Questions: How was it discovered that the Keto diet could be used in children with epilepsy? How does a doctor decide how long a child should remain on the Keto diet? Why is this diet not used in adults with epilepsy? At what point does a doctor decide that going on the keto diet is worth potential negative impacts?

Important Terms:

• Nonpharmacologic

• Refractory epilepsy

• Starvation

• Ketone bodies (substitute for glucose)

Authors Credentials: Runyon - clinical pharmacist with expertise in pediatric pharmacotherapy / So - clinical pharmacist specialized in pediatric pharmacotherapy -> he has published many peer-reviewed (reputable) medical journals

Bias: The authors are not biased because they are not trying to convince the reader of anything. They are just publishing research that was discovered.

Reliable: This source is very reliable because it was written by two medical professionals who specialized in pharmacotherapy.

Possible Limitations: this article does not focus and go into detail on the children who did not have success with the diet. It also does not go into detail depth about the negative affects of the diet (it only briefly mentions them)

has been successfully used since 1920

Over half of the children with refractory epilepsy who try the keto diet have their seizures reduced by 50%, while 10-15% become seizure free

Children that benefit the most from the diet are between ages 1-10

It can take a while for the diet to work which leads to around half of patients discontinuing the diet before it takes full affect

It causes the patients to lose weight

The child’s body no longer can metabolize carbohydrates and instead must use ketone bodies created by the liver

A short term affect is mild metabolic acidosis and hypoglycemia

overall less seizures

Constipation

Nausea, vomiting, diarrhea

Short term - dehydration, mild metabolic acidosis, hypoglycemia

Long term - nephrolithiasus, vitamin/mineral deficiencies, increased cholesterol, stunted growth in young children, decreased bone mineral density

Any of these affects (severe and not severe) can severely hinder liver function

diet that focuses on the exclusion of carb-rich foods

people maintain 70-75% of their calories from fat

must exclude processed items

sends the body into a state of ketosis (basically starvation)

it can be hard for children to do the diet due to its strict rules

it can have negative effects on the liver because the liver plays a role in:

• ketone production

• gluconeogenesis

• fat metabolism/energy processing

overall, children handle the diet better than adults making it easier for them to use the diet to combat epilepsy

liver is hurt because of the high-fat intake, metabolic shifts, and nutrient deficiencies

it can cause Hapatic Steatosis (Fatty Liver Disease)

Elevated Liver Enzymes (Liver stress)

Increased Cholesterol and Lipid imbalance

since these effects can be caused when children are put on the diet their liver enzymes (ALT and AST) are monitored through blood tests

Questions: What does current research suggest about the difference in the impacts on children's livers compared to adults? What do previous cases say the impact on the liver was in children with epilepsy? How does a doctor decide when to stop using the keto diet? Are certain children more susceptible to liver function changes when on the keto diet?

Important Terms:

• Pharmacoresistant Epilepsy

• Seizure frequency

• Efficacy

• Adverse effects

• Ketosis

• Dietary Therapy

Author Credentials: Isabella D'Andrea Meira - Neurology specialist who focuses on different forms of epilepsy / Tayla Taynan Romao - Neurology specialist who focuses on cures for epilepsy

Bias: The authors and this article are not based. The article is an informational article that publishes information about epilepsy. It is not trying to convince the reader, nor does it express any opinion.

Reliable: This article is reliable because it was written by two specialists who focus on epilepsy and completed extensive research about the correlation between the keto diet and epilepsy.

Possible limitation: The main limitation of this article is that it does not go into depth about the effects that it has on children. It gives the general affects that it has, and why it is used, but it does not specifically talk about children.

for certain families that have children with epilepsy, they do not feel comfortable risking the health of their children's diet with the keto diet, so they choose to use diets that are less harmful, but also less effective.

Modified Atkins Diet - a less restrictive version of the keto diet, it allows for a high carbohydrate balance. The diet may reduce the strain on the liver because it allows for more carbohydrates, which reduces the risk of hepatic stress.

Low Glycemic Index Treatment - IT is a diet that focuses on controlling a child's blood sugar with low-glycemic carbohydrates. The diet may place lass metabolic burden on the liver. Many families opt to use this one, because it is safer for long-term use.

The article compares the liver function of patients on these diets to patients on the keto diet, and their livers tend to be slightly healthier, but they see less of an increase in their seizures.

