bims-kimdis Biomed News
on Ketones, inflammation and mitochondria in disease
Issue of 2024–04–28
eight papers selected by
Matías Javier Monsalves Álvarez, Universidad Andrés Bello



  1. Epilepsia Open. 2024 Apr 20.
      The ketogenic diet (KD) can have a negative impact on the linear growth and body composition of children. The aims of this study were to review two centers' experience with children who developed height deceleration on the KD and determine if the height deceleration was secondary to growth hormone deficiency (GHD), and if growth hormone therapy (GHT) would be effective and safe (not altering ketosis or seizure frequency). Retrospective chart reviews were performed on patients with KD referred to Endocrinology between 2013 and 2018. Seventeen children were identified. Data reviewed included: demographics, growth velocity, KD ratio, protein/calorie intake, lab results, GH dosage, Tanner stage, and seizure frequency, and endocrine recommendations. Descriptive statistics were performed. Of the 17 children referred to the Endocrine Division, seven children were growth hormone deficient and began GHT. Data were provided for six patients (2 males, 4 females; age 2-7 years at the start of KD) on the KD for >6 years and on GHT for >4 years. Growth for all patients stabilized or increased. IGF-1 z-scores normalized. GHT did not affect seizure frequency or ketosis. GHT in those with GHD can be an appropriate option allowing better growth while still maintaining ketogenic therapy and seizure control. PLAIN LANGUAGE SUMMARY: The KD can be an effective treatment for difficult-to-control epilepsy and some disorders of carbohydrate metabolism. The KD can adversely affect the linear growth (height) of children. This case series reviewed six patients who had slow linear growth. It was found that all six children had growth hormone deficiency, grew better with growth hormone treatments, and that their seizures and ketone levels were not affected.
    Keywords:  epilepsy; growth; growth hormone treatment; ketogenic diet; seizures; stature
    DOI:  https://doi.org/10.1002/epi4.12942
  2. Front Endocrinol (Lausanne). 2023 ;14 1287140
      Bone health encompasses not only bone mineral density but also bone architecture and mechanical properties that can impact bone strength. While specific dietary interventions have been proposed to treat various diseases such as obesity and diabetes, their effects on bone health remain unclear. The aim of this review is to examine literature published in the past decade, summarize the effects of currently popular diets on bone health, elucidate underlying mechanisms, and provide solutions to neutralize the side effects. The diets discussed in this review include a ketogenic diet (KD), a Mediterranean diet (MD), caloric restriction (CR), a high-protein diet (HP), and intermittent fasting (IF). Although detrimental effects on bone health have been noticed in the KD and CR diets, it is still controversial, while the MD and HP diets have shown protective effects, and the effects of IF diets are still uncertain. The mechanism of these effects and the attenuation methods have gained attention and have been discussed in recent years: the KD diet interrupts energy balance and calcium metabolism, which reduces bone quality. Ginsenoside-Rb2, metformin, and simvastatin have been shown to attenuate bone loss during KD. The CR diet influences energy imbalance, glucocorticoid levels, and adipose tissue, causing bone loss. Adequate vitamin D and calcium supplementation and exercise training can attenuate these effects. The olive oil in the MD may be an effective component that protects bone health. HP diets also have components that protect bone health, but their mechanism requires further investigation. In IF, animal studies have shown detrimental effects on bone health, while human studies have not. Therefore, the effects of diets on bone health vary accordingly.
    Keywords:  Mediterranean diet (MD); bone health; caloric restriction (CR); high-protein diet; intermittent fasting (IF); ketogenic diet (KD)
    DOI:  https://doi.org/10.3389/fendo.2023.1287140
  3. Obesity (Silver Spring). 2024 May;32(5): 949-958
       OBJECTIVE: We investigated how changes in 24-h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake.
    METHODS: Forty-four healthy, weight-stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m2) underwent 24-h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24-h fasting. Immediately after each chamber stay, participants were allowed 24-h ad libitum food intake from computerized vending machines.
    RESULTS: Twenty-four-hour RER decreased by 9.4% (95% CI: -10.4% to -8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], -2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24-h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24-h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting (r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = -0.27, p = 0.07, respectively).
    CONCLUSIONS: Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake.
    DOI:  https://doi.org/10.1002/oby.24011
  4. J Leukoc Biol. 2024 Apr 22. pii: qiae097. [Epub ahead of print]
      Link et al. conducted a controlled study comparing the impacts of ketogenic and vegan diets on energy intake and immune function in humans. Deep -omics analyses revealed distinct effects of each diet on the immune system, including changes in cell populations and blood transcriptomes indicative of diet-induced shifts between adaptive and innate immunity. The study highlights the potentially significant, rapid impact of diet on immune function and health.
    Keywords:  immunity; ketogenic diet; microbiome; vegan diet
    DOI:  https://doi.org/10.1093/jleuko/qiae097
  5. Clin Nutr. 2024 Apr 09. pii: S0261-5614(24)00115-8. [Epub ahead of print]43(6): 1250-1260
       BACKGROUND & AIM: Dysfunction of skeletal muscle satellite cells might impair muscle regeneration and prolong ICU-acquired weakness, a condition associated with disability and delayed death. This study aimed to elucidate the distinct metabolic effects of critical illness and β-OH-butyrate on satellite cells isolated from these patients.
