General Nutrition/MS Research

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2014 study: Dietary habits and serum selenium in RRMS

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eat yer brazil nuts, kids!

Dietary habits and selenium, glutathione peroxidase and total antioxidant status in the serum of patients with relapsing-remitting multiple sclerosis
https://nutritionj.biomedcentral.com/tr ... entral.com

Background: Dietary habits and adequate dietary intake of antioxidants in the diet may be one of the most
important environmental factors for the prevention of Multiple Sclerosis (MS).
Objectives: The aim of this study was to estimate selenium (Se) concentration, glutathione peroxidase (GSH-Px)
activity and total antioxidant status (TAS) in the serum of patients with MS and the influence of dietary habits on
the status.

Methods: 101 patients with relapsing-remitting MS (aged 18-58 years), as well as control group of 63 healthy
people (aged 19-65 years) were studied. Food-frequency questionnaires were implemented to collect the dietary
data. Se concentration in the serum samples was determined by atomic absorption spectrometry. GSH-Px activity
and TAS in examined serum was measured using the ready-made sets of tests by Randox Laboratories Ltd., UK.
Results: Serum Se concentration and GSH-Px activity in the serum of patients with MS (55.2±16.2 μg/L,
6676.1±2386.4 U/L; respectively) were significantly decreased (p<0.01, p<0.05; respectively) compared with control
group (79.2±20.6 μg/L, 8029.9±2650.1 U/L; respectively).
A significant correlation (r=0.39, p<0.01) was observed
between Se concentration and GSH-Px activity in the serum of examined patients. TAS value in the serum of
patients with MS (1.03±0.37 mmol/L) was also significantly lower (p<0.01) than in healthy volunteers (1.48±0.41 mmol/L).
Frequent consumption of poultry, bakery products, pulses and fish seemed to increase serum Se concentration
in the group of patients; whereas frequent consumption of butter, wholegrain bread, sweet beverages and
sugar was found to accompany with lower values of Se in the serum. We have observed significant decrease TAS
(p<0.05, p<0.01; respectively) in the serum of smokers and those patients who received immunomodulatory
drugs (0.95±0.39 mmol/L, 0.92±0.34 mmol/L; respectively) compared with no-smoking patients and not taking
immunomodulators (1.14±0.33 mmol/L, 1.31±0.31 mmol/L; respectively).

Conclusions: Serum Se concentration, GSH-Px activity and TAS value were significantly lower in patients with
relapsing-remitting MS compared with healthy volunteers. Dietary habits have a significant influence on Se status.
Smoking cigarettes and intake of immunomodulatory drugs therapy have a negative impact on TAS of examined
patients.
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2017: Iron, Zinc & Oxidative Status in Neuroinflammation

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Chapter 5 – Chemical Elements and Oxidative Status in Neuroinflammation
https://www.sciencedirect.com/science/a ... 5626000051
Abstract
"Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and neurodegeneration. It is believed to be caused by the interaction between genetic susceptibility and environmental factors.

Evidence from several epidemiological and clinical studies suggested that changes in metal levels and oxidative status may contribute to the development of various neurological diseases, including MS. Many studies have been conducted to evaluate the mechanisms by which the metals induce neuroinflammation and neurotoxicity. Here, we review the literature regarding the role of metals with supposed pathogenic relevance in MS.

We also discuss the results of our previous studies showing chemical elements and oxidative status imbalance in the serum of patients with MS and other neurodegenerative diseases, as well as in people with clinically isolated syndrome (CIS, considered an early phase of MS).

Descriptive statistics revealed numerous differences between each disease and healthy status. A concordant imbalance (reduction in Fe, Zn, and serum antioxidant capacity, and increase in serum oxidative status) was shared by Alzheimer’s disease, Parkinson’s disease, and MS. The peculiar imbalance in serum elements and oxidative status that characterizes CIS people may predict conversion to clinically definite MS."

i like how they specified healthy vs normal. will be interesting to get into the full text on this one.
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2017 Review: C, D & Zinc: Synergistic Roles Immune Function

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Vitamins C, D and Zinc: Synergistic Roles in Immune Function and Infections (2017)
free full text: https://pdfs.semanticscholar.org/2c3b/8 ... 4b12f2.pdf

