The challenge of multimorbidity

Multimorbidity, the coexistence of two or more long-term medical conditions or diseases^{(Reference Wallace, Salisbury and Guthrie1)}, is becoming increasingly common in the UK with an estimated prevalence of 27 % of those in primary care, a higher prevalence in women than men (30 % v. 24 %), in those with lower socioeconomic status and increasing with age (3·8 % in 18–24 y olds to 83 % in those aged 85 y and above)^{(Reference Cassell, Edwards and Harshfield2)}. There are many health and nutrition implications of suffering from multimorbidity which is often, but not always, observed in older persons. As life expectancy increases and individuals acquire a variety of chronic illnesses, multimorbidity is a huge challenge facing healthcare and social services. This is confirmed in the recent report by the Chief Medical Officer for England^{(Reference Whitty3)} who highlighted the challenge we face from the ‘inexorable rise of multimorbidity’ and the need for the right resources and skills to manage the complexity of multiple long-term conditions. One of these complexities is the nutritional consequences of multimorbidity which can result in malnutrition and the need for the right skills and resources to deliver effective and appropriate dietary and nutritional care to improve outcomes. As part of the National Institute for Health and Care Excellence (NICE) guidelines (NG56, 2016)⁽⁴⁾ and standard (QS153)⁽⁵⁾ for managing multimorbidity they recommend reviewing non-pharmacological treatments, such as diets (and exercise) to assess likely benefits, harms and outcomes for the individual patient. Furthermore, the WHO Integrated Care of Older People report, which considers the challenges associated with ageing, with multiple conditions and the associated frailty, also refers to malnutrition and the need to consider dietary advice and nutritional interventions when managing the decline in intrinsic capacity in older people⁽⁶⁾. The purpose of this review is to focus on the inter-relationship of malnutrition and multi-morbidity, exploring both the identification and management of malnutrition and the potential for reductions in treatment burden with appropriate nutritional management in primary care.

Inter-relationship of malnutrition and multi-morbidity

Malnutrition can result from the effects of chronic diseases and conditions, the associated symptoms (e.g. breathlessness, gastrointestinal symptoms, pain etc) and management (including the effects of pharmacotherapy and polypharmacy) on appetite and nutritional intake, sometimes resulting in an inability to meet nutritional requirements from food alone^{(Reference Stratton, Green and Elia7,Reference Elia8)} . In addition to anorexia, individuals may have problems eating (due to dentition, difficulty swallowing etc), weakness and disability limiting shopping, cooking, preparing or eating food and drink, or psycho-social challenges that impair intake. The ongoing gap between nutritional intake and nutritional requirements for energy, protein and other nutrients, including micronutrients, leads to malnutrition^{(Reference Stratton, Green and Elia7,Reference Elia8)} . Although in practice the indicators that are used initially to screen for malnutrition can include thinness (low BMI) and unintentional weight loss (that result from inadequate nutritional intake), these indicate risk of malnutrition, as malnutrition per se can encompass physical loss of body tissue, loss of fat mass and loss of muscle mass (sarcopenia), the resulting loss of function (e.g effects on immune system, loss of muscle strength, reduced activity or quality of life etc.) and the poorer outcomes that result from these nutritional deficits^{(Reference Elia8–Reference Elia and Stratton10)}. In many older individuals with multi-morbidity, frailty is present, a multi-component geriatric syndrome^{(Reference Fried, Tangen and Walston11)}. Malnutrition, which includes the loss of muscle mass & strength because of nutritional deficits (as opposed to age-related and other causes of sarcopenia), can be one of many contributors to this condition^{(Reference Fried, Tangen and Walston11,12)} .

