By Gabriella Wan

CBD, or cannabidiol, is a non-psychoactive component of the cannabis plant with anti-inflammatory properties.[1]  To ensure avoidance of psychoactive effects, CBD must be extracted from hemp, not traditional marijuana.[2] In recent years, CBD has become a popular supplement. CBD works in the body through the endocannabinoid system, which is highly upregulated during chronic liver disease, affecting multiple steps along the disease’s progression.[3]

Some research has been done concerning the interactions between CBD and liver disease, with mixed but promising results. The first thing to understand about CBD is that there are two important related receptors in our bodies, called CB1 and CB2. As noted in a 2008 study, cannabinoid receptors (CB1 and CB2) and their binding molecules (endocannabinoids) have emerged as novel mediators of liver diseases. While activation of CB1 receptors can contribute to NAFLD and fibrosis, activation of CB2 receptors have been characterized as antifibrogenic and regulators of inflammation.[4] With this understanding, it makes sense that inhibiting CB1 receptors has been shown to inhibit the progression of fibrosis, while activating CB2 receptors has been shown to inhibit growth and cause cell death for cultured liver fibrogenic cells. Because CB1 and CB2 receptors exert opposite effects on liver fibrosis, evaluating the net impact of using endocannabinoid signaling on liver fibrosis in a clinical setting is complicated and far from clear cut.[5]

“EC receptors expression and functions in the liver. Cannabinoid receptors CB1 and CB2 are expressed in all liver cell types at different basal levels. Both receptors are upregulated during chronic liver damage and mediate opposite functions: CB1 promotes and CB2 protects from liver damage. The experimental and clinical evidences indicate CB1 as a stronger player, contributor and an attractive target in the development of CLD. Abbreviations: ALD, alcoholic liver disease; HCC, hepatocellular carcinoma; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; TG, triglyceride; VLDL, very low density lipoprotein.”[6]

In animal tests, the relationship between CB1 receptors and fatty liver (both diet-induced and obesity-associated) has been made clear. Research has shown that high-fat diets induce fatty liver via activation of CB1 receptors, which are necessary for the development of diet-induced steatosis, dyslipidemia, and insulin resistance.[7] Studies with obese rats have shown that the administration of CB1 inhibitors reduced obesity-associated hepatic steatosis and certain features of metabolic syndrome.[8] The drug Rimonabant was the first selective CB1 inhibitor used in clinical practice after clinical trials showed its benefit on weight reduction, abdominal obesity, liver steatosis, and other cardiometabolic syndromes.[9] Though this may seem like good news, it is important to note the increased appearance of psychiatric disorders including depression, anxiety, irritability, and aggression.[10] Consequently, the FDA never approved Rimonabant for the treatment of obesity.

While we have lots of research on CB1 receptors and fatty liver, investigations regarding the role of CB2 receptors in this disease area are minimal. In human studies, liver samples from patients with steatosis and steatohepatitis have expressed CB2 receptors, while liver samples from normal livers showed no CB2 receptor expression.[11] In fibrogenesis, CB2 activation has exhibited some evidence of an anti-fibrogenic role.[12] In rats, studies have shown that activating CB2 receptors in the liver significantly reduced collagen content in rats with pre-existing cirrhosis and improved regenerative response to acute liver injury.[13] It is important to note that other studies have shown conflicting results regarding CB2 and NAFLD.[14]

While you should always consult with your doctor before starting to use any supplement, CBD has some special considerations. If you decide to take it even though the jury is still out on the effects of CB1 and CBD on NAFLD, please be cautious of the following things:

• Dosage
  • The amount of CBD recommended for therapeutic use in humans ranges from 0.5mg/kg/day to 20mg/kg/day.[15]
  • FDA hasn’t created any measures to regulate CBD products, so potency labels can be inaccurate.
• Quality
  • FDA hasn’t created any measures to regulate CBD products, so they may be contaminated or misrepresented.
  • To find safe and reputable products, make sure the company has third-party lab testing, good reviews, and transparency for its products (including sourcing, extraction methods, packaging, and return policies).
• Interactions with other medications being processed by CYP450 family of liver enzymes
  • Many conventional doctors do not know much about CBD since it’s not taught in medical school, so it may be best to ask them if any of the drugs you’re taking are affected by eating grapefruits, since grapefruit also affects the same liver functionality.[16]

Gabriella Wan is a Program Coordinator at the Fatty Liver Foundation with a background in public health. She is passionate about improving quality of life through lifestyle change, awareness raising, and education.

