![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 41. This is the beginning of the thread.
Posted by freedom2001 on November 22, 2002, at 1:34:44
Hi,
the reason why I keep posting about fish oil
1. is to educate new depressed users about its healing potential and to try out fish oil 1st before going to SSRI drugs.
2. make existing depressed people make use of fish oil more, perhaps enabling them to lower their medication dosage.
3. people with other disorders may give fish oil supplementation a try and post their results.
4. Appeal to all to have large scale studies of fish oils on OCD. May be
a. fish oil Vs placebo
b. fish oil/SSRI Vs SSRI Vs placebo
Hopefully some professor or doctor will listen to me here.
Posted by BeardedLady on November 22, 2002, at 4:06:36
In reply to FISH OIL, EPA, DHA , posted by freedom2001 on November 22, 2002, at 1:34:44
Hey, keep posting. My mom cut out an article the other day (that syndicated vitamin couple's column, "The People's Pharmacy," that mentioned the fish oil study (EPA, specifically) from the Journal of American Psychiatry (?). She called me and said, "Remember that fish oil you bought? Take it!"
I believe the folks in the study took a gram, and it augmented their ADs (all were on ADs). It was a significant study. And taking a couple mg. of fish oil isn't likely to hurt anyone. Many would argue that it's better to eat fish and get the nutritional benefits, but how much fish can you eat to get that much Omega 3 every day?
Anyway, I haven't slept without a sleeping pill in the middle of the night for several weeks. I took 2,000 mg. of fish oil (half after lunch, half after dinner) and slept about 6 hours. I woke up at 3:30 a.m. too excited to go back to sleep.
Let's hope this is just the boost I need to get me over this insomnia hump.
Thanks for your persistence.
beardy
Posted by NikkiT2 on November 22, 2002, at 7:44:20
In reply to FISH OIL, EPA, DHA , posted by freedom2001 on November 22, 2002, at 1:34:44
I can't seem to eat amything vaguely oily at the moment without retching something terrible... would this effect it do you think??
I recth alot of the time anyway, but oil seems to make it worseAlso, is there a vegetarian option??
I refuse to ever go near an SSRI again in my life, and have taken myself off all my meds (with psychologist approval)...
Nikki
Posted by Larry Hoover on November 22, 2002, at 8:24:37
In reply to Re: FISH OIL, EPA, DHA » freedom2001, posted by NikkiT2 on November 22, 2002, at 7:44:20
> I can't seem to eat amything vaguely oily at the moment without retching something terrible... would this effect it do you think??
> I recth alot of the time anyway, but oil seems to make it worseHi, Nikki. May I ask....do you have an eating disorder, or a digestive disorder? It would help to know a little bit more, if it's not too personal.
> Also, is there a vegetarian option??
There is an algae-based product called Neuromin, but I don't know a whole lot about it, other than it is said to be a good source of DHA.
If you eat eggs, you should definitely try to get free-range eggs, and/or those from chickens fed flax seed as part of their ration. The chicken enzymes do a fair bit of the conversion of alpha-linolenic acid to EPA and DHA for you.
> I refuse to ever go near an SSRI again in my life, and have taken myself off all my meds (with psychologist approval)...
>
> NikkiOne thing about certain nutritional deficiencies is that being deficient in something can make future absorption of that nutrient problematic. For example, being magnesium deficient makes you uptake magnesium poorly, and being deficient in essential fatty acids makes their uptake less efficient. Your body has a lot of "use it or lose it" about it. It's not going to waste precious resources in preparation for taking up a nutrient it doesn't ordinarily get. Sometimes it takes a while for your body to get pumped up again. With your delicate stomach, you may need to go very slowly, gradually raising the dose as your tolerance progresses. Make very sure to get a fish oil with vitamin E added (some form of tocopherol) to protect against rancidity, and take it right after a meal.
Lar
Posted by NikkiT2 on November 22, 2002, at 11:37:19
In reply to Re: FISH OIL, EPA, DHA, posted by Larry Hoover on November 22, 2002, at 8:24:37
Difficult question.. do i have an eating disorder... hmmm... well nothing official as such, but I do ahve a problem with food and am currenlty obese.. but am dieting and have lost about 22 lbs so far (in 2months). I am dieting sensibly though, under doctors watchful eye, but I don't eat eggs on this diet. (but when I do, I use a range of eggs that are epurely fed a vegetarian diet (well, the chickens are!) and contain omega 3's, I know that!!). I eat tofu about 3 times a week, and a little low fat cheese, and lots of veggies and normally 2 peices fo fruit a day.
