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Magnesium: The cure to all disease?

Having spent many evenings and weekends working in a retail pharmacy with a thriving vitamin and supplement aisle, I’m no longer surprised at the purchasing habits of consumers. The setting gave me not only the opportunity to learn about the latest supplement fads, but also to speak with consumers that place great faith in these products. A recent paper suggests 25% of CAM users account for 75% of all expenditures on CAM. And that’s consistent with what I saw in the pharmacy. Some consumers spend hundreds per month on supplements, so the belief that these products are beneficial must be very strong. So I like to ask about reasons for use. Many attribute their current health status to supplements, and usually tell me that their supplements are for preventing disease, optimizing health, or “boosting” the immune system. And while I’m encouraged to see these consumers take an active interest in maximizing their own health, I’m often puzzled by the decision-making that’s occurring. In some cases, beliefs about health, medicine, or the effectiveness of their supplements are misguided, or flat-out wrong. They’re getting expensive urine and positive feelings, but there’s little evidence to suggest the supplementing is having any objective benefits. More surprisingly, some consumers take products for which there is no medical indication at all – it’s intended as “primary prevention” of a medical condition they believe they can avoid through supplement use. Afraid of macular degeneration? Take lutein. Or worried about Alzheimer’s? Grab some ginkgo biloba. No matter your anxiety, there’s a supplement marketed for your. One supplement with enduring popularity is magnesium.  It cures cancer. And depression. Throw away your inhalers, because it cures asthma too. Read enough online, and you’ll conclude that magnesium is quite possibly the prevention and the cure to all disease.

Magnesium really is everywhere in the body – it’s the 4th most abundant mineral. It’s involved in hundreds of different biochemical reactions and enzyme systems, supporting processes like protein synthesis, cell growth, and energy production. It has roles in nerve function, muscle control, and blood pressure. Even blood sugar regulation depends on magnesium.  The body has several mechanisms to stabilize levels. We’re carrying about 25 grams in total, much of which of which is locked in the skeleton. Some magnesium sits on the surface of bone and helps (slowly) regulate levels in the rest of the body: Only a tiny fraction of the total body’s magnesium (1%) is actually in the blood.

We obtain magnesium in our diet, with an “average intake” of 360mg per day. Most foods contain magnesium, though some have more than others. After ingestion, magnesium enters the blood stream through a combination of diffusion and also active absorption at sites throughout the bowel. Some of this effect appears to be influenced by vitamin D. Kidneys manage most of the excretion of magnesium and actively control the amount that is eliminated to maintain steady levels. Interestingly, almost all magnesium filtered out initially, and then about 95% of it reabsorbed. Drugs which inhibit the regular function of the kidney, like diuretics (“water pills”) can affect magnesium levels. Some diuretics promote excretion of magnesium, while others promote retention – it depends on their mechanism of action. There are a long list of other drugs that can influence magnesium levels, most by affecting the kidney’s filtration process. Proton pump inhibitors (e.g., Nexium) are among the offenders, and can cause hypomagnesemia in some. Given its multiple actions, low magnesium levels are associated with conditions like hypertension, cardiovascular disease, and diabetes. Other medical conditions can affect magnesium levels, either through action on absorption or elimination. Alcoholism, kidney or liver disease, and various gastrointestinal malabsorbtion conditions (e.g., Crohn’s disease) can all reduce magnesium levels.

Does magnesium have medicinal effects when consumed? In medical and pharmacy practice, it has several demonstrated uses – the most well known are probably as an antacid or laxative. Good old milk of magnesia (MOM) works because magnesium is partially absorbed – enough stays in the bowel, drawing water into the colon and softening and dislodging anything below.  Injectable magnesium, sold as a prescription drug,  allows large doses to be given quickly, and is ued for the treatment of preeclampsia (pregnancy-induced hypertension) and eclampsia (the resulting seizures) – it’s well tolerated and better than other drugs.  Magnesium also seems to be effective for treating some forms of arrhythmia, as well as asthma exacerbations. Some types of migrane and cluster headaches also seem to respond to magnesium supplements.

In other medical conditions, magnesium’s role is less clear. Magnesium levels may be related to osteoporosis, but the role of supplements is still being established. Diets high in magnesium seem to reduce the risk of stroke, but supplementation doesn’t seem to offer the same benefit. The same can be said for managing high blood pressure – effects with supplements are inconsistent and unimpressive.  For treatments of conditions like anxiety, ADHD, muscle cramps, and restless leg, more data is required before we can determine if supplements are beneficial.

In cases where drugs or diseases have reduced blood magnesium levels, supplementation is appropriate. Magnesium supplements effectively treat and prevent low magnesium. There’s debate over which type of oral supplement is “best”, fueled by a lack of studies that have actually examined how much magnesium is actually absorbed. Magnesium gluconate and magnesium chloride seem to be preferred over magnesium oxide and magnesium sulfate, which are associated with more diarrhea. Some pharmacies manufacture  magnesium glycinate, which is claimed to be superior. There is little credible information to guide selection, unless you are a rat. Given the influence of food and other factors, the specific version used may depend more on individual preferences and side effects. Magnesium is often combined with calcium in tablets, sometime in specific ratios (e.g., (3:1). There’s no scientific basis for these proportions.

Supplements or Diet?

Having established magnesium’s bona fides as a drug, with medicinal uses, what does this suggest about supplementation in the absence of a confirmed deficiency? Given the number of systems and processes that are controlled by magnesium, supplementation could plausibly have biological effects. However, for it to do so, it would need to act against all of our regulatory systems that work to keep our levels fairly constant. Magnesium supplements are generally well tolerated and toxicity is rare. But here’s where we run into questions about correlation and causation. Without prospective data from randomized controlled trials, we cannot infer that supplements have the same effects as dietary changes. Benefits in studies seem to be related consuming foods rich in magnesium, not necessarily magnesium supplements.

