haidut

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Despite the ongoing assault against "ineffective" dietary supplements, the evidence in favor of them keeps piling on. One of the favorite targets of mainstream media is vitamin D, and multiple claims of "ineffectiveness" based on "meta" studies have come out in the last 5 years. Usually, this is a sign that something big, and financially unfavorable for Big Pharma, is brewing. That something may very well be the intervention studies below, which demonstrated that administration of 5,000 IU vitamin 3 daily for 6 months in patient with type II diabetes dropped their blood glucose by a whopping 55%, reduced their risk of metabolic syndrome by 51% and risk of CVD by 33%! In addition, the vitamin D improved function of pancreatic beta-cells, which reduced the risk of the type II diabetes turning into type I. No pharma drug, already in clinical use or still under development can claim such success. This should be front page news on CNN, Fox, etc yet the only popular press outlet that reported on it is a virtually unknown foreign media with no influence in the Western world.

Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial in: European Journal of Endocrinology Volume 181 Issue 3 (2019)
Vitamin D may increase insulin sensitivity and β-cell function in diabetes

"...Vitamin D supplementation may slow down metabolic deterioration in Type 2 diabetes patients, revealed a study published in the European Journal of Endocrinology. Vitamin D deficiency is associated with impaired glucose homeostasis. Association of vitamin D supplementation with various health benefits is of particular interest in nutritional research. Prior studies from the same group demonstrated that higher serum vitamin D levels were associated with a 55% reduction in the blood sugar, a 51% decreased risk of the metabolic syndrome and a 33% lower risk of cardiovascular disease (CVD). The present study demonstrated that high-dose vitamin D supplementation (5000 IU daily) for 6 months significantly improved peripheral insulin sensitivity and beta-cell function in individuals at high risk for diabetes or newly diagnosed type 2 diabetes (T2D), thus confirming the results of earlier studied by the same group."
 

rob

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Second that, great stuff. Given the positive impact they have on the vitamin D pathway, wonder whether things like boron and magnesium would show benefit as well.
 

baccheion

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Megadose vitamin D3 (50,000 IU/day) and iodine (100 mg+/day) have a similar effect. Both are sometimes used as treatment. Vitamin D deficiency is associated with metabolic syndrome.

Added vitamin K2 MK-4 (10 IU : 2 mcg+) additionally increases insulin sensitivity. Magnesium buffers against too much insulin release.
 
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Megadose vitamin D3 (50,000 IU/day) and iodine (100 mg+/day) have a similar effect. Both are sometimes used as treatment. Vitamin D deficiency is associated with metabolic syndrome.

Added vitamin K2 MK-4 (10 IU : 2 mcg+) additionally increases insulin sensitivity. Magnesium buffers against too much insulin release.

Interesting comparison. I was thinking that higher dose vitamin D seems to do a lot of what regular dose thyroid hormone is said to do.
 

baccheion

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Interesting comparison. I was thinking that higher dose vitamin D seems to do a lot of what regular dose thyroid hormone is said to do.
Vitamin D is said to increase conversion to T3 without affecting T4 or TSH levels. Sufficient vitamin D is also needed for uptake into cells. Same with cortisol.
 

haidut

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Bulgarian semi-god, what would happen to subjects that started from "adequacy" of killcidiol?

I think the optimal levels of D3 have been shown to be around 40-50 nM / L. If the person is already in that range or above it then I would not supplement. Given how widespread vitamin D deficiency is, I doubt there are many people that fall into that category but obviously my intention is not suggest everybody should start downing massive doses D3 regardless of their vitamin D status. If a person's levels are above 40 then sunlight and food are probably enough. However, the studies with diabetes populations work alost exclusively with vitamin D deficient people, so the findings are probably applicable for most people who carry extra weight and/or have fating blood sugar above 90.
 

Amazoniac

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I think the optimal levels of D3 have been shown to be around 40-50 nM / L. If the person is already in that range or above it then I would not supplement. Given how widespread vitamin D deficiency is, I doubt there are many people that fall into that category but obviously my intention is not suggest everybody should start downing massive doses D3 regardless of their vitamin D status. If a person's levels are above 40 then sunlight and food are probably enough. However, the studies with diabetes populations work alost exclusively with vitamin D deficient people, so the findings are probably applicable for most people who carry extra weight and/or have fating blood sugar above 90.
An interesting aspect of venom D research that isn't much explored is the refractoriness to correction in disease. It seems that when threatened, the body gets wiser in expelling this toxin.
 
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nigma

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Interesting comparison. I was thinking that higher dose vitamin D seems to do a lot of what regular dose thyroid hormone is said to do.

It would make sense that exposure to sunlight (and subsequent increase of VitD) would be the master controller of metabolism rather than thyroid. Since that would be an intelligent way for the organism to regulate energy expenditure. If you are getting a lot of UVB (produces VitD), you are either at the equator or not too far from it. At the equator resources incl, food and warmth are abundant and the adaptive capacity of the body is less necessary to be engaged, this allows thyroid to rise uninhibited from stress hormones. This results in greater caloric expenditure towards activity, play and exploration rather than storage of calories for reserve energy for a resource insecure future. Conversely, at the poles of the planet where UVB is at the lowest levels, stress hormones (cortisol, serotonin) will play a larger, more dominant role, inhibiting thyroid to provide short term survival at the expense of life span. Higher serotonin will oppose the explorative nature of dopamine and instead make one look for shelter and warmth, to be anxious and concerned for the future, make plans for the next harsh winter, expect the worst, respect tradition, etc., all things which help survival in the short term.

