observed compared with controls, or early changes were not sustained over time. Intervention-control comparisons within the remaining lifestyle patterns showed smaller dietary changes compared with the fitness lifestyle. This finding was similar to previously published results. CONCLUSIONS: This randomized controlled trial had limited power to detect subgroup differences; however, these results suggest that lifestyle patterns may be useful in the development of effective, targeted interventions to change behavior.

Data Collection↗

Lipid patterns and dietary habits of healthy subjects living in urban, suburban and rural areas.

Lipid patterns were determined in 167 healthy subjects in the age group 28 to 50 years living in an urban area, a suburban area and two rural areas to determine a possible relationship between their serum lipid patterns and food habits. Total cholesterol, high density lipoprotein (HDL)-cholesterol, and triglyceride concentrations were determined in the sera of fasting subjects, and low density lipoprotein (LDL)-cholesterol concentration was calculated. Risk of coronary heart disease as assessed by the body mass index, ratios of total cholesterol to HDL-cholesterol, and LDL-cholesterol to HDL-cholesterol, was significantly lower in subjects in rural area 2, who were agricultural workers with a high degree of physical activity, subsisting on a diet consisting mainly of plant food, despite a higher consumption of coconut, a saturated fat. It is possible that the hypercholesterolaemic effect of saturated fats was mitigated by the high fibre content of their diets.

Adult↗

A dietary oxidative balance score of vitamin C, beta-carotene and iron intakes and mortality risk in male smoking Belgians.

The purpose of this study was to investigate, in smokers, whether the oxidative balance of their dietary pattern affected mortality risk. To evaluate the oxidative balance of the dietary pattern, an oxidative balance score was constructed that summarized the combined intake of dietary antioxidants (vitamin C and beta-carotene) and a prooxidant (iron). The low oxidative balance score group included smokers with a diet high in vitamin C and beta-carotene and/or low in iron and the high oxidative balance score group included those with a diet low in vitamin C and beta-carotene and/or high in iron. Using the 10-y follow-up mortality data from the Belgian Interuniversity Research on Nutrition and Health (BIRNH) study, the association of this oxidative balance score with all-cause, cardiovascular disease (CVD) and total cancer mortality was investigated in 2814 male smokers. In multivariate-adjusted Cox models, men in the highest oxidative balance score group had a higher relative risk (RR) of all-cause [RR = 1.44, 95% confidence interval (CI): 1.13, 1.82] and of total cancer mortality (RR = 1.62, 95% CI: 1.07, 2.45) compared with men in the lowest score group. This association was less pronounced for CVD mortality risk and was not significant (RR = 1.31, 95% CI: 0.86, 2.00). The risk of all-cause and total cancer mortality was driven principally by the high score group, which suggested a threshold effect for risk rather than a linear trend. The findings are consistent with the hypothesis that the oxidative balance of the diet is associated with subsequent mortality. Smokers whose diet is unbalanced in terms of anti- and prooxidants may therefore benefit from a recommendation to consume more servings of fresh fruits and vegetables and less meat.

Antioxidants↗

Effects of lighting pattern and dietary tryptophan supplementation on growth and mortality in broilers.

The effect of lighting pattern and supplementation of the diet with Trp on growth and mortality of male broiler chickens was evaluated in three experiments using 2,392, 2,608, and 2,400 chickens, respectively. There were two lighting treatments, either a constant 23 h of continuous light/24-h period or an increasing photoperiod lighting system, i.e., 0 to 3 days, 23 h light (L):1 h dark (D); 4 to 14 days, 6L:18D; 15 to 21 days, 10L:14D; 22 to 28 days, 14L:10D; 29 to 35 days, 18L:6D; 36 to 42 days, 23L:1D. The design was a completely randomized 2 x 2 factorial, with four replicates per treatment. In the first two experiments, a starter diet with or without .2% supplemental L-Trp (feed grade) was fed from 0 to 3 wk of age and a finisher diet with or without .2% supplemental Trp was fed from 3 to 6 wk of age. In the third experiment, the level of supplemental Trp was .4% in the starter and finisher diet. Birds raised on the increasing light pattern consumed less feed during the first 3 wk, were lighter in weight at 3 wk, and had lower feed:gain ratios (P < .001) than their counterparts on constant light. By market age (6 wk) they had similar body weight but feed intake was significantly (P < .05) lower in all experiments, and feed:gain ratio was significantly lower in these birds in Experiment 3 (P < .05) than in their counterparts on constant light.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Increases in plasma carotenoid concentrations in response to a major dietary change in the women's healthy eating and living study.

