Podcasts about ast alt

rWotD Episode 2922: Aspartate transaminase Welcome to Random Wiki of the Day, your journey through Wikipedia's vast and varied content, one random article at a time.The random article for Sunday, 4 May 2025, is Aspartate transaminase.Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme (EC 2.6.1.1) that was first described by Arthur Karmen and colleagues in 1954. AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in amino acid metabolism. AST is found in the liver, heart, skeletal muscle, kidneys, brain, red blood cells and gall bladder. Serum AST level, serum ALT (alanine transaminase) level, and their ratio (AST/ALT ratio) are commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.The half-life of total AST in the circulation approximates 17 hours and, on average, 87 hours for mitochondrial AST. Aminotransferase is cleared by sinusoidal cells in the liver.This recording reflects the Wikipedia text as of 00:09 UTC on Sunday, 4 May 2025.For the full current version of the article, see Aspartate transaminase on Wikipedia.This podcast uses content from Wikipedia under the Creative Commons Attribution-ShareAlike License.Visit our archives at wikioftheday.com and subscribe to stay updated on new episodes.Follow us on Mastodon at @wikioftheday@masto.ai.Also check out Curmudgeon's Corner, a current events podcast.Until next time, I'm neural Joey.

High dose Niacin is effectively reducing Lp(a) however it has been causing my liver enzymes to increase. For the past month I've been taking Milk Thistle and it's has effectively reduce the liver enzymes back to normal.    ------------ WEBSITES -----------  ⁠https://johnbarban.com⁠ ⁠https://bradpilon.com⁠ ⁠Total T Clinic⁠ ⁠https://eatstopeat.com

Episode 172: NAFLD and ObesityFuture Dr. Nguyen explains the pathophysiology of non-alcoholic fatty liver disease and how it relates to obesity. Dr. Arreaza gives information about screening and diagnosis of NAFLD. Written by Ryan Nguyen, MS4, Ross University School of Medicine. Comments by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Introduction/PathophysiologyNonalcoholic fatty liver disease (NAFLD) refers to the buildup of excess fat in liver cells, occurring without the influence of alcohol or drugs. Nonalcoholic steatohepatitis (NASH) represents a more severe form of NAFLD, characterized by inflammation and liver cell injury due to fat accumulation. If left untreated, NASH can progress to liver fibrosis or cirrhosis. Typically, NAFLD/NASH is diagnosed after other liver conditions are ruled out, making it a diagnosis of exclusion.NAFLD -> NASH -> Cirrhosis -> Liver failure. Another term for NAFLD is metabolic dysfunction-associated steatotic liver disease. Fatty liver disease is identified when more than 5% of liver weight consists of fat, whereas, NASH is diagnosed when this fat accumulation is accompanied by inflammation and liver cell injury, sometimes leading to fibrosis. Understanding these distinctions is crucial in recognizing and managing the spectrum of liver conditions associated with obesity and metabolic syndrome.BMI serves as a tool to gauge body fat levels: individuals are categorized as normal weight if their BMI falls between 18.5 and 24.9, overweight if it ranges from 25 to 29.9. Class I obesity is diagnosed with a BMI of 30 to 34.9, class II obesity between 35 and 39.9, and class III obesity when BMI exceeds 40.Obesity puts you at risk of NAFLD, but you can also see NAFLD in non-obese patients, but the prevalence is very low, about 5%. What did you learn about the demographics of NAFLD?NAFLD is most widespread in regions like South Asia, the Middle East, Mexico, Central and South America, with prevalence rates exceeding 30%. In the United States, prevalence varies with approximately 23-27%, notably higher among Asians at 30%, followed by Hispanic individuals at 21%, White individuals at 12.5%, and Black individuals at 11.6%. Across all racial groups, obesity plays a significant role, affecting more than two-thirds of individuals diagnosed with NAFLD. Understanding these demographics underscores the global impact of obesity on NAFLD prevalence.Diagnosis: Screening/Labs/Imaging/ToolsThe American Association for the Study of Liver Diseases does not recommend screening for NAFLD, but if it is discovered an appropriate workup is warranted. AST/ALT RatioLiver health can be assessed by a series of tests aimed at assessing fat accumulation, inflammation, and fibrosis. Initial screening often includes laboratory tests such as measuring the ratio between aspartate transaminase (AST) and alanine transaminase (ALT), where a ratio less than 1 may suggest possible NAFLD, although it is not diagnostic on its own. Normally, AST is slightly more elevated than ALT. So, if the AST/ALT ratio is lower, then means that ALT is higher than AST. FibroSure®.Additionally, you can measure indirect markers of fibrosis with tests such as FibroSure or FibroTest blood tests that combine several biomarkers including age, sex, gamma-glutamyl-transferase (GGT), total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, and ALT to provide insights into liver health.Some people may be more familiar with FibroSure before Hepatitis C treatment. You can get a fibrosis score (F0-F4), and it is considered significant fibrosis if the score is > or equal to F2. Imaging plays a crucial role in diagnosing NAFLD without the need for invasive procedures like liver biopsy. Vibration-controlled transient elastography (Fibroscan) uses ultrasound to measure liver stiffness, indicating potential fibrosis and inflammation. While noninvasive and portable, it focuses solely on liver ultrasound and may not be universally accessible. MRI with proton density fat fraction (MRI-PDFF) offers a comprehensive assessment of liver fat content, commonly used in clinical and research settings for NAFLD and NASH evaluation.For evaluating hepatic fibrosis in patients with suspected NAFLD, tools like the Fibrosis-4 Index (FIB-4) incorporate age, AST, ALT, and platelet count to estimate the likelihood of liver disease progression. These screening methods collectively aid in diagnosing and monitoring NAFLD, particularly in individuals at risk due to factors like prediabetes, type 2 diabetes, obesity, and abnormal liver enzyme ratios. With the FIB-4 you can get a faster answer than FibroSure because you only need 4 elements: Age, platelet count, AST and ALT. Cirrhosis is less likely if FIB-4 is 3.25. Understanding these diagnostic approaches is essential for early detection and management of NAFLD in clinical practice.Some researchers are invested in diagnosis and treating NAFLD while others recommend against labeling patients with NAFLD. A 2018 Lancet article concluded that the risks of over-diagnosing and overtreating NAFLD exceed the benefits of screening or periodic imaging because of “the low hepatic mortality, high false-positive rate of ultrasonography, selection bias of current studies, and lack of viable treatment.” However, patients who suffer from metabolic syndrome should be counseled about dietary modification and physical activity regardless of their liver condition. NAFLD and obesityFatty liver disease is often caused by multiple insults towards either genetically or environmentally predisposed individuals. Family history of NAFLD and having specific genetic variants are important risk factors for NAFLD. Those with prior health conditions can have increased susceptibility to NAFLD including T2DM leading to insulin resistance, metabolic syndrome, sleep apnea, hepatitis C, and cardiovascular or chronic kidney disease. A sedentary lifestyle and unhealthy nutrition (especially high intake of processed carbohydrates) cause an increase in free fatty acids leading to hepatic fat deposition → ballooning of hepatocytes → leading to hepatocyte injury/death → inflammation with fibroblast recruitment → end result of fibrosis/cirrhosis. Just a quick reminder, NAFLD is defined as fatty liver with >5% hepatic fat and NASH is defined as fatty liver with >5% hepatic fat with inflammation, hepatocyte injury, with or without fibrosis that we can determine through imaging. A leading concern for the development of NAFLD is the consumption of high fructose corn syrup.  High fructose corn syrup (HFCS), commonly found in candy, processed sweets, soda, fruit juices, and other processed foods, is linked to non-alcoholic fatty liver disease (NAFLD). Unlike natural whole fruits, which contain fiber and are generally healthier due to their slower absorption, HFCS lacks fiber and is quickly absorbed, leading to rapid transport to the liver. This process contributes to NAFLD by increasing the hepatic synthesis of lipids and interfering with insulin signaling. To avoid HFCS, individuals are encouraged to consume whole fruits rather than fruit juices and adopt diets rich in whole grains, lean meats, plant-based proteins, fruits, and vegetables, such as the Mediterranean or DASH diets, which are less likely to promote NAFLD, especially in those with healthy body weight.NAFLD treatment.Avoiding alcohol seems very obvious, but we need to mention it. Avoiding heavy alcohol consumption is recommended and complete abstinence is suggested.Weight loss is crucial; even a modest reduction of 3–5% in body weight can alleviate hepatic steatosis, with greater improvements typically seen with 7–10% weight loss, particularly beneficial for addressing histopathological features of NASH, such as fibrosis. We must focus on tailored medical nutrition therapy and regular physical activity. A strategic meal plan is essential, emphasizing achieving a healthy body weight while limiting trans fats and ultra-processed carbohydrates. Options like the Mediterranean diet, which balances lean proteins and restricts processed carbohydrates have shown promise. Dynamic aerobic and resistance exercises play a significant role in managing NAFLD. They help maintain a healthy weight and enhance peripheral insulin sensitivity, reduce circulating free fatty acids and glucose levels, and boost intrahepatic fatty acid oxidation while curbing fatty acid synthesis. These benefits contribute to mitigating liver damage associated with NAFLD, offering therapeutic advantages beyond mere weight reduction.Exercise may not be a great tool for weight loss, but it is a great tool for weight maintenance, liver health, and overall health as well. “Most patients with NAFLD die from vascular causes, but NAFLD puts patients at increased risk of cardiovascular death”. Medications for NAFLD.Regarding pharmacotherapy, while no medications are currently FDA-approved specifically for NAFLD treatment, some options show promise in clinical settings. Vitamin E supplementation at 800 IU (international units) daily has demonstrated biochemical and histological improvements in NASH cases without diabetes or cirrhosis, though long-term use may elevate prostate cancer risks. It is important to make a shared decision with the patient before starting Vitamin E supplementation. Medications like pioglitazone can reduce liver fat and improve NASH, even as they may increase body weight. But our favorite, GLP-1 receptor agonists, such as liraglutide and semaglutide, also show potential in reducing liver fat and improving NASH symptoms, and this is an emerging therapeutic option for managing this condition.If you decide to treat, then you should monitor as part of the treatment. An aminotransferase check is recommended 6 months after starting a weight loss program. If levels do not improve or do not return to normal after 5-7% of weight loss, another cause of elevated transaminases needs to be investigated.You also need to monitor fibrosis in patients with >F2. If fibrosis has been proven by liver biopsy, you can order FibroSure every 3-4 years. Having a fatty liver may be a red flag that your patient has a metabolic problem. If you discover it, start interventions that would benefit not only the liver but the whole metabolic profile of your patient. The Obesity Medicine Association (OMA) issued a Clinical Practice Statement (CPS) regarding NAFLD and obesity stating that patients with obesity are at increased risk for NAFLD and NASH. It recommends that clinicians strive to understand the etiology, diagnosis, and optimal treatment of NAFLD with a goal to prevent NASH in their patients.Regular exercise, even walking 30 minutes a day can show many benefits in curbing fatty accumulation in the liver. Having a proper diet with avoidance of high fructose corn syrup can overall help in reducing NAFLD/NASH. _____________________Conclusion: Now we conclude episode number 172, “NAFLD and Obesity.” Future Dr. Nguyen explained that NAFLD and obesity are closely related and NAFLD can lead to NASH and cirrhosis in some patients. Dr. Arreaza explained that screening may not be recommended by some medical societies, but others are in favor of screening and treating this disease. However, most people agree that NAFLD is a sign of metabolic disease and a good reason to talk about healthy eating and physical activity with our patients. There are no FDA-approved medications to treat NAFLD, but some evidence suggests that Vitamin E can improve it and GLP-1 receptor agonists are a promising option. This week we thank Hector Arreaza and Ryan Nguyen. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Karjoo S, Auriemma A, Fraker T, Edward H. Nonalcoholic fatty liver disease and obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022. https://doi.org/10.1016/j.obpill.2022.100027.Curry M, Afdhal N. Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations.  https://www.uptodate.com/contents/noninvasive-assessment-of-hepatic-fibrosis-overview-of-serologic-tests-and-imaging-examinationsRoyalty-free music used for this episode: Cool Groove (Alt-Mix) by Videvo, downloaded on Nov 06, 2023, from https://www.videvo.net

