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Ray Peat Email Advice Depository

Discussion in 'Email Advice' started by charlie, Jan 14, 2013.

  1. paymanz

    paymanz Member

    Jan 6, 2015
    i asked dr peat about silicon :

  2. EndAllDisease

    EndAllDisease Member

    Jul 6, 2014
    Hey Ray!
    In an interview with John Barkhausen you mentioned that "A millionth of a gray is known to produce bystander effects."

    - Do you have any studies suggesting this?
    English, russian, whatever language they're in, they would be very useful.
    Also, what is you opinion on the new 'millimetre wave machines' at US airports?

    Ray's response:
  3. Lilac

    Lilac Member

    May 6, 2014
    My 86-year-old mother developed a migraine in early February. It persisted for weeks and soon involved hallucinations, plus many other symptoms, such as internal tremors, sweats, indigestion, and emotional meltdowns. We went to many doctors. A few were interested and thoughtful, but even the good ones did not fix anything. I finally asked Dr. Peat for a recommendation. We had been using the 3-drop doses of Progest-E, spaced 10 minutes apart.

    Dr. Peat's response:
    "An eighth of a teaspoon [of Progest-E] (taken with a little food is o.k.) might be enough for her to notice a definite effect. All of the symptoms you mention, even without the high TSH, should have made the doctors think of hypothyroidism. (Did they even take her temperature?) A blood test for T3, reverse T3, T4, and cortisol would probably show that the synthroid isn’t what she needs. The liver’s ability to change T4 to T3 decreases with age."

    The bigger dose a few times a day has been helpful, as has the coming of spring.

    And, no, nobody took her temperature.
  4. Lightbringer

    Lightbringer Member

    Jan 24, 2014
    A few people on the forum have started using a couple of liquid t3 products. Would you have any concerns with ingesting t3 in a liquid form ?

  5. paymanz

    paymanz Member

    Jan 6, 2015
    if EFAs are absolutely unessential then what is the explanation for symptoms carnivore animals such as cats get when their diet are devoid of Arachidonic acid ?


    [ moderator edit: related disussion PUFAs Role On Skin ]
  6. paymanz

    paymanz Member

    Jan 6, 2015
    on jacuzzi and hot tubs,

  7. Dan Wich

    Dan Wich Member

    Jan 22, 2013
    In response to a question about DMSO:
  8. Dan Wich

    Dan Wich Member

    Jan 22, 2013
    In response to a question about sugar bleaching:
  9. narouz

    narouz Member

    Jul 22, 2012
    He kinda skimped on the references.;)
  10. Dan Wich

    Dan Wich Member

    Jan 22, 2013
    In response to a question about magnesium malate:
  11. Dan Wich

    Dan Wich Member

    Jan 22, 2013
    In response to a question about the theory of body weight having a "set point":
  12. Makrosky

    Makrosky Member

    Oct 5, 2014
    I asked Peat about MDMA :

    Question :
    Do you think it's an overall serotonergic substance and hence bad for health ? Do you think the possibly biochemical bad effects are a minor side-effect of the positive ones ? I'm interested on any comment, idea or feeling about it that you might have.

    Answer :

    In pure form and moderate dose (e.g., 1 to 1.5 mg per kg body weight), I think it’s likely to be helpful for changing the pattern of chronic stress/learned helplessness, and maybe the chronic degenerative diseases produced by inescapable stress. The production of nitric oxide is likely to be a problem with large doses or chronic use.

    1FASEB J. 2005 Jul;19(9):1187-9.
    The serotonin transporter (SLC6A4) is present in B-cell clones of diverse
    malignant origin: probing a potential anti-tumor target for psychotropics.
    Meredith EJ(1), Holder MJ, Chamba A, Challa A, Drake-Lee A, Bunce CM, Drayson MT,
    Pilkington G, Blakely RD, Dyer MJ, Barnes NM, Gordon J.
    (1)Division of Immunity and Infection, The Medical School, Birmingham, UK.
    Following our previous description of the serotonin transporter (SERT) acting as
    a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in
    Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell
    malignancy, while exploring additional SERT substrates for potential therapeutic
    activity. SERT was readily detected in derived B cell lines with origins as
    diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma,
    diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse
    kinetics for the antiproliferative and proapoptotic activities of the amphetamine
    derivatives fenfluramine (an appetite suppressant) and
    3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being
    similar to the endogenous indoleamine. A tricyclic antidepressant, clomipramine,
    instead mirrored the behavior of the selective serotonin reuptake inhibitor
    fluoxetine, both being effective in the low micromolar range. A majority of
    neoplastic clones were sensitive to one or more of the serotonergic compounds.
    Dysregulated bcl-2 expression, either by t(14;18)(q32;q21) translocation or its
    introduction as a constitutively active transgene, provided protection from
    proapoptotic but not antiproliferative outcomes. These data indicate a potential
    for SERT as a novel anti-tumor target for amphetamine analogs, while evidence is
    presented that the seemingly more promising antidepressants are likely impacting
    malignant B cells independently of the transporter itself.

