Overweight and diabetes prevention: is a low-carbohydrate–high-fat diet recommendable?

Abstract

In the past, different types of diet with a generally low-carbohydrate content (< 50–< 20 g/day) have been promoted, for weight loss and diabetes, and the effectiveness of a very low dietary carbohydrate content has always been a matter of debate. A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of fat and to a lesser extent, also protein. Accordingly, using the term “low carb–high fat” (LCHF) diet is most appropriate. Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to be difficult. A non-ketogenic diet supplying 100–150 g carbohydrate/day, under good control, may be more practical. (4) There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.

Full text

Vol.:(0123456789)
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European Journal of Nutrition (2018) 57:1301–1312
https://doi.org/10.1007/s00394-018-1636-y
REVIEW
Overweight anddiabetes prevention: isalow-carbohydrate–high-fat
diet recommendable?
FredBrouns1
Received: 10 July 2017 / Accepted: 12 February 2018 / Published online: 14 March 2018
© The Author(s) 2018. This article is an open access publication
Abstract
In the past, different types of diet with a generally low-carbohydrate content (< 50–<20g/day) have been promoted, for
weight loss and diabetes, and the effectiveness of a very low dietary carbohydrate content has always been a matter of debate.
A significant reduction in the amount of carbohydrates in the diet is usually accompanied by an increase in the amount of
fat and to a lesser extent, also protein. Accordingly, using the term “low carb–high fat” (LCHF) diet is most appropriate.
Low/very low intakes of carbohydrate food sources may impact on overall diet quality and long-term effects of such drastic
diet changes remain at present unknown. This narrative review highlights recent metabolic and clinical outcomes of studies
as well as practical feasibility of low LCHF diets. A few relevant observations are as follows: (1) any diet type resulting
in reduced energy intake will result in weight loss and related favorable metabolic and functional changes; (2) short-term
LCHF studies show both favorable and less desirable effects; (3) sustained adherence to a ketogenic LCHF diet appears to
be difficult. A non-ketogenic diet supplying 100–150g carbohydrate/day, under good control, may be more practical. (4)
There is lack of data supporting long-term efficacy, safety and health benefits of LCHF diets. Any recommendation should
be judged in this light. (5) Lifestyle intervention in people at high risk of developing type 2 diabetes, while maintaining a
relative carbohydrate-rich diet, results in long-term prevention of progression to type 2 diabetes and is generally seen as safe.
Keywords Low-carbohydrate diet· High-fat diet· Ketogenic diet· Type 2 diabetes· Obesity.
Introduction
The World Health Organisation (WHO) and various national
authorities have recently made recommendations urging a
limitation of the daily consumption of carbohydrates, more
specifically that of rapidly digestible starches and sugars.
These recommendations play a key role in reducing the risks
of obesity, diabetes, and cardiovascular diseases [1–8]. In
the past, there have been various diets that centre on a low-
carbohydrate content, such as the Atkins Diet, the Zone Diet,
the South Beach Diet and the ketogenic diet [9–13].
In this respect, it should be pointed out that although many
studies refer explicitely to “diets with a low-carbohydrate
content”, this in fact goes hand in hand with “elevated
fat”. This well-known “seesaw effect” is present in many
nutritional intervention studies in which a decrease of one
particular component always is accompanied by a paral-
lel increase of another component. In other words, effects
observed are then based on two dietary factors that were
changed in parallel and any conclusion drawn should be
viewed in this light. Accordingly the term “low carbohy-
drate–high fat diet” (LCHF diet) is more appropriate than
“low carbohydrate” alone, also in terms of interpretation of
results. For this reason, the term LCHF will be used through-
out this paper.
Feinman etal. [14] proposed that dietary carbohydrate
restriction is the first approach in diabetes management, the
authors refer to much data showing that favorable effects
such as improvement of insulin sensitivity/needs occurred
along with significant weight loss. However, many of the
cited studies concerned relatively small groups of indi-
viduals, often with poor diet adherence and relatively high
dropout rates. Accordingly, one may question the validity of
their proposal, especially since recent meta-analyses, which
* Fred Brouns
fred.brouns@maastrichtuniversity.nl
1 Department ofHuman biology, Faculty ofHealth,
Medicine andLife Sciences, NUTRIM-School ofNutrition
andTranslational Research inMetabolism, Maastricht
University, Post Box616, 6200MDMaastricht,
TheNetherlands
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1302 European Journal of Nutrition (2018) 57:1301–1312
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did include well-controlled studies did not see beneficial
changes in many parameters on the longer term (this will
be discussed further in detail below). Important questions
that ought to be put in this respect include: (a) what are
the real long-term effects of very low-carbohydrate, thus
high-fat intake; (b) are the effects observed rather the result
of weight loss than of low carbohydrate per se, and (c) are
there less drastic alternatives, i.e. more moderate changes of
carbohydrate and fat intake that are easier to adhere to and
lead to similar favorable results. These questions are also
relevant, given that most chronic diseases such as diabetes,
cardiovascular diseases and other chronic conditions have
a development period of 10–20years or more. Long-term
data, demonstrating favorable effects of a (very) LCHF diet
in this regard, is absent. In addition, there is also a plethora
of studies that show that maintaining a relatively high-car-
bohydrate, low-glycemic–high-fiber diet (vegetarian, vegan)
results in favorable long-term effects. Such diet patterns
deviate less drastically from our normal eating patterns and
are easier to implement in the long term [15–21]. In this
respect, observations made in the so-called “blue zones”,
e.g. Sardinia, Okinawa (Japan), Loma-Linda (California),
are intriguing, given their commonality is their relatively
high-carbohydrate and low-saturated fat content of their
daily diet, which allow them to stay healthy until very high
age. The Okinawa inhabitants, for example, originally ate
a daily diet that contained an amount of carbohydrates that
exceeded daily energy intake by 60%, consisting primarily
of sweet potatoes and the foliage, supplemented with sea-
weed and fruit. The recent introduction of a more Western
lifestyle, containing more saturated fats, added sugars and
alcohol, has gone to the significant detriment of the longev-
ity prospects of the youngest generation [22], which indi-
cates that diet (carbohydrate and fat quality), in combination
with other lifestyle factors is crucial for health.