The JournalFeed podcast for the week of May 27-31, 2024.These are summaries from just 2 of the 5 articles we cover every week! For access to more, please visit JournalFeed.org for details about becoming a member.Monday Spoon Feed:A retrospective study of 60 patients who received a fixed-dose ketamine of 250 mg by EMS observed that 6 were intubated in the ED. There was no association between weight-based dose of ketamine and risk for intubation.Thursday Spoon Feed:In a large retrospective review of patients with out-of-hospital-cardiac-arrest (OHCA) there was a very small, and probably clinically insignificant, association with favorable neurological outcome and survival in those who underwent early as opposed to late advanced airway management.

2:38 Facts & Figures 1 in 8 women will develop a thyroid disorder, 20 million American have some form of thyroid condition, 95% of time thyroid nodules are benign, women are 5-8 x more likely to develop a thyroid disorder than men 3:50 Root Causes Iodine deficiency is the main cause, Hashimoto's (autoimmune) is common when iodine is adequate, iatrogenic (eg. radiation, medication) 6:08 Diagnosis elevated TSH, low T4 sub-clinical TSH (call for T4), eventually T4 drops and TSH increases autoimmune anti-body labs ideally run complete thyroid labs - TSH, T4, and antibody labs 11:25 Basics Start climbing the ladder at the bottom! Hydration, food intake, data of food intake, bowel movements, supplements, sleep, movement, labs13:53 Thyroid NutrientsIron, iodine, tyrosine, zinc, selenium, vitamins E, B2, B3, B6, C & D Ferritin - women feel best when around 90 ng/mL Iodine - in iodized salt but may not be in sea salt, can be diluted and sprayed on skin (and on dense breasts) 22:49 What can inhibit synthesis of T4?stress, infection, trauma, fluoride, certain medications, radiation, toxins, pesticides, mercury, cadmium, leadautoimmune disease (celiac) 27:00 Active form is T3 (so T4 must be converted into T3) - need selenium and zincOnly eat 1-2 Brazil nuts daily (not more) for selenium Zinc needs to be balanced with copper (needed to carry iron in blood)28:55 Lifestyle factors that can mess up the conversion of T3RT3 sits in receptor and blocks T3stress, trauma, low-calorie diet, inflammation, toxins, infections, certain medications, liver/kidney dysfunction31:20 May need thyroid support if on a keto diet 34:24 Get T3 into the cell (cellular sensitivity)vitamin A, zinc and exercise 34:50 optimizing liver and kidney function - AST/ALT (ideally below 20 IU/L) and eGFR (over 60 mL/min/1.73m2, higher is better) gluten-free diet and alcohol reduction or abstinence is beneficial 40:40 Food that may antogonize thyroid activity Cynogenic glycosides: linseed, sweet potato, fava bean, lima bean, sorghum - may compete with iodine Glucosinolates - cruciferous - cabbage, kale, broccoli, cauliflower, canola, radish, arugula (consume when cooked) - may compete with iodine uptake Flavonoids - soy and millet - adequate iron and selenium help, may impair TPO activity Angela Taylor, MS, CNS, LDN Angela is board-certified in Clinical Nutrition and currently serves as adjunct faculty at Johns Hopkins University, Brooklyn College, and Nova Southeastern University College of Medicine. Additionally, she is the author of ⁠The BrainFood Cookbook - Autism / ADHD Recovery using the SCD / GAPS / Paleo diet, ⁠and is certified as a Personal Fitness Trainer by AAAI-ISMA. Find Angela at www.brainfood-nutrition.com Laurel Brennan, MOTR/L, RYT Resources: ⁠⁠www.rootcauseology.com for information on Brain Health Services, Yoga, and⁠ ⁠Brain Health Retreats⁠ Instagram @rootcauseology⁠⁠ ⁠⁠TikTok @rootcauseology⁠⁠ ⁠⁠Facebook @rootcauseology⁠⁠ and private⁠ ⁠Facebook Group, Brain Wellness & Dementia Prevention Youtube @rootcauseologywithlaurel

This episode is a a high yield "just the facts" break down of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations. This was released alongside a full interview with the consensus statement corresponding author Dr. Richard Dart MD, PhD. Be sure to check out the full interview to hear it straight from the source! (link in show notes).Link to the guidelines:Full interview with consensus statement author Dr. Richard Darthttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062Definitions made by the guidelineAcute ingestion>7.5 g in 24 h per Rummack Matthew initial studies10 g/d or 200 mg/kg/day in 48 hHigh risk ingestionReported dose >30 grams OR[APAP] 2 x Rummack-Matthew nomogram treatment lineNAC stopping criteriaAPAP4 g x >48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)Treat if APAP >20 ug/ml OR AST/ALT elevatedAcuteNon-detectable [APAP] between 2 and 4 hours excludes ingestionGive SDAC w/in 4 hours (something I've been a proponent of since ATOM2)Start treatment with NAC if unable to plot on nomogram by 8 hoursNAC dose“Higher dose” NAC (undefined) for high risk ingestionMinimum NAC regimen should include 300 mg/kg orally or within 20-24 hoursCAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)Unique scenariosLine crossersAPAP with anticholinergic or opioidIf 1st  concentration below treatment line repeat in 4-6 hoursAPAP Extended releaseIf 1st  concentration below treatment line @ 4-12 hours, repeat in 4-6 hoursDialysis-Dialyze If APAP >900 w/ AMS or acidosis.NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failureThe addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement In this Ryan sits down with Dr. Richard Dart MD, PhD. He is the lead author of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations.  They dive in to the definitions established by the guideline and notable treatment recommendations, dissecting the ratinonale for each desiscion point and how to apply the guidelines. A mini episode was released along side this episode that is a high yield review of major treatment recommendations and definitions estabilished by the consensus statement.  Links :Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement Guidelines https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062Definitions made by the guidelineAcute ingestionAny overdose taken with 24 hours periodOverdose "dose" not defined>7.5 g in 24 h was criteria for Rumack Matthew nomogramConsensus statementAdult overdose at 10g/d or 200 mg/kg/d in 48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)Treat if APAP >20 ug/ml OR AST/ALT elevatedAcuteNon-detectable [APAP] between 2 and 4 hours excludes ingestionGive SDAC w/in 4 hours (something I've been a proponent of since ATOM2)TreatStart treatment with NAC if unable to plot on nomogram by 8 hoursNAC dose“Higher dose” NAC (undefined) for high risk ingestionMinimum NAC regimen should include 300 mg/kg orally or within 20-24 hoursCAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)Unique scenariosLine crossersAPAP with anticholinergic or opioidIf 1st  concentration below treatment line repeat in 4-6 hoursAPAP Extended releaseIf 1st  concentration below treatment line @ 4-12 hours, repeat in 4-6 hoursDialysis-Dialyze If APAP >900 w/ AMS or acidosis.NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failureThe addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

Interpreting Your Own Labs For Health Optimization With Dr. Yablonsky “Normal” lab results doesn’t mean you are optimized. Become the CEO of your own health! On today’s podcast I have returning guest, Dr. David Yablonsky on to help you learn how to take control of your health and be able to interrupt and understand your lab results. We believe in bringing your labs into optimal range, not just out of a disease state. This is going to be a multipart series as there are a lot of different panels to cover. Lab panels discussed: Hemoglobin A1C A hemoglobin A1C test is a blood test that shows what your average blood sugar (glucose) level was over the past three months. Optimal: < 5.2 Pre-diabetic: 5.7 Diabetes > 6.4 AST & ALT Rising levels of ALT are often the first clue that something is wrong in the liver. Women ALT: < 25 Men ALT: < 33 PSA Age specific Watch for velocity changes Know that certain medications such as Finasteride falsely lower a PSA by 50% These are rough averages: 20-30 years of age < 1 30-40 years of age < 1 40-50 years of age < 2.0 50-60 years of age < 3.0 * Velocity changes is one of the most important indicators which is why establishing a baseline PSA is so important. Never a PSA > 4 unless you are 80+ years of age. Iron Iron is commonly miss understood. Checking your Ferritin and Iron % Saturation are important to understand your iron levels. Ferritin levels are a measure of your iron stores, which should remain < 50 ng/mL. Although, elevated ferritin levels > 300 ng/mL can be an indicator for inflammation in the body. Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder. To contact Amy Stuttle email podcast@amystuttle.com To visit Victory Men's Health This podcast is not medical advice. Consult your doctor.

Thank you for listening to the episode today!    Special links mentioned in the episode:   Castor oil pack   The labs that I look at give clues the liver needs support:  low platelets high BUN low creatinine low CO2 low protein high globulin low albumin high or low AST/ALT low cholesterol high or low triglycerides low HDL high LDL high non HDL low Free T3, which signifies a thyroid conversion issue low vitamin D ( below 25) low or high GGT low PH high TBIC high iron high ferritin     Let's connect!

