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Impact of changes in physical activity or BMI on risk of heart failure in women - the prospective population study of women in Gothenburg.
Halldin, AK, Lissner, L, Lernfelt, B, Björkelund, C
Scandinavian journal of primary health care. 2020;38(1):56-65
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Heart failure (HF) is a severe and progressive condition with poor prognosis. Obesity is a risk factor for HF. The aim of this study was to investigate the impact of change in physical activity or change in body mass index on the risk of later developing HF in women without a previous diagnosis of HF. This study is prospective longitudinal study which includes 1749 healthy women from the Prospective Population Study of Women in Gothenburg. Results indicate that gaining weight in early middle age is more harmful than gaining weight later in life, with regard to the risk of developing HF later in life. Furthermore, reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. Authors conclude that the role of physical activity in preventing the development of obesity must be taken into account.
Abstract
Objective: To longitudinally evaluate the impact of change in physical activity or change in body mass index (BMI) over time on the risk of developing heart failure (HF) in women without a previous diagnosis of HF.Design and setting: Longitudinal, observational, prospective study of women in Gothenburg, Sweden. Data on BMI and level of physical activity were collected from examinations 1968-1992 and hospital diagnoses and mortality data were ascertained from 1980 to 2012.Subjects: Data were obtained from 1749 women included in the Prospective Population Study of Women in Gothenburg.Main outcome measures: Hazard ratio (HR) for HF was calculated, using a Cox regression model.Results: Women with stable high physical activity during 1968-1980 and 1980-1992 reduced their risk of subsequent HF compared to the non-active women (for 1968-1980 HR 0.66, 95% Confidence Interval (CI) 0.44-0.99 and for 1980-1992 HR 0.47, 95% CI 0.29-0.74). Women with increasing levels of physical activity during 1980-1992 reduced their risk of HF compared to the non-active women (HR 0.40, 95% CI 0.22-0.72). Increase in BMI from overweight to obesity during 1968-1980 predicted increased risk of developing HF (HR 1.93, 95% CI 1.18-3.14).Conclusions: Reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. This is particularly important for sedentary women in middle age. The role of physical activity in preventing the development of obesity must be taken into account.Key pointsA sedentary lifestyle and obesity are risk factors for developing heart failure (HF) in women.The risk of developing HF may be reduced by increasing the level of activity in sedentary middle-aged women.For younger women, avoiding obesity is most important to reduce the risk of later HF.Primary care has a key role in guiding women towards the most effective lifestyle changes to prevent development of HF.
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Brain-Behavior-Immune Interaction: Serum Cytokines and Growth Factors in Patients with Eating Disorders at Extremes of the Body Mass Index (BMI) Spectrum.
Caroleo, M, Carbone, EA, Greco, M, Corigliano, DM, Arcidiacono, B, Fazia, G, Rania, M, Aloi, M, Gallelli, L, Segura-Garcia, C, et al
Nutrients. 2019;11(9)
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Eating disorders such as anorexia, binge eating and night-time eating cause great fluctuations in body mass and have also been shown to alter the immune system, and more specifically markers of inflammation called cytokines. In this observational study of 90 patients with known eating disorders, the researchers tried to identify how much BMI, ‘underweightness’ and malnutrition influenced the body’s pro-inflammatory response and upset the normal immune response. They found that many inflammatory cytokines were elevated in the blood samples taken, a likely response to the conditions of stress in the body. These cytokines are known to interact with the nervous system and were also influenced by other common symptoms such as depression. They were able to group the differences in cytokines for anorexia nervosa, binge-eating disorder, post-dinner eating, night-eating, sweet-eating and fasting. These markers of dysfunctional eating behaviours may help form part of a therapeutic approach to treating eating disorders based on supporting the immune response and reducing inflammation to stabilise metabolic processes. Future studies in a larger population of patients is necessary to determine the relevance of these findings.
Abstract
Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1α, IL-10, EGF, and IFN-γ were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-γ levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-γ.
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What is the effect of a Mediterranean compared with a Fast Food meal on the exercise induced adipokine changes? A randomized cross-over clinical trial.
