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mitochondrial dysfunction

Discussion in 'General Treatment' started by rydra_wong, Oct 27, 2011.

  1. rydra_wong

    rydra_wong Guest

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    I thought some might find this of interest - couldn't figure out where to put it, so here it is:
    http://www.jneurosci.org/content/18/2/687.short

    Mitochondrial Manganese Superoxide Dismutase Prevents Neural Apoptosis and Reduces Ischemic Brain Injury: Suppression of Peroxynitrite Production, Lipid Peroxidation, and Mitochondrial Dysfunction Jeffrey N. Keller1,2, Mark S. Kindy2,3, Fredrick W. Holtsberg1, Daret K. St. Clair4, Hsiu-Chuan Yen4, Arriane Germeyer2, Sheldon M. Steiner1, Annadora J. Bruce-Keller2, James B. Hutchins6, and Mark P. Mattson2,5

    Abstract
    Oxidative stress is implicated in neuronal apoptosis that occurs in physiological settings and in neurodegenerative disorders. Superoxide anion radical, produced during mitochondrial respiration, is involved in the generation of several potentially damaging reactive oxygen species including peroxynitrite. To examine directly the role of superoxide and peroxynitrite in neuronal apoptosis, we generated neural cell lines and transgenic mice that overexpress human mitochondrial manganese superoxide dismutase (MnSOD). In cultured pheochromocytoma PC6 cells, overexpression of mitochondria-localized MnSOD prevented apoptosis induced by Fe2+, amyloid ?-peptide (A?), and nitric oxide-generating agents. Accumulations of peroxynitrite, nitrated proteins, and the membrane lipid peroxidation product 4-hydroxynonenal (HNE) after exposure to the apoptotic insults were markedly attenuated in cells expressing MnSOD. Glutathione peroxidase activity levels were increased in cells overexpressing MnSOD, suggesting a compensatory response to increased H2O2 levels. The peroxynitrite scavenger uric acid and the antioxidants propyl gallate and glutathione prevented apoptosis induced by each apoptotic insult, suggesting central roles for peroxynitrite and membrane lipid peroxidation in oxidative stress-induced apoptosis. Apoptotic insults decreased mitochondrial transmembrane potential and energy charge in control cells but not in cells overexpressing MnSOD, and cyclosporin A and caspase inhibitors protected cells against apoptosis, demonstrating roles for mitochondrial alterations and caspase activation in the apoptotic process. Membrane lipid peroxidation, protein nitration, and neuronal death after focal cerebral ischemia were significantly reduced in transgenic mice overexpressing human MnSOD. The data suggest that mitochondrial superoxide accumulation and consequent peroxynitrite production and mitochondrial dysfunction play pivotal roles in neuronal apoptosis induced by diverse insults in cell culture and in vivo.

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    Has anyone tried supplementing with MnSOD? Also note that uric acid is a peroxynitrite scavanger, which may be why uric acid seems to protect against multiple sclerosis. I think pursuing anything the deals with lipid peroxidation will help mitochondrial dysfunction. I can't really reasearch it now because w/o a mouse I am slower than if I was dargging a railroad tie behind me. Please don't get riled about the term "mitochondrial dysfunction" _ I say just use the search string the researchers use and mine their info and go on. The object is to gain knowledge, IMHO.
     
  2. rydra_wong

    rydra_wong Guest

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    Another study of interest to some (regarding male hormones):

    Cactus flower extracts may prove beneficial in benign prostatic hyperplasia due to inhibition of 5? reductase activity, aromatase activity and lipid peroxidation
    Adi Jonas, Gennady Rosenblat, Daniel Krapf, William Bitterman and Ishak Neeman

    http://www.springerlink.com/content/jauhkk4m9whr4cqt/

    The cactus flower is deemed to be helpful in benign prostatic hyperplasia (BPH) therapy, although there is no published information regarding its clinical effect in patients and on the mechanism of its biological activity. The present study evaluated the ability of cactus flower extracts to exert an effect on BPH through possible inhibition of such processes as lipid peroxidation, androgen aromatization and testosterone reduction. Cactus flower extracts indeed inhibited aromatase and 5? reductase activity in cultured foreskin fibroblasts, and also in human placental and prostatic homogenates. The inhibitory activity in both instances was associated with the dichloromethane or ethanol (methanol) extracts, while a marked antioxidative activity was associated with the aqueous extract. The finding that cactus flower extracts interfere concurrently in vitro with aromatase and reductase activity as well as with free radical processes suggests that these substances may prove beneficial in BPH treatment.
     
