Gnolls.org Opens The Door To Obesity Fight

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READERS SUMMARY:

1. WHY IS MAGNESIUM SO IMPORTANT? DID THE OBESITY BATTLE OF THE BLOGS MISS IT?
2. HOW SHOULD YOU THINK ABOUT MAGNESIUM AND HOW TO TEST IT CORRECTLY?
3. WHAT DOES MAGNESIUM REALLY DO?
4. THE MISSING LINK IN TAUBES, GUYENET, LUSTIG, AND EENFELDT’S RECENT COMMENTS?
5. ITS THE BRAIN GUYS……WHEN THE SQUABBLE ENDS WE WILL ALL BE SITTING AT THE HYPOCRETIN NEURONS!

Magnesium (Mg) is an ion that is often spoken about in the blogosphere but its importance has been under-emphasized. After speaking to Gnolls.org blogger/author/hairstylist J. Stanton ………about this issue at the AHS I decided to publish this blog a bit earlier on Magnesium to help clear the air on this cation. I also think it may help bring some clarity to the new paleo “squabble” that has begun with Taubes, Guyenet, Lustig, and Eenfeldt. And I do love this type of passion. It helps solves scientific problems. Failure of the hypothesis should make us all seek the answers. We have heard many podcasts from the paleo community leaders espousing the use of this supplement for muscle aches, constipation, and improving sleep and metabolism. But what we have not heard is why this is important and how should we attack the low magnesium clinically.

Magnesium comes in many forms medically and each formulation has specific benefits based upon its specific chemical structure which confers its ideal biologic availability. Medically-prescribed magnesium supplements such as Slo-Mag and Mag-SR contain magnesium chloride which is slowly released from its chemical matrix. However, since magnesium is absorbed best by the body in ionic form such supplements have no advantage over any soluble magnesium salt (for example, magnesium citrate or magnesium aspartate).  Magnesium threonate is the one version I use clinically in most neurologic applications.

Magnesium citrate works by attracting water through the tissues by a process known as osmosis. Once in the intestine, it can attract enough water into the intestine to induce defecation. This is why Mg citrate is best for constipation. Magnesium aspartate is a salt of magnesium that works to replete Mg but requires a higher dose than other formulations. If one is trying to restore initial sleep disturbances this is a good option. It does not work as well as magnesium malate for these indications. Mg malate is better absorbed from the gut and reaches higher blood levels than most other supplements. This is especially true when you use it in combination with a Mg oil or gel formulation. Supplementation generally takes 30-90 days to replete a minor to moderate deficiency. In diabetes the patients need a much higher daily dose until their diabetes can be reversed. I like to use Mg malate in severe muscle cramping, in diabetics with severe sleep apnea and in patients with severe PAD, CAD or restless leg syndrome. Mg glycinate is helpful if one has a leaky gut or autoimmune disease like type 1.5 diabetes. Epson salts (Mg sulfate) can be used topically or orally but when they are used orally one must be careful because of the dose of Mg one gets from this salt. I teaspoon has 100 times the RDA of Mg at 3.5 grams. Magnesium sulfate contains only 10 percent magnesium available for absorption. (MgCl) magnesium chloride has approximately 12 percent magnesium available for absorption and is useful in mild Mg deficiency cases. Most doctors check ionic Mg blood levels which are not all that accurate and gives many docs a false sense of security. I find this is the most inaccurate test in my own lab. You need better testing and equipment to diagnose Mg deficiency. I good history and physical is best both those seem to be relics of the past these days. Serum Mg levels are 90% false positives in my own practice. That is a function of how bad our clinical testing is. I prefer the EXATest which measures direct Mg bioavailability on red cells in cases with high risk patients with neuropathy, osteoporosis, migraine, and high cortisol levels. We can also use a direct Mg challenge test but it is not often done because it is a pain in the ass to perform and most hospitals are not set up to do it. I asked for it last week and got the most empty look you could imagine. It requires two separate 24 hour urine collections and two IV infusions of Mg salt. In fact in medical school we learned about Chvostek’s and Trousseau’s sign for calcium deficiency but they actually also tell us more about Mg deficiency. I use these tests in osteoporosis and migraine patients daily. I see these more commonly in diabetics today than any other sign. I wonder why you might be asking Dr. Kruse? Its coming trust me.

What exactly does Magnesium do to keep us optimal, Doc?

Magnesium is vital to human biochemistry. All life is tied to the production of ATP because ATP = energy. As I laid out in my mitochondrial series, foods provide electrons to our mitochondria to make energy in the form of ATP. ATP (adenosine triphosphate), the main source of energy in cells, and must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP molecule. That is just how important Mg is. Without it we call the human a cadaver! Mg is also vital for chemical stabilization of our DNA and RNA. Nucleic acids have an important range of interactions with Mg2+. The binding of Mg2+ to DNA and RNA stabilizes its structure. Additionally, ribosomes contain large amounts of Mg2+ and the stabilization provided is essential to the complexation of this ribo-protein. A large number of enzymes involved in the biochemistry of nucleic acids bind Mg2+ for activity, using the ion for both activation and catalysis. Finally, the autocatalysis of many ribozymes (enzymes containing only RNA) is also Mg2+ dependent. Most of the biologic enzymes that catalyze the stress response in humans are also catalyzed using Magnesium. This is true as well in the sleep hormone cascade of optimal sleep.
Both Mg2+ and Ca2+ regularly stabilize membranes by the cross-linking of carboxylated and phosphorylated head groups of lipids. This allows for cohesive architecture of cells but also allows for optimal cellular communication. When Mg levels are low it can cause bad signaling between cells and allow the cellular terroir to be more prone to cancer. After all, cancer is a disease of genetic chaos and bad signaling. To make this clear…..Mg is the major co factor in most key critical enzymatic steps activating proteins in our cells. The transport of Mg2+ between intracellular compartments may be a major part of regulating enzyme activity. The interaction of Mg2+ with proteins must also be considered for the transport of the ion across biological membranes as well. So if magnesium concentration or transport are altered you can bet your ass bad things are going to follow.

