Digestive / Gastroinestinal System

 The digestive system is a complex network of organs responsible for the  breakdown, absorption, and assimilation of nutrients from food and the  elimination of waste products from the body. It includes the alimentary  canal (digestive tract) and accessory organs. The alimentary canal  consists of the mouth, pharynx, esophagus, stomach, small intestine,  large intestine (colon), rectum, and anus, where digestion and  absorption occur. Accessory organs include the salivary glands, liver,  gallbladder, and pancreas, which produce digestive enzymes, bile, and  other substances essential for digestion. The digestive process begins  with ingestion, where food is consumed and broken down into smaller  particles by mechanical and chemical digestion in the mouth and stomach.  Nutrients are then absorbed through the walls of the small intestine  into the bloodstream and transported to cells throughout the body for  energy, growth, and repair. Waste products are eliminated as feces  through the large intestine and expelled from the body through the  rectum and anus. 

• Gastroesophageal Reflux Disease (GERD): A chronic condition characterized by the backward flow of stomach acid into the esophagus, causing symptoms such as heartburn, regurgitation, chest pain, and difficulty swallowing.
• Peptic Ulcer Disease: Open sores or ulcers that develop in the lining of the stomach, esophagus, or duodenum (first part of the small intestine), often caused by infection with Helicobacter pylori bacteria or long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), leading to abdominal pain, bloating, and gastrointestinal bleeding.
• Inflammatory Bowel Disease (IBD): A group of chronic inflammatory disorders, including Crohn's disease and ulcerative colitis, characterized by inflammation and damage to the gastrointestinal tract, leading to symptoms such as abdominal pain, diarrhea, rectal bleeding, weight loss, and fatigue.
• Irritable Bowel Syndrome (IBS): A functional gastrointestinal disorder characterized by abdominal pain, bloating, diarrhea, and/or constipation, often triggered by stress, dietary factors, or hormonal changes.
• Gallstones: Hardened deposits that form in the gallbladder, usually consisting of cholesterol or bilirubin, which can obstruct bile flow and cause symptoms such as abdominal pain, nausea, vomiting, and jaundice.
• Pancreatitis: Inflammation of the pancreas, often caused by gallstones or excessive alcohol consumption, leading to abdominal pain, nausea, vomiting, and potentially life-threatening complications.

 Can lead to diabetic gastroparesis, enteropathy, and an increased risk of non-alcoholic fatty liver disease (NAFLD). 

 Hyperinsulinemia, insulin resistance, and metabolic syndrome may contribute to the development or exacerbation of digestive system disorders through various mechanisms:

• Inflammation: Insulin resistance and metabolic abnormalities are associated with chronic low-grade inflammation, which may contribute to the pathogenesis of inflammatory bowel diseases like Crohn's disease and ulcerative colitis.
• Gut Microbiota Dysbiosis: Metabolic disturbances can alter the composition and function of the gut microbiota, leading to dysbiosis, impaired intestinal barrier function, and increased susceptibility to gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome.
• Obesity: Metabolic syndrome components such as obesity are significant risk factors for digestive system disorders such as gastroesophageal reflux disease (GERD), peptic ulcer disease, and gallstones, leading to increased intra-abdominal pressure, reflux, and bile flow abnormalities.
• Insulin and Growth Factors: Insulin and insulin-like growth factors (IGFs) may promote cell proliferation and mucosal growth in the gastrointestinal tract, potentially contributing to the development of gastrointestinal tumors and malignancies.
• Dyslipidemia: Metabolic abnormalities such as dyslipidemia (elevated levels of cholesterol and triglycerides) are associated with an increased risk of gallstone formation, due to alterations in bile composition and cholesterol metabolism.

Overall, while the direct influence of metabolic abnormalities on digestive system disorders may vary, their effects on inflammation, gut microbiota, obesity, insulin signaling, and lipid metabolism may indirectly contribute to the development or exacerbation of gastrointestinal diseases.

  Contributes to conditions like fatty liver disease, gastroesophageal reflux disease (GERD), and gallstones. 

 Can lead to diabetic gastroparesis, enteropathy, and an increased risk of non-alcoholic fatty liver disease (NAFLD) 

Gastroesophageal reflux disease (GERD), commonly known as acid reflux, is a chronic condition characterized by the reflux of stomach acid and digestive juices into the esophagus. This occurs when the lower esophageal sphincter (LES), a ring of muscle at the bottom of the esophagus that normally closes after food passes into the stomach, becomes weakened or relaxes inappropriately. When the LES fails to function properly, stomach acid can flow back up into the esophagus, leading to irritation, inflammation, and symptoms such as heartburn, regurgitation, chest pain, difficulty swallowing, and a sour taste in the mouth.

Insulin resistance, hyperinsulinemia, and metabolic syndrome can impact  gastrointestinal reflux disease (GERD) through several mechanisms.  Firstly, they stimulate gastric acid production, increasing the  likelihood of acid reflux episodes. Additionally, delayed gastric  emptying prolongs contact between stomach acid and the esophageal  lining, heightening the risk of reflux and irritation. Esophageal  dysmotility, associated with insulin resistance-related neuropathies,  can further impede clearance, exacerbating reflux symptoms. Obesity,  common in metabolic syndrome, raises intra-abdominal pressure, promoting  reflux of stomach contents into the esophagus. Moreover, dietary habits  linked to these conditions, such as high consumption of fatty and  acidic foods, caffeine, and alcohol, can trigger or worsen reflux  symptoms. Although the precise mechanisms are not fully elucidated,  addressing insulin resistance and metabolic syndrome through lifestyle  changes and medications may alleviate GERD symptoms. Management  strategies include dietary modifications, weight management, and  medications to reduce gastric acid production. 

1. Wu  K-L, Kuo C-M, Yao C-C, et al. The effect of dietary carbohydrate on  gastroesophageal reflux disease. J Formos Med Assoc.  2018;117(11):973-978. doi:10.1016/j.jfma.2017.11.001
2. Pointer  SD, Rickstrew J, Slaughter JC, Vaezi MF, Silver HJ. Dietary  carbohydrate intake, insulin resistance and gastro-oesophageal reflux  disease: A pilot study in European- and African-American obese women.  Aliment Pharmacol Ther. 2016;44(9):976-988. doi:10.1111/apt.13784
3. Yancy  WS, Provenzale D, Westman EC. Improvement of gastroesophageal reflux  disease after initiation of a low-carbohydrate diet: Five brief case  reports. Altern Ther Health Med. 2001;7(6):120, 116-119. PMID:11712463 PDF
4. Austin  GL, Thiny MT, Westman EC, Yancy WS, Shaheen NJ. A very low-carbohydrate  diet improves gastroesophageal reflux and its symptoms. Dig Dis Sci.  2006;51(8):1307-1312. doi:10.1007/s10620-005-9027-7 ABSTRACT

  The Acid in your stomach is ideally at a pH of 1-3 (lower number more acidic). 