I have been suffering terrible nausea for 3 months and its gettingw orse.. retching over anything and everything, about 3 times an hour, and normally 4 or 5 retches within an attack, usually on the last retch I burp loudly!! About 1/4 of the time solids come back up. But I've noticed it is at its worst if I have eaten oily / fatty food.
I know its something I must see my doc about... but getting there si really hard for me at the moment!
Ta
nikki x
Posted by Pfinstegg on November 22, 2002, at 14:44:10
In reply to FISH OIL, EPA, DHA , posted by freedom2001 on November 22, 2002, at 1:34:44
For Larry and Freedom - this has been a terrific discussion on fish oil- very much appreciated! An an AD failure/dropout, I am relying on fish oil, but also on all the fat-soluble vitamins in normal amounts, B vitamins in high amounts (100 mcg. B12 and 400-800 mg. folic acid, plus normal amounts of all the others), 100 mg. each of ALA and phosphadadtylserine, a diet which consists almost entirely of cold-water fish, fruits and vegetables, an early-morning ride on a horse and a 45-minute walk with the dog in late afternoon after work. I really think all this has modified the severity of my MDD quite a bit. I am curious as to whether you have come across a role for B vitamins in helping neurotransmitters function more normally. I have a scientific background also, but recognize superior researchers when I come across them! If this is of interest to you, I'd love to hear of anything you come across.
Pfinstegg
Posted by Pfinstegg on November 22, 2002, at 15:55:05
In reply to FISH OIL, EPA, DHA , posted by freedom2001 on November 22, 2002, at 1:34:44
Oops! In all the flood of information about fish oil, I didn't notice at first HOW MUCH you are taking. I'm only taking about a quarter of your dosage, but will go out this evening and buy the stronger form so that I'll also get to 5000 mg. EPA-DPA..all I seem to be doing is saying "thanks", but you know I really mean it!
Pfinstegg
Posted by Larry Hoover on November 22, 2002, at 17:14:36
In reply to In addition to fish oil... , posted by Pfinstegg on November 22, 2002, at 14:44:10
> For Larry and Freedom - this has been a terrific discussion on fish oil- very much appreciated! An an AD failure/dropout, I am relying on fish oil, but also on all the fat-soluble vitamins in normal amounts, B vitamins in high amounts (100 mcg. B12 and 400-800 mg. folic acid, plus normal amounts of all the others), 100 mg. each of ALA and phosphadadtylserine, a diet which consists almost entirely of cold-water fish, fruits and vegetables, an early-morning ride on a horse and a 45-minute walk with the dog in late afternoon after work. I really think all this has modified the severity of my MDD quite a bit. I am curious as to whether you have come across a role for B vitamins in helping neurotransmitters function more normally. I have a scientific background also, but recognize superior researchers when I come across them! If this is of interest to you, I'd love to hear of anything you come across.
>
> PfinsteggThanks for the support. I fear sometimes becoming too technical; I don't want to overwhelm anybody.
About the B-vitamins....here's a pretty good overview of the water-solubles, including the B's, C, and a few extras. You'll note that folate in particular bears on neurotransmitter formation directly, and indirectly via DNA synthesis (gene regulation). B-12 has an indirect role via promotion of SAMe formation(homocysteine/methionine cycle).It also is an essential nutrient to promote proper digestion, through the release of stomach acid. You'll get more out of your protein if your acid works better, because the enzyme pepsin needs acid to activate. Achlorhydria/hypochlorhydria (low or absent stomach acid) causes B-12 deficiency, which in turn causes low stomach acid. B-12 deficiency also promotes GERD (gastro-esophageal reflux disorder), despite low stomach acid. GERD is poorly timed stomach acid, which also benefits from bromelain and betaine supplements.
You need Adobe Acrobat to read this:
http://www.unr.edu/hcs/nutrition/pdf/223-10-o.pdfOne nutrient that you haven't mentioned is magnesium. It has an inhibitory effect at NMDA/glutamate receptors, and thus has an overall modulating or calming effect. It also participates in over 200 enzymatic reactions. Most people are magnesium deficient. Stress cause magnesium loss in urine.
Start out at 200-300 mg/day, to avoid diarrhea. Gradually increase to a target of 600 mg/day, up to 1,000 mg/day. If diarrhea occurs, drop the dose 100 mg, and hold there for a bit. Try and increase dose later. Magnesium oxide is cheap, but is less well absorbed than e.g. magnesium citrate, or chelated magnesium.
