Causes and Effects of Non-Alcoholic Fatty Liver Disease

By Dr. Mercola

Non-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of fats, often accompanied by elevated enzyme levels, in your liver in the absence of significant alcohol consumption.

While it's normal for your liver to contain some fat, accumulations of more than 5 percent to 10 percent of your liver's weight are problematic.¹
Alcohol consumption is a leading cause of fatty liver, but in the case of NAFLD, it occurs in people who are overweight or obese, have high cholesterol, or high triglycerides, and who consume little or no alcohol.

Some people develop NAFLD even without any known risk factors, and this condition affects up to 25 percent of Americans.²
NAFLD often has no symptoms, although it may cause fatigue, jaundice, swelling in the legs and abdomen, mental confusion, and more. If left untreated, it can cause your liver to swell, called non-alcoholic steatohepatitis (NASH), or even contribute to liver cancer or liver failure.
One of the most important aspects to remember if you're dealing with NAFLD is this: eating right and exercising can often prevent this condition and may even reverse it in its early stages.³

Excess Fructose Is a Leading Cause of Non-Alcoholic Fatty Liver Disease

In your quest for a healthier diet, the first ingredient to eliminate would be fructose – the sugar found in everything from high-fructose corn syrup (HFCS) and fruit juice to agave syrup and honey. It's harmful when consumed in excess – which is exactly what many (if not most) Americans do.

Fructose is, in many ways, very similar to alcohol in the damage that it can do to your body… and your liver. Unlike glucose, which can be used by virtually every cell in your body, fructose can only be metabolized by your liver, because your liver is the only organ that has the transporter for it.

Since all fructose gets shuttled to your liver, and, if you eat a typical Western-style diet, you consume high amounts of it, fructose ends up taxing and damaging your liver in the same way alcohol and other toxins do. In fact, fructose is virtually identical to alcohol with regard to the metabolic havoc it wreaks.

According to Dr. Robert Lustig, a neuroendocrinologist in the Division of Endocrinology at the University of California, fructose is a "chronic, dose-dependent liver toxin." And just like alcohol, fructose is metabolized directly into fat – not cellular energy, like glucose.

His findings were published in the Journal of the Academy of Nutrition and Dietetics,⁴ where Dr. Lustig explained the three similarities between fructose and its fermentation byproduct, ethanol (alcohol):

1. Your liver's metabolism of fructose is similar to alcohol, as they both serve as substrates for converting dietary carbohydrate into fat, which promotes insulin resistance, dyslipidemia (abnormal fat levels in the bloodstream), and fatty liver
2. Fructose undergoes the Maillard reaction with proteins, leading to the formation of superoxide free radicals that can result in liver inflammation similar to acetaldehyde, an intermediary metabolite of ethanol
3. By "stimulating the 'hedonic pathway' of the brain both directly and indirectly," Dr. Lustig noted, "fructose creates habituation, and possibly dependence; also paralleling ethanol."

How Excess Fructose Directly Contributes to NAFLD

Writing in the journal Hepatobiliary Surgery and Nutrition, researchers noted that the rapid rise in NAFLD prevalence supports the role of environmental factors.

The overconsumption of high-fructose corn syrup (HFCS) in soda is associated with NAFLD, while the study also concluded "ingested carbohydrates are… more likely to directly contribute to NAFLD than dietary fat intake."⁵

The fat-forming and pro-inflammatory effects of fructose appear to be due to transient ATP (the chemical storage form of energy) depletion, according to the study. This, in turn, leads to uric acid formation.

Fructose increases uric acid through a complex process that causes cells to burn up their ATP rapidly, leading to "cell shock" and increased cell death. After eating excessive amounts of fructose, cells become starved of energy and enter a state of shock, just as if they have lost their blood supply.

Cells that are depleted of energy become inflamed and more susceptible to damage from oxidative stress. Fat cells actually become "sickly," bloating up with excessive amounts of fat.

Massive cellular die-off leads to increased uric acid levels. Uric acid is a normal waste product found in your blood. It functions both as an antioxidant and as a pro-oxidant once inside your cells.

So, if your uric acid levels are too high, it tends to increase to harmful levels inside your cells as well, where it acts as a pro-oxidant. According to Dr. Richard Johnson, who conducted years of research on the role of fructose in obesity uric acid appears to take on a lead role in creating health problems when it reaches levels in your body of 5.5 mg per dl or higher.

At this level, uric acid is associated with an increased risk for developing high blood pressure, as well as diabetes, obesity, and kidney disease. The ideal range for uric acid lies between 3 to 5.5 mg per dl.