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. I am Pradip Kamat. I am Rahul Damania, a current 3rd year pediatric critical care fellow. I am Kate Phelps- a second year pediatric critical care medicine. We come to you from Children's Healthcare of Atlanta Emory University School of Medicine. We are delighted to be joined by guest expert Dr Stephanie Jernigan Assistant Professor of Pediatric-Pediatric nephrology, Medical Director of the Pediatric Dialysis Program at Children's Healthcare of Atlanta. She is the Chief of Medicine and Campus Medical Director at Children's Healthcare of Atlanta, Egleston Campus. Her research interests include chronic kidney disease, and dialysis. She is on twitter @stephaniejern13 I will turn it over to Rahul to start with our patient case... A 3 year old previously healthy male presents with periorbital edema. Patient was initially seen by a pediatrician who prescribed anti-histamines for allergy. After no improvement in the eye swelling after a two week anti-histamine course, the patient was given a short course of steroids, which also did not improve his periorbital edema. The patient progressed to having abdominal distention and was prescribed miralax for constipation. Grandparents subsequently noticed worsening edema in his face, eyes, and feet. The patient subsequently had low urine output, low appetite and lack of energy patient was subsequently brought to an ED and labs were obtained. Grandparents denied any illness prior to presentation, fever, congestion, sore throat, cough, nausea, vomiting, gross hematuria, or diarrhea. In ED patient was noted to be hypertensive (Average systolic 135-highest 159mm HG), tachycardic (HR 130s-140s), breathing ~20-30 times per minute on RA with SpO2 92%. Admission weight was recorded at 16.5Kg. Physical exam showed periorbital edema, edema of ankles, there was mild abdominal distention (no tenderness and no hepatosplenomegaly), heart and lung exams were normal. There were no rashes on extremities. Labs at the time of transfer to the PICU: WBC 10 (62% neutrophils, 26% lymphocytes) Hgb 7.2, Hct 21, Platelets 276. BMP: Na 142/K 8.4/Cl 102/HCO3 19/BUN 173/creatinine 5.8. Serum phosphorus was 10.5, Total Ca 6.4 (ionized Ca= 3.4), Mag 2.0, albumin 2.6, AST/ALT were normal. An urine analysis showed: 1015, ph 7.5, urine protein 300 and rest negative. Chest radiograph revealed small bilateral pleural effusions. After initial stabilization of his hyperkalemia-patient was admitted to the PICU. PTH intact 295 (range 8.5-22pg/mL). Respiratory viral panel including for SARS-COV-2 was negative. C3 and C4 were normal. A nephrotic syndrome/FSGS genetic panel was sent. A renal US showed: bilateral echogenic kidneys and ascites (small volume). Pradip: Dr Phelps what are the salient features of the above case presented? Kate Phelps: This patient has a subacute illness characterized by edema, anemia, and proteinuria. His labs show that he has severe acute kidney injury with significantly elevated BUN and Creatinine, hyperkalemia, hyperphosphatemia, and hypocalemia. Rahul: Dr Jernigan welcome to PICU Doc on Call Podcast. Thanks Kate, Rahul and Pradip for inviting me to your podcast. This is a such a great way to provide education and it is my pleasure to come today to speak about one of my favorite topics, pediatric dialysis. I have no financial disclosures or conflicts of interest and am ready to get started. Rahul: Dr Jernigan as you get that call from the ED and then subsequently from the PCCM docs, as a nephrologists whats going on in your mind ? When I get the call from the outside hospital my first job is to make sure the patient is safe and stable for transfer to a tertiary care center. This includes concern about airway, breathing and level of alertness. From a renal standpoint, I am worried about elevated blood pressure, electrolyte abnormalities, in this case primarily the hyperkalemia, and fluid...

This episode follows S2 E43 in discussing the possible role of NASH cirrhosis clinical trials in the transition from biopsy as gold standard to a post-biopsy world. Stephen Harrison starts this conversation by reviewing a post hoc analysis of Phase 2 belapectin data from Galectin Therapeutics, followed by a review of the FALCON 2 stud of pegbelfermin in NASH cirrhosis, sponsored by Bristol Myers Squibb. Jörn Schattenberg, Mazen Noureddin and Roger Green add their perspectives to the conversation.Stephen's primary point from the belapectin post hoc analysis is a practical one: the high correlation between an AST:ALT ratio>1 and HVPG levels can help clinicians suspect which patients have cirrhosis and possibly define candidates for NASH cirrhosis clinical trials. Mazen states that given the lack of trial data in this area, any secondary data that can be interpreted or integrated into a broader analysis is exceptionally helpful. Stephen asks what the ideal design would be for a NASH cirrhosis trial starting today. While answers vary, they all rely heavily on non-invasive tests to provide richness to the data and possibly set a foundation to become primary endpoints over time. This leads Roger to observe how much more complex and disease-focused trial design discussions have become over just the past two or three years.

Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 9. View the complete issue: https://www.oncotarget.com/archive/v12/i9/ Oncotarget Volume 12, Issue 9 features: COVER PAPER: “Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore” https://doi.org/10.18632/oncotarget.27933 EDITORIAL: “Is there a role for CDK 4/6 inhibitors in breast cancer brain metastases?” https://doi.org/10.18632/oncotarget.27904 (PDF Download) EDITORIAL: “Epigenetic effects of pharmacologic ascorbate” https://doi.org/10.18632/oncotarget.27911 (PDF Download) RESEARCH PAPER: “Activation of plasmacytoid dendritic cells promotes AML-cell fratricide” https://doi.org/10.18632/oncotarget.27949 RESEARCH PAPER: “Piperlongumine promotes death of retinoblastoma cancer cells” https://doi.org/10.18632/oncotarget.27947 RESEARCH PAPER: “A higher De Ritis ratio (AST/ALT) is a risk factor for progression in high-risk non-muscle invasive bladder cancer” https://doi.org/10.18632/oncotarget.27944 RESEARCH PAPER: “Down regulation of lactate dehydrogenase initiates apoptosis in HeLa and MCF-7 cancer cells through increased voltage-dependent anion channel protein and inhibition of BCL2” https://doi.org/10.18632/oncotarget.27950 REVIEW: “Multigene tests for breast cancer: the physician’s perspective” https://doi.org/10.18632/oncotarget.27948 Keywords - breast cancer, bladder cancer, glioblastoma, plasmacytoid dendritic cells, pharmacologic ascorbate, retinoblastoma, cancer cells, cancer, science, research, oncology About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary - Case media - Case teaching - References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid-60s presented to the ED after an episode of unwitnessed syncope while drinking. Patient had suddenly passed out from a seated position with no prodrome or post-ictal state. He had episodes like this in the past, which were thought to be seizures, but otherwise PMHx only notable for alcohol use disorder. He denied any FH of SCD or syncope. In the ED, exam was unremarkable. Labs notable for mild thrombocytopenia, mild hyponatremia with AKI, 2:1 AST/ALT ratio, elevated NT-proBNP, and a very high lactate that rapidly corrected with fluids. EKG was notable for sinus tachycardia, short PR interval, wide QRS, and delta waves consistent with Wolff-Parkinson-White (WPW) pattern. Echo showed preserved LVEF, thickened LV septum (1.6 cm) and posterior wall (1.3 cm) concerning for hypertrophic cardiomyopathy (HCM). No outflow tract gradient was noted at rest or with stress, and the strain pattern demonstrated apical sparing. Evaluation for cardiac amyloid, including plasma cell dyscrasia and PYP scan, was negative. Cardiac MRI confirmed severely thickened LV inferior and inferolateral walls at 1.7 cm with no LVOT obstruction. 25% of the myocardium demonstrated patchy LGE.   Due to concern for WPW syndrome, the patient underwent an EP study. This revealed a malignant septal accessory pathway that was successfully ablated with resolution of the WPW EKG features. Given large LGE burden in setting of HCM, patient underwent placement of primary prevention ICD. Genetic testing for PRKAG2 mutation is pending given comorbid WPW and HCM.  Case Media ABCDEFClick to Enlarge A. CXR: Slightly increased interstitial markings in the lung bases, an elevated right hemidiaphragm. No acute airspace disease or pulmonary edemaB. ECG: Sinus tachycardia rate 120bpm, PR interval 80ms, QRS 130ms, WPW pattern.  Arruda algorithm localizes to posterior septum.C. CMR:  Myocardium nulls before blood pool.D. CMR:  Delayed gadolinium enhancementE. Follow up ECG: NSR 78, repolarization abnormalities.  T wave memory inferior leads.F.

In this episode, Ben Azadi shares his 40-day carnivore experience. Ben reviews his complete lab work from day 1, and compares it to day 40. Get your grass fed beef, wild caught fish, and healthy carnivore protein at U.S. Wellness Meats. Click here to visit U.S. Wellness Meats website. Use the coupon code ketokamp for 15% off your entire order. Become a Keto Kamp Academy member today at 50% off. Visit http://www.kkaspecial.com Use the coupon code keto50 to be locked in at this rate. // E P I S O D E   S P ON S O R S  PureForm Omega Plant Based Oils (Best Alternative to Fish Oil): http://www.purelifescience.com Use ben4 for $4.00 off. http://www.Kettleandfire.com/ketokamp and use KETOKAMP at checkout to save 15% on your entire order. ☕️ Purity Coffee: http//:www.ketokampcoffee.com, use ketokamp at checkout for 10% off *Some Links Are Affiliates* // C A R N I V O R E  N U G G E T S Methionine glycine balance. It’s important to include collagen via organ meats, supplements, and bone broth.  Methionine is commonly found in muscle meat. Glycine is found in connective tissue and organ meat.  Methionine is a carrier of methyl groups, when you have too much methionine  it uses up your bodies glycine to buffer up the methyl groups. This will mess up your biochemistry. Glycine balances methionine and helps the amino acid ratio. If you are glycine deficit it will be difficult to make collagen and glutathione (meaning you won’t feel as good) Key Supplements For Carnivore: Boron Paleo Valley Bone Broth Powder Paleo Valley Organ Meat Complex Another tip for not feeling well is to increase your fat to protein ratio.  The organ meats are key, it is nature’s multivitamin. Especially liver! B vitamins Methionine Riboflavin Selenium Choline Vitamin A in retinol form Vitamin C A popular objection to eating liver is the belief that the liver is a storage organ for toxins in the body. While it is true that one of the liver’s role is to neutralize toxins (such as drugs, chemical agents and poisons), it does not store these toxins. Toxins the body cannot eliminate are likely to accumulate in the body’s fatty tissues and nervous systems. On the other hand, the liver is a is a storage organ for many important nutrients (vitamins A, D, E, K, B12 and folic acid, and minerals such as copper and iron). These nutrients provide the body with some of the tools it needs to get rid of toxins. Ben Carnivore Lab Work Notes: BUN went up moving more protein through my kidneys  Blood Urea Nitrogen and Creatinine these are byproducts of different functions in the body BUN/CREATININE ratio went up Albumin protein went up   AST ALT went down    Ferritin went up but this can be an issue if there’s oxidized fats in the body. It’s important to look at other oxidative stress markers. C-Reactive protein went down more than 50% (inflammation in the blood vessels) Homocysteine dropped vascular and brain inflammation  Cholesterol and LDL’s went up. The body is clearing the system with cholesterols, cholesterol is a band aid, a healer. This shows up with inflammatory markers coming down.  Cholesterol makes hormones, cells, and gives the cell membrane what it wants. Inflammation markers all dropped but all particles went up. The oxidative component rules. I’m using cholesterol as an energy source therefore I have more particles that are shuttling more cholesterol. Cholesterol becomes a major fuel source, makes sense.  Insulin resistance score 35 to 29 // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so Disclaimer: This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.