BACKGROUND: Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events. Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis. METHODS: In a randomized trial of 2,922 breast cancer survivors, we examined blood and self-reported diet at baseline and 1 year. Intensive telephone counseling encouraged a plant-based diet in the intervention group. Diet was measured via 24-hour recalls, and a panel of plasma carotenoid concentrations was assessed at both time points. RESULTS: The study intervention was associated with a 51% increase in total carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L, achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta-carotene, and lutein. For each of these targeted carotenoids, the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half. After 1 year of study, half of the intervention group was in the highest baseline quartile. No change in distribution was observed in comparison group. Intervention participants achieved this change by both dietary pattern and vegetable juice consumption. Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75% of the level of change observed in other intervention participants. CONCLUSIONS: Innovative telephone counseling intervention and dietary targets in the Women's Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies.

Adolescent↗

Asian students change their eating patterns after living in the United States.

OBJECTIVE: To collect information on changes in dietary patterns among Asian students before and after immigration to the United States. DESIGN: A questionnaire designed to collect information about background, changes in food habits, and frequency of food consumption from a 72-item food list was mailed to subjects. SUBJECTS/SETTING: Potential participants were students of local universities and junior colleges who were born in China, Taiwan, Hong Kong, Japan, or Korea and were aged 18 years or older. All subjects were required to have been residing in the United States for at least 3 months before the start of the study. Questionnaires were mailed to 120 potential participants. STATISTICAL ANALYSIS: Paired t tests were used to determine differences in eating patterns and frequency of food consumption of subjects before and after immigrating to the United States. RESULTS: Seventy-one questionnaires were returned. Because of missing information on 8 of these questionnaires, only 63 were used in the analysis, which gave a response rate of 53%. The number of students consuming only 2 meals per day increased significantly; 29 (46%) respondents skipped breakfast because of their school schedules. Despite no significant change in the frequency of snack consumption, a majority (n = 46; 73%) of the respondents were consuming more salty and sweet snack items. Subjects were eating out less often, but they were selecting more American-style fast foods when they did eat out. Significant increases were noted in consumption of fats/sweets, diary products, and fruits, and significant decreases were noted in the consumption of meat/meat alternatives and vegetables after immigration to the United States. APPLICATIONS/CONCLUSIONS: Results of this study could be useful to dietetics practitioners as they observe changes in dietary patterns of Asian immigrants. These health professionals can use this information to plan nutrition education programs for Asian groups so that they can make informed decisions in adapting to new eating patterns and make wise food choices in their new environment. It is important to help Asian immigrants retain healthful food habits from their original country and to encourage them to choose eating patterns of the new culture that are nutritionally sound.

Adult↗

Vitamin D intake: a global perspective of current status.

Global high prevalence of vitamin D insufficiency and re-emergence of rickets and the growing scientific evidence linking low circulating 25-hydroxyvitamin D to increased risk of osteoporosis, diabetes, cancer, and autoimmune disorders have stimulated recommendations to increase sunlight (UVB) exposure as a source of vitamin D. However, concern over increased risk of melanoma with unprotected UVB exposure has led to the alternative recommendation that sufficient vitamin D should be supplied through dietary sources alone. Here, we examine the adequacy of vitamin D intake worldwide and evaluate the ability of current fortification policies and supplement use practices among various countries to meet this recommendation. It is evident from our review that vitamin D intake is often too low to sustain healthy circulating levels of 25-hydroxyvitamin D in countries without mandatory staple food fortification, such as with milk and margarine. Even in countries that do fortify, vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited use of dietary supplements, or loss of traditional high fish intakes. Our global review indicates that dietary supplement use may contribute 6-47% of the average vitamin D intake in some countries. Recent studies demonstrate safety and efficacy of community-based vitamin D supplementation trials and food staple fortification introduced in countries without fortification policies. Reliance on the world food supply as an alternative to UVB exposure will necessitate greater availability of fortified food staples, dietary supplement use, and/or change in dietary patterns to consume more fish.

Chronic Disease↗

Parental smoking and the nutrient intake and food choice of British teenagers aged 16-17 years.

