Tag: vitamins

Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency.

Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12.

Results: Mean symptom change was -6.7 in the intervention group versus -1.2 in the control group (between-group difference -5.6; 95% CI: -7.2, -3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts.

Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC.

Source: Kodama S, Nakata M, Konishi N, Yoshino M, Fujisawa A, Naganuma M, Kobayashi Y, Hirai Y, Kitagawa A, Miyokawa M, Mishima R, Teramukai S, Fukushima M. Vitamin D in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After COVID-19 or Vaccination: A Randomized Controlled Trial. Nutrients. 2026 Feb 3;18(3):521. doi: 10.3390/nu18030521. PMID: 41683343. https://www.mdpi.com/2072-6643/18/3/521 (Full text)

Specialised care for severely affected ME/CFS patients

Abstract:

Introduction: A specialised care unit for severely and very severely ill ME/CFS patients opened in 2021. The results from the first 3 years are reported.

Methods: People with ME/CFS who were diagnosed according to the Canadian Consensus Criteria, who are aged 18 or above with severe or very severe ME/CFS according to the UK NICE guidelines, are eligible to stay at Røysumtunet. The study design is a retrospective review of medical records.

Results: Between June 2021 and June 2024, 24 ME/CFS patients, 20 women and 4 men with a confirmed diagnosis of ME, were admitted to the unit for stays of at least 3 months. Seventeen were very severely affected and 7 were severely affected. Ages ranged from 18 to 68 years, with mean (SD) 37.5 (12.8) years. Seven patients showed significant improvement (p < 0.01), and five others showed some improvement. In total 50% improved (p < 0.01). Patients who improved were borderline significantly younger than those who did not, with a mean age of 30.3 (SD 12.6) years compared to 39.8 (SD 11.8) years (p = 0.06). The mean duration of disease was 2.3 (1.3) years for those who improved versus 6.7 (3.9) years for those who did not improve (p < 0.05).

Conclusion: This is the first report of a specialised care unit for the most severely ill ME/CFS patients. Fifty per cent of patients showed significant or partial improvement. The mechanisms behind these improvements are discussed but require further exploration in future studies.

Source: Saugstad, O. D., Sollie, M. G., Torp, H. A., & Storla, D. G. (2025). Specialised care for severely affected ME/CFS patients. Fatigue: Biomedicine, Health &amp; Behavior, 1–13. https://doi.org/10.1080/21641846.2025.2565101 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2565101 (Full text)

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

Abstract:

Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles.

Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD.

Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%).

Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19.

Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.

Source: Gomaa, A.A., Abdel-Wadood, Y.A., Thabet, R.H. et al. Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01383-x https://link.springer.com/article/10.1007/s10787-023-01383-x (Full text)

Long COVID, POTS, CFS and MTHFR: Linked by Biochemistry and Nutrition

Abstract:

The recent pandemic has energized research spotlighting chronic fatigue disorders. The similarities between Long COVID (LC) and Chronic Fatigue Syndrome (CFS), often accompanied by postural orthostatic tachycardia syndrome (POTS) are striking.

Furthermore, the majority afflicted with LC and CFS may be those with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, present in the majority of Americans and characterized by hypomethylation. Elevated homocysteine (Hcy) and depressed B9 and B12 may be links. Speculation about an association between these laboratory analytes and MTHFR abnormalities has been previously reported (Regland et al., 2015).

The absence of a blood-brain barrier (BBB) in CNS circumventricular organs (CVOs) that control autonomic and neuroendocrine functions, problematic in LC, CFS, POTS, and MTHFR, is provocative. Diffusion of CNS Hcy is associated with brain fog, cognitive impairment, and dementia. This provides a distinct link between MTHFR variants and the fog of LC, CFS, and POTS.

Small intestine bacterial overgrowth (SIBO), present in about 17% of Americans, is linked to POTS, mast cell activation syndrome (MCAS), and Ehlers Danlos syndrome (EDS). All exhibit histamine intolerance and female predominance. This may be due to hypomethylation and/or intestinal diamine oxidase (DAO) deficiency.

Metabolism of monoamines and histamine requires methylation. Specific CNS nuclei in CVOs may also provide insight to the POTS paradox. The similar gut microbiomes of LC/CFS (and vitamin D deficiency) may via CVOs trigger an imbalance in glutamate/GABA neurotransmission that translates to neuroendocrine and baroreflex dysfunction. Homozygosity for the MTHFR 677T allele can facilitate hypermethylation via an alternative “rescue” riboflavin pathway triggered by significant Hcy increase.

Hypermethylation predominates in Long Covid. The primary problem in these syndromes is compromised mitochondrial function due to oxidative stress induced by an antioxidant shortfall.

Victims are also frequently deficient in 25(OH)D3 (the storage form of vitamin D), magnesium, and B vitamins, consumed by the persistent chronic inflammatory state. Estrogen increases histamine, norepinephrine, and bradykinin (BKN), which may in part explain the brain fog and its predilection for females.

Source: Patrick W Chambers. Long COVID, POTS, CFS and MTHFR: Linked by Biochemistry and Nutrition. Journal of Orthomolecular Medicine. 38. https://www.researchgate.net/publication/373073968_Long_Covid_POTS_CFS_and_MTHFR_Linked_by_Biochemistry_and_Nutrition#fullTextFileContent (Full text)

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID

Abstract:

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed.
Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs–fMRI).
Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127–175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs–fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group.
Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.
Source: Chung TW-H, Zhang H, Wong FK-C, Sridhar S, Lee TM-C, Leung GK-K, Chan K-H, Lau K-K, Tam AR, Ho DT-Y, et al. A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID. Brain Sciences. 2023; 13(7):1014. https://doi.org/10.3390/brainsci13071014 https://www.mdpi.com/2076-3425/13/7/1014 (Full text)

Nutritional deficiencies that may predispose to long COVID

Abstract:

Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.

