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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
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Association of meal timing with body composition and cardiometabolic risk factors in young adults.
Dote-Montero, M, Acosta, FM, Sanchez-Delgado, G, Merchan-Ramirez, E, Amaro-Gahete, FJ, Labayen, I, Ruiz, JR
European journal of nutrition. 2023;62(5):2303-2315
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Despite the known consequences of excess body weight, the prevalence of obesity continues to rise. Body weight regulation and obesity are highly influenced by several factors such as genetics, physiology, and socioeconomic factors. The aim of this study was to elucidate the association of meal timing with anthropometry body composition and cardiometabolic risk factors in young adults. This study was a cross-sectional study of 118 young adults (n=82 women). Results showed that meal timing is not related to anthropometry or body composition parameters in young adults. Similarly, caloric midpoint, eating jetlag and the time from last food intake to midsleep point are not associated with cardiometabolic risk factors. However, a longer daily eating window and a shorter time from midsleep point to first food intake (i.e., earlier first food intake in a 24 h cycle) are associated with a healthier cardiometabolic profile in young men. Authors concluded that eating early in alignment with circadian rhythms may improve cardiometabolic health.
Abstract
PURPOSE To investigate the association of meal timing with body composition and cardiometabolic risk factors in young adults. METHODS In this cross-sectional study participated 118 young adults (82 women; 22 ± 2 years old; BMI: 25.1 ± 4.6 kg/m2). Meal timing was determined via three non-consecutive 24-h dietary recalls. Sleep outcomes were objectively assessed using accelerometry. The eating window (time between first and last caloric intake), caloric midpoint (local time at which ≥ 50% of daily calories are consumed), eating jetlag (variability of the eating midpoint between non-working and working days), time from the midsleep point to first food intake, and time from last food intake to midsleep point were calculated. Body composition was determined by DXA. Blood pressure and fasting cardiometabolic risk factors (i.e., triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and insulin resistance) were measured. RESULTS Meal timing was not associated with body composition (p > 0.05). The eating window was negatively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.348, β = - 0.605; R2 = 0.234, β = - 0.508; all p ≤ 0.003). The time from midsleep point to first food intake was positively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.212, β = 0.485; R2 = 0.228, β = 0.502; all p = 0.003). These associations remained after adjusting for confounders and multiplicity (all p ≤ 0.011). CONCLUSIONS Meal timing seems unrelated to body composition in young adults. However, a longer daily eating window and a shorter time from midsleep point to first food intake (i.e., earlier first food intake in a 24 h cycle) are associated with better cardiometabolic health in young men. CLINICAL TRIAL REGISTRATION NCT02365129 ( https://www. CLINICALTRIALS gov/ct2/show/NCT02365129?term=ACTIBATE&draw=2&rank=1 ).
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners.
Vaisberg, M, Paixão, V, Almeida, EB, Santos, JMB, Foster, R, Rossi, M, Pithon-Curi, TC, Gorjão, R, Momesso, CM, Andrade, MS, et al
Nutrients. 2019;11(7)
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Athletes undergoing high-intensity efforts show increased incidence of upper respiratory tract infections (URTI), both in the context of competitions and during strenuous training. The aim of this study was to evaluate the influence of the daily intake of fermented milk (containing Lactobacillus casei Shirota) on the systemic and upper airway immune/inflammatory responses before and after a race in marathon runners who previously reported upper respiratory symptoms (URS) after an exhaustive physical exercise session. The study is a double-blind randomised clinical study which recruited 42 male amateur marathon runners with an average age of 39 years. The participants were randomly separated into two groups: Lactobacillus casei Shirota group (n=20) or the placebo group (n=22). Results indicate that daily ingestion of fermented milk (containing Lactobacillus casei Shirota) was able to control both immunological and inflammatory responses in the blood and also in the upper airways mucosal of amateurs´ runners after a marathon. Authors conclude that Lactobacillus casei Shirota is able to modulate the systemic and airways immune responses post-marathon, presenting protective effects.
Abstract
BACKGROUND Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. METHODS Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. RESULTS Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. CONCLUSION For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.
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Regaining body weight after weight reduction further increases pulse wave velocity in obese men with metabolic syndrome.
