Blackwell Science, LtdOxford, UKOBRobesity reviews1467-78812005 The International Association for the Study of Obesity.
74958Review ArticleLow-carbohydrate diets and healthA. Adam-Perrot
et al.
obesity reviews
Low-carbohydrate diets: nutritional and physiological
aspects
A. Adam-Perrot1, P. Clifton2 and F. Brouns1,3
1
Cerestar R&D Vilvoorde Center, Havenstraat
84, 1800 Vilvoorde, Belgium; 2Clinical research
unit, CSIRO HSN, Adelaide SA, Australia;
3
Nutrition and Toxicology Research Institute
(NUTRIM), Maastricht University, The
Netherlands
Received 10 January 2005; revised 28 June
2005; accepted 29 July 2005
Address for correspondence: F Brouns,
Cerestar Vilvoorde R&D Centre, Havenstraat
84, B-1800 Vilvoorde, Belgium. E-mail:
Fred_brouns@cargill.com
Introduction
Recently diets low in carbohydrate (low-CHO diets) have
become the focus of international attention since the recent
WHO recommendations to reduce the overall consumption
of sugars and some health professionals recommendations
to reduce the consumption of rapidly digestible starches
that lead to high glycaemic responses. Low-CHO diets
generally are considered to contain less than 100-g CHO
© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
Summary
Recently, diets low in carbohydrate content have become a matter of international
attention because of the WHO recommendations to reduce the overall consump-
tion of sugars and rapidly digestible starches. One of the common metabolic
changes assumed to take place when a person follows a low-carbohydrate diet is
ketosis. Low-carbohydrate intakes result in a reduction of the circulating insulin
level, which promotes high level of circulating fatty acids, used for oxidation and
production of ketone bodies. It is assumed that when carbohydrate availability is
reduced in short term to a significant amount, the body will be stimulated to
maximize fat oxidation for energy needs. The currently available scientific litera-
ture shows that low-carbohydrate diets acutely induce a number of favourable
effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels,
reduction of circulating triglyceride levels and improvement of blood pressure.
On the other hand some less desirable immediate effects such as enhanced lean
body mass loss, increased urinary calcium loss, increased plasma homocysteine
levels, increased low-density lipoprotein-cholesterol have been reported. The long-
term effect of the combination of these changes is at present not known. The role
of prolonged elevated fat consumption along with low-carbohydrate diets should
be addressed. However, these undesirable effects may be counteracted with con-
sumption of a low-carbohydrate, high-protein, low-fat diet, because this type of
diet has been shown to induce favourable effects on feelings of satiety and hunger,
help preserve lean body mass, effectively reduce fat mass and beneficially impact
on insulin sensitivity and on blood lipid status while supplying sufficient calcium
for bone mass maintenance. The latter findings support the need to do more
research on this type of hypocaloric low-carbohydrate diet.
Keywords: Cardiovascular risk factors, cholesterol, low-carbohydrate diets, low-
fat diets.
obesity reviews (2006) 7, 49–58
per day with a nutrient distribution being 50–60% from
fat, less than 30% from CHO, and 20–30% from protein
(1). A frequently cited type of such a diet is the ‘Atkins low-
CHO diet’. This diet is in principle based on a consumption
of £50-g CHO per day and involves several steps, starting
with a 2-week ‘ketogenic induction’ period, during which
the goal is to reduce CHO intake to <20 g d-1. During that
phase, protein intake from foods such as beef, turkey, fish,
chicken and eggs are encouraged and an unlimited con-
49
50 Low-carbohydrate diets and health A. Adam-Perrot et al.
sumption of fat is allowed. This phase of the diet allows
no sweets and snacks, but also no fruits, bread, grains,
starchy vegetables or dairy products other than cheese,
cream or butter. During the subsequent steps it is advised
to individually modify CHO intake gradually to a level that
is on the border to ketosis and that still promotes further
weight loss (2). For some individuals, this level of CHO
restriction could be as low as 25 g d-1 and for others it
could be as high as 90 g d-1. One of the common metabolic
changes assumed to take place when a person follows a
low-CHO diet is ketosis (formation of ketone bodies).
Ketone bodies (acetone, acetoacetate, and b-hydroxybu-
tyric acid) are by-products resulting from a partial oxida-
tion of fatty acids in the liver (1). It is assumed that when
CHO availability (liver glycogen and exogenous CHO sup-
