Anal Fissure

[Travis]

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

Wow. That is interesting. That is a neat way to measure intracellular potassium levels. Apparently erythrocytes aren't reliable, and don't change in potassium concentration upon exercise. And I'm not even sure erythrocyes have mitochondria, they could just be almost pure hemoglobin—almost more like a serum protein than an actual cell.

Kilburn, Kaye H. "Muscular origin of elevated plasma potassium during exercise." Journal of applied physiology (1966)​

There is elevated potassium as a result of excercise, which the author explains with non‐ATP hormonal and glycogen mechanisms. But could this be simply the result of lower ATP? Is our explanation more realistic?

Karlsson, J. "Muscle lactate, ATP, and CP levels during exercise after physical training in man." Journal of applied physiology (1972)​

This has been studied, and ATP levels do drop after exercise:

'Muscle glycogen, lactate, ATP, and CP were determined from needle biopsy specimens according to the methods described by Karlsson et al. ( 10, 13).' ―Karlsson​

click to embiggen
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'But at the end of the exhaustive exercise maximal depletion ( 14-15 mmoles kg⁻¹ of wet muscle) of these stores was found, regardless of the training status.' ―Karlsson
​

Interesting. But does Ca²⁺ enter the cell as ATP is depleted? perhaps drawn in by the −150·mV mitochondrial membrane potential?

Friden, J. "Eccentric exercise‐induced injuries to contractile and cytoskeletal muscle fibre components." Acta Physiologica (2001)​

This does appear to be the case.

Exercise is characterized by increased exrtracellular potassium (Kilburn, 1966), decreased intracellular ATP (Karlsson, 1972), and increased intracellular calcium (Friden, 2001):

'Several studies indicate that disturbances in calcium metabolism may be associated with muscle changes and weakness after heavy exercise (Reid et al. 1994).' ―Friden​

'He postulated that early mechanical events which initiate injury and which result in later in inflammation require an intermediate event. A most likely intermediate event is an increase in intracellular calcium level (Balnave & Allen 1995).' ―Friden​

'While cyclic calcium concentration changes are normal in the muscle contraction cycle, chronically elevated intracellular calcium can activate endogenous proteases (e.g. calpain), causing muscle deterioration. As a result, increased intracellular calcium remains an attractive feature for most muscle injury models.' ―Friden​

And below is a study I pulled from his citations, if anyone needs to see the experimental evidence. I think it's most plausible that ATP, inositol phosphates, and mitochondrial membrane potential regulate Ca²⁺/Mg²⁺ balance because it's the only think that makes sense—the only physical explanation that doesn't involve a 'membrane pump.' Prolactin can increase intracellular calcium, but it doesn't wave a magic wand. Prolactin activates phosphilipase C which cleaves inositol phosphates from the cell membrane—actual calcium chelators. Although inositol hexaphosphate (IP₆) is a bit stronger, the endogenous inositol triphosphate (IP₃) can still chelate calcium. All that an inositol phosphate needs to do this are two phosphate groups on the inositol ring, placed equatorially, separated by one carbon atom.

Balnave, C.D. "Intracellular calcium and force in single mouse muscle fibres following repeated contractions with stretch." J Physiol (1995)
Luttrell, B. M. "The biological relevance of the binding of calcium ions by inositol phosphates." Journal of Biological Chemistry (1993)​

 

[haidut]

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.

Exactly, but I think the erythrocyte magnesium test is not covered by most insurances as it has to be sent to a special lab (at least in the USA). I like the idea about whole blood magnesium/calcium ratio. Are whole blood tests for calcium and magnesium being done by the big labs like LabCorp? Maybe @Dan Wich can shed some light on this. I think blood tests for inosine/hypoxanthine and possibly adenosine would also be very helpful as they show breakdown of ATP. In fact, a few studies have found these tests to be highly predictive of athlete training status and cellular fatigue, which of course reflects intracellular magnesium levels as well. Hey @Dan Wich - can you also look into this? Namely, blood tests for hypoxanthine and inosine?
Hypoxanthine: A Universal Metabolic Indicator of Training... : Exercise and Sport Sciences Reviews
Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: from bench to point-of-care. - PubMed - NCBI

A few other biomarkers like urea, CK, T, etc can also probably correlate well with ATP breakdown and thus predict intracellular magnesium status.
Blood-Borne Markers of Fatigue in Competitive Athletes – Results from Simulated Training Camps

 

[Dan W]

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

Oh, that's interesting, I was pretty sure the company was out of business. But apparently they're providing results through doctors, though it's a good $300.

Are whole blood tests for calcium and magnesium being done by the big labs like LabCorp?

