A ketone-supplemented diet may protect neurons from death during the progression of Alzheimer’s disease

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A ketone-supplemented diet may protect neurons from death during the progression of Alzheimer’s disease, according to research in mice recently published in Journal of Neuroscience.

Early in the development of Alzheimer’s disease, the brain becomes over excited, potentially through the loss of inhibitory, or GABAergic, interneurons that keep other neurons from signaling too much.

Because interneurons require more energy compared to other neurons, they may be more susceptible to dying when they encounter the Alzheimer’s disease protein amyloid beta. Amyloid beta has been shown to damage mitochondria – the metabolic engine for cells – by interfering with SIRT3, a protein that preserves mitochondrial functions and protects neurons.

Cheng et al. genetically reduced levels of SIRT3 in mouse models of Alzheimer’s disease. Mice with low levels of SIRT3 experienced a much higher mortality rate, more violent seizures, and increased interneuron death compared to the mice from the standard Alzheimer’s disease model and control mice.

However, the mice with reduced levels of SIRT3 experienced fewer seizures and were less likely to die when they ate a diet rich in ketones, a specific type of fatty acid. The diet also increased levels of SIRT3 in the mice.

This shows neurons from the study

Decreased levels of SIRT3 triggers loss of interneurons in Alzheimer’s disease mouse models. The image is credited to Cheng et al., JNeurosci 2019.

Increasing SIRT3 levels via ketone consumption may be a way to protect interneurons and delay the progression of Alzheimer’s disease.


Alzheimer’s disease (AD) is the most significant cause of dementia that affects around 50 million people worldwide [1]. It is a heterogeneous and multifactorial disorder, characterized by cognitive impairment with a progressive decline in memory, disorientation, impaired self-care, and personality changes [2,3].

The most common symptom present at the beginning of AD is associated with short term memory deficit, which affects daily activities [3]. Cognitive deficits, resulting from the loss of neurons, are susceptible to neurofibrillary degeneration located in the limbic system, subcortical structures, archicortex and neocortex, and progressive synaptic dysfunction [4]. Pathologically, AD involves progressive deposition of amyloid β-peptide (Aβ) as amyloid plaques, hyperphosphorylated tau protein intracellularly as neurofibrillary tangles (NFTs) and neuronal loss in the hippocampus [2].

Moreover, patients with AD present mitochondrial dysfunction and metabolic changes, such as impaired glucose utilization in the brain (glucose hypometabolism) [5].

Mitochondrial dysfunction and a decline in respiratory chain function alter amyloid precursor protein (APP) processing, which leads to the production of the pathogenic amyloid-β fragments [6,7].

On the other hand, the reduced glucose uptake and inefficient glycolysis have been strongly associated with progressive cognitive deficiency [8], due to the downregulation of the glucose transporter GLUT1 in the brain of patients with AD [9]. Clinical studies have demonstrated an association between a high-glycemic diet and increased cerebral amyloid deposition in mice [10,11,12,13,14] and humans [15], suggesting that insulin resistance of brain tissue may contribute to the development of AD [16].

To date, there are only a few FDA approved drugs, such as acetylcholinesterase inhibitors and memantine. Drugs that regulate the activity of the neurotransmitters and partly ameliorate behavioral symptoms [17].

Another treatment option includes active and passive immunization, anti-aggregation drugs, γ- and β-secretases inhibitors [18]. Currently, there is no effective treatment to prevent the risk of AD development or modify its progress. Therefore, emerging results from preclinical and clinical studies show that change in dietary and lifestyle modifications may have a potential interest in the treatment of AD [19].

These recommendations include minimizing the intake of trans fat and saturated fats, dairy products and increased consumptions of vegetables, fruits, legumes (beans, peas, and lentils), and whole grains [19,20]. Moreover, various dietary patterns are suggested in order to reduce the neuropathological hallmarks of AD, including ketogenic diet (KD), caloric restriction (CR), the Mediterranean diet (MedDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) [20].

The ketogenic diet was initially established in the 1920s to be used in refractory epilepsy therapy [21,22].

To date, there are pieces of evidence showing that it has gained interest as a potential therapy for neurodegenerative disorders, such as AD [10,23], Parkinson’s disease [24], amyotrophic lateral sclerosis [25], and insulin resistance in type 2 diabetes [26]. Moreover, because of altered glucose metabolism, it may have anti-tumor effects, as well as, for example, in glaucoma [27], or gastric cancer [28]. Despite the growing number of evidence that dietary treatment works, the exact mechanism of its protective activity remains unknown.