Unfortunately, malnutrition (undernutrition) remains prevalent in our society despite all the advances and innovations in medical care^{(Reference Elia and Stratton13)}. A recent survey undertaken by the Malnutrition Action Group of BAPEN using ‘MUST’ showed that malnutrition was common in primary care including in individuals in their own homes (56 % at risk) and in care homes (55 % at risk) as well as in those in hospital settings (44 %) (Fig. 1)^{(Reference Stratton, Cawood and Anderson14)}. The main cause of malnutrition remains disease, accentuated by multiple co-morbidities and in the survey, malnutrition prevalence was highest in individuals with cancer (62 %), gastrointestinal conditions (50 %), respiratory conditions (48 %), frailty (45 %) and neurological diseases (43 %).

Fig. 1. Malnutrition risk according to setting in the UK

Other research using a secondary analysis of data from the National Diet and Nutrition Survey (NDNS)^{(Reference Finch, Doyle and Lowe15)} has indicated the greater prevalence of malnutrition with increasing age^{(Reference Elia and Stratton13)}, 10·7 % aged 65–74y; 14·7 % 75–84y; 17·7 % > 85 y; overall 13·9 % of older people (aged 65 y and over) are at risk of malnutrition in England)^{(Reference Elia and Stratton13)} within which the higher prevalence of multimorbidities will be a factor. In addition, the same analysis showed geographical inequality with a north-south divide showing a higher prevalence of malnutrition in older people in the North v. the South of England^{(Reference Elia and Stratton13)(Reference Stratton16)}). Similarly, there is a higher prevalence of both multimorbidity and disease-related malnutrition in areas of greater socioeconomic deprivation (using the Index of Multiple Deprivation)^{(Reference Cassell, Edwards and Harshfield2,Reference Whitty3,Reference Stratton16,Reference Stratton and Elia17)} . Alongside protein-energy malnutrition in older individuals with multimorbidities, research also indicates low intakes and/or poor status of some key micronutrients (e.g. Table 1),^{(Reference Stratton, Green and Elia7,Reference Elia and Stratton13,Reference Stratton16,Reference Elia and Stratton18)} .

Table 1. Poorer vitamin status with risk of malnutrition in community living elderly individuals (secondary analysis of NDNS^{(Reference Elia and Stratton18)})

Results presented as mean ± se.

* Number of subjects varies according to vitamin measured.

With the ongoing high rates of malnutrition, this condition is extremely costly for our society. In England, it is estimated to cost at least ∼£19·6 billion (published in 2015) (∼£23·5 billion for the UK)^{(Reference Elia19)} (Fig. 2), about 15 % of the total expenditure on health and social care. Most of the costs of malnutrition are in health care (£15·27bn), mostly secondary care, with £4·36bn from social care. The health and social care costs are estimated to be 3x greater for a malnourished patient (£7408) than a non-malnourished patient (£2155). Costs of malnutrition are likely to rise in the future as the population ages and multimorbidity grows. Older adults (aged 65 years and over) already account for 52 % of the total costs of malnutrition, with the remainder from younger adults (< 65 years) and children (see Fig. 2)^{(Reference Elia19,Reference Stratton, Smith and Gabe20)} .

Fig. 2. Estimated costs of malnutrition in England according to age group

Most of the costs arise due to the deleterious effects of malnutrition on individual’s function, clinical outcome and recovery leading to a substantially greater burden on treatment and health care resources. The consequences of untreated malnutrition include physical decline (loss of muscle mass, impaired growth in infants and children), impaired psychosocial function, functional decline with reduced muscle strength, fatigue and inactivity, reduced quality of life, poorer clinical outcomes (e.g. increased infections, poor wound healing, mortality), and greater health care use (more hospital (re)admissions, longer hospital stays, more general practitioner (GP) and health care professional (HCP) visits, increased prescription costs) (see^{(Reference Stratton, Green and Elia7)} for more details). The high costs are not because of expenditure on strategies to manage malnutrition, estimated to be a very small proportion of the overall costs of malnutrition (<2·5 %)^{(Reference Stratton, Smith and Gabe20)}. Indeed, some reports still indicate that not only is malnutrition under-identified, but that a significant proportion do not get nutritional support^{(Reference Stratton, Cawood and Anderson14,Reference Stratton, Smith and Gabe20–Reference Stratton, Beggs and Holmes22)} .

