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A Short-Term Ketogenic Diet Impairs Markers of Bone Health in Response to Exercise.

ABSTRACT: Objectives: To investigate diet-exercise interactions related to bone markers in elite endurance athletes after a 3.5-week ketogenic low-carbohydrate, high-fat (LCHF) diet and subsequent restoration of carbohydrate (CHO) feeding. Methods: World-class race walkers (25 male, 5 female) completed 3.5-weeks of energy-matched (220 kJ·kg·d-1) high CHO (HCHO; 8.6 g·kg·d-1 CHO, 2.1 g·kg·d-1 protein, 1.2 g·kg·d-1 fat) or LCHF (0.5 g·kg·d-1 CHO, 2.1 g·kg·d-1 protein, 75-80% of energy from fat) diet followed by acute CHO restoration. Serum markers of bone breakdown (cross-linked C-terminal telopeptide of type I collagen, CTX), formation (procollagen 1 N-terminal propeptide, P1NP) and metabolism (osteocalcin, OC) were assessed at rest (fasting and 2 h post meal) and after exercise (0 and 3 h) at Baseline, after the 3.5-week intervention (Adaptation) and after acute CHO feeding (Restoration). Results: After Adaptation, LCHF increased fasting CTX concentrations above Baseline (p = 0.007, Cohen's d = 0.69), while P1NP (p < 0.001, d = 0.99) and OC (p < 0.001, d = 1.39) levels decreased. Post-exercise, LCHF increased CTX concentrations above Baseline (p = 0.001, d = 1.67) and above HCHO (p < 0.001, d = 0.62), while P1NP (p < 0.001, d = 0.85) and OC concentrations decreased (p < 0.001, d = 0.99) during exercise. Exercise-related area under curve (AUC) for CTX was increased by LCHF after Adaptation (p = 0.001, d = 1.52), with decreases in P1NP (p < 0.001, d = 1.27) and OC (p < 0.001, d = 2.0). CHO restoration recovered post-exercise CTX and CTX exercise-related AUC, while concentrations and exercise-related AUC for P1NP and OC remained suppressed for LCHF (p = 1.000 compared to Adaptation). Conclusion: Markers of bone modeling/remodeling were impaired after short-term LCHF diet, and only a marker of resorption recovered after acute CHO restoration. Long-term studies of the effects of LCHF on bone health are warranted.

SUBMITTER: Heikura IA

PROVIDER: S-EPMC6985427 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Short-Term Ketogenic Diet Impairs Markers of Bone Health in Response to Exercise.

Heikura Ida A IA Burke Louise M LM Hawley John A JA Ross Megan L ML Garvican-Lewis Laura L Sharma Avish P AP McKay Alannah K A AKA Leckey Jill J JJ Welvaert Marijke M McCall Lauren L Ackerman Kathryn E KE

Frontiers in endocrinology 20200121

Objectives: To investigate diet-exercise interactions related to bone markers in elite endurance athletes after a 3.5-week ketogenic low-carbohydrate, high-fat (LCHF) diet and subsequent restoration of carbohydrate (CHO) feeding. Methods: World-class race walkers (25 male, 5 female) completed 3.5-weeks of energy-matched (220 kJ·kg·d-1) high CHO (HCHO; 8.6 g·kg·d-1 CHO, 2.1 g·kg·d-1 protein, 1.2 g·kg·d-1 fat) or LCHF (0.5 g·kg·d-1</su ...[more]

PMID: 32038477

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Project description:There is increasing interest in utilizing short-term dietary interventions in the contexts of cancer, surgical stress and metabolic disease. These short-term diets may be more feasible than extended interventions and may be designed to complement existing therapies. In particular, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used to treat epilepsy, has gained popularity as a potential strategy for weight loss and improved metabolic health. In mice, long-term KD improves insulin sensitivity and may extend lifespan and healthspan. Dietary protein restriction (PR) causes increased energy expenditure, weight loss and improved glucose homeostasis. Since KD is inherently a low-protein diet (10% of calories from protein vs. >18% in control diet), here we evaluated the potential for mechanistic overlap between PR and KD via activation of a PR response. Mice were fed control, protein-free (PF), or one of four ketogenic diets with varying protein content for 8 days. PF and KD both decreased body weight, fat mass, and liver weights, and reduced fasting glucose and insulin levels, compared to mice fed the control diet. However, PF-fed animals had significantly improved insulin tolerance compared to KD. Furthermore, contrary to the PF-fed mice, mice fed ketogenic diets containing more than 5% of energy from protein did not increase hepatic Fgf21 or brown adipose Ucp1 expression. Interestingly, mice fed KD lacking protein demonstrated greater elevations in hepatic Fgf21 than mice fed a low-fat PF diet. To further elucidate potential mechanistic differences between PF and KD and the interplay between dietary protein and carbohydrate restriction, we conducted RNA-seq analysis on livers from mice fed each of the six diets and identified distinct gene sets which respond to dietary protein content, dietary fat content, and ketogenesis. We conclude that KD with 10% of energy from protein does not induce a protein restriction response, and that the overlapping metabolic benefits of KD and PF diets may occur via distinct underlying mechanisms.

Project description:Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6-12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups-exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases structural strength after 8 weeks, making bones best able to resist fracture.

Project description:Postprandial glycemia (PPG) predicts cardiovascular disease, and short-term physical inactivity increases PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if postprandial interstitial glucose (PPIG) was impaired in active older adults following the removal of exercise for 3 days (NOEX) compared to active young adults. In this randomized, crossover study, 11 older (69.1 ± 1.9 years) and 9 young (32.8 ± 1.8 years) habitually active (≥90 min/week of exercise) adults completed 3-days of NOEX and 3-days of normal habitual exercise (EX), separated by ≥1 week. Diet was standardized across phases. Glycemic control (3-day average) was assessed via continuous glucose monitoring during both phases. Significant main effects of age and phase were detected (p < 0.05), but no interaction was found for steps/day (p > 0.05) (old EX: 6283 ± 607, old NOEX: 2380 ± 382 and young EX: 8798 ± 623, young NOEX: 4075 ± 516 steps/day). Significant main effects of age (p = 0.002) and time (p < 0.001) existed for 1-h PPIG, but no effect of phase or interactions was found (p > 0.05). Significant main effects (p < 0.05) of age (old: 114 ± 1 mg/dl, young: 106 ± 1 mg/dl), phase (NOEX: 112 ± 1 mg/dl, EX: 108 ± 1 mg/dl), and time (0 min: 100 ± 2, 30 min: 118 ± 2, 60 min: 116 ± 2, 90 min: 111 ± 2, 120 min: 108 ± 2 mg/dl) in 2-h PPIG were detected, but no interaction was found (p > 0.05). However, only significant main effects of phase (NOEX: 14 ± 1 and EX:12 ± 1, p > 0.05) were found for 24-h blood glucose standard deviation. Older adults appear to have impaired glycemic control compared to young adults and exercise removal impairs glycemic control in both populations. Yet, the impairment in glycemic control with exercise removal is not different between old and young adults.

Dataset Information

A Short-Term Ketogenic Diet Impairs Markers of Bone Health in Response to Exercise.

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A Short-Term Ketogenic Diet Impairs Markers of Bone Health in Response to Exercise.

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