Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer's Disease.

BACKGROUND: Multiple sclerosis (MS) is a prototype neuroinflammatory disorder with increasingly recognized role for neurodegeneration. Most first-line treatments cannot prevent the progression of neurodegeneration and the resultant disability. Interventions can improve symptoms of MS and might provide insights into the underlying pathology. OBJECTIVE: To investigate the effect of intermittent caloric restriction on neuroimaging markers of MS. METHODS: We randomized ten participants with relapsing remitting MS to either a 12-week intermittent calorie restriction (iCR) diet (n = 5) or control (n = 5). Cortical thickness and volumes were measured through FreeSurfer, cortical perfusion was measured by arterial spin labeling and neuroinflammation through diffusion basis spectrum imaging. RESULTS: After 12 weeks of iCR, brain volume increased in the left superior and inferior parietal gyri (p: 0.050 and 0.049, respectively) and the banks of the superior temporal sulcus (p: 0.01). Similarly in the iCR group, cortical thickness improved in the bilateral medial orbitofrontal gyri (p: 0.04 and 0.05 in right and left, respectively), the left superior temporal gyrus (p: 0.03), and the frontal pole (p: 0.008) among others. Cerebral perfusion decreased in the bilateral fusiform gyri (p: 0.047 and 0.02 in right and left, respectively) and increased in the bilateral deep anterior white matter (p: 0.03 and 0.013 in right and left, respectively). Neuroinflammation, demonstrated through hindered and restricted water fractions (HF and RF), decreased in the left optic tract (HF p: 0.02), and the right extreme capsule (RF p: 0.007 and HF p: 0.003). CONCLUSION: These pilot data suggest therapeutic effects of iCR in improving cortical volume and thickness and mitigating neuroinflammation in midlife adults with MS.

Nutritional quality of calorie restricted diets in the CALERIE™ 1 trial.

OBJECTIVES: The aim was to determine the nutritional adequacy of calorie restricted (CR) diets during CR interventions up to 12 months. METHODS: The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) phase 1 trial consisted of 3 single-site studies to test the feasibility and effectiveness of CR in adults without obesity. After baseline assessments, participants who were randomized to a CR intervention received education and training from registered dietitians on how to follow a healthful CR diet. Food diaries were completed at baseline and during the CR interventions (~6, 9, and 12 months) when participants were self-selecting CR diets. Diaries were analyzed for energy, macronutrients, fiber, 11 vitamins, and 9 minerals. Nutritional adequacy was defined by sex- and age-specific Estimated Average Requirement (EAR) or Adequate Intake (AI) criteria for each nutrient. Diet quality was evaluated using the PANDiet diet quality index. RESULTS: Eighty-eight CR participants (67% women, age 40 ± 9 y, BMI 27.7 ± 1.5 kg/m2) were included in the analysis. Dietary intake of fiber and most vitamins and minerals increased during CR. More than 90% of participants achieved 100% of EAR or AI during CR for 2 of 4 macronutrients (carbohydrate and protein), 6 of 11 vitamins (A, B1, B2, B3, B6, B12), and 6 of 9 minerals assessed (copper, iron, phosphorus, selenium, sodium, zinc). Nutrients for which <90% of participants achieved adequacy included fiber, omega-3 fatty acids, vitamins B5, B9, C, E, and K, and the minerals calcium, magnesium, and potassium. The PANDiet diet quality index improved from 72.9 ± 6.0% at baseline to 75.7 ± 5.2% during CR (p < 0.0001). CONCLUSION: Long-term, calorie-restricted diets were nutritionally equal or superior to baseline ad libitum diets among adults without obesity. Our results support modest calorie restriction as a safe strategy to promote healthy aging without compromising nutritional adequacy or diet quality.

Influence of weekend lifestyle patterns on body weight.

OBJECTIVE: To determine whether alterations in diet and/or activity patterns during weekends contribute to weight gain or hinder weight loss. METHODS AND PROCEDURES: Randomized, controlled trial comparing 1 year of caloric restriction (CR) with 1 year of daily exercise (EX). Subjects included 48 healthy adults (30F, 18M) aged 50-60 years with BMI 23.5-29.9 kg/m(2). Body weight was measured on 7 consecutive mornings for a total of 165 weeks at baseline and 437 weeks during the 1-year interventions. Daily weight changes were calculated for weekends (Friday to Monday) and weekdays (Monday to Friday). Daily energy intake was estimated using food diaries; daily physical activity was measured using accelerometers. Both measures were validated against doubly labeled water (DLW). RESULTS: At baseline, participants consistently gained weight on weekend days (+0.06 +/- 0.03 kg/day, (mean +/- s.e.), P = 0.02), but not on weekdays (-0.02 +/- 0.02 kg/day, P = 0.18). This was attributable to higher dietary intake on Saturdays and lower physical activity on Sundays relative to weekdays (both P < 0.05). During the interventions, both CR and EX participants were in negative energy balance on weekdays (P < 0.005). On weekends, however, CR participants stopped losing weight, and EX participants gained weight (+0.08 +/- 0.03 kg/day, P < 0.0001) due to higher dietary intakes on weekends. This helps to explain the slower-than-expected rate of weight loss during the interventions. DISCUSSION: Alterations in lifestyle behaviors on weekends contribute to weight gain or cessation of weight loss on weekends. These results provide one explanation for the relatively slow rates of weight loss observed in many studies, and the difficulty with maintaining significant weight loss.