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Do ketogenic diets really suppress appetite? A systematic review and meta-analysis
Abstract
Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.
... With weight loss, feelings of hunger are promoted to restore a normal body weight status. These compensatory changes are thought to be induced by alterations in expression of hypothalamic regulators of energy balance as well as adaptive changes in gut function, which alter the concentration of appetite-regulating hormones, such as ghrelin, cholecystokinin and peptide tyrosine tyrosine (PYY) (8) . These are likely some of the reasons that weight loss is difficult to maintain for most people (7)(8)(9) . ...
... These compensatory changes are thought to be induced by alterations in expression of hypothalamic regulators of energy balance as well as adaptive changes in gut function, which alter the concentration of appetite-regulating hormones, such as ghrelin, cholecystokinin and peptide tyrosine tyrosine (PYY) (8) . These are likely some of the reasons that weight loss is difficult to maintain for most people (7)(8)(9) . Furthermore, the homeostatic control of food intake is strongly influenced by hedonistic impulses, the reward system and eating experiences (10,11) . ...
... When applied long term, one strategy thought to suppress appetite, while simultaneously avoiding the compensatory increases in hunger that usually occur during energy restriction, is very-low-calorie diets (VLCDs) ≤3347 kJ/d (800 kcal/d) (2,8) . These diets use severe energy restriction, including a low carbohydrate intake, which creates a metabolic response with an increased circulation of ketone bodies produced by the liver, which is also called the metabolic switch (2,8) . ...
Alternate day fasting (ADF) with consumption of calories up to 25 % of the daily energy intake on fast days is one of the most used intermittent fasting regimens and promoted as a promising, alternative approach for treating obesity. Feelings of appetite are critical for adherence to dietary approaches, and therefore the success of dietary interventions. This systematic review aimed to assess the effects of a minimum of 8 weeks of ADF on subjective feelings of appetite and body weight for adults with overweight and obesity. We conducted the review in accordance with the Cochrane guidelines, including systematic searches in four databases. Because of the high level of clinical and methodological heterogeneity, a narrative approach was used to synthesise the results. Eight studies with a total of 456 participants met the eligibility criteria: three randomised controlled trials and five uncontrolled before-after studies. Seven of the studies had high risk of bias. Feelings of appetite were assessed by hunger in eight studies, fullness in seven studies, satisfaction in four studies and desire to eat in one study. All the studies assessed weight loss. The certainty of the evidence was rated low or very low for all outcomes, thus no firm conclusions can be drawn about the potential benefits of ADF on subjective feelings of appetite and body weight. Despite the high interest in ADF, good quality evidence is still needed to determine its effectiveness and if offered in clinical practice, ADF should be offered cautiously while concomitantly evaluated.
... Evidence also suggests significant amelioration of metabolic parameters and inflammation markers [16,17]. Adherence to VLCKD seems to be facilitated by the effect of ketone bodies in controlling appetite and improving food control [18]. All these data might make VLCKDs a valuable option for the management of poor responder subjects after bariatric surgery. ...
... Regarding the subjective feelings of appetite and control of eating, ketone bodies seem to have an appetite-suppressing effect [18,31]. The COEQ results showed a significant reduction in hunger and food craving and a significant improvement in control of eating during the nutritional program. ...
Purpose
Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition.
Methods
A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated.
Results
A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected.
Conclusion
Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.
... However, one has to note that reductions in IHLC were comparable after 7% weight loss 32 , supported by Haufe et al (2011) 30 who also showed comparable reductions in IHLC after 6 months. Nevertheless, an increase in total energy expenditure by about ~50kcal for every 10% decrease in the contribution of carbohydrates to total energy intake has been postulated 40 , together with a decrease in ghrelin and leptin levels contributing to decreased appetite and satiety 41 following a LCD independently of body mass index (BMI). Importantly, these changes might be 8 linked to an increase in ketogenesis and favorable changes in gut microbiota, which were even observed after an isocaloric LCD 42 . ...
... Here, insulin resistance directly correlates with hepatic de-novo lipogenesis (DNL) 57 , which has been shown to significantly contribute to IHLC in lean individuals without NAFLD (~11%), but being even more pronounced in obese individuals (~19%) and obese NAFLD patients (~38%). Most importantly, Luukkonen and colleagues (2022) 58 In summary, specific beneficial aspects include the above-mentioned increase in energy expenditure 40 and requirement 64 , increase in satiety 41 , lower insulin and ghrelin action in adipose tissue, higher glucagon action in non-adipose sites, and increased leptin sensitivity in the muscle 51 . ...
Nutrition and dietary interventions are a central component in the pathophysiology, but also a cornerstone in the management of patients with non-alcoholic fatty liver disease (NAFLD). Summarizing our rapidly advancing understanding of how our diet influences our metabolism and focusing on specific effects on the liver, we provide a comprehensive overview of dietary concepts to counteract the increasing burden of NAFLD. Specifically, we emphasize the importance of dietary calorie restriction independently of the macronutrient composition together with adherence to a Mediterranean diet low in added fructose and processed meat seems to exert favorable effects beyond calorie restriction. Also, we discuss intermittent fasting as a type of diet specifically tailored to decrease liver fat content and increase ketogenesis, awaiting future study results in NAFLD. Finally, personalized dietary recommendations could be powerful tools to increase the effectiveness of dietary interventions in patients with NAFLD considering the genetic background and the microbiome, among others.
... Most sources would suggest these diets contain around 800 calories per day which usually includes less than 50 g of carbohydrate and a moderate intake of protein [40][41][42]. However, the carbohydrate intake required to induce ketosis is vastly different between individuals [43]. Some studies suggest ketosis can occur even when greater than 150 g carbohydrate per day is consumed [44][45][46]. ...
... Subjective appetite ratings were also lower during ketosis [38,58]. This data, and that of other studies including administration of ketones [43,59], suggest that ketosis may facilitate dietary adherence by influencing hormones which control appetite. ...
Obesity in women of reproductive age is common. Emerging evidence suggests that maternal obesity not only increases the risk of adverse pregnancy outcomes but also has an enduring impact on the metabolic health of the offspring. Given this, management of obesity prior to pregnancy is critically important. Almost all international guidelines suggest that women with obesity should aim to achieve weight loss prior to pregnancy. However, current pre-conception weight loss therapies are sub-optimal. Lifestyle modification typically results in modest weight loss. This may assist fertility but does not alter pregnancy outcomes. Bariatric surgery results in substantial weight loss, which improves pregnancy outcomes for the mother but may be harmful to the offspring. Alternative approaches to the management of obesity in women planning pregnancy are needed. Very low energy diets (VLEDs) have been proposed as a possible tool to assist women with obesity achieve weight loss prior to conception. While VLEDs can induce substantial and rapid weight loss, there are concerns about the impact of rapid weight loss on maternal nutrition prior to pregnancy and about inadvertent exposure of the early fetus to ketosis. The purpose of this review is to examine the existing literature regarding the safety and efficacy of a preconception VLED program as a tool to achieve substantial weight loss in women with obesity.
... Where the prescribed intake was ≈45 kcal·kg −1 ·d −1, at the end of the eight weeks, the reported mean was ≈40 kcal·kg −1 ·d −1 , unlike the group that did not engage in a KD, who reached the prescribed calorie intake at the beginning of the study. Therefore, and given that energy surplus is currently considered the main factor in increasing muscle mass [20], we must consider the main limitation to achieving it: the satiety generated by KD diets [39,40]. In fact, ad libitum KDs have shown a lower energy consumption [40], indicating it is difficult to reach an adequate intake of calories, and thus impairing adherence to the diet. ...
... Therefore, and given that energy surplus is currently considered the main factor in increasing muscle mass [20], we must consider the main limitation to achieving it: the satiety generated by KD diets [39,40]. In fact, ad libitum KDs have shown a lower energy consumption [40], indicating it is difficult to reach an adequate intake of calories, and thus impairing adherence to the diet. The satiating effect of KDs that do not produce an increase in FFM can optimize the reduction in fat mass [8,31]. ...
Reviews focused on the ketogenic diet (KD) based on the increase in fat-free mass (FFM)
have been carried out with pathological populations or, failing that, without population differentiation. The aim of this review and meta-analysis was to verify whether a ketogenic diet without programmed energy restriction generates increases in fat-free mass (FFM) in resistance-trained participants. We evaluated the effect of the ketogenic diet, in conjunction with resistance training, on fat-free mass in trained participants. Boolean algorithms from various databases (PubMed, Scopus. and Web of Science) were used, and a total of five studies were located that related to both ketogenic diets and resistance-trained participants. In all, 111 athletes or resistance-trained participants (87 male and 24 female) were evaluated in the studies analyzed. We found no significant differences between groups in the FFM variables, and more research is needed to perform studies with similar ketogenic diets and control diet interventions. Ketogenic diets, taking into account the possible side effects, can
be an alternative for increasing muscle mass as long as energy surplus is generated; however, their application for eight weeks or more without interruption does not seem to be the best option due to the satiety and lack of adherence generated.
... In summary, in both inpatient settings and free-living conditions, KDs do not reduce appetite or energy intake compared to non-KDs, either during weight stability, weight loss, or weight loss J o u r n a l P r e -p r o o f maintenance. Low-calorie KDs (and VLCKDs) remain an effective way to reduce energy intake, but no more so than low-calorie non-KD approaches (100). supplemented at lunch, energy intake at an ad libitum dinner was reduced, again without any effect on subjective appetite ratings (37). ...
... Ketosis notoriously reduces the perception of hunger [47]; induces nausea, vomiting, stomach pain, or flu-like symptoms ( Table 1); and predisposes [3,11] to kidney stone formation. On the other hand, ketosis boosts the immune response and has anti-inflammatory and anti-infectious effects [3,18,25,33,48]. ...
The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of β-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and β-hydroxybutyrate.
... To the possible direct appetite suppressant action of the ketones bodies [125]; d. Or to the combination of of all three factors. ...
The ketogenic diet (KD) is, nowadays, considered an interesting nutritional approach for weight loss and improvement in insulin resistance. Nevertheless, most of the studies available in the literature do not allow a clear distinction between its effects on insulin sensitivity per se, and the effects of weight loss induced by KDs on insulin sensitivity. In this review, we discuss the scientific evidence on the direct and weight loss mediated effects of KDs on glycemic status in humans, describing the KD’s biochemical background and the underlying mechanisms.
