- •Both diets had significant improvements in anxiety and depression scores.
- •Serum levels of homocysteine were reduced, and folate and vitamin B12 increased.
- •No association of depressive symptoms changes with serum homocysteine or vitamin B12.
Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS).
In a previously conducted randomized parallel-arm trial, participants with RRMS (n = 77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively.
Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p ≤ 0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20 nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p > 0.05).
Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p > 0.05).
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Multiple Sclerosis and Related Disorders
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- A new look at the statistical model identification.IEEE Trans. Autom. Control. 1974; 19: 716-723
- Dietary interventions and multiple sclerosis.Curr. Neurol. Neurosci. Rep. 2017; 17: 28
- Hyperhomocysteinemia and neurologic disorders: a review.J. Clin. Neurol. 2014; 10: 281-288
- Health-related quality of life in multiple sclerosis: direct and indirect effects of comorbidity.Neurology. 2016; 86 (Neurology): 1417-1424
- Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.J. Neurol. Neurosurg. Psychiatry. 2022; 93: 637-644
- B Vitamins in the nervous system: current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin.CNS Neurosci. Ther. 2020; 26: 5-13
- Treatment of depression: time to consider folic acid and vitamin B12.J. Psychopharmacol. 2005; 19: 59-65
- Relation of serum levels of homocysteine, vitamin B12 and folate to cognitive functions in multiple sclerosis patients.Int. J. Neurosci. 2018; 128: 835-841
- Diet quality is associated with disability and symptom severity in multiple sclerosis.Neurology. 2018; 0: e1-e11
- Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.Mult. Scler. Relat. Disord. 2018; 23: 33-39
- Associations between fatigue and disability, functional mobility, depression, and quality of life in people with multiple sclerosis.Int. J. MS Care. 2016; 18: 71-77
- Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study.Degener. Neurol. Neuromuscul. Dis. 2017; 7: 1-18
- Introduction to mediation analysis and examples of its application to real-world data.J. Prev. Med. Public Health. 2021; 54: 166-172
- The role of diet in multiple dclerosis: mechanistic connections and current evidence.Curr. Nutr. Rep. 2018; 7: 150-160
- Mediterranean diet is linked to less objective disability in multiple sclerosis.Mult. Scler. 2022; (13524585221127414)
- A systematic review of the effectiveness of self-management interventions in people with multiple sclerosis at improving depression, anxiety and quality of life.PLoS ONE. 2017; 12e0185931
- Cognition in multiple sclerosis.Curr. Opin. Neurol. 2011; 24: 244-249
- A multimodal, nonpharmacologic intervention improves mood and cognitive function in people with multiple sclerosis.J. Am. Coll. Nutr. 2017; 36: 150-168
- Serum levels of homocysteine, vitamin B12 and folate in patients with multiple sclerosis: an updated meta-analysis.Int. J. Med. Sci. 2020; 17: 751-761
- B vitamins and one-carbon metabolism: implications in human health and disease.Nutrients. 2020; 12
- A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview.Mult. Scler. 2015; 21: 263-281
- Generalized Linear Mixed Models.Wiley StatsRef: Statistics Reference Online, 2014 (Balakrishnan, N., Colton, T., Everitt, B., Piegorsch, W., Ruggeri, F., Teugels, J.L. (Eds.))
- Change in clinician-assessed measures of multiple sclerosis and subject-reported quality of life: results from the IMPACT study.Mult. Scler. 2006; 12: 180-186
- Homocysteine, vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: a case control study.Clin. Neurol. Neurosurg. 2013; 115: 1802-1805
- CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials.J. Clin. Epidemiol. 2010; 63: e1-37
- The association between serum homocysteine and depression: a systematic review and meta-analysis of observational studies.Eur. J. Clin. Investig. 2021; 51: e13486
- The effects of modified anti-inflammatory diet on fatigue, quality of life, and inflammatory biomarkers in relapsing-remitting multiple sclerosis patients: a randomized clinical trial.Int. J. Neurosci. 2021; 131: 657-665
Multiple Sclerosis International Federation, 2020. Atlas of MS. https://www.msif.org/wp-content/uploads/2020/12/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases.Clin. Chem. Lab. Med. 2007; 45: 1590-1606
- Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis.Metab. Brain Dis. 2018; 33: 1393-1399
- A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients.J. Am. Geriatr. Soc. 1975; 23: 433-441
- Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.Ann. Neurol. 2011; 69: 292-302
- Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients.Lipids Health Dis. 2010; 9: 19
- Associations between diet quality and depression, anxiety, and fatigue in multiple sclerosis.Mult. Scler. Relat. Disord. 2022; 63103910
- Omega-3 fatty acids for depression in multiple sclerosis: a randomized pilot study.PLoS ONE. 2016; 11e0147195
- Efficacy of diet on fatigue and quality of life in multiple sclerosis.Neurology. 2023; 100: e357
- Depression in multiple sclerosis: epidemiology, aetiology, diagnosis and treatment.CNS Drugs. 2018; 32: 117-133
- The hospital anxiety and depression scale.Occup. Med. 2014; 64: 393-394
- Change in micronutrient intake among people with relapsing-remitting multiple sclerosis adapting the swank and wahls diets: an analysis of weighed food records.Nutrients. 2021; 13
- Increased plasma homocysteine levels in patients with multiple sclerosis and depression.Ann. Gen. Psychiatry. 2008; 7: 17
- Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial.Trials. 2018; 19: 309
- Review of two popular eating plans within the multiple sclerosis community: low saturated fat and modified paleolithic.Nutrients. 2019; 11
- Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: the WAVES randomized parallel-arm clinical trial.Mult. Scler. J. Exp. Transl. Clin. 2021; 720552173211035399
- Validation of mood measures for people with multiple sclerosis.Int. J. MS Care. 2014; 16: 105-109
Published online: May 01, 2023
Accepted: April 30, 2023
Received in revised form: April 16, 2023
Received: February 2, 2023
© 2023 Elsevier B.V. All rights reserved.