Nutritional Management of NAFLD

By
Yasmin Saad
Professor of Hepatogastroenterology
Cairo University
Consultant of Clinical Nutrition, 57357 CCHE
NNI Diploma & ESPEN Certified
 Introduction of NAFLD

 Prevalence of NAFLD

 Management lines

 Dietary guidelines

 Macronutrient distribution

 Different dietary types

 Exercise
 NAFLD
 NAFLD is a major health problem because of its high prevalence.

 NAFLD is associated with obesity, insulin resistance, DM2,

hyperlipidemia, hypertension and metabolic syndrome

 It covers a wide pathological spectrum ranging from steatosis to

steatohepatitis (NASH) progressing to different degrees of liver fibrosis,
cirrhosis and hepatocellular carcinoma (HCC)
 Prevalence of NAFLD
 Despite regional variation, the global prevalence of NAFLD is increasing
overall

 The pooled global prevalence of NAFLD was 29.8%

 South America and North America had the highest NAFLD prevalence at
35.7% and 35.3% respectively.

 From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to
37.3% (yearly increase of 0.7%, P < .0001), with South America showing
the most rapid change of 2.7% per year, followed by Europe at 1.1%.
Clinical Gastroenterology and Hepatology, 2021
 NAFLD-related HCC

 NAFLD is the fastest growing cause of hepatocellular carcinoma (HCC) in the USA,
France and the UK.

 Globally, the prevalence of NAFLD-related HCC is likely to increase concomitantly

with the growing obesity epidemic.

 The estimated annual incidence of HCC ranges from 0.5% to 2.6% among patients
with NASH cirrhosis.

Nature Reviews Gastroenterology & Hepatology, 2021

 NAFLD-related HCC

 The incidence of HCC among patients with non-cirrhotic NAFLD is

lower, approximately 0.1 to 1.3 per 1,000 patient-years.

 Emerging evidence indicates that reduced immune surveillance,

increased gut inflammation and gut dysbiosis are potential key steps in
tumorigenesis.

Nature Reviews Gastroenterology & Hepatology, 2021

 Management of NAFLD

 There is no clear consensus on the pharmacological treatment of NAFLD.

 It is clear that therapeutic approaches should focus on lifestyle

modification.

 Diet and exercise interventions remain the first line of therapy and studies
have shown that a healthy diet and weight loss in the early stages of
NAFLD could be sufficient to control disease progression.

 Despite clear evidence that dietary interventions are effective, the extent
and the composition of the diet has not been clearly established
 EASL, EASD, EASO, AASLD, ESPEN,
AISF (2020)

 Collectively, these groups all advocate for lifestyle

modification that involves a hypocaloric diet, engagement
in physical activity, limited sugar intake, and achievement
of 7% weight loss
Weight loss %

Nutrients, 2020
 Dietary plan
 The primary diet goal is to implement a hypocaloric diet to
create a caloric deficit.

 Energy deficit between 500 and 1000 kcal per day will lead to
weight loss of 0.5–1 kg per week but it should not exceed 1 kg
per week
 Energy Requirements

 Nutrition guidelines for population with NAFLD recommended a

hypocaloric diet based on individual needs to promote weight
loss1200-1500 kcal/ day

 Energy requirements for patients with NAFLD are: 25 to 30 kcal/ kg,

based on dry weight or an adjusted ideal weight, or add 20% to 40%
to basal energy expenditure (BEE) by using the Harris-Benedict
equation
 Energy Requirements
 Rapid and uncontrolled weight loss may:

 Worsen clinical symptoms of NAFLD

 Increase the risk of gallstone disease if the rate of weight loss exceeds 1.5 kg/
wk.

