Low Free Sugar Diet for Nonalcoholic Fatty Liver Disease in Adolescent Boys

A recent randomized study (Jeffrey B. Schwimmer, MD1,2Patricia Ugalde-Nicalo, MD1Jean A. Welsh, PhD, MPH, RN3,4,5et al JAMA. 2019;321(3):256-265. doi:10.1001/jama.2018.20579) examined the beneficial effects of a low free sugar diet for Nonalcoholic Fatty Liver Disease (NAFLD) in adolescent boys.  Congratulations to the authors, particularly to Miriam Vos (my Emory colleague & corresponding author) and Jeffrey Schwimmer (whose training overlapped with mine in Cincinnati).

Key finding:

“In this randomized clinical trial that included 40 adolescent boys aged 11 to 16 years with nonalcoholic fatty liver disease followed up for 8 weeks, provision of a diet low in free sugars compared with usual diet resulted in a greater reduction in hepatic steatosis [based on MRI] from 25% to 17% in the low free sugar diet group and from 21% to 20% in the usual diet group, a statistically significant difference of −6.23% when adjusted for baseline.”

Summary of this study in NY Times: To Fight Fatty Liver, Avoid Sugary Foods and Drinks

An excerpt from NY Times:

To make the diet easier and more practical for the children in the limited-sugar group to follow, the researchers asked their families to follow it as well. They tailored the diet to the needs of each household by examining the foods they consumed in a typical week and then swapping in lower sugar alternatives. If a family routinely ate yogurts, sauces, salad dressings and breads that contained added sugar, for example, then the researchers provided them with versions of those foods that did not have sugar added to them.

Fruit juices, soft drinks and other sweet drinks were forbidden. They were replaced with unsweetened iced teas, milk, water and other nonsugary beverages. Dietitians prepared and delivered meals to the families twice a week, which helped them stick to their programs.

Full abstract:

Importance  Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment.

Objective  To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD.

Design, Setting, and Participants  An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017.

Interventions  The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet.

Main Outcomes and Measures  The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence.

Results  Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was −6.23% (95% CI, −9.45% to −3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study.

Conclusions and Relevance  In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes.

 

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Better Diet -Less Fatty Liver

A recent study (J Ma et al. Gastroenterol 2018; 155: 107-17) shows that a “better diet” was associated with less liver fat.

Among the 1521 participants form a Framingham Heart Study cohort (Mean age 51 years at start of study), the authors assessed diet with a 125-item Harvard food frequency questionnaire and liver fat using liver-phantom ratio (LPR) on CT images between 2002-2005 and then again 2008-2011.  They specifically looked at 2 diet scores:

  • Mediterranean-style diet score (MDS)
  • Alternative Healthy Eating Index (AHEI)

Key findings:

  • For each 1 standard deviation increase in MDS, the LPR increased (less liver fat) by 0.57 and the odds for incident fatty liver decreased by 26% (P=.002)
  • Similarly, for each 1 standard deviation increase in AHEI, LPR increased by 0.56 and the odds for incident fatty liver decreased by 21% (P=.02)

My take: This study shows that Improved diet quality over 6 years was associated with reduced liver fat accumulation

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Lake Louise, Banff

 

Dietary Patterns in First Year of Life May Increase Risk of Celiac Autoimmunity

M Barroso et al. Gastroenterol 2018; 154: 2087-96.

Background: “Western-like diets –mainly characterized by high intake of red and processed meats, refined grains, simple sugars, and saturated fats and low intake of fruits, vegetables, and whole grains– have been associated with low-grade chronic inflammation, which is involved in the etiology of inflammatory conditions.” Ref: Br J Nutr 2015; 114: 999-1012.

To examine how diet may influence the development of celiac autoimmunity, defined by TG2A positivity, the authors examined a subset of patients (n=1997) from the prospective Generation R study (Netherlands); 27 in this cohort developed celiac autoimmunity (1.4%).

Key finding:

  • Higher adherence to a “prudent” diet which had a higher intake of vegetables, vegetable oils, pasta, and grains and low consumption of refined cereals and sweet beverages at 1 year of age was associated with a lower odds of celiac autoimmunity at 6 years of age with an odds ratio of 0.67.