Posted by Larry Hoover on November 22, 2002, at 17:24:03
In reply to Re: FISH OIL, EPA, DHA » Larry Hoover, posted by NikkiT2 on November 22, 2002, at 11:37:19
> Difficult question.. do i have an eating disorder... hmmm... well nothing official as such, but I do ahve a problem with food and am currenlty obese.. but am dieting and have lost about 22 lbs so far (in 2months).
My intuition suggested some element of anxiety in what you described.....call it my gut reaction to your gut reaction. Heh, heh.
>I am dieting sensibly though, under doctors watchful eye, but I don't eat eggs on this diet. (but when I do, I use a range of eggs that are epurely fed a vegetarian diet (well, the chickens are!) and contain omega 3's, I know that!!).I wonder why you are exluding eggs....if you like them and can get good quality ones, like you describe.
>I eat tofu about 3 times a week, and a little low fat cheese, and lots of veggies and normally 2 peices fo fruit a day.
What you need to watch is alternating high glycemic and low glycemic foods. High glycemic ones are the ones which quickly convert to sugar (or contain sugar), while low glycemic ones are complex starchy foods. Your body will respond to that with what is called de novo lipogenesis, "new fat synthesis", turning carbs directly into saturated fat for storage.....not what you want. Fat, believe it or not, does not really affect this process.
> I have been suffering terrible nausea for 3 months and its gettingw orse.. retching over anything and everything, about 3 times an hour, and normally 4 or 5 retches within an attack, usually on the last retch I burp loudly!! About 1/4 of the time solids come back up. But I've noticed it is at its worst if I have eaten oily / fatty food.Oily fatty food can stick around in the stomach longer. But the problem sounds more like a motility issue. Have you tried digestive enzymes? They're not very expensive, and they might just smooth things out. You didn't just one day start doing this, did you?
> I know its something I must see my doc about... but getting there si really hard for me at the moment!
>
> Ta
>
> nikki xNo probs. Just don't push yourself too hard, 'kay?
Lar
Posted by Pfinstegg on November 22, 2002, at 18:27:40
In reply to Re: In addition to fish oil... , posted by Larry Hoover on November 22, 2002, at 17:14:36
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.
Your most recent post gave me some valuable information; I didn't know that folate actually did have a positive influence on neurotransmitters, nor did I know that B12 favored the transformation of homocysteine into methionine, and thus into the SAM-e pathway. 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. 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.
I hope you will keep posting- and, for sure, thank you! 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.
Pfinstegg
Posted by NikkiT2 on November 22, 2002, at 20:49:22
In reply to Re: FISH OIL, EPA, DHA, posted by Larry Hoover on November 22, 2002, at 17:24:03
Thanks again!!
OK...
This has been coming on since about feb of this year.. at first it was just when i coughed I would retch and it has slowly built up getting worse and worse...
I don't think its anxiety.. my anxiety is much much better (been doing CBT) and it doesn't feel like th enormal nausea I get from anxiety.Eggs are very high in fat, and I'm doing a low fat diet, so thats why I've cut eggs out at the moment.
Its just getting to worry me.. I even did a pregnancy test (though there was no way I could have been pregnant!!)!!! And its obviously getting me down
Gonna investigate veggie versions of the fish oil over here in the UK next week though :o)
Nikki x
Posted by henryO on November 23, 2002, at 2:02:15
In reply to FISH OIL, EPA, DHA , posted by freedom2001 on November 22, 2002, at 1:34:44
This first link is an exhaustive letter and contains some valuable info:
http://www.bipolarchild.com/newsletters/0501.html
The second link is a bit less concise but intresting:
http://www.positivehealth.com/permit/Articles/Nutrition/sald19.htm
The last link is a commercial site:
This last link is for Omegabrite fish oil capsules, the highest EPA to DHA ratio available in a completely scent free formula. (No fish burps) It promotes a book by Andrew L. Stoll, M.D., Director of the Psycho-pharmacology Research Laboratory at Harvard's McLean Hospital, about the latest fish oil / essential fatty acids research. (conducted by him) I read it. It basicly says that he belives it is the EPA at 1000mgs a day that does the trick. Not cod liver oil, too much vitamin A. He sells the Omega brite. Yes, he admits it looks like a conflict but says he could not get his patients a contaminant free reliable source for EPA so he contracted for one. At least he's open about it.
