Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease
Am J Clin Nutr
Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease1-3
Angela M Zivkovic
J Bruce German
Arun J Sanyal
Nonalcoholic fatty liver disease (NAFLD) is a significant health problem and affects 70 million adults in the United States (30% of the adult population), and an estimated 20% of these individuals have the most severe form of NAFLD-nonalcoholic steatohepatitis (NASH). The mechanisms underlying disease development and progression are awaiting clarification. Insulin resistance and obesityrelated inflammation, among other possible genetic, dietary, and lifestyle factors, are thought to play a key role. A program targeting gradual weight reduction and physical exercise continues to be the gold standard of treatment for all forms of NAFLD. Even though weight loss and dietary and lifestyle changes are recommended as primary treatment for fatty liver, little to no scientific evidence is available on diet and NAFLD. This article reviews the implications of current dietary approaches, including national guidelines and popular weight-loss diets, with a focus on determining the optimal diet to prescribe for NAFLD and NASH patients. The effects of macronutrient content (carbohydrate, fat, and protein ratios) and specific food components, such as soluble fiber, n 3 fatty acids, and fructose, are discussed. The premises, effects, barriers, and issues related to current dietary guidelines and specific diets are discussed, and the question, “Will it work for the pathogenesis of NAFLD and NASH? ”, is addressed. Am J Clin Nutr 2007;86:285-300.
Nonalcoholic fatty liver disease; NAFLD; nonalcoholic steatohepatitis; NASH; diet; weight loss
The rising incidence of obesity in today’s environment is
associated with many obesity-related health complications (
including cardiovascular disease, diabetes, hyperlipidemia,
hypertension, and nonalcoholic fatty liver disease (NAFLD) (
This constellation is also recognized as the metabolic syndrome
and is characterized by underlying insulin resistance. NAFLD is
defined as the accumulation of lipid, primarily in the form of
triacylglycerols in individuals who do not consume significant
amounts of alcohol ( 20 g ethanol/d) and in whom other known
causes of steatosis, such as certain drugs and toxins, have been
excluded (6). The spectrum of NAFLD includes steatosis alone
(type 1), steatosis plus inflammation (type 2), steatosis plus
hepatocyte injury or ballooning degeneration (type 3), and steatosis
plus sinusoidal fibrosis, Mallory bodies (type 4), or both (
NASH is considered to be the most severe form of NAFLD (types
3 and 4) and is associated with an array of adverse clinical
outcomes, including cirrhosis (7), hepatocellular carcinoma
), and advanced liver disease, which leads to liver-related
Given the close relations between obesity, the metabolic
syndrome, and the development of NAFLD, it is not surprising that
many NAFLD patients have multiple components of the
metabolic syndrome, whether or not they are overweight or obese.
Insulin resistance is present in and is a significant predictor of
NAFLD and NASH in most patients (
), even the 10 –15% of
patients who are not overweight (
). NAFLD is a
multifactorial disease that involves a complex interaction of genetics,
diet, and lifestyle, all of which combine to form the NAFLD
phenotype, as discussed in several recent reviews (
A cornerstone of the management strategy in such patients is
the use of diet to decrease body weight, and improve glycemic
control, dyslipidemia, and cardiovascular risks, as well as to treat
fatty liver. There is a bewildering array of diets that have been
recommended for the prevention and treatment of all of the
components of the metabolic syndrome. Their utility for the treatment
of NAFLD remains mostly unknown. It is also important to note
that cognitive-behavioral approaches, in addition to dietary
modification, are necessary for the long-term success of dietary and
lifestyle interventions; however, this is outside the scope of the
In this article, we review the current concepts about the
pathogenesis of hepatic steatosis and steatohepatitis and evaluate the
existing diets in the context of this knowledge and the available
literature. The intent is to enable clinicians to evaluate the diets
of NAFLD and NASH patients and make rational decisions
based on this perspective—in the absence of controlled trials—to
help their patients. Finally, a tailored approach for the dietary
treatment of NAFLD is offered as a way to optimize the dietary
management of this condition.
NAFLD PATHOPHYSIOLOGY AND DIET
The pathophysiology of NASH is not fully understood. The
complexities related to disease development and progression are
discussed in detail elsewhere (
) and will not be reviewed in
detail here. The main aspects of NAFLD and NASH
pathophysiology as they relate to diet and nutrition are briefly discussed
Dietary effects on whole-body metabolism and its regulation
via effects on hormones, transcription factors, and lipid
metabolic pathways are considered to play a central role in NAFLD.
Insulin resistance is currently thought to be a key factor in the
development of both NAFLD and NASH (
). Many studies
have shown an association of insulin resistance with NAFLD and
NASH on the basis of impaired glucose tolerance or impaired
fasting glucose (
). Despite elevated insulin concentrations,
adipose tissue fatty acid flux was not suppressed in NAFLD
), which indicated the presence of peripheral insulin
In most patients, overnutrition or inappropriate diet are
thought to lead to chronically elevated glucose, insulin, and free
fatty acid (FFA) concentrations in the blood. Both excessive
carbohydrate intake (Figure 1) and excessive fat intake (Figure
2) could play a role in increasing blood glucose, FFA, and insulin
concentrations, independently or together. These dietary
conditions (Figure 3) contribute to resistance to insulin-stimulated
glucose uptake at the level of the adipose tissue and skeletal
muscle as well as resistance to the insulin-mediated suppression
of TG hydrolysis in adipose tissue (
). Glucose uptake in the
liver is not insulin dependent, and increased glucose
concentrations in the blood lead to increased glucose uptake by the liver.
Insulin-mediated stimulation of de novo lipogenesis (DNL)
leads to an increased conversion of glucose to fatty acids (31).
Together, the increased concentrations of both glucose and
FFA in the blood contribute to excessive accumulation of neutral
lipids in the liver. A recent study by Donnelly et al (
), using a
multiple-stable-isotope labeling approach, showed that in
NAFLD patients plasma FFAs were the primary contributor to
the liver triacylglycerol content in the fasted state (50 –70% of
total FA) and to the lipoprotein triacylglycerol content in both the
fed and the fasted state (50 –75% of total FAs). Most of the
plasma FFAs were from adipose tissue, which accounted for
70 –90% of FAs in the fasted state and 50 –70% in the fed state.
The de novo synthesis of FAs from glucose, fructose, and amino
acids was also dysregulated in NAFLD patients. DNL was
elevated in the fasting state—accounting for 25% of liver and VLDL
triacylglycerols compared with 5% in healthy individuals (
)—and failed to increase postprandially. Moreover, this study
showed that there were likely 2 distinct pools of FAs in the liver,
which were handled differently. Plasma FFAs—representing
mainly adipose-derived FAs—were thought to be part of a
fastturnover pool that was preferentially incorporated into VLDLs,
whereas FAs synthesized de novo were thought to enter a hepatic
holding pool. Therefore, especially in the presence of peripheral
insulin resistance, in which the flux of FAs from the adipose is not
suppressed by insulin and plasma FFAs are persistently high,
elevated rates of lipogenesis may be a significant source of
accumulated triacylglycerol in the liver.