Silva, D, Moreira, R, Beltrão, M, Sokhatska, O, Montanha, T, Pizarro, A, Garcia-Larsen, V, Villegas, R, Delgado, L, Moreira, P, et al
PloS one. 2019;14(4):e0215475
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Unhealthy dietary intake and sedentary behaviour in a genetically susceptible individual have been associated with adipokine dysregulation (adipokines are small proteins secreted by the fat tissue) resulting both in adverse metabolic and immune responses. The aim of this study was to evaluate the effect of a Mediterranean (MdM) compared with a Fast Food (FFM) iso-energy meal on the acute exercise-induced adipokine changes. The study is a double-blind randomised crossover clinical trial. Participants (n = 46) were randomly assigned to the intervention order in a double-blinded fashion, stratified by asthma diagnosis. Outcomes were measured blinded to the participant’s allocation order. Results indicate that MdM may blunt the adipsin (an adipokine) immediate response and potentiate its exercise induced increase in comparison with a FFM. MdM slightly attenuated the exercise induced cortisol increase. Authors conclude that their findings highlight the importance of the pre-exercise dietary intake on both the immune and metabolic response to acute exercise.
Abstract
BACKGROUND Adipose tissue-derived adipokines are pro-inflammatory cytokines involved in metabolic-related diseases and can be influenced by diet and exercise. We aimed to compare the effect of a Mediterranean (MdM) compared with Fast Food (FFM) meal on the exercise induced adipokines changes. METHODS In a double blinded cross over trial, 46 participants were randomly assigned to one of two standardized iso-energy pre-exercise meals: FFM or MdM-type. Three hours after each meal, participants completed a treadmill exercise test (EC). Serum adiponectin, resistin, PAI-1, lipocalin-2/NGAL and adipsin were determined by Luminex magnetic bead immunoassay. Wilcoxon signed rank test compared changes before/after meal and before/after EC and a linear mixed model evaluated the effect of meals on the adipokine response to exercise, adjusted for confounders. RESULTS Thirty-nine participants (mean age of 25, with a standard deviation of 5 years) completed the trial (56% females). For both interventions, a significant reduction of adipsin after each meal and a significant increase of lipocalin, PAI-1, adipsin and resistin, after exercise was observed. When exercise was preceded by a MdM meal a higher increase in adipsin levels was seen. CONCLUSION Acute exercise induced an increase of circulatory levels of adipsin, resistin, lipocalin and PAI-1, but not adiponectin. A pre-exercise Mediterranean meal potentiated the increase of adipsin after the exercise test, which possibly relates to the immune regulatory role of adipsin. These changes suggest a cross-talk between the immune and metabolic immediate response to exercise and its modulation by the pre-exercise diet composition.
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Health Biomarkers in Adults Are More Closely Linked to Diet Quality Attributes Than to Plant-Based Diet Categorization.
Mayra, S, Ugarte, N, Johnston, CS
Nutrients. 2019;11(6)
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Plant-based diets rich in fruits, vegetables, whole grains, nuts, and legumes are consistently linked to reduced risk for chronic disease, improved cognition, and longevity. The aim of the study was to examine the diet quality and blood metabolites of vegetarian and omnivore adults to determine adherence to plant-based diets compared to high-quality eating patterns. The study is a cross-sectional investigation. Thirty-three participants (17 vegetarians: 3 men/14 women; 16 omnivores: 3 men/13 women) aged between 18 and 65 years were enrolled for the study. Results indicate the health biomarkers did not differ between vegetarians and omnivores matched for gender, age, and adiposity. However, when participants were regrouped by low-quality versus high-quality diets, data suggests that several common health biomarkers are more closely aligned with diet quality attributes than with plant-based diet categorisation. Authors conclude that healthcare practitioners should emphasize diet quality in their messages to their clients and discuss the importance of eating whole, minimally processed foods with less added fat and sugars.
Abstract
Although plant-based diets are promoted for healthy outcomes, these diets are not synonymous with high-quality diets. Plant-based diets can include highly processed, less healthful foods, including savory snacks, pastries, and sugary fruit drinks. This cross-sectional study examined the diet quality of vegetarian and omnivorous adults, matched for gender, age, and adiposity, and related diet quality to standard health biomarkers. Diet quality was assessed using the Rapid Eating and Activity Assessment for Participants Short Version questionnaire. Participants (17 vegetarians and 16 omnivores; 28.2 ± 8.9 years; 22.5 ± 2.7 kg/m2) were non-smokers and healthy by self-report. The median duration of adherence to the vegetarian diet was 27 months. Physical activity level and diet quality did not differ significantly between diet groups. Moreover, health biomarkers did not differ by diet groups. When participants were regrouped by low versus high diet quality, health biomarkers differed significantly between groups for fasting insulin, HOMA-IR, triglyceride (TG)/HDL ratio, and blood folate, with more favorable levels in the group with high diet quality. These data suggest that health biomarkers more closely align with diet quality attributes than with plant-based diet categorization. Thus, messaging focused on healthy diet attributes may lead to better health outcomes than the simple promotion of plant-based diets.