 VLCD (388 kcal/ day) can cause the activation of overall inflammation and a
rise in serum bilirubin levels
 Energy Requirements

 In NASH patients, a dietary intervention and weight loss > 7 %

was associated with improvement in:

 Liver histology (steatosis, lobular inflammation, & ballooning injury)

 Liver enzymes

 Intra-hepatic lipid content

 Insulin resistance
 Western Diet
 The Western diet is usually described as being high in total energy with an
elevated content of saturated fat and refined sugars.

 These macronutrients influence metabolic pathways that contribute to liver

fat accumulation.
o A hyperenergetic diet with excess energy predominantly from saturated fatty acids
elevated intrahepatic triglycerides (55%) by stimulating adipose tissue lipolysis.

o Extra energy from simple sugars increased liver triglycerides (33%) by stimulating de
novo lipogenesis

Diabetes Care 2018

 Macronutrients distribution

 Current evidence does not provide a consensus on the

ideal macronutrient composition of the diet
Dietary approaches based on macronutrient
restriction
Dietary approaches based on Energy
Requirements
What is The Favorable Diet?
 1- What is favorable Diet?
 The Mediterranean diet (MD) is the most
recommended diet pattern for NAFLD management.

 It has shown the ability to improve liver steatosis in

several studies, independent of caloric restriction

Clinical liver Disease, April 2020

 Mediterranean diet

 Higher Mediterranean diet scores and inversely related to IR, & NAFLD
severity in observational studies

 It has been hypothesized that MeDiet may have role in preventing or

slowing oxidative stress

 Vegetables (MeDiet) are important source of phytosterols, a natural

cholesterol lowering agent which reduce CV risk
 Mediterranean diet MD

 The MD is traditionally plant based (whole

grains, legumes, fruit, vegetables), lower in
carbohydrates (limited simple sugars and refined
carbohydrates), and rich in monounsaturated
(mostly olive oil) and omega-3 fats, and
incorporates limited red meat and limited low-fat
dairy
 Med Diet
 In general, MedDiet provides around 13–18% of energy from
protein, 43–48% from carbohydrates, and 35–41% from fat, and it
tends to be low in saturated fat whereas monounsaturated fatty acids
(MUFA) intake is especially abundant (8–11% from saturated fat,
16–23% from MUFA, 4–6% from polyunsaturated fats).
Furthermore, it provides approximately 33 g of fiber per day
 Fibers
 Soluble ones:
Slow gastric emptying & absorption of glucose & cholesterol
 represented by
 Pectin (fruits)
 Gums (beans, peas, lentils & chickpeas)
 Fibers

 Insoluble ones:
Increase satiety & regulate intestinal motility
 Represented by
 Cellulose (wheat)
 Hemicellulose (grains)
 Lignin (green vegetables)
 Fibers
 Considering the high prevalence of NAFLD in patients with MS, the use of
fibers as therapeutic strategy for glycemic, lipid and weight control in
patients with steatosis seems reasonable.

 Requirements for general population are set at 38 g/ day for men and 25 g/
day for women aged 19 to 50 years (5-15 g/day from soluble fibers)
 Protein

 A high protein hypocaloric diet (1,200- 1,400 kcal/day), 35% of mixed

animal & plant vegetables was associated with improvement of :

 Lipid profile

 Glucose homeostasis

 Liver enzymes

In NAFLD patients independently of reduction in BMI or body fat mass.

 Protein

 Malnutrition caused by protein

deficiency leads to steatosis

 On the other hand; excessive protein

intake may cause glomerular
sclerosis, HTN & kidney failure in
patients susceptible to kidney disease
 Protein

 In NAFLD patients, moderate protein intake (20-25% of total

calories) may both be safe and have a positive impact in weight
loss and improvement of IR

 For patients with T2DM , ADA recommend 15-20% of total

daily energy from protein
 Protein
 Protein intake must be adjusted for body weight and medical
condition.

 According to the most recent data, normal protein intake in

adults is around 16–17% of energy intake.

