The Interplay of Sarcopenic Obesity and Mental Health: A Complex Relationship

1.1 Background of sarcopenic obesity and mental disorder

Obesity and mental health issues are two pressing concerns today across the entire population in this planet. The World Obesity Atlas 2023 estimates that the global overweight and obesity (BMI ≥ 25 kg/m²) prevalence will increase from 38% in 2020 to over 50% of the world’s population by 2035 [1]. On the other hand, the prevalence of obesity alone (BMI ≥30 kg/m²) is expected to rise from 14–24%, affecting nearly 2 billion individuals, including adults, adolescents and children [1]. A growing number of high- and middle-income countries are presently facing severe obesity epidemic, while among low-income countries, steeper increase in the prevalence of obesity is observed [2]. The high prevalence of obesity will put economic in burden in terms of healthcare costs, economic productivity, as well as premature retirement or death [1].

Besides the rise in obesity prevalence, attention should be paid to the global prevalence of mental illness. A large-scale epidemiology study conducted in 29 nations revealed the risk for any mental illness by age 75 years to be around one in two people [3] suggesting by age 75 years, approximately half the population can be expected to develop one or more mental illnesses. This is a concerning issue as the predicted prevalence was a significant increase from data available from WHO just a few years back in 2019, whereby, one in every eight people, or 970 million people around the world were living with a mental illness [4]. Mental illnesses are associated with poor health outcomes in the affected individuals [5]. Mental illnesses encompass substantial disruptions in thinking, emotional regulation or behaviour [4], which may additionally impact individuals experiencing comorbidities such as obesity, including specific conditions, such as sarcopenic obesity.

Sarcopenic obesity is a condition, whereby there is coexistence of sarcopenia and obesity and is characterised by decreased muscle mass, strength and performance along with abnormally excessive fat mass [6]. There have been varying definitions and criteria for sarcopenic obesity. It is worthy to note that in 2022, a consensus on definition and diagnostic criteria has been reached jointly by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), as shown in Figure 1 [6].

Based on the consensus, the evaluation of sarcopenic obesity is divided into two stages: screening and diagnosis [6]. At the screening stage, patients will be assessed based on:

1. Body mass index (BMI) or waist circumference using ethnicity-specific cut points, and;

2. Indicators for sarcopenia, which can include clinical evaluation or validated questionnaires.

If the patient has positive screening of both the condition of obesity and sarcopenia, the evaluation will move on to the diagnosis phase, which will be performed in the order of two steps:

1. Assess for altered skeletal muscle functional parameters, for example, hand-grip strength and chair stand test, if the finding is positive, proceed to the following step.

2. Assess for altered body composition, aiming to look for increased fat mass and reduced muscle mass. Assessment techniques can be dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA).

Computerised tomography (CT) imaging is not usually needed unless clinically indicated for additional diagnostic reasons in specific cases.

This approach demonstrates a comprehensive evaluation combining both functional and compositional aspects for an accurate diagnosis of sarcopenic obesity.

As for mental illness, the diagnosis is usually made based on the below three available diagnostic manuals, namely the eleventh revision of the International Classification of Diseases (ICD) by WHO in 2018 [7], the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric Association (APA) in 2013 [8] and the Research Domain Criteria (RDoC) project initiated by the U.S. National Institute of Mental Health (NIMH) in 2009 [9]. The DSM-5 and the ICD Classification of Mental and Behavioural Disorders are the most widely recognised frameworks for both classifying and making psychiatric diagnoses. With a standardised framework and set of criteria that the clinicians can follow, they promote uniformity and accuracy in the identification and classification of mental health conditions.

Evidence shows that sarcopenic obesity in adults is associated with adverse mental health and a lower quality of life compared to body mass index-based general obesity [10]. Among all the mental illnesses, depressive symptoms are the most commonly studied conditions within the sarcopenic obesity population, particularly among older adults [11, 12]. The evidence indicates that sarcopenia and obesity appear to exert a synergistic impact on the risk of mental health compared to obesity alone. However, it is acknowledged that younger populations are also susceptible to developing sarcopenic obesity [13], as well as experiencing mental illness [14].

