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Fighting Fatty Liver, Part 2 of 2

Fighting Fatty Liver, Part 2 of 2

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Clinically studied botanicals and nutrients for the treatment of fatty liver disease

As discussed in Fighting Fatty Liver, Part 1 of 2, the progression of NAFLD is influenced by insulin resistance, fat accumulation in the liver, intestinal imbalance, and inflammation/oxidative stress. Strategies to prevent and resolve NAFLD must therefore not only target the liver, but also balance blood sugar, soothe the gut, and fight inflammation and oxidative stress. In addition to the dietary changes addressed in Part 1 of 2, some simple-yet-powerful evidence-based strategies for improving the health of the liver and reducing the cellular changes and inflammation associated with NAFLD include milk thistle, vitamin E, phosphatidylcholine, and berberine.

Milk thistle (Silybum marianum) seed

Perhaps the best-known botanical with respect to liver health, milk thistle has been shown in animal studies to reduce liver injury caused by a number of different agents.[1] Silymarin, a mixture of the active constituents of milk thistle, also has been shown to increase hepatic and intestinal levels of the powerful antioxidant glutathione[2] and to further combat oxidative stress by enhancing the activity of Nrf2, a cell-signaling pathway that regulates antioxidant production, detoxification, and cell survival in response to injury and inflammation.[3],[4] Silymarin has also been shown to decrease inflammation and combat insulin resistance – two of the hallmarks of NASH, the more severe form of NAFLD – by activating a bile acid receptor known as farnesoid X receptor (FXR).[5],[6],[7]

Silymarin, a mixture of the active constituents of milk thistle, also has been shown to increase hepatic and intestinal levels of the powerful antioxidant glutathione.

Milk thistle has also been studied specifically within the context of patients with NAFLD. A 2017 meta-analysis demonstrated the herb’s efficacy in significantly reducing the liver enzymes alanine aminotransferase (or ALT, also called SGPT) and aspartate transaminase (or AST, also known as SGOT) in those with NAFLD (by −5.08 IU/L and −5.44 IU/L, respectively),[8] with dosages ranging from 140 mg once a day to 200 mg three times a day. Even at the lowest dose of 140 mg once daily, significant improvements in fasting blood sugar, cholesterol, insulin levels, and liver enzymes were observed.[9]

Vitamin E

Both the tocopherol and tocotrienol forms of vitamin E have been shown to reduce the accumulation of triglycerides in the liver and lower markers of liver inflammation. (Remember, the hallmark of NAFLD is an excess of hepatic triglycerides, while NASH, the more aggressive form of NAFLD, is associated with liver inflammation.) By regulating fatty acid synthesis, vitamin E may not only reduce the amount of fat stored in the liver, but also quench inflammation and oxidative stress.[10],[11]

By regulating fatty acid synthesis, vitamin E may not only reduce the amount of fat stored in the liver, but also quench inflammation and oxidative stress.

Vitamin E has even shown promise in children with NAFLD. In an open-label pilot study, 11 children with NAFLD took a daily dose of 400 to 1,200 IU of vitamin E daily for a period of 4 to 10 months. Liver transaminase (AST and/or ALT) and alkaline phosphatase (another liver enzyme) normalized during the treatment phase in these children but returned to abnormal ranges when vitamin E supplementation was discontinued.[12] (Another study showing the promise of vitamin E supplementation in children with NASH is explored below, in the section on phosphatidylcholine.)

The majority of research pertaining to vitamin E focuses on a form known as tocopherols, which is commonly found in nature. Another form of vitamin E known as tocotrienols have even greater antioxidant potential than the tocopherol form, and also may improve NAFLD and high cholesterol levels.[13] At a dosage of 200 mg twice daily for one year, tocotrienols significantly improved hepatic echogenicity (how dense the liver appears on ultrasound, a marker of the disease) and increased the rate of disease remission compared to placebo.[14] Tocotrienols have also been shown to improve total and LDL cholesterol by 15 to 20%,[15],[16] and triglyceride levels by almost 30%.[17]

In another study of patients with NAFLD who also had elevated liver enzymes, 300 mg of tocotrienols taken twice daily for 12 weeks not only significantly decreased both AST and ALT levels, but also reduced markers of inflammation (high sensitivity C-reactive protein, or hs-CRP) and oxidative stress (malondialdehyde).[18] Fatty liver index scores were also improved as compared to placebo.