In healthy individuals, elevated lipid concentrations in the
liver lead to increased VLDL production and secretion; however,
in NAFLD and NASH patients, this increase in fat export via
VLDL may be impaired or insufficient to prevent fatty liver (
Hypertriglyceridemia, low HDL concentrations, and small,
dense LDL particles often result from an increase in the
concentration, size, or both of circulating VLDL (
), which together
confer an increased risk of cardiovascular disease (
NAFLD and NASH patients, blood lipid concentrations may be
normal or elevated, and many patients have the atherogenic
dyslipidemia associated with the metabolic syndrome, which
includes high triacylglycerol, low HDL, and increased small,
dense LDL (45).
The original “two-hit hypothesis” of NASH asserts that the
accumulation of lipid in the liver (hit one) is followed by a
cascade of prooxidative, hepatotoxic events (hit 2), which are
caused by an as yet unknown mechanism (
dysfunction has been considered to be such a second hit (
There are several other mechanisms being investigated also. The
increased secretion of tumor necrosis factor (TNF- ) and other
proinflammatory cytokines by adipocytes and infiltrating
macrophages is thought to lead to chronic systemic inflammation
(Figure 4) as well as obesity-linked insulin resistance (
Elevated concentrations of circulating TNF- have been
documented in NAFLD patients (
) and have been implicated in the
manifestation of fatty liver disease (
). Small intestinal
bacterial overgrowth (
) and deficiencies in various nutrients,
including essential fatty acids (
), choline (
), and amino acids
), may also be involved in the development and
progression of this disorder; however, limited evidence exists to support
DIETARY TREATMENT OF NAFLD AND NASH
Because of the strong association of obesity and the metabolic
syndrome across the entire spectrum of NAFLD, current
recommendations for the treatment of fatty liver disease are aimed at
weight loss and dietary modification (
). For unknown
reasons, sudden or quick weight loss achieved through dietary
modification may lead to the progression of liver failure in some
NAFLD patients (60). On the other hand, weight reduction
through surgical methods, even with quick weight-loss after
surgery, has been successful in reducing disease progression (
). Despite the fact that weight loss and dietary and lifestyle
changes are recommended as primary treatment for fatty liver, no
specific guidelines exist pertaining to diet. Very few studies of
the effects of different diets on NAFLD have been performed.
The premises, effects, barriers, and issues related to current
dietary guidelines and specific popular weight-loss diets as they
relate to NAFLD are discussed below.
EFFECT OF INDIVIDUAL DIETARY COMPONENTS ON
THE METABOLIC SYNDROME, INSULIN RESISTANCE,
HEPATIC LIPID METABOLISM, AND
INFLAMMATORY AND FIBROTIC PATHWAYS
A recent study in a rat model of hepatic steatosis showed that
saturated fatty acids (SFAs) promote endoplasmic reticulum
stress as well as hepatocyte injury (
). Accumulation of SFAs in
the liver due to high-SFA or high-fructose diets led to an increase
in markers associated with endoplasmic reticulum stress and
liver dysfunction. This, along with ample evidence associating
high-SFA intakes with an increased risk of cardiovascular
), suggests that the intake of dietary saturated fats
should be limited in NAFLD patients. However, what saturated
fat intake should be recommended?
A study comparing 25 overweight (BMI 30; in kg/m2)
NASH patients and 25 age- and BMI-matched controls collected
7-d food records and assessed dietary patterns (
patients had higher intakes of SFA at 14% of total energy, compared
with 10% in controls. Insulin resistance, as measured by the
insulin sensitivity index, was correlated with SFA intake.
Therefore, a SFA intake 10% of total energy may contribute to
insulin resistance and may not be suitable for NASH patients.
A randomized, double-blind, crossover study examined the
effects of 3 diets in 86 free-living healthy men: a control diet
(38% fat with 14% SFAs), the National Cholesterol Education
Program Step I diet (30% fat with 9% SFAs), and the National
Cholesterol Education Program Step II diet (25% fat with 6%
). Although both reduced-fat diets decreased LDL,
they also decreased HDL and increased plasma triacylglycerol
after 6 wk compared with the control diet. In response to the
6%-SFA diet, subjects who were insulin resistant, who had a
higher percentage of body fat, and/or who had a higher BMI—
characteristics that describe most NAFLD patients—
experienced smaller reductions in LDL, larger reductions in HDL, and
increases in triacylglycerol compared with subjects who were
insulin sensitive. On the basis of this evidence, SFA intakes 7%
of total energy may not offer any further improvements in blood
lipids in patients with insulin resistance and may even be
It is still unclear whether a minimum intake of SFAs in the diet
is beneficial or perhaps even required for optimal health (
the basis of the clinical evidence discussed above, SFA intakes
7% and 10% of energy may be suboptimal for NAFLD
Monounsaturated fatty acids
Monounsaturated fatty acids (MUFAs) are a class of fatty
acids that are found in foods such as olive oil, nuts, and
avocadoes. The beneficial effects of MUFAs on cardiovascular disease
risk and blood lipid profiles have been extensively studied (
In particular, dietary MUFAs decrease oxidized LDL (
), total cholesterol (TC), and triacylglycerol
concentrations, without the concomitant decrease in HDL typically
seen with low-fat diets (
). Additionally, the replacement
of carbohydrate and saturated fat with MUFAs leads to
reductions in glucose and blood pressure and to an increase in HDL
in patients with diabetes (
). A MUFA-rich diet (40% of
energy as fat) also decreased VLDL-cholesterol and
VLDLtriacylglycerol more and was more acceptable to patients with
non-insulin dependent diabetes mellitus (type 2 diabetes) than
was a high-carbohydrate diet (28% of energy as fat) (
Therefore, an increase in the intake of MUFAs, particularly as a
replacement for SFAs and as a higher proportion in the diet in lieu
of carbohydrate, may be beneficial for NAFLD patients.