Your stomach can deal with this Acidic environment because of the Mucus layer.  Your body's primary anti-reflux barrier is a type of muscle called a sphincter.  A sphincter is a highly specialized type of muscle that allow or restrict passage of fluids and materials through your body. LES or Lower Esophageal Sphincter is the valve that restricts the flow of stomach acid to the food pipe.  This valves close when the abdominal acidity & pressure builds up preparing for digestion. When your Stomach Acid is too LOW (higher pH), the stomach fails to signal your brain to close the valves at the right times & with sufficient pressure.  When this happens, the stomach acid refluxes into the Esophagus & thats what causes the burning sensation. So how burning sensation with less acidity? Even though it's less acidic, it is still an Acid & highly corrosive. Unlike the stomach with mucus lining, other parts of the body (in this case esophagus) can't handle it. The main reasons for low stomach acid are:  Diet , Stress,  Medication, Solution: Limit Grains,  Avoid Sugar, Avoid Seed Oils, Avoid Alcohol ,Avoid frequent Eating.   Antacids provide temporary relief by neutralizing the acid, but that doesn't address the root cause. It will keep making the problem worse in the long run & effect your health in other ways too. 

Carbohydrate malabsorption refers to a condition where the body has difficulty digesting and absorbing certain types of carbohydrates. Normally, carbohydrates are broken down into simpler sugars during digestion and absorbed into the bloodstream to provide energy for the body's cells. However, in individuals with carbohydrate malabsorption, this process is impaired, leading to symptoms such as bloating, gas, diarrhea, and abdominal discomfort.

There are several types of carbohydrate malabsorption, including:

1. Lactose intolerance: Lactose intolerance is the most common type of carbohydrate malabsorption. It occurs due to a deficiency of lactase, the enzyme responsible for breaking down lactose, the sugar found in dairy products. Without enough lactase, lactose remains undigested in the intestine, leading to symptoms such as bloating, gas, abdominal pain, and diarrhea.
2. Fructose malabsorption: Fructose malabsorption occurs when the small intestine is unable to absorb fructose, the sugar found in fruits, honey, and some vegetables. This can be due to a deficiency of the enzyme responsible for transporting fructose across the intestinal lining. Undigested fructose can ferment in the colon, causing symptoms similar to lactose intolerance, including bloating, gas, diarrhea, and abdominal pain.
3. Sucrose intolerance: Sucrose intolerance is rare and occurs due to a deficiency of sucrase-isomaltase, the enzyme responsible for breaking down sucrose (table sugar) into glucose and fructose. Without enough sucrase-isomaltase, sucrose remains undigested in the intestine, leading to symptoms similar to lactose intolerance and fructose malabsorption.
4. Other carbohydrate malabsorption disorders: Other less common types of carbohydrate malabsorption include maltose intolerance (due to a deficiency of maltase), sorbitol intolerance, and mannitol intolerance. These conditions involve difficulty digesting and absorbing specific types of sugars found in certain foods.

Diagnosis of carbohydrate malabsorption typically involves a combination of medical history, physical examination, and specialized tests, such as breath tests or stool tests, to assess carbohydrate absorption and fermentation in the digestive tract. Treatment usually focuses on dietary modifications, such as reducing or eliminating the problematic carbohydrates from the diet, and may include the use of enzyme supplements to aid digestion.

1. Goebel-Stengel  M, Stengel A, Schmidtmann M, van der Voort I, Kobelt P, Mönnikes H.  Unclear Abdominal Discomfort: Pivotal Role of Carbohydrate  Malabsorption. J Neurogastroenterol Motil. 2014;20(2):228-235. doi:10.5056/jnm.2014.20.2.228
2. Born  P. Carbohydrate malabsorption in patients with non-specific abdominal  complaints. World J Gastroenterol. 2007;13(43):5687-5691. doi: 10.3748/wjg.v13.i43.5687
3. Goldstein  R, Braverman D, Stankiewicz H. Carbohydrate malabsorption and the  effect of dietary restriction on symptoms of irritable bowel syndrome  and functional bowel complaints. Isr Med Assoc J. 2000;2(8):583-587. PMID:10979349 ABSTRACT 
4. Born  P, Sekatcheva M, Rösch T, Classen M. Carbohydrate malabsorption in  clinical routine: A prospective observational study.  Hepatogastroenterology. 2006;53(71):673-677. PMID:17086866 ABSTRACT 
5. Fernández-Bañares  F, Rosinach M, Esteve M, Forné M, Espinós JC, Maria Viver J. Sugar  malabsorption in functional abdominal bloating: a pilot study on the  long-term effect of dietary treatment. Clin Nutr. 2006;25(5):824-831.  doi:10.1016/j.clnu.2005.11.010 ABSTRACT
6. Hammer HF, Hammer J. Diarrhea Caused By Carbohydrate Malabsorption. Gastroenterology Clinics. 2012;41(3):611-627. doi:10.1016/j.gtc.2012.06.003 ABSTRACT

There is a  general lack of consensus regarding  regarding  best management of various gastrointestinal disorders and supports  individual tailoring through elimination protocols. Common themes  include whole foods, reduced carbohydrate, FODMAP and low/no/high fibre. .

 Removing fiber can be the key to solving almost all digestive pain. Here is one of the only controlled trials looking at fiber and constipation. Removing it helped dramatically! 

1. Suskind DL, Lee D, Kim  Y-M, et al. The Specific Carbohydrate Diet and Diet Modification as  Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet  Controlled Trial. Nutrients. 2020;12(12):3749. doi:10.3390/nu12123749
2. Alsharairi,  N.A. (2022) ‘The Therapeutic Role of Short-Chain Fatty Acids Mediated  Very Low-Calorie Ketogenic Diet–Gut Microbiota Relationships in  Paediatric Inflammatory Bowel Diseases’, Nutrients, 14(19), p. 4113. Available at: https://doi.org/10.3390/nu14194113.
3. Jiang  Y, Jarr K, Layton C, et al. Therapeutic Implications of Diet in  Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory  Diseases. Nutrients. 2021;13(3). doi:10.3390/nu13030890
4. Konijeti  GG, Kim N, Lewis JD, et al. Efficacy of the Autoimmune Protocol Diet  for Inflammatory Bowel Disease. Inflamm Bowel Dis.  2017;23(11):2054-2060. doi:10.1097/MIB.0000000000001221
5. Kakodkar  S, Mutlu EA. Diet as a therapeutic option for adult inflammatory bowel  disease. Gastroenterol Clin North Am. 2017;46(4):745-767. doi:10.1016/j.gtc.2017.08.016 
6. Burgis  JC, Nguyen K, Park K, Cox K. Response to strict and liberalized  specific carbohydrate diet in pediatric Crohn’s disease. World J  Gastroenterol. 2016;22(6):2111-2117. doi:10.3748/wjg.v22.i6.2111
7. Tóth  C, Dabóczi A, Howard M, J. Miller N, Clemens Z. Crohn’s disease  successfully treated with the paleolithic ketogenic diet. International  Journal of Case Reports and Images. September 2016. doi:10.5348/ijcri-2016102-CR-10690
8. Lowery  RP, Wilson JM, Sharp MH, Wilson GJ, Wagner R. The effects of exogenous  ketones on biomarkers of Crohn’s disease: A case report. Journal of  Gastroenterology and Digestive Diseases. 2017;2(3). 
9. Mehrtash F. Sustained Crohn’s Disease Remission with an Exclusive Elemental and Exclusion Diet: A Case Report. Gastrointestinal Disorders. 2021;3(3):129-137. doi:10.3390/gidisord303001
10. Rashid  T, Wilson C, Ebringer A. The Link between Ankylosing Spondylitis,  Crohn’s Disease, Klebsiella, and Starch Consumption. Journal of  Immunology Research. doi:10.1155/2013/872632 
11. Norwitz  NG, Loh V. A Standard Lipid Panel Is Insufficient for the Care of a  Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet. Front Med.  2020;7. doi:10.3389/fmed.2020.00097 (IBD)
12. Simon, D. et al. (2023) ‘Food for Thought: Remission of Perianal Pediatric Crohn’s Disease on Specific Carbohydrate Diet Monotherapy’, JPGN Reports, 4(3), p. e343. Available at: https://doi.org/10.1097/PG9.0000000000000343.

