Life Extension Magazine December 2010
The Liver Disease Epidemic You Need to Know About
By Kirk Stokel
Most people associate liver damage with alcohol abuse or hepatitis. Yet a stealth liver condition of epidemic proportions lurks in this country that may pose an even greater threat to the public health.
Roughly one-third of the American population1-3 suffers from nonalcoholic fatty liver disease or NAFLD. Many of its victims don’t know they have it. NAFLD can go undetected for years and may eventually progress to inflammation and scarring of the liver (cirrhosis) and, in some cases, full-blown liver failure.
A formerly rare condition, its rapid emergence has been linked to skyrocketing rates of metabolic syndrome3-5 and “diabesity,” the term many experts use for co-occurring diabetes and obesity. While poor dietary choices are often to blame, cutting-edge research suggests that hidden genetic factors may also play a role, as some people do not metabolize polyunsaturated fats properly, resulting in fatty deposits in the liver.6
As mainstream medicine continues to struggle in the search for drugs to manage this widespread condition, emerging scientific evidence has shed light on effective natural interventions that may halt or even reverse its progress.
In this article, you will learn about NAFLD and its impact on overall health in aging individuals, along with the various stages of the condition, ranging from barely detectable indicators to cirrhosis and liver failure. You will also discover compelling evidence for seven potent interventions that may effectively combat this challenging and widespread disease.
Fat Overload, Liver Damage, and the Inflammatory Storm
NAFLD (nonalcoholic fatty liver disease) is defined as deposition of fat in the liver cells of patients with minimal or no alcohol intake and with no other known cause.7 The term “NAFLD” refers to a group of related and progressive conditions closely associated with overweight and obesity.2
NAFLD starts off as a low-level disturbance characterized by dull right upper-quadrant abdominal discomfort and fatigue in most patients, but it is hardly benign.8 Early NAFLD can ultimately progress to a more serious condition, nonalcoholic steatohepatitis or NASH.9 About a third of people with NAFLD will develop NASH.8 And about 20% of people with NASH will go on to liver fibrosis and cirrhosis, with its accompanying risk of liver failure and even liver cancer.2,8,10 Overall, people with NAFLD stand a 12% increased risk of liver-related death over 10 years.8
As the prevalence of overweight and obesity rises, so do the rates of NAFLD, NASH, and their end-stage consequences. Together, these conditions affect roughly 30% of US adults and, shockingly, up to 10% of our children.2
NAFLD has multiple interrelated causes. Primary mechanisms include obesity leading to steadily increasing insulin resistance coupled with an overabundance of circulating fatty acids. These factors fuel one another in a destructive cycle.4 Together with the recently-recognized role of advanced glycation end-products (AGEs), these events lead to increased oxidant stress and ultimately inflammation, cell death, and fibrous destruction of liver tissue.3,4,8
An overload of fatty acids and abnormal lipid profiles factor so heavily in the onset of NAFLD that they’re now referred to as “lipotoxicity” because of the ways they directly poison liver tissue.9,11,12 And as fat builds inside liver cells, they begin churning out a storm of fat-related cytokines known as adipokines, which fan the inflammatory flames of the metabolic syndrome and NAFLD.1
Unfortunately, despite a growing understanding of what goes wrong in NAFLD, scientists have been persistently baffled in their attempts to prevent and treat it with drug therapies. Lifestyle interventions such as steady, gentle weight loss and regular exercise have been the only interventions that offered any hope at all.2,9 Insulin-sensitizing drugs, while theoretically of value, have proved disappointing in clinical trials.
The only successful pharmaceutical intervention for dealing with NAFLD has been metformin, which will be examined below.
Cholesterol-lowering drugs like statins have no proven benefit to date.4 Further studies are needed to determine if bariatric surgery to induce weight loss benefits patients with NAFLD.9,13
Given the nutritional origins of NAFLD, it comes as no surprise that a handful of nutrients with targeted antioxidant, anti-inflammatory, and metabolic properties have emerged in recent years as the most promising preventive therapies. A recent clinical trial of vitamin E versus the prescription drug pioglitazone (Actos®) provided some compelling results, and serves as an excellent introduction to a broader examination of the most promising, safe, low-cost interventions.