Vitamin D levels are correlated to hypothyroidism and diseases associated to hypothyroidism, including diabetes, cancer, inferitily, autonomic dysfunction (e.g. orthostatic hypotension). Vitamin D increases the activity of the immune system, which may help with the abundance of pathogens in the complex ecosystem of the jungle. Also the gut contents from a higher latitude diet would generally include more fats, which are antibiotic and thus make up for a lack of immune function. Conversely the gut contents of an equator diet would generally include more fruit, complex plant matter and pathogenic organisms, this scenario is where higher vitamin D with its higher immune function and increased digestive function makes sense.

Vitamin D is thought to primarily play a role in calcium regulation, but actually to be more specific it keeps blood calcium at saturated levels. Perhaps this is a more fundamental control level of the organism for metabolism than thyroid hormone? Since calcium is obviously needed for growth, maintaining high levels is critical. Calcium is also pro metabolic from a Peat point of view, with low levels giving rise to higher parathyroid hormone, which is not a pro metabolic hormone at all.

Just trying to pull everything together with introverted intuition.
 

LeeLemonoil

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@nigma

Interesting, relevant thoughts. Maybe the Calcium-bit needs consideration from another angle. Calcium is an ancient major environmental toxin for cells. Keeping blood saturated might be a phenomenon of keeping it out of the cells, which wouldn’t make Vit Ds role in ca-homeostasis no less crucial
 

LeeLemonoil

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Calcitox-aging counterbalanced by endogenous farnesol-like sesquiterpenoids: An undervalued evolutionarily ancient key signaling pathway

Cells are powerful miniature electrophoresis chambers, at least during part of their life cycle. They die at the moment the voltage gradient over their plasma membrane, and their ability to drive a self-generated electric current carried by inorganic ions through themselves irreversibly collapses. Senescence is likely due to the progressive, multifactorial damage to the cell's electrical system. This is the essence of the “Fading electricity theory of aging” (De Loof et al., Aging Res. Rev. 2013;12:58–66). “Biologic electric current” is not carried by electrons, but by inorganic ions. The major ones are H+, Na+, K+, Ca2+, Mg2+, Cl− and HCO3−. Ca2+ and H+ in particular are toxic to cells. At rising concentrations, they can alter the 3D-conformation of chromatin and some (e.g. cytoskeletal) proteins: Calcitox and Protontox. This paper only focuses on Calcitox and endogenous sesquiterpenoids. pH-control and Ca2+-homeostasis have been shaped to near perfection during billions of years of evolution. The role of Ca2+ in some aspects of aging, e.g., as causal to neurodegenerative diseases is still debated. The main anti-Calcitox mechanism is to keep free cytoplasmic Ca2+ as low as possible. This can be achieved by restricting the passive influx of Ca2+ through channels in the plasma membrane, and by maximizing the active extrusion of excess Ca2+ e.g., by means of different types of Ca2+-ATPases. Like there are mechanisms that antagonize the toxic effects of Reactive Oxygen Species (ROS), there must also exist endogenous tools to counteract Calcitox. During a re-evaluation of which mechanism(s) exactly initiates the fast aging that accompanies induction of metamorphosis in insects, a causal relationship between absence of an endogenous sesquiterpenoid, namely the farnesol ester named “juvenile hormone,” and disturbed Ca2+-homeostasis was suggested. In this paper, this line of thinking is further explored and extended to vertebrate physiology. A novel concept emerges: horseshoe-shaped sesquiterpenoids seem to act as “inbrome” agonists with the function of a “chemical valve” or “spring” in some types of multi-helix transmembrane proteins (intramolecular prenylation), from bacterial rhodopsins to some types of GPCRs and ion pumps, in particular the SERCA-Ca2+-pump. This further underpins the Fading Electricity Theory of Aging.
 
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It would make sense that exposure to sunlight (and subsequent increase of VitD) would be the master controller of metabolism rather than thyroid. Since that would be an intelligent way for the organism to regulate energy expenditure. If you are getting a lot of UVB (produces VitD), you are either at the equator or not too far from it. At the equator resources incl, food and warmth are abundant and the adaptive capacity of the body is less necessary to be engaged, this allows thyroid to rise uninhibited from stress hormones. This results in greater caloric expenditure towards activity, play and exploration rather than storage of calories for reserve energy for a resource insecure future. Conversely, at the poles of the planet where UVB is at the lowest levels, stress hormones (cortisol, serotonin) will play a larger, more dominant role, inhibiting thyroid to provide short term survival at the expense of life span. Higher serotonin will oppose the explorative nature of dopamine and instead make one look for shelter and warmth, to be anxious and concerned for the future, make plans for the next harsh winter, expect the worst, respect tradition, etc., all things which help survival in the short term.

Vitamin D levels are correlated to hypothyroidism and diseases associated to hypothyroidism, including diabetes, cancer, inferitily, autonomic dysfunction (e.g. orthostatic hypotension). Vitamin D increases the activity of the immune system, which may help with the abundance of pathogens in the complex ecosystem of the jungle. Also the gut contents from a higher latitude diet would generally include more fats, which are antibiotic and thus make up for a lack of immune function. Conversely the gut contents of an equator diet would generally include more fruit, complex plant matter and pathogenic organisms, this scenario is where higher vitamin D with its higher immune function and increased digestive function makes sense.

Vitamin D is thought to primarily play a role in calcium regulation, but actually to be more specific it keeps blood calcium at saturated levels. Perhaps this is a more fundamental control level of the organism for metabolism than thyroid hormone? Since calcium is obviously needed for growth, maintaining high levels is critical. Calcium is also pro metabolic from a Peat point of view, with low levels giving rise to higher parathyroid hormone, which is not a pro metabolic hormone at all.

Just trying to pull everything together with introverted intuition.

Excellent thought continuation, sir.
 

Nemo

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Another terrifically helpful thread. Thanks very much, guys.
 
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