NAFLD, Non-Alcoholic Fatty Liver Disease, the Gateway to Diabesity - Which Supplements Help? A Dozen Suggestions
There's a whole arsenal of vitamins & herbals that's supposed to either protect you from or even cure NAFLD. |
It's directly liked to diabesity by its ties to insulin-resistance, obesity, and dyslipidemia, which are the main features of the metabolic syndrome (MS). NAFLD and MS are often seen in the same individual, and it has been reported that nearly 90% of the subjects affected by NAFLD, have more than one component of metabolic syndrome.
You can learn more about NAFLD at the SuppVersity
- an individualization of the diet aim to achieve energy restriction of 500-1000 kcal/d,
- a reduction of total fat and reduced saturated fat intakes to less than 30% of the total energy input,
- an increase in soluble fibre intake, and
- most importantly, a decrease or total elimination of refined sugars from the diet
Compared to the profound changes in how you life, medications and supplements are of reduced importance - if you don't change the former, the latter are not going to save you.
To understand which supplements are and which aren't useful NAFLD treatments, we have to initially learn about the pathogenesis of this ailment:
The pathogenesis of NAFLD is complicated and while its exact mechanism remains largely unknown, different genetic factors and/or environmental elements seem to influence it. The “two-hit hypothesis” of NASH, originally explained by Day and James suggests that lipid deposition in the liver (first hit) is followed by a series of other, oxidative and hepatotoxic processes (second hit), caused by a mechanism currently not known. Several factors such as genetics, epigenetic mechanisms, as well as environmental elements, appear to promote hepatocyte fat deposition and insulin resistance, both of which further lead to the secondary pathologic events, such as oxidative stress, lipid peroxidation, increased inflammatory responses, hepatic fibrosis and apoptosis. Other triggers such as lipotoxicity, endotoxemia, and adipocytokines or other inflammatory signals released from fat-infiltrated hepatocytes and adipose tissue, may promote oxidative stress in the liver, inducing the progression of NAFLD to NASH (Eslamparast. 2015 | my emphases).In view of the oxidative / inflammatory component of NAFLD, it is little surprising that the wide range of drugs and supplements that has been trialed as NAFLD treatment includes antioxidants and anti-inflammations. Likewise on the list of agents with positive short-term, but lacking long-term data on their efficacy are insulin sensitizers, and lipid lowering agents (Gossard. 2011). Accordingly, I do advise you to take none of the following agents, the description of which I partly borrowed from Eslamparast et al. (2015), not as proven NAFLD treatments, but as suggestions that may support the inevitable life-style changes described before:
- Vitamin E and vitamin C - not promising: No additional advantage over diet and exericse, alone for vitamin C supplements. A recent review article concluded that vitamin E is only recommended in adults with NASH who do not have diabetes or cirrhosis, or an aggressive histology (Pacana. 2012).
- Resveratrol - only low dose, long term: Just as it is always the case with resveratrol (3,5,4-trihydroxystilbene), a natural phenol produced by certain plants and found in the skin of red grapes, we do have promising rodent studies, in humans, however, clinical trials evaluating the effects of Resveratrol supplementation on NAFLD characteristics are scarce.
As Elsamparast et al. (2015) war, "a recent study, administering Resveratrol vs placebo for eight weeks, not only failed to show any significantly improvements in any NAFLD features in the Resveratrol group", what's worse, the study by Chachay et al. (2015) which used a high dose of 3,000mg of resvertrol per day also showed an increase in hepatic stress. - Anthocyanin - possible benefits: Anthocyanins (ACNs) are water-soluble bioactive compounds of the polyphenol class that are present in many plant based products such as blueberries, purple sweet potatoes and other dark blue / purple fruits and veggies. It has been reported that ACNs decrease hepatic lipid accumulation and may counteract oxidative stress and hepatic inflammation in animal studies.
Evidence from human studies is, you've guessed it, quasi non-existent. As Eslamparast et al. point out, "[t]here is only one study evaluating the effects of ACN on NAFLD patients; Suda et al. (2008) found that a high intake of a purple sweet potato beverage containing 400mg of acylated ACNs can reduce the levels of liver enzymes, in particular gamma-glutamyl transferases in patients with NAFLD - direct evidence of decreased liver damage or reductions in liver fat were yet not diagnosed, because they were simply not evaluated. - Green tea extract - insufficient evidence, but promising: In spite of a whole host of studies in mice and rats, there is no convincing evidence that green tea and EGCG helps with NAFLD in humans.
In contrast to what Eslamparast et al. say, there are yet studies that prove that green tea with high-density catechins can improves liver function and fat infiltration in non-alcoholic fatty liver disease (NAFLD) patients when it's consumed for 12 weeks (Sakata. 2013). - Coffee - protective effects proven, acute benefits exist, as well: While epidemiological and animal data leave little doubt that regular coffee consumption can protect you from developing NAFLD and T2DM, direct evidence as it is available in the form of a recent case-control study that compared coffee vs non-coffee drinkers and found that fatty liver occurred less frequently in coffee drinkers, and that drinking coffee was inversely associated with the degree of liver brightness, as well as obesity and insulin resistance is scarce (Catalano. 2010).
Figure 2: Scatter plot of fibrosis as a function of regular coffee caffeine (mg/day) - the more coffee he / she consumes the lower an NFLD patients risk of fibrosis (Molloy. 2012).
