Published July 21 2014
I have written about the importance of the liver in past articles and blog posts. The liver of course is important for the removal of toxins from the body, but it is also involved in carbohydrate, fat, and protein metabolism. The liver stores certain vitamins, plays a role in vitamin D metabolism, and is also involved in blood clotting. Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver. In this article I’ll discuss the causes of NAFLD, how it relates to thyroid health, how to prevent this condition from developing, and how to reverse this condition for those who already have it.
The prevalence of NAFLD is up to 30% in developed countries and nearly 10% in developing nations, making NAFLD the most common liver condition in the world (1). Nonalcoholic steatohepatitis (NASH) is a significant form of chronic liver disease, and NAFLD may lead to the development of NASH (2). NAFLD is commonly asymptomatic, and those people with NAFLD have a higher mortality rate than the general population and are at increased risk of developing cardiovascular disease and diabetes in the future (1). The diagnosis of NAFLD usually involves a biopsy, although other methods that are used include ultrasound and serum cytokeratin-18 (3). To no surprise, many people with NAFLD are unaware that they have this condition, as it’s usually detected during routine lab examination, and it might result in elevation of the liver enzymes and/or alkaline phosphatase. Sometimes it’s detected during an ultrasound conducted on someone who is suspected of having gallbladder disease.
What Causes NAFLD?
Why do so many people have NAFLD? The evidence supports an association between NAFLD and metabolic syndrome (4). Both NAFLD and metabolic syndrome have common pathophysiological mechanisms, with insulin resistance being a key factor. Diet and lifestyle factors play a big role in the development of insulin resistance. I put together a separate article entitled “Insulin Resistance and Thyroid Health“, and so for more information on this topic I would read this when you get the chance.
Healthy adipose tissue is required for the normal secretion of adipokines, which include leptin and adiponectin (5). These both enhance insulin sensitivity. So adipose tissue is important, but problems occur when adipose tissue becomes dysfunctional. When someone becomes overweight or obese, the adipocytes (fat cells) enlarge. Accumulated visceral adipose tissue produces and secretes a number of adipocytokines, such as TNF-α and IL-6, which in turn leads to inflammation and exacerbates the insulin resistance (6).
Although poor diet and/or lack of exercise are the most common causes of NAFLD, there can be other factors involved. These include bacterial endotoxins, small intestinal bacterial overgrowth, certain medications, and environmental toxins such as petro-chemicals and organic solvents (7). So while it’s important to eat well and exercise regularly, these other factors need to be considered.
NAFLD and Gallbladder Disease
Patients with NAFLD have a high prevalence of gallbladder disease (8). Since there are similar risk factors with NAFLD and gallbladder disease, it has been suggested that a cholecystectomy (surgical removal of the gallbladder) may represent a risk factor for NAFLD (9). However, an earlier study showed that fifty-five percent of people with gallbladder disease had NAFLD (10). And since insulin resistance is a factor with both NAFLD and gallbladder disease (11), chances are that gallbladder disease or surgical removal of the gallbladder doesn’t cause NAFLD, but instead both gallbladder disease and NAFLD are caused by insulin resistance.
NAFLD and Inflammation
As mentioned earlier, NAFLD patients have elevated levels of the pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 (12). These pro-inflammatory cytokines play a role in metabolic and liver disorders in the fat accumulation, and thereby cause insulin resistance, inflammation, and liver fibrosis (13). So What exactly does this mean? Well, I’ve discussed pro-inflammatory cytokines in the past in a post entitled “The Role of Cytokines In Autoimmune Thyroid Conditions“, and these cytokines are elevated in NAFLD. TNF-alpha not only causes inflammation, but it is associated with an increase in insulin resistance. However, insulin resistance can also lead to an increase in TNF-alpha, and so a vicious cycle develops. TNF-alpha also seems to play a role in liver fibrosis (fibrous scar tissue in the liver). Liver fibrosis is associated with most chronic liver diseases, and advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation (14).
What Role Does NAFLD Play In Thyroid Health?
Hypothyroidism seems to be more prevalent in those who have NAFLD. One study involving 246 patients with biopsy-proven NAFLD showed that hypothyroidism was more frequent among those with NAFLD (15). But why is this the case? The authors of this study didn’t give a specific answer, other than mentioning that hypothyroidism is associated with insulin resistance, obesity, and diabetes.
