Age-related changes in physical health and increased occurrence of diseases predispose elderly people to adverse health outcomes, including malnutrition. Recent evidence suggests that polypharmacy may promote the occurrence of poor nutritional status, most commonly as a manifestation of adverse drug effects [1,2▪▪–4▪▪]. Concern about the role of drug treatment is relevant, as several studies of elderly populations have shown polypharmacy to be very prevalent . Even so, research on the role of polypharmacy on nutritional status in elderly people is scarce.
Drug treatment may contribute to poor nutritional status, for example, by causing loss of appetite, nausea, diarrhea, weight changes, taste alterations, decrease in saliva secretion, modifications in lipid profile, alterations in electrolyte balance, and changes in glucose metabolism [6,7]. Nutritional status is also of great concern because of its impact on the pharmacology of many drugs . Food can affect on drug absorption and metabolism, which means decreased drug effects or overdose of drugs. Malnutrition may also lead to decreased amount of serum protein, meaning a higher unbound drug fraction. This can lead to increased drug effects, as only unbound drug fractions have pharmacological activity.
Nutritional status is commonly evaluated as a part of comprehensive geriatric assessment by validated tests. It is known that drug treatment may influence both positively and negatively on different health indicators, including nutritional status. When prescribing drugs for elderly people, declined nutritional status means more challenges in balancing between benefits and harms of drug treatment.
Recently, more attention has been given to health-related effects of polypharmacy, but the evidence on associations between polypharmacy and nutritional status is still limited. This review focuses on summarizing the findings published on the relationship between polypharmacy and nutritional status in elderly people. Relevant literature was identified through searches of the PubMed and Scopus.
CHARACTERISTICS OF POLYPHARMACY
There is no generally accepted consensus for the definition of polypharmacy, except that it indicates the use of multiple drugs by a single person . However, most studies have defined polypharmacy quantitatively as a specific number of drugs in use: five or more drugs are used most frequently as a cut-off . A separate definition for excessive polypharmacy, meaning usually the use of nine or 10 or more drugs concomitantly, has also been recently adapted for use [9–12].
Review of published literature has shown a clear worldwide increasing trend in the quantity of drug use over the past decades . A mean number of drugs used by community-dwelling elderly people have varied from 3.5 to 6.9, when taking into account both prescription and over-the-counter drugs [10,13–15]. According to a recent study, cardiovascular drugs (82%), nervous system drugs (62%), drugs for blood and blood forming organs (63%), and drugs for alimentary tract and metabolism (60%) were the most commonly used drug groups in a population-based sample of elderly people aged 75 years and older .
Approximately, every other community-dwelling elderly person have polypharmacy [16–19] and every fifth have excessive polypharmacy [4▪▪,9,13,16]. Studies conducted among institutionalized elderly people have reported about every other patient to have excessive polypharmacy [20–22]. A large European study conducted among elderly people receiving home care services revealed the prevalence of polypharmacy (six or more drugs in use) to be highest in the Czech Republic (86%) and Finland (73%) . The lowest prevalence rates were observed in Norway (34%), the Netherlands (35%), and Italy (36%). The differences in prevalences can be partly explained by country-specific drug policies, prescribing patterns, and refund systems. Differences in socioeconomic status of elderly populations between countries may also influence the reported findings.
ASSESSMENT OF NUTRITIONAL STATUS
The Mini Nutritional Assessment (MNA) test is the most widely used and validated test to assess nutritional status of elderly people [24,25]. The test is composed of 18 measures encompassing anthropometry, dietary assessment, clinical global assessment, and subjective evaluation of health and nutritional status. The total scores of the MNA test range from 0 to 30, with scores 24 or above indicating sufficient nutritional status, 23.5–17 risk of malnutrition, and below 17 malnutrition. Another commonly used nutritional tool is the 10-statement DETERMINE checklist, which is designed to be self-administered but can also be used by healthcare professionals . Statements that cover dietary, general, and social assessments have weighted scores: scores 0–2 reflect good nutritional status, and scores 3–5 moderate and 6–21 high nutritional risk.
Drug use is a domain of the tests used to assess the nutritional state of elderly patients. Both the MNA and DETERMINE include a question on whether the person is taking three or more drugs daily. When this criterion for polypharmacy is used, a high proportion of elderly people fall into this category [27,28]. In addition, the dichotomous question about drug use is relatively crude which limits detailed analysis about the role of drug treatment on nutritional status. A cut-off value for number of drugs, which carries an increased risk for nutritional problems in elderly people, is not known. Apparently, five or more drugs daily would be more appropriate than the currently used three or more drugs. Another solution would be adding more response choices to questions dealing with drug use in the nutritional assessments.
Poor nutritional status is a serious and common problem in elderly people. Recent publications using the MNA test in the assessment indicated that quite a high proportion of community-dwelling (13–34%) [29–32] and a vast majority of institutional living (71–97%) [31,33–36] elderly people are malnourished or at risk of it. A study conducted in low-level care facilities reported that one-third of elderly people are protein malnourished and two-thirds have energy deficits based on information gained from 3-day weighted food records, anthropometric and biochemical indicators .
