Ray Peat Email Advice Depository

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
i asked dr peat about silicon :

Dr Peat said:
I recommend many foods containing considerable amounts of silicon, such as meats, liver, shell fish, bamboo shoots, and mushrooms, but there are many products on the market that contain silicon in forms that can be harmful.
 

EndAllDisease

Member
Joined
Jul 6, 2014
Messages
195
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:
I don’t remember the context, but it probably referred to in vitro experiments, in which alpha particles produce very large bystander effects with very little energy. A slight disturbance of cell water activates nitric oxide synthesis, and that interacts both directly and indirectly with many things, including reduced energy production and destabilization of DNA. Martin Pall and others have shown that millimeter waves, too, can interact with cell water and increase nitric oxide, suggesting that some of their effects will be the same as those of ionizing radiation. An article by Betskii and Lebedeva says millimeter waves are being used therapeutically in Russia, so the harmful effects that Pall and others describe apparently aren’t immediately apparent.

Bioelectromagnetics. 2010;31:656–63. Protein changes in macrophages induced by plasma from rats exposed to 35 GHz millimeter waves. Sypniewska RK, Millenbaugh NJ, Kiel JL, et al.

J Cell Mol Med. 2013 Aug; 17(8): 958–965.
Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects
Martin L Pall

Dose Response. 2007; 5(3): 204–213.
Targeted Radiotherapy: Microgray Doses and the Bystander Effect
Robert J. Mairs,a Natasha E. Fullerton,a,* Michael R. Zalutsky,b and Marie Boydc
Indirect effects may contribute to the efficacy of radiotherapy by sterilizing malignant cells that are not directly irradiated. However, little is known of the influence of indirect effects in targeted radionuclide treatment. We compared γ-radiation-induced bystander effects with those resulting from exposure to three radiohaloanalogues of meta-iodoben-zylguanidine (MIBG): [131I]MIBG (low linear energy transfer (LET) α-emitter), [123I]MIBG (high LET Auger electron emitter), and meta-[211At]astatobenzylguanidine ([211At]MABG) (high LET α-emitter). Cells exposed to media from γ-irradiated cells exhibited a dose-dependent reduction in survival fraction at low dosage and a plateau in cell kill at > 2 Gy. Cells treated with media from [131I]MIBG demonstrated a dose-response relationship with respect to clonogenic cell death and no annihilation of this effect at high radiopharmaceutical dosage. In contrast, cells receiving media from cultures treated with [211At]MABG or [123I]MIBG exhibited dose-dependent toxicity at low dose but elimination of cytotoxicity with increasing radiation dose (i.e. U-shaped survival curves). Therefore radionuclides emitting high LET radiation may elicit toxic or protective effects on neighboring untargeted cells at low and high dose respectively. We conclude that radiophar-maceutical-induced bystander effects may depend on LET and be distinct from those elicited by conventional radiotherapy.

Exp Oncol. 2013 Mar;35(1):58-64.
Nitric oxide coordinates development of genomic instability in realization of
combined effect with ionizing radiation.
Mikhailenko VM(1), Diomina EA, Muzalov II, Gerashchenko BI.
(1)R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
NAS of Ukraine, Kyiv 03022, Ukraine. [email protected]
The aim of this study was to investigate the ability of environmental nitrogen
oxides or natural nitric oxide (NO) donors to modify free radicals ba-lance and
development of genomic instability alone or in combination with ionizing
radiation.METHODS: Genotoxicity and cytogenetic abnormalities were assessed in
vitro in peripheral blood lymphocytes (PBL) isolated from healthy humans or in
vivo in rats PBL. Human PBL were treated with physiologically relevant NO donor -
S-Nitrosoglutathione and X-ray irradiation. The inhalation treatment of animals
with NO was carried out in chamber with purified gaseous NO mixed inside with
air. Levels of S-Nitrosohemoglobin and methemoglobin in the blood were assessed
with electron paramagnetic resonance. The total level of reactive oxygen and
nitrogen species in PBL was determined fluorometrically, and serum levels of
reactive oxygen species was determined by spectrophotometric assay. DNA damages
were assessed by alkaline single-cell gel electrophoresis. The frequency of
chromosomal aberrations in human PBL measured with the conventional cytogenetic
assay in metaphase cells on short-term (52 h) and long-term (72 h) cultures.
RESULTS: Environmental nitrogen oxides or release of NO from stable complexes
with biomolecules (such as S-Nitrosothiols) intensified generation of free
radicals, DNA damage and development of genomic instability alone or in
combination with ionizing radiation. Treatment of PBL by S-Nitrosoglutathione
caused prevalent induction of chromatid type but irradiation - chromosome
aberrations. The dose dependence of chromatid-type aberrations observed in human
PBL after combined influence of S-Nitrosoglutathione and ionizing radiation
indicates a crucial role of NO in the formation of chromosomal instability.
CONCLUSION: NO can deregulate free radicals balance resulted in genotoxic effect,
posttranslational modification of repair enzymes and thus coordinated development
of genomic instability and increase of cancer risk.

BMC Cancer. 2008 Jun 30;8:184.
Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted
irradiation.
Shao C, Folkard M, Held KD, Prise KM.
Institute of Radiation Medicine, Fudan University, No.2094 Xie-Tu Road, Shanghai
200032, PR China. [email protected]
BACKGROUND: Radiation-induced bystander responses, where cells respond to their
neighbours being irradiated are being extensively studied. Although evidence
shows that bystander responses can be induced in many types of cells, it is not
known whether there is a radiation-induced bystander effect in breast cancer
cells, where the radiosensitivity may be dependent on the role of the cellular
estrogen receptor (ER). This study investigated radiation-induced bystander
responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative
MDA-MB-231 breast cancer cells. METHODS: The influence of estrogen and
anti-estrogen treatments on the bystander response was determined by individually
irradiating a fraction of cells within the population with a precise number of
helium-3 using a charged particle microbeam. Damage was scored as chromosomal
damage measured as micronucleus formation. RESULTS: A bystander response measured
as increased yield of micronucleated cells was triggered in both MCF-7 and
MDA-MB-231 cells. The contribution of the bystander response to total cell damage
in MCF-7 cells was higher than that in MDA-MB-231 cells although the
radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with
17beta-estradiol (E2) increased the radiosensitivity and the bystander response
in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM).
E2 also increased the level of intracellular reactive oxygen species (ROS) in
MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence
on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the
treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS
increase and E2-enhanced bystander response triggered by the microbeam
irradiation, which indicates that ROS are involved in the E2-enhanced bystander
micronuclei formation after microbeam irradiation. CONCLUSION: The observation of
bystander responses in breast tumour cells may offer new potential targets for
radiation-based therapies in the treatment of breast cancer.