Therefore, we should raise awareness of the potential development of both mental health conditions and sarcopenic obesity as they can manifest in individuals of any age. The interrelated relationship between sarcopenic obesity and mental health highlights the importance of recognising and addressing these conditions comprehensively. By promoting awareness and understanding of the potential coexistence of mental health challenges and sarcopenic obesity across all age groups, we can foster early detection, intervention and holistic care strategies for individuals facing these interconnected health concerns.

1.2 Pathogenesis of sarcopenic obesity

As sarcopenic obesity is a syndrome consisting of two multifactorial and overlapping mechanisms of clinical condition (i.e., sarcopenia and obesity), it is difficult to pinpoint one clear disease mechanism [15]. However, there are a few proposed theories to explain the pathogenesis of sarcopenic obesity.

1.2.5 Ageing and lifestyle factors

With ageing, it is common to observe reduced physical activities and inadequate dietary intake of protein, which could cause sarcopenic obesity [19]. Not to mention ageing itself is associated with reduced resting metabolic rate, reduced muscle mass, increased visceral fat and ectopic fat accumulation [12].

The pathogenesis of sarcopenic obesity is summarised in Figure 2. Collectively, the typical physiological changes associated with ageing, coupled with environmental factors, such as sedentary lifestyle and an unhealthy diet, create a foundation for the development of sarcopenic obesity. The intricate interplay of these elements sets the stage for interacting and overlapping mechanisms, including inflammation, oxidative stress and insulin resistance. Increased awareness of these interconnected mechanisms is essential for developing targeted interventions that address both the physiological aspects of ageing and the lifestyle factors that contribute to the complex landscape of sarcopenic obesity.

2.1 Sarcopenic obesity and its impact to physical health

Sarcopenic obesity is related to several physical health consequences:

1. Increased ADL disability, increased frailty, increased fall risk, reduced grip strength and poor functional outcomes [12, 24, 25].

2. Higher risk of cardiovascular disease (CVD) and mortality [18]. Pro-inflammatory state in sarcopenic obesity as depicted under pathogenesis induces vascular endothelium damage and leads to atherosclerosis—a common pathological culprit for many cardiovascular diseases. It also exacerbates insulin resistance, which also triggers endothelial dysfunction [18], forming a vicious cycle, which is a phenomenon commonly observed in the complex disease mechanism of sarcopenic obesity.

3. Positive correlation to diabetes, hypertension, dyslipidaemia and non-alcoholic fatty liver disease [12, 26, 27].

4. Higher risk of knee osteoarthritis and osteoporosis [12], and poorer therapeutic outcomes for osteoarthritis with increased surgical risk post-joint arthroplasty [28]. Therapeutic outcomes for osteoarthritis and surgical risk and recovery after joint arthroplasty.

5. Higher CVD-related and all-cause mortality [12, 29].

In a broader context, the complex clinical syndrome of sarcopenic obesity demonstrates more pronounced adverse effects on physical health when compared to obesity alone [30]. Overall, sarcopenic obesity is associated with various adverse physical health outcomes, including increased disability in activities of daily living, heightened frailty, elevated fall risk, diminished grip strength and poorer functional outcomes. It also contributes greater effect on metabolic disorders driven by a pro-inflammatory state, inducing vascular damage and atherosclerosis.

2.2 Sarcopenic obesity (SO) and its relationship to mental health

From the previous epidemiological, cross-sectional and longitudinal studies, there is an established association between obesity and mental health disorders, most commonly mood disorders [10]. Several studies have also shown relation between sarcopenia and depression [31, 32, 33]. But when the focus is zoomed into the specific clinical syndrome of sarcopenic obesity, there are less studies available. Furthermore, mixed findings have been reported with some studies found no signification correlation between the complex clinical syndrome and mental health impact. One example is a cross-sectional study, involving over 7000 patients conducted in Korea from 2010 to 2011 [34].