The connection between fructose consumption and increased uric acid is so reliable that a uric acid level taken from your blood can actually be used as a marker for fructose toxicity. I now recommend that a uric acid level be a routine part of your blood screening.

One Sugary Drink Daily Increases Your Risk of NAFLD

Sugary beverages, including not only soda but also fruit juice, lemonade, fruit punch, and the like, are a major source of fructose in the US diet.

New research from Tufts University revealed this could be putting your health at risk, as those who consumed at least one sugary drink daily had a higher risk of liver damage and NAFLD.⁶

Sugary drinks are likely one major factor in why even children are developing NAFLD at alarming rates. The longer you have NAFLD, the more likely it is to progress into more serious disease like liver fibrosis (accumulation of abnormal fibrous tissue), cirrhosis (accumulation of scar tissue), and NASH.

In fact, the Hepatobiliary Surgery and Nutrition study linked HFCS consumption to the severity of fibrosis in patients with NAFLD.⁷ Therefore, it's very concerning that children are developing this so early in their lives. The following facts about pediatric NAFLD are disturbing:⁸

• Nearly 10 percent of US children have NAFLD
• This includes 1 percent of 2- to 4-year-olds and 17 percent of 15- to 19-year-olds
• Approximately 38 percent of obese children have NAFLD
• Children with NAFLD are at particular risk of complications and poor prognosis, including the need for a liver transplant in adulthood

How Much Fructose Is Too Much?

Most overweight Americans have some degree of insulin and leptin resistance. This also includes people with diabetes, and many individuals with high blood pressure or high cholesterol (the same individuals at increased risk of NAFLD).

If you fall into this category, it would be prudent for you to restrict your fructose consumption to about 15 grams of fructose per day from all sources. Remember, fructose isn't only found in sugary beverages; it's also found in many processed foods and even "healthy" sweeteners like agave.

Those who are normal weight and relatively healthy may also benefit from reducing their intake of fructose to 25 grams a day, particularly from foods containing high-fructose corn syrup or sugar, as the effects of high sugar and HFCS intake may have effects that build up over time.

Naturally, fruits also have fructose but contain many beneficial nutrients and antioxidants. For someone who is obese or suffering from NAFLD, one has to be careful with eating fruits that have substantial fructose content.

Some fruits, such as lemons and limes, have minimal fructose content and are safe. Other fruits, such as grapefruit, kiwi, and berries, also have relatively low fructose content and high levels of nutrients. However, fruit juices, dried fruits, and some fruits that are rich in fructose (such as pears, red apples, and plums) should be eaten relatively sparingly.

According to Dr. Johnson, if you exercise regularly, a small amount of fructose can actually be quite beneficial, because the fructose will accelerate glucose absorption in your gut and improve muscle performance. But it really depends on how your body metabolizes the fructose.

Your body normally cannot absorb fructose well. But the more fructose you eat, the more the transporters that allow for fructose uptake in your gut are turned on. Hence, the more fructose your body will absorb. Lean children, for instance, tend to only absorb about half of the fructose they consume, whereas obese children who have fatty liver disease absorb close to 100 percent.

Exercise Is Also Important for Treating NAFLD

The current standard of treatment for NAFLD centers around dietary changes to promote weight loss, which is important, but research shows exercise is also incredibly important, regardless of whether or not you lose weight. In fact, just exercising for more than 150 minutes per week for three months, or increasing fitness levels, was enough for participants to show improvements in fatty liver disease.⁹

Another study published in the European Journal of Gastroenterology and Hepatology in 2006 also found that three months' worth of nutritional guidance, plus a pair of one-hour exercise sessions each week, helped obese teens improve fatty liver disease.¹⁰ Before the study, more than half of the patients had fatty liver disease on the right side of their organ and almost half had it on their left side. Afterward, fatty liver disease -- on either side -- fell sharply to 29 percent, and almost half of the young patients lost weight.

Endocrine-Disrupting Chemicals May Also Contribute to Fatty Liver Disease

Endocrine-disrupting chemicals are similar in structure to natural sex hormones such as estrogen. By mimicking natural hormones, they have a number of adverse effects on both humans and wildlife, including developmental, reproductive, neurological, and immune system damage. Research presented at the Endocrine Society's 2015 annual meeting in San Diego, California, revealed that such chemicals, and particularly bisphenol-A (BPA), could contribute to fatty liver disease later in life when exposures occur shortly after birth.

In an animal study, even brief exposures to low doses of the chemical appeared to alter gene expression in the liver and "induced developmental reprogramming of the animals' epigenomes" in a way that could contribute to fatty liver disease.¹¹ Cheryl Lyn Walker from the Texas A&M Health Science Centre's Institute of Biosciences and Technology noted:¹²

"'Even a short exposure to these endocrine disruptors at the wrong time of development has a life-long effect on the individual."