  3. alex3619

    alex3619 Senior Member

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    Hi rydra_wong, I have not tried SOD but I am interested in it. It is one of the most important antioxidants we have, but I don't know how well absorbed it is. SOD may well be effective against all sorts of things, including progeria. Bye, Alex
     
  4. baccarat

    baccarat Senior Member

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    Last time I tested I had low manganese and zinc SOD enzymes. I was advised to supplement with both minerals, as well as other stuff supposed to help mitochondria but didn't see much change, in the end I gave up.
     
  5. rydra_wong

    rydra_wong Guest

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    Alex, yes, I don't know how well absorbed it is either. Unfortunately it takes a lot of time to connect all the dots. This is phase 1, which is "generate a list of things that affect things that affect mitochondrial dysfunction". The first thing I thought I'd look at is "lipid peroxidation" which causes mitochondrial dysfunction.

    But backing up a little bit -->

    I place the highest priority on anti-oxidant supplements (even above my methylation supplements).
    I take these anti-oxidants (and have for decades, and before that still high doses):
    2 g mineral ascorbates (C)
    1. E (d alpha)
    200 mg E (gamma tocopherol)
    100 mg alpha lipoic acid
    50-100mg CoQ10 (ubiquinol)
    1 g Olive Leaf Extract (polyphenols)
    200-400 m(c?)g selenium

    oil of oregano if needed to kill something

    I have high uric acid (gout runs in my family) and that is a cellular antioxidant. Look up "uric acid" on wiki to find the things to eat to raise it if you have m.s. (those with m.s. have low uric acid)

    ---------------------------------
    My functionality score I guess is 7.

    I take 42 pills a day so I can't think of all of the antioxidants right now - these are the main ones.

    The question is -- could it be that a high anti-oxidant intake separates those with high mitochondrial dysfunction from those with lesser m.d.?

    How about stating what anti-oxidants you take vs. your functionality score?
     
  6. u&iraok

    u&iraok Senior Member

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    Rydra,

    I feel the same way about antioxidants. Notice I say 'feel' because we're kinda feeling our way through the dark.

    When I was seeing an ND an antioxidant test showed I really needed them and even after I took antioxidants the test didn't improve, so I kept adding more, though I was a little nervous to take so many.

    So now I take a lot of antioxidants. I've kind of tested to see if they help by stopping taking them to see how I felt, then taking them again, stopping again, taking them, stopping again, to try and see if each and every time I stopped I felt worse. And I did.

    I take Life Extension Mix which I've found to help the best of all the things I tried, though it does have NAC in it which I'm a little concerned about. It has what I think are high quality, cutting edge antioxidants. Right now I'm also taking additional C, resveratrol and a high ORAC greens powder. (I take more supplements, not 42 but at times it's felt like that many! but just focusing on antioxidants here.) I also eat a lot of fruits and vegetables because I find I feel the best on at least 5 servings a day, but I try to take 7 or 8 servings.

    I haven't tried SOD.

    Life Extension Mix

    Supplement Facts
    Serving Size 3 scoops (per day)

    Servings Per Container 35

    Amount Per Serving
    Vitamin A (as 90% Betatene1 D. salina natural beta-carotene with mixed carotenoids and 10% acetate)
    5000 IU

    Vitamin C (as ascorbic acid, calcium ascorbate, ascorbyl palmitate, magnesium ascorbate, niacinamide ascorbate, and acerola extract)
    2000 mg

    Vitamin D3 (as cholecalciferol)
    2000 IU

    Vitamin E (as D-alpha tocopheryl succinate)
    400 IU

    Thiamine (vitamin B1) (as thiamine HCI)
    125 mg

    Riboflavin (vitamin B2) (with 2 mg riboflavin 5-phosphate coenzyme)
    50 mg

    Niacin (vitamin B3) (as 53% niacinamide, 38% niacin, 9% niacinamide ascorbate)
    190 mg

    Vitamin B6 (as 100 mg pyridoxal 5-phosphate coenzyme and 5 mg pyridoxine HCI)
    105 mg

    Folate [from (Citrus limon) extract (peel)]
    400 mcg

    Vitamin B12 (as 42% cyanocobalamin, 42% hydroxylcobalamin, 16% ion exchange resin)
    600 mcg

    Biotin
    3000 mcg

    Pantothenic acid (as D-calcium pantothenate with 5 mg pantethine)
    600 mg

    Calcium (as calcium carbonate, calcium ascorbate, D-calcium pantothenate, Calcium D-Glucarate2)
    218 mg

    Iodine (as potassium iodide)
    150 mcg

    Magnesium (as magnesium oxide, citrate, glycinate, taurinate, arginate, ascorbate)
    400 mg