... A meta-analysis reported that both LCD and lowcalorie diets decreased hunger in participants with obesity: a low-calorie diet favored increased satiety, whereas LCD favored decreased appetite; appetite suppression was attributed to ketosis (β-hydroxybutyrate ≥ 0.3 mmol /L) [20]. However, the study only evaluated fasting appetite at baseline and after intervention and did not evaluate postprandial appetite. ...
Background
Low-carbohydrate diet (LCD) is an emerging therapy for type 2 diabetes mellitus (T2DM). Although its effect on glucose control has been confirmed in previous clinical trials, most of those studies have focused on comparing calorie-restricted LCD to iso-caloric low-fat diets. In this study, we aim to compare the effects of LCD and canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with T2DM.
Methods
This is a multicenter, randomized controlled trial. We will recruit 120 patients with poor-controlled T2DM. Participants will be randomly divided into canagliflozin and LCD groups in a 1:1 ratio. The primary outcome is the change in hemoglobin A1C levels after the 3-month intervention. The secondary outcomes are the time in range and cost of antihyperglycemic agents. Exploratory outcomes include physical examination, body composition, glucose variability, appetite, glycolipid metabolism, liver lipid content, and urine glucose threshold.
Discussion
No previous study has compared an LCD with antihyperglycemic agents. In LoCaT, participants’ metabolism will be assessed from multiple perspectives. It is believed that the finding obtained from this trial will optimize the treatments for patients with T2DM.
Trial registration
Chinese Clinical Trial Registry ChiCTR1900027592. Registered on November 20, 2019.
... Hallberg et al did assess compliance of the ketogenic diet among diabetic patients using objective serum ketone monitoring and demonstrated that 87% of their participants were able to maintain a ketogenic diet for at least a year [56]. Dietary fats appear to play a role in mood stability [57], and endogenously produced ketone bodies (by-product of a ketogenic diet) naturally suppress appetite [58] both of which may assistin improving patient satisfaction and compliance with this nutritional methodology. A recent meta-analysis by Sainsbury et al however found that while carbohydrate-restricted dietsproduced greater reductions in HBA1C at 3 and 6 months, there was no statistically significant difference at 12 or 24 months [59]. ...
... Meidenbauer et al. [86] also pointed out the possibility that mice tend to self-restrict their energy intake when switched to an unfavourable KD despite ad libitum feeding. In humans KDs frequently suppress appetite or hunger [87], so that many patients also involuntarily self-restrict their energy intake; in this case, however, ketosis and sufficient protein intake may help to preserve muscle mass [88,89]. ...
Background
Ketogenic diets (KDs) are high-fat diets with putatively anti-tumor effects. The aim of this study was to synthesize the evidence for anti-tumor effects of KDs in mice, with a focus on their possible synergism with chemotherapy (CT), radiotherapy (RT) or targeted therapies (TT).
Materials and methods
Relevant studies were retrieved from a literature search. A total of 43 articles reporting on 65 mouse experiments fulfilled the inclusion criteria, and 1755 individual mouse survival times were collated from the study authors or the publications. The restricted mean survival time ratio (RMSTR) between the KD and control group served as the effect size. Bayesian evidence synthesis models were used to estimate pooled effect sizes and to assess the impact of putative confounders and synergism between KD and other therapies.
Results
Overall, there was a significant survival-prolonging effect of KD monotherapy (RMSTR=1.161±0.040), which was confirmed in meta-regression accounting for syngeneic versus xenogeneic models, early versus late KD start and subcutaneous versus other organ growth. Combining the KD with RT or TT, but not CT, was associated with a further 30% (RT) or 21% (TT) prolongation of survival. An analysis accounting for 15 individual tumor entities showed that KDs exerted significant survival-prolonging effects in pancreatic cancer (all treatment combinations), gliomas (KD+RT and KD+TT), head and neck cancer (KD+RT) and stomach cancer (KD+TT).
Conclusions
This analytical study confirmed the overall anti-tumor effects of KDs in a large number of mouse experiments and provides evidence for synergistic effects with RT and TT.
... Different levels of ketosis around the start of feeding may be part of the explanation for the early divergence of body weights in birds that later grow to be small or large compared to their cohort, that we have reported previously . This may be related to ketones directly affecting feed intake as increased ketosis has been shown to reduce appetite in humans (Gibson et al., 2015). ...
Intermittent fasting (IF) is the practice of temporal food restriction to promote metabolic switching between a glucose- and a ketone-based metabolism, which has been reported to come with diverse health benefits. IF practices appear to confer many of the advantages of caloric restriction without restricting total energy intake, and studies in both rodents and humans suggest organism-wide improvements in neurological, cardiovascular and metabolic health. IF is also commonly employed in the commercial rearing of breeding meat-type poultry, i.e. broiler breeders, which require strict feed restriction throughout life to maintain physical health. While the scientific poultry literature holds vast amounts of data on such “skip-a-day” feeding schedules, it has been unclear to what extent avian and mammalian literature may be compared as broiler breeders are typically feed-restricted to around 30% of ad libitum intake even in IF schedules. In this study, we set out to disentangle the effects of IF and caloric restriction in meat-type poultry by employing both IF and daily feeding schedules at two different restriction levels. Our results suggest that the physiological response to IF in chickens is only marginally affected by the intensity of feed restriction, while behavioural parameters are more closely related to feeding level and are expected to better mirror animal welfare. Our results suggest that avian and mammalian literature on IF should be comparable. Meat-type chickens do show some peculiarities in response to IF, such as a reduced insulin sensitivity, but it is currently unclear whether this is true for all chickens or is an effect of the intense selection for rapid growth in meat-type chickens.
... The results of previous studies have shown that decreased carbohydrate availability due to fasting or a ketogenic diet (KD), metabolic consequences of an intense physical exercise session, or impaired insulin signaling might lead to increased production of ketone bodies (KBs) [38]. KDs appear to reduce appetite, which in turn leads to a decrease in kilocalorie intake [39][40][41][42]. In addition, it has been proposed that KBs could lead to the modulation of circadian rhythms, including appetite, sleep, and hormone release [43]. ...
Background:
To examine the relationship between the frequency of physical activities and food product consumption with body composition change after two years in a sample of older people.
Methods:
Body composition, mass change, frequency of physical activity, and food products consumption were measured. Depression severity, health self-assessment, cognitive function, and demographic data were included as confounders.
Results:
There were no significant changes in body composition except for a reduction in visceral fat level within two years (p < 0.05). Drinking beer and eating sweets a few times per week were associated with a significant increase in body fat percentage (p < 0.05). Drinking green or white tea more frequently than a few times per year was related to an increase in body fat (3.18 to 3.88%, p < 0.05). Contrarily, daily consumption of coffee was related to a decrease in body fat (p = 0.029). Subjects who ate sweets once a week or more frequently consumed coffee more often.
Conclusions:
More frequent drinking of beer or of green or white tea and consumption of sweets were related to an increase in body fat percentage, while daily coffee consumption was related to a decrease in body fat percentage after two years in older, healthy subjects. Noteworthily, the frequencies of food product consumption are interrelated.
... In addition to treating epilepsy, the ketogenic diet has shown to be an effective strategy for managing type 2 diabetes [5]. Indeed, there seems to be a positive correlation between weight loss and the ketogenic diet due to this regime's ability to reduce appetite and the amount of body fat [6,7]. In point of fact, it was shown that a low-carbohydrate diet is much more effective in reducing body weight compared to a low-fat diet [8], most likely due to the presence of ketone bodies coming from excessive fatty acid metabolism. ...
The ketogenic diet, known as a low-carbohydrate, high-protein, and high-fat diet, drastically restrains the major source of energy for the body, forcing it to burn all excess fat through a process called ketosis—the breaking down of fat into ketone bodies. First suggested as a medical treatment for children suffering from epilepsy, this diet has gained increased popularity as a rapid weight loss strategy. Over the past few years, there have been numerous studies suggesting that the ketogenic diet may provide therapeutic effects for several psychiatric conditions such as mood- and anxiety-related disorders. However, despite significant progress in research, the mechanisms underlying its therapeutic effects remain largely unexplored and are yet to be fully elucidated. This chapter provides an in-depth overview of preclinical and clinical evidence supporting the use of a ketogenic diet in the management of mood and anxiety disorders and discusses its relationship with inflammatory processes and potential mechanisms of actions for its therapeutic effects.KeywordsAnxietyBipolar disorderInflammationKetogenic dietMajor depressive disorderMood disorders
Schizophrenia
... What is discussed less is the fact that the KD can be accompanied by CR itself. The KD is proposed as an approach for obesity treatment because it effectively reduces appetite [112][113][114]. The exact molecular mechanisms by which KDs suppress appetite remain to be established. ...
The ketogenic diet (KD) has been used as a treatment for epilepsy since the 1920s, and its role in the prevention of many other diseases is now being considered. In recent years, there has been an intensive investigation on using the KD as a therapeutic approach to treat acute pathologies, including ischemic ones. However, contradictory data are observed for the effects of the KD on various organs after ischemic injury. In this review, we provide the first systematic analysis of studies conducted from 1980 to 2022 investigating the effects and main mechanisms of the KD and its mimetics on ischemia–reperfusion injury of the brain, heart, kidneys, liver, gut, and eyes. Our analysis demonstrated a high diversity of both the composition of the used KD and the protocols for the treatment of animals, which could be the reason for contradictory effects in different studies. It can be concluded that a true KD or its mimetics, such as β-hydroxybutyrate, can be considered as positive exposure, protecting the organ from ischemia and its negative consequences, whereas the shift to a rather similar high-calorie or high-fat diet leads to the opposite effect.
... The restriction of carbohydrates induces the lipolysis of fat depots and leads to nutritional ketosis, modulating the gut microbiome (2) and inducing a metabolic effect that stabilizes glucose levels and minimizes insulin release (3). Circulating levels of ketone bodies, especially B-hydroxybutyrate (BHB), promote an anorexigenic effect, reducing appetite and food intake (4,5), which is one of the mechanisms accounting for the tolerability and high adherence to such a restrictive diet (6). Recently, a meta-analysis was conducted to assess the efficacy of the VLCKD in subjects with overweight and obesity (7). ...
Introduction:
The Very Low-Calorie Ketogenic Diet (VLCKD) has emerged as a safe and effective intervention for the management of metabolic disease. Studies examining weight loss predictors are scarce and none has investigated such factors upon VLCKD treatment. Among the molecules involved in energy homeostasis and, more specifically, in metabolic changes induced by ketogenic diets, Fibroblast Growth Factor 21 (FGF21) is a hepatokine with physiology that is still unclear.