Speaking of bad things lets talk about the disease where intracellular magnesium is totally disordered. Let’s talk diabetes. High levels of insulin make cells store excess Mg, but if you become insulin resistant you can no longer store Mg and begin to lose it at high concentrations in your urine. So all diabetics are seriously deficient in Mg. This is why they all have neolithic diseases. It directly affects their energy production, their DNA and RNA is more susceptible to cancer, and they develop sleep apnea quickly because they ruin the coupling of energy and sleep metabolism signaling of their hormone cascade.

Doc, where do you weigh in on the Guyenet, Lustig, Taubes and now Eenfeldt arguments on obesity?

Muscle become affected because Mg helps relax muscles and blood vessels. If you’re deficient you have more muscle cramps and higher rates of peripheral artery disease (PAD). Can you say hello to fibromyalgia, restless leg syndrome and arterial disease all seen in T2DM? Connecting the dots yet? Moreover, when your intracellular Mg level drops your vessels tighten and your BP goes up too. And to make matters worse for T2 DM patients Mg is also a co factor the action of insulin production and manufacture and release! I have seen in the recent blog comments of Stephan Guyenet, Kurt Harris and Andreas Eenfledt and many people comment we don’t know what initially causes insulin resistance. I completely disagree with that statement. My answer is Oh…..yes we do! Its low intracellular magnesium levels that causes the genesis of insulin resistance peripherally. And we have known it for a long time but have done little in clinical medicine to treat it. This is why so few people know about it. Peripheral leptin and insulin resistance (at muscles and fat cells) occurs first for this to happen but the depletion of Magnesium always predates insulin resistance. So when blood insulin rises, you lose intracellular Mg and this feedback loop makes the peripheral cells even more insulin resistant because we can’t make insulin or let it act properly on target cells. Simultaneously, arteries constrict decreasing blood flow and glucose and insulin to the target tissues. This worsens the magnesium deficits going forward. This feedback loop continues daily in all diabetics until the brain becomes leptin resistant at the hypocretin neurons. Once this occurs, epigenetic switches are thrown in the hypocretin neurons for leptin and insulin signaling at the brain level…again this occurs because of the poor magnesium concentration at these cells and our DNA/RNA then become “hard wired” for a diabetic metabolism at the brain level. This allows for the human brain to become exquisitely sensitive to the dopamine reward of foods. The reward of foods are important when the brain is already LR because this is an outflow only tract of the hypocretin neurons in the hypothalamus. This is why I have said many times I don’t agree that SG position of reward being the dominant cause of obesity is correct. Do I think he has more correct than the rest of the crew? Yes, I do. The real issue is what is happening to the main nucleus in the brain that controls all energy balance as insulin wrecks the periphery and the liver. That nucleus is the hypocretin neurons. That is where I separate myself from SG views. Obesity is a brain disorder. It also fully explains why no macronutrient is the major cause of obesity. And it ironically, shows why carbs appear to be the major macronutient that causes obesity. Its because of insulin’s affect on Magnesium directly. I fully understand why we have the Kitavins and the Taubian view of obesity. It’s called an incomplete our of context story that can be fully understood by biochemistry.

Doc, how do you explain the central affects of leptin and insulin and the contrary data on their signaling?

If this disease process goes on long enough we will eventually see hypocretin neuron death and the numbers of these neurons then become less. Humans only have 50,000 hypocretin neurons and they cannot be restored as we can other neurons. This makes the brain blind to leptin on a more permanent basis when their numbers are decreased permanently. We learned this from the Amgen trials on synthetic leptin…… the morbidly obese became dependent upon the synthetic leptin because their signaling at the blood brain barrier was destroyed. So the receptor had to be flooded with leptin to get the hypocretin neurons to react to it. This is precisely what goes on when someone is really fat and making a ton of leptin. To be clear from the trial data, not everyone gets to this point. When a patient gets to this point they will not be able to control their weight unless they severely carb restrict and monitor their calories diligently. The reason? The master control nucleus…the hypocretin neurons absolute numbers were lowered. This is an event that changes how calories will be partitioned by hormones. Increasing the synthetic leptin is the only way to turn these cells off at this point. Leptin, is not as Dr. Lustig says, just a starvation hormone. LR is clinically evident in the morbidly obese and anorexic by both patients having high reverse T3 levels. A high reverse T3 is a biochemical marker for leptin resistance. I have several blog posts dedicated to this on my site. These two types of patients have completely opposite phenotypes, but have the same biochemical problem. So Dr. Lustig’s theory is only partially correct in my view. He must consider this biologic fact and when he does he will get to the seat of the problem. The hypocretin neurons! And yes, when that gets published in the Journal of Pediatrics next week, we will see if they take my question on it. Anorexics and some of the morbidly obese, “french fried” their hypocretin neurons by different paths but they both destroyed how the brain senses energy balance. The problem is a leptin problem now and not an insulin one. Insulin is an anabolic only hormone with local affects. When it is injected into CSF it actually causes weight loss. When you understand this post you will understand fully why Taubes and Eenfledt beliefs are also only partially correct too. It does begins as an insulin problem peripherally in the liver and muscles, and the major initial player is the intracellular loss of Magnesium. I think these guys really need to rethink their positions. This is precisely why a T1DM patient long term, looks exactly like an anorexia nervosa patient. They can’t keep any weight on at all because they have damaged their hypothalamus. To a degree they are all correct in part…but they are missing the forest view because they have allowed their biases to fog their excellent minds. Obesity is an inflammatory brain disease that has numerous causes. But how carbs start the process is known…it just does not appear to be well known, based upon their own comments lately in the blogosphere. Insulin is merely the initial trigger that starts the cascade in on pathway to obesity and loss of hypocretin neurons can be the last step in all pathways. There are other ways to obesity and LR too…see the omega six pathway with a heavy preponderance of trans- omega six fats. Obesity is a disease with an allostatic load. It depends upon stimulus and intensity and duration of the inflammatory cytokines affect at the brain level. If it is large and sustain and colored by an emotional stressor the obesity is more likely to damage the hypothalamus. If it is due to heavy fructose and PUFA intake it is likely reversible with a leptin reset protocol. Each one of these paths turns on different epigenetic switches and alters our genes. The result is measured in our hormonal response to foods. This is why so many people react differently to dietary macronutrients. The obesity epidemic spans the spectrum in between these two opposite positions and is why we see so many incongruent details that confuse the players. That is my view.