Magnesium is abundant on earth and so it’s also abundant in food.  In general, the absorption of magnesium from the diet is estimated at about 50%. Despite the prevalence in food there is information to suggest that dietary magnesium consumption can still be insufficient. Plants, and particularly grains, have more magnesium than meat or dairy. A simple rule of thumb is that magnesium usually accompanies fiber. The water supply can also contribute to magnesium intake, particularly in areas with “hard” water. There’s epidemiological evidence that connects water hardness with cardiovascular disease. While the data are interesting, few studies have measured consumption and correlated it with magnesium levels. Given that most of our magnesium consumption is from food, the current consensus does not support minimum hardness levels being established in the water supply.

Risk and Benefit

No harms or adverse effects have been observed when magnesium is consumed as a food ingredient. Supplements, however can cause adverse effects – diarrhea being the most common when daily doses exceed 350mg. High levels, hypermagnesemia, is uncommon but has been reported, particularly with regular consumption of magnesium supplements in people with decreased kidney function. In the absence of risk factors, particularly undiagnosed kidney disease, magnesium supplementation is generally considered safe.

Conclusion

Magnesium supplementation has an established role for some diseases and medical conditions, and looks promising for others. Whether supplementation is required in the absence of a relevant disease or documented deficiency is unclear. While it is tempting to extrapolate the relationship between low magnesium and various diseases into an argument for supplements, the issue of confounding in dietary studies cannot be ignored.  As we have seen with other vitamin studies, the long-term benefits of supplementation should not be assumed until they have demonstrated.  Given the complexity of magnesium’s role in the body, the best way to answer questions about the benefit of supplements is with randomized trials. But there’s another approach that has an attractive risk/benefit perspective: Boosting magnesium intake through dietary changes. Helpfully, foods rich in magnesium are already recommended in diets associated with  positive health outcomes: Green vegetables, beans, whole grains, nuts and seeds are all good sources of magnesium. Supplementation may not turn out to be harmful, but it may be unnecessary. And it may distract people from making positive changes to their diet. Without a confirmed deficiency, or specific medical need, magnesium supplementation seems unnecessary.

Posted in: Herbs & Supplements

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48 thoughts on “Magnesium: The cure to all disease?

  1. nybgrus says:

    Magnesium is indeed a very important electrolyte. It is a co-factor in many processes – on medicine rounds we typically focus on its role in kidney function for the retention of potassium. In other words, if a patient has low potassium and we need to supplement it, if the magnesium is low we must also supplement the mag or else the potassium simply won’t go up.

    However, it is also a cell membrane stabilizer. When you are low on mag, the resting membrane potential of your cells shifts to become less negative. Without going into painful details I’m sure most readers here would not be interested in, that essentially means that whatever cells in your body can “fire” will do so more easily – whether that is nerve cells or muscle cells. So if you have someone with seizures you can give magnesium as an adjunct if the levels are low to help stabilize the nerve cells. That is also why the data Scott was talking about shows some help with high blood pressure – increased mag makes muscle cells more stable (a muscle cell “firing” is it contracting) and thus more relaxed and since your arteries are lined with muscle, having that more relaxed will decrease the tone and thus decrease blood pressure. In obstretics, mag is used in pre-ecclampsia for two reasons. The first one is the blood pressure (pre-ecclampsia is, in part, defined as hypertension in a pregnant woman) and to help prevent seizures (which is when pre-ecclampsia becomes ecclampsia). I did a couple weeks of high-risk pregnancy wards and had a chance to see this all in vivo. Since asthma is a function of mast cell degranulation stabilizing the cell membrane with magnesium would also help decrease asthma attacks.

    The point I am getting to is that for this sort of suppression of blood pressure and seizure activity we gave a lot of intravenous mag. And a lot of times it was hard to get the levels up. And once they were, we needed to keep these patients on a constant drip. And I had to do regular checks to make sure we didn’t go too far and send them into mag toxicity. This usually wasn’t a problem since there is a wide therapeutic window for hypermagnesemic (is that a word? lol) treatment, but a distinct possibility because of how much and by what route we were giving it.

    So the real point is that a person buying supplements would be incredibly hard pressed to get to those kind of levels of magnesium to see a drop in blood pressure, etc. And they wouldn’t want to anyways – our patients felt terrible on those levels. You feel lethargic, groggy, weak, and nauseated (because your bowels slow down too). So if you are not actually deficient, trying to supplement won’t to anything positive for you no matter how hard you try (including help your asthma). I suppose the argument could be made that going to the high end of normal would offer some additional membrane stabilization that would help with these various processes, but besides the fact that this would be a very clinically insignificant effect it would be hard to maintain since, as Scott said, the body is quite good at regulating mag levels.

    Out of curiosity I looked to see if there was any data on the prevalence of hypomagnesemia. In other words, is it worth it for the average person to “play it safe” and just supplement anyways? Well, the data is heterogeneous, and it depends on your definition of hypo. One study from the Journal of Family Practice looked at data from 11,000 white Americans aged 45-64, 4,000 black Americans, and 16,000 Germans and did a lit review and found that rates of hypomagnesemia ranged from 2-15%. Using a cutoff of 0.76mmol/L they found 14.5% prevalance. Drop that cutoff to 0.7mmol/L and the same population is at 2%. Values at which we typically see effects from hypomagnesemia is around 0.5mmol/L (for the docs out there, note this is in SI units, not the typical units we use in the US which is mg/dL). Another study out of the Middle East showed prevalance of 4.6%, but also a 12.2% rate of hypermagnesemia. Both studies noted a difference in sexes, with women having a higher likelihood of lower magnesium levels overall.

    So all in all, this seems to me – along with everything Scott wrote about – to be yet another example of supplementation being almost entirely worthless outside of clinical deficiency. If you are clinically deficient you will have symptoms. If you don’t have symptoms, supplementing really won’t do anything useful either because the clinical effect will be very small, non-existent, or hard to achieve through supplementation anyways. If you have conditions which could be helped by making sure you have a normal mag level, then you should hopefully be seeing your doctor anyways, and get a mag level which is part of a “Comprehensive Metabolic Panel” or CMP which is commonly ordered on yearly physicals anyways.

    Just my two cents (ok maybe a nickel) as I kill some time waiting for my exit exam for internal medicine in 6 hours.

  2. nybgrus says:

    Seems my HTML tag didn’t work for that other study out of the Middle East.