"Abstract
The immune system is a complex and sophisticated network of specialized tissues, organs, cells, proteins, and chemicals which has evolved in order to protect the host from a range of dangerous agents such as bacteria, virus, fungi, and parasites. There is a close relationship between nutritional status and immune function. Hence, immunocompetence can be regarded as a measure of adequate nutrition. Inter-individual variations in many immune functions exist within the normal healthy population and are due to age, genetics, gender, ethnic background, socioeconomic situation, diet, stress, habitual levels of exercise, alcohol consumption, smoking habits, etc. In addition, seasonal and temperature changes as well as being in crowded spaces (e.g., while commuting in public means of transportation, or working in open space offices) pose an additional burden on the immune system.
Among the essential micronutrients required to support a normal immune function, vitamin C, vitamin D and the mineral zinc play a central role. Through their complementary and synergistic effects, they support components of both innate and adaptive immunity which comprise epithelial barriers, cellular defense and antibodies constituting the three main lines of immune defense. Furthermore, vitamin C, D and zinc are actively used by cells of the immune system engaged in fighting infections like upper respiratory tract infections and a state of micronutrient deficiency can arise during severe infections.
Here we review the literature on the immune supportive properties of vitamins C, D and zinc and the impact of their supplementation in reducing the incidence or ameliorating symptoms of upper respiratory tract infections, which are among the most common infections in humans. Finally, we discuss their relevance in situations known to challenge the immune system such as exposure to temperature changes, to pollutants, or being in crowded spaces which serve as mixers where pathogens can stay suspended and transfer from host to host thereby increasing the risk of spreading infectious diseases because of close contact and long exposure."

i recall answering a question in 2012 re whether lowered nutrient levels were in response to or causal when it comes to human disease. setting aside obvious deficiency conditions like scurvy etc, i answered 'both'. this abstract reminded me of that question. yes in some cases the body sequesters certain nutrients. in others, marginally adequate supplies are rapidly used up so repletion is beneficial. and in other cases an underlying deficit can increase susceptibility in the first place. all fascinating.
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1974 study: Mg deficit: poss cause of refractory low vit B1

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happened on this tiny old study while looking at something else altogether:

Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy
http://jnnp.bmj.com/content/37/8/959.short

The determination of blood transketolase before and serially after thiamine administration, and the response of clinical symptomatology after thiamine are reported in two normomagnesaemic patients and one hypomagnesaemic patient with acute Wernicke-Korsakoff encephalopathy. The response of the depressed blood transketolase and the clinical symptoms was retarded in the hypomagnesaemic patient. Correction of hypomagnesaemia was accompanied by the recovery of blood transketolase activity and total clearing of the ophthalmoplegia in this patient, suggesting that hypomagnesaemia may be a cause of the occasional thiamine refractoriness of these patients.
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abridged peer review: Matsugasumi et al, 2018 zinc study

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The Association between Taste Impairment and Serum Zinc Concentration in Adult Patients with Type 2 Diabetes (Matsugasumi et al, 2018)
https://www.sciencedirect.com/science/a ... 7117303751
Abstract
Objectives
In this study, we aimed to elucidate the association between taste acuity and serum zinc concentration in patients with type 2 diabetes.
Methods
We enrolled 29 patients who were hospitalized to attend a 2-week diabetes educational program. Fasting blood samples were obtained on the morning of the next day and 2 weeks after hospitalization. The acuity of sweet, salty, sour, or bitter taste was evaluated with a filter-paper disk method. Correlations among taste acuity, glycemic control, and serum zinc concentration were analyzed using Spearman's rank correlation coefficient.
Results
The following parameters (mean ± standard deviation) were improved after 2 weeks' hospitalization: taste acuity (sweet: 3.5 ± 1.0 to 2.9 ± 1.1, salty: 3.3 ± 1.1 to 2.6 ± 1.0, sour: 3.6 ± 1.2 to 2.7 ± 0.8, and bitter: 3.3 ± 1.3 to 2.7 ± 1.1; all P <0.001), glycemic control (fasting plasma glucose: 9.4 ± 3.0 to 7.1 ± 1.8 mmol/L, and glycoalbumin: 26.3 ± 7.7 to 22.7 ± 5.9 %; both P <0.001), and serum zinc concentration (1.2 ± 0.2 to 1.3 ± 0.2 mmol/L, P <0.001). Sour and bitter taste acuity were significantly associated with serum zinc concentration (sour, r = -0.50, P = 0.005; bitter, r = -0.40, P = 0.033).
Conclusions
Glycemic control, serum zinc concentration and taste acuity were improved after the short-duration educational program. Sour and bitter taste acuity were significantly associated with serum zinc concentration.
How to Write a Peer Review for an Academic Journal: Six Steps
http://www.phd2published.com/2012/05/09 ... lash-boza/