  Crohn's disease is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation of the digestive tract. While hyperinsulinemia isn't directly linked to Crohn's disease, it may indirectly influence its development and exacerbation through its effects on immune function and inflammation. Insulin resistance, often associated with hyperinsulinemia and metabolic syndrome, can lead to chronic low-grade inflammation and immune dysregulation, which may contribute to the development of Crohn's disease. Additionally, hyperinsulinemia may exacerbate symptoms of Crohn's disease by promoting inflammation and impairing the integrity of the intestinal mucosal barrier. Managing hyperinsulinemia through lifestyle changes, medication, or other interventions may help reduce inflammation and improve symptoms of Crohn's disease by addressing underlying metabolic abnormalities and promoting better gastrointestinal health. However, the relationship between hyperinsulinemia and Crohn's disease is complex, and additional research is needed to fully understand their interplay.

1. Suskind DL, Lee D, Kim  Y-M, et al. The Specific Carbohydrate Diet and Diet Modification as  Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet  Controlled Trial. Nutrients. 2020;12(12):3749. doi:10.3390/nu12123749
2. Alsharairi,  N.A. (2022) ‘The Therapeutic Role of Short-Chain Fatty Acids Mediated  Very Low-Calorie Ketogenic Diet–Gut Microbiota Relationships in  Paediatric Inflammatory Bowel Diseases’, Nutrients, 14(19), p. 4113. Available at: https://doi.org/10.3390/nu14194113.
3. Jiang  Y, Jarr K, Layton C, et al. Therapeutic Implications of Diet in  Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory  Diseases. Nutrients. 2021;13(3). doi:10.3390/nu13030890
4. Konijeti  GG, Kim N, Lewis JD, et al. Efficacy of the Autoimmune Protocol Diet  for Inflammatory Bowel Disease. Inflamm Bowel Dis.  2017;23(11):2054-2060. doi:10.1097/MIB.0000000000001221
5. Kakodkar  S, Mutlu EA. Diet as a therapeutic option for adult inflammatory bowel  disease. Gastroenterol Clin North Am. 2017;46(4):745-767. doi:10.1016/j.gtc.2017.08.016 
6. Burgis  JC, Nguyen K, Park K, Cox K. Response to strict and liberalized  specific carbohydrate diet in pediatric Crohn’s disease. World J  Gastroenterol. 2016;22(6):2111-2117. doi:10.3748/wjg.v22.i6.2111
7. Tóth  C, Dabóczi A, Howard M, J. Miller N, Clemens Z. Crohn’s disease  successfully treated with the paleolithic ketogenic diet. International  Journal of Case Reports and Images. September 2016. doi:10.5348/ijcri-2016102-CR-10690
8. Lowery  RP, Wilson JM, Sharp MH, Wilson GJ, Wagner R. The effects of exogenous  ketones on biomarkers of Crohn’s disease: A case report. Journal of  Gastroenterology and Digestive Diseases. 2017;2(3). 
9. Mehrtash F. Sustained Crohn’s Disease Remission with an Exclusive Elemental and Exclusion Diet: A Case Report. Gastrointestinal Disorders. 2021;3(3):129-137. doi:10.3390/gidisord303001
10. Rashid  T, Wilson C, Ebringer A. The Link between Ankylosing Spondylitis,  Crohn’s Disease, Klebsiella, and Starch Consumption. Journal of  Immunology Research. doi:10.1155/2013/872632 
11. Norwitz  NG, Loh V. A Standard Lipid Panel Is Insufficient for the Care of a  Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet. Front Med.  2020;7. doi:10.3389/fmed.2020.00097 (IBD)
12. Simon, D. et al. (2023) ‘Food for Thought: Remission of Perianal Pediatric Crohn’s Disease on Specific Carbohydrate Diet Monotherapy’, JPGN Reports, 4(3), p. e343. Available at: https://doi.org/10.1097/PG9.0000000000000343.

 Gallstones are solid particles that form in the gallbladder, typically  composed of cholesterol or bilirubin. Hyperinsulinemia, characterized by  elevated levels of insulin in the blood, can contribute to the  formation of gallstones through several mechanisms. Insulin resistance, a  hallmark of hyperinsulinemia and metabolic syndrome, is associated with  dyslipidemia, which can lead to increased cholesterol saturation in  bile and the formation of cholesterol gallstones. Additionally,  hyperinsulinemia may promote the secretion of cholesterol-rich bile and  reduce gallbladder motility, both of which can contribute to the  formation and retention of gallstones. Over time, these processes can  lead to the development of symptomatic gallstones, which may cause  abdominal pain, nausea, vomiting, and other digestive symptoms.  Therefore, managing hyperinsulinemia through lifestyle modifications,  insulin-sensitizing medications, and appropriate dietary changes is  crucial for reducing the risk of gallstone formation and associated  complications. 

 Gut microbial dysbiosis refers to an imbalance in the composition and  function of the microbiota in the gastrointestinal tract.  Hyperinsulinemia, characterized by elevated levels of insulin in the  blood, can contribute to gut microbial dysbiosis through several  mechanisms. Insulin resistance, a hallmark of hyperinsulinemia and  metabolic syndrome, is associated with chronic low-grade inflammation,  which can disrupt the delicate balance of gut bacteria. Additionally,  hyperinsulinemia may promote the growth of pathogenic bacteria and  reduce the diversity of beneficial bacteria in the gut. Over time, these  processes can lead to alterations in gut permeability, immune function,  and metabolism, increasing the risk of gastrointestinal disorders such  as inflammatory bowel disease, irritable bowel syndrome, and colorectal  cancer. Therefore, managing hyperinsulinemia through lifestyle  modifications, insulin-sensitizing medications, and dietary changes  aimed at promoting a healthy gut microbiota is essential for maintaining  gut health and reducing the risk of associated complications. 

