Last update
3/31/2026
Research Authors

Overview

SCIENTIFIC SCORE
Questionable
Based on 11 Researches
6.3
USERS' SCORE
Good
Based on 6 Reviews
8.3
Supplement Facts
Serving Size: 1 Vegetarian Capsule
Amount Per Serving
%DV
Folate (as L-5-Methyltetrahydrofolate calcium salt)
680 mcg°
170%
Vitamin B12 (as methylcobalamin)
300 mcg
12,500%
📅 Last updated:

Top Medical Research Studies

0
Vitamin B12 ineffective for CFS
We explored the effectiveness of high-dose vitamin B12 injections on chronic fatigue syndrome (CFS) through two case reports that utilized N of 1 trials. This approach allowed us to make tailored treatment decisions based on individual responses to the therapy.

In one case, we found that high-dose vitamin B12 injections did not yield positive results, leaving the patient without significant relief from their symptoms. Conversely, in another case, we observed that nimodipine proved to be a very effective treatment for that patient’s chronic fatigue.

These findings suggest that while vitamin B12 may not be helpful for everyone suffering from CFS, other treatments like nimodipine can be beneficial. Thus, personalized treatment strategies are key in managing this complex and varied condition.
Read More
9
Folinic acid improves CFS symptoms
We aimed to explore the effects of folinic acid, also known as leucovorin, on patients suffering from chronic fatigue syndrome (CFS). Our investigation revealed some fascinating findings about this often misunderstood condition, particularly the links to immune response and Epstein-Barr virus (EBV) infection.

In our evaluation of 58 CFS patients, we discovered that nearly all had previously been exposed to EBV, with a striking 72% showing signs of active reactivation. Additionally, an overwhelming 94% were found to have a severe B-cell immunodeficiency, evidenced by a marked reduction in their CD19+IgM+ mature B-lymphocyte population.

What stood out was that after treatment with folinic acid, an impressive 81% of the participants reported experiencing a noticeable improvement in their symptoms. This suggests that folinic acid might play a significant role in the management of CFS, particularly for those struggling with related immune deficiencies and EBV responses.

Our findings bring new insights into CFS, indicating that it may be a condition responding well to folinic acid treatment. This opens up exciting avenues for further research into effective therapies for those affected by this challenging syndrome.
Read More
8
Folate improves fatigue-related disorders
We examined two groups of patients who exhibited neurological and psychiatric disorders responsive to folic acid treatment. The first group of seven individuals suffered from an acquired folate deficiency due to either poor absorption of nutrients or an inadequate diet. Their symptoms included significant fatigue, weight loss, and various neurological impairments. The second group, consisting of nine patients, presented idiopathic folate deficiency with chronic fatigue and family histories of restless legs syndrome.

Through neuropsychological testing, we observed abnormal intellectual functioning in all patients, along with issues highlighted on imaging studies like computerized transaxial tomography. Remarkably, after 6 to 12 months of folic acid therapy, a substantial improvement in their cognitive abilities and overall functioning was recorded.

This suggests that addressing folate deficiency might alleviate some aspects of fatigue and cognitive decline commonly associated with chronic fatigue syndrome. Our findings imply that long-term folate supplementation may lead to positive changes in those struggling with fatigue-related conditions, although the label of chronic fatigue syndrome was not explicitly used.
Read More

Most Useful Reviews

9
Enhanced vitality
I adore these tiny capsules! The quality is excellent and suits my needs perfectly. They are easy to swallow and have greatly assisted my mother, who suffers from Chronic Fatigue Syndrome; she feels remarkably better. I take them too, and there’s no unpleasant taste. Additionally, they've provided numerous benefits, including support for my metabolism and nervous system.
Read More
7.5
Improved wellbeing
I have Chronic Fatigue Syndrome and take one capsule each morning, which noticeably improves my condition. My family appreciates this positive change. My husband takes a higher dosage due to his homozygous MTHFR mutation, while my heterozygous status makes this dosage suitable for me. Thankfully, the drug does not cause any allergic reactions, despite my heightened sensitivity to various foods and medicines.
Read More
7.5
Menopausal relief
2 people found this helpful
I've just started these supplements, but already, my menopausal symptoms seem less severe. I'm relieved not to be troubled by chronic fatigue syndrome anymore. I’m quite happy with the results!
Read More

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Medical Researches

SCIENTIFIC SCORE
Questionable
Based on 11 Researches
6.3
  • All Researches
9
Folinic acid improves CFS symptoms
We aimed to explore the effects of folinic acid, also known as leucovorin, on patients suffering from chronic fatigue syndrome (CFS). Our investigation revealed some fascinating findings about this often misunderstood condition, particularly the links to immune response and Epstein-Barr virus (EBV) infection.