Methods:
We evaluated the impact of a VLCKD on weight loss and metabolic parameters and assessed weight loss predictors, including FGF21. VLCKD is a severely restricted diet (<800 Kcal/die), characterized by a very low carbohydrate intake (<50 g/day), 1.2-1.5 g protein/kg of ideal body weight and 15-30 g of fat/day. We treated 34 patients with obesity with a VLCKD for 45 days. Anthropometric parameters, body composition, and blood and urine chemistry were measured before and after treatment.
Results:
We found a significant improvement in body weight and composition and most metabolic parameters. Circulating FGF21 decreased significantly after the VLCKD [194.0 (137.6-284.6) to 167.8 (90.9-281.5) p < 0.001] and greater weight loss was predicted by lower baseline FGF21 (Beta = -0.410; p = 0.012), male sex (Beta = 0.472; p = 0.011), and central obesity (Beta = 0.481; p = 0.005).
Discussion:
VLCKD is a safe and effective treatment for obesity and obesity related metabolic derangements. Men with central obesity and lower circulating FGF21 may benefit more than others in terms of weight loss obtained following this diet. Further studies investigating whether this is specific to this diet or to any caloric restriction are warranted.
... This ensured that a state of ketosis did not occur in the control group, as the percentages and the amounts of macronutrients were not characteristic of a ketogenic diet. 36 Placebo (capsules containing microcrystalline cellulose, matching in size and color) was also administered to the control group with the same instructions as the intervention group. ...
Multiple sclerosis (MS) is a neurodegenerative disease that progressively decreases the muscular and functional capacity. Thus, there is an alteration in the ability to walk that affects balance, speed and resistance. Since MS pathology involves neuroinflammation, cellular oxidation and mitochondrial alterations, the objective of the study was to assess the impact of a nutritional intervention with coconut oil and epigallocatechin gallate (EGCG) on gait and balance. In order to do this, 51 patients with MS were enrolled and randomly distributed into an intervention group and a control group, which received either a daily dose of 800 mg of EGCG and 60 ml of coconut oil, or a placebo, all during a period of 4 months and which followed a Mediterranean isocaloric diet. Initial and final assessments consisted of the evaluation of quantitative balance (Berg scale), perceived balance (ABC scale), gait speed (10MWT) and resistance (2MWT). Besides, muscle strength was measured using a dynamometer and levels of β-hydroxybutyrate (BHB) were measured in serum samples. In the intervention group, there was a significant improvement in the gait speed, quantitative balance and muscle strength of the right quadriceps; an improvement in gait resistance was observed in both groups. There were also significant and positive correlations between balance and gait scales. In conclusion, the administration of EGCG and coconut oil seems to improve gait speed and balance in MS patients, although the latter was not perceived by them. Furthermore, these variables appear to be related and contribute to functionality.
... Ponadto drastycznie zredukowana ilość węglowodanów w diecie przyczynia się do zmiany mikroflory jelitowej, która produkuje kwas foliowy poprawiający metabolizm lipidów, a także ogranicza stres oksydacyjny i stany zapalne [62]. Dodatkowo ciała ketonowe wywołują uczucie sytości, co prowadzi do ograniczenia ilości przyjmowanych kalorii, a przez to do utraty wagi [63]. Sugeruje się także, że keton -â-hydroksymaślan, może działać uodparniająco na stres oksydacyjny [64]. ...
Introduction and purpose: Ketogenic diet (KD) is a form of nutrition based on usage of ketone bodies, received from transformation of consumed fats as a main source of energy. Advantages of this type of metabolism are used in treatment of various diseases. Our purpose is to sum up and present what we know about its usage, as a therapeutic tool, so far.
Description of the state of knowledge: The use of ketone bodies, instead of glucose, as a main source of energy is more efficient, reduces oxidative stress and inflammation. Furthermore, it modulates gut microbiota. KD is used in the treatment of drug-resistant epilepsy in children and is proved to be useful in the treatment of type 2 diabetes. It can improve health of patients with non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases and psychiatric diseases. The usage in other areas is still under research. It is also necessary to take into consideration adverse effects of KD such as an increase in level of LDL-cholesterol and a potential lack of some macro- and microelements. Additionaly, maintaining the diet seems to be difficult, therefore, there is no enough data to fully describe its impact on human health in long-term perspective.
Conclusions: The findings presented in this paper suggest that a ketogenic diet can constructively supplement the treatment of drug-resistant epilepsy in children and aid the treatment of type 2 diabetes. Regarding diseases associated with oxidative stress and inflammation, the reviewed data indicates that KD could be of use. However, KD is not recommended to be routinely ordered before further studies have substantiated and observable effect.
... Considerable decreases in FGF21 (85 pg mL −1 ) and leptin (3.5 ng mL −1 ) concentrations were observed with 24 h of carbohydrate (but not sugar) restriction, alongside markedly increased βOHB (0.35 mmol L −1 ). Diet-induced ketogenesis achieving βOHB concentrations ~ 0.5 mmol L −1 after 4-8 weeks are associated with increased subjective feelings of satiety and fullness and decreased hunger and desire to eat [46]; however, similar concentrations of βOHB in the (a, b), non-esterified fatty acids (c, d), glycerol (e, f), and β- hydroxybutyrate (g, h). n = 24. ...
Purpose
To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h.
Methods
In a randomized, open-label crossover design, twenty-five healthy men ( n = 10) and women ( n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning.
Results
The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d ⁻¹ ; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d ⁻¹ ; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast ( P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations ( P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG ( p < 0.01).
Conclusion
When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes.
Clinical trials registration ID
NCT03509610, https://clinicaltrials.gov/show/NCT03509610
... The very low carbohydrate ketogenic diet (VLCKD) represents the most widespread KD type and is traditionally characterized by carbohydrate limitation (<50 g per day) with unrestricted fat consumption and a moderate increase in protein intake (0.8-1.2 g per day) (27). The total amount of calories to be provided for a single individual is based on anthropometric measurements, dietary intake and physical activity (28). ...
Ketogenesis takes place in hepatocyte mitochondria where acetyl-CoA derived from fatty acid catabolism is converted to ketone bodies (KB), namely β-hydroxybutyrate (β-OHB), acetoacetate and acetone. KB represent important alternative energy sources under metabolic stress conditions. Ketogenic diets (KDs) are low-carbohydrate, fat-rich eating strategies which have been widely proposed as valid nutritional interventions in several metabolic disorders due to its substantial efficacy in weight loss achievement. Carbohydrate restriction during KD forces the use of FFA, which are subsequently transformed into KB in hepatocytes to provide energy, leading to a significant increase in ketone levels known as “nutritional ketosis”. The recent discovery of KB as ligands of G protein-coupled receptors (GPCR) - cellular transducers implicated in a wide range of body functions - has aroused a great interest in understanding whether some of the clinical effects associated to KD consumption might be mediated by the ketone/GPCR axis. Specifically, anti-inflammatory effects associated to KD regimen are presumably due to GPR109A-mediated inhibition of NLRP3 inflammasome by β-OHB, whilst lipid profile amelioration by KDs could be ascribed to the actions of acetoacetate via GPR43 and of β-OHB via GPR109A on lipolysis. Thus, this review will focus on the effects of KD-induced nutritional ketosis potentially mediated by specific GPCRs in metabolic and endocrinological disorders. To discriminate the effects of ketone bodies per se , independently of weight loss, only studies comparing ketogenic vs isocaloric non-ketogenic diets will be considered as well as short-term tolerability and safety of KDs.
... Le rôle de l'effet rassasiant des protéines et la réduction de l'appétit liée aux corps cétoniques est évoqué [34,35]. Dans des études sans groupe contrôle, la faim est réduite, le désir de manger également [36], l'appétit est réduit, le rassasiement augmenté [37], s'opposant ainsi à l'augmentation de ghréline associée à la reprise de poids sous régime amaigrissant. Mais ceci reste à démontrer chez l'homme [37]. ...
Résumé
Depuis les années 1920, les diètes cétogènes ont été utilisées avec succès pour traiter des épilepsies résistantes au traitement pharmacologique. Des études complémentaires ont proposé que les corps cétoniques puissent avoir également des effets bénéfiques sur la santé et sur d’autres pathologies que les épilepsies. Nous proposons ici de résumer les effets bénéfiques démontrés des corps cétoniques sur la masse musculaire et la sarcopénie, sur l’insuffisance cardiaque, sur la fonction rénale, sur les troubles neuropsychiques, et sur le poids corporel. D’autre part, les variations des concentrations de corps cétoniques dans le sang circulant pourraient expliquer une partie des effets bénéfiques des gliflozines sur la dysfonction myocardique et l’insuffisance rénale. L’ensemble de ces données ouvre une nouvelle stratégie thérapeutique basée sur l’amélioration de l’énergétique métabolique et de la génération de l’ATP dans les organes pathologiques.
... Specifically, diets with a low proportion of CHO increase energy expenditure, perhaps due to the changes in catecholamines and thyroid hormones, although the mechanisms contributing to this effect are incompletely understood [117]. Moreover, low and very low-CHO diets reduce hunger and appetite due to the changes in gastrointestinal hormones [126]. Nonetheless, the effect of a CHOrestriction diet on weight loss in an intervention longer than six months promotes the same change in weight loss compared with a calorie-restricted low-fat diet [127]. ...
Foods high in carbohydrates are an important part of a healthy diet, since they provide the body with glucose to support bodily functions and physical activity. However, the abusive consumption of refined, simple, and low-quality carbohydrates has a direct implication on the physical and mental pathophysiology. Then, carbohydrate consumption is postulated as a crucial factor in the development of the main Western diseases of the 21st century. We conducted this narrative critical review using MedLine (Pubmed), Cochrane (Wiley), Embase, and CinAhl databases with the MeSH-compliant keywords: carbohydrates and evolution, development, phylogenetic, GUT, microbiota, stress, metabolic health, consumption behaviors, metabolic disease, cardiovascular disease, mental disease, anxiety, depression, cancer, chronic kidney failure, allergies, and asthma in order to analyze the impact of carbohydrates on health. Evidence suggests that carbohydrates, especially fiber, are beneficial for the well-being and growth of gut microorganisms and consequently for the host in this symbiotic relationship, producing microbial alterations a negative effect on mental health and different organic systems. In addition, evidence suggests a negative impact of simple carbohydrates and refined carbohydrates on mood categories, including alertness and tiredness, reinforcing a vicious circle. Regarding physical health, sugar intake can affect the development and prognosis of metabolic disease, as an uncontrolled intake of refined carbohydrates puts individuals at risk of developing metabolic syndrome and subsequently developing metabolic disease.
