Category Archives: liver disease

Non-Alcoholic Fatty Liver Disease: Ketogenic Diet Reduced Liver Fat Quickly

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.

Here’s the abstract:

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.

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.

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Advanced Liver Fibrosis Is Common in Patients With 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 liver fat (aka hepatic steatosis), a precursor to fibrosis, can be reversed to a great degree.

Steve Parker, M.D.

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Three Ways to Prevent Non-Alcoholic Fatty Liver Disease (NAFLD)

Where does bile come from? The liver.

I found this study a while back. TL;DR: Physical activity, the Mediterranean diet, and legume consumption are linked to lower incidence of liver fat. At least in a Spanish population with metabolic syndrome.

Abstract

Objective

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver morbidity. This condition often is accompanied by obesity, diabetes, and metabolic syndrome (MetS). The aim of this study was to evaluate the connection between lifestyle factors and NAFLD in individuals with MetS.

Methods

A cross-sectional study with 328 participants (55–75 y of age) diagnosed with MetS participating in the PREDIMED-Plus trial was conducted. NAFLD status was evaluated using the non-invasive hepatic steatosis index (HSI). Sociodemographic, clinical, and dietary data were collected. Adherence to the Mediterranean diet (mainly assessed by the consumption of olive oil, nuts, legumes, whole grain foods, fish, vegetables, fruits, and red wine) and physical activity were assessed using validated questionnaires.

Results

Linear regression analyses revealed that HSI values tended to be lower with increasing physical activity tertiles (T2, β = –1.47; 95% confidence interval [CI], –2.73 to –0.20; T3, β = –1.93; 95% CI, –3.22 to –0.65 versus T1, Ptrend = 0.001) and adherence to the Mediterranean diet was inversely associated with HSI values: (moderate adherence β = –0.70; 95% CI, –1.92 to 0.53; high adherence β = –1.57; 95% CI, –3.01 to –0.13 versus lower, Ptrend = 0.041). Higher tertiles of legume consumption were inversely associated with the highest tertile of HSI (T2, relative risk ratio [RRR], 0.45; 95% CI, 0.22–0.92; P = 0.028; T3, RRR, 0.48; 95% CI, 0.24–0.97; P = 0.041 versus T1).

Conclusion

Physical activity, adherence to the Mediterranean diet, and consumption of legumes were inversely associated with a non-invasive marker of NAFLD in individuals with MetS. This data can be useful in implementing precision strategies aimed at the prevention, monitoring, and management of NAFLD.

Source: Influence of lifestyle factors and staple foods from the Mediterranean diet on non-alcoholic fatty liver disease among older individuals with metabolic syndrome features – ScienceDirect

Steve Parker, M.D.

low-carb mediterranean diet

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The Best 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.

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.

Click the pic to purchase at Amazon.com. E-book versions also available at Smashwords. com

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If You Have T2 Diabetes, Odds Are Good That You Already Have Fatty Liver (NAFL)

Stages of liver damage: healthy, fatty, liver fibrosis, and cirrhosis. 

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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What’s the Optimal Diet for Fatty Liver (Hepatic Steatosis)?

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

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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Worrisome Liver Fat? Low-Carb Mediterranean Diet Works Better Than Low-Fat Diet

From the article at International Business Times:

Reducing hepatic [liver] fat or fat around the liver by 30%, along with moderate weight loss is an important part in reducing obesity-related health risks from a long-term perspective, the researchers of the study said. In addition to moderate weight loss, visceral fat or fat stored within the abdominal cavity was reduced by 25% and fat around the heart decreased by 11%. Fat in and around the muscle and pancreas was also reduced by 1 to 2%.

“Reduction in liver fat is a better predictor of long-term health than reduction of visceral fat, which was previously believed to be the main predictor,” Professor Shai explained in a press release. “The findings are a significant contributor to the emerging understanding that for many obese individuals, excess liver fat is not merely a sign of health risks associated with obesity, including cardiovascular disease and diabetes, but is likely also a cause.”

Source: Scientists Reveal Most Effective Diet For Weight Loss, And It’s Not Keto

Click for details of the study.

Steve Parker, M.D.

PS: There’s a low-carb Mediterranean diet in this book.

Click the pic to purchase at Amazon.com. E-book versions also available at Smashwords. com

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