In this podcast, Matt Bigos, MD, FACOG an obstetrician/gynecologist with OB-GYN West, presented at Ridgeview Medical Center's Live Friday CME Series on March 13, 2020. At the event, Dr. Bigos talked about hypertension in the OB patient. Enjoy the podcast! OBJECTIVES:    Upon completion of this podcast, participants should be able to: Identify signs and symptoms of gestational hypertension and pre-eclampsia. Identify signs and symptoms of acute onset severe hypertension. Express when to promptly initiate treatment. CLICK ON THE FOLLOWING LINK FOR YOUR CME CREDIT: CME Evaluation: "Update on Hypertensive Disorders of Pregnancy" Note: CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition. FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: PART 1: Hypertension in pregnancy is one of the worldwide leading causes of mortality, affecting 2-8% globally. That's 76,000 maternal and 500,000 infant deaths per year in the world. RISK FACTORS: Nulliparity Multiple gestation Size of placenta/multiple placentas Hx of preeclamsia HTN hx Gestational diabetes Thrombophilia Lupus Obesity before pregnancy Antiphospholipid aby syndrome Older pregnancy Kidney dz IVF OSA Exact mechanisms is unknown, but probably due to the placenta itself. Many theories exist, and there is a familial component. Physiology changes with pre-eclampsia. With pregnancy in general, blood volume increases by 50%. Most of which is serum. In preeclampsia, oncotic pressure in the blood vessels decreases, and fluid leaking occurs, hence edema. Kidneys also lose protein which aids in losing intravascular volume. Be cautious with IV hydration in preeclampsia. Intense vasospasm also occurs. Thrombocytopenia occurs due to overuse of platelets. Hemolysis occurs as well. Look for elevations of LDH and bilirubin. Schistocytes can be seen if you can find a microscope. Periportal necrosis leads to elevated AST>ALT. Coagulation factors won't produce as well either. In the kidney, protein leaks through porous glomeruli. Urine output will decrease due to intrarenal vasospam. Uric acid levels can help differentiate chronic vs new HTN in pregnancy. Less amniotic fluid and smaller fetus size occurs. Placental abruption may happen, in addition. PART 2: Gestational HTN is a BP of 140/90 (either or both) or greater. These must be noted on two separate occasions at least four hours apart. Diagnosed after 20 weeks of gestation in a woman with previously normal BP. Preeclampsia is the same criteria, along with proteinuria. 24-hour urine collection for protein is the historic best way to check. Protein: Creatinine ration is the easiest to do, though. 2+ protein on the urine dipstick may also suffice. Preeclampsia with severe features: BP 160/110 or both (= or >) on 2 occasions, 4 hrs apart. Or if you move to treating the BP, this would signify "severe" feature. Other features include: Mild HTN with platelets

Welcome to another MedTTW. This week I am joined by Dr. Tony Breu who helps me look at a recent #MedThread/#Tweetorial that he did on AST/ALT and Alcoholic Hepatitis. We dive into the reasons why he wrote it and discuss Dr. Glaucomflecken's TikTok and the TV show “The Office” Week of May 3rd, 2020 Host: Chris "The Chiu Man" Chiu, MD Guest: Tony Breu, MD Tweets Discussed: - https://twitter.com/tony_breu/status/1256616387553959939?s=21 - https://twitter.com/dglaucomflecken/status/1256304372977291264?s=21