And J. Stanton…thanks for asking for the Magnesium blog at AHS…the subsequent “SG vs GT squabble” got me motivated to post it. Go check out Gnolls.org. It rocks! And I think you need to go read the comments in SG latest blog. Passion mixed with emotion. Scientific gravity will bring it all back to the brain, the ultimate judge.

CITES:
1. The Miracle of Magnesium by Carol Deans
2. http://bcs.whfreeman.com/lehninger/default.asp?s=&n=&i=&v=&o=&ns=0&t=&uid=0&rau=0

Comments

  1. Dr. Kruse:

    I'm honored by the plug, and thankful for all the great information on Mg! (As well as the rest, which will take some time for me to digest.)

    Come see me at http://www.gnoll.org!!!!

    It was a pleasure to meet you at AHS, and I'm presently leaning things by burrowing through your archives.

    JS

  2. I have tried to supplement Magnesium with Mag Citrate and ended up constipated. It is possible to OD on Mag Citrate and cause this problem or should I try another method? It would be nice if I could determine my Mg levels and supplement accordingly but as you say there is no real good accessible test. I have substantially changed my diet to mostly veggies and grass fed beef so the only supplements I believe I need are D3 and Mg. I have always known Mg was important but this post really puts the mechanisms together for me.

    • If Citrate binds you up try adding magnesium oil with Mg malate. Malate is my workhorse supplement. Glycinate is really good too if you have gut issue. But use the oil with it.

  3. Mind trip! I have read your first cite, great stuff. That's why I always suggest magnesium to people looking to lose weight. A kink in ATP synthesis is kinda like a big deal if you are trying to burn a lot of energy. Apparently some people don't think that mitochondrial dysfunction and deficiencies in the cofactors for metabolic reactions affect the ability to expend energy. Wtf.

  4. Thanks for your nutrition articles. Good stuff. I'm a big fan of Eenfeldt, Lustig, & Taubes' views on causes of obesity. I've had great success changing up my diet this year by eliminating sugar, which in turn eliminated my need to take allopurinol for gout. Down 32# so far, feeling great, and no medications.

  5. Cameron House says:

    Hey I tried Gnolls.com and it is a godaddy hosting page. I did a little more searching and I am pretty sure you menat Gnolls.org

    Thanks

  6. Yep gnolls.org. I'm reading the knoll credo right now.

    Anyway how much mg malted do you have your patients taking?

  7. @stabby the comments at SG page from some of the docs hurt our profession. These guy don't realize the first step in IR is intracellular loss of Mg……then calcium too. Just freaking wow. That is why I had to post this. Dr Eenfeldts comments about not knowing what caused this hurt. And SG did not comment about it either but he gets a pass from me because he is a researcher and not clinician. Not even Kurt mentioned it and he is a sharp cat. But did they both not talk about Mg at some point in the past?

  8. For this who may be unfamiliar with Stephan's excellent Mag post of about 17 months ago…
    http://wholehealthsource.blogspot.com/2010/02/mag

    • @mem I thought he had a post about this a while ago. But I have to say this does not make me feel any better. This makes it even more concerning considering how the comments read.

  9. So being morbidly obese and having severe sleep apnea, magnesium malate is the type that would be most beneficial?

  10. @ Marie……depends upon your current fasting insulin level. If it's real high you need to add Mg oil or gel to the malate because the insulin just makes you urinate it out. This is why giving a diabetic with osteoporosis calcium is a joke

  11. You state that if LR/obesity continues long enough, hypocretin neurons will be permanently destroyed. Ballpark wise, what levels of obesity or how long of a period of being LR are you talking about? Like anyone who has been very obese, or older demographics who have been obese/diabetic for decades?

    • @DH This is a loaded question. To give an honest answer Id need to see and examine you and get labs……but I am going to tell you something to is important. In cases where stress is high….IE cortisol……neurons can be damaged. For example, the driver of Princess diana's car to this day still has no recall of the events of that night because the cortisol release was so high it would not allow the hippocampus (memory part of the brain) make any new memories. This is an extreme example but it happens with PTSD and in anorexia too. We learned in the Amgen trials even in the morbidly obese only ten percent of those patients destroyed their hypocretin neurons. Those are the patients who needed synthetic leptin to keep the weight off. Most obese dont have that. One way to tell is to do the leptin reset and see if your cravings go away and yoru sleep improves. If those things happen your hypocretin neurons are likely still OK as are your leptin receptors. You can follow the thread over at Marks Daily Apple on my protocol under his nutrition tab. It has 100K hits and there are many people doing this reset and you can see how it works and how they do.