However, these authors failed to mention how many of these people with hypothyroidism have an autoimmune thyroid condition. Remember that most people with hypothyroidism have Hashimoto’s Thyroiditis. And Hashimoto’s Thyroiditis is associated with proinflammatory cytokines, which also are associated with NAFLD. So it is possible that NAFLD can potentially trigger an autoimmune response, causing an increase in Hashimoto’s Thyroiditis. Although this hasn’t been proven, this would explain the increased prevalence of hypothyroidism in people with NAFLD.
Prevention and Treatment Of NAFLD
By reading this information you probably understand that the best way to prevent the development of NAFLD is to do what is necessary to prevent insulin resistance from occurring. On the other hand, for those who already have NAFLD, correcting insulin resistance should be the primary goal. Since oxidative stress plays a role in NAFLD, this also is something that should be addressed. Obviously eating well is important with anyone who has insulin resistance, as they want to eat a whole foods diet, while avoiding the refined foods and sugars. Regular exercise is also an important factor.
Supplementation is often necessary to help improve insulin sensitivity along with reducing inflammation and oxidative stress. Here are some nutrients which might prove to be beneficial in NAFLD:
Magnesium. A number of studies have demonstrated that magnesium improves insulin sensitivity and reduces insulin resistance (16) (17). And since insulin resistance is a key factor in NAFLD, oral supplementation with magnesium can potentially help to improve the health of people with this condition.
Chromium. Since chromium can also regulate glucose and improve insulin sensitivity it’s no surprise that there is evidence that chromium could serve as a hepatoprotective agent and prevent the progression of NAFLD (18).
Betaine. Aberrant DNA methylation contributes to the abnormality of hepatic gene expression, which is one of the main factors in the pathogenesis of NAFLD (19). Betaine is a methyl donor, and therefore plays an important role in methylation. One study showed that by restoring the methylation capacity, betaine supplementation might help to improve NAFLD (19). However, another study showed that betaine didn’t improve hepatic steatosis but may protect against worsening existing steatosis (20).
CoQ10. Since oxidative stress is a major factor with the development of NAFLD, many people with this condition can benefit from taking antioxidants such as CoQ10. Supplementation with CoQ10 can lower hepatic oxidative stress and inflammation (21).
Alpha Lipoic Acid. Alpha lipoic acid (ALA) is another powerful antioxidant, and it can also help with insulin sensitivity. As a result, it’s no surprise that there is evidence that ALA supplementation can help to prevent NAFLD, as well as benefit those who already have this condition (22) (23). Another study showed that the combination of flaxseed oil and ALA can prevent NAFLD (24).
Vitamin E. Due to its antioxidant properties, vitamin E can also be beneficial for those with NAFLD (25).
Omega 3 Fatty Acids. Omega 3 fatty acids can potentially help with NAFLD. One study showed that daily treatment with fish oil for six months improved lipid profile and blocked the oxidative stress and cytokines release (26). A few other studies show that omega-3 fatty acids can be beneficial in people with NAFLD (27) (28).
Vitamin D. Low vitamin D levels are associated with many chronic conditions, and insulin resistance is no exception. One study I came across showed that patients with NAFLD have significantly decreased serum vitamin D levels, suggesting that low vitamin D status might play a role in the development and progression of NAFLD (29). Since vitamin D modulates the immune system, a vitamin D deficiency is associated with numerous inflammatory conditions.
As I mentioned earlier, factors other than diet and exercise can be responsible for the development of NAFLD. For example, I mentioned earlier how someone might have NAFLD due to the presence of endotoxins or small intestinal bacterial overgrowth. Or perhaps they are taking a medication which is responsible for the condition.
In summary, there is a high prevalence of non-alcoholic fatty liver disease, and many people are unaware that they have this condition. Insulin resistance seems to be a big factor in the development of this condition, and oxidative stress is also a factor. As a result, doing things to help overcome insulin resistance and combat oxidative stress will help a great deal with this condition. With regards to thyroid health, NAFLD seems to be more common in people with hypothyroid conditions, although this doesn’t mean that people with hyperthyroidism and Graves’ Disease can’t have NAFLD. Certain nutrients which might be beneficial for people with NAFLD include magnesium, chromium, betaine, CoQ10, alpha lipoic acid, vitamin E, vitamin D, and the omega 3 fatty acids.