Inflammation and the Liver

Non-alcoholic fatty liver disease (NAFLD) is nothing short of an epidemic in the U.S. and other modern, industrialized countries. If you read my link on Insulin Resistance and the Liver, you’ll see that NAFLD is very tied to insulin resistance and Metabolic Syndrome, so it is no wonder. Again, it is not unreasonable to assume about half of the men reading this page have NAFLD and that this is a very serious threat to not only their sex life but their life in general. The moral of the story: you can’t ignore your liver!

Yes, the liver is important and, as you probably remember from your high school biology, is that the liver performs many critical functions: detoxification, processing medications, building proteins – the list could go on and on. And here is why you absolutely MUST take fatty liver disease very seriously:

1. NASH. Non-alcoholic steatohepatitis (NASH) is the ugly end point for some men who develop NAFLD. All men with NAFLD have steatosis, which simply means fatty acids accumulating in the liver cells. However, in some men this turns very ugly and you end up with steatohepatitis, or a form of liver disease that mimics classic hepatitis. NASH is basically a condition that includes an inflamed liver with classic cirrhosis that is often debilitating and in some cases life-threatening. [10] Scientists have noted that there is little difference between the damaged liver that results from non-alcoholic fatty liver disease versus alcoholic fatty liver disease – it’s all bad news.

2. Cardiovascular Risk Factors. NAFLD has become one of the many new risk factors for heart disease. In other words, if you develop this type of liver disease, you are at increased risk for cardiovascular events and even death. So one should treat NAFLD as erectile dysfunction, which also is a new predictor of impending heart problems.

3. Type II Diabetes. A fatty liver also increases your risk for type 2 diabetes. (The two conditions are highly interrelated.)

NAFLD appears to be such a powerful predictor that one recent study out of Japan found that it even foretold heart disease strongly than Metabolic Syndrome. Furthermore, it was found to be an independent risk factor for cardiovascular disease independent of all others.[3] Researchers have noted that it is no wonder since “the liver, once fatty, overproduces most of the known cardiovascular risk factors such as very low density lipoprotein (VLDL), glucose, C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), fibrinogen and coagulation factors.” [8]

All of that said, what makes this type of liver disease so problematic is that it appears benign to the men diagnosed with it. In fact, many men have it and do not even know it. NAFLD is definitely not an immediate death warrant and the great majority of men with this type of liver disease – 90% and above – do not even have symptoms. It is somewhat like most prostate cancers: it exists for years often before it rears its ugly head.

The Role of Inflammation

Researchers now believe that the reason that the liver begins to store fats (triglycerides) is primarily protective. In other words, the fats stored in liver cells are “more a marker rather than a cause of insulin resistance.” [4] So what is the liver trying to protect itself from? You guessed it: inflammation (and oxidation).

When one overconsumes calories or has an increased oxidative (free radical) load due to being overweight, the liver begins to accumulate these to protect itself from toxic triglyceride byproducts. Evidence is mounting in animal studies that endotoxins, which result from out-of-whack intestinal bacteria and dysfunctional TLRs (toll-like receptors), which result from being overweight, increase systemic inflammation and lead to NAFLD. [4] Several studies have also shown that adiponectin, a key inflammatory cytokine, regulates liver fat. [5][6] As you put on weight, your body lowers adiponectin levels and your liver fat increases – it’s that simple. Furthermore, adiponectin is strongly (and inversely) correlated to body fat. [7] And our old archenemies TNF alpha and IL-6 also have been found in animal studies to directly cause liver inflammation, which can accelerate the nasty liver-destroying cirrhosis called NASH mentioned above. [9]

The bottom line is that almost every major inflammatory cytokine involved in disease and cancer plays an active role in the initiation and progression of non-alcoholic fatty liver disease as well. And these cytokines all become misaligned through growing body fat. That has lead researchers to observe that your fat (adipose) tissue literally attacks your liver. Your liver is ground zero when it comes to the battle for your health.

When you put on enough weight, you are literally pitting one organ against the other and creating a sort of internal war on yourself: the fat tissue makes war on the liver, which in turn assails both the heart and penis.