  3. Jeff says:

    More surprisingly, some consumers take products for which there is no medical indication at all – it’s intended as “primary prevention” of a medical condition they believe they can avoid through supplement use. Afraid of macular degeneration? Take lutein.

    There is some evidence that lutein could either prevent ARMD or at least slow the progression of the disease

    A couple of small studies suggest carotenoids plus antioxidants might even improve the vision of those with ARMD (pubmed/15117055, pubmed/17716735).

  4. Janet Camp says:

    Many years ago I bought a book about controlling bp with a “magnesium diet”. I quickly realized that this was really just a high fiber diet since I had previously bought a weight loss book that was also a high fiber diet. I was already a vegetarian eating a lot of beans, nuts, seeds and veggies, so I figured I was okay and that any problems I was having should be left to my doctor. I got on bp meds, which I was able to reduce dramatically when I finally lost the weight–by eating less (fiber or no fiber).

    I feel simply awful about highly educated pharmacists having to do duty at some place like Walgreen’s/WallMart, etc., where they are subject to the widespread ignorance of the general public. While there is the opportunity for education, it seems that most people who use supplements do not change their minds–or at least that hard core 25% who spend the 75% do not.

  5. Chris says:

    Woot! I just bought a soil amendment (fertilizer) that specifically contains potassium, sulfur and magnesium. I was initially just looking for sulfur to reduce the pH around my blueberries, and that box was next to the sulfur soil amendment.

    So it is nice to know that my veggies will not be lacking in magnesium. Because I’d rather eat the homegrown veggies over taking a supplement.

  6. stanmrak says:

    Anyone who buys their supplements at a pharmacy is badly misinformed. Drug store brands of supplements are rubbish. Anyone well-educated about nutrition would know this.

  7. WilliamLawrenceUtridge says:

    Stan, you could remove the words “their”, “at a pharmacy” and “drug store brands of” and you’d have a more accurate statement. People who are actually educated about nutrition, people who went to real schools and got real degrees, know that supplements are not magic, bar deficiency vitamins are not necessary, and that for most people, food is more than an adequate source of everything they need. People who proclaim supplements are necessary and drugs are poison are not even tenuously connected to science.

    But hey, enjoy your expensive urine.

  8. Alia says:

    Well, I have a tendency to get painful leg muscle cramps (usually in the middle of the night or sometimes during exercises). That’s why I always keep magnesium/potassium pills in my cabinet (however, over here they are not branded as supplements, only as OTC drugs). And they do help, although I believe it’s mostly because of their potassium content and magnesium is there for potassium retention (what nubgrus wrote).
    And diet certainly helps – in the summer, when I eat loads of fresh tomatos, I usually do not get those nasty cramps.

  9. Scott Gavura says:

    @stanmrak:

    [citation required]

  10. Krebiozen says:

    Here are a few random thoughts on magnesium that might be of interest to some of you, some based on my experience measuring serum magnesium as a biomedical scientist in clinical biochemistry.

    Frank hypomagnesemia is pretty rare, and almost all the cases I have seen have been in patients who are very sick indeed. Elderly people not infrequently end up malnourished for various reasons, and that can include hypomagnesemia. Blaming a deficiency of one nutrient for various conditions in a patient who is generally malnourished can be very misleading. Whole blood magnesium is supposed to give a better idea of body stores than serum levels, but this has not caught on, mainly because homeostatic mechanisms keep serum levels up at the expense of intracellular and skeletal magnesium, and serum magnesium is what is important in the short term, not least because it keeps the heart beating. Long term adequate nutrition should be enough to supply adequate magnesium to replenish magnesium stores.

    In the long term, adequate magnesium intake usually means that a person eats lots of fruit and vegetables, which means any correlations between magnesium (and potassium) intake should be taken with a pinch of (low sodium) salt, as there may be several other reasons that people who eat lots of fruit and vegetables are healthier than those who don’t. The kinds of surveys Nybgrus refers to are of limited use, as reference ranges are usually established by taking blood from normal healthy volunteers (often lab staff like me) and and taking the mean plus or minus 2 standard deviations as the normal range on the basis that 95% of normal people will have results within that range. That means, of course, that 5% of normal people will have results outside that range. Higher serum magnesium (and other nutrients like vitamin C) may be a marker of high fruit and veg consumption, the same problem I mentioned in relation to consumption.

    Just because someone is not consuming the RDA of magnesium in their diet does not mean they are deficient in magnesium, contrary to the claims of CAM proponents like Mark Sircus (ugh), who claims that we are nearly all deficient in magnesium because many of us consume less than the RDA. The RDA is calculated to give an intake at which no one would be deficient, which is not quite the same thing. Incidentally, a very good source of magnesium is white bread (which is evil according to Sircus), if you look at the USDA website’s nutrient content of foods pages.

    Claims that the nutrient content of fruits and vegetables, including magnesium, have fallen catastrophically over the last century do not appear to be true, based on some research I did a couple of years ago, comparing nutrients in various crops in the 1940s to the present day (which I can dig out if anyone is interested). Since plants don’t grow well if they don’t get enough nutrients, and farmers are highly motivated to increase yields of healthy crops, this is not very surprising.

    CAM proponents often recommend magnesium applied topically, often as a solution of magnesium chloride (so-called ‘magnesium oil’) or by soaking in a bath of Epsom salts (magnesium sulfate). There is some limited evidence that magnesium salts are absorbed transdermally in some circumstances, but the wisdom of bypassing the body’s natural defenses against excessive absorption (such as diarrhea) seems questionable to me. There have been a few cases of serious overdose and even deaths in children from Epsom salts enemas (is there nothing nutty parents won’t squirt up their children’s rear ends?).

  11. nybgrus says:

    The kinds of surveys Nybgrus refers to are of limited use, as reference ranges are usually established by taking blood from normal healthy volunteers (often lab staff like me) and and taking the mean plus or minus 2 standard deviations as the normal range on the basis that 95% of normal people will have results within that range.

    Indeed – all “normal” lab values are determined that way. I didn’t discuss it in great detail, but hence the two papers with slightly different “normal” values demonstrating a tremendous shift in how many people are “hypomagnesemic.” And that does not account for the 2.5% who will be “hypo” and still be quite normal, nor the people actualy hypo who are sub clinical.

