Higher diet quality is associated with short and long-term benefits on SF-6D health state utilities: a 5-year cohort study in an international sample of people with multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative autoimmune condition of the central nervous system, characterised by axonal injury and demyelination [1]. The progressive loss of motor function, alongside other clinical manifestations such as fatigue and depression [2‐5], can have a substantial effect on physical and/or psychosocial aspects of wellbeing, leading to reduced health-related quality of life (HRQoL) for people with MS (pwMS) [6, 7]. Multiple modifiable lifestyle behaviours have been associated with MS progression and decreased HRQoL in pwMS, including negative impacts from smoking and BMI, and positive effects of physical activity and meditation [8, 9]. Accumulating evidence has suggested beneficial relationships between healthier quality-of-diet and MS onset and disease progression [10], including relapse rate, disability progression, and depression [11‐15].

Health state utilities (HSU) are a subjective measure of an individual's HRQoL, adjusted by societal or patient relative preference weights for living in different states of health-related quality of life (HRQoL), derived from patient-reported responses to a multi-attribute utility instrument’s (MAUI) questionnaire (e.g., SF-6D, EQ-5D-5L, EQ-5D-5L-Psychosocial, or AQoL-8D MAUIs [16‐19]) about symptoms, functional limitations, and overall functions relating to HRQoL [20]. The derived HSU is a measure between ‘0’ and ‘1’, with 0 representing “death” and 1 representing full health. Importantly, HSUs are an input metric to quality-adjusted life years (QALYs) in cost-utility analysis, both critical to translation to practice [21]. HSUs are used in clinical practice settings and as predictors of health [22‐25]. Most MAUIs have country-specific population norms and minimal important differences (to assess clinically meaningful change) that can be used for the disease-specific setting, including MS [26, 27].

While dietary intake has been implicated in the onset and clinical progression of MS, there is a paucity of studies assessing the relationship between diet and HRQoL and HSUs in pwMS. Our prior cross-sectional study found an association between higher quality-of-diet (assessed by the modified Diet Habits Questionnaire, DHQ [28]) and higher mental and physical HRQoL (MSQOL-54 [29]), such that a 1-point higher DHQ score was associated with 0.6 higher physical health scores and 0.5 higher mental health scores [30]. Another cross-sectional study by Evers and colleagues examining associations between adherence to the Dutch-Healthy Living Standard (DHLS, which recommends a high consumption of fruits/vegetables and abstaining from high salt, red meat, and processed sugar) and HRQoL and found each 1-point increase in DHLS adherence was associated with 0.41 and 0.46 higher physical and mental health scores in females, respectively [31]. We previously assessed lifestyle and clinical characteristics of the SF-6D HSU in the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) cohort at baseline, finding pwMS in the top two quartiles of total DHQ (> 80–89 and > 89–100) had 0.04 (95%CI: 0.03–0.05) and 0.05 (95%CI: 0.04–0.06) higher HSUs, respectively, than those in the bottom DHQ quartile [32]. In the Australian MS Longitudinal Study, Marck and colleagues found those in the highest vs lowest quintile of dietary quality (DHQ > 90) had 8.7% (95%CI: 1.5%–15.8%) higher AQoL-8D HSU [12]. Further, Coe and colleagues [33] found pwMS who consumed more fruits/vegetables and fiber had significantly higher EQ-5D-3L HSU, whereas higher red meat consumption showed inverse trends [34].

While there is promising evidence that quality-of-the-diet may be cross-sectionally associated with HSU, prospective relationships have not been explored. Here, we assessed short- and long-term prospective relationships of DHQ scores and HSUs over a 5-year follow-up in a large international cohort of pwMS. Based on the literature and particularly our previous cross-sectional findings, we hypothesised that higher quality-of-the-diet, as defined by a higher DHQ score [28, 35] would predict higher subsequent HSU, while meat and dairy consumption would have deleterious effects.

Using HSUs as a measure of HRQoL, we found that better quality-of-diet at baseline was predictive of higher HSU up to 5-years later, with higher baseline DHQ scores associated with 0.02–0.03 higher HSU at 2.5- and 5-year reviews, respectively. These results are at or close to the threshold for a minimally clinically important difference of 0.03 [27], indicating the potential HRQoL benefit of quality-of-the-diet for pwMS [27]. Of the DHQ subscores, the strongest associations with total HSU were seen for fat and fiber subscores, evident cross-sectionally and in prospective analyses. Further, dairy consumption was associated with 0.02 lower HSUs, though meat consumption was not robustly associated. Of the HSU subdomains, the strongest and most consistent prospective associations were seen for the pain, physical health, and vitality subdomains.