The unclear relation warranting more reliable studies with larger sample size and consistent criteria to be done is supported by a systemic review by Pilati et al. published in 2021, with conflicting results among a few of the cross-sectional studies included [35, 36]. Nonetheless, the heterogenous results are not surprising given the inconsistent definition and measurement criteria of sarcopenic obesity [37]. When the measurement is based on muscle strength, there is a great association with depressive symptoms [34, 35]. Having said that, and with the challenge of sarcopenic obesity being a relatively newly recognised clinical syndrome, we managed to collate some evidence that exhibits positive correlation between sarcopenic obesity and negative mental health impacts:

3.1 Bulimia nervosa

Recurrent episodes of binge eating in a discrete period of time, involving a large amount of food and a sense of lack of control, with inappropriate compensatory behaviours, which have occurred for at least once weekly for 3 months.

3.2 Binge-eating disorder

Recurrent episodes of binge eating as described above, with the features of eating more quickly than usual, eating until feeling uncomfortably full, eating large amount of food despite not feeling hungry, eating alone because of embarrassment, feeling of guilt and disgust and depression after the episodes, which have occurred for at least once weekly for 3 months.

3.3 Night-eating syndrome (listed under “other unspecified eating disorders” in DSM-5)

Recurrent episodes of night eating, usually characterised by eating after waking up from sleep, or by excessive food intake after evening meal, which causes marked distress or functional impairment.

The prevalence of binge-eating disorder, night-eating disorder, and bulimia nervosa increases with increasing BMI [50, 51]. For example, individuals with binge-eating disorders are at three to six times risks suffering from obesity than general population, apart from having higher prevalence of obesity-associated physical comorbidities [50]. Data from a study conducted in the United States involving over a thousand of patients showed that among patients with binge-eating disorder and bulimia nervosa, 87 and 33% of the respective group also experienced obesity [52].

The bidirectional relationship between eating disorders and obesity has been well-studied. The factors contributing to that include genetic predisposition and personality risk factors, whereby mood dysregulation and negative evaluation of self and body image contribute to the vicious cycle of binge eating and poor weight control, dysregulated hypothalamic-pituitary-adrenal axis, which is associated with both obesity and eating disorders, disrupted gut microbiota, which has recently raised academic interest in regards to its association with metabolic disorders and the link between gut microbiota and eating disorder has been demonstrated to affecting up to 10% of the population [53].

Focusing specifically on sarcopenic obesity, to date, there is no established evidence of its correlation with eating disorders in general. Eating disorders are prevalent among adolescents and young adults, particularly among females. A large sample study conducted in Austria showed that as high as 31% of females aged 10–18 years old are at risk of developing eating disorder [54], and that is associated with risk factors of vulnerable self-image and body image dissatisfaction as supported by a systemic review in 2015 and a Swedish study [55, 56]. In contrast, sarcopenia is an age-related clinical condition and is more commonly found among elderly patients with multiple comorbidities [57].

Having said that, eating disorders do occur among elderly age group. Such evidence has been available from a systemic review conducted 10 years ago, looking into reported cases of eating disorders among those who are over the age of 50 [58]. The reported age of onset ranged from 50 to 94 years old, with 88% of them being females. While more than half of the reported cases were anorexia nervosa, 10% of the cases were bulimia nervosa [58]. An epidemiological study focusing on 342 females with age of 65–94 years in Portugal demonstrated binge-eating episodes among around 6% of the females, and 18.9% prevalence of picking/nibbling, which is associated with increased BMI [59].

Although eating disorder is rarely considered among elderly patients in day-to-day clinical practice, the above information is valuable to remind us not to overlook the possibility of eating disorder in older age groups. In these cases, especially among patients with comorbid mental health conditions, such as depressive disorders, sarcopenia can become another possible comorbid clinical condition. The mechanisms are as discussed in previous section. With that predisposition, elderly patients, particularly those with eating disorders, can be at risk of developing sarcopenic obesity. However, in a practical clinical setting, it can be challenging to pinpoint this specific condition as elderly patients with complex medical conditions often do not present with only one specific issue. There might be other more pressing medical issues that need prioritisation compared to sarcopenic obesity itself. In an ideal circumstance where there is a realistic capacity to deal with a patient holistically, managing both the eating disorder and sarcopenic obesity can evidently improve the quality of life of the patient.