Polyunsaturated fatty acids
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids
that include n 6 and n 3 fatty acids. The n 3 fatty acid
-linolenic acid is a precursor for the long-chain products
docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
PUFAs have been shown to decrease the risk of heart disease when
consumed in lieu of SFAs in both epidemiologic (
clinical (78) studies. The ratio of n 6 to n 3 fatty acids seems
to be important in determining the effect of PUFAs on various
lipid and nonlipid indexes. Replacement of n 6 PUFAs with
-linolenic acid improved peripheral insulin sensitivity and
lowered cholesterol concentrations in rats with fructose-induced
insulin resistance (
). An approximate dietary intake of 6% n 6
and 1% n 3 fatty acids as percentage of energy has been
recommended to maximize the cardiovascular benefits of these
essential fatty acids (
Several studies have shown a link between essential fatty acid
deficiency and the development of steatosis in animal models
51, 53, 55, 81– 85
), a link that was first observed almost 30 y ago
(86). There is also an indication that essential fatty acids may be
essential for VLDL secretion (
). In geese overfed with corn,
liver steatosis is accompanied by a reduced essential fatty acid
content of membrane phospholipids despite an adequate dietary
supply of both linoleic and -linolenic acid (
n 3 Fatty acids
The effects of n 3 fatty acids on dyslipidemia and insulin
resistance have been extensively reviewed (
) and provide
convincing evidence that n 3 fatty acids should be an important
dietary component in patients with NAFLD and NASH.
Specifically, DHA and EPA induce fatty acid catabolism through the
activation of peroxisome-proliferator activated receptor
(PPAR)–mediated pathways (
) and down-regulate DNL through
sterol regulatory element binding protein (SREBP) pathways (
The effects of dietary fish oil, which is high in DHA and EPA, in
animal models of insulin resistance are impressive. The
beneficial effects include 1) decreased plasma triacylglycerol, FFAs,
glucose, and insulin; 2) prevention of peripheral insulin
resistance; 3) decreased triacylglycerol concentrations, VLDL
secretion, and lipogenesis in the liver; 4): decreased lipid
concentrations and utilization and storage of glucose in skeletal muscle;
and 5) decreased adipocyte cell size and visceral fat content and
increased insulin-stimulated glucose transport in the adipose
Walnuts, a good source of -linolenic acid, may also be
beneficial. When patients with type 2 diabetes were placed on diets
that included 30 g walnuts/d, plasma HDL and the ratio of HDL
cholesterol to TC increased, and LDL decreased after 8 wk (
In another study, hypercholesterolemic men and women who
substituted 32% of their MUFA intake with walnuts had
significant decreases in TC and LDL and improved endothelial
function compared with controls (
The first studies to have examined the effects of n 3 fatty acid
supplementation in NAFLD patients were recently published.
One such study found that 1 g fish oil/d for 12 mo decreased blood
triacylglycerol concentrations, liver enzymes, fasting glucose,
and steatosis in NAFLD patients (
). Another study also found
decreased blood triacylglycerol, liver enzymes, and TNF- and
regression of steatosis as assessed by ultrasonography after 6 mo
of supplementation with 2 g fish oil/d (
). These preliminary
results, along with the evidence reviewed above, suggest that the
consumption of n 3 fatty acids found in fish oils and walnuts is
likely to improve blood lipid profiles and to reduce
inflammation, steatosis, and liver damage in NAFLD patients.
trans Fatty acids
trans Fatty acids occur naturally in foods such as dairy
products as a result of bacterial metabolism and in foods such as
margarines as a result of hydrogenation. trans Fatty acids consist
of multiple isomers that have differential effects on human
). The bacterially derived cis-9, trans-11 conjugated
linoleic acid and trans-11 oleic acid typically found in dairy
products do not have adverse effects on lipoprotein profiles (
Conversely, intake of trans-10, cis-12 conjugated linoleic acid
from hydrogenated oils has been found to increase inflammatory
), induce endothelial dysfunction (
unfavorably alter the blood lipid profile by increasing the LDL:HDL and
TC:HDL ratios (
Effective 1 January 2006, after reviewing available scientific
evidence regarding the effect of trans fats on cardiovascular
health, the Food and Drug Administration ruled that food
manufacturers are required to include the content of trans fats on
nutrition labels (
). Although the specific mechanisms of action
are not yet clear, the recommendation to avoid the intake of trans
fatty acids from hydrogenated oils seems well founded for those
at risk of dyslipidemia.
Glycemic index and fiber
Several trials have shown decreases in TC in response to intake
of soluble fiber from sources such as oats (
). This type of
evidence has led the Food and Drug Administration to approve a
claim of cardiovascular disease risk reduction for the labeling of
oat products and foods containing soluble fiber (102). The
socalled “second-meal effect” of low-glycemic index (GI) foods or
slow-release carbohydrates improves the glycemic response to a
subsequent meal and was first described in the early 1980s (
The effects of high-fiber, low-GI carbohydrates on glycemic
response and cholesterol concentrations were reviewed recently
in a meta-analysis (
) and provide evidence that these dietary
components may be beneficial to individuals with impaired
A breakfast containing a high-fiber indigestible and
fermentable starch compared with a low-GI starch reduced FFAs in the
blood after a subsequent meal (
). Whereas both breakfasts
lowered glucose concentrations, only the breakfast containing
the low-GI starch decreased insulin concentrations. Although the
results of this study cannot be generalized to long-term effects on
glycemic control or lipid profiles, it seems reasonable to
conclude that the inclusion of carbohydrates that are high in
indigestible and fermentable fiber and low in GI can be helpful in
maintaining glucose, insulin, and FFA concentrations in
individuals with insulin resistance and NASH.
Sucrose and fructose
Several studies have shown that high intakes of fructose
increase DNL in animal models and in humans (
study of lean and obese women found that 4 d of overfeeding with
either a glucose or sucrose drink increased DNL 2–3-fold (
The higher the woman’s baseline lipogenesis rate, the higher the
increase in DNL in response to the 4 d of overfeeding, with a
trend toward a higher increase with sucrose than with glucose.
These data suggest that some individuals may be more sensitive
to fructose-induced stimulation of DNL.
Studies of the effects of fructose consumption on whole-body
energy metabolism were reviewed recently by Havel (
feeding study showed that 2 d of a high fructose intakes (30% of
kcal/d, consumed as a sweetened beverage at every meal)
resulted in decreased postprandial glucose concentrations and
insulin responses and prolonged alimentary lipemia in women
). High glucose intakes with meals, on the other hand,
resulted in a suppressed postprandial response of the orexigenic
hormone ghrelin. These data suggest that a high consumption of
fructose and glucose in the form of sweetened beverages may
lead to changes in long-term energy balance regulation at the
level of the central nervous system, which favors increased
calorie consumption and weight gain.
Sweetened drinks, such as sodas, are typically consumed as
additional calories and lead to excess intake of as much as 150 –
300 kcal/d (
). It is recommended that intakes of refined sugars
and high-fructose or high-glucose foods and beverages should be
reduced in the NAFLD population. High intakes of fructose and
glucose as simple sugars stimulate the de novo synthesis of fatty
acids, especially in individuals with insulin resistance and in
those who are overweight (
32, 109, 113, 114
There is little information on the effect of protein quantity,
quality, and composition on the pathophysiology of NAFLD and
NASH. It is known that protein deficiency or malnutrition can
cause steatosis (
). Considering that the total protein
content and quality are typically high in the average American diet,
protein deficiency is highly unlikely in NAFLD patients.