Even though the keto diet does have a lot of success in children, it is up to families and doctors to decide if they should risk the health of the child's liver. Some children do not have a choice but to do the keto diet, while others, who suffer from other illnesses, can not risk the keto diet.

the keto diet forces a body into a shift from glucose metabolism to fat metabolism (something that naturally occurs when a body is in a state of starvation)

• by putting the body in a state of starvation, ketosis, the body is forced to produce ketone bodies

The liver is the primary site for ketone production, so the keto diet places extreme metabolic demand on the liver. This demand often leads to an increase in fat metabolism, but it also alters liver enzyme activity

chronic ketosis can increase fatty acid oxidation in the liver which can lead to oxidation stress and inflammation. This is one of the leading factors that damage liver health.

in many cases, if the keto diet is followed strictly for a long time, it will result in hepatosteatosis (aka fatty liver). This results in a long-term negative effect on the hepatic tissue in the user's body.

overall, the diet increases the risk of liver damage, which is especially harmful for children whose organs and bodies are still growing.

the diet is proven to reduce seizures in children with epilepsy

around 40-50% of children who use the diet as a way to treat their epilepsy experience a significant reduction in their seizure frequency

For the diet to work, the children must remain on the diet for prolonged periods of time, commonly for month to years. This means that their bodies are exposed to continuous ft metabolism, which increases their risk of liver complications. Additionally, it is hard for many children to get all the nutrients that they need to grow while being on the keto diet for years at a time.

Since the diets must be implemented for long periods of time in the children, they have to be continuously monitored. Their liver enzymes, specifically ALT, and AST, are always watched to hopefully detect early signs of hepatic stress or damage. Once these are detected, the children are usually pulled off the diet even if that means their seizures will come back. In some instances, the children are not pulled off the diet because they feel the seizures are more dangerous than the liver damage (this usually indicates that there are other medical conditions present)

Many of the children who use the keto diet experience elevated levels of liver enzymes. This suggests liver stress and inflammation which can lead to liver damage.

It is up to doctors and families to decide if the benefits of the keto diet outweigh the possible liver damage and risks.

The liver is the main organ that is affected by the keto diet

Liver enzymes must be monitored (liver function tests) in children when they are on the diet because of the risks of hepatotoxicity

Fatty liver disease risk - children who are on a diet for a long period of time often develop non-alcoholic fatty liver disease because of the excessive fat accumulation in the liver

Gallstone formation and bile issues - since gallstone formation and bile issues increase from high-fat intake, many children develop these issues which lead to liver complications

nutrient deficiencies affecting live health - children suffer from micronutrient deficient (carnitine and selenium) which compromises liver function

Questions: What were the characteristics of the children, did they have past medical conditions? How strictly was the diet followed? How was the children's growth measured specifically? What proportion of the children experienced growth retardation after 1 year?

Important Terms:

• Linear Growth

• Growth Retardation

• Drug-Resistant Epilepsy

• Retrospective Analysis

• Z-Score

Author Credentials: Cinzia Ferraris - registered dietitian expert who is currently a researcher at the University of Pavia (Italy) / Monica Guglielmetti- registered dietitian expert who is currently a researcher at the University of Pavia (Italy)

Bias: These authors are not biased because they do not express any opinions but rather factual information about case studies.

Reliable: This is a reliable source because the authors are registered dieticians who focus on the effects that certain diets have on children, in the instance, the ketogenic diet.

Possible Limitations: While this article does talk about the effect of the ketogenic diet on children, it only briefly talks about the effect that it has on children with epilepsy specifically. Though it can be inferred that the effects would be the same if not similar, it is hard to fully know.

the keto diet places extreme strain on the liver

This commonly results in higher levels of liver enzymes, such as ALT and AST

80% of children maintained normal growth during the 12-month period

The other 20% of children experienced growth retardation

The diet tends to be safe for children, but there are cases where it interferes with linear development

Growth retardation was more commonly observed in younger children on the dirt

Children with a longer duration of seizure control on the diet had better growth outcomes

despite making sure echildren on the diet had nutritional adequacy through supplementation, some children on the keto diet still had growth issues

• This led to the development of individual variation in how the diet affects growth

Nutritional adequacy was carefully managed with supplements (vitamins, minerals, and citrate) —> this did not prevent growth retardation