4.1 First-line management: exercise programme

Resistance exercise is presently recognised as the most effective exercise programme for sarcopenic obesity, having demonstrated its ability to enhance and preserve muscle mass, improve muscle function [60], and increase both muscle strength and overall physical performance [61]. Additionally, resistance exercises play a crucial role in mitigating the pathological progression of sarcopenic obesity by downregulating inflammatory cytokines, reducing oxidative stress and enhancing mitochondrial function [62].

Aerobic exercise is recommended as a strategy to address sarcopenic obesity given its known benefits of enhancing insulin sensitivity [63] and reducing oxidative stress [64]. Although there is limited evidence available regarding the specific effects of aerobic exercise on sarcopenic obesity, it appears to be an effective approach for reducing excess fat mass and enhancing muscle performance in this population [65]. Despite the limited evidence, aerobic exercise is recognised as a valuable therapeutic intervention for weight control management.

Recent meta-analysis evidence indicates that BMI decreases only in the group that undergoes combined resistance and aerobic training. While per cent body fat decreases with both resistance and aerobic training, the most significant reduction occurs in the group that engaged in both exercise types. Notably, muscle strength shows substantial improvement with resistance exercise [66]. Implementing an exercise programme that combines both resistance and aerobic exercises appears to offer additional benefits to individuals with sarcopenic obesity. However, it is crucial to acknowledge that there is no one-size-fits-all approach, the key lies in determining the specific needs of each individual with sarcopenic obesity to tailor a beneficial exercise regime [67].

4.2 Weight management: dietary therapy

Hypocaloric diet with the restriction of energy intake has been proposed as a weight loss strategy for sarcopenic obesity. The optimal and safe range of energy restriction is an energy deficit of about 200–700 kcal per day [68] or prescription of 1200–1800 kcal/day calorie-restricted diet for sarcopenic obese older adults [69]. However, in obese older adults, an energy-restricted diet designed for weight loss often results in the simultaneous loss of both fat mass and skeletal muscle mass. This is particularly concerning for sarcopenic obese older adults as the loss of skeletal muscle mass significantly impacts their ability to walk or climb stairs, highlighting the potential negative consequences of calories restriction weight loss interventions in this population [65].

Studies suggest that a high protein intake may enhance muscle mass and strength during calorie restriction for sarcopenic obesity [70]. Therefore, a weight loss diet in this population should prioritise the preservation of muscle mass and could benefit from incorporating a high protein diet and/or protein supplementation [71]. Generally, the recommended protein intake for sarcopenic obesity individuals falls within the range of 1.0 to 1.8 g/kg BW/day [71]. Some literature suggests a more conservative protein intake recommendation, ranging from 1.0 to 1.2 g/kg BW, with an even higher intake (1.2–1.5 g/kg BW), especially for individuals dealing with chronic diseases [65]. However, caution is advised for a protein intake of 1.4 g/kg BW in individuals with kidney disease [71].

According to the latest evidence, the most promising approach to sarcopenic obesity involves a combination of exercise training, especially resistance training, and an increased protein intake using protein supplements [71]. Regarding sarcopenia, protein supplementation, with or without exercise, has been shown to positively improve muscle mass, strength and physical function in older adults with sarcopenia [72]. A recent systematic review identifies whey protein supplementation as effective for individuals in the sarcopenic obesity population [60, 71]. Simultaneously, it is also acknowledged that a proper diet and exercise are crucial components in the prevention of sarcopenic obesity [60]. Recognising the varied presentations of sarcopenic obesity, such as constraints in performing resistance exercises for certain patients, a patient-centred approach tailored to the individual’s lifestyle is essential in the treatment of both sarcopenic obesity and mental health. Additionally, micronutrient supplementation should be considered in the event of deficiencies occurring during the weight loss intervention period.