Conversely, an excessive intake of protein may cause glomerular
sclerosis, intrarenal capillary hypertension, and eventually renal
malfunction in certain vulnerable individuals who have
underlying renal insufficiency (
). Studies of high protein
intakes and their possible effects on NAFLD are lacking.
CURRENT DIETARY GUIDELINES
US Department of Agriculture Dietary Guidelines for
The official dietary recommendations for healthy Americans,
the Dietary Guidelines for Americans, is published every 5 y as
a joint effort of the Department of Health and Human Services,
and the US Department of Agriculture (USDA) (
guidelines provide advice about dietary habits to promote health and
reduce the risk of major chronic diseases. The USDA guidelines
are meant for health maintenance and are not guidelines for the
treatment of any health condition.
In brief, it is recommended that individuals take in an
appropriate amount of calories for body size and activity level. They
are encouraged to eat a variety of foods, choose from several food
groups, and include predominantly whole grains and their
products in the diet. Nine or more daily servings of fruit and
vegetables are recommended. Servings of meats, fish, vegetable
proteins, dairy, and dairy products are based on energy needs, with
fats and sweets to be consumed sparingly as “discretionary
calories.” The most recent version of the guidelines, published in
2005, for the first time recognizes and discusses the notion of
individual differences and customizes the recommendations,
providing sample meal plans, based on height, weight, and
activity level estimates.
These basic guidelines do not address the special needs of
individuals with various metabolic disorders. NAFLD and
NASH patients are typically overweight, with central adiposity
). As such, their primary nutritional focus must be on weight
and body fat reduction rather than on maintenance, for which the
USDA Dietary Guidelines are primarily designed. Evidence
indicates that NAFLD patients may have increased lipogenesis
and that this, in part, contributes to the accumulation of lipid in
the liver (
). A higher carbohydrate intake was also associated
with a greater odds of inflammation in morbidly obese patients
with NAFLD than was a higher fat intake (
). The emphasis of
the USDA Dietary Guidelines on the consumption of
carbohydrates may therefore be inappropriate for certain patients with
NAFLD and NASH.
American Dietetic Association
The basic dietary recommendation of the American Dietetic
Association for healthy adults is to follow the USDA Dietary
Guidelines, as described above. However, the American Dietetic
Association also maintains an annually updated Manual of
Nutritional Therapy for all known metabolic disorders and other
diseases that registered dietitians and other nutrition
professionals can use to develop diets for their patients. The manual is
available by subscription to nutrition professionals (
Although there are no specific recommendations in the manual
for NAFLD, it does include suggestions for patients with the
metabolic syndrome. The first-line therapy for all lipid and
nonlipid risk factors associated with the metabolic syndrome is a
program incorporating weight loss and exercise. Additional
recommendations include a reduction in the intakes of total fat,
SFAs, and trans fat, and, conversely, an increase in the intakes of
PUFAs and MUFAs. There is also a recommendation to include
long-chain n 3 fats and plant stanols or sterol esters. The
physical activity goal is based on the America on the Move program
), which specifies a goal of increasing the number of steps
per day by 2000 steps above baseline and decreasing energy
intake by 100 kcal/d. It is suggested that the calorie goal be
reached by opting for regular instead of super-size meals, leaving
a few bites on the plate, and drinking water instead of juices and
other beverages. Finally, it is stated that the scientific evidence
does not support any specific generalized nutritional approach
for the metabolic syndrome and, therefore, that interventions
must be individualized.
The recommendations regarding fats and plant stanols and
sterols are well-founded because of the increased risk of
cardiovascular disease in patients with the metabolic syndrome. The
specific goals for increasing physical activity and specific
suggestions for ways to decrease calorie intake are also prudent and
appropriate for NAFLD patients, especially because these
approaches are moderate and would likely lead to gradual,
longterm, sustained weight loss. The American Dietetic Association
recommendations, however, do not address specific approaches
for decreasing insulin resistance and do not provide guidance
regarding carbohydrate and protein intakes.
American Heart Association
Studies have shown associations between fatty liver and
) and increased carotid intima-media thickness
), both of which are indicators of an increased risk of
cardiovascular disease in NAFLD patients. Several recent
investigations have shown associations between insulin resistance, the
metabolic syndrome, and cardiovascular disease (
38 – 40, 42,
); therefore, NAFLD patients having characteristics of the
metabolic syndrome should be treated to reduce their risk of
cardiovascular disease (
The position of the American Heart Association (AHA) on
scientific on healthy food habits focuses on the 3 main risk factors
associated with heart disease— high blood cholesterol, high
blood pressure, and excess body weight (
). The same basic
guidelines put forth by the USDA are recommended by the AHA,
with several modifications. These include recommendations to
eat fish twice a week, avoid trans fats, limit SFA intakes to 10%
of total calories, and limit cholesterol to 300 mg/d. The AHA/
National Heart Lung and Blood Institute (NHLBI) joint scientific
statement on the Diagnosis and Management of the Metabolic
) further recommends decreasing SFA intakes to
7% of total daily calories, maintaining a fat intake of 25–35%
of total calories, reducing overall calorie intake, avoiding simple
sugars, and consuming higher amounts of fruit, vegetables, and
The AHA recommendations to decrease SFA, trans fat, and
cholesterol intakes and to avoid simple sugars, while consuming
more low-GI foods and fish, are all reasonable suggestions for
NAFLD and NASH patients. An SFA intake of 10% of daily
calories, which corresponds with the AHA scientific position
statement, rather than the 7% recommendation in the AHA/
NHLBI joint statement, is recommended for reasons already
National Heart, Lung, and Blood Institute
The NHLBI has a set of recommendations that is published on
the NHLBI website (
), which recommends the Therapeutic
Lifestyle Changes (TLC) diet described below. The Dietary
Approaches to Stop Hypertension (DASH) plan, designed for
individuals with hypertension, and recommendations specifically
pertaining to the dietary management of the metabolic syndrome
are also addressed.
National Cholesterol Education Program
The National Cholesterol Education Program (NCEP) has
been developing guidelines for reducing the incidence of
coronary heart disease (CHD) since 1985. The Step I and Step II diets
were created by the Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults through 2
guideline reports, the Adult Treatment Panel I and II, respectively
). The Step I diet is a strategy for the prevention of CHD in
individuals with LDL concentrations 160 mg/dL or in those
with a borderline high LDL concentration (130 –159 mg/dL) and
2 risk factors, including cigarette smoking, hypertension, low
HDL, family history of premature CHD, and age (men: 45 y;
women: 55 y). This diet restricts total fat intake to 30% of
total daily calories, SFA intake to 10% of total daily calories,
and cholesterol to 300 mg/d.
