Anal Fissure

[raypeatclips]

Up to 2000IU in divided doses is reasonable. Above the upper limit of 4000IU warrants more attention to your diet.
Calcirol - Liquid Supplement With Vitamin D3 (I believe he considers 10000 already a high dose)
Multiple Sclerosis (MS) Can Be Caused Quite Easily By Change In Hormones (for precautions when it comes to higher doses)
Vit K2 does nothing in terms of regulating calcium absorption as far as I know, and here lies the problem that goes back to issues with magnesium retention, which in turn warrants caution with the combination of dairy and vit D (to a much lesser degree, even from sun) in any amount.

Dairy is very positive and protective, but we can't deny that it's not suitable for adults in large amounts. Various things can go wrong with it as well and this is the case with many of us. Milch, for example, excess calcium or liquid, problems with protein digestion or its carbs. Perhaps the reason why I appear to be against it is because it's promoted here as a risk-free food and so I'm on board with others that say it's not.

It's difficult to find intelligent people that consume a lot of calcium, Ray is not a good example because he's assisted by thyroid supplements and some other hormones. It seems to against thinking fluidity, but it can be just my own impression.

Those seem very reasonable doses and fit into what I'm doing already and what I think.

The thing about taking vitamin D supplements is you throw large doses at the intestines. Now I know cholecalciferol is not generally thought to be active until it reaches the kidneys, but I had read one experiment showing epithelial cells capable of transforming cholecalciferol into active calcitriol.

I had thought perhaps that taking supplements could lead to an unusually high calcium absorption for this reason. I use it transdermally now once in a while, on the skin, and can feel the hormonal effects (but not that hypercalcemic, stiff joint feeling I notice from taking it orally.)

What doses do you take topically of D? I started to get strange chest inflammation symptoms after a few days of oral vitamin D supplementation (at only 2000iu) which I haven't experienced with topical D. But perhaps the topical doses aren't as high as the internal ones.

 

[Travis]

How do you match the doses for an even comparison? Or the same thing happens in varied doses?
Did you get an alert from this post? I tried to exclude the member code.

I did get an alert from this post, and I don't bother trying to compare absorption efficiencies; I just use about 5,000 international units applied directly to the belly.

 

[raypeatclips]

I did get an alert from this post, and I don't bother trying to compare absorption efficiencies; I just use about 5,000 international units applied directly to the belly.

What are your thoughts on using different body parts for vit D absorption? I usually put it on my feet and my stomach is significantly hairier than my feet so I am not sure how that would expect absorption, but I can't say I have noticed much from topical absorption.

 

[Travis]

What are your thoughts on using different body parts for vit D absorption? I usually put it on my feet and my stomach is significantly hairier than my feet so I am not sure how that would expect absorption, but I can't say I have noticed much from topical absorption.

I weigh 158 pounds and don't eat much for endogenous steroids; perhaps it's fair to consider me steroid‐sensitive for this reason.

The nonpolar steroids—like androgens and progesterone—seem to be well‐absorbed, but the more polar mineralocorticoids less so. An article on spironolactone⁽¹⁾ has informed me that while it's absorbed topically, it will not percolate into the circulation—serum spironolactone levels were undetectable after application over 55% of total body area. Vitamin D is a secosteroid, and a bit more fluid, so perhaps it penetrates even better than androgens?

Perhaps there is a study on the skin penetrance of steroids, measuring how much is then found in the circulation?

Scheuplein, R. J. "Percutaneous absorption of steroids." Journal of Investigative Dermatology (1969)​

It appears that the expected trend is indeed found: Nonpolar steroids are absorbed far better; the mineralocorticoids penetrate the skin, but are bound by their polar groups to proteins and will continue further only at a snail's pace:

'Molecular weight (MW) per se, can have no measurable effect on the differences in the permeability within this group of steroids, as only a 25% difference in MW exists between estrone (MW = 270.3) and hydrocortisone (360.4). Nevertheless there is approximately a 1000 fold difference in permeability between these two compounds.' ―Scheuplein

'It is quite apparent from these data that the more polar molecules are not rigorously excluded from the membrane but rather much more firmly bound within it. This latter conclusion follows from the decrease in the diffusion coefficient, Dm, which accompanies the inclusion of additional polar groups (see below). Consequently, the lesser permeability of the polar steroids does not arise from a limited solubility within the membrane but from their decreased mobility due to stronger chemical binding.' ―Scheuplein​