Suggests that while adequate calories and nutrients are essential for supporting general health and growth, outcome are influences by other factors (genetic predisposition, age at diet initiation, and duration of diet adherence)

Some children with adequate nutritional support still showed signs of nutritional stress as they experienced growth delays —> suggests that other metabolic/hormonal factors could be at play

deeper ketosis might be associated with a higher likelihood of growth delay

Children who maintained higher levels of ketosis were more likely to experience growth retardation

Intense ketosis may affect metabolic processes related to growth (but it is not the sole factor in causing the growth issues)

There was significant association between elevated ketone levels at 12 months and growth delays

• Especially in children who were on the keto diet for a long period of time

it is extremely important to monitor children on the keto diet (specifically those at risk of growth retardation

To protect children on the keto diet, children should have personalized care and tailored monitoring plans

Regularly monitoring of height and weight was considered essential for tracking growth

Children on the keto diet show undergo frequent growth assessments to ensure they are growing at an appropriate rate

Growth patterns in children have to be monitored if they are on the keto diet

When children are on the keto diet, during the first years they are expected to see the most amount of growth delays

Individual monitoring helps detect growth issues early and allow for prompt intervention that still allows the patient to address their epilepsy

Overall, growth outcomes vary between children so they have to be monitored individually

children may experience liver dysfunction due to the increased demand on the liver to metabolize fates and produce ketone bodies

High-fat content of the ketogenic diet necessitates increased hepatic activity

• Leads to various liver-related complications

Children tend to tolerate the diet well, however, some still develop elevated liver enzymes and fatty liver disease

Children with pre-existing liver conditions and those who are genetically predisposed are at risk of developing liver-related complications

Th liver’s role in metabolizing fats and producing ketone bodies is crucial during ketogenic therapy

during the early phases of the keto diet, it is necessary for children to be monitored because of the implications that it could have

Liver enzymes have to be monitored because of the negative impacts they have

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are crucial because fluctuations in their levels are early signs of liver dysfunction and liver stress which can have detrimental effects on the patients

If elevated enzyme levels are detected, adjustments to their diet or medical interventions may be necessary, even if the keto diet is helping the patient with the keto diet

It is recommended to establish baseline liver function test before initiating the diet and conducting follow-up tests

genetic predispositions may influence how a child’s liver responds to the ketogenic diet

Children with certain metabolic disorders, such as mitochondrial disorders, may be at a higher risk of developing liver dysfunction

Genetic factors can affect the metabolism of fats and ketone bodies —> potentially leading to an increased risk of liver-related complications

Children with underlying metabolic disorders may have a reduced capacity to process the high-fat content of the keto diet

one of the ost serious potential liver related side effects of th keto diet is hepatic steatosos, also known as as fatty liver disease

• This occurs die to the high fat content of the diet

Hepatic steatosis is characterized by the accumulation of fat within liver cells —> this often leads to impaired liver function

Some cases of fatty liver disease are asymptomatic and resolve with dietary adjustments while other cases lead to more severe liver conditions

It is important to have early detection of fatty liver disease to prevent long term complications for patients

Questions: How does long term ketosis impact liver health in developing children? Are certain children more genetically predisposed to liver complications on the ketogenic diet? What are the best practices for monitoring liver function in children on the ketogenic diet?

Important Terms:

• B-Hydroxybutyrate

• GLUT1 Deficiency Syndrome

• Hepatic Steatosis

• Mitochondrial Disorders

• Acidosis

Author Credentials: Dr. Carl E. Stafstrom, MD, PhD - director of the division of pediatric neurology at John Hopkins’s School of Medicine / Dr. Jong M. Rho, MD - Section Chief of Pediatric neurology at Yale School of Medicine

Bias: These authors are not biased because they are sharing data and evidence they have gathered and are not trying to share any opinions.