An important question is why a challenging LCHF diet,
with risks of poor adherence, should be implemented when
less drastic changes in diet and lifestyle have proven effects
and are known to be safe and easier to follow on the long
run. Opinions seem to be sharply divided on the matter. This
narrative review will shine a light on the various interna-
tional opinions on the matter.
Is ahigh carbohydrate content ofthediet
unhealthy?
There are various publications that assert that high levels of
carbohydrates are unhealthy. The arguments to support this
are often based on assumptions on how man was to have
eaten long ago, before the agricultural and industrial revo-
lution. This is referred to as the Paleo Diet. Some authors
explicitly claim that our ancestors ate a diet high in fat and
protein and that starches and cereals were not part of the
daily diet [23]. Historical data available to us, however,
have shown that the diet 50,000years ago, in fact, was rela-
tively high in carbohydrates, that it contained a high level
of fiber (from plant-based foods) and that the level of fats
primarily depended on the fat content of the various types
of meat and fish available [24]. The Paleo diet contained
an estimate of ≈ 35 percent of energy (en%) from fats, ≈ 35
en% from carbohydrates and ≈ 30 en% from proteins, with
approx. 100g of dietary fiber a day [24–26]. Consequently,
in quantitative terms, the Paleo diet contained roughly as
much fat as does our modern Western diet. Observations
made by Kaplan etal. [27] who studied the Tsimane popu-
lation in South America are of great interest in this respect.
This population lives a traditional hunter–gatherer lifestyle
and ingests an estimated 14% of their average caloric diet as
protein, 14% as fat, and 72% as carbohydrate. Yet, despite
this very high-carbohydrate intake, the Tsimane have the
lowest reported levels of chronic disease of any population
ever recorded to date! Today, there are no arguments to sug-
gest that the diet of our ancestors was low in carbohydrate.
Quality but not quantity of carbohydrates appears to be a key
aspect to be considered.
What does “low carbohydrate”
and“ketogenic” refer to?
A large number of publications refer to a diet “low in car-
bohydrates” or to “ketogenic”. But what levels of carbo-
hydrate correspond to these concepts? We could start by
assuming that low refers to lower than the current average
intake or lower than current recommendations. According
to the most recent Dutch Food Consumption Survey (FCS,
2007–2010; 7–69years), the average daily intake of macro-
nutrients is 45 en% from carbohydrates (of which 21 en%
from sugars and 24 en% from starch), 35 en% from fats, 15
en% from protein and 15–23g of fiber [28]. On that basis,
the term "low" could refer to lower than 45 en% derived
from carbohydrates. However, does that necessarily mean
low in terms of the effects on our metabolism? Currently,
only guidelines exist regarding the recommended daily
intake of foods and there are no international guidelines on
high- or low-limit values. Anything above or below the rec-
ommended intake amounts can, respectively, be referred to
as high or low. Therefore, the question is which bandwidth
is defined as ‘low carbohydrate’ when comparing studies
to one another to draw conclusions regarding the effects.
Westman [29] describes this problem as follows: “Much
of the controversy when studying the outcomes of LCHF
diets stems from the lack of a clear definition. The guiding
principle of carbohydrate limitation is that, in response to
the reduced availability of glucose and lower insulin values
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1303European Journal of Nutrition (2018) 57:1301–1312
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in the blood, the body should enter a state of increased fat
burning, leading to ketosis. It would appear that a type of
threshold value for carbohydrate intake exists above which
this metabolic change does not clearly occur. For that reason,
ketogenic studies are interpreted assuming only 20–50g of
carbohydrates per day and, if possible, a maximum of 20g
per day [29, 30]. Fewer ketone bodies are formed in the liver
upon intake of more carbohydrates. In such cases, the term
used is a low-carbohydrate diet rather than a ketogenic diet,
the former containing 50 to max. 150g of carbohydrates
per day”.
