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Should you freak out about a small increase in body weight in a small-scale rodent study that is attributed to the consumption of saccharin in yogurt?

While epidemiological studies show that the consumption of products containing non-nutritive sweeteners (NNS) is associated with increased adiposity (Colditz. 1990; Fowler. 2008), type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular disease (Dhingra. 2007; Lutsey, Steffen. 2008). A mechanistic link between aspartame, sucralose, stevia & co and weight gain as well as its ill metabolic and cardiovascular consequences in humans is non-existent (learn more).

Rather than weight increases controlled human studies show that the consumption of artificially sweetened foods promote, not hinder the loss of body fat (Sørensen. 2014).
In animal models, though, the results have been more conflicting. While many studies show no effect of artificial sweetener consumption, the latest stud by Kelly Carraro Foletto and colleagues is not the first rodent study to suggest that non-nutritive sweeteners may also interfere in the regulation of compensatory appetite promoting weight gain (Davidson. 2011; Polyák. 2010; Rogers. 1988). This does yet not refute the findings of one of the latest meta-analysis of the effects of low-energy sweetener consumption on energy intake and body weight in man - a meta-analysis published in Nature's prestigious International Journal of Obesity that says...

Figure 1: The forest plots of the practically most relevant data of individual and combined effect sizes for sustained intervention studies comparing the effects on body weight of sweeteners versus sugar (upper panel) and versus water (lower panel) shows that not a single long(er) term study found negative effects - the exact opposite is the case. Even compared to water the use of low-energy sweeteners (artificial or not) lead to measurable, yet not always significant decreases in body weight in human trials (Rogers. 2015).

"that the balance of evidence indicates that use of LES [low or no energy sweeteners] in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water" (Rogers. 2015 | my emphasis).

And with respect to the often-cited "evidence" from animal and observational studies, the autors of the meta-analysis submit that...

"[...] the present review of a large and systematically identified body of evidence from human intervention studies, with varying designs, settings and populations (including children and adults, males and females, and lean, overweight and obese groups), provide no support for that view. The question then is whether those hypotheses should be rejected or whether, as seems unlikely, the relevant human intervention studies are consistently flawed in a way that leads, in most cases, to exactly the opposite outcome" (Rogers. 2015)

I do thus want to warn you: Do not overrate the already relatively small amount of extra-weight the rodents in saccharin group of Foletto's recent study gained (see Figure 2, left).

Figure 2: Cumulative weight gain and total cumulative energy intake of (only) 16 male Wistar reds fed diets that were supplemented with either saccharin-sweetened or non-sweetened yogurt added (Foletto. 2015)

In a previous study, Folleto et al. had already observed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. In their latest study they did not try to prove that this effect is independent of the rodents' energy intake and mediated by insulin-resistance and / or modified levels of leptin and PYY in the fasting state.
To this ends, the researchers randomly assigned 16 male Wistar rats to receive ~78kcal per week from either saccharin-sweetened (0.3% saccharin) yogurt or non- sweetened yogurt (0.5 kcal/g) in addition to chow (2.93 kcal/g) and water ad lib. For 14 weeks, Foletto, et al. measured the total food intake (from yogurt and chow) daily and the weight gain on a weekly basis (the results are plotted in Figure 2). Fasting leptin, glucose, insulin, PYY and HOMA-IR levels were measured only at the end of the 14-week study period, though.

Table 1: In view of the fact that any existing negative effects of dietary sweeteners may well be compound-specific. It is certainly worth noting that saccharin is no longer used in modern sweetener formulations of sodas (Wikipedia. 2015)

In spite of the already reported ~5% increase in cumulative weight gain over 14 weeks (p=0.027), the researchers found no differences in HOMA-IR (=insulin resistance), fasting leptin or PYY levels between groups that could mechanistically explain why the rodents who received saccharin sweetened yogurt gained more weight than their peers who received non-sweetened yogurts.
References:

• Foletto, Kelly Carraro, et al. "Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats." Appetite (2015).
• Rogers, P. J., et al. "Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies." International Journal of Obesity (2015).
• Sørensen, Lone B., et al. "Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects." The American journal of clinical nutrition (2014): ajcn-081554.

Whether having breakfast will help or hinder glucose control will also depend on its macronutrient composition and carbohydrate content. In their 2011 study Pereira et al. were able to show that a high carbohydrate, high GI breakfast will have a similarly negative impact on glucose control of adults and children as having no breakfast at all (Pereira. 2011).

