General Nutrition/MS Research

[jimmylegs]

@david hi any news on a reworking of the B-vit regimen? i still wonder if thiamine depletion, possibly resulting from B3 excess, might be a factor where your symptoms are concerned.

[jimmylegs]

@david hi, any updates to report on your regimen?

re b complex imbalance concerns: recall that the klenner protcol (and for whatever it may or may not be worth it did work for me) strongly emphasized the entire b complex.

in that protocol, the base amount for each input of vitamin B1/thiamine is 3 times higher than the base amount for each input of vitamin B3/niacin.

i very much hope you are able to use this info to your advantage

[jimmylegs]

i noticed this in passing early last year - posting again, with more detail:

Nutritional optic neuropathies (2007)
https://www.sciencedirect.com/science/a ... 0X07004595

Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system. Nutritional optic neuropathies are usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific retrobulbar optic neuropathy. The differential diagnosis with other causes of optic nerve involvement, in particular of toxic origin, may be particularly difficult. Nutritional deficits are often associated with toxic effects from alcohol and tobacco; therefore, the separation of the nutritional and toxic components is often illusory and artificial. The pathophysiological mechanisms involved in nutritional - and toxic - optic neuropathies affect biochemical pathways involved in cell energetic production, correction of oxidative stress and quenching of free radicals. The recognition of these mechanisms could provide future therapeutic alternatives. Currently, the treatment is limited to the intensive use of vitamins with variable results in individual cases, and to the implementation of preventive measures, when feasible.
...
3. Etiologies of nutritional optic neuropathies
The role of the nutritional factors in the causation of nutritional optic neuropathies has been known for many years [2]. Following the World War II, epidemic outbreaks of
neuropathies were mentioned. Their origin remained poorly explained for a long time. Nevertheless, the existence of food deprivation causing deficiencies of proteins, anti-oxidants, B-group vitamins, is generally considered the main cause of these outbreaks, eventually in association with toxic factors. Such nutritional deficits can result in numerous ophthalmic (i.e., keratitis, retinopathies) and neuroophthalmologic pathologies [19]. We will review the role of vitamin deficits in the genesis of iatrogenic neuroophthalmologic complications, as well as the role of certain substances in triggering hereditary optic neuropathies [20–22].

3.1. Toxic and nutritional causes
An epidemic of optic neuropathy associated to peripheral neuropathy occurred in Cuba in 1991, demonstrating the interactions between nutritional deficits and toxic exposure. The cases of optic neuropathy were similar to those observed during war times [23]. Although, the main cause of the Cuban epidemic could be traced to malnutrition secondary to the economic problems met by this country, numerous studies achieved to understand the mechanisms of this epidemic equally pointed the role of excessive use of tobacco and of alcohol [7,9]. Susceptibility to the optic neuropathy increased with low serum levels of carotenoids principally lycopene, or low consumption of animal protein and B-group vitamins [7,8,24]. The protective effect of lycopene, a strong antioxidant of plant origin, is superior to all other carotenoids. A diet rich in riboflavin, a cofactor in the synthesis of glutathione, also a powerful intracellular anti-oxidant, was also associated with decrease risk of neuropathy [25]

3.2. Pure nutritional deficiencies
There are authentic instances of optic neuropathies that appear as a result of pure nutritional imbalances [5,6]. Thus, optic neuropathies have been reported in strict vegan patients without intake of vitamin supplements. Certain weight reduction methods may result in deficits of protein, vitamins and anti-oxidants and can be complicated by optic neuropathy. The clinical picture is characterized by decrease of visual acuity without abnormalities of the ocular fundus. Nevertheless, questioning allows sometimes the discovery of associated etiologies, including in the first place toxic ingestion [22]. More rarely, the vitamin deficits are secondary to different pathologies, such as beriberi due to thiamin (vitamin B1) deficiency, pernicious anemia with abnormal vitamin B12 levels, or intestinal pathologies that cause malabsorption [6,32].
Authentic optic neuropathies of diabetic origin have been reported [33] and several publications confirm their occurrence. These neuropathies are manifested by decreased vision, often asymmetric in the initial stages.

[jimmylegs]

this just in: useless zinc intakes (7 mg/d) don't make an appreciable difference to serum zinc levels!!!

*whew* how lucky am i that my stupid doctor's advice to take 100 mg/d, ie over 10 times useless, actually *does* do something (ie more than doubles serum levels), or my serum zinc would have been deficient to this day! s. m. h.