This review summarizes the experimental and clinical data, which suggest that the ketogenic diet could be a potential therapy option for AD, due to its neuroprotective properties.Go to:

Etiopathogenesis of Alzheimer’s Disease

The etiology of AD remains not fully explained, but both genetic and environmental risk factors have been proposed to be involved. Thus, the etiopathogenesis of AD has been linked to hypometabolism [29,30], mitochondrial dysfunction [31], inflammation [32,33], and oxidative stress [21]. Some more cellular events associated with AD neuropathogenesis include impairment of calcium homeostasis and disturbed autophagy [32].

On the brain tissue level, neurons loss, brain atrophy, and cerebral amyloid angiopathy have to be mentioned [32]. In addition, the systems-level characteristic for AD involves the blood-brain barrier (BBB) abnormalities, brain arteries atherosclerosis, and brain hypoperfusion [32]. Moreover, genome-wide association studies (GWAS) have revealed that more than 20 genetic loci may be implicated with the risk of AD development [34].

The primary gene is the apolipoprotein E (ApoE), and the epsilon 4 (E4) variant of ApoE was found to increase the risk for AD generation [34]. Insulin resistance and type 2 diabetes mellitus are the essential risk factors of AD [3].

The neuropathological features of the AD brain include extracellular diffuse and senile amyloid plaques and intracellular neurofibrillary tangles. Amyloid plaques contain amyloid β peptides consisting of 38 to 43 amino acids generated by cleavage of neuronal cell membrane glycoprotein (APP) by β- and γ-secretases [32].

The main isoforms of Aβ have been distinguished: Aβ1-40 (90%) and Aβ1-42 (10%) [35]. β-secretase by cleaving the extracellular domain of APP and releasing the soluble N-terminal of APP into the extracellular space initiates the amyloidogenic pathway. Subsequently, the C-terminal of APP is cleaved by γ-secretase eventually yielding Aβ and APP intracellular domain (AICD) [35].

As a matter of fact, the non-amyloidogenic processing does not result in the production of Aβ, due to the cleavage of APP by α-secretase, leading to the release into the extracellular space of a soluble neuroprotective protein—sAPPα. Finally, γ-secretase cleaves the remaining the C-terminal fragment C83, yielding P3 and AICD. The increase in the concentration of Aβ leads to neurotoxicity and neurons loss. Interestingly, Aβ at brain lower concentrations seems to promote neurogenesis and plasticity, exert neurotrophic functions, influence calcium homeostasis, antioxidative processes, and redox sequestration of metal ions. Elevated generation of Aβ accompanied by its reduced clearance clearly results in the accumulation of Aβ and its subsequent neurotoxicity.

The accumulated Aβ1-42 can undergo aggregation, which eventually leads to the formation of insoluble oligomers and fibrillary arrangement, the final step being senile amyloid plaques [36].

NFTs are composed of abnormally hyperphosphorylated tau protein, located within neurons [36]. The assembly and stabilization of microtubules requires tau protein, being crucial for cytoskeleton and transport of vesicles and organelles along the axons. Moreover, they play a role in the regulation of synaptic plasticity and synaptic function [37]. Under physiologic conditions, phosphorylation of tau protein by kinases is balanced by dephosphorylation by phosphatases, but the change in structure is observed when tau protein is hyperphosphorylated. The development of paired helical filaments (PHFs) and/or NFTs, causing destabilization of microtubules, as well as synaptic and neuronal injury [36].Go to:

Ketogenic Diet

The ketogenic diet assumes a very high-fat and low-carbohydrate diet, reducing carbohydrate to ≤10% of consumed energy. This restriction triggers a systemic shift from glucose metabolism toward the metabolism of fatty acids (FAs) yielding ketone bodies (KBs), such as acetoacetate (AcAc) and β-hydroxybutyrate (β-OHB) as substrates for energy [38]. Approximately 20% of basal metabolism for the adult brain is provided by the oxidation of 100–120 g of glucose over 24 h [39].

The KD provides sufficient protein for growth and development, but insufficient amounts of carbohydrates for the metabolic requirements [40].

Thus, energy is mostly derived from fat delivered in the diet and by the utilization of body fat [40].