In our evaluation of 58 CFS patients, we discovered that nearly all had previously been exposed to EBV, with a striking 72% showing signs of active reactivation. Additionally, an overwhelming 94% were found to have a severe B-cell immunodeficiency, evidenced by a marked reduction in their CD19+IgM+ mature B-lymphocyte population.

What stood out was that after treatment with folinic acid, an impressive 81% of the participants reported experiencing a noticeable improvement in their symptoms. This suggests that folinic acid might play a significant role in the management of CFS, particularly for those struggling with related immune deficiencies and EBV responses.

Our findings bring new insights into CFS, indicating that it may be a condition responding well to folinic acid treatment. This opens up exciting avenues for further research into effective therapies for those affected by this challenging syndrome.
Read More
We aimed to evaluate how folic acid, in combination with vitamin B12, impacts individuals with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). Our study focused on a group of 38 patients who had received weekly B12 injections for six months to several years.

During our research, we categorized the patients into two groups: Good responders and Mild responders, based on their improvement in symptoms. We found that those who responded positively had received B12 injections more frequently and at higher doses compared to those with lesser improvement. They also tended to use more folic acid daily and were less likely to use strong analgesics.

Our findings suggested a clear relationship between the dosage of B12 and folic acid and the degree of improvement reported by the participants. However, we noted a higher occurrence of fibromyalgia among those with milder responses, indicating that the presence of additional conditions might affect outcomes.

Overall, we observed a dose-response effect suggesting that B12 and folic acid together could bring about meaningful improvements in CFS symptoms. Also, we identified the importance of being aware of possible thyroid issues and highlighted the need for more precise research regarding their interaction with other medications.
Read More
8
Folate improves fatigue-related disorders
We examined two groups of patients who exhibited neurological and psychiatric disorders responsive to folic acid treatment. The first group of seven individuals suffered from an acquired folate deficiency due to either poor absorption of nutrients or an inadequate diet. Their symptoms included significant fatigue, weight loss, and various neurological impairments. The second group, consisting of nine patients, presented idiopathic folate deficiency with chronic fatigue and family histories of restless legs syndrome.

Through neuropsychological testing, we observed abnormal intellectual functioning in all patients, along with issues highlighted on imaging studies like computerized transaxial tomography. Remarkably, after 6 to 12 months of folic acid therapy, a substantial improvement in their cognitive abilities and overall functioning was recorded.

This suggests that addressing folate deficiency might alleviate some aspects of fatigue and cognitive decline commonly associated with chronic fatigue syndrome. Our findings imply that long-term folate supplementation may lead to positive changes in those struggling with fatigue-related conditions, although the label of chronic fatigue syndrome was not explicitly used.
Read More
8
Vitamin B12 drops show promise
We examined the impact of vitamin B12 nasal drops on individuals suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study involved fifty-one patients, predominantly female, with an average age of 42 and an average illness duration of 16 years.

After three months of treatment, we measured their vitamin B12 serum levels, physical activity, and fatigue and concentration levels. Interestingly, we found that the participants who responded positively to the treatment experienced significant improvements in their vitamin B12 levels, daily step count, and overall physical activity. Moreover, those who reported a positive response noted a decrease in fatigue levels.

On the flip side, those categorized as non-responders had only a modest increase in vitamin B12 levels, with no notable improvement in other measures. Overall, our findings suggest that nasal drops could serve as a viable alternative to vitamin B12 injections, especially since around two-thirds of participants reported feeling better after treatment. This pilot study opens up new avenues for interventions in managing ME/CFS and highlights the importance of considering alternative treatment methods.
Read More
8
Potential effects on chronic fatigue
We recently came across an intriguing study that highlighted the potential benefits of a combination therapy involving lofepramine, L-phenylalanine, and vitamin B12 for patients suffering from multiple sclerosis (MS). Conducted as a randomized, placebo-controlled double-blind trial, the research aimed to evaluate how this combination could help alleviate various symptoms associated with MS and chronic pain.