Intermittent fasting (IF), i.e. skipping breakfast and/or other meals in order to stay fasted for ~16h+ per day is no longer "all the rage", but still highly popular among people who believe in its health and weight loss benefits. And in fact, there is some research (also from a couple of Ramadan studies) that appears to confirm the notion that it is healthy and may - even without deliberate caloric restriction - facilitate weight and more importantly fat loss.

On the other hand, intermittent fasting conflicts with everything we've been (falsely?) told about the benefits of frequent meals. Benefits of which waredownloadsoft readers know that they are quasi-non-existent, in most healthy individuals and sometimes even counter-productive in obese and diabetic individuals, where most studies refute that eating more frequently provides significant weight loss benefits in the context of a calorically restricted diet.
Now, a recent study from the Diabetes Unit, Wolfson Medical Center of the Sackler Faculty of Medicine at the Tel Aviv University, the Lund University in Sweden and the Hebrew University of Jerusalem (Jakubowicz. 2015) suggests that extending your overnight fast by skipping breakfast may have real (not just corollary) detrimental effects on habitual breakfast eaters (learn why this is important) who are suffering from type II diabetes (with glycated hemoglobin (HbA1c) levels of 7–9% (the subjects in the study at hand were more than just pre-diabetic).

In this group of subjects, skipping breakfast increases post-prandial hyperglycemia (PPHG) after lunch and dinner. It lowers the important GLP-1 response to the meals (learn more about how GLP-1 is important in "Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?") and impairs the subjects' already messed up insulin response. More specifically,

• Three meals may be ok, but six meals are actually counterprodutive in T2DM.

  the lunch AUC0-180 for glucose, FFA, and glucagon were 36.8, 41.1 and 14.8% higher, respectively, and the AUC0-180 for insulin and  iGLP-1 17.0% and 19.0% lower, respectively, on the NoB[reakfast] day compared with the YesB[reakfast] day (P < 0.0001), 
• the dinner AUC0-180 for glucose, FFA, and glucagon were 26.6, 29.6, and 11.5% higher, respectively, and the the AUC0-180 for insulin and iGLP-1 were 7.9% and 16.5% lower on the NoB day compared with the YesB day (P < 0.0001), on the other hand

Whether the conclusion that "[b]reakfast consumption could be a successful strategy for reduction of PPHG [prostprandial hyperglycemia] in type 2 diabetes" applies to every type II diabetic is yet as questionable as the assumption that you could extrapolate the data from this acute phase study and use it to predict the long-term response in diabetics, let alone health individuals.

Figure 2: Hunger, satiety, plasma glucose and insulin in the Eaters and Skippers in the two conditions in Thomas (2015).

If we go back to Thomas' recently published study (I have discussed it in detail here), it is after all obvious that the scientists choice of subjects who consume breakfast regularly may have thwarted their results. I mean, the researchers from the University of Colorado School of Medicine and the Denver Health Medical Center have shown quite conclusively that one's breakfast habits will determine whether skipping breakfast increases insulin, hunger and blood lipids or not.
References:

With the right diet and lifestyle, stem cell treatments, probiotic supplements or xylose-laden "functional foods" wouldn't be necessary in the first place.

You're probably used to it, but I am in the mood for bragging: The waredownloadsoft is where you'll read about the latest nutrition, exercise and supplement related studies first. In research updates like the one today, I am trying to provide a little more information than in the SV Facebook News, though, where I usually stick only to the main results of studies that have just been published or at least accepted for publication.

In today's installment of what I often call the "Short News", I will discuss three papers that are going to be published in one of the next issues of the peer-reviewed scientific journal Nutrition News.

Studies dealing with a pre-clinical, but promising stem cell therapy for diabetics, the verdict on probiotic supplements (including my evaluation of the scientists' verdict ;-) for weight loss and an update on the effects of the xylitol precursor d-xylose and its effect on mammalian fat cells in vivo.

• Stem Cells as Diabetes Treatment (Xing. 2015) - In software development you'd probably call the latest study from the Cangzhou City Central Hospital an "early alpha version" of an intriguing new way of treating type II diabetes.
  
  In their latest rodent study, Baoheng Xing et al. build on previous experiments in which pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice (Kroon. 2008). In their study, however, Xing et al. went one step further and developed a system for treating diabetes using human embryonic stem cell–derived pancreatic endoderm in a mouse model of gestational diabetes mellitus.
  

  Figure 1: Glucose (a), insulin (b) and body weight (c) levels of wild type (wt) and treated (db/+PE) vs. untreated (db/+) pregnant mice before and during gestation, as well as Kaplan-Meier survival curves of litters show significant improvement right into the normal range in response to treatment (Xing. 2015)

  To this ends, the researchers had human embryonic stem cells differentiate in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus.
  