  12. Last year in August I had a "Magnesium, RBC" test done. It was 5.8 mg/dL, which is within the reference range of 4.2 – 6.8 I also had a reverse T3 done at that time and got 252 pg/mL, which is within the reference range of 90 – 350. In April of 2010, my c- reactive protein was 0.18.

    Everything is looking good, right?? I have lots of bone loss in my jaw and my gums have receded a lot- that was even pre-paleo, but it has not seemed to improve post-paleo. I don't have tooth loss yet, but I had to have a graft done as a "plug" since I was having the most recession on my front/bottom teeth.

    I know you were also a dentist. Any insights of gum recession/bone loss? Can I be satisfied my calcium intake in adequate if i am within the serum calcium reference range on a blood panel? I hardly take in any dairy, but was supplementing pretty regularly with viactiv calcium chews.

    PS i just bought a jar of virgin coconut oil. the girl at the register kept flipping the jar around to figure out what it was 🙂

  13. PS I got that magnesium number just by eating paleo foods, not by supplementing. and i don't buy grass-fed cuz it's too expensive for me.

  14. Pat Palmese says:

    Since I started taking the magnesium supplement in March I no longer have restless leg syndrome and my sleep is very restfull. Great article Jack!

  15. Magnesium (both as dietary magnesium deficiency and related hypomagnesiumia) indeed seems very promising for taking at least a part of the causation story one step back from IR. Just looking around the lit, there are many recent quality studies like this one:

    "Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects – a double-blind, placebo-controlled, randomized trial"
    http://www.ncbi.nlm.nih.gov/pubmed/21205110

    Why haven't we heard more about this?

  16. Fat Nurse says:

    HCG Diet, safe? or Dangerous? What is your advise on this

  17. It really surprises me how many people can't actually connect the dots…The brain is the organ that controls the actions of the organism — it also controls sleep, energy balance, etc. It surprises me how people focus on insulin and not on the interactions of leptin with the hypocretin neurons; at least Stephan Guyenet focuses on the food reward going on in the BRAIN!

    BTW, doc, can you start writing some blog posts about mental disorders? It'd be very interesting to see your take on the subject of mental disorders from a biochemical perspective!

    Also, why don't you devote any of your levees to organs such as the thymus, kidneys, and spleen? I know research about improving thymus function, for example, is hard to come by, but I really wish you could make some blog posts about these topics!

    Thanks for a very informative site 🙂

  18. Adriana G says:

    Dr. Eades has been a major promoter of magnesium:

    "In fact, there exists an entire school of thought that posits that the entire Metabolic Syndrome is nothing but a manifestation of a a magnesium deficiency. Which isn't as crazy as it sounds since virtually all the components of the Metabolic Syndrome – diabetes, high blood pressure, obesity and lipid disorders – are associated with low magnesium."
    http://www.proteinpower.com/drmike/uncategorized/

  19. Terry McGinnis says:

    I was wondering, given how highly you stress the importance of Mg, do you believe supplementation is beneficial or even necessary for someone who was never obese or anorexic and maintains a diet of whole foods with roughly a 10:50:40% ratio of carbohydrate, protein and fat respectively?

    If you consider the above a loaded question, then please tell me what your stance on the RDA values for Mg is?

    • @ Terry Since we have 40-60 million T2 DM……the answer to the RDA should be simple on a population basis. Of course its too low. And RDA is based on those type of parameters. Do I think everyone needs it? Nope. But to make sure go get an EXATEST and you'll know. The easiest way to avoid it is to assess sleep and fasting BG or one hour post prandial glucoses with 15 min splits…….Then you can extrapolate.

  20. Jack, are you in the camp that believes insulin resistance causes obesity? Thanks.

    • @ Carb Sane It's a path to obesity. I think the bigger path to obesity is excessive omega 6 contents on the diet as measured by O6/O3 ratios. This is the number one thing I see clinically. In children it's the perfect storm……it's the fructose and PUFA content together and this is why the NHANES data the Lustig et al have found to be so dramatic. Some of my patients hormonal response to carbs clearly shows that their epigenetic switches have made carbs a dirty word for them……but I have found they are easier to treat. Proof of that……go check out the thread on MDA under his nutriton tab called the leptin reset and see what has happened there for people just following my Leptin Rx. It works. It was never about macronutrients……its about epigenetics.

  21. GAWD I love your brain, I want to marry it and have it's babies. Oh, sorry for putting that on a public forum but your biochemical kung-fu is the best! Guess I'll just settle for reading your posts, and reading yours obviates having to read SG & some of the others, great time saver!

    Avoid mag oxide because absorption is minimal to nonexistent.

    Blood testing for MG levels is not so much bad as much as it is the wrong test and is not indicative. From Wikipedia: "The body contains 21-28 grams of magnesium (0.864-1.152 mol). Of this, 53% is located in bone, 19% in non-muscular tissue, and 1% in extracellular fluid. For this reason, blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium."

    "The result is measured in our hormonal response to foods" but the hormonal response to foods depends on the foods themselves since, again, trans fat intake and avoidance of good fats dictate. Patricia Kane PhD., Lorenzo's Oil article: "The ingestion of trans fats literally blocks fatty acid metabolism, hormonal production and the fatty acid metabolism. The synthesis of prostaglandins-local hormones that control ALL cell to cell interactions within the body-are *completely* dependent upon the ingestion of high quality, unaltered fatty acids. The body requires specific fatty acids to create gastrointestinal integrity, bilipid membranes, hormones, neurohormones, prostaglandins and immune modulators all derived from fatty acids and these fats must be supplied and trans fats avoided if modulation of the faulty metabolism is to be achieved." (Emphasis added by me.)