BPA is often found in:

• Soda cans and other canned goods
• Certain plastics and food packaging
• Certain tooth sealants
• Certain BPA-free plastics
• Receipts and currency (seek to limit or avoid carrying receipts in your wallet or purse, as it appears the chemical is transferring onto other surfaces it touches.

Although NAFLD should primarily be addressed through dietary changes and exercise, avoiding exposures to endocrine-disrupting chemicals also makes sense, especially for pregnant women, women of reproductive age, infants, and children. It's virtually impossible to steer clear of all endocrine-disrupting chemicals, but you can certainly minimize your exposure by keeping some key principles in mind.

1. Eat mostly fresh whole foods. Processed and packaged foods are a common source of BPA and phthalates—particularly cans, but also foods packaged in plastic wrap.
2. Buy products that come in glass bottles and jars rather than plastic or cans. Brick-shaped cardboard cartons may also be preferable to plastic or cans.
3. Store your food and beverages in glass, rather than plastic, and avoid using plastic wrap. Use glass containers if heating food in your microwave, as heat tends to increase the release of chemicals from plastic.
4. Use glass baby bottles for your infants.
5. Be careful with cash register receipts. If you use a store regularly, encourage the management to switch to BPA-free receipts. I shop at Publix for my food and when I called them about the receipts it turns out they had already switched. Nevertheless it is wise to limit your contact with all these receipts.
6. Look for products that are made by companies that are earth-friendly, animal-friendly, sustainable, certified organic, and GMO-free. This applies to everything from food and personal care products to building materials, carpeting, paint, baby items, furniture, mattresses, and more. When redoing your home, look for "green," toxin-free alternatives in lieu of regular paint and vinyl floor coverings, the latter of which is another source of phthalates.
7. Choose toys made from natural materials to avoid plastic chemicals like phthalates and BPA/BPS, particularly for items your child may be prone to suck or chew on.
8. Breastfeed your baby exclusively if possible, for at least the first year (as you will avoid phthalates exposure from infant formula packaging and plastic bottles/nipples).
9. Use natural cleaning products, or make your own.
10. Switch over to organic toiletries, including shampoo, toothpaste, antiperspirants, and cosmetics. EWG's Skin Deep database can help you find personal care products that are free of phthalates and other potentially dangerous chemicals.¹³
11. Replace your vinyl shower curtain with a fabric one.
12. Replace feminine hygiene products (tampons and sanitary pads) with safer alternatives. While most ingredients in feminine hygiene products are undisclosed, tests suggest they may contain dioxins and petrochemical additives.
13. Look for fragrance-free products; phthalates are often used to help the product hold its fragrance longer. Artificial fragrance can also contain hundreds—even thousands—of potentially toxic chemicals. Avoid fabric softeners, dryer sheets, air fresheners, and scented candles for the same reason.
14. Check your home's tap water for contaminants and filter the water if necessary. You may also want to use an alternative to PVC pipes for your water supply.
15. Teach your children not to drink water from the garden hose, as many are made with phthalate-containing plastics.

Two Supplements for Liver Disease

In addition to eating right (and in particular limiting your fructose intake) and exercising, the natural plant compound berberine has also been found to reduce fat build-up in the liver, which may protect against NAFLD.¹⁴ You might consider this supplement along with your lifestyle changes, particularly until your liver heals and normalizes. In addition, vitamin E may help relieve the majority of symptoms associated with nonalcoholic steatohepatitis (NASH), the more severe form of NAFLD.

One study tested the hypothesis that low levels of vitamin E may be linked to liver disease and indeed found that in mice bioengineered to have inadequate vitamin E levels there was increased oxidative stress, fat deposition, and other signs of liver injury.¹⁵

When the mice were supplemented with vitamin E, the majority of NASH-related symptoms were relieved. Likewise, a second study looking into the role of vitamin E on NASH showed that rats with the liver disease that were supplemented with both full spectrum d-mixed tocotrienols and alpha-tocopherol had multiple improvements compared to those supplemented with only alpha-tocopherol or mixed tocotrienols.¹⁶ Benefits included:

• Reduced triglyceride accumulation in the liver
• Decreased level of lipid peroxides
• Improved liver damage markers
• Inhibited liver fibrosis (scarring)

Like NAFLD, NASH is often a slow-growing disease than can take years or decades to progress. The process can stop and even spontaneously reverse, or it may progress with worsening scarring to cirrhosis.

Once this occurs, the disease progression will continue on to liver failure and little can be done to stop it. Supplementing with vitamin E, or increasing intake via your diet, may therefore be a crucial step that can help you halt the progression of this disease.