Br J Cancer. 2000 May;82(10):1740-6.
Involvement of energy metabolism in the production of 'bystander effects' by
radiation.
Mothersill C, Stamato TD, Perez ML, Cummins R, Mooney R, Seymour CB.
Radiation Science Centre, Dublin Institute of Technology, Ireland.
These experiments were done to determine if interference with energy metabolism
and REDOX biochemistry during low LET radiation exposure would alter the ability
of medium harvested from the irradiated cells to induce a bystander effect in
unirradiated cells. Human keratinocyte cells and CHO-K1 mutant cell lines were
irradiated using cobalt 60. Clonogenic assays were used to determine the
reproductive death of the cells exposed to direct irradiation or medium from
irradiated cells. The persistence in progeny was also examined. Use of apoptosis
inhibitors or medium from the LDH or G6PD null cell lines, reduced or prevented
the bystander effect. Transfection with G6PD recovered the effect. Treatment with
anti-oxidant substances, L-lactate and L-deprenyl prevented bystander factor
associated cell kill. The lactate analogue, oxamate, was less effective. Data
from experiments where media harvested from the different cell lines was
exchanged suggest that signal production and cellular response may involve
different mechanisms. The effects on exposed cells were transmitted to progeny
which also showed excessive levels of cell death for several generations. The
results suggest that energy/REDOX metabolism may be involved in the expression of
a radiation induced bystander response. Given the aberrant energy metabolism in
tumour cells, this may have implications for dose escalation in radiotherapy.
 

Lilac

Member
Joined
May 6, 2014
Messages
636
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.
 

Lightbringer

Member
Joined
Jan 24, 2014
Messages
235
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 ?

Trace impurities can inactivate it, but some liquid forms have worked.
 

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
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 ?

Ray Peat said:
I think people have extrapolated ideas from EFAD rats to cats, without recognizing that carnivores have higher metabolic rates and nutritional needs, so that the mistakes of the Burrs are even easier to make.

Br J Nutr. 1981 Jul;46(1):93-6.
Essential fatty acid deficiency and evidence for arachidonate synthesis in the
cat.
Sinclair AJ, Slattery W, McLean JG, Monger EA.
1. There is controversy regarding the capacity of the cat to convert 18: 2 omega
6 to 20: 4 omega 6 and the ability of the essential fatty acid (EFA)-deficient
cat to produce 20: 3 omega 9. 2. This paper reports the isolation and
identification of 20: 3 omega 9 from kidney phospholipids of EFA-deficient cats.
3. The results suggest that the cat is capable of limited synthesis of 20: 4
omega 6 using a delta 5- and delta 8-desaturase.

..........

[ moderator edit: related disussion PUFAs Role On Skin ]
 
Last edited by a moderator:

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
on jacuzzi and hot tubs,

Ray peat said:
Getting the body temperature too high can deplete glycogen and lower blood glucose, sometimes causing fainting, probably why people occasionally drown in hot tubs; high temperature can damage the testes, reducing sperm production.
 

Dan W

Member
Joined
Jan 22, 2013
Messages
1,528
In response to a question about DMSO:
Ray Peat said:
I got interested in it in 1965, after reading about Stanley Jacob’s ideas, and experimented with it occasionally over the next several years. I was interested in its effects on cell water, stabilizing it in a way that reduces some kinds of inflammation. It seems to accelerate some enzyme reactions. I later started to think about its own chemical properties, rather than thinking of it as just a solvent. It isn’t stable in the presence of water, and the odor seems to indicate the degree of its decomposition. It occasionally helps slightly with joint pain, but it can cause intense skin reactions, rashes; I think some of its effects depend on the breakdown products. People often forget that it has an intrinsic oxidative effect when they are thinking of it as just a solvent, to transport drugs. I saw a product sold as eye drops, consisting of vitamin C and glutathione in DMSO. Each of those reductants, in the presence of DMSO, immediately breaks down into other substances, and the composition changes continually over a long period. There has been very little investigation of the actual composition of solutions of DMSO with other substances. At least some of the mixtures will produce sulfite and metabisulfite, which are very allergenic for some people. Small amounts are probably harmless; even large amounts seem harmless for some people. Its ability to release histamine and nitric oxide and to inhibit cholinesterase (articles below) suggest that its use shouldn’t be prolonged.

Arch Dermatol. 1988 Feb;124(2):182-3.
Systemic contact dermatitis medicamentosa occurring after intravesical dimethyl
sulfoxide treatment for interstitial cystitis.
Nishimura M, Takano Y, Toshitani S.

Eye (Lond). 2001 Jun;15(Pt 3):332-3.
Lens deposits associated with RIMSO-50 (dimethylsulphoxide).
Rowley S, Baer R.

Cornell Vet. 1986 Jan;76(1):61-90.
Dimethyl sulfoxide (DMSO): a review.
Brayton CF.
Dimethyl sulfoxide (DMSO) is a very simple compound that has stimulated much
controversy in the scientific and popular literature. Fig. 1 It is an aprotic
solvent. Therapeutic and toxic agents that are not soluble in water are often
soluble in DMSO. DMSO has a very strong affinity for water; on exposure to air,
pure DMSO is rapidly diluted. DMSO's physiologic and pharmacologic properties and
effects are incompletely understood. Properties that are considered to be
particularly important to its therapeutic and toxic effects include: its own
rapid penetration and enhanced penetration of other substances across biologic
membranes; free radical scavenging; effects on coagulation; anticholinesterase
activity; and DMSO-induced histamine release by mast cells. DMSO's systemic
toxicity is considered to be low. Combinations of DMSO with other toxic agents
probably constitute its greatest toxic potential. The scientific literature is
reviewed with particular attention to mechanisms underlying DMSO's reported
therapeutic and toxic effects. Currently approved, veterinary applications of
DMSO are limited. DMSO's potential value in specific, approved and unapproved
veterinary applications is discussed.

Ukr Biokhim Zh (1999). 2001 Jul-Aug;73(4):114-9.
[Potentiation of the cataractogenic effect of light by dimethylsulfoxide and
adrenaline].
[Article in Russian]
Metelitsyna IP(1).
(1)Filatov Institute of Eye Diseases and Tissue Therapy, Academy of Medical
Sciences of Ukraine, Odessa. [e-mail redacted]
On the basis of the data about possible potentiation of polychromatic light
cataractogenic effect by adrenaline and dimethylsulfoxide preparations, obtained
by us earlier (increasing of animals number with changes of lenses and metabolic
disturbances, of the first clinical signs of cataract in more earlier terms, more
rapid development occurred in lenses opacities, more intensive changes of lenses
substance), we have studied some biochemical parameters (peroxide resistance of
erythrocyte, the level of free amine nitrogen, activity of Na,K-ATP-ase,
gamma-glutamiltranspeptidase, ceruloplasmin) in blood, liver and tissues of
rabbits eyes, during modelling of the light cataract on the background of
supplementary application of adrenalin and dimethylsulfoxide. It was shown that
one of the possible mechanisms of cocataractogenic action of the studied
substances is the revealed fact of increasing the metabolic systems disturbances,
caused by long-term irradiation of the animals.