I didn't find anything except an old calcium test code for Quest that I think must have been discontinued.

Spectrum seems to have a whole blood magnesium code, but it seems like it has to be drawn locally if anyone's planning a trip to Michigan :)

Hey @Dan Wich - can you also look into this? Namely, blood tests for hypoxanthine and inosine?

I couldn't find anything at all for those. But I think IdeaLabs should expand into labs...

 

[mattyb]

Urinary Mg is the best measure of magnesium status. Easy to detect magnesium wasting or outright deficiency.

RBC magnesium is not reliable. RBC synthesize ATP through glycolosis, not via the ETC (since they don't have mitochondria). So ATP in RBC (and therefore Mg) is more of a proxy measure of glycolosis, not oxidative metabolism. This will obviously effect Mg levels in RBC in a way that is not an honest reflection of most other tissues that rely predominantly on oxidative metbaolism. Can't rely on interpreting Mg levels from RBC - although it likely will be a good measure of intracellular Mg in tissues with similar metabolic (non-oxidative) profiles.

I guess hair testing could be okay as well, but I've always been skeptical of hair testing and it seems to require frequent repeat testing. Urinary Mg is probably the most accurate and most accessible test you can get.

 

[Travis]

RBC magnesium is not reliable. RBC synthesize ATP through glycolosis, not via the ETC (since they don't have mitochondria). So ATP in RBC (and therefore Mg) is more of a proxy measure of glycolosis, not oxidative metabolism. This will obviously effect Mg levels in RBC in a way that is not an honest reflection of most other tissues that rely predominantly on oxidative metbaolism. Can't rely on interpreting Mg levels from RBC - although it likely will be a good measure of intracellular Mg in tissues with similar metabolic (non-oxidative) profiles.

I guess that's why the ATP concentration of erythrocytes wasn't changed upon excercise, while the intracellular ATP levels in muscle was.

But wouldn't urinary Mg²⁺ be a measurement of extracellular magnesium? and prone to fluctuations? And like exercise, could perhaps stress also deplete ATP leading to the outflux of cellular Mg²⁺ while raising urinary Mg²⁺ levels? perhaps leading to an artificially‐high plasma and urine levels?

For the price of a Mg²⁺ test kit, a person can buy . . . [calculating] . . . approximately 49.5 pounds of magnesium chloride from Amazon.com (shipping not included).

 

[mattyb]

I guess that's why the ATP concentration of erythrocytes wasn't changed upon excercise, while the intracellular ATP levels in muscle was.

But wouldn't urinary Mg²⁺ be a measurement of extracellular magnesium? and prone to fluctuations? And like exercise, could perhaps stress also deplete ATP leading to the outflux of cellular Mg²⁺ while raising urinary Mg²⁺ levels? perhaps leading to an artificially‐high plasma and urine levels?

For the price of a Mg²⁺ test kit, a person can buy . . . [calculating] . . . approximately 49.5 pounds of magnesium chloride from Amazon.com (shipping not included).

Urinary Mg will point you towards a situation of either acute wasting or acute deficiency. It can't do anything else, but it's still better than other tests.

It's not just a measure of extracellular magnesium because the kidney's will retain or excrete the magnesium depending on the overall status of the organism. Extracellular magnesium will dip or be excreted based off of demand from cells. Mg in intracellular and skeletal pools are not as freely available compared to something like calcium, instead the kidneys are largely responsible for maintaining serum Mg. Movement of serum Mg to intracellular compartment is largely demanded by intracellular forces (e.g. ATP). Ergo, reabsorption of magnesium from the kidneys is largely determined by intracellular demand.

Since true hypermagnesemeia is so rare (since you can really only get it from some drugs, rare diseases, and through ridiculously high dietary supplementation of Mg) urinary Mg can be a good measure of the overall demand for Mg from other tissues. Low levels of urinary Mg mean that the body has a strong demand to retain Mg, while high levels of Mg predominantly means that the body is wasting it for some reason. So the test is good for informing what Mg is doing in the body, but does very little to tell us why - like most tests, in complete isolation it's almost completely useless. For example, in Mg wasting it could be caused by metabolic acidosis (where Mg is displaced by high levels of H+), low intracellular ATP (where Mg can't be retained in the cell because there's nothing for it to bind to), or calcium influx (in the case of cell death). Unsurprisingly, each of these conditions can exist separately or simultaneously, and only scratch the surface of things that can affect intracellular Mg balance.

Overall, I think there are better tests than any kind of measure of magnesium to take if you want to figure out what's going on. Magnesium is so... general. Tells us very little in terms of specificity.

