Love Your Liver

The liver is a crucial organ in the body, playing a vital role in metabolism, detoxification, digestion, blood sugar regulation, and vitamin storage. Today, we start with a story about the liver damage caused by Herbalife supplements.

Herbalife is a multi-billion-dollar, multi-level marketing supplement company that was forced to pay hundreds of millions of dollars to settle charges of deception and corrupt business practices. It also holds the distinction of being the dietary supplement most frequently implicated in injuring the livers of consumers.

Herbal does not mean innocuous. Cases of severe liver toxicity associated with Herbalife supplements started to be published in 2007 around the world. As the accompanying editorial summarized, there were 22 cases of liver damage following Herbalife intake in those first two reports, with two patients developing fulminant liver failure requiring liver transplantation. Only one survived. The editorial concluded that this clearly shifts the risk-benefit ratio against its use. Maybe it’s contamination with chemicals or heavy metals, maybe due to contamination with a liver-toxic bacteria found in implicated products.

Additional reports continued to be published, followed by rebuttals written by Herbalife company representatives, questioning cause-and-effect. It’s no small task, given that people were taking up to seventeen different Herbalife products at one time.

So how strong is the evidence? A key factor to look for is re-challenge tests, or “positive re-exposure.” Did someone decide to take the product again after their initial liver injury resolved, and did their symptoms return on re-challenge? Based on stringent causality assessment methods like positive re-exposure tests, cause and effect is considered probable for at least a few Herbalife products. They are such a moving target though, with “hundreds of different products marketed globally in over 88 markets where in many cases the formula is unique to a country or region…”

Positive rechallenge cases continue to be published, confirming the toxic cause of liver damage from Herbalife products, perhaps by triggering an autoimmune reaction. This fatal case of a 24-year-old woman was attributed to Herbalife products, which were evidently found to contain heavy metals, traces of a psychotropic recreational agent, and pathogenic bacteria. This paper was subsequently taken down for “legal reasons” after legal threats by Herbalife.
LiverTox is a federal initiative between the National Institutes of Health and the National Library of Medicine to categorize the likelihood that substances can damage the liver, all the way up to the highest likelihood—Category A—meaning it is a well-known, well-described, and well-reported cause of liver damage. And that’s exactly how it characterized Herbalife supplements: A well-established cause of clinically-apparent liver injury.

In our next story, we look at how sugary and cholesterol-laden are the most common cause of chronic liver disease.

In the documentary Super Size Me, Morgan Spurlock eats exclusively at McDonald’s for a month, and predictably his weight, blood pressure, and cholesterol go up—but so do his liver enzymes, a sign his liver cells are dying and spilling their contents into the bloodstream. His one-man experiment was actually formally replicated. A group of men and women agreed to eat two fast food meals a day for a month, and most of their liver values started out normal—under 30 here for men. But within just one week, most were out of whack: a profound pathological elevation in liver damage.

What’s happening is NAFLD, non-alcoholic fatty liver disease, the next global epidemic. Fatty deposits in the liver can result in a disease spectrum—from asymptomatic fat buildup, to NASH, nonalcoholic steatohepatitis, which can lead to liver scarring and cirrhosis, which can result in liver cancer, liver failure, and death.

It’s now the most common cause of chronic liver disease in the U.S., affecting 70 million Americans—that’s like one in three adults. And fast food is a great way to bring it on, since it’s associated with the intake of soft drinks and meat. One can of soda a day may raise the odds of fatty liver 45%, and those eating the equivalent of 14 chicken nuggets’ worth of meat a day have nearly triple the rates of fatty liver, compared to seven nuggets or less.

It’s been characterized as a tale of fat and sugar—but evidently, not all types of fat. Those with fatty hepatitis ate more animal fat and cholesterol, and less plant fat, fiber, and antioxidants, which may explain why adherence to a Mediterranean-style diet—characterized by high consumption of foods such as fruits, vegetables, whole grains, and beans—is associated with less severe non-alcoholic fatty liver disease, perhaps because of its anti-inflammatory and antioxidant effects. Maybe it is also because of specific phytonutrients, like the purple, red, blue anthocyanin pigments in berries, as well as in grapes, plums, red cabbage, red onions, and radicchio. These anthocyanin-rich foods may be promising for the prevention of fatty liver, but that’s mostly based on Petri dish experiments. There was one clinical trial that found that drinking a purple sweet potato beverage seemed to successfully dampen liver inflammation.

A more plant-based diet may also improve our microbiome, the good bacteria in our gut. The old adage, “we are what we eat,” may be changing to “we are what our bacteria eat.” And when we eat fat, we may facilitate the growth of bad bacteria, which can release inflammatory molecules that increase the leakiness of our gut and contribute to fatty liver disease.

