Deze pagina hoort bij hoofdstuk 4 van het boek Hersenvoer

In hoofdstuk 4 laat ik zien dat hersenen liever ketonen gebruiken als brandstof dan glucose en dat het regelmatig verbranden van ketonen de hersengezondheid ten goede komt.

Hieronder vind je de belangrijkste wetenschappelijke bronnen die dit onderbouwen. Ze vormen de academische basis onder de inzichten die ik in Hersenvoer vertaal naar voeding, leefstijl en herstel.

De onderbouwing is niet bedoeld als volledig overzicht, maar geeft een selectie van beschikbare wetenschappelijke papers die de kernlijnen van dit hoofdstuk onderbouwen.

4.1: Twee soorten brandstof

4.1.3 Ketonen als efficiënte, schone brandstof

• Cunnane et al. (2020) – Deze uitgebreide review vormt de basis voor hoofdstuk 4 in Hersenvoer. Het beschrijft de rol van energietekort in de hersenen. In deze review wordt veel uitgelegd over de potentiële rol van ketonen voor de gezondheid van de hersenen. Het stuk heeft neurodegeneratieve ziektes als insteek, maar de uitleg over de rol van ketonen in hersengezondheid is generaliseerbaar naar andere hersenaandoeningen.
  DOI: 1038/s41573-020-0072-x

“Als er genoeg glucose in het bloed zit en er tevens ketonen aanwezig zijn, schroeven de hersenen het gebruik van glucose naar beneden om ruimte te maken voor ketonen”

• Courchesne-Loyer et al. (2017) – “After four days on the KD [ketogenic diet]…. The CMR [cerebral metabolic rate] of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements”
  DOI: 10.1177/0271678X16669366
• Li et al. (2026) – “Ten participants … received two … brain scans—one after taking 395 mg/kg KE [ketone esters, een ketonensupplement] and one at baseline—in a randomized order.” “KE lowered blood glucose and increased BHB [β-hydroxybutyrate, een keton]…. Brain scans revealed a 17% reduction in glucose metabolism” “These findings suggest that a single KE dose can rapidly shift brain energy use from glucose to ketones”
  DOI: 10.1016/j.pscychresns.2026.112154

Figuur 4.2 “Ketonen vergelijk ik graag met schoonmakers en opruimcoaches. Ze maken schoon, ruimen rommel op, herstellen foutjes en ze structureren en optimaliseren diverse processen in de hersenen”

• Hu et al. (2020) – Beta-hydroxybutyrate [een van de ketonen] “regulates cellular signaling and multiple histone modifications to cooperatively modulate BDNF [een groeifactor in de hersenen die het leggen van nieuwe verbindingen stimuleert], suggesting a wide range of regulatory effects of BHBA [beta-hydroxybutyrate] in the central nervous system.”
• Maar zie Kackley et al. (2022) – Zij dezen drie experimenten om te onderzoeken hoe verschillende manieren om in ketose te komen BDNF concentraties in het bloed beïnvloeden. Hun onderzoek “does not support a strong association [van ketose] with temporally matched BHB concentrations.”

Kader – De hersenen zijn een bijzonder orgaan:

Energieproblemen in de hersenen spelen een rol in zowel onderactiviteit als overactiviteit

• Kann et al. (2014) – “the available evidence indicates that information processing in the cortex critically depends on the activity of a specific type of inhibitory interneurons”
  “these interneurons feature particularly high energy utilization, which puts them into a critical position for the maintenance or failure of cognitive functions when metabolic stress occurs (‘interneuron energy hypothesis’)” p. 1271
  “fast-spiking interneurons may dramatically lower the threshold for neuronal network dysfunction during metabolic stress” p. 1276

Met ‘neuronal network function’ bedoelen de auteurs “the coordinated activation of defined sets of neurons, which constitute functional ensembles” which may “form a crucial prerequisite for the unity of perception, attention and, perhaps, consciousness” p. 1271
“Even moderate metabolic stress … might cause dramatic decreases in ATP levels and GABA release [belangrijkste remmende stof in de hersenen]. This is associated with a decrease of higher brain functions.” P. 1277
doi: 10.1038/jcbfm.2014.104

