The ACT-OUT Trial: ACTivity OUTcomes Based on High Carbohydrate or High Fat Diet in Metabolic Syndrome
The ACT-OUT Trial: ACTivity OUTcomes Based on High Carbohydrate or High Fat Diet in Metabolic Syndrome
Current obesity prevention emphasizes caloric restriction and avoidance of high fat foods.
 The result is an approach that replaces dietary fat with carbohydrates. There has, however,
 since been an obesity epidemic with an increased prevalence of metabolic syndrome (MetS) and
 type II diabetes. Negative results from trials of low fat diets for weight loss, prevention
 of heart disease and malignancies are consistent with the inadequacy of low fat/high
 carbohydrate approach. One of the findings of trials comparing low fat, calorie reduced diets
 to ad lib carbohydrate restricted diets is that subjects randomized to a low carbohydrate
 intake lose more weight despite equivalent intake. This equates to a 200 kcal/day greater
 weight loss on a carbohydrate restricted diet. Some investigators have speculated the
 metabolic advantage of carbohydrate restriction is due to increased energetic costs of
 gluconeogenesis. Alternatively, carbohydrate restriction is associated with increases in
 spontaneous physical activity.

 This protocol has three aims. First, adherence to a carbohydrate restricted diet in subjects
 with metabolic syndrome will cause an increase in spontaneous physical activity, independent
 of weight changes. Second, cardiometabolic risk factors (ApoB, TG, HDL, blood pressure, CRP)
 will show greater improvement on a carbohydrate restricted diet compared to a low-fat, high
 carbohydrate diet. Finally the investigators will interview a sub-sample of participants to
 better understand quality of life issues with respect to the dietary assignment or lifestyle
 intervention.

 The investigators will recruit 72 participants with MetS, from the Metabolic Syndrome Program
 at St. Paul's Hospital, Vancouver. Individuals will be randomized to either a
 low-carbohydrate diet or a calorie restricted, low fat diet and followed for 6 months. The
 investigators will measure body composition with bioelectrical impedance at baseline, 3 and 6
 months. The investigators will also examine cardiometabolic changes due to the standard
 lifestyle intervention compared to the carbohydrate restricted treatment. The investigators
 will examine blood pressure, triglycerides, LDL-chol, HDL-chol, C-reactive protein,
 apolipoprotein B, glucose, insulin, hemoglobin A1c and leptin at baseline, 3 and 6 months.
 The investigators will use accelerometers to assess changes in physical activity. The
 investigators will use three-way repeated-measures ANOVA, with changes in body weight and
 insulin levels as covariates in the model with time as the repeated factor for statistical
 analyses.
1. BACKGROUND AND RATIONALE:

 Current obesity prevention emphasizes increasing physical activity and a low-fat,
 calorie restricted diet to produce a negative caloric balance. Caloric restriction is
 associated with decreases in energy expenditure. The other mainstay of obesity
 prevention increasing levels of physical activity is associated with greater caloric
 intake. Failure of the eat less-exercise more strategy is evident with epidemic of
 obesity, metabolic syndrome (MetS) and type II diabetes. Moreover, the displacement of
 dietary fat in the diet has led to compensatory increases in carbohydrate intake that is
 associated with untoward metabolic effects.

 Carbohydrate restricted diets are controversial despite benefits of this approach. The
 controversy stems from a compensatory increase in dietary fat intake associated with
 carbohydrate restriction and fears that greater fat intake increases risk of
 cardiovascular disease. Carbohydrate restriction decreases insulin resistance and
 ameliorates MetS. This protocol aims to establish a greater evidence base for
 carbohydrate restricted diets as a therapeutic option for MetS. The investigators will
 review current knowledge with respect to: (i) obesity and insulin resistance in Canada,
 (ii) positions of major medical organizations (iii) shortcomings of the current obesity
 prevention paradigm (iv) why carbohydrate restricted diets work.