 

[Dave Clark]

Didn't read through all the posts, or if anyone mentioned it, but rectal ozone insufflations will fix anal fissures.

 

[haidut]

RBC synthesize ATP through glycolosis

I thought RBC synthesize ATP primarily through scavenging-resynthesis using inosine as raw material?
Inosine from liver as a possible energy source for pig red blood cells - ScienceDirect

As far as kidneys maintaining serum magnesium based on cellular demands - I think this is a good assumption for only the people with well working kidneys. Most people above 50 have deteriorating kidney function so the urine tests need to be taken with a grain of salt. Also, any person with elevated FFA due to stress, insulin resistance, high dietary PUFA intake, infection, chronic inflammation, etc is effectively in a mild form of chronic renal insufficiency and electrolyte retention would be skewed. I think blood electrolyte tests + the urine Magnesium & Potassium would be a better measure.
As far as hair - Peat said nails, and especially toenails, would be better for analysis but he did not elaborate why. Do you know of any lab that does nail analysis?

 

[Mito]

Oh, that's interesting, I was pretty sure the company was out of business. But apparently they're providing results through doctors, though it's a good $300.

Not easy to find practicianers that administer the EXA test. Here is one if you happen to live in Philadelphia. DIAGNOSTIC TESTING

 

[Mito]

Urinary Mg will point you towards a situation of either acute wasting or acute deficiency. It can't do anything else, but it's still better than other tests.

“Another approach for the assessment of magnesium status is urinary magnesium excretion. This test is cumbersome, especially in the elderly, since it requires at least a reliable and complete 24-h time frame [54]. As a circadian rhythm underlies renal magnesium excretion, it is important to collect a 24-h urine specimen to assess magnesium excretion and absorption accurately. This test is particularly valuable for assessing magnesium wasting by the kidneys owing to medication or patients’ physiological status [7]. The results will provide aetiological information: while a high urinary excretion indicates renal wasting of magnesium, a low value suggests an inadequate intake or absorption [7].” Magnesium basics

 

[haidut]

The results will provide aetiological information: while a high urinary excretion indicates renal wasting of magnesium, a low value suggests an inadequate intake or absorption

Unfortunately, neither one of these would mean much for intracellular magnesium status.

 

[Regina]

I thought RBC synthesize ATP primarily through scavenging-resynthesis using inosine as raw material?
Inosine from liver as a possible energy source for pig red blood cells - ScienceDirect

As far as kidneys maintaining serum magnesium based on cellular demands - I think this is a good assumption for only the people with well working kidneys. Most people above 50 have deteriorating kidney function so the urine tests need to be taken with a grain of salt. Also, any person with elevated FFA due to stress, insulin resistance, high dietary PUFA intake, infection, chronic inflammation, etc is effectively in a mild form of chronic renal insufficiency and electrolyte retention would be skewed. I think blood electrolyte tests + the urine Magnesium & Potassium would be a better measure.
As far as hair - Peat said nails, and especially toenails, would be better for analysis but he did not elaborate why. Do you know of any lab that does nail analysis?

What strategies could people over 50 use to improve kidney function? Thank you
Duh, just searched the forum:
Niacinamide Can Treat Kidney Failure

 

[haidut]

What strategies could people over 50 use to improve kidney function? Thank you
Duh, just searched the forum:
Niacinamide Can Treat Kidney Failure

So can thiamine and charcoal, also searchable but more easily found through a Google search on the forum
Thiamine Reverses Diabetic Kidney Damage In Humans
Thiamine Reverses Diabetic Kidney Damage In Humans

Anything that keeps FFA low will protect kidneys from degeneration. Raising NAD/NADH ratio was recently shown to reverse aging in any organ studied. Steroids like androsterone have been known as kidney-anabolic since the 1940s. It is also anti-aging for heart, liver, and skin. Progesterone and DHEA share many of the same effects as do testosterone and DHT.
The Anabolic Effects Of Androsterone

 

[mattyb]

I thought RBC synthesize ATP primarily through scavenging-resynthesis using inosine as raw material?
Inosine from liver as a possible energy source for pig red blood cells - ScienceDirect

As far as kidneys maintaining serum magnesium based on cellular demands - I think this is a good assumption for only the people with well working kidneys. Most people above 50 have deteriorating kidney function so the urine tests need to be taken with a grain of salt. Also, any person with elevated FFA due to stress, insulin resistance, high dietary PUFA intake, infection, chronic inflammation, etc is effectively in a mild form of chronic renal insufficiency and electrolyte retention would be skewed. I think blood electrolyte tests + the urine Magnesium & Potassium would be a better measure.
As far as hair - Peat said nails, and especially toenails, would be better for analysis but he did not elaborate why. Do you know of any lab that does nail analysis?