The ketogenic diet is a biochemical model of fasting [41], which promotes organs to utilize KBs as the dominant fuel source to replace glucose for the central nervous system (CNS) [42].

Within hours of starting the diet, changes in plasma KBs, glucose, insulin, glucagon, and FAs levels are observed [43], which results in a drop in blood glucose concentration, as well as the insulin-to-glucagon ratio.

An increased glucagon concentration is associated with the mobilization of glucose from its liver resources. Thus, the inhibition of glycogenesis and glucose reserves become insufficient for the fat oxidation process [44]. After 2–3 days of fasting, the primary source of energy is KBs, produced in the mitochondrial matrix of hepatocytes [45].

The higher level of KBs in the blood and their elimination via urine cause ketonemia and ketonuria [45]. Under physiological conditions, the blood concentration of KBs ranges from <0.3 mM, compared to glucose concentration ~4 mM, to 6 mM during prolonged fasting [46]. When KBs achieve concentrations above 4 mM, they become a source of energy for the CNS. In diabetic ketoacidosis, KBs may reach the level of 25 mM [39], resulting from an insulin deficiency with an increased glucose concentration (>300 mg/dL) and decreased blood pH (pH < 7.3), which may cause the death of the patient [45].

The KD allows ~90% of total calorie income from fat and much lower from protein (6%) and carbohydrate (4%) [21]. This may be achieved, due to a macronutrient ratio of 4:1 (4 g fat to every 1 g protein and carbohydrates) [21]. Thus, it includes replacing carbohydrates by fats in daily meals [41].

The most common KD form contains mainly long-chain fatty acids, although KD requires changes in eating habits, which is challenging to maintain, especially from a long-term perspective [44].

Therefore, a new form of KD was proposed. A diet based on medium-chain triglycerides (MCT) leads to similar effects by increasing the concentration of KBs in the blood, even if carbohydrates were present in the diet [44,47]. Another version of KD is the Atkins diet, in which carbohydrates are limited to 5% of energy in the diet [44].

As already mentioned, due to the restriction of glucose metabolism, KD requires to obtain energy from FAs of adipose tissue. Remarkably, the brain, due to its reduced ability to utilize FAs as an energy source, has to use KBs instead. KBs, through the mitochondrial β-oxidation of FAs yielding acetyl-CoA, are synthesized in the liver [7,48].

Some acetyl-CoA molecules remaining may be utilized in the Krebs cycle or to produce AcAc, further being converted spontaneously to acetone or β-OHB by β-OHB dehydrogenase (BDH) [7,48,49,50]. Later on, KBs enter the bloodstream and are available for brain, muscle, and heart, where they generate energy for cells in mitochondria [51]. β-OHB and AcAc can cross the BBB through proton-linked, monocarboxylic acid transporters, and provide an alternative substrate for the brain. Their expression is related to the level of ketosis [52]. During the long period of starvation, KBs may provide up to 70% of cerebral energy requirements [46]. When KBs are present at sufficient concentrations, they can maintain the basal (non-signaling) neuronal energy needs and up to ~50% of the activity-dependent oxidative neuronal requirements [53].

Research studies evoked that KBs provide a more efficient energy source compared to glucose. They are metabolized faster than glucose and are able to bypass the glycolytic pathway by directly entering the Krebs cycle, whereas glucose needs to undergo glycolysis [7,46,54]. Because it leads to fatty acid-mediated activation of peroxisome proliferator-activated receptor α (PPARα), the glycolysis and FA are inhibited [50,55].

Thus, KBs reduce glycolytic ATP production and elevate ATP generation by mitochondrial oxidation [50], which enhances oxidative mitochondrial metabolism resulting in beneficial downstream metabolic changes. It includes the ketosis, higher serum fat levels, and lower serum glucose levels contributing to protection against neuronal loss by apoptosis and necrosis. Bough et al. [56]

found that KD modulates the upregulation of hippocampal genes, which encode mitochondrial and energy metabolism enzymes [56]. Consequently, therapeutic ketosis can be considered as a form of metabolic therapy by providing alternative energy substrates.

Through these metabolic changes, brain metabolism is improved, and ATP production in mitochondria is restored. Moreover, decreased reactive oxygen species (ROS) production, antioxidant effects, lower inflammatory response, and increased activity of neurotrophic factors are observed [7]. Another impact includes stabilization of the synaptic activity between neurons through increased levels of Krebs cycle intermediates, increased GABA-to-glutamate ratio, and activation of ATP-sensitive potassium channels [7]. Probable mechanisms underlying the beneficial influence of KD on AD development are presented in Figure 1.

