Bone microstructure and metabolism changes under the combined intervention of          ketogenic diet with intermittent fasting: an &lt;i&gt;in vivo&lt;/i&gt; study of          rats

Xu, Xiaolin; Ding, Jianyang; Wu, Xiuhua; Huang, Zucheng; Kong, Ganggang; Liu, Qi; Zhou, Yang; Huang, Zhiping; Zhu, Qingan

doi:10.1538/expanim.18-0084

Cited by 19 publications

(25 citation statements)

References 36 publications

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“…However, it was firstly reported by Hahn that KD had deleterious effects on bone mass in children who maintained this regimen in long term (13). Our previous studies also confirmed that KD compromised bone micro-structures and reduced bone biomechanics in rodents (14)(15)(16)(17)(18). However, the different effects of streptozotocin-induced hyperglycemia and KD-induced hyperketonemia on bone microstructures and biomechanics have not been elucidated.…”

Section: Introductionsupporting

confidence: 64%

“…Researches on the effects of hyperketonemia induced by KD on bone microstructures and bone qualities in rodents were performed in our previous studies. KD deteriorated microstructures of cancellous bone by decreasing bone mass and impairing biomechanical properties, as well as inhibiting osteogenic process and enhancing osteoclastic process in the BMSCs (15,17). Akihiro et al (33) found that ketone bodies bidirectionally modulate osteoblast functions, which suggests that ketone bodies is an important endogenous factor that regulates bone metabolism in both physiological and pathological situations.…”

Section: Discussionmentioning

confidence: 99%

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The Hyperglycemia and Hyperketonemia Impaired Bone Microstructures: A Pilot Study in Rats

Zhou

Xie

et al. 2020

Front. Endocrinol.

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Though diabetes mellitus (DM) is one of the known causes of osteoporosis, it is also realized that ketogenic diet (KD), an effective regimen for epilepsy, impairs bone microstructures. However, the similarities and differences of effects between these two factors are still unknown. The purpose of this study is to identify different effects between hyperglycemia and hyperketonemia, which are manifestations of DM and KD, on bone in rats. Thirty male Sprague-Dawley rats were randomly divided into three groups: the sham, DM, and KD groups. Hyperglycemia was achieved by intravenous injection of streptozotocin in DM group, while hyperketonemia was induced by application of ketogenic diet (carbohydrates-to-fat as 1:3) in KD group. The body weight, blood ketone body, and blood glucose were recorded, and the bone turnover markers, bone length, bone microstructures, bone biomechanics and histomorphology were measured after 12 weeks intervention. Compared with the control and KD groups, a significant body weight loss was found in the DM group, and the bone lengths of tibia and femur of the group were shortened. The blood glucose and blood ketone were noticeably increased in the DM and KD rats, respectively. Microstructures and properties of cancellous bone were significantly deteriorated in both the DM and KD groups compared with the sham group, as the bone volumes were decreased and the bone trabecula structures were disturbed. Meanwhile, the thickness and strength of cortical bone was reduced more in the DM group than those in the sham and KD groups. The HE staining showed that bone trabecula was significantly decreased in both the DM and KD groups, and more adipose tissue was observed in the KD rats. The activity of osteoblasts was decreased more in both the KD and DM groups than that in the sham group, while the activity of osteoclasts of the two groups was remarkably increased. The present study indicates that both hyperglycemia and hyperketonemia have adverse effects on bone. Therefore, it is worth paying more attention to the bone status of patients with hyperglycemia and hyperketonemia in clinic.

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Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

The Hyperglycemia and Hyperketonemia Impaired Bone Microstructures: A Pilot Study in Rats

Zhou

Xie

et al. 2020

Front. Endocrinol.

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“…Studies examining the effect of KD on liver steatosis [125,126], glucose homeostasis [126,127], and dyslipidemia [53,128] remain controversial. Recent evidence expresses potential concerns with the LC/KD compromising bone health in rodents as several studies reported decreases in bone mineral content and bone density [129,130,131]. In a transgenic mouse model of neurodegeneration, KD caused acceleration of the neurodegenerative process and induced mitochondrial dysfunction, despite the promotion of mitochondrial biogenesis [132].…”

Section: Potential Side Effects Of Ketogenic Dietsmentioning

confidence: 99%

Ketogenic Diets and Exercise Performance

2019

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The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed.

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“…Serum ketone testing may also provide us with a regulatory measure to confirm dietary adherence. Not all tissues, however, may benefit from these dietary regimens, particularly bone tissue with concern for resorption and increased catabolism under a ketogenic diet [ 84 , 85 ]. Nevertheless, the behavioral basis of these interventions, along with its unfamiliarity amongst patients and providers, may require the expertise and services of nutritionists to implement these dietary regimens safely and adequately.…”

Section: Discussionmentioning

confidence: 99%

Nerve injury and repair in a ketogenic milieu: A systematic review of traumatic injuries to the spinal cord and peripheral nervous tissue

Sayadi

Satteson

et al. 2021

PLoS ONE

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Dietary interventions such as intermittent fasting and the ketogenic diet have demonstrated neuroprotective effects in various models of neurological insult. However, there has been a lack of evaluation of these interventions from a surgical perspective despite their potential to augment reparative processes that occur following nerve injury. Thus, we sought to analyze the effects of these dietary regimens on nerve regeneration and repair by critical appraisal of the literature. Following PRISMA guidelines, a systematic review was performed to identify studies published between 1950 and 2020 that examined the impact of either the ketogenic diet or intermittent fasting on traumatic injuries to the spinal cord or peripheral nerves. Study characteristics and outcomes were analyzed for each included article. A total of 1,890 articles were reviewed, of which 11 studies met inclusion criteria. Each of these articles was then assessed based on a variety of qualitative parameters, including type of injury, diet composition, timing, duration, and outcome. In total, seven articles examined the ketogenic diet, while four examined intermittent fasting. Only three studies examined peripheral nerves. Neuroprotective effects manifested as either improved histological or functional benefits in most of the included studies. Overall, we conclude that intermittent fasting and the ketogenic diet may promote neuroprotection and facilitate the regeneration and repair of nerve fibers following injury; however, lack of consistency between the studies in terms of animal models, diet compositions, and timing of dietary interventions preclude synthesis of their outcomes as a whole.

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Bone microstructure and metabolism changes under the combined intervention of ketogenic diet with intermittent fasting: an <i>in vivo</i> study of rats

Cited by 19 publications

References 36 publications

The Hyperglycemia and Hyperketonemia Impaired Bone Microstructures: A Pilot Study in Rats

The Hyperglycemia and Hyperketonemia Impaired Bone Microstructures: A Pilot Study in Rats

Ketogenic Diets and Exercise Performance

Nerve injury and repair in a ketogenic milieu: A systematic review of traumatic injuries to the spinal cord and peripheral nervous tissue

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