Women’s Health Update

by Tori Hudson, ND

Fatty Acid Supplementation: Liver Fat and Cardiovascular Disease

Polyunsaturated Fatty Acid Supplementation and Nonalcoholic Steatohepatitis

The prevalence of non-alcoholic fatty liver diseases (NAFLD) has increased substantially in the past decade or more. Non-alcoholic steatohepatitis (NASH) and liver failure induced by NAFLD are associated with morbidity and mortality with no specific or highly effective conventional treatments for NAFLD or NASH. Dyslipidemia from years of high simple-carbohydrate and high-fat diets are a fundamental element for the development of NASH. The pathophysiology of NAFLD and NASH includes lipid overload and lobular liver tissue inflammation

Because polyunsaturated fatty acids (PUFAs) can improve lipid disorders and reduce inflammation and oxidation, it is a reasonable hypothesis that PUFA supplementation might be able to improve NASH. The current randomized, prospective, controlled trial was conducted to investigate this possibility.

All participants had a NASH diagnosis, and not due to excess alcohol consumption, medications, viral hepatitis or autoimmune diseases. A total of 78 participants were enrolled and randomly assigned to either the control group or the PUFA group of 50 ml of PUFA with a 1:1 ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both groups were advised to exercise 30 minutes at least 5 days per week along with low-fat, low-cholesterol, and low-carbohydrate diets. Several laboratory tests of metabolic function were tested at the initial visit and at 6 months posttherapy. In addition, liver biopsies were taken at the initial visit and at the 6 months post PUFA that assessed steatosis grade, necroinflammatory grade, fibrosis stage, and ballooning. Most of the patients were male, overweight or obese with elevated liver enzymes, elevated triglycerides, total cholesterol and LDL cholesterol, elevated markers of inflammation, and higher fibrotic parameters.

After 6 months of PUFA therapy, liver function was significantly improved in the treatment group compared with the control group as indicated by significant reduction in the liver enzymes/triglycerides/total cholesterol, profound reduction in the inflammatory markers, and significant improvement in the fibrotic parameters. In addition, after 6 months of PUFA therapy, all the histopathological parameters as seen from the liver biopsies demonstrated that the severity of NASH was significantly improved in the PUFA group when compared to the control group.

Comment

: Lipid-lowering medications, insulin-sensitizing agents such as metformin, and antioxidants such as vitamins C and E have previously been studied with disappointing results. Previous studies reveal that increased PUFA nutrition is known to modulate lipids, provide some glycemic control, improve hypertension, and reduce inflammation. These effects prompt the reasonable consideration that PUFAs could also improve NAFLD and NASH. In the current study, after just 6 months of PUFA treatment, the laboratory parameters improved, and most importantly, the cellular changes of the chronic liver disease profoundly improved. It appears from this simple study and simple treatment that PUFA supplementation inhibited lipid accumulation, ameliorated inflammation, and reduced the hepatic fibrosis involved in NASH and NAFLD.

Yun-Hua Y, Lu-Hua Y, Kai-Hui S, et al. Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis. World J Gastroenterol. 2015;21(22):7008–7013.

The Effect of Docosahexaenoic Acid Supplementation on Hepatic Fat in Children with Nonalcoholic Fatty Liver Disease

As is true in adults, children and adolescents with fatty liver have metabolic abnormalities that are risk factors for cardiovascular disease and include insulin resistance, glucose intolerance, and dyslipidemia. There are important associations between NAFLD and subclinical atherosclerosis. It might be said that NAFLD is the hepatic aspect of metabolic syndrome (MetS) and a significant risk factor for atherosclerotic disease, even in children. NAFLD is also a risk factor for myocardial insulin resistance, abnormal left ventricular and diastolic function, and altered metabolism of cardiac energy.

Weight loss and increased physical activity are the currently accepted approaches to decrease hepatic fat with no pharmacologic approved options for NAFLD in children. However, omega-3 fatty acids may have benefit for NAFLD in children as well as adults.