He says that vegetable sources are not converted internally by the body at sufficent amounts to achive the desired levels. So Flax and Perilla etc. are certainly beneficial to your diet but not sufficent.
Personally, so far, after about a month on fish oil, at doses enough to supply 1gm of EPA per day, I think that I am experiencing positive effects, i.e. elevated mood. But I have not taken it long enough to say with conviction. I'll keep posting about it, but I would have to have at least two years of experience with it to feel that the effect was trustworthy. I am hopeful.
Posted by Larry Hoover on November 23, 2002, at 9:09:27
In reply to Fish oil - EPA / DHA a few good links, posted by henryO on November 23, 2002, at 2:02:15
> Personally, so far, after about a month on fish oil, at doses enough to supply 1gm of EPA per day, I think that I am experiencing positive effects, i.e. elevated mood. But I have not taken it long enough to say with conviction. I'll keep posting about it, but I would have to have at least two years of experience with it to feel that the effect was trustworthy. I am hopeful.
Thank you for the links.
Crude calculations I have made suggest that it can take 3-4 months to resupply your basic stores of the fatty acids in fish oil. And, by inference from knowledge about other nutritional deficiency disorders, it can take 2-3 times longer for the body to get itself 'fine-tuned' and balanced again.
Not only is mood elevation a potential outcome, but also mood stabilization. A smoother existence (I don't know what else to call it).
I hope you look at fish oil supplementation as a life-long commitment, until we smarten up and get omega-3 fats back into the food supply the way they used to be.
I've committed to fish oil for its cardio-pulmonary benefits (proven and without doubt). Mood effects (and others) are merely bonus round rewards.
Lar
Posted by bubblegumchewer on November 23, 2002, at 10:02:22
In reply to Re: In addition to fish oil... » Larry Hoover, posted by Pfinstegg on November 22, 2002, at 18:27:40
I haven't been around in a while but I've never been able to find anyone who know s**t about fish oil, EPA, etc. so I'm excited to see that there are some fish brains around here. Please help me with this. I'm not asking for medical advice; I'll take that up with my doctor and I'll be responsible for myself. But I have two concerns about the supplements I've been taking and they have to do with two areas: anticoagulation and immunosuppression.
First, I'm about to deliver my fourth baby in 7 weeks. I'd like to give my unborn baby and myself the benefits of the fish oil I've been taking (Nordic Naturals, 1000 mg. each capsule, 600 mg. omega-3 fatty acids, 450 mg. EPA, 100 mg. DHA, 4.5 I.U. mixed tocopherols)
I have never been clear about the anticoagulant properties so I've been taking only two capsules per week. I know, pretty puny. I am paranoid about risking a big hemorrhage at the time of delivery. Truthfully I don't even bother asking doctors if it's ok to take these things because they look at me as if they have no idea what I'm talking about. So I'm just wondering if you have opinion/knowledge about how much I have to worry about anticoagulation.
My other question is: Last winter before being pregnant at all I was taking two of these capsules a day plus my kids were taking omegabrite capsules, only one per day. We all suddenly came down with the WORST ear/sinus/throat infection in the history of my family. I mean that we are healthy and have only occasionally needed antibiotics but all THREE of my young sons were instantly put on antibiotics, plus me, mom who hardly gets seriously sick, needed antibiotics also, and I mean two rounds for each of us. It suddenly felt as if someone had kicked me hard in the jaw with a boot and I went to the doctor, and sure enough, my ear was infected. I haven't had an ear infection since I was a kid (according to my mom, I can't remember it.) Could this have had anything to do with immunusuppression and could it have had to do with the fish oil??
Thanks, and sorry if I appear to be an ignoramus. I can't ask doctors these questions because they know so little about fatty acids that it's as if I'm asking them questions in Klingon or something.
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
Posted by Larry Hoover on November 23, 2002, at 11:08:23
In reply to Hey! I sense a EFA guru here! QUESTION....., posted by bubblegumchewer on November 23, 2002, at 10:02:22
If you mean *me*, I'm only too happy to serve as a resource. :-)
> I haven't been around in a while but I've never been able to find anyone who know s**t about fish oil, EPA, etc. so I'm excited to see that there are some fish brains around here.
I'll take that in the manner in which it was intended.
>Please help me with this. I'm not asking for medical advice; I'll take that up with my doctor and I'll be responsible for myself. But I have two concerns about the supplements I've been taking and they have to do with two areas: anticoagulation and immunosuppression.