 1.1) Obesity and insulin resistance in Canada In the 1980s low fat, caloric restricted
 diets became the cornerstone of dietary advice to reduce obesity. This approach
 successfully reduced the percent of calories from fat with a consequential increase in
 carbohydrate consumption. In the ensuing years, obesity become epidemic. In Canada, the
 prevalence of obesity (BMI ≥ 30 kg/m2) increased from 10% in 1970s to 23% in 2004 with
 an additional 36% considered overweight (BMI 25-29.9). As obesity is a risk factor for
 MetS and type II diabetes, the prevalence of these disorders has also reached epidemic
 proportions. Approximately 2 million Canadians were living with diabetes in 2007 and by
 2012 it is estimated that 2.8 million Canadians will be living with diabetes. First
 Nations communities have been especially hard hit, with a prevalence 3-4 times higher
 and a younger age of onset than non-First Nations individuals. Novel chronic disease
 prevention strategies are needed to address this crisis.

 Insulin resistance underpins the pathophysiology of obesity, Insulin resistance is a
 condition in which normal amounts of insulin are inadequate to produce a normal insulin
 response from fat, muscle and liver cells. As a result, insulin resistant individuals
 have both elevated blood glucose, fasting insulin and secrete greater amounts of insulin
 in response to dietary carbohydrate. This compensatory hyperinsulinemia is associated
 with adverse effects in tissues which retain their sensitivity to insulin. Elevated
 blood glucose levels are associated with advanced glycation end products, reactive
 oxygen species and low grade inflammation. These exposures are associated with increased
 risk of cardiovascular disease & diabetes. Despite the evidence associating elevated
 insulin levels to atherogenic changes in the vasculature, it remains a matter of
 controversy as to whether persistently elevated insulin levels are pathogenic.

 The diagnosis of MetS represents an entry-point for disease prevention efforts in
 individuals with diabetes and cardiovascular disease. MetS is defined as a high waist
 circumference in addition to two of the following: high triglycerides, low HDL and
 elevated blood pressure. Other pathophysiologic changes are also observed including low
 grade inflammation, increased uric acid, prothrombotic state, elevated ApoB, small dense
 atherogenic LDL and endothelial dysfunction.

 First line treatment for MetS is weight loss leading to reductions in insulin
 resistance. Intensive lifestyle interventions reduce diabetes in high risk subjects.
 Most lifestyle interventions for MetS are predicated on the hypothesis that individuals
 can initiate and maintain weight loss by restricting calories and increasing physical
 activity. The Diabetes Prevention Program showed that intensive intervention including a
 low-fat calorie reduced diet and increase in physical activity was associated 1.5 kg/m2
 decrease in BMI and a 58% reduction in incidence of diabetes in individuals at high risk
 of diabetes. Less intensive interventions are associated with more modest changes. A
 study of nutritional counselling was associated with a 0.4 kg/m2 decrease in BMI. Thus,
 lifestyle interventions which emphasize 'eating less or exercising more have limited
 value. The optimal diet for subjects with MetS has not been examined with hard
 end-points. Small trials have compared carbohydrate restricted diets and low fat diets
 using surrogate markers. A trial of severely obese subjects found greater weight loss
 and greater improvements in lipid levels and hemoglobin A1c on carbohydrate restricted
 diet than low fat/calorie restricted diets. In a study of adults with MetS, those
 randomized to the carbohydrate restriction had greater weight loss, lower triglycerides
 and lower insulin levels than individuals on a calorie restricted, low fat diet. These
 results are consistent with a meta-analysis where carbohydrate restricted diets were
 associated with improvements in atherogenic dyslipidemia, greater weight loss and better
 compliance than low fat, calorie restricted diets. These studies highlight the
 advantages of carbohydrate restriction.

 1.2) Fat, sugar and positions of major medical organizations One of the principal
 barriers to the widespread implementation of carbohydrate restricted diets is the fear
 that increase in saturated fat consumption with its association with increase in
 LDL-chol, will result in greater risk of cardiovascular disease (CVD). This diet-heart
 hypothesis has formed the cornerstone of dietary advice for prevention of chronic
 disease. The avoidance of saturated fat has led to general avoidance of dietary fat.
 There is weak and contradictory evidence that both saturated fat and dietary fat
 restriction are associated with health benefits. The largest test of the diet-heart
 hypothesis was the Women's Health Initiative (WHI). This study randomized women to
 either a low saturated fat diet or a regular diet. After 8 years, women randomized to
 the low fat diet had lower LDL-chol but no decrease in CVD mortality, incidence of
 breast or colorectal cancer. Consistent with the results of the WHI, a meta-analysis
 which included 347,747 subjects found no relationship between saturated fat intake and
 CVD.