​

'Permeability of the steroids. The average measured permeability constants of 14 common steroids are listed in Table I. These data were computed from the steady state portions of the flux–time curves as described. Figure 2 shows a typical plot for three different steroids of widely different permeability' ―Scheuplein

'Approximately 100 μc of radioactive steroid was dissolved in 2.5 ml of H₂O in each donor. Penetration rates and water solubilities of the steroids are low. Therefore high specific activities were required, i.e., in the range 1—33 curies per millimole. Individual fluxes are given in Table II.' ―Scheuplein​

​

'Introducing additional polar groups into the molecule lowers the diffusion constant still further. Figures 3A and 3B indicate the progressive decrease in the permeability constant as the steroid becomes increasingly more polar going from progesterone to cortisol.' ―Scheuplein

'Introducing successive hydroxyl groups into the molecule starting with progesterone (0), then to cortexone (1), cortexelone (2) and finally cortisol (3) leads to a cumulative decrease in both the diffusion and permeability constants. Figure 4 illustrates the same phenomenon for the steroids containing an aromatic A-ring.' ―Scheuplein​

​

'The figure illustrates an important experimental difficulty when measuring, concurrently, the permeability of both rapidly and slowly diffusing molecules, i.e. the very large range in the lag times. The steady state permeability for the more rapidly diffusing molecule is fully developed while the slower moving molecules have not yet diffused in measurable amounts.' ―Scheuplein

'This is illustrated in Figure 2 in comparing testosterone (τ = 2 hours) with cortisone (τ = 220 hours). Lag times (τ) were extrapolated from the steady state portions of these "penetration curves."' ―Scheuplein
​

And he introduces the concept of the lag time, which increases dramatically as the molecule becomes more polar. Even though aldosterone could theoretically be eventually adsorbed, after about nine days, it's binding to the cell would likely preclude any significant amount actually doing so. The cell membrane has many mineralocorticoid receptors (Na⁺/K⁺‐ATPase), and so does the cytosol (MR). A slow adsorbing molecule would also have to fight the skin turnover rate, and incorporation in hair in the case of cortisol.

Progesterone and pregnenolone were the best adsorbed, but vitamin D wasn't tested in the experiment. Progesterone has two carbonyls (C=O), and these are polar, but not as polar as hydroxyl groups (C–OH). Although cholicalciferol contains the more polar hydroxyl group, it has only one.

I'm suspecting that the broken‐chain secosteroid ring of vitamin D further increases it's adsorption over its nonbroken analogue, 7‐dehydrocholesterol, lending it the ability to be absorbed even better than 7‐dehydrocholesterol—and perhaps even better than progesterone. It has been proven to be adsorbed transdermally, in multiple experiments, but I don't know if a direct comparison with progesterone has been made.

'Non-polar steroids penetrate more rapidly than polar steroids in vitro and this appears entirely consistent with the pattern observed in clinical experiments and also the work of McKenzie (10) Malkinson (11) and Coldzieher and Baker (12).' ―Scheuplein

'It is evident that the solubility of the steroids is increased appreciably when the solvent possesses both polar and non-polar character.' ―Scheuplein​

And the solvent, of course, can play a role. The studies I had read indicated that oleic acid had increased the topical adsorption of cyclosporine over all other fatty acids tested. But since cyclosporine is a large cyclic protein, I don't know how well this would apply to steroids.

[1] Rey, F. O. "Lack of endocrine systemic side effects after topical application of spironolactone in man." Journal of endocrinological investigation (1988)​

 

[Amazoniac]

Patent US4439432 - Treatment of progesterone deficiency and related conditions with a stable composition of progesterone and tocopherols

 

[raypeatclips]

@Amazoniac Are you aware of which B vitamins cause magnesium issues, or whether it is a trait of all of them?

 

[Wilfrid]

@raypeatclips a very good book on that subject is Handbook of vitamins, minerals and hormones by Roman J.Kutsky, Ray recommended it to me when I was asking him about vitamins, minerals and hormones interactions. Vitamins B1, D, B6 and C as well as minerals molybdenum, phosphorus and, to a lesser extent, manganese are very likely, depending on the dosage, to interact with magnesium. @Amazoniac as well as @Travis have already provided incredible informations about the subject and I think that also a customer on iherb ( healthiswealth) have, on his iherb profile, an incredible amount of helpful infos about those interactions too.

