^*Correspondence to Mark A. Tarnopolsky, Department of Medicine, Room 4U4, McMaster University, 1200 Main Street W., Hamilton, Ontario, L8N 3Z5, Canada

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Accepted: 28 January 2005

10.1002/mus.20317  About DOI

Patients with muscular dystrophy may be at risk for nutritional inadequacy due to impaired mobility, dysphagia, limited ability to shop for food, and socioeconomic issues related to employment. Most studies regarding nutritional intake and neuromuscular disorders have focused on adults with amyotrophic lateral sclerosis[4][9][25][31] and children with Duchenne muscular dystrophy.[3][24][37] We are unaware of reports on nutritional issues related to myotonic muscular dystrophy type 1 (DM1). Some of the signs and symptoms of DM1 relevant to nutrition include facial weakness, tongue myotonia, oropharyngeal dysphagia, hypersomnolence, cognitive impairment, gastrointestinal dysmotility, and distal muscle weakness and myotonia, which can impair the ability to cut and manipulate food.[14] The prevalence of DM1 is at least 1 in 8,000,[11][23] which is six to seven times more prevalent than amyotrophic lateral sclerosis and almost as prevalent as Duchenne muscular dystrophy.[23]

Nutritional inadequacy may be associated with impaired muscle strength,[6][27][38] and poor nutrition has a major influence on morbidity and mortality in patients with certain other neuromuscular disorders. It is therefore important to assess nutritional intake in patients with muscular dystrophy, especially those whose swallowing is impaired (such as occurs in DM1).

The purpose of this study was to evaluate nutritional intake, body composition, pulmonary function, and muscle function in a cohort of adults with DM1 and in another cohort with other types of adult muscular dystrophies including limb-girdle, facioscapulohumeral, and oculopharyngeal muscular dystrophy. We also sought to determine whether nutritional intake was correlated with pulmonary function, muscle strength, or anthropometric measurements. It was hypothesized that patients with DM1 would show evidence of inadequate nutritional intake in a variety of macro- and micronutrients and that these nutritional deficiencies would be more apparent than in other dystrophic patients due to the involvement of the gastrointestinal tract that occurs in DM1.

METHODS

Subjects.

A group of adult patients with muscular dystrophy were recruited from our Neuromuscular Clinic as part of a prospective study evaluating the therapeutic role of creatine monohydrate. The 51 patients reported here represented those patients who completed full diet records on two occasions out of a total of 68 adult patients. Some of the strength data from the DM1 patients has been published elsewhere,[33] but the other data are novel. The diagnosis of DM1 was confirmed genetically by demonstrating a CTG repeat expansion >50 bp repeats in all cases (mean, 290); diagnosis of other categories of muscular dystrophy was based on genetic analysis or muscle biopsy with appropriate immunohistochemistry. Twenty-nine patients were diagnosed with DM1 (15 male, 14 female), and the other 22 patients (13 male, 9 female) had facioscapulohumeral (8), limb-girdle (8), Becker (3), and oculopharyngeal (3) muscular dystrophy. There were no differences between the two groups of patients with respect to age. The study received ethical approval from the Hamilton Health Sciences Corporation and all participants provided informed written consent to participate.

Design.

Data were collected under identical conditions on four occasions in each patient before and after a 4-month placebo (7 g/day of dextrose) and 4-month creatine monohydrate (5 g/day + 2 g/day of dextrose) trial. The data in the current study was taken from the baseline data for each of the aforementioned trials (the placebo data was only obtainable after the main study was analyzed and the code broken). The participants did not take any over-the-counter supplements or defined formula diets during the study, and no subject had a feeding tube currently or in the past. Because of a minimum 8-week wash-out period between trials, the replicated data were collected with a 6-month interval. The dietary assessment, pulmonary function and strength, and anthropometric measurements were made at the same time of day on both occasions.

Dietary Assessment.

Diet records were completed after the subjects were given detailed instructions on accurate record keeping by the same instructor. Subjects were asked to keep a record of all food immediately after consumption and to include packaging data (including the package labels) with their completed food diaries. Participants were also instructed to place liquids and appropriate foods into a measuring cup prior to consumption and to use a ruler to measure the dimensions of solid foods or a scale for weights. The collection instructions also included a statement that they were to record their intake during a period of time that was representative of their habitual diet (i.e., records were not to be taken during a period of illness, travel, or a special event such as a wedding). Each trial had participants prospectively collect food records over 2 weekdays and 1 weekend day. The same researcher completed all diet records using a computerized nutrient analysis program (Nutritionist 5, Palo Alto, California) and without knowledge of disease category. Based upon the approximately 18% underreporting when using dietary food records,[7][13][15][18] a correction factor (+18%) was added to the total intake values for each individual. All values represent the mean of the two 3-day collections. The test-retest coefficient of variation for total energy intake was 29% and the Pearson r-value was 0.52.

