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MITO 101 –Supplements and Nutrition

Discussion in 'Other Health News and Research' started by heapsreal, Jun 18, 2014.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    http://www.umdf.org/atf/cf/{28038c4c-02ee-4ad0-9db5-d23e9d9f4d45}/supplements and nutrition - tarnopolsky.pdf


    Supplements
    • Mitochondrial dysfunction leads to increased free radical production, a reduction
    in aerobic energy provision, and increased flux through anaerobic pathways that
    can increase serum lactate (lower pH) and deplete tissue phosphocreatine 1
    . Many
    of the suggested supplements for mitochondrial disease have been based upon
    the predicted ability to mitigate against these effects and are often given in
    combination (“mitochondrial cocktail”) 2
    .
    • No long-term (> several months), randomized studies have been completed to
    date and all recommendations are somewhat empiric and must be individualized.
    In theory, combinations of supplements that target more than one of the
    consequences of mitochondrial dysfunction should be superior to single agents,
    and some evidence suggests that combination therapies can improve surrogate
    markers of efficacy, including oxidative stress markers and lactate, and improved
    mitochondrial function 3-5. Most studies have evaluated coenzyme Q10, creatine
    monohydrate, riboflavin, vitamin E, vitamin C, α-lipoic acid, and thiamine (Table 1).
    Until evidence of safety and efficacy is established, patients should avoid the
    hundreds of other supplements on the market.
    • Coenzyme Q10 is a co-factor involved in electron transfer from complex I and II to
    complex III of the electron transport chain and can function as an anti-oxidant.
    There are many studies that have evaluated the potential efficacy of CoQ10 in
    mitochondrial disease, but the literature is not conclusive due to different
    formulations (some of which are poorly absorbed), small sample size, and
    variability in clinical features and outcome variables. The balance of data
    suggests that CoQ10 is likely to be of benefit in primary, and some secondary,
    mitochondrial disorders (review see 1, 2, 6).
    • Alpha-lipoic acid is an anti-oxidant located in the mitochondria with high
    theoretical potential for use in mitochondrial disease 1
    , although to date it has
    been studied only as part of a combination 3
    .
    • Creatine monohydrate is a quanidino compound that is consumed in meat/fish
    and produced endogenously. It is involved in temporal and spatial energy
    buffering in the cell and has anti-oxidant and neuroprotective effects 7-9. Animal
    models of complex I and II deficiency, cerebral ischemia, seizures, and oxidative
    stress, all show beneficial effects from creatine supplementation 7-10. Human
    studies using creatine monohydrate in isolation have been equivocal: some have
    reported benefit11-14, others have not 15, 16.
    • L-carnitine is required for the entry of long-chain fatty acids into the mitochondria
    for β-oxidation. Supplementation is recommended if plasma levels are low, or if
    patients are taking valproic acid or statins (both relatively contraindicated in
    mitochondrial disease).
    • A randomized double-blind, cross-over study using a combination of α-lipoic acid
    + creatine monohydrate + CoQ10 in proven mitochondrial disease showed
    decreased levels of lactate and of a marker of oxidative stress 3
    , and another similar
    combination also found evidence for efficacy 5
    .
    • Vitamins E and C are lipid- and water-soluble anti-oxidant vitamins, respectively.
    Free radicals are produced in excess from complex I and III of the electron
    transport chain in response to mitochondrial dysfunction and results in oxidative
    stress. It is important that anti-oxidants be given as redox-couples because each
    anti-oxidant can become a pro-oxidant. Examples of redox-couples include
    vitamin E and C, vitamin C and CoQ10. The use of a mitochondrial cocktail avoids
    the use of single anti-oxidants and reduces the risk that they become pro-oxidants.
    • A wide variety of other supplements have been advocated for use in mitochondrial
    cytopathies including: riboflavin (co-factor for complex II), thiamine (co-factor for
    pyruvate dehydrogenase), vitamin K3 (electron donor), succinate (co-factor for
    complex II), yet none have been independently evaluated in a randomized clinical
    trial. Most physicians do not prescribe vitamin K3 anymore as there may be the
    potential for blood clotting issues.
    • Supplements should be introduced in a step-wise fashion and increased slowly to
    identify and minimize potential intolerances.
    • All supplements can lead to drug interactions with prescription medications. In
    those people taking concomitant medications, it is important to evaluate drug
    levels (when possible) after starting a mitochondrial cocktail, especially if there is a
    change in clinical condition or if a new sign/symptom emerges.
    • With the exception of coenzyme Q10, where there is some evidence that
    liquid/hydrosoluble formulations are better absorbed and lead to higher blood
    levels than powder preparations 3
    , for the other components of mitochondrial
    cocktails there is no credible data to suggest that one formulation is better than
    any other (Table 1).
    • Targeted formulations have been designed to be more specific for the
    mitochondria (e.g. MitoQ) 17, and future clinical trials will be important to evaluate
    their clinical utility.