This study is limited by the relatively low number who had celiac autoimmunity and by its use of a food questionnaire.

My take: This study indicates that diet plays a role in the development of celiac along with other disease, but this likely involves a complex mix of components rather than a single toxic agent.

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Diet and Stress in Pediatric Eosinophilic Esophagitis

When it comes to eosinophilic esophagitis (EoE), I sometimes worry that some treatments are worse than the disease, depending on the severity of the EoE. A recent study (C Case et al. JPGN 2017; 65: 281-84) indicates that dietary therapy is often stressful for families.

This study examined children ages 2-18 during an annual American Partnership for Eosinophilic Diseases (APFED.org) patient education conference. What I found most interesting was Table 3. “Stress associated with eosinophilc esophagitis.”

Some of the data:

  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE?’ Family structure at mealtimes: Not stressful 13.5%, somewhat stressful 21.6%, moderate stressful 16.2%, significant stressful 32.4%, and severe stressful 16.2%
  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE? Buying and cooking separate foods/meals for your child: Not stressful 2.6%, somewhat stressful 21.1%, moderate stressful 21.1%, significant stressful 31.6%, and severe stressful 23.7%
  • In response to ‘how stressful do you find the following since your child’s diagnosis of EoE? Financial strain due to cost of food: Not stressful 10.5%, somewhat stressful 21.1%, moderate stressful 18.4%, significant stressful 23.7%, and severe stressful 36.3%
  • What is your current stress level in response to your child’s EoE? Not stressful 2.6%, somewhat stressful 15.8%, moderate stressful 36.8%, significant stressful 42.1%, and severe stressful 2.6%
  • 62% of respondents indicated that child’s EoE has affected marital relationship.

In addition, the study documented that “half of youth were affected by worry, anger, and sadness related to specialized diets.”  As this study relied on participants at an APFED meeting, this could skew the EoE population to be more severely affected.

My take: This study shows the emotional burden that dietary treatment of EoE places on families.

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Berry College

Little Evidence to Support Dietary Intervention in Autism Spectrum Disorders

Thanks to Kipp Ellsworth Twitter feed for reference:  Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review N Sathe Pediatrics 2017; vol 139.

Abstract:

CONTEXT: Children with autism spectrum disorder (ASD) frequently use special diets or receive nutritional supplements to treat ASD symptoms.

OBJECTIVES: Our objective was to evaluate the effectiveness and safety of dietary interventions or nutritional supplements in ASD.

DATA SOURCES: Databases, including Medline and PsycINFO.

STUDY SELECTION: Two investigators independently screened studies against predetermined criteria.

DATA EXTRACTION: One investigator extracted data with review by a second investigator. Investigators independently assessed the risk of bias and strength of evidence (SOE) (ie, confidence in the estimate of effects).

RESULTS: Nineteen randomized controlled trials (RCTs), 4 with a low risk of bias, evaluated supplements or variations of the gluten/casein-free diet and other dietary approaches. Populations, interventions, and outcomes varied. Ω-3 supplementation did not affect challenging behaviors and was associated with minimal harms (low SOE). Two RCTs of different digestive enzymes reported mixed effects on symptom severity (insufficient SOE). Studies of other supplements (methyl B12, levocarnitine) reported some improvements in symptom severity (insufficient SOE). Studies evaluating gluten/casein-free diets reported some parent-rated improvements in communication and challenging behaviors; however, data were inadequate to make conclusions about the body of evidence (insufficient SOE). Studies of gluten- or casein-containing challenge foods reported no effects on behavior or gastrointestinal symptoms with challenge foods (insufficient SOE); 1 RCT reported no effects of camel’s milk on ASD severity (insufficient SOE). Harms were disparate.

LIMITATIONS: Studies were small and short-term, and there were few fully categorized populations or concomitant interventions.

CONCLUSIONS: There is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD.