The Step II diet was created to address the need for further risk
reduction in persons with established CHD and in those who are
already at Step I goals and with a high-risk TC concentration of
240 mg/dL. This diet restricts SFA intake further to 7% of
total calories and cholesterol to 200 mg/d. The terms Step I and
Step II are no longer used in the new literature; however, the Step
I diet is still recommended for the general public, whereas the
Step II diet has been updated and renamed the TLC diet.
Therapeutic lifestyle changes
The Adult Treatment Panel III was published in 2001 and
describes the updated TLC diet (
). The TLC recommends
lowering LDL cholesterol with plant sterols and stanols (2 g/d)
and viscous and soluble fiber (20 –30 g/d), weight reduction, and
increased physical activity. The TLC diet guidelines recommend
a decrease in SFA to 7% of daily calories, a reduction in total fat
intake to 25–35% of daily calories, 200 mg cholesterol/d,
2400 mg Na/d, PUFA up to 10% of daily calories, MUFA up
to 20% of total calories, carbohydrate intake of 50 – 60% of
calories, protein at 15% of calories, and calorie intakes that
lead to the achievement and maintenance of a healthy weight
As discussed above, the severe restriction of SFA to 10% of
daily calories recommended by the Step II and TLC diets had less
benefit in terms of LDL reduction, yet was accompanied by a
further decrease in the HDL:TC ratio, than did a more moderate
9 –10% SFA intake in individuals with insulin resistance (
This may be particularly true for patients with fatty liver disease,
especially if the fat calories are replaced with simple
carbohydrates, which are known to increase DNL. The TLC diet
recommends a saturated fat intake that may not be suitable for NAFLD
patients with a high BMI and low insulin sensitivity but that may
be appropriate for patients with established CHD or for those
with LDL concentrations 160 mg/dL and multiple CHD risk
Dietary Approaches to Stop Hypertension
The DASH eating plan is recommended for lowering blood
pressure and has been found to lower blood cholesterol (
DASH is a modification of the USDA Dietary Guidelines, with
specifications related to sodium intake. Studies have shown that
reducing sodium intake to 1500 mg/d as part of the DASH diet,
alone or in conjunction with medication in more severe cases,
effectively lowers blood pressure in prehypertensive patients
Hypertension is associated with NAFLD (
Americans appear to be especially sensitive to the blood
pressure–lowering benefits of low-sodium diets that incorporate
reductions in salt intake and increases in potassium intake (136).
One study found particularly favorable results for African
Americans and hypertensive patients with high adherence rates
( 90%) in the 11-wk period of the clinical study (
). Little to
nothing is known about the pathogenesis of NAFLD in the
African American population.
The DASH diet plan, however, is not particularly palatable to
many individuals, the menu is rather limiting, and adherence is
low in the long term. Outpatient studies that more closely mimic
free-living conditions, compared with inpatient clinical trials,
have much lower adherence rates (
). Because of its effects in
lowering blood pressure, the DASH diet may be a reasonable and
preferable solution in some NASH patients, particularly in those
who are African American, those who have increased salt
sensitivity and high blood pressure, and those who are able to
maintain this diet in the long term despite lower palatability.
American Diabetes Association
The American Diabetes Association has developed its own
food pyramid, which uses the same basic layout of the USDA
Food Guide Pyramid, to illustrate the dietary recommendations
for patients with diabetes. This food pyramid can be found on the
official American Diabetes Association website, along with
other information pertaining to nutrition, including
recommendations on eating out, holiday meal planning, recipes, and
exchange lists (
). The American Diabetes Association pyramid
groups foods on the basis of their carbohydrate and protein
contents rather than on their classifications as foods. For example,
starchy vegetables such as potatoes are placed in the “breads,
grains and other starches category rather than the “vegetables”
category because of their high starch content. Serving sizes for
foods containing high amounts of carbohydrate are smaller in the
American Diabetes Association pyramid than in the USDA
The American Diabetes Association position statement on
evidence-based nutritional recommendations for diabetic
) presents specific goals and recommendations based
on A-, B-, and C-level evidence, depending on the quality and
quantity of scientific evidence collected through clinical trials
and evaluated using the American Diabetes Association
evidence grading system. The goals of nutritional therapy for both
type 1 and type 2 diabetes, as outlined in this position statement,
are to attain normal glucose concentrations, improve health
through nutrition and physical activity, and prevent and treat
obesity, dyslipidemia, cardiovascular disease, hypertension, and
Although the basic nutritional recommendations of the
American Diabetes Association are similar to those of the USDA
Dietary Guidelines, the American Diabetes Association
recommendations further discuss carbohydrates by subdividing them
into the 3 categories of sugars, starch, and fiber. Specifically, the
benefits of low-GI diets and the inclusion of fiber and resistant
starch are discussed. According to the American Diabetes
Association, clinical trials show no significant differences between
sources or types of carbohydrates on glycemic response if the
total amount of carbohydrate is the same. The American Diabetes
Association also concludes that there are no consistent long-term
benefits with low-GI diets compared with high-GI diets, that the
intake of fiber shows no metabolic benefit unless it is consumed
in very high amounts likely to produce gastrointestinal side
effects and that dietary sucrose does not induce hyperglycemia
more than do equal caloric amounts of starch.
The conclusions of the American Diabetes Association are
surprising in light of trials showing decreases in serum
cholesterol concentrations in response to the intake of soluble fiber
) and of the Food and Drug Administration’s approved
claim of cardiovascular disease risk reduction for the labeling of
oat products and foods containing soluble fiber (102). The
conclusion of the American Diabetes Association that the intake of
simple sugars, such as sucrose, has no adverse effect on patients
with type 2 diabetes is particularly surprising given the evidence
discussed above, which points to the effects of simple sugars,
specifically fructose, on DN, and the resulting increases in
circulating FFAs (
) and plasma triacylglycerol (
). The exchange lists, recipes, and other support
materials provided on the American Diabetes Association website
) are valuable. However, the lack of recommendation to limit
the intake of simple carbohydrates, especially fructose, and to
include low-GI carbohydrates and fiber in the diet are at odds
with other evidence discussed previously.
WEIGHT-LOSS DIETS, POPULAR DIETS, AND FAD
Mediterranean dietary pattern
The Seven Countries Study, an epidemiologic survey of
dietary patterns and incidence of CHD published in 1970, first
identified a lower risk of CHD in Mediterranean countries where
the consumption of fruit, vegetables, grains, nuts, legumes, dairy,
olive oil, and small amounts of poultry, fish, red meat, and red
wine were emphasized (
). Since then, clinical trials have
repeatedly shown this Mediterranean dietary pattern to be
beneficial. Several recent reviews concluded that adherence to the
Mediterranean dietary pattern leads to improvements in
lipoprotein indexes, insulin sensitivity, endothelial function, and
cardiovascular mortality (
It is unclear which specific features of the Mediterranean
dietary pattern are responsible for the observed beneficial effects.