Okey-dokey.
> First, I'm about to deliver my fourth baby in 7 weeks. I'd like to give my unborn baby and myself the benefits of the fish oil I've been taking (Nordic Naturals, 1000 mg. each capsule, 600 mg. omega-3 fatty acids, 450 mg. EPA, 100 mg. DHA, 4.5 I.U. mixed tocopherols)You already have. Placental circulation is preferentially enriched in long-chain omega-3 fatty acids, by some unrecognized mechanism. During the first two years of a child's life, it has been estimated that they need one kilogram of dietary DHA for full brain development. For some totally incomprehensible reason, baby formula in North America does not require *any* of this nutrient. Take fish oil, and breast feed, or make sure that you use a formula that contains substantial amounts of DHA.
> I have never been clear about the anticoagulant properties so I've been taking only two capsules per week. I know, pretty puny. I am paranoid about risking a big hemorrhage at the time of delivery. Truthfully I don't even bother asking doctors if it's ok to take these things because they look at me as if they have no idea what I'm talking about. So I'm just wondering if you have opinion/knowledge about how much I have to worry about anticoagulation.You have nothing whatsoever to worry about. Eskimos eat 14-20 grams a day, on average, of EPA and DHA combined. And, during pregnancy, it is a cultural practice for women to eat even more. No shit. I've looked at this closely.
The anticoagulant activity is a relative phenomenon. Most people, otherwise considered to be "normal", have hypercoaguability. For some, with diagnosed consequences of such activity, like deep vein thrombosis, doctors prescribe so-called blood-thinners like coumadin. For such people, taking an exogenous anti-coagulant, changing the diet to include fish oils can cause an additive effect that can become life-threatening. Basically, the body wants blood that's less likely to coagulate than most people's already is. Fish oil lets your body have what it wants.
> My other question is: Last winter before being pregnant at all I was taking two of these capsules a day plus my kids were taking omegabrite capsules, only one per day. We all suddenly came down with the WORST ear/sinus/throat infection in the history of my family. I mean that we are healthy and have only occasionally needed antibiotics but all THREE of my young sons were instantly put on antibiotics, plus me, mom who hardly gets seriously sick, needed antibiotics also, and I mean two rounds for each of us. It suddenly felt as if someone had kicked me hard in the jaw with a boot and I went to the doctor, and sure enough, my ear was infected. I haven't had an ear infection since I was a kid (according to my mom, I can't remember it.) Could this have had anything to do with immunusuppression and could it have had to do with the fish oil??No.
This is a case of coincidental correlation. In debate, you would call it the logical fallacy of 'post hoc ergo propter hoc', or 'after this, therefore, because of this'.
You were breathing at the time. Is that suspect? (Just putting another coincidental correlation up for consideration.)
Children are extraordinary disease vectors. Need any more be said?
> Thanks, and sorry if I appear to be an ignoramus. I can't ask doctors these questions because they know so little about fatty acids that it's as if I'm asking them questions in Klingon or something.Now that's funny. <smirk>
You're not an ignoramus. Your doctors are.
Lar
Posted by bubblegumchewer on November 23, 2002, at 11:15:51
In reply to Re: In addition to fish oil..., posted by Larry Hoover on November 23, 2002, at 10:32:46
whoever was intelligently discussing the subject with you. Any insight into my questions about anticoagulation and immunosuppresion?
If you want a bonus question: I had my cholesterol profile done and it appears that despite my slight overweight status and my propensity to eat every unhealthy fat possible, my cholesterol is low (140) and my HDL and LDL are in the ideal ranges. (I'm 37 years old and female.) Meaning the ones that everyone else strives for. This is obviously a genetic trait because my mother has the same profile. We are just not a "heart disease" family.
Does this mean that I may not be a person who is in need of the blood-fat benefits of taking omega-3 fatty acids? Or is that question just way too hard to speculate on?
A bonus-bonus question: I spoke to the resident who was treating me a year and a half ago (he was also a horse's a**) about the correlation between low cholesterol and depression. He pooh-poohed the idea, saying that 140 is not low. From my research it appears that 140 in a non-athletic person with an average American junk-food diet is teetering on abnormally low. Any opinion?
Posted by bubblegumchewer on November 23, 2002, at 11:28:01
In reply to I was directing my above question to Larry and/or , posted by bubblegumchewer on November 23, 2002, at 11:15:51
Thanks, Lar. Of course I posted before seeing your nice, detailed answer. I thought I was pretty sure that the anticoagulation effect was nothing to worry about but I wanted to hear it from someone who seems to know.