    Nutrition.
    • Before starting any diet or dietary supplement, ensure that energy, protein, and
    micronutrient intake are sufficient. Some patients have increased energy
    expenditure (e.g. because of fever, rigidity, dystonia) and/or reduced energy intake
    (e.g. because of low intake due to oro-facial weakness or dyskinesia), or poor
    absorption (e.g. due to intestinal pseudo-obstruction) that can lead to relative
    under-nutrition. Identification of deficiencies that may require specific
    supplementation can be done with blood tests and are most commonly seen for
    protein (albumin or pre-albumin), folate (RBC folate), vitamin B12 (B12 level), and
    carnitine (total and free carnitine levels). Other deficiencies reported include; zinc,
    selenium, vitamin A, vitamin D, and vitamin E.
    • A multivitamin supplement is safe and may alleviate micronutrient deficiencies.
    Patients with LHON, NARP, or other mitochondrial disorders with eye involvement
    should take a multivitamin with lutein.
    • Some patients require a G- or J-tube to safely provide adequate nutrition +/-
    medications.
    • There is no scientific data to support specific macronutrient profiles (protein,
    carbohydrate and fat) in mitochondrial disease, but protein needs should at least
    meet the guidelines set out in the Dietary Reference Intake Tables prepared by the
    US Department of Agriculture,
    http://fnic.nal.usda.gov/nal_display/index.php?info_center=4&tax_level=3&tax_su
    bject=256&topic_id=1342&level3_id=5140

    A ketogenic diet is used in the treatment of refractory seizures and is not
    contraindicated in mitochondrial disease. Although there may be potential
    benefits from a ketogenic diet in complex I deficiency 18, the long-term health risks
    would preclude its use except in the case of severe refractory seizures.
    • Fasting should be avoided and frequent small meals are preferable. If fasting is
    unavoidable (e.g. for religious reasons), a meal with fat and protein (slow digestion)
    and complex carbohydrates (slow absorption) should be taken prior to a planned
    fast.
    • Fluid intake is essential during times of increased heat and metabolic stress to
    avoid heat stroke. Fluid intake should match the environmental demands (more
    fluid intake in hot/humid conditions). A general rule is to consume or administer
    adequate fluids to keep the urine color light yellow or clear. Absence of sweating
    in a warm environment is a serious sign of heat stress and must be dealt with
    promptly. Guidelines on the recognition of heat stress and heat stroke and
    prevention can be best obtained through documents designed for sporting events:
    http://www.acsm-msse.org/pt/pt-core/template-journal/msse/media/0207.pdf

    Table 1. Nutraceutical compounds often used with mitochondrial cytopathies

    Compound Dose (mg/kg/d) Rationale
    Coenzyme Q10 3.5 – 15.01
    By-pass complex I defect/anti-oxidant
    Creatine monohydrate 100.02
    (max, 7g/d) Alternative energy
    source/neuroprotection
    Riboflavin 2.5 – 5.0 By-pass complex I defect
    Αlpha-lipoic acid 3.5 – 10.0 Anti-oxidant
    Vitamin E 5.0 – 10.03
    Anti-oxidant
    Vitamin C 5.0 – 10.0 Anti-oxidant
    L-carnitine 15.0 – 50.04
    Free fatty acid transport/neuroprotection
    Thiamine 2.5 – 5.0 Enhance pyruvate entry into mitochondria


    Although most of the above compounds are Generally Regarded As Safe (GRAS), none
    of the above have been proven to be safe during pregnancy. Since pregnancy is a
    metabolic stress and the developing fetus may be affected with mitochondrial disease,
    the risk/benefit ratio is unclear and must be individualized. The doses given are the
    best estimate from studies and empirical experience and the total daily doses should
    be divided twice daily. The supplements are best given with food to enhance
    tolerance. Gastrointestinal upset is the most common side effect (seen in about 5 % of
    patients with creatine for example). 1 – Higher doses are required for coenzyme Q10
    deficiency; 2 – Uptake into the brain may require higher doses or a loading with up to
    300 mg/kg/d for 4 weeks to increase levels by ~ 9 % 19 (consequently, using creatine in
    an acute stroke or seizure situation is totally useless), uptake into muscle can occur
    after 30 days with the above dose and 5 days with loading (300 mg/kg/d) 20; 3 –
    maximum daily dose should not exceed 800 mg = IU; 4 – I tend to adjust the dose to
    get plasma levels into the mid-normal range for the reference laboratory used
     
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  2. adreno

    adreno 3% neanderthal

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    The usual suspects, that Myhill et al. has suggested for years.
     
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  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    good place for someone to start i guess.
    I think the doses suggested are much higher then what alot of us here use.
    @SOC recently posted about the doses of q10 used for mito disorders. Many would probably need to take over 1000mg of q10 if going by the dosages recommended.

    I am going to look at pushing my antioxidant/mito doses higher and add a few other things i have used in the past and a couple new things. We will see if it helps me find another gear and reduce PEM abit further??
     
  4. adreno

    adreno 3% neanderthal

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    Because oxidative stress damages mitochondria, I would focus on polyphenol antioxidants as well, quercetin for example, has been shown to promote mito biogenesis.
     
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  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    @adreno, so green tea extract, pine bark extracts, maybe resveratrol?
    Something thats been on my to do list for awhile is benfotiamine.
    I do want to try creatine and ribose again, i have had some good effects from it but im inconsistent with powders and making drinks etc. So i was just looking at taking low dose tablets eg creatine 2400mg bid, ribose chews 3000mg bid and add pyruvate 1000mg in the morning and see if they all have a synergistic effect on improving mito function by having the raw materials available.

    I think my nac, vit e/c doses are good but need to increase my acetyl carnitine, q10 and lipoic acid doses.

    I dont know if its directly from the antioxidants and mito supps and or the pregnenolone and dhea, but i think my metabolism has improved and general function. i guess im going off body temps here which would always be low 35c and now come in at 36.7c which i cant ever remember seeing since cfs. Maybe an indicator that things are moving??
     
  6. Thinktank

    Thinktank Senior Member

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    @heapsreal , a tip on using creatine, dissolve the powder in warm water. When creatine monohydrate is mixed in cold water it often leaves residue and that's what causes irritation to the intestinal lining.
     
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