    2. Invest New Drugs. 2012 Aug;30(4):1471-83.
    Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine
    ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell
    Wasik AM(1), Gandy MN, McIldowie M, Holder MJ, Chamba A, Challa A, Lewis KD,
    Young SP, Scheel-Toellner D, Dyer MJ, Barnes NM, Piggott MJ, Gordon J.
    (1)School of Immunity & Infection, The Medical School, Birmingham, University of
    Birmingham, Edgbaston, Birmingham B15 2TT, UK.
    While 3,4-methylenedioxymethamphetamine (MDMA/'ecstasy') is cytostatic towards
    lymphoma cells in vitro, the concentrations required militate against its
    translation directly to a therapeutic in vivo. The possibility of 'redesigning
    the designer drug', separating desired anti-lymphoma activity from unwanted
    psychoactivity and neurotoxicity, was therefore mooted. From an initial analysis
    of MDMA analogues synthesized with a modified α-substituent, it was found that
    incorporating a phenyl group increased potency against sensitive, Bcl-2-deplete,
    Burkitt's lymphoma (BL) cells 10-fold relative to MDMA. From this lead, related
    analogs were synthesized with the 'best' compounds (containing 1- and 2-naphthyl
    and para-biphenyl substituents) some 100-fold more potent than MDMA versus the BL
    target. When assessed against derived lines from a diversity of B-cell tumors
    MDMA analogues were seen to impact the broad spectrum of malignancy. Expressing a
    BCL2 transgene in BL cells afforded only scant protection against the analogues
    and across the malignancies no significant correlation between constitutive Bcl-2
    levels and sensitivity to compounds was observed. Bcl-2-deplete cells displayed
    hallmarks of apoptotic death in response to the analogues while BCL2
    overexpressing equivalents died in a caspase-3-independent manner. Despite
    lymphoma cells expressing monoamine transporters, their pharmacological blockade
    failed to reverse the anti-lymphoma actions of the analogues studied. Neither did
    reactive oxygen species account for ensuing cell death. Enhanced cytotoxic
    performance did however track with predicted lipophilicity amongst the designed
    compounds. In conclusion, MDMA analogues have been discovered with enhanced
    cytotoxic efficacy against lymphoma subtypes amongst which high-level
    Bcl-2--often a barrier to drug performance for this indication--fails to protect.

    Chem Biol Drug Des. 2010 Nov;76(5):425-32.
    Computational studies on effects of MDMA as an anticancer drug on DNA.
    Riahi S(1), Eynollahi S, Ganjali MR.
    (1)Institute of Petroleum Engineering, University of Tehran, Iran.
    This research is designed to further understand the effects of the novel drug
    MDMA on biologic receptor of DNA. The ultimate goal is to design drugs that have
    higher affinity with DNA. Understanding the physicochemical properties of the
    drug as well as the mechanism by which it interacts with DNA should ultimately
    enable the rational design of novel anticancer or antiviral drugs. Molecular
    modeling on the complex formed between MDMA and DNA presented this complex to be
    fully capable of participating in the formation of a stable intercalation site.
    Furthermore, the molecular geometries of MDMA and DNA bases (Adenine, Guanine,
    Cytosine, and Thymine) were optimized with the aid of the B3LYP/6-31G* method.
    The properties of the isolated intercalator and its stacking interactions with
    adenine···thymine (AT) and guanine···cytosine (GC) nucleic acid base pairs were
    studied with the DFTB method. DFTB method is an approximate version of the DFT
    method that was extended to cover the London dispersion energy. The B3LYP/6-31G*
    stabilization energies of the intercalator···base pair complexes were found to be
    -9.40 and -12.57 kcal/mol for AT···MDMA and GC···MDMA, respectively. Results from
    comparison of the DFTB method and HF method conclude close results and support
    each other.
    © 2010 John Wiley & Sons A/S.

