MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Ketodiety

Ketodiety - Ketogenic diets

  • Comprise very low carbohydrate levels
  • Substantial amounts of protein
  • High fat levels
  • Production of high levels of ketone bodies (3HB, AcAc and acetone)

Terapeutické využití

  • One of the most effective therapies for
    • Drug-resistant epilepsy
  • Specific benefits in:
    • GLUT protein I (GLUT-I) deficiency
    • Pyruvate dehydrogenase deficiency,
    • Myoclonic astatic epilepsy (Doose syndrome)
    • Tuberous sclerosis complex
    • Rett syndrome
    • Severe myoclonic epilepsy in infancy (Dravet syndrome)

Mechanismus působení

  • Modulation of ATP-sensitive potassium channels,
  • Enhanced neurotransmission
  • Increased brain-derived neurotrophic factor expression due to glycolytic restriction
  • Reduced neuroinflammation
  • Rats maintained on a KD display
    • Altered influx of nutrients to the brain
      • Up-regulation of both ketone transporters and GLUT type 1
  • Classic KD leads to a higher risk of atherosclerosis
  • Fatty acid content of the KD influences this risk of atherosclerosis:
    • Classic KD contains a 4:1 or 3:1 ratio (by weight) of fat to combined protein and carbohydrate
      • Most of this fat being LCFA
  • Altered KD that are rich in MCFA, sometimes known as the MCT-KD
    • More nutritionally adequate than classic KD
    • Still effective in treating epilepsy disorders
      • And reduce cardiac risk [9]

MCT-KD

  • Countenances more fruits and vegetables
  • More food choices
  • Causes lesser incidence of kidney stones, hypoglycaemia, constipation, low bone density and growth retardation
  • Contains less fat overall
  • Includes MCFA (from coconut oil)
    • Can provide a greater amount of ketone bodies per gram of fat
      • Thus allows more carbohydrate and protein in the diet
        • Making the diet more palatable than the classic KD
  • KD rich in MCFA have significant effects on
    • Lowering the cholesterol:HDL ratio compared with the classic KD [9]

DM1

  • Would also benefit considerably from sources of energy other than glucose to maintain brain energy homeostasis
  • Elevation in 3HB levels in plasma
    • Observed when coconut oil has been consumed

Effectiveness of KD diets

  • In raising ketone body levels is measurable in plasma
    • Increased 3HB levels in rat plasma

