vitamin C – American ME and CFS Society

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial

Abstract:

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis.

A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence.

Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03).

The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Source: Tosato M, Calvani R, Picca A, Ciciarello F, Galluzzo V, Coelho-Júnior HJ, Di Giorgio A, Di Mario C, Gervasoni J, Gremese E, Leone PM, Nesci A, Paglionico AM, Santoliquido A, Santoro L, Santucci L, Tolusso B, Urbani A, Marini F, Marzetti E, Landi F; Gemelli against COVID-19 Post-Acute Care Team. Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial. Nutrients. 2022 Nov 23;14(23):4984. doi: 10.3390/nu14234984. PMID: 36501014; PMCID: PMC9738241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738241/ (Full text)

Effect of high dose vitamin C on Epstein-Barr viral infection

Abstract:

Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection.

Material and Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection.

Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.

Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.

Source: Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014 May 3;20:725-32. doi: 10.12659/MSM.890423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015650/ (Full article)

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins

Abstract:

OBJECTIVES: A history of high-level physical activity and/or acute infection might constitute stress factors affecting the plasma oxidant-antioxidant status and levels of heat shock proteins (HSPs) in patients with chronic fatigue syndrome (CFS).

DESIGN: This case-control study compared data from 43 CFS patients to results from a matched control group of 23 healthy sedentary subjects.

SETTING AND SUBJECTS: Five patients had no relevant previous history (group I). Eighteen had practised high-level sport (group II), and severe acute infection had been diagnosed in nine patients (group III). A combination of sport practice and infection was noted in 11 patients (group IV).

INTERVENTIONS: After examination at rest, all subjects performed a maximal cycling exercise test. Plasma levels of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)] and both HSP27 and HSP70 were measured.

RESULTS: At rest, compared with the control group, the TBARS level was higher in groups II, III and IV patients, and the RAA level was lower in groups III and IV. In addition, HSP70 levels were significantly lower in all CFS groups, compared with controls, but negative correlations were found between resting HSP27 and HSP70 levels and the history of physical activity. After exercise, the peak level of TBARS significantly increased in groups II, III and IV, and the variations in HSP27 and HSP70 were attenuated or suppressed, with the greatest effects in groups III and IV.

CONCLUSION: The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.

Source: Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med. 2012 Jul;272(1):74-84. doi: 10.1111/j.1365-2796.2011.02488.x. Epub 2012 Jan 4. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02488.x/full

The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex

Abstract:

The year 1995 marked the onset of interstitial pneumonia spread in Nagoya, Japan. For the last 9 years, we have been accumulating clinical experience with the disease control using the combination of prophylactic use of anti-biotics and regular practice of megadose vitamin C infusion with either dehydroepiandrosterone-annex or dehydroepiandrosterone-cortisol annex. The purpose of this study is to assess the usefulness of our new treatment system for the control of interstitial pneumonia alias chronic fatigue syndrome.

The results obtained are given as follows:

i) The long-term maintenance of the above treatment system was effective not only for decreasing the risk for recurrence of active form pneumonia, but also for prevention of malignancy emergence in aged patients with interstitial pneumonia.

ii) Evidence is presented to indicate that interstitial pneumonia was associated with increased risk for depression of which the emergence is a candidate subject causally related to the long-term use of glucocorticoid.

iii) A patient with both interstitial pneumonia and depression was found to be less responsive to our treatment system. It is suggested that the use of more dehydroepiandrosterone at the sacrifice of cortisol in the infusion annex may be a choice for the control of both interstitial pneumonia and depression.

iv) The description of chronic fatigue syndrome as regards the endocrinological, epidemiological and psychiatric characteristics are in good agreement with our experience on patients having interstitial pneumonia, evidence in support of our proposal that there is no convincing reasoning to separate chronic fatigue syndrome from interstitial pneumonia.

v) The long-term practice of our treatment system for the control of interstitial pneumonia (an autoimmune disease) was found to suppress the inflammatory process but not the fibrotic process in the long run. vi) A few innovations were made in our treatment system to reduce the risk of bleeding or thrombosis–vascular complications of pneumonia.

vii) The merit of our treatment system is to create a new hormonal environment to improve the state of immunodeficiency by use of a non-steroid substance–vitamin C which encounters little resistance from the feedback mechanism of steroid metabolism in the in vivo system.

Source: Kodama M, Kodama T. The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex. Int J Mol Med. 2005 Jan;15(1):109-16. http://www.ncbi.nlm.nih.gov/pubmed/15583836

Nutritional strategies for treating chronic fatigue syndrome

Abstract:

Despite considerable worldwide efforts, no single etiology has been identified to explain the development of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome.

A detailed review of the literature suggests a number of marginal nutritional deficiencies may have etiologic relevance. These include deficiencies of various B vitamins, vitamin C, magnesium, sodium, zinc, L-tryptophan, L-carnitine, coenzyme Q10, and essential fatty acids. Any of these nutrients could be marginally deficient in CFS patients, a finding that appears to be primarily due to the illness process rather than to inadequate diets. It is likely that marginal deficiencies not only contribute to the clinical manifestations of the syndrome, but also are detrimental to the healing processes.

Therefore, when feasible, objective testing should identify them and their resolution should be assured by repeat testing following initiation of treatment. Moreover, because of the rarity of serious adverse reactions, the difficulty in ruling out marginal deficiencies, and because some of the therapeutic benefits of nutritional supplements appear to be due to pharmacologic effects, it seems rational to consider supplementing CFS patients with the nutrients discussed above, along with a general high-potency vitamin/mineral supplement, at least for a trial period.

Comment in: Nutritional strategies for treating chronic fatigue syndrome. [Altern Med Rev. 2001]

Source: Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev. 2000 Apr;5(2):93-108. http://www.altmedrev.com/publications/5/2/93.pdf (Full article)

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment

Abstract:

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons:

i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment;

ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS.

We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows:

a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes.

b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies.

c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS.

d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment.

e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS.

f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS.

g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment. In Vivo. 1996 Nov-Dec;10(6):585-96. http://www.ncbi.nlm.nih.gov/pubmed/8986468

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient

Abstract:

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment.

We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids.

We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows:

a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS.

b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995).

c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment.

d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc).

e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS.

f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS.

In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient. In Vivo. 1996 Nov-Dec;10(6):575-84. http://www.ncbi.nlm.nih.gov/pubmed/8986467