The consequences and costs of malnutrition could be significantly curtailed if malnutrition was prevented or identified and treated earlier and/or more effectively^{(Reference Elia19)}. For effective prevention strategies, a far greater awareness is needed in the population about malnutrition, with appropriate public health and government policies and resources in place to tackle the causes early⁽²³⁾. However, the scope of this review is the identification and management of malnutrition in those with multimorbidity rather than prevention.

Identification of risk of malnutrition in multi-morbidity

Effective ways of identifying malnutrition in those with multimorbidity in primary care are needed that are simple, practical and easy to implement and that are linked to an appropriate treatment and action plan. The first step to tackling malnutrition in those with multimorbidity is to undertake routine screening, as NICE CG32⁽²⁴⁾ and QS24⁽²⁵⁾ recommend, incorporating use of a simple, validated nutritional screening tool into pathways of care for multimorbidity where feasible and ethical in individual patients. The Malnutrition Universal Screening Tool ‘MUST’^{(Reference Elia8,Reference Todorovic, Russell and Stratton26)} can be used by health and social care professionals to screen for malnutrition in all settings in adults (see resources for HCPs to freely use on the BAPEN website and an online ‘MUST’ calculator (www.bapen.org.uk/screening-and-must/must-calculator)). Other screening tools are available for HCPs to use to screen infants, children and adults (see^{(Reference Elia and Stratton10)} for more information). The objective measures in ‘MUST’ were carefully chosen and validated to predict those adults who will benefit from nutritional intervention, whilst keeping the tool simple and fast to complete. Some other screening tools, and assessments that have compared different screening tools, have focussed primarily on a tool’s ability to predict outcomes^{(Reference Elia and Stratton10,Reference Elia and Stratton27)} . This serves a different purpose, which may or may not relate to an individual’s response to nutritional treatment (see^{(Reference Elia and Stratton10)} for a more detailed review of screening tools and a very recent publication addressing this topic^{(Reference Wunderle, Siegenthaler and Seres28)}).

Screening is likely to be needed regularly as an individual with multiple clinical conditions (who also often requires many different medications) means nutritional problems and requirements may frequently change. Re-screening is also important when an individual moves between different health and social care settings and as such using the same tool (like ‘MUST’) facilitates continuity. Embedding the results of malnutrition screening into GP systems is vitally important, especially in those with multimorbidity, with the aim to ultimately have fully integrated systems to monitor individuals across all health and social care settings.

The results of screening must be linked to an action plan that meets the complex needs of the individual with co-morbidities. In some cases, a more detailed nutritional assessment will be needed, especially where multiple conditions mean individualised assessments and treatments are required, with consideration for the requirements of the full spectrum of macro- and micro-nutrients. Dietitians are specifically trained and expert in this area and can also advise many of those with multiple complex conditions identified with malnutrition who will require some form of nutritional support.

There is also a role for empowering both patients with multimorbidity and their carers to take more ownership of their nutrition. A self-screening version of ‘MUST’ has been developed for patients and carers to use to screen themselves (www.malnutritionselfscreening.org), and this and other resources (e.g. www.malnutritionpathway.co.uk ⁽²⁹⁾) provide simple information for patients.

Nutritional management of malnutrition in multi-morbidity

Once identified with screening and assessment as relevant, malnutrition should be managed in a timely, tailored and evidence-based way with an optimal diet, and provision of nutritional support, such as prescription of oral nutritional supplements for those who can be managed orally, and with the use of enteral tube feeding and/or parenteral nutrition where indicated⁽²⁴⁾.

By improving the nutritional intake and status of those with malnutrition associated with multimorbidity, relevant outcomes can be improved and the burden on society reduced (Fig. 3). If nutritional and dietary interventions do not improve nutritional intake, they are unlikely to be effective.