What are themetabolic eects
ofalow‑carbohydrate availability?
Two processes that come into play when glucose availability
is in decline: (1) gluconeogenesis, (2) ketogenesis. Below
these aspects will be explained in short.
Gluconeogenesis
A very low-carbohydrate intake (< 50g per day) will result
in a decreasing glucose supply to the liver, muscles and
brain, resulting in a decline in the amount of glucose stored
as glycogen. When glucose availability is limiting the body
will activate a process called gluconeogenesis. Gluconeo-
genesis (endogenous production of glucose) and glycolysis
(breakdown of glucose) are processes that always take place
simultaneously and are reciprocal (if one is high, the other is
low, and vice versa). The primary carbon skeletons required
for the synthesis of glucose in gluconeogenesis (Fig.1) come
from lactic acid, glycerol and the amino acids alanine and
glutamine [31].
Ketogenesis
When endogenous production of glucose by gluconeogenesis
remains too low to cover the body’s glucose needs of cells
that primarily rely on glucose as a fuel, ketone bodies will
be produced as an alternative to glucose [32]. In this condi-
tion, insulin levels in the blood will be low, sharply reducing
the stimulus for fat and glucose storage. This observation is
often referred to when promoting a high fat diet for weight
maintenance and reduction of diabetes risk factors (see also
further below). Other hormonal changes would subsequently
lead to an increase in the breakdown of fat from the fat cells
and making more fatty acids available as fuel. In this situ-
ation of a continuous elevated supply of fatty acids, not all
fatty acids will be burnt completely. Acetoacetic acid (ace-
toacetate) is then created which is subsequently converted
into the ketones beta-hydroxybutyric acid (β-hydroxybutyric
acid) and acetone. For that reason, ketones are to be regarded
as “a type of emergency generator that kicks in when there
is a power outage”. Figures2, 3, 4 and 5 give a schematic
representation of the metabolic processes in case of a nor-
mal carbohydrate intake and after limitation of carbohydrate
intake leading to ketosis.
Do frequent carbohydrate‑induced insulin
responses drive overweight?
According to Hall [32], the carbohydrate–insulin model of
obesity theorizes that diets high in carbohydrate are par-
ticularly fattening due to their propensity to elevate insulin
secretion. Insulin directs the partitioning of energy toward
storage as fat in adipose tissue and away from oxidation
by metabolically active tissues and purportedly results in a
perceived state of cellular internal starvation. In response,
hunger and appetite increases and metabolism is sup-
pressed, thereby promoting the positive energy balance
associated with the development of obesity. Hall states
that this hypothesis, which is cited by many to support
recommendations for a LCHF diet, cannot be verified by
controlled studies. He also suggests that the mechanisms
most likely are far more complex than previously thought,
given that the differences in energy consumption and body
fat, as observed in the controlled case studies, are contrary
to the differences that are predicted based on the carbo-
hydrate–insulin model. Hall claims that although the rise
of the prevalence of obesity may be put down to elevated
consumption of refined carbohydrates, the mechanisms
are most likely completely different from what we think
Gluconeogenesis:
Synthesis of glucose in the liver from “non-carbohydrates”
Lactic acid
A
minoacids
Glycerol
Gluconeogenesis glucose
Blood
Fig. 1 Gluconeogenesis (production of glucose) and glycolysis
(breakdown of glucose) are processes that always take place simul-
taneously and are reciprocal (if one is high, the other is low, and vice
versa). In cases of low-glucose availability from glycogen, glycolysis
will be conducted at a low level and there will be a stimulus for glu-
coneogenesis
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1304 European Journal of Nutrition (2018) 57:1301–1312
1 3
they are. For example, consumption of foods with a high level of added sugars could result in a greater total energy
Fig. 2 In a high-carbohydrate
diet, the glucose reserves in the
liver and muscles are usually
well stocked. In fasting condi-
tions, blood glucose levels are
kept steady by breakdown of
glucose from the liver glycogen.
