High-protein diets and renal health.

High-protein diets (i.e., protein content of more than 25% of energy or more than 2 g/kg body weight per day) based on meat and dairy products are repeatedly promoted for weight reduction and better health, but the evidence supporting these notions is quite dubious. As described in the present review, there is a reason to be concerned about adverse effects of such diets, including glomerular hyperfiltration, hypertensive effects of a concomitant increase in dietary sodium, and an increased risk of nephrolithiasis. These diet-induced physiological consequences might lead to an increase in the prevalence of chronic kidney disease in the general population without preexisting kidney disease. Accordingly, we find medical reasons to refrain from promoting high-protein diets, in particular those based on meat and dairy products, until clear-cut evidence for the safety and for the superiority of such diets on human health has been provided.

Blood haemoglobin concentrations are higher in smokers and heavy alcohol consumers than in non-smokers and abstainers: should we adjust the reference range?

The blood haemoglobin concentration is one of the most frequently used laboratory parameters in clinical practice. There is evidence that haemoglobin levels are influenced by tobacco smoking. The objective of this study was to evaluate the impact of smoking and alcohol consumption on haemoglobin concentrations in apparently healthy subjects living at sea level. A retrospective, epidemiological cohort study was performed in 1984. Participants were 1,503 men and 1,437 non-pregnant women evenly distributed in age cohorts of 30, 40, 50, and 60 years. Information of smoking habits and alcohol consumption were obtained by a questionnaire. Haemoglobin was measured in the fasting state on Coulter-S. Men displayed no difference in mean haemoglobin levels in the four age groups. In women, mean haemoglobin increased gradually with age (p = 0.001). Fifty-nine percent of men and 50% of women were daily smokers. Female smokers displayed a significant positive correlation between number of cigarettes/day and haemoglobin concentrations (r = 0.12, p = 0.002). Heavy smokers (more than ten cigarettes/day) had significantly higher mean haemoglobin (1.4% higher in men, on average 3.5% higher in women) than non-smokers (p < 0.01). Smokers demonstrated a significant correlation between cigarettes/day and drinks/week in men (r = 0.24, p < 0.001) and women (r = 0.16, p < 0.001). Non-smokers displayed a significant positive correlation between drinks/week and haemoglobin concentrations in men (r = 0.14, p = 0.001) and women (r = 0.08, p = 0.05). In non-smokers, alcohol consumption >14 drinks/week and more than seven drinks/week for men and women, respectively, increased mean haemoglobin by 1.3% in men and by average 1.9% in women compared with those consuming < or =14 and less than or equal to seven drinks/week. Smokers displayed similar results. Body mass index per se had no direct influence on haemoglobin levels but had indirect positive influence in men through its correlation with tobacco smoking and alcohol consumption. Tobacco smoking has an increasing effect on haemoglobin concentrations in both genders, which is proportional to the amount of tobacco smoked. The effect appears to be more pronounced in women. Likewise, high alcohol consumption has an increasing effect on haemoglobin in both genders, being most pronounced in women. However, in clinical biochemistry, the relatively small changes in haemoglobin do not justify the use of separate reference ranges in smokers and alcohol consumers.

The IL-6 -174G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans.

Chronic low-grade elevations in circulating levels of interleukin (IL)-6 act as a marker of subclinical cardiovascular diseases (CVD) and provide an independent predictor of increased mortality in elderly populations. The purpose of the present study was to test the hypothesis that the IL-6 -174G>C promoter polymorphism was associated with a high prevalence of CVD and acted as an independent predictor of mortality in a longitudinal study of 324 relatively healthy 80-year-old people with a history of CVD in 18% of the cases. The C allele was associated with elevated serum levels of IL-6 at baseline and the CC genotype had a high prevalence of CVD. A Cox regression model was used to explore the effect of the polymorphism on survival in the following six years. A significant interaction was found between smoking status and the polymorphism. Thus, C allele carrier status was associated with increased all-cause mortality risk in non-smokers independently of sex, body mass index, co-morbidity, and low-grade elevations in serum levels of IL-6. This effect was not detected among smokers. We conclude that the IL-6 -174G>C polymorphism was an independent predictor of all-cause mortality in octogenarians but the effect was complex and interacted with the smoking status.