POLYPHARMACY AND NUTRITIONAL STATUS
The probability of nutritional problems as a consequence of drugs is highest in elderly people suffering from multiple diseases which consequently are treated with multiple drugs. It is apparent that some diseases increase the likelihood of poor nutritional status; thus, the independent role of drugs on nutritional status is challenging to determine. To address this issue, we performed comorbidity-adjusted analyses in the study of community-dwelling elderly people (n = 294, age 75 years or older) which showed excessive polypharmacy to be a significant correlate of declined nutritional status, whereas for polypharmacy (six to nine drugs) no such association was found [4▪▪]. Studies analyzing the number of drugs as a continuous exposure have shown inverse association between the number of drugs and nutritional status [38,39,40▪] but have not determined cut-off values for the risk of malnutrition. On the basis of these findings, it can be assumed that polypharmacy may contribute to poor nutritional status, even beyond current diseases. However, most likely the impact of drugs on nutritional status is significant only when using fairly high numbers of drugs. Further research is also needed to clarify the role of certain specific drug groups on nutritional status.
The majority of studies examining the association between polypharmacy and nutritional status have been conducted with cross-sectional designs. A small study of retirement home residents (n = 81) showed that an increasing number of drugs in use was associated with lower MNA scores . The average number of drugs in those having severe nutritional problems (7.3 drugs, MNA <17) was significantly higher compared to those with better nutritional status (4.5 drugs, MNA 17 or more). However, these results were cross-sectional in nature and lack some potential confounders in adjusting, and therefore results should be interpreted with caution. Studies among elderly hospital patients have also shown that polypharmacy is a predictor of poor nutritional status after adjustments for sociodemographic factors and health status indicators [39,41]. To confirm these findings, larger cohorts of community-dwelling people and hospitalized patients with more complete adjustment with diseases are needed.
A recent study of community-dwelling elderly people (n = 294) reported that in a cross-sectional setting, those having excessive polypharmacy (10 or more drugs in use) had an average of 0.6 points lower MNA-SF scores (maximum 14 points) compared to those without polypharmacy (five or less drugs in use) when adjusted for sociodemographic factors, functional comorbidity index (FCI), and self-reported health status [4▪▪]. However, in prospective analysis, the polypharmacy status did not predict the 3-year change in nutritional status. In further studies, the important viewpoint that should be taken into account is the quality of drug treatment in those having polypharmacy. There are no available studies on the role of inappropriate medication for nutritional status.
The risk of developing malnutrition is particularly high in people with dementing disorders who confront considerable difficulties in their eating as the disease progresses [42,43]. Their poor nutritional status may also reflect the occurrence of nausea and diarrhea, which are the common side-effects of acetylcholinesterase inhibitors used widely in the treatment of Alzheimer's disease . With regard to polypharmacy, a recently published study of demented nursing home patients observed no correlation between the number of drugs and current nutritional status . It is likely that the role of drugs in development of poor nutritional status is not as important as the eating problems related to the disease itself.
POLYPHARMACY AND CHANGES IN WEIGHT
One component of nutritional assessment is weight loss, which can be used as an indicator of insufficient energy intake. A cross-sectional study of community-dwelling elderly persons revealed almost a three-fold risk of experiencing weight loss (≥4.5 kg during a 1-year period) for those using five or more drugs compared to those using less drugs after adjustments for sociodemographic factors, overall health status, diseases, and previous hospitalizations . Another cross-sectional study reported three or more drugs in use to correlate with weight change (BMI less than 20.0 kg/m2 or weight loss of ≥5% or more during the last 6 months) in women, but the association attenuated after adjusting for sociodemographic factors, diseases, and correlates of physical and psychological status [40▪]. Of individual drug groups, the association with weight changes has been reported for some cardiovascular (e.g. cardiac glycosides, and diuretics) drugs and psychotropics (e.g. antipsychotics and antidepressants) [1,46].
In addition to weight loss, also obesity (BMI ≥30 kg/m2 or more) has been found to be associated with polypharmacy [15,47,48▪▪]. In a Swedish study, obese (BMI ≥30.0 kg/m2 or more) elderly people had over two-fold risk of polypharmacy compared to those with lower BMI . However, this finding should be interpreted with caution because of cross-sectional study setting and incomplete adjustments, as only sex, current smoking, self-rated health, diabetes, and hypertension were included in the analysis. Support for this finding was presented in a US study that reported elderly people taking seven or more prescription drugs to have higher BMI than those taking less drugs [48▪▪]. The most likely explanation for these associations is that obese elderly people have greater comorbidity burden, meaning increased need of drug treatments, rather than polypharmacy promoting the weight gain. The cross-sectional findings on associations of polypharmacy and BMI should be interpreted with caution because of incomplete adjustment for diseases [15,48▪▪]. Also, longitudinal studies would provide more reliable evidence about the effects of polypharmacy on body weight.