    For my money trans fats are the mother of all metabolic disregulations and mineral deficiencies only a secondary problem. Take trans fats out of the diet "picture" and a whole foods diet including good fats will normalize & even optimize most peoples systems, vitamin & mineral balances with little extra supplementation needed.

    • @ cancer classes Many other bloggers out there approach this from a bottom up research approach. I am a clinician and have a ton of experience fixing people live in vivo. My approach was honed by emperic evidence, sound clinic judgement and marrying it with the best academic and clinic data. This is why medicine is an art and not a strict science and it is what separates me from a SG or a Chris Masterjohn. Their expertise and mine overlap but there is ahuge divergence as well. I use a top down approach that looks at the brain's biochemistry first…….and then I use labs to decipher how the brain is partitioning calories based upon the epigenetic settings for the patients. In my view if you dont understand hormones clinically you dont understand anything period and you are apt to make huge thinking errors and clinical mistakes. This is why I test and test a lot. I do it to myself and my family, Every quarter I want to know what response my brain is giving me and I tweek things. When I first started this out as an obese surgeon I deduced from my labs that Omega 6 fats, fructose, grains were my major problem. Now years later I know that I can eat carbs to a great degree without any problems because I have clearly flipped my own switched over the years due to dietary modifications. I did not fry my own hypocretin neurons. The one thing I have noticed is that most obese people are very sensitive to the omega 6 content of their diet……the O6/O3 ratio with a HS CRP is a great tell of health in my clinical estimation. Most fit people woudl be sick if they drew their O6/O3 ratio as I do. Their dietary advice would certainly adapt. You only get that level of knowledge from feedback testing.

  22. Magnesium probably competes for absorption with calcium. That may be an issue for some trying a larger dose. For maintenance of CA/MG that is probably less of a problem. Some of the CA/MG tabs are a good choice for long term. But for someone with true MG deficiency that could be a long haul to "tank up".

    Mg/6:3 omega ratio treatment/Vit D is foundational and gets lost in all the excitement of competing hypotheses of late. MG is the one that probably has to be done by supplement. (Although practically balancing 6:3 will need supplementation at first).

    For memory, the only pill Kurt Harris takes daily is Mg.

  23. Adriana G says:

    Here is an excellent discussion of the bioavailability of magnesium, in particular magnesium glycinate. I will definitely be switching from mg citrate and looking for the Albion chelated ones:

    http://www.afibbers.org/resources/magnesiumabsorp

  24. I've had very good experience with Jigsaw Health (malate) and Solgar (glycinate) with Albion chelated magnesium.

  25. @ Fat Nurse…..very loaded question. I wrote about this on PaleoHacks.com You can search it over there. I am not a fan of the homeopathic dosing of HCG…..but the IV dosing is a way to get thru a leptin reset quick. But within 6-8 weeks you must transition to a paleolithic diet as outlined in the Paleo 1.0 books. My name over at PH is "The Quilt" for searching purposes.

  26. @Daule That is why I came up the idea of the QUILT. I think it may help patients and doctors start to realize how this is all tied together. Every time I post we add to the that framework. I hope people go back to The Quilt often. I think its a great place to start to understand this process.

  27. PigeonOrStatue says:

    Maths question:

    Mg sulfate (Epson salts) … 1 teaspoon has 100 times the RDA of Mg at 3.5 grams. It contains only 10 percent magnesium available for absorption.

    Mg RDI is 400mg so at 10% absorption you would need to take 4g. So how can 3.5g by 100x requirement?

    • The recommmendation changed since Dr Deans book was written……that is all. The experts realized they still had their heads in the sand. Its still too low if you ask me.

  28. PigeonOrStatue says:

    Just went to the bathroom and got my Epson Salts, then to the kitchen for a 5ml spoon, poured the salts, leveled off and weighed the resultant quantity of salts: 4.243g.

  29. PigeonOrStatue says:

    Have now read your post three times. Fantastic. I don't know enough to comment on it's validity but it certainly sounds plausible to me.

    Sorry to be such a pedant, but, I read "I teaspoon has 100 times the RDA of Mg at 3.5 grams." and thought that the RDA would be 0.035g and so a small box of Epson Salts would last me a lifetime. Why pay for expensive Mg supplements?

    @cancerclasses I thought Mg oxide was a laxative.

  30. Question: With all the coffee and cocoa consumption, why is there a magnesium deficiency? Is this form of magnesium poorly absorbed?

    P.S. I started the "Dr. Robert Lustig Fan Club" group on Facebook after hearing Sugar: the bitter truth. Just quoted you on Dr. Lustig at AHS

    • @Deb Simple…..if your eating sugars with those things its spikes your insulin and you urinate the Mg and Ca…….and lose it. You never absorb it.

  31. @PigeonOrStatue I've never had any health problem other than being a little fluffy around the edges caused by sitting in front of my computer 24/7 reading health & nutrition blogs for the last 2 years while on unemployment, so all I know about mag oxide is what I've seen & read on the web.

    From Wikipedia search of 'Magnesium': "Numerous magnesium dietary supplements are available. Magnesium oxide, one of the most common because it has high magnesium content per weight, has been reported to be the least bioavailable. Magnesium citrate has been reported more bioavailable than oxide or amino-acid chelate (glycinate) forms." Other sites say mg oxide is used in common off the shelf supplements because it's cheap.

