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The Effect of Gluten Free Diet on Components of Metabolic Syndrome: A Randomized Clinical Trial
Ehteshami, M, Shakerhosseini, R, Sedaghat, F, Hedayati, M, Eini-Zinab, H, Hekmatdoost, A
Asian Pacific journal of cancer prevention : APJCP. 2018;19(10):2979-2984
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Metabolic syndrome is a cluster of conditions related to cardiovascular disorders risk factors such as blood pressure, dyslipidaemia, hyperglycaemia, excess body fat around the waist and insulin resistance. The aim of this study was to assess the effects of a gluten-free diet on components of metabolic syndrome in patients diagnosed with metabolic syndrome. The study is a randomised control trial that recruited fifty subjects diagnosed with metabolic syndrome. Subjects were block randomised by gender into control and gluten-free diet groups. Results showed that a gluten-free diet induces significant reduction in waist circumference in comparison to control diet. Reduction in waist circumference without significant reduction in body weight may indicate preferential loss of abdominal fat. Furthermore, results indicate that a gluten-free diet improved glucose tolerance. Authors conclude that a gluten-free diet significantly improved some key features of metabolic syndrome including blood glucose and serum triglycerides.
Abstract
Background: This study aimed to assess the effects of Gluten free diet (GFD) on components of metabolic syndrome (MES). Materials and Methods: In this randomized clinical trial, 50 subjects diagnosed with MES were randomly divided into two groups (n=25). The first group received a GFD and the second group continued their regular diet. Biochemical markers of MES and blood pressure were measured before and after 8-week intervention. Results: Forty five subjects completed the study. A post-hoc comparison of the groups showed no effects of the GFD and control diet on LDL cholesterol, total cholesterol, fasting insulin, HOMA-IR, systolic and diastolic blood pressure levels. The GFD reduced fasting blood glucose, waist circumference (WC) and serum triglyceride concentration significantly compared with the control diet (p<0.05). Conclusion: Short-term GFD reduced WC and improved glycemic control and Triglyceride level in subjects with the metabolic syndrome.
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The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study.
Bauersfeld, SP, Kessler, CS, Wischnewsky, M, Jaensch, A, Steckhan, N, Stange, R, Kunz, B, Brückner, B, Sehouli, J, Michalsen, A
BMC cancer. 2018;18(1):476
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Short-term fasting (STF) has been shown to protect healthy cells against the adverse effects of chemotherapy while making tumor cells more vulnerable to it. The present randomised pilot cross-over study was designed to assess the effect of a 60 hour STF on quality of life (QOL), well-being and fatigue in patients with gynaecological cancer undergoing chemotherapy. Group A was randomised to a STF during the first three of six scheduled chemotherapies (36 h before to 24 h after the chemotherapy) followed by non-calorie restricted nutrition during the following three chemotherapies. During the fasting period subjects received unrestricted amounts of water, herbal tea, 2x100cl vegetable juice and small standardized quantities of light vegetable broth with a maximum total daily energy intake of 350 kcal. Group B was allocated to a vice versa sequence of nutrition. All measurements were performed at baseline and eight days after each chemotherapy cycle. A variety of questionnaires were used for assessment of QOL, general well-being and fatigue. 34 patients with breast or ovarian cancer completed the study. Fasting was safe and all reported side effects were of low grade. STF led to a better tolerance to chemotherapy with less compromised QOL and reduced fatigue within the 8 days after chemotherapy. At the final consultation the majority of patients reported better tolerance to chemotherapy with STF. The authors conclude that STF during chemotherapy is feasible and has beneficial effects on QOL, well-being and fatigue.
Abstract
BACKGROUND This pilot trial aimed to study the feasibility and effects on quality of life (QOL) and well-being of short-term fasting (STF) during chemotherapy in patients with gynecological cancer. METHODS In an individually-randomized cross-over trial patients with gynecological cancer, 4 to 6 planned chemotherapy cycles were included. Thirty-four patients were randomized to STF in the first half of chemotherapies followed by normocaloric diet (group A;n = 18) or vice versa (group B;n = 16). Fasting started 36 h before and ended 24 h after chemotherapy (60 h-fasting period). QOL was assessed by the FACIT-measurement system. RESULTS The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference (MID; FACT-G = 5) with STF but greater than the MID for non-fasted periods. The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects. CONCLUSION STF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy. Larger studies should prove the effect of STF as an adjunct to chemotherapy. TRIAL REGISTRATION This trial was registered at clinicaltrials.gov: NCT01954836 .