Alzheimerova choroba a kteideta-MCT

  • Glucose for energy is vital in the brain
    • Impaired in AD
    • Low glucose utilisation has been demonstrated in many studies by fluoro-2-deoxy-D-glucose positron emission tomography imaging in AD subjects
      • Also been detected in elderly people who later develop AD
  • Strikingly reduced expression in the central nervous system of genes encoding
    • Insulin,
    • Insulin like growth factor I (IGF-I)
    • Insulin like growth factor II (IGF-II)
    • Insulin and IGF-I receptors
      • AD may represent a neuroendocrine disorder = ‘Type 3 diabetes’
  • Energy provision via glucose
    • Appears to be inadequate in emergent (pre-clinical) AD as well as established AD
  • Enhanced supply of ketone bodies may be beneficial
    • Due to the resultant enhanced ATP output of mitochondria
  • AD or mild cognitive impairment patients
    • Have reported positive effects on cognitive performance after consuming MCFA-rich foods
      • Observing significant increases in blood 3HB levels after treatment
    • Cognitive improvement has not been seen in ApoE-14 allele carriers
  • KD diets in AD patients
    • Raised mean serum 3HB levels from about 0·1 mmol/l to about 0·4 mmol/l in these patients
      • Demonstrated improvement in cognition measured at 45 and 90 d post ketone supplementation
    • Benefits were seen only in ApoE4-14 allele-negative patients
    • Adverse events
      • Diarrhoea, flatulence and dyspepsia
  • Baran~ano & Hartman - concept that
    • KD can enhance the mitochondrial production of ATP
    • ATP production
    • Altered brain pH affecting neuronal excitability
    • Direct inhibitory effects on ion channels
    • Increasing levels of both ketone transporters and GLUT-1
    • Increasing capillary density
    • Improving the regulation of sirtuins (anti-ageing effects of energy restriction)
  • Deposition of aggregated Ab peptides in the brain
    • Formed by proteolytic cleavage of the amyloid precursor protein (APP) by various proteases,
  • Ketones may be able to sustain neuronal viability.
  • Dual-tracer positron emission tomography imaging study of rats on a KD
    • Diet caused increases in brain uptake of the two tracers 11C-AcAc and 18F-fluorodeoxyglucose
    • 14-d KD could increase the cerebral metabolic rate of AcAc by 28% and glucose by 44 % in aged (24-month) rats [1]
  • Amyloid-(A) peptide in vitro
    • Neuron survival in cultures co-treated with coconut oil and Ab is rescued
    • Compared with cultures exposed only to Ab
  • Coconut oil co-treatment
  • Van der Auwera et al.- young transgenic AD mice over expressing the London APP mutation fed with KD for 1·5 months
    • Decrease of Ab in the brain
  • Aged dogs
    • Effect of KD on Ab is restricted to the parietal lobe of the brain
  • Kashiwaya et al. - longterm (8 months) feeding of a ketone ester in middle-aged mice (8·5 months old)
    • Improved cognition
    • Reduced Ab and t pathology
  • AD mice model fed with a high-fat, low-carbohydrate KD
    • Improved motor function
    • But without changes in Ab
    • Further support for the benefits of high dietary MCFA levels against AD
  • In vitro study demonstrated that the addition of ketone bodies (b-hydroxybutyrate)
    • Protects the hippocampal neurons from Ab toxicity
    • Possible therapeutic roles for KD on mitochondrial defects related to AD
  • Few studies have demonstrated that KD could significantly
    • Improve glucose homeostasis
    • Reducing metabolic dysregulation and insulin resistance (IR)
      • Important to reduce the pathology of AD

Adverse effects of ketones

  • Significant rise in the mean blood cholesterol level to over 2500 mg/l following a prolonged intake of a KD
    • May be atherogenic
  • Some researchers have observed dilated cardiomyopathy in patients on the KD
    • Due to the toxic effects of elevated plasma NEFA
  • Increased incidence in nephrolithiasis
  • Increases in serum uric acid levels
  • Some side effects are common following administration of ketone bodies
    • Dehydration
    • Hypoglycaemia
  • Growth retardation, obesity, nutrient deficiency, decreased bone density, hepatic failure and immune dysfunction
    • Are also observed, but not frequently
  • Hiraide et al.(103) reported
    • Significant increase in pH and Na concentrations
      • Following the administration of a 20 % solution of Na b-hydroxyl butyrate (BHB) to severe trauma patients
  • Hasselbalch et al.
    • Reduction in glucose cerebral metabolism
    • Increase in cerebral blood flow during the administration of intravenous BHB
  • Long-term consequences of these deviations are not yet known.
  • KD with high-protein diets
    • May cause possible kidney damage due to
      • High levels of N excretion during protein metabolism
    • Several researches have reported that even high levels of protein in the diet do not damage renal function
  • KD with very low carbohydrate
    • Can cause a regression of diabetic nephropathy due to acidosis
    • Concentration of ketone bodies never rises above 8 mmol/l
      • This risk is minimum with normal insulin function subjects
https://www.cambridge.org/core/services/aop-cambridge-core/content/view/1C610ECEA7E7D7CD3E7323A0477E6731/S0007114515001452a.pdf/role_of_dietary_coconut_for_the_prevention_and_treatment_of_alzheimers_disease_potential_mechanisms_of_action.pdf


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Poslední aktualizace: 22. 4. 2019 14:33:03