Sources

[1] Avraham, Y, et al, Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice, British Journal of Pharmacology, April 2011, doi: 10.1111/j.1476-5381.2010.01179.x

[2] Tesséra Naturals, Does CBD cause liver damage?, CBD Education, August 2020, https://tesseranaturals.com/does-cbd-cause-liver-damage/

[3] Mallat, A and Lotersztajn, S, Endocannabinoids and liver disease. I. Endocannabinoids and their receptors in the liver, American Journal of Gastrointestinal Liver Physiology, January 2008, doi: 10.1152/ajpgi.00467.2007

[4] Mallat, A and Lotersztajn, S.

[5] Mallat, A and Lotersztajn, S.

[6] Patsenker, E and Stickel, F, Cannabinoids in liver diseases, Clinical Liver Disease, February 2016, doi: 10.1002/cld.527

[7] Osei-Hyiaman, D, et al, Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice, Journal of Clinical Investigation, September 2008, doi: 10.1172/JCI34827

[8] Gary-Bobo, M, et al, Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats, Hepatology, July 2007, doi: 10.1002/hep.21641

[9] Christopoulou, FD and Kiortsis DN, An overview of the metabolic effects of rimonabant in randomized controlled trials: Potential for other cannabinoid 1 receptor blockers in obesity, Journal of Clinical Pharmacy and Therapeutics, February 2011, doi: 10.1111/j.1365-2710.2010.01164.x

[10] Christopoulou, FD and Kiortsis DN

[11] Mendez-Sanchez, N, et al, Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease, Liver International, March 2007, doi: 10.1111/j.1478-3231.2006.01401.x

[12] Julien, B, et al, Antifibrogenic role of the cannabinoid receptor CB2 in the liver, Gastroenterology, March 2005, doi: 10.1053/j.gastro.2004.12.050

[13] Muñoz-Luque, J, et al, Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats, Journal of Pharmacology and Experimental Therapeutics, November 2007, doi: 10.1124/jpet.107.131896

[14] Dibba, P, et al, Mechanistic Potential and Therapeutic Implications of Cannabinoids in Non Alchoholic Fatty Liver Disease, Medicines, May 2018, doi: 10.3390/medicines5020047

[15] Curley, Christopher, Worried About CBD Hurting Your Liver? Here’s What the Experts Have to Say, healthline.com Health News, August 2019, https://www.healthline.com/health-news/can-cbd-hurt-your-liver-what-to-know-about-a-new-study?c=672391731507

[16] Tesséra Naturals.

Intercept and the associated logos are trademarks of Intercept Pharmaceuticals, Inc.

We’re excited to be joining with Intercept for the TRUTH About NASH roundtable discussion in Washington, DC. We’ve assembled a dynamic group of people who all touch this disease in diverse ways, and look forward to a robust conversation encompassing varying viewpoints. As NASH progresses to becoming the leading indication for liver transplants in the U.S., we believe cross-stakeholder discussions like this are imperative – not only to help identify barriers to care and gaps in knowledge, but also to begin to pave the road to potential solutions for this community. 

We will be reviewing the findings from a new survey that takes a 360º look at NASH from the perspectives of healthcare professionals, diagnosed patients, and the American public. We believe the survey will provide great stimuli for a discussion of some of the challenges facing people living with NASH.

This effort is part of our program to expand the discussion of liver disease and seek better solutions for patients and those who are asymptomatic but at risk.

THE PROBLEM: The real liver experts don’t offer effective diet advice

(click here for a pdf with all the science references)

Currently, the experts who treat liver disease, (the specialists of AASLD), do not officially recommend any specific diet for liver health. The reason is because there are not enough well-designed dietary clinical trials focused specifically on the liver to give the organ experts confidence to make official dietary recommendations. This creates a serious dilemma. As patients we don’t have that luxury. We must make choices. We must live every day making food decisions and hope that our diet is a healthy one even if the experts can’t help us. No wonder we see endless variety in dietary advice and “experts” of all persuasions.