This is regulated by the insulin/
glucagon ratio. The low insulin
levels ensure that relatively few
fatty acids are stored in the adi-
posecells, while the secretion
of fatty acids by the break-
down of stored lipid(lipolysis)
ensures elevated blood plasma
fatty acid levels. This leads
to a high degree of fatty acids
oxidation and relatively low oxi-
dation of glucose. This is then
expressed in a low respiratory
quotient (RQ), usually 0.75–0.8
Glucose
Lactate
Fatty acids
Glycerol
Aminoacids
Ketones3
Energy
Muscle
Brain
Glycogen Glucose
Lactate
Ketones3
Glycogen1Glucose
Lactate
IMTG2 Fattyacids
Glycerol
Ketones3
NO FOOD
Blood
Fasted energy metabolism, whilebeing on a carbohydrate rich diet**
1 = Intramuscular glycogen
2 = Intramusculartriglycerides
3
= ketones from the liver
Glucose store
–liver
Lipidstore -adipocytes
Energy
Glucose
Lactate
Fatty acids
Glycerol
Aminoacids
Ketones3
Energy
Muscle
Brain
GlycogenGlucose
Lactate
Ketones3
Glycogen1Glucose
Lactate
IMTG2 Fattyacids
Glycerol
Ketones3
FOOD
•Carbohydrate > 50%En5,
•Lipid 35%En,
•Protein12- 15%En
Sign. glucose-supply from gut to blood,
insulin rises, lipolysis decreases
Blood
Energy metabolism aftera meal, while being on a carbohydrate rich diet
1 = Intramuscularglycogen
2 = Intramusculartriglycerides
3= ketonesfromthe liver
4= % of dailyenergy intake
Glucose store – liver
Lipidstore -adipocytes
Energy
Fig. 3 Following a carbohydrate-rich meal, the blood glucose is ele-
vated by the supply of glucose from the intestine, resulting in elevated
insulin levels and a temporary decrease in glucagon levels. This com-
bination results in a sharp decrease in glucose production from the
liver glycogen. At the same time, the release of fatty acids from the
adipose cells is inhibited and the uptake of both glucose and fatty
acids from the blood is stimulated. In this case, the burning of pri-
marily fatty acids in a fasting condition shifts to a combination of
elevated glucose- and reduced fat oxidation. This is expressed in an
elevated respiratory quotient (RQ), depending on the carbohydrate
intake and the magnitude of the insulin response, between 0.85 and
1.0. There is also a small contribution from amino acids, which are
converted into glucose via gluconeogenesis. Under normal condi-
tions, this amounts to approx. 1–3%, although in cases of acute or
chronic carbohydrate restriction resulting in significant glycogen
breakdown and depending on the degree of adaptation to the situation
this can even rise to > 15% [32–37]
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1305European Journal of Nutrition (2018) 57:1301–1312
1 3
Glucose
Lactate
Fatty acids
Glycerol
Aminoacids
Ketones3
Energy
Muscle
Brain
Glycogen Glucose
Lactate
Ketones3
Glycogen1Glucose
Lactate
IMTG2 Fattyacids
Glycerol
FOOD
•Carbohydrate <20%En4,
•Lipid> 50%En,
•Protein> 20%En
Very low glucose supply from gut to
blood, low glycogen stores low
glucose supply to cells
Blood
Energy metabolism during a high Fat –low Carb diet
1 = Intramuscular glycogen
2 = Intramusculartriglycerides
3= ketonesfromthe liver
4= % of dailyenergy intake
Glucose store – liver
Lipidstore -adipocytes
Energy
Fig. 4 When following an LCHF diet, the amount of glucose that is
taken up in the blood from the food each day is insufficient to main-
tain the glycogen stores in the liver and muscles. This results in an
reduction of glycogen stores, reduced glucose release and conse-
quently to reduced blood glucose levels. The body experiences this
as stress and will do everything it can to ensure it burns fatty acids
as much as possible with the aim of preventing utilization of glu-
cose, which is needed primarily for the central nervous system and
the red blood cells, as much as possible. This is achieved by a sharp
decrease in insulin and an increase of stress hormones. This results
in an excess supply of fatty acids, leading to a partially incomplete
metabolism in which ketones are produced (ketogenesis) from a part
of the produced acetyl-CoA. These ketones can then be used by the
brain and the muscles as an alternative fuel source instead of glu-
cose. This is crucial to the brain, as fatty acids cannot pass through
the blood–brain barrier, while glucose and ketones can. In the case
of a shortage of glucose, the brain cells and neurons are able to use
ketones as an alternative fuel source. There is also a small to medium
contribution from amino acids, which are converted into glucose via
gluconeogenesis
Fig. 5 Ketogenesis is a process
that takes place entirely in the
liver
Fa
t depot
High
fat diet
Fay acids
Glycerol
Triglycerides
Fay acids
Citric acid
cycle
Oxalic acid
Citric acid
Liver
Acyl CoA
Acetyl CoA
AcetoacetylCoA
HMG CoA
Acetoacetate
3-OH-butyrate
β-oxidaon
ketogenesis
Succinyl-CoA
Succinic acid
Acetoacetate
3-OH-butyraat
AcetoacetylCoA
Acetyl CoA
ketosis
Glucose
Pyruvic acid
Acetyl coA
Muscle, Brain
Ketogenesisandketosis
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1306 European Journal of Nutrition (2018) 57:1301–1312
1 3
intake because they have a more attractive taste, stimulate
to eat more or reduce satiety. Most recently, Hall and Guo
postulated that while low-carbohydrate diets have been
suggested to partially subvert these processes by increas-
ing energy expenditure and promoting fat loss, their meta-
analysis of 32 controlled feeding studies, with isocaloric
substitution of carbohydrate for fat, found that both energy
expenditure (26kcal/day; P < 0.0001) and fat loss (16g/
day; P < 0.0001) were greater with lower fat diets [38].
Does LCHF diet improve insulin action?