7 Interventions to Heal and Protect Your Liver
Liver scientists at the Virginia Commonwealth University Medical Center began a series of studies on NASH (the advanced middle stage of NAFLD) and vitamin E in 2004. Based on their knowledge that NASH arises from persistent insulin resistance and oxidative stress, they examined the effects of pioglitazone (Actos®), an insulin-sensitizing drug, and vitamin E.14 Their initial hypothesis was naturally that the combination of vitamin E plus the drug would produce greater benefits than vitamin E alone. And indeed, looking at liver biopsies that seemed to be the case. Patients receiving both vitamin E (400 IU per day) and pioglitazone (30 mg per day) had improvements in more parameters than did patients on vitamin E alone (though the vitamin E patients did show some improvement).14
Encouraged (and curious), the researchers designed an additional trial aimed at evaluating the effects of vitamin E and pioglitazone independently in patients with NASH.15 In this study, published in mid-2010, subjects received either vitamin E (800 IU per day) or pioglitazone (30 mg per day), or placebo, for 96 weeks.16 The results were surprising, to say the least.
Only vitamin E, and not pioglitazone, produced significant improvements in the appearance of liver tissue on biopsies.16 Both treatments improved levels of liver cell-injury markers in blood, and both reduced liver fat levels and inflammation. This study showed that vitamin E, formerly thought to be additional therapy for NASH, was actually superior to pioglitazone at improving liver damage. Let’s now look at some clues that might have predicted these otherwise startling results, based on what was already known about vitamin E in liver disease.
Vitamin E is a powerful antioxidant, and hence an obvious choice once the role of oxidant stress was made clear in NAFLD.17 We had known since at least 1992 that people with fatty liver disease and NASH had depressed levels of vitamin E in their blood, the result of that increased oxidation.18,19 By the beginning of this century, relatively low-dose vitamin E (450 IU/day) was shown to reduce circulating liver enzymes, a chemical marker of liver cell injury.20,21
Clinical trials of combination antioxidants, including one with silybin (milk thistle) and phospholipids showed good results at improving insulin resistance and reducing markers of liver cell fibrosis (a finding in advanced liver disease).22,23 In patients receiving vitamin E 1,200 IU mg per day, overall fasting glucose levels improved while markers of liver cell damage decreased.24 In a subgroup of those patients, there was evidence of reduced inflammation and improved expression of PPAR-alpha, a vital metabolic sensor complex, providing evidence of new and separate mechanisms of action.
Important animal studies began to appear around 2009 that refined our understanding of how vitamin E works. One study provided the first evidence that vitamin E can prevent NAFLD before it develops, largely by reducing oxidative stress, inflammation, and liver cell death by apoptosis.25 Another study demonstrated a vitamin E-related reduction in oxidative damage and tissue levels of the inflammatory mediator TNF-alpha, while beneficially reducing PPAR-gamma activity.26 This wealth of animal and now human data clearly supports daily use of 800-1,200 IU of vitamin E for prevention and treatment of NAFLD and NASH. Let’s look at the other nutrients known to be helpful in preventing this troubling suite of conditions.
This wealth of animal and now human data clearly supports daily use of 800-1,200 IU of vitamin E for prevention and treatment of NAFLD and NASH.
Omega-3 Fatty Acids
Just as vitamin E fights the oxidant and inflammatory components of NAFLD, the omega-3 fatty acids attack the problem of lipotoxicity, while contributing considerable anti-inflammatory activity of their own.12 People and experimental animals with insufficient omega-3 in their diets are prone to the development of NAFLD and type 2 diabetes, suggesting that supplementation might reverse (or prevent) the process.12,27-29
In fact, both in the laboratory and at the bedside, there are impressive results from omega-3 supplementation. Increasing the amount of unsaturated fats like omega-3s in cell membranes is associated with improved insulin sensitivity.30 And fish oil supplements rich in omega-3 result in activation of the important metabolic sensor called PPAR-alpha in liver cells, suppressing liver production of new fat molecules.31 The omega-3s also contribute to improved insulin sensitivity, accompanied by a reduction in serum triglycerides and stimulation of fat utilization or burning in liver tissue and skeletal muscle.32
A compelling, long-term human trial using 1,000 mg per day of omega-3 in patients with NAFLD revealed significant decreases in serum markers of liver cell damage, triglyceride levels, and fasting glucose.33 Importantly, circulating levels of the inflammatory fat arachidonic acid were also significantly reduced. Most impressively, supplemented patients display improvement of their livers’ appearance and blood flow on ultrasound exams, providing graphic evidence of the supplements’ benefits.33 Another study found that supplementation with 751 mg eicosapentaenoic acid (EPA) and 527 mg docosahexaenoic acid (DHA) 3 times daily for 24 weeks decreased triglyceride levels in individuals with NAFLD.34
Clearly the omega-3 fatty acids deserve a place in our armamentarium of supplements to fight NAFLD, and have earned their designation as “a specific liver drug for nonalcoholic fatty liver disease.”35