In adults, we have published clinical trials which have shown that supplementation with fish oils can reduce hepatic fat. In children, DHA supplementation improves liver steatosis and reduces serum alanine aminotransferase (ALT) and triglycerides, and improves insulin sensitivity. Whether or not this then leads to cardiovascular benefit in children with NAFLD is unknown.

The current study investigated the influence of omega-3 fatty acids, specifically DHA, on hepatic fat, abdominal visceral fat, subcutaneous fat, epicardial fat, and associated cardiovascular risk factors.

This double-blind, parallel-group, placebo-controlled, randomized trial was conducted in 58 children in which 51 completed the study with a total of 25 receiving the DHA and 26 the placebo. A supplement of 250 mg/day of DHA or placebo was given for 6 months. After 6 months, the liver fat was reduced by 53.4% in the DHA group and 22.6% in the placebo group. The DHA group also had 7.8% reduced visceral abdominal fat and 14.2% epicardial fat vs. 2.2% and 1.7% respectively, in the placebo group. Fasting insulin and triglycerides significantly decreased in the DHA group although there were no changes in ALT or body mass index.

Comment

: The effects of DHA in this study confirm the results of previous studies in children that used 250mg/day of DHA, and 500 mg/day of DHA combined with diet and exercise. In these studies, liver steatosis improved, insulin sensitivity improved, and serum triglycerides and ALD were reduced.

Children with NAFLD should be encouraged to take fish oil supplements, and in particular at least 250 mg/day of DHA in order to decrease liver and visceral fat and improve metabolic abnormalities with the longer-term benefit of reducing their cardiovascular risk factors.

Pacifico L, Bonci E, Di Martino M, et al. A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2015;25:734–741.

Grapefruit Juice Flavonoids Reduce Arterial Stiffness in Postmenopausal Women

There is an increased risk of cardiovascular disease in postmenopausal women. This randomized, double-blind, controlled, crossover trial investigated the effects of grapefruit on the vascular function of postmenopausal women.

Women were between the ages of 50 and 65, were 3 to 10 years postmenopause, Caucasian, nonsmokers, and had normal blood pressure, normal electrocardiogram, and a body mass index (BMI) between 19 and 30 kg/m². Exclusions included those on hormone replacement therapy within 3 months prior, on drugs that could interact with grapefruit juice, allergy to citrus, on specialized diets or supplements, exercising >5 hours/week, and a diet higher in flavonoids.

A concentrated grapefruit juice drink was standardized to contain the flavonoid naringenin at 212.9 mg per 340 ml. A control drink without naringenin was also provided. Women were randomized and each drink was ingested daily for 6 months, 170 ml with morning and midday meals. There was then a 2-month washout period and each group then consumed the opposite drink for 6 months.

The primary outcome in this study was brachial artery flow-mediated dilation. Blood pressure, carotid-femoral pulse wave velocity, and digital peripheral arterial tonometry, cellular markers of vascular activity, glycemia, and insulinemia were secondary outcomes. Measurements were taken at baseline and following the 6-month consumption of each drink.

A total of 52 postmenopausal women were included and randomly assigned with 26 in each group, although during follow-up,4 women in the grapefruit juice group were excluded due to abnormal electrocardiograms.

After 6 months of grapefruit juice consumption, pulse wave velocity measurements of carotid and femoral arteries, which indicates improved vascular stiffness, were significantly decreased as compared with those in the control drink group. Flow-mediated dilation and peripheral arterial tonometry measurements were not different between the groups. Blood pressure and cellular markers of endothelial function were not significantly different, nor was body weight, plasma glucose and insulin, inflammation, and antioxidant capacity between the grapefruit juice and control groups.

Comment

: Grapefruit juice, high in the flavonoid naringenin, showed a significant decrease of arterial stiffness in certain vascular tissues of postmenopausal women without improving blood pressure or endothelial function in this study. I am not in the habit of recommending daily intake of citrus juice, or any fruit juice for that matter, to my patients. While this study is interesting, and flavonoids are an important compound that can potentially reduce cardiovascular risk, I’m not sure that grapefruit juice will find its way into my clinical advice.

Habauzit V, Verny M-A, Milenkovic D, et al. Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial. Am J Clin Nutr. July 2015;102(1):66–74.