 The requirement of protein in hepatitis is estimated minimally at

1.0 to 1.2 g/kg/day and may range up to 1.5 g/ kg if patients
have cirrhosis.
 Saturated fatty acids

 Excessive consumption of SFA (milk, coconut,

lard) promotes endoplasmic reticulum stress and
hepatobiliary injury.

 However sever restriction may not be beneficial

in cases of NAFLD
 Saturated fatty acids

 McCarthy and Rinella’s review identified evidence to support

negative effects of high (>10%) and low (6%) dietary SFAs
consumption, and suggested that a range of SFA between 6%
and 10% may be most beneficial to patients with NAFLD
 Monounsaturated fatty acids
 MUFA typically represented by olive oil, nuts,& avocado

 Diet in which MUFA > 20% of total daily caloric intake have shown
benefit in NAFLD patients because:

o Reduce LDL, VLDL, TG & glucose level especially in Diabetic patient

o Reduce lipogenesis

o Increase HDL and oxidation of other FA

 Omega 6 Polyunsaturated fatty acids

 Regarding omega 6 PUFA , represented mostly by vegetable oils

(soy, corn, cotton & sunflower)

 AMDR is 5% to 10% of total daily calories

 AI for linolenic acid (17 g/ day for young men and 12 g/ day for
young women)
 Omega 6 Polyunsaturated fatty acids

Excessive intake of omega 6 is not encouraged

as it :
 Alter Production of inflammatory markers

 Increase lipid peroxidation & HDL reduction

 Omega 3 Polyunsaturated fatty acids

 Omega 3 is found in fish oil and walnuts

 They improve blood lipid profile

 Reduce inflammation

 Reduce steatosis

 Reduce liver damage in NAFLD patients

 Omega 3 Polyunsaturated fatty acids

 AMDR for alpha linolenic acid is 0.6% to 1.2% of energy

 Up to 10% of the AMDR consumed as eicosapentaenoic acid

(EPA) and/ or docosahexaenoic acid (DHA)

 AI is 1.6 g/ day for men and 1.1 g/ day for women.

 Omega 3 Polyunsaturated fatty acids

 The DHA and EPA deficiency can contribute to the

development of NAFLD, which was confirmed by an
experimental study on animals
 Omega 3 Polyunsaturated fatty acids

 According to ADA , supplementation with omega 3 as a specific

adjuvant therapy for NAFLD is not recommended because of
heterogenicity of the studies.

 It may be considered to reduce high TG by supplementation of

2 g/ day for 6 months, it decrease the level of steatosis as well
as serum ALT activity, and serum TG levels
 Trans Fatty acids

 Ingestion of large amounts of trans fatty acids (TFA, hydrogenated

oils) :

 Increase inflammatory markers

 Endothelial dysfunction

 Alteration in lipid levels (++ LDL, TG & lipoproteins, ---HDL)

 A daily in take < 1% of total daily calories in the form TFA is suggested
 Mediterranean lifestyle

 the Mediterranean lifestyle also involves regular physical

activity, and healthy sleep habits. In this regard, a recent
randomized controlled single-blinded clinical trial, evaluated
the effects of a MedDiet and a Mediterranean lifestyle
(moderate-vigorous intensity, at least 30 min/day; optimal sleep
duration: ≥7 and ≤9 h/day, and mid-day rest)
 The reversal of NAFLD by KD: By markedly altered hepatic
mitochondrial fluxes and redox state to promote ketogenesis rather
than synthesis of IHTG= reduction of hepatic steatosis
 KD
 It might lack fiber-rich foods as well as water-soluble vitamin sources in
situations when the diet plan does not take these elements in consideration.

 Long-term ketosis and food restriction are not harmful, but diet compliance
are questionable.

 Greater LDL-cholesterol levels associated with a KD during weight loss has

been previously reported, lipid profile changes raised by KD may need a
deeper analysis, considering also lipid sub-fractionations
 IF
 Intermittent fasting (IF) is inducing a certain degree of ketosis.

 It involves a great variety of eating patterns.