Functional decline from age 80 to 85: influence of preceding changes in tiredness in daily activities.

OBJECTIVE: To analyze whether functional decline from age 80 to 85 is influenced by changes in self-reported tiredness in daily activities in the preceding 5-year period. METHOD: A prospective study of 226 75-year-old men and women with 5- and 10-year follow-up in the Western part of Copenhagen County. Tiredness in daily activities was measured at age 75 and 80 by a validated scale. Changes in tiredness from age 75 to 80: 1) Sustained no tiredness, 2) not tired-tired, 3) tired-not tired, 4) sustained tiredness. Functional decline from age 80 to 85:1) Sustained no need of help; 2) need of help at age 85, alive; 3) need of help at age 85 or dead; 4) dead. RESULTS: The analyses among the survivors showed a slight tendency to an association between having sustained tiredness or development of tiredness from age 75 to 80 and functional decline from age 80 to 85. Persons with sustained tiredness from age 75 to 80 were at significantly larger risk of functional decline and mortality from age 80 to 85. These results were not attenuated when adjusted by the covariates. CONCLUSION: The results in the present study indicate that it is important to take continuous complaints about tiredness in daily activities seriously, because this is an early sign of functional decline.

The tumor necrosis factor alpha -308G>A polymorphism is associated with dementia in the oldest old.

OBJECTIVES: To test the hypothesis that the tumor necrosis factor (TNF) -308 G>A promoter gene polymorphism is a risk factor in age-related dementia and longevity. DESIGN: A cross-sectional and a longitudinal study. SETTING: A population-based sample of Danish centenarians. PARTICIPANTS: One hundred-year-old Danes (n=122) from "The Longitudinal Study of Danish Centenarians." Octogenarians (n=174) and healthy volunteers aged 18 to 30 (n=47) served as reference groups. METHODS: Whether the distribution of TNF -308 GG/GA/AA genotypes were different in centenarians than in younger age groups was investigated (Fischer exact test). Furthermore, whether the TNF -308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF-alpha (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort of centenarians was tested. RESULTS: The distribution of TNF -308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-alpha, but the significance was questionable due to a low number of subjects with this genotype. CONCLUSION: It is possible that the TNF -308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory response with regard to protection against age-related neurodegeneration.

Health effects of protein intake in healthy elderly populations: a systematic literature review.

The purpose of this systematic review is to assess the evidence behind the dietary requirement of protein and to assess the health effects of varying protein intake in healthy elderly persons in order to evaluate the evidence for an optimal protein intake. The literature search covered year 2000-2011. Prospective cohort, case-control, and intervention studies of a general healthy population in settings similar to the Nordic countries with protein intake from food-based sources were included. Out of a total of 301 abstracts, 152 full papers were identified as potentially relevant. After careful scrutiny, 23 papers were quality graded as A (highest, n=1), B (n=18), or C (n=4). The grade of evidence was classified as convincing, probable, suggestive, or inconclusive. The evidence is assessed as: probable for an estimated average requirement (EAR) of 0.66 g good-quality protein/kg body weight (BW)/day based on nitrogen balance (N-balance) studies and the subsequent recommended dietary allowance (RDA) of 0.83 g good-quality protein/kg BW/day representing the minimum dietary protein needs of virtually all healthy elderly persons. Regarding the optimal level of protein related to functional outcomes like maintenance of bone mass, muscle mass, and strength, as well as for morbidity and mortality, the evidence is ranging from suggestive to inconclusive. Results from particularly prospective cohort studies suggest a safe intake of up to at least 1.2-1.5 g protein/kg BW/day or approximately 15-20 E%. Overall, many of the included prospective cohort studies were difficult to fully evaluate since results mainly were obtained by food frequency questionnaires that were flawed by underreported intakes, although some studies were 'calibrated' to correct for under- or over-reporting. In conclusion, the evidence is assessed as probable regarding the EAR based on N-balance studies and suggestive to inconclusive regarding an optimal protein intake higher than the estimated RDA assessed from N-balance studies, but an exact level cannot be determined. Potentially adverse effects of a protein intake exceeding 20-23 E% remain to be investigated.

