Chia Supplementation and Non Alcoholic Fatty Liver Disease
Condition: Non-Alcoholic Fatty Liver Disease; Dietary Modification
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional

Summary: 
      Parallel to epidemic obesity, non-alcoholic fatty liver disease (NAFLD) prevalence has
      markedly increased during the last years, and recent data point out that one of three adults
      courses with this disease. NAFLD etiopathogeny is multifactorial, an inadequate diet
      characterized by high fructose content and deficient consumption of omega-3 fatty acids,
      scarce physical activity, excess abdominal visceral fat (AVF), insulin resistance, and
      genetic susceptibility have shown to be relevant determinants. Although NAFLD can progress to
      cirrhosis and hepatic carcinoma, its most frequent complications are type 2 diabetes mellitus
      (DM2) and coronary artery disease (CAD); therefore, NAFLD is considered a multisystemic
      disease and a public health problem.

      Currently, no specific pharmacological treatment is available for NAFLD, hence, modifications
      in life style, including weight loss by caloric restriction and increased physical activity,
      are still the treatment of choice for this type of patients. Recent studies indicate that the
      supplementation of the diet with omega-3 fatty acids of marine origin (eicosapentanoic acid
      [EPA]/docosahexaenoic acid [DHA]) and the Mediterranean-style diet (rich in omega-3,
      antioxidants, and fiber) are efficient for NAFLD treatment, because they diminish the
      intrahepatic fat content and improve the metabolic profile, even in non-caloric restriction
      diets. However, the socioeconomic and cultural characteristics make the consumption of these
      food difficult in some populations, which has led to the search of alternative vegetal
      sources rich in these nutrients.

      Although, there is evidence in animal models suggesting that chia (Salvia hispanica L.) could
      be an alternative able to reduce the intrahepatic fat content, its effect on NAFLD has not
      been studied in humans. Hence, the objective of this study was to analyze whether the
      consumption of an isocaloric diet supplemented with 25 g/day of chia can diminish NAFLD and
      the metabolic anomalies that accompany the disease.
    

Detailed description: 
      Participants were chosen from the control group of the Genetics of the Atherosclerotic
      Disease (GEA, for its initials in Spanish) study, performed at the Institute National of
      Cardiology "Ignacio Chávez" in Mexico City, Mexico. The protocol was approved by the Research
      and Ethics Committee of the Instituto Nacional de Cardiología "Ignacio Chavez" under the
      number 16-980. Candidates that accepted to participate in the study signed voluntarily the
      informed consent.

      In order to know eating habits and standardize macronutrient dietary composition, 24-hour
      dietary recalls will be applied in the first visit, considering two weekdays and one day of
      the weekend. Patients will be instructed to maintain constant their physical activity
      throughout the study. To standardize macronutrient dietary composition, an isocaloric diet
      (55% carbohydrate, 30% fat, and 15% protein diet) will be indicated two weeks before starting
      chia supplementation. After this, participants will be instructed to keep up this
      macronutrient composition during all the intervention period. 30 packages of 25 g of chia
      seeds will be provided to each patient monthly, with the instruction to mill one package per
      day, pointing out on the relevance of consume the milled chia accompanied by with water,
      salads, cereal, or other dishes, from breakfast through lunch but always before 6:00 PM. To
      favor treatment adherence and record adverse events (loss appetite loss, constipation,
      diarrhea, flatulence and nausea, allergy or chía chia intolerance), patients will be
      contacted once a week during the intervention. Adherence will be determined by counting empty
      chia packages, and evaluation of alpha linolenic acid (ALA) concentration in plasma, which is
      the chia's seeds main fatty acid compound.

      Anthropometric evaluation, laboratory test, and computed tomography studies will be made at
      baseline and after the 8-wk intervention.

