Posted by Larry Hoover on November 23, 2002, at 10:32:46
In reply to Re: In addition to fish oil... » Larry Hoover, posted by Pfinstegg on November 22, 2002, at 18:27:40
> I don't think you need to worry at all about being too technical or overwhelming people; the numerous, rapid and enthusiastic responses to your posts must be occurring because so many of us simply cannot get this kind of information from our physicians- whether psychiatrists, endocrinologists, internists or neurologists- they just don't know very much about human metabolism, or what food and vitamins to take to help our stressed brains function, maybe not normally, but closer to it.
Sadly true, but you're right. Most physicians received one three-hour lecture on nutrition, during their graduate studies to become doctors. Only if they take a more personal interest in the subject can they learn about it. So, it's a crapshoot whether or not your doctor has that initiative.
You might want to read this essay, "The Vitamin Paradigm Wars":
http://www.internetwks.com/pauling/hoffer.html
> Your most recent post gave me some valuable information; I didn't know that folate actually did have a positive influence on neurotransmitters,
More on folate. Our diets and supplements provide us with a non-active form, called a pro-vitamin. There are numerous enzymes which act on the ring structure to activate it. One such product is tetrahydrofolate (THF), but there is more than one structure for THF. Another is tetrahydrobiopterin, which is an essential co-factor (a co-enzyme, which enhances the enzyme activity by hundreds of times) in the conversion of tyrosine to L-DOPA (which then converts to dopamine).
All amino acids which are precursors to neurotransmitters must be decarboxylated. That is, they must have the acid part removed. The enzymes which accomplish this are dependent on the activated form of pyridoxine, called pyridoxal-5-phosphate (P5P).
Some people have antibodies to their own enzymes. This may be a reason why some people do not respond positively to B-vitamins when they are taken in normal physiological doses (e.g. the RDA). If they (B-vitamins) must compete with antibodies for the activation sites on enzymes, this is a concentration-dependent process.
>nor did I know that B12 favored the transformation of homocysteine into methionine, and thus into the SAM-e pathway.
B-12 is literally the source of the methyl group which remethylates the methyl-donor methionine. The form we ingest is always the pro-vitamin, e.g. cyanocobalamin. Your liver needs to remove the CN (cyanide) part, and methylate it. It gives a methyl group back to homocysteine so methionine can lose it later. B-12 is also essential for proper regulation of digestion. The process is complex.
>Another thing new to me: that magnesium has an inhibitory effect on the NMDA/glutamate receptors. That's not a transmitter group which is talked about very much here, but I have read that over-excitation of that pathway is one of the cascade effects of HPA axis dysregulation, so it makes a lot of sense to take a really adequate amount of magnesium.
Here's some more on that:
J Neurochem 1992 Oct;59(4):1211-20
Evidence that the loss of the voltage-dependent Mg2+ block at the N-methyl-D-aspartate receptor underlies receptor activation during inhibition of neuronal metabolism.
Zeevalk GD, Nicklas WJ.
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854.
In this study, the importance of the Mg2+ blockade of the N-methyl-D-aspartate (NMDA) receptor during metabolic stress was examined in embryonic day 13 chick retina. Retina exposed to mild conditions of metabolic stress (i.e., blockade of glycolysis with 1 mM iodoacetate for 30 min) underwent acute histological somal and neuritic swelling and an increase in gamma-aminobutyric acid (GABA) release into the medium. These acute signs of metabolic stress were eliminated by NMDA antagonists present during pharmacological blockade of glycolysis, occurred in the absence of a net increase in extracellular glutamate or aspartate, and were not affected by the presence or absence of Ca2+ in the incubation medium. One possible explanation for the activation of NMDA receptors in the absence of an increase in extracellular ligand is that NMDA sensitivity during metabolic stress may be governed at the receptor level. Depolarization of membrane potential during metabolic stress may result in the loss of the Mg2+ blockade from the NMDA receptor channel, resulting in an increased potency for glutamate. To test this, the dose-response characteristics for NMDA, glutamate, and kainate in the presence or absence of extracellular Mg2+ and the effects of Mg2+ on metabolic inhibition were examined. The potency for NMDA- or glutamate-mediated acute toxicity was enhanced two- to fivefold in the absence of Mg2+. Omission of Mg2+ greatly decreased the minimal concentration of agonist needed to produce acute excitotoxicity; 25 versus 5 microM for NMDA and 300 versus 10 microM for glutamate in 1.2 or zero Mg2+, respectively. Elevating external Mg2+ to 20 mM completely protected against NMDA-mediated acute toxic effects. In contrast, varying external Mg2+ had no effect on kainate-induced toxicity. Acute toxicity caused by inhibition of metabolism was not potentiated in the absence of Mg2+ but was attenuated by elevating extracellular Mg2+. The protective effect of Mg2+ during metabolic inhibition was not additive with NMDA antagonists, suggesting that the action of Mg2+ was at the level of the NMDA receptor. These findings are consistent with the hypothesis that the Mg2+ block is lifted during metabolic inhibition and may be the primary event resulting in NMDA receptor activation.
Neuroreport 1997 Apr 14;8(6):1383-6
Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor antagonist MK801.Dubray C, Alloui A, Bardin L, Rock E, Mazur A, Rayssiguier Y, Eschalier A, Lavarenne J.
Groupe NPPUA, Faculte de Medecine, Clermont-Ferrand, France.