    J Neurochem. 2016 Jan;136(1):148-62.
    Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic
    neuron degeneration and neuroinflammation is age-dependent.
    Frau L(1), Costa G(1), Porceddu PF(1), Khairnar A(2), Castelli MP(3), Ennas
    MG(3), Madeddu C(3), Wardas J(4), Morelli M(1,)(5).
    (1)Department of Biomedical Sciences, Section of Neuropsychopharmacology,
    University of Cagliari, Cagliari, Italy. (2)Applied Neuroscience Research Group,
    CEITEC - Central European Institute of Technology, Masaryk University, Brno,
    Czech Republic. (3)Department of Biomedical Sciences, Section of Neuroscience and
    Clinical Pharmacology, University of Cagliari, Monserrato (CA), Italy.
    (4)Department of Neuropsychopharmacology, Institute of Pharmacology, Polish
    Academy of Sciences, Krakow, Poland. (5)CNR, Institute of Neuroscience, Cagliari,
    Previous studies have demonstrated that caffeine administration to adult mice
    potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA).
    As neuroinflammatory response seems to correlate with neurodegeneration, and the
    young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine
    neuron degeneration and glial activation in the caudate-putamen (CPu) and
    substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were
    treated with MDMA (4 × 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin
    (IL)-1β, tumor necrosis factor (TNF)-α, neuronal nitric oxide synthase (nNOS)
    were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic
    protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA
    decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers
    in CPu were only decreased in adults. In CPu of adolescent mice, caffeine
    potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b,
    whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS,
    IL-1β, and TNF-α were increased by MDMA in CPu of adults, whereas in adolescents,
    levels were only elevated after combined MDMA plus caffeine. Caffeine alone
    modified only nNOS. Results suggest that the use of MDMA in association with
    caffeine during adolescence may exacerbate the neurotoxicity and
    neuroinflammation elicited by MDMA. Previous studies have demonstrated that
    caffeine potentiated glial activation induced by
    3,4-methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine
    was shown to potentiate MDMA-induced dopamine neuron degeneration in substantia
    nigra pars compacta, astrogliosis, and TNF-α levels in caudate-putamen of
    adolescent mice. Results suggest that combined use of MDMA plus caffeine during
    adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA.
    © 2015 International Society for Neurochemistry.

    Clin Exp Pharmacol Physiol. 1995 May;22(5):381-2.
    Involvement of oxidative and L-arginine-NO pathways in the neurotoxicity of drugs
    of abuse in vitro.
    Cerruti C(1), Sheng P, Ladenheim B, Epstein CJ, Cadet JL.
    (1)Molecular Neuropsychiatry Section, NIH/NIDA/Division of Intramural Research,
    Baltimore, Maryland 21224, USA.
    1. Inhibitors of nitric oxide (NO) formation or ADP-ribosylation attenuate
    methamphetamine (METH)- and methylenedioxymetamphetamine (MDMA)-induced
    neurotoxicity on dopaminergic and serotonergic cells in primary cultures. 2. They
    also prevent METH-induced reactive gliosis in dopaminergic cultures. 3.
    Overexpression of superoxide dismutase (SOD) in cells obtained from
    SOD-transgenic mice also attenuates drug-induced toxicity. 4. These data indicate
    a role for oxygen-based and NO free radicals in the mechanisms of cell death
    associated with drugs of abuse in vitro.