It has been difficult to define the Mediterranean Diet because the
Mediterranean region represents a large diversity of cultures and
lifestyles. Nonetheless, diets that are higher in MUFAs, have a
lower GI, and are higher in fiber than the average American diet,
which are characteristics of the Mediterranean dietary pattern,
tend to have beneficial effects on insulin sensitivity (
A randomized study comparing the effects of a Mediterranean
dietary pattern with a “prudent diet,” consisting of 50 – 60%
carbohydrates, 15–20% protein, and total fat 30%, found that
at 2 y of follow-up, a higher proportion of patients in the
Mediterranean dietary pattern group (50/90) than in the prudent diet
group (12/90) no longer had features of the metabolic syndrome
). In this study of 180 patients, the Mediterranean dietary
pattern was more effective than a low-fat diet at reducing body
weight, BMI, waist circumference, inflammatory markers,
glucose, TC, triacylglycerol, and insulin resistance, as well as
improving endothelial function and increasing HDL
concentrations. Patients also had a lower ratio of plasma n 6 to n 3 fatty
acids after the Mediterranean dietary intervention (
The Mediterranean dietary pattern emphasizes the inclusion of
particular foods rather than the limitation of particular
macronutrients. Because of this, it may be easier for individuals to
understand and follow the diet. It is also a highly palatable diet that
is well-liked and may lead to a higher adherence among dieters
in the long term. The effectiveness of this diet on multiple factors
of the metabolic syndrome in the 2-y randomized trial discussed
above provides convincing evidence that the combination of high
MUFA and high fiber intakes, a low GI, and the emphasis on lean
protein sources may be a good option for NAFLD patients.
The Ornish Diet was developed as a preventive lifestyle
approach for the treatment and management of CHD (
program consists of intensive lifestyle changes incorporating
moderate fat-burning exercise, relaxation and stress-relief
techniques, and a low-fat, high-fiber vegetarian diet. The diet allows
the unlimited consumption of fruit, vegetables, grains, beans, and
legumes and suggests moderate consumption of nonfat dairy
products and nonfat or very-low-fat commercially available
products, such as nonfat frozen yogurt bars. The diet restricts the
intake of all meats (including fish), oils and fats, nuts, avocados,
dairy products, sugar and simple carbohydrates, alcohol, and
commercially prepared foods that have 2 g fat per serving.
Several studies have shown the effectiveness of the Ornish
Diet in preventing and even reversing CHD in patients who had
moderate-to-severe artery disease as assessed by coronary
). In fact, in one study, patients following the
low-fat, vegetarian, Ornish Diet experienced more regression of
atherosclerosis after 5 y than after 1 y, whereas the control group
following a usual care diet experienced progression of
atherosclerosis at both 1 and 5 y of follow-up (
One of the main criticisms of the Ornish Diet for NASH is the
severe restriction of all fats, including n 3 fats and MUFAs. As
mentioned above, these fats have been associated with
improvements in metabolic measures related to NAFLD, including
insulin resistance, inflammation, and blood lipids. Furthermore,
many low-fat and non-fat commercially prepared foods contain
high levels of simple sugars and are high-GI foods, which would
tend to exacerbate insulin resistance. Finally, although it is
reasonable to suggest higher intakes of fruit, vegetables, legumes,
and whole grains, a vegetarian diet may be too drastic and too
limiting for most patients in the long term. The effects of different
vegetarian diets on NAFLD patients have not been studied. It is
also possible that, with such low fat intakes, phospholipid
production would be impaired, which would decrease the ability to
synthesize lipoproteins. The Ornish Diet may be an option for a
highly motivated NAFLD patient who has already developed
concomitant CHD and who needs a drastic change to reverse the
progression of atherosclerosis. However, this diet is likely to be
too drastic for most NAFLD patients.
The Atkins Diet focuses on high-protein and high-fat intakes
and drastically low carbohydrate intakes (
). The premise is to
eat as much as one needs to “feel satisfied.” The dieter should
limit carbohydrates and focus on protein, leafy vegetables, and
healthy oils. Specifically, during the 2-wk phase one of the diet,
carbohydrate intake is limited to 20 g/d and should come
primarily from salad and other nonstarchy vegetables. During phase 2,
the carbohydrate intake is gradually increased by 5 g/wk until the
desired weight is achieved or the dieter stops losing weight. At
this point, the dieter has found their “carbohydrate equilibrium”
(ranging from 25 to 90 g carbohydrate/d) and should use this
carbohydrate intake for the maintenance of weight in the long
term. The diet accounts for increases in carbohydrate intake
beyond 90 g/d for those who exercise regularly (vigorous
exercise 5 d/wk for 45 min).
A recent trial showed that obese men and women lost more
weight with the Atkins Diet than with the conventional low-fat
diet at 3 and 6 mo, but the difference was not significant at 12 mo
). Individuals consuming the Atkins Diet had lower
triacylglycerol and higher LDL and HDL concentrations throughout the
study than did those consuming the low-fat diet, who
experienced the opposite effect. Both diets significantly decreased
blood pressure and the insulin response to an oral glucose load.
Another study in obese, insulin-resistant women found that
those consuming the Atkins Diet had significantly greater
reductions in triacylglycerol, body weight, and waist
circumference than did women consuming either the
highcarbohydrate or the high-protein Zone diet after 24 wk (
However, 25% of the women consuming the Atkins Diet
experienced a 10% increase in LDL.
The long-term effects of the Atkins Diet and other high-fat,
high-protein diets are still controversial, especially with regard to
increasing the risk of CHD and possible effects on renal function.
The consistent increases in LDL and TC, high intakes of SFAs,
and low intakes of fiber associated with the Atkins Diet are
contraindicated for NAFLD patients because of their proven
effects in increasing CHD risk. The Atkins Diet tends to induce
sudden weight loss and ketosis, especially in the first 3 mo, which
may also be deleterious in NAFLD patients. This diet is unlikely
to be suitable for most NAFLD patients.
The Zone Diet is designed to modulate macronutrient balance
at each meal for improved glycemic control (
). The dieter is
allowed to eat as much as desired at each meal. The emphasis is
on eating smaller meals throughout the day, preferably 3 meals
with 2 snacks in between. The proportions of carbohydrate, fat,
and protein are to be kept constant at 40%, 30%, and 30%,
respectively. The Zone Diet also emphasizes supplementation
with a high-dose of fish oil (4 g/d).