Step Four: Write out your major criticisms of the article
"-Are you convinced by the author’s results? Why or why not?"

i personally tend to think math errors make research findings less convincing, but will move on to....

Step Five: Write out any minor criticisms of the article.
"-Once you have laid out the pros and cons of the article, it is perfectly acceptable (and often welcome) for you to point out that the table on page 3 is mislabeled, that the author wrote “compliment” instead of “complement” on page 7, or other minutiae. Correcting those minor errors will make the author’s paper look more professional if it goes out for another peer review, and certainly will have to be corrected before being accepted for publication. ... be mindful that you are critiquing the article in question – not the author. Thus, make sure your critiques are constructive"

In review:

to the authors,

apologies for skipping the more general pros and cons. at this time, this reviewer has access to the article's abstract only. it appears that this article would benefit from a close review of the units for serum zinc as described in the abstract, specifically "serum zinc concentration (1.2 ± 0.2 to 1.3 ± 0.2 mmol/L, P <0.001)."

i suspect the units shown in this paper's abstract for the given serum zinc results should be µmol/dL and not mmol/L, given the implications when the stated levels are converted from mmol/L to µmol/l and compared to serum zinc reference ranges.

relatively few papers report on serum zinc using µmol/dL. to simplify comparison with other research findings, it may be of value to report serum zinc findings in both µmol/L and in µg/dL. patient improvement from average 12 to 13 µmol/l (78.43 to 84.97 µg/dL) would be a logical result, consistent with other studies' serum zinc findings.

consider:

1.2 µmol/dL x 10 dl/L - 12 µmol/l

1.2 mmol/L x 1000 µmol/mmol = 1200 µmol/l

consider also the toxic serum zinc levels and reference ranges described in the study below:

Zinc-Induced Copper Deficiency
A Report of Three Cases Initially Recognized on Bone Marrow Examination
(2005)
https://academic.oup.com/ajcp/article/123/1/125/1759557

..........................................Case 1...........Case 3..............Reference............Case 2...........Reference
Serum Zinc, µg/dL (µmol/L).....193 (29.5).....428 (65.5)*.....66-110 (10.1-16.8 ).....145 (22.2).....55-150 (8.4-23.0)

thank you for the opportunity to provide this abridged review.
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2018 paper: Role of divalent metals in infectious disease

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i look forward to digging in on this one.

Role of divalent metals in infectious disease susceptibility and outcome
http://www.clinicalmicrobiologyandinfec ... ltext#sec2
"...From the microbial perspective, divalent metals are essential for growth and pathogenicity and to mount effective protection against antimicrobial host responses, including toxic radical formation. Microbes have evolved multiple strategies to control their access to divalent metals. From the clinical perspective, alterations of divalent metal levels may result in increased or decreased susceptibility to infection and often occur in response to infections. However, keeping in mind the strategies underlying such alterations, for which the term ‘nutritional immunity’ was coined, the uncritical correction of such divalent metal imbalances may cause harm to patients. This review addresses the role of the divalent metals iron, selenium, zinc, manganese and copper in infectious diseases from a mechanistic and clinical perspective...."
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Re: 2018 paper: Role of divalent metals in infectious diseas

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related new study. found when searching for new research on response to infectious challenge in subjects with high normal zinc status