HSUs are an understudied aspect in epidemiological studies in MS, despite being a critical nexus point between the assessment of HRQoL in this population and the translation of research findings to practice and policy. Nonetheless, there is a dearth of literature on the relationship of diet and HSUs in pwMS and these were previously only cross-sectional in nature [31, 52]. Our study addresses this gap, with HSU results potentially of use in health economics MS-prevention models. We investigated the prospective relationships of diet and HSU via two different analyses, enabling both overall, as well as short and long-term effects, to be assessed. In the main prospective analysis evaluating pooled results at each 2.5-year interval, we observed a dose-dependent positive association of total DHQ score with HSU outcomes at both the 2.5- and 5-year review. Evaluated as a continuous 10-unit term, total DHQ score was associated with 0.010 higher HSU, and each higher quartile of total DHQ was associated with 0.01 higher HSU, and the highest quartile (> 92–100) of total DHQ had 0.03 higher HSU than the reference (< 72), in line with the minimum clinically important difference for the SF-6D. We also evaluated short- and long-term effects, showing that the associations of baseline DHQ with subsequent HSU 2.5 and 5-years later were comparable, each 10-unit increase in continuous DHQ associated with 0.012 and 0.008 higher HSU, and those in the top quartile having 0.03 higher HSU. This substantiates the pooled prospective analyses we present, while also suggesting that improved dietary quality may have short and long-term beneficial impacts on HSU in this population. It would be of interest to evaluate these dynamics further in a population surveyed at more frequent intervals, to ascertain how quickly diet may realise such positive effects. Subject to such replication, interventional studies of quality-of-the-diet improvement could then be implemented with a goal to validating the utility of diet in improving HSUs and HRQoL.

In general, our results here are in keeping with previous studies, including our own cross-sectional analysis of HOLISM data at baseline [32]. The cross-sectional results of the present study show a dose-dependent positive association at both 2.5- and 5-year reviews, similar in magnitude to that previously observed [32]. Marck and colleagues also showed cross-sectional relationships between quality-of-the-diet and HSU [12] in the Australian MS Longitudinal Study (AMSLS), with participants in the top two quartiles (80–90 and > 90) of DHQ scores associated with 6.6 and 8.7% higher HSU as measured by the AQoL-8D (out of 100%), respectively, with dose–response patterns. While the AMSLS analyses found no associations between meat or dairy consumption and HSUs [51], both the present study and our baseline study of the HOLISM cohort showed consistent and robust negative associations [30]. The AMSLS cohort had a slightly lower overall dietary quality (mean DHQ = 73.4) than the HOLISM study (mean DHQ = 82.9), and lower proportions of pwMS who avoided meat and dairy (7.9% and 8.1%, respectively) compared with HOLISM (baseline [32]: 27% and 38%, respectively). Marck and colleagues utilised the AQoL-8D, which is known to be preferentially sensitive to psychosocial health, whereas previous studies have noted that the SF-6D is preferentially sensitive to physical HRQoL [17, 53]. Relationships between diet and HSUs have also been explored in other studies with distinct methods. Coe and colleagues cross-sectionally evaluated individual food and nutritional components in the UK MS Register cohort, and found higher fish intake and nutrient content were associated with better EQ-5D-3L, and meat consumption associated with worse fatigue and anxiety/depression dimensions of the EQ-5D, and increased pain [33]. Despite the differences in diet and HSU measures, all studies had similar cross-sectional results for overall dietary quality and HSU, with this external consistency supportive of our prospective results.

Of the HSU subdomains, the strongest and most consistent prospective associations were seen for the pain subdomain, with those in the top quartile of total DHQ having 0.08 higher score in the lagged analysis and 0.05–0.08 higher scores in the prospective analyses at 2.5- and 5-year reviews. Positive associations were also seen for the physical health and vitality subdomains. The associations of better quality-of-the-diet with physical health and vitality are somewhat intuitive and align with the expectation of improved diet acting upon perceived physical health. The mechanisms underlying the associations seen for the pain subdomain, however, are less apparent. The pain HSU subdomain comprises two questions regarding how much pain a participant has and how much this interferes with activities and quality of life. Pain could act alongside or via disability, fatigue, and/or depression but our models controlled for these factors. Also, adjustment for prescription analgesic medication did not affect our results (data not shown). Studies of diet and HSU, particularly using the SF-6D, represent an understudied area, and comparators for the relationships observed are sparse. An RCT of a multimodal lifestyle intervention that included diet in a population at risk of diabetes assessed HSU using the SF-6D [53], finding that those in the intervention group had a 1.6-point higher pain subdomain score, though this association was abrogated on adjustment for change in BMI. We found in our sensitivity analyses that the diet-HSU relationships were independent of BMI, but this could reflect differences in the population or the RCT design of the Florez study. The mechanisms by which diet could impact upon pain-related HRQoL merit further study.

This longitudinal observational study supports a strong and robust prospective association between a higher quality diet and higher HSU in pwMS. Those who maintained the healthiest dietary practices as defined by the DHQ had significantly higher HSU up to 5 years later. These results support the findings in our previous baseline study [32], and reinforce the relationship between the quality-of-the-diet and HRQoL in pwMS. Higher scores in the fat and fiber DHQ subscores appear to be important dietary factors for higher HSU. Subject to replication and substantiation in clinical trials, behaviour modification interventions to improve the quality-of-the-diet of participants' diet may be a potential point of intervention to improve health and wellbeing in pwMS.