Yet Again, Serum Zinc Concentrations Are Unrelated to Zinc Intakes (2018)
https://academic.oup.com/jn/article-abs ... 99/5079797

Data from NHANES 2011–14 surveys, reported in the August 2018 issue of the Journal, showed that the serum zinc concentrations of the 4347 children, men, and women surveyed were unrelated to their zinc intake from either diet or supplements (1). This is not the first report that serum zinc concentrations are unrelated to zinc intakes. Three recent meta-analyses came to the same conclusion (2–4). Data from 10 randomized controlled trials and 3 observational studies in adults showed that doubling zinc intake changed the serum or plasma zinc concentrations by 6%. Thus, an adult consuming 14 mg Zn/d has a serum concentration that is only 6% higher than that of an individual consuming 7 mg/d. (The differences between serum and plasma zinc concentrations are very small and these 2 sources of circulating zinc are used interchangeably. The term serum zinc concentrations will be used throughout this paper when the source may be serum or plasma.) A 6% difference falls within the margin of error in measuring serum zinc. In fact, it represents only about one-fourth of the usual 22% drop in serum zinc concentrations from the peak fasting morning value to the lowest evening value about 3–4 h after the last meal (5). Meta-analyses done in children and pregnant or lactating women also found small changes in serum zinc when dietary zinc was doubled (3, 4). Doubling dietary zinc predicted a 9% increase in serum zinc concentrations in children, a 3% increase in pregnant women, and only a 1% increase in lactating women. These results along with the NHANES data in the August 2018 issue (1) suggest that strong homeostatic mechanisms are in place to prevent deviations in serum zinc when dietary intakes fluctuate.

[jimmylegs]

Copper/zinc ratio and systemic oxidant load: effect of aging and aging-related degenerative diseases (1998)
https://www.sciencedirect.com/science/a ... 4998001099

Abstract
There is evidence that copper and zinc have pro-oxidant and antioxidant properties, respectively, so that their imbalance may be expected to condition oxidative stress status. Oxidative stress is relevant in aging and in age-related degenerative diseases. In this study, blood content of copper, zinc, and ceruloplasmin as well as of lipid peroxides were investigated in 81 healthy and 62 disabled octo-nonagenarians affected by chronic degenerative diseases, and in 81 healthy adults. Serum copper/zinc ratio and ceruloplasmin were significantly higher in the elderly than in the healthy adults. Moreover, all these parameters were significantly higher in the disabled than in the healthy elderly. Notably, the increased copper/zinc ratio found in healthy elderly was due to high copper values, whereas in the disabled, both high copper and low serum zinc concentrations were present. The copper/zinc ratio was significantly and positively related to systemic oxidative stress status in all groups. The higher the serum copper/zinc ratio the higher the lipid peroxides plasma content. We conclude that there is a strict relationship between copper/zinc ratio and systemic oxidant burden. Moreover, advanced age and, particularly, advanced age-related chronic degenerative diseases are associated with a significant increase in the copper/zinc ratio and systemic oxidative stress.

Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects (2018)
https://www.sciencedirect.com/science/a ... 3918300875

Highlights
• An analysis of copper levels in serum and cerebrospinal fluid of Multiple Sclerosis patients is carried out.
• Ceruloplasmin, a peripheral marker of copper metabolism, is impaired in activity in Multiple Sclerosis subjects.
•A systemic state of high oxidative stress in MS subjects is observed.

Abstract
Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis.

Lower Serum Zinc Levels in Patients with Multiple Sclerosis Compared to Healthy Controls (2018)
https://www.mdpi.com/2072-6643/10/8/967/htm

Abstract
Objective: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and to investigate a potential correlation with clinical state, through analysis of serum zinc concentration in MS patients suffering from different disease subtypes. Methods: Serum zinc concentrations of 133 patients with relapsing (RMS) and 18 patients with the progressive form of MS (PMS), according to the McDonald criteria of 2010, were measured. Clinical status was quantified using the Expanded Disability Status Scale (EDSS). Zinc concentrations were also determined in the sera of 50 HCs, matched for age and sex at a group level. Results: MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8). Patients receiving disease-modifying treatment showed lower mean (SD) serum zinc levels than untreated cases (12.3 (1.9) µmol/L vs. 13.5 (3.2) µmol/L, p < 0.03). Zinc levels were not related to disease duration, EDSS, annual relapse rate, or the median number of relapses. Conclusions: The data suggest that a diagnosis of MS is related to lower serum zinc concentrations than in HCs, and concentrations were lower still under disease-modifying therapy. However, zinc levels did not predict disease subtypes or disability status.