ply) is reduced in the short term to a significant degree, the
body will be stimulated to maximize fat oxidation. In that
condition, ketone bodies become an important fuel for the
body.
Other types of CHO-focused diets are:
1. Carbohydrate Addict’s Diet, which aims to break
cravings for ‘fat-causing CHOs’ by limiting the intake of
CHO-containing foods to only one meal per day (3).
2. Protein Power Diet, which provides for 0.75 g d-1 of
protein per kilogram of body weight with less than 30 g of
CHOs per day allowed in the induction phase and up to
55 g d-1 thereafter (4).
3. Sugar Busters! Diet, which advises the avoidance of
sucrose and high-glycaemic index CHOs such as potatoes,
pasta, corn, white rice and carrots. According to the Sugar
Busters! Diet, high-glycaemic index foods cause frequent
spikes in insulin, which are responsible for the deposition
of fat and a cause of insulin resistance (5).
4. The South Beach diet: This diet tries to teach dieters
about ‘bad and good’ CHO. It starts with a 2-week ‘CHO
detoxification’ period, during which all ‘bad’ CHO should
be avoided (bread, rice, potatoes, pasta and baked goods),
followed by a second phase where the right CHO (whole
grains and fruits) are reintroduced till a certain level to not
go above the goal weight.
In some studies, authors reported high drop-out rates
and adverse effects in individuals that follow strict low-
CHO diets such as dehydration, headache, gastrointestinal
symptoms (constipation), hypoglycaemia, elevation of
blood uric acid levels, vitamin deficiencies (1,6–8).
The paragraphs below deal in more detail with physio-
logical and health aspects of diets that are low in CHO and
relatively high in fat.
Effect of low-CHO diets on nutrient adequacy
Low-CHO diets are at greater risk of being nutritionally
inadequate as they enforce restriction of food choices. The
© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
obesity reviews
generally low consumption of fruits, vegetables and whole
grain products, during low-CHO dieting, reduces the over-
all intake of dietary fibres, vitamins, calcium, potassium,
magnesium and iron. In this respect, the Continuing Survey
of Food Intake by Individuals (CSFII 1994–1996) examined
the relationship between popular diets and diet quality (as
measured by the healthy eating index, consumption pat-
terns, and body mass index) (9,10). The study showed that
high-CHO diets (defined as greater than 55% of energy
from CHO) gave the highest dietary adequacy score (82.9)
whereas low-CHO diets (defined as less than 30% of energy
from CHO) gave the lowest dietary adequacy score (44.6)
(9,10). Accordingly, there may be a risk of low micronutri-
ent intakes when consuming a low-CHO diet. At present
and there are no biochemical data to support any suggestion
that low-CHO diets lead to an impaired nutritional status.
Short-term health implications
Glycogen availability and ketosis
When dietary CHO are chronically limited, the body utilizes
at least part of its reserves of glycogen in order to meet
demands for blood glucose maintenance. Glycogen stores
in the body are small, with approximately 70–100 g stored
in the liver and about 400 g in muscle. Most of these
glycogen stores are reduced significantly within 48 h of total
CHO restriction (especially in the liver), but total depletion
may take a much longer time depending on the daily amount
of CHO consumed and on the daily energy expenditure.
Once glycogen stores are depleted, the body begins to
increase fat oxidation as a means of meeting the majority
of its energy demands that cannot otherwise be met by
gluconeogenesis (production of glucose from certain amino
acids and glycerol). Gluconeogenesis will be enhanced to
maintain a sufficient amount of circulating glucose for the
central nervous system and the red blood cells. Fatty acids
liberated into the blood can be oxidized by the liver and
muscle for energy production. Fatty acids can also be par-
tially oxidized by the liver to form acetoacetate, which,
subsequently can be converted to b-hydroxybutyric acid
and acetone. These ketone bodies can be used as a fuel by
all mitochondria-containing tissues including muscle and
brain (1).
There is at present no consensus as to what is the CHO
cut-off limit to induce ketosis, because this may vary on
individual basis. However, intakes below 50 g of CHO per
day are generally reported to induce ketosis (11).
Effects on blood glucose, insulin response
and weight
In the studies listed in Table 1, significant decreases in fasting
and postprandial glucose responses have been observed after
obesity reviews Low-carbohydrate diets and health A. Adam-Perrot et al. 51