    Neuroscience. 2006;139(3):1069-81.
    Ecstasy-induced cell death in cortical neuronal cultures is serotonin
    2A-receptor-dependent and potentiated under hyperthermia.
    Capela JP(1), Ruscher K, Lautenschlager M, Freyer D, Dirnagl U, Gaio AR, Bastos
    ML, Meisel A, Carvalho F.
    (1)Rede de Química e Tecnologia, Toxicology Department, Faculty of Pharmacy,
    University of Porto, Porto, Portugal. joaocapela@ff.up.pt
    Studies on 3,4-methylenedioxymethamphetamine ("ecstasy")-induced neurotoxicity
    mainly focus on damage of serotonergic terminals. Less attention has been given
    to neuronal cell death produced by 3,4-methylenedioxymethamphetamine and other
    amphetamines in areas including the cortex, striatum and thalamus. In the present
    study we investigated 3,4-methylenedioxymethamphetamine-induced neurotoxicity in
    neuronal serum free cultures from rat cortex. Since
    3,4-methylenedioxymethamphetamine intake induces hyperthermia in both animals and
    humans, the experiments were performed under normal (36.5 degrees C) and
    hyperthermic conditions (40 degrees C). Our findings showed a dose-, time- and
    temperature-dependent apoptotic cell death induced by
    3,4-methylenedioxymethamphetamine in cortical neurons.
    3,4-Methylenedioxymethamphetamine-induced damage was potentiated under
    hyperthermia. The neurotoxicity was reduced by the serotonin 2A-receptor
    antagonists, ketanserin and
    hydrochloride, in both normothermic and hyperthermic conditions.
    (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride, a model agonist for the
    serotonin 2A-receptor, also induced a dose- and time-dependent apoptotic cell
    death. Again, protection was provided by ketanserin and
    hydrochloride against (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-induced
    neurotoxicity, thereby indicating that the 3,4-methylenedioxymethamphetamine
    stimulation of the serotonin 2A-receptor leads to neurotoxicity. This study
    provides for the first time evidence that direct
    3,4-methylenedioxymethamphetamine serotonin 2A-receptor stimulation leads to
    neuronal cortical death. alpha-Phenyl-N-tert-butyl nitrone a free radical
    scavenger and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine as well
    as the NMDA-receptor antagonist MK-801 provided protection under normothermia and
    hyperthermia, thereby suggesting the participation of free radicals in
    3,4-methylenedioxymethamphetamine-induced cell death. Since
    3,4-methylenedioxymethamphetamine serotonin 2A-receptor agonistic properties lead
    to neuronal death, clinically available atypical antipsychotic drugs with
    serotonin 2A-antagonistic properties could be a valuable therapeutic tool against
    3,4-methylenedioxymethamphetamine-induced neurodegeneration.

    Pharmacol Ther. 2006 Jan;109(1-2):246-62.
    Role of nitrergic system in behavioral and neurotoxic effects of amphetamine
    Itzhak Y(1), Ali SF.
    (1)Department of Psychiatry and Behavioral Sciences, 1011 NW 15th Street Gautier
    503, University of Miami School of Medicine, Miami, FL 33136, USA.
    Several amphetamine analogs are potent psychostimulants and major drugs of abuse.
    In animal models, the psychomotor and reinforcing effects of amphetamine,
    methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), and
    methylphenidate (MPD; Ritalin) are thought to be dependent on increased
    extracellular levels of dopamine (DA) in mesocorticolimbic and mesostriatal
    pathways. However, amphetamine analogs that increase primarily serotonergic
    transmission, such as p-chloroamphetamine (PCA) and fenfluramine (FEN), have no
    potential for abuse. High doses of METH, MDMA, PCA, and FEN produce depletions of
    dopaminergic and serotonergic nerve terminal markers and are considered as
    potential neurotoxicants. The first part of this review briefly summarizes the
    behavioral and neurotoxic effects of amphetamines that have a different spectrum
    of activity on dopaminergic and serotonergic systems. The second part discusses
    evidence supporting involvement of the nitrergic system in dopamine-mediated
    effects of amphetamines. The nitrergic system in this context corresponds to
    nitric oxide (NO) produced from neuronal nitric oxide synthase (nNOS) that has
    roles in nonsynaptic interneuronal communication and excitotoxic neuronal injury.
    Increasing evidence now suggests cross talk between dopamine, glutamate, and NO.
    Results from our laboratory indicate that dopamine-dependent psychomotor,
    reinforcing, and neurotoxic effects of amphetamines are diminished by
    pharmacological blockade of nNOS or deletion of the nNOS gene. These findings,
    and evidence supporting the role of NO in synaptic plasticity and neurotoxic
    insults, suggest that NO functions as a neuronal messenger and a neurotoxicant
    subsequent to exposure to amphetamine-like psychostimulants.