The aim of this study was to determine the changes of the nociceptive thresholds in response to an acute mechanical stimulus (paw pressure) in magnesium (Mg)-deficient rats, and the involvement of the NMDA receptor in these changes. Changes in vocalization thresholds was determined after 7 days of feeding with a Mg-depleted diet. Compared with the control group, Mg-deficient rats showed a significant decrease in the vocalization thresholds (-35.8 +/- 2.5%, p < 0.001) reflecting hyperalgesia. In Mg-deprived rats, three doses (0.06, 0.12 and 0.24 mg/kg s.c.) of dizocilpine (MK801), a non-competitive NMDA receptor antagonist, significantly reversed the hyperalgesia in a dose-dependent manner for at least 48 h. No effect of MK801 was observed in the control group. These data provide evidence that Mg deficiency could constitute a new model of hyperalgesia involving NMDA receptors.
Brain Res 2001 Jan 26;890(1):177-83
Magnesium deprivation decreases cellular reduced glutathione and causes oxidative neuronal death in murine cortical cultures.Regan RF, Guo Y.
Department of Surgery, Division of Emergency Medicine, Thomas Jefferson University, 1020 Sansom Street, 239 Thompson Building, Philadelphia, PA 19107, USA. Raymond.F.Regan@mail.tju.edu
The vulnerability of cultured cortical neurons to oxidative injury is an inverse function of the extracellular Mg2+ concentration. In order to test the hypothesis that depolarization-enhanced release of reduced glutathione (GSH) contributes to this phenomenon, we assessed the effect of Mg2+ deprivation on cellular and medium glutathione levels. Incubation of mixed neuronal and glial cultures in Mg2+-free medium resulted in a decline in cellular total glutathione (GSx) within 8 h, without change in oxidized glutathione (GSSG); no effect was seen in pure glial cultures. This decrease in cellular GSx was associated with a progressive increase in GSx but not GSSG in the culture medium. Cellular GSH loss was not attenuated by concomitant treatment with antioxidants (ascorbate, Trolox, or deferoxamine), but was prevented by the NMDA receptor antagonist MK-801. Mg2+ deprivation for over 24 h produced neuronal but not glial death, with release of about 40% of neuronal lactate dehydrogenase by 48-60 h. Most of this cytotoxicity was prevented by treatment with either antioxidants or MK-801. These results suggest that Mg2+ deprivation causes release of neuronal reduced glutathione via a mechanism involving excessive NMDA receptor activation. If prolonged, cellular GSH depletion ensues, leading to oxidative neuronal death.
>Of course, in checking my (very expensive) multivitamin, I found that it has magnesium OXIDE, and only 250 mg.at that. I intend to try the citrate up to the levels you suggested.
Magnesium oxide dissolves poorly, even in stomach acid. You can't uptake the Mg++ ion if the ion is bound tightly in an insoluble salt.
Magnes Res 2001 Dec;14(4):257-62
Bioavailability of US commercial magnesium preparations.
Firoz M, Graber M.
Department of Veterans Affairs Medical Center, Northport, NY 11768, USA.
Magnesium deficiency is seen with some frequency in the outpatient setting and requires oral repletion or maintenance therapy. The purpose of this study was to measure the bioavailability of four commercially-available preparations of magnesium, and to test the claim that organic salts are more easily absorbed. Bioavailability was measured as the increment of urinary maginesium excretion in normal volunteers given approximately 21 mEq/day of the test preparations. Results indicated relatively poor bioavailability of magnesium oxide (fractional absorption 4 per cent) but significantly higher and equivalent bioavailability of magnesium chloride, magnesium lactate and magnesium aspartate. We conclude that there is relatively poor bioavailability of magnesium oxide, but greater and equivalent bioavailability of magnesium chloride, lactate, and aspartate. Inorganic magnesium salts, depending on the preparation, may have bioavailability equivalent to organic magnesium salts.
J Am Coll Nutr 1990 Feb;9(1):48-55Magnesium bioavailability from magnesium citrate and magnesium oxide.
Lindberg JS, Zobitz MM, Poindexter JR, Pak CY.
Center for Mineral Metabolism and Clinical Research, University of Texas, Southwestern Medical Center, Dallas 75235.
This study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. The solubility of 25 mmol magnesium citrate and magnesium oxide was examined in vitro in solutions containing varying amounts of hydrochloric acid (0-24.2 mEq) in 300 ml distilled water intended to mimic achlorhydric to peak acid secretory states. Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion (24.2 mEq hydrochloric acid/300 ml). Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Reprecipitation of magnesium citrate and magnesium oxide did not occur when the filtrates from the solubility studies were titrated to pH 6 and 7 to stimulate pancreatic bicarbonate secretion. Approximately 65% of magnesium citrate was complexed as soluble magnesium citrate, whereas magnesium complexation was not present in the magnesium oxide system. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load. The increment in urinary magnesium following magnesium citrate load (25 mmol) was significantly higher than that obtained from magnesium oxide load (during 4 hours post-load, 0.22 vs 0.006 mg/mg creatinine, p less than 0.05; during second 2 hours post-load, 0.035 vs 0.008 mg/mg creatinine, p less than 0.05). Thus, magnesium citrate was more soluble and bioavailable than magnesium oxide.
> I hope you will keep posting- and, for sure, thank you!
This is an outlet for me. I enjoy it when people are interested. So, it's a win-win.
>If I keep on enhancing my nutrition the way you are suggesting, perhaps I won't have to keep that December 30th date with the TMS machine at Emory! Just kidding- my HPA axis is so dysregulated that I need all the help I can get! But, that aside, what you have taught me is invaluable. Thank you, Larry.
>
> PfinsteggGlad to help. Just a philosophical note: Nutritional support encourages the body, with all its myriad inter-relationships and feedback controls(of which we have so little real understanding), to work better. Drugs force it to do one, or a few things, differently. There may well be a role for both, in an individual. But the former approach is seldom used, and even more seldom used effectively.
Regards,
Lar
poster:Larry Hoover
thread:128719
URL: http://www.dr-bob.org/babble/20021122/msgs/128912.html