The effect of the ketogenic diet on the developing skeleton

Simm, Peter; Bicknell-Royle, Jillian; Lawrie, Jock; Nation, Judy; Draffin, Kellie; Stewart, Karen; Cameron, Fergus; Scheffer, Ingrid E.; Mackay, Mark T

doi:10.1016/j.eplepsyres.2017.07.014

Cited by 52 publications

(45 citation statements)

References 22 publications

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“…No significant alteration of osteocalcin on cellular levels was found in mice fed with ketogenic diet . Similarly, human data also suggested that no changes were found in osteocalcin levels in patients receiving ketogenic diet treatment . Furthermore, we did not find significant changes in bone‐specific alkaline phosphatase (BSAL), another marker that represented bone formation.…”

Section: Discussionsupporting

confidence: 45%

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes

Zhu

Lin

Chen

et al. 2020

Diabetes Metabolism Res

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Aims: Osteocalcin contributes to the regulation of endocrine system. However, the association between osteocalcin and ketosis has not been evaluated. We thus aimed to explore the relationship between total osteocalcin and risk of ketosis in type 2 diabetes (T2DM). Materials and methods:We identified 6157 diabetes patients from Shanghai Tenth People's Hospital between 1 January 2011 and 1 March 2017. Six hundred eight subjects were enrolled in the retrospective cross-sectional study: 304 T2DM patients with ketosis whose age, gender, and body mass index were matched with 304 T2DM patients without ketosis. A further retrospective nested case-control study was conducted in 252 T2DM patients without ketosis for a mean duration of 21.58 ± 12.43 months to investigate the occurrence of ketosis. Results: Osteocalcin levels were negatively correlated with blood ketones (adjusted r = −0.263) and urine ketones (adjusted r = −0.183). The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio [95% CI] = 2.56 [0.80-8.17], 3.71 [0.90-15.29], 10.77 [2.63-44.15], 23.81 [4.32-131.17] per osteocalcin quintile, respectively). Ketosis occurred in 17 of the 252 T2DM patients during follow-up. The Cox regression analysis indicated that osteocalcin was an independent protective factor against development of ketosis (adjusted hazard ratio [95% CI]: 0.668 [0.460-0.971]). Conclusions: Total osteocalcin can be used as a predictor of ketosis in T2DM. K E Y W O R D S ketosis, total osteocalcin, type 2 diabetes Bing Zhu and Ziwei Lin contributed equally as co-first authors.

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Section: Discussionsupporting

confidence: 45%

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes

Zhu

Lin

Chen

et al. 2020

Diabetes Metabolism Res

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“…One explanation for these divergent outcomes involves interactions of the LCHF diet with the level of habitual contractile activity. Indeed in mice, a LCHF diet negated the positive benefits of exercise on BMD in trabecular bone (16), while in children with epilepsy, the rate of bone loss was greater in the more active patients (14). Therefore, the hormonal response to exercise undertaken with low CHO availability was of particular interest in our study.…”

Section: Discussionmentioning

confidence: 87%

“…However, data from animal studies (12,13) demonstrate that chronic LCHF diets are associated with impaired bone growth, reduced bone mineral content, compromised mechanical properties, and slower fracture healing. Furthermore, increased bone loss has been reported in children with intractable epilepsy placed on a medically supervised LCHF diet for 6 months (14,15). In contrast, adults with type 2 diabetes mellitus who self-selected to consume a LCHF diet for 2 years experienced no changes in spinal BMD in comparison to a "usual care" group (22).…”

Section: Discussionmentioning

confidence: 99%

“…Whether these changes in markers of bone metabolism persist (or are amplified) after chronic exposure to low CHO availability around exercise remains unknown, but is of relevance in view of the promotion of a ketogenic low CHO-high fat (LCHF) diet to athletes and its putative benefits for endurance performance (11). To date, no studies have examined the effects of longerterm restriction of CHO at rest or in relation to exercise, although in animal models and children with intractable epilepsy, chronic adaptation to a ketogenic LCHF diet is associated with poor bone health (12)(13)(14)(15)(16). In view of our recent observations of increased post-exercise IL-6 concentrations in elite race walkers following a 3.5-week adaptation to a LCHF diet (17), we investigated the interaction of this diet and strenuous exercise on markers of bone modeling/remodeling as secondary outcomes of our larger study.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Patients on a ketogenic diet have been shown to have low BMD, and there was a significant association between low BMD and duration of dietary therapy. 76) Ketogenic diet-induced ketosis causes a chronic ketoacidotic state, which leads to decreased absorption of vitamin D, secondary activation of PTH, and increased bone resorption. 6) The high incidence of renal calculi and the elevated urine calcium:creatinine ratio observed in patients on a ketogenic diet also indicate a major effect of the www.e-apem.org ketogenic diet on calcium metabolism.…”

Section: Ketogenic Dietmentioning

confidence: 99%

Bone health in pediatric patients with neurological disorders

Kong

Samadov

et al. 2020

Ann Pediatr Endocrinol Metab

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Patients with neurological disorders are at high risk of developing osteoporosis, as they possess multiple risk factors leading to low bone mineral density. Such factors include inactivity, decreased exposure to sunlight, poor nutrition, and the use of medication or treatment that can cause lower bone mineral density such as antiepileptic drugs, ketogenic diet, and glucocorticoids. In this article, mechanisms involved in altered bone health in children with neurological disorders and management for patients with epilepsy, cerebral palsy, and Duchenne muscular dystrophy regarding bone health are reviewed.

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The effect of the ketogenic diet on the developing skeleton

Cited by 52 publications

References 22 publications

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes

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

Bone health in pediatric patients with neurological disorders

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