Overview

Methods to Study the Association Between Nutrition and Frailty

Diet is one of the most important modifiable factors that can affect frailty and the aging process (Kiefte-de Jong et al. 2014; Schoufour et al. 2019b). It can be studied from different perspectives. Traditionally, most research on nutrition and frailty is concentrated on the effects of single nutrients (e.g., proteins, vitamin D), single foods (e.g., kiwis, wine), or food groups (e.g., vegetables, dairy). The advantage of this approach is that they lead to clear dietary advice, often supported by biological pathways. For example, the established association between low protein intake and frailty has led to increased awareness of protein supplementation in frail older populations. Nevertheless, this approach also has its limitations. People do not consume single nutrients but foods that are combined into meals and follow a pattern throughout the day. Nutrients and foods may interact together in influencing physiological processes. Additionally, the intake of nutrients and foods is highly correlated with each other (Cespedes and Hu 2015). For example, people consuming a high amount of fatty fish generally also consume more fruits and vegetables. These interactions and correlations can be captured in dietary pattern analyses – a method that has emerged as an important research field complementary to the focus on single compounds (Kant 2004; Hu 2002).

Malnutrition Among Older Adults

Malnutrition, which is very prevalent in geriatric populations, has been identified as one of the major risk factors for frailty (Artaza-Artabe et al. 2016). Malnutrition is a condition in which one or more nutrients are either deficient or abundant. Malnutrition can involve calories, macronutrients, or micronutrients. Both undernutrition and overnutrition (obesity) are associated with an increased risk to develop frailty in community-dwelling older adults (Cruz-Jentoft et al. 2017; Hubbard et al. 2010; Bollwein et al. 2013b). In a metabolic state, there is sufficient energy for organs and muscles to function. If insufficient energy is consumed, the body starts to catabolize fat mass and muscle mass to provide this energy. Older adults often do not consume sufficient calories, as a result of among others reduced appetite, physiological changes, and tooth problems (Kruizenga et al. 2003; Agarwal et al. 2013). When muscle mass is lost, this will eventually also lead to loss of muscle function and physical performance, both important aspects of frailty. Indeed, several studies show that a lower energy intake is associated with a higher prevalence of frailty and higher risk to develop frailty (Schoufour et al. 2019a; Bartali et al. 2006; Smit et al. 2013).

Physical Frailty

By far, most research on nutrition and frailty focused on physical frailty (Fried et al. 2001). In a recent review, Lorenzo-López et al. identified five studies that found independent associations between a broad range of micronutrients and frailty (Lorenzo-López et al. 2017). Among others, frailty has been linked to low levels of vitamin D, vitamin C, vitamin E, and β-carotene (Kelaiditi et al. 2015; Bollwein et al. 2013a; Bonnefoy et al. 2015; Artaza-Artabe et al. 2016).

Because physical frailty is highly influenced by loss of muscle mass and muscle strength (Cesari et al. 2014; Keevil and Romero-Ortuno 2015), the effect of the macronutrient protein has received particular attention. Dietary protein stimulates skeletal protein synthesis, and insufficient supply can affect muscle integrity (Beasley et al. 2013; Cermak et al. 2012). Nevertheless, not all observational studies report a beneficial association of protein intake with frailty (Artaza-Artabe et al. 2016; Schoufour et al. 2019a). These inconsistencies could be caused by other factors that may influence the association, such as physical activity (Tribess et al. 2012; Blodgett et al. 2015; Tieland et al. 2012), protein source (i.e., plant- versus animal-derived), and the distribution of protein throughout the day (Bonnefoy et al. 2015; Lana et al. 2015). Other macronutrients received far less attention. One cross-sectional study taking into account the intake of proteins, carbohydrates, and fats did not find any association with frailty (Schoufour et al 2019a).

Several studies observed that a high dietary quality is inversely associated with the risk of being frail. Both adherence to the Mediterranean diet and local dietary guidelines have been associated with lower frailty risks in different populations (Bollwein et al. 2013a; Talegawkar et al. 2012; León-Muñoz et al. 2014; Haines et al. 1999; Shikany et al. 2014). Additionally, diets high in antioxidants may prevent frailty (Cruz-Jentoft et al. 2017; Kim et al. 2010). These results indicate that nutrition can play a key role in the prevention of frailty. Specifically, among older adults that are already frail, protein-energy supplementation may reduce the further progression of frailty and functional decline (Cruz-Jentoft et al. 2017). However strong evidence, based on large longitudinal studies and/or clinical trials, is still required.

Frailty as a Measure of Overall Health

In addition to the well-known physical frailty definition, Rockwood and Mitnitski presented their operationalization of frailty as the accumulation of deficit approach (Mitnitski et al. 2001). These deficits cover multiple health domains and can include variables such as diseases, disabilities, abnormalities, and symptoms. As such, the frailty index can be considered an overall measure of health. Only few studies focused on the association between nutrition and the frailty index. In a study among 3378 Hong Kong inhabitants (65 years and over), it was observed that a high dietary quality was associated with less frailty (Woo et al. 2010). Similarly, in a large Dutch cohort, it was found that adherence to the Dutch dietary guidelines could help to prevent, delay, or even reverse frailty levels (de Haas et al. 2018; Brinkman et al. 2018). Furthermore, there was no association found between the intake of fat or carbohydrates and the frailty index overtime in 5205 Dutch middle-aged elderly. The authors did observe that people consuming more animal protein had higher frailty scores (Verspoor et al. 2019). 

Prospects and Summary

Although the number of studies looking into nutrition and frailty is increasing, there are still several gaps in knowledge that hamper strong conclusions. First of all, most studies are based on observational data. Confounding by other lifestyle factors such as smoking and physical activity and socioeconomic factors makes it complicated to determine the causality of such associations. Second, the association between nutrition and more holistic frailty approaches is lacking. Regardless of these limitations, diet seems to be an important modifiable determinant of frailty. Although clinical trials are required to strengthen the evidence, the abovementioned studies suggest that a diet with a sufficient amount of protein and high in fruits, vegetables, legumes, fish, and whole grains and low in red meat and sugar-rich foods could help with the prevention of frailty.

Cross-References