AJNR Am J Neuroradiol. 1999 Mar;20(3):401-10.
A reexamination of the angiotoxicity of superselective injection of DMSO in the
swine rete embolization model.
Chaloupka JC(1), Huddle DC, Alderman J, Fink S, Hammond R, Vinters HV.
(1)Department of Diagnostic Radiology, Yale University School of Medicine, USA.
BACKGROUND AND PURPOSE: There are a variety of embolization applications for
non-adhesive, liquid agents. We reevaluated the potential microvascular
angiotoxicity of superselective infusions of dimethyl sulfoxide (DMSO) using very
long infusion rates in a previously described animal model.
METHODS: Twenty-six swine underwent percutaneous femoral puncture for
superselective catheterization of the artery of the rete while being continuously
monitored for ECG and intraarterial pressure. Two volumes (0.5 or 0.8 mL) and
three durations (30, 60, and 90 seconds) of superselective infusion of DMSO were
used to evaluate the effect of a single-dose rate within an ipsilateral rete.
Contralateral control infusions of normal saline were also administered. Acute
hemodynamic and angiographic outcomes were assessed. After recovery, follow-up
angiography and sacrifice were performed at either 10 or 28 days. Brains and
retia were harvested for gross and microscopic histopathologic evaluation.
RESULTS: No significant hemodynamic alterations occurred acutely. Twenty-three of
the 24 infused retia showed variable acute vasospasm that typically was mild to
moderate in severity and transient (10 to 20 minutes). Follow-up angiography at
sacrifice always showed normal retial arterial anatomy. No adverse clinical
sequelae were noted. Gross inspection of brains showed no evidence of infarction
or subarachnoid hemorrhage. Microscopic histopathologic examination of retia
showed mostly nonspecific changes in both exposed and control samples. Possible
causal histotoxicity was seen in four retia (three of four exposed to higher dose
rates), in which involvement was limited to one to three retial arteries.
CONCLUSION: Lower total dose and dose rates of superselective infusion of DMSO
into the retial microarterial network resulted in substantially less
angiotoxicity than that found in a previous study, as defined by clinical,
angiographic, gross, and histopathologic criteria.

Anticancer Res. 1998 Nov-Dec;18(6B):4705-8.
Clinical toxicity of cryopreserved circulating progenitor cells infusion.
Zambelli A(1), Poggi G, Da Prada G, Pedrazzoli P, Cuomo A, Miotti D, Perotti C,
Preti P, Robustelli della Cuna G.
(1)Divisione di Oncologia Medica, IRCCS Fondazione S. Maugeri, Centro Medico di
Pavia, Italy.
BACKGROUND: We evaluated the infusion-related toxicity of cryopreserved
autologous circulating progenitor cells transplanted in 22 patients receiving
high dose chemotherapy and stem cells transplantation for malignancy.
MATERIALS AND METHODS: Progenitor cells were collected following mobilization
with chemotherapy plus filgrastim and stored in liquid nitrogen in the presence
of 10% dimethylsulfoxide (DMSO). Before infusion of the graft, patients were
medicated with mannitol, hydrocortisone and clorphenamine. The amount of DMSO
infused as well as the number of dead and damaged cells were evaluated as
possible cause of toxicity.
RESULTS: Eleven patients (50%) experienced symptoms related to graft infusion,
nausea and vomiting being the most common adverse events. Hypotension was
documented in 3 patients (one of them developing transient bradycardia resolved
with atropin administration) and one had hypertension with tachycardia. Other
observed side effects were: chest tightness (2 pts), fever and chills (3 pts),
associated with abdominal cramps (2 pts). 7 out of 8 (88%) patients infused with
greater than 30 mL volume of DMSO experienced side-effects, the grade of toxicity
being significantly less in those receiving lower amount (< 30 mL) of DMSO. Two
out of 4 pts who received the highest number of dead cells (> 10 x 10(9))
developed toxicity.
CONCLUSIONS: In our experience the infusion of cryopreserved peripheral blood
progenitors caused minor to moderate toxicity in most cases and, when present,
side effects were observed only during infusion. The amount of DMSO present in
the graft is related to the grade of toxicity.

Cytotherapy. 1999;1(6):439-46.
Post-thaw removal of DMSO does not completely abrogate infusional toxicity or the
need for pre-infusion histamine blockade.
Rowley SD(1), Feng Z, Yadock D, Holmberg L, Macleod B, Heimfeld S.
(1)Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle,
Washington, USA.
BACKGROUND: The infusion of PBSC or BM cells cryopreserved with DMSO is
associated with frequent, but generally minor, toxicity. The incidence and
severity of infusion-related toxicity is proportional to the amount of DMSO
infused. In an attempt to reduce the incidence of symptoms reported by patients
receiving cryopreserved PBSC and to avoid the necessity of diphenhydramine
premedication, we studied the infusion of PBSC components from which the DMSO was
depleted after thawing.
METHODS: This was a Phase I/II study of post-thaw removal of DMSO. Patients
undergoing autologous PBSC transplantation with components cryopreserved using
10% DMSO were eligible. The PBSC components were thawed, diluted with 10%
dextran-40 and 5% HSA, centrifuged to remove the DMSO, resuspended in dextran and
HSA, and infused without prior medication of the patient. Visual analog scale
questionnaires were used for measurement of infusion-related symptoms.
RESULTS: Five patients were enrolled on this study and received washed PBSC
components. One patient experienced severe infusion-related toxicity and the
study was stopped for safety reasons. Events experienced by these patients
included flushing (two patients), emesis (three patients), and post-infusion
rigors (two patients). Two patients reported an increase in nausea after the
infusion. All patients achieved granulocyte engraftment (an ANC > 0.5 x 10(9)/L)
at a median of 14 days and platelet engraftment (platelet count without
transfusion > 20 x 10(9)/L) at a median of 11 days. No patient required infusion
of additional cells because of engraftment failure.
DISCUSSION: In theory, the post-thaw reduction of DMSO should reduce the risk of
infusion-related toxicity that is commonly attributed to DMSO. Although not
demonstrated by the data developed from this study, effective reduction in DMSO
could also eliminate the need for pre-infusion histamine blockade. However, the
technique used in this study was not adequate and a more rigorous depletion
technique must be developed to completely abrogate clinical infusion-related
toxicity.