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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.
Murtola, TJ, Vihervuori, VJ, Lahtela, J, Talala, K, Taari, K, Tammela, TL, Auvinen, A
British journal of cancer. 2018;118(9):1248-1254
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Studies have shown that people with diabetes mellitus have lower risk of developing prostate cancer compared with non-diabetics. Glucose metabolism (the process by which simple sugars found in food are processed and used to produce energy) may have an independent role in prostate cancer development and progression. The aim of this study was to investigate the associations between fasting blood glucose and glycaemic control and prostate cancer risk. The study recruited 80,144 men who were randomly assigned either to be screened with PSA at four-year intervals (the screening arm, 31,866 men) or to control arm with no intervention and followed through national registries (48,278 men). Results indicate an association between fasting blood glucose level and elevated prostate cancer risk. This association was more noticeable in the screening arm, and concerned both poorly and well-differentiated cancers. Furthermore, compared to the normoglycemic men, overall prostate cancer risk was elevated in diabetic, but not in pre-diabetic men. Authors conclude that diabetic fasting blood glucose level is associated with elevated prostate cancer risk in a population-based cohort of Finnish men.
Abstract
BACKGROUND Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.
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Effects of Fasting on 18F-DCFPyL Uptake in Prostate Cancer Lesions and Tissues with Known High Physiologic Uptake.
Wondergem, M, van der Zant, FM, Vlottes, PW, Knol, RJJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59(7):1081-1084
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Prostate-specific membrane antigen (PSMA) (PSMA is a type II membrane protein)–targeted PET imaging is being increasingly applied in prostate cancer. The aim of this study was to determine the impact of fasting on 18F-DCFPyL (is a fluorine-18 labelled ligand binding specifically to PSMA) uptake in organs with known high physiologic uptake and in lesions characteristic of prostate cancer metastases. The study is a cohort study in which 50 and 48 patients were analysed in the fasting and non-fasting cohorts, respectively. Results showed that lesions characteristic of prostate cancer showed similar uptake in both the fasting and the non-fasting cohorts (number of lesions characteristic of prostate cancer totalled to 152 and 131 respectively). Authors conclude that fasting for up to 6 h before 18F-DCFPyL PET/CT does not significantly affect uptake in suspected malignant lesions but significantly lowers uptake in tissues with high physiologic uptake, such as the salivary glands, liver, and spleen.
Abstract
In the literature, a 4- to 6-h fast is recommended before a patient undergoes PET/CT with 2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL); however, a scientific underpinning for this recommendation is lacking. Therefore, we performed a study to determine the impact of fasting on 18F-DCFPyL uptake. Methods: The study included 50 patients who fasted at least 6 h before 18F-DCFPyL administration and 50 patients who did not. Activity (SUVmax) was measured in lesions characteristic of prostate cancer and in normal tissues known to express high physiologic uptake. Results: Uptake in suspected lesions did not differ between the cohorts. 18F-DCFPyL uptake in the submandibular gland, liver, and spleen was significantly higher in the fasting than the nonfasting cohort. Conclusion: Our data show that fasting does not significantly affect 18F-DCFPyL uptake in suspected malignant lesions but does result in significantly lower 18F-DCFPyL uptake in tissues with high physiologic uptake. The absolute differences in uptake were relatively small; therefore, the effects of fasting on the diagnostic performance can be considered negligible.
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A review of adherence to the Mediterranean diet and breast cancer risk according to estrogen- and progesterone-receptor status and HER2 oncogene expression.
Coughlin, SS, Stewart, J, Williams, LB
Annals of epidemiology and public health. 2018;1
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Epidemiological evidence suggests that eating a Mediterranean diet is associated with a reduced risk of breast cancer. The aim of this review, which includes seven epidemiological studies, was to examine the association between a Mediterranean diet and risk of breast cancer according to molecular subtype: oestrogen-receptor (ER) and progesterone-receptor (PR) status and human epidermal growth factor 2 (HER2) oncogene expression. The authors define a Mediterranean diet as high in fruit and vegetables, fish, whole grains, nuts, seeds and olive oil; low to moderate in alcohol, dairy products, eggs, and poultry; and low in red and processed meats and sweets. The authors find that eating a Mediterranean diet is associated with a reduced risk of breast cancer in postmenopausal women, particularly among ER negative tumours, with a less clear association for other subtypes and premenopausal women.