Dietary habits; concentration of copper, zinc, and Cu-to-Zn ratio in serum and ability status of patients with relapsing-remitting multiple sclerosis (2017)
https://www.sciencedirect.com/science/a ... 071730059X

Highlights
•Copper (Cu) and zinc (Zn), due to their antioxidant activity, are important in the setting of multiple sclerosis (MS).
•Decreased Zn concentration in serum and a higher ratio of Cu to Zn may suggest a connection between MS and oxidative stress.
•Various internal and external factors may have an influence on Cu and Zn concentration in serum.
•A higher ratio of Cu to Zn in serum may be associated with inferior ability status.

Abstract
Objective
Dietary habits and adequate intake of antioxidants in the diet—for example, copper (Cu) and zinc (Zn)—may be an environmental factor in the occurrence of multiple sclerosis (MS). The aim of this study was to estimate the influence of dietary habits on the concentration of Cu, Zn in the serum, and the effect of Cu-to-Zn ratio on the ability status of patients with relapsing-remitting MS.

Methods
This was an observational case-control study that included 101 individuals with MS and 68 healthy individuals (controls). Food frequency questionnaires were used to collect dietary data. Serum concentrations of Cu and Zn were determined by the electrothermal and flame atomic absorption spectrometry method, respectively. The ratio of Cu to Zn was calculated and compared with the Expanded Disability Status Scale of patients.

Results
The concentration of Zn was significantly lower in the serum of individuals with MS (0.776 ± 0.195 mg/L) than in the control group (0.992 ± 0.315 mg/L). The ratio of Cu to Zn was higher in the examined patients (1.347 ± 0.806) than in the healthy volunteers (1.012 ± 0.458). Lower ability status (P < 0.05) was revealed in patients with an abnormal ratio of Cu to Zn, particularly, in cerebellar function, pyramidal tracts, and emotional conditions. Selected dietary habits have a significant influence on Cu and Zn concentration in the serum of patients with MS.

Conclusions
Lower serum concentrations of Zn and higher ratio of Cu to Zn in patients with MS can suggest a relationship between MS and oxidative stress. Products that are a source of Zn should be included in the diet, which can improve the clinical condition of people with MS.

[jimmylegs]

somehow, not already posted:

Role of Magnesium in Vitamin D Activation and Function
fft: http://jaoa.org/article.aspx?articleid= ... ultClick=1

Abstract
Nutrients usually act in a coordinated manner in the body. Intestinal absorption and subsequent metabolism of a particular nutrient, to a certain extent, is dependent on the availability of other nutrients. Magnesium and vitamin D are 2 essential nutrients that are necessary for the physiologic functions of various organs. Magnesium assists in the activation of vitamin D, which helps regulate calcium and phosphate homeostasis to influence the growth and maintenance of bones. All of the enzymes that metabolize vitamin D seem to require magnesium, which acts as a cofactor in the enzymatic reactions in the liver and kidneys. Deficiency in either of these nutrients is reported to be associated with various disorders, such as skeletal deformities, cardiovascular diseases, and metabolic syndrome. It is therefore essential to ensure that the recommended amount of magnesium is consumed to obtain the optimal benefits of vitamin D.

[jimmylegs]

finally...

Abstract CT093: Bimodal relationship between magnesium supplementation and vitamin D status and metabolism: Results from a randomized trial (2018)

Abstract
Background: There is inconsistent evidence from epidemiologic studies and randomized trials on the role of vitamin D on colorectal adenoma recurrence, colorectal cancer incidence, and total cancer incidence. Previous in vitro and in vivo studies indicate vitamin D synthesizing and metabolizing enzymes are Mg-dependent. The 2015 Dietary Guidelines Advisory Committee determined that magnesium (Mg) is under consumed relative to the Estimated Average Requirement (EAR) in the US population. In a single study, patients with Mg-dependent vitamin-D-resistant rickets received intramuscular infusion with vitamin D up to 600,000 IU which did not lead to any improvements in vitamin D deficiency. However, supplementation with Mg substantially reverse the resistance to vitamin D treatment. We previously reported from observational studies that Mg intake significantly interacted with vitamin D in affecting vitamin D status and risk of mortality. In this first randomized trial examining the interaction between Mg and vitamin D, we tested our hypothesis that Mg supplementation alters vitamin D synthesis and metabolism depending upon baseline circulating 25(OH)D concentration.

Methods: The Personalized Prevention of Colorectal Cancer Trial (PPCCT) is a double-blind 2×2 factorial randomized controlled trial which enrolled 250 participants and randomized them to placebo or a customized dose of Mg supplementation based on background dietary intakes levels. The current study is an NCI-independently funded ancillary study nested in the PPCCT. High-resolution accurate-mass (LCMS) was used to measure plasma levels of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 1,25(OH)2D2, 24,25(OH)2D3.