• Huang et al. (2024) – “After energy depletion … the membrane potential of neurons and glia is dampened” [dat betekent dat hersencellen moeilijk te activeren zijn] (p. 2690)
  “Cerebral ischemia-reperfusion [een onderzoeksmodel voor energietekort in de hersenen] results in the blockage of Glu release and reuptake [glutamaat is het belangrijkste activerende signaalstofje in de hersenen] in the CNS, resulting in the excessive activation of Glu receptors on the postsynaptic membrane. This overactivation results in … overload and eventually neuronal necrosis.” [door overprikkeling raken hersencellen beschadigd en sterven uiteindelijk zelfs af] p. 2691
• De La Rossa et al. (2022) – “MPC-deficient mice [onderzoeksmodel voor energietekort in de hersenen] … were normal at rest. Surprisingly, in response to mild inhibition of GABA mediated synaptic activity [de belangrijkste remmende boodschapper in de hersenen werd minder bruikbaar gemaakt], they rapidly developed severe seizures” [overactieve hersencellen veroorzaakten epileptische aanvallen]
  “Provision of ketone bodies restored energy status, … and attenuated seizures in animals fed a ketogenic diet.” [ketonen temperden de hyperactiviteit]

4.2 Insulineresistentie: vriend en vijand

De waardes uit Figuur 4.4 zijn afkomstig uit Wang et al. (2019) (doi: 10.1186/s12916-019-1440-4). Dr. Kraft presenteert heel vergelijkbare grafieken in zijn boek Diabetes Epidemic and You.

Omdat oxidatieve stress (4.1.2), insulineresistentie (4.2) en neuro-inflammatie (4.2.2) nauw aan elkaar en aan problemen met de energievoorziening gerelateerd zijn, heb ik een algemene referentielijst gemaakt waarin per aandoening onderbouwd wordt dat problemen met de energievoorziening van de hersenen een rol spelen, en dat die problemen omzeild en zelfs gerepareerd kunnen worden door te zorgen dat er ketonen in de hersenen komen.

ADHD en autisme

• Omori et al. (2024) – “In ASD, there is reasonable evidence … associating ketosis … with behavioral improvement.” “In ADHD associations between ketosis and behavioral improvement are less clear” “The safety and tolerability of ketogenic diets and ketogenic supplements is such that there would be value in exploring further clinical studies.”
  DOI: 10.3389/fnut.2024.1485280
• Marcelli et al. (2025) – “There is a robust, bidirectional link between ADHD and metabolic disorders” “These overlapping pathways suggest that therapeutic strategies targeting both neurodevelopmental and metabolic dysfunctions may yield significant clinical benefits. However, further research is necessary to … refine personalized treatment approaches that integrate metabolic and psychiatric care.” (p. 13)
  DOI: 10.3390/diabetology6050040
• Zarnowska et al. (2018) – “We report a case of a 6-year-old patient with high-functioning autism and subclinical epileptic discharges who responded poorly to several behavioural and psychopharmacological treatments. The patient was subsequently placed on the KD [ketogenic diet] due to significant glucose hypometabolism in the brain as revealed by an 18FDG PET [hersenscan]. As soon as one month after starting the KD, the patient’s behavior and intellect improved (in regard to hyperactivity, attention span, abnormal reactions to visual and auditory stimuli, usage of objects, adaptability to changes, communication skills, fear, anxiety, and emotional reactions); these improvements continued until the end of the observation period at 16 months on the KD.”
  DOI: 10.1007/s11011-018-0219-1

• Joseph et al. (2015) – “These results … suggest … that their [patienst with ADHD] response to oxidative stress is insufficient, leading to oxidative damage.”
  DOI: 10.1177/1087054713510354

Migraine

• Neri et al. (2023) – “there is strong evidence to suggest that migraine is an energy deficit syndrome” Meta-analysis showed that “interventions had an overall significant positive effect, … regardless of the type of endogenous of exogenous induction of ketosis” “we can assert with greater certrainty that the strategy of increasing ketone bodies in the body can bring benefits in the relief and prevention of migraine”
  DOI: 10.3389/fnut.2023.1204700