Abstract
BACKGROUND Previous observational studies and systematic reviews have suggested that adherence to the Mediterranean diet is associated with a reduced risk of breast cancer, but have not examined associations with molecular subtypes of breast cancer. The current review examines the association with adherence to the Mediterranean diet and risk of breast cancer according to molecular subtypes. METHODS Bibliographic searches were conducted in PubMed and CINAHL using relevant MeSH search terms and Boolean algebra commands. RESULTS Six cohort studies and one case-control study have examined adherence with the Mediterranean diet and risk of breast cancer according to estrogen-receptor (ER) and progesterone-receptor (PR) status and human epidermal growth factor 2 (HER2) oncogene expression. Taken overall, studies suggest that the Mediterranean dietary pattern is inversely associated with breast cancer risk in postmenopausal women, and that the inverse association is somewhat stronger among ER- tumors. Although there is a suggestion that the Mediterranean diet is inversely associated with PR- tumors and with ER-/PR-/HER2- ("triple negative" tumors), results to date have been mixed and the number of studies that have examined associations with this dietary pattern among tumors characterized by multiple molecular subtypes remains small. CONCLUSIONS The results of this systematic review suggest that consumption of a Mediterranean diet pattern is associated with a reduced risk of postmenopausal breast cancer, particularly among ER- tumors. Additional cohort studies that have sufficient sample sizes and long-term follow-up are warranted to identify sizeable numbers of invasive breast cancer cases, thereby allowing for characterization of the tumors by molecular subtype.
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Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial.
Adams, JB, Audhya, T, Geis, E, Gehn, E, Fimbres, V, Pollard, EL, Mitchell, J, Ingram, J, Hellmers, R, Laake, D, et al
Nutrients. 2018;10(3)
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People with autism spectrum disorder (ASD) often have significant nutritional deficiencies, metabolic imbalances, and digestive problems. Many studies have previously looked at individual nutrients for ASD. This study was designed to look at the accumulative effect of using a wide range of dietary and nutritional interventions, including vitamin and mineral supplements, essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a gluten-free, casein-free, soy-free (HGCSF) diet. The objective being to see if combining multiple interventions for a 12-month period, had greater benefits versus single nutrient interventions, and shorter trials. This US study recruited a wide age range of participants from 3-58yrs because it targeted, and was funded, by family groups of the Autism Society of Greater Phoenix. The study was deliberately single-blinded (meaning the participants knew what they were being given, but the clinical evaluators did not), as it was thought this would be more compelling and lead to less dropouts, especially considering the 12-month timing. In total 67 participants with ASD were recruited and 50 controls. Blood and urine samples were taking at the beginning and end of the study alongside autism severity assessments. Results showed an improvement in nutrient profiles for vitamins, minerals, fatty acids and carnitine alongside a significant decrease in homocysteine. There was an improvement in non-verbal IG test and cognitive function, and gastro-intestinal symptoms. There were no significant differences in complete blood count, blood chemistry panels or markers for inflammatory C-reactive protein (CRP). There was no change to BMI. Three exceptional cases of improvement were recorded in the control group and made into case studies highlighting improved physical strength and ability to walk, and resolution of urinary issues and pica eating disorder. Because it was single blinded there may be some ‘placebo effect’ but overall the researchers conclude that the study demonstrates how interventions can be safely and effectively implemented in families, with minimal adverse effect. And that combined nutrient and diet interventions should be considered for use in clinical practice.
Abstract
This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3-58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 ± 11 IQ points vs. -0.6 ± 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.
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Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.