Liang, KW, Lee, WJ, Lee, IT, Lin, SY, Wang, JS, Lee, WL, Sheu, WH
Medicine. 2018;97(40):e12730
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Atherosclerosis can increase stiffness of the aorta and, therefore, increased pulse wave velocity (PWV), which is a predictor for cardiovascular disease and mortality. Metabolic syndrome (MetS), diabetes and obesity increase the risk of aortic stiffness and higher PWV. Weight loss may reduce arterial stiffness but mechanisms are not known. The aim this study was to investigate changes over time of PWV, ankle-brachial index (ABI, a marker for arterial disease of the leg), insulin resistance and inflammatory markers after weight loss and regained weight in obese non-diabetic men with MetS compared to lean controls. Obese participants followed a three months weight loss programme based on diet and exercise during which they lost an average of 8.6kg and saw statistically significant improvements in blood pressure and many biochemical markers but not in PWV or ABI. At the second follow-up visit, at 60 months, they had regained their weight, blood pressure and most biochemical markers were back to baseline whilst PWV and adiponectin were worse than before weight loss. Increases in blood pressure but not weight, hs-CRP (an inflammatory marker) or insulin resistance correlated with the increase in PWV after weight regain. Although healthy controls also gained weight over the 60 months study duration, their increase in PWV was significantly lower than in obese participants. Their PWV was also lower at baseline.
Abstract
Subjects with metabolic syndrome (MetS) or obesity have worse arterial stiffness. However, there have been no studies addressing time-sequential changes in pulse wave velocity (PWV) after weight loss and then regaining weight in obese non-diabetic men with MetS.We prospectively enrolled 40 obese, non-diabetic men with MetS undergoing a 3-month weight reduction program. Another 26 lean and healthy men were recruited for comparisons. Oral glucose tolerance test and brachial ankle (ba) PWV were assessed in study subjects. Eighteen obese non-diabetic MetS and 15 lean control subjects had follow-ups at the 60th month.The body weight of obese MetS decreased from 94.8 ± 7.6 to 86.1 ± 9.0 (N = 18, P < .001) after a 3-month weight reduction program but regained gradually thereafter to 93.6 ± 11.6 kg at the 60th month (P < .001 versus 3rd month). baPWV decreased after weight loss slightly (P = .240) while weight regain significantly increased the baPWV (from 3rd month, 1358 ± 168 to 60th month 1539 ± 264 cm/sec, P < .001). Systolic and diastolic blood pressure increments correlated with the increment of baPWV after weight regain. At the 60th month, lean controls (N = 15) had increases in body weight while their baPWV increased non-significantly. The increments of baPWV after weight regain in obese MetS were significantly higher than the increment of baPWV in lean controls after weight gain.In conclusion, regaining body weight after weight reduction worsened arterial stiffness with significant increase of baPWV in obese non-diabetic MetS.
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The Effect of a 12-Week Health Training Program on Selected Anthropometric and Biochemical Variables in Middle-Aged Women.
Pilch, W, Tota, Ł, Sadowska-Krępa, E, Piotrowska, A, Kępińska, M, Pałka, T, Maszczyk, A
BioMed research international. 2017;2017:9569513
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Regular physical activity is an important factor for health. This study evaluated physiological and biochemical changes induced by a 12 week regular exercise programme in healthy middle-aged women. 15 healthy women aged 42-47 participated in this programme which consisted of three 45 minutes high and low impact aerobics classes for 12 weeks. Body composition and biochemical markers were determined at baseline and after 12 weeks. The investigators observed a significant increase in lean body mass, and a decrease in total weight and fat mass. Biochemical markers showed decreased inflammation, increased antioxidant status and an improvement in lipid profiles (these had been within normal range at baseline). The authors also determined vitamin D status of the participants. Vitamin D levels were within normal range at baseline and did not change during the duration of the study. Higher vitamin D levels were correlated with better antioxidant status. The authors conclude that regular aerobic exercise had beneficial effects on body composition, antioxidant status, inflammatory markers and lipid profiles. The main limitation of this study was a lack of control group.
Abstract
Regular moderate physical activity positively affects health, fitness, and body composition; it regulates the pro- and anti-inflammatory cytokines levels. Vitamin D plays an important regulatory role; its adequate levels correlate with low values of inflammation markers and an increase in muscle strength and fitness in exercising people. The study's aim was to evaluate changes in somatic variables, oxidative stress, and inflammation markers, as well as blood calcidiol concentration in middle-aged healthy women after 12 weeks of aerobics classes-endurance exercises, including choreographic sequences, aiming to improve fitness and motor coordination. The training led to a significant reduction of body mass and fat tissue; it induced an increase in lean body mass. After the 12-week training program, plasma antioxidant status increased (0.65 ± 0.21, p < 0.01) and the concentration of lipid peroxidation products decreased (0.07 ± 0.02, p < 0.001). A significant increase in plasma antioxidant status associated with training could have reduced the level of proinflammatory interleukin as indicated by a positive correlation between these variables (rs = 0.64, p < 0.05). The study proved that a 12-week health training program in physically inactive middle-aged women might provide improvements in their anthropometric parameters and selected biochemical indicators.
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Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males.