Cell Biol Int. 2005 Jul;29(7):529-36.
NF-kappaB and NOS may play a role in human RPMI-8402 cell apoptosis.
Trubiani O(1), Salvolini E, Vignini A, D'Arcangelo C, Di Primio R, Mazzanti L.
(1)Dipartimento di Scienze Odontostomatologiche, Università di Chieti-Pescara,
Via Dei Vestini, 35, 66100 Chieti, Italy.
Apoptosis is a fundamental process that is required for the normal development
and functioning of the immune system. It can be induced in different ways
depending on cell type and acquired signal. Since the NF-kappaB transcription
factor complex is believed to be involved in nitric oxide-induced apoptosis, the
aim of this study was to investigate NF-kappaB and nitric oxide synthase (NOS)
activity during dimethyl sulphoxide (DMSO)-dependent cell death of RPMI-8402
human pre-T cells. Our results show that NF-kappaB activation is associated with
a significant up-regulation of NOS activity and induction of apoptosis.
Furthermore, the inhibition and reversal of these effects by parthenolide
treatment or DMSO removal indicate that these molecules are directly involved in
the progression of cell death.

Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):253-9.
DMSO modifies structural and functional properties of RPMI-8402 cells by
promoting programmed cell death.
Trubiani O(1), Salvolini E, Staffolani R, Di Primio R, Mazzanti L.
(1)Dipartimento di Scienze Odontostomatologiche, University of Chieti, Italy.
Apoptosis in lymphoid cells can be induced in different ways depending on cell
type and acquired signal. Biochemical modifications occur at an early phase of
cell death while at late times the typical morphological features of apoptosis
can be visualized. The aim of this study is to verify by multiparametric analyses
the plasma membrane fluidity, the intracellular Ca2+ concentration and the nitric
oxide synthase (NOS) activity during cell death progression induced by DMSO
treatment. The RPMI-8402 human pre-T lymphoblastoid cell line was induced to cell
death by DMSO. Analyses rescued at early times of treatment prove a substantial
modification of plasma membrane fluidity associated with an increase of
intracellular Ca2+. Moreover, these modifications are associated with an up
regulation of NOS activity. Our results are consistent with the hypothesis that
programmed cell death can be induced by up regulation of the intracellular Ca2+
associated with an increase of cell membrane fluidity. The apoptotic mechanisms
seem to involve not only membrane damage and increased intracellular calcium
levels but also production of nitric oxide.


Vet Hum Toxicol. 1998 Apr;40(2):87-9.
Sulfhemoglobinemia after dermal application of DMSO.
Burgess JL(1), Hamner AP, Robertson WO.
Author information:
(1)Washington Poison Center, Seattle 98125-8012, USA.
A 43-y-old Caucasian female applied 4 ounces of dimethyl sulfoxide (DMSO) to her
lower abdomen for treatment of interstitial cystitis. Within 24 h she developed
fatigue, cyanosis and dyspnea with mild exertion. She sought medical attention 10
d later, at which time initial laboratory tests revealed a methemoglobin level of
47%. Two doses of 1 mg methylene blue/kg i.v. were given without significant
improvement in either her cyanosis or methemoglobin level. Repeat analysis the
day following admission using an outside lab demonstrated a sulfhemoglobin level
of 6.2% and a methemoglobin level of < 0.1%. No prior reports have associated
sulfhemoglobin formation with DMSO application. Carbon monoxide-oximetry may
falsely identify sulfhemoglobin as methemoglobin; sulfhemoglobinemia should be
considered in cases of methemoglobinemia refractory to methylene blue therapy.

Nephron. 1996;72(2):356-7.
Multiple organ failure associated with dimethylsulfoxide and hydroxyethyl starch
in autologous blood stem cell transplantation.
Nishihara G, Sakemi T, Ikeda Y, Baba N, Shimamoto Y.

Contact Dermatitis. 1998 Feb;38(2):90-5.
Susceptibility to skin stinging, non-immunologic contact urticaria and acute skin
irritation; is there a relationship?
Coverly J(1), Peters L, Whittle E, Basketter DA.
(1)Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Adverse skin reactions cover many types of response: toxic, irritant, allergic,
urticarial, sensory, etc. The relationships between an individual's tendency to
develop different types of skin response are not well-described. We examined
whether those who perceive stinging might be more likely to experience
urticarial, sensory and irritation reactions in skin. A panel of 86 volunteers
was tested with 10% lactic acid in the nasolabial fold to assess their ability to
perceive stinging. At the same time, their capacity to develop non-immunologic
contact urticaria was evaluated using chemicals of different structural type and
urticant ability: methyl nicotinate, benzoic acid, cinnamic acid, cinnamaldehyde
and dimethyl sulfoxide (DMSO). DMSO was also used to assess sensory effects and
skin irritation. 44 were classes as "stingers" and 42 as "non-stingers". The
pattern of urticant reactivity in the stingers and non-stingers was essentially
the same, with neat DMSO generating the strongest reactions in both groups.
Sensory reactions to DMSO (stinging, itching, tingling or burning) were similar
in stingers and non-stingers; although the former may have reacted more quickly,
a smaller proportion reacted (64% versus 76%). The skin irritation response to
DMSO was also identical in stingers and non-stingers and the intensity of the
urticant response in an individual did not correlate with the intensity of their
subsequent irritant reaction. In conclusion, this study demonstrated that an
individual's ability to perceive skin stinging does not give a general indication
of their susceptibility to other types of non-immunologic skin response. Indeed,
there appeared to be little evidence of correlations between any of the skin
effects studied.

Urology. 1981 Jul;18(1):21-6.
Prospective study of intravesical dimethyl sulfoxide in treatment of suspected
early interstitial cystitis.
Fowler JE Jr.
The efficacy of intravesical instillations of dimethyl sulfoxide (DMSO) in the
treatment of suspected early interstitial cystitis was investigated in a
prospective study. Among 20 patients treated, complete symptomatic remissions
were achieved in 3, partial symptomatic remissions were achieved in 16, and 1 had
no symptomatic improvement. However, functional bladder capacities following
treatment were increased by more than 25 per cent in only 4 cases. Among 16
patients who experienced symptomatic remissions and who have been followed for
greater than or equal to four months, 14 had sustained remissions (mean follow-up
eleven months) and 2 had unsustained remissions. Clinically apparent toxicity was
minimal but transient elevation of the serum lactic acid dehydrogenase was
occasionally observed during treatment. DMSO appears to be useful in the
management of carefully selected patients with suspected early interstitial
cystitis.