  12. BillyJoe says:

    Scott Gravura: ” For treatments of conditions like anxiety, ADHD, muscle cramps, and restless leg, more data is required before we can determine if supplements are beneficial.”

    Alia: “I have a tendency to get painful leg muscle cramps…That’s why I always keep magnesium/potassium pills in my cabinet”

    Seems personal anecdote trumps lack of evidence again. :|
    Here’s my anecdote:
    I get cramps whenever the involved muscle is tight due to exercising without active stretching afterwards.

  13. Alia says:

    @BillyJoe – I think I’ve written quite clearly that my muscle cramps are the result of potassium deficiency and magnesium is there to help potassium retention. And believe me, muscle cramps due to excercise without active stretching later are nothing compared to cramps (usually in calf muscles) that you get in the middle of the night due to hypokalemia.

  14. Krebiozen says:

    nybgrus,

    Indeed – all “normal” lab values are determined that way.

    That’s why they are usually referred to as ‘reference ranges’ rather than ‘normal ranges’ these days. People tend to panic more when a result is slightly outside a ‘normal range’ than if it is outside a ‘reference range’.

    OT, but lab staff often end up getting blood tests that are not clinically indicated, either through someone establishing a reference range, or because they have had blood drawn for some reason, run it through a machine out of curiosity, and find an abnormal result they were not expecting. Then they have to decide what to do with it, just as a clinician on a fishing expedition does. Two of my colleagues found abnormal results this way that were then investigated to eliminate any nasty causes; one of them was subjected to a muscle biopsy before finding that there was nothing wrong with him. The first case was an elevated bilirubin that turned out to be Gilbert’s and the other an elevated creatine kinase, what turned out to be because of my colleague’s African origin. Despite a large population of Africans in our area no one had previously noticed that they have normal CKs significantly higher than the rest of the population (this was several years ago, I hasten to add). I can’t help but wonder how many people with chest pains in the past were assumed to have had a heart attack because of an elevated CK that wasn’t elevated at all.

  15. Krebiozen says:

    Typo – should be, “that turned out to be”. I ain’t a ignoramus.

  16. Alia says:

    Well, as an anecdote – my mother in law one Sunday went to ER because of chest pains. She had blood test, which showed highly elevated CK and ECG that showed nothing. But still she was assumed to have had a heart attack because “you know, in women ECG is often inconclusive” and so on. We were all scared out of our wits. And then, a few hours later someone realised that they had far too many patients with elevated CKs. So some nurses and lab staff had blood tests – and, surprise surprise, they also had highy elevated CKs. As it turned out, there was nothing wrong with my mother in law, it was the analytic machine. And later it turned out that her chest pain was due to spinal problems.

  17. BillyJoe says:

    alia,

    “I think I’ve written quite clearly that my muscle cramps are the result of potassium deficiency and magnesium is there to help potassium retention. ”

    Okay, on re-reading your post, I see that is the case. I just didn’t read it clearly, sorry.
    (I ‘m going to blame my 100km cycle through the Dandenong Ranges this morning)
    As a matter of interest, have they determined the cause of your potassium deficiency?

  18. Alia says:

    @BillyJoe
    Yup, it’s UTIs – you lose a lot of potassium through urine then.

  19. BillyJoe says:

    I’m pretty sure that my CK is elevated after this morning’s ride through the hills. I also have chest pain which I’m pretty sure is just muscle strain from pulling on the handle bars on the uphill sections. I think perhaps I’ll not attend A&E in case I end up spending the night in ICU.
    (In any case, in advanced nations like Australia, they do Troponin because it can be distinguished from the troponin in skeletal muscle)

  20. BillyJoe says:

    Alia,

    “Yup, it’s UTIs – you lose a lot of potassium through urine then.”

    Ah, you are a female.
    But have they considered any other diagnoses…

    http://www.livestrong.com/article/464766-is-low-potassium-associated-with-utis/

    …chronic kidney failure, eating disorders, excessive use of laxatives, diarrhea, use of water pills, vomiting, diabetic acidosis, low magnesium levels, acute tubular necrosis and Cushing’s syndrome.

  21. Alia says:

    @BillyJoe – I think we’re hijacking the thread but anyway, I can assure you that I do not use laxatives, water pills and do not suffer from eating disorders. ;-)

  22. nybgrus says:

    nowadays we have criteria for determining MI (myocardial infarction – heart attack). Elevated troponins are pretty much a clincher, though not always. The problem is that they elevate many hours (4ish) after the onset of the actual heart attack so you don’t want to actually wait for them to be positive before you call it. CK elevates within one hour, and so is the better marker to go off of. Nowadays we can fractionate that into the MB portion which is more specific for heart muscle than other muscle. We then use the absolute amount of CK-MB and the fraction as a diagnostic criterion. EKG changes is another, but those are only about 85% sensitive depending on what series you read. And lastly is the clinical picture – which is considered to be the most important. Any two of those is sufficient for a diagnosis of MI.

    In other words if you are happy as a clam and claim nothing is wrong but you have elevated serum enzymes (CK-MB and/or troponin) and a characteristic EKG – you are having an MI.

    If I think you are having an MI and your enzymes are normal but your EKG has changes…. or no EKG changes but enzymes… you get the picture.

    That said, without EKG changes we don’t call it an MI. We call it Acute Coronary Syndrome (ACS). There are a couple different things that can cause death of cardiac muscle and characteristic symptoms and not actually be an MI. And we even break down MI into sub-types: STEMI and NSTEMI. The characteristic change is ST-segment (a part of the EKG) elevation. If you see that, pretty much nothing else can cause it except an MI and we are rushing you off to the catheterization lab. However, you can have an MI that is Non-ST-segment Elevation – which is when you have enzymes positive and look like you are having a heart attack but, as the name implies, no ST-segment elevations. You can also have a sub-endocardial MI which creates depressions in the ST segment. Then there is unstable angina (which is still ACS), Prinzmetal’s variant angina, and angina (which are not ACS).

    So one can understand how there can be mistakes made and considering the diagnosis in question it is typically a better idea to get worried over nothing than not to worry about someone actually having a heart attack.