    A year or so ago I stumbled across a short article by Anthony Colpo titled The Most Important Supplement You Will Ever Take, where he also says to avoid the oxide form because of it's poor absorbtion. Then after reading about electrolytes and the biochemistry of muscle cramps & cardiac health over at Ed & Patricia Kane's bodybio website I started supplementing with a half ounce of Aaron Brands liquid mag citrate (with Pleasing Lemony Flavor!) that I get at the 99 cent store. It's sold as a laxative, but for that you have to drink 1/2 or the entire 10 ounce bottle either in divided doses or all at once along with at least 8 ounces of water.

    Since I'm not plugged up or have any bowel problems either I just put around a half ounce or less of the mag citrate in the bottle I use to mix up my first thing in the AM Emergen-C vitamin drink pack, which already has 60 mg of mag hydroxide & carbonate. The Aaron mag cit has 1745 mg of mag per ounce, so I only take it every other day or so. Seems ok, but then not having any health problems it's hard for me to notice any difference, but I do seem to be dropping body fat fairly fast, but that may also be from not eating so I stay in ketosis & maximize the fat burning. I was close to 240lbs in January this year, but at 205 lbs this AM with little to no exercise I'm real close to getting under 200lbs for the first time in over 10 years.

  32. PigeonOrStatue says:

    @cancerclass Thanks for the Anthony Colpo article "The Most Important Supplement You Will Ever Take".

  33. @PigeonOrStatue No problem. If that's the only thing I do for you in this life I'm a sorry son of a biscuit eater.

  34. Adriana G says:

    I have been testing my Fasting Blood Glucse over the past two weeks and it has been consistently running between 104 to 106. You made it clear this should be below 89 and my GP considers this a sign of pre diabetes. Over the 2 weeks I have been experimenting with different things to see if I could drop the FBG: zero carbs all day, carbs below 30, Exercise after dinner, protein snack, carb snack – nada, zip, FBG >89 day after day.

    Then I read your magnesium blog. I was aware of the importance of mg because I strted my journey in the Eades camp, so I have been supplementing with 400 mg magnesium citrate inconsistently, using it primarily for sleep, with so-so results. Ditto Natural Calm.

    The last two nights, before bedtime, I have taken 400 mg. Magnesium citrate capsules washed down with a half dose (1 rounded tsp.) of Natural Calm diluted in 6 oz water, which adds another 175 mg citrate for a total of 575, much higher than the recommended doses. I have seen an immediate and amazing improvement on FBG:

    Day 1 – 92

    Day 2 – 84

    This is an N=1 experiment over just 2 nights, but I'm pretty confident mg in the right dose is driving the numbers down as this s the only significant change I have made. I will continue to test to see if it the dose , the source or the combination. I'll be testing my husband as well, since his FBG has been running 106-110.

    Stay tuned! Dr. K would it make sense to get an Exatest? Once you get mg levels up will they stay up with a paleo diet or will ongoing supplementation be required?

  35. It would but since you responded that fast I would dose escalate to 1000 to 1200 mgs a day for two weeks and see what happens

  36. Adriana G says:

    1000 to 1200 at bedtime or can I add the additional 400-500 mg throughout the day?

    I know lots of people can't handle 400 mg without getting the runs, so far so good for me on bumping to 600.

  37. majkinetor says:

    Hello Jack and thanks for great info.

    I hope you don't mind few questions.

    – What do you think about hair test for magnesium and X/MG ratios.

    – What is your opinion on supplementing Mg via carbonated water, for instance the one like this: http://goo.gl/k5GIW
    It contains over 1g/L Mg++. Is this better or worse then chelated forms. I drink water containing Mg++ entire day, does this frequency makes things different then single a day pill.

    – How do I recognize difference between Mg deficiency cramps and Ca deficiency cramps, since extra Mg might lead to lower Ca levels.

    Thx in advance

    • @maj….1. It is not as accurate as the Exatest.

      2. Not a fan of it at all

      3. Without testing youre flying blind.

  38. For J. Stanton: you'll want to fix the link in your comment above. Comment #6. It points to gnoll.org rather than gnolls.org. Gnoll.org is unrelated. It's some kind of open source SDK.

  39. Thanks for the clarification Jack. I'll check out that thread.

  40. @majkinetor Cramps are caused by potassium deficiency, not just mg deficiency, you need both. Calcium is the signaling molecule for sodium that causes muscle to contract, mg signals potassium to enter the cells and causes muscles to extend & release the contraction.

  41. Adriana G says:

    Update – day 3 of super sizing Mg supplements before bed was out of line with previous 2 nights with FBG jumping to 113, the highest of the past 2 weeks. Go figure!

  42. Dr. Kruse,

    You said "In children its the perfect storm……its the fructose and PUFA content together and this is why the NHANES data the Lustig et al have found to be so dramatic." If your child if at 150 carbs/day or under and on a paleolithic diet, should fruit be limited to a number of carbs/day or should it be eliminated to avoid problemss?

    Thanks.

    • Depends upon other variables. Everything must be done in context. Carbs are not everyone's enemy. Carbs and PUFA to excess however are very problematic for anyone who is HUMAN.

  43. Jack, can you provide the support for this statement:

    depletion of Magnesium always predates insulin resistance

    Thanks.

  44. I am at goal weight and generally eat no more than arouBoth my parents and brother are type 2s and this is why I've lowcarbed for over a decade — paleo lowcarbed for the last few years. I take small amount of thyroid medication (armour and cytomel) and generally eat 30 carbs per day. I've gotten into the bad of eating late suppers — 9:30PM or later — largest meal of the day. My fasting glucose is normally around 85 but lately it's occassionally gone as high as 107 — this happens after very large late evening meal. Can having to digest large meals at night during sleep impact magnesium levels by raising cortisol and insulin?