STUDY OBJECTIVE: To examine the association between parental smoking habits and the nutrient intake and food choice of teenagers aged 16-17 years, allowing for differences in teenage smoking and the social class and regional distribution of the participants. DESIGN: Data were collected from the 1970 longitudinal birth cohort, cross-sectionally at 16-17 years. The smoking habits of teenagers were evaluated from a questionnaire completed by the subjects themselves, and the smoking habits of parents by interview. The nutrient and food intakes of teenagers were quantitatively assessed using a four day unweighed dietary diary. SETTING: The participants were distributed throughout Britain. PARTICIPANTS: A subsample of 1222 males and 1735 females was isolated from respondents to the 1970 birth cohort 16-17 year data collection sweep undertaken in 1986-87. MAIN RESULTS: Parental smoking habits were associated with different dietary patterns among teenagers regardless of whether the teenagers themselves smoked. Dietary differences noted were similar to those observed previously among smokers, with lower intakes of fibre, vitamin C, vitamin E, folates, and magnesium in particular reported among both males and females in households where parents were smokers. These lower intakes were associated with lower intakes of fruit juices, wholemeal bread, and some vegetables. CONCLUSION: Teenagers who lived with parents who smoked had different nutrient and food intakes to those with non-smoking parents, and teenagers exposed to parental smoking appeared to have similar dietary patterns to teenagers who themselves smoked.

Adolescent↗

Is diet an independent risk factor for mortality? 20 year mortality in the Italian rural cohorts of the Seven Countries Study.

The relation of diet to mortality is examined using the data of the Italian rural cohorts of the Seven Countries Study, a prospective investigation of factors related to cardiovascular disease. The present analysis includes 1536 men aged 45-64 years, whose dietary habits and food consumption, including alcoholic beverages, were measured in 1965. Of the 1536, 668 (43.5%) died during a follow-up period of 20 years. Large differences in survival probabilities were observed for different dietary patterns (i.e. for different intakes of energy and nutrients). The dietary pattern that corresponded to the lowest mortality rate (27% after 20 years) was: more than 2800 kcal/d (11.7 MJ/d), with more than 41% of the calories coming from carbohydrates, more than 9% from proteins, between 16% and 23% from unsaturated lipids, and between 13% and 19% from alcohol. As the number of disagreements from the previous conditions increases, the mortality rate increases to reach 69% in 20 years in the worst case. Differences in mortality persisted after adjustment for confounders and some major established mortality risk factors.

Cardiovascular Diseases↗

Nutritional assessment of patients affected by porphyria variegata.

AIMS: To describe the nutritional status and dietary practices of patients affected by porphyria variegata, paying special attention to the consumption of nutrients that may help or hinder the condition, and to assess the compliance with prevalent nutritional recommendations. METHODS: Cross-sectional study. 24 individuals affected by porphyria variegata (16 females and 8 males; mean age 46.8 (SD 19.5) years) from the Balearic Islands (Spain) recruited through the Balearic Porphyria Association. Dietary questionnaires (7-day dietary record and a semi-quantitative food frequency questionnaire), socio-demographic, lifestyle and health status interviews and anthropometric measurements were carried out. RESULTS: According to current recommendations for the Spanish population and to specific recommendations for porphyria patients, the daily intake of saturated fat (13.2% of total energy), sugars (16.9% of total E), cholesterol (387 mg) and alcoholic beverages (1.1 servings per day) were too high whereas the consumption of total carbohydrates (43.5% of total E), vitamin E (69.5% of RDI), beta-carotene (63.1% of RDI) and vitamin D (42.4% of RDI) was lower than recommended. CONCLUSIONS: Dietary pattern observed among porphyria variegata patients was in line with current dietary trends in the Balearic Islands. Nutritional recommendations to these individuals for the management of porphyria are poorly met. It is necessary to translate these recommendations into food-based dietary guidelines based on prevailing dietary patterns.

Anthropometry↗

Dietary intake in five ageing cohorts of men in Finland, Italy and The Netherlands.