Lancet. 1981 Jan 31;1(8214):276-7.
Dimethylsulphoxide toxicity.
Greenfield C.

Med Sci Sports Exerc. 1981;13(4):215-9.
The use of DMSO in tennis elbow and rotator cuff tendonitis: a double-blind
study.
Percy EC, Carson JD.
Over a 1-yr period, 102 patients with a clinical diagnosis of either medial or
lateral epicondylitis (tennis elbow) or rotator cuff tendonitis were treated with
topical applications of dimethyl sulfoxide (DMSO). A double-blind controlled
study was carried out on these patients in the private practice of an orthopaedic
surgeon to determine the efficacy of this material in the treatment of these two
common clinical conditions. Beneficial effects were assessed with respect to
improvement in pain, tenderness or swelling, and increase in the range of motion.
Forty patients were treated for each of the two ailments; patients treated with
the 70% DMSO aqueous solution did not receive any more beneficial effect from the
drug than patients who received 5% DMSO aqueous placebo solution.

Lancet. 1980 Nov 8;2(8202):1004-6.
Dimethylsulphoxide-induced toxicity.
Yellowlees P, Greenfield C, McIntyre N.
Two elderly people were given intravenous infusion of dimethylsulphoxide (DMSO)
as treatment for arthritis. One became seriously ill, the other remained well.
Both had similar changes in aspartate transaminase, hydroxybutyrate
dehydrogenase, and creatine kinase and evidence of haemolysis. This is the first
report of serum enzyme changes and anaemia after intravenous DMSO in man.

Med Monatsschr. 1974 Aug;28(8):325-6.
[Dimethyl sulfoxide is not dead].
[Article in German]
Simon KH.

Med Klin. 1974 Oct 18;69(42):1683-8.
[Iatrogenic cataracts].
[Article in German]
Koch HR, Hockwin O.

Am J Optom Arch Am Acad Optom. 1972 Apr;49(4):308-19.
Cataracts induced in guinea pigs by acetone, cyclohexanone, and dimethyl
sulfoxide.
Rengstorff RH, Petrali JP, Sim VM.

CRC Crit Rev Toxicol. 1971 Sep;1(1):93-118.
The cataractogenic activity of chemical agents.
Gehring PJ.

Arch Geschwulstforsch. 1971;37(1):1-3.
[Question of carcinogenic action of dimethyl sulfoxide (DMSO)].
[Article in German]
Lohs K, Damerau W, Schramm T.

Ophthalmologica. 1969;158 Suppl:488-93.
Changes in rabbit lenses following DMSO therapy.
Wood DC, Wirth NV.

Int Ophthalmol Clin. 1970 Fall;10(3):553-619.
Some iatrogenic ocular diseases from systemically administered drugs.
Bernstein HN.

J Pharmacol Exp Ther. 1969 Dec;170(2):364-70.
The ocular effects of repeated dermal applications of dimethyl sulfoxide to dogs
and monkeys.
Smith ER, Mason MM, Epstein E.

Northwest Med. 1969 Jan;68(1):39-41.
Eye effects of DMSO. Report of negative results.
Hull FW, Wood DC, Brobyn RD.

Schweiz Med Wochenschr. 1968 Nov 16;98(46):1829-37.
[About some effects of dimethyl sulfoxide (DMSO) in percutaneous use].
[Article in German]
Kappert A.

Exp Pathol (Jena). 1975;10(5-6):364-5.
Tumor-inducing effect of trinitroso-trimethylene-triamine (TTT) when orally
applied in dimethylsulphoxide (DMSO) for solvent.
Urban H, Amlacher E, Danz M.
By oral application of TTT, disolved in concentrated DMSO, it was possible by
means of a long-term experiment to produce tumors in female rats (Wistar strain).
Contrary to all previous findings the tumor-inducing effect of this substance has
been proved in this way for the first time.

Ann Hematol. 2015 Mar;94(3):511-3.
DMSO induced myocardial infarction during allogeneic cryopreserved bone marrow
transplant.
Khawandanah M(1), Hopps S, Nabeel S, Ahmad B, Weiss S, Holter Charkrabarty J,
Yuen C, Selby G.
(1)Hematology-Oncology Section, Department of Medicine, The University of
Oklahoma Health Sciences Center, Oklahoma City, OK, USA,
[e-mail redacted]

Ann Hematol. 2013 Nov;92(11):1571-2.
Severe vasospastic angina with hemodynamic compromise related to the infusion of
dimethyl sulfoxide (DMSO)-cryopreserved autologous peripheral blood stem cells.
Bambace NM(1), Lachance S.
(1)Blood and Marrow Transplant Program, Division of Hematology and Medical
Oncology, Hôpital Maisonneuve-Rosemont, Université de Montréal, 5415 Boul. de
L'Assomption, Montreal, Quebec, H1T 2M4, Canada, [e-mail redacted]

Ann Pharm Fr. 1970 Apr;28(4):263-70.
[Damage of limb buds of chicken embryos by dimethyl sulfoxide].
[Article in French]
Cros S, Voisin MC, Tollon Y, Oreglia J.

Int Ophthalmol Clin. 1971;11(2):63-97.
Effects of drugs on the lens.
Paterson CA.
PIP: The effects of drugs that cause changes in the lens, principally cataractous
changes, are discussed. The cataractogenic compounds reported on include 1) drugs
used in ophthalmic practice (miotics and topical steroids), 2) compounds used in
systemic therapy of a wide range of disorders (corticosteroids
andphenothiazines), and 3) compounds that are known to be cataractogenic in
animals but not in man (Myleran). Of special interest to family planners is a
section on the effects of oral contraceptives on lens changes. Whether long-term
use of oral contraceptives would produce ocular complications was queried by
Cogan. The influence of these drugs on ocular tissues was subsequently studied,
but no significant lens changes were described. Other ocular abnormalities were,
however, detected. In rabbit studies, it was shown that mestranol in
norethynodrel caused anterior lens changes. Cataracts and other lesions were
produced in rats fed a synthetic progestin-estrogen. In vitro changes in lens
permeability caused by progestins and progestins and estrogens were demonstrated
by Lambert. A dose-dependent increase in rubidium-86 efflux (a measure of lens
cell permeability) was demonstrated for several progestins and estrogens. An
alteration in cation and water content and lens clarity was also observed. Such
physiological changes are similar to those induced by progestins and estrogens in
erythrocytes, mitochondria, and lysosomes. It is noted that although the
concentrations of drugs used in animals and in vitro studies are high, there is a
need for well-controlled, long-term opthalmological studies on women who have
chosen oral contraceptives.