  45. From your own linked abstract we have: We further suggest that a reduced intracellular magnesium concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension. This seems like a far cry from your definitive statement that (bolded in this post of yours) depletion of Magnesium always predates insulin resistance.

    Would Guyton & Hall's textbook of Medical Physiology qualify as one of those "any biochem or endocrine book that has ever been printed"?

    So I ask again for specific references (full text preferably but I'm usually able to get those from abstracts) to support your assertion. Not that Mg is involved in cellular function. That is a given. But that the deficiency always predates — e.g. in effect causes — insulin resistance.

    • Again I will answer this for you. Any recent textbook used in medical schools will clearly talk about this issue. In fact any endocrinologist who treats diabetes knows this information. It is a clinical axiom that is taught in medicine. Its a cornerstone of diabetic pathophysiology.

  46. Eveyln – these may or may not be bulletproof support you are looking for but it was easily found in google search and looks like there are more articles to be assimilated if need be. Also, I do not believe the phrasing "MG deficiency predates IR" is necessarily tantamount to [i]causing[/i] it, although maybe that is true too.

    http://www.mgwater.com/diabetes.shtml

    http://www.drmortonwalker.com/2011/04/magnesium-d

    MG, IR, and Children http://care.diabetesjournals.org/content/28/5/117

    http://www.ncbi.nlm.nih.gov/pubmed/19629403

    http://www.ncbi.nlm.nih.gov/pubmed/2253826

    There seem to be plenty of related articles.

  47. majkinetor says:

    Doc, how come that loss of hypocretin neurons doesn't always induce anorexia ? If orexins are major food promoters, how loss can induce obesity ?

    Thx.

    • @majkinetor This has to do with the specific hypocretin neurons that are lost….because the brain is different than all other organs. Every neuron is specialized in the hypothalamus. This part of the brain is only the size of a small grape and humans have but 50,000 hypocretin neurons in the entire brain. Each neuron and receptor codes for multiple responses and are also impacted by the surrounding cells synapses and the pre and post synaptic changes. This is why leptin can cause obesity and anorexia. Certain hypocretin neurons get knocked off by apoptosis die to long term inflammation or by dramatic increases in cortisol that induce these changes. Once the cells are lost they can be replaced because whne one is LR you have a pregnenolone steal syndrome and repair of neurons requires BDNF which is stimulated by progesterone. Well, in Pregnenolone steal your progesterone levels are low…….so you can induce stem cells to replace the hypocretin neurons and if you knock out the parts that control certain parts you wind up with a different phenotype. This is how leptin can make you obese or Karen Carpenter thin. You must read my central leptin series that was completed in late August 2011. I think you will find it informative.

  48. Dr. Kruse, have you seen this blog?
    http://carbsanity.blogspot.com/2011/08/why-insuli

    She's trying to help people in their fight for health, too. Uses a lot of scientific info to back up her stuff. This particular blog disses Taubes and his theories.

    • Carb Sane is well known. SGuyenet and Kurt Harris got into it with her over fatty acids and diabetes in the past. After that series of blog comments and seeing her response I decided I would just remain out of it. I dont subscribe to her mechanisms of how diabetes occurs. And I really have nothing more to say on it.

  49. Thanks for commenting. I just saw her today and wasn't really impressed by anything but her "good intentions" … your mind blowing science is much easier to understand than hers. Probably because you do connect thoughts from one "lesson" to the next, and back around to fill the spaces in the Quilt.

    Thanks for what you do.

  50. Grammasmitty says:

    How does all this relate to Type I DM? Whan they do for weight loss?

    • @Grammmasmitty First I would make sure you really are a type one Diabetic. More and more are finding out that they really have type one 1.5 diabetes or what many refer to as the autoimmune type. You can have no insulin at all…..but the cause maybe autoimmune. The diet I would suggest then would be pretty different than for one who was a regular type one DM. Ask your doctor.

  51. Grammasmitty says:

    OK, need a little education here. This is my daughter-in-law. Type 1 for at least 15 years. How do you know if it is autoimmune? What symptoms, what's the difference? What tests? What help to overcome?

  52. From what I understand after finding out about coconut oil as a possible help for dementia, coconut oil helps reverse dementia because it is an excellent source of ketone bodies – brain cells are able to use the ketone whereas they have been having problems utilizing glucose, which is why the brain cells die – Alzheimer's might even be called Type 3 diabetes. So,

    This story is about using insulin so the brain can utilize glucose. If you use coconut oil, you go around the need to use insulin to process the glucose.

    Dr. Mary Newport (a neonatologist in Florida) had been desperately looking for a way to help her husband, Steve, who had the symptoms of early onset Alzheimer's. Dr. Newport found out about medium chain triglycerides and that coconut oil is a good source. She began by stirring two tablespoons of non-hydrogenated coconut oil into her husband's oatmeal and he began to demonstrate improvement within about three hours. An MRI in 2009 indicated that the brain atrophy had been arrested. A scientist at NIH, Dr. Richard Veech, has been researching MCT oil and how it can help the brain and is now working on developing a synthetic form.

    Regarding Steve and Mary Newport, you can go to their website at http://www.coconutketones.blogspot.com for more information.

    Also check out youtube.com for stories of other people who have been taking coconut oil for dementia and brain fog.

    "Ian Blair Hamilton"

    "Bruce Flett" (a minister in Canada who was afflicted with dementia as a result of endocarditis).