Sutton, EF, Beyl, R, Early, KS, Cefalu, WT, Ravussin, E, Peterson, CM
Cell metabolism. 2018;27(6):1212-1221.e3
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Studies have shown that intermittent fasting (IF) can reduce body weight or body fat, as well as a number of metabolic markers. However, it is unknown whether the metabolic benefits are solely due to the weight loss. In addition, data from circadian studies suggest that eating earlier in the day has a positive effect on metabolism. The aim of this randomised, cross-over, controlled feeding trial was to evaluate the effects of early time-restricted feeding (eTRF) on weight and metabolic markers. eTRF was implemented as consuming all calories within a 6 hours window with the last meal no later than 3pm. 8 overweight men with prediabetes were randomized to either eTRF or a control schedule (12-hr feeding period) for 5 weeks, and later crossed over to the other schedule. During both eating regimes the same meals and calories were consumed in both groups in a controlled environment. eTRF improved insulin metabolism, blood pressure and oxidative stress, but not glucose levels, cholesterol or inflammatory markers. No weight loss occurred either during eTRF or control period, suggesting that the observed changes are independent of weight loss. The authors conclude that eTRF improves some aspects of cardiometabolic health and that these effects are not solely due to weight loss.
Abstract
Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.
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Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.
Cignarella, F, Cantoni, C, Ghezzi, L, Salter, A, Dorsett, Y, Chen, L, Phillips, D, Weinstock, GM, Fontana, L, Cross, AH, et al
Cell metabolism. 2018;27(6):1222-1235.e6
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Calorie restriction (CR) has potent anti-inflammatory effects and has shown beneficial effects in an animal model for Multiple Sclerosis (MS). Intermittent Fasting (IF) has similar effects as CR and may be more acceptable long term than CR. This paper reports results from both an animal study and a pilot randomised controlled human clinical trial on IF and MS. The animal study showed that IF had beneficial effects on the MS animal model and that these effects were at least in part mediated by changes in the gut microbiome. 16 patients with relapsing remitting MS were enrolled during a relapse and randomised to either IF (6-7 fasting days during the two-week study) or normal eating. Changes in immune inflammatory parameters and gut flora were seen in the IF group which were similar to the beneficial changes in the animal model. The authors conclude that larger clinical studies to test IF and microbiome manipulation as a potential treatment in MS are warranted.
Abstract
Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.
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A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics.
Han, K, Nguyen, A, Traba, J, Yao, X, Kaler, M, Huffstutler, RD, Levine, SJ, Sack, MN
Journal of immunology (Baltimore, Md. : 1950). 2018;201(5):1382-1388
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Previous studies have shown that caloric restriction and fasting may modulate immune function and have positive effects in asthmatics. The aim of this pilot study was to evaluate the effects of fasting on specific inflammatory markers that might mediate such benefits. 18 mild asthmatics, 5 of whom were not on steroid inhalers, fasted for 24 hours. Lung function and immune parameters were evaluated at baseline and 2.5 hours after the first meal following the fast. There were significant differences between subjects who were and were not on steroid inhalers. Whilst one day of fasting did not affect lung function, a number of inflammatory parameters were improved by fasting in those not taking steroid inhalers, but not in those who were taking steroids. The authors conclude that caloric restriction might be considered as a strategy to improve systemic and pulmonary inflammation in asthma.
Abstract
A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4+ T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
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Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.
Fitzgerald, KC, Vizthum, D, Henry-Barron, B, Schweitzer, A, Cassard, SD, Kossoff, E, Hartman, AL, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
Multiple sclerosis and related disorders. 2018;23:33-39
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Multiple sclerosis (MS) is a disease of the central nervous system. Dietary modification is emerging as a safe intervention to potentially modify disease course. The main aim of this study was to assess the safety and feasibility of an intermittent fasting diet in people with MS. Secondary outcomes explored the effects of calorie restriction (CR) diets on body weight and anthropometric characteristics as well as on patient-reported outcomes including fatigue, sleep and mood. The study is a pilot randomised controlled feeding study of three different types of diets. Each participant (n=36) was randomized to 1 of 3 diets: a control diet (placebo), a daily CR diet and intermittent CR diet. Results indicate that daily CR diet was associated with marginally greater weight loss than the intermittent CR diet. Both CR diets were associated with trends toward improvements in cardiometabolic outcomes. Furthermore, CR diets were associated with in improvements in emotional well-being. Authors conclude that CR and weight loss represent interventions for clinically relevant symptoms due to MS, such as emotional well-being, without adding meaningful risks or adverse outcomes.
Abstract
An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.