Nevertheless, ,ore research is needed to determine the NAFLD protective properties of caffeine and/or other coffee constituents like certain phytochemicals with potential antioxidant properties, which may also be protective against cardiovascular and liver diseases, and malignancies. - Garlic - smells promising, but proven only in in animal models: Garlic-derived S-allylmercaptocysteine (SAMC) has a therapeutic role in diabetes and nonalcoholic fatty liver disease due to its properties in the regulation of lipogenesis and glucose metabolism, it's effecs have been proven only in rodents (Xiao. 2013). In addition SAMC has more of ameliorative than protective effects and slows the progression, but does not block the development of NAFLD.
Figure 3: Graphical overview of the potential mechanisms by which garlic oil protects rodents from developing fatty liver; RCTs in human beings are still lacking (Lai. 2014). - Ginger - promising, but unproven: In theory ginger is an excellent anti-NAFLD agent that acts via both the activation of peroxisome proliferator-activated receptor gamma and the suppression of the fructose-stimulated overexpression of carbohydrate response element-binding protein (ChREBP) at the mRNA and protein levels in hepatocytes to reduce the inflammation and the development of fatty streaks in the liver.
Randomized clinical trials to confirm beneficial (long(er) term) effects in patients with NAFLD are yet missing... but I guess you already expected that ;-) - Insulin & lipid lowering supplements and anti-inflammatory agents like cinnamon, curcumin, quercetin, berberine, lipoic acid, coq10, carnitin and, as previously discussed, enough choline and whey protein - all promising, but insufficient evidence: Will probably help control many of the side effects of NAFLD and thus slow down it's progression. The evidence can be considered conclusive only for choline or rather the avoidance of choline defiency, though.
For the others, the only thing we have are impressive rodent studies with often exorbitant amounts of the active ingredients and a lack of clinical human studies like small scale study by Bortoletti et al. showing sign. reductions in liver fat in response to 60 g/day whey protein supplement (WPS) for 4-weeks in women with NAFLD (Bortolotti. 2011).Figure 4: Between-group comparisons of changes in biochemical and anthropometric variables in 44 men and women with NAFLD after 4 weeks on 100mg/day CoQ10 (Farhangi. 2014).
Complement A-C by ALA and vitamin E to protect yourself | more |
As previously stated, though, the lack of convincing evidence that any of the aforementioned interventions can totally protect you / even revers NAFLD is not the only reason you mustn't rely solely on supplements and minor changes of your diet. If you want to rid yourself of NAFLD, the most important thing you have to to is to rid yourself of the sedentary lifestyle and diet that's at the heart of (almost) all modern diseases | Comment on Facebook!
- Abenavoli, Ludovico. "Non-alcoholic fatty liver disease and beneficial effects of dietary supplements." World Journal of Hepatology 7.12 (2015): 1723.
- Bortolotti, Murielle, et al. "Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients." Clinical Nutrition 30.4 (2011): 494-498.
- Catalano, Daniela, et al. "Protective role of coffee in non-alcoholic fatty liver disease (NAFLD)." Digestive diseases and sciences 55.11 (2010): 3200-3206.
- Chachay, Veronique S., et al. "Resveratrol does not benefit patients with nonalcoholic fatty liver disease." Clinical Gastroenterology and Hepatology 12.12 (2014): 2092-2103.
- Eslamparast, Tannaz, et al. "Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease." World journal of hepatology 7.2 (2015): 204.
- Faghihzadeh, Forouzan, et al. "Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease." Nutrition Research 34.10 (2014): 837-843.
- Gossard, A. A., and K. D. Lindor. "Current therapies for nonalcoholic fatty liver disease." Drugs of today (Barcelona, Spain: 1998) 47.12 (2011): 915-922.
- Hashemi, Mohammad, Ali Bahari, and Gholamreza Bahari Saeid Ghavami. "Coenzyme Q10 may be effective in the treatment of non alcoholic fatty liver disease (NAFLD)." Journal of Medical Hypotheses & Ideas 2.1 (2008): 9-10.
- Lai, Yi-Syuan, et al. "Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver disease through modulation of lipid metabolism and oxidative stress." Journal of agricultural and food chemistry 62.25 (2014): 5897-5906.
- Molinari, Michele, et al. "Acute liver failure induced by green tea extracts: case report and review of the literature." Liver transplantation 12.12 (2006): 1892-1895.
- Molloy, Jeffrey W., et al. "Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis." Hepatology 55.2 (2012): 429-436.
- Pacana, Tommy, and Arun J. Sanyal. "Vitamin E and nonalcoholic fatty liver disease." Current Opinion in Clinical Nutrition & Metabolic Care 15.6 (2012): 641-648.
- Sakata, Ryuichiro, et al. "Green tea with high-density catechins improves liver function and fat infiltration in non-alcoholic fatty liver disease (NAFLD) patients: A double-blind placebo-controlled study." International journal of molecular medicine 32.5 (2013): 989-994.
- Sarkhy, Ahmed A., Abdulrahman A. Al-Hussaini, and Valerio Nobili. "Does vitamin E improve the outcomes of pediatric nonalcoholic fatty liver disease? A systematic review and meta-analysis." Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association 20.3 (2014): 143.
- Tarantino, Giovanni, and Carmine Finelli. "What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome?." World journal of gastroenterology: WJG 19.22 (2013): 3375.
- Xiao, Jia, et al. "Garlic-derived S-allylmercaptocysteine ameliorates nonalcoholic fatty liver disease in a rat model through inhibition of apoptosis and enhancing autophagy." Evidence-Based Complementary and Alternative Medicine 2013 (2013).
- Zelber-Sagi, Shira, et al. "Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up." Journal of hepatology 56.5 (2012): 1145-1151.