OUR GOAL: Design a diet strategy that minimizes the liver workload

THE PROBLEM: The liver experts don’t offer effective diet advice

(click here for a pdf with all the science references)

(click here for a one-page guide to the Liver Friendly Diet)

Currently, the experts who treat liver disease (AASLD), recommend no specific diet for liver health. There are not enough well-designed clinical trials focused specifically on the liver to give the organ experts confidence to make official dietary recommendations. This creates a serious dilemma. As patients we don’t have that luxury. We must make choices. We must live every day making food decisions and hope that our diet is a healthy one even if the experts can’t help us. No wonder we see endless variety in dietary advice and “experts” of all persuasions.

THE GOAL: Design a diet strategy that minimizes the liver workload

The Fatty Liver Foundation recommends a diet high in oleic acid (omega 9) unsaturated fat (30%), primarily from extra virgin oil, low in saturated and trans fats (7%), with a omega 3 and 6 fatty acids approximately equal (8% each). Protein is about 20% of calories and carbohydrates are primarily in the form of fruits, non-starchy vegetables, and whole grains (27%). Simple carbs, such as sugars and refined grains, are minimized. The goal for salt intake is about 70% of the USDA recommendation. Processed foods and red and processed meats are avoided. (see this pdf for the research supporting this strategy)

Nonalcoholic fatty liver disease (NAFLD) affects approximately one third of adults in the United States and is the most common cause of chronic liver disease worldwide. About 20% of patients develop the more serious steatohepatitis (NASH) which is becoming epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of greater than 10% of body weight is beneficial in resolving steatosis and reversing fibrosis due to NASH.

The liver disease specialists don’t have enough proof that they are willing to endorse a specific diet, so keep that in mind as you listen to the sales pitches. There are thousands of claims about food. Here we are trying to give you the most complete picture that we can, but just remember, if someone is selling you something, they have an agenda and real evidence is hard to get.

As patients where do we look for dietary guidance?

We understand the challenge for science to provide specific and verifiable data, but as patients we still have to live each day and we make decisions about our diet by making use of whatever information is available to us. We also must live within the cultural and food availability situations that we find ourselves. 

It is very difficult to do effective random, blinded, controlled trials (RCTs) of the diets of humans. There are myriad ethical and cultural concerns with human experimentation and the human diet is vastly complex within different cultures and practices. In our role as the voice of the patient, we believe that a position of offering very limited guidance is inadequate so we are providing this information as a patient resource for those who seek to understand the components of diet and available research which we believe offers a coherent view from which to make decisions about diet. The goal of our lifestyle strategy is not to diet but to adopt habits that are fundamentally healthy long term and probably contribute to a healthier liver and a better life.

Making the best choices we can with the information we have

A lifestyle that is fundamentally healthy is built on a vast series of small choices made each day over a lifetime. It is a pattern of behavior based upon choices which are, on average, neutral to healthy while minimizing ingesting things that compromise function.  There is no one size fits all solution. Human metabolism is quite robust and is able to accept a wide range of inputs and to use them to sustain bodily functions.

In our role as a supporter of people concerned about liver health, our goal is to support a lifestyle which minimizes the work that the liver must do to sustain our lives. Conceptually, when any of the parallel processes taking place within a liver cell is either oversupplied with or denied those dietary elements that it needs to maintain a stable response we have failed in that goal.  In making decisions about food, the goal is stability of function, stability of supply, and minimizing toxins. A sick liver benefits from a strategy of making it do as little work as possible.

Talk to your doctor

All patients should discuss dietary strategies with their doctor. This information cannot substitute for guidance by your physician. This material provides research-based information that will help you better understand your doctor’s advice but cannot be relied upon for personal health decisions.  Information is critical to help plan and implement a strategy to adopt lifestyle change but there is no single solution to decisions about diet and this information is therefore incomplete and may well be proven to be incorrect as research is performed in the future. This discussion provides information from a health perspective broadly which can inform choices about what constitutes a liver supportive diet.  A broader benefit is that this approach provides a holistic regimen which benefits many co-morbid conditions such as diabetes and cardiovascular health as well.  In many ways, what is good for the liver is beneficial for the body as a whole.