Table 1 Influence of the low-carbohydrate (low-CHO) diets on weight loss and on the different physiological parameters

Subjects/duration Diets D kcal d-1 Body weight Fat loss Lean mass Fasting blood Fasting blood Reference
loss loss glucose insulin

51 obese <25 g d-1, no limit ≥460 -10%* (9 kg) 6 kg* 3 kg* (8)
(6 months) caloric intake
(1447 ± 350 kcal)
20 overweight <71 g d-1, 632 -6%* (5 kg) 4 kg* 1 kg* No No (19)
women (8 weeks) (1373 kcal d-1)
(21% C, 25% P, 45% F)

20 normal weight 8% C, 30% P, 61% F – -34% (16)

subjects (6 weeks) 47% C, 17% P, 32% F –

42 obese women Low-CHO (<60 g d-1) 306 -9%*† (8 kg) 5 kg*† 2 kg*† -9%* -15%* (12)
(6 months) diet ad libitum
(30% C, 23% P, 46% F) 460 -4%* (4 kg) 2 kg 1 kg -4%* -23%*

Calorie-restricted with
(53% C, 18% P, 29% F)

22 overweight Low-CHO (<20 g d-1) – -11%† (10 kg) (18)

adolescents diet ad libitum
(12 weeks) (8% C, 32% P, 60% F)
(1830 kcal d-1)

Low-fat diet (<30% fat) – -4% (4 kg)

(56% C, 32% P, 12% F)
(1100 kcal d-1)
132 severely obese Low-CHO (30 g d-1) 460 -4%† (6 kg) -9%† -27%† (6)
(6 months) (37% C, 22% P, 41% F)

Low-fat 272 -1% (2 kg) -2% +5%

(51% C, 16% P, 33% F)

63 obese subjects Low-CHO (<20 g d-1) – -10%*†/-7%* (17)

(6 months/1 years) (no data on caloric content)
Low-fat (<1500 kcal) – -5%*/-5%*
(60% C, 15% P, 25% F)

15 overweight men Low-CHO (1860 kcal) 739 -6%† (-6 kg) -6%*† -41%* (13)
(6 weeks) (10%C, 30%P, 60%F)
Low-fat (1560 kcal) 1033 -4% (-3 kg) -4% -28%*
(55%C, 20%P, 25%F)

31 overweight Low-CHO (1454 kcal) 764 -8%* (-7 kg) -4 kg* -2 kg* -3% -28.7%* (27)
and obese adults (15%C, 26%P, 56%F)
(10 weeks)

Low-fat (1536 kcal) 607 -7%* (-7 kg) -5 kg* -1 kg -10% -8%
(62%C, 19%P, 18% F)

No, no significant effects; C, carbohydrate; P, protein; F, fat.