Moro, T, Tinsley, G, Bianco, A, Marcolin, G, Pacelli, QF, Battaglia, G, Palma, A, Gentil, P, Neri, M, Paoli, A
Journal of translational medicine. 2016;14(1):290
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Time-restricted feeding (TRF) allows subjects to consume ad libitum energy intake within a defined window of time, which means a fasting window of 12–21 h per day is employed. The aim of the present study was to investigate the effects of an isoenergetic TRF protocol on body composition, athletic performance, and metabolic factors during resistance training in healthy resistance trained males. The study enrolled thirty-four resistance-trained males. The participants were randomly assigned to a TRF group (n = 17) or standard diet group (n = 17). Training was standardized for both groups. Results indicate that after 8 weeks, a significant decrease in fat mass was observed in the TRF group, while fat-free mass was maintained in both groups. The same trend was observed for arm and thigh muscle cross-sectional area. Leg press maximal strength increased significantly, but no difference was present between treatments. Authors conclude that TRF can maintain muscle mass, reducing body fat, and reducing inflammation markers and anabolic hormones. This kind of regimen could be adopted by athletes during maintenance phases of training in which the goal is to maintain muscle mass while reducing fat mass.
Abstract
BACKGROUND Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males. METHODS Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1β, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested. RESULTS After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group. CONCLUSIONS Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.
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Functional biochemical and nutrient indices in frail elderly people are partly affected by dietary supplements but not by exercise.
de Jong, N, Chin A Paw, MJ, de Groot, LC, de Graaf, C, Kok, FJ, van Staveren, WA
The Journal of nutrition. 1999;129(11):2028-36
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Elderly people are at risk of nutritional deficiencies for a variety of reasons including reduced appetite, increased medication, and alterations in the absorption and metabolism of vitamins and minerals with age. The aim of this study was to measure the influence of exercise, and supplementing the diet with vitamins and minerals, on indicators of nutritional and health status in frail elderly people. A 17-week randomised controlled trial was carried out on 145 frail elderly people living in the community. Participants were given either; 1) food products enriched with vitamins D, E, thiamine, riboflavin, B6, folic acid, B12, calcium, magnesium, zinc, iron and iodine; 2) an exercise programme; 3) both enriched food products and exercise programme; or 4) food products that had not been enriched and a social programme (the control group). At the end of the study, significant improvements in the blood levels of vitamins B6, B12, C and D were detected in the groups receiving the enriched food products compared to the controls. There was no additional benefit to be gained from exercise. The improvement in nutritional status did not appear to influence several other biological indicators of health, perhaps because these indicators were already within normal levels at the start of the study. Despite this, the authors concluded that long-term supplementation may help to maintain optimal vitamin and mineral levels in elderly people, and therefore reduce the chance of this population developing health problems related to malnutrition.
Abstract
A decline in dietary intake due to inactivity and, consequently, development of a suboptimal nutritional status is a major problem in frail elderly people. However, benefits of micronutrient supplementation, all-round physical exercise or a combination of both on functional biochemical and hematologic indicators of nutritional and health status in frail elderly subjects have not been tested thoroughly. A 17-wk randomized controlled trial was performed in 145 free-living frail elderly people (43 men, 102 women, mean age, 78 +/- 5.7 y). Based on a 2 x 2 factorial design, subjects were assigned to one of the following: 1) nutrient-dense foods, 2) exercise, 3) both (1) and (2) or 4) a control group. Foods were enriched with micronutrients, frequently characterized as deficient [25-100% of the recommended daily allowance (RDA)] in elderly people. Exercises focused on skill training, including strength, endurance, coordination and flexibility. Dietary intake, blood vitamin levels and nutritional and health indicators, including (pre)albumin, ferritin, transferrin, C-reactive protein, hemoglobin and lymphocytes were measured. At baseline, 28% of the total population had an energy intake below 6.3 MJ, up to a maximum of 93% having vitamin intakes below two thirds of the Dutch RDA. Individual deficiencies in blood at baseline ranged from 3% for erythrocyte glutathione reductase-alpha to 39% for 25-hydroxy vitamin D and 42% for vitamin B-12. These were corrected after 17 wk in the two groups receiving the nutrient-dense foods, whereas no significant changes were observed in the control or exercise group. Biochemical and hematologic indicators at baseline were within the reference ranges (mean albumin, 46 g/L; prealbumin, 0.25 g/L; hemoglobin, 8.6 mmol/L) and were not affected by any of the interventions. The long-term protective effects of nutrient supplementation and exercise, by maintaining optimal nutrient levels and thereby reducing the initial chance of developing critical biochemical values, require further investigation. Other indicative functional variables for suboptimal nutritional status, in addition to those currently selected, should also be explored.