Related blog post: Gluten-free, Casein-free -No improvement in Autism

Bayeux, France

POWER — Practice Guide on Obesity and Weight Management, Education, and Resources

Recently, the American Gastroenterological Association (AGA) has published a large amount of information regarding obesity and the potential role for gastroenterologists.  In addition to publishing an entire Special Issue supplement of Gastroenterology (152: (7): 1635-1801, the AGA has published a “white paper” (Clin Gastroenterol Hepatol 2017; 15: 631-49).  The AGA has also addressed coding issues and episodic care issues: Clin Gastroenterol Hepatol 2017; 15: 650-64.

Some useful points from these articles:

  • “Severe obesity [as classified by] the American Heart Association…BMI>120% of the 95% for age and sex or a BMI ≥35” (“class 2 obesity in adults”) Class 3 obesity is BMI >140% of 95% for age and sex or a BMI ≥40.
  • Intensive lifestyle interventions ‘average weight losses of up to 8 kg in 6 months’ but maintaining weight loss has been a challenge. “However, both the DPP and Look AHEAD have shown that weight loss, followed by substantial weight regain, was associated with greater improvements in health than not having lost weight at all.”
  • Good idea to review medications that affect weight.  Medications associated with weight gain include antidiabetics, some antihypertensives (eg. nadolol, propranolol), antidepressants (eg. lithium, mirtazapine, SSRIs, tricyclic antidepressants), antipsychotics (clozapine, olanzapine, quetiapine, risperdione), some antieleptics (carbamazepine, gabapentin, pregabalin, valproic acid), 1st generation antihistamines and glucocorticoids.
  • Is there a best diet? On this topic, the authors (pg 1749 of supplement): “there appears to be little weight loss advantage or difference in metabolic health outcomes between dietary approaches and improvements in health are relative to degrees of weight loss.  Caloric restriction is the fundamental premise of every successful weight loss strategy, whether that is achieved by lowering fat or carbohydrate, fasting, or using meal replacements...the best diet ultimately is the one you can stick to long enough

The information available in these publications are overlapping and cannot be summarized adequately in a short post.  The white paper, in particular, does an excellent job of summarizing the reasons for obesity, the steps a clinician should take, identification of comorbidities, management (diet, exercise, pharmacologic agents, endoscopic therapies, and surgery), and outcomes.

My take (borrowed from the authors):  “obesity is possibly the greatest health care issue of our day…Although lifestyle changes, including an individualized reduced-calorie diet and physical activity, are the cornerstones of treatment, new medications and bariatric endoscopic therapies and surgery can be effective tools.”

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Mural Near Sullivan’s Island

 

Nutrition Week (Day 7) Connecting Epidemiology and Diet in Inflammatory Bowel Disease

A supplement in Gastroenterology (2017; 152: 309-462) provides a great update on a lot of topics.  These include pathophysiology articles (eg. role of Paneth cell, role of microbiome), treatment/development of fibrosis, management advances in endoscopy and biomarkers, newest treatments and emerging treatments, complementary medicine approaches, pain/psychology issues, medications in pregnancy, and detecting dysplasia.

For me, the update on epidemiology and its relationship to diet (pgs 313-321) as well as the review on diet as a trigger or therapy for inflammatory bowel disease (398-414) were most interesting.  Though, I will keep the update on complementary and alternative medicines article at my desk in case questions come about this topic

GG Kaplan, SC Ng. “Understanding and Preventing the Global Increase of Inflammatory Bowel Disease”  Gastroenterology 2017; 152: 313-321

Epidemiology:

1st case of ulcerative colitis was reported in 1859.  !st cases of Crohn’s disease reported in 1932 (BB Crohn et al. JAMA 1932; 99: 1323-29).

Olmstead County, Minnesota –cases per 100,000:

  • 1965: 28
  • 1980: 90.5
  • 1991: 132.7
  • 2001: 213.9
  • 2011: 246.7

While rates of IBD have “shown signs of stabilization…pediatric-onset IBD continues to increase steadily in incidence.”