Fortschr Ophthalmol. 1988;85(4):396-9.
[Significance of experimental cataracts for the development of senile cataracts
exemplified by naphthalene and dimethyl sulfoxide-induced lens opacities].
[Article in German]
Rossa V, Kluxen G.

Ann N Y Acad Sci. 1975 Jan 27;243:98-103.
Toxicity of dimethyl sulfoxide, alone and in combination.
Rubin LF.

Med Klin. 1974 Oct 18;69(42):1683-8.
[Iatrogenic cataracts].
[Article in German]
Koch HR, Hockwin O.

Invest Ophthalmol. 1974 Oct;13(10):713-24.
Mechanisms initiating cataract formation. Proctor Lecture.
Kinoshita JH.

Exp Eye Res. 1972 Sep;14(2):91-8.
Some changes in the lens of the dimethylsulphoxide-fed rabbit.
Van Heyningen R, Harding JJ.

CRC Crit Rev Toxicol. 1971 Sep;1(1):93-118.
The cataractogenic activity of chemical agents.
Gehring PJ.

Int Ophthalmol Clin. 1970 Fall;10(3):553-619.
Some iatrogenic ocular diseases from systemically administered drugs.
Bernstein HN.

Radiology. 1969 Jan;92(1):156-8.
Anomalous effects of dimethyl sulfoxide on the response of the mouse lens and
cornea to x-irradiation: "protection" of lens and "sensitization" of cornea.
Hagemann RF, Evans TC, Riley EF.

Ann N Y Acad Sci. 1967 Mar 15;141(1):392-401.
Dimethyl sulfoxide in ophthalmology, with especial reference to possible toxic
effects.
Gordon DM.

Br Vet J. 1971 Jul;127(7):301-3.
Drug-induced lenticular lesions in the dog.
Heywood R.
 

Dan W

Member
Joined
Jan 22, 2013
Messages
1,528
In response to a question about sugar bleaching:
Ray Peat said:
The bleaching is essentially washing, washing the molasses residue away from brown sugar, and I think charcoal is used to absorb the last traces of impurities. The products vary in the thoroughness of the washing, some have a faint yellow color and weak molasses taste; the whitest is least likely to be allergenic.
 

Dan W

Member
Joined
Jan 22, 2013
Messages
1,528
In response to a question about magnesium malate:
Ray Peat said:
I haven’t seen it sold for a long time, but I think it’s o.k.; it’s good to watch for allergy reactions such as a headache.
 

Dan W

Member
Joined
Jan 22, 2013
Messages
1,528
In response to a question about the theory of body weight having a "set point":
Ray Peat said:
I think habituation to a certain environment and way of living is another way of saying it.
 

Makrosky

Member
Joined
Oct 5, 2014
Messages
3,982
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
death.
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.
[email protected]
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,
Italy.
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. [email protected]
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
(2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrolidinol
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
(2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrolidinol
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
analogs.
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.
[email protected]
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. [email protected]
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.
 
Joined
Nov 11, 2014
Messages
585
Millet Flour and Goitrogens
Is there any validity to the claim that millet flour contains substances (i.e. "goitrogens") that suppress thyroid function?
Ray Peat said:
It’s only a diet dominated by goitrogenic foods that’s a problem, small amounts don’t have noticeable effects.

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?
Ray Peat said:
Aspirin increases oxygen consumption; although niacinamide can reduce excessive lipolysis, I don't know whether it would lower resting lipolysis.

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.
Ray Peat said:
It mitigates the damage produced by the stress response to hypoglycemia.

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?
Ray Peat said:
Relative to PUFA, yes. When the body contains a lot of PUFA, eating coconut oil increases oxidative metabolism, partly because of the shorter fatty acids that are more quickly oxidized, like sugar, and partly because of the antimetabolic effects of the PUFA that they displace. More recently, several investigators have found that a “deficiency of essential fatty acids” is highly protective against diabetes.
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?
Ray Peat said:
Potatoes are much better, unless you’re allergic to them (it usually goes with allergy to tomato and bell peppers).
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?
Ray Peat said:
The toxicity of DNP was known from the beginning of the 20th century. The cataract epidemic came on suddenly in the spring of 1935, probably because of a product with a larger dose. The cataracts caused by DNP appear within a few hours or days of taking the drug, and disappear spontaneously when the drug is stopped, more quickly with vitamin C supplement. The FDA used the cataract outbreak to get new powers. The production of permanent cataracts by estrogens and glucocorticoids hasn’t led to any action at all by the FDA.
References:
Klin Monbl Augenheilkd. 1973 May;162(5):621-9.
[Ophthalmological complications after oral contraceptives].
[Article in German]
Varga M.

Bull Soc Ophtalmol Fr. 1972 Apr;12(4):441-2.
[3 cases of cataract occurring in women taking the same oral contraceptive. Is
this a coincidence?].
[Article in French]
Goddé-Jolly D, Ruellan YM, Bremme C, Théron HP.

Bull Soc Ophtalmol Fr. 1974 Dec;74(12):1119-23.
[Contraceptive agents and cataract].
Offret G, Haut J, Limon S, Clay C.
PIP: 3 cases of cataracts in young women after regular and prolonged use of an
oral contraceptive (Stediril, used by 80-90% of the women under such treatment in
France) are reported. In 1 case, after thorough examination, the use of
contraceptives was ruled out as a factor causing the cataract. However, the
authors are of the opinion that cataract cases among young women are increasing,
and recommend further studies to establish a possible correlation with the use of
oral contraceptive. The report is followed by a discussion with a panel of
colleagues, some of whom report similar cases.

Lancet. 1987 Nov 7;2(8567):1070-2.
Tamoxifen and benign breast problems.
Fentiman IS(1), Powles TJ.
(1)Clinical Oncology Unit, Guy's Hospital, London.
The agent tamoxifen plays an important part in the treatment of breast cancer.
Although it acts as an antioestrogen by binding to oestrogen receptors, it also
has oestrogen agonistic effects on the liver. Recent toxicity studies in rats
have revealed that after high dosages both cataracts and hepatocellular
carcinomas develop. For these reasons it has been suggested that use of tamoxifen
be discontinued for the treatment of benign conditions such as severe cyclical
mastalgia and also for trials on the prevention of breast cancer. It is argued
that the development of hepatocellular carcinomas in rats is the result of the
known oestrogen agonist activity of tamoxifen, with similar results being found
in a few women receiving oral contraceptives,
the use of which still continues.
Studies of the use of the agent for benign conditions should evolve in the
context of controlled clinical trials in order that important new indications for
tamoxifen are not overlooked.