*Significantly different from base line within the group.
†
Significantly different between the groups.

consumption of low-CHO, high-fat diets, especially in dia-
betic subjects (6,12). This may in part be explained by a
reduction of the abnormally high hepatic glucose output
observed in these subjects with poor metabolic control.
Nevertheless, a dramatic reduction in CHO intake
(<10% CHO) can also lead to a significant decrease of
fasting glucose in healthy overweight subjects (13). Previ-
ous studies demonstrated that during a keto-acid infusion,
hepatic glucose output and glycaemia decreased in both
non-diabetic individuals and in patients with Non-Insulin
Dependent Diabetes Mellitus (NIDDM), suggesting that
ketosis may lower basal hepatic glucose output in subjects
consuming a low-CHO diet (14). Weight loss itself is also
known to affect basal insulin secretion and insulin sensitiv-
ity and may thus also impact on hepatic glucose output and
blood glucose levels.
Low-CHO diets also result in a reduction of the circu-
lating insulin level (13,15,16), which promotes degradation

© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
52 Low-carbohydrate diets and health A. Adam-Perrot et al. obesity reviews

of triacylglycerol into free fatty acids and glycerol. Elevated
levels of circulating fatty acids will promote their utiliza-
tion as a fuel by muscle, which will help promote fat loss.
Generally, individuals who are on ad libitum low-CHO diet
experience a rapid initial weight loss (Table 1).
However, after 1 year of dieting, the level of weight loss
in individuals who followed either a high-CHO or a low-
CHO diet is similar (7,17).
Induction of a rapid initial weight loss with low-CHO
diets may be partly explained by a reduction in overall
caloric intake, which may be the result of a great limita-
tion of food choices by the requirements of minimizing
CHO intake (12,18), to the initial increase in circulating
b-hydroxybutyrate, which may suppress appetite (19) and
to the satiating effect of low-CHO diets containing rela-
tively high amounts of protein (20,21). It has indeed been
shown that calorie for calorie protein is more satiating
than either CHO or fat (22). Thus, it may be that a higher
consumption of protein in very-low-CHO dieters plays a
role in limiting food intake (23). It is noteworthy that in
general the greatest weight loss occurs in individuals with
the lowest caloric intake and the highest initial body
weight (24).
Some of the initial weight loss may also be explained by
a reduction of glycogen stores from liver (5% of liver
weight) and muscle (1% of muscle weight). Each gram of
glycogen is stored with approximately 3 g of water (25).
Therefore a weight loss of 1–2 kg can theoretically be
achieved within the first week of the diet because of sub-
stantial glycogen reductions in liver and muscle and excre-
tion of the liberated water in urine. Depending on the rate
of glycogen depletion this process may last up to 7–14 d,
after which weight loss slows (26). It should be noticed in
this respect that loss of glycogen and water is not a true
measure of weight loss, as their stores will be replenished
once the diet is stopped.
It is noteworthy that when fat loss is the same or higher,
during a low-CHO, high-fat diet compared with a hypo-
energetic low-fat diet, losses of lean body mass (protein)
also seem to be higher (12,15,27). Interesting in this respect
are the observations of Layman et al. who observed that a
hypo-energetic high protein diet appeared to enhance
weight loss because of a greater reduction of body fat while
loss of lean body mass was reduced (21,28). They observed
that elevated protein intakes in general were associated
with a better diet compliance because of a higher degree of
satiety and less hunger. Based on these observations they
hypothesized that a reduced ratio of CHO to protein and
an elevated supply of the amino acid leucine help modify
insulin action and stimulate muscle protein synthesis (28).
Thus it may be hypothesized that ‘low-CHO high-protein
diets’ exert effects that are more favourable than ‘low-
CHO high-fat diets’.
Recently, authors of a systematic review of studies pub-
lished between 1966 and February 2003 on the safety and
efficacy of low-CHO diets concluded that among all pub-
lished studies, participant weight loss while using low-
CHO diets was principally associated with decreased
caloric intake and increased diet duration but not with
reduced carbohydrate content. Accordingly, they suggested
that there is insufficient evidence to specially recommend
or advise against use of such diets (24).