 

[Amazoniac]

@Amazoniac Are you aware of which B vitamins cause magnesium issues, or whether it is a trait of all of them?

This is useful:
http://traceelements.com/Docs/The Nutritional Relationships of Magnesium.pdf

__

Salt, energy, metabolic rate, and longevity

The sodium, by increasing carbon dioxide production, protects against the excitatory, toxic effects of the intracellular calcium.

IIRC sodium depletion kickstarts milk alkali syndrome

Influence of the thyroid on exocrine pancreatic function

"In this study, plasma amino acid uptake by the pancreas was significantly reduced in patients with hypothyroidism and returned to normal ranges after thyroid replacement. Moreover, in the 2 hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was significantly decreased. These findings clearly demonstrate that the thyroid gland is essential for the maintenance of the functional integrity of the exocrine pancreas in humans."​

Impaired thyroid often appears along with impaired kidneys as well. Sodium is lost at a fast rate, whereas bicarbonate production is compromised and perhaps the body can't cope with.. copious amounts of dietary chloride salts (sodium, magnesium, calcium, etc). Hyperchloremia might play a role in edema of hypopboydism.
all there

It's a real possibility in excess of table salt and dairy.

 

[Travis]

I don't know of all the ways B vitamins could interact with magnesium, but they do increase metabolism—oxidative respiration specifically. Such an increase in metabolism creates ATP, which is the well‐known endogenous magnesium chelator. Some enzymes which use ATP as a cofactor even need Mg²⁺ to function, and ATP and Mg²⁺ go together like coconuts and coffee (i.e. inextricably bound).

You would think an increase in respiration would increase the intracellular Mg²⁺ levels. This is a testable hypothesis, and I'm sure there has been studies on this . . .

 

[raypeatclips]

I don't know of all the ways B vitamins could interact with magnesium, but they do increase metabolism—oxidative respiration specifically. Such an increase in metabolism creates ATP, which is the well‐known endogenous magnesium chelator. Some enzymes which use ATP as a cofactor even need Mg²⁺ to function, and ATP and Mg²⁺ go together like coconuts and coffee (i.e. inextricably bound).

You would think an increase in respiration would increase the intracellular Mg²⁺ levels. This is a testable hypothesis, and I'm sure there has been studies on this . . .

Thank you once again for your posts Travis, but they usually leave me confused and with more questions than when I started! So you think an increase in respiration would result in a net positive result with intracellular magnesium, rather than deplete it?

@raypeatclips a very good book on that subject is Handbook of vitamins, minerals and hormones by Roman J.Kutsky, Ray recommended it to me when I was asking him about vitamins, minerals and hormones interactions. Vitamins B1, D, B6 and C as well as minerals molybdenum, phosphorus and, to a lesser extent, manganese are very likely, depending on the dosage, to interact with magnesium. @Amazoniac as well as @Travis have already provided incredible informations about the subject and I think that also a customer on iherb ( healthiswealth) have, on his iherb profile, an incredible amount of helpful infos about those interactions too.

Perfect, thank you! Did you find an online copy or this or did you go for a physical copy?

This is useful:
http://traceelements.com/Docs/The Nutritional Relationships of Magnesium.pdf

__

"In this study, plasma amino acid uptake by the pancreas was significantly reduced in patients with hypothyroidism and returned to normal ranges after thyroid replacement. Moreover, in the 2 hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was significantly decreased. These findings clearly demonstrate that the thyroid gland is essential for the maintenance of the functional integrity of the exocrine pancreas in humans."​

It's a real possibility in excess of table salt and dairy.

Thank you. I think I have had an excess of sodium and dairy, yet any blood tests have come back within range for calcium. Things do seem to be improving with a reduction in cheese however.

 

[Such_Saturation]

Thiamine deficiency inhibits magnesium depletion?

 

[Travis]

Thank you once again for your posts Travis, but they usually leave me confused and with more questions than when I started! So you think an increase in respiration would result in a net positive result with intracellular magnesium, rather than deplete it?