Do you happen to know anything about the immunosuppression subject which I touched on? I remember doing research and hearing rumblings of suppression of natural killer cell activity, and of proliferation of colon tumors upon administration of certain PUFAs. Just curious if you know what is up with this subject. Is there a threshhold amount or proportion of blood fats that predisposes one to non-optimal immune status? Thanks in advance for letting me pick your brain.
Posted by Larry Hoover on November 23, 2002, at 12:26:36
In reply to Thanks for the answer; last question, I promise, posted by bubblegumchewer on November 23, 2002, at 11:28:01
> Thanks, Lar. Of course I posted before seeing your nice, detailed answer. I thought I was pretty sure that the anticoagulation effect was nothing to worry about but I wanted to hear it from someone who seems to know.
Emphasis on the "seemed to know". My advice might be worth what you pay for it.
> Do you happen to know anything about the immunosuppression subject which I touched on? I remember doing research and hearing rumblings of suppression of natural killer cell activity, and of proliferation of colon tumors upon administration of certain PUFAs. Just curious if you know what is up with this subject. Is there a threshhold amount or proportion of blood fats that predisposes one to non-optimal immune status? Thanks in advance for letting me pick your brain.
Again, the modulation of immunoreactivity has to be seen in the context of the baseline immunological function. Omega-6 fats increase immunoreactivity, whereas omega-3 fats diminish it, in broad strokes. The increase in autoimmune disease over the last century alone argues for an excessive immunoreactivity in the general population, which correlates nicely with the massive distortion in omega-6:omega-3 intake ratios over that period. Studies showing inhibition of T-cell lymphocyte activity and so on, after administration of fish oil, are probably a good thing. There is no evidence that high omega-3 intake leads to a compromisation of immune function.
Also, the fact that certain cancer lineages employ products of omega-3 fatty acid metabolism ought not to be too surprising. The cancer cells are, after all, human cells to begin with. For a cancer line to flourish, it must first pass through a number of stages of promotion. In the context of overall morbidity, fish consumption reduces cancer risk in the entire digestive tract, not just the colon.
The PUFAs in fish oil can be thought of as being highly reactive because they have multiple reaction sites (each unsaturated position is a reactive site). Oxidation at a reactive site, under enzymatic control, turns the PUFA into a potential signalling compound. The products are highly specific, and chiral (having three-dimensional uniqueness). Formation of signalling compounds through selective oxidation is just one of the ways we know that the PUFAs in fish oil have regulative capacity. The cancer link is because one such compound promotes the formation of new blood vessels. This feeds the tumour. But, it's perfectly natural.
Posted by Larry Hoover on November 23, 2002, at 12:43:18
In reply to I was directing my above question to Larry and/or , posted by bubblegumchewer on November 23, 2002, at 11:15:51
> If you want a bonus question: I had my cholesterol profile done and it appears that despite my slight overweight status and my propensity to eat every unhealthy fat possible, my cholesterol is low (140) and my HDL and LDL are in the ideal ranges. (I'm 37 years old and female.) Meaning the ones that everyone else strives for. This is obviously a genetic trait because my mother has the same profile. We are just not a "heart disease" family.
Very good of you to choose such good genes. <wink>
> Does this mean that I may not be a person who is in need of the blood-fat benefits of taking omega-3 fatty acids? Or is that question just way too hard to speculate on?
What is important is how genes interact with their environment. From a gene's perspective, that has multiple applications. The external environment of a gene is the inside of a cell. How the machinery there interacts with the gene determines the activity of a gene. But, the cell interacts with cells around it, so you have organ-specific gene effects. And, you have the organs interacting together to have more collective effects (e.g the digestive tract, as opposed to just the stomach). Then, of course, you have systemic interactions (whole body effects). Finally, you have all the external environment to consider (food, disease, toxins, and so on). All of these are, at their core, gene/environment interactions.
Focussing on one factor, as you have, may not be instructive. People who eat fish and fish products are healthier than those who do not. Risk of dementia alone is less than half in people who eat fish.
> A bonus-bonus question: I spoke to the resident who was treating me a year and a half ago (he was also a horse's a**) about the correlation between low cholesterol and depression. He pooh-poohed the idea, saying that 140 is not low. From my research it appears that 140 in a non-athletic person with an average American junk-food diet is teetering on abnormally low. Any opinion?The correlation of serum cholesterol with mood is equivocal. Studies do not always agree.