OBJECTIVE: To obtain insight into dietary habits of elderly people and how these habits have evolved from middle to old age. DESIGN: Cross-sectional study of dietary patterns around 1990; retrospective cohort study of changes in dietary intake since middle age. SETTING: Five cohorts: East and West Finland, Zutphen (Netherlands), Crevalcore (Italy), and Montegiorgo (Italy). SUBJECTS: Men aged 70-90 years around 1990. METHODS: Food intake was estimated using a cross-check dietary history adjusted to the local situation. RESULTS: (i) Cross-sectional: Significant differences were observed between the countries for all food groups, energy and nutrients (P < 0.05). The Finnish diet was characterised by a high consumption of animal products and potatoes, the Italian diet by a high consumption of cereals, vegetables, fruits and alcohol. The Dutch diet was generally intermediate. (ii) Longitudinal: The decrease in energy intake since middle age varied from 4.2 MJ/day in the Finnish cohorts to 2.1 MJ/day in Italy. Also the consumption of most food groups decreased but the consumption of vegetables and fruits increased. Saturated fatty acid intake decreased by 3 E% in the Finnish cohorts and decreased by < 1 E% in Italy. Alcohol intake decreased by approximately 7 E% in Italy while it increased by 2.5 E% in the Netherlands. CONCLUSIONS: Although the general patterns of dietary intake of the different cultures still can be recognised at old age, the variation between them has become smaller. Compared to their dietary intake at middle age, however, the dietary pattern of the Finnish and Dutch cohorts has changed slightly in the direction of a healthy diet, while the diet of the Italian men remained Mediterranean, and thus more healthy, at old age.

Aged↗

Age, diet, maximal aerobic capacity and serum lipids.

Eighty males ranging in age from 21 to 75 years were examined for maximal aerobic capacity (VO2max expressed in ml/kg x min-1), serum cholesterol (total, HDL, LDL, and VLDL-cholesterol), serum triglycerides, body fatness (%) and dietary patterns including total and constituent (protein, fat and carbohydrate) kilocalories and dietary cholesterol and alcohol intake. With age, subjects demonstrated a decreased maximal aerobic capacity, increased total serum cholesterol and LDL-cholesterol, increased serum triglycerides and body fatness. Dietary characteristics and HDL-cholesterol did not change with age. Older males (N = 27) with a mean age of 51.7 (+/- 7.2) years were matched for maximal aerobic capacity with younger males (N = 27) with a mean age of 34.2 (+/- 4.5) years. Dietary patterns and total serum cholesterol and HDL, LDL, and VLDL-cholesterol did not differ significantly between groups. Older subjects demonstrated significantly greater body fatness and serum triglycerides. It was concluded that a relationship exists between maximal aerobic capacity and serum cholesterol concentrations. This relationship did not appear to be influenced by dietary characteristics. It was further concluded that the gradual increase in body fatness with age was not attributable to quantitative or qualitative changes in caloric intake.

Adult↗

The effect of modifying dietary calcium intake pattern on the circadian rhythm of bone resorption.

In order to assess day-to-day variations of the circadian rhythm of biochemical bone resorption markers, urinary morning (6-8 a.m.) and evening (7-10 p.m.) samples from 35 individuals were monitored during 3 subsequent days. The bone-specific deoxypyridinoline (DPD) crosslinks of type I collagen followed a circadian rhythm in all individuals. In contrast, no such pattern was observed in the urinary hydroxyproline/creatinine and calcium/creatinine measurements. The DPD crosslink measurements showed a much larger difference between the morning and evening samples collected within 1 day compared with the variation between the samples collected in the morning or evening on subsequent days, indicating the importance of adequate timing of urine sampling for clinical trials aiming to monitor effects on bone resorption. The analysis of DPD crosslinks was then used to evaluate the effects of different patterns of dietary calcium intake on the circadian rhythm of bone resorption in osteoporotic patients. No significant effect on the circadian rhythm of the DPD crosslinks was found after concentrating the normal daily calcium intake to the evening (6-10 p.m.) during 8 days (n = 7). Ingestion of a dietary calcium supplement (600 mg) at 10 p.m. during 8 days (n = 7) resulted in an increased urinary calcium excretion in the morning, and a flattening of the circadian peak and nadir concentrations of urinary DPD/creatinine. The absolute levels of DPD/creatinine in the morning and evening urine samples, respectively, were not significantly altered compared with the control day. We conclude that dietary calcium supplementation in the evening only marginally affects the circadian rhythm of urinary DPD crosslinks in established osteoporosis patients.

Aged↗