 While most experts would agree that it's too early to vindicate saturated fat as the
 foremost dietary evil, evidence is accumulating highlighting the obesigenic and
 atherogenic nature of refined carbohydrates. A trial aiming to decrease sweetened
 beverage consumption found the intervention group had 7.7% less overweight and obese
 children than controls. In NHANES (2006), consumption of added sugar was associated with
 higher triglycerides and lower HDL. A prospective study of Dutch adults found that
 replacing 5% of calories from saturated fat with high glycemic carbohydrates was
 associated with a 33% increase in risk of myocardial infarction.

 The current state of scientific confusion over the health effects of (refined)
 carbohydrates is reflected in the diversity of dietary recommendations. American
 Diabetes Association (ADA) dietary guidelines have suggested that carbohydrate
 restricted diets are an option for weight loss for up to 1 year. In contrast, Canadian
 Diabetes Association recommends a diet with 45%-60% of calories from carbohydrate with a
 sucrose intake up to 10% of daily intake. The contradictory nature of these positions
 highlights the need for more research into the health effects of carbohydrate restricted
 diets. The endorsement of carbohydrate restriction by ADA suggests that these diets are
 valid therapeutic options.

 1.3) Shortcomings of the traditional obesity prevention paradigm The current obesity
 prevention paradigm emphasizes caloric reduction and/or increased physical activity to
 produce negative caloric balance. While physical activity has established benefits,
 increasing physical activity as a weight loss strategy has met with disappointing
 results. Observational studies associating high levels of physical activity with lower
 adiposity are difficult to interpret as individuals with higher physical activity also
 benefit from other (unmeasured) health promoting behaviours. In randomized trials,
 physical activity interventions have shown equivocal results with respect to weight
 loss. The physiologic limitation of this approach is that it is difficult to augment
 physical activity without a compensatory increase in dietary intake. In studies where
 physical activity is directly supervised and in the absence of a compensatory increase
 in caloric intake, physical activity has been associated with weight loss < 3% of
 initial body weight. In physical activity interventions of lower intensity, results are
 less promising. A meta-analysis of school based physical activity interventions in youth
 found no effect on BMI. The ineffectiveness of physical activity as a means of weight
 loss is reflected in the American Heart Association and American College of Sports of
 Sports Medicine position statements where they recommend 60-90 minutes of moderate
 intensity activity/day to lose or maintain weight loss. Not surprisingly, there is a
 very low prevalence of individuals who are moderately active for 60-90 minutes/day in
 the general population. Ironically, insulin resistant individuals who would reap the
 greatest health benefits from physical activity may have a reduced physiologic tolerance
 for it as insulin resistance has been associated with reduced exercise tolerance through
 reversible changes in muscle mitochondria, reduced VO2 max and possibly other
 mechanisms.

 The failure of low fat, calorie restricted diets to curb the prevalence of obesity is
 exemplified by the WHI. After 7.5 years of follow-up, the women randomized to the low
 fat group decreased their weight by 0.8 kg but had a 1 cm increase in waist
 circumference despite a reported decrease in caloric intake of 360 calories. Weight loss
 in the low fat group was not different than women in the control group, who were
 consuming a typical American diet. Calorie restricted diets emphasize the avoidance of
 energy dense foods high in dietary fat. While avoidance of dietary fat has intuitive
 appeal, calorie restriction is associated with a corresponding decrease in energy
 expenditure, in effect, stimulating a starvation response. The compensatory decrease in
 energy expenditure is associated with a plateauing of weight loss, an increased desire
 to eat and weight gain.

 Low fat/high carbohydrate diets require weight loss to produce positive metabolic
 effects. This dependence on weight loss for health benefits combined with the inevitable
 rebound weight gain associated with this dietary strategy has the potential to worsen
 metabolic markers over the long term. The untoward metabolic changes associated with a
 high carbohydrate intake are particularly deleterious in individuals with MetS. This
 contrasts with the physiologic effects of carbohydrate withdrawal in insulin resistant
 subjects that mirrors reversal of MetS. In addition to improvements of MetS,
 carbohydrate restricted diets are associated with less dense and therefore less
 atherogenic LDL particles and decreases in inflammatory markers.