    As for the lab making mistakes… yeah, it happens. One night in the ER we had a bunch of patients come back with crazy high potassium levels. Turns out the calibration on the machine was off. That is why it is important to teach doctors what the values mean and what to expect from them so when an error happens we have other ways of confirming it and choosing to act. Pretty much nothing in medicine is determined by a single test out of context – we need a few lines of converging evidence to point us to a diagnosis and management plan.

    And BJ – your CK would be up, but not your CK-MB, so I would still not call you an ACS if you came to see me in the ED for your post-ride chest pain.

  23. BillyJoe says:

    Well, I’m not even going to the local A&E, let alone flying al the way over to America. :)
    I think I’ll just take my chest pain and elevated CK to bed and see if I wake up in the morning.
    If you never hear from me again….

  24. BillyJoe says:

    Alia,

    “I can assure you that I do not use laxatives, water pills and do not suffer from eating disorders. ”

    Chronic renal failure as a result of recurrent UTIs/pyelonephritis?

  25. nybgrus says:

    aww come on mate! I’ll do the EKG for free ;-)

  26. Alia says:

    @BillyJoe, fortunately chronic renal failure was ruled out. I must admit, my problem might also be my diet – I eat a lot of fruit and vegetables, but only in summer. In winter they are much more expensive and they do not taste that good, which means I stick to apples and pears, really. Perhaps I shoud drink more tomato juice in winter, that should help.

  27. nybgrus says:

    Orange juice has a suprising amount of potassium. We advise our end stage renal patients to avoid it for exactly this reason.

    Out of curiosity has your potassium level ever actually been measured? A case of genuine hypokalemia would warrant daily supplementation with actual prescription potassium.

    You’ll also have to forgive my skepticism (not about your cramps, but about the cause) since the only two oral potassium supplementations that don’t take hours and hours to actually raise your serum level are both liquid and the really fast acting one tastes terrible. So I find it suspect that your cramps are actually relieved by the repletion of a tablet supplement.

    There is a set of rare disorders called periodic paralysis that involves transient hypo and hyper kalemic states modulated by electrolyte channels. However, the long term treatment is not potassium supplementation and the treatment for acute attacks is the nasty tasting liqiud potassium I had already mentioned (the pills just won’t act in time). Also, the symptoms are paralysis and weakness, not pain and cramping, though there are variants and different people interpret their symptoms differently as well.

    http://emedicine.medscape.com/article/1171678-clinical

    If it is just a diet issue, then I would bet that the pills are more placebo than anything in the short term and perhaps help a little bit in the long term to decrease the frequency and severity of attacks.

  28. Alia says:

    Well, if I get a bad case of cramps (like I had last year), it takes about two weeks of taking potassium tablets to get rid of it – so it’s by no means fast. But maybe you’re right and it’s more of a placebo – in this case I’d take anything, even acupuncture (only joking, of course) not to wake every night with a dreadful pain in my calf.
    Thanks for the tip about orange juice, but I’d rather stick to tomato juice because it contains less sugar.

  29. Krebiozen says:

    I’m in the UK and we do troponin and CK-MB here too, but I believe cardiologists mostly go by the ECG (why is it EKG in the US?), though I have had a cardiologist hassling me for a troponin result more than once in the middle of the night. CK-MB has been around for a long time – I remember doing it at least 20 years ago – but it used to be a pain to do, not something we offered routinely. Now it’s just another test on a great big analyzer [drifts off into misty nostalgia for the days when we used test tubes, pestles and mortars in the lab...]. My Nigerian colleague with the high CK had all his CK isoenzymes measured, but they were all elevated, so it didn’t help much.

    The people in the labs should have noticed those elevated CKs and potassiums and checked the calibration – didn’t they use quality controls? That’s why it’s a good idea to have someone with some clinical training, not just technical training, who would notice things like that.

  30. nybgrus says:

    @alia:

    My apologies. My read of what you had written about the condition made it sound more often and that the tablets were a quick bedside remedy. In that case, then yes, I suppose you are probably correct and the tabs are not primarily placebo, though I am sure there is a certain amount of it there in the immediate decrease in acute symptoms you likely experience knowing that relief will come at some point in the future.

    And fair enough on the OJ – though perhaps a glass or two from time to time may prove beneficial to you in the winter months.

    @krebozien:

    We call it EKG to be contrarian. And because the German word is electrokardiogram. And clearly, it makes sense for us to use the German acronym.

    Cardiologists mostly go by ECG because of the time frame of the rise. In most modern cities, people will present to ED (or A&E in your modern cities) before the troponin elevates. CK-MB is used as an earlier marker, but mostly it exists as a marker of reinfarction as the CK-MB levels drop much more quickly than troponin. The reason it has been around so long is because the troponin tests a vastly smaller amount of protien (CK was first at 10s-100s of nanograms, then CK-MB >3ng, and troponin at >0.4ng).

    Your Nigerian friend sounds like an interesting anomaly. Not every test is perfect, as you clearly know. And not every lab or every shift in a lab runs perfectly. That is why systems level checks are important because at some point there will be mistakes. Catching them before they adversely influence outcomes is the important part.

  31. Krebiozen says:

    And clearly, it makes sense for us to use the German acronym.

    Clearly, since the US was just one vote away from adopting German as its official language in 1794. What do you mean it’s an urban myth? :-)

    Your Nigerian friend sounds like an interesting anomaly.

    Not really, his CK was normal for his ethnic group. We later adopted CK reference ranges specific for ethnic origin to avoid any confusion. It’s worth bearing in mind that an elevated CK in a person of African origin, particularly if they are young and male, may be quite normal.

  32. lilady says:

    Okay, at the risk of going (further) off-topic.

    My son had pancytopenia and ITP. After yet another episode of internal bleeding following yet another of his “viral syndromes”, a hospital-staff pediatric hematologist , came to his bedside to speak with me. My son had his “very own” pediatric hematologist associated with another hospital who had tested him for von Willebrand Disease (my sister has that disorder), and other platelet tests and his moderate anemia and abnormal RBC morphology. He was negative for von Willebrand disease but found to have a platelet aggregation and adhesion problem.

    I recall the “new” (black) pediatric hemotologist stating, “he has a very low white blood count…especially for a white kid”.