The nutrient data were compared to defined indices, and specifically to recommended nutrient intake, dietary reference intake (DRI), acceptable macronutrient distribution range, and estimated average requirement. The DRI is a reference value that is a quantitative estimate of a nutrient intake. The DRIs are meant to expand on the former recommended dietary allowance in the United States and in Canada. DRI include four nutrient-based reference values, including recommended dietary allowance, adequate intake, tolerable intake level, and estimated average requirement. The estimated average requirement is the median usual intake value that is estimated to meet the requirement of half of the healthy individuals in a specific age and gender group.[22] The recommended dietary allowance is defined as the average daily intake level sufficient to meet the nutrient requirement of nearly all (97%-98%) healthy individuals in a particular life stage and gender group.[22] Recommended nutrient intake values were used for energy since there were no DRI values available at the time of analysis. Calculations were made to determine percentage of individuals with muscular dystrophy who were not meeting these requirements.

Anthropometric Assessment.

A dual energy X-ray absorptiometry scan (Hologic QDR 4500A, Bedford, Massachusetts) was completed on the same day as the strength assessment and used for determination of fat-free mass, percent body fat, and bone mineral density. The body mass index (BMI) was calculated from the equation, weight (kg)/[height (m)][2].

Pulmonary Function and Muscle Strength Testing.

Pulmonary function tests including functional vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were done using a computerized spirometer (Koko, PDS Instrumentation Inc., Louisville, Colorado). Isometric handgrip strength was assessed using a handgrip dynamometer (Jamar, Bollingbrook, New York). The values for both the right and left hand grip strength were averaged to obtain a mean value. Isometric knee extension strength was determined from the dominant leg with the knee positioned at 90 degrees of flexion using a custom-made dynamometer, as previously described.[32] Maximum isometric strength was determined from the highest of three 4-s contractions separated by a period of 30 s. All strength measurements were completed by the same graduate-level research coordinator with test-retest coefficient of variation values of <7% for each measurement.

Analysis.

The mean values and proportions were compared between groups using a nonpaired t-test. Correlations between the anthropometry, strength tests, pulmonary function, and the dietary assessment was done using Pearson r-correlation statistic (Excel; Microsoft Corp., Redmond, Washington). A P-value of <0.05 was considered to be significant.

RESULTS

Subjects' Characteristics, Pulmonary Function, and Strength.

The subjects' characteristics (age, weight, height, body mass index, and fat-free mass) and pulmonary function tests (FEV1, FVC) were similar between the two groups of patients with muscular dystrophy. As expected,[20] handgrip strength was lower for the DM1 group (19.6 ± 13.1 kg) than those with other muscular dystrophies (26.4 ± 11.9 kg; P < 0.05). In contrast, knee extension strength was lower for the other muscular dystrophies (61.1 ± 40.6 N.m) than DM1 group (103.1 ± 46.9 N.m; P < 0.01).

Dietary Assessment.

None of the dietary assessments revealed a significant between-group difference. Consequently, all of the subsequent data contains the combined data unless otherwise specified.

Energy/Macronutrients.

About 62% of the DM1 group and 82% of the patients with other muscular dystrophies did not meet their daily recommendations for energy (Table 1). The protein intake appeared adequate as a mean value but 10% of the DM1 patients and 5% of the patients with other muscular dystrophies did not meet the DRI for protein; 55% of DM1 patients and 86% of the other patients had a daily fat intake above the acceptable macronutrient distribution range (Table 1).

Table 1. Diet assessment for macronutrients and energy.*

Factor DM1 Other dystrophies Value % < RNI % < RDI Value % < RNI % < RDI Total energy (kcal/d) 1,838 ± 498 62 N/A 1,651 ± 404 82 N/A Protein (g/d) 68.1 ± 20.5 N/A 10% 68.8 ± 17.2 N/A 5   DM1 Other dystrophies Value % AMDR Value % AMDR Carbohydrate (%) 48.6 ± 6.9 41 50.3 ± 7.1 31 Protein (%) 14.8 ± 2.3 0 16.2 ± 2.7 3 Fat (%) 33.0 ± 4.7 55 30.5 ± 6.5 86

 

DM1, myotonic muscular dystrophy type 1; N/A, not applicable; % AMDR, percent outside of the acceptable macronutrient distribution range; RDI, recommended daily intake; RNI, recommended nutrient intake.   * Values are mean ± standard deviation.

Vitamins and Minerals.

A large proportion of patients in both groups did not meet either the estimated average requirement or the DRI for vitamins or minerals (Table 2). Of particular relevance to muscular dystrophy was the strikingly low intake of vitamin E and calcium (Table 2).