IMPACT OF DRUGS ON THE INTAKE OF ENERGY AND NUTRIENTS
The main nutritional problem in elderly people is insufficient energy and protein intake, often combined with deficient supply of essential nutrients . It is apparent that aging itself and several diseases often lead to decreased food and concomitant energy and nutrient intake, but side-effects of various drugs (e.g. loss of appetite, gastrointestinal problems, and alterations in body function) may also affect the nutrient intake. This was observed in a study that reported polypharmacy to associate with low energy intake among elderly people . High number of drugs in use means also increased risk of drug–nutrient interactions leading to decreased absorption of essential nutrients [51,52]. In addition, age-related changes in body composition and function alter drug responses but affect also markedly the metabolism and kinetics of nutrients.
The number of studies assessing the effect of polypharmacy on the intake of nutrients is limited and based mainly on cross-sectional studies with incomplete adjustment for confounding factors. In a recent cross-sectional study of community-dwelling elderly (n = 1065) aged over 65 years, the number of drugs in use correlated with worsened quality of diet [3▪▪]. With regard to specific nutrients, the study found a significant decrease in the intake of fiber, several fat-soluble vitamins (A, D, and E), and some water-soluble vitamins (B1, B3, and B7) with increasing number of drugs in use. Contrary, an increased intake of glucose, sodium, and dietary cholesterol with the number of drugs in use was observed. Another study that concentrated more specifically on vitamin status of noninstitutionalized elderly people (n = 102) reported the intake of three or more drugs to associate with decreased concentration of vitamins D, K, and B6[2▪▪]. No association was observed between polypharmacy and concentration of vitamin C. There is also evidence on the association between polypharmacy and low levels of folate [2▪▪,53]. According to a descriptive study among statins users, the levels of vitamin B12, vitamin K, and potassium were lower compared to those not taking statins .
One issue raised in the recent publications was insufficient fiber intake in those having polypharmacy [2▪▪,3▪▪]. A large amount of drugs have anticholinergic effects, which means increased anticholinergic load for those with polypharmacy. Specific attention to fiber and fluid intake should be paid when polypharmacy is present, because constipation is a common adverse effect caused by anticholinergics . It has been reported that about every fifth elderly person uses laxatives [56–59] which calls for increasing use of fibre supplements or adding dietary supply of fiber from whole grains, fruits, and vegetables to the diet of elderly people . Fiber promotes the normal bowel movements and thus acts as a less invasive treatment of constipation than laxatives.
An added concern about glucose balance is that age-related impairments in glucose metabolism result in reduced glycemic control. Drug treatment (e.g. diuretics, beta blockers, and corticosteroids) may also lead to disturbances in glucose homeostasis . In elderly people, sodium levels need to be followed, because the capacity of kidneys in regulating the correct amount of sodium decreases markedly with aging. Some drugs (e.g. diuretics, antidepressants, antipsychotics, and NSAIDs) have modest effect on sodium retention . The clinical significance of these drugs, however, more often is the development of hyponatremia rather than hypernatremia. These drugs may promote hyponatremia especially in elderly people with inappropriate antidiuretic hormone secretion.
Published evidence on polypharmacy relations with quality of diet in elderly people is scarce. The two available studies are cross-sectional and therefore causal relationships between polypharmacy and nutritional status have not been established [2▪▪,3▪▪]. In addition, analyses of these studies were not adjusted for potential confounders, and thus the role of polypharmacy as an independent risk factor cannot be assessed. Reported results in these studies are not fully comparable because of differences in data collection. In the US study, the information was collected by a questionnaire on food consumption, whereas the Austrian study used plasma levels of vitamins as a measure. Properly collected food consumption data offer comprehensive information on diet, whereas hematological and biochemical markers can give information on limited sections of diet only. Combining self-reported data with biochemical markers in longitudinal study designs would be ideal in order to confirm association between polypharmacy and nutritional status.
Previous studies have shown that polypharmacy strongly correlates with unnecessary drug treatment and drug-related problems in elderly people [63–65]. The number of drugs itself is usually a marker of declined health status, and thus it has only a limited role as an independent factor for nutritional status. However, it is possible that problems occurring in drug treatment worsen the overall health of elderly people, and thus promotes also the occurrence of nutritional problems. These call for additional research on the association of polypharmacy with nutritional status, taking into account the rationality of medication and allowing adjustment for disease status.
On the basis of limited current evidence, the independent role of polypharmacy on nutritional status is unclear, calling for more studies on the subject. Results are mainly based on cross-sectional studies, often without proper adjustment for potential confounders. To confirm the association between polypharmacy and nutritional status, more studies of larger populations that allow more complete adjustment for diseases are needed, especially with longitudinal study designs.
Current knowledge on polypharmacy relations with nutritional status emphasizes the idea of adding nutritional evaluations as a routine part of comprehensive geriatric assessment, especially for those elderly people suffering several diseases needing drug treatment. Multiprofessional teams including physician, pharmacist, and dietitian would most probably help to identify earlier those at risk of nutritional problems. Co-operations offer also a comprehensive approach to care and would result in better outcomes in ensuring best possible health for an aging population.
Conflicts of interest
The support for this study was obtained from the Finnish Cultural Foundation (Jyrkkä).
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 92).
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