The scientific literature shows that individuals suffer-
ing from pre-diabetes (as shown by fasting glucose and
insulin levels) or suffering from diabetes and who switch
to a LCHF diet soon notice a number of effects, such as
weight loss, improved insulin sensitivity, fewer fluctua-
tions in blood glucose levels and lower fasting blood glu-
cose levels. Such changes indirectly entail reduced risks
of cardiovascular diseases [13, 14, 39]. However, there are
also scientists that consider these effects primarily to be
the results of weight loss and not necessarily the result of a
reduction in carbohydrate intake itself. Westman etal. [29]
published a thematic review of the metabolic effects of
LCHF diets, and concluded that LCHF diets lead to reduc-
tion of appetite and, consequently, to weight loss and cor-
responding improvements of various disease risk factors.
Does LCHF reduce dietary ber intake?
In general, most natural carbohydrate-rich food sources
are high in dietary fibers and micronutrients. For that rea-
son, the key question arises whether switching to a LCHF
diet would not lead to a significant decrease in the sup-
ply fiber, known to impact negatively on gut function and
overallhealth [40]. A study that conducted an accurate
analysis of this issue and of the relationship between popu-
lar diets and food quality (expressed as a food index score)
showed that diets with less than 30 en% carbohydrates
ended up in the lowest index score [41, 42], indicating
that there is a realistic risk of low fiber and micronutrient
intakes when consuming an LCHF diet.
Based on various meta-analysis, an appropriate dietary
fiber intake, for example by consuming more whole grain
compared to alow intakeof whole grain, is linked to a
significant disease risk reductions for diabetes type 2, car-
diovascular disease [43, 44], while evidence is growing
that weight management may also be supported favorably
[45, 46]. The fact that LCHF diets may reduce diet quality
is of concernand indicates a need for carefull nutritional
guidance when following such diets.
What dometa‑analyses ofLCHF diets tell us?
Astrup etal. [47] initially set out to study the effects of a
high-carbohydrate diet, relatively low in fat low-fat. They
asserted that the effectiveness of an adlibitum diet, rela-
tively high in carbohydrate, as was often recommended
for the prevention of weight gain in patients with normal
weight, or a decrease in body weight in the case of obe-
sity, was controversial. This resulted in a meta-analysis into
the effects of intervention studies which included studies in
which non-diabetic individuals consumed a low-fat (thus,
consequently, a relatively carbohydrate-rich) diet, a normal
diet, or a diet moderately rich in fat (control group). Follow-
ing a stringent selection process, the details of 16 studies
were evaluated (duration of 2–12 months, 19 intervention
groups, 1910 people). At the inception of the studies, the
average fat consumption of the persons in the low-fat group
was 37.7% (95% Cl 36.9–38.5). In the control group, this
was 37.4% (36.4–38.4). Consequently, fat consumption was
equal in both the low-fat and control groups. The low-fat
intervention reduced fat intake in the low-fat test groups to
10.2% (8.1–12.3) while fat intake remained unchanged in
the control groups. The data showed that the energy intake
of the LFHC intervention groups was lower (1138kJ/day,
P < 00.002) and that they showed more weight loss than
the control groups (3.2kg, Cl 1.9–4.5kg, P < 0.0001). The
authors concluded that a reduction of the fat content in
the diet, without targeted restriction of the energy intake,
resulted in higher weight loss, especially in persons with
the highest body weight. The foregoing corresponds to the
considerations put forward by Hall etal. [48] in a publica-
tion, which bore the self-explanatory title ‘Calorie for calo-
rie’, dietary fat restriction results in more body fat loss than
carbohydrate restriction.
In 2012, Hu etal. published a meta-analysis of rand-
omized controlled clinical studies on the effects of diets
containing < 45 en% carbohydrates compared to diets that
contained less than 30 en% of fat [40]. This meta-analysis
also mapped the risk factors to metabolic processes. Data
from 23 studies from various countries, with a total of
2788 participants (study duration of 6–24 months, includ-
ing 6 studies of 15–24 months), met the inclusion criteria
and were included inthe analysis. Both the low-carbo-
hydrate diet and the low-fat diet resulted in a decrease in
body weight and an improvement of metabolic risk fac-
tors. The two groups showed no significant divergences
in terms of decrease of body weight, waist circumference
and metabolic risk factors. The authors claim that these
findings suggest that low-carbohydrate and low-fat diets
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1307European Journal of Nutrition (2018) 57:1301–1312
1 3
have similar effects on body weight reduction and related
risk factors for diseases.
A recent meta-analysis by Mansoor etal. [49] con-
cerned data of 11 randomized controlled studies (total of
1369 participants). The study revealed that participants
experienced a greater decrease in body weight and of
plasma triglycerides when being on a LCHF diet. How-
ever, an increase in LDL cholesterol was also observed,
which is in line with the earlier observations of [50]. It has
been questioned whether the overall benefits observed do
outweigh that of an unfavorable LDL increase [51].
Is aLCHF diet healthy andsafe?