Reliable: This source is reliable because both the authors are qualified to write about the topic and because is was peer reviewed by many other reliable authors

Possible Limitations: Some limitations are how long ago the book was published, 2004, and how information about the topic has changes since then. Additionally, there is limited focus on liver function, and there is a lack of comparative dietary analysis.

liver enzymes (ALT and AST) were part of routine lab checks during the study to detect early hepatic stress

Regular monitoring helped assess whether the high fat diet negatively impacted liver function in metabolically immature infants

No infants in the study showed elevated liver enzymes, which indicates good short-term hepatic tolerance

Monitoring included not just liver enzymes but also other metabolic indicators like glucose and lipid levels

Clinical best practice is to continue enzyme testing at intervals, especially during dietary adjustments or if symptoms arise

across the 13 infants, no cases of liver toxicity, jaundice, or significant metabolic acidosis were reported

This suggests that, when properly managed, keto can be safe from a hepatic standpoint, even in very young patients

The study emphasized how slow dietary initiation and careful macronutrient calculation to reduce metabolic stress

Nutritional and biochemical tolerability was assessed by tracking liver related conditions

The absence of symptoms may reflect individualized diet planning and close clinical supervision.

infants with genetic causes of epilepsy had better seizure outcomes, suggestion possible metabolic advantages

Some genetics epilepsies (GLUT1 deficiency) are known to benefit from keto without stressing the liver

Genetic profiles may influence how efficiently fats are metabolized, which could affect liver workload

The study implies that children with certain gene mutations might have improved tolerance to the diet, including hepatic aspects

Personalize medicine approaches could one day predict hepatic safety based on a child’s genetic profile

the study lasted 6 months so that is could assess short-term effects

• Not a long enough study to see if there were any delayed liver issues

Hepatic complications life fatty liver or cumulative enzyme elevation could emerge after prolonged fat intake

• This means that the effects of th keto diet on the liver in the children could have started after the trial was finished

The authors recommend extended follow up to see if there are late-onset complications with the keto diet in the children

Long term use of high fat diets carry rights that require reevaluations later on. Even if the diet is being used to treat epilepsy

Monitoring could include blood tests and abdominal imaging if a doctor suspects liver stress in a patient

Questions: How does the immature liver in infants handle the metabolic stress of high fat intake short-term? Are there specific warning signs of early liver stress in infants on the keto diet that might be missed without monitoring? Could certain genetic epilepsy syndromes predict better or liver outcomes during the keto diet?

Important Terms:

• Liver enzymes

• Genetic etiology

• Biochemical monitoring

Author Credentials: Dr. Tzu-Yun Hsieh - attending physician in pediatric neurology, specialized in pediatric neurology with a focus on epilepsy management / Dr. Ting-Yu Su - attending physician in pediatric neurology, specialized in pediatric neurology with expertise in refractory epilepsy

Bias: There are no biases in this article because it is an article about the evidence gathered from a study. At the end of the article the authors talk about what doctors should do, but this is based on evidence.

Reliable: This is a reliable source because the authors have good credentials and can be considered reliable. Also, the authors have expertise on what they are studying, and the study they completed was monitored by other organizations and doctors with reliable credentials.

Possible Limitations: the sample size of the study was very small, only 13 infants, meaning that the statistical accuracy of the study is limited. also the study was done for a short period of time (6 months) and complications could have occurred after those 6 months. Finally, the article only focuses on children under the age of 2 making this study and its findings limiting.

the study measured common liver health markers: AST, GGT, and bilirubin

No significant differences in these makers were observed between the control, BCAA and BCKA groups

This suggests neither BCAA or BCKA infusions caused liver damages over the 21 day infusion period

Stable liver enzyme levels indicate that hepatic cellular integrity was maintained

The findings support the safety of these amino acid derivatives in terms of liver enzyme response

BCKA infusion led to a significant reeducation in liver triglyceride accumulation

• Suggests improved hepatic lipid metabolism/enhances fat export and use in liver

• BCAA infusion did not significantly change liver triglyceride levels

BCKA infused cows had increased plasma thrill and albumin which indicates stronger antioxidant capacity

Liver glutathione was significantly higher in the BCK groups

Expression of glutathione reductive (antioxidant ant enzyme) was elevated in the liver of BCK cows

These changes point to improved redox balance and reduced oxidative stress in the liver

The BCAA group did not show the same antioxidant benefits, highlighting the unique effects of BCKA

BCK cows had higher plasma albumin which correlates with inflammation

• Reflects a milder inflammatory states in the BCKA group despite no major shifts in standard markers

Neither infusion group showed signs of promoting liver or systematic inflammation

Questions: how do branched-chain keto acids influence liver metabolism in children on keto diet? What impact does the keto diet have on liver lipid metabolism in children? Do keto diets reduce oxidative stress in the liver in children with epilepsy?