Found in every cell in the body, phosphatidylcholine (PC) is especially important when it comes to the health of gallbladder and the liver. Inadequate PC levels can lead not only to fatty liver,[19] but also to muscle damage, inadequate bile production, and gallstones.[20],[21]

Choline is also important for the production of betaine,[22] an important amino acid that helps reduce the cardiovascular disease risk-associated inflammatory compound homocysteine. Betaine primarily supports the body by donating methyl groups, and is thus sometimes referred to as trimethylglycine (TMG). In addition to supporting cardiovascular health, the methyl groups provided by betaine are also important for hepatic fat metabolism. Inadequate choline levels – and thus low betaine levels – have been associated with steatosis (fat accumulation around the liver) and subsequent abnormal blood cholesterol levels.[23]

Yet despite the importance of this nutrient, choline deficiency is shockingly common. It’s estimated that a mere 8% of Americans consume adequate amounts of choline in the diet, with vegetarians at particular risk of deficiency.[24],[25] When it comes to NAFLD, choline deficiency is especially harmful, as it’s significantly associated with increased fibrosis according to one study performed in postmenopausal women with NAFLD.[26] Another study done on mice found that supplementation of choline and betaine protected against the type of obesity associated with fatty liver and hyperlipidemia (high cholesterol).[27]

It’s estimated that a mere 8% of Americans consume adequate amounts of choline in the diet, with vegetarians at particular risk of deficiency.

Pediatric populations also require choline for optimal health. In a study done in children and adolescents with NASH, supplementation with a combination of choline, vitamin E, and docosahexaenoic acid (abbreviated DHA, an omega-3 fatty acid found in fish oil) yielded promising outcomes. Compared to placebo, a significant decrease in severe steatosis was observed in the children taking the combination, as well as significant decreases in ALT and fasting glucose levels.[28]

PC is also important for digestive health, as it makes up over 90% of the phospholipids in the protective mucus lining the gut wall, thereby protecting against leaky gut and its complications.[29],[30] Treatment with PC has also been shown to restrict the migration of endotoxins across the gut lining, thereby lowering the risk of inflammation and further damage to the intestinal epithelium.[31],[32]


The orange-yellow constituent found in herbs like goldenseal and Oregon grape root is also helpful in addressing many facets of NAFLD. In the intestines, berberine shifts the microbial balance in favor of Akkermansia muciniphila,[33],[34] a bacterium associated with leaner body mass, balanced blood sugar, and improved intestinal integrity (decreased leaky gut).[35],[36] These effects in turn reduce the risk of toxins entering the body through the gut lining, thus reducing inflammation.[37]

In addition to showing promise in the management of type 2 diabetes, berberine has also been shown to support healthy cholesterol levels.[38] This is especially relevant within the context of NAFLD, given that the condition is defined by excess fat (or cholesterol) in the liver and exacerbated by insulin resistance and high blood sugar levels.[39],[40] In a study done in adults with NAFLD comparing berberine plus lifestyle changes versus lifestyle changes alone, berberine was shown to restore normal hepatic architecture, lipid (cholesterol) breakdown, and blood sugar metabolism.[41]

Like silymarin, berberine also interacts with FXR, thus enhancing gallbladder function and ergo the digestion of fats.[42],[43] In mice with diet-induced obesity, berberine was shown to suppress obesity-related inflammation and hepatic steatosis by decreasing the phosphorylation of something called JNK1,[44] a protein kinase strongly activated by environmental stressors and implicated in the development of steatohepatitis.[45]

It doesn’t have to be this way

Despite the commonality of NAFLD and its associated metabolic diseases, these conditions are often preventable and manageable with nutrition and natural remedies. Through an integrated approach blending healthy lifestyle choices (as discussed in Part 1), evidence-based natural therapies, and a balanced diet, it’s possible to give the liver – and the whole body – a major upgrade.

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