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Figure 1
Hypothesized mechanisms through which ketogenic diet (KD) influence Alzheimer’s disease (AD) development. ↓—decreased; ↑—increased. Based on Reference [7].

The Impact of the Ketogenic Diet on Amyloid and Tau Protein

Defects in mitochondrial and respiratory chain function may alter APP processing, resulting in production neurotoxic Aβ [57]. The ketogenic diet could alleviate the effects of impaired glucose metabolism [8,58] by providing ketones as alternative metabolic substrates for the brain. Besides, this diet may help to reduce the deposition of amyloid plaques by reversing the Aβ(1–42) toxicity [58,59]. Studies suggest that KD may affect neuropathological and biochemical changes observed in AD. Rodents treated with the KD, exogenous β-OHB, and MCT display reduced brain Aβ levels, protection from amyloid-β toxicity, and improved mitochondrial function [10,30]. In the transgenic mice model of AD, it was observed that KD made soluble Aβ deposits level in their brain 25% less after only 40 days [60]. Also, in humans, this process may be determined by the presence or absence of the ApoE4 genotype; however, the presence of which is a risk factor for AD development [23,47].

Evidently, AD neuropathology is associated with aberrant hyperphosphorylation of tau protein. Mitochondrial dysfunction and decreased neuronal and glial mitochondrial metabolism follow in older people. The mitochondrial dysfunction results in diminished energy generation from the oxidation of glucose/pyruvate, and it can also increase Aβ accumulation and tau protein dysfunction. Consequently, the abnormal mitochondria could be characterized by an increased superoxide generation with subsequent oxidative injury, a decrease in oxidative phosphorylation, and finally resulting impairment of the mitochondrial electron transport chain [61].

The Impact of the Ketogenic Diet on Inflammation

Inflammation and oxidative stress are two essential factors recognized in the neuropathology of AD, underlying neurotoxic mechanisms leading to neuronal loss, which is present in the brain regions responsible for memory and cognitive processes [21,62]. It involves releasing proinflammatory cytokines, NO, and inhibition of neurotrophins, resulting in damage to surrounding tissues [62].

Because a great proportion of cells in the immune system (e.g., macrophages or monocytes) express abundant GPR109A, KD may actually affect neuroinflammatory mechanisms [63]. GPR109A, which was found in the brain tissue is, in fact, a G protein-coupled receptor known as hydroxy-carboxylic acid receptor 2 (HCA2) [63]. Moreover, the β-OHB may directly bind to HCA2, which is expressed on microglia [63], dendritic cells, and macrophages [64]. Its activation induces the neuroprotective subset of macrophages, which depend on PGD2 production by COX1 [64]. Consequently, neuroinflammation is reduced [63].

KD has also been proved to exert effects on inflammatory processes [65] by inhibiting the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). It results in the downregulation of COX2, and inducible nitric oxide synthase expression, associated with increased immune response [55]. Moreover, the activity of cytokines, such as IL-1b, IL-6, CCL2/MCP-1, TNF-α, is diminished [66]. Besides, peroxisome proliferator-activated receptor γ (PPARγ) can reduce the expression of NF-kB, therefore alleviating the neuronal damage caused by excitotoxicity of N-methyl-D-aspartate (NMDA) [67,68].

Moreover, the KD diet influences the anti-inflammatory action via activation of microglial cells [69], pro-apoptotic properties, and elevated concentrations of neuroprotective mediators, including neurotrophins {neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF)}, and molecular chaperones (proteins preventing aggregation of polypeptides into potentially toxic molecules) [44,70].

Another mechanism of KD is the inhibition of histone deacetylases (HDACs), which play a role in altering chromatin structure, and accessibility [21]. β-OHB inhibits HDACs 1, 3, and 4 (class I and IIa) in vitro, leading to memory function improvement and synaptic plasticity [56,71]. Besides, ketones are able to inhibit the innate immune sensor NOD-like receptor 3 (NLRP3) inflammasome, which controls the activation of caspase-1, and the release of proinflammatory cytokines, such as IL-1β and IL-18 by limiting the K+ efflux from cells [42,50,72].