Source: Schloss, J.V. Nutritional deficiencies that may predispose to long COVID. Inflammopharmacol (2023). https://doi.org/10.1007/s10787-023-01183-3 https://link.springer.com/article/10.1007/s10787-023-01183-3 (Full text)

Long COVID in the Older Adult and Vitamin D

Abstract:

Background: The coronavirus COVID-19 strain that emerged in December 2019 continues to produce a widespread and seemingly intractable negative impact on health and longevity and life quality in all parts of the world, especially, among older adults with chronic health conditions.

Objectives: The first aim of this updated review article was to examine, summarize, synthesize, and report on the research base concerning the possible use of vitamin D in the realm of the recently emergent syndrome termed long or post-acute COVID-19 disease. A second was to establish any health associated preventive and intervention recommendations for the older adult with long COVID-19 manifestations, who may yet be susceptible to future COVID-19 variant infections and others.

Methods: To examine the association between vitamin D and long COVID-19 illness manifestations, articles responding to several key words entered into leading data bases were examined: These included the terms: Vitamin D, Long/Post-Acute COVID-19 and/or COVID-19. Databases employed were PUBMED, PubMed Central and Google Scholar. All relevant articles were carefully examined and those meeting the review criteria were carefully read, and described in narrative form.

Results: Data reveal some possible benefits may accrue in the context of COVID-19 illness prevention and rehabilitation by efforts to ensure optimal vitamin D serum levels among high risk, vitamin D deficient, and chronically challenged post-acute COVID-19 older adults.

Conclusion: More rigorous and carefully construed research efforts to examine vitamin D implications and its moderating or mediating role in averting or mitigating long COVID-19 health complications are strongly warranted.

Source: Ray Marks (2023) Long COVID in the Older Adult and Vitamin D. J Gerontol Geriatr Med 9: 155. https://www.heraldopenaccess.us/openaccess/long-covid-in-the-older-adult-and-vitamin-d (Full text)

The Role of Immunity and Inflammation in ME/ CFS and Post-COVID Syndrome: Implications for Treatment

Abstract:

Probably one in seven patients who have experienced acute COVID-19 continue having long-lasting complaints, called post-COVID syndrome or long-COVID, that are similar to those observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

There are good reasons to believe that common immunological, epigenetic and inflammatory mechanisms are involved in the pathogenesis both diseases.

To date, various therapeutic approaches have been recommended, but with moderate success. In the present opinion paper, the author weights his clinical experience against data from the literature, and suggests novel approaches.

In addition to general measures and paramedical approaches, food supplementation with a specific nutraceutical can be completed by oral administration of sodium dichloroacetate and Meldonium to optimize glucose metabolism and mitochondrial energy generation.

Alternatively, intravenous infusions with magnesium salt and multivitamins can be completed with glutathione, m-tranexamic acid, and cultured stem cells.

Preliminary results of an open-label, prospective, two-centre trial suggest more than four in five patients benefit from combined oral and infusion therapy with significantly diminished fatigue and improved well-being.

Monoclonal antibodies in “biologicals”, blocking the effects of cytokines, and “small molecules” with Janus kinase inhibiting activity may offer novel opportunities by focusing on both immunologic and inflammation targets. A pilot trial with, in particular, one of the Janus kinase inhibitors could be considered.

Source: Comhaire F. The Role of Immunity and Inflammation in ME/CFS and Post-COVID Syndrome: Implications for Treatment. MedLife Clinics 2022, Volume 4 (2), Article 1043 http://www.medtextpublications.com/open-access/the-role-of-immunity-and-inflammation-in-me-cfs-and-1254.pdf (Full text)

Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome

Abstract:

Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) is a complex chronic condition, characterized by periods of extreme fatigue, for which an underlying medical condition has previously not been identified.

Many of the symptoms of CFS/ME, are, though, similar to those with vitamin B12 deficiency. In contrast to nutritional vitamin B12 deficiency, the majority of individuals with CFS have been shown to have functional vitamin B12 deficiency as well as functional vitamin B2 deficiency.

This functional B12 deficiency occurred despite elevated serum B12 being found, and hence presents as Paradoxical vitamin B12 deficiency. As such, CFS due to functional B2 deficiency presents as Paradoxical B12 deficiency.

Maintenance of vitamin B12 functional activity is critically dependent upon functional B2 sufficiency, and hence resolution of CFS there must first be resolution of functional B2 deficiency before treatment with vitamin B12 can be effective.

Disclosures: Gregory Russell-Jones is the director of B12 Oils Pty Ltd, a company that specializes in the manufacture and supply of vitamin B12 Oils.

Source: Gregory Russell-Jones.(2022). Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome. Int J Psychiatry 7(3): 153-158. https://www.researchgate.net/publication/362644480_Functional_Vitamin_B12_deficiency_in_Chronic_Fatigue_Syndrome_International_Journal_of_Psychiatry_Corresponding_author (Full text available as PDF file)

Multivitamin mineral supplementation in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched.

MATERIAL AND METHODS: This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36).

Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found.

CONCLUSIONS: Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

 

Source: Maric D, Brkic S, Tomic S, Novakov Mikic A, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Med Sci Monit. 2014 Jan 14;20:47-53. doi: 10.12659/MSM.889333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907507/ (Full article)