Fig. 3. Pathway by which nutritional interventions improve nutritional intake to improve outcomes

Maximising food intake

In patients at risk of malnutrition, dietary intake should be maximised as much as is feasible in those with multimorbidity and polypharmacy^{(Reference Stratton30,Reference Cawood and Gandy31)} . Food-based interventions (snacks, dietetic-led dietary advice) and other ways to encourage food intake (music, physical therapy, socialising etc.) exist that may support those with malnutrition in primary care, subject to the right resources. Both the British Dietetic Association⁽³²⁾ and the malnutrition pathway⁽²⁹⁾ have further tailored information on maximising dietary intake in those with disease-related malnutrition, although further individualisation is likely in those with multimorbidity. Whilst maximising oral intake from the diet is a crucial first and fundamental step, where its safe and not contra-indicated, the ability of these interventions alone to improve total nutritional intakes enough may be limited by disease or medication-related anorexia. Skilled dietetic resource and expertise is needed in the primary care setting to enable effective nutritional intervention and as highlighted in the recent Chief Medical officers report^{(Reference Whitty3)}, further investment in resources skilled in managing multimorbidity is needed in the future.

Role of oral nutritional support in malnourished, multimorbid individuals

Nutritional intake

A more ‘medicalised’ dietary approach using liquid oral nutritional supplements in conjunction with maximising the intake of food, can be a useful addition to the toolkit for managing the malnourished person with multiple chronic illnesses in primary care and beyond. A wealth of evidence has shown the value of using oral nutritional supplements, in addition to the diet, improving intake in individuals with a variety of illnesses and diseases^{(Reference Stratton, Green and Elia7,Reference Hubbard, Elia and Holdoway33–Reference Kaegi-Braun, Kilchoer and Dragusha37)} . In RCT, ONS typically have little impact on appetite sensations, adding to rather than replacing food intake, and so effectively improving energy, protein and micronutrient intakes^{(Reference Stratton, Green and Elia7)}. In comparative trials in older patients, in both care homes and free-living individuals, ready-made liquid ONS improve nutrient intakes to a significantly greater degree than food alone over 12 weeks (e.g.^{(Reference Smith, Cawood and Walters38–Reference Elia, Parsons and Cawood40)} see Table 2). Despite significantly greater energy and protein intakes with liquid ONS in very elderly individuals with multimorbidity in care homes, sensations of hunger were not suppressed (ONS group 38mm, dietary advice group 39mm) and fullness sensations were significantly lower (ONS group 46mm, dietary advice group 60mm), all measured using visual analogue scales^{(Reference Blundell and Turner41,Reference Stubbs, Hughes and Johnstone42)} . New longitudinal research has also highlighted the value of ready-made plant-based medical nutrition to improve intakes of energy, and protein with no suppression of appetite sensations and no reduction in food intake^{(Reference Delsoglio, Griffen and Syed43)}. Similarly, the total intake of a range of vitamins and minerals was increased, more effectively enabling individuals to meet dietary reference values (Reference Nutrient Intakes⁽⁴⁴⁾) for 14 micronutrients (v. 7 before intervention), including those often lacking in a plant-based diet^{(Reference Delsoglio, Griffen and Syed43)}. It may be that supplying energy and nutrient-dense formulations in a liquid may have less effect on appetite than using semi-solid and solid foods^{(Reference Leidy, Apolzan and Mattes45)}. It is important to note that the evidence for the effectiveness of ONS is for liquids in a ready-made (ready-to-drink) format as opposed to powders that have to be reconstituted with a liquid^{(Reference Cawood, Burden and Smith46)}. The reasons for this are more likely to be due to poorer compliance and adherence, due to the larger volumes and the practicalities of reconstituting such formats for those who are sick, with multiple diseases and conditions, and/or the resource pressures of health care professionals in institutions unable to spare the time for preparation and serving. In terms of the value of separate micronutrient supplementation in addition to nutritional support, a recent review suggested there was currently insufficient evidence and further research required^{(Reference Kaegi-Braun, Germann and Faessli47)}.