All right. Welcome to the gut check project. I'm here with your host, Dr. Kenneth Brown. I'm Eric Rieger. This is gut check project, Episode Number 26. We're going to wind up 2019 with some awesome info. What's up, Ken?What's going on Eric? How are you doing, man? Episode 26. Unbelievable. I apologize if I'm a little too sexy today because I'm just coming off of a small cold. I think the hottest people are those that are sick.Well, I'm not sick. I'm post sick. Remember, the viral prodrome. The reason why we always like pass so many viruses is that you tend to pass the virus before you even know that you're sick by the time you're actually sick. You're probably okayYeah. At that point you can go back and say I heard you might be sick. I was too back then.Yeah, exactly. Good to see you?Well, today's episode is going to be pretty awesome. We're going to tackle number one, we've received tons of email in your clinic because you also sell the KBMD CBD at your clinic, you get these questions. These have been coming in Fast and Furious over the last little over 14 days. And it's questions about the safety of CBD oil and its application. So we're going to tackle that I do need to tell everyone. Thank you. We're on episode 26 because the first 25 shows were so well supported by all of you who've been keeping up with a gut check project. We grow every single day. Paul, the guy who's helping us put together the production now and helping us spread the word. We just hung up the phone with him. We've gotten more and more downloads each week. So thank thank you every single one of you for liking, sharing, emailing, telling your friends about it. We sincerely appreciate it.We learned so much about it like today we have a new a different guests we do Instead of gutsy our little mascot or green frog, but since we do film on a green screen, he gets blocked out did not know that didn't even realize that. So now we're going to go with a dung beetle, right here? Yeah, yeah, we did. So that's Dilbert, the dung beetle,Dilbert, the dung beetle. So one of my favorite things is whenever we're bringing any patients back and somebody sees you, and they're like, hey, you're Eric, I watch your show that just warms my heart. So if you happen to be a patient and show up and you watch the show, if you say that it just makes us both feel really, really well...needed wanted, appreciated.Yeah. At least outside of me putting you to sleep. Take five or six good deep breaths. Exactly. Today's episode is sponsored by Atrantil. Your bloating relief, it's what we do. So go to Atrantil.com or lovemytummy.com/KBMD. Today it's also sponsored by KBMD CBD oil. You can find your own KBMD CBD oil at kbmdhealth.com which of course, the initials KB, Kenneth Brown, it's endorsed by the guy who's sitting across the table from me. So Ken, why is...What does MD stand for? Well, I'm not really sure.I thought it was your buddy Mike Doyle, but I don't know.Yeah, it's probably. So tell us a little bit about KBMD CBD. Alright, so KBMD CBD oil. I got involved with the science of CBD because I saw the beneficial effect with my patients when we developed Atrantil I then learned that the science of Atrantil the polyphenols in it actually augment CBD. So I'm seeing this combination do incredible things for people. So this particular CBD is one that we have researched, I've seen it work clinically. And we know that it comes with a certificate of analysis. It is organically grown, it is naturally extracted with co2, so it meets all the criteria that you want in your CBD because this is important. The rest of this podcast is going to be all about the dangers of CBD.Definitely and It's really interesting since we do have so many people who have begun to purchase CBD find benefit. It's really kind of weird what's occurred over the last two weeks. And what I would say is a little bit of misinformation. But it's more or less probably just misunderstood information and or or misapplied information. But regardless, the benefits of CBD used correctly, have been undeniable with the people who've come back through the clinic with people that we've scoped, and how well that they are doing. And so, hopefully today, we're going to provide some context on why more or less the dangers that you may or may not have read about in the news recently are really a little concerned. But we'll, we'll see. We'll see how far along we get in at the last. The last thing. Our last sponsor is the KBMD health box. You can find KBMD health box by going to kbmdbox.com. Now last week we did a full unboxing which is something I think we're going to try to do at least once a month. But essentially, if you want almost $300 of physician vetted supplements that can help you benefit your life and get them for only $147 which you would spend, not you would spend more than $147 worth of time driving somewhere to pick them out for yourself and having someone handpick them for you. Go to KBMDbox.com. What was one of the things that we had a patient come through just earlier this week, who showed us his lab results that he took to his primary care physician? So we're starting to make a difference in the landscape of health here in the DFW Metroplex and different places. I've been getting emails and calls from people around the country that will actually hear the podcast and then they'll want to sign up for the box. And what we're seeing is that these vetted supplements actually are making a difference with both subjective how they feel and objective the labs. So the reason why I chose these things is they all have third party analysis. And they all have some scientific background that actually explains how they're going to help you. So much so that I'm thinking of ordering my household, another box. So although it is the KBMD Health box, I actually I love the fact that I can get these things that I'm going to purchase anyways, they come into my house, so my whole family's on it. Now we're running out of stuff. So I'm gonna end up having to double up on everything. So it's one of those things that I feel really good that we can look at different aspects. And when somebody says, Oh, I tried X, Y, and Z, I didn't notice anything. I'm like, oh, did you try one that had a third party analysis? No. And then they do and they're like, Oh my gosh, big difference. Same thing with CBD. I mean, a lot of CBD out there doesn't really have what's on the label. And we're going to get into that because we're going to talk about what the FDA thinks about it. We're going to talk about the different media and what they're doing, and hopefully get into all that but that's the whole point of that box is I want to deliver these vetted things to your house monthly so that you can continue to improve your health. Hundred percent. So without further adieu, be sure to like and share the gut check project. We certainly appreciate all of the support to date. We're going to hop right into it. So what we've received here recently is a lot of speculation and concern from people who have said, Hey, I'm interested in CBD. I know that you and Dr. Brown have heavily studied, been entrenched with CBD and its application over the last few years. I just learned that the FDA is associated or made public a study that says that it may be hepatic toxic or bad for my liver. It's, unfortunately, it's a weird jump off point. So I'm going to kick it to you. Because immediately I had lots of different thoughts and instead of getting emotional, what did we do? We went and tried to find the sources of where this information came from. We want to backtrack on how they got to that conclusion. And I think that we can put a lot of questions at ease and even help people learn how to be a little bit more critical with the data that they receive when they receive it. Because let's face it, lots of stuff that we see on the internet, or that we hear on the news or reading the paper, it's basically clickbait. It's basically things to keep you engaged, whether or not the actual substance is worth the headlines that are written so...So what you're referring to is recently the FDA put out a statement, a consensus statement in the news and it's making all kinds of traction in the news that they're saying that CBD is not as safe as people think not only that it can be harmful. Now this has bled onto TV and my patients have been asking me about this FDA statement. Then there's been other news articles like the one that Forbes published, read said that CBD causes liver failure. Failure. That was the title liver failure caused by CBD. I want to get into all that I wanted to take a really deep dive into the science of all of this as a gastroenterologist, I'm board certified gastroenterologist, which means not only am I a simple country, butt doctor from Texas, but we actually have to learn liver disease, hepatology, I'm not a hepatologist like some of my other friends where I send like really complex things, but we at least have to understand the liver, how it works and what it does. So a lot of these articles discuss this but they don't clarify so many little things. Because and they shouldn't it's a it's a journalist writing an article they want they want it to be shared. And anytime you mentioned CBD, anytime that that is thrown out there, you're going to get some clicks, you're going to get a whole lot more clicks. If you say you're going to die from taking CBD. It reminds me of the I remember Jerry Seinfeld was on Saturday Night Live one time and they were making fun of the nightly news where they always do the promo at like three o'clock. Like five household items that are guaranteed to kill you, tonight at six.You're like what? If it was so important, they probably wouldn't make you wait.No, I'm gonna die before you put this on the air. So what I'd like to do is talk about the briefly the science of the endocannabinoid system and CBD, then do a little bit deeper dive into the liver. So everyone's going to get a primer on the liver 101 here, because these studies don't make sense unless you know, some of this knowledge. It's just sensationalism. For some of it, some of it is a little bit unfair. I think some of it is for what the FDA got, and it's there. But I just want this podcast today to be something that can be useful for industry people that can be useful for patients or people that are thinking about taking CBD and it can be useful for a subset a small subset of people that may be should not consider taking it. Yeah. So all of this is kind of, you know, for the future of this podcast, It's almost going to be a bit of a rebuttal. Not necessarily a defense of hemp derived CBD. But let's just buckle up and kick some science. This might be a little bit I don't know how long we're going to go where we're going to go with this. We're just going to feel it out and see what happens. But I at least want to be able to explain why I still believe that a lot of people should be taking CBD even though Forbes is like you're gonna die from this.Yeah. It's not arsenic people. No it isn't and I think another cool application here is there are people out there who have been on the fence on whether or not I should try CBD or is this something that's good for a family member for me? And unfortunately, there you hit this intersection, where a news headline is written that CBD causes liver failure. Well, if they've been on the fence, that's a pretty big No, no, right? So now you've taken away maybe an avenue that they were considering to help them out. What I hope that we can do with this particular episode is basically let's temper and let's see things in context. I think context is a word that as you get into sensationalism is something that is kind of the rescue item. If I could put something into context, then at least I'm giving someone a fair chance to understand the information that's before them. I don't feel like sensationalized headlines do things like that. Then again, I also don't feel like someone who shakes, hand picked or cherry pick studies is doing that either. So what I think today that we can do is fairly evaluate and talk about the process of how the liver works, and why some of these studies are or are not applicable to the nature they were presented.Absolutely. So the first one we got to discuss is what what what the heck did the FDA say? Sure. So the FDA came out and they mentioned that they've got several issues with the safety of CBD. The two main ones that they're really concerned about are potential for liver injury, and interactions with other drugs. What they actually said is that they're concerned that people may mistakenly believe that trying CBD can't hurt the agency wants to be clear that they have seen only limited data about CBD safety. And these data point to two real risks that need to be considered as part of the drug review and approval process for the prescription drug containing CBD. Interesting. Now, what I say this is because the FDA is referring to the data that was presented to them by GW Pharmaceuticals, who has a epid... eipdi..x you know?E-p-i-d-i-o-l-e-xYes, which is the first FDA approved prescription CBD isolate,Right,for seizure disorders.It's important to point out that is not full spectrum. Correct. That is not full spectrum. And there's some that's important because here later in the podcast, and think we're going to draw some comparisons and just if you're listening, just remember, epidiolex is a CBD Only isolate it is not a full spectrum product.So let's talk about what the FBA what the FDA actually does. So the FDA has a really daunting task. The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy and security of products. So it is super daunting because there's a lot of products hitting the market, and the FDA has tried keep up with this to try and protect people. And let's be honest, let's look at the elephant in the room. The elephant in the room is that there are a lot of bad CBD products out there. Yep. In fact, in a jam article 2017 showed that 70% of the CBD products that they looked at did not have what was on the label and what was there could be higher levels of CBD could be lower levels of CBD. So it's a gamesmanship that's going on right now. So it is totally true that you need to make sure that you've done your homework on what type of CBD that you're actually taking. There currently is little to no regulation in the CBD industry. There is the President and CEO of Natural Products Association NPA. His name is Daniel Fabricant. He's a PhD. I love this quote. He's quoted as saying it is well past time to bring science into the equation, as federal rules require safety and Consumer Protection must come first. I agree. And we all agree with that. Sure. And I think that all companies that have reputable CBD companies, they all want that. Problem is when you have these different stories leaking out, which gain much more traction, it just starts creating a little bit of confusion misconception, and then people don't really know where to turn. So the feeling is, is that possibly statements by the FDA saying that it creates this narrative that questions the safety of CBD overall, strictly to address a few number of companies which are producing quite frankly, some crap products.What was the number that we learned the last time that we were in Utah at meeting I believe it was one out of every 23 to 24, I could be off it was definitely in the 20s. But every to every 23 or 24,25, CBD labels available for retail purchase. One is seen as a reputable well marketed or correctly labeled product, which means that even if it happens to be off a little bit, you've got 23 or 24 other labels which are just not truthful or probably not correct, don't have a certificate of analysis or are blatantly, just not even what's in the bottle.100%. There's a lot of people out there trying to take advantage of this wave that's coming. So I do not. I believe that the FDA is doing their job by looking at the data that was actually presented to them Agree. So let's take some time and break all this down for the consumers, health care providers, industry personnel. Starting with the question, does CBD cause liver damage? Unfortunately, or fortunately, because I like science we really need to talk about what the endocannabinoid system is. Because if somebody's listening to this, they're like, Well, I was thinking about taking this but I'm worried becasue it can cause liver failure. I don't know why I'm taking it. Why in the world should I be taking it? So let's do a quick one minute discussion of the endocannabinoid system. Let's do it!All right, the endocannabinoid system. The endocannabinoid system is a system which was discovered in the 90s that we now realize it's probably everywhere in the body. There's primarily two different types of receptors, but essentially, the way that I try to explain it to my patients, it's concentrated more so in the neural areas, nerves, brain and the immune areas. Although we now know it's in every single organ, that's where all the original research was. We now realize that its job, the endocannabinoid system is to produce these products called endocannabinoids. Which work as traffic cops. They just kind of get your body to get back to an area of balance. If you've got too much activity, they go Whoa, slow down a little bit. If it's not enough, they go, come on. Let's go ahead and get some more going here. So you have this fantastic system in your body that really just tries to keep balanced. Think of it that way. And you're going to hear a little bit later why I think most of America is out of balance. I think most of America needs some replenishment of their own endocannabinoid system. So that's the important thing is is that there's a dire need to try and get us all back to a certain balance, because the reality is we're getting sicker as a nation. And one of the causes could be that we took hemp derived foods out of our diet and out of our livestock diet. And there's a theory on that, that possibly that's one of the reasons why we're having more autoimmune diseases, why we're having more of the other problems that we're seeing, Well at least contributing factor.Certainly at least a contributing factor. So keep this in mind. So the the primer on the endocannabinoid system is if you're, if you have ears and you're hearing this, you also have an endocannabinoid system, and you have a higher than likely chance that you are out of balance with that. And if you are out of balance with that, then you probably could benefit from some of this. Sure. So right now you're going well, I'm out of balance, I'm going to probably benefit but I'm going to go into liver failure if I do this. So let's talk about what liver failure means. You have a genius living within you. You probably have multiple geniuses living within you.Thank you. That feels great. Sometimes the voices in your head don't say to do bad things.The evil genius. Yeah.Well, one of the geniuses living within you as this beautiful origin called your liver. So you have this and it's amazing. So to understand where they're going with this, let's talk about what the liver actually does. So we all have livers. And they work differently in every single person, and they can continue to adapt, evolve and change. One of the only organs that you can transplant a partial portion of it and it will grow into a full liver. So the nephrologist think that the kidneys, the smartest organ, the neurologists will think that the brain is the smartest organ The cardiologist says if you don't have blood, you can't think so It must be the heart. Yeah, yeah, exactly. I'm gonna say, well, for health span, smartest organ in the body is the endocannabinoid system. So eventually, we're going to have Endocannabinoidologists. Because what ends up turning out is that the endocannabinoid system is in all these different organs.Correct.They're not completely separated. So let's talk about the liver. The liver is responsible if you ever wonder what the liver does. So do you have any idea what the liver does? I've got a little bit of an idea... Little bit of an idea. So the liver is responsible for selective uptake, concentration, metabolism, and excretion of the majority of drugs and toxins, also known as xenobiotics. So let me just say that again. Basically, the liver takes the crap that you bring into the world. And it says, I'm going to convert it to something useful, or I'm gonna get rid of it for you. Yeah, it can detoxify it, or it can say, Oh, you need to be this and then you're useful. That's why I say it's a genius in your body. And it the liver figures this out, it figures out what you need, and it determines if it's a drug, or if it's a toxin, and it can turn into a better form. Now, one of the problems I have with these different articles that I've been reading, is that they discuss that then enzymatic process called the P 450 system, and they just write it like that they're like, CBD has been shown to affect the P 450 system. What doesn't affect the P450? So that's the issue. So let me break that down, I bring up the P 450 because in the lay literature without even describing what it is, it is a complex. It's called a phase one metabolism of the liver. Under p 450. It's an umbrella term that has over 60 different genes, that code for hundreds of enzymes to break down anything that comes your way. So the P 450 enzyme is like saying, Oh, I don't even know an analogy, but it's top of the funnel down. It's like you just so generic,  that you can't just say that. So but they write it in the lay literature almost as a sounds sciency so I'm sure that it's, I'm sure that it's right. That's kind of my feeling on I'm like, why would and all these people it's almost like these news articles parrot each other. And nobody's stopping going, wait a minute, because as it turns out, the P450 system, not the P450 enzyme, the system breaks down almost everything that we put in our bodies. Yeah, no joke. So a lot of going back to the pharmaceutical days, I remember that was one of the biggest challenges with with any of the drugs that we detailed a physician on was, how is it affecting the P 450. And that would be something that they would be all salespeople be coached on that before they would go on calling a physician. But the truth is, it doesn't have to be a compound. It doesn't have to be a medical pharmaceutical compound for that to be somewhat important. Something as simple as grapefruit juice. Also, detectibily inhibits the metabolic ability of the P 450. So there's all there's a handful of different drugs that people who are elderly, maybe caution, don't drink grapefruit juice, because it will inhibit your ability for your body to clear this particular drug. And I say that to say this. It's not nothing is inherently just special because it does or does not directly affect the P450, almost everything you take into your body is either cleared quickly or slowly by that same system.Yeah, so they kind of imply like CBD is the only thing that gets...Not even close....that gets processed in the in the P450 system. In fact, we know that there are multiple medications that can be altered by certain foods. Grapefruit is the most common one, and that really affects like immunosuppressants tremendously and that's where it really came up. When they realized, oh my gosh, you have these different drugs, let's say blood thinners and immunosuppressants, which have a very narrow therapeutic window, you have to have these things like right dialed in. Yeah. And then people talk about grapefruit but you know, other things that have actually been shown to do this cranberry juice, black tea, pepper, even chocolate Yep. has been shown to affect drug absorption and they have been shown to affect certain pharmaceuticals. We don't even know the tip of the iceberg on this because you have to do the study on it. You have to do the pharmaco kinetics, the PK is what it's called to actually determine that which is so funny because they say oh CBD is metabolized by the P450 system. That means nothing. And so if you take CBD and or chocolate and or drink tea, be careful. I mean...I think a good analogy a seriously a good analogy is it the P450 being metabolized by the P450. It may be good for base knowledge, but the truth is, is does it overwhelm that, as you put it system, if it is overwhelming that system, chocolate, for instance, for most intents and purposes would be like a single car driving down a six lane highway by itself. It's not really if the highway was a P450 and the car was the chocolate. It doesn't take anything to funnel that that car through.Correct.The problem is is whenever you happen to overwhelm that system. And that is important to know. But I would say in terms of context, kind of the way that we started this discussion in context. It's not my belief through what I've read and seen that CBD inherently overwhelms or becomes more than a single car down that six lane highway.So not only is it just one single car going down the highway, remember that not only foods but drugs, nobody's talking about drug drug interaction.Right.So there's a reason. So I see a lot of patients that one drug may be very effective one thing may be very effective, but there's so many variables like for instance, drugs, the sex of the person plays a role, you may have different levels, the age of the person and any diseases can all affect this whole system called the P 450 which produces enzymes. So not only that, but then genetics play a huge factor, alcohol intake.Alcohol intake, all of that. I mean, genetically, this may be why some drugs work on certain people and why they don't work and others fact there's a whole field of science right now where people are trying to determine the genetics ato go, Oh, you're going to need a higher level of whatever Plavix which is one that they've actually looked at. Or you can, you're going to take less. So we this is a whole field of this beautiful science where we can go Okay, genetically, you're going to be predisposed to need more medications. So when these enzymes get used up, basically if you've got this one chocolate, which is a car, one on six lane highway, and then you add fluconazole, which is an antifungal, that's an but that's not a car, that's a semi now and then you add alcohol, which is a minivan could be ccould be a couple minivansand then you do whatever something else, but you can see that the liver has to try and process this right. So what happens is it becomes this once it becomes a traffic jam. Then people start getting angry, they start honking their horn that is a rise in your what we call lfts liver function panels liver function test Yeah, so AST and ATL are the two ones that we always talk about, that's exactly what the FDA was referencing. So I want everybody hear this. When you overwhelm the liver with multiple cars using your analogy, then honking starts and the honking the warning sign is this rise in AST and ALT. So, for instance, your body can adapt to it. We've seen this all the time. If you drink alcohol on a regular basis. you build more lanes, you build more lanes, you get really good at metabolizing alcohol. Build tollways. I'll use myself as an example.Not with alcohol.With coffee, Okay.I always have to laugh. Whenever I go to the my own doctor. They say how much coffee do you take? I just write obscene amount because I've down regulated by receptors or I've had the ability to ramp up my my livers ability to convert that coffee into an inert thing and there it is. So you see it as an anesthesiologist or as a crna. I mean, describe what your experiences whenever you try and put somebody to sleep using propofols, different medications.Yeah, well, I mean, definitely, if someone says that they happen to be a large consumer of or a consumer of large amounts of alcohol, it generally takes anywhere between 20 and 30% more of an agent to put them to, to sleep safely, say, But back to your point of body habitus, for whatever reason, even just something as simple as someone being a redhead fair skinned, those people generally take more agent to make them go to sleep. Yeah, let's go ahead and clarify this. This is a well known thing in anesthesia. You're not being prejudiced? No, not at all. No, they literally just for whatever reason, the metabolism rate of someone who's fair skinned with red hair is typically higher than the average calculation and you can go through any types of weight based medications that we use to bring sedation to someone and generally fair skin redhead folks just take more. Is that interesting?Yeah, it is. So that is more than just anecdotal like they've actually done some studies on this and they've actually shown probably because whatever lineage, they come from Scotland, Ireland, they have a higher P450 to metabolize that particular or a higher subset of the P450 systems. So just keep that in mind. So when you take certain foods or drugs, everything's competing for your liver, to do to just say, hey, fix me, you know, figure out what's going on. Fortunately, it is a badass organ and the liver is tough and it can handle a lot, the largest solid organ that we have in the body. So usually it can handle everything. Now the most common example like we've talked about, if you take grapefruit juice with certain immunosuppressants and things then that particular combo because those drugs need exact or how they were manufactured need exact metabolism numbers. Not only that, did you know that like nutrition plays a big role. So, high protein diet will actually affect your P 450 and malnutrition will affect it. of course it will. So those are all of our paleo friends over at paleo FX and such those guys have revved up p 450s. Eating a lot of protein working out a whole lot, they're able to do this. Unfortunately, malnourished people probably can't tolerate as muchNo and they aren't they aren't they honestly they don't have the supply to rebuild the enzymes that are that are used within the P 450 I mean it's just malnutrition is going to deplete all different types of systems, not just the liver.So in the intro, I kind of mentioned that we're getting sicker. And so let's use nutrition as an example. federal policies tightened by the controlled substance act of 1970 essentially banned the production of industrial hemp during the war on drugs effectively we made hemp CBD illegal and put it under the umbrella of cannabis cultivation. Now what were we were talking with Will Clyden of O-hi energetics right, who actually discussed this and he said some cool stuff on this. He back before this when they were they were using hemp and hemp has been used for ever like since we landed in America, hemp has been using hemp has been used in China for thousands of years and all this other stuff that we were feeding because it's a fantastic crop. It's it detoxifies the soil. And it actually works. It grows quick. It's a great crop industrial. What were we thinking making it a banned substance, I don't know, separate discussion. But they've got data to show that when they were feeding chickens, so for everybody out there I had a patient today who said I said Oh, she was suffering from some things and I think CBD would help with and I mentioned Hey, have you ever considered CBD Oh, I would never ever, ever, ever do anything like that. I am not like that. I said, Okay, that's cool. said hey, let me tell you something. Do you know that before 1970 we were actually feeding animals like chickens and cattle. One of the primary things that we would feed them would be hemp, and it's been shown that you can take a chicken egg and it had over 250 milligrams of CBD, right so right now if you're somebody that just spent $200 on your CBD that has 300 milligrams in 1968 you could've just had an egg.A three cent egg.I know 3 cent egg. And I looked at the literature and I and I could not find anything that said death by egg otoxicity. It didn't so everybody that's sitting there thinking oh my gosh, no. I'm not going to do CBD. We were having CBD in our diet. A great Great example, to learn a lot more about this and do a deep dive. Our friend Chris kresser had Will Clyden and the CEO of O-hi, O-hi energetics on and he went into this tremendously. It was so cool. It was just like I just it's crazy that we stopped like, and I as a physician have seen that we are getting sicker as a country. So in 1970, we've got