... While a KD can be a viable therapeutic option for pediatric epilepsy, the energy requirement of these patients must be considered to minimize disruptions in growth. The high fat content of KDs decreases appetite, which in theory would lead to inadequate caloric intake and reduced growth [100]. A study by Groleau and colleagues partly supports this idea. ...
Ketogenic diets (KDs) are highly effective in the treatment of epilepsy. However, numerous complications have been reported. During the initiation phase of the diet, common side effects include vomiting, hypoglycemia, metabolic acidosis and refusal of the diet. While on the diet, the side effects involve the following systems: gastrointestinal, hepatic, cardiovascular, renal, dermatological, hematologic and bone. Many of the common side effects can be tackled easily with careful monitoring including blood counts, liver enzymes, renal function tests, urinalysis, vitamin levels, mineral levels, lipid profiles, and serum carnitine levels. Some rare and serious side effects reported in the literature include pancreatitis, protein-losing enteropathy, prolonged QT interval, cardiomyopathy and changes in the basal ganglia. These serious complications may need more advanced work-up and immediate cessation of the diet. With appropriate monitoring and close follow-up to minimize adverse effects, KDs can be effective for patients with intractable epilepsy.
... Previously Kozue et al. and Evan et al. reported that prolonged KD did not affect body weight in mice [27,28], indicating that KD causes a rapid drop in body weight, but then it gradually returns to the initial level, and may even increase afterwards. There are several hypothesized mechanisms for its weight loss effect including reduction in appetite, reduction in lipogenesis and increased lipolysis, increased metabolic costs of gluconeogenesis and greater metabolic efficiency in consuming fats [29,30], but how KD really causes weight loss still remains unknown. While the effect of KD on blood ketone levels is already established, its effect on blood glucose regulation is known to treat diabetes [31]. ...
Background
The ketogenic diet (KD) has anti-tumor and anti-diabetic effects in addition to its anti-epileptic role. It could also improve cardiac function and attenuate neurological insult. However, the effect of KD on blood perfusion or tissue recovery after ischemia remains largely unknown. Thus, we observed blood flow and ischemic tissue recovery following hind limb ischemia (HLI) in mice.
Methods
C57 mice were fed with either a KD or normal diet (ND) for 2 weeks, before inducing hind limb ischemia, blood perfusion of ischemic limb tissue was observed at 0, 7, and 21 days post operation.
Results
KD not only decreased blood perfusion of ischemic limb tissue but also delayed muscle recovery after ischemia, induced muscle atrophy of non-ischemic tissue compared to mice fed with ND. Furthermore, KD delayed wound healing at the surgical site and aggravated inflammation of the ischemic tissue. At the cellular level, KD altered the metabolic status of limb tissue by decreasing glucose and ketone body utilization while increasing fatty acid oxidation. Following ischemia, glycolysis, ketolysis, and fatty acid utilization in limb tissue were all further reduced by KD, while ketogenesis was mildly increased post KD in this mice model.
Conclusion
The KD may cause impaired tissue recovery after ischemia and possible muscle atrophy under a prolonged diet. Our results hint that patients with limb ischemia should avoid ketogenic diet.
... As a result, KE beverages provide a one-of-a-kind chance to isolate and utilize the effects of ketosis on hunger without requiring any additional dietary changes [4]. Even in calorie deficits, Angela M. Poff revealed that KDs (ketogenic diets) result in subjective perceptions of lower hunger and desire to eat (Figure 4), and these effects have been linked to the condition of NK (nutritional ketosis) [5]. Acute NK generated by the consumption of the R-BD (ketogenic precursors redenced) R-βHB monoester lowered subjective evaluations of hunger and desire to eat evaluated by visual analog scales, which correlated with ghrelin suppression [6]. ...
According to statistics and surveys by the World Health Organization, the obesity ratio of people in the world nearly tripled since 1975; in 2016, more than 1.9 billion adults aged 18 and older were overweight. Obesity and overweight are defined as abnormal or excessive fat accumulation that presents a risk to health. Obesity prevention and intervention is a serious health problem facing humanity. This article is an analysis of interventions for obesity from the perspective of ketogenic metabolism, by supplementing exogenous ketones or increasing endogenous ketone levels. By analyzing experimental data on the metabolic mechanisms of ketones, exogenous ketones esters on body weight, food intake and satiety hormones, this paper concludes that exogenous ketones have a positive effect on interventions in obesity. A study of the literature revealed that the involvement of ketogenesis in the process of fat metabolism is still a very vague concept.
... However, similar to our findings, previous studies have observed appetite suppression after 4 and 12 weeks of KD in obese individuals. 17,36,37 By contrast, Struik et al. 38 have observed the increased PFC after 4 weeks of the KD in overweight or obese individuals with type 2 diabetes. It is noteworthy that several mechanisms, including direct effects of ketone bodies on reducing central orexigenic signaling, changes in appetite-regulating hormones, changes in the gut microbiota, increased fatty acids, and elevated postprandial blood glucose concentrations, may contribute to the appetite-suppression effects of KD. 20,26 However, contradictory results have been reported for changes in appetite after long-term exercise. ...
Exercise and diet are two essential interventions in weight control. The purpose of this study was to compare the effectiveness of two exercise training types during a ketogenic diet (KD) on appetite sensation, appetite-regulating hormones, and body composition in overweight or obese man. Thirty-six men, overweight or with obesity, voluntarily participated in this study. The participants were randomly assigned into three groups, including KD ( n = 12), aerobic training during KD (AT-KD) ( n = 12), and resistance training during KD (RT-KD) ( n = 12) groups. The participants followed a low-carbohydrate diet for 6 weeks. Exercise training programs consisted of three sessions per week over 6 weeks. Appetite sensation was analyzed using a visual analogue scale (VAS) in fasting and postprandial states. The Enzyme-Linked Immunosorbent Assay (ELISA) method analyzed appetite-regulating hormones, including spexin, leptin, and acylated ghrelin, in a fasting state. Body composition was measured using bioelectrical impedance analysis (BIA). Furthermore, the ketosis state was monitored by measuring urinary ketones weekly. The results indicated that in both AT-KD and RT-KD groups, spexin and acylated ghrelin increased while leptin decreased without any between-group differences. Hunger and prospective food consumption (PFC) declined while satiety and fullness increased in all groups. The AT-KD group experienced a significant decrease in hunger and PFC, while fullness increased compared with the KD group. Fat mass, weight, and body mass index (BMI) decreased in all groups. Lean body mass increased in the RT-KD group (+2.66 kg) compared with both AT-KD and KD groups (−1.71 and −1.33 kg, respectively). This study demonstrated that AT-KD and RT-KD effectively altered appetite-regulating hormones and suppressed appetite sensation. In addition, both interventions had a favorable effect on weight loss and body fat reduction, with a more pronounced effect of RT-KD on maintaining lean body mass in overweight or obese men.
Objectives
Shift work is associated with various health challenges, including obesity and metabolic disturbances. To address these concerns, a randomised controlled clinical trial was conducted to evaluate the efficacy of a low-calorie meal replacement (MR) dietary intervention for dinner among shift workers with obesity. This study focuses on the qualitative aspects of this intervention, aiming to explore the experiences and perceptions of shift workers who participated in the trial.
Design
Following the completion of the intervention, semi-structured face-to-face or telephone interviews were conducted with a purposive sample of trial participants. Data analysis was inductive, thematic using NVivo V.10 software.
Setting
The intervention was conducted among shift workers with obesity in a private hospital in Sri Lanka and resulted in a modest decrease in weight.
Participants
Using purposeful maximum variation sampling, we recruited eight healthcare shift workers who took part in a weight loss intervention.
Results
All participants expressed satisfaction with the MR meal for dinner, highlighting its positive impact on their well-being. Despite initial difficulties, strong determination and motivation by results supported adherence. Some participants suggested that the MR could be improved with sweeter taste and more flavour options. Few reported mild bloating at the beginning, but no serious side effects were noted. Participants felt lighter in their bodies due to weight loss. The method’s simplicity was the most frequently reported benefit, making it feasible even during busy night shifts. Overall, participants highly recommended the intervention to others in need.
Conclusion
Participants experienced weight loss by replacing their dinner with the MR. This study offers valuable insights for tailoring future workplace-based dietary interventions for this vulnerable population.
Trial registration number
ACTRN12622000231741.
Obesity is a multifaceted and complex condition that requires holistic management. It currently affects nearly one in four adults in the UK, with the UK ranked 10th globally for the highest obesity rates. Obesity is projected to have an economic burden of ∼£2 billion per year by 2030 in the UK.1 Excess weight gain can coincide with myriad health concerns and multiple health conditions, which can be physical, metabolic or psychosocial. This includes type 2 diabetes mellitus (T2DM), hypertension, coronary heart disease, osteoarthritis, obstructive sleep apnoea, reproductive disorders, depression and cancer2; hence, there has been a significant emphasis on obesity prevention. Obesity is often associated with weight stigma, impacting psychological wellbeing and quality of life. This can influence an individual's likelihood of seeking support, delaying appropriate input from healthcare professionals, with a knock-on effect on pre-existing health conditions. This review explores the management of obesity from a nutritional perspective, because modifying dietary intake is essential to reduce the risk of non-communicable diseases, including those associated with obesity.
Background: Insulin resistance is a condition in which body cells become less responsive to the effects of insulin, leading to elevated blood glucose levels and an increased risk of developing type 2 diabetes and cardiovascular disease. Triglycerides are a type of fat found in the blood that can also contribute to cardiovascular disease risk. There is evidence to suggest that dietary interventions, such as a low-starch diet, may improve triglyceride levels in individuals with insulin resistance.
Methods: In this study, 12 participants with insulin resistance were placed on a low-starch diet for 12 weeks. Blood samples were taken before and after the intervention to measure triglyceride levels. Paired t-tests were used to compare mean triglyceride levels before and after the intervention.
Results: The mean level of triglycerides before the intervention was 1.16, with a standard deviation of 0.56. After the intervention, mean triglyceride levels decreased to 0.98, with a standard deviation of 0.44. The paired t-test showed that there was a significant difference in mean triglyceride levels before and after the intervention (t = 3.41, df = 11, p-value = 0.006). These results suggest that a low-starch diet intervention can be effective in improving triglyceride levels in individuals with insulin resistance.