1. Sholl  J, Mailing LJ, Wood TR. Reframing Nutritional Microbiota Studies To  Reflect an Inherent Metabolic Flexibility of the Human Gut: a Narrative  Review Focusing on High-Fat Diets. mBio. 2021;12(2). doi:10.1128/mBio.00579-21
2. Attaye, I. et al. (2022) ‘The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets’, Nutrients, 14(1), p. 191. doi:10.3390/nu14010191
3. Zhang  S, Wu P, Tian Y, et al. Gut Microbiota Serves a Predictable Outcome of  Short-Term Low-Carbohydrate Diet (LCD) Intervention for Patients with  Obesity. Microbiology Spectrum. 0(0):e00223-21. doi:10.1128/Spectrum.00223-21
4. Rondanelli  M, Gasparri C, Peroni G, et al. The Potential Roles of Very Low  Calorie, Very Low Calorie Ketogenic Diets and Very Low Carbohydrate  Diets on the Gut Microbiota Composition. Front Endocrinol. 2021;12. doi:10.3389/fendo.2021.662591
5. Jaagura  M, Viiard E, Karu-Lavits K, Adamberg K. Low-carbohydrate high-fat  weight reduction diet induces changes in human gut microbiota. MicrobiologyOpen. 2021;10(3):e1194. doi:https://doi.org/10.1002/mbo3.1194
6. Fan  Y, Wang H, Liu X, Zhang J, Liu G. Crosstalk between the Ketogenic Diet  and Epilepsy: From the Perspective of Gut Microbiota. Mediators Inflamm.  2019;2019:8373060. doi:10.1155/2019/8373060 
7. Klement  RJ, Pazienza V. Impact of Different Types of Diet on Gut Microbiota  Profiles and Cancer Prevention and Treatment. Medicina (Kaunas).  2019;55(4). doi:10.3390/medicina55040084
8. Paoli  A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and  Microbiota: Friends or Enemies? Genes (Basel). 2019;10(7). doi:10.3390/genes10070534 
9. Reddel  S, Putignani L, Del Chierico F. The Impact of Low-FODMAPs, Gluten-Free,  and Ketogenic Diets on Gut Microbiota Modulation in Pathological  Conditions. Nutrients. 2019;11(2). doi:10.3390/nu11020373
10. Sun, S. et al. (2022) ‘Effects of Low-Carbohydrate Diet and Exercise Training on Gut Microbiota’, Frontiers in Nutrition, 9, p. 884550. doi:10.3389/fnut.2022.884550.
11. Murtaza  N, Burke LM, Vlahovich N, et al. Analysis of the Effects of Dietary  Pattern on the Oral Microbiome of Elite Endurance Athletes. Nutrients.  2019;11(3). doi:10.3390/nu11030614 
12. González  Olmo BM, Butler MJ, Barrientos RM. Evolution of the Human Diet and Its  Impact on Gut Microbiota, Immune Responses, and Brain Health. Nutrients. 2021;13(1):196. doi:10.3390/nu13010196
13. Alsharairi  NA. The Role of Short-Chain Fatty Acids in Mediating Very Low-Calorie  Ketogenic Diet-Infant Gut Microbiota Relationships and Its Therapeutic  Potential in Obesity. Nutrients. 2021;13(11):3702. doi:10.3390/nu13113702
14. Tang Y, Wang Q, Liu J. Microbiota-gut-brain axis: A novel potential target of ketogenic diet for epilepsy. Current Opinion in Pharmacology. 2021;61:36-41. doi:10.1016/j.coph.2021.08.018
15. Gutiérrez-Repiso  C, Hernández-García C, García-Almeida JM, et al. Effect of Synbiotic  Supplementation in a Very-Low-Calorie Ketogenic Diet on Weight Loss  Achievement and Gut Microbiota: A Randomized Controlled Pilot Study. Mol  Nutr Food Res. July 2019:e1900167. doi:10.1002/mnfr.201900167 ABSTRACT
16. Ang  QY, Alexander M, Newman JC, et al. Ketogenic Diets Alter the Gut  Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell.  2020;0(0). doi:10.1016/j.cell.2020.04.027 ABSTRACT
17. Donatella  P, Aurelio C. KETOGENIC DIET AND GUT MICROBIOTA. :7. Pharmacology  Online; Special issue; 2020; vol.3; 175-181. Mini-Review   PDF

  Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory conditions that affect the digestive tract, including  Crohn's disease and ulcerative colitis. While hyperinsulinemia isn't  directly linked to IBD, it may indirectly influence its development and  exacerbation through its effects on immune function and inflammation.  Insulin resistance, often associated with hyperinsulinemia and metabolic  syndrome, can lead to chronic low-grade inflammation and immune  dysregulation, which may contribute to the development of IBD. Additionally, hyperinsulinemia may exacerbate symptoms of IBD by  promoting inflammation and impairing the integrity of the intestinal  mucosal barrier. Managing hyperinsulinemia through lifestyle changes,  medication, or other interventions may help reduce inflammation and  improve symptoms of IBD by addressing underlying metabolic abnormalities  and promoting better gastrointestinal health. However, the relationship  between hyperinsulinemia and IBD is complex, and additional research is  needed to fully understand their interplay. 

1. Suskind DL, Lee D, Kim  Y-M, et al. The Specific Carbohydrate Diet and Diet Modification as  Induction Therapy for Pediatric Crohn’s Disease: A Randomized Diet  Controlled Trial. Nutrients. 2020;12(12):3749. doi:10.3390/nu12123749
2. Alsharairi,  N.A. (2022) ‘The Therapeutic Role of Short-Chain Fatty Acids Mediated  Very Low-Calorie Ketogenic Diet–Gut Microbiota Relationships in  Paediatric Inflammatory Bowel Diseases’, Nutrients, 14(19), p. 4113. Available at: https://doi.org/10.3390/nu14194113.
3. Jiang  Y, Jarr K, Layton C, et al. Therapeutic Implications of Diet in  Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory  Diseases. Nutrients. 2021;13(3). doi:10.3390/nu13030890
4. Konijeti  GG, Kim N, Lewis JD, et al. Efficacy of the Autoimmune Protocol Diet  for Inflammatory Bowel Disease. Inflamm Bowel Dis.  2017;23(11):2054-2060. doi:10.1097/MIB.0000000000001221
5. Kakodkar  S, Mutlu EA. Diet as a therapeutic option for adult inflammatory bowel  disease. Gastroenterol Clin North Am. 2017;46(4):745-767. doi:10.1016/j.gtc.2017.08.016 
6. Burgis  JC, Nguyen K, Park K, Cox K. Response to strict and liberalized  specific carbohydrate diet in pediatric Crohn’s disease. World J  Gastroenterol. 2016;22(6):2111-2117. doi:10.3748/wjg.v22.i6.2111
7. Tóth  C, Dabóczi A, Howard M, J. Miller N, Clemens Z. Crohn’s disease  successfully treated with the paleolithic ketogenic diet. International  Journal of Case Reports and Images. September 2016. doi:10.5348/ijcri-2016102-CR-10690
8. Lowery  RP, Wilson JM, Sharp MH, Wilson GJ, Wagner R. The effects of exogenous  ketones on biomarkers of Crohn’s disease: A case report. Journal of  Gastroenterology and Digestive Diseases. 2017;2(3). 
9. Mehrtash F. Sustained Crohn’s Disease Remission with an Exclusive Elemental and Exclusion Diet: A Case Report. Gastrointestinal Disorders. 2021;3(3):129-137. doi:10.3390/gidisord303001
10. Rashid  T, Wilson C, Ebringer A. The Link between Ankylosing Spondylitis,  Crohn’s Disease, Klebsiella, and Starch Consumption. Journal of  Immunology Research. doi:10.1155/2013/872632 
11. Norwitz  NG, Loh V. A Standard Lipid Panel Is Insufficient for the Care of a  Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet. Front Med.  2020;7. doi:10.3389/fmed.2020.00097 (IBD)
12. Simon, D. et al. (2023) ‘Food for Thought: Remission of Perianal Pediatric Crohn’s Disease on Specific Carbohydrate Diet Monotherapy’, JPGN Reports, 4(3), p. e343. Available at: https://doi.org/10.1097/PG9.0000000000000343.

 Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder  characterized by abdominal pain, bloating, diarrhea, and/or  constipation. While hyperinsulinemia isn't directly linked to IBS, it  may indirectly influence its development and exacerbation through its  effects on gut motility and inflammation. Insulin resistance, often  associated with hyperinsulinemia and metabolic syndrome, can lead to  alterations in gut motility and visceral sensitivity, potentially  contributing to IBS symptoms. Additionally, hyperinsulinemia may  exacerbate symptoms of IBS by promoting inflammation and altering the  gut microbiota. Managing hyperinsulinemia through lifestyle changes,  medication, or other interventions may help improve symptoms of IBS by  addressing underlying metabolic abnormalities and promoting better  gastrointestinal health. However, the relationship between  hyperinsulinemia and IBS is complex, and additional research is needed  to fully understand their interplay. 

1. Nilholm  C, Roth B, Ohlsson B. A Dietary Intervention with Reduction of Starch  and Sucrose Leads to Reduced Gastrointestinal and Extra-Intestinal  Symptoms in IBS Patients. Nutrients. 2019;11(7):1662. doi:10.3390/nu11071662
2. Nilholm  C, Larsson E, Sonestedt E, Roth B, Ohlsson B. Assessment of a 4-Week  Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal  Symptoms and Inflammatory Parameters among Patients with Irritable Bowel  Syndrome. Nutrients. 2021;13(2):416. doi:10.3390/nu13020416
3. Nilholm  C, Larsson E, Roth B, Gustafsson R, Ohlsson B. Irregular Dietary Habits  with a High Intake of Cereals and Sweets Are Associated with More  Severe Gastrointestinal Symptoms in IBS Patients. Nutrients. 2019;11(6):1279. doi:10.3390/nu11061279
4. Austin  GL, Dalton CB, Hu Y, et al. A Very Low-Carbohydrate Diet Improves  Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel  Syndrome. Clinical Gastroenterology and Hepatology.  2009;7(6):706-708.e1. doi:10.1016/j.cgh.2009.02.023
5. Algera  J, Colomier E, Simrén M. The Dietary Management of Patients with  Irritable Bowel Syndrome: A Narrative Review of the Existing and  Emerging Evidence. Nutrients. 2019;11(9):2162. doi:10.3390/nu11092162
6. Chumpitazi  BP, Shulman RJ. Dietary Carbohydrates and Childhood Functional  Abdominal Pain. Ann Nutr Metab. 2016;68(Suppl 1):8-17. doi:10.1159/000445390
7. Saidi  K, Nilholm C, Roth B, Ohlsson B. A carbohydrate-restricted diet for  patients with irritable bowel syndrome led to lower serum levels of  C-peptide, insulin, and leptin without any correlation with symptom  reduction. Nutrition Research. Published online December 4, 2020. doi:10.1016/j.nutres.2020.12.001
8. Nilholm  C, Larsson E, Roth B, Gustafsson R, Ohlsson B. Irregular Dietary Habits  with a High Intake of Cereals and Sweets Are Associated with More  Severe Gastrointestinal Symptoms in IBS Patients. Nutrients. 2019;11(6):1279. doi:10.3390/nu11061279
9. Van  den Houte K, Colomier E, Schol J, Carbone F, Tack J. Recent advances in  diagnosis and management of irritable bowel syndrome. Curr Opin Psychiatry. 2020;33(5):460-466. doi:10.1097/YCO.0000000000000628 ABSTRACT
10. Chimienti  G, Orlando A, Lezza AMS, et al. The Ketogenic Diet Reduces the Harmful  Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of  Irritable Bowel Syndrome. International Journal of Molecular Sciences. 2021;22(7):3498. doi:10.3390/ijms22073498 (pre-clinical)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newer term proposed to replace NAFLD, reflecting a broader understanding of the disease's underlying metabolic factors. MAFLD emphasizes the association between fatty liver disease and metabolic dysfunction, including obesity, insulin resistance, dyslipidemia, and hypertension. The term MAFLD aims to capture the heterogeneity of the condition and its association with metabolic risk factors more accurately.

 Non-alcoholic fatty liver disease (NAFLD) is an older  term used to describe a spectrum of liver conditions characterized by excess fat accumulation in the liver, typically in individuals who do not consume significant amounts of alcohol. NAFLD encompasses a range of conditions, from simple fatty liver (steatosis) to more severe forms such as non-alcoholic steatohepatitis (NASH), which involves inflammation and liver cell damage.

The main difference between NAFLD and MAFLD lies in their conceptual frameworks and diagnostic criteria. While NAFLD focuses primarily on liver fat accumulation, MAFLD integrates metabolic risk factors as essential components of the disease definition. MAFLD criteria include evidence of liver fat accumulation plus one of the following: obesity, type 2 diabetes, or evidence of metabolic dysregulation. This broader definition aims to encompass a more diverse population affected by fatty liver disease and emphasizes the underlying metabolic dysfunction associated with the condition.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newer term proposed to replace NAFLD, reflecting a broader understanding of the disease's underlying metabolic factors. MAFLD emphasizes the association between fatty liver disease and metabolic dysfunction, including obesity, insulin resistance, dyslipidemia, and hypertension. The term MAFLD aims to capture the heterogeneity of the condition and its association with metabolic risk factors more accurately.

 Non-alcoholic fatty liver disease (NAFLD) is an older  term used to describe a spectrum of liver conditions characterized by excess fat accumulation in the liver, typically in individuals who do not consume significant amounts of alcohol. NAFLD encompasses a range of conditions, from simple fatty liver (steatosis) to more severe forms such as non-alcoholic steatohepatitis (NASH), which involves inflammation and liver cell damage.

The main difference between NAFLD and MAFLD lies in their conceptual frameworks and diagnostic criteria. While NAFLD focuses primarily on liver fat accumulation, MAFLD integrates metabolic risk factors as essential components of the disease definition. MAFLD criteria include evidence of liver fat accumulation plus one of the following: obesity, type 2 diabetes, or evidence of metabolic dysregulation. This broader definition aims to encompass a more diverse population affected by fatty liver disease and emphasizes the underlying metabolic dysfunction associated with the condition.