    You can find the Spectrum brand of coconut oil at Wal-Mart and other stores (whatever brand you buy, make sure it says non-hydrogenated or "contains no hydrogenated fat").

    Also check out Dr. Jack Kruse's website – he is a neurosurgeon who also talks about the benefits of coconut oil:

    jackkruse.com

    When we heard this morning they were going to talk about a new discovery for Alzheimer's, that could possibly even reverse it, I thought they were going to talk about coconut oil.

  53. My sincere apologies for my post appearing 3 times!

  54. @Jody I agree with you about Guyenet. He wrote some great articles about Magnesium but he seems to have completely forgot about that link. In clinical medicine it's common knowledge that magnesium deficiency leads to sugar craving behavior. Moreover, intracellular magnesium loss also decreases brain dopamine in the reward tracts and makes you gain weight. I am at a loss to explain his theory based upon what he already wrote. I really think this is more about proving Taubes wrong than being right for the lay public in some warped sense.

  55. @Jody I just saw this at Peter's site and posted it here for you to read. "BTW, that bland liquid diet (Renutryl) that Stephan told us causes weight loss despite being full of refined carbs, including sugar, also contains magnesium."

    Its just kinda nuts really

  56. @Carb Sane

    Insulin Resistance Is a Natural Defense Against Energy Excess

    Superoxide sensing and insulin resistance protect cells against too much energy input and oxidative stress, but without the ability to reduce blood sugar, hyperglycemia leads to the suite of degenerative reactions that provide the symptoms of type 2 diabetes.

    reference

    Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, James DE.Insulin resistance is a cellular antioxidant defense mechanism.Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17787-92. Epub 2009 Sep 30.

  57. I have had a problem with leg and foot cramps for years. Some nights I would wake up 3 or 4 times with excruciating cramps. I took magnesium, but it was the oxide or citrate forms, and they didn't help much. After reading this blog, I started taking 600mg of magnesium malate at night. Within 2 weeks, I had no more cramps. Even after an epic mountain hike, where my legs were sore and I was sure I would have cramps that night, I didn't. It's been a miracle for me. Thank you!

    • @ Owl…….your welcome. Loss of Intracellular magnesium is a huge problem for most people who energy efficient. This was one of the first things I learned about in biochemistry and it seems everyone else forgot it.

  58. Jean Sullins says:

    Heya i am for the first time here. I found this board and I find It really useful; it helped me out much. I hope to present something again and help others like you aided me.

  59. Dr.K, Could you recommend a good multivitamin? There is a dizzying number of them on the market.

  60. I work an early morning (3am), very physical job. I have been doing the LR for 10 days. My question is, is the physicalness of my job going to make my body think i am exercising after my BAB? Is treating my lunch as the big ass meal an option?

  61. This may not be the best place to ask this, but, I'm looking for a good fresno dentist and I don't know where to look has anyone heard of this fresno dentist? They're located in Fresno, 20 min from my home I can't find reviews on them — Fresno Dentist, 411 North First Street, Fresno, CA 93701 – (559) 472-9613

  62. @Jane here are the Magnesium links you emailed me about.

    1. http://www.ncbi.nlm.nih.gov/pubmed/8505087
    2. http://www.ncbi.nlm.nih.gov/pubmed/14684759

  63. I am just curious, if one keeps their insulin levels nice and steady (and not too particularly high), does this change the dynamic of magnesium requirement?

    • @Gladina………it depends upon case and what you call low and I call low or nice and steady. Generally I want insulin levels below 3 and I want the person very insulin sensitive so they can maximally use insulin for body comp building when their liver and muscles are in Optimal shape.

  64. Thanks Jack, your dedication and clear science are invaluable. I have been reading about Magnesium L-Threonate – any thoughts on its role please? (from lef.org)

Trackbacks

  1. […] deficiency, Metabolic syndrome, diabetes, obesity prevention. 1. WHY IS MAGNESIUM SO IMPORTANT? DID THE OBESITY BATTLE OF THE BLOGS MISS IT? 2. HOW SHOULD YOU THI… Bear in mind what Jack says "Supplementation generally takes 30-90 days to replete a minor to […]

  2. […] ATP and of Magnesium (Mg) because they are coupled together by our ATPase enzyme as we saw in this post. This is classically seen in diabetes development as we mentioned there. Another interesting thing […]

  3. […] and why evolution seems to have coupled sleep and energy metabolism.  If you remember from the Gnolls post I spoke about how magnesium is a co-factor in ATP production at the mitochondria.  In people who […]

  4. […] the systemic role of trace elements in glucose metabolism (Magnesium and Zinc). Remember, from the Gnolls blog post we spoke about how the loss of intracellular magnesium was the first biochemical step in developing […]

  5. […] This excess glucose production leads to chronic surges in insulin and a simultaneous drop of intracellular magnesium. To understand the role of mangnesium and insulin please read the link once again. Once enough time […]

  6. […] blog readers I talked about the Magnesium link in disease months ago after controversy developed at AHS 2011 here between Taubes and […]

  7. […] injury can be from metabolic damage, trauma, or from dietary toxins. We also showed how devastating magnesium depletion is in the development of insulin resistance and diabetes in this blog. Nutrient depletions can play […]

  8. […] Remember from the mitochondrial series or the Gnoll’s post that Magnesium is a co factor in making every last bit of ATP in the mitochondria. So if you […]

  9. […] chronically.  Acutely,  it changes it at the intestinal brush border.  I mentioned here in this blog that is precisely how diabetes actually  begins.  This lowers the magnesium available to make […]

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