Looks like we don't have to speculate too much, because there has been measurements of this:

'In this study the metabolic inhibitors iodoacetate and NaCN [sodium cyanide; decreases respiration by binding Fe²⁺ in heme] were used to deplete ATP levels, liberating into the cytosol Mg²⁺ that had been bound to nucleotide. The amount of Mg²⁺ released was calculated and compared to the change in cytoplasmic free Mg²⁺ measured with mag-fura-2 to determine a value for BMg. Values ranging from 1.4 to 5.4 were obtained depending on assay conditions, indicating that Mg²⁺ is weakly but effectively buffered. Thus, when 2.7 mM was liberated, cytosolic free Mg²⁺ increased only from 1.1 mM to 2.7 mM over a period of 10 min. Under physiological conditions, i.e, in the presence of ATP, energy dependent efflux mechanisms would presumably have reduced this increase by exporting ‘excess’ Mg²⁺ from the cells.' ―RDG​

If one thing is certain, it is that decreasing ATP leads to greater free Mg²⁺. The author apparently 'presumes' that Mg²⁺ concentrations within the cell would be reduced by oxidative metabolism because MgATP transports Mg²⁺ out of the cell. I'm not certain about this. Free Mg²⁺ has a similar electrophoretic migration speed as Ca²⁺, meaning that they both are similarly diffusable in response to charge—such as the −150·mV mitochondrial membrane potential in living cells. I had imagined that lowered ATP increased intracellular Ca²⁺ as Mg²⁺ diffused into the extracellular fluid. Wherever you see cAMP formation, you very often see Ca²⁺. Cyclic AMP can be seen as ATP which has lost its ability to chelate Mg²⁺.

Here is the MgATP complex (on left):

[With heme at center.]

So ATP and Mg²⁺ are fundamentally related, and B vitamins tend to increase ATP by becoming cofactors for enzymes having a primary role in glucose metabolism. This could only be expected to influence Mg²⁺ distribution between the inside and outside of the cell.

Grubbs, Robert D. "Intracellular magnesium and magnesium buffering." Biometals (2002)​

 

[Wilfrid]

I bought mine on abebooks.

 

[raypeatclips]

Looks like we don't have to speculate too much, because there has been measurements of this:

'In this study the metabolic inhibitors iodoacetate and NaCN [sodium cyanide; decreases respiration by binding Fe²⁺ in heme] were used to deplete ATP levels, liberating into the cytosol Mg²⁺ that had been bound to nucleotide. The amount of Mg²⁺ released was calculated and compared to the change in cytoplasmic free Mg²⁺ measured with mag-fura-2 to determine a value for BMg. Values ranging from 1.4 to 5.4 were obtained depending on assay conditions, indicating that Mg²⁺ is weakly but effectively buffered. Thus, when 2.7 mM was liberated, cytosolic free Mg²⁺ increased only from 1.1 mM to 2.7 mM over a period of 10 min. Under physiological conditions, i.e, in the presence of ATP, energy dependent efflux mechanisms would presumably have reduced this increase by exporting ‘excess’ Mg²⁺ from the cells.' ―RDG​

If one thing is certain, it is that decreasing ATP leads to greater free Mg²⁺. The author apparently 'presumes' that Mg²⁺ concentrations within the cell would be reduced by oxidative metabolism because MgATP transports Mg²⁺ out of the cell. I'm not certain about this. Free Mg²⁺ has a similar electrophoretic migration speed as Ca²⁺, meaning that they both are similarly diffusable in response to charge—such as the −150·mV mitochondrial membrane potential in living cells. I had imagined that lowered ATP increased intracellular Ca²⁺ as Mg²⁺ diffused into the extracellular fluid. Wherever you see cAMP formation, you very often see Ca²⁺. Cyclic AMP can be seen as ATP which has lost its ability to chelate Mg²⁺.

Here is the MgATP complex (on left):

[With heme at center.]

So ATP and Mg²⁺ are fundamentally related, and B vitamins tend to increase ATP by becoming cofactors for enzymes having a primary role in glucose metabolism. This could only be expected to influence Mg²⁺ distribution between the inside and outside of the cell.

Grubbs, Robert D. "Intracellular magnesium and magnesium buffering." Biometals (2002)​

Thank you for such a detailed reply. Your ability to understand scientific phrases and concepts is far above mine, but from what i gather anything that increases ATP should increase intracellular magnesium which is what we want and B vitamins could assist with that.

I bought mine on abebooks.

Thanks I did find one there that was reasonably priced!

 

[Wilfrid]

Thiamine deficiency inhibits magnesium depletion?