1. Watanabe  M, Tozzi R, Risi R, et al. Beneficial effects of the ketogenic diet on  nonalcoholic fatty liver disease: A comprehensive review of the  literature. Obesity Reviews. n/a(n/a). doi:10.1111/obr.13024
2. Worm N. Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD. Nutrients. 2020;12(5):1316. doi:10.3390/nu12051316
3. Schugar  RC, Crawford PA. Low-carbohydrate ketogenic diets, glucose homeostasis,  and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care.  2012;15(4):374-380. doi:10.1097/MCO.0b013e3283547157 PDF
4. Gunaseelan  L, Khan US, Khalid F, Hamid MA. Non-alcoholic Fatty Liver Disease and  Carbohydrate Restricted Diets: A Case Report and Literature Review. Cureus. 2021;13(10). doi:10.7759/cureus.18641
5. Parra-Vargas  M, Rodriguez-Echevarria R, Jimenez-Chillaron JC. Nutritional Approaches  for the Management of Nonalcoholic Fatty Liver Disease: An  Evidence-Based Review. Nutrients. 2020;12(12):3860. doi:10.3390/nu12123860
6. Pugliese N, Torres MCP, Petta S, Valenti L, Giannini EG, Aghemo A. Is there an “ideal” diet for patients with NAFLD? European Journal of Clinical Investigation. n/a(n/a):e13659. doi:10.1111/eci.13659
7. El-Agroudy  NN, Kurzbach A, Rodionov RN, et al. Are Lifestyle Therapies Effective  for NAFLD Treatment? Trends in Endocrinology & Metabolism.  2019;0(0). doi:10.1016/j.tem.2019.07.013
8. Rosa  SC da S, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin  resistance and the cross-talk with liver and adipose tissue.  Physiological Reports. 2020;8(19):e14607. doi:10.14814/phy2.14607
9. Chakravarthy MV, Neuschwander‐Tetri BA. The metabolic basis of nonalcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4). doi:10.1002/edm2.112
10. Risi R, Tozzi R, Watanabe M. Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction. Current Opinion in Clinical Nutrition & Metabolic Care. 2021;24(4):349-353. doi:10.1097/MCO.0000000000000762  ABSTRACT
11. Różański, G. et al. (2022) ‘Effect of Different Types of Intermittent Fasting on  Biochemical and Anthropometric Parameters among Patients with  Metabolic-Associated Fatty Liver Disease (MAFLD)—A Systematic  Review’, Nutrients, 14(1), p. 91. doi:10.3390/nu14010091.

1. Holmer  M, Lindqvist C, Petersson S, et al. Treatment of NAFLD with  intermittent calorie restriction or low-carb high-fat diet – a  randomized controlled trial. JHEP Reports. Published online February 17, 2021:100256. doi:10.1016/j.jhepr.2021.100256
2. Gepner  Y, Shelef I, Komy O, et al. The Beneficial effects of Mediterranean  diet over low-fat diet may be mediated by decreasing hepatic fat  content. J Hepatol. May 2019. doi:10.1016/j.jhep.2019.04.013
3. Vilar-Gomez  E, Athinarayanan SJ, Adams RN, et al. Post hoc analyses of surrogate  markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis  in patients with type 2 diabetes in a digitally supported continuous  care intervention: an open-label, non-randomised controlled study. BMJ  Open. 2019;9(2):e023597. doi:10.1136/bmjopen-2018-023597 (5 year data https://doi.org/10.2337/db22-212-OR. )
4. Skytte  MJ, Samkani A, Petersen AD, et al. A carbohydrate-reduced high-protein  diet improves HbA1c and liver fat content in weight stable participants  with type 2 diabetes: a randomised controlled trial. Diabetologia. July  2019. doi:10.1007/s00125-019-4956-4 
5. Kord-Varkaneh, H. et al. (2022) ‘Effects of time-restricted feeding (16/8) combined with a  low-sugar diet on the management of non-alcoholic fatty liver disease: A  randomized controlled trial’, Nutrition (Burbank, Los Angeles County, Calif.), 105, p. 111847. Available at: https://doi.org/10.1016/j.nut.2022.111847.
6. Crabtree  CD, Kackley ML, Buga A, et al. Comparison of Ketogenic Diets with and  without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in  Overweight Adults. Nutrients. 2021;13(3):966. doi:10.3390/nu13030966
7. Rinaldi, R. et al. (2023) ‘The Effects of Eight Weeks’ Very Low-Calorie Ketogenic Diet  (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity’,  Nutrients, 15(4), p. 825. Available at: https://doi.org/10.3390/nu15040825.
8. Luukkonen  PK, Dufour S, Lyu K, et al. Effect of a ketogenic diet on hepatic  steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty  liver disease. Proc Natl Acad Sci U S A. 2020;117(13):7347-7354. doi:10.1073/pnas.1922344117
9. De Nucci, S. et al. (2023) ‘Effects of an Eight Week Very Low-Calorie Ketogenic Diet  (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic  Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with  Overweight and Obesity’, Nutrients, 15(20), p. 4468. Available at: https://doi.org/10.3390/nu15204468.
10. Belopolsky  Y, Khan MQ, Sonnenberg A, Davidson DJ, Fimmel CJ. Ketogenic,  Hypocaloric Diet Improves Nonalcoholic Steatohepatitis. J Transl Int  Med. 2020;8(1):26-31. doi:10.2478/jtim-2020-0005
11. Unwin  D, Cuthbertson D, Feinman R, Sprung V. A pilot study to explore the  role of a low-carbohydrate intervention to improve GGT levels and HbA 1  c. Diabesity in Practice Vol 4 No 3 2015.  PDF
12. Mardinoglu  A, Wu H, Bjornson E, et al. An Integrated Understanding of the Rapid  Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic  Steatosis in Humans. Cell Metab. 2018;27(3):559-571.e5. doi:10.1016/j.cmet.2018.01.005 
13. Khorunzha  V, Samiilenko N, Bielokoz H, et al. Effects of a Low Carbohydrate Diet  on Patients With Metabolic Syndrome Complicated by Non-alcoholic Fatty  Liver Disease (NAFLD). Current Developments in Nutrition. 2021;5(Supplement_2):1221-1221. doi:10.1093/cdn/nzab055_031
14. Tendler  D, Lin S, Yancy WS, et al. The Effect of a Low-Carbohydrate, Ketogenic  Diet on Nonalcoholic Fatty Liver Disease: A Pilot Study. Dig Dis Sci.  2007;52(2):589-593. doi:10.1007/s10620-006-9433-5 ABSTRACT 
15. Cunha  GM, Correa de Mello LL, Hasenstab KA, et al. MRI estimated changes in  visceral adipose tissue and liver fat fraction in patients with obesity  during a very low-calorie-ketogenic diet compared to a standard  low-calorie diet. Clin Radiol. Published online March 20, 2020. doi:10.1016/j.crad.2020.02.014 ABSTRACT
16. Watanabe  M, Risi R, Camajani E, et al. Baseline HOMA IR and Circulating FGF21  Levels Predict NAFLD Improvement in Patients Undergoing a Low  Carbohydrate Dietary Intervention for Weight Loss: A Prospective  Observational Pilot Study. Nutrients. 2020;12(7):2141. doi:10.3390/nu12072141
17. Thomsen, M.N. et al. (2022) ‘Dietary carbohydrate restriction augments weight loss-induced  improvements in glycaemic control and liver fat in individuals with type  2 diabetes: a randomised controlled trial’, Diabetologia [Preprint]. doi:10.1007/s00125-021-05628-8.