Important Terms:

• Inrantile epilepsy

• Refractory epilepsy

• Triglycerides

• Oxidative Stress

Authors credentials: Ahmad - department of Animal Science / Daddam - Department of Animal Science

Bias: there is not bias in this article because its purpose is to provide information and evidence of the effect of the keto diet on cows.

Reliable: this is a reliable source because the authors have the credibility to write the article, and because it is based on a peer reviewed study

Limitations: The main limitations of this article is that it does not talk about the effect it has on kids with epilepsy, and it focuses on infusing cows with amino acids that mimic the keto diet instead of putting cows on the keto diet

liver function tests are part of the baseline assessments when children are referred for the keto diet

The keto-reg registry includes fields for ongoing liver enzyme monitoring (AST, ALT)

Regular monitoring is crucial for identifying early signs of liver stress or dysfunction, especially during long-term KDT

The registry aims to standardize data collection on liver health across multiple epilepsy center

Data entry from multiple sites make it possible to compare liver function trends across different treatment protocols

The study validates feasibility by showing clinicians could enter this liver related data accurately and consistently

The registry sets the stage for future longitudinal studies that could assess liver effects over time in large pediatric populations

one of the registry’s primary goals is to gather data on adverse events, including hepatic complications linked to KDT

Safety reporting includes tracking of biochemical markers and any clinical signs of liver distress

The article identifies the importance of having systematic approach to flag liver related concerns in children on KDT

Professionals expressed concern about time and funding needed for continued liver safety surveillance

The register was shown to be usable across international centers, meaning wider safety trends (like liver impact) can be studied globally

Including parental and patient feedback in future registry versions may enhance the reporting of subtle or early hepatic side effects

These safety measures are part of a broader effort to ensure the risk benefit profile of KDT remain favorable, especially for long term pediatric use

Questions: How does long term use of keto affect children with epilepsy? Are certain children more vulnerable to side effects of keto? How frequently should liver function be monitored in children on KDT to ensure safety?

Important terms:

• Keto-Reg

• Liver Function Tests

• Feasibility Study

• Adverse Effects

Author credentials: Elizabeth Neal - Senior Research Fellow and Specialist Paediatric Dietitian / Victoria J. Whiteley - Registered dietitian with a background in Paediatric nutrition

Bias: There is some bias in this article because the authors are sharing their opinions on why they believe a registry should be created. However, the evidence they use to support themselves is beneficial to the EE

Reliable: This is a reliable source because of the authors and their credibility. Additionally, the article is peer-reviewed and published by a trusted organization

Limitations: The main limitation with this is the amount of irrelevant information provided in the article about the registry.

regular liver function tests monitor enzymes and is essential to detect any hepatic dysfunction early

Conducting LFTs before initiating keto diet is necessary to establish baseline liver function

Regular intervals of LFTs are used during periodic monitoring to identify any emerging liver issues

Doctors monitored the children for signs of liver dysfunction pointing towards jaundice or hepatomegaly

Modifying the keto diet to specific individuals is needed if significant liver enzymes are elevated, and the diet is necessary for the children to handle their epilepsy

Collaboration between pediatric neurologist, dietitians, and hepatologists is important to manage liver health and the child’s overall health

Accurate recording of liver function data from similar patients is used to assess what arrogance certain individuals duals should try.

Constipation - reported as the most common side effect, it potentially affects the liver function indirectly

Irritability and nausea - gastrointestinal symptoms that many be associated with liver stress

Vomiting - often leads to dehydration which impacts liver function and overall health

Weight loss - unintended weight loss may indicate metabolic disturbances affecting the liver

Fatigue - generalized fatigue could be a sign of liver dysfunction or metabolic imbalance

Hypoglycemia - low blood sugar levels may result from impaired liver gluconeogenesis

Pancreatitis - inflammation of the pancreas can affect liver function due to shared metabolic pathways (this is rare)

Questions: What is the risk of liver stress or damage when children are placed in KD, especially those with pre-existing metabolic vulnerabilities? Does the type of keto diet make a difference in terms of liver impact?

Important Terms:

• Genetic epilepsy syndromes

• Seizure reduction rate

• Adverse effects

Author credentials: Both authors work together in the Department of Pediatric, Faculty of Medicine, King Abdulaziz University in Jeddah, Saudi Arabia. They are both pediatric neurologists.

Bias: this article does not have any basis because it is the authors sharing the results of a study. They are not trying to convince the reader of anything.

