Category Archives: Liver Disease

Ketogenic Diet Improved Non-Alcoholic Fatty Liver Disease In Just Six Days

stages of liver damage

There’s a silent epidemic in folks with type 2 diabetes: 50 to 70% have non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease is an important contributor to cirrhosis, i.e., scarring in the liver that impairs liver function. In the study at hand, a ketogenic diet reduced liver fat by 31% over just six days. I don’t have many details of the diet used, but it reduced carbohydrates to 20 grams/day.

Significance

Ketogenic diet is an effective treatment for nonalcoholic fatty liver disease (NAFLD). Here, we present evidence that hepatic mitochondrial fluxes and redox state are markedly altered during ketogenic diet-induced reversal of NAFLD in humans. Ketogenic diet for 6 [days] markedly decreased liver fat content and hepatic insulin resistance. These changes were associated with increased net hydrolysis of liver triglycerides and decreased endogenous glucose production and serum insulin concentrations. Partitioning of fatty acids toward ketogenesis increased, which was associated with increased hepatic mitochondrial redox state and decreased hepatic citrate synthase flux. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by ketogenic diet and highlight hepatic mitochondrial fluxes and redox state as potential treatment targets in NAFLD.

Abstract

Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (−58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (−53%) and hepatic citrate synthase flux (−38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (−45%) and triiodothyronine (−21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.

Source: Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease | PNAS

Steve Parker, M.D.

Liver Fat and Fibrosis Are Common in Type 2 Diabetes

A 2021 issue of Diabetes Care reveals the shocking prevalence of advanced liver fibrosis (scarring) in folks with type 2 diabetes: one of every six. Fibrosis may eventually lead to cirrhosis and require a liver transplant. The study at hand used vibration-controlled transient elastography to measure liver stiffness. The more fibrosis, the stiffer the liver. The measuring device “uses a pulse-echo ultrasound technique to quantify the speed of mechanically induced shear wave within liver tissue,” which correlates with the severity of fibrosis. Liver fat, i.e., steatosis, can also be quantified at the same time by measuring the ultrasonic attenuation of the echo wave. 

Here’s the study abstract:

OBJECTIVE

Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.

RESULTS

The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).

CONCLUSIONS

Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.

Source: Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening | Diabetes Care

The good news is that excessive liver fat (aka hepatic steatosis), a precursor to fibrosis, can be reversed to a great degree.

Steve Parker, M.D.

What’s the Optimal Diet to Reverse Non-Alcoholic Fatty Liver Disease (NAFLD)?

Stages of liver damage. Healthy, fatty, liver fibrosis, and finally cirrhosis

A recent article in Gastroenterology Clinics suggests this one:

•Prioritize intact starches such as brown rice, quinoa, and steel-cut oats, and limit or avoid refined starches such as white bread and white rice

•Replace some of the CHO [carbohydrate], especially refined CHO, in the diet with additional protein from a mixture of animal or vegetable sources, including chicken, fish, cheese, tofu, and pulses

•Include a variety of bioactive compounds in the diet by consuming fruits, vegetables, coffee, tea, nuts, seeds, and extra virgin olive oil

•Get most fat from unsaturated sources, such as olive oil (ideally extra virgin), rapeseed oil, sunflower oil, safflower oil, canola oil, or nuts and seeds

•Limit or avoid added sugars, whether sucrose, fructose, maltose, maltodextrin, or any syrups. If any of these words appear in the first 3–5 ingredients of any food item, it is best to avoid that item and choose a no-sugar version instead. Examples are yogurts and commercial cereals•In particular, avoid liquid sugar such as carbonated sugary drinks/sodas, lemonade, any juices, smoothies, and added sugar to tea and coffee

Source: Nutrition and Nonalcoholic Fatty Liver Disease – Gastroenterology Clinics

See the article for a typical daily menu. Looks like a Mediterranean diet to me. I’m not aware of the paleo diet being used to combat NAFLD.

Excessive fructose and saturated fatty acid consumption appear to be particularly harmful to the liver.

The authors also seem to endorse exercise: 150 t0 300 minutes per week of moderate- to vigorous intensity aerobics exercise, performed at least thrice weekly.

And all experts recommend loss of excess fat weight.

If you really want to get into the weeds, read about how fat deposits in liver and muscle lead to metabolic inflexibility, resulting in insulin resistance and mitochondrial dysfunction, which alters lipid metabolism, releasing free fatty acids (some of which are lipotoxic), leading to lipotoxic molecules (like ceramides), causing inflammation and fibrosis.

Steve Parker, M.D.

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If You Have T2 Diabetes, You May Already Have Fatty Liver

Stages of liver damage. Healthy, fatty, liver fibrosis and cirrhosis. Vector illustration

I’ve written before about fatty liver here, here, and here, for example. Fatty liver by itself may not be very harmful but sometimes it progresses to liver inflammation called steatohepatitis. Which can lead to cirrhosis. Non-alcoholic fatty liver disease is the second leading cause for liver transplantation in the U.S., after viral hepatitis.

You only have one liver, so be nice to it.

How common is fatty liver in the U.S. among those with T2 diabetes? From Diabetes Care:

The overall prevalence of NAFLD [non-alcoholic fatty liver disease] was >70% (47% with NAFL [non-alcoholic fatty liver] plus 26% with NASH [non-alcoholic steatohepatitis], for a total of >18 million patients with T2D having NAFLD (not including patients in the U.S. with undiagnosed T2D).

Source: Time to Include Nonalcoholic Steatohepatitis in the Management of Patients With Type 2 Diabetes | Diabetes Care

Steve Parker, M.D.

PS: One way to get fat out of your liver is to lose excess fat body weight. Let me help you.

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Is There and Optimal Diet For Liver Fat (Hepatic Steatosis)?

Stages of liver damage: Healthy, fatty liver, fibrosis, and cirrhosis

From Dr Bret Scher at DietDoctor:

Fortunately, we have emerging evidence that low-carb and ketogenic diets improve fatty liver while also helping with glycemic control and weight loss, an impressive combination rarely seen with medications. As we reported earlier, studies have shown that carbohydrate restriction changes liver metabolism, stimulating the breakdown of liver fat. Another study mentioned in the same post showed that when children substitute complex forms of starch to replace sugar, they experience reduced amounts of liver fat.

Yet another impressive study found that despite equal weight loss, a low-carb Mediterranean diet was better than a low-fat diet for reversing liver fat and signs of NAFLD. And finally, Virta Health published a subset of its data showing that one year on a ketogenic diet improved non-invasive tests for NAFLD and liver scarring.

Source: Limiting Carbs Likely Better Than Drugs for Fatty Liver — Diet Doctor

Steve Parker, M.D.

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