Conclusion: The findings of this study provide evidence that a low-starch diet may be an effective dietary intervention to improve triglyceride levels in individuals with insulin resistance. However, more research is needed to confirm these findings and determine the long-term effects of a low-starch diet on triglyceride levels and general health outcomes in this population.
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Alzheimer’s disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain. The ketogenic diet, a widely recognized therapeutic intervention for refractory epilepsy, has recently been proposed as a potential treatment for a variety of neurological diseases, including Alzheimer’s disease. However, the efficacy of ketogenic diet in treating Alzheimer’s disease and the underlying mechanism remains unclear. The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer’s disease. Male amyloid precursor protein/presenilin 1 (APP/PS1) mice were randomly assigned to either a ketogenic diet or control diet group, and received their respective diets for a duration of 3 months. The findings show that ketogenic diet administration enhanced cognitive function, attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice, and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway. Collectively, these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer’s disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation. This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer’s disease.
Background:
Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), while preserving fat-free mass (FFM). Additionally, animal data supports the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge a potential association between ß-hydroxybutyrate (ßHB) plasma concentrations and changes in body composition has never been explored.
Objective:
The main aim of this analysis was to determine if ßHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity.
Methods:
Data from 199 individuals (BMI= 36.6±4.3 kg/m2; age= 43.6±9.8 years; 82 men) were collated from three weight loss studies employing common measures of body composition (air displacement plethysmography) and ßHB plasma concentration (ELISA). The association between ßHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multivariable linear regression was used to determine if ßHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors.
Results:
ßHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r=0.182, P=0.01, n=199) and a trend with weight loss (r=0.128, P=0.072, n=199). ßHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study.
Conclusion:
The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved.
Clinical trial registration:
ClinicalTrials.gov identifier: NCT01834859, NCT04051190, NCT02944253.
Background & aims:
Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as β-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception.
Methods:
Eight healthy young adults (4 women, 4 men, age 24 ± 3 years, BMI 24.3 ± 3.1 kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7 g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured.
Results:
Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p > 0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110 ± 54 kcal/d vs. ISO, p < 0.05) and SEE (+201 ± 90 kcal/d vs. ISO, p < 0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48 ± 27 g/d, p < 0.05) resulting in a positive CHO balance (p < 0.05). No differences between the interventions were found for subjective appetite ratings (all p > 0.05).
Conclusion:
A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance.
Clinical trial registration:
NCT04490226 https://clinicaltrials.gov/.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is mainly characterized by cognitive deficits. Although many studies have been devoted to developing disease-modifying therapies, there has been no effective therapy until now. However, dietary interventions may be a potential strategy to treat AD. The ketogenic diet (KD) is a high-fat and low-carbohydrate diet with adequate protein. KD increases the levels of ketone bodies, providing an alternative energy source when there is not sufficient energy supply because of impaired glucose metabolism. Accumulating preclinical and clinical studies have shown that a KD is beneficial to AD. The potential underlying mechanisms include improved mitochondrial function, optimization of gut microbiota composition, and reduced neuroinflammation and oxidative stress. The review provides an update on clinical and preclinical research on the effects of KD or medium-chain triglyceride supplementation on symptoms and pathophysiology in AD. We also detail the potential mechanisms of KD, involving amyloid and tau proteins, neuroinflammation, gut microbiota, oxidative stress, and brain metabolism. We aimed to determine the function of the KD in AD and outline important aspects of the mechanism, providing a reference for the implementation of the KD as a potential therapeutic strategy for AD.
The ketone bodies beta-hydroxybutyrate and acetoacetate are hepatically produced metabolites catabolized in extrahepatic organs. Ketone bodies are a critical cardiac fuel and have diverse roles in the regulation of cellular processes such as metabolism, inflammation, and cellular crosstalk in multiple organs that mediate disease. This review focuses on the role of cardiac ketone metabolism in health and disease with an emphasis on the therapeutic potential of ketosis as a treatment for heart failure (HF). Cardiac metabolic reprogramming, characterized by diminished mitochondrial oxidative metabolism, contributes to cardiac dysfunction and pathologic remodeling during the development of HF. Growing evidence supports an adaptive role for ketone metabolism in HF to promote normal cardiac function and attenuate disease progression. Enhanced cardiac ketone utilization during HF is mediated by increased availability due to systemic ketosis and a cardiac autonomous upregulation of ketolytic enzymes. Therapeutic strategies designed to restore high-capacity fuel metabolism in the heart show promise to address fuel metabolic deficits that underpin the progression of HF. However, the mechanisms involved in the beneficial effects of ketone bodies in HF have yet to be defined and represent important future lines of inquiry. In addition to use as an energy substrate for cardiac mitochondrial oxidation, ketone bodies modulate myocardial utilization of glucose and fatty acids, two vital energy substrates that regulate cardiac function and hypertrophy. The salutary effects of ketone bodies during HF may also include extra-cardiac roles in modulating immune responses, reducing fibrosis, and promoting angiogenesis and vasodilation. Additional pleotropic signaling properties of beta-hydroxybutyrate and AcAc are discussed including epigenetic regulation and protection against oxidative stress. Evidence for the benefit and feasibility of therapeutic ketosis is examined in preclinical and clinical studies. Finally, ongoing clinical trials are reviewed for perspective on translation of ketone therapeutics for the treatment of HF.
Gut microbiota plays a fundamental role within human health, and exerts key functions within the human body. Diet is one of the most powerful modulators of gut microbiota functions and composition. This complex interplay involves also the immune system and the intestinal barrier, highlighting the central role of diet in the pathogenesis and treatment of multiple diseases. In this review article we will paint the landscape of the effects of specific dietary nutrients, and of the detrimental or beneficial outcomes of different dietary patterns, on the composition of human gut microbiota. Moreover, we will discuss the potential application of diet as a therapeutic modulator of gut microbiota, including cutting-edge ways of exploitation, including the use of dietary components as adjuvants to promote microbial engraftment after fecal microbiota transplantation, or personalized nutritional approaches, targeted to the patient microbiome.
Background:
Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared.
Objectives:
To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000-2500 kcal/d) and with varying carbohydrate quality or quantity.
Methods:
We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970.
Results:
Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%-7%) and visceral fat volume (12%-17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: -16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: -39.6 pg/mL; 95% CI: -76, -3.3]). No significant between-group differences were seen in feelings of hunger.
Conclusions:
Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3-0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.
Scope:
The primary aim of the present study was to study the effect of acute ketosis on parameters of appetite regulation in prediabetes. The secondary aim was to investigate whether the effect is influenced by eating behaviours.
Methods and results:
This was a randomised controlled trial. After an overnight fast, 18 adults with prediabetes (defined in line with the American Diabetes Association criteria) were assigned to consume either a ketone monoester (D-β-hydroxybutyrate-(R)-1,3 butanediol) drink (energy content 123 kcal) or a placebo drink (containing virtually no calories) in cross-over fashion. Blood samples were collected every 30 mins, from baseline to 150 minutes. Paired t-test was used to compare the total area under the curve (AUC) for the changes in parameters of appetite regulation (acylated ghrelin, peptide YY (PYY), and hunger) following both drinks. Eating behaviours were determined with the use of the three-factor eating questionnaire. Significant elevation in blood β-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 minutes. Acute ketosis did not result in statistically significant differences in the AUCs for ghrelin, PYY, and hunger. No statistically significant difference in the AUCs was also observed when participants were stratified by their eating behaviours.
Conclusion:
Acute ketosis consistently did not affect both objective and subjective parameters of appetite regulation in prediabetes. No subset of people with prediabetes according to eating behaviours had a significant effect of acute ketosis on appetite regulation. This article is protected by copyright. All rights reserved.
Objective
Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity. Prevention and management of obesity, which represents the main cause of morbidity and mortality in these patients, is essential. Ketogenic diet (KD) is used in the treatment of various disorders, however knowledge on its effect in PWS is lacking. The present study assesses the characteristics of patients with PWS who were on ketogenic diet.
Patients
This is a retrospective, cross-sectional descriptive study investigating the subjects with PWS, who had received KD for at least 6 months.
Results
Ten patients with PWS [median age 52.5 (47-77) months] complied with KD. The median treatment period was 16.5 [11-52] months. Of the daily calorie, 75-85% were from fat, and 15-25% from protein+carbohydrate. The baseline body weight SD score prior to diet therapy was 2.10 [-1.11-4.11], whereas it was 0.05 [-0.92-1.2] at final evaluation (p=0.007). The baseline median BMI SD score prior to diet therapy was 3.05 [-0.21-3.72], whereas it was 0.41 [-0.87-1.57] at final evaluation (p=0.002). The height SD score remained unchanged. Mild hypercholesterolemia was the most common biochemical abnormality during treatment with KD.
Conclusion
Our results indicate that KD might have a favorable effect on weight management in PWS.