Reliable: this is a reliable source because it was written by credible authors and reviewed by credible authors.

Possible Limitations: The study only focuses on genetic syndromes and not all possible outcomes / the study only evaluates the short-term effects of the keto diet and not the long term effects.

Phase 1 - Cholestasis and Inflammation

• Characterized by elevated serum conjugated bilirubin level and histological features such as canalicular cholestasis and portal inflammation

• Associated with ongoing PN administration

• May progress to fibrosis if not address immediately

Phase 2 - Fribrosis and Steatosis

• Occurs after discontinuation of PN

• Persistent hepatic fibrosis and steatosis can remain, even without ongoing cholestasis

• Liver histology may show peri portal fibrosis and steatosis without active inflammation

Clinical significance

• Persistent liver damage in phase2 can lead to long-term complication, including cirrhosis and potentially a liver transplantation

• Early detection and intervention are necessary to prevent progression

Intestinal barrier dysfunction - increase intestinal permeability allows endotoxins and other harmful substances to enter the portal circulation, this can trigger hepatic inflammation

Microbial dysbiosis - altered gut microbiota composition (with an overgrowth of harmful bacteria) can contribute to liver injury / reduced microbial diversity and increase intestinal permeability allows proteobacteria (ex. Enterobacteriaceae) have been associated with hepatic steatosis

Parenteral nutrition components - phytosterols in lipid emulsion can accumulate in the liver encouraging inflammation and cholestasis / lack of antioxidant in PN formulations my increase oxidative stress and liver damage

Immune Response - activation of hepatic macrophages and pro-inflammatory cytokine release play a central role in the progression of liver injury / targeting inflammatory pathways may offer therapeutic benefits

Questions: Why does liver damage in children with intestinal failure sometimes continue even after stopping parenteral nutrition? Con improving the intestinal barrier or restoring health gut microbiota effectively prevent/reverse liver disease in children?

Important terms:

• Intestinal failure

• Parenteral nutrition

• Cholestasis

• Phytosterols

Author credentials: Both authors work with the section of pediatric gastroenterology, hepatology, and nutrition at the university of Colorado school of medicine and children hospital Colorado. Racha is a pediatric gastroenterologist and Sokol is a expert in pediatric hepatology

Bias: there is not bias in this article because it is sharing information that was gathered by many scientist and put together in a journal to teach others.

Reliable: this is a reliable source because it was written by credible authors. The article was revised by many others and both eh authors are considered experts in their fields

Limitations: This article is review based on original research, meaning that the authors did not conduct the research themselves. The article was written in 2020 and pediatric hepatology is a rapidly evolving field.

obesity is the primary risk factor for pediatric NAFLD and the keto diet is used for weight loss which. Could reeducate NAFLD risk

Children with metabolic syndrome (insulin resistance and dyslipidemia) are at a higher risk for NAFLD, the keto diet can improve insulin sensitivity

Genetic predispositions (PNPLA 3 variants) contribute to individual susceptibility

A high carbohydrate diet is more commonly linked to hepatic fat accumulation potentially affecting liver lipid metabolism

Early weight gain in childhood is a predictor of NAFLD

The link between fructose consumption and liver fat can be dangerous. By eliminating fructose sources the keto diet could be beneficial

The keto diets high fat content could worsen liver fat accumulation in certain individuals, especially is weight loss is not achieved or maintained

ultrasound imaging is often the first tool for detecting hepatic steatosis

ALT (Alanine aminotransferase) is used as a liver injury marker, it commonly becomes elevated during the keto diet

The elevations of ALT and AST can not be the only diagnosis of liver stress.

Liver biopsy is used to diagnose NAFLD, but it is invasive and many children chose not to have it done

Transient elastography (FibroScan) and MRI-PDFF are non-invasive tools that asses how liver fate changes during the keto diet

Inflammatory markers and lipid profiles can show indirect measures of liver stress. The keto diet changes the makers

If doctors have an over-reliance on liver enzyme normalization then they can miss potential signs as fatty liver disease can happen even if labs appear to be normal

Questions: how does the keto diet affect liver fat accumulation in children with are already at risk for NAFLD? Can the KD trigger/worsen hepatic steatosis in children with no current liver issues?