Table 2 Influence of the LC and LF diets on the lipid profile

Diet type Total cholesterol LDL-C HDL-C TG TG/HDL ratio Reference

LC -5%* -7%* +19%* -43%* -53%* (8)

LC -20%* -27%* 0% -40%* -35%* (19)
LC +5% +4% +11% -33%* (16)
LF -3% -5% 0% -5%
LC 0% 0% +13% -23%*† (12)
LF -1% -5% +8% 0%
LC -2% +3% +8% -40%* (18)
LF -9%* -21%*† +4% -5%
LC +1% +2% 0% -20%† (6)
LF 0% +4% -2% -4%
LC +3%/0% +4%/0% +20%*†/+18%*† -21%*/-28%*† (17)
LF -4%/-5% -3%/-6% +4%/+3% -13%*/+1%
LC -11%* -6% -3% -44%*† -42%*† (13)
LF -15%* -17%*† -7% -15% -8%
LC 0% 0% +12%* -29%* -42%*† (27)
LF -27%*† -31%*† -15%*† -25%* -9%*

LC, low-carbohydrate; LF, low-fat; LDL-C, low-density lipoprotein- cholesterol; HDL-C, high-density lipoprotein-cholesterol; TG, triacylglycerol.
*Significantly different from base line within the group.
†
Significantly different between the groups.

© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
obesity reviews Low-carbohydrate diets and health A. Adam-Perrot et al. 53

Adipose tissue Muscle

Triacylglycerol Brain and
CO2 other organs/
tissues
Fatty acids

Fatty acids Fatty acids

Low insulin level

VLDL – +

Fatty acid HMGCoA HMGCoA

reductase lyase

acyl-CoA

Triacylglycerol acetyl-CoA
Figure 1 Branch points of regulatory signifi- +
cance in the pathway of ketone body formation Cholesterol Ketone bodies
during a low-carbohydrate diet. The branch Liver
points are encircled.

acylglycerol concentration (Table 2). Postprandial triacylg-

Effects on lipid profiles
Individuals who follow low-CHO, high-fat diets have a
significant reduction in their fasting triacylglycerol and
postprandial lipaemia (Table 2). Such a reduction in fasting
triacylglycerol has been observed independent of the fat
composition of the diet but seems to be more pronounced
with a polyunsaturated fatty acids (PUFA) rich diet (29,30).
This observation is important because elevated triacylglyc-
erol levels are a risk factor for cardiovascular disease
(CVD).
It may be speculated that reductions in plasma triacylg-
lycerol are the result of a combination of a reduced very-
low-density lipoprotein (VLDL) production rate (Fig. 1)
and an increase in triacylglycerol removal from blood.
Noteworthy is the observation that no significant increase
in total cholesterol and low-density lipoprotein-cholesterol
(LDL-C) was observed, despite an increase of cholesterol
intake when subjects switched to the low-CHO diet
(Table 2).
A low insulin level activates HMG-CoA-lyase (enzyme
of ketone bodies synthesis) and inhibits HMG-CoA reduc-
tase (enzyme of cholesterol synthesis in the liver), which
may provoke a decrease or a stabilization of the blood
cholesterol and the LDL-C despite high cholesterol con-
sumption with a low-CHO diet. Both low-fat and low-
CHO diets exert a similar effect on serum total cholesterol
while no effects on oxidized LDL have been observed.
Although low-fat diets would favour a significant
decrease of fasting LDL-C (13), low-CHO diets favour
particularly a significant decrease of the fasting serum tri-
lycerol levels are significantly reduced after consumption of
both diets, but this reduction is generally greater on the
low-CHO diet (13).
Effects on physical performance
In short-term studies (4 weeks), it was shown that the
physical performance was not altered in well-trained
individuals using a iso-caloric low-CHO diet (<20-g CHO)
with an adequate vitamin, minerals and protein (1.75 g
kg-1 d-1) supply, compared with when being on a normal
diet (31,32). This is most probably explained by a physio-
logic adaptation to preserve endogenous CHO and stimu-
late fat to become the predominant muscle substrate.
However, this observation does not preclude the possibility
that hypocaloric low-CHO diets may impact on high inten-
sity performance or performance in untrained subjects as
it is known that reduced level of glycogen and CHO avail-
ability lower performance capacity at exercise intensities of
>50% maximal work capacity (33).
Potential long-term health implications
Insulin sensitivity and insulin resistance
One of the major unresolved issues in the field of nutrition
concerns the optimal intake of dietary fat relative to other
macronutrients, particularly CHO. Many investigators
state that a high percentage of total energy consumed in
the form of fat may lead to overweight and may increase

© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
54 Low-carbohydrate diets and health A. Adam-Perrot et al.
the risk for chronic diseases because of overweight-related
metabolic abnormalities (34). Studies in experimental ani-
mals have shown that prolonged elevated fat intakes poten-
tially may lead to insulin resistance. Rodents appear to be
particularly susceptible for developing insulin resistance in
response to high-saturated fat diets (35,36). Although
chronically increased saturated fatty acids intakes are con-
sistently associated with high insulin resistance, monoun-
saturated fatty acids and polyunsaturated fatty acid intake,
without increasing total fat intake, seems to improve insu-
lin sensitivity (36).
Nevertheless, in the studies listed in Table 1, significant
decreases in fasting and postprandial insulin responses after
the low-CHO, high-fat diets have been observed. More-
over, under circumstances of ketosis, it was shown that the
consumption of a polyunsaturated fat-rich low-CHO diet
(70% fat, 15% CHO and 15% protein) for 5 d induced a
greater level of ketosis and improved insulin sensitivity
without negatively affecting total or LDL-C levels, com-
pared to a traditional very low-CHO diet high in saturated
fats in healthy subjects (29).
However, it may be speculated that insulin sensitivity
may be negatively affected in the long term as low-CHO,
high-fat diets favour an increase of plasma circulating free
fatty acids (37–39), which under usual dieting conditions
is typically associated with many insulin-resistant states in
humans (40,41). Several data are consistent with the
hypothesis that altered fatty acid metabolism contributes
to insulin resistance because of alterations in the partition-
ing of fat between the adipocyte and muscle or liver. This
change leads to the intracellular accumulation of fatty acid
and fatty acid metabolites in these insulin-responsive tis-
sues, which leads to acquired insulin signalling defects and
insulin resistance resulting in a reduced glucose transport
(42). The latter is thought to result from fatty-acid-induced
Insulin
IRS-1/IRS-2serine/threonine phosphorylation
IRS-1/IRS-2 tyrosine phosphorylation
PI 3 kinase
Fatty acyl CoA
Diacylglycerol
Glucose eramides
GLUT 4
Plasma glucose Fatty acids
© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
obesity reviews
alterations in upstream insulin signalling events, resulting
in decreased GLUT 4 translocation to the plasma mem-
brane. Schulman and co-workers showed that an increased
level of intracellular fatty acid metabolites, such as diacylg-
lycerol, fatty acyl CoA’s, or ceramides activates a serine/
threonine kinase cascade, possibly initiated by protein
kinase Cq. The latter leads to a non-desired phosphoryla-
tion of serine/threonine sites on insulin receptor substrates,
which then fail to associate with or to activate PI 3-kinase,
resulting in decreased activation of glucose transport and
other downstream events (Fig. 2).
In this respect, it needs to be pointed out that low-CHO,
high-protein diets do not seem to impact as severely circu-
lating free fatty acids levels as low-CHO, high-fat diets
(43,44).
Effects on cardiovascular health
Short-term studies suggest that low-CHO diets do not neg-
atively impact on CVD risk profiles as they have been
shown to help reduce fasting insulin and glucose levels,
improve blood pressure and lipid disorders that are char-
acteristic of atherogenic dyslipidaemia by favouring an
increase of LDL size, an increase of high-density lipopro-
tein-cholesterol (HDL-C) levels and a decrease of plasma
triacylglycerol (Table 3). Moreover, low-CHO diets as well
as low-fat diets significantly decreased several biomarkers
of inflammation (hs-CRP, hs-TNFa, hs-IL-6, s-ICAM-1, s-
P-selectin), which play a key role in all stages of the patho-
genesis of atherosclerosis. Fat loss, however, achieved is the
driving force underlying the reductions in most of the
inflammatory markers (45).
However, data from longer-term studies are clearly
required as recently an increased plasma homocysteine
level (+6.6%) was observed in individuals that follow
Serine/threonine
kinase cascade
PKCθ
Figure 2 Mechanisms of reduced glucose
transport from fatty-acid-induced alterations in
upstream insulin signalling events, IRS, insulin
receptors substrate; PI 3, Phosphatidylinositol
3-kinase; PK Cq, Protein kinase C isoenzyme q.
obesity reviews Low-carbohydrate diets and health A. Adam-Perrot et al. 55