Many food authorities recommend relatively high-carbo-
hydrate and high-fiber intakes as being healthy [52]. Seen
in the recommendations, discussed above, the question is
what the long-term health implications of LCHF diets would
be, given the relatively short duration of virtually all avail-
able studies [53, 54]. The limited literature, in which LCHF
studies were compared to relatively high-carbohydrate
studies, does not show consistent differences in effects on
body weight. The only way to get an answer to this question
would be to conduct robustly controlled long-term studies
(minimum of 2years) in which carbohydrate, fat, energy
and dietary fiber intake are carefully monitored along with
changes in body weight. Such studies are hard to carry out
and are costly and for that reason have as yet not been car-
ried out. One study that did conduct an evaluation of this
issue, and was subject to strict controls, albeit also with a
relative short duration of 8 weeks [55], resulted in the con-
clusion that under conditions of a steady level of energy
intake during a hypocaloric diet (− 500kcal/day) a LCHF
diet is just as effective as a low-fat high-carbohydrate diet.
In this study weight loss wassignificant in both groups and
improvements in insulin sensitivity were alsosimilar. This
is a strong indication that LCHF effects are primarily related
to weight loss and corresponding changes to central body fat
and the associated metabolic processes.
Two reviews drew the conclusion that the short-term
effects of LCHF diets are positive on weight loss and
blood glucose management, but also that the long-term
effects have not been studied [11, 56]. Theauthors indi-
cate that observed effects seemed primarily to relate to
weight loss and that, for that reason, the effect of changes
in the intake of carbohydrates and fats remained “unclear”.
Brinkworth etal. [57] concluded that a combination of
a low-carbohydrate diet combined with a restriction of
energy intake would, due to reductions of fiber intake,
lead to adverse effects on the quality of bowel movements
and the production of short-chain fatty acids by the flora of
the large intestine. They claim that it seems as if this may
potentially lead to bowel disease in the long term. After
a systematic review and meta-analysisNaude etal. [58]
concluded that here is probably little or no difference in
weight loss and changes in cardiovascular risk factors up
to 2years of follow-up when overweight and obese adults,
with or without type 2 diabetes, are randomized to low
CHO diets and iso-energetic-balanced weight loss diets. In
a more recent review, bearing the title “Low-carbohydrate
diets and type-2 diabetes: the current status of the evi-
dence”, in the journal Diabetes Therapy, Dyson expressed
that the state of affairs has not changed much [59]. He con-
cluded that low-carbohydrate diets for people with type-2
diabetes could in the short-term lead to an improvement
in blood glucose regulation, weight loss, and reduction
of cardiovascular risk factors, but that this appeared no
longer to be the case in the longer term. Overall, LCHF
diets did not seem to show any superiority compared to
diets with a higher carbohydrate intake. On the basis of
these findings, he concludes that low-carbohydrate diets
are indeed safe in the short term and are effective, but
that there are no statistical differences compared with diets
containing a higher carbohydrate content. For this reason,
Dyson suggests that an LCHF diet should not be recom-
mended as the standard treatment of people with type-2
diabetes [59]. This view is supported by Wyk etal. [31]
who describe that “total energy intake remains the best
predictor of changes in body weight. A low-carbohydrate
diet, in terms of metabolic indicators and blood glucose
response, does not differ a great deal from a diet with the
usual amount of carbohydrates”. Very low-carbohydrate
diets seems to score slightly better in this regard, but are
harder to adhere to over a longer period of time (more
than 6months). Daily carbohydrate intake, for example,
seemed to amount to 132–162g per day, despite over a
year of dieting and a guiding principle of less than 50g
per day. The foregoing also implies that there is still a lack
of clarity regarding the long-term effects of an LCHF diet
on both effectiveness as well as food safety.
The observations of Noto etal. [60] are also relevant
in this regard. These authors assessed the effects of low-
carbohydrate diets on probability of mortality, by way of a
systematic review and a meta-analysis of the available obser-
vational studies. 17 studies were included in total, containing
the data of 272,216 people of which 15,981 (5.9%) were
reported dead. The results showed that the risk of mortality
under conditions of LCHF diets was significantly higher. In
accordance with these findings, many insiders feel that an
LCHF diet should only be recommended for persons suf-
fering from overweight and pre-diabetes or type-2 diabetes,
for the reduction of bodyweight and hyperglycemia risks.
They recommend that the diet only be followed under strict
medical and nutritional supervision.
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1308 European Journal of Nutrition (2018) 57:1301–1312
1 3
Regarding the question whether long-term LCHF diets
may pose health risks it should also be noted that a series of
recent animal experiments and human studies into the effects
of an LCHF diet, for example, show adverse effects in cho-
lesterol, homocysteine, vascular elasticity parameters have
been observed during LCHF, indicating that any potential
adverse long-term effects of an LCHF vascular health cannot
be ruled out [29, 40, 49, 51].