since 1970. We've got more chronic disease, we've got more dementia, we've got more autoimmune disease. coincidence, like we said in the intro, maybe it's at least a contributing factor. And now we have the FDA saying that CBD can be harmful yet it was in our food supply up until 1970.That's nuts, dude.It is nuts. And it doesn't make sense and if you look at mean hemp seed, birds eat seeds, birds consume seeds, they do all kinds of things where they can they take in product, What's the matter? No, I'm just looking at I'm trying to make sure we get through everything.Okay good, but I mean they eat everything and people have been consuming eggs from not just chickens they've been consuming eggs from all different birds on the planet for that long. The fact that we've restricted hemp growth etc has only taken away one of the natural things that birds were eating.If you're if you're really interested in this like I said go to Chris Cressors podcast where he's got Will Clyden on there is really cool wills smart dude Chris is super smart dude. So those guys those guys kick some crazy knowledge.Right?So that is it's weird that we're talking on this episode about CBD causing hepatotoxicity. And we've already shown that the liver's pretty badass, right? It can do a whole lot and we've already shown that the endocannabinoid system is necessary and since 1970, or up until 1970. We are taking in significant amounts of CBD in our dietRight.Weird.It is weird, but it's not so weird when we get down to why everyone's alarmed. So you want to get into a...Now let's go ahead and look at the studies. So that is sort of the phase one of this podcast because now we're going to start geeking out a lot. So I hope I didn't hope I didn't lose everybody with a but you kind of need that background to understand what we're going to talk about next.Sure, you definitely that background.Alright. So what they're talking about is the FDA published this revised consumer update. So this is the consumer update that they put out there for everybody detailing the safety concerns about CBD products. Now, this was based on the studies provided by GW Pharmaceuticals, GW Pharmaceuticals has done multiple different studies looking at different things to get their FDA approval. And I'm going to say right now, that kudos to GW for being the first company to step up and really try and make something for a group of people with intractable seizures have an alternative. Kudos to the FDA for doing their job and looking at the data that was presented to them. What I'm going to do is go next level and say, Well, you didn't look at everything. That's the bottom line here. So I'm not bashing anybody. Let's make let's make certain of this. Sure. So there have been several randomized, controlled and open label trials that studied the effects of epidolex, I'm going to call it epidolex from now on it's just easier, which is a 99% pure oral CBD extract on patients with refractory epilepsy. So this in turn led to the FDA approval for two diseases, dravet syndrome and Lennox-Gestaut syndrome. So if you recognize those names, bless you, because you're dealing with some serious stuff, It's a serious seizure issue. If you don't know those. Count your blessings. It's one of those times to go well, no matter where you're at in life. It's like well, thank goodness that I don't have to Deal with a child that has this because that's, that's a really big deal. These are intractable seizures. So they looked at the data on that. And in these studies, the kicker here is I'm going to say it again, getting back to the lane highway, the patients maintained on their stable drug regimen with a median of three anticonvulsant drugs. That's important. It's super important. Three anticonvulsant drugs. So when we use the analogy of the car on the road, imagine a six lane road. And three of those roads. Three of those lanes are double semis.Yeah, that are closed construction... Or closed, Yeah, that's more likely or closed. So let's talk about that. So when we're talking about three different agents used to control seizures, some of those agents would be and I'm assuming here, but probably Depakote, probably Dilantin, also known as phenytoin, or fosphenytoin, which is seravex. There's a handful of anti seizure medications and through my knowledge, all of them, all of them have been recorded as raising the enzyme levels used by the liver which of course would lead to ALT and AST elevation, showing that the liver is essentially working overtime to long term process these drugs right or wrong?Correct. Correct, which is exactly what the FDA is supposed to do. They're supposed to look at this data and go Okay, so let's just look at the study that they're talking about. So the FDA accumulated this data, and they looked at what GW presented GW presented in isolette of CBD, not a full spectrum. And the dose they ramped up to 20 mg's per kick 20 mg's per kick. What that means is a guy like me would take 1954 milligrams a day.That's a lot more...of CBD isolate. Now I see the effects, beneficial effects of taking KBMD health CBD 15 milligrams twice a day,that's 30 milligrams,that's 30 milligrams.The exact dose of what makes people feel better is very argued because all the data coming out of Israel shows that a lot higher doses, but I'm seeing effects at these doses So let's be real quick let's stop for context. So right now at this intersection what we're what you're saying is with a full spectrum and we said this at the beginning of the podcast that what GW Pharmaceuticals has with epidiolex is a CBD isolate and what they've done...You're saying epidiolex now that's funny. Yeah, whatever it is, Well, because I started with that. Then you told me no, that's not how you say it.I think we should switch it up the whole time. EPA max the way it was edimax. What they did is they were able to establish that almost 2000 milligrams for you would be the ideal dosage however, you...isn't that correct? That's the dosage that they went for or the dosage that they felt was safe, Safe. Okay, I'm sorry. So but but on the upper end of... That was what they were aiming for on everybody. In essence, though, from where you have had beneficial effects, you're talking 60 times that amount, two months worth, is what they are saying the safe level would be in one day where you're finding the beneficial spectrum. So just just in terms of context, full spectrum, CBD, one 60th of the dose that they're saying it's a it's a safe level is really all that you need from our experience.Yeah. Now in GW's defense, let's look at the data. So in dravet syndrome, seizures dropped 39% and in Lennox-Gestaut 42%. So... that's good. So they probably did their homework and said, well, we need to get up that high to actually help that so I don't know anything about that. I'm not a neurologist. That's where it's at. But I'm just saying that when we look at that dose, no average consumer is going to be able to consume that Much CBD in a single day, unless it comes through this 2 full grams a day is more than most take Yes,yeah. Now here's the problem 94% of the people had side effects. Okay 94% at the highest dose compared to 75% placebo, kind of weird. So there's just a huge placebo side effect profile that doesn't get discussed at all.Did they say what it just had a curiosity do they state with the placebo was for the control,They did not stay with the placebo was oh, I take that back. I don't know what they use, but basically they left people on the same medications. So, essentially, let's just look at this and say okay, but the good news is, most of it was not a big deal. Most of it was what the FDA also discussed beyond the liver tests and beyond the drug metabolism. They also said Oh, CBD can cause nausea. It can cause drowsiness. It can cause all these other kind of nuisance things. That's what they're referring to right here. It's interesting though, that have a side effect profile assigned to a placebo that's that exceeds around the 30% range, because that's generally the throwaway number. Yeah. So we've gone twice away from the throwaway number. And they've had they've had reported side effects, which I'm not trying to over draw conclusions here, but it could at least indicate that side effect profiles assigned to CBD in this study probably weren't solely to CBD, Well, you're dealing with one of the highest risk populations you can get your hands on, when I did clinical research and when we would do a moderate to severe Chron's study. The placebo arm would have tons of side effects because the disease is bad. That's what's going on here also. So most was not a big deal, upper respiratory tract infection, somnolence, decreased appetite, diarrhea, blah, blah, blah, blah, blah. But the one that they focused on is the increase in amino transferase concentrations. This once again was a revised consumer update, they put this out to the public and their statement is increase in liver amino transferase concentrations when I just got done explaining what the liver does. Did I ever say amino transferase concentrations? No. I said liver enzymes. right? frickin talk to the public if you're going to release a consumer paper. yeah, liver enzymes. AST ALT. This is hiding behind scientific garbaly goop. It's like you're doing half science half anyway. But but whatever. So a patient show up and they're like, I need you to check my amino transferase concentrations. I'm like, Whoa, why? They Hand me this, this, this news article. Right? This is what we're trying to address right here. So what they found is that in the higher dose, 20 mgs per kg, there was a rise in some patients in three times the level which is significant, so if your normal is 20. You can be 60 if your normal is 40 it can be 120. When patients come into me and it's three times the level it sounds alarming. Do you know what happens when somebody gets hepatitis A acute infection? It's way more than that thousands of times the level when somebody goes into foaming at failure there AST and ALT will go from 40 to 10,000.AST and ALT have risen for almost everyone who's listened here, way more than three times throughout their lifetime multiple times in acute or in very isolated settings. It happens with illness.So getting back to your highway analogy, which I think is really cool analogy. I'm glad you came up with that. Thank you .Getting back to the highway analogy. 80% of them were taking a drug called valproic it matters Depakote Yeah, that matters. That matters a lot.It's when you take these medications, which is why at the beginning of the show, I said you're more likely don't have to worry about it. But if you're on certain medications, keep it in mind. Now that being said at the lower dose didn't see this stuff. So there is a dose dependent usage of the P450 enzyme you can if I give you one drink, or if I give you a bottle of tequila 512 which in my opinion is really one of the tastiest, most fantastic tequilas you can ever get your hands on. It is delicious. It's delicious. I'm gonna I'm gonna digress right here. Oh my God, Tequila 512... Also sponsored by Tequila 512Tt was really good seriously, ummm in every single person with liver test rose.They went back to normal if they decreased the anticonvulsant or decreased the CBD. So either one it went back to normal. So it wasn't number one, it wasn't permanent liver damage. More than likely correct they were able to  return back to normal. And number two, it was simply A case of an overwhelmed P450 pathway more more than likely.So you want to get really confusing? Not really but we might as well try. I don't want to but here's what's really interesting, then they kind of get a little geeky. So GW presented their their stuff and then they showed that the P450 in this enzymes and they went into will, the CYP to, 2c19 CYP three a four can inhibit the CYP blah, blah, blah. Those are all just cytochromes people. Those are all just cytochromes It's under the umbrella of P 450. That's how complex this is. Yeah,It is nuts how complex. The highest plasma concentration to CBD occurs within two to three hours after exposure to the Epidolex. With medication, so timing of these medications going to play a role, which actually got me down a weird rabbit hole where i started thinking. We haven't done this much analysis on what happens if you take your Ace inhibiter and you take your cholesterol medicine, timing wise PK analysis on different people and everything. Because when they do these pharmacokinetics, they do it to get the FDA approval, they do it on people that are healthy, that they can understand it. Let's put this into context again, if you're listening to this you've ever taken tagamet. Have you ever thought about when you take your tagamet, you probably only take it whenever you're afraid that you're going to have acid problems, right? Cimetidine?Yeah, guess what? It's also known as a high level p 450 inhibitor if it's over consumed. So I guess what I'm saying here is, there's probably way more alarms being driven over something that yes, is handled by the P 450 system, but is far less invasive or it's much it's a much smaller vehicle on this highway than some of the other things that the alarms are not sounding over.And then surprise surprise after I just got done talking about the liver and the genetic variability and all these other things. When they looked at the pharmacokinetics there was tremendous variation. Hmm. Weird. Yeah. Odd, right? So and anybody that's listening to this that is a, a pharmacist or is a scientist or like Well, yeah, duh. Like I know, duh. But why put out such an alarming statement? Yeah. Without context.Yeah, yeah, you're right. So it for Okay, so it's a little bit of clickbait stuff, right. And so maybe even the journalist who wrote it doesn't understand specifically, the implication, they may have only seen P450, written somewhere turned to a health care provider and said, What is this? Well, that's indicating that things are rising up, they freak out. They write a headline that says CBD causes liver failure. I just learned that from this health care provider. So I'm going to write this piece.Well, that we're going to get into that. The liver failure. This is still just the FDA. Oh, yeah. To the consumer. So I hope that the FDA looks at this and says, You know what? That's right. All that stuff that was just being said it's right. But we didn't have the time to do it. We couldn't sit there put that on paper, we'd lose everybody. I get it. It's quite true. We all we all but we all have a responsibility, much like any doctor to try and explain. You and I have this ability to have this forum to reach hundreds of trillions of people.Yeah. It eflects in our subscriptions on YouTube. They so many trillions of people subscribed, they started his back over to about 200. Yeah, so every time we got trillions, they start back over. Yeah. So So anyways, so what what you're realizing here is exactly what we're talking about. When you put stress on the liver. The liver honks its horn and does a little rise and the lfts goes, Well, hey, guys, maybe not so much. Can we just back off the traffic a little bit and see what's happening here. So additional studies have shown that levels of the anticonvulsant drugs actually caused the daily effects. So now we start wondering that the that the CBD may actually rise some of the anticonvulsants and then you have more side effects from that comes down to the same thing we're talking about how many things do you want to tax your liver, that's the bottom line. To summarize high dose of a pure CBD isolate, not full spectrum, while using a mean of three other anticonvulsants can cause temporary rise in liver tests and affect the metabolism slightly of the anticonvulsant. Of note, it did not happen at lower doses. So one more time, if you are on an anticonvulsant discuss with your doctor and make sure that you stay well below the 2000 milligrams a day. Yep. So this whole thing of Oh We're going to block the P 450 the P450 is So frickin complex, it is nuts. So anything you want to add to that, because I'm going to move on to the thing that I really want to, like kind of make fun of No, not really, I just want to say that I think that the FDA, unfortunately, is a very important and serious organization within our government. And I think that for all of the flack that they take their, unfortunately, with any other entity, there are limitations on what it is that they can do. And I do believe that they try their best to fairly ascertain and address situations as they are presented to them. Regardless of how frustrated that one of this may get is we don't get a result from them. A lot of it is just simply because there's not enough manpower. Oh, absolutely. They get thrown everything think about, think if you're in an organization where you know that 70% of the crap that's out there needs to be pulled off the shelves and you're limited. It's a government organization. These people making these statements are MD's. I'm really limited fortunately, I have well, we have the show where I kind of enjoy looking up some of this stuff. Fortunately, we have some friends of ours that are that work in the nutrition industry that are fantastic at researching articles. And some of that gets gets brought to me I want to make sure that we all get better this is the whole purpose of this.Hundred percent.I want to help the FDA and help GW I want to help the CBD industry. I want to help all of it. But let's just talk about this because something super weird happened. And this is the one that got the most press A Forbes article came out that promoted a mouse study and made the sensational claim that CBD causes liver failure.Yeah, that's kind of what I was referencing earlier. I may steal the thunder but yeah, you're right.Yeah, so this is you're exactly right. In the intro, you said it was clickbait. I really after looking at this study after pulling the study, because how many people read that article are actually going to pull the study.Well is the is the person who wrote this study that well versed in reading studies like that. I mean, that's that's an important thing. I mean, they I think that probably even the author of the article feels like that they are doing a service to the reader, but probably doesn't understand. And if they do, then shame on them, but if they don't, I think that would be a better explanation doesn't fully understand how to read the study and the quality and the qualifications of that study to make a statement like that.Yeah. And you know, this, this could be an arguable point, I'm sure that the person that that wrote this feels very strongly that what they said was right, the bottom line is the goal of this study was to investigate CBD cannabidiol hepatic toxicity, meaning liver issues in an eight week old male mouse. So they they took a group of eight week old male mice, and then they gave them a CBD that they produced. The CBD that they produced and Will Clyden will just jump up and down when he hears this because he decided Is this on Chris Cresser's podcast. The CBD that they produced was used to extract using hexane, which is a molecule that is known to be hepatotoxic. Yeah, you're not supposed to have heaxane. Don't do that! Will Clyden talked about the fact that if you find a CBD with an outrageously high amount of of CB, if you find a full spectrum CBD with an outrageously high amount of CBD more so and the price ranges, okay? Because what they did is they extracted that with hexane in a cheap way and threw it in their bottle and said, there you go. Now you can check that's got 10,000 milligrams of CBD or whatever. And it's really interesting because there's so much going on in the industry like this. So this particular study out of the University of Arkansas, took the CBD, or they made their own CBD using hexane which is a hepatotoxic in itself and in their certificate of analysis. It was there and then they gave it to these mice. Second thing neatI don't even know there has to be a second but we can hear it. Because I mean seriously, that's, that's like saying, I know your stomach hurts. You should take this Pepto bismol. And then I don't tell you that I've broken up some glass shards and have you drink it and you're like i'm bleeding now! What's going on? I'm like, I don't know. Yeah, but you only paid half the price.I made it myself.Which, by the way, that last batch of propophol that you did in your bathtub is working phenomenally. I'm sure it is. Now we do not make propophol in our bathtubs.Alright, so the second issue. If we have any mice that are subscribers to our show, or listening, I would like you to have your children removed from the room at this moment. Because they took these poor mice, and they gavaged to them. Would you mind defining what gavaged is? I think it's when you kind of force feed somebody I don't think it's willing. That's your I think gavaged something you kind of threw one at me there I think to gavaged someone you basically introduce a funnel to the esophagus and well you kind of get after it, don't you? Yes, I'm currently gavaging my mic right now trying to figure it out. I just undid everything. You're gavaging our ears with your, your microphone adjustments?All right, so gavage is they forcibly give these mice?The CBD extract? Yeah, I don't think it's comfortable nor pleasant.No typically through a tube feeding or down the throat to the stomach is how they generally gavage things. A quick side note, now because I'm now all of a sudden I feel like I'm living in a glass house when I was an undergraduate student. I actually did my first surgery on a rat and we took out their adrenal glands. And I'm just saying that so I don't want to sit there and pretend like I'm not done mean things to an animal. But that was when I knew immediately I could not be a bench researcher. I did not like that. At all, now I was like, I need to, I want to heal. I want to heal. I don't want to hurt these animals, but it's it's a whole separate discussion. So anyways, so they gavage these animals with different doses, and it's really interesting. Now in what they call their defense, they call it allometric dosing, which means they're trying to get the body weight to human weight ratio appropriate. I've read some rebuttals of this article where it is a joke, you just can't do that. And when I read vitamin weed Michelle Ross? Michelle Ross, when I read vitamin weed she dis... she specifically discusses why research on CBD versus mice is very difficult to do because the weight basing the endocannabinoid system is different, all these other things. So allometric dosing being said, assuming that they're saying it's right, so the dose would be the equivalent of what they gave and What a human would give So I'm doing the allometric dosing, which I think is actually higher than what it actually is separate thing. They took mice and they gavaged them with zero milligrams of hexane derived CBD 246 milligrams per kilogram 738 milligrams per kilogram or 2460 milligrams per kilogram of dirty CBD. It doesn't make sense dirty CBD isolate. So for instance, in a horrible alternate universe where humans are now the test subjects and we have large mice which are running tests on us, and they decided to gavage me with the same thing. That would be the equivalent at the highest dose of 241,080 milligrams of hexane derived CBD isolate. I'm not even sure what the hexane would do it 240,000 milligrams 242,000 milligrams.No I mean that being the more or less than now at this point, it's just an additive. It's just I mean it's it's not an excipient It's a straight up additive. That would not make sense at all. Oh, it's crazy.It's poison.This article came out in Forbes and said CBD causes hepatotoxicity. Also hexane causes hepatotoxicity.It is nuts. Alright, spoiler alert. The mice suffered hepatic toxicity and death at the highest dose. Shocking... You know what? I also hear it's bad to have breakfast cereal with not milk but drain-o. Just something that I'm gonna go out on a whim. Don't think you're supposed to do that. It just doesn't make sense. It's It's It's not. That is not an apples to apples comparison if you're talking Okay, so we talked about it earlier. reputable CBD source there is no reputable CBD producer that's going to have and Will special shout out to you it's going to have hexane as a byproduct or an excipient in their full spectrum COA approved which is also why KBMD Health with powered by olyxenol hundred percent is does not have that. I mean they do co2 extraction, which is the important thing which is a reason why we partnered with them to make that product. So we are the one out of the 23 or 24 that is the safe and trusted COA back no hexane etc etc. Doing this study is not an apples to apples comparison on what would happen because who knows? Who Okay, I don't get it because GW we already did that study. They determined that 20 Meg's per kg which is still a shit ton. It's a lot. It's a lot. Yeahis the safe maximum dose. These guys went times it by 100.Yeah, they did.And see what happens? Yeah, it's it's a bad it's a bad comparison. I mean, yeah, honestly, if you wanted to find out if CBD plus hexane causes liver toxicity at a ridiculous amount, top to bottom, then that's a great study outside of that, since nobody does it, I would say it's a bad study. Speaking of road, that's a road to nowhere.Yeah. And so study like this, uh, like you had mentioned is essentially it's not science. It's clickbait. Yeah. And right now that that author, that journalist is just kind of laughing. He's like, I know, and now you're bringing it up, and I'm going to get another whatever, because that's what people are trying to do. They're trying to get attention at this point.So at that point, good for you, you got to click but I would be truly interested if possibly that particular journalists would say, you know what, I didn't fully understand it. I mean, that's okay. Let's look reading studies, right? There's there's a study to reading studies. I mean, we heard that we heard the breakdown that kresser did on Joe Rogan is he Twice had to address his approach to completely different topic about the the plant based diet and then how he had to re approach that with the rebuttal. All that just simply to say, there is a science to reading studies and being really good at understanding what is and is not applicable and then how to find studies that you can compare to each other for good meta analyses. So what we're doing right now is I'm telling you that maybe sometimes there aren't studies, but my anecdotal evidence, I have a busy practice, you hear the patients, we hear them talk I listen to them, when they say that doesn't work. I go, Okay, I'm not publishing it. I don't have time to do that. I wish I did. If I published everything that we're gathering data on, if we're looking at, you know, just so many different things, CBD is just one of them. We've got I love I'm a huge fan of brain.FM for the ability to use sound to change your mood. I Would love to they're unpublished, a lot of studies on stuff like that. There's, there's tons of stuff. So when people go, oh, the studies aren't out there, there is something to be said about the Socratic method, or I'm sorry, the paternalistic method, the way that medicine used to be where the guy in front of you that saw thousands of patients, this is the method that he has. You see me scope, I mean, there's a difference in scope techniques.So they, although some may even still say it qualifies as anecdotal, I will say that there's objective data in both in a scope, somebody can't just come, anybody can come to you say I feel better. Anybody can even if they don't mean it. But they can't make the disease disappear from the imaging that we see in their colonoscopy, or the the mucosal samples that you take. And that's something that's completely objective data. That we see. So those are the everyday results that we see from these types of applications where you just, look it's not made up whenever we okay full pleasure when we first started looking at CBD, I thought was bullshit. Who you looking at?Just anybody who's out there. But when we first started talking about it, I didn't believe it. I was like, man, let's see, because we've been down this road before but we tried new, new without throwing a bunch of things under the bus. We tried new or innovative different things and high hopes. And unfortunately, low expectations and the expectations get met and the hopes are never never realized. The opposite for me personally occurred with CBD over the last three and a half years. And that is it actually stinking works.Dude, I knew that we were onto something with Atrantil, because after we did the initial studies,  everybody came back and said, I want more. I knew that I was onto something or I was not on something. I knew that CBD had a viable place in my practice, because I bought and the story goes all the way back which is why we work with which is why it's powered by elyxenol right now, when we went to paleo FX, and I ordered a couple cases and I just gave them away to patients. That was not cheap. Not because I was sitting there trying to be altruistic, not because I was doing charity. I'm like, I don't know. I didn't. And I told everybody, I don't have a clue. I haven't even looked at this yet. All I know is try this. Tell me what happens. And when about 80% of them came back said I want more. And I went, Okay, we're onto something. And that's when I took my clothes off the deep dive into the science and went, holy cow. Yeah,this is crazyUp until that point, I just didn't know there was a whole lot to it. I mean, it really didn't. And then the fact is, oh, and to clarify, it's not like Brown just handed out CBD to just anybody who came to the clinic. You literally just like we did with Atrantil you found very diseased patients to say and who had gone through a gamut of different pharmaceuticals and weren't finding relief, and suddenly they're like, this is working for me. Tell me more about it. And I was, I was blown away.So let's talk a little bit. So we're I'm over here going well studies I haven't published and everything. Let's talk about a few studies. So I've got a Mendeley account, I know how to look at PubMed. I know how to get a Google Scholar, I just want to talk about a couple studies have come out recently. And let's kind of compare it and see if it still makes people concerned that they're going to die of liver failure.Sure. Alright. So in the Journal of Clinical Pharmacology published in 2019, the this was actually a study, also sponsored by GW Pharmaceuticals, as part of the process of getting the FDA approval that the FDA did not reference the best I can tell they did not reference this. This is way more complex and it gets super cool, because what they're looking at is the pharmacokinetics or how CBD is actually metabolized by that beautiful genius called a liver. In high doses in people with liver disease. Yeah, they went through the trouble to take high doses of CBD and give it to people People that did not have liver disease had mild liver disease moderate and severe. This was ballsy to say the least, because using a product like this in somebody with liver disease is is risky. This thing could backfire and it could shut down the whole process. Here's what's nuts, the pharmacologic and safety of a single oral dose of 200 milligrams of epidolex, which is the CBD isolate. They were assessed in subjects they had eight people with moderate or with mild disease, six people with moderate and eight people with severe and then they had this collection of normal people. Blood samples were collected to check for the pharmacokinetics This is how drugs are looked at. They give you a drug and then they check your levels. Basically, the blood concentration was higher in the hepatic impairment and they describe it in nanograms. So the nanogram comparison is that it's a little bit higher in those with severe hepatic impairment. But this is what's nuts there was no increase in adverse reactions. There was no change in blood levels. So basically, the only adverse reaction that they found was a little bit of diarrhea. And it all happened in the mild hepatic impairment. So the FDA had mentioned Oh, studies have shown that it causes diarrhea. What was really funny about