I'll give you my opinion. I suspect that any correlation between cholesterol and mood falls under the concept of correlation with an unidentified independent variable. If B depends on A (and thus correlates), and C depends on A, then B and C stand a good chance of correlating as well, but they may not be related in any way.
For example, if you studied the use of makeup in a primary school female cohort, you might find that height and makeup use were highly correlated, although there is no causal relationship between them. Both depend, quite separately, on maturation.
Posted by bubblegumchewer on November 23, 2002, at 13:16:01
In reply to Re: I was directing my above question to Larry and/or , posted by Larry Hoover on November 23, 2002, at 12:43:18
assume, as I've been doing, that fish oil is not something likely to harm me, so I'll keep on taking it. If I understand correctly, what you're saying about tumor proliferation is that the few cases of omega-3 acids encouraging cancer growth are basically flukes in the world of cancer. I'm going to assume that the benefits far outweigh the few possible unfortunate non-benefits.
I was just wondering because I don't seem to fit the normal blood fat "profile" that we as modern Western people seem to be grouped into. On the contrary, my family members seem to be those who live till their nineties and then drop dead of a (I presume hemorrhagic but I don't know) stroke. Which is probably a natural and biologically proper way to go, so to speak, since few live longer than that. I'm just hoping that since I appear to be from a line of non-clotting, non-inflammatory cardiovascular people that I'm not pushing things in the hemorrhagic direction by encouraging thinner and thinner blood... but I think what I understand is that the anticoagulant effect is more of a NORMALIZATION than actually pushing it too far the other way.
Thanks for the "good genes" compliment but alas, it it's not one thing, it's another, right? My poor dad was plagued by mental illness; thus me, here (my mom does not like to believe in any biological or genetic basis... ha!) and both parents have/had different leukemias. My dad finally developed deep vein thrombosis (I have my suspicions that it arose from the Tegretol he took) but I believe it was the leukemia that finally killed him. Also his mother died of colon cancer so I was wondering about that too.
My interest in fatty acid balance arose from a desire to not land in the hospital with disabling anxiety (they called it depression; whatever) like I did a year ago (really thought I was going to die it was so bad) so whether the fish oil is barking up the wrong tree for me or not, I figure it won't hurt me. Strangely enough I've spend most of my life on no antidepressants and felt mostly just fine, just like I do now, on no antidepressants. I haven't figured this stuff out yet at all. But if fish oil just MAY prevent another such episode I'm all for it.
Ok, enough thinking for today... my brain hurts!
Posted by Larry Hoover on November 23, 2002, at 13:38:30
In reply to Thank you Larry, for your input. I'm going to, posted by bubblegumchewer on November 23, 2002, at 13:16:01
> assume, as I've been doing, that fish oil is not something likely to harm me, so I'll keep on taking it.
That's the broad message. Not likely to harm, likely to help.
> If I understand correctly, what you're saying about tumor proliferation is that the few cases of omega-3 acids encouraging cancer growth are basically flukes in the world of cancer.
It has to already be cancer before this mechanism operates. It's not a cause of cancer.
>I'm going to assume that the benefits far outweigh the few possible unfortunate non-benefits.
Yes.
> I was just wondering because I don't seem to fit the normal blood fat "profile" that we as modern Western people seem to be grouped into. On the contrary, my family members seem to be those who live till their nineties and then drop dead of a (I presume hemorrhagic but I don't know) stroke. Which is probably a natural and biologically proper way to go, so to speak, since few live longer than that. I'm just hoping that since I appear to be from a line of non-clotting, non-inflammatory cardiovascular people that I'm not pushing things in the hemorrhagic direction by encouraging thinner and thinner blood... but I think what I understand is that the anticoagulant effect is more of a NORMALIZATION than actually pushing it too far the other way.Yes, normalization appears to be what happens.
> Thanks for the "good genes" compliment but alas, it it's not one thing, it's another, right? My poor dad was plagued by mental illness; thus me, here (my mom does not like to believe in any biological or genetic basis... ha!) and both parents have/had different leukemias. My dad finally developed deep vein thrombosis (I have my suspicions that it arose from the Tegretol he took) but I believe it was the leukemia that finally killed him. Also his mother died of colon cancer so I was wondering about that too.