So what will your physician do if you are diagnosed with non-alcoholic fatty liver disease? You and your physician need to agree on a course of action andt there are several common elements in current treatment. [1]

1. Treat any underlying diabetes, insulin resistance or Metabolic Syndrome. This can involve pharmeutical solutions in some cases. Metformin and thiazolidinediones, insulin sensitizing drugs, have been popular in studies and done quite well. [2]

2. Improve insulin sensitivity by encouraging exercise and weight loss.

NOTE: A higher fat diet will also actually induce insulin resistance and so care must be taken. Although consuming a diet higher than about 40% fat is probably not that common, care should be taken.

3. Protect the liver through antioxidants and other supplements and agents.

Obviously, this is not where you want to be in the sense that you want to stay off of pharmaceuticals if at all possible. Phamaceuticals always have side effects and long term unintended consequences. It is always better to let the body heal itself if one can and go about things naturally.

Here are some ideas to keep your liver fat free:

1. Insulin Resistance. Read my link on Insulin Resistance and the Liver and battle the underlying insulin resistance at the same time that you battle the underlying inflammation.

2. Dietary Fat. Be very careful with dietary fat levels. Remember that high fat diets are used in laboratory animals to induce insulin resistance and high fat diets will often increase inflammation as well. Fat is also very calorically dense and can lead to weight gain, leading to a viscious cycle of increasing inflammation and insulin resistance. (By the way, this is yet another reason that many of the Atkins, Paleo and Low Carb diets can get you into trouble quickly. They seem like a good idea but can be very hard on the heart and liver.)

3. Weight Loss and a Low Fat Diet. A whole foods Low Fat Diet can decrease control and even decrease liver fat content. One study noted that “liver fat content can be decreased by weight loss and by a low as compared to a high fat diet.” [8]

4. Fructose. Watch your fructose! It is known for both increasing insulin resistance and inflammation. Read my links on

5. Anti-inflammation. Yes, a little inflammation is a good things for figthing infections and basic immunity. However, the vast majority of us in modern societies have the opposite problem: an overactive inflammatory response. Read this link on How to Control Inflammation for many ideas on how to get out of the inflammation rat race.

Viagra (sildenafil citrate) is a specific phosphodiesterase-5 (PDE-5) inhibitor, which has been approved for the treatment of erectile dysfunction in men . Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological condition characterized by the accumulation of triglycerides in hepatocytes and frequently associated with obesity, dyslipidemia, diabetes mellitus type 2, and insulin resistance ¹.

A study conducted on male mice and patients with erectile dysfunction found that sildenafil citrate improved liver enzymes, insulin resistance, and lipid levels compared to the control group in animal models. However, there were insignificant changes as regards lipid profile, fasting serum insulin, and liver enzymes (alkaline phosphatase, alanine 2-oxoglutarate aminotransferase) after sildenafil treatment for 8 weeks in NAFLD group in human study. There was a significant decrease in aspartate 2-oxoglutarate aminotransferase (AST) level after sildenafil treatment in NAFLD. There were significant negative correlations between International Index of Erectile Function (IIEF) score and Body Mass Index (BMI), cholesterol, and triglycerides levels .

It is important to note that sildenafil is well-tolerated and safe in NAFLD patients. However, further investigation is needed to test the effect of long-term sildenafil administration on insulin resistance and lipid profile .

1) Postgrad Med J, 2006, 82:315-322 “Treatment of non-alcoholic fatty liver disease”

2) World J Gastroenterol, 2006 Dec 28, 12(48):7826-31, “Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review.

3) World J Gastroenterol, 2007 March 14, 13(10):1579-1584, Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease”

4) HEPATOLOGY, 2010, 52(5), “Evolution of Inflammation in Nonalcoholic Fatty Liver Disease: The Multiple Parallel Hits Hypothesis”

5) J Clin Invest. 2003, 112(1):91–100, “The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice”

6) The Journal of Clinical Endocrinology & Metabolism, Jun 1 2005, 90(6):3498-3504, “Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to Hepatic Insulin Resistance and Hepatic Fat Content, Not to Liver Disease Severity”

7) J Mol Med (Berl), 2002 Nov, 80(11):696-702, “Adiponectin: a link between excess adiposity and associated comorbidities?”

8) Ann Med, 2005, 37(5):347-56, “Fat in the liver and insulin resistance”

9) Cancer Cell, 17 Feb 2010, 17(2):115-117, “Obesity, Inflammatory Signaling, and Hepatocellular Carcinoma—An Enlarging Link”

10) Gastroenterology, Jul 2005, 129(1):113–121, “The Natural History of Nonalcoholic FattyLiver Disease: A Population-Based Cohort Study”