In addition, adverse effects as result of high-fat expo-
sure were reported in the following areas: brain, cognition,
memory, mental well-being, Alzheimer’s, autistic behaviour
[33, 34, 61–63]; obesity, metabolic dysfunction, inflamma-
tion, liver damage, cardiometabolic risks’ [34, 38, 64–68];
risks of cancer [66, 69]; osteoporosis [70]. In elegant animal
models, Cani etal. [71] clearly demonstrated that high fat
feeding, which induces low intakes of fermentable dietary
fibers, may lead to intestinal microbiota changes which are
associated with an increased intestinal permeability resulting
in endotoxemia and triggers for inflammation and metabolic
disorders (note: the examples are only given as an illustra-
tion, not for an exhaustive picture). These data point to pos-
sible long-term negative effects on health that should be
addressed in future studies.
LCHF forspecic patient groups
Within this context, it should be noted that a Ketogenic-
LCHF (KLCHF) diet is used for specific pathologies such
as epilepsy and autism epilepsy and that positive effects
have been documented to decrease epileptic seizures. Simi-
larly in this instance, this is also paired with adverse side
effects; in addition, the long-term effects on overall health
are unknown. Following a robust Cochrane meta-analysis,
for example, Martin etal. [72] concluded that randomized,
controlled KLCHF studies showed promising results follow-
ing application in epilepsy patients, but that the limited num-
ber of studies, small samples, and one-sided data from child
populations, resulted in poor evidential quality. Within all
KLCHF studies, short-term side effects were recorded such
as gastrointestinal disorders, and cardiovascular complica-
tions in the longer term. For all KLCHF studies, “compli-
ance” was a problem due to the lack of effectiveness and/or
problematic diet tolerance. The authors believe that there is a
lack of evidence to support a clinical application of KLCHF
in adults with epilepsy.
New insights?
A very recent overview [73] concerned randomized inter-
vention studies, with control group, carried out between
2001 and 2015. The authors concluded as follows: a
slight though significant decrease of glycated hemoglobin
(HbA1c) entails a restriction of carbohydrates (CH) at
all levels: 2.2% at 30g CH/day, − 0.7% at ≤ 75 CH/day,
− 1.1% at 80–90g CH/day and − 0.9% with CH intake to
120g/day (a logical consequence of less glucose supply
to the blood, under conditions of insulin resistance) [73].
The fasting blood values and the required medication, as
such, were lower which resulted in people feeling “better”.
At an intake of 58% fat and 14% carbohydrates, compared
with 30% fat and 53% carbohydrates, blood triglycerides
decreased and HDL cholesterol increased. Decreases in
body weight varied from − 8.6 to 0.9kg, with slightly
more weight loss in favor of greater carbohydrate restric-
tion. This study, therefore, shows favorable effects in dia-
betes patients following a controlled LCHF diet lasting to
a maximum of ≈ 2years. To ensure the correct interpreta-
tion of this data, it should be noted that only an abstract
was published and that this abstract also contains citations
that lead to further questions. We must wait for the com-
prehensive peer reviewed publication before we can make
definitive statements on this matter.
Recent work addressed the potential effectiveness of diets
differing in the contents of carbohydrate and fat on weight-
loss, in dependence of insulinemic and glycemic status and
sheds a differentiating light on the question about which diet
type may be most effective to lose weight. Hjorth etal. [74]
re-evaluated the effects of diets with different glycemic loads
or different fiber and whole-grain content as assessed in three
large randomized trials in overweight participants (1: the
DiOGenes—Diet, Obesity, and Genes study, 2: the OPUS—
New Nordic Diet study and 3: the NUGENOB—Nutrient-
Gene Interactions in Human Obesity-study). Effects on the
concentrations of fasting plasma glucose (FPG) and fasting
insulin (FI) as possible prognostic markers for successful
weight loss and weight maintenance were determined. It
was observed that pre-diabetic (elevated FPG) and diabetic
individuals lost more weight or regained less weight when
consuming a high-fat and low-carbohydrate diet than when
consuming a low-fat and high-carbohydrate diet. On the
contrary, in insulin-sensitive individuals, expressing normo-
glycemia, beneficial effects observed were favorable when
consuming a low-fat and relatively high-carbohydrate diet.
Wan 2017 observed that a relatively high carbohydrate was
effective for weight loss in healthy obese individuals. Based
on this data, [75] concluded that disturbed insulin sensitivity
and elevated FPG are important determinants for the dietary
treatment of choice, being either low fat–high carbohydrate
or alternatively, low carbohydrate–high fat. Accordingly,
they proposed that stratifying patients for personalized die-
tary guidance based on pre-diet FPG outcomes may be rec-
ommendable. In another paper, however, by Snorgaard and
Astrup etal. [14, 76], the same author concluded as follows:
“in addition to improvements in HbA1c in the short term,
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1309European Journal of Nutrition (2018) 57:1301–1312
1 3
there is no superiority of low-carbohydrate diets in the field
of glycemic control, weight or LDL cholesterol.
Based on these observations and the seemingly conflict-
ing conclusions, there is a need for controlled studies, “with
intention to treat”, to verify these effects as a base for future
evidence-based dietary recommendations.
Is life style intervention thefavorable way
togo?