    Proteomics. 2008 Sep;8(18):3906-18.
    Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated
    mitochondrial dysfunction in rat liver.
    Moon KH(1), Upreti VV, Yu LR, Lee IJ, Ye X, Eddington ND, Veenstra TD, Song BJ.
    (1)Laboratory of Membrane Biochemistry and Biophysics, National Institute on
    Alcohol Abuse and Alcoholism, Bethesda, MD 20892-9410, USA.
    Despite numerous reports citing the acute hepatotoxicity caused by
    3,4-methylenedioxymethamphetamine (MDMA) (ecstasy), the underlying mechanism of
    organ damage is poorly understood. We hypothesized that key mitochondrial
    proteins are oxidatively modified and inactivated in MDMA-exposed tissues. The
    aim of this study was to identify and investigate the mechanism of inactivation
    of oxidatively modified mitochondrial proteins, prior to the extensive
    mitochondrial dysfunction and liver damage following MDMA exposure. MDMA-treated
    rats showed abnormal liver histology with significant elevation in plasma
    transaminases, nitric oxide synthase, and the level of hydrogen peroxide.
    Oxidatively modified mitochondrial proteins in control and MDMA-exposed rats were
    labeled with biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized
    proteins, purified with streptavidin-agarose, and resolved using 2-DE.
    Comparative 2-DE analysis of biotin-NM-labeled proteins revealed markedly
    increased levels of oxidatively modified proteins following MDMA exposure. Mass
    spectrometric analysis identified oxidatively modified mitochondrial proteins
    involved in energy supply, fat metabolism, antioxidant defense, and chaperone
    activities. Among these, the activities of mitochondrial aldehyde dehydrogenase,
    3-ketoacyl-CoA thiolases, and ATP synthase were significantly inhibited following
    MDMA exposure. Our data show for the first time that MDMA causes the oxidative
    inactivation of key mitochondrial enzymes which most likely contributes to
    mitochondrial dysfunction and subsequent liver damage in MDMA-exposed animals.

    Br J Pharmacol. 2010 May;160(2):233-45.
    Methylenedioxymethamphetamine inhibits mitochondrial complex I activity in mice:
    a possible mechanism underlying neurotoxicity.
    Puerta E(1), Hervias I, Goñi-Allo B, Zhang SF, Jordán J, Starkov AA, Aguirre N.
    (1)Department of Pharmacology, University of Navarra, Spain.
    Comment in
    Br J Pharmacol. 2010 May;160(2):217-9.
    BACKGROUND AND PURPOSE: 3,4-methylenedioxymethamphetamine (MDMA) causes a
    persistent loss of dopaminergic cell bodies in the substantia nigra of mice.
    Current evidence indicates that such neurotoxicity is due to oxidative stress but
    the source of free radicals remains unknown. Inhibition of mitochondrial electron
    transport chain complexes by MDMA was assessed as a possible source.
    EXPERIMENTAL APPROACH: Activities of mitochondrial complexes after MDMA were
    evaluated spectrophotometrically. In situ visualization of superoxide production
    in the striatum was assessed by ethidium fluorescence and striatal dopamine
    levels were determined by HPLC as an index of dopaminergic toxicity.
    KEY RESULTS: 3,4-methylenedioxymethamphetamine decreased mitochondrial complex I
    activity in the striatum of mice, an effect accompanied by an increased
    production of superoxide radicals and the inhibition of endogenous aconitase.
    alpha-Lipoic acid prevented superoxide generation and long-term toxicity
    independent of any effect on complex I inhibition. These effects of alpha-lipoic
    acid were also associated with a significant increase of striatal glutathione
    levels. The relevance of glutathione was supported by reducing striatal
    glutathione content with L-buthionine-(S,R)-sulfoximine, which exacerbated
    MDMA-induced dopamine deficits, effects suppressed by alpha-lipoic acid. The
    nitric oxide synthase inhibitor, N(G)-nitro-L-arginine, partially prevented
    MDMA-induced dopamine depletions, an effect reversed by L-arginine but not
    D-arginine. Finally, a direct relationship between mitochondrial complex I
    inhibition and long-term dopamine depletions was found in animals treated with
    MDMA in combination with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
    CONCLUSIONS AND IMPLICATIONS: Inhibition of mitochondrial complex I following
    MDMA could be the source of free radicals responsible for oxidative stress and
    the consequent neurotoxicity of this drug in mice.