Results: All but one participant in this trial had normal plasma Mg at baseline. We found treatment with Mg significantly interacted with baseline plasma concentrations of 25(OH)D in altering plasma concentrations of 25(OH)D3, 25(OH)D2 and 24,25(OH)2D3. The test for interactions were statistically significant after Bonferroni corrections. 25(OH)D3 increased after Mg supplementation when baseline 25(OH)D concentrations were below around 30 ng/ml, but reduced in a dose-response manner when baseline 25(OH)D levels were greater (from about 30 to 50 ng/ml). The bimodal relationship between Mg treatment and 24,25(OH)2D3 was very similar to the pattern found for 25(OH)D3. Conversely, Mg treatment elevated 25(OH)D2 as baseline 25(OH)D levels increased.

Conclusions: We provided the first evidence that Mg has bimodal relationships with 25(OH)D3 and 24,25(OH)2D3. Also, we found the association between Mg treatment with 25(OH)D2 differed from that with 25(OH)D3. Thus, optimal Mg status may be crucial for optimizing 25(OH)D status and metabolism. These findings may help to explain some of the previously inconsistent role of vitamin D in risks of colorectal neoplasia and total cancer."

[jimmylegs]

i'm reading this doc this eve called "The rise and fall of dietetics and of nutrition science, 4000 BCE–2000 CE". fascinating stuff!!

[ElliotB]

You may also enjoy:

The Perfect Human Diet

A video available on Amazon, free for Prime members:

https://www.amazon.com/Perfect-Human-Di ... B00AX4QF70


This is probably one of the best documentaries on diet I have seen - the ideas presented make a tremendous amount of sense.

[jimmylegs]

should be useful for others i don't have the patience for video usually, other than for pure entertainment. re info, so much faster to read vs listen. search-ability also wins.

[ElliotB]

the video is long and boring but the information is invaluable.

[jimmylegs]

sounds like transcript would defs be the best bet in my case.

[jimmylegs]

i should have filed this here years ago. it's been kicking around the forum since 2013:

Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency (2006)

"intro: Vitamin D insufficiency is common, however within individuals, not all manifest the biochemical effects of PTH excess. This further extends to patients with established osteoporosis. The mechanism underlying the blunted PTH response is unclear but may be related to magnesium (Mg) deficiency.

methods: 30 patients (10 women in 3 groups) were evaluated prospectively measuring calcium, PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D, Mg) and bone turnover markers (serum CTX & P1CP).

results: All subjects, within the low vitamin D and low PTH group following the magnesium loading test had evidence of Mg depletion ... Following oral supplementation bone turnover increased

conclusions: This study confirms that in patients with established osteoporosis, there is also a distinct group with a low vitamin D and a blunted PTH level and that Mg deficiency (as measured by the Mg loading test) is an important contributing factor."

[NHE]

Here's a link to the full abstract.

Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency. Osteoporos Int. 2006;17(7):1013-21.

https://www.ncbi.nlm.nih.gov/pubmed/16596461

[jimmylegs]

Vitamin D-Intoxicated Patient With Hypoparathyroidism
Hypercalcemia, Acute Cerebellar Ataxia, and EEG Changes: Magnesium Sulfate Therapy (1964)

Abstract 1
"A patient presenting with an acute cerebellar ataxia, nausea, and vomiting of approximately one week's duration was found to have a serum calcium of 23.7 mg/100 ml. This was attributed to calcium and vitamin D therapy following previous thyroidectomy on July 3, 1962. Immediately after baseline studies, 20 cc of 50% magnesium sulfate were administered intramuscularly. No further therapy was given. The neurologic findings, as well as the nausea and vomiting, resolved rapidly within 24 hours in conjunction with decreasing serum calcium levels which reached a normal level of 10.9 mg at the end of five days. The urinary calcium excretion in the first 24 hours following MgSO4 was elevated to 803 mg. The EEG changed from abnormal diffuse slow alpha activity to normal within four days. An elevated spinal fluid protein (58 mg%) returned toward normal (43 mg%) in approximately three weeks."

Abstract 2
"The patient, a woman of 26, hypoparathyroid after subtotal thyroidectomy, developed severe signs of vitamin D poisoning, including ataxia and changes in the electroencephalogram, after maintenance for about 2 1/2 months on 100, 000 "units" of vitamin D and 16 g calcium lactate daily. Signs and symptoms rapidly responded to an intramuscular injection of 20 ml 50% magnesium sulfate, and serum Ca fell from 23.7 mg per 100 ml to normal in 5 days. The patient was subsequently maintained on 25, 000 units of vitamin D and 10 g calcium lactate daily. It is suggested that the neurological findings may have been due partly to Mg deficiency secondary to hypercalcasmia."

yikes um yeah, maybe. 7:\