    So yes, there is a difference in “normal” lab reference ranges for WBCs as well as RBC morphology, when testing individuals who are black Americans.

    http://bloodjournal.hematologylibrary.org/content/106/2/740.full.html

    I believe these “normal” hematological differences between black and white patients has implications for medical oncologists who are treating black patients.

    P.S. I’m fairly certain that there is no black heritage in my family or my husband’s family.

  33. nybgrus says:

    @krebiozen:

    Ah. I just assumed you meant higher than that even.

    @lilday:

    You do. We all do. In fact only about 11% of the genomic variation in humans can be ascribed to geographic location. Everything else is basically the same mish-mash.

    http://www.youtube.com/watch?v=teyvcs2S4mI&feature=plcp

  34. lilady says:

    @ nybgrus: I’m not denying that my kid might have had some gmish of heritage, causing leukopenia…but he also was anemic with abnormal RBC morphology (megaloblastic anemia/anisocytosis and poikilocytosis)…in addition to ITP.

    He never had surgery and he was given “a unit of blood” (20 cc) when he was eight days old after undergoing heart catheterization.

    He was taken off his phenytoin for a number of years, supplemented with folate and B-12 and nothing changed. It was just one of the many problems that my son had, that has never been associated with the rare genetic disorder that he was diagnosed with.

  35. mousethatroared says:

    Ah! This discussion has actually been quite helpful in explaining why my docs haven’t been very interested in attributing any of my various subjective annoying complaints to some of my mildly “abnormal” lab values (very mild anemia, C3 and C4 a few points low, etc)

    I didn’t really realize that there was such a…margin of error (is that the correct description?) in these tests.

    Unfortunately, my more definitive abnormal results (ANA and TPO antibodies) don’t correlate to my symptoms.

    What’s a poor mismatched patient to do? Strangely enough, I end up thinking I should probably take magnesium supplements – (joking!)

    BillyJoe – what does your wife think you should do, go to the ER or go to bed. I find the wife is usually a better judge of these things.

  36. nybgrus says:

    @lilady:

    My apologies for not explaining fully. If you watch the video – and the second part as well – there is a section discussing the notion of “race medicine” – i.e. stating that a race has a particular propensity or lack thereof regarding a certain medical trait or condition. The example used was that of Bidil – a drug marketed specifically for African American hypertensives. The rationale is reasonably correct in that there is a difference in the morphology of a particular receptor which is more comman in AA people than whites (20% vs 10ish% IIRC). However, the point was that the surrogate marker used – self identification as a particular race – was very poor because so many “non-blacks” had the morphologically different receptor as well. Additionally, there is such a surprisingly staggering amount of genomic homogeneity that, once again, “race” is a very poor surrogate marker for genomic and molecular phenotypic differences.

    The reality is that single genes rarely – really almost never – fully explain a trait. Genes work in concert, have epigenetic controls, and proteomic controls all of which vary depending on the admixture present in the person. So even if one does or doesn’t have a particular gene, the expression of it, degree to which it creates pathology, and responsiveness to treatment vary drastically because of other ways of protein expression control in the cells.

    So for your son – whom I am sorry to hear has had such a medically troubled life already – the rare genetic disease could easily be affecting the proteome and thus higher orders of gene and protein control thus leading to down stream effects we could not possibly predict or expect (because we don’t know and can’t calculate such complex pathways). Having a slight shift in African haplotype markers could contribute all while you – quite reasonably – think there is no African heritage in your family that could effect or contribute to such an effect.

    Right now we still use “race” as a surrogate marker for these differences to help determine pre-test probability. Sometimes that is because it is the best we got, sometimes because the association is actually that robust, but often because it is a lazy and easy way to make a quick assumption. Testing for specific markers – like in the case of Bidil – is simply more costly and time consuming, even though it would lead to better outcomes. Eventually, however, we will do full genome assays from a drop of blood and crank out some calculations to tailor drugs and dosages individually. We need a lot more knowledge of the genotype and the pathways and quantum computing. To put it in perspective, the amount of data that would need to be crunched in order to come up with such calculation is something that our best super and cloud computing systems wouldn’t be able to handle… even if we had the data to plug into them, which we still don’t.

  37. nybgrus says:

    @mouse:

    I suppose one can think of it as “margin of error.” More accurately it would be “margin of variance” in that we simply don’t know the true variance and we can’t determine whether your variance would be in line with that of the aggregate population variance. As in the comment to lilady and the video I referenced, you can imagine that a) our sample size is inevitably pretty small, so true population variance is going to be an approximation and b) there are various haplotypes and genotypes within a population – and most importantly even within what we would “obviously” call a “race” – such that the average across these groups is really still much too broad.

    As an example, we feel that we can identify a “black” person or “asian” person pretty easily. But in reality we are actually pretty poor at it and the definition changes depending on how fine a resolution you want of the haplotypes. So when we say that “normal reference ranges for black (or African American) people are…” we are still lumping together a large amount of rather disparate groups and excluding groups that should actually be included based on detailed haplotype sequencing. So when we do all the math and come up with ranges, we find that some African Americans still aren’t in that range (krebiozen’s Nigerian friend for example) and some “white” people are best described by the African American ranges. So our marker to define what group fits what range is simply very poor.

    That said, there are some things that are pretty certain. A potassium level of 6. The extremes (in certain things) can be pretty easy to pick up, but the normal variation in the middle is much harder to define. Vitamin D is an excellent example of where it is difficult. We have an idea for what “really low” is and some clinical data to back up supplementation as being useful. We have an idea of what “really high” is and Gary Null to show us that this too can be bad. But the middle is really tough – where do we supplement? To what level? Is there a benefit in supplementation? Where does that benefit end? What about negatitves? Etc.

    So we need to put things in context… which is why I reckon your doc’s aren’t too concerned about your slightly low C3/C4 levels.

    And then we scratch our heads at the ANA and TPO levels… and are forced to relegate that to the big black box of proteomics I described above since we simply don’t have better understanding and resolution of what those mean in the context of unusual cases.

    And as for the wife test for chest pain…. I agree. Poor specificity but usually a good sensitivity. If your wife doesn’t think you should go in, that shouldn’t’ necessarily dissuade you. But if she thinks you should go in, then you’d be a smarter man for listening.