 A final limitation of the current obesity prevention paradigm is that macronutrients
 (fat, protein and carbohydrates) are assumed to have equivalent metabolic effects. The
 investigators will review metabolic effects of macronutrients relating to the insulin
 response and energy balance. Carbohydrates are potent secretagogues of insulin that is
 the primary regulator of adipose tissue metabolism and partitions dietary energy into
 either storage (higher insulin) or oxidation (lower insulin). Mice genetically
 engineered to lack the insulin receptor on fat cells consume more calories per gram of
 body weight but are resistant to obesity. In type II diabetics, administrations of
 exogenous insulin or drugs which stimulate insulin release from the pancreas are
 associated with weight gain. Dietary fat has no effect on insulin secretion but delays
 gastric emptying. Dietary protein lowers the glucose response to insulin 2-3 times more
 effectively than dietary fat and plays an important role in appetite suppression and
 potentially weight regulation. The addition of dietary fat, protein and fiber to dampen
 the untoward effects of dietary carbohydrate in a meal is the concept behind the
 glycemic index. Low glycemic index diet may be of less relevance to type II diabetics,
 however, as the effect of dietary fat and protein in blunting glucose responses is
 attenuated or absent. If obesity prevention is indeed evidence base then there are only
 two tools left in the public health arsenal, bariatric surgery or carbohydrate
 restriction.

 1.4) Why do carbohydrate restricted diets work? There are at least two physiologic
 characteristics of carbohydrate restricted diets which contribute to weight loss. First,
 ad lib carbohydrate restricted diets have been associated with spontaneous reductions in
 caloric intake. Second, these diets are associated with greater weight loss per calorie
 than low-fat diets with an unexplained caloric deficit of about 200 kcal/day. The
 preferential weight loss of carbohydrate restricted diets was termed 'the metabolic
 advantage'. The concept of a metabolic advantage associated with carbohydrate restricted
 diets has been controversial among experts. While there is evidence supporting its
 existence in animal models and in humans, this phenomena remains poorly understood.

 Ad lib carbohydrate restricted diets are often associated with spontaneous decreases in
 caloric intake. This is caused by the insulin lowering effects of carbohydrate
 restricted diets as high insulin levels have been associated with partitioning of
 metabolic fuels into adipose tissue and greater food intake. A trial of obese subjects
 found that those consuming a carbohydrate restricted diet had nearly a 30% decrease in
 fasting insulin levels and a 570 kcal decrease in energy intake. Thus lower insulin
 levels are a key mediator between lower carbohydrate consumption and weight loss. A
 study in men found that 70% of the variability in weight loss from a carbohydrate
 restricted diet was explained by changes in fasting insulin.

 A number of trials have shown a metabolic advantage of carbohydrate restricted diets
 compared to low fat diets. There are three possible explanations. First, there might be
 greater energetic costs associated with metabolic interconversions of nutrients on
 carbohydrate restricted diets. Second, individuals on a lower carbohydrate diet may have
 higher energy expenditure due to a greater resting metabolic rate and/or greater levels
 of physical activity. A final possibility is that lower weight loss is due to the
 selective under-reporting of dietary intake in individuals randomized to low fat diets.
 This latter explanation is not likely as this finding has been observed in numerous
 randomized controlled trials.

 Diet induced thermogenesis may have a small contribution to the metabolic advantage of
 carbohydrate restricted diets. It accounts for 5-15% of total energy expenditure. The
 energetic costs to metabolize macronutrients vary from 2.5% with dietary fat, 7-15% with
 carbohydrate and 28-35% with protein. One study found that energy expenditure was 4%
 higher in a diet containing 30% compared to 10% of calories from protein. Thus the
 modest increase in energy expenditure due to a higher protein intake would not likely be
 enough to account for the metabolic advantage of carbohydrate restricted diets.