      Nutritional intervention and food intake evaluation In order to know eating habits and
      standardize macronutrient dietary composition, 24-hour dietary recalls will be applied in the
      first visit, considering two weekdays and one day of the weekend. Patients will be instructed
      to maintain constant their physical activity throughout the study. To standardize
      macronutrient dietary composition, an isocaloric diet (55% carbohydrate, 30% fat, and 15%
      protein diet) will be indicated two weeks before starting chia supplementation. After this,
      participants will be instructed to keep up this macronutrient composition during all the
      intervention period. 30 packages of 25 g of chia seeds will be provided to each patient
      monthly, with the instruction to mill one package per day, pointing out on the relevance of
      consume the milled chia accompained by with water, salads, cereal, or other dishes, from
      breakfast through lunch but always before 6:00 PM. To favor treatment adherence and record
      adverse events (loss appetite loss, constipation, diarrhea, flatulence and nausea, allergy or
      chía chia intolerance), patients will be contacted once a week during the intervention.

      Adherence will be determined by counting empty chia packages, and evaluation of alpha
      linolenic acid (ALA) concentration in plasma, which is the chia's seeds main fatty acid
      compound. Participants wre excluded when the adherence was lower tan 80% according to the
      package counting, or when plasma ALA concentration increased less than 30%.

      Anthropometric evaluation, laboratory test, and computed tomography studies will be made at
      baseline and after the 8-wk of diet intervention.

      Anthropometric evaluation: Weight and height will be recorded using a calibrated scale and
      wall stadiometer, with an accuracy of 0.1 Kg kg and 0.1 cm, after removing excess clothing
      and shoes. The body mass index (BMI) was calculated as weight (kg)/height (m2). Waist
      circumference will be measured with a non-stretch tape, at the midway between the lowest rib
      and the iliac crest without clothes around the waist.

      Laboratory tests: After 10-h fasting and 20 min in sitting position, venous blood will be
      collected in assay tubes without anticoagulant and in tubes with K2-EDTA (1.8 mg/mL).
      Glucose, total cholesterol, triglyceride, and high density lipoprotein cholesterol (HDL-C)
      concentrations will be determined using direct standard enzymatic colorimetric methods on a
      COBAS c311 (Roche Diagnostics, Mannheim, Germany). Low density lipoprotein cholesterol
      (LDL-C) concentration was estimated using the De Long formula. The reproducibility and
      precision of these determinations in our laboratory is assessed by the Center for Disease
      Control and Prevention Lipids Standardization Program (LSP-CDC, Atlanta, GA, USA). Plasma
      free fatty acids (FFA) will be measured by an enzymatic-colorimetric assay (Wako Diagnostics,
      Chuo-Ku Osaka, Japan). Total fatty acids, including ALA will be extracted according to Folch
      method, and analyzed in a Shimadzu GC-8A gas chromatograph equipped with an SP2330 capilar
      column (25m x 0.25 mm x 0.25). Fatty-acid concentrations will be calculated in relation to
      heptadecanoic acid methyl ester as internal standard, fatty acids peaks will be identified by
      using the Supelco 37 component FAME Mix (CRM47885). A plasma control sample will be run in
      each extraction assay, to obtain an ALA inter-assay coefficient variation.

      Computed tomography study: Computed tomography (CT) is a validated method for measuring
      visceral adipose tissue (VAT) and evaluate non alcoholic fatty liver disease. In the present
      study, these measurements will be obtained using a 64-slice scanner (Somatom Cardiac
      Sensation 64, Forcheim, Bavaria, Germany). To determine the liver and spleen attenuation
      index, a single slice CT scan is obtained at the level of T11-T12 or T12-L1. Fatty liver is
      defined as a liver/spleen attenuation ratio lower than 1.0. To calculate the amount of total
      abdominal tissue (TAT) and VAT, a single slice scan is obtained at the level of L4-L5, the
      area is expressed in square centimeters (cm2). Subcutaneous abdominal tissue (SAT) was
      calculated by subtracting the VAT from the TAT area.
    

Intervention name(s): Milled chia seeds
Intervention type(s): Dietary Supplement
Intervention description(s): 8 weeks of an isocaloric diet supplemented with 25 g/day of milled chia
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non-Alcoholic Fatty Liver Disease; Milled chia seed suplementation