    (of course, I know BJ is not genuinely in need of this consideration since he was referencing being a bit out of shape after a hard ride. The conversation is academic and for the lulz, at it were)

  38. mousethatroared says:

    @nybrgus – yes, margin of variance, that phrase seems to make more sense. Somehow I thought it was all a bit more concrete than that, sigh, my quest for a grand unified “things making sense” theory fails again. :)

  39. lilady says:

    @ nybgrus and mtr: Remember the time when Tay-Sachs Disease, was considered to be only a *problem* for Ashkenazi Jewish couples?

    http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/Screening_for_Tay_-_Sachs_Disease

    “….Based on the preceding information, the Committee on Genetics makes the following recommendations:

    Screening for TSD should be offered before pregnancy if both members of a couple are of Ashkenazi Jewish, French–Canadian, or Cajun descent. Those with a family history consistent with TSD also should be offered screening.
    When one member of a couple is at high risk (ie, of Ashkenazi Jewish, French–Canadian, or Cajun descent or has a family history consistent with TSD) but the other partner is not, the highrisk partner should be offered screening. This is particularly important if there is uncertainty about ancestry or if there is a family history consistent with TSD. If the high-risk partner is determined to be a carrier, the other partner also should be offered screening. If the woman is already pregnant, it may be necessary to offer screening to both partners simultaneously to ensure that results are obtained promptly and that all options are available to the couple.
    Biochemical analysis should be used for individuals in low-risk populations.
    If TSD biochemical screening is performed in women who are pregnant or taking oral contraceptives, leukocyte testing must be used.
    Ambiguous screening test results or positive screening test results in individuals should be confirmed by biochemical and DNA analysis for the most common mutations. This will detect patients who carry genes associated with mild disease or pseudodeficiency states. Referral to a specialist in genetics may be helpful in these cases.
    If both partners are determined to be carriers of TSD, genetic counseling and prenatal diagnosis should be offered.”

  40. lilady says:

    Even more confusing about Tay Sachs Disease are the types of Tay Sachs Disease (Infant Onset, Juvenile Onset and Chronic and Adult Onset)…plus the addition of another group, Pennsylvania Amish, at higher risk for Tay Sachs Disease:

    http://www.intelihealth.com/IH/ihtIH/WSIHW000/32193/35422.html

  41. Krebiozen says:

    nybgrus – nice explanation of the uncertainties involved in “normal” ranges, and lilady, as always your account of your son’s problems is both interesting and poignant.

    We noticed that people from the Caribbean do have CKs higher than (South) Asians,but not as high as those from Africa, presumably as they have a more diverse genetic ancestry. Most Africans in the UL are from west Africa, and it would not surprise me in the least to find that CK levels in people from other parts of Africa (a large and genetically diverse continent) are different. Race is a cultural construct, not something that can be measured scientifically – I believe genetic variation within racial groups is greater than that (on average) between racial groups. Anyway,as nybgrus points out, reference ranges are not an exact science and all you can do is find the best range you can for your population, bearing in mind that 5% of normal people will fall outside that range. What’s normal for me may not be what is normal for themousethatroared, or for my Nigerian friend.

    Back on topic, I just came across this meta-analysis looking specifically at the effect of magnesium supplementation on hypertension. From the abstract:

    Effect size increased in line with increased dosage. Although not all individual trials showed significance in BP reduction, combining all trials did show a decrease in SBP of 3-4 mmHg and DBP of 2-3 mm Hg, which further increased with crossover designed trials and intake >370 mg/day. To conclude, magnesium supplementation appears to achieve a small but clinically significant reduction in BP, an effect worthy of future prospective large randomised trials using solid methodology.

    I am always a bit suspicious of meta-analyses that only find a clinically significant effect when large numbers of trials are combined, as publication and other biases may be involved, but the dose-related effect is interesting, especially as the effect size is considerably larger (by a factor of about 10) than some calcium channel blockers. Have I missed something here?

  42. Krebiozen says:

    I just spotted what I missed – I had my effect size units mixed up. Magnesium supplementation resulted in, perhaps, a decrease in SBP of 3-4 mm Hg and DBP of 2-3 mm Hg, and amlodipine resulted in a decrease in SBP of 17.3 mmHg and DBP of 10.5 mmHg. As you were.

  43. BillyJoe says:

    Michele,

    My wife would probably call the ambulance, so I didn’t tell her. :)
    (she always worries that one day I will not return from one of my Sunday morning jaunts and she will have to call the police who will find me dead in the hills somewhere)

  44. nybgrus says:

    @ Krebiozen:

    Nicely done. I had caught that and was starting to formulate the response in my head when I read your next comment.

    Also, a decrease of 3-4ish mmHg is really not all that clinically significant. Using their top numbers the decrease in Mean Arterial Pressure (MAP) which is truly what is of interest in cardiovascular disease is 3.33. And they do note specifically that not all trials had significance and it was only the highest does trials that did. But we’ve already discussed that this makes some sense and mag should have some minor effect on BP. I just don’t see it as clinically useful as a single agent and it could prove difficult to manage in multi-agent regimens. One of the adverse affects of ACI inhibitors and to a lesser extent ARBs is hyperkalemia. Chronic high level supplementation of mag would likely worsen this effect which would greatly outweigh the benefit of a 3mmHg drop in MAP. I can see mag supplementation as potentially useful for patients with adverse affects to many first line drugs but with a need for additional BP reduction. The problem is that these are also often quite comorbid patients and mag supplementation would not be very straightforward with them and I conjecture would become more complicated to manage than it is worth.

  45. mousethatroared says:

    BillyJoe – (sigh) Oh your are one of those silly “tough guys” who makes everyone around them do the work of trying to figure out if they are sick, well or dead in a ditch.

    My husband had mono after we brought my daughter home. He didn’t tell me how awful he felt and I didn’t figure it out til we were out hiking. He was carrying our daughter in a backpack. I looked at him and realized he was sheet white and looked like he was going to keel over. I immediately took our daughter off his back and yelled at him for endangering our child. I then took him home and refused to let him do anything beside desk work until he got better.

