“When we supplemented with dietary nitrate to mice fed with a high-fat and sugar Western diet, we noticed a significantly lower proportion of fat in the liver,” says Mattias Carlström, Associate Professor at the Department of Physiology and Pharmacology, Karolinska Institutet. Their results were confirmed by using two different cell culture studies in human liver cells. Apart from a lower risk of steatosis, the researchers also observed reduction of blood pressure and improved insulin/glucose homeostasis in mice with type 2 diabetes. Isabel Cordero-Herrera, Mikael Kozyra, Zhengbing Zhuge, Sarah McCann Haworth, Chiara Moretti, Maria Peleli, Mayara Caldeira-Dias, Arghavan Jahandideh, Han Huirong, Josiane de Campos Cruz, Andrei L. Kleschyov, Marcelo F. Montenegro, Magnus Ingelman-Sundberg, Eddie Weitzberg, Jon O. Lundberg, and Mattias Carlstrom PNAS published ahead of print December 17, 2018 https://doi.org/10.1073/pnas.1809406115
Camu Camu may increase metabolism through the Gut Microbiome
The researchers found that camu camu improved glucose tolerance and insulin sensitivity and reduced the concentration of blood endotoxins and metabolic inflammation. “All these changes were accompanied by a reshaping of the intestinal microbiota.
Fernando F Anhê, Renato T Nachbar, Thibault V Varin, Jocelyn Trottier, Stéphanie Dudonné, Mélanie Le Barz, Perrine Feutry, Geneviève Pilon, Olivier Barbier, Yves Desjardins, Denis Roy, André Marette. Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice. Gut, 2018; gutjnl-2017-315565 DOI: 10.1136/gutjnl-2017-315565
Some omega-3 oils better than others for protection against liver disease
CORVALLIS, Ore. – Research at Oregon State University has found that one particular omega-3 fatty acid has a powerful effect in preventing liver inflammation and fibrosis – common problems that are steadily rising along with the number of Americans who are overweight.
The American Liver Foundation has estimated that about 25 percent of the nation’s population, and 75 percent of those who are obese, have nonalcoholic fatty liver disease. This early-stage health condition can sometimes progress to more serious, even fatal diseases, including nonalcoholic steatohepatitis, or NASH, as well as cirrhosis and liver cancer.
The study, published online in the Journal of Nutrition, was one of the first to directly compare the effects of two of the omega-3 fatty acids often cited for their nutritional value, DHA and EPA.
In research with laboratory animals, it found that EPA had comparatively little effect on preventing the fibrosis, or scarring, that’s associated with NASH. However, DHA supplementation reduced the proteins involved in liver fibrosis by more than 65 percent.
“A reduction of that magnitude in the actual scarring and damage to the liver is very important,” said Donald Jump, a principal investigator with the Linus Pauling Institute at OSU and a professor in the College of Public Health and Human Sciences.
“Many clinical trials are being done with omega-3 fatty acids related to liver disease,” Jump said. “Our studies may represent the first to specifically compare the capacity of EPA versus DHA to prevent NASH. It appears that DHA, which can also be converted to EPA in the human body, is one of the most valuable for this purpose.”
The issues have taken center stage as the weight of Americans continues to rise, with a related increase in the incidence of fatty liver disease and liver damage.
NASH is a progressive form of liver disease that is associated with chronic inflammation and oxidative stress, resulting from excess fat storage in the liver. Chronic inflammation can eventually lead to fibrosis, cirrhosis, or even liver cancer. While management of lifestyle, including weight loss and exercise, is one approach to control the onset and progression of fatty liver disease, other approaches are needed to prevent and treat it.
About 30-40 percent of people with nonalcoholic fatty liver disease progress to NASH, which in turn can result in cirrhosis, a major risk factor for liver cancer. While this research studied the prevention of fatty liver disease, Jump said, ongoing studies are examining the capacity of DHA to be used in NASH therapy.
The levels of omega-3 oils needed vary with the health concern, officials say.
“Omega-3 fatty acids are typically recommended for the prevention of cardiovascular disease,” Jump said. “Recommended intake levels of omega-3 fatty acids in humans for disease prevention are around 200-500 milligrams of combined DHA and EPA per day.”