Health effects of protein intake in healthy adults: a systematic literature review.

The purpose of this systematic review is to assess the evidence behind the dietary requirement of protein and to assess the health effects of varying protein intake in healthy adults. The literature search covered the years 2000-2011. Prospective cohort, case-control, and intervention studies were included. Out of a total of 5,718 abstracts, 412 full papers were identified as potentially relevant, and after careful scrutiny, 64 papers were quality graded as A (highest), B, or C. The grade of evidence was classified as convincing, probable, suggestive or inconclusive. The evidence is assessed as: probable for an estimated average requirement of 0.66 g good-quality protein/kg body weight (BW)/day based on nitrogen balance studies, suggestive for a relationship between increased all-cause mortality risk and long-term low-carbohydrate-high-protein (LCHP) diets; but inconclusive for a relationship between all-cause mortality risk and protein intake per se; suggestive for an inverse relationship between cardiovascular mortality and vegetable protein intake; inconclusive for relationships between cancer mortality and cancer diseases, respectively, and protein intake; inconclusive for a relationship between cardiovascular diseases and total protein intake; suggestive for an inverse relationship between blood pressure (BP) and vegetable protein; probable to convincing for an inverse relationship between soya protein intake and LDL cholesterol; inconclusive for a relationship between protein intake and bone health, energy intake, BW control, body composition, renal function, and risk of kidney stones, respectively; suggestive for a relationship between increased risk of type 2 diabetes (T2D) and long-term LCHP-high-fat diets; inconclusive for impact of physical training on protein requirement; and suggestive for effect of physical training on whole-body protein retention. In conclusion, the evidence is assessed as probable regarding the estimated requirement based on nitrogen balance studies, and suggestive to inconclusive for protein intake and mortality and morbidity. Vegetable protein intake was associated with decreased risk in many studies. Potentially adverse effects of a protein intake exceeding 20-23 E% remain to be investigated.

Mobility-related fatigue, walking speed, and muscle strength in older people.

BACKGROUND: Fatigue is an important early marker of functional decline among older people, but the mechanisms underlying this association are not fully understood. The purpose of the present study was to examine the association between mobility-related fatigue and walking speed and to test the degree to which muscle strength accounts for this association. METHODS: The study is based on baseline (n = 523) and 5-year follow-up data (n = 292) from a cohort of 75-year-old persons. Standardized assessments include self-report measures of mobility-related fatigue (score range 0-6) and medical history, as well as performance-based assessment of walking speed and maximal isometric strength of knee extension, body extension, and handgrip. RESULTS: In the cross-sectional baseline analysis, one unit increase in fatigue score was associated with 0.03 m/s (ß = -.03, p < .001) and 0.05 m/s (ß = -.05, p < .001) slower maximum walking speed among women and men, respectively, while adjusting for important covariates. Among women, muscle strength accounted up to 21% and among men up to 24% for the association. In the prospective analysis, fatigue at baseline was predictive of change in walking speed among men (ß = -.04, p < .001) but not among women (ß = -.005, p = .64). Among men, muscle strength accounted up to 15% for the association between baseline fatigue and change in maximum walking speed. CONCLUSIONS: Mobility-related fatigue is associated with slower walking speed in older adults. The results suggest that muscle strength is one of the underlying factors explaining this association.

Evaluation of dietary intake in Danish adults by means of an index based on food-based dietary guidelines.