    Ann N Y Acad Sci. 2004 Oct;1025:119-28.
    Differential response of nNOS knockout mice to MDMA ("ecstasy")- and
    methamphetamine-induced psychomotor sensitization and neurotoxicity.
    Itzhak Y(1), Anderson KL, Ali SF.
    (1)Department of Psychiatry & Behavioral Sciences, University of Miami School of
    Medicine, Miami, Florida 33136, USA. yitzhak@med.miami.edu
    It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS)
    gene are resistant to cocaine-induced psychomotor sensitization and
    methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was
    undertaken to investigate the hypothesis that nNOS has a major role in dopamine
    (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of
    psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to
    the psychomotor-stimulating and neurotoxic effects of
    3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated.
    Repeated administration of MDMA for 5 days resulted in psychomotor sensitization
    in both WT and nNOS KO mice, while repeated administration of METH caused
    psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA
    and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These
    findings suggest that the induction of psychomotor sensitization to MDMA and METH
    is NO independent and NO dependent, respectively, while the persistence of
    sensitization to both drugs is NO dependent. For the neurochemical studies, a
    high dose of MDMA caused marked depletion of 5-HT in several brain regions of
    both WT and KO mice, suggesting that the absence of the nNOS gene did not afford
    protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic
    neurotoxicity caused by high doses of MDMA and METH in WT mice was partially
    prevented in KO mice administered with MDMA, but it was fully precluded in KO
    mice administered with METH. The differential response of nNOS KO mice to the
    behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is
    required for the expression and persistence of DA-mediated effects of METH and
    MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT
    depletion) are not dependent on nNOS.

    J Pharmacol Exp Ther. 2005 Feb;312(2):694-701.
    Evidence for the involvement of nitric oxide in
    3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain.
    Darvesh AS(1), Yamamoto BK, Gudelsky GA.
    (1)University of Cincinnati, College of Pharmacy, 3223 Eden Ave., Cincinnati, OH
    45267, USA.
    Production of reactive oxygen and/or nitrogen species has been thought to
    contribute to the long-term depletion of brain dopamine and serotonin (5-HT)
    produced by amphetamine derivatives, i.e., methamphetamine and
    3,4-methylenedioxymethamphetamine (MDMA). In the present study, the effects of
    nitric-oxide synthase (NOS) inhibitors were examined on the long-term depletion
    of striatal dopamine and/or 5-HT produced by the local perfusion of malonate and
    MDMA or the systemic administration of MDMA. The effect of MDMA on nitric oxide
    formation and nitrotyrosine concentration also was determined. Perfusion with
    MDMA and malonate resulted in a 34% reduction of 5-HT and 49% reduction of
    dopamine concentrations in the striatum. The systemic administration of NOS
    inhibitors, N(omega)-nitro-l-arginine methyl ester hydrochloride and
    S-methyl-l-thiocitrulline (S-MTC), and the peroxynitrite decomposition catalyst
    Fe(III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride attenuated the
    MDMA- and malonate-induced depletion of striatal dopamine and 5-HT. S-MTC also
    attenuated the depletion of 5-HT in the striatum produced by the systemic
    administration of MDMA without attenuating MDMA-induced hyperthermia.
    Additionally, the systemic administration of MDMA significantly increased the
    formation of nitric oxide and the nitrotyrosine concentration in the striatum.
    These results support the conclusion that MDMA produces reactive nitrogen species
    in the rat that contribute to the neurotoxicity of this amphetamine analog.
  13. cantstoppeating

    cantstoppeating Member

    Nov 11, 2014
    Millet Flour and Goitrogens
    Is there any validity to the claim that millet flour contains substances (i.e. "goitrogens") that suppress thyroid function?
    Fat oxidation and niacinamide/aspirin
    In some of your interviews you said that fat oxidation is best left to the muscle at rest, since this is their preferred fuel. Wouldn't taking substances like niacinamide and aspirin interfere with the muscles' ability to oxidise fat?
    Protein's affect on insulin
    In your article titled "Glycemia, starch, and sugar in context" you stated,
    "...If protein is eaten without carbohydrate, it will stimulate insulin secretion, lowering blood sugar and activating the stress response, leading to the secretion of adrenalin, cortisol, growth hormone, prolactin, and other hormones."