Important Terms:

• NAFLD - nonalcoholic fatty liver disease

• NASH - nonalcoholic steatohepatitis

• Insulin resistance

Authors Credentials: Dr. Pietro Varro - Chair of pediatrics at the university of Salerno, Italy / Dr. Selvaggia Lenta - Works at the university of Naples, Italy

Bias: There is some bias in this article because it talks about supporting the ESPGHAN hepatology committee. However, the source is still reliable because the authors use trusted evidence to support themselves.

Reliable: This is a reliable source because the authors have the crediatials to write about the topic. furthermore, the article is based on evidence collected from many different scientist and doctors.

Limitations: The main limitations of this article is that it primarily is about the ESPGHAN committee and only has some information about the effects of fatty liver disease in children. It also does not talk about children with epilepsy.

Questions: Could the keto diet disrupt normal BCAA balance in children? How does the keto diet affect shorten with BCAA metabolism disorders?

Important Terms:

• Breached chain a-keto acid dehydrogenase complex (BCKDH)

• BCKDH Kinase (BDK)

• Seizures

• Neurological abnormalities

Author Credentials: both authors work together at the department of biochemistry and molecular biology, Indiana University School of Medicine, Indianapolis, IN

Bias: there is no bias in this article because the authors are not attempting to convince readers of anything and they are only trying to share information

Reliable: This is a reliable source because the authors are creditable and because they based their information off of research that was gathered by many scientist and doctors

Possible Limitations: the main problem with this source is that it does not talk about the effect of the keto acids on children and only focuses on mice.

disruption in the BCAA metabolism due to BDK deficiency can lead to neurological abnormalities like seizures and motor dysfunction

• This raises concerns about the the keto diet, which can affect amino acid metabolism and increase BCAA intake, might impact brain development in children

  • Especially those with underlying metabolic vulnerabilities

  • The keto diet might affect neurotransmitter balance, cognitive function, or seizure risk even if it is being used to treat non drug responsive epilepsy

BDK-deficient mice have impaired grwother, which is partially corrected by a high protein diet

The keto diet includes high fat and high protein which suggests that it could influence growth in children depending on their metabolic capacity to process amino acids

The Keto diet can support and limit growth in children depending on the genetic makeup of up of children and their critical developmental stages

Questions: does the increase mitochondrial activity form the ketogenic diet place stress on developing livers in children? Can pediatric livers adapt as efficiently as adult livers to the fat oxidation demands imposed by a ketogenic diet?

Important Terms:

• Mitochondrial metabolism

• Insulin Sensitivity

• B-Oxidation

Author Credentials: Luukkonen - department of internal medicine, Yale School of medicine, Minerva foundation institute for medical research, department of medicine, university of Helsinki / Dufour - department of internal medicine, Yale school of medicine, Yale diabetes research center

Bias: There is not bias in this article because it does not have any opinions to share, rather it informs the reader of research that was gathered from different sources

Reliable: This is a reliable source because it was written by trustworthy authors, and was also reviewed by multiple people who have the credentials and a trusted reputation

Limiting Factors: the limitations factor of this article is that it does not talk about children with epilepsy, rather it talks about the effect of the keto diet on the general population

there was a significant decrease in liver fat content after 6 days on the keto diet in adults with NAFLD

Liver triglyceride levels dropped by an average of 31% which shows the rapid impact of carbohydrate restriction

Magnetic resonance spectroscopy was sued to quantify liver fat reeducation, providing non invasive by precise data

The diet suppressed de novo kipogenesis which is the process by which th liver turn carbs into fat

Plasm insulin levels decrease which improved insulin security, which is a key factor in reducing liver fat accumulation

The participant shows reduced intrahepatic glycogen stores, which reflects the body’s switch from carbs to fat metabolism

The keto diet may offer therapeutic potential for liver conditions characterized by fat buildup

diet led to a marked increase in hepatic mitochondrial oxidation, which indicated enhanced fat burning activity

Researches observes a shift from glucose bases to fate based energy metabolism in the liver

Increase B-hydroxybutyrate levels confirmed that mitochondrial ketogenesis was happening

Hepatic ATP production remained stable

• Suggest efficient energy generation during the dietary switch

Reduced malonyl-CoA levels were measured which promotes mitochondrial fatty acid entry and oxidation

Changes in liver metabolites indicated upregulation of mitochondrial enzymes tied to fat metabolism

The keto diet enhances liver energy metabolism, but it also increase metabolic demand in liver which can make it unsafe for long term use on children

Questions: Could some of the side effect reported by parents )fatigue, vomiting, loss of appetite) be early signs of liver stress? Are families equipped to recognize symptoms that may indicate liver dysfunction during dietary therapy?