4.3 Weight management: medical/surgical

Medication option for weight loss in sarcopenic obesity could be glucagon-like peptide-1 receptor agonist (GLP-1RA) [18]. GLP-1 agonist is a drug commonly used in obesity and diabetes mellitus with reasonable safety profile [73]. Apart from anti-diabetic function, GLP-1 analogues or agonists result in weight loss by decreasing appetite and delaying gastric emptying. Most critically, it reduces fat mass as opposed to lean muscle mass [74].

Semaglutide is a GLP-1 agonist known for its substantial impact on weight loss and is among the FDA-approved drugs for treating obesity, along with liraglutide [75]. However, its potential influence on muscle improvement is a relatively recent consideration. In a recent animal study, semaglutide and liraglutide are shown to be able to decrease excessive lipid deposition and improve obesity-induced muscle atrophy at the same time [76]. The findings support a previous animal study in 2022, which reported the effect of muscle protein synthesis in obesity from semgalutide [75].

Bariatric surgery is an effective surgical procedure to help with weight loss in sarcopenic patients, but the outcome in improvement of daily living activities is elusive [77]. A 2-year follow-up study in 2021 observed early loss of fat-free mass in patients with sarcopenic obesity post-bariatric surgery [78]. However, it is essential to highlight that the study lacks a control group for comparison. Further, research is warranted to thoroughly investigate the suitability of bariatric surgery for individuals with sarcopenic obesity. On a positive note, there is a potential solution to address or prevent sarcopenia postoperatively implementing an exercise intervention programme to counteract muscle mass loss following bariatric surgery [79].

4.4 Hormonal replacement

While testosterone replacement may appear to be a plausible treatment from a physiological perspective, it is currently not recommended for addressing obesity or sarcopenia [18]. Looking ahead, selective androgen receptor modulators (SARMs) emerge as a potential future hormonal treatment given their selective binding to androgen receptors in muscles and bones, promoting anabolic processes without exerting systemic effects [18, 80]. However, due to potential side effects, further clinical studies are necessary before their clinical use can be approved [80].

4.5 Management of comorbid mental illness

The connection between sarcopenic obesity and mental illness remains unclear, with evidence suggesting a potential link between sarcopenic obesity and depressive disorders [12]. However, a systematic review has indicated that the results are heterogeneous due to significant variability in assessment methods and outcome measurements for sarcopenic obesity and depressive disorders [81]. Notably, patterns of comorbidity between sarcopenic obesity and the prevalence of depression have been observed, as highlighted in a recent systematic review and meta-analysis reporting a high prevalence of depression in patients with sarcopenia across nineteen included articles [82]. Research focusing on other mental health conditions is relatively scarce.

Selective serotonin reuptake inhibitors (SSRIs), namely escitalopram, sertraline, paroxetine, fluvoxamine, vortioxetine and fluoxetine, are widely prescribed as a first-choice treatment for various mental health conditions [83]. While SSRIs are popular, it is important to note their contraindication with concurrent use of MAOIs (e.g., linezolid), which can elevate serotonin levels and pose a risk of life-threatening serotonin syndrome [84]. Clinical responses to SSRIs may take several weeks (e.g., 6 weeks) as adaptive processes require time to take effect [85]. During the treatment process, it is imperative to closely monitor any adverse metabolic changes and vital signs, especially considering that sarcopenic obesity is associated with several clinical complications.

The treatment model combining a selective serotonin reuptake inhibitor (SSRI) with psychotherapy, such as cognitive behavioural therapy (CBT), has proven to be more effective. A meta-analysis of randomised trials utilising regression analyses to test the relationship between continuous variables and effect size concluded that monotherapy with medication may not be optimal for common mental illness. The combined treatment approach was found to be more effective than medication alone, particularly for mental illness, such as depression [86]. These findings are, further, supported by recent meta-analysis review papers, focusing on adults with depression [86].

Another treatment model, known as the sequential model treatment, involves the sequential combination of pharmacotherapy and psychotherapy and has been investigated in patients with major depressive disorder (MDD). The findings from this comprehensive examination and meta-analysis suggest that the sequential incorporation of psychotherapeutic treatment following a positive response to acute-phase drug therapy, either independently or in conjunction with antidepressant medication, is correlated with a reduced likelihood of relapse and recurrence in MDD patients [87].