Three of (of many) sources showing RBC use glycolysis and have glycolytic intermediates:
Control of Glycolysis in the Human Red Blood Cell
The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis
https://pdfs.semanticscholar.org/5adb/d753d9dfb4bb9edb14663bb23de6eae8d562.pdf

Kidney function does not just randomly decline after 50. I see about 3 kidney lab tests a day for the last 1.5 years from relatively unhealthy people over the age of 50 and maybe ~5% of them have kidney pathology, and if we include major electrolyte disturbances into that I'd bump it up to about 15%. The major thing that changes with age in the kidney is increased retention of H+ and decreased retention of bicarb, but this is most prominent in people over 70.

The renal insufficiency comment is a massive hyperbole. You pee a little bit more in those conditions, but you increase sodium retention. The kidney's don't just stop functioning, and they certainly aren't starved of blood like in CRI.

Anyway, that's why I said just testing magnesium alone is a waste of time. It has to be taken in the proper context and for the right reasons.

 

[haidut]

The renal insufficiency comment is a massive hyperbole

How often do you check for albuminuria in people over 50, especially in the morning? They may have normal eGFR and BUN values on blood tests but the foamy urine in the morning is a common sing for most people over 50, and often much younger. Maybe I should not have said "renal insufficiency" but "filtering dysfunction" to make it less controversial. In my experience, any elevation in FFA leads to disturbed electrolyte balance and kidney resorption function.
But anyways, what do you think about the whole blood test for calcium/magnesium and their ratio?

 

[mattyb]

How often do you check for albuminuria in people over 50, especially in the morning? They may have normal eGFR and BUN values on blood tests but the foamy urine in the morning is a common sing for most people over 50, and often much younger. Maybe I should not have said "renal insufficiency" but "filtering dysfunction" to make it less controversial. In my experience, any elevation in FFA leads to disturbed electrolyte balance and kidney resorption function.
But anyways, what do you think about the whole blood test for calcium/magnesium and their ratio?

We check urinary albumin, creatinine, and ACR for everyone. Tests are always done in the morning.

Any test can be useful given the proper context. What sort of context are you considering blood Mg/Ca for?

I have also never heard of nail testing, but it does sound interesting. I don't know what it would offer that hair doesn't though.

 

[haidut]

We check urinary albumin, creatinine, and ACR for everyone. Tests are always done in the morning.

Any test can be useful given the proper context. What sort of context are you considering blood Mg/Ca for?

I have also never heard of nail testing, but it does sound interesting. I don't know what it would offer that hair doesn't though.

Well, given that the RBC magnesium is probably a useless test (as you said) then the calcium/magnesium ratio in whole blood won't tell much.
Peat mentioned nails as more reliable for mineral analysis. Can't find the quote right now but I think he said nails have reduced turnover and thus are more reflective of long-term electrolyte status.

 

[Regina]

So can thiamine and charcoal, also searchable but more easily found through a Google search on the forum
Thiamine Reverses Diabetic Kidney Damage In Humans
Thiamine Reverses Diabetic Kidney Damage In Humans

Anything that keeps FFA low will protect kidneys from degeneration. Raising NAD/NADH ratio was recently shown to reverse aging in any organ studied. Steroids like androsterone have been known as kidney-anabolic since the 1940s. It is also anti-aging for heart, liver, and skin. Progesterone and DHEA share many of the same effects as do testosterone and DHT.
The Anabolic Effects Of Androsterone

Woot! Thx

 

[Koveras]

We check urinary albumin, creatinine, and ACR for everyone. Tests are always done in the morning.

Any test can be useful given the proper context. What sort of context are you considering blood Mg/Ca for?

I have also never heard of nail testing, but it does sound interesting. I don't know what it would offer that hair doesn't though.

Well, given that the RBC magnesium is probably a useless test (as you said) then the calcium/magnesium ratio in whole blood won't tell much.
Peat mentioned nails as more reliable for mineral analysis. Can't find the quote right now but I think he said nails have reduced turnover and thus are more reflective of long-term electrolyte status.

Here you go

"Toenails are much better, because they absorb more from the body, less from environmental air and water exposure."

 

[haidut]

Here you go

"Toenails are much better, because they absorb more from the body, less from environmental air and water exposure."

Thanks, for some reason this quote would not show up on a Google search or a forum search. Maybe it was just not indexed yet.
So, the bigger question is - what labs would accept nails for analysis?