    Zinc (as OptiZinc3 zinc monomethionine, zinc succinate]
    35 mg

    Selenium [as 50% Se-Methyl L-Selenocysteine, 25% L-selenomethionine (yeast free) (SelenoPure4), and 25% sodium selenate]
    200 mcg

    Copper (as copper bisglycinate chelate)
    1 mg

    Manganese (as manganese gluconate)
    1 mg

    Chromium [as Crominex5 3+ chromium stabilized with (Capros standardized Phyllanthus emblica extract (fruit) and PrimaVie purified and standardized Shilajit)]
    500 mcg

    Molybdenum (as sodium molybdate)
    125 mcg

    Potassium (as potassium chloride)
    37.4 mg

    N-acetyl-L-cysteine (NAC)
    600 mg

    Taurine
    200 mg

    Inositol
    250 mg

    Phosphatidylcholine (from soy)
    150 mg

    Choline (as choline bitartrate)
    120 mg

    Boron (as boron citrate/aspartate/glycinate complex)
    3 mg

    Ascorbyl palmitate (fat-soluble vitamin C)
    250 mg

    para-Aminobenzoic acid (PABA)
    200 mg

    Trimethylglycine (TMG) (as betaine anhydrous) (from sugar beets)
    100 mg

    Citrus bioflavonoid complex (Citrus aurantium L.) (peel and fruit) [std. to 50% hesperidin (100 mg)]
    200 mg

    Broccoli sprout concentrate (A proprietary blend of broccoli sprout concentrates and Calcium D-Glucarate2) (providing glucosinolates, sulforaphane, D-3T, and PEITC)
    525 mg

    Calcium D-Glucarate2
    200 mg

    Decaffeinated Green tea (Camellia sinensis) extract (leaf) [standardized to 98% polyphenols (318.5 mg) and 45% Epigallocatechin gallate (EGCG) (146.25 mg)]
    325 mg

    Acerola (Malpighia punicifolia) extract 4:1 (berry)
    300 mg

    Ginger (Zingiber officinale) extract (root) [standardized to 5% gingerols (10 mg)]
    200 mg

    HiActives 100% fruit/berry complex (A proprietary blend of concentrated blackberry, blueberry, cherry, cranberry, elderberry, persimmon, prune powders)
    200 mg

    Wild Blueberry (Vaccinium angustifolium) standardized anthocyanin extract (fruit)
    150 mg

    Milk thistle (Silybum marianum) extract (seeds) [standardized to 85% silymarin (85 mg)]
    100 mg

    POMELLA10 Pomegranate (Punica granatum) extract (fruit) [std. to 30% punicalagins (25.5 mg)]
    85 mg

    Bilberry (Vaccinium myrtillus) extract (fruit) [standardized to 36% anthocyanins (10.8 mg)]
    30 mg

    Leucoselect6 grape seed (Vitis vinifera) (seeds) extract [std. to 95% proanthocyanidins (23.75 mg)]
    25 mg

    BioVin7 grape (Vitis vinifera) extract (whole grapes) [std. to 95% proanthocyanidins (23.75 mg)]
    25 mg

    Bromelain (from pineapple) (Ananas comosus) (stem) (2400 gelatin digestive units per gram)
    15 mg

    Lutein (purified concentrate from marigold flowers) (Tagetes erecta) (providing 465 mcg trans-zeaxanthin)
    15 mg

    Olive juice (Olea europea) extract (fresh fruit) [std. to 15% polyphenols (1.875 mg)] (providing hydroxytyrosol, tyrosol and oleuropein)
    12.5 mg

    Sesame seed (Sesamum indicum) lignan extract
    10 mg

    Luteolin (high purity luteolin, as Pureolin8)
    8 mg

    Lycopene (from Lyc-O-Mato9 natural tomato extract)
    3 mg

    Cyanidin-3-glucoside (C3G)
    1.25 mg

    trans-Pterostilbene (from pure Pterospan11 and SMART11 pterostilbene)
    0.5 mg

    Other ingredients: maltodextrin, natural orange flavor, stevia, silica.

    Contains soybeans. Contains corn and sesame.
    This product contains NO milk, egg, fish, peanuts, crustacean shellfish (lobster, crab, shrimp), tree nuts, wheat, yeast, gluten, or rice. Contains NO artificial sweeteners, flavors, or colors
     
  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Antioxidants i use a vit e and c as well as lipoic acid and NAC. Lipoic acid and NAC are useful for liver protection but amongst the methylation guys these to seem to concern them but i have never had any problems with them and continue to use them. I use other vits but these are mymain antiox. The life extension mix looks like a good all round supp as it covers alot of bases.

    cheers!!!
     