In the case of eating disorders, multidisciplinary approach is essential to ensure input from medical, mental health and dietetics team. The framework of management will only be discussed briefly here for an overview understanding as eating disorder is a broad topic with different management plan depending on the specific type of diagnosis. According to Clinical Practice Guidelines in Australia, the first-line treatment for bulimia nervosa and binge-eating disorders is psychological therapy, that is, CBT. Behavioural weight loss can be initiated for weight management. Tricyclic antidepressants have shown to be of use to patients with bulimia nervosa, but this class of medication is notorious for their wide range of side effects. High-dose fluoxetine up to 60 mg per day can be effective in controlling bulimia nervosa. Other SSRIs can be considered for both bulimia nervosa and binge-eating disorder. Topiramate, an antiepileptic medication, is useful for both the conditions as well and is associated with weight loss, but there are side effects of taste changes and paraesthesia [88]. It is important to keep in mind the criteria for medical admission if there is significant physical deterioration from eating disorders; otherwise, the management is generally outpatient-based [88].

In summary, a multidisciplinary management approach tailored to each patient should be adopted for sarcopenic obesity with mental disorders. Figure 3 above summarises the multidisciplinary management for sarcopenic obesity with mental disorders discussed earlier. First-line management includes foundational exercise programmes, while second-line strategies encompass high protein intake or micronutrient supplementation. We do not recommend weight loss diets for this population. If necessary, hormonal replacement therapy may be considered. In cases of sarcopenic obesity with mental illnesses, the patients should be referred to the psychiatric or mental health team as appropriate for further evaluation and consideration of the adoption of SSRIs and psychotherapy.

4.6 Multidisciplinary management: final consideration/challenges

Sarcopenic obesity treatment is a comprehensive undertaking that involves a combination of muscle training exercises and dietary therapy. However, if mental illness coexists with sarcopenic obesity, the treatment process becomes even more complex. An essential aspect of the treatment approach is to assess the patient’s readiness to accept the proposed treatment plan. On the other hand, the socio-economic status of the individual can influence access to resources, affordability of specialised treatments and overall healthcare engagement. Additionally, understanding the patient’s eating behaviours, nutritional preferences and lifestyle choices becomes crucial in tailoring an effective and sustainable treatment regimen.

Depending on the priority and severity of each condition, whether to focus on addressing the mental disorder first, sarcopenic obesity or both concurrently, requires careful planning. Given the lack of specific evidence guiding this specific decision making process, clinical judgement plays a significant role in guiding the direction of management. Early referral and involvement of multidisciplinary and interdepartmental team would evidently be beneficial in dealing with the complex clinical syndrome. For example, in patients with co-existing sarcopenic obesity and depressive disorders, involvement of medical team for physical assessment and addressing further underlying medical issues would be essential. Involvement of dietetics and physiotherapy team is valuable to offer input on dietary or nutritional advice and appropriate exercise programme to address the sarcopenic obesity. If the disordered mood is suspected, mental health team should be referred for further assessment and specialised management. This is a significant step as depressive mood can cause lack of motivation for patients to take part in a comprehensive plan in managing this complex clinical syndrome and cause further deterioration in physical health, contributing to the vicious cycle of the bidirectional relationship between sarcopenic obesity and depressive disorders. Eating disorders are rarely directly related to sarcopenic obesity, but if found to be the case, should be dealt with as well. But as discussed prior, the management would depend on the clinical priority and multidisciplinary team discussion as those patients often have complex chronic medical conditions.

Additionally, considerations of the cost of treatment and the potential economic burden on the country should not be overlooked, adding another layer of complexity to the overall treatment strategy. Balancing these various factors is crucial for developing a tailored and effective treatment plan for individuals dealing with both mental disorders and sarcopenic obesity. This broader perspective ensures a more nuanced and personalised treatment strategy that addresses the complex interplay between mental health, sarcopenic obesity and the broader contextual factors influencing the patient’s well-being.