Also, it has been observed that β-OHB may revert the increased expression of inflammatory cytokines [73]. Lee et al. [74] have observed an elevated expression of cytokine interferon γ in the hippocampus of rats, which leads to protecting cells against excitotoxicity [74]. Ultimately, reducing inflammation could be one of the most crucial AD modifying effects of a KD.

The Impact of the Ketogenic Diet on Dementia

The main symptom of some neurodegenerative disorders is dementia, and it includes thinking difficulties, loss of memory, and obstacles in problem-solving. Progressive impairment of cognitive functions in AD patients was associated with a reduction in glucose uptake and metabolism [8], especially if genetic risk factors for AD or positive family history are present. Another possible mechanism is that lower glucose uptake in the brain may contribute to the development of AD neuropathology [45]. The study of Vanitallie [75] shows that an early disturbance in brain glucose metabolism can be detected before any measurable cognitive decline [75]. Moreover, it correlates with the downregulation of glucose transporter GLUT1 in people with AD [76]. It is observed that a high-glycemic diet is associated with increased insulin resistance and a higher risk of AD development [15]. Few studies have demonstrated that supplementation with MCT and KD improves cognitive performance [23,47,77,78,79,80,81,82].

The hypometabolism in brain tissue has been referred to indicate a risk for the development of dementia in the future [83], following chronic brain energy deprivation, then impairment of neuronal function, and in later stages decline in glucose demand along with the progression difficulties of cognitive performance [84]. In addition, progressive dementia was correlated with reduced blood flow and oxygen consumption in the brain [84].

The altered glucose metabolism and mitochondrial function may result from the accumulation of advanced glycation end products (AGEs) [85]. Although the presence of AGEs in cells and tissues is a characteristic feature of the aging process, it may be enhanced in AD pathology. Also, AGEs molecules can be found in amyloid plaques and neurofibrillary tangles resulting from oxidative stress, protein crosslinking, and neurons cell loss. To sum up, the reduced glycemia could advance these pathophysiological features in AD [45].

The Impact of the Ketogenic Diet on Neurodegeneration

AD is associated with energy imbalance caused by impaired glucose transport and metabolism and mitochondrial dysfunction. Energy deficiency may be observed in different brain structures, especially in the hippocampus [29]. Within the AD neuropathology, there is a shift in brain metabolism, which results in diminished cerebral glucose utilization [86]. On the other hand, increased ketogenesis is observed during the aging process [86].

Mitochondrial dysfunction and oxidative stress play a significant role in neurodegeneration. Both processes are known to generate higher concentrations of ROS, which are harmful to all cellular macromolecules, including nucleic acid, lipid, and protein damage [87]. Therefore, KD may provide neuroprotective benefit by improving mitochondrial function through biochemical changes resulting from glycolysis inhibition and increased KBs formation. It is observed that metabolic ketosis may decrease ROS production improving mitochondrial respiration and bypassing complex 1 dysfunction [48].

Moreover, KD modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH). An increased NAD+/NADH ratio plays a role in protection against ROS and improves redox reactions, mitochondrial biogenesis, and cellular respiration, which stabilizes synaptic action [56,88]. A significant increase in the NAD+/NADH ratio was found in the brain cortex and hippocampus of KD-fed rats after two days [54]. After all, it induces the gene expression via sirtuin 1 (SIRT1), a type 3 histone deacetylase [89], involved in different processes related to deacetylating histone and non-histone targets [21,90]. Also, SIRT1 may limit the oxidative stress by improving the synthesis of heat shock proteins [91], promoting DNA repairing activity of forkhead transcription factor (FOXO) and protein p53 [92], and deacetylation of nuclear factor erythroid 2-related factor 2 (Nrf2), the primary inducer of detoxification genes [93]. In addition, the increased activation of Nrf2 results from the increased production of hydrogen peroxide in the mitochondria, and elevated level of lipid peroxidation product—4-hydroxy-2-nonenal (4-HNE) [94]. In addition, Nrf2 is capable of inducing glutathione reductase, peroxiredoxin and thioredoxin, the primary enzymes responsible for the regeneration of the active form of endogenous antioxidant agents [95], followed by the expression of heme oxygenase-1 (HO-1), an antioxidant protein considered to be one of the key molecules in neuroprotection against oxidative stress [67].

Therefore, KD increases the efficiency of the electron transport chain through the increased expression of uncoupling proteins (UCP), and their activity in the hippocampus [96] by blocking voltage-gated sodium and calcium channels, and regulates the membrane receptors in neurons [97]. Thus, mitochondrial energy reserves may be increased [70,96]. UCP moderates the mitochondrial membrane potential and declines the production of ROS and reactive nitrogen species (RNS) [98].