Ann Ophthalmol. 1992 Nov;24(11):418-9.
Hyperprolactinemia and lens opacities.
Costagliola C(1), Mastropasqua L, Amato G, Carella C.
(1)Eye Clinic, 1st School of Medicine, Federico II University, Naples, Italy.
We report the presence of lens opacities in patients with prolactin-secreting
microadenomas of the pituitary gland. The occurrence of lens opacities was
related to prolactin serum levels and appeared only in women. The mechanism by
which prolactin induces cataract is not known, although this hormone could affect
the lens's permeability to ions, water, sugars, and amino acids. Moreover, the
lens opacities found in women but not in men seem to indicate synergism with
estrogens.

J Clin Invest. 1994 Oct;94(4):1690-7.
Tamoxifen blocks chloride channels. A possible mechanism for cataract formation.
Zhang JJ(1), Jacob TJ, Valverde MA, Hardy SP, Mintenig GM, Sepúlveda FV, Gill DR,
Hyde SC, Trezise AE, Higgins CF.
(1)Department of Physiology, University of Wales, Cardiff, United Kingdom.
Tamoxifen is an antiestrogen frequently used in the treatment of breast cancer
and is currently being assessed as a prophylactic for those at high risk of
developing tumors. We have found that tamoxifen and its derivatives are
high-affinity blockers of specific chloride channels. This blockade appears to be
independent of the interaction of tamoxifen with the estrogen receptor and
therefore reflects an alternative cellular target. One of the clinical side
effects of tamoxifen is impaired vision and cataract. Chloride channels in the
lens of the eye were shown to be essential for maintaining normal lens hydration
and transmittance. These channels were blocked by tamoxifen and, in organ
culture, tamoxifen led to lens opacity associated with cataracts at clinically
relevant concentrations. These data suggest a molecular mechanism by which
tamoxifen can cause cataract formation and have implications for the clinical use
of tamoxifen and related antiestrogens.

Int Ophthalmol Clin. 1971;11(2):63-97.
Effects of drugs on the lens.
Paterson CA.
PIP: The effects of drugs that cause changes in the lens, principally cataractous
changes, are discussed. The cataractogenic compounds reported on include 1) drugs
used in ophthalmic practice (miotics and topical steroids), 2) compounds used in
systemic therapy of a wide range of disorders (corticosteroids
andphenothiazines), and 3) compounds that are known to be cataractogenic in
animals but not in man (Myleran). Of special interest to family planners is a
section on the effects of oral contraceptives on lens changes. Whether long-term
use of oral contraceptives would produce ocular complications was queried by
Cogan. The influence of these drugs on ocular tissues was subsequently studied,
but no significant lens changes were described. Other ocular abnormalities were,
however, detected. In rabbit studies, it was shown that mestranol in
norethynodrel caused anterior lens changes. Cataracts and other lesions were
produced in rats fed a synthetic progestin-estrogen. In vitro changes in lens
permeability caused by progestins and progestins and estrogens were demonstrated
by Lambert. A dose-dependent increase in rubidium-86 efflux (a measure of lens
cell permeability) was demonstrated for several progestins and estrogens. An
alteration in cation and water content and lens clarity was also observed. Such
physiological changes are similar to those induced by progestins and estrogens in
erythrocytes, mitochondria, and lysosomes. It is noted that although the
concentrations of drugs used in animals and in vitro studies are high, there is a
need for well-controlled, long-term opthalmological studies on women who have
chosen oral contraceptives.

Curr Eye Res. 2015 May;40(5):541-8.
Estradiol biosynthesis in canine lens epithelial cells.
Colitz CM(1), Lu P, Sugimoto Y, Barden CA, Chandler HL.
(1)Veterinary Clinical Sciences .
PURPOSE: To confirm that lens epithelial cells (LEC) synthesize 17β-estradiol,
active estrogen, and to identify the pathway(s) by which normal and cataractous
LEC synthesize 17β-estradiol.
METHODS: ELISA was used to measure estradiol in aqueous humor;
immunohistochemical staining was used to localize estradiol, testosterone and
sulfatase; tritiated water release assay was used to measure aromatase activity;
and qRT-PCR was used to quantify expression of aromatase and sulfatase in normal
and cataractous canine and human LEC.
RESULTS: Canine eyes with and without cataracts had no differences in aqueous
humor estradiol levels; however, cataractous LEC had more intense
immunoreactivity for estradiol than normal LEC.
There were little to no
differences in canine sulfatase protein and mRNA expression when normal and
cataractous LEC were compared. qRT-PCR demonstrated that canine cataractous LEC
had significantly higher expression of aromatase; this was confirmed with the
tritiated water release assay. Similar to dogs, human cataracts had both
sulfatase and aromatase mRNA expression.
CONCLUSIONS: Normal and cataractous LEC can synthesize estradiol by the sulfatase
pathway; however, cataractous LEC appear to use the aromatase pathway as well.
Because no differences in aqueous humor estradiol levels were detected, we
suspect that estradiol synthesized by the sulfatase pathway is secreted into the
aqueous humor; whereas, estradiol synthesized by the aromatase pathway is used
for, as yet unknown, intracrine purposes.

Radiat Res. 2012 Oct;178(4):260-5. Epub 2012 Aug 10.
Age and hormonal status as determinants of cataractogenesis induced by ionizing
radiation. II. Sparsely ionizing (low-LET) radiation.
Dynlacht JR(1), Valluri S, Garrett J, Nees J, Caperell-Grant A, DesRosiers C,
Bigsby RM.
(1)Department of Radiation Oncology, Indiana University of Medicine,
Indianapolis, Indiana, USA. [email protected]
Age at the time of exposure to sparsely ionizing radiation has been established
as a key determinant of radiation cataractogenesis. However, while some reports
suggest that the lenses of the young are hypersensitive, data from older studies
are often conflicting and somewhat difficult to interpret when the radioresponse
of young lenses is compared to that of adult lenses. Moreover, the mechanism of
the age-response function for radiation cataractogenesis has yet to be
identified. Since steroid sex hormones, notably estradiol, appear to play a role
in age-related cataractogenesis, we hypothesized that the age response for
radiation cataractogenesis could be dictated by estradiol status. We recently
showed that exposure to high-linear energy transfer (LET) radiation resulted in a
reduced latent period for, and enhanced progression of cataracts in rats that
were 1 year old at the time of exposure compared to those that were 56 days old.
However, the enhanced sensitivity of older lenses compared to younger lenses was
independent of estradiol status. In the current study, we found that for
1-year-old rats exposed to 10 Gy of low-LET (60)Co γ rays, the rate of increase
in the development of posterior and anterior subcapsular cataracts was higher in
older ovary-intact rats compared to young rats. However, cataracts were detected
much earlier in ovary-intact 56-day-old rats
compared to 1-year-old rats,
regardless of their treatment groups (ovary-intact, ovariectomized, or
ovariectomized and implanted with capsules containing estradiol). Thus, despite a
consistent estradiol response (potentiating effect of estrogen) within a given
age group, the differences between the radiation response of old and young lenses
cannot be accounted for solely by estradiol status.