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Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women.
Khaw, KT, Sharp, SJ, Finikarides, L, Afzal, I, Lentjes, M, Luben, R, Forouhi, NG
BMJ open. 2018;8(3):e020167
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Blood lipids is a term used for fatty substances found in the blood such as cholesterol and triglycerides. When these fatty substances are above a normal level it may increase an individual’s risk factors for coronary heart diseases. A diet high in saturated fats is linked to an increased amount of these fats in the blood. Recent renewed interest in the health effects of saturated fats based on their composition (long chain, medium chain, and short chain) brought about this randomised control trial. The aim of the study was to compare the effects of butter, extra virgin coconut oil and olive oil on blood lipids. The study population were men and women aged between 50 and 70 years who did not have any known medical history of heart disease or were on any medication related to heart disease. At the end of the four week trial period, significant changes in the blood lipids were observed within the three intervention groups. The concentration of LDL cholesterol in the butter group when compared with coconut oil and olive oil showed a significant increase, whilst no difference was observed in the LDL cholesterol concentration between the olive oil and coconut oil group. The concentration of HDL cholesterol in the coconut oil group increased significantly in comparison to the butter or olive oil group. However, the authors concluded that as further trials between different fatty acids and health are required, the current recommendation of the American Heart Association - to reduce saturated fat in general - is strongly recommended.
Abstract
INTRODUCTION High dietary saturated fat intake is associated with higher blood concentrations of low-density lipoprotein cholesterol (LDL-C), an established risk factor for coronary heart disease. However, there is increasing interest in whether various dietary oils or fats with different fatty acid profiles such as extra virgin coconut oil may have different metabolic effects but trials have reported inconsistent results. We aimed to compare changes in blood lipid profile, weight, fat distribution and metabolic markers after four weeks consumption of 50 g daily of one of three different dietary fats, extra virgin coconut oil, butter or extra virgin olive oil, in healthy men and women in the general population. DESIGN Randomised clinical trial conducted over June and July 2017. SETTING General community in Cambridgeshire, UK. PARTICIPANTS Volunteer adults were recruited by the British Broadcasting Corporation through their websites. Eligibility criteria were men and women aged 50-75 years, with no known history of cancer, cardiovascular disease or diabetes, not on lipid lowering medication, no contraindications to a high-fat diet and willingness to be randomised to consume one of the three dietary fats for 4 weeks. Of 160 individuals initially expressing an interest and assessed for eligibility, 96 were randomised to one of three interventions; 2 individuals subsequently withdrew and 94 men and women attended a baseline assessment. Their mean age was 60 years, 67% were women and 98% were European Caucasian. Of these, 91 men and women attended a follow-up assessment 4 weeks later. INTERVENTION Participants were randomised to extra virgin coconut oil, extra virgin olive oil or unsalted butter and asked to consume 50 g daily of one of these fats for 4 weeks, which they could incorporate into their usual diet or consume as a supplement. MAIN OUTCOMES AND MEASURES The primary outcome was change in serum LDL-C; secondary outcomes were change in total and high-density lipoprotein cholesterol (TC and HDL-C), TC/HDL-C ratio and non-HDL-C; change in weight, body mass index (BMI), waist circumference, per cent body fat, systolic and diastolic blood pressure, fasting plasma glucose and C reactive protein. RESULTS LDL-C concentrations were significantly increased on butter compared with coconut oil (+0.42, 95% CI 0.19 to 0.65 mmol/L, P<0.0001) and with olive oil (+0.38, 95% CI 0.16 to 0.60 mmol/L, P<0.0001), with no differences in change of LDL-C in coconut oil compared with olive oil (-0.04, 95% CI -0.27 to 0.19 mmol/L, P=0.74). Coconut oil significantly increased HDL-C compared with butter (+0.18, 95% CI 0.06 to 0.30 mmol/L) or olive oil (+0.16, 95% CI 0.03 to 0.28 mmol/L). Butter significantly increased TC/HDL-C ratio and non-HDL-C compared with coconut oil but coconut oil did not significantly differ from olive oil for TC/HDL-C and non-HDL-C. There were no significant differences in changes in weight, BMI, central adiposity, fasting blood glucose, systolic or diastolic blood pressure among any of the three intervention groups. CONCLUSIONS AND RELEVANCE Two different dietary fats (butter and coconut oil) which are predominantly saturated fats, appear to have different effects on blood lipids compared with olive oil, a predominantly monounsaturated fat with coconut oil more comparable to olive oil with respect to LDL-C. The effects of different dietary fats on lipid profiles, metabolic markers and health outcomes may vary not just according to the general classification of their main component fatty acids as saturated or unsaturated but possibly according to different profiles in individual fatty acids, processing methods as well as the foods in which they are consumed or dietary patterns. These findings do not alter current dietary recommendations to reduce saturated fat intake in general but highlight the need for further elucidation of the more nuanced relationships between different dietary fats and health. TRIAL REGISTRATION NUMBER NCT03105947; Results.