    The only way I ever get him to go to the doctor when he’s sick is by telling him that his mom won’t stop nagging me to tell him to go. So will he please go, so I can have some peace from his mom? THAT he understands. :)

    Things would be a lot easier if he’d speak up when he’s sick.

  46. Alia says:

    Sounds exactly like my father. He’s almost 80 and he spent most of last winter with pneumonia. My mother is a retired nurse so she knew by his coughing that it’s not an ordinary cold but he simply wouldn’t go to a doctor. Finally she made him go to a doctor, telling him that it was the time for his regular checkup and chest X-ray. He went, had a chest X-ray and then a round of heavy-duty antibiotics.
    And I’m afraid I’ve inherited that from him. I have all the necessary regular checkups and vaccines but it’s really hard for me to admit that I may be having a cold and that going out to gym this afternoon may not be my brightest idea after all. I think my motto should be “I will survive”.

  47. asolis says:

    Redox Signaling Molecules and ASEA

    ASEA
    Let’s start at the beginning.The human body is made up of somewhere in the range of 100 trillion cells. Within each cell are mitochondria, which are responsible for the creation of energy by way of what is called the Krebs Cycle. This process entails the conversion of glucose to ATP. The byproducts of the Krebs Cycle along the Electron Transport Chain are what are known as redox signaling molecules (“RSM”). Originally, scientists perceived these byproducts as metabolic waste – oxidants and reductants that must be purged from the cell in order to remain healthy. However, current research suggests otherwise. That in fact a proper homeostatic balance of oxidants and reductants is absolutely necessary for maintaining cellular health, including virtually all of the functions of the immune system and tissue regeneration response.

    In the most simplistic terms, they provide a means by which cells
    participate in intra- and inter-cellular damage-control
    communications, activation of antioxidants, cellular protection and
    defense against toxins and free radicals, and in the healing
    response. The human body is constantly working to maintain cellular health by balancing these redox signaling molecules to rid the body of harmful components and to clean up the oxidative stress and free radical damage that occurs at the cellular level, while simultaneously ensuring the cell’s ability to maintain proper
    communication with its environment. When these reactive molecules are in the proper balance, the immune system and healing process function at their optimal level.

    Virtually all disease and bodily challenges are caused by what is
    called oxidative stress – a increasingly salient reality of living
    in modern times attributable to a wide variety of factors, including
    sun damage, excessive exercise, electromagnetic radiation, food
    additives and preservatives, x-ray radiation, prescription drugs,
    heavy metals, stress, anxiety, air & water pollution, lack of
    sleep, and toxic industrialized chemicals to name a few. These
    factors cause our cells to produce an excess of oxidants in
    comparison to reductants – thus throwing off the cell’s
    homeostatic balance of RSMs and promoting the proliferation of
    harmful free radicals. But this imbalance is how the cell detects
    damage and is signaled to repair itself. The immune system is
    summoned, prompting repair, or replacement of the cell via mitosis (cell division) of a neighboring healthy cell. Without this excess of oxidants indicating oxidative stress, the cell wouldn’t know to reach out for restorative help. Too many oxidants leads to a proliferation of damaged cells. But too few oxidants impairs the cell’s ability to signal an immune response and to repair damage. Therefore, balance – homeostasis – is key.

    However, chronic oxidative stress leads to a
    proliferation of free radicals that unless neutralized, lead to cell
    damage that will continue to worsen – damaging the cell walls,
    vessel walls, proteins, fats and even the DNA nucleus of our cells
    until the cell can no longer properly function. The result advances
    the aging of tissues, leading to poor health and the potentiality for
    degenerative disease.

    It is for this reason that we are constantly inundated with the
    health benefits of anti-oxidants. The idea is that these molecules
    combat the proliferation of free radicals in an effort to bring the
    cell back to healthy homeostasis. But herein lies the rub. First,
    most antioxidant supplements are molecules far too large to pass
    through the cell wall, averaging about 200 atoms in diameter.

    Therefore, most (some scientists estimate about 90%) are denied entry to the place where they are needed most – inside the cell where the free radicals are found. Second, one anti-oxidant molecule is empowered to combat one free radical molecule before becoming essentially inert. It is thus a 1:1 ratio. However, the body generally harbors about 100 sextillion free radicals a day. That’s a heck of a lot! Due to this restrictive 1:1 ratio, scientific studies show that your body can’t possibly ingest enough antioxidants to eliminate the number of free radicals your body makes every day. For example, you would have to eat 32 pounds of strawberries, 31 pounds of raspberries, AND 15 pounds of dark chocolate per day to achieve the antioxidant power that it would take to eliminate the free radicals that are created naturally in the body.
    ASEA

    This is where ASEA comes in – as the first and only RSM
    supplement. As stated above, stable RSMs are central to the body’s healing mechanisms, mediating multiple cellular defense, repair & replacement signaling pathways. ASEA purports to have determined a completely stable, balanced, bio-available and entirely non-toxic formula of RSMs native to the body that can effectively penetrate the cell wall (unlike most anti-oxidant supplements), efficiently combat free radicals, stimulate the body’s production of its own anti-oxidant defenses, and stabilize the proper homeostasis of oxidants to reductants to optimize cellular communication, repair, and replacement, thus enhancing the body’s ability to properly function, recover, and simply work as designed.

    Moreover, independent studies show that ASEA when in contact with living cells increased the efficiency of some of our body’s most important native antioxidants inside living cells – such as
    glutathione peroxidase and superoxide dismutase (SOD) — more than 500%. In other words, ASEA is purported to significantly stimulate the cell’s own production of the master antioxidants inside the cells without causing an inflammatory immune system response.

    What does this mean?

    It means that the body becomes empowered to
    neutralize approximately 70,000,000 free radicals per second — the rate at which native Glutathione Peroxidase is able to process
    oxidative free radicals. Quite an improvement over the results that can be achieved by a diet rich in anti-oxidants.

    “Asea merely enhances the body’s innate ability to repair itself”

  48. Harriet Hall says:

    @asolis,

    You posted this on the wrong thread. The article on ASEA is elsewhere. You have recapped the company’s rationale for their product, but you have not presented any evidence that ASEA is more than salt and water or that it provides actual clinical benefits to people using it.

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