  As the data in Figure 1 goes to show you, the transplant, of which the researchers expect that it could be used in humans, too, greatly improved the glucose metabolism and reproductive outcome of the treated female rats compared with the control groups. With their results Xing et al. do thus contribute to the growing evidence that diabetes may (sooner or later) be a "curable" disease when we are eventually mastering the use of differentiated human embryonic stem cells for treating general and gestational diabetes mellitus patients.
• Probiotics and weight loss - reviewed (Park. 2015): What's the verdict? You will remember that I am still skeptical with respect to the real world benefits of the new en-vogue supplements that contain billions of life or dead bacteria and promise benefits from increased gut health to... you guessed it, the most marketable of all benefits: weight loss!
  
  A recent systematic review by scientists from the Hoseo University and the Keimyung University in Korea presents the first attempt to summarize and critically evaluate the evidence from clinical trials that have tested the effectiveness of probiotics or foods containing probiotics as a treatment for weight loss. Literature searches of electronic databases such as PubMed, Cochrane Library, and EMBASE were conducted. Methodological quality was assessed using body weight and body mass index (BMI). Initial searches yielded 368 articles. Of these, only 9 met the selection criteria. Because of insufficient data, only 4 of the studies were randomized controlled trials (RCTs) that compared the therapeutic efficacy of probiotics with placebo.
  
  As my skepticism would have made me believe, the meta-analysis of these data showed no significant effect of probiotics on body weight and BMI (body weight, n = 196; mean difference, −1.77; 95% confidence interval, −4.84 to 1.29; P = .26; BMI, n = 154; mean difference, 0.77; 95% confidence interval, −0.24 to 1.78; P = .14).
  

  Figure 3: It's not like there were no benefits. You just have to look at the right parameters to see them. Studies like Kadooka et al. show that the effects on BMI are small compared to those on metabolically more relevant markers like total fat mass, waist circumference and visceral fat (Kadooka. 2015).

  That does not mean that there are no benefits at all, though. I reviewed the few studies that measured not just body weight and BMI, but also the subjects' body fat levels. This is an important difference, because a focus on BMI ignores potentially health relevant changes in body composition. Changes as they were observed by Kadooka et al. (2013; see Figure 3), for example, who found a significant time x group differences for visceral fat, fat percentage, fat mass, and waist circumference with much less pronounced effects on BMI (too low to influence the result of a systematic review significantly) in their 12-week study. In this context, it is also worth mentioning that Sanchez et al. (2014) observed a significant beneficial effect in obese women (but not man) for whom the consumption of 1.6 × 10^8 colony-forming units of LPR/capsule with oligofructose and inulin made it significantly easier to maintain their body weight after a weight loss intervention. Another benefit that must not be ignored.

• Overall, I still feel obliged to repeat what I wrote in my recent article on the effects of sweeteners on the microbiome: We still have to learn very much about the effects of probiotics in general and individual types of gut bacteria, in particular, before we can actually give good strain-specific supplement recommendations. It's after all possible that the same strains that work in the obese subjects of studies like Kadooka (2015) won't work or even do the opposite in lean individuals.
• D-Xylose Exerts Epigenetic Anti-Obesity Effects and Stops Fat Cell Growth (Lim. 2015) - Yes, this is not the first study to show that the provision of D-Xylitol or, as in the case of a 2011 study by Amo,et al., its cousin and "artificial sweetener" xylitol can reduce the weight gain due to obesogenic diets. What makes it interesting, though, is that it involved two different, relatively low dosages of D-xylitol as they could easily be added to our own food chain.
  

  Figure 4: While the effects on body weight and fat gain were significant, the differences (expressed relative to the rodents on regular chow) are still significant, so even if you replace 5-10% of the sugar in your junkfood diet with the low calorie sweetener (2.4kcal/g), you will get fat. If anything it may completely prevent the increase in liver fat - albeit only if the dosage is high enough and the effects are identical in humans (data from Lim. 2015)

  With only 5% and 10% of the sucrose content of the high fat chow of the rodents in Lim et al.'s latest study being replaced by D-Xylose, the scientists observed
  • significant reductions in weight and more importantly fat gain
  • significant reductions in hepatic steatosis (NAFLD),
  • a reduction of the genes that are responsible for the storage of fat to normal (5%) and sub-normal (10% D-Xylose) levels, and
  • significant reductions in total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and the important total cholesterol/high-density lipoprotein ratio.
  In view of the fact that replacing just a relatively small amount of sucrose in our diet with D-Xylose (and probably xylitol) can ameliorate the weight and adipose tissue gain, normalize blood glucose levels and blood lipid profiles and lower the lipid accumulation in the liver by "regulating expression of lipogenesis- and β-oxidation–related genes" (Lim. 2015), it is probably actually warranted to speculate, just like Lim et al., about a "possible application of d-xylose as a dietary supplement for the prevention of obesity-related metabolic disorders" (Lim. 2015) - even though clinical human trials are still warranted.