Milde cognitieve achteruitgang / Dementie / neurodegeneratieve ziektes

• Jensen et al. (2020) –onderstreept de glucosetekorten én ketonen als alternatief energiebron, relevant voor MCI/dementie-strategieën.
  DOI: 10.3390/ijms21228767
• Kapogiannis et al. (2020) – “Glucose metabolism dysregulation is a common feature in neurodegenerative disease, such as Alzheimer’s, Parkinson’s, Huntington’s and in frontotemporal lobar degeneration.”
  DOI: 10.1016/bs.irn.2020.03.015
• Cunnane et al. (2020) – “In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner” “precedes the onset of clinical symptoms” “ketones … have much to offer in developing brain energetic rescue strategies in neurodegenerative disorders”
  10.1038/s41573-020-0072-x
• Butterfield & Halliwell (2019) – “in AD [Alzheimer’s disease] and amnestic mild cognitive impairment (aMCI) glucose metabolism is dramatically decreased” (p. ) “This defect likely results in significant part from oxidative damage” (p. 12) “leading to diminished learning and memory and ultimately dementia.” “Clinical trials … using antioxidants have been disappointing,” “better therapeutic approaches to preserve and/or improve glucose utilization, decrease oxidative damage and protect the brain against neuropathological changes will be needed.” (p. 13) – Ik denk dat een interventie op het niveau van het hele voedingspatroon hierin kansrijker is dan interventies die zich alleen richten op antioxidanten. Zoals ik schrijf in paragraaf 5.1.3, worden de meest betrouwbare antioxidanten voor de hersenen in de hersenen zelf geproduceerd. ‘Normale’ antioxidanten kunnen vaak de bloed-hersenbarrière niet (goed) passeren.
  DOI: 10.1038/s41583-019-0132-6

Depressie / Angst / Paniek

• Kovács et al. (2019) – “recent studies have demonstrated that widespread changes of … metabolic pathways may partially underlie the pathophysiology of many psychiatric diseases” “such as anxiety disorder, bipolar disorder, schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD)” “We conclude that … ketosis leads to metabolic … improvements, … and suggest that development of specific adjunctive ketogenic protocols for psychiatric disorders should be actively pursued.”
  DOI: 10.3389/fpsyt.2019.00363

Epilepsie

• Martin-McGill et al. (2020) – Ketogenic Diets “could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KD’s in adults remains uncertain”
  DOI: 10.1002%2F14651858.CD001903.pub5

Parkinson

• Dai et al. (2023) – “Impairments in systematic and regional glucose metabolism exist in patients with PD at every stage of the disease course” “These impairments may be attributed to various mechanisms, such as insulin resistance, hyperglycemia-induced damage, oxidative stress, abnormal glycated modification, and BBB dysfunction, resulting in energy supply insufficiency”
  DOI: 10.1016/j.brainresbull.2023.110672

• Chen et al. (2025) – “Glucose metabolism impairment observed in PD patients involves glucose transport, glycolysis, TCA, OXPHOS, PPP [stappen in glucosemetabolisme] and gluconeogenesis.” “there are few studies on the treatment of glucose metabolism impairment in PD patients.”
  DOI: 10.1186/s40035-025-00467-8

Neurologische aandoeningen algemeen

• Stafstrom & Rho (2012) – “Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis.” “there is an emerging literature supporting the broad use of the KD [ketogenic diet] (and its variants) against a variety of neurological conditions. These preliminary studies are largely based on the fundamental idea that metabolic shifts may lead to neuroprotective actions” “Alterations in energy metabolism appear to be a common theme.” “the details of how that altered metabolism reduces neuronal excitability, abrogates ongoing neurodegeneration, or mitigates functional disability remain unknown. Herein lay rich opportunities for further investigation, in both the laboratory and the clinic, in the broad realm of translational neurosciences.”
  Deze review is uit 2012. Inmiddels zijn er wel concretere ideeën over hóe ketonen kunnen helpen de symptomen van neurologische aandoeningen te verminderen. Ik heb het opgenomen om te laten zien dat er al langere tijd interesse bestaat, en tegelijk dat de kennis daarover heel langzaam doorsijpelt naar de klinische praktijk.
  DOI: 10.3389/fphar.2012.00059

4.2.3 Bloed-hersenbarrière

Een beschadigde bloedhersenbarrière (BHB)is gevonden in uiteenlopende hersenaandoeningen:

• Lemarchant et al. (2025) – “41% of neurological diseases and related conditions/injuries display a co-pathology of blood-brain and blood-spinal cord barrier alterations and dysfunctions, and we discuss why this figure may represent only a fraction of a larger phenomenon.” Bewijs is het sterkst voor
  • Alzheimer,
  • beroertes,
  • epilepsie,
  • Huntington,
  • MS,
  • niet aangeboren hersenletsel en
  • Parkinson.