    METHODS: Satellite cells were extracted from vastus lateralis muscle biopsies of patients with ICU-acquired weakness (n = 10) and control group of healthy volunteers or patients undergoing elective hip replacement surgery (n = 10). The cells were exposed to standard culture media supplemented with β-OH-butyrate to assess its influence on cell proliferation by ELISA, mitochondrial functions by extracellular flux analysis, electron transport chain complexes by high resolution respirometry, and ROS production by confocal microscopy.
    RESULTS: Critical illness led to a decline in maximal respiratory capacity, ATP production and glycolytic capacity and increased ROS production in ICU patients' cells. Notably, the function of complex II was impaired due to critical illness but restored to normal levels upon exposure to β-OH-butyrate. While β-OH-butyrate significantly reduced ROS production in both control and ICU groups, it had no significant impact on global mitochondrial functions.
    CONCLUSION: Critical illness induces measurable bioenergetic dysfunction of skeletal muscle satellite cells. β-OH-butyrate displayed a potential in rectifying complex II dysfunction caused by critical illness and this warrants further exploration.
    Keywords:  Critical illness; ICU-acquired muscle weakness; Mitochondria; Skeletal muscle cells; β-OH-butyrate
    DOI:  https://doi.org/10.1016/j.clnu.2024.04.009
  6. Nutrition. 2024 Mar 09. pii: S0899-9007(24)00070-4. [Epub ahead of print]124 112420
       OBJECTIVES: A ketogenic diet reduces pathologic stress and improves mood in neurodegenerative and neurodevelopmental disorders. However, the effects of a ketogenic diet for people from the general population have largely been unexplored. A ketogenic diet is increasingly used for weight loss. Research in healthy individuals primarily focuses on the physical implications of a ketogenic diet. It is important to understand the holistic effects of a ketogenic diet, not only the physiological but also the psychological effects, in non-clinical samples. The aim of this cross-sectional study with multiple cohorts was to investigate the association of a ketogenic diet with different aspects of mental health, including calmness, contentedness, alertness, cognitive and emotional stress, depression, anxiety, and loneliness, in a general healthy population.
    METHODS: Two online surveys were distributed: cohort 1 used Bond-Lader visual analog scales and Perceived Stress Scale (n = 147) and cohort 2 the Depression Anxiety Stress Scale and revised UCLA Loneliness Scale (n = 276).
    RESULTS: A ketogenic diet was associated with higher self-reported mental and emotional well-being behaviors, including calmness, contentedness, alertness, cognitive and emotional stress, depression, anxiety, and loneliness, compared with individuals on a non-specific diet in a general population.
    CONCLUSION: This research found that a ketogenic diet has potential psychological benefits in the general population.
    Keywords:  Anxiety; Depression; Ketogenic diet; Loneliness; Mood; Stress
    DOI:  https://doi.org/10.1016/j.nut.2024.112420
  7. Biomolecules. 2024 Apr 18. pii: 493. [Epub ahead of print]14(4):
       BACKGROUND: Mitochondria are the 'powerhouses of cells' and progressive mitochondrial dysfunction is a hallmark of aging in skeletal muscle. Although different forms of exercise modality appear to be beneficial to attenuate aging-induced mitochondrial dysfunction, it presupposes that the individual has a requisite level of mobility. Moreover, non-exercise alternatives (i.e., nutraceuticals or pharmacological agents) to improve skeletal muscle bioenergetics require time to be effective in the target tissue and have another limitation in that they act systemically and not locally where needed. Mitochondrial transplantation represents a novel directed therapy designed to enhance energy production of tissues impacted by defective mitochondria. To date, no studies have used mitochondrial transplantation as an intervention to attenuate aging-induced skeletal muscle mitochondrial dysfunction. The purpose of this investigation, therefore, was to determine whether mitochondrial transplantation can enhance skeletal muscle bioenergetics in an aging rodent model. We hypothesized that mitochondrial transplantation would result in sustained skeletal muscle bioenergetics leading to improved functional capacity.
    METHODS: Fifteen female mice (24 months old) were randomized into two groups (placebo or mitochondrial transplantation). Isolated mitochondria from a donor mouse of the same sex and age were transplanted into the hindlimb muscles of recipient mice (quadriceps femoris, tibialis anterior, and gastrocnemius complex).
    RESULTS: The results indicated significant increases (ranging between ~36% and ~65%) in basal cytochrome c oxidase and citrate synthase activity as well as ATP levels in mice receiving mitochondrial transplantation relative to the placebo. Moreover, there were significant increases (approx. two-fold) in protein expression of mitochondrial markers in both glycolytic and oxidative muscles. These enhancements in the muscle translated to significant improvements in exercise tolerance.
    CONCLUSIONS: This study provides initial evidence showing how mitochondrial transplantation can promote skeletal muscle bioenergetics in an aging rodent model.
    Keywords:  endurance; energy production; exercise physiology
    DOI:  https://doi.org/10.3390/biom14040493
  8. J Physiol. 2024 Apr 23.
      
    Keywords:  glycogen depletion; journal club; metabolic stress; muscle excitability; muscle fatigue; protein signalling
    DOI:  https://doi.org/10.1113/JP286454