1. Chen J, Huang Y, Xie H,  et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic  fatty liver disease. Asia Pacific Journal of Clinical Nutrition.  2020;29(3):483-490. doi:10.6133/apjcn.202009_29(3).0006
2. D’Abbondanza  M, Ministrini S, Pucci G, et al. Very Low-Carbohydrate Ketogenic Diet  for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty  Liver Disease: The Role of Sex Differences. Nutrients. 2020;12(9):2748.  doi:10.3390/nu12092748

1. Katsagoni  CN, Papachristou E, Sidossis A, Sidossis L. Effects of Dietary and  Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in  Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A  Systematic Review. Nutrients. 2020;12(9):2864. doi:10.3390/nu12092864
2. Schwimmer  JB, Ugalde-Nicalo P, Welsh JA, et al. Effect of a Low Free Sugar Diet  vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A  Randomized Clinical Trial. JAMA. 2019;321(3):256-265. doi:10.1001/jama.2018.20579 
3. Mandala  A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic  Fatty Liver Disease: Nutritional Origins and Potential Molecular  Mechanisms. Nutrients. 2020;12(10):3166. doi:10.3390/nu12103166
4. Schwarz  J-M, Noworolski SM, Erkin-Cakmak A, et al. Effects of Dietary Fructose  Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in  Children with Obesity. Gastroenterology. 2017;153(3):743-752. doi:10.1053/j.gastro.2017.05.043
5. Goss  AM, Dowla S, Pendergrass M, et al. Effects of a carbohydrate-restricted  diet on hepatic lipid content in adolescents with non-alcoholic fatty  liver disease: A pilot, randomized trial. Pediatr Obes. Published online  March 4, 2020:e12630. doi:10.1111/ijpo.12630 ABSTRACT

1. Wijarnpreecha  K, Thongprayoon C, Edmonds PJ, Cheungpasitporn W. Associations of  sugar- and artificially sweetened soda with nonalcoholic fatty liver  disease: a systematic review and meta-analysis. QJM: An International Journal of Medicine. 2016;109(7):461-466. doi:10.1093/qjmed/hcv172
2. Chen  H, Wang J, Li Z, et al. Consumption of Sugar-Sweetened Beverages Has a  Dose-Dependent Effect on the Risk of Non-Alcoholic Fatty Liver Disease:  An Updated Systematic Review and Dose-Response Meta-Analysis. Int J Environ Res Public Health. 2019;16(12). doi:10.3390/ijerph16122192
3. Nier  A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-Alcoholic Fatty  Liver Disease in Overweight Children: Role of Fructose Intake and  Dietary Pattern. Nutrients. 2018;10(9). doi:10.3390/nu10091329
4. Ma  J, Fox CS, Jacques PF, et al. Sugar-sweetened beverage, diet soda, and  fatty liver disease in the Framingham Heart Study cohorts. J Hepatol. 2015;63(2):462-469. doi:10.1016/j.jhep.2015.03.032
5. Abdelmalek MF, Day C. Sugar sweetened beverages and fatty liver disease: Rising concern and call to action. Journal of Hepatology. 2015;63(2):306-308. doi:10.1016/j.jhep.2015.05.021

1. Drinda  S, Grundler F, Neumann T, et al. Effects of Periodic Fasting on Fatty  Liver Index—A Prospective Observational Study. Nutrients.  2019;11(11):2601. doi:10.3390/nu11112601

 Non-alcoholic fatty liver disease (NAFLD) is a term used to describe a spectrum of liver conditions characterized by excess fat accumulation in the liver, typically in individuals who do not consume significant amounts of alcohol. NAFLD encompasses a range of conditions, from simple fatty liver (steatosis) to more severe forms such as non-alcoholic steatohepatitis (NASH), which involves inflammation and liver cell damage.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newer term proposed to replace NAFLD, reflecting a broader understanding of the disease's underlying metabolic factors. MAFLD emphasizes the association between fatty liver disease and metabolic dysfunction, including obesity, insulin resistance, dyslipidemia, and hypertension. The term MAFLD aims to capture the heterogeneity of the condition and its association with metabolic risk factors more accurately.

The main difference between NAFLD and MAFLD lies in their conceptual frameworks and diagnostic criteria. While NAFLD focuses primarily on liver fat accumulation, MAFLD integrates metabolic risk factors as essential components of the disease definition. MAFLD criteria include evidence of liver fat accumulation plus one of the following: obesity, type 2 diabetes, or evidence of metabolic dysregulation. This broader definition aims to encompass a more diverse population affected by fatty liver disease and emphasizes the underlying metabolic dysfunction associated with the condition.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased  significantly over the last few decades mirroring the increase in  obesity and type II diabetes mellitus. NAFLD has become one of the most  common indications for liver transplantation. The deleterious effects of  NAFLD are not isolated to the liver only, for it has been recognized as  a systemic disease affecting multiple organs through protracted  low-grade inflammation mediated by the metabolic activity of excessive fat tissue. Extrahepatic manifestations of NAFLD such as cardiovascular  disease, polycystic ovarian syndrome, chronic kidney disease, and  hypothyroidism have been well described in the literature. In recent  years, it has become evident that patients suffering from NAFLD might be  at higher risk of developing various infections. The proposed mechanism  for this association includes links through hyperglycemia, insulin  resistance, alterations in innate immunity, obesity, and vitamin D  deficiency. Additionally, a risk independent of these factors mediated  by alterations in gut microbiota might contribute to a higher burden of  infections in these individuals. In this narrative review, we synthetize  current knowledge on several infections including urinary tract  infection, pneumonia, Helicobacter pylori, coronavirus disease 2019, and Clostridioides difficile as they relate to NAFLD. Additionally, we explore NAFLD's association with hidradenitis suppurativa. 

 NAFLD stands for Non-Alcoholic Fatty Liver Disease. It's a condition  where excess fat accumulates in the liver of people who drink little to  no alcohol. NAFLD can range from simple fatty liver (steatosis) to more  severe forms such as non-alcoholic steatohepatitis (NASH), which can  lead to liver inflammation and scarring. 

"Chronic kidney disease (CKD) is a frequent, under-recognized  condition and a risk factor for renal failure and cardiovascular  disease. Increasing evidence connects non-alcoholic fatty liver disease  (NAFLD) to CKD. 