It is important to remember that your doctor may have little nutrition education.  We rely on them, but many are unprepared to really help us with diet decisions. Current medical education does not provide much focus on the issues of diet. This paper contains references to research which we have relied upon in developing it so you may be able to use it to engage your physician in the science argument about various aspects of diets. The material presented is not exhaustive or necessarily authoritative but is a coherent way to approach the lifestyle challenge.

As I write this I see the covid numbers are rising again. I hear people in denial, it could never happen to them. Today I have something equally life threatening to write about. It is not about Covid. It’s about ANOTHER little recognized epidemic. I lived it. I will be very happy if this resonates with just one person.

Here’s my story.

Christmas Eve 2013, I was feeling pretty proud of myself. I was on my way to a healthier life. Earlier in the year I joined my local YMCA. I exercised 6 days a week. I was eating healthy and watching calories. All in an effort to lose weight. I had been overweight since I was a child. Smaller clothes was just a small part of why after 30 years I was losing weight. Feeling good was a great reason but what gave me real motivation was the fact I wanted to be a living kidney donor for a family member. I had lost 96 pounds in 7 months. Then I woke up with what I thought was the flu. By evening I thought I was doing better. When I got sick and vomited up a huge amount of red blood. I found myself in my local ER where I was literally bleeding to death with no clue why. I was taken to the back where I was still very much awake and scared to death.

Welcome to the Fatty Liver Foundation's Webinar Hub!

Here you can find all of the info about our upcoming webinars, as well as the details and links to recordings of previous webinars.

NEXT WEBINAR: Wednesday February 3, 2021

Wellness Webinar Part 1 (COVID-19 and Liver Disease) click here to register!

In 2020 we produced the LIVER (Live Interactive Virtual Education and Review) Webinar Series, consisting of four parts.

In 2021 we are producing the Wellness Webinar Series, consisting of six parts.

This is what you will find here:

• Non-technical explanation of how your body actually works
• How the liver develops disease over time
• Why fats are a critical source of fuel for your cells
• How the liver manages triglycerides
• How the course of fatty liver disease depends on triglycerides and carbohydrates
• How the kind of dietary fat you use matters
• Information by a liver patient for liver patients
• Information about diet based upon bio-chemistry not fads

We are a nonprofit foundation and we do not represent anyone but the patient. If you are looking for advice on supplements or quick fixes this is not the place for you. We offer extensive information about the body in general, the liver specifically, and we recommend lifestyle strategies that have worked for me specifically and which I believe are valuable for anyone concerned about liver health to be familiar with.

What You Should Know (CDC) 

CDC Interim Clinical Guidance for Management of Patients with Confirmed Covid-19

Why outbreaks like coronavirus spread exponentially, and how to “flatten the curve” (Washington Post) 

Coronavirus Live Updates (NYTimes)

Coronavirus: Why You Must Act Now (Medium)

COVID Tech Handbook: Resources for Doctors (Crowdsourced)

COVID-19 Maps & visuals (CIDRAP) 

COVID-19 Disease Resources (WHO) 

COVID-19 diagnosis and treatment (JAMA)

How to get a COVID-19 Vaccine: a State by State Guide (WSJ)

Helping with Seniors' mental health

Tracking Every Coronavirus Case in the U.S.: Full Map (NYTimes)

A detailed guide to the coronavirus drugs and vaccines in development (STAT)

Identifying Communities at Risk of COVID-19 (XY.AI)

Center for Infectious Disease Research and Policy

Centers for Disease Control and Prevention

Johns Hopkins

World Health Organization

-CDC Interim Clinical Guidance for Management of Patients with Confirmed Covid-19

-UCSF COVID-19 Clinical Resources

-CDC Information for Healthcare Providers

-New England Journal Of Medicine, COVID Resources

-Lancet- COVID-19 Response Center

-JAMA Updates on COVID Diagnosis and Treatment

-Detailed Notes from an ICU Doctor in Seattle on COVID Experience

-Up to Date: COVID-19 Testing Capacity

-Dispatch #3: Dr. Shlain reporting from the front lines

-Coronavirus: Why You Must Act Now (Politicians, Community Leaders and Business Leaders: What Should You Do and When?)

-More COVID-19 Resources here (including patient facing ChatBots and more).