Table 3 Influence of the LC diets on the differ-

Diet Urinary calcium Acid uric Blood urea/ Blood pressure References
ent physiological parameters
type excretion excretion creatinine (mmHg)

LC +53%* +17%* +27%* Systolic: -8* (8)

Diastolic: -3*
LC Systolic: -9* (19)
Diastolic: -7*
LC No (12)
LF No
LC +1.5% +1% Systolic: -2 (6)
Diastolic: -1
LF -3% -3% Systolic: -2
Diastolic: -2
LC No (17)
LF No
LC Systolic: -10* (27)
Diastolic: -6*
LF Systolic: -11*
Diastolic: -5*

LC, low-carbohydrate; LF, low-fat; No, no changes were observed compared with the control.
*Significantly different from base line within the group.

strictly a low-CHO diet for several months (15). In con-
trast, a low-fat diet induced a decrease of plasma homocys-
teine by -6.8%. This may be an important observation as
the relationship between total plasma homocysteine and
CVD is dose dependent and independent of other risk
factors. In humans, the effects of homocysteine on endot-
helial and vascular function and blood coagulation provide
explanations for increased CVD risk (46–48). The impact
of these observations for people that follow low-CHO diets
remains unknown at present. The mechanism of the
observed increase in homocysteine is unknown as well. On
the one hand blood lipid profiles generally improve in
people that are on a low-CHO diet and any increase in
CVD risks because of homocysteinemia may be counter-
acted.
Based on the information given above it may be con-
cluded that low-CHO, high-fat diets result in improve-
ments in some CVD risk factors, while impacting less
favourably on others. Thus far, no long-term study has
focused on the insulin sensitivity and CVD risk factors in
individuals that are on strict low-CHO, high-fat diets for
1 year or more. Such studies are needed to answer any
question addressing long-term health benefits.
Effects on bone health
It has been suggested that low-CHO diets may impact
negatively on bone health because of promotion of urinary
calcium loss. This may be of importance to women and the
elderly as they are prone to developing low bone mineral
density and osteoporosis. Low-CHO diets generate acidosis
(because of the presence of ketone bodies in blood), which
promotes calcium mobilization from bone to buffer blood
and maintain a neutral pH, finally leading to an increase
of urinary calcium (Table 3). This may be explained by the
fact that blood acidification is known to increase glomer-
ular filtration rate and decrease renal tubular re-absorption
of calcium with a concomitant increase in activity of osteo-
clasts and inhibition of osteoblasts, further increasing bone
resorption. In this respect, a recent study confirmed that
consumption of a low-CHO diet leads to an increase in
urinary calcium loss without an increase in compensating
intestinal calcium absorption and a decrease in markers for
bone formation (49).
Generally speaking, low-CHO diets also go hand in hand
with an increased consumption of animal protein. Depend-
ing on the protein source, its metabolism may impact on
blood acidity and calcium loss, because sulphur amino
acids increase calcium, potassium, sodium and ammonia
loss because of a change in blood acidity. It has been shown
that in short term, high-protein diets are not detrimental
to bone (50) and that dietary protein increases circulating
insulin-like growth factor (IGF)-1, a growth factor believed
to play an important role in bone formation (51). Despite
these observations, evaluation of the effects of chronically
high dietary protein intakes along with low-CHO dieting
is required to evaluate its long-term safety.
Overall health and cancer prevention
There is epidemiological evidence for a protective effect of
fruits, vegetables and whole grains in almost all major
cancers afflicting western society today including colorec-
tal, breast, pancreatic, lung, stomach, oesophageal, and

© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
56 Low-carbohydrate diets and health A. Adam-Perrot et al.
bladder cancer (52–62). Fruits and vegetables contain a
large variety of compounds such as antioxidants, dietary
fibres, isothiocyanates, polyphenols, which are implicated
in providing protection against cancer. Dietary fibres can
have a myriad of benefits in the colon such as diluting
carcinogenic compounds, reducing stool transit time, pro-
duction of beneficial fermentation products such as butyric
acid and a lowering of pH, all of which have been proposed
as being helpful in reducing colon cancer risks. The current
scientific evidence strongly suggests that it is not the con-
sumption of one or two varieties of vegetables and fruit
that confer a benefit, but rather the intake of a wide variety
of plant foods (63–65).
Low-CHO diets, however, generally are low in fruits,
vegetables (if starchy foods are not adequately replaced by
other types of low-CHO-containing vegetables) and grains.
This may theoretically place an individual at an increased
disease risk if such a diet is followed long term and fruit
and vegetable intakes remain low.
As low-CHO dieting is often associated with increased
consumption of meat, it should be noted that a potential
link between increased intakes of meat and the incidence
of colorectal cancers has been observed in some epidemio-
logical studies (66–68). Thus, it has been shown that a daily
increase of 100 g of all meat or red meat is associated with
a significant 12–17% increased risk of colorectal cancer
(69). However, the weight loss induced by dieting may
counteract the observed epidemiological risks of increased
meat consumption.
Kidney health aspects
Multiple aspects of very-low-CHO, high-fat, high-protein
diet likely contribute to a potential for kidney stone forma-
tion. Low-CHO diet enhances ketone bodies production
which may remain elevated for several months (3 months
or more) (12,17). Ketone bodies-induced acidosis, results
in hypocitruria and in an increase of un-dissociated uric
acid (49). Urinary citrate is an important inhibitor of cal-
cium crystal formation and a low urinary level increases
the risk of calcium stone formation while patients on the
very-low-CHO diet have also hypercalciuria (8,70).
Conclusions
Any diet that is hypo-energetic will result in weight loss
(24). Long-term compliance to low-CHO, high-fat diets
may theoretically induce some less favourable metabolic
effects. However there are no long-term data (no longer
than 12 months) regarding efficacy and side effects of low-
CHO diets. Recent reviews have concluded that diets that
are high in fruits and vegetables, whole grains, legumes,
and low-fat dairy products, as well as being moderate in
fat and calories, would result in the greatest chance of
© 2006 The International Association for the Study of Obesity. obesity reviews 7, 49–58
obesity reviews
weight loss and maintenance. Such diets are associated with
fullness and satiety and have a very good dietary adequacy
and may reduce the risk of chronic disease. The currently
available scientific literature shows that low-CHO diets
acutely induce a number of favourable effects, such as
reduction of circulating triacylglycerol levels and rapid
weight loss, while promoting some less desirable immediate
effects such as enhanced lean body mass loss, increase
urinary calcium loss, increased plasma homocysteine levels,
increased LDL-C in some studies and increased circulating
fatty acids as well as relatively low micronutrient intakes.
The long-term effect of the combination of these changes
is at present not known. The role of prolonged elevated fat
consumption along with low CHO diets should be
addressed. The recent data from Luscombe (2002, 2003),
Farnsworth (2003), Johnston (2004) and Layman (2004)
suggest that some undesirable effects of a low-CHO diet
may be counteracted by a higher protein intake and by a
lower fat intake, as high-protein diets have been shown to
induce favourable effects on feelings of satiety and hunger,
help preserve lean body mass, effectively reduce fat mass
and beneficially impact on insulin sensitivity and on blood
lipid status (20,28,44,71,72). The latter findings support
the need to do more research on this type of hypocaloric
diet.
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