 Physical activity is the greatest modifiable source of energy expenditure. The
 hypothesis that the metabolic advantage of carbohydrate restricted diets could explain
 lower insulin levels associated with spontaneous increases in physical activity has
 received scant attention. This hypothesis is based on a number of well established
 observations. First, type II diabetics taking exogenous insulin have decreases in energy
 expenditure and weight gain. When insulin levels are lowered through carbohydrate
 restriction or pharmacotherapy there is an attendant loss of fat mass and some evidence
 for a modest increase in energy expenditure. A short study of obese individuals found
 that a ketogenic, low carbohydrate diet with a 30% decrease in insulin resistance was
 associated with a 20% increase in resting energy-expenditure, though physical activity
 was not assessed in this study. Similarly, in a 6 month randomized trial of obese women,
 those on the carbohydrate restricted diet had a non-significant 5% increase in resting
 energy expenditure per kg of body weight compared to baseline. This study also assessed
 physical activity using pedometers and found no difference in steps/day between the
 carbohydrate restricted group and the low-fat group despite a 3.7kg greater weight loss
 in the former and no difference in reported caloric intake between groups. Measurement
 of physical activity in free-living individuals is complex. Pedometers are an objective
 assessment of physical activity but are unable to assess intensity, frequency and
 duration of activity. They are also unsuitable for estimation of energy expenditure.

 In summary, intensive lifestyle interventions reduce the incidence of type II diabetes
 in individuals with metabolic syndrome. Central to the therapeutic effect of these
 interventions is weight loss. There is a lack of consensus over what constitutes 'best
 practices' for lifestyle interventions. Physical activity is associated with numerous
 health benefits but is not an efficacious prescription for weight loss or weight
 maintenance. Moreover, the optimal dietary prescription is controversial; some experts
 suggest individuals with MetS should restrict their dietary fat intake while other
 experts suggest dietary carbohydrate should be restricted. This controversy in dietary
 prescription is reflected in the positions of major medical organizations. The American
 Diabetes Association has endorsed carbohydrate restriction for weight loss since 2008.
 The Canadian Diabetes Association, however, favours lower glycemic index foods and the
 restriction of dietary fat. Despite the equivocal evidence, a low fat, calorie
 restricted diet coupled with increased physical activity are considered the standard
 lifestyle interventions for MetS.

 2. OBJECTIVES This protocol has three aims. First, the investigators hypothesize that
 adherence to a lower carbohydrate diet in individuals with MetS, resulting in lower
 insulin resistance; will cause an increase in levels of spontaneous physical activity,
 independent of changes in weight. Second, the investigators will examine changes in
 cardiometabolic risk factors (ApoB, TG, HDL, blood pressure, CRP) when individuals are
 randomized to either a carbohydrate restricted diet or a low fat/high carbohydrate diet.
 Finally, the investigators will interview a sub-sample of participants from both study
 arms (5 in each arm) to conduct open-ended interviews to better understand quality of
 life issues with respect to the dietary assignment or lifestyle intervention.

 3. RESEARCH PLAN Our group has generated cross-sectional data showing a clinically
 meaningful association between higher carbohydrate intake and lower physical activity,
 assessed by accelerometer in glucose intolerant individuals. The limitation of these
 findings relate to the inability to assess causality; that is, if carbohydrate
 restriction causes increases in physical activity. The strength of the ACTout study is
 its ability to delineate causal direction using a prospective design and randomization
 to control for known and unknown confounders.

 Study design and participants: Study participants will be randomized to an ad lib
 carbohydrate restricted group or a low fat, calorie reduced diet for 6 months. The
 investigators will recruit individuals with metabolic syndrome (MetS) from St. Paul's
 Metabolic Syndrome Program. Inclusion criteria include a diagnosis of MetS defined as an
 increased waist circumference and two or more of the following: fasting blood sugar greater
 than 5.6 mmol/L, fasting triglycerides greater than 1.7 mmol/L, high density lipoprotein
 (HDL) less than 1.0 mmol/L in men and less than 1.3 mmol/L in women and blood pressure
 greater than 135/85 or on antihypertensive medication. Potential participants will be
 excluded if they are following a weight reducing diet, are abusing alcohol or other
 psychoactive substances, are on psychiatric medication associated with weight gain or have
 plans to travel during the study period.

 Sample size calculation: To calculate sample size the investigators used cross-sectional data
 with accelerometer measured physical activity and excellent quantitative measures of diet.
 The investigators assumed a 15% difference in calories consumed as carbohydrates between the
 dietary treatments. With a significance value of p < 0.05 (two sided test) the investigators
 found that 27 participants would be required in each group to detect a significant difference
 in accelerometer measured intensity of activity. To account for possible attrition the
 investigators will overestimate the sample size by 10 in each arm. The investigators will
 recruit 72 individuals with 36 in each arm. Based on our sample size calculation, the
 investigators expect to detect time and diet based differences in addition to a diet*time
 interaction.

 Recruitment strategy: The investigators will recruit individuals with metabolic syndrome from
 the Metabolic Syndrome Program. Flyers will be posted in the waiting room and the examination
 rooms of the Program. Flyers will also be given to the administrative assistants responsible
 for intake of participants into the Program who may choose to notify participants of the
 study. If a potential participant expresses interest the coordinator will explain the study
 in sufficient detail to enable informed consent. To assess diet prior to inclusion into the
 study the investigators will ask potential participants to complete a 3 day diet history and
 wear the accelerometer for 7 days to ensure that they are not already following a weight
 reducing diet and to assess baseline physical activity. Individuals compliant with both the
 dietary recall and baseline assessment of physical activity will be randomized into one of
 the two dietary assignments.

 Randomization: The investigators will use block randomization to prevent the biasing of the
 randomization process. After each block of subjects is enrolled, the investigators will use a
 computerized randomization program to randomly assign participants to one of the two dietary
 assignments. Due to the difficulty in concealing the dietary assignment, the randomized trial
 will not be blinded; as both researchers and participants will be aware of their dietary
 assignment. To minimize the contamination of study groups, individual and group sessions will
 be scheduled at different times.

 Carbohydrate restricted diet: Participants will be instructed to restrict carbohydrate
 consumption to < 20 grams/day while not restricting their caloric intake. Participants will
 be encouraged to consume vegetables with low carbohydrate content every day including 2 cups
 of salad greens and 1 cup of vegetables 'that grow above the ground'. One of the physiologic
 changes associated with a low carbohydrate intake is a loss of salt through the urine. If
 salt is not replaced participants may experience headaches, nausea, dizziness, lethargy and
 constipation. Participants will be counselled to increase their salt intake. This has been
 shown to correct the natiuresis associated with carbohydrate restriction which can cause the
 aforementioned side effects. Participants will be advised to continue their baseline level of
 physical activity.

 Control group: The control group will be randomized to the intensive lifestyle intervention
 currently used by the Healthy Heart Program at St. Paul's Hospital to reduce symptoms
 associated with metabolic syndrome. Participants will be instructed to replace high fat,
 energy dense foods with foods rich in whole grains, fruits and vegetables. The macronutrient
 distribution of this diet will be approximately 55% carbohydrate, 15% protein and 30% fat.
 Individuals will also be instructed to reduce sodium intake to <2300 mg/day and in
 individuals with hypertension, <1500 mg/day. At the end of the study, participants will have
 the option to continue on either of the study diets.

 Methods to ensure compliance to the dietary assignment: The study coordinator will facilitate
 activities to support compliance to the dietary assignment, either one-on-one or in a group
 setting. Group meetings will reinforce compliance by sharing cooking tips, behaviour
 modification and relapse prevention strategies. In the one-on-one sessions, the study
 coordinator will review 3 day food records and discuss strategies to increase compliance.
 Participants from both groups will meet with their clinician after 3 months to assess health
 indicators and to assure participants of the safety of their dietary assignment.

 Qualitative interviews: The investigators will conduct hour long open-ended interviews with
 8-10 participants from the study to understand the lived experience of a prudent diet and a
 carbohydrate restricted diet. Interviews will be recorded and transcribed. The investigators
 will use grounded theory to look for theories which emerge from the data as opposed to having
 interpreting the data with an a priori analysis. The investigators will then assign
 descriptive categories to themes which emerge from the data, such themes could include:
 effect of their diet on diabetes, perceptions of hunger, mood etc. These descriptive
 categories will then be placed into thematic categories and analyzed in light of the existing
 of the literature.

 Measurement of body composition and estimation of resting energy expenditure:

 The investigators will use bioelectrical impedance to assess body composition at baseline and
 at 6 months. Bioelectrical impedance has been shown to provide a reasonable assessment of
 body composition compared to DXA, which is considered a gold standard. The investigators will
 normalize fat mass and fat-free mass to height by using a fat-mass index and a fat-free mass
 index (kg/m2), respectively. Height will be measured with a stadiometer at baseline. Waist
 circumference will be assessed at baseline and at 6 months, after exhalation, using a
 flexible tape measure half way between the hip bone and the lowest rib. The investigators
 will estimate energy expenditure using previously published equations which take into account
 fat-free mass, fat mass, gender and age.