Moreover, KD increases levels of superoxide dismutase 2 (SOD2), mitochondrial mass, and regulators, such as SIRT1 and mitochondrial fission 1 protein (FIS1); thus, appears to upregulate γ-aminobutyric acid (GABA) A receptor subunits α1, and downregulate NMDA receptor subunits NR2A/B [87].

In addition, KBs may regulate the homeostatic status of mitochondria by changing the calcium-induced membrane permeability transition (mPT) and inhibit opening the pores [42,99]. Also, the selected polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid, arachidonic acid, or docosahexaenoic acid may promote excitability of neuron-cell membranes by suppressed ROS production, decreased inflammatory mediators, and blocking voltage-gated sodium and calcium channels [100]. In addition, KD increases glutathione levels and glutathione peroxidase (GSH-Px) activity in the hippocampus [101], which is the main enzyme affecting the formation of ROS [97].

The potential mechanism of action may be through modulation of intracellular signaling pathways, including the mammalian target of rapamycin (mTOR). Studies show that KD decreases insulin levels and reduces the phosphorylation of Akt and S6, which results in diminished mTOR activation [42,102]. KD also leads to elevated brain ATP and phosphocreatine concentrations, and stimulates mitochondrial biogenesis, which may be interpreted in terms of enhanced metabolic efficiency [56]. Finally, neuronal cells can be considered to have improved resistance and adaptability to stress and metabolic challenges [50,56].

Adverse Effects of the Ketogenic Diet

Data on the adverse effects of KD administration is limited in the adult population, but some effects are predictable, such as hypoglycemia and dehydration. Other side effects are less common and present following long-term treatment.

Previously, KBs were considered toxic resulting from the association of therapeutic ketosis with diabetic ketoacidosis, which results in ketone concentrations higher than 20 mM, which can be reversed with insulin administration [103]. Hyperketonemia resulting from insulin deficiency, in severe cases, may lead to severe acidosis, and even death of the individuals [45,104].

The adverse effects frequently reported by patients with epilepsy on KD are gastrointestinal effects, weight loss, and transient hyperlipidemia [42]. Gastrointestinal side effects can include constipation, nausea, vomiting, and lower appetite [42,105]. Weight loss may be a welcomed effect, especially in an obese patient, but it should be regulated and monitored. In addition, the change in lipid profile, such as fasting total serum cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol is increased at the beginning of the KD treatment then it normalizes (after ~1 year) [106]. Moreover, dehydration, hepatitis, pancreatitis, hypoglycemia, hyperuricemia, hypertransaminemia, hypomagnesemia, and hyponatremia are among the adverse effects of the KD [44,105]. On the other hand, prolonged KD may cause enhanced atherosclerosis, cardiomyopathy, nephrolithiasis, impaired hepatic functions, neuropathy of the optic nerve, anemia, reduction of mineral bone density, and deficiencies of vitamins and mineral components [44].

Chronic KD treatment may cause disturbances in catabolism and reduced synthesis of functional proteins (membrane proteins, enzymes, etc.). Considering the loss of appetite and lower organoleptic attractiveness, it would be difficult to achieve an appropriate supply of protein and energy in patients on the KD, because any energetic deficiency or insufficient protein intake may have severe consequences for health [44,81]. Any significant adverse effects were not observed in 83 obese patients when the KD was administered for 24 weeks [107]. Additionally, in patients with AD, KD may significantly affect food consumption via disturbances in the senses of smell and taste, neurological symptoms, such as apraxia, dysphagia, and behavioral disturbances during eating [44].


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SfN
Media Contacts:
Calli McMurray – SfN
Image Source:
The image is credited to Cheng et al., JNeurosci 2019.

Original Research: Closed access
“SIRT3 Haploinsufficiency Aggravates Loss of GABAergic Interneurons and Neuronal Network Hyperexcitability in an Alzheimer’s Disease Model”. Aiwu Cheng, Jing Wang, Nathaniel Ghena, Qijin Zhao, Isabella Perone, M. Todd King, Richard L. Veech, Myriam Gorospe, Ruiqian Wan and Mark P. Mattson.
Journal of Neuroscience doi:10.1523/JNEUROSCI.1446-19.2019.

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