Non-Alcoholic Fatty Liver Disease - part 1

Non-Alcoholic Fatty Liver Disease (NAFLD) is a growing concern, especially for post-menopausal women. It is a chronic progressive disease that develops as a result of excessive accumulation of triglycerides in the liver in the absence of excessive alcohol consumption.

It affects roughly 30% of the population. This is based on a 2019 global systemic review and meta-analysis involving over 5 million people. What is scary is the speed of increase with this upward trend, especially for women. The general prevalence is higher in men than women but this trend is rapidly changing especially for post-menopausal women. The peak age for diagnosis in women is between 60-69. The other alarming change is that women are not only developing this disease more often but they are also progressing through the stages faster with a higher need for a liver transplant and an increased mortality rate overall. 

In case you are wondering there are 3 stages. The stages are assessed by looking at how many hepatocytes (liver cells) contain visible triglycerides. It is considered normal to have under 5%. Grade 1 is 5-33%, Grade 2 is 34-66% and grade 3 is SEVERE and is greater than 66%.

If you qualify and are lucky enough to receive a liver transplant, NAFLD reoccurrence is common and can be present in 3/4 of the recipients. So you can see it's all about the terrain. If you continue with the dietary and lifestyle factors that produced a fatty liver in the first place, replacing it may give you some more time but ultimately it doesn’t solve your problem.

The development of NAFLD is linked with both the rising obesity epidemic and the diagnosis of type 2 diabetes. More than half of post-menopausal women with type 2 diabetes also have NAFLD.

Heart disease also falls under this umbrella, it may be a 2 way street (with low HDL cholesterol levels having a plausible role to play) but it's more likely to be a part of the disease progression.

So everyone agrees these 3 organs are intimately linked together. A weakness in one area increases your risk for issues in the other organs. These 3 organs are the pancreas, the liver, and the heart.

So why the increase in diagnosis for post-menopausal women? 

Many studies imply it must be due to the reduction in estrogen levels that is causing this. 

Estrogen is thought to slow the progression by suppressing inflammation, improving mitochondrial function, alleviating oxidative stress, insulin resistance, and fibrogenesis. The loss of estrogen is also linked with metabolic changes and the increase in both the diagnosis of diabetes and heart disease.

This is where a conflict in the research lies. If estrogen is the causative factor you would think that taking hormone replacement may be the answer but this may not be the case, it may actually increase your risk. This is very controversial, the jury is out here, and more research is definitely needed.  

One study that pointed to the increased risk is called “The association of endogenous sex hormones with fatty liver” (link in references below). They understood that circulating sex hormones change our ability to metabolism glucose and store fat. They also understood that more hormonal changes occur with menopause than just estrogen reduction. They also looked at Testosterone, DHEA, and Sex Hormone Binding Globulin (SHBG). This study involved 2835 post-menopausal women. They found that having lower levels of estrogen is protective against the development of NAFLD compared to higher levels of estrogen. The form of estrogen they measured in this study was estradiol or E2. E2 is the main form of estrogen produced by the ovaries in fertile-aged women and found in most Menopause Hormone Therapy (MHT) but not the main form produced by a woman who has naturally transitioned into menopause. This form is estrone or E1. 

The other findings mentioned in this study included an increased risk with lower SHBG, lower DHEA, and increased testosterone. These findings link these results with other studies that found women of reproductive age who have polycystic ovarian syndrome are also at an increased risk of NAFLD, as this hormone pattern especially the increased testosterone and lowered SHBG match these findings.

Just to summarise lower estradiol and lower testosterone levels may be protective against developing NAFLD.  Having higher SHBG and higher DHEA is seen to be protective.

For those who haven’t heard of SHBG before it's a globulin produced by the liver that binds to sex hormones, especially estrogen and testosterone. You may have seen in your blood work before a result for free and total hormones and these numbers will be different. The free hormone is the active hormone, the total figure includes the free hormones plus the bound inactive hormones. SBHG is the difference. So when SHBG goes down, free estrogen and testosterone numbers go up. 

What you need to take away today is that insulin plays a controlling role in the production of SHBG. The higher your insulin levels the lower your SHBG. As discussed before insulin and blood sugar dysregulation increase fatty liver. Can you see its all connected? One of the joys of being a naturopath is looking at the body as a whole and connecting the dots. 

You need to address the elephant in the room. Insulin. How can you improve your insulin sensitivity and reduce your overall insulin production? It may start with increasing your exercise, maybe you add a daily walk to your routine. It may start by removing and reducing sugar and other processed foods, maybe it starts with adding more protein and better-quality fats to your diet. I really hope you understand the difference between good fats and bad fats as increasing good fats may actually be a part of your solution. Maybe you stop snacking. Maybe you start a nutritional supplement or pharmaceutical medication. You need to start here,  part 2 builds on this and adds further steps.

It is my professional opinion that elevated insulin levels and reduced insulin sensitivity are the starting point. This is the reason many start gaining weight, it's the difference between having normal blood sugar readings and pre-diabetes and its progression into type 2 diabetes. It's the reason why SHBG lowers and there’s one more thing. Higher insulin levels may also increase uric acid levels. Elevated uric acid has been found to be yet another independent and significant risk factor in the development of NAFLD. If you are wondering if this is the same uric acid as the one linked to gout, yes it is. It’s the natural waste product from the digestion of foods that contain purine. 

Stay tuned for Part 2 for a deeper dive into the prevention and possible treatment for Non Alcoholic Fatty Liver. 

I also offer private consultations if you would like a hand in creating a unique treatment plan just for you. Click here to book an initial appointment

References

Menopause and Non Alcoholic Fatty Liver Disease:  A review focusing on Therapeutic Perspectives. 

https://pubmed.ncbi.nlm.nih.gov/29992886/

The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause. 

https://pubmed.ncbi.nlm.nih.gov/34446275/

The association of Endogenous sex hormones with liver fat

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500744/

2019 Global NAFLD Prevalence: a Systematic Review and Meta-Analysis

https://www.sciencedirect.com/science/article/abs/pii/S1542356521012805

Non alcoholic steatohepatitis reoccurrence after liver transplant

https://www.sciencedirect.com/science/article/abs/pii/S1542356521012805