 Questionnaire: The investigators will use the Applied Health Indicators Questionnaire and the
 Patient Health Questionnaire, to collect relevant health information from the patient. These
 self-administered questionnaires will be completed at baseline, 3 and 6 months.

 Physical activity assessment: Participants will wear an accelerometer to assess physical
 activity at baseline and week of every month for 6 months. An accelerometer is a small
 electronic monitor worn on the waist that measures vertical accelerations and is thus
 considered an objective measure of physical activity. Patients will be instructed to wear the
 accelerometer during waking hours for 1 week of every month, exclusive of time spent bathing
 or when in water. Data will be downloaded in one-minute epochs and categorized as light,
 moderate or vigorous activity. Days will be excluded when the accelerometer is worn for less
 than 80% of the average time worn on the other days. The investigators will estimate
 activity-based energy expenditure using previously validated equations. As accelerometers do
 not capture activity associated with cycling, swimming or skiing the investigators will ask
 participants about the number of times they did these activities in the period that they wore
 the accelerometer.

 Cardiometabolic indices: Blood samples will be drawn and placed in individually labelled
 tubes with EDTA, centrifuged immediately and stored at -70°C. As changes in insulin action
 are central to our hypothesis the investigators will assess two distinct aspects of insulin
 metabolism in this study, insulin secretion and insulin resistance. The investigators will
 assess insulin resistance using HOMA assessment of insulin resistance calculated from fasting
 insulin and fasting glucose. The investigators will assess the concentration of C-peptide, a
 cleavage product related to insulin synthesis that is synthesized in equimolar concentrations
 to insulin. As C-peptide has a longer half-life than insulin, it can be used a marker of
 insulin secretion from the pancreas. Blood Pressure will be assessed at baseline, 3 and 6
 months using BP-TRU monitors. Lipid, lipoprotein and C-reactive protein levels will be
 measured at baseline, 3 and 6 months. Total cholesterol, triglyceride, high-density
 lipoprotein cholesterol and apolipoprotein B will be measured using previously described
 methods. LDL-chol levels will be calculated using the Friedewald formula for patients whose
 plasma triglyceride level is less than 4 mmol/L. β-hydroxybutyrate will also be assessed in
 both groups at the aforementioned time points and will be used as a biomarker of adherence to
 a carbohydrate restricted diet. The investigators will also assess serum Leptin and uric acid
 at baseline and 6 months.

 Statistical analyses: The investigators will use two different approaches to analyze the
 data. First the investigators will use an intention to treat analysis using baseline values
 to impute missing data in participants who may drop-out of the study. The investigators will
 also examine the effect of the dietary assignment on outcomes in participants who were
 compliant with their dietary assignment. Baseline characteristics will be compared between
 the two groups using t tests. The investigators will examine three inter-related dependent
 variables, capturing different aspects of physical activity, in the analysis strategy. First,
 the investigators will examine the association between dietary assignment and changes in
 accelerometer variables. The investigators will also examine time spent in
 moderate-to-vigorous physical activity and activity based energy expenditure. As activity
 based energy will be estimated from accelerometer , the investigators will not consider it a
 unique comparison. The investigators will thus set the level of statistical significance at
 p<0.025 to adjust for multiple comparisons. The investigators will obtain differences in key
 variables such as physical activity and change in insulin concentration. To assess the
 effects of the dietary assignment on physical activity, the investigators will use three-way
 repeated-measures ANOVA, including change in body weight in the model with time as the
 repeated factor.
Inclusion Criteria:

 -  presence of metabolic syndrome by International Diabetes Foundation criteria

 -  referral to metabolic syndrome program at St. Paul's Hospital

 -  age > 19 years

 Exclusion Criteria:

 -  unwillingness to participate in research study

 -  unwillingness to comply with dietary intervention

 -  following a weight reducing diet

 -  abusing alcohol or other psychoactive substances

 -  on psychiatric medication associated with weight gain

 -  plans to travel during the study period

 -  food allergies or intolerances that will interfere with their adherence to either of
 the study diets