Is the adaptive immune response in murine Trypanosoma cruzi infection influenced by zinc supplementation?
https://www.sciencedirect.com/science/a ... 8717305584
Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease. Twenty female Wistar rats were infected with 1 × 105 blood trypomastigotes (Y strain) and 30 days after infection the animals were mated and grouped: pregnant infected (PI–n = 5), pregnant infected/zinc supplied (PIZ–n = 5), pregnant control (PC–n = 5), control/zinc supplied (PCZ–n = 5). Zinc supplementation: 20 mg of zinc/Kg/day (gavage) for 18 days followed by euthanasia. The immune parameters showed: decreased percentages of CD62LlowCD44high surface marker for infected and treated group (PIZ) when compared to PI (p < 0.05). Concerning to T regulatory cells (Treg cells), a significantly lower percentage of splenic Treg cells was found in the infected and treated group (PIZ) as compared to the PI group (p < 0.05). The expression of the co-stimulatory molecule CD28+ displayed a significant reduced percentage in TCD8+ for infected and zinc treated group (PIZ) as compared to (PI). The percentages of CD4+/CD11a+ T cells subsets were lower on PIZ as compared to PI. Concerning to CD45RA+ (B lymphocytes) analysis, infected pregnant and treated group (PIZ) showed a significant decrease in CD45RA percentage when compared to (PI) (p < 0.05). The intracellular cytokine profiles for TCD4+ and TCD8+ producing IL-4 and IFN-γ revealed that zinc treated and untreated infected pregnant group (PI and PIZ) displayed increased cytokines concentrations as compared to zinc treated and untreated pregnant controls (PC and PCZ). Our data revealed the involvement of zinc as a signaling molecule in the modulation of the inflammatory process and immune response which occurs during pregnancy of T. cruzi infected rats. Zinc acted in a dual fashion, modulating the host's immune response in a way to protect the organism against the deleterious effects of the infection and an overwhelming pro-inflammatory response during pregnancy.
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Inhibition of Histamine Response by Zinc

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Inhibition of Histamine Response by Zinc
https://www.karger.com/Article/Abstract/135963

"Zinc cream has been used for many years in the treatment of skin conditions and allergy. In modern times it has been replaced by cortisone and antihistamine. Zinc has also recently been advised in cases of malnutrition, where zinc levels are low, to aid wound healing.
In this paper we have investigated the effect of zinc on histamine and SRS responses as histamine and SRS play a part in allergy (Kellaway and Trethewie, 1940) and histamine and zinc stimulate healing in wounds."

can't get full text :( it is just guinea pigs though...

not a rich vein of research out there using "serum histamine" and "serum zinc"
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Re: Inhibition of Histamine Response by Zinc

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kind of thing that *is* available

Association between itching and the serum zinc levels in patients with varicose veins
fft: https://www-ncbi-nlm-nih-gov.proxy.lib. ... MC5609042/

"The zinc content was significantly lower in the patients with itching (72.5 ± 7.1 μg/dL) compared to that in the control group (79.1 ± 8.1 μg/dL) (p < 0.05)"

ire 11.1 umol/L vs 12.1 umol/L ie deficient vs nearly so

https://www-ncbi-nlm-nih-gov.proxy.lib. ... gure/Fig3/

sadly, histamine only comes into it in the references.

12. Sanada S, Kuze M, Yoshida O. Beneficial effect of zinc supplementation on pruritus in hemodialysis patients with special reference to changes in serum histamine levels. Hinyokika Kiyo. 1987
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Re: Inhibition of Histamine Response by Zinc

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Serum zinc concentrations in patients on maintenance hemodialysis and its relationship with anemia, parathyroid hormone concentrations and pruritus severity
fft: http://www.sjkdt.org/article.asp?issn=1 ... -Khavidaki

Some authors proposed Zn deficiency as a possible cause of histamine release and the de­velopment of uremic pruritus in HD patients...

...Control group included healthy volunteers who were matched in age and sex with the case group and did not use any supplementary Zn products or were not on severe weight reducing diet...

...The mean serum Zn concentration in patients on maintenance HD was significantly lower than that of the control group (69.16 ± 17.29 μg/dL vs 82.93 ± 14.75 μ/dL; P= 0.001); how­ever, it was not different with the cut-off point of 70 μ/dL that is recommended by Gibson [7] (P= 0.66)....

...we did not find any correlation bet­ween serum Zn concentration of the patient and their pruritus severity, a Japanese study suggests that Zn deficiency may participate in increase histamine level in HD patients and result in the development of uremic pruritus. Oral Zn sulfate supplementation relieved pru­ritus in 53% of their patients. They explained this finding with the inhibitory effect of Zn on various functions of some cells including mast cells.

so 10.6 umol/L vs 12.7 umol/L

again, deficient vs nearly so. would rather they'd actually measured histamine than pruritis severity.
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2018 meta analysis: zinc and autoimmunity

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this is close to what my thesis was *supposed* to be like
at least it got done by somebody!

Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis
fft: http://www.mdpi.com/2072-6643/10/1/68/htm

Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell communication, proliferation, differentiation and survival. Zinc plays also a role in regulating the immune system with implications in pathologies where zinc deficiency and inflammation are observed. In order to examine the experimental evidence reported in the literature regarding zinc levels in the body of patients with autoimmune disorders compared to control individuals, a systematic review and meta-analysis were performed. From 26,095 articles identified by literature search, only 179 of them were considered potentially relevant for our study and then examined. Of the 179 articles, only 62 satisfied the inclusion criteria. Particularly for Fixed Model, Zn concentration in both serum (mean effect = −1.19; confidence interval: −1.26 to −1.11) and plasma (mean effect = −3.97; confidence interval: −4.08 to −3.87) samples of autoimmune disease patients was significantly lower than in controls. The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.

fig 2 - forest plot
http://www.mdpi.com/nutrients/nutrients ... 8-g002.png
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2017 meta analysis: zinc and parkinson's

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Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: a Meta-Analysis
https://link.springer.com/article/10.10 ... 017-0941-2

Recent studies have found that the serum zinc levels were associated with the risk of Parkinson’s disease (PD), but the results were inconsistent. Thus, we conducted a meta-analysis to summarize the evidence from observational studies between them. Pertinent studies were identified by a search in PubMed, Embase, and Web of science up to July, 10, 2016. Standardized mean difference (SMD) and 95% confidence intervals (CI) with random-effect model was used to combine the results. Subgroup analysis and meta-regression were also conducted. Publication bias was estimated using Begg’s regression asymmetry test. A total of 11 articles involving 822 PD patients and 777 healthy controls were included in the meta-analysis. Our meta-analysis results revealed that the serum zinc levels in PD patients were significantly lower than those in health controls (SMD = −0.779, 95%CI = [−1.323, −0.234], P < 0.001). The association was also significant oriental studies (SMD = −1.601, 95%CI = [−2.398, −0.805], P < 0.001). No publication bias was found. The current study indicated that serum zinc levels in PD patients were significantly lower than those in healthy controls.


probably still 'normal' though :roll:
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2018 viewpoint - disclosures in nutrition research

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Disclosures in Nutrition Research
Why It Is Different
https://jamanetwork.com/journals/jama/a ... irect=true

Nutrition research is among the most contentious fields of science. Although the totality of an individual’s diet has important effects on health, most nutrients and foods individually have ambiguously tiny (or nonexistent) effects.1 Substantial reliance on observational data for which causal inference is notoriously difficult also limits the clarifying ability of nutrition science. When the data are not clear, opinions and conflicts of interest both financial and nonfinancial may influence research articles, editorials, guidelines, and laws.2 Therefore, disclosure policies are an important safeguard to help identify potential bias. In this Viewpoint, we contend that current norms for disclosure in nutrition science are inadequate and propose that greater transparency is needed, including a broader definition of what constitutes disclosure-worthy information.


can't get into the full text yet if at all. only a tidbit for now

"For example, if at some point strict vegan diets are shown definitively to confer unmatched health benefits, an … For example, smoking increases the risk of many cancers approximately 10- to 20-fold, but red meat intake may increase the risk of colorectal cancer 1.02-fold (or ... "
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2018 review: vitamins & MS incidence,progression,improvement

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A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis
https://www.sciencedirect.com/science/a ... 0218300078

Highlights
•Vitamin D has important roles in MS and can be measured as precursor, or used as treatment.
•B6, B9, and B12 deficiency can elevate serum level of homocysteine, which may lead to an inflammatory state in the CNS.
•Vitamins A, E, and B1 deficiencies are believed to play important roles in MS pathophysiology according to animal models.
•Using high doses of vitamin C can worsen MS conditions because of promoting Fenton reaction.
•Vitamins D, B9, B12, A, B1, and B3 may improve relapses, degeneration rate, inflammation, and clinical symptoms.

Abstract
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review.
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Re: 2018 review: vitamins & MS incidence,progression,improve

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Note that the full text for this article is freely available.
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