Important Terms:

• Parental perception

• Dietary adherence

• Therapeutic impact

Author Credentials: both work at School of health professions, Faculty of health, University of Plymouth, Devon, United Kingdom

Bias: This article is not bias because the authors are presenting data and evidence gathered form a study

Reliable: this is a reliable source because it was published by a credible journal, reviewed by reliable authors, and based on evidence that is accepted as the truth worldwide

Limitations: the main problem with this article is that it did not include the long-term mealtime tracking of the children on the keto diet

parents reported limited understanding of the full range of possible side effects of the KD

The parents lack of understanding led them to not notice the early signs of fatty liver disease

Most families focuses on seizure control as the main benefit, and some overlooked the concerns about the long term metabolic and hepatic effects

Liver related side effects (vomitting, fatigue, and appetite loss) were commonly not recognized as potentially diet related

Not families in the study mentaions liver enzyme monitoring

The lack of clinical data in the study limits the ability to evaluate whether any children developed hepatic issues while on keto

Many parents were unable to manage the keto diet for their children

Families need to be educated on the potential impacts of the keto diet before they opt to implement it for their child with epilepsy

families described high stress levels and effort to maintain the diet which leads to inconsistent nutritional intake

Inconsistencies in dietary adherence affect metabolic stability and place additional strain on the liver as it adapts to fluctuating fat and protein loads

Parents shared challenges with the child not adhering to the die which can lead to imbalanced intake and potential metabolic side effects

Some families discontinued the diet early due to side effects (nausea/fatigue) this could be linked to liver strain even if it was not diagnose

The qualitative stay means liver-related effects were only indirectly reported or suspected (not confirmed through testing)

Lack of adherence might lead to partial ketosis, which may reduce the therapeutic benefit while still imposing metabolic demands on the liver

Questions: what are the long term outcomes for children who experience liver complications while on keto? Can liver related side effects of the keto diet be reversed upon diet modification or cessation?

Important Terms:

• Medium-Chain Triglyceride Ketogenic Diet (MCTKD)

• Modified Atkins Diet

• Low Glycemic Index Treatment

• Gallstones

Author Credentials: Faheem - Pediatrics, California Institute of Behavioral Neurosciences and psychology / Jaiswal - Internal medicine, California institute of behavioral neurosciences and psychology

Bias: There is no basis in this article because it is an information article that is sharing statistics and evidence about a study that was conducted

Reliable: This is a reliable source because both authors are experts in their field and have a reputation for being credible.

Limitations: the article does not focus solely on the liver, and the study test many different groups of people on different versions of of the keto diet making it hard to draw clear conclusion about liver effects.

the keto diet is effective in reducing seizure frequency in many children with drug-resistant epilepsy

Talks about multiple studies that show a significant portion of pediatric patients experiencing over 50% of seizure reduction

Some cases report complete seizure freedom while on the diet, especially in syndromes like GLUT1 deficiency and Doose syndrome

Ketone bodies predicted during the diet may alter neuronal excitability and reduce seizure activity

The keto diet is seem as a viable alternative when anti-epileptic drugs fail or produce intolerable side effects

Questions: how does the intensive dietetic care time correlate with the monitoring and management of liver function in pediatric patients on keto? Are there specific aspects of keto that require more dietetic time and may have implications for liver health?

Important Terms:

• Direct contact time

• Dietetic care contact time

• Comorbidities/Complex medical conditions

Author Credentials: Both work at Leeds Children’s Hospital

Bias: There is not any bias in this article because the article is sharing information that it put together, and not trying to convince the reader of anything.

Reliable: this is a reliable source because the authors have credibility and it was published by a reliable journal. Additionally, the information it provides is globally accepted.

Limitations: this article does not focus on specific medical outcomes like liver health, and it does lack a tone of clinical data such as specific liver enzyme levels, ketone levels, and lipid profiles.

if the keto diet is going to be used, it requires significant dietetic support

Different keto variations are used and personalized for each patient depending on what it is being used for and what their bodies can handle

The high fat content in the keto dies increase the risk of liver complications long term (fatty liver, hepatic steatosis)

Children with complex medical condition need more support on the keto diet as they are more vulnerable to liver stress