 No or few calories are consumed for time periods that can range from
12 h to several days.

 One key mechanism appears to be the body's preferential shift from

glycogenolysis-derived glucose to lipolysis-derived ketones
 DASH diet
 DASH (Dietary Approach to stop Hypertension)
consists of vegetables, low fat dairy products,
fruits, integral cereals, fish, poultry, & nuts

 Avoidance of SFA, red meat & sugars

 Daily Na content max 2.3 g/d with best blood

pressure control if Na intake 1.5 g/d

 DASH diet may be beneficial for NAFLD patients

by directly acting on risk factors especially HTN,
IR & dyslipidemia
 DASH diet in NAFLD
 A randomized controlled trial conducted for 8 weeks in patients with
overweight/obesity and NAFLD showed significant beneficial effects on:
(1) bodyweight

(2) liver transaminases

(3) markers of insulin sensitivity

(4) lipid profile

(5) serum biomarkers of inflammation

(6) oxidative stress in the DASH diet group compared to low-energy diet
Liver Int. 2015
 Fructose

 It is mainly derived from sucrose (table sugar) and

corn syrup which is abundantly used in sugar-
sweetened beverages
 Fructose
 Fructose metabolism increases:
 Lipogenesis

 Free radical oxygen species production

 Gut permeability

 Bacterial overgrowth

 Serum lipopolysaccharide levels

 Reduce lipid oxidation

o It is important to note that whether this effect is specific for an excess intake of
fructose or is only a consequence of calorie excess, Is still under debate
 Prebiotics & Probiotics

 Prebiotics are non-digestible CHO that stimulate

probiotic (beneficial bacteria) growth & activity
mainly lactobacilli & bifidobacteria

 Studies in animal models show promising evidence

of prebiotic use in the treatment of hepatic steatosis
 Prebiotics & Probiotics
 Probiotics have been used to treat & prevent hepatic steatosis
through:

 Modification of local microbiota

 Improvement of epithelial barrier

 Attenuation of intestinal inflammation & oxidative stress

 Studies showed improvement in liver enzymes and total &

LDL cholesterol levels
 Prebiotics & Probiotics

 No sufficient robust data to support the recommendation of

their use as alternative to NAFLD treatment
 Vitamin E

 Oxidative stress is considered as one of mechanisms of

hepatocellular injury & fatty liver disease progression

 Vitamin E (antioxidant) is suggested to be used to improve

steatosis, inflammation, lower transaminases level
What about Coffee?
 Coffee & Phenolic compounds

 Coffee is composed of more than 1.000 substance, caffeine is

the main one

 It was investigated in NASH & NAFLD to find inverse

relationship between coffee intake & aminotransferases levels,
inflammation, hepatic fibrosis & disease progression

 Heterogenicity of studies in this field doesn’t augment use of

coffee as adjuvant therapy in NAFLD
 Phenolic compounds

 Other notable sources of natural phenols include berries, tea,

chocolate or cocoa, fruits and vegetables.

 Herbs, spices, nuts (walnuts, peanuts) & algae

 Although studies indicate a beneficial effects of isolated

polyphenols or in extract in reducing liver fat accumulation, it
is still necessary to establish the adequate dose and needed
time for treatment steatosis with these substances
 Take home message
 The global prevalence of NAFLD is increasing overall.

 Urgent measures that increase global awareness and tackle the

metabolic risk factors are necessary to reduce the impending burden
of NAFLD-related HCC

 Promoting healthy lifestyle environments must be done.

 Take home message
 The most effective type of long-term treatment remains diet therapy.

 Deciding on which diet regimen is best for a patient or group of patients is

still a hard task due to the multiple factors that need to be considered.

 There is no consensus as to what diet or lifestyle approach is the best for

NAFLD patients.

 The most popular diets in NAFLD: overall calorie count, food choices,
distribution of energy from fat and carbohydrates, and timing