  8. alex3619

    alex3619 Senior Member

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    Hi rydra-wong, my original protocol back in the late 90s was high in antioxidants and a few other things, including pycnogenol (grape seed derived) and several amino acids. For a while I had full energy though it would not touch the fatigue much. However two things happened. First I began getting daily migraines, second i ran out of money. I could no longer afford $100 a week on supplements on a pension with a low bank balance. So I stopped. I have always wanted to go back and experiment to find out how to keep the energy without getting the migraines but the opportunity has never really presented itself. My list of antioxidant priorities has been very much like yours too, although with pycnogenol rather than olive oil extract. One notable thing, which you are probably taking but it would be on my short list, is CoEnzyme Q10. I also used to take a lot of B vitamins.

    Just to clarify, I went from struggling to walk a few yards to being able to fast walk five hours a day on this protocol. The deep core of fatigue was still there though. Low energy is not the same as high fatigue, they are overlapping symptoms in my view and my experience, not identical.

    Bye
    Alex
     
  9. rydra_wong

    rydra_wong Guest

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    Thanks everyone. (BTW I editted my post to add CoQ10 which I've taken for 20 years, but ntil recently it was ubiquinone 100mg and I was tested low so I switched to 50mg ubiquinol (cost)).

    I was hoping for 4 bits of info:
    what antioxidants you take
    how much
    your rating on the scale at your setting / profile

    I was looking for the effect of quantity of antioxidants on endothelial dysfunction because one of the things that causes it is lipid peroxidation and sufficient and the right kind of antioxidants will stop that. (It may not be practoical to take the amount needed but I think antioxidants would help tremendously). I think I spend about $200/month n vitamins and yes it's scarey because I can foresee a day when I won't be able to afford it and I know many of you can't. Unfortunately all I know is vitamins).

    I am not an energetic person but a lot of the people here are tremendously worse and so it seems potentially worthwhile to see what the differences between us are that might cause that. Maybe there is a clue.
     
  10. rydra_wong

    rydra_wong Guest

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    u&iraok

    (your avatar name is very hard to remember and type!)

    I wish I could take Life Extension products but all of their multi-type products, B-complexes, and such contain non-active B's and I will not clog my system up with them. If you have methylation problems (and I assume you do since you are here) then I would srongly discourage you from taking any supplement with non-active B's in it - especially cyanocobalamin and folic acid. I will not even take a product with B6 in it rather than P5P. B6 can cause neuropathy and does not protect your kidneys from kidney failure, but the opposit is all true of P5P.

    I am a member of Life Extension and I have emailed them to ask that they replace these with active forms -- that many people would be interested -- but they say that only a small percentage of people with genetic defects are interested in active forms of the vitamins. If others sent them email regarding this, maybe they would listen. I also wrote Jarrow regarding B Right because their tablet excipients contain Titanium Dioxide which the Canadian government lists as a carcinogen, but they didn't even respond. (I take Thorne Basic B and Thorne Multi - I love their products and even though Fredd says folinic acid is a problem for him, my genetics demands it (according to my doctor) and it does not seem to bother me).

    I take the Life Extension Cruciferous Vegetables supplement which keeps my hormones right where they should be and my doctors happy. I order almost all my bloodwork through Life Extension and enjoy going over it with their super well informed and helpful doctors.
     
  11. rydra_wong

    rydra_wong Guest

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    I have a project to do for my class in addition to everything else so I won't be able to respond for awhile. Life sometimes gets too demanding and squeezes out time. Take care.
     
  12. u&iraok

    u&iraok Senior Member

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    Darn, I thought it would be easy to remember and to type, except for the '&' sign. Did you notice it's you-and-I-are-aok? If you didn't, maybe that will make it easier. But with our problems, I should have named myself ME, both for me, myself and I and Myalgic Encephalomyletis. Now THAT would have been easy! Some people call me u&i. You can call me 'u'. :)

    I read about your B problem, I thought Life Extension Mix might not work for you. I don't know if this is a problem for me. I get so overwhelmed with our complicated reactions to thing, this helps that but could do that, etc. What an appreciation I have for the human body especially when it works right and you don't have to think about it! Wow, have we only just scratched the surface of understanding.

    I did Rich's protocol using the B's. I had been doing something like it with what I was taking over a period of years before I did the actual protocol, including taking immunocal, and had been doing lots of detoxes so I didn't have much reaction. Now I'm using up some Bs I had--Intrinsi B/12/Folate (800 mcg folate, 500 mcg B12) from Metagenics and methylcobalamin (1,000 mcg). Taking one Intrinsi et al under the tongue and 5 methyl Bs under the tongue once a day and no reactions, just getting a little energy. Next, I'm going to try Fredd's protocol.

