Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis.

Background: Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Methods: Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology-supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise were investigated. Results: pwMS-ON had significantly lower (p < 0.01) disability (Expanded Disability Status Scale) than pwMS not on the program (1.91 ± 0.75 vs 3.87 ± 2.32). A genetic variant in the lipid transporter FABP2 gene (rs1799883; 2445G>A, A54T) was significantly associated (p < 0.01) with disability in pwMS not on the program, but not in pwMS-ON (p = 0.88). Vascular blood flow velocities were lower in the presence of the A-allele. Conclusion: Pathology-supported genetic testing may provide guidance for lifestyle interventions with a significant impact on improved disability in pwMS.

This study investigated the role of a genetic variant that increases saturated fat absorption and may make people with multiple sclerosis (MS) more susceptible to disability progression. Of 51 people with MS, 19 had followed a program which includes normalization of blood test results and daily intake of unsaturated fatty acids for more than 10 years, while the others had not. The latter group had significantly greater disability than the people who had followed the program, suggesting that the unsaturated fatty acids modulated the effect of the genetic variant. Six MS cases are presented as examples, including a marathon athlete (Case 1) and a patient who showed a dramatic decrease in disability from being wheelchair-bound for 15 years to walking freely (Case 2).

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases.

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors.

UNLABELLED: The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. AIM: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p = 0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p = 0.045) and total cholesterol levels (p = 0.048). Both homocysteine (p = 0.011) and BMI (p = 0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p < 0.01) and low physical activity (p < 0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p = 0.035), while smoking increased MS disability (p < 0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.

Development of a performance-rating scale for a nutrition knowledge test developed for adolescents.

OBJECTIVE: The objectives of the present study were to (i) develop and validate a norm-referenced performance-rating scale to interpret a nutrition knowledge test developed for urban adolescents and (ii) develop a prototype for other researchers to follow when developing nutrition knowledge tests. DESIGN: For norm development the nutrition knowledge test (questionnaire) was administered to a sample representative of the questionnaire target group, referred to as the norm group. These included 512 adolescents in grades 8 (n 158), 10 (n 149) and 12 (n 205) at three randomly selected schools in Soweto and Johannesburg. The performance scores (in percentages) obtained by the norm group were transformed to Z-scores which were categorised into stanines using established Z-score cut-off points. For validation purposes the questionnaire was completed by 148 volunteers: sixty university dietetics students, nineteen non-nutrition university students and sixty-nine primary-school teachers. RESULTS: As required of an ideal norm group, the Z-scores formed a normal distribution (a bell-shaped curve). To facilitate interpretation of the results, the Z-score cut-off points for these categories were transformed back to performance scores (percentages) so that the performance of a testee could be interpreted directly from his/her performance in percentage. As is recommended, the nine stanine categories were reduced to five: very poor, fair/below average, good/average, very good/above average and excellent. The discriminatory validity of the norms was substantiated by showing that groups with known nutrition knowledge levels were rated appropriately and that the performance ratings of these groups differed significantly, with university dietetics students scoring 98.3%, primary-school teachers 20.3% and non-nutrition university students 31.6%. CONCLUSIONS: The norm-referenced performance-rating scale can be used with confidence to interpret the performance score achieved by a testee on the nutrition knowledge test developed for urban adolescents in South Africa. The methodology used in the study serves as a prototype for other researchers who are developing knowledge tests.

How well do adolescents determine portion sizes of foods and beverages?

In the present study, we examined how well adolescents (12-13 years) are able to select the correct dietary aid portion sizes after having been shown different food items. We also evaluated the effectiveness of two-dimensional life-size drawings and three-dimensional food models, used as dietary aids in this process. Fifty black children and 42 white children from Johannesburg participated in the study (N = 92). Trained interviewers individually tested each child following a prescribed sequence, throughout. Each participant was shown a plate of actual food of a pre-determined weight. The participant was required to select a two-dimensional drawing, and thereafter a three-dimensional food model, which most closely resembled the real food portion. In this manner, portion size estimation was evaluated with respect to 11 different food items. Correlations between nutrients calculated from actual weight of food portions and estimates ranged from 0.842 to 0.994 (P < 0.0001), indicating a significant positive linear association between the actual and estimated nutrients, using either of the dietary aids. However, findings also suggest that the drawings provided a better estimate of actual energy, fat and carbohydrates than did the food models (with respect to lying within the limits of agreement). On the other hand, the food models were more frequently selected correctly than the drawings. Hence, both methods had advantages and disadvantages. Overall, it was found that there were no gender differences (P < 0.05) when using either the models or drawings to estimate portion size, however, there were significant ethnic differences (P < 0.05). With two exceptions, black children selected the correct aids (drawings and models), more often compared with white children. It is recommended that in dietary interviews undertaken in black children in urban areas one could use either aid; while in white adolescents the use of the food models is recommended.