Nonalcoholic Fatty Liver Disease, or NAFLD, is a widespread disease that affects about one-fourth of the world's population. It is also the most common chronic liver disorder, as discussed in this article link:
https://medlineplus.gov/fattyliverdisease.html
Here is a relevant quote from the article:
'NAFLD affects about 25% of people in the world. As the rates of obesity, type 2 diabetes, and high cholesterol are rising in the United States, so is the rate of NAFLD. NAFLD is the most common chronic liver disorder in the United States.'
The above article further shows the following important facts about NAFLD in these quoted statements:
1. Both NAFLD and alcoholic fatty liver disease are usually silent diseases with few or no symptoms. If you have symptoms, you may feel tired or discomfort in the upper right side of your abdomen.
2. There are no medicines that have been approved to treat NAFLD. Studies are investigating whether a certain diabetes medicine or Vitamin E can help, but more studies are needed.
3. Both alcoholic fatty liver disease and one type of nonalcoholic fatty liver disease (nonalcoholic steatohepatitis) can lead to cirrhosis. Doctors can treat the health problems caused by cirrhosis with medicines, operations, and other medical procedures. If cirrhosis leads to liver failure, you may need a liver transplant.
4. Doctors recommend weight loss for nonalcoholic fatty liver. Weight loss can reduce fat in the liver, inflammation, and fibrosis. If your doctor thinks that a certain medicine is the cause of your NAFLD, you should stop taking that medicine. But check with your doctor before stopping the medicine. You may need to get off the medicine gradually, and you might need to switch to another medicine instead.
Doctors typically suggest exercise, weight loss, reduced fat intake, and a healthier diet to improve NAFLD. This often proves challenging to do faithfully, making NAFLD a problematic health issue for many people.
Another problem is that the lack of potential symptoms means that many people never even realize they have NAFLD until significant liver damage has occurred.
Given the above information, it would be advantageous to find supplements that can help to reduce NAFLD and help protect the liver in a meaningful way. Along that line of thinking, the following studies will illustrate how the common supplement Astaxanthin (AST) may be just such a supplement!
In this first 2020 study, it is suggested that AST in previous studies has shown the potential to act as a preventative and offers benefits against liver fibrosis, NAFLD, liver cancer, and other forms of liver injury :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293384/
Here is a relevant quote:
In clinical trials, a prospective, randomized, double-blind study confirmed the effect of astaxanthin on oxidative stress in overweight and obese adults in Korea. Twenty-three adults with a body mass index >25.0 kg/m2 were enrolled in this study and randomly divided into two dosage groups: astaxanthin 5 mg or 20 mg once a day for 3 weeks. The results showed that the oxidative stress markers, malondialdehyde (MDA), isoprostane (ISP), SOD, and total antioxidant capacity (TAC) were significantly improved.
In this next 2020 research paper, it is suggested that AST has liver fat-reducing effects:
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.15099
Here is an important conclusion from their research:
Astaxanthin attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by up-regulating FGF21/PGC-1α pathway. Our results suggest that astaxanthin may become a promising drug to treat or relieve NAFLD.
In yet another more recent study (August 2022), AST also showed itself to be interestingly beneficial in the fight against NAFLD via manipulation of the gut microbiome:
https://pubmed.ncbi.nlm.nih.gov/35973099/
Here is a relevant quote from the study illustrating multiple positive effects of AST :
Significant mitigation in lipid metabolism-related disorders and decreased oxidative stress in HFD-induced mice were observed due to AT, and significant changes in the gut flora of the model mice were also observed. The in vitro study showed that AT considerably lowered the protein expression level of fatty acid synthetase (FAS), sterol regulatory element-binding protein-1c (SREBP-1c), and acetyl-COA carboxylase (ACC) and increased the protein expression of nuclear factor-E2 associated factor 2 (Nrf2) and AMP-activated protein kinase (AMPK) in oleic acid (OA) and palmitic acid (PA)-induced HepG2 cells. Additionally, mechanistic studies revealed that compound C (AMPK inhibitor, CC) inhibited the regulatory effect of AT on the SREBP-1c and Nrf2 signaling pathways.
In this concluding study, there is further confirmation of the ability of AST to ameliorate NAFLD via multiple protective activities in the liver:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293384/
Here is a relevant quote from the study identifying some of the liver protective actions of AST:
Studies have shown that astaxanthin has preventive and therapeutic effects on liver fibrosis, liver tumors, liver ischemia-reperfusion injury, non-alcoholic fatty liver and other related diseases. Astaxanthin not only has a strong antioxidant effect but also can regulate many signal pathways. For example, it reduces JNK and ERK-1 activity to improve liver insulin resistance, inhibits PPAR-γ expression to reduce fat synthesis in the liver, down-regulates the expression of TGF-β1/Smad3 to inhibit the activation of HSCs and liver fibrosis, inhibits the JAK/STAT3 and Wnt/β-catenin signaling pathways to inhibit liver tumors, and inhibits apoptosis and autophagy to protect against liver ischemia-reperfusion injury.