Table 2. Liquid oral nutritional supplements (ONS) effectively improve total energy and protein intakes in older people in primary care

Treatment burden and costs

Systematic reviews and meta-analyses have also indicated the value of oral nutritional interventions when used in community settings in those with morbidities, reducing treatment burden by improving clinical outcomes (such as fewer infections and wounds) and reducing health care use (e.g. fewer admissions to hospital, fewer GP visits, shorter hospital stays) and costs^{(Reference Elia, Normand and Laviano50,Reference Elia, Normand and Norman51,Reference Stratton, Hebuterne and Elia53)} . Recently we published a systematic review and meta-analysis showing that improving nutritional intakes with liquid ONS (mean intake 588 kcal and 22 g protein daily) in individuals (mean age 67 (35–87) y) in the community with a variety of morbidities significantly reduced complications, including infections, pressure ulcers and poor wound and fracture healing^{(Reference Cawood, Burden and Smith46)}. Meta-analysis of 39 RCT showed an OR of 0·68 (95 % CI 0·59, 0·79), P < 0·001; I ² 0·0) and the calculated number needed to treat was 14^{(Reference Cawood, Burden and Smith46)}. Reductions in complications were only seen in those trials in which adherence to ONS was high^{(Reference Cawood, Burden and Smith46)}. Fewer complications, in addition to better functional recovery, can be reasons for the lower health care use associated with nutritional interventions including oral nutritional supplements^{(Reference Elia, Normand and Laviano50,Reference Elia, Normand and Norman51)} . In addition to fewer health care professional and general practitioner visits in free-living older people^{(Reference Smith, Cawood and Walters38)} and shorter hospital stays in acutely ill individuals(^{(Reference Elia, Normand and Norman51,Reference Kaegi-Braun, Faessli and Kilchoer54)} ), there have been a variety of analyses showing significant reductions in hospital (re)admissions with the use of oral nutritional supplements^{(Reference Elia, Normand and Laviano50,Reference Stratton, Hebuterne and Elia53)} and with nutritional support generally^{(Reference Gomes, Baumgartner and Bounoure36,Reference Kaegi-Braun, Faessli and Kilchoer54)} . Consequently, the use of nutritional support to manage malnourished patients with a variety of morbidities can lead to lower health care costs and economic analyses also show the cost effectiveness of nutritional support^{(Reference Elia19,Reference Schuetz, Sulo and Walzer55–Reference Elia, Stratton and Russell57)} .

To complement RCT, the pragmatic implementation of screening and nutritional support in free-living malnourished individuals with a variety of morbidities has also shown improvements in outcomes and reductions in costs^{(Reference Brown, Fry and Cawood58–Reference Cawood, Smith and Pickles60)}. Furthermore, the reduction in treatment burden and health care costs has been nicely evaluated in a complex analysis and detailed publication by Elia et al. ^{(Reference Elia19)} that assessed the costs and the cost savings of implementing the NICE nutritional guidelines in the population of England (CG32⁽²⁴⁾). As shown in Fig. 4, although there are costs associated with implementing screening and assessment and nutritional management, these are more than offset by the reduced costs associated with fewer hospital readmissions, shorter hospital stays etc. The calculated net cost saving was £123 530 per 100 000 population leading to an estimated net saving of £65M in England alone (see^{(Reference Stratton, Smith and Gabe20)} for a summary).