While this study did address the role of vitamin B12, it was examined alongside lofepramine and phenylalanine. This makes it challenging for us to pinpoint the specific impact of vitamin B12 in the context of chronic fatigue syndrome on its own. The treatment showed effectiveness in improving symptoms within just two to four weeks, but due to the combination of treatments, we need more focused studies to assess vitamin B12's distinct role.

Overall, it's exciting to see a potential link between this therapy and symptom relief, yet we must remain cautious about attributing the benefits solely to vitamin B12, given the blended approach of the therapy used in the trial.
Read More

User Reviews

USERS' SCORE
Good
Based on 6 Reviews
8.3
  • All Reviews
  • Positive Reviews
  • Negative Reviews
9
Enhanced vitality
I adore these tiny capsules! The quality is excellent and suits my needs perfectly. They are easy to swallow and have greatly assisted my mother, who suffers from Chronic Fatigue Syndrome; she feels remarkably better. I take them too, and there’s no unpleasant taste. Additionally, they've provided numerous benefits, including support for my metabolism and nervous system.
Read More
7.5
Improved wellbeing
I have Chronic Fatigue Syndrome and take one capsule each morning, which noticeably improves my condition. My family appreciates this positive change. My husband takes a higher dosage due to his homozygous MTHFR mutation, while my heterozygous status makes this dosage suitable for me. Thankfully, the drug does not cause any allergic reactions, despite my heightened sensitivity to various foods and medicines.
Read More
7.5
Menopausal relief
2 people found this helpful
I've just started these supplements, but already, my menopausal symptoms seem less severe. I'm relieved not to be troubled by chronic fatigue syndrome anymore. I’m quite happy with the results!
Read More
9
Fatigue vanished
1 people found this helpful
Superb vitamins! After completing the course, I felt great improvement; my chronic fatigue syndrome has significantly diminished, and I feel energised.
Read More
7.5
Energy boost
1 people found this helpful
Suffering from Irritable Bowel Syndrome and a lack of B vitamins, I’ve gained more energy by supplementing with folic acid and vitamin B12. It has positively impacted my chronic fatigue syndrome.
Read More

Frequently Asked Questions

We aimed to evaluate how folic acid, in combination with vitamin B12, impacts individuals with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). Our study focused on a group of 38 patients who had received weekly B12 injections for six months to several years.

During our research, we categorized the patients into two groups: Good responders and Mild responders, based on their improvement in symptoms. We found that those who responded positively had received B12 injections more frequently and at higher doses compared to those with lesser improvement. They also tended to use more folic acid daily and were less likely to use strong analgesics.

Our findings suggested a clear relationship between the dosage of B12 and folic acid and the degree of improvement reported by the participants. However, we noted a higher occurrence of fibromyalgia among those with milder responses, indicating that the presence of additional conditions might affect outcomes.

Overall, we observed a dose-response effect suggesting that B12 and folic acid together could bring about meaningful improvements in CFS symptoms. Also, we identified the importance of being aware of possible thyroid issues and highlighted the need for more precise research regarding their interaction with other medications.
9
Folinic acid improves CFS symptoms
We aimed to explore the effects of folinic acid, also known as leucovorin, on patients suffering from chronic fatigue syndrome (CFS). Our investigation revealed some fascinating findings about this often misunderstood condition, particularly the links to immune response and Epstein-Barr virus (EBV) infection.

In our evaluation of 58 CFS patients, we discovered that nearly all had previously been exposed to EBV, with a striking 72% showing signs of active reactivation. Additionally, an overwhelming 94% were found to have a severe B-cell immunodeficiency, evidenced by a marked reduction in their CD19+IgM+ mature B-lymphocyte population.

What stood out was that after treatment with folinic acid, an impressive 81% of the participants reported experiencing a noticeable improvement in their symptoms. This suggests that folinic acid might play a significant role in the management of CFS, particularly for those struggling with related immune deficiencies and EBV responses.