Table 2. Vitamin and mineral intake.*

Daily intake DM1 Other dystrophies Mean ± SD % < DRI % < EAR Mean ± SD % < DRI % < EAR Vitamin A ( g/d) 907 ± 487 48 N/A 826 ± 381 45 N/A Vitamin C (mg) 84.4 ± 40.3 38 31 99.4 ± 49.2 41 18 Vitamin D ( g) 2.6 ± 2.1 79 N/A 3.4 ± 2.5 73 N/A Vitamin E (mg) 5.5 ± 2.8 100 90 5.8 ± 3.2 95 86 Vitamin K ( g) 51.5 ± 45.1 83 N/A 45.4 ± 40.4 91 N/A Thiamine (mg) 1.3 ± 0.4 34 10 1.4 ± 0.5 14 0 Riboflavin (mg) 1.0 ± 0.7 48 45 1.4 ± 0.6 18 14 Niacin (mg) 17.8 ± 5.8 21 7 19.0 ± 4.0 9 0 Vitamin B6 (mg) 1.4 ± 0.6 38 24 1.8 ± 1.5 23 18 Folate ( g) 238 ± 113 86 68 246 ± 94 77 59 Vitamin B12 ( g) 3.0 ± 1.6 31 17 3.4 ± 1.5 14 5 Pantothenic acid (mg) 2.9 ± 1.4 76 N/A 3.1 ± 1.1 82 N/A Biotin ( g) 14.7 ± 15.2 86 N/A 13.6 ± 6.3 95 N/A Calcium (mg) 664 ± 291 76 N/A 693 ± 299 73 N/A Copper ( g) 935 ± 421 45 N/A 896 ± 280 27 N/A Iron (mg) 12.7 ± 5.1 41 N/A 11.9 ± 3.4 27 N/A Magnesium (mg) 214 ± 100 86 72 225 ± 66 91 77 Zinc (mg) 8.5 ± 4.0 59 N/A 8.3 ± 2.6 50 N/A

 

EAR, estimated average requirement; DM1, myotonic muscular dystrophy type 1; DRI, dietary reference intake.   * Values are mean ± SD or the percentage (%) of people below the DRI or EAR.

Correlations between Pulmonary Function and Strength Tests, Anthropometry, and Dietary Intakes.

Pulmonary Function Tests.

Significant positive correlations (P < 0.05) were found between FVC and various nutritional intakes for the DM1 group including vitamins A (0.59), E (0.70), B₁₂ (0.64), pantothenic acid (0.73), biotin (0.57), copper (0.61), and zinc (0.56). Similarly, significant positive correlations were also present when correlating FEV1 with vitamin A (0.51), vitamin D (0.35), vitamin E (0.65), vitamin B₆ (0.52), vitamin B₁₂ (0.67), pantothenic acid (0.73), biotin (0.59), calcium (0.52), copper (0.61), and zinc (0.57) (P < 0.05).

Strength.

There were significant (P < 0.05) positive correlations among mean DM1 grip strength and vitamin A (0.67), folate (0.64), and iron (0.56). Significant (P < 0.05) correlations were also present between DM1 knee extension strength and vitamin C (0.70), vitamin E (0.60), niacin (0.55), vitamin B₆ (0.73), folate (0.57), copper (0.79), iron (0.54), and zinc (0.59).

Anthropometric Correlations.

Fat-free mass was positively correlated (P < 0.05) with bone mineral content (0.55), FEV1 (0.54), FVC (0.55), height (0.85), and weight (0.71). Body fat was inversely correlated (P < 0.05) with energy (0.64) and bone mineral content (0.52). There were no significant correlations between bone mineral density and any of the nutritional intakes or functional outcomes.

DISCUSSION

We have comprehensively evaluated the nutritional adequacy of patients with several types of nondystrophin-related types of muscular dystrophy. The strikingly inadequate intake for many of the micro- and macronutrients was higher than expected, and the correlation between several of these and muscle mass or strength highlights the importance of nutritional assessment and counseling in patients with muscular dystrophy.