There's a whole arsenal of vitamins & herbals that's supposed to either protect you from or even cure NAFLD.

NAFLD is emerging as one of the most common chronic liver diseases worldwide, and represents one of main cause of hepatology referral in some centers. NAFLD is a clinical syndrome that ranges from simple fatty liver, to non-alcoholic steatohepatitis, to advanced fibrosis, and cirrhosis.

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.
In that, the reasons for developing NAFLD are not fully elucidated, but observational studies clearly point to the high(er)energy, and in particular to a greater carbohydrate intake of NAFLD patients compared with the healthy subjects (Tarantino. 2013). In spite of the fact that Abenavoli is right when he says that supplements can only be an adjunct to lifestyle modifications, i.e. modifications and physical exercise, or as he specifies it,

• 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

These dietary modifications alongside physical activity of at least 60 min/d on initially 3 d/wk, later 5 d/wk should aim for a weight loss of 5% to 10%, which in turn will ameliorate the effects of NAFLD, even before any weight is lost (Keating. 2012).

Table 1: Meta-analysis of the pooled effect of exercise vs. control on liver fat with sub-analysis of: the effect of combined exercise and diet vs. diet and exercise vs. non-exercise control (Keating. 2012).

Only in conjunction with significant and permanent weight reductions, though it is possible you can hope to send NAFLD into remission.

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).
  

  Table 2: The meta-analysis comparing the effect of vitamin E to the placebo for the proportion of participants with normalized ALT is more than disappointing, because there's no effect of vitamin E (Sarkhy. 2015)

  In a meta-analysis, adjuvant vitamin E was not shown to have a significant effect on normalizing serum ALT levels. Using higher doses of vitamin E, a longer duration of therapy or adding vitamin C did not alter the effect of these antioxidants on the measured outcomes either (Sarkhy. 2014). As Elsamparast et al. (2015) point out, there's a paucity of evidence "on the long-term effects of vitamin E use on histological improvements of NAFLD patients, which calls for larger, well-designed randomized controlled trials (RCTs) with histological endpoints, to really determine the efficacy of its use".
• 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.
  

  Table 3: The effects of resveratrol and placebo intake on serum level of liver enzymes and bilirubin at baseline and after 12-week treatment; in contrast to high dose short-term resvertrol treatments that even had detrimental effects, the Fagihzadeh study (2014) shows unmistakable benefits.

  In view of the fact that a different trial did find a significant improvement in NAFLD characteristics after 12 wk of supplementation with 500 mg Resveratrol (Faghihzadeh. 2014), it does yet appear logical to assume that dose and duration of Resveratrol administration is important in its efficacy.
• 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).
  

  Figure 1: It's not as if there was no human data suggesting that consuming high polyphenol green tea for 12 weeks can have beneficial effects no NAFLD patients like this (Sakata. 2013), but the number of randomized controlled studies is still low and the evidence inconclusive.

  With the Sakata study being the only double-blind placebo-controlled study in humans, the evidence must still be considered preliminary, though, and could be related (solely?) to the reduction in body fat of which the only longer-term study investigating correlates of NAFLD remission says that it is the #1 (if not only) predictor of NAFLD remissin (Zelber-Sagi. 2012). In addition the possibility of heavy metal contamination may more than reverse any beneficial effect and have green tea and green tea extracts - as it has previously been demonstrated, by the way (Molinari. 2006) - contribute to instead of relieve liver disease.
• 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).

  What is beyond doubt, though, is that among NASH patients, coffee consumption has been shown to be significantly associated with a reduced 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).

  The same can and must be said for garlic essential oil (GEO) and its major organosulfur component diallyl disulfide (DADS), which has anti-obesity and anti-hyperlipidemic and may thus slow down the progression of NAFLD (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).

  In addition, if there's evidence that something works, like CoQ10, for example, the human data that's available for CoQ10 (see Figure 4) may be considered problematic, because many other studies have been heavily sponsored.

References:

• 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.