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Comparison of low calorie high protein and low calorie standard protein diet on waist circumference of adults with visceral obesity and weight cycling.
Witjaksono, F, Jutamulia, J, Annisa, NG, Prasetya, SI, Nurwidya, F
BMC research notes. 2018;11(1):674
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Obesity has become one of the world’s biggest health problem. Obese individuals with a history of repeated weight loss and regain (called weight cycling) have a higher risk of developing chronic disease and increased fat mass in every cycle. The objective of the study was to evaluate the effect of a low calorie high protein diet compared to a low calorie standard protein diet on waist circumference in adults with visceral obesity. The open, randomised clinical trial recruited 61 obese subjects who are older than 20 years of age and had a history of weight cycling. Participants were randomly assigned to one of the two diet groups; high protein or standard protein. Results showed that following a low-calorie diet resulted in waist circumference reduction thus reducing visceral fat. However, protein composition in the diet plan did not affect waist circumference reduction. Authors conclude that calorie restricted diets could be suggested in the treatment of visceral obesity. Macronutrient composition can be adjusted to meet the patient’s individual needs.
Abstract
OBJECTIVES Many individuals with visceral obesity who previously had succeeded in reducing body weight regain and this loss-gain cycle repeats several times which is called as weight cycling. We aimed to evaluate the effect of a low calorie high protein diet (HP) compared to a low calorie standard protein diet (SP) on waist circumference of visceral obese adults with history of weight cycling. RESULTS In this open-randomized clinical trial, participants were asked to follow dietary plan with reduction in daily caloric intake ranging from 500 to 1000 kcal from usual daily amount with minimum daily amount of 1000 kcal for 8 weeks and were divided in two groups: HP group with protein as 22-30% total calorie intake; and SP group with protein as 12-20% total calorie intake. There was a statistically significant difference (P < 0.001) between waist circumference before and after the dietary intervention among both groups. Meanwhile, there was no statistically significant difference in the mean reduction of waist circumference between HP and SP groups (P = 0.073). Taken together, the protein proportion does not significantly affected waist circumference. Trial registration ClinicalTrials.gov NCT03374150, 11 December 2017.
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Acute Endothelial Benefits of Fat Restriction over Carbohydrate Restriction in Type 2 Diabetes Mellitus: Beyond Carbs and Fats.
Barbosa-Yañez, RL, Dambeck, U, Li, L, Machann, J, Kabisch, S, Pfeiffer, AFH
Nutrients. 2018;10(12)
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The control of type 2 diabetes mellitus has become a global challenge. Cardiovascular disease is a major cause of mortality in type 2 diabetes. The aim of the study is to examine and compare the effect of a hypocaloric very low carbohydrate diet versus hypocaloric low-fat diet on vascular function and visceral adipose tissue in type 2 diabetic patients. The study is a randomised parallel group intervention study with adult type 2 diabetes patients with an age range between 42 and 76 years. Results show that both dietary strategies effectively reduced body weight, total adipose tissue, visceral adipose tissue and lipid accumulation in the liver. However, participants following the low-fat diet experienced greater vascular function enhancements. Authors conclude that low-fat diet elicited advantageous effects on vascular function in patients with type 2 diabetes.