Fatty liver disease can also be caused by cholesterol overload. The thought is that dietary cholesterol, found in eggs, meat, and dairy, oxidizes and then upregulates liver X receptor alpha, which can upregulate something else called SREBP, which can increase the level of fat in the liver.

Cholesterol crystals alone cause human white blood cells to spill out inflammatory compounds, just like uric acid crystals in gout. That’s what may be triggering the progression of fatty liver into serious hepatitis, the accumulation of sufficient concentrations of free cholesterol within fatty liver cells to cause crystallization of the cholesterol—one of several recent lines of evidence suggesting that dietary cholesterol plays an important role in the development of fatty hepatitis, fatty liver inflammation.

In a study of 9,000 American adults followed for 13 years, they found a strong association between cholesterol intake and hospitalization, and death from cirrhosis and liver cancer, as dietary cholesterol can oxidize and cause toxic and carcinogenic effects. To limit the toxicity of excess cholesterol derived from the diet, the liver tries to rid itself of cholesterol by dumping it into the bloodstream. And so, by measuring the non-HDL cholesterol in the blood, one can predict the onset of fatty liver disease. If you subtract HDL from total cholesterol, none of the hundreds of people they followed with a value under 130 developed the disease. Drug companies view non-alcoholic fatty liver disease as a bonanza, as is the case of any disease of affluence, considering its already high and rising prevalence, needing continuous pharmacologic treatment. But maybe it’s as easy as changing our diet—avoiding sugary and cholesterol-laden foods.

The unpalatable truth is that non-alcoholic fatty liver disease could almost be considered the human equivalent of foie gras, as we “force-feed” ourselves foods that can result in serious health implications. However, having such a buttery texture in human livers is not a delicacy to be enjoyed by liver doctors in clinical practice, as it can have serious consequences.

Finally today, did you know that cancer-causing viruses in poultry may explain increased risks of death from liver and pancreatic cancers? Here’s the story.

Thousands of Americans continue to die from asbestos exposure decades after many uses were banned, because the cancers can take years to show up. We’re now in the so-called “third wave of asbestos-related disease.” The first wave was in the asbestos miners, which started in the 1920s. The second phase was in the workers—the shipbuilders and construction workers that used the stuff in the 30s, 40s, and 50s. Now, as “buildings constructed with asbestos over the past six decades begin to age and deteriorate,” not only are workers at risk, but “[p]otential also exists for serious environmental exposure to asbestos among residents, tenants, and users of these buildings, such as school children, office workers, maintenance workers, and the general public.” The [CDC], the American Academy of Pediatrics, and the [EPA] have projected…over the next 30 years approximately 1,000 cases of mesothelioma and lung cancer will occur among persons in the United States exposed to asbestos in school buildings as school children.” But, it all started with the workers. As one internal industry memo callously put it, “If [you’ve] enjoyed a good life while working with asbestos products why not die from it.”

To see if something is carcinogenic, you study those who have the most exposure. That’s how we learned about the potential cancer-causing dangers of asbestos, and that’s how we’re learning about the potential cancer-causing dangers of poultry viruses. For years, I’ve talked about the excess mortality in poultry workers associated with these wart-causing chicken cancer viruses that may be transmitted to those in the general population handling fresh or frozen chicken. Last year, I talked about the largest study to date at the time, confirming “the findings of three other…studies that workers in poultry slaughtering and processing plants have increased risk of dying from certain cancers,” and adding death from penis cancer to the risks linked to poultry exposure. That was looking at 20,000 poultry workers. Well, we have yet another study, looking at 30,000.

The purpose of the study was to “test the hypothesis that exposure to poultry [cancer-causing] viruses that widely occurs occupationally in poultry workers [not to mention the general population] may be associated with increased risks of deaths from liver and pancreatic cancers…” They found that those who slaughter chickens have about nine times the odds of both pancreatic cancer and liver cancer.

Just to put that in context, the most carefully studied risk factor for pancreatic cancer, one of our deadliest cancers, is cigarette smoking. Even if you smoke for more than 50 years, though, you only about double your odds of pancreatic cancer. Those that slaughter poultry appear to have nearly nine times the odds.

For liver cancer, it’s more alcohol. Those that consume more than a four drinks a day have triple the odds of liver cancer, whereas poultry slaughtering appears to increase one’s odds nine-fold.

There are diseases unique to the meat industry, like the newly described “salami brusher’s disease” that affects those whose job it is to wire brush off the white mold that naturally grows on salami for eight hours a day, but most diseases suffered by meat workers are more universal.

The reason the connection between asbestos and cancer was so easy to nail down is that asbestos caused a particularly unusual cancer, which was virtually unknown until there was widespread asbestos mining and industrial use. But the pancreatic cancer one might get from handling chicken is the same pancreatic cancer one might get smoking cigarettes; so, it’s more difficult to tease out a cause-and-effect-relationship. So, don’t expect to see an asbestos-type ban on Kentucky Fried Chicken anytime soon.