BACKGROUND: Data on dietary intake and physical activity has been collected from a representative sample of the Danish population from 2003-2008. OBJECTIVES: The aim of the present study was to describe the habitual diet in Denmark and to evaluate the overall diet quality using a diet quality index based on the National Food-Based Dietary Guidelines (FBDG), which consists of seven guidelines regarding diet and one regarding physical activity. DESIGN: Data from the Danish National Survey of Diet and Physical Activity 2003-2008 (n=3354) were included. The diet quality index was constructed based on five of the seven dietary guidelines. Individuals were categorised according to quartiles of the diet quality index, and food and nutrient intakes were estimated in each of the groups. RESULTS: Macronutrient distribution did not meet recommendations in any of the groups, as energy from total fat and especially saturated fat was too high. A high intake of high-fat milk products, fat on bread and processed meat contributed to a high intake of total fat and saturated fat, and sugar-sweetened soft drinks contributed to a high intake of added sugars in the group below the lowest quartile of the diet quality index. Individuals above in the highest quartile had higher intakes of 'healthy foods' such as fish, fruit and vegetables, rye bread, and also a higher consumption of water and wine. Overall, intakes of micronutrients were sufficient in all groups. CONCLUSIONS: The diet quality index is a useful tool in assessing food and nutrient intake in individuals with high vs. low degree of compliance towards the dietary guidelines, and provides a valuable tool in future studies investigating variations in dietary intakes with respect to lifestyle, demographic and regional differences in Denmark.

Brain-derived neurotrophic factor predicts mortality risk in older women.

OBJECTIVES: To test the hypothesis that low circulating brain-derived neurotrophic factor (BDNF), a secretory member of the neurotrophin family that has a protective role in neurodegeneration and stress responses and a regulatory role in metabolism, predicts risk of all-cause mortality in 85-year-old men and women. DESIGN: Longitudinal study with 50- to 58-month follow-up. SETTING: The 1914 cohort, a population-based cohort established in 1964 by the Research Center for Prevention and Health at Glostrup Hospital. PARTICIPANTS: One hundred eighty-eight unselected 85-year-old Danes. MEASUREMENTS: BDNF was measured in plasma and serum. The Danish National Register of Patients was used to collect data on morbidity. The primary outcome in Cox regression analyses was all-cause mortality. RESULTS: Women with low plasma BDNF (lowest tertile) had greater all-cause mortality risk than women with high plasma BDNF (highest tertile) (hazard ratio=2.2, 95% confidence interval=1.1-4.7). Low plasma BDNF predicted mortality independently of activities of daily living; education; and a history of central nervous system disease, cerebrovascular accidents, cardiovascular disease, cancer, respiratory disease, and low-grade inflammation. No association was found between plasma BDNF and mortality in men, and serum BDNF did not influence mortality in either sex. CONCLUSION: Low plasma BDNF is a novel, independent, and robust biomarker of mortality risk in old women. BDNF may be a central factor in the network of multimorbidity in old populations.

Hemoglobin concentrations in 358 apparently healthy 80-year-old Danish men and women. Should the reference interval be adjusted for age?

BACKGROUND AND AIMS: In elderly Danes, reference intervals for hemoglobin (Hb) concentrations are derived from younger population groups. The aim was to examine reference intervals for Hb and cut-off limits for anemia by application of criteria for normality to a representative population of 80-year-olds. METHODS: Participants in this epidemiological health survey cohort were 358 subjects (171 men) 80 years of age. A dietary survey was performed in 232 subjects. Blood samples included Hb, red cell indices, serum ferritin, serum C-reactive protein, renal and hepatic function tests. Normality criteria for Hb were: 1) values in all participants; 2) values in apparently healthy subjects; 3) values in 10-year survivors. Hb was compared with muscle strength, physical performance and diet. RESULTS: In the entire series, median Hb was 140 g/L, 5-95 percentile 116-160 g/L in men, and 131 g/L, 5-95 percentile 114-147 g/L in women (p<0.001). The prevalence of anemia, as defined by World Health Organization (WHO) criteria, was 18% in men and 17% in women. Apparently healthy iron-replete men (n=129) and women (n=141) had median Hb of 141 g/L and 131 g/L. Median Hb levels were higher in 10-year surviving men (143 g/L) than in deceased men (139 g/L), whereas surviving and deceased women had similar median Hb (131 g/L). Hb and muscle strength were significantly correlated. Subjects with physical performance score >or=20 had a lower frequency of anemia. There was no correlation between Hb and dietary or supplemental iron intake. In men, Hb was correlated to meat consumption. CONCLUSIONS: WHO decision limits for anemia should not be lowered in 80-year-old subjects. "Optimal" Hb concentrations with respect to survival appear to be at least 140 g/L in men and 131 g/L in women. Further research should evaluate whether not only treating anemia, but also increasing Hb by using erythropoietin and hematinics, may improve functional status and survival in the elderly.