    How does eating carbohydrate with protein mitigate insulin secretion? Wouldn't the presence of carbohydrate, along with the protein, simply stimulate more insulin resulting in low blood sugar and the consequent rise in stress hormones?

    Unless by carbohydrate you mean fructose, and that it has the same affect on protein stimulated insulin secretion as it does on glucose stimulated insulin secretion i.e. it inhibits it.
    Coconut Oil and the Randle Cycle
    It's known that in the 1940s Bernardo Houssay found that coconut oil protected animals from poison-induced diabetes and in 1963 Randle described the inhibition of glucose oxidation by free fatty acids. I'm trying to reconcile the above two facts; is coconut oil exempt from becoming free fatty acids and competing with glucose in the randle cycle?
    Well cooked potatoes or ripe bananas?
    As a main carbohydrate source, between well cooked potatoes and ripe bananas, which is preferable?
    I'm currently limited to either potatoes or bananas as my main carbohydrate source. I understand that potatoes can feed bacteria in the gut resulting in endotoxin and serotonin production; bananas contain serotonin -- yet which of the two is the lesser evil?
    Cataracts and DNP
    You have an article about Cataracts and one about Fatigue, that mentions the use of DNP as an uncoupler.
    Many incidences of cataracts were reported among those who underwent DNP treatment for weight loss during the 1930s (Horner 1941).

    Do you have any thoughts on the relation between DNP and cataract formation?

    My initial thoughts after reading your articles are that the type of fat stores determined the incidence rate of cataracts i.e. if you burned PUFA via DNP, the resulting prostaglandins would cause damage to the eye. Ogino & Yasukura 1950's however found that guinea pigs fed vitamin C deficient diet developed cataracts while those that were supplemented with vitamin C did not. They went on to isolate the cataractogenic metabolite of DNP and concluded with, "This suggests that a genetic predisposition plays an important role in susceptibility to this cataract. This notion is strengthened by the fact that, in spite of extensive experiments of long duration by many authors, it has been found impossible to produce dinitrophenol cataract experimentally in various other species, namely, in rats, rabbits, guinea pigs, and dogs, although Bettman observed dinitrophenol cataract in a special strain of mice."

    Could both the type of fat stored, antioxidant deficiency and a genetic susceptibility explain the incidence rate of cataracts after DNP treatment?
    Topical thyroid (NDT) for male pattern baldness
    In a radio interview, you mentioned the use of caffeine in ethanol solution as a topical remedy for hairloss or male pattern baldness.
    I have access to a natural desiccated thyroid supplement (NDT) that's in a solution of DMSO and ethanol. Would applying this to the scalp be superior to applying caffeine to the scalp?
    Topical testosterone for Secondary Hypogonadism
    Is the use of topical testosterone 5mg/day (in 1% gel) physiologically sound for correcting low testosterone levels as a result of secondary hypogonadism?
    After reading many of your articles, my assumption is that a better solution to secondary hypogonadism is to correct steroid metabolism through diet (orange juice, milk, eggs, cheese) and a thyroid supplement. This can be augmented with a supplement of DHEA along with vitamin E, or progesterone, or pregnenolone which would convert into testosterone and DHT while minimizing conversion to estrogen.
    Is my assumption correct? Would the addition of topical testosterone supplement work in the same direction as the diet and thyroid supplement?
    Satiety with OJ and Milk
    In a number of your articles and in a radio interview, you mention the use of 1-2 quarts of OJ and 2 quarts of milk as a daily therapeutic diet.
    I have tried varying the amounts of OJ and milk for myself but have found that in order to feel satiated I often have to over consume both which causes me to put on excess body fat.
    If I count calories to ensure a daily deficit, it often means I have to reduce saturated fat intake to meet protein and sugar requirements. This however contributes to the lack of satiety.
    Do you have any thoughts on how to manage satiety levels while maintaining a small calorie deficit, or at least to stop over consumption of foods like OJ and milk?