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiP Trinity solve the case of the Peace Corps volunteer with diarrhea, and reveal how immunizing against a virus ameliorates exacerbated leishmaniasis. Become a patron of TWiP. Links for this episode: Viral vaccine prevents exacerbated leishmaniasis (PLoS NTD) For whom the trich tolls (TWiP 47) A virus in a parasite in a human (virology blog) Virologists in the mist (TWiV 128) Letters read on TWiP 126 This episode is brought to you by Blue Apron. Blue Apron is the #1 fresh ingredient and recipe delivery service in the country. See what’s on the menu this week and get your first 3 meals free - WITH FREE SHIPPING - by going to blueapron.com/twip. Case Study for TWiP 126 Another Peace Corps volunteer in Fiji. 24 yo male, several days of fever, headache, dry cough, rash. Feels poorly, starts diarrhea. No blood or mucus, no vomiting but abdominal discomfort. Heart rate over 100. At private nearby hospital for evaluation: no prior med probs or surgeries. Social history: MSM, not always protected, drinks every weekend. Home blown away by cyclone. Alcohol: drinks beer, a lot. White rice, split peas, bread diet. Fan of cava, also drank unfiltered water. He is admitted, continues to feel poorly. Continued fevers, localized abdominal pain RUQ. On exam he has tender palpable liver, elevated WBC 17.8, eosinopenia, 0 cells. AST/ALT slightly above normal. Dengue, chick, lepto, blood all negative. Ultrasound of liver: shows 8x8 cm mixed echogenic lesion in right lobe. HIV negative.  Send your case diagnosis, questions and comments to twip@microbe.tv