DOI: 10.1186/s12987-025-00688-z

Migraine

Wiggers et al. (2022) – Voor structureel verhoogde doorlaatbaarheid van de BHB bij migraineurs is het directe bewijs beperkt, maar er zijn wel aanwijzingen voor een verhoogde doorlaatbaarheid van de bloed-hersenvochtbarrière (blood-cerebrospinal fluid barrier of BCSFB).
DOI: 10.1186/s10194-021-01365-w

Zie ook:

• Dreier (2016) – “it could well be that spreading depolarization opens the blood–brain barrier under one set of tissue conditions but not another.” “universal validity of this link cannot be derived from these findings.”
  DOI: 10.1093/brain/aww112
• Moskowitz (2017) – “MRI [hersenscans] in patients has informed us about the role of CSD [cortical spreading depolarisation] and helped us characterize attendant blood flow changes that occur during headache. It has also informed us that brainstem activation is a consistent, albeit poorly understood feature of attacks, whereas BBB disruption does not appear to characterize the sustained headache.”
  DOI: 10.1093/brain/awx089
• Cowan et al (2021) – “the transport of … blood-derived proteins is disturbed at the BCSFB [bloed-hersenvochtbarrière] in persons with migraine”
  DOI: 10.1111/head.14088
• Yücel et al. (2016) – Migraineurs hebben zowel tijdens als een week na een migraineaanval meer claudin-5 in hun bloed dan mensen zonder migraine (Figuur 2). Claudin-5 is een eiwit dat de doorlaatbaarheid van de BHB reguleert (p. 94)

Bipolaire stoornissen

Alonso et al. (2024) – “The results of this systematic review provide converging evidence to suggest the involvement of BBB dysfunction in BD [Bipolar Disorder]. While a synthesis of the literature is challenging given the heterogeneity in study methods, participants and design, there is some evidence for BBB dysfunction from serum-based and CSF [CerebroSpinal Fluid]-based, post-mortem, neuroimaging, and genetic studies. The most extensive and perhaps convincing evidence is from serum and CSF studies, where 25 out of 29 included studies found evidence in favour of an association between BD and markers of BBB disruption, including 22 studies reporting a difference in levels of BBB markers between participants with BD and healthy controls, and 7 studies reporting a difference in levels of BBB markers across mood states in BD.”
DOI: 10.1016/j.jad.2024.06.032

Psychose

Li et al. (2023) – “Overall, we revealed that psychotic disorders are associated with increased CSF-to-serum albumin ratio, and increased blood S100B, MMP-9, and zonulin. … these findings in part support the role of vascular pathology in psychosis” (p. 5)
DOI: 10.3389/fpsyt.2023.1241422

4.5 Metabole flexibiliteit

Er zijn steeds meer aanwijzingen dat je je metabole flexibiliteit daadwerkelijk kunt verbeteren door te zorgen dat je vaker en/of langer in ketose bent:

• Luong et al. (2024) – “A KD [ketogenic diet] increased skeletal muscle IS in individuals with obesity.”
  DOI: 10.2337/db24-0162
• Noakes et al. (2023) – “a LCHF [Low Carb High Fat] diet may also reverse features of pre-diabetes and future metabolic disease risk … even in athletic populations.”
  DOI: 10.3389/fphys.2023.1150265

Kader Exogene Ketonen

Metabolic Mind heeft een hele mooie podcast over exogene ketonen:

https://open.spotify.com/episode/03khUz8DYV8Tp6btPtUgQj?si=v63LfNF7Q4aM8uIQ9fqLpQ

https://www.youtube.com/watch?v=Cwb3FoMswms