A progressive loss of skeletal muscle contractile protein is a characteristic of patients with muscular dystrophy and is ultimately due to an imbalance between muscle protein synthesis and protein degradation.[12][28] It appears that a reduction in protein synthesis is the main factor contributing to a net negative protein balance in patients with DM1,[12] yet strategies such as corticosteroid administration may enhance muscle mass and strength by reducing protein breakdown.[28] Nutrition has a major effect on protein metabolism, predominantly by increasing synthesis and possibly by decreasing breakdown.[39] Patients with muscular dystrophy are often in a state of net negative protein balance, and attention to nutritional adequacy may be particularly important. Issues such as reduced mobility, oropharyngeal weakness, reflux, and socioeconomic status (e.g., employability issues due to disability) may further reduce the ability of a person with muscular dystrophy to ensure adequate nutrition.[34][36][37]

In this study, 10% of patients with DM1 and 5% of those with other forms of muscular dystrophy did not meet the DRI for daily protein intake. If muscular dystrophy increases protein requirements,[12][28] then the proportion of those in our study who did not meet recommended protein intakes will be an underestimate. The low protein intakes may be a consequence of the relatively low energy intake: 62% of patients with DM1 and 82% of patients with other types of muscular dystrophy did not meet their daily energy needs according to government recommendations. By comparison, our group has reported higher energy intakes for both healthy older (N = 28, > 65 y, 2,063 ± 454)[2] and younger men and women (N = 30, 21-24 y, 2,290 ± 395),[21] using identical diet analysis methods. We had considered a priori that patients with DM1 would have lower energy intake levels than patients with other types of muscular dystrophy due possibly to oropharyngeal abnormalities, dysmotility, socioeconomic status, and hand weakness, but we did not find this to be the case. This may relate to the fact that there are ubiquitous generic issues common to most types of muscular dystrophy that may influence nutritional intake. The muscle weakness in patients with muscular dystrophy often leads to a sedentary lifestyle, and therefore the recommended nutrient intake levels for the general population may overestimate the needs for such patients. Consequently, the apparently low energy intakes may be compensating for lower energy expenditure. With such a low energy intake, however, it is difficult to meet recommended protein, vitamin, and mineral needs.

We found that 55% of the DM1 patients and 86% of the other muscular dystrophy patients had a fat intake above the suggested acceptable macronutrient distribution range. As a possible consequence of a high fat intake, 10% of the DM1 group and 18% of the other group were categorized as obese (BMI > 30). In addition to displacing energy from protein and carbohydrates in the diet, a high fat intake is not consistent with dietary guidelines for optimal cardiovascular health, and a high saturated fat intake is an important risk factor for type 2 diabetes, obesity, hypertension, and gallbladder disease.[16][17] In contrast, 13% of the DM1 patients and 9% of patients with other types of muscular dystrophy had BMI values less than 18.5, which is in the underweight category.

In addition to the macronutrient and energy intake insufficiencies noted above, a substantial proportion of patients with DM1 and other types of muscular dystrophy had DRI or estimated average requirement intake levels for vitamins below recommendations. Vitamin E intake was the most consistently inadequate across all recommendations for both groups. Vitamin E is a potent antioxidant, and our group has found an increase in oxidative stress in patients with Duchenne muscular dystrophy, but not DM1.[29] Although supplemental vitamin E did not appear to have a beneficial effect on strength in small cohorts of patients with Duchenne muscular dystrophy,[1][10] it would seem prudent for patients to at least meet the DRI intake level for vitamin E. In addition, positive correlations were obtained between vitamin E intake and FVC (0.70), FEV1 (0.65), and knee extension strength (0.60) in the DM1 patients. Vitamin D intake was below the DRI for over 70% of patients in our study. Studies have found that age-associated sarcopenia is associated with suboptimal vitamin D status,[5][40] and severe deficiency of vitamin D can result in a myopathy.[26][30] Additionally, a low vitamin D concentration in associated with osteopenia.[8][35] Although a significant correlation was not found between vitamin D intake and bone mineral content, it should be noted that measurement of bone mineral content was a whole-body and not a regional measurement, and that much of the vitamin D in serum comes from sunlight exposure and not dietary intake.[35] Given the significant relationship between several of the vitamin intake levels and measurements of muscle function, and due to the suboptimal intake levels reported herein, it may be necessary to recommend vitamin supplements to patients with muscular dystrophy in order to increase their micronutrient intake to DRI levels if they are unable to meet these needs through a balanced diet.

Many patients did not meet their recommended DRI for various minerals. Copper and zinc were both positively correlated with measurements of pulmonary function and strength, and were deficient in 27% and 59% of patients, respectively. Although these observations are correlational and do not prove cause and effect, suboptimal mineral intake can lead to impairments in physical performance.[19] A low energy intake is a risk factor for suboptimal mineral intakes,[19] and this is the likely reason for the low mineral intakes in this study. Calcium intake was also below the DRI in over 70% of patients. Although calcium intake was not positively correlated with whole-body bone mineral content in our study, a long-term deficiency could eventually lead to osteopenia.

Our study provides a starting point from which to further explore nutritional issues in patients with muscular dystrophy. One of our most striking finding was the overall low energy intakes. This severely limits the available energy from which to derive important nutrients such as protein, vitamins, and minerals. Future studies will need to address whether serum and tissue markers of nutrient adequacy are also deficient and whether nutritional counseling or supplementation can ameliorate possible deficiencies.

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