Question: Does the increase in the n6/n3 ratio, common in the Wester diet, cause deposition of fat in the liver? Does decreasing the fatty acid ratio to the lower levels that were common decades ago promote the shedding of liver fat?
Takeaway: A simple reduction of the n6/n3 ratio, even without a caloric reduction, will reduce fatty liver in adolescents in the absence of weight loss.
One of the characteristics of the modern Western diet is a massive imbalance in the ratio of omega-6 fats (n6) to omega-3 fats (n3) (i.e., the n6/n3 ratio). This change has been driven primarily by an enormous increase in n6 fat intake over the past 40 years, while the amount of n3 fats in the diet has remained stable or even decreased a little. The typical n6/n3 ratio in Westernized countries is ~15:1 (if not higher), whereas that in pre-industrial-seed-oil times was closer to ~4:1 (if not lower).
Concurrent with this enormous distortion of the n6/n3 ratio has been an increased prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and even children. Medical authorities have posited multiple causes for this troubling increase in NAFLD, which could be considered to have reached epidemic proportions, since estimates suggest approximately a quarter to a third of adults are affected. The condition is now common even in adolescents.
The authors of this 2019 study hypothesized the increase in the n6/n3 ratio causes deposition of fat in the liver, and decreasing the fatty acid ratio to the lower levels that were common decades ago might promote the shedding of liver fat. Toward that end, they designed the experiment to determine what, if any, reduction in liver fat would occur solely from a change in diet that achieved a large decrease in the n6/n3 ratio while maintaining a weight-stable caloric intake.
In this single-arm trial, investigators recruited 20 obese adolescents, all of whom had fatty livers, into the study. They chose adolescents, because NAFLD is a growing problem in this demographic, and adolescents are notorious for consuming copious amounts of junk foods typically composed of a combination of wheat and/or corn, sugar, and vegetable oils with a high n6/n3 ratio.
The subjects then were prescribed a diet equal in calories to their starting diets but with a much lower n6/n3 ratio; they consumed only foods provided by the investigators. Calories were adjusted throughout the 12-week duration of the study to ensure the subjects were adhering to intake levels sufficient to maintain their starting weight, obviating weight loss as an attributable cause for any changes observed.
Abdominal MRI and oral glucose tolerance testing were performed at the start and again at the end of the 12-week trial. During the trial, investigators monitored OXLAMs (oxidized derivatives of linoleic acid, the primary unsaturated fat in vegetable and seed oils) to ensure compliance.
By the end of the study, among the 17 subjects who had completed the trial, liver fat had decreased by 26 percent. Also, ALT concentrations (an enzymatic measure of liver health), triglycerides, cholesterol, and insulin resistance had all improved by a significant amount.
The results imply that a simple reduction of the n6/n3 ratio, even without a caloric reduction, will reduce fatty liver in adolescents in the absence of weight loss.
Comments on Effect of a Low n6/n3 PUFA Diet on Intrahepatic Fat Content in Obese Adolescents
Can anyone please help me understand what does p-value in the study signify?
Given that this is just an abstract, there are limits to how much I can draw from it. BUT, I also think it's preliminary to dismiss this as meaningless.
First off, from what I've gathered, anything that leads to a calorie-independent reduction in liver fat (i.e., leads to loss of liver fat without overall caloric restriction) is of both academic and clinical interest. I've seen the debate over whether sugar causes fatty liver disease circle around this question for years, with anti-sugar researchers arguing sugar has detrimental effects independent of its caloric value and others arguing sugar overconsumption is merely a marker for caloric overconsumption. It's a politically, clinically, and academically important debate, as it helps us understand the specific factors that contribute to disease, and so the specific factors that we need to focus on reducing in our diets (by whichever means you prefer socially and politically).
I'm very sympathetic to the argument that to any extent the data indicates sugar has contributed to the major epidemics of metabolic disease, much of the same data (especially larger-scale, correlative data) could be used to point the finger at distortions in omega 3 and omega 6 fatty acid ratios. To the extent we can interpret these results, they would seem to provide compelling evidence that omega 6 fatty acids are specifically deleterious, and not merely a marker for poor diet. The magnitude of effect is less than that shown in similar, calorie-independent sugar restriction studies (see link below), but if these effects are additive, it would indicate the rise in the prevalence of fatty liver disease, especially among adolescents, may be attributable to a specific type of food - i.e., that rich in both sugars and n6 fatty acids.
At a glance, I've found a handful of other papers exploring this same issue, and I'm looking forward to diving into them. That suggests this is a hypothesis with at least some substance, particularly given these other sources suggest elevated n6 consumption may also exacerbate inflammation, fibrosis and other forms of NAFLD progression. I'm looking forward to reading these and better understanding this hypothesis.
I also am sympathetic to the predicament these researchers may be facing. NAFLD, despite its prevalence, appears to be a condition where (1) its clinical significance is broadly under-appreciated and (2) the majority of the funding and interest supporting its research is oriented toward pharmaceutical solutions, despite the wealth of data indicating dietary changes can dramatically prevent or reverse disease severity. Accordingly, I wouldn't be surprised if funding for studies like this one is hard to come by. While I'd love to believe we are past the point of studying this hypothesis using small, uncontrolled trials, this may be just the data necessary to justify a larger, more rigorously designed trial to more clearly understand the consistency and the magnitude of any negative impact omega 6 fatty acids may have on liver condition.
https://www.sciencedirect.com/science/article/abs/pii/S0016508517356858
https://www.ncbi.nlm.nih.gov/pubmed/23862644
I don't understand. This doesn't show anything meaningful at all. What does the change in the average fat of a population show (especially with such large errors)? Did everybody lose a little fat (not likely with the error), etc. Did one guy lose a lot while all the others, gained?
This is, of course, an un-reviewed (why?) abstract but one figure could have told the story: values for each participant before and after. None of the authors know this?
I had the same thoughts after reading this. While I believe there is some validity in decreasing the ratio through a healthy diet. The assumption that the population was healthier in the pre-industrial, seed oil era is speculative at best. Coupled with either an incomplete article or results biased research, this is not the best article ever posted on this site.
Effect of a Low n6/n3 PUFA Diet on Intrahepatic Fat Content in Obese Adolescents
5