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Bu araştırma iki aşamalı olarak planlanmış olup, ilk aşamada Ağırlık Yönetimi Beslenme Bilgisi Ölçeği'nin (AYBBÖ) Türkçe uyarlaması için geçerlik ve güvenirlik çalışması yapılmış, ikinci aşamada ise hafif şişman/şişman üniversite öğrencilerine verilen ağırlık yönetimi eğitiminin çeşitli parametreler üzerindeki etkisi değerlendirilmiştir. Çalışmanın ilk aşaması yaş ortalaması 20.6±1.50 yıl olan 392 üniversite öğrencisi ile yapılmıştır. Kırk üç maddeden oluşan AYBBÖ'nün, orijinal ölçekte olduğu gibi beş faktör (boyut) altında toplandığı sonucuna varılmıştır. Her boyuttaki maddelerin faktör yükü 0.40'ın üzerinde ve toplam varyans açıklama yüzdesi %47.3 olarak bulunmuştur. AYBBÖ puanı ile alt boyutlarının korelasyonu incelendiğinde, tüm alt boyutların puanları AYBBÖ toplam puanı ile pozitif korelasyonlu olup istatistiksel açıdan önemli bulunmuştur (p<0.0001). AYBBÖ'nin güvenirlik (iç tutarlılık) analizinde toplam ölçek maddeleri arasında orta düzeyde güvenilirlik sağlanmıştır (Cronbach's alfa=0.75). Çalışmanın ikinci aşaması ise yaş ortalaması 21.0±1.27 yıl olan 18 kadın ve 7 erkek olmak üzere toplamda 25 üniversite öğrencisi ile yapılmıştır. Araştırma kapsamında çalışmaya katılan üniversite öğrencilerine Türkiye Beslenme Rehberi (TÜBER) 2015 kaynak alınarak hazırlanmış ağırlık yönetimi eğitimi 4 ay boyunca, on beş günde bir kez en az 30 dakikalık olacak şeklinde toplamda 9 kez çevrim içi olarak verilmiştir. Eğitimlerden önce çalışmaya katılan üniversite öğrencilerine çevrim içi yöntemler kullanılarak anket formu, AYBBÖ, Sağlıklı Beslenmeye İlişkin Tutum Ölçeği (SBİTÖ), besin tüketim sıklık formu ve antropometrik ölçüm formu uygulanmıştır. Eğitimlerin bitişinden 2 hafta sonrasında AYBBÖ, SBİTÖ, besin tüketim sıklık formu ve antropometrik ölçüm formu tekrar uygulanmıştır. Çalışmanın ikinci aşamasına katılan bireylerin eğitim öncesi AYBBÖ puan ortalamaları 23.6±4.95 puan iken, eğitim sonrası 35.6±4.06 puan olarak yükselmiş ve bu değişim anlamlı bulunmuştur (p<0.05). Eğitim öncesi ve sonrası SBİTÖ gruplarındaki değişim istatistiksel olarak önemli bulunmuş olup, eğitim öncesi orta düzey tutuma sahip olan bireylerin eğitim sonrası yüksek iii ve ideal tutuma sahip oldukları belirlenmiştir (p<0.05). Üniversite öğrencilerinin eğitim öncesi günlük enerji alım ortalamaları 2568.3±692.06 kkal iken, eğitim sonrası 2126.3±530.95 kkal olarak azalmış ve bu değişim istatistiksel olarak önemli bulunmuştur (p<0.05). Bireylerin günlük enerjilerinin protein ve yağlardan gelen oranı, posa, n-3 yağ asidi, sıvı, A vitamini, B2 vitamini, B6 vitamini, folat, C vitamini, kalsiyum, fosfor, potasyum ve magnezyum alımları anlamlı şekilde yükselmiştir (p<0.05). Bireylerin vücut ağırlığı, BKİ'leri, bel çevreleri ve bel kalça oranları eğitim sonrası anlamlı şekilde azalmıştır (p<0.05). Sonuç olarak verilen ağırlık yönetimi eğitimi üniversite öğrencileri, beslenme bilgi düzeylerini artırmış, besin tüketimlerini ve antropometrik ölçümlerinin olumlu şekilde gelişmesini sağlamıştır.
The present study was planned in two stages, at the first stage of the study validity and reliability studies were performed for the Turkish version of the Weight Management Nutrition Knowledge Questionnaire (WMNKQ), and at the second stage of the study, the effect of weight management education given to overweight/obese university students on various parameters were evaluated. The first stage of the study was conducted on 392 university students with a mean age of 20.6±1.50 years. WMNKQ consisting of 43 items, was gathered under five factors (dimensions) as in the original questionnaire. The factor load of the items in each dimension was found over 0.40 and the percentage of total variance explanation was found 47.3%. When the correlation of the WMNKQ score and its subdimensions is examined, scores of all sub-dimensions were positively correlated with the total score of WMNKQ and found to be statistically significant (p<0.0001). In the reliability (internal consistency) analysis of WMNKQ, moderate reliability was achieved among the total scale items (Cronbach's alpha=0.75). The second stage of the study was conducted on 25 university students, 18 females and 7 males, with a mean age of 21.0±1.27 years. Within the scope of the research, weight management education intervention, which was prepared based on the Turkey Dietary Guidelines (TUBER) 2015, was given to university students online 9 times, at least 30 minutes, once every fortnight, for 4 months. Before the intervention, a questionnaire form, WMNKQ, Attitude Scale for Healthy Nutrition (ASHN) food frequency questionnaire and anthropometric measurement form were applied to university students using online methods. Two weeks after the end of the intervention, WMNKQ, ASHN, food frequency questionnaire and anthropometric measurement form were applied again. While the mean WMNKQ score was 23.6±4.95 points before the intervention, it increased to 35.6±4.06 points after the intervention and this change was found to be significant (p<0.05). The change in ASHN groups before and after the intervention was found to be statistically significant, and it was determined that the v individuals who had a moderate attitude before the intervention had a high and ideal attitude after the intervention (p<0.05). While university students' mean daily energy intake was 2568.3±692.06 kcal before the intervention, it decreased to 2126.3±530.95 kcal after the intervention, and this change was found to be statistically significant (p<0.05). In addition to this, the daily average energy rates from proteins, energy rates from fats, fibre, n-3 fatty acids, liquids, vitamin A, vitamin B2, vitamin B6, folate, vitamin C, calcium, phosphorus, potassium, magnesium and iodine intakes of individuals significantly increased (p<0.05). Individuals' body weight, BMI, waist circumference and waist-hip ratios decreased significantly after the intervention (p<0.05). As a result, the weight management education given to university students increased their nutritional knowledge level and provided a positive development in their food consumption and anthropometric measurements.
Growth differentiation factor 15 (GDF15) increases with acute fast in animals, and high GDF15 reduces food intake in rodents. We explored whether GDF15 was altered following intermittent fasting (IF) versus caloric restriction (CR), and associations with energy intake. Females with obesity received all foods at 70% (IF70 and CR70) or 100% of energy requirements for 8 weeks. IF ate 2-9% less than provided on refeeding days, resulting in greater weight losses. GDF15 was increased 5% more in IF70 versus CR70, but not associated with energy intake. This rise in GDF15 is unlikely to explain restriction of energy intake during IF.
Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile.
Diabetes mellitus (DM) is a global epidemic causing significant morbidity and mortality. The most occurring DM is type 2 diabetes mellitus (T2DM) which has similar symptoms as type 1 diabetes mellitus (T1DM). However, it is less marked, making it difficult to diagnose during the early stages. The management of T2DM is usually based on weight and glycemic control, which can be achieved through dietary interventions such as intermittent fasting (IF) and the ketogenic diet (KD). Therefore, this systematic review and meta-analysis aim to demonstrate the role of IF and KD in glycemic and weight control among patients with T2DM.
Two methods, including an electronic database search through ScienceDirect, Google Scholar, PubMed, Scopus, Embase, and Web of Science, and a manual search were used to identify relevant studies published between 2000 and 2022. The search yielded 1299 articles, of which only 12 met the inclusion criteria. In addition, study quality appraisal was performed using Review Manager software (RevMan 5.4.1). The pooled results have shown that IF had a similar effect on HBA1c reduction as control interventions (standardized mean differences [SMD]: 0.36%; 95% CI; -0.37, 1.10; P = 0.33, I2 = 87%). Similarly, an insignificant difference in weight reduction between IF and control interventions was recorded (SMD: -1.05%; 95% CI; -2.29, 0.19; P = 0.10, I2 = 96%). On the other hand, KD significantly reduced body weight compared with control diets (SMD: -1.91 kg; 95% CI; -2.96 kg, -0.85 kg; P = 0.0004, I2 = 96%). Similarly, KD had a better effect on the HBA1c percentage reduction than control diets (SMD: -2.00%; 95% CI; -3.76, -0.25; P = 0.03, I2 = 97%). IF and KD have shown reductions in HBA1c and body weight among patients with T2DM. However, the interventions are subject to side effects and should be used with caution and under the supervision of a health professional.
Ketogenic diets have been used to treat epilepsy for nearly a century. Alongside enduring clinical success with a ketogenic diet, metabolism’s critical role in health and in diseases in the central nervous system and throughout the body is increasingly appreciated. Furthermore, metabolism-based strategies have been proven equal or even superior to pharmacological treatments in specific cases and for specific diseases. Rather than causing unwanted off-target pharmacological side effects, addressing metabolic dysfunction can improve overall health simultaneously. Enduring interest in the ketogenic diet’s proven efficacy in stopping seizures and emerging efficacy in other disorders has fueled renewed efforts to determine key mechanisms and diverse applications of metabolic therapies. In parallel, multiple strategies are being developed to mobilize similar metabolic benefits without reliance on such a strict diet. Research interest in metabolic therapies has spread into laboratories and clinics of every discipline, and could yield entirely new classes of drugs and treatment regimens. This work is the first comprehensive scientific resource on the ketogenic diet, covering the latest research into the mechanisms, established and emerging applications, metabolic alternatives, and implications for health and disease. Experts in clinical and basic research share their research into mechanisms spanning from ion channels to epigenetics, their insights based on decades of experience with the ketogenic diet in epilepsy, and their evidence for emerging applications ranging from autism to Alzheimer’s disease to brain cancer.
Both scientific evidence and popular diet trends have sought to identify the ideal diet for weight loss with strategies focused on either restricting carbohydrates or fat. While there is a strong physiologic rationale for either carbohydrate restriction or fat restriction to achieve a calorie deficit needed for weight loss, evidence from randomized controlled trials suggest either type of diet is effective for weight loss. The level of adherence, rather than macronutrient content, is the driver of successful weight loss.
Background
Frequent dieting is common in athletes attempting to achieve a body composition perceived to improve performance. Excessive dieting may indicate disordered eating (DE) behaviors and can result in clinical eating disorders. However, the current nutrition patterns that underly dieting culture are underexplored in endurance athletes. Therefore, the purpose of this study was to identify the sex differences in nutrition patterns among a group of endurance athletes.
Methods
Two-hundred and thirty-one endurance athletes (females = 124) completed a questionnaire regarding their dieting patterns and associated variables.
Results
The majority of athletes did not follow a planned diet (70.1%). For endurance athletes on planned diets (n = 69), males were more likely follow a balanced diet ( p = 0.048) and females were more likely to follow a plant-based diet ( p = 0.021). Female endurance athletes not on a planned diet (n = 162) were more likely to have attempted at least one diet ( p < 0.001). Male athletes attempted 2.0 ± 1.3 different diets on average compared to 3.0 ± 2.0 for females ( p = 0.002). Female athletes were more likely to attempt ≥ three diets ( p = 0.022). The most common diet attempts included carbohydrate/energy restrictive, plant-based, and elimination diets. Females were more likely to attempt ketogenic ( p = 0.047), low-carbohydrate ( p = 0.002), and energy restricted diets ( p = 0.010). Females made up the entirety of those who attempted gluten-/dairy-free diets (F = 22.0%, M = 0.0%).
Conclusions
Being a female athlete is a major determinant of higher dieting frequency and continual implementation of popular restrictive dietary interventions. Sports dietitians and coaches should prospectively assess eating behavior and provide appropriate programming, education, and monitoring of female endurance athletes.