    Also, Rich did have a good explanation for why the methyl B's might not be good for some PWCs. See, all the this-but-that going on. I'm just an experiment!

    How many people do you think have this problem?

    I like that product but it's not organic and I only take organic or locally grown by a farmer who's not organic certified but uses organic practices. I just can't take any more toxins than I can help since we're practically stewing in them in the U.S. Though organic is supposed to be about 20% contaminated with pesiticide residues and you have to worry about the hormones and freaky junk in the manure they may use.

    I really like Life Extension and their panel of doctors/experts. And now Russell Blaylock, M.D. is on the panel, which is great.
     
  13. u&iraok

    u&iraok Senior Member

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    One antioxidant that may be good for this is Krill Oil. I am not taking it now, but had been for a while and plan to get some in the next month. (Changing things up seems to be a good idea as we seem to get used to things and they stop working as well.)

    Krill has a good combination of EPA, DHA and astaxanthin, which is supposed to be a superior antioxidant. It also keeps the oil in krill from spoiling. Also, with the world's fish supply greatly depleted and the mercury contamination as well as the processing required to strip the mercury and othertoxins from the fish oil, it seems to be a good choice. There's supposed to be a huge supply of krill, but some say there's not.
     
  14. taniaaust1

    taniaaust1

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    I myself havent found that anti-oxidents improve my functionality score. High dose vit C thou (2-3g twice per day) does help when Im getting allergy symptoms and snuffy nose in the mornings with just those symptoms.

    Anti-oxidant wise Im only currently taking Selenium (Bioceuticals brand) and 2g Melatonin (and Vit C only when Ive got allergy issues). The molybdenum I take for deficiency is also thought to have anti-oxidant properties.
    (Either the selenium or the molybdenum did improve quite a bit my brain fog and inability to think).
     
  15. rydra_wong

    rydra_wong Guest

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    Hey u,
    I think a majority of people have problems with B vitamins, not due to genetics but due to diet. If the methyl cycle block is true then it's a vicious cycle when you get depleted for whatever reason. Look at the junk food diets these days. Also, if you care to look at almost any other topic at BetterMedicine (than the B12 site) you will soon see that the kids these days don't have the faintest idea of good nutrition. I was raised with Adele Davis when Mom's stayed home and cooked from scratch. I feel very sorry for the kids these days. So when they get sick, and they do, not any old B vitamin will do, at least for starters! I think the market is the there.

    Ok, I get your name. It's kindof cool as long as I don't have to type that non-alphabetic character that shall remain nameless! Take care,
    Rydra

    Oh, P.S. I love Life Extension too. They are very knowledgeable and I like being able to phone their informative doctors whenever I need to.
     
  16. Adster

    Adster Senior Member

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    Hi u&iraok. My understanding is that krill fishing is now at a level that is unsustainable, and because it is at the bottom of the food chain, a depletion of krill means a whole lot of sea life is then also threatened as so many species depend on it. I think it's probably one to avoid if possible. Bottom of food chain overfishing is really bad news. That said, almost all commercial fishing is at unsustainable levels. Anyway, worth considering if you would like to do your bit for the ocean :)
     
  17. u&iraok

    u&iraok Senior Member

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    I don't want to take away food needed by whales and other species but I understood that krill reproduces faster than it's taken (sardines are another example) and that fish higher on the food chain are at unsustainable levels because they reproduce more slowly and live longer and are taken faster than they are replenished.

    I got my info from this article. What do you think? (Sorry, it's long.)

     
  18. u&iraok

    u&iraok Senior Member

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    Duplicate - couldn't delete it no matter how many times I tried!
     
  19. Adster

    Adster Senior Member

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  20. u&iraok

    u&iraok Senior Member

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    Okay, sorry, just now getting to this!

    Well, I don't know how to reconcile the two articles, the one I quoted and the one you quoted. Well, that is, except, I think we call all agree on this from the article you quoted:

    If that happens, fergetaboutit.

    If we westerners weren't so out of balance with our nutrition we wouldn't need fish oil. I mean, what did inlanders who didn't live by lakes traditionally eat? Not everyone ate fish.

    And there's some evidence that it's fatty acids in general that we're deficient in, not just Omega 3s. Hopefully, we'll hear more about that. I've had really good success with Rice Bran Oil which is all omega 6 fatty acids.

    The article you quoted said they are using krill as fish feed. That could be a problem, too. I had heard they were using fish as fish feed, but not krill.
     

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