A recent study in obese women following a diet that had
nutrient ratios similar to those recommended in the Zone Diet
(46% carbohydrate, 20% fat, and 34% protein) compared with a
higher carbohydrate diet (64% carbohydrate, 20% fat, and 17%
protein) found that triacylglycerol decreased more in women
following the Zone-like diet, although weight loss, LDL, HDL,
glucose, insulin, FFAs, and C-reactive protein decreased equally
in both groups and were correlated with the extent of weight loss
). Women who had higher baseline triacylglycerol
concentrations lost more fat mass and had greater decreases in
triacylglycerol with the higher-protein Zone-like diet than with the
Another study in obese adults compared a diet of 40%
carbohydrates, 30% fat, and 30% protein, which was termed the
nonketogenic diet, with an Atkins-like higher-fat diet consisting of
10% carbohydrates, 60% fat, and 30% protein, which was termed
the ketogenic diet (
). The 6-wk trial showed that blood
concentrations of -hydroxybutyrate in the ketogenic diet group
were almost 4 times those in the nonketogenic diet group and that
LDL was directly correlated with -hydroxybutyrate
concentrations. Insulin sensitivity and energy expenditure increased in
both diet groups.
The Zone Diet may be an option for reducing weight,
controlling insulin resistance, and reducing the risk of CHD in some
NAFLD patients. The emphasis on MUFAs in lieu of saturated
fats, high-dose fish-oil supplements, fruit, vegetables, and
highfiber, low-GI carbohydrates are all especially relevant for
NAFLD patients. However, the high protein intakes associated
with this diet may not be appropriate for patients with underlying
kidney dysfunction (
). Type 2 diabetes is associated
with higher morbidity and mortality rates linked to kidney
dysfunction, especially in youth-onset compared with adult-onset
). Overall, the Zone Diet has favorable elements for
most NAFLD patients, but may be inappropriate for those
patients at risk of renal dysfunction.
South Beach Diet
The South Beach Diet is based on the GI and entails an
induction phase in which very little carbohydrate is consumed. This
phase is followed by the gradual addition of “the right”
carbohydrates in the second phase and a maintenance phase (
Three daily meals and 2 snacks in between are “mandatory.” The
theory is that eating these snacks, even when not hungry, will
keep the dieter from overeating at the next meal. The dieter
chooses foods from the allowable list for each phase and avoids
foods that are on the “avoid list.” The emphasis is on foods that
have a low GI and are high in MUFAs throughout the diet phases.
In the first phase, all fruit, bread, rice, potatoes, pasta, sugar,
alcohol, and baked goods are eliminated from the diet, whereas
meat, chicken, turkey, fish, eggs, shellfish, vegetables, cheese,
nuts, and salad vegetables are to be eaten at each meal until full.
In phase 2, the dieter gradually re-introduces carbohydrates by
adding one serving of a low-GI, high-fiber carbohydrate to one
meal per day for 1 wk and then another serving and so on.
Supplemental fiber in the form of psyllium husks added to water
is recommended before lunch and dinner to help the dieter reach
a point of satiety more quickly.
One study compared the effects of the South Beach Diet,
which has been described as a modified carbohydrate diet, with
those of the NCEP Step II diet in 60 overweight adults (
Individuals in the South Beach group lost more weight, had a
greater decrease in waist-to-hip ratio, and experienced decreases
in triacylglycerol, whereas those following the NCEP diet
experienced decreases in LDL and HDL. In both groups, weight and
TC decreased significantly, whereas there were no changes in
glucose, insulin, or inflammatory markers after 12 wk. However,
exercise and total calorie intake were not monitored in this trial;
therefore, it is impossible to discern whether the observed effects
were due to differences in the effectiveness of the diets, exercise,
or weight loss in and of itself.
The South Beach Diet incorporates some of the main issues
pertinent to NAFLD patients that have already been discussed
above, including a focus on the consumption of low-GI foods,
fiber, and MUFAs. However, sudden weight loss is often a result
of phase 1 of this diet, and this is not advisable in NAFLD
patients, as mentioned above. The fat content of this diet
throughout the 3 phases is high, ranging from 40% to 60%, which can
lead to an increased risk of CHD. Studies of the long-term effect
of high protein and fat intakes in NAFLD patients are lacking.
Weight Watchers Diet
The Weight Watchers Diet provides 2 options, both of which
focus on reduced calorie consumption within an intensive
support community (
). In one plan, the dieter consumes foods
throughout the day and monitors total intake by making sure not
to exceed a certain number of allowable points. Foods with a
higher nutrient density, such as fruit and vegetables, are worth
fewer points, whereas foods that have a low nutrient density
“cost” more and, therefore, are to be consumed in smaller
amounts or not at all. With the second plan, instead of counting
points, the dieter focuses on the consumption of “wholesome”
foods that are higher in nutrient density and avoids empty
calories, with the exception of an occasional treat consumed in small
The true advantage of the Weight Watchers Diet is the built-in
support structure that accompanies the diet. The diet itself does
not go beyond a simple recommendation to eat less to lose weight
and basically adheres to the USDA Dietary Guidelines. Weight
Watchers is known for its strong community support network and
high success rates because dieters attend motivational meetings
regularly. This support strategy may be critical because
adherence to modified-calorie diets in the long term is very poor (
SPECIFIC RECOMMENDATIONS AND FUTURE
Taking into account the evidence discussed in this article, the
authors recommend a highly individualized approach for the
dietary treatment of NAFLD and NASH based on a thorough
assessment of individual metabolic, physiologic, and nutritional
status and personal goals and preferences. The effects of each diet
discussed in this article on specific health indexes, such as blood
triacylglycerol concentration and insulin sensitivity, are shown
in Table 1 and are based on a review of the references included
in this article. The composition and the relative macronutrient
content of each diet are shown in Table 2. Most NAFLD patients
would benefit from the guidelines given below.
1 SFA, saturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; USDA, US Department of Agriculture; AHA,
American Heart Association; NCEP, National Cholesterol Education Program; DASH, Dietary Approaches to Stop Hypertension; TLC, Therapeutic Lifestyle
1 An “up” arrow indicates a likely increase, and a “down” arrow indicates a likely decrease in the index based on studies reviewed in this article. A blank
space indicates that there is not enough evidence to predict outcomes. DNL, de novo lipogenesis; TC, total cholesterol; TG, triacylglycerol; USDA, US
Department of Agriculture; AHA, American Heart Association; NCEP, National Cholesterol Education Program; DASH, Dietary Approaches to Stop
Hypertension; TLC, Therapeutic Lifestyle Changes.
2 Based on the insulin sensitivity index.
3 Determined on the basis of plasma cytokine and C-reactive protein concentrations.
4 This diet may cause rapid or sudden weight loss in the induction period, which may be deleterious in patients with NAFLD and NASH.