Levels used in therapy to lower blood triglycerides, also a risk factor for cardiovascular disease, are higher, about 2-4 grams of combined EPA and DHA per day. The OSU studies with mice used DHA at levels comparable to the triglyceride therapies.
“DHA was more effective than EPA at attenuating inflammation, oxidative stress, fibrosis and hepatic damage,” the researchers wrote in their conclusion. “Based on these results, DHA may be a more attractive dietary supplement than EPA for the prevention and potential treatment of NASH in obese humans.”
This work was the result of a four-year study supported by the USDA National Institute of Food and Agriculture, as well as the National Institutes of Health. Co-authors on the paper included Christopher M. Depner and Kenneth A. Philbrick, both graduate students in the Nutrition Graduate Program at OSU.
Condition prevalent among those with heart disease and obesity
Non-alcoholic fatty liver disease (NAFLD) is a common condition associated with obesity and heart disease long thought to undermine health and longevity. But a new study by Johns Hopkins researchers suggests the condition does not affect survival.
A report on the study was published online last week in BMJ, the British medical journal.
“Physicians have considered fatty liver disease a really worrisome risk factor for cardiovascular disease,” says study leader Mariana Lazo, M.D., Ph.D., a postdoctoral fellow at the Johns Hopkins University School of Medicine’s Welch Center for Prevention, Epidemiology, and Clinical Research. “Our data analysis shows this doesn’t appear to be the case. We were surprised to say the least because we expected to learn by how much non-alcoholic fatty liver disease increased the risk of death and instead found the answer was not at all.”
Using health information collected from 11,371 Americans between 1994 and 1998 and followed for up to 18 years as part of the Third National Health and Nutrition Examination Survey (NHANES III), the researchers checked liver enzyme levels and ultrasound tests for evidence of NAFLD, and ultimately looked at death rates associated with NAFLD. The participants ranged in age from 20 to 74 during the data collection years. Because the ultrasounds were originally taken to assess gallbladder health, Lazo and colleagues from Johns Hopkins looked at each recording to determine the presence of fat in each person’s liver. People whose livers are 5 percent fat or more are considered to have NAFLD.
The Johns Hopkins team found no increase in mortality among those with NAFLD, which was identified in approximately 20 percent of the NHANES participants. At the end of the follow-up period, mortality from all causes was 22 percent, or 1,836 individuals. Cardiovascular disease was the cause of death for 716 participants, cancer for 480 and liver disease for 44.
Although the researchers found no increase in deaths, Lazo says further study is needed to determine whether more advanced NAFLD has serious long-term consequences for the liver, a vital organ that turns what we eat and drink into nutrients and filters harmful substances from the blood.
NAFLD, which some researchers have called the nation’s next epidemic, is characterized by the liver’s inability to break down fats and fatty build up in the organ. Found in roughly one in three Americans, it is most prevalent in those who are obese, and those with diabetes and cardiovascular disease. The spectrum of disease ranges from simple fat build-up to inflammation to the scarring and poor liver function that characterize cirrhosis. Chronic liver disease has long been associated with long-term alcohol consumption, but as the name suggests, NAFLD is found in those who are not heavy drinkers.
“We don’t yet know why mortality is not affected or whether there might be some actual protective effect of non-alcoholic fatty liver disease,” she says, “but it looks like the liver’s ability to accumulate fat may somehow shield the body from the detrimental effects of other health problems such as obesity and diabetes,” she says.
There is no treatment for NAFLD, other than lifestyle changes, including weight loss, and only a liver biopsy can determine how serious NAFLD is. Lazo says she hopes new methods are developed that more easily identify more advanced stages of NAFLD, which may not be harmless.
Still, she says, her research suggests that with respect to long-term survival of people with non-alcoholic fatty liver disease, “it may not matter if you have the disease or not.”
The research was supported by grants from the National Institute of Diabetes and Digestive Diseases and the American Diabetes Association.
Other Johns Hopkins researchers involved in the study include Ruben Hernaez, M.D., Ph.D.; Susanne Bonekamp, Ph.D.; Ihab R. Kamel, M.D., Ph.D.; Frederick L. Brancati, M.D.; Eliseo Guallar, M.D., M.P.H.; and Jeanne M. Clark, M.D., M.P.H.
For more information:http://www.jhsph.edu/welchcenter/