>
> My interest in fatty acid balance arose from a desire to not land in the hospital with disabling anxiety (they called it depression; whatever) like I did a year ago (really thought I was going to die it was so bad) so whether the fish oil is barking up the wrong tree for me or not, I figure it won't hurt me. Strangely enough I've spend most of my life on no antidepressants and felt mostly just fine, just like I do now, on no antidepressants. I haven't figured this stuff out yet at all. But if fish oil just MAY prevent another such episode I'm all for it.
>
> Ok, enough thinking for today... my brain hurts!Fish oil should help with brain hurt.....just kidding. ;-)
Posted by disney4 on November 24, 2002, at 13:32:36
In reply to Re: Thank you Larry, for your input. I'm going to, posted by Larry Hoover on November 23, 2002, at 13:38:30
Hi Larry,
I have another question for you about fish oil. In the link to the Bipolar Child there is some mention about cell membranes becoming stiff when people eat a diet high in trans fatty acids and take fish oil. I am not careful about my diet, and would hate to think I am doing more harm than good by taking fish oil.
******************************************
The Diet of the Child is of Utmost Importance. Parents need to look not only to capsules, however, but to the total diet of their children. Because, as we said earlier, other lipids compete in the cell membranes for the spots that the omega-3's would occupy, a diet high in fat and trans-fatty acids will interfere with omega-3 integration in the cell membrane and the membranes will become stiff and inflexible.
Posted by Larry Hoover on November 24, 2002, at 14:15:16
In reply to Re: Thank you Larry, for your input. I'm going to » Larry Hoover, posted by disney4 on November 24, 2002, at 13:32:36
> Hi Larry,
>
> I have another question for you about fish oil. In the link to the Bipolar Child there is some mention about cell membranes becoming stiff when people eat a diet high in trans fatty acids and take fish oil. I am not careful about my diet, and would hate to think I am doing more harm than good by taking fish oil.
> ******************************************
> The Diet of the Child is of Utmost Importance. Parents need to look not only to capsules, however, but to the total diet of their children. Because, as we said earlier, other lipids compete in the cell membranes for the spots that the omega-3's would occupy, a diet high in fat and trans-fatty acids will interfere with omega-3 integration in the cell membrane and the membranes will become stiff and inflexible.I take it that the latter paragraph is a quotation? I see it as a comparison of taking fish oil *or* consuming trans fatty acids.
Trans fats, although they are unsaturated, have a different three-dimensional structure that do cis fats. Trans fats condense at a higher tremperature than do cis ones. We see that as trans fats solidifying at room temperature, whereas cis fats remain liquid, often even under refrigeration.
An unsaturated fat has carbon-carbon double bonds. If there is only a single bond, each carbon is free to rotate about the axis of the bond. However, a double bond is rigid, pinning the orientation of the carbons.
Because the single bonds of a saturated carbon chain can reorient themselves, they can line up in neat rows beside other chains. When they do that, they stop moving around, and the fatty acids are said to condense, or solidify.
Trans fatty acids aren't very much different than saturated fatty acids in the overall orientation of the carbon chain, and they also solidify fairly readily.
Cis fats have a kink in the long carbon chain, sending the chain off at a 120 degree angle. If there's more than one cis bond, there's more than one kink. The "kinkier" a fatty acid is, the harder it is for it to align with other fatty acids and come to rest in a solid form.
Neuronal membranes depend on the long-chain polyunsaturated fatty acids like DHA and AA for their fluid nature, because the kinky fatty acids cannot condense. If your brain only has trans fatty acids available when it comes time to replace membrane constituents, then that's what it will use, but the membranes will be stiffer, or less fluid, as a result.
Part of the mechanism by which neurotransmitters dock at membrane receptors requires the membrane to be quite flexible. A stiffer membrane has the effect of reducing the signal arising from a particular amount of a neurotransmitter; it's as if there is a deficiency in the neurotransmitter itself.
It's been estimated that the daily turnover rate for membrane fats is no more than 3%. For technical reasons, it is an exponential relationship between supply of DHA and DHA replacement in the membrane, but it might take four months (ballpark) of fish oil supplementation to get the brain replenished in the necessary omega-3 fatty acids.
Posted by disney4 on November 24, 2002, at 14:29:07
In reply to Re: Thank you Larry, for your input. I'm going to, posted by Larry Hoover on November 24, 2002, at 14:15:16
You really do know your material! So basically the combination of trans fatty acids and fish oil would not cause the stiff cell membranes, but rather if you eat a lot of trans fatty acids and don't use fish oil you could cause that to happen. Am I following you correctly?
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