5 This diet may be deleterious in patients with hyperuricemia or kidney dysfunction because of its high protein content.
Moderate calorie restriction of 100 –500 kcal/d through a
decrease in portion sizes is recommended by the American
Dietetic Association (
) and the America on the Move program
). Evidence of beneficial effects from weight loss through
surgical methods in obese patients with NAFLD (
suggests that weight reduction through dietary means would also
have positive effects. Specifically, weight loss resulted in a
significant decrease in the prevalence of the metabolic syndrome
and marked improvements in liver steatosis, inflammation, and
fibrosis (58). However, very few studies examining the effects of
different dietary and lifestyle approaches in achieving weight
loss in NAFLD have been done, and further studies are urgently
NASH patients have a higher postprandial triacylglycerol
response and an increased production of large VLDL detected by
an oral fat load compared with controls, despite normal fasting
blood lipid concentrations, which suggests that the metabolism
of dietary fat is impaired in these individuals (
total fat consumption could lead to a decrease in postprandial
lipemia and the associated disruptions in lipid metabolism.
Further studies are needed to ascertain whether the consumption of
smaller meals that are lower in total fat may be helpful in NAFLD
Regular, moderate exercise is independently associated with a
25–35% decrease in CHD risk over a 20-y period (
regardless of diet and other risk factors. An exercise strategy of walking
a distance of 2 miles, 3 d/wk, at a target heart rate of 60% of heart rate
reserve (as measured by peak oxygen uptake) resulted in increases
in HDL and fitness equivalent to a more rigorous exercise program
of walking 3 miles, 3 d/wk, at 80% of heart rate reserve (
Further studies are needed to elucidate the effects of specific
exercise strategies in the NAFLD and NASH populations.
Cholesterol Fiber Sodium
% of daily energy % of daily energy % of daily energy % of daily energy % of daily energy % of daily energy
n 3 Fatty acid intake—specifically DHA and EPA— has
been shown to improve CHD risk by affecting metabolic
variables such as blood triacylglycerol concentrations (
80, 169 –171
and through independent mechanisms related to antiarrhythmic
). -Linolenic acid from walnuts also improves
blood lipid profiles (
79, 91, 178
). Furthermore, n 3 fatty acids
have been found to decrease steatosis in both preliminary trials in
) and in animal models (
). More studies are
needed to clarify the specific dosages, formulations, and effects
of n 3 fatty acids in individuals with NAFLD.
Beneficial effects on both insulin sensitivity and lipid markers
have been found in response to low-GI carbohydrates and
highfiber intakes from fresh fruit, vegetables, legumes, and grains
33, 68, 100, 101, 103–105, 146, 147, 171, 179 –182
reduction in the amount of total carbohydrates, especially simple
sugars, would reduce the total pool of acetyl CoA in the liver and,
therefore, reduce the flux through the DNL pathway. The
reduction in fatty acid synthesis would also result in reduced
triacylglycerol synthesis and prevent the excess accumulation of total
fat in the liver. A reduction in the rate at which glucose enters the
bloodstream, via the consumption of lower-GI carbohydrates
and higher amounts of fiber, would also reduce the subsequent
exaggerated insulin excursions and thereby reduce insulin
resistance. However, nutritional studies of the specific effects of
modulating carbohydrate type and quantity on insulin resistance
and disease progression in NAFLD patients are needed.
The intake of diets that are lower in carbohydrate, lower in
saturated fat, but higher in protein than the average American
diet—which consists of 47% carbohydrate, 38% fat (20%
SFA), and 15% protein—tend to be beneficial for ameliorating
features of the metabolic syndrome, including effects on insulin
sensitivity and blood lipids (
85, 115, 123, 134, 140, 141, 153,
154, 156, 160, 183, 184
). Certain individuals may be susceptible
to renal malfunction associated with high protein intakes (116);
therefore, an increase in total protein intake may not be
appropriate in these patients. Studies are needed to examine the effects
of modifying the protein content in NAFLD patients.
An emphasis on MUFAs from foods such as olive oil, in favor
of high-SFA foods such as fatty meats and full-fat dairy products,
is advisable because SFAs have deleterious effects on liver
) and raise blood LDL concentrations (
68, 134, 186 –
), whereas MUFAs are beneficial in reducing the risk of CHD
and type 2 diabetes through effects on blood lipids, endothelial
function, and insulin sensitivity (
74, 75, 104, 144, 146, 147, 184,
186, 190, 191
The recommendation to avoid the intake of sodas and other
sweetened drinks is substantiated by observations that high
fructose intakes, high sucrose intakes, or both can induce DNL,
which leads to higher blood triacylglycerol concentrations and
lower insulin sensitivity (
33, 106 –108, 114
). Soda consumption
contributes a substantial proportion of the calorie intake in many
overweight and obese individuals (
). A reduction in the
consumption of simple sugars, especially in the form of
sweetened beverages, which provide sugar in a very accessible and
easily absorbable form, would help to reduce the exaggerated
glucose and insulin excursions that are associated with insulin
resistance. In addition, a reduction in the consumption of
sweetened beverages would lead to a reduction in total calories
consumed, which would facilitate weight loss.
Poor adherence in weight loss and lifestyle modification is a
crucial issue in overweight and obese individuals (
138, 153, 162,
). Weight loss through diet and exercise tends to be
successful in the first 6 mo, but in the long-term, most individuals
are unable to maintain this weight loss (167). Strategies to
improve adherence and long-term behavioral modification are
therefore imperative for the successful treatment of NAFLD
through dietary approaches.
There is no consensus as to what diet or lifestyle approach is
the right one for NAFLD and NASH patients, largely because of
a lack of scientific evidence. It is likely that there will be no one
correct approach for all NAFLD patients, and diets will therefore
need to be tailored to individual needs. The inclusion of n 3 fatty
acids, high-MUFA foods, fruit, vegetables, and low-GI,
highfiber foods and reduced intakes of saturated fats, simple
carbohydrates, and sweetened drinks may be universally
recommended to NAFLD patients. More studies are needed to clarify
the specific effects of different diets and dietary components on
the health of NAFLD patients. The general recommendations
described in this review may be a useful guide for determining the
appropriate diet for individual patients now, while
evidencebased recommendations from future clinical trials are assembled.
We acknowledge CJ Dillard for her invaluable help with editing.
The authors’ responsibilities were as follows—AMZ: prepared the
manuscript, researched the references, and created the figures and tables; JBG:
provided critical input on content and manuscript development; AJS:
provided critical input on content and manuscript development and had the
original vision for the manuscript, the tables, and the figures. AJS was a
consultant to Oridion, Orphan Therapeutics, Sanofi, and Pfizer but had no
stocks or direct financial interests and no direct conflicts. JBG was a
consultant to Nestlé Research Center and Lipomics Technologies, Inc, but had no
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