44. Bull Soc Belge Ophtalmol. 1964;138:586-92.
[Cortisone-induced cataract].
[Article in French]
François J.

45. JAMA. 1963 Aug 10;185:448.
Cataracts in asthmatics treated with corticosteroids.
LEIBOLD JE, ITKIN IH.

46. Md State Med J. 1963 Sep;12:436-8.
CATARACT FORMATION AND CORTICOSTEROIDS.
VITALE WJ.

47. Acta Ophthalmol (Copenh). 1963;41:515-23.
THE OCCURRENCE OF POSTERIOR SUBCAPSULAR CATARACTS IN PATIENTS ON LONG-TERM
SYSTEMIC CORTICOSTEROID THERAPY.
SUNDMARK E.

49. Rinsho Ganka. 1962 Sep;16:935-8.
[Effects of eye surgery on cutaneous capillary permeability. Effectiveness of
dexamethasone and vitamin C on an increase in cutaneous capillary permeability
after cataract surgery].
[Article in Japanese]
UCHIDA S.

50. Bull Soc Ophtalmol Fr. 1962 Apr;62:238-43.
[Cataracts and prolonged general corticotherapy].
[Article in French]
BOUZAS A.

51. Arch Ophthalmol. 1961 Nov;66:625-30.
Cataracts in patients with rheumatic diseases treated with corticosteroids.
Further observations.
OGLESBY RB, BLACK RL, VON SALLMANN L, BUNIM JJ.

52. Arch Ophthalmol. 1961 Oct;66:455.
Cataracts caused by corticosteroids.
COGAN DG.

53. Eye Ear Nose Throat Mon. 1961 Apr;40:266-8.
Cataracta complicata and corticosteroids. The question of a possible relationship
between posterior subcapsular cataracts and corticesteroids.
ABRAHAMSON IA Jr, ABRAHAMSON IA Sr.

54. JAMA. 1961 Jan 14;175:127-9.
Examination for posterior subcapsular cataracts. A preliminary report of results
in forty-five rheumatoid patients treated with corticosteroids.
GORDON DM, KAMMERER WH, FREYBERG RH.

55. JAMA. 1960 Sep 10;174:166-71.
Posterior subcapsular cataracts induced by corticosteroids in patients with
rheumatoid arthritis.
BLACK RL, OGLESBY RB, VON SALLMANN L, BUNIM JJ.

56. Klin Monbl Augenheilkd. 1967;151(1):1-8.
[On the problem of the development of lenticular opacities in long term treatment
with glucocorticoids].
[Article in German]
Benthien H, Knoke M.

57. Br Med J. 1963 Jun 22;1(5346):1644-7.
Posterior subcapsular lens opacities in patients on longterm corticosteroid
therapy.
CREWS SJ.

JAMA Ophthalmol. 2015 Apr;133(4):375.
Expression of concern: Thakur A, Kadam R, Kompella UB. Trabecular meshwork and
lens partitioning of corticosteroids: implications for elevated intraocular
pressure and cataracts. Arch Ophthalmol. 2011:129(7):914-920.
Bressler NM(1), Bauchner H(2).
(1)Editor, JAMAOphthalmology2Wilmer Eye Institute, Johns Hopkins University
School of Medicine, Baltimore, Maryland. (2)Editor in Chief, The JAMA Network.
Comment on
Arch Ophthalmol. 2011 Jul;129(7):914-20.
JAMA Ophthalmology has been notified by the University of Colorado Denver
Anschutz Medical Campus that the university completed a scientific misconduct
investigation involving research published by Rajendra Kadam, MPharm, and has
determined that 10 papers with Kadam as an author contain falsified and/or
fabricated data. For the article published in 2011 by Kadam et al in JAMA
Ophthalmology, then known as Archives of Ophthalmology, the original liquid
chromatographic/mass spectrometric data were not available to compare with the
data used in the analysis, and the investigative committee was unable to validate
the data reported in the study. Therefore, the committee was unable to reach any
definitive conclusion related to the integrity or reliability of the data in this
report. This Editorial Expression of Concern is to inform readers about possible
concerns related to data therein. If additional information becomes available
about the integrity of the data reported in this article, we will determine
whether additional action is warranted.
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?
Ray Peat said:
Desiccated thyroid gland doesn’t contain any free hormone; the gland contains thyroglobulin, a protein, which when digested releases the hormones.
cleardot.gif
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?
Ray Peat said:
Yes, I think a small supplement of testosterone will work in the same direction.
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?
Ray Peat said:
Coconut oil (I prefer hydrogenated) helps satiety, while tending to increase the metabolic rate. Cheese can be especially satisfying, partly because of the flavor. Sometimes trace nutrient deficiencies lead to over-eating; liver, oysters, and cooked mushrooms can satisfy appetite without high calories. Sometimes hypothyroidism, a tendency to hypoglycemia, is responsible for weight gain.

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?
Ray Peat said:
In low concentrations DMSO is usually safe, but since I have seen allergy-like reactions to it, and since the biological chemisty is complex (e.g., J Phys Chem A. 2006 Jun 22;110(24):7628-36. Theoretical study of the reduction mechanism of sulfoxides by thiols. Balta B, Monard G, Ruiz-López MF, Antoine M, Gand A, Boschi-Muller S, Branlant G.), I think it’s good to use it cautiously and watchfully.
cleardot.gif
 

milk_lover

Member
Joined
Aug 15, 2015
Messages
1,909
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."
 

milk_lover

Member
Joined
Aug 15, 2015
Messages
1,909
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."
 

FiveAsh

Member
Joined
May 17, 2016
Messages
27
Location
England
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."
 

raypeatclips

Member
Joined
Jul 8, 2016
Messages
2,555
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?

Ray Peat said:
I think it’s healthiest for the bowel to move after each meal, chewing the gum might be reinforcing a natural reflex.
 

blob69

Member
Joined
Nov 6, 2015
Messages
362
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.
 

blob69

Member
Joined
Nov 6, 2015
Messages
362
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.
 

Similar threads

Back
Top Bottom