Abstract
BACKGROUND Cardiovascular diseases (CVD) are the major cause of mortality in type 2 diabetes patients (T2DM). The causes are embedded in a complex interplay between excess body fat, insulin resistance and serum lipid anomalies. Endothelial homeostasis is strongly affected by this pathogenic network. Even though metabolic changes and weight loss improve vascular endothelial function, the effect of different dietary approaches is still uncertain for type 2 diabetes patients. OBJECTIVE We aimed to compare the acute effects of a hypocaloric very low carbohydrate (VLC) diet versus a hypocaloric low fat (LF) diet on flow mediated dilation (FMD), intrahepatic lipid (IHL) accumulation and visceral adipose tissue as independent risk factors of CVD in T2DM patients. DESIGN 36 T2DM patients (age 63 ± 8 years, 60% females) were randomly assigned to the VLC diet (4⁻10% of total energy intake (E)) or to the LF diet (<30% E) for 3 weeks. Endothelial function was assessed by the flow mediated dilation (FMD) method. Adipose tissue depots and IHL were determined by magnetic resonance. RESULTS Both dietary strategies reduced body weight, body fat content and IHL. Unexpectedly, the LF group experienced significantly greater enhancement of FMD, compared to the VLC group. The FMD showed a positive correlation with protein intake and fat intake in the LF group, while it revealed a negative correlation with protein intake in the VLC diet group. CONCLUSIONS Reduction of total and hepatic adiposity was shown to be successful using either the VLC or LF hypocaloric diets, however, improvements in FMD may be related to the interplay of fat and protein intake.
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Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program.
Kim, C, Dabelea, D, Kalyani, RR, Christophi, CA, Bray, GA, Pi-Sunyer, X, Darwin, CH, Yalamanchi, S, Barrett-Connor, E, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2017;102(9):3381-3389
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It is not currently known to what extent changes in different types of fat stores (visceral fat that surrounds organs and subcutaneous fat that sits under the surface of the skin) relate to changes in sex hormones. This study was a secondary analysis of a randomised controlled trial including 555 individuals. It examined whether changes to visceral and subcutaneous fat were associated with changes in sex hormones (DHEA, testosterone, oestrogen and sex hormone binding globulin - SHBG) among overweight individuals with glucose intolerance under the care of a diabetes program. Participants were randomly assigned to an intensive lifestyle modification programme (goals for weight reduction and 150 mins exercise weekly), medication (metformin) or placebo for 12 months. The authors found that among men, reductions in both types of fat were associated with significant increases in total testosterone and SHBG. Among women, reductions in both types of fat were associated with increases in SHBG and associations with estrone differed by menopausal status. No associations were found between changes in fat stores and estradiol or DHEA. The authors conclude that weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat. -
Abstract
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design: Secondary analysis of a randomized trial. Participants: Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions: Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main Outcome Measures: Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results: Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions: Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.
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Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial.
Villareal, DT, Fontana, L, Das, SK, Redman, L, Smith, SR, Saltzman, E, Bales, C, Rochon, J, Pieper, C, Huang, M, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2016;31(1):40-51
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While there is increasing evidence that caloric restriction (CR) can extend a healthy lifespan in humans, it is not known whether weight loss is linked to reductions in bone mineral density (BMD) in younger adults. The aim of this trial was to assess the effect of prolonged caloric restriction on bone mass density and bone metabolism in 218 healthy adults aged 21 to 40. Participants were randomised to either a 25% caloric restriction or ad libitum diet for two years. The findings of this study showed that the CR group had a larger increase in markers of bone turnover and caused a modest but significant decline in bone mineral density. Based on these findings, the authors suggest that further research is needed to determine whether bone loss increases fracture risk, and whether interventions can prevent bone loss that occurs with CR-induced weight loss.
Abstract
Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1 ± 1.7 kg/m(2) ), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (-5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat-free mass (-2.2 ± 0.2 versus -0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (-0.013 ± 0.003 versus 0.007 ± 0.004 g/cm(2) ; p < 0.001), total hip (-0.017 ± 0.002 versus 0.001 ± 0.003 g/cm(2) ; p < 0.001), and femoral neck (-0.015 ± 0.003 versus -0.005 ± 0.004 g/cm(2) ; p = 0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone-specific alkaline phosphatase (BSAP) (-1.4 ± 0.4 versus -0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (-1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ∼31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long-term studies are needed to determine if CR-induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise.