Application of nutrient essentiality criteria to dietary carbohydrates.

The purpose of the present review is to describe how human physiology at very low carbohydrate intakes relates to the criteria for nutritional essentiality. Although we did not limit ourselves to one particular type or function of carbohydrates, we did primarily focus on glucose utilisation as that function was used to determine the recommended daily allowance. In the general population, the human body is able to endogenously synthesise carbohydrates, and does not show signs of deficiency in the absence of dietary carbohydrates. However, in certain genetic defects, such as glycogen storage disease type I, absence of dietary carbohydrates causes abnormalities that are resolved with dietary supplementation of carbohydrates. Therefore, dietary carbohydrates may be defined as conditionally essential nutrients because they are nutrients that are not required in the diet for the general population but are required for specific subpopulations. Ketosis may be considered a physiological normal state due to its occurrence in infants in addition to at very low carbohydrate intakes. Although sources of dietary carbohydrates can provide beneficial micronutrients, no signs of micronutrient deficiencies have been reported in clinical trials of low-carbohydrate ketogenic diets. Nonetheless, more research is needed on how micronutrient requirements can change depending on the dietary and metabolic context. More research is also needed on the role of dietary fibre during a low-carbohydrate ketogenic diet as the beneficial effects of dietary fibre were determined on a standard diet and several studies have shown beneficial effects of decreasing non-digestible carbohydrates.

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy.

A review of decision aids to assess cardiovascular risk.

PURPOSE OF REVIEW: Cardiovascular disease remains one of the leading causes of morbidity and mortality today. The major risk factors for cardiovascular disease include type 2 diabetes mellitus, hypertension, tobacco smoking, elevated body mass index, and hyperlipidemia. The decision to use medication treatment for hyperlipidemia can be assisted using computerized decision tools. RECENT FINDINGS: The treatment of hyperlipidemia with 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has become widely recommended even though most people treated with them do not get clinical benefit, and the magnitude of their effect is dependent upon prior clinical risk. This article reviews recent research about the effectiveness of HMG-CoA reductase inhibitors, and the use of decision-making tools to assist the clinician in advising patients about the use of these medications. SUMMARY: On-line decision tools are available to estimate cardiovascular risk and to assist clinicians in helping their patients make their own decision about whether to take HMG-CoA reductase inhibitor medication to reduce cardiovascular risk.

The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients.

Background and Hypothesis: The robust evidence base supporting the therapeutic benefit of ketogenic diets in epilepsy and other neurological conditions suggests this same metabolic approach may also benefit psychiatric conditions. Study Design: In this retrospective analysis of clinical care, 31 adults with severe, persistent mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) whose symptoms were poorly controlled despite intensive psychiatric management were admitted to a psychiatric hospital and placed on a ketogenic diet restricted to a maximum of 20 grams of carbohydrate per day as an adjunct to conventional inpatient care. The duration of the intervention ranged from 6 to 248 days. Study Results: Three patients were unable to adhere to the diet for >14 days and were excluded from the final analysis. Among included participants, means and standard deviations (SDs) improved for the Hamilton Depression Rating Scale scores from 25.4 (6.3) to 7.7 (4.2), P < 0.001 and the Montgomery-Åsberg Depression Rating Scale from 29.6 (7.8) to 10.1 (6.5), P < 0.001. Among the 10 patients with schizoaffective illness, mean (SD) of the Positive and Negative Syndrome Scale (PANSS) scores improved from 91.4 (15.3) to 49.3 (6.9), P < 0.001. Significant improvements were also observed in metabolic health measures including weight, blood pressure, blood glucose, and triglycerides. Conclusions: The administration of a ketogenic diet in this semi-controlled setting to patients with treatment-refractory mental illness was feasible, well-tolerated, and associated with significant and substantial improvements in depression and psychosis symptoms and multiple markers of metabolic health.

Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

Type 2 Diabetes Mellitus: A Pathophysiologic Perspective.

Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5-10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.

A case study of overfeeding 3 different diets.

PURPOSE OF REVIEW: Quality or quantity of food has been at the heart of the diet debate for decades and will seemingly continue for many to come unless tightly controlled studies are conducted. To our knowledge, there has never been an overfeeding study comparing the effects of multiple diets. RECENT FINDINGS: This study reports a case study of an individual who ate 5800 Calories per day of 3 different diets for 21 days at a time. The 3 different diets were low-carb, low-fat, and very-low-fat vegan. The weight gain over 21 days was 1.3 kg for low-carb, 7.1 kg for low-fat, and 4.7 kg for very-low-fat vegan. SUMMARY: In this n-of-1 study, consuming 5800 Calories/day of 3 different diets for 21 days did not lead to the same amount of weight gain. Further research should be conducted on how the human body gains weight with an emphasis on how different foods affect physiology. If these findings are replicated, there would be many ramifications for obesity treatment and healthcare guidelines.

Carbohydrate-restricted diets and Type 1 diabetes mellitus: research considerations.

PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is managed via careful control of blood glucose, exogenous insulin, diet, exercise, and other physiologic factors. Interestingly, the dietary recommendations for T1DM have had very little systematic research. Many clinical observations, as well as emerging research studies, have noted that a carbohydrate-restricted diet can lead to normalization of blood glucoses with reduction in hypoglycemic reactions among motivated individuals. RECENT FINDINGS: In this paper, we review observations of carbohydrate restriction and propose a series of studies to test two levels of dietary carbohydrate intake for the management of individuals affected by T1DM. We recommend that the studies start in otherwise healthy adults with hemoglobin A1c > 8%, and then progress to more complicated populations including children, those with secondary complications and/or good glycemic control. Larger, long-term studies would then address growth in children, and diabetic complications including cardiovascular outcomes. SUMMARY: Due to the clinical observations of improvements using carbohydrate-restricted nutrition for T1DM, we recommend that these types of studies addressing the level of dietary carbohydrate be urgently conducted.

The carbohydrate-insulin model: a physiological perspective on the obesity pandemic.

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body-resulting from the hormonal responses to a high-glycemic-load diet-drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.

Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss.

OBJECTIVES: This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC) or reduced fat (RF) weight maintenance diet for 9 months following significant weight loss. METHODS: Thirty-five (21 RC; 14 RF) overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of approximately 2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (approximately 20%) or fat (approximately 30%) intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. RESULTS: Body weight change was not significantly different within or between groups during weight maintenance (p>0.05). The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p<0.05). Group*time interactions were significant for large and medium VLDL (p>0.05). CONCLUSION: Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

Using a low-carbohydrate diet to treat obesity and type 2 diabetes mellitus.

PURPOSE OF REVIEW: This study will provide a narrative review of the history of the clinical use of low-carbohydrate diets and give a practical example of how to implement a low-carbohydrate diet, with an emphasis on deprescribing medications. RECENT FINDINGS: Low-carbohydrate diets have been used since the late 19th century to treat obesity and type 2 diabetes mellitus (T2DM). Recently, clinical research has validated the use of low-carbohydrate diets for individuals affected by obesity and T2DM, and these diets are included in several national clinical guidelines. Because medications are commonly used to treat hypertension and T2DM, special consideration must be made to monitor and reduce these medications to avoid overmedication. Clinic visits and home monitoring of blood pressure and glucose levels are important tools to alert clinicians that a reduction in medication levels may be indicated. SUMMARY: Low-carbohydrate diets have been utilized clinically for many years to treat obesity and T2DM and can be used alongside effective monitoring to safely deprescribe dispensable medications for these diseases.

Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series.

BACKGROUND: Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known. CASE PRESENTATIONS: We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6-7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale-Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10-24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9-17 months after initiation and continued adherence to diet. CONCLUSIONS: Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies.

A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome.

BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D. METHODS: Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured. RESULTS: Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 +/- 0.8/d to 1.4 +/- 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 +/- 0.7 to 3.8 +/- 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss. CONCLUSIONS: A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.

Carbohydrate-restricted diets for obesity and related diseases: an update.

Basic, clinical, and epidemiologic research on carbohydrate-restricted dietary patterns continues to grow, evaluating the impact of this way of eating on weight loss, obesity-associated comorbidities, and development of any adverse effects. Randomized, controlled, dietary weight loss trials conducted in adults in the past 2 years reinforce previous findings that carbohydrate-restricted diets (CRDs) promote weight loss while increasing serum high-density lipoprotein cholesterol, lowering serum triglycerides, and improving glucose homeostasis. Studies showing that reduction of dietary carbohydrate leads to reduced postprandial serum glucose and insulin levels have spurred further research on CRDs in patients with type 2 diabetes. Emerging interest into the effect of diet on endothelial function has spawned studies that are harnessing new technologies, such as flow-mediated vascular dilation, to gain insight into the impact of diet on long-term cardiovascular disease outcomes. Studies on the effect of a CRD on appetite, health-related quality of life, bone density and turnover, acid-base metabolism, and potassium equilibrium help clinicians better weigh the perceived risks of the diet with the recognized benefits. This review synthesizes important clinical and physiologic studies on CRDs published between January 2007 and May 2009.

Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment.

INTRODUCTION: Previous studies have reported that smoking abstinence rates are increased when nicotine skin patch treatment is initiated prior to the target quit smoking date, as compared with conventional treatment beginning on the quit date. We hypothesized that smoking in the presence of continuous levels of nicotine would attenuate the reinforcing effects of cigarette smoking and lead to a decline in dependence on inhaled nicotine, thus facilitating cessation. METHODS: This study involved four groups of smokers (n = 100 per group) who received either nicotine patch (21 mg/24 hr) or placebo patch treatment for 2 weeks before the quit smoking date, and during this period, smoked their usual brands of cigarettes or switched to low-tar and nicotine cigarettes: a 2 (nicotine patch) x 2 (cigarette type) factorial design. From the quit date on, all groups received standard nicotine patch treatment, consisting of 6 weeks of 21 mg/24 hr, 2 weeks of 14 mg/24 hr, and 2 weeks of 7 mg/24 hr. Abstinence was defined as self-report of no smoking from the quit date on, confirmed by expired-air carbon monoxide. RESULTS: Continuous abstinence rates were approximately doubled by precessation nicotine patch treatment. The treatment mainly benefited smokers with lower levels of dependence, based on Fagerström Test for Nicotine Dependence score. All treatments were well tolerated. DISCUSSION: In view of these findings and similar results from previous studies, current labeling of the nicotine patch, which recommends using nicotine replacement therapy only after the quit date, should be reexamined.

Clinical Experience of a Diet Designed to Reduce Aging.

OBJECTIVE: Aging is associated with elevated levels of glucose, insulin, and triglycerides. Our objective was to assess the effect of a nutritional program designed to reduce these correlates of aging. DESIGN: This is a retrospective chart review of patients attending an outpatient metabolic management program including a high-fat, adequate-protein, low-carbohydrate diet, nutritional supplementation and periodic individual visits. Outcomes measured at baseline and follow-up included body weight, fasting serum glucose, insulin, leptin, lipids, and thyroid hormone. RESULTS: Thirty-one patients were identified with complete information. The mean age of patients was 57.6 ± 2.4 consisting of 53% female and 47% male patients. The average duration between follow up visits was 91.5 ± 8.5 days. Of the parameters measured at the follow-up visit, body weight, serum leptin, insulin, fasting glucose, triglyceride, and free T(3) significantly decreased by 8.1 ± 0.8%, 48.2 ± 3.8%, 40.1 ± 4.7%, 7.6 ± 2.1%, 28.3 ± 5.7%, and 10.8 ± 1.8%, respectively. Furthermore, the triglyceride/high density lipoprotein ratio decreased from 5.1 ± 1.7 to 2.6 ± 0.5. CONCLUSIONS: In the context of an outpatient medical clinic, a high-fat, adequate-protein, low-carbohydrate diet with nutritional supplementation led to improvements in serum factors related to the aging process. Further research regarding this dietary approach and its relationship to aging is in order.

Clinical experience using appetite suppressants and SSRIs.

The use of sympathomimetic appetite suppressants and serotonin-selective reuptake inhibitors (SSRIs) has been questioned due to anecdotal reports of serotonin syndrome. This survey of bariatric physicians using these medications in clinical practice did not find any cases of serotonin syndrome among 1174 patients. The monitored use of the combination of these medicines by trained practitioners is justifiable.

Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the modern world. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity, and T2DM. AREAS COVERED: Reducing carbohydrate intake to a certain level, typically below 50 g per day, leads to increased ketogenesis in order to provide fuel for the body. Such low-carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the 19th and early 20th centuries. Recent clinical research has reinvigorated the use of the ketogenic diet for individuals with obesity and diabetes. Although characterized by chronic hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin resistance, typically as a result of increased energy intake leading to obesity. The ketogenic diet substantially reduces the glycemic response that results from dietary carbohydrate as well as improves the underlying insulin resistance. This review combines a literature search of the published science and practical guidance based on clinical experience. EXPERT COMMENTARY: While the current treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the ketogenic diet is an effective alternative that relies less on medication, and may even be a preferable option when medications are not available.