Our findings bring new insights into CFS, indicating that it may be a condition responding well to folinic acid treatment. This opens up exciting avenues for further research into effective therapies for those affected by this challenging syndrome.
2
No significant benefit from folate
We conducted a carefully designed study to investigate the effects of an injectable treatment combining bovine liver extract, folic acid, and cyanocobalamin on chronic fatigue syndrome (CFS). This involved a double-blind, placebo-controlled crossover trial with 15 patients who met definitive criteria for CFS.

Throughout the study, patients received both the treatment and a placebo in alternating phases. While we observed that both the treatment and placebo seemed to provide some improvement in functional status for the patients, our analysis showed no significant advantage of the liver extract and folic acid combination over the placebo.

This indicates that the response to folate, particularly, is unclear as the placebo effect appeared to be notably strong among participants. Overall, the findings suggest that further research may be needed to ascertain the definitive role of folate in managing chronic fatigue syndrome.
7
Vitamin B12 shows unclear benefits
We explored the effect of vitamin B12 on individuals diagnosed with chronic fatigue syndrome. The study focused on assessing how this vitamin might alleviate the symptoms associated with the condition. While many participants underwent concurrent treatments, which complicates isolating vitamin B12's specific impact, the research still provides insightful data.

Participants were monitored to see if vitamin B12 made a notable difference in fatigue levels and overall well-being. However, it appeared that the results were not overwhelmingly positive. The concurrent treatments among participants diluted our ability to assess the true effectiveness of vitamin B12 on its own, leading to an inconclusive outcome.

While we acknowledge the interest in vitamin B12 as a potential remedy for chronic fatigue syndrome, the findings suggest no significant benefits can be attributed to it directly. More focused research might be necessary to fully understand how—or if—vitamin B12 can support those dealing with this challenging syndrome.
8
Vitamin B12 drops show promise
We examined the impact of vitamin B12 nasal drops on individuals suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our study involved fifty-one patients, predominantly female, with an average age of 42 and an average illness duration of 16 years.

After three months of treatment, we measured their vitamin B12 serum levels, physical activity, and fatigue and concentration levels. Interestingly, we found that the participants who responded positively to the treatment experienced significant improvements in their vitamin B12 levels, daily step count, and overall physical activity. Moreover, those who reported a positive response noted a decrease in fatigue levels.

On the flip side, those categorized as non-responders had only a modest increase in vitamin B12 levels, with no notable improvement in other measures. Overall, our findings suggest that nasal drops could serve as a viable alternative to vitamin B12 injections, especially since around two-thirds of participants reported feeling better after treatment. This pilot study opens up new avenues for interventions in managing ME/CFS and highlights the importance of considering alternative treatment methods.

References

  1. Regland B, Forsmark S, Halaouate L, Matousek M, Peilot B, et al. Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. PLoS One. 2015;10:e0124648. 10.1371/journal.pone.0124648
  2. Lundell K, Qazi S, Eddy L, Uckun FM. Clinical activity of folinic acid in patients with chronic fatigue syndrome. Arzneimittelforschung. 2006;56:399. PubMed
  3. Jacobson W, Saich T, Borysiewicz LK, Behan WM, Behan PO, et al. Serum folate and chronic fatigue syndrome. Neurology. 1993;43:2645. PubMed
  4. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med. 1989;149:2501. PubMed
  5. Botez MI, Fontaine F, Botez T, Bachevalier J. Folate-responsive neurological and mental disorders: report of 16 cases. Neuropsychological correlates of computerized transaxial tomography and radionuclide cisternography in folic acid deficiencies. Eur Neurol. 1977;16:230. PubMed
  6. van Campen CLM, Riepma K, Visser FC. Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders. Front Pharmacol. 2019;10:1102. 10.3389/fphar.2019.01102
  7. Loder C, Allawi J, Horrobin DF. Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical importance: roles of the locus coeruleus and central noradrenergic systems. Med Hypotheses. 2002;59:594. PubMed
  8. Devitt NF. Chronic fatigue syndrome. JAMA. 1998;279:432. PubMed
  9. Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997;26:301. PubMed
  10. Wiebe E. N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports. Can Fam Physician. 1996;42:2214. PubMed
  11. Demitrack MA, Engleberg NC. Chronic fatigue syndrome. Curr Ther Endocrinol Metab. 1994;5:135. PubMed
Data last updated:
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