Health behaviors in elderly people. A 5-year follow-up of 75-year-old people living in three Nordic localities. Smoking, physical activity, alcohol consumption, and healthy eating, and attitudes to their importance.

Few studies about health behavior among elderly persons in the Nordic countries are available, and our knowledge about longitudinal changes is especially limited. The purpose of this study was to assess the prevalence of selected health behaviors as reported at age 75 years in Finland, Sweden and Denmark together with answers regarding attitudes to such habits, and study longitudinal changes between 75 and 80 years. The study population included 499 men and 704 women born in 1914/15 and examined in 1989/90 in Jyväskylä (Finland), Göteborg (Sweden), and Glostrup (Denmark). Survivors were re-examined in 1994/95. A self-administered validated questionnaire developed from the Danish Nationwide Health Surveys was given to the participants during a home visit and checked when the subjects came to the laboratory examination. The Danes had the highest proportion of smokers and persons with daily alcoholic beverage consumption and the smallest proportion of healthy eaters, but the Swedes had the most sedentary life-style. Women had the healthiest life-style. Between ages 75 and 80 years, the proportion of participants who tried to improve their health decreased, but there was no change in believing the importance of one's own effort in maintaining health. The free-time physical activity decreased, but there was no change in the attitude towards physical activity. There were major cross-national differences among the three Nordic localities, but the health behaviors were rather stable, though the proportion of participants who tried to improve their health decreased. Not more than 60 to 70% of the subjects believed that their own efforts are important to health.

Iron status in 358 apparently healthy 80-year-old Danish men and women: relation to food composition and dietary and supplemental iron intake.

In Denmark, the intake of dietary iron has decreased since 1987, when the mandatory iron fortification of flour (30 mg carbonyl iron/kg) was stopped. Since there have been no studies of iron status in elderly Danes after the abolishment of iron fortification, there is a need to assess actual iron status in the elderly population. The objective was to evaluate iron status and the relationship with food composition and dietary and supplemental iron intake in an elderly population in Copenhagen County. Participants in this health examination survey were 358 subjects (171 men, 187 women) 80 years of age from a 1914 cohort study. Blood samples included serum ferritin and hemoglobin (Hb). A dietary survey was performed in 232 subjects (120 men, 112 women) using a dietary history method. Median serum ferritin was 100 microg/l in men and 78 microg/l in women ( p<0.001). Ferritin concentrations <16 microg/l (i.e., depleted iron stores) were found in three men (2%) and in ten women (5%). Median Hb was 140 g/l in men and 131 g/l in women ( p<0.001). Three subjects (0.84%) had iron deficiency anemia (i.e., ferritin <13 microg/l and Hb <5th percentile for iron-replete subjects (121 g/l in men, 114 g/l in women). Ferritin concentrations >300 microg/l (i.e., iron overload) were found in 15 (9%) men and in 5 (3%) women. Median dietary iron intake was higher in men (8.7 mg/day) than in women (7.3 mg/day) ( p<0.001). Serum ferritin was positively correlated to dietary intake of iron, meat, and alcohol and to body mass index in men. Serum ferritin displayed a negative correlation to the consumption of tea. The use of vitamin-mineral supplements containing iron had no influence on iron status. Dietary intake of iron and/or the bioavailability of dietary iron were adequate to maintain a favorable iron status in 80-year-old subjects displaying a low prevalence of iron deficiency and a moderate prevalence of iron overload.