Background
This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of 30 common obesity myths, misunderstandings, and/or oversimplifications.
Methods
The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership.
Results
This CPS discusses 30 common obesity myths, misunderstandings, and/or oversimplifications, utilizing referenced scientific publications such as the integrative use of other published OMA CPSs to help explain the applicable physiology/pathophysiology.
Conclusions
This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on 30 common obesity myths, misunderstandings, and/or oversimplifications is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of obesity. Knowledge of the underlying science may assist the obesity medicine clinician improve the care of their patients with obesity.
Background/objectives:
Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss.
Subjects/methods:
Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding.
Results:
During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding.
Conclusions:
The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.
Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.
Liver fructose-1,6-bisphosphatase (FBPase) is a regulatory enzyme in gluconeogenesis that is elevated by obesity and dietary fat intake. Whether FBPase functions only to regulate glucose or has other metabolic consequences is not clear; therefore, the aim of this study was to determine the importance of liver FBPase in body weight regulation. To this end we performed comprehensive physiologic and biochemical assessments of energy balance in liver-specific transgenic FBPase mice and negative control littermates of both sexes. In addition, hepatic branch vagotomies and pharmacologic inhibition studies were performed to confirm the role of FBPase. Compared with negative littermates, liver-specific FBPase transgenic mice had 50% less adiposity and ate 15% less food but did not have altered energy expenditure. The reduced food consumption was associated with increased circulating leptin and cholecystokinin, elevated fatty acid oxidation, and 3-β-hydroxybutyrate ketone levels, and reduced appetite-stimulating neuropeptides, neuropeptide Y and Agouti-related peptide. Hepatic branch vagotomy and direct pharmacologic inhibition of FBPase in transgenic mice both returned food intake and body weight to the negative littermates. This is the first study to identify liver FBPase as a previously unknown regulator of appetite and adiposity and describes a novel process by which the liver participates in body weight regulation.
After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.
We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.
Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).
One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).
Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss.
To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program.
Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936)
3 academic medical centers.
307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)).
A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; <or=30% calories from fat). Both diets were combined with comprehensive behavioral treatment.
Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study.
Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years.
Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high.
Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years.
National Institutes of Health.
Two types of relatively high-protein diets, with a normal or low proportion of carbohydrates, have been shown effective for weight loss. The objective was to assess the significance of the presence or absence of carbohydrates and the proportion of fat in high-protein diets for affecting appetite suppression, energy expenditure, and fat oxidation in normal-weight subjects in energy balance. Subjects (aged 23 (sd 3) years and BMI 22·0 (sd 1·9) kg/m2) were stratified in two groups. Each was offered two diets in a randomised cross-over design: group 1 (n 22) - normal protein (NP; 10, 60 and 30 % energy (En%) from protein, carbohydrate and fat), high protein (HP; 30, 40 and 30 En%); group 2 (n 23) - normal protein (NP-g; 10, 60 and 30 En%), high protein, carbohydrate-free (HP-0C; 30, 0 and 70 En%) for 2 d; NP-g and HP-0C were preceded by glycogen-lowering exercise (day 1). Appetite was measured throughout day 2 using visual analogue scales (VAS). Energy expenditure (EE) and substrate oxidation (respiratory quotient; RQ) were measured in a respiration chamber (08.00 hours on day 2 until 07.30 hours on day 3). Fasting plasma β-hydroxybutyrate (BHB) concentration was measured (day 3). NP-g and NP did not differ in hunger, EE, RQ and BHB. HP-0C and HP v. NP-g and NP, respectively, were lower in hunger (P < 0·05; P < 0·001) and RQ (P < 0·01; P < 0·001) and higher in EE (P < 0·05; P = 0·07) and BHB (P < 0·05; P < 0·001). Hunger and RQ were lower with HP-0C than HP (693 (sd 208) v. 905 (sd 209) mm VAS × 24 h, P < 0·01; 0·76 (sd 0·01) v. 0·81 (sd 0·02), P < 0·01); BHB was higher (1349 (sd 653) v. 332 (sd 102) μmol/l; P < 0·001). ΔHunger, ΔRQ, and ΔBHB were larger between HP-0C-NP-g than between HP-NP ( - 346 (sd 84) v. - 107 (sd 52) mm VAS × 24 h, P < 0·01; - 0·09 (sd 0·00) v. - 0·05 (sd 0·00), P < 0·001; 1115 (sd 627) v. 104 (sd 42) μmol/l, P < 0·001). In conclusion, appetite suppression and fat oxidation were higher on a high-protein diet without than with carbohydrates exchanged for fat. Energy expenditure was not affected by the carbohydrate content of a high-protein diet.
Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.
Two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), are available to the public but, to our knowledge, have never been compared.
Overweight or obese outpatients (n = 146) from the Department of Veterans Affairs primary care clinics in Durham, North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus low-fat diet instruction (<30% energy from fat, 500-1000 kcal/d deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters.
The mean age was 52 years and mean body mass index was 39.3 (calculated as weight in kilograms divided by height in meters squared); 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Weight loss was similar for the LCKD (expected mean change, -9.5%) and the O + LFD (-8.5%) (P = .60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs 1.5 mm Hg) and diastolic (-4.5 vs 0.4 mm Hg) blood pressures (P < .001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A(1c) levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant.
In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters and was more effective for lowering blood pressure.
clinicaltrials.gov Identifier: NCT00108524.
The aim of the present study was to examine how weight loss treatment modulates plasma concentrations of ghrelin and insulin-like growth factor 1 (IGF-1) in obese women and to determine whether there is any association with possible changes in plasma concentrations of these hormones after weight loss.
The study group consisted of 22 obese women without additional disease (age 40.6 +/- 12.9 years; BMI 37.2 +/- 4.6 kg/m(2)). All subjects participated in a 3-month weight reduction program. The measurements were performed at baseline and after weight loss. Plasma concentration of ghrelin and IGF-1 were measured by enzyme - linked immunosorbent assay (ELISA) kit. Serum concentrations of insulin were measured by radioimmunoassay (RIA). Body composition was determined by bioelectrical impedance analysis using a Bodystat analyser.
The mean weight loss was 9.3 +/- 4.1 kg (9.7 +/- 4.3%). Following weight loss, plasma ghrelin and IGF-1 concentrations increased significantly (63.5 +/- 13.0 vs. 72.8 +/- 15.1 pg/ml; p < 0.01; 126.9 +/- 67.0 vs. 170.5 +/- 83.3 ng/ml p < 0.01, respectively) and serum insulin concentrations decreased significantly (17.5 +/- 8.5 vs. 14.8 +/- 10.4 mIU/ml p< 0.05). We observed a significant positive correlation between the increase of ghrelin and decrease of body fat percentage after weight loss (r = 0.44, p = 0.03). There are no correlations between change of ghrelin and IGF-1concentrations and between changes of insulin and IGF 1 concentrations.
Plasma concentrations of ghrelin and IGF-1 increased after weight loss. However, it seems there is no association between serum concentrations of ghrelin and IGF-1 in obese women.
To determine the optimal energy intake of very-low-calorie diets (VLCDs), 76 obese women were randomly assigned, in a double-blind fashion, to one of three liquid-formula diets: 1758 kJ/d (420 kcal/d), 2763 kJ/d (660 kcal/d), or 3349 kJ/d (800 kcal/d). Weight, body composition, symptoms, mood, and acceptability of the diet were assessed throughout the 6-mo study. There were no significant differences in weight losses or changes in body composition among the three dietary conditions at the end of treatment, nor were there significant differences among conditions in acceptability of the diet, symptoms, or mood. These results suggest that there is no clinical advantage to using VLCDs that provide less than 3349 kJ/d (800 kcal/d).
Mood, hunger, and energy intake were monitored in eight obese women before, during, and after 2 wk on a very-low-calorie diet (VLCD). Energy intake was significantly lower by approximately 30% in the week after the VLCD compared with the prediet week, both from food diaries and at a controlled ad libitum test meal. There was a gradual reduction in hunger, irritability, and urge to eat after 1 wk on the VLCD, which persisted through the postdiet week. Hunger and discontent were greatest in the evening during the first few days of the VLCD but diminished as the duration of the VLCD increased.
To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days.
On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions.
55 healthy men (age 25.6+/-0.6 y, BMI 22.6+/-0.3 kg¿m2).
VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals. Subsequently an ad libitum lunch was served and energy intake was recorded. Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 4.5 h and peak/nadir values.
CRs (range 20-61 mm) were larger for fasting and peak/nadir values compared with mean 4.5 h values. No parameter seemed to be improved by diet standardization. Using a paired design and a study power of 0.8, a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects. When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation. The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake (r=+/-0.50-0.53, P<0.001).
VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization. However, consideration should be given to the specific parameters being measured, their sensitivity and study power. International Journal of Obesity (2000)24, 38-48
The aim of the present study was to determine the impact of weight loss on appetite as measured by visual analog scale (VAS).
Seventeen subjects (10 men and seven women) took part in a 15 week weight loss program which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an energy restriction (-2930 kJ/day; phase 1) followed by an 18 week low-fat diet-exercise follow-up (phase 2). Subjects were given a standardized breakfast before and after phase 1 as well as after phase 2. Individuals were asked to fill out VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood samples were drawn before the meal and at 0, 30 and 60 min postprandially and analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also determined.
An increase in the fasting desire to eat, hunger and prospective food consumption (PFC) was observed after phase 1 and to an even greater extent after phase 2 in both men and women. In the fasting state, positive correlations were observed between changes in the desire to eat (r=0.76; P<0.05) as well as changes of PFC (r=0. 82; P<0.05) and changes in cortisol at the end of phase 1 for women. In response to phase 1, statistically significant correlations were found between changes of hunger (r=0.64; P<0.05) and desire to eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of fasting plasma cortisol in men. The most consistent predictor of changes of baseline desire to eat (r=0.68 P<0.05), fullness (r=-0.78, P<0.05) and PFC (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men. Changes of fullness were also associated with changes of fasting leptin in men (r=0.68; P<0. 05) during phase 2.
These results suggest that weight loss is accompanied by an increase of baseline appetite in both men and women and that the most consistent predictor of these changes in appetite seems to be changes in fasting plasma cortisol.
Background: Results of leptin administration in mice, rats, and humans provide a rationale for therapeutic augmentation of circulating leptin (OB protein) concentrations in obese humans; this may reduce food intake, increase metabolic rate, and lower body mass.
Objective: We assessed the effects of weekly subcutaneous pegylated polyethylene glycol (PEG)-OB protein administration on appetite and energy metabolism in obese men.