 The presence and severity of NAFLD are associated with an increased risk and severity of CKD" 

1. Watanabe  M, Tozzi R, Risi R, et al. Beneficial effects of the ketogenic diet on  nonalcoholic fatty liver disease: A comprehensive review of the  literature. Obesity Reviews. n/a(n/a). doi:10.1111/obr.13024
2. Worm N. Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD. Nutrients. 2020;12(5):1316. doi:10.3390/nu12051316
3. Schugar  RC, Crawford PA. Low-carbohydrate ketogenic diets, glucose homeostasis,  and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care.  2012;15(4):374-380. doi:10.1097/MCO.0b013e3283547157 PDF
4. Gunaseelan  L, Khan US, Khalid F, Hamid MA. Non-alcoholic Fatty Liver Disease and  Carbohydrate Restricted Diets: A Case Report and Literature Review. Cureus. 2021;13(10). doi:10.7759/cureus.18641
5. Parra-Vargas  M, Rodriguez-Echevarria R, Jimenez-Chillaron JC. Nutritional Approaches  for the Management of Nonalcoholic Fatty Liver Disease: An  Evidence-Based Review. Nutrients. 2020;12(12):3860. doi:10.3390/nu12123860
6. Pugliese N, Torres MCP, Petta S, Valenti L, Giannini EG, Aghemo A. Is there an “ideal” diet for patients with NAFLD? European Journal of Clinical Investigation. n/a(n/a):e13659. doi:10.1111/eci.13659
7. El-Agroudy  NN, Kurzbach A, Rodionov RN, et al. Are Lifestyle Therapies Effective  for NAFLD Treatment? Trends in Endocrinology & Metabolism.  2019;0(0). doi:10.1016/j.tem.2019.07.013
8. Rosa  SC da S, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin  resistance and the cross-talk with liver and adipose tissue.  Physiological Reports. 2020;8(19):e14607. doi:10.14814/phy2.14607
9. Chakravarthy MV, Neuschwander‐Tetri BA. The metabolic basis of nonalcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4). doi:10.1002/edm2.112
10. Risi R, Tozzi R, Watanabe M. Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction. Current Opinion in Clinical Nutrition & Metabolic Care. 2021;24(4):349-353. doi:10.1097/MCO.0000000000000762  ABSTRACT
11. Różański, G. et al. (2022) ‘Effect of Different Types of Intermittent Fasting on  Biochemical and Anthropometric Parameters among Patients with  Metabolic-Associated Fatty Liver Disease (MAFLD)—A Systematic  Review’, Nutrients, 14(1), p. 91. doi:10.3390/nu14010091.

1. Holmer  M, Lindqvist C, Petersson S, et al. Treatment of NAFLD with  intermittent calorie restriction or low-carb high-fat diet – a  randomized controlled trial. JHEP Reports. Published online February 17, 2021:100256. doi:10.1016/j.jhepr.2021.100256
2. Gepner  Y, Shelef I, Komy O, et al. The Beneficial effects of Mediterranean  diet over low-fat diet may be mediated by decreasing hepatic fat  content. J Hepatol. May 2019. doi:10.1016/j.jhep.2019.04.013
3. Vilar-Gomez  E, Athinarayanan SJ, Adams RN, et al. Post hoc analyses of surrogate  markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis  in patients with type 2 diabetes in a digitally supported continuous  care intervention: an open-label, non-randomised controlled study. BMJ  Open. 2019;9(2):e023597. doi:10.1136/bmjopen-2018-023597 (5 year data https://doi.org/10.2337/db22-212-OR. )
4. Skytte  MJ, Samkani A, Petersen AD, et al. A carbohydrate-reduced high-protein  diet improves HbA1c and liver fat content in weight stable participants  with type 2 diabetes: a randomised controlled trial. Diabetologia. July  2019. doi:10.1007/s00125-019-4956-4 
5. Kord-Varkaneh, H. et al. (2022) ‘Effects of time-restricted feeding (16/8) combined with a  low-sugar diet on the management of non-alcoholic fatty liver disease: A  randomized controlled trial’, Nutrition (Burbank, Los Angeles County, Calif.), 105, p. 111847. Available at: https://doi.org/10.1016/j.nut.2022.111847.
6. Crabtree  CD, Kackley ML, Buga A, et al. Comparison of Ketogenic Diets with and  without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in  Overweight Adults. Nutrients. 2021;13(3):966. doi:10.3390/nu13030966
7. Rinaldi, R. et al. (2023) ‘The Effects of Eight Weeks’ Very Low-Calorie Ketogenic Diet  (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity’,  Nutrients, 15(4), p. 825. Available at: https://doi.org/10.3390/nu15040825.
8. Luukkonen  PK, Dufour S, Lyu K, et al. Effect of a ketogenic diet on hepatic  steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty  liver disease. Proc Natl Acad Sci U S A. 2020;117(13):7347-7354. doi:10.1073/pnas.1922344117
9. De Nucci, S. et al. (2023) ‘Effects of an Eight Week Very Low-Calorie Ketogenic Diet  (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic  Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with  Overweight and Obesity’, Nutrients, 15(20), p. 4468. Available at: https://doi.org/10.3390/nu15204468.
10. Belopolsky  Y, Khan MQ, Sonnenberg A, Davidson DJ, Fimmel CJ. Ketogenic,  Hypocaloric Diet Improves Nonalcoholic Steatohepatitis. J Transl Int  Med. 2020;8(1):26-31. doi:10.2478/jtim-2020-0005
11. Unwin  D, Cuthbertson D, Feinman R, Sprung V. A pilot study to explore the  role of a low-carbohydrate intervention to improve GGT levels and HbA 1  c. Diabesity in Practice Vol 4 No 3 2015.  PDF
12. Mardinoglu  A, Wu H, Bjornson E, et al. An Integrated Understanding of the Rapid  Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic  Steatosis in Humans. Cell Metab. 2018;27(3):559-571.e5. doi:10.1016/j.cmet.2018.01.005 
13. Khorunzha  V, Samiilenko N, Bielokoz H, et al. Effects of a Low Carbohydrate Diet  on Patients With Metabolic Syndrome Complicated by Non-alcoholic Fatty  Liver Disease (NAFLD). Current Developments in Nutrition. 2021;5(Supplement_2):1221-1221. doi:10.1093/cdn/nzab055_031
14. Tendler  D, Lin S, Yancy WS, et al. The Effect of a Low-Carbohydrate, Ketogenic  Diet on Nonalcoholic Fatty Liver Disease: A Pilot Study. Dig Dis Sci.  2007;52(2):589-593. doi:10.1007/s10620-006-9433-5 ABSTRACT 
15. Cunha  GM, Correa de Mello LL, Hasenstab KA, et al. MRI estimated changes in  visceral adipose tissue and liver fat fraction in patients with obesity  during a very low-calorie-ketogenic diet compared to a standard  low-calorie diet. Clin Radiol. Published online March 20, 2020. doi:10.1016/j.crad.2020.02.014 ABSTRACT
16. Watanabe  M, Risi R, Camajani E, et al. Baseline HOMA IR and Circulating FGF21  Levels Predict NAFLD Improvement in Patients Undergoing a Low  Carbohydrate Dietary Intervention for Weight Loss: A Prospective  Observational Pilot Study. Nutrients. 2020;12(7):2141. doi:10.3390/nu12072141
17. Thomsen, M.N. et al. (2022) ‘Dietary carbohydrate restriction augments weight loss-induced  improvements in glycaemic control and liver fat in individuals with type  2 diabetes: a randomised controlled trial’, Diabetologia [Preprint]. doi:10.1007/s00125-021-05628-8.

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