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The case of the Man from Assam is solved, and phagocytosis of Leishmania by B-1 cells is brought to you by the Three Twipeteers on this episode of TWiP.   Subscribe to TWiP (free) in iTunes, Google Play Music, by the RSS feed or by email Links for this episode: Kalazar detect (pdf) Phagocytosis of Leishmania promastigotes by B-1 cells (Parasite Immunol) Image credit Letters read on TWiP 108 This episode is sponsored by ASM Agar Art Contest and ASM Microbe 2016 Case study for TWiP 108 Todays case is a 26 yo male longhaul truck driver from northern tiger country of India. Comes into hospital at end of rainy season with 6 days of fever, chills, muscle aches, small loose stools, vomiting, trouble breathing, cough, decreased urine output. Lives in mud hut with coconut leaf roof. No one else in family  is sick (wife, two children). Significant animal and insect exposure (dogs, cows, monkeys). Got sick after coming home from a trip up north. No significant medical probs, no surgery. Really sick. Pain everywhere. Occasionally drinks palm wine. Some yellowing of eyes. Has lost a little weight. Ketonic breath. Exam: 39 fever, bp 100/71, 126 heart rate, 24 resp rate. Looks distressed, not fully sharp. Nothing focal on lung exam. Belly tender, esp upper right, spleen enlarged. Liver is tender but not enlarged. Some labs: bun elevated 102, creatinine elevated, Hg decreased 11, platelets 9000 (down), white count 10.3 no eosinophils. LDH 8000 AST/ALT normal, bilirubin 21. Never been this sick. Send your diagnosis to twip@microbe.tv Send your questions and comments to twip@microbe.tv