Design: We performed a randomized, double-blind, placebo-controlled trial in 30 obese men [body mass index (in kg/m²): 34.2 ± 3.6; age: 44.7 ± 7 y]. Subjects received 20 mg PEG-OB protein/wk for 12 wk while limiting their energy intake to 2.1 MJ/d.
Results: During treatment, appetite and hunger before breakfast decreased and remained lower in the PEG-OB-protein group, whereas they increased and remained higher in the placebo group (P < 0.0001). During treatment, hunger decreased in the PEG-OB-protein group (P < 0.05) and cognitive restraint increased in the placebo group (P < 0.0001). Neither appetite nor food intake changed significantly during the ad libitum evening meal. Under energy balance conditions in the respiration chamber, appetite at the end of treatment was not significantly different from baseline despite similar, significant reductions in 24-h energy intake, energy expenditure, sleeping metabolic rate, body mass, fat mass, and fat-free mass (P < 0.01 for all) in both groups.
Conclusion: Treatment with PEG-OB protein modified subjective appetite at a dosage that produced no changes in body composition, energy expenditure, or body mass loss relative to placebo treatment, suggesting that PEG-OB protein has central rather than peripheral biological activity in obese men.
Background:
Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss.
Objective:
To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program.
Design:
Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936)
Setting:
3 academic medical centers.
Patients:
307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)).
Intervention:
A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; <or=30% calories from fat). Both diets were combined with comprehensive behavioral treatment.
Measurements:
Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study.
Results:
Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years.
Limitation:
Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high.
Conclusion:
Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years.
Primary funding source:
National Institutes of Health.
Aim: Very low-energy diets are a weight loss strategy that utilises severe and controlled energy restriction to induce rapid weight loss. This review aimed to evaluate their use in terms of efficacy and safety, and to identify for whom they may be effective for weight loss.
Methods: English-language papers examining the use of very low-energy diets for weight loss in adults with a body mass index ≥30 kg/m2 and published between March 2003 and March 2010 were retrieved from health and medical databases.
Results: Eight randomised control trials, two cohort and six pre-post studies were eligible for inclusion and were assessed for methodological quality and had data extracted. The greatest initial weight loss was −22 kg, after 16 weeks of a very low energy diet. Greatest weight loss after follow up was −13.1 ± 8.0 kg and 9.1 ± 9.7 kg (7.7 ± 8.1%) after 1 and 2 years, respectively. Studies comparing the effects in males versus females yielded conflicting results. Very low-energy diets are effective for producing short-term weight loss. However not all initial weight loss is maintained long term.
Conclusion: Future studies using very low-energy diets should conduct more rigorous analyses of dietary adherence and physical activity and should be required to document side effects experienced in order to identify how and for whom they are effective in facilitating long-term weight loss in adults.
Background:
Low-carbohydrate diets remain popular despite a paucity of scientific evidence on their effectiveness.
Objective:
To compare the effects of a low-carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol, reduced-calorie diet.
Design:
Randomized, controlled trial.
Setting:
Outpatient research clinic.
Participants:
120 overweight, hyperlipidemic volunteers from the community.
Intervention:
Low-carbohydrate diet (initially, <20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (<30% energy from fat, <300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings.
Measurements:
Body weight, body composition, fasting serum lipid levels, and tolerability.
Results:
A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; P = 0.02). At 24 weeks, weight loss was greater in the low-carbohydrate diet group than in the low-fat diet group (mean change, -12.9% vs. -6.7%; P < 0.001). Patients in both groups lost substantially more fat mass (change, -9.4 kg with the low-carbohydrate diet vs. -4.8 kg with the low-fat diet) than fat-free mass (change, -3.3 kg vs. -2.4 kg, respectively). Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels (change, -0.84 mmol/L vs. -0.31 mmol/L [-74.2 mg/dL vs. -27.9 mg/dL]; P = 0.004) and greater increases in high-density lipoprotein cholesterol levels (0.14 mmol/L vs. -0.04 mmol/L [5.5 mg/dL vs. -1.6 mg/dL]; P < 0.001). Changes in low-density lipoprotein cholesterol level did not differ statistically (0.04 mmol/L [1.6 mg/dL] with the low-carbohydrate diet and -0.19 mmol/L [-7.4 mg/dL] with the low-fat diet; P = 0.2). Minor adverse effects were more frequent in the low-carbohydrate diet group.
Limitations:
We could not definitively distinguish effects of the low-carbohydrate diet and those of the nutritional supplements provided only to that group. In addition, participants were healthy and were followed for only 24 weeks. These factors limit the generalizability of the study results.
Conclusions:
Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.
Obesity is a serious health problem because of its co-morbidities. The solution, implying weight loss and long-term weight maintenance, is conditional on: (i) sustained satiety despite negative energy balance, (ii) sustained basal energy expenditure despite BW loss due to (iii) a sparing of fat-free mass (FFM), being the main determinant of basal energy expenditure. Dietary protein has been shown to assist with meeting these conditions, since amino acids act on the relevant metabolic targets. This review deals with the effects of different protein diets during BW loss and BW maintenance thereafter. Potential risks of a high protein diet are dealt with. The required daily intake is 0·8-1·2 g/kg BW, implying sustaining the original absolute protein intake and carbohydrate and fat restriction during an energy-restricted diet. The intake of 1·2 g/kg BW is beneficial to body composition and improves blood pressure. A too low absolute protein content of the diet contributes to the risk of BW regain. The success of the so-called 'low carb' diet that is usually high in protein can be attributed to the relatively high-protein content per se and not to the relatively lower carbohydrate content. Metabolic syndrome parameters restore, mainly due to BW loss. With the indicated dosage, no kidney problems have been shown in healthy individuals. In conclusion, dietary protein contributes to the treatment of obesity and the metabolic syndrome, by acting on the relevant metabolic targets of satiety and energy expenditure in negative energy balance, thereby preventing a weight cycling effect.
Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of β-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1h for β-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.
The study objective was to evaluate the effect of prescribing a low-carbohydrate diet (LCD) and a low-fat diet (LFD) on food cravings, food preferences, and appetite. Obese adults were randomly assigned to a LCD (n = 134) or a LFD (n = 136) for 2 years. Cravings for specific types of foods (sweets, high-fats, fast-food fats, and carbohydrates/starches); preferences for high-sugar, high-carbohydrate, and low-carbohydrate/high-protein foods; and appetite were measured during the trial and evaluated during this secondary analysis of trial data. Differences between the LCD and LFD on change in outcome variables were examined with mixed linear models. Compared to the LFD, the LCD had significantly larger decreases in cravings for carbohydrates/starches and preferences for high-carbohydrate and high-sugar foods. The LCD group reported being less bothered by hunger compared to the LFD group. Compared to the LCD group, the LFD group had significantly larger decreases in cravings for high-fat foods and preference for low-carbohydrate/high-protein foods. Men had larger decreases in appetite ratings compared to women. Prescription of diets that promoted restriction of specific types of foods resulted in decreased cravings and preferences for the foods that were targeted for restriction. The results also indicate that the LCD group was less bothered by hunger compared to the LFD group and that men had larger reductions in appetite compared to women.
Our objective was to examine whether elevated α-lactalbumin (αlac) protein intake compared to elevated supra sustained milk protein (SSP) and sustained milk protein (SP) intake results into a difference in body weight and body composition over a 6-month energy-restriction intervention. Body weight, body composition, resting energy expenditure (REE), satiety and blood- and urine-parameters of 87 subjects (BMI 31 ± 5 kg/m(2) and fat percentage 40 ± 8%) were assessed before and after daily energy intakes of 100, 33, and 67% for 1, 1, and 2 months respectively (periods 1, 2, and 3), with protein intake from meal replacements and 2 months of 67% with ad libitum protein intake additional to the meal replacements (period 4). The diets resulted in 0.8 ± 0.3 g/kg body mass (BM) for SP and significant higher protein intake (24-h nitrogen) of 1.2 ± 0.3 and 1.0 ± 0.3 g/kgBM for SSP and αlac (P < 0.05). Body weight and fat percentage was decreased in all groups after 6 months (SP -7 ± 5 kg and -5 ± 3%; SSP -6 ± 3 kg and -5 ± 3%; αlac -6 ± 4 kg and -4 ± 4%, P < 0.001; there was no significant group by time difference). Furthermore, sparing of fat-free mass (FFM) and preservation of REE in function of FFM during weight loss was not significantly different between the αlac-group and the SSP- and SP-groups. In conclusion, the efficacy of αlac in reduction of body weight and fat mass (FM), and preservation of FFM does not differ from the efficacy of similar daily intakes of milk protein during 6 months of energy restriction.
This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.
Acute or long-term energy deficit in lean or obese rodents or humans stimulates food intake or appetite and reduces metabolic rate or energy expenditure. These changes contribute to weight regain in post-obese animals and humans. Some studies show that the reduction in metabolic rate with energy deficit in overweight people is transient. Energy restriction has been shown in some but not all studies to reduce physical activity, and this may represent an additional energy-conserving adaptation. Energy restriction up-regulates expression of the orexigenic neuropeptide Y, agouti related peptide and opioids and down-regulates that of the anorexigenic alpha-melanocyte stimulating hormone or its precursor pro-opioomelanocortin and the co-expressed cocaine and amphetamine-regulated transcript in the arcuate nucleus of the hypothalamus. Recapitulating these hypothalamic changes in sated animals mimics the effects of energy deficit, namely increased food intake, reduced physical activity and reduced metabolic rate, suggesting that these energy-conserving adaptations are at least partially mediated by the hypothalamus.
The 825T allele of the G protein beta3-subunit gene (GNB3) is a thrifty genotype associated with an increased risk for obesity. We aimed to determine whether the 825T allele is modifying the subjective response to extended fasting.
We genotyped 108 subjects who underwent an 8-day modified medical fasting treatment [total energy intake <350 kcal (1465 kJ)/day] for the GNB3 C825T polymorphism. Perceived hunger and mood were recorded daily by self-rating visual analogue scales.
Whereas weight loss was not dependent on genotype, both mood and hunger were significantly associated with genotype, with homozygous CC genotype carriers having best mood (p = 0.004) and least hunger (p = 0.036) during fasting compared to TT genotype carriers.
Pronounced mental discomfort during fasting in 825T allele carriers might partly explain their increased risk for obesity. The strong association between the subjective response to fasting with GNB3 genotypes indicates a role of the gene in the behavioural regulation of food intake, which should be further considered in nutritional intervention studies.
Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.