Fig. 4. Cost savings of implementing NICE guidelines for nutrition support in England

Mortality

Research has highlighted the benefits of interventions to improve nutritional intake showing lower mortality in individuals with a wide variety of morbidities (focussed on individuals in acute settings)^{(Reference Gomes, Baumgartner and Bounoure36,Reference Stratton and Elia52,Reference Kaegi-Braun, Faessli and Kilchoer54,Reference Stratton and Elia61–Reference Wong, Huang and Sowa63)} . Wong et al. 2023^{(Reference Wong, Huang and Sowa63)} recently published an umbrella review and meta-analysis showing that interventions to improve oral intake (including ONS, dietary intake, exercise etc) reduced mortality at 30 d (RR 0·72 (95 % CI 0·55, 0·94), 15 RCT (n 4156)), and at 6 months (RR 0·81 (95 % CI 0·71, 0·92) and one year (RR 0·80 (95 % CI 0·67, 0·95); 27 RCT (n 6387)) compared to placebo/standard care. In polymorbid patients, a systematic review and meta-analysis of 27 trials indicated significantly lower rates of mortality in patients receiving nutritional support whilst acutely ill in hospital (OR, 0·73; 95 % CI 0·56, 0·97))^{(Reference Gomes, Baumgartner and Bounoure36)}, with a similar 30 % reduction shown in a more recent larger review of a broader patient group^{(Reference Kaegi-Braun, Kilchoer and Dragusha37)}. In the 2019 systematic review of patients with polymorbidity, the sensitivity analyses suggested a more pronounced reduction in risk of mortality in those patients with established malnutrition, in those with greater adherence and in more recent trials^{(Reference Gomes, Baumgartner and Bounoure36)}. This review paper indicated the importance of interventions continuing outside of the hospital when patients with polymorbidity have returned home and when benefits can still be evident. Indeed, in malnourished patients given post-discharge nutritional support as outpatients, significantly lower mortality was found from a meta-analysis of 14 RCTs^{(Reference Kaegi-Braun, Kilchoer and Dragusha37)}.

Guidelines

With the rise in the prevalence of individuals with multimorbidities, particularly in primary care, specific guidelines on nutrition to inform treatment protocols will be needed. There is very little mention of nutrition and diet in the NICE guidelines for multimorbidity⁽⁴⁾, although the NICE nutritional support guidelines (CG32) are a good reference document⁽²⁴⁾. An excellent set of nutritional guidelines has been developed for hospitalised patients with polymorbidity (multimorbidity) by ESPEN^{(Reference Wunderle, Gomes and Schuetz64)}. There are 32 practical recommendations to guide clinicians in treating polymorbid inpatients that cover screening, assessment, calculation of nutritional requirements, monitoring and interventions. They highlight the importance of individualisation of nutritional therapy due to the complexities of managing multiple diseases and conditions, the critical need for community-based approaches for those at nutritional risk and more research in primary care to inform the creation of more tailored guidelines for community nutritional support for this growing group of patients. Undoubtedly, in addition, greater allocation of resources to facilitate appropriate and effective nutritional management of individuals with multimorbidity will need to accompany the implementation in practice of the optimal guidelines for managing malnutrition now and in the future.

Summary

In summary, there are many nutritional challenges arising from the growing population of individuals with multimorbidity in our society. One of the key challenges is disease-related malnutrition, a prevalent and costly condition that is underdetected and undertreated. Greater awareness and prompt identification of malnutrition by health and social care professionals, or patients and carers themselves is important. Nutrition and dietetic expertise and resources plus the use of a variety of medical nutrition interventions in the treatment ‘toolkit’ need to be embedded into the care of individuals with multimorbidity in primary care as well as when admitted into hospitals. Making sure the right training, expertise and resources are allocated to managing multimorbidity, including the nutritional aspects in the community, will be key for the future ageing society. There is a wealth of evidence to support the use of nutritional intervention to manage malnutrition across many different patient groups, diseases and settings, with benefits nutritionally, functionally, clinically and economically with reduced treatment burden. However, there is a need to strengthen the data and guidelines specifically for managing multimorbidity, particularly in community settings and to further empower patients and care-givers, where appropriate, about nutrition. Subsequently, with the right investment in nutrition and dietetic services in primary care, an appropriate nutritional management plan can be put in place to optimally support the multimorbid patient in order to benefit the individual themselves, and the wider society.