    Potentiation of synthetic thyroid dissolved in DMSO.
    I have access to a synthetic thyroid solution containing T3 and T4 in a 1:2 ratio with DMSO and ethanol as the solvent.
    In either oral or topical ingestion, would the DMSO specifically potentiate or otherwise alter the effect of the thyroid mixture?
  14. raypeatclips

    raypeatclips Member

    Jul 8, 2016
    In response to common causes of chest pain:


    [ moderator edit: related thread RP Email Advice Discussion: Causes Of Chest Pain ]
  15. milk_lover

    milk_lover Member

    Aug 15, 2015
    My question to RP: "What is the optimal dose of DHEA if someone opts to supplement it orally?"

    RP's response: "Its production decreases fairly steadily with age, from a daily maximum of 12 to 15 mg in the teens, to nearly zero at 90, so supplements of 5 to 10 milligrams are usually safe for middle aged people."
  16. milk_lover

    milk_lover Member

    Aug 15, 2015
    milk_lover: "The last week or so, I have been taking shower with instant coffee (1 tablespoon in water) and I’ve noticed my mood is happier, my hair looks nicer, and my gyno went down a little. The problem is I get water retention. Is this normal and how do I combat that?"

    RP: "Some caffeine can be absorbed through the skin, but caffeine is a diuretic, so you probably aren’t absorbing enough. Do you drink coffee with your meals?"

    milk_lover: "Yeah I drink coffee almost after every meal. I like its effect so much that I tried it on my body and hair. Why does my mind feel better after taking the instant coffee shower if little caffeine is absorbed in the blood? Could it be the niacin? My beard gets so thick and my voice becomes deeper after the shower. I still don’t know what it is doing in my body. Coffee is truly a magical drink :)"

    RP: "It might be from the cafestol and kahweol—they are fat soluble and well absorbed by the skin."
  17. FiveAsh

    FiveAsh Member

    May 17, 2016
    I asked ray about how he supposed long distance migratory birds like swallows (trans-european to africa) could generate enough energy for the intense and prolonged muscle work of the flight without a seeming abundance of dietary enegry or large endogenous reserves of substrates for energy that a human being at its disposal like muscle and fat.

    RP said:

    "Studies in insect flight muscle found that ATP is synthesised when the muscle is (passively) stretched; i suppose it happens in birds too. Studies of nerves show that after heat is emmited during activity, heat is absorbed during recovery, i.e. The nerve slightly refrigerates its surroundings. The absorbtion of heat (besides preventing over-heating) as ATP is resynthesized would make the usual Expectations about chemical energy and work less applicable."
  18. raypeatclips

    raypeatclips Member

    Jul 8, 2016
    Q: I've recently been having one or two pieces of xylitol based gum after meals. I usually have 1 bowel movement a day but noticed after chewing gum it goes up to 3-5. Is this artificial increase in bowel movements a beneficial effect?

  19. blob69

    blob69 Member

    Nov 6, 2015
    Q: In your opinion, is a blood test for testosterone accurate for measuring its adequacy?

    A: It has to be interpreted in relation to cortisol, estrogen, and sex hormone binding globulin.

    Q: Would you mind explaining how we can compare these measurements in more detail? Is estrogen blood test reliable? This is for a male, 35 years old.

    A: It’s best to have cortisol no higher than the middle of the range, estrogen below the middle, testosterone above the middle. A vitamin D supplement often helps to improve the balance, good thyroid function is essential, adequate protein, good digestion.

    Q: By "estrogen", do you mean blood test for estradiol? What about SHBG, is it not useful for a male?

    A: Yes, blood test. I think the SHBG might be less important for men than for women.

    Q: How about if a woman decides to check these hormones, how would SHBG play into it? At what point in her menstrual cycle is it best to do the tests, or is that not relevant for these ratios?

    A: It’s best to check around the middle of the luteal phase.
  20. blob69

    blob69 Member

    Nov 6, 2015
    Q: What do you think could be the cause of a very low vitamin D blood level? Is it simply sunlight deficiency or could it indicate something else, like hypothyroidism or an inefficient liver? I wonder because so many illnesses are associated with a low vitamin D status, but on the other hand I don't see many reports of improvements when people supplement it.

    A: I’ve seen some quick improvements from serious symptoms with a supplement of it. I think low thyroid could increase the need for it. It takes lots of summer sun direct exposure of a lot of skin to make enough vitamin D.