Thanks so much for this, @such. ( @haidut too has made very helpful posts about thiamine. )
Thiamine and enzymes in need of thiamine as a co-factor are present in all body cells, thiamine action/interaction on/with sodium, magnesium, manganese, vitamin D, thyroid hormones, oxydative phosphorylation, insulin ( who also strongly interact with magnesium ) ect...are so important that I wonder how much people are still struggling with health issues while suffering even mild thiamine deficiency.
If only one deficiency has to be considered, it's probably the one involving this vitamin.

 

[DaveFoster]

@raypeatclips

Anal fissures or red blood in the stool indicate bowel inflammation, and anything that speeds peristalsis (such as cascara sagrada or carrot fiber) can eliminate the problem.

 

[Amazoniac]

There's an extense list with good books (including our dominator's recommendation above) and articles that's constantly being updated:

HTMA Science — References · Nutritional Balancing.org

 

[haidut]

Looks like we don't have to speculate too much, because there has been measurements of this:

'In this study the metabolic inhibitors iodoacetate and NaCN [sodium cyanide; decreases respiration by binding Fe²⁺ in heme] were used to deplete ATP levels, liberating into the cytosol Mg²⁺ that had been bound to nucleotide. The amount of Mg²⁺ released was calculated and compared to the change in cytoplasmic free Mg²⁺ measured with mag-fura-2 to determine a value for BMg. Values ranging from 1.4 to 5.4 were obtained depending on assay conditions, indicating that Mg²⁺ is weakly but effectively buffered. Thus, when 2.7 mM was liberated, cytosolic free Mg²⁺ increased only from 1.1 mM to 2.7 mM over a period of 10 min. Under physiological conditions, i.e, in the presence of ATP, energy dependent efflux mechanisms would presumably have reduced this increase by exporting ‘excess’ Mg²⁺ from the cells.' ―RDG​

If one thing is certain, it is that decreasing ATP leads to greater free Mg²⁺. The author apparently 'presumes' that Mg²⁺ concentrations within the cell would be reduced by oxidative metabolism because MgATP transports Mg²⁺ out of the cell. I'm not certain about this. Free Mg²⁺ has a similar electrophoretic migration speed as Ca²⁺, meaning that they both are similarly diffusable in response to charge—such as the −150·mV mitochondrial membrane potential in living cells. I had imagined that lowered ATP increased intracellular Ca²⁺ as Mg²⁺ diffused into the extracellular fluid. Wherever you see cAMP formation, you very often see Ca²⁺. Cyclic AMP can be seen as ATP which has lost its ability to chelate Mg²⁺.

Here is the MgATP complex (on left):

[With heme at center.]

So ATP and Mg²⁺ are fundamentally related, and B vitamins tend to increase ATP by becoming cofactors for enzymes having a primary role in glucose metabolism. This could only be expected to influence Mg²⁺ distribution between the inside and outside of the cell.

Grubbs, Robert D. "Intracellular magnesium and magnesium buffering." Biometals (2002)​

ADP has high affinity for calcium, while ATP for magnesium. So, a breakdown of ATP necessarily leads to loss of magnesium from the cell and accumulation of calcium. It is an intracellular mineral and just like potassium, having higher levels in the blood is a biomarker of pathology, not health. Yet, most doctors love to see blood magnesium levels right at the top of the "normal" range.

 

[Travis]

ADP has high affinity for calcium, while ATP for magnesium. So, a breakdown of ATP necessarily leads to loss of magnesium from the cell and accumulation of calcium.

I have been saying that for some time now.

It is an intracellular mineral and just like potassium, having higher levels in the blood is a biomarker of pathology, not health. Yet, most doctors love to see blood magnesium levels right at the top of the "normal" range.

So plasma levels could just indicate low intracellular Mg²⁺ concentration, making the plasma measurement indicate exactly opposite of what it's generally believed? Perhaps then a better indication would be the intracellular erythrocyte Mg²⁺ concentration, which could be measured nearly just as easily. Or even better: the whole‐blood Mg²⁺/Ca²⁺ ratio.

 

[Mito]

Perhaps then a better indication would be the intracellular erythrocyte Mg²⁺ concentration, which could be measured nearly just as easily. Or even better: the whole‐blood Mg²⁺/Ca²⁺ ratio.

Or maybe something like this Magnesium Test: Intracellular Analysis for Heart Disease, A Fib, Arrhythmia, Stroke: EXA Test?