As you can see from these studies, AST appears likely to be beneficial in fighting NAFLD and in liver protection in general from multiple liver health issues.
Although only one of these studies details the dosing used, which was 5 mg or 20 mg of AST, both of which were beneficial in that study, other human studies utilizing AST have found beneficial effects in a similar dosing range, with the highest dose used being 24 mg/day.
I personally take 24 mg per day now after having taken 48 mg/day for a test of AST, which I wrote about here:
https://www.earthclinic.com/supplements/astaxanthin-for-endurance.html.
AST has a very good safety profile at study dosing of 24 mg or less and, from my perspective, has been very well tolerated as in I have experienced no negative side effects from taking it.
In my previous test of Astaxanthin for improving endurance, I used this product on Amazon to good effect.
The next supplement for NAFLD that I would like to discuss is Melatonin which also has a very good safety profile, is inexpensive, and has shown benefits against NAFLD in human studies.
The first study (2017) link is a randomized controlled trial (RCT) which used a total of 100 participants and cuts clearly to the point in their conclusion :
Here is the straightforward conclusion that this study reached :
The findings of this study show that melatonin significantly decreases liver enzymes in cases than placebo, therefore, the use of melatonin in patients with NAFLD can be effective. Also, NAFLD as the fast developing disorder needs serious and immediate attention, especially in the context of modern life style.
In this next study (2020), another RCT utilizing 45 participants, they go into more detail of the effects that melatonin is having in people with NAFLD :
https://www.sciencedirect.com/science/article/abs/pii/S0965229920304258?via=ihub
Here is a relevant and descriptive quote from the study:
The current randomized clinical trial administrated 6 mg/day melatonin and showed significant improvement in most factors related to NAFLD, such as anthropometric measurements (weight, waist and abdominal circumference), systolic and diastolic blood pressure, lipid profiles, inflammatory mediators, also serum levels of leptin and adiponectin. In addition, the important signs of NAFLD such as liver enzymes and the grade of fatty liver were improved.
In this final study using melatonin in people with NASH, they highlight the liver enzyme lowering effects of melatonin, which of course would be very important in treating liver diseases in general. What is interesting and very important about this study is that NASH would be considered a more advanced form of NAFLD because NASH not only means there is elevated fat levels in the liver, but there are also elevated inflammatory levels, elevated oxidative stress levels and there are also elevated liver enzyme levels present.
https://www.jpp.krakow.pl/journal/archive/02_12/pdf/35_02_12_article.pdf
Here is an important statement from the study:
Enrolled patients had biochemical determinations every six weeks during the melatonin treatment period and again after 12 weeks of follow-up. Significant reduction in median alanine aminotransferase (ALT) levels between baseline and week 18, week 24 and follow-up was observed in both MT-treated and control group: 43% and 31%, 42% and 33%, 32% and 31%. Aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) levels decrease significantly only in MT-treated group. In MT-treated group mean percentage change in AST level below baseline at week 18, at week 24 and at follow-up was 45%, 33% (p<0.05) and 8% (ns), respectively. The evolution of GGT levels was as follows: the mean percentage reduction in GGT below baseline level at week 18,24 and follow-up was: 48%, 52% and 38% (p<0.05), respectively. In both MT-treated and control group plasma cholesterol, triglicerydes and glucose concentrations as well as plasma alkaline phosphatase persisted within normal values during the prolonged study period. Plasma concentration of melatonin (pg/ml) in MT-treated group averaged 7.5±3.5 at baseline and increased to 52.5±17.5 at 24th week. The results of our study demonstrating beneficial effect of melatonin on liver enzymes in patients with NASH would seem to encourage further controlled trials of melatonin given over a longer period of time with liver histology as end point.
In the second study, they used 6 mg of melatonin per day. In the third study, they used 10 mg per day in two divided doses of 5 mg each. The 10 mg study seemed to have significantly lowered liver enzyme levels. Since I take both of these supplements myself, I have some familiarity with them. I now take 24 mg/day of Astaxanthin with melatonin because of hundreds of studies showing many health benefits from its use, I also take it every day at high doses as a potential preventative against multiple health issues, with the number one issue being the prevention of CVD because heart disease is the number one killer in the world and melatonin is heart protective.
As regards NAFLD dosing, 10 mg/day was clearly beneficial in the third study.
I have written extensively about melatonin on Earth Clinic, so I am aware of many of the effects of melatonin in humans, and there is an important point I would like to make here. NAFLD affects approximately 25% of the world's population!
When you have NAFLD, you are at increased risk for more serious liver disease, but the downside doesn't stop there because when you have NAFLD, you are also at increased risk for cardiovascular disease (CVD). Previously I have written about how melatonin helps protect against CVD and has also shown benefits as a treatment for CVD. In other studies, melatonin has shown benefits in different types of liver disease.
Here is a link to the article on the use of melatonin for CVD:
https://www.earthclinic.com/cures/melatonin-for-cardiovascular-disease.html
Add in the multiple potent effects of Astaxanthin, and you not only have a combination of supplements to combat NAFLD but also protect and improve your health in general!
Art
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