Based on the information presented above, it cannot be
concluded that LCHF diets result in favorable effects that
outweigh effects observed with less-drastic diet regimen,
containing more carbohydrate quantitiesthat are closer to
daily practise.
One might argue that an improvement of the daily diet
is relatively easy to achieve and also effective for disease
prevention. Recent expert panels, including those of the
WHO [5], the Dutch Health Council [2], the German Food
Council [1], Nordic Dietary Recommendations (Scandi-
navian countries) [77], and the Scientific Advisory Com-
mittee on Nutrition in England [3], have concluded that
diets rich in fruit, vegetables, cereals, legumes, but also
moderately rich in fat and calories, combined with a suf-
ficient amount of daily physical activity constitute the
best scenario for maintaining a healthy body weight and
for the prevention of chronic lifestyle diseases. This also
entails moderation of (added/free) sugar intake and select-
ing whole-wheat products over low-fiber starch products.
The quantity of fat that is unanimously recommended by
all these advisory bodies is less than 40% of daily energy
intake. The recommended quantity of carbohydrates for
each of these advisory bodies and others [52] is over 40%
of energy intake, which corresponds to more than 180g
of carbohydrates per day.
In addition to this, it is important to notice that life-
style interventions that also focus on other factors than
diet alone have been shown to result is long-term benefits.
Lindström etal. [78] described long-term effects of life-
style intervention in a Finnish population. The specific
intervention goals were weight reduction (5% or more
from baseline weight), dietary modification [energy pro-
portion of total fat less than 30% and saturated fat less
than 10% of total energy, dietary fiber intake 3.6g/MJ
(15g/1000kcal)] or more and increased physical activity
(4h per week or more). The authors showed that lifestyle
intervention while being on a relative carbohydrate-rich
diet in people at high risk of type 2 diabetes induces sus-
taining lifestyle change and results in long-term preven-
tion of progression to type 2 diabetes. Schellenberg etal.
[79] performed a meta-analysis of lifestyle programs and
concluded that interventions that include exercise, dietary
changes, and at least one other component are effective in
decreasing the incidence of type 2 diabetes in high-risk
patients, and the benefit extends beyond the active inter-
vention phase. However, in patients who have already been
diagnosed with type 2 diabetes, the evidence for benefit of
comprehensive lifestyle interventions on patient-oriented
outcomes was less clear.
Key points
1. Each type of diet that results overweight—diabetic indi-
viduals to eatless food and taking in less energy will
initially result in weight loss, which in itself will lead to
favorable metabolic and functional changes.
2. The available scientific literature shows that controlled
diet studies (several weeks to < 2year) with LCHF in
persons with obesity and diabetes do induce favorable
effects on weight loss, blood glucose and insulin as well
as some less desirable effects (increase LDL cholesterol,
decrease vascular reactivity).
3. Compliance with KLCHF diets appears to be poor and
after some time many individuals appear to shift to
higher intakes in the range of 130–160g/day. Accord-
ingly, targeting 100–150g/day may be better achievable.
4. There is lack of data supporting long-term efficacy,
safety and health benefits of LCHF diets. Any recom-
mendation should be judged in this light.
5. Persons with type 2 diabetes or borderline diabetes are
recommended to restrict their daily intake of rapidly
digestible carbohydrates (sugars, syrups, potato, white
rice, white bread, etc.). In addition, it is recommended
that when switching to a diet that includes a higher por-
tion of fat, people should primarily select products that
are rich in unsaturated fatty acids.
6. Lifestyle interventions in people at high risk of devel-
oping type 2 diabetes, while maintaining a relative car-
bohydrate-rich diet, results in long-term prevention of
progression to type 2 diabetes and are generally seen as
safe.
7. Due to the complexity of the potential mechanisms, their
interactions, and an absence of data from robustly con-
trolled long-term studies (> 2years), a general public
evidence based recommendation to support KLCHF
and LCHF diets as a preventive measure to help reduce
risks of type 2 diabetes, seems premature. The role of
long-term elevated consumption of fat combined with
low-carbohydrate consumption warrants further study
before general recommendations can be made.
Acknowledgements The base paper preceding this publication was
critically reviewed and by Prof. Dr. Ellen Blaak, Professor of Physi-
ology of Fat Metabolism (Maastricht University, The Netherlands)
and Prof. Dr. Henk Bilo, Professor of Internal Medicine, diabetes
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1310 European Journal of Nutrition (2018) 57:1301–1312
1 3
(University of Groningen, The Netherlands). I am grateful for their
comments and suggestions.
Compliance with ethical standards
Conflict of interest This publication has been made WITHOUT any
involvement of the Food Industry. The sole intention of the author is
to help create transparency to the academia, public, industry and poli-
cymakers on truthful interpretation of science. The opinions expressed
are based on current scientific evidence as available in scientific jour-
nals and publicly accessible. The author has no conflicts of interest.
Open Access This article is distributed under the terms of the Crea-
tive Commons Attribution 4.0 International License (http://creat iveco
mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribu-
tion, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
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