IBD Around the World –cases per 100,000:

  • 2005 Japan: 76
  • 2005 S Korea: 42
  • 2013 India: 9.3
  • 2013 China: 3.3.  The greatest incidence is noted in areas of increased urbanization and economic advancement.
  • 2005: Brazil: 9.7

Environmental factors/associations:

  • Cigarette smoking –increases risk of Crohn’s disease in Western countries, and has protective effect against Ulcerative colitis
  • Antibiotic use –increases risk of IBD in Western countries, but may be protective in developing countries.  “Antibiotic-induced dysbiosis may not develop as easily in developing countries, owing to ubiquitous exposure to a diverse range of microbiota that rapidly repopulate the intestinal tract.”
  • Breastfeeding –protects against developing IBD
  • Vitamin D –low levels increase risk of IBD in Caucasians.
  • Fiber –a “diet high in fiber protects against Crohn’s disease.”

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JD Lewis, MT Abreu.”Diet as a Trigger or Therapy for Inflammatory Bowel Disease”  Gastroenterology 2017; 152: 398-414.

“The most common question asked by patient is …’Doctor, what should I eat?'”

Key points:

  • Data from studies of immigrants to higher-IBD prevalence countries show an increasing incidence of IBD, leading to the hypothesis that environmental factors such as diet affect risk of IBD.
  • In early life, breast milk, in some but not all studies, has been associated with a lower risk of childhood-onset IBD.
  • Before development of IBD, studies have shown lower risk of IBD “among people who consume more fruits and vegetables, and a higher risk in people who consume less of these and more animal fats and sugar.”
  • “There is little information about which foods induce flares.” However, for UC, “a high intake of meat, especially red and processed meat, protein, alcoholic beverages, sulfur, and sulfate increased the likelihood of a flare” based on food questionnaires.  In patients with CD, diet with higher “total fat, saturated fat, monounsaturated fatty acids, and a higher ratio of omega-6:omega-3 PUFAs was associated with disease relapses.”
  • “Only approximately half of patients have ever received advice from a dietitian.”
  • Oral iron may trigger flares in a small percentage of patients with IBD.  The authors note that adherent E coli express genes for iron acquisition and require iron for growth.

Specific Diets/Additives:  Most of these diets have been discussed in previous posts, including:

Exclusive (and Partial) Enteral Nutrition:

  • “The most widely studied dietary intervention.” It has been shown to be effective for CD.  More elemental formulas have NOT been shown to be more effective.  “EEN and PEN therapy is less likely to normalize fecal levels of calprotectin in children.”
  • “Dietary therapy reduced inflammation and led to changes in the microbiome within 1 week. Unlike TNF antagonists, however, the changes to the microbiome induced by EEN did not lead to a microbiome resembling that of healthy individuals.”

Specific Carbohydrate Diet (SCD):

  • This diet has been studied in small populations.  Suskind et al reported SCD effectiveness “in 7 children with CD…showed that fecal calprotectin level decreased from a mean of 685 mcg/g to 213 mcg/g at 2-6 after starting the diet.”  “Cohen et al used video capsule endoscopy…in 10 children with CD…Four of 10 children achieved complete mucosal healing (Lewis score <135) and 6 of 10 children achieved clinical remission.”

Low FODMAP diet:

  • While the diet may induce symptom improvement, there is no “evidence that a low FODMAP diet reduces inflammation.”

Vitamin D supplementation:

  • “Vitamin D has multiple potential beneficial effects on intestinal inflammation.” The authors review studies that report lower risk of CD in patients with higher vitamin D levels and on the reduction in relapse in a study of CD patients who were in remission and  treated with Vitamin D (1200 IU daily)

Curcumin supplementation:

  • The authors review two small studies which suggested that curcumin for patients with ulcerative colitis increased clinical remission (when used with mesalamine)

The overall advice the authors give is that patients “should be advised to eat a well-balanced diet, such as the Mediterranean-style diet, avoiding processed foods or foods that they self-identify as worsening their symptoms.  Patients who are committed to attempting to manage their disease predominantly through dietary modification should be counseled about the importance of assessing for resolution of inflammation in addition to symptoms.”

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.