Just Read: How a low-carbohydrate diet rapidly reverses risk factors in people with high liver fat, in the disease we’ll all be hearing about – NAFLD, NASH, Diabetes Reversal

I am back from #LCB18 in time to review this paper that just came out, which presents several important points of view

  • Less confusion about the best way to treat non-alcoholic fatty liver disease
  • The near immediate impact of using a low-carbohydrate diet to reverse the fatty liver condition
  • Impacts beyond liver fat into the gut microbiome to support further positive metabolic changes (increases in folate with reduction of inflammation)

NAFLD, the disease we will all be hearing more about

As mentioned in previous posts, the prevalence of non-alcoholic fatty liver disease (NAFLD) is as high as the number of people that have high blood pressure (see: Just Read: The Disease You’ll be Hearing a Lot more About: Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action).

It’s going to be a big deal:

Increasing evidence also indicates that NAFLD is a significant independent risk factor for cardiovascular disease and type 2 diabetes (Lonardo et al., 2015; Targher et al., 2016), and the dyslipidemia that is present in many individuals with NAFLD potentially contributes to the link between these diseases (Gaggini et al., 2013).Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, et al. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab [Internet]. Elsevier; [cited 2018 Feb 19];0(0). Available from: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30054-8

Treatment is lifestyle, but which kind?

The treatment approach looking at the literature, appears “confused” in my opinion, with a focus on weight loss and less clarity over the way the weight is to be lost (see: Just Read: The role of diet and nutritional intervention for the management of patients with non-alcoholic fatty liver disease (NAFLD).)

That’s not the presentation in this paper, which is why it’s significant.

Low Carbohydrate isocaloric high-protein diet

The study authors employed a low-carbohydrate isocaloric diet in a small group of volunteers, without a control group. The isocaloric is significant because left to their own, subjects eating a low-carbohydrate diet will often reduce their calories because of satiation (which is why these diets are so successful in weight loss). To feed someone an isocaloric diet means that you have to essentially overfeed them. And that’s what they did, as much as they could, to add food to the diet, to try to have the subjects not lose weight.

The dietician also instructed the participants to increase their daily energy intake by 200 kcal from macadamia nuts whenever their weight decreased between two study days by more than 0.2 kg.

The high-protein part was intended to differentiate the situation from people with bariatric surgery, who are often protein “malnourished” which may contribute to increased expression of a not-helpful growth factor (FGF21) in the setting of liver disease

Immediate (within 1 day) and significant changes

The absence of control group and small sample size is offset by the amount of testing the authors did on subjects, including liver fat (by magnetic resonance and biopsy) as well as comprehensive genetic testing of liver tissue and gut microbiomes.

In contrast to the small reduction in weight loss, we observed dramatic reductions in liver fat, as measured by magnetic resonance spectroscopy (MRS), in all the individuals over the 14-day study period (mean reduction 43.8%; Figure 1E). Of note, the reduction was significant just 1 day after the start of the diet intervention (p = 0.027) and was paralleled by a significant decrease in total liver volume (Figure S1).Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, et al. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab [Internet]. Elsevier; [cited 2018 Feb 19];0(0). Available from: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30054-8

Several other metabolic changes were noted from the testing, including:

  • Significant changes in the way the liver metabolizes fat (makes less of its own, burns more of it)
  • Significant changes in the microbiome, resulting in the production of more usable folate, which may reduce oxidative stress
  • Significant changes in the genetic expression of liver cells

Analysis of liver biopsies taken from these subjects 7 days before the study start and after 7 days of dietary intervention showed that the diet significantly reduced the hepatic triglycerides by a mean of 43.9% (Table S4). Notably, we also observed a significant increase in serum folate concentrations in this cohort (Table S4)Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, et al. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab [Internet]. Elsevier; [cited 2018 Feb 19];0(0). Available from: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30054-8

Is it the low carbohydrate diet or something else?

As the authors point out, there’s no control group, so we can’t know for sure. It could be a transition to a real, non-processed food diet. What’s impressive here is that in the absence of weight loss, considered the standard of treatment, less fat was produced by the liver, more was burned, and there was less fat left over.

It’s biologically plausible that less carbohydrates change fat metabolism, as has been shown previously (see: Just Read: Putting insulin resistance into context by dietary reversal of type 2 diabetes ). This study provides a platform for learning more about what can be done to reverse NAFLD, and ultimately diabetes and cardiovascular disease risk.

Citation: Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, et al. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab [Internet]. Elsevier; [cited 2018 Feb 19];0(0). Available from: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30054-8

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