Ray Peat Email Advice Depository

charlie

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This thread will be for posting email exchanges from Ray Peat.

This thread is reserved for email advice exchanges only. If you would like to discuss anything posted in this thread, feel free to make your own thread, or you can go over the Ray Peat Email Advice Depository Discussion/Comment Thread

Please help by posting email exchanges you have had, or any exchange that you run across on the web. Please give citation or hat tip when possible.





Anon said:
Hello Mr. Peat,

This inquiry concerns the use of vitamin A supplement, specifically NutrisorbA. For the past year, I have found that if I take less than 100,000 iu per day I get acne, and upon increasing my dose to 100,000 iu, the acne goes away within a day or two. I have tried, on various occasions, to reduce the supplement, and simultaneously increase liver, or decrease sun exposure, etc. I avoid PUFA, drink lots of milk and orange juice, eat eggs, cheese, and a carrot salad every day. I get quite a bit of sun (1 to 2 hours per day), and sit under the IR lights every day. I take between 25-50mcg of t3 per day, and my temperatures seem to be healthy - oral temperature in the morning is around 98.5, which increases to 99.5 - 99.7 by midmorning. My resting heart rate is between 80 - 90 bpm. I have also tried taking a b6 supplement, and while it made me feel very merry, it did not decrease the acne.

My question: Is this dose of vitamin A safe, or is there some other factor that could be wasting vitamin A of which I am unaware?

Thank you for reading,
Anon

Ray Peat said:
For several years, I had a similar need to take 100,000 i.u. daily to prevent acne and ingrown whiskers, so I read a lot about its effects. The toxic effects of extremely big doses, such as 500,000 to a million i.u., seem to be from either oxidative processes (rancidity) that are prevented by adequate vitamin E, or by antithyroid effects. I found that when my need for vitamin A began to decrease I tended to accumulate carotene in my calluses; that happens when the thyroid function is lower, reducing the need for vitamin A. Since you are eating foods with carotene, the calluses on your palms or soles should serve as an indicator of when your tissues are saturated with vitamin A. About 100 i.u. of vitamin E would help to keep the vitamin A from being wasted by oxidation, and possibly could reduce your requirement for it.
 

charlie

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Re: Ray Peat Email Advice: Light Therapy

When asked about light therapy:

Ray Peat said:
"Incandescent bulbs have a continuous spectrum, luminous gases have intermittently distributed wavelengths. Orange and red are the metabolically most important wavelengths. I don't think the far infrared does anything special, besides heat. Ordinary incandescent bulbs have a slightly orange color compared to sunlight, and the bulbs I have mentioned are just slightly warmer in color, with very little blue, and more red. Ordinary incandescent bulbs are good, if there are enough of them, directed toward your skin."
 

charlie

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Re: Ray Peat Email Advice: Restoring Color to Gray Hair

mmartian said:
I emailed Dr. Peat about restoring color to my graying hair a few days ago. This was his response:

Ray Peat said:
Do you know how your thyroid function is? Thyroid regulates copper assimilation, and also the hormones that regulate pigment.

I found that applying a weak solution of copper just once would restore color immediately to eyebrows, or to about 10% of sideburn hairs, apparently because the very long-lived hairs have to be in the right phase of growth, and eyebrows, with a very short life, seem to stay receptive to the stimulation. But I also found that a slightly too strong solution could cause a mole to develop almost instantly, with an invasion of pigment cells. I think a safer alternative would be to supplement, either topically or orally, a little DHEA.
 

charlie

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:hattip Kasra over at Peatarian.

Kasra said:
(5/22/12) What is your opinion of alcohol and cannabis? What is the best immediate measure to mitigate any harmful effects you see in these two drugs?

Ray Peat said:
Small amounts of alcohol can have some good antioxidant effects, but beer, wine, and dark whiskey, etc., contain enough estrogen to be harmful. Cannabis is antiandrogenic or estrogenic, but it can be protective in some situations. Protein, thyroid, sugars, and saturated fats are protective against both.

Kasra said:
(5/27/12) Do carbonated drinks have a significant effect on tissue concentrations of CO2?

Ray Peat said:
In a crisis situation, it (or baking soda in water) can be helpful, but it's more effective to rebreathe in a paper bag.

Kasra said:
(8/30/12) What is your view on the chronic use of smokeless tobacco like snus?

Ray Peat said:
In old people, a little nicotine can have a balancing effect, improving alertness, and probably protecting nerves, for example in the negative association with Parkinson's disease. But in younger people, its vasoconstrictive effect tends to promote the development of wrinkles in the skin, and I think it's likely to contribute to periodontal disease.

Kasra said:
(9/25/12) Would vitamin-free powdered milk be a preferable alternative to commercial US milk with added vitamins?

Ray Peat said:
I think it's a matter of watching for any effects associated with a particular product; if nothing is obvious, the fresher milk is preferable.

Kasra said:
(10/11/12) How beneficial are coconut oil and coffee to a healthy person with a good diet?

Ray Peat said:
If the basic foods were chosen for minimal unsaturated fats, then coconut oil wouldn't add much of value. Coffee is a good source of magnesium and niacin, and has smaller amounts of other essential nutrients, besides the caffeine and antioxidants.

Kasra said:
(10/18/12) What is a safe upper limit of aspirin consumption?

Ray Peat said:
It depends on the context; aspirin makes you need more vitamin K, even when you aren't using much. People who use aspirin for arthritis or cancer often take several grams a day.

Kasra said:
(10/24/12) In what way would a large brain affect a person's dietary requirements? Would caffeine be particularly useful for a person with a large brain?

Ray Peat said:
It makes the body's glycogen stores more important, so thyroid function can benefit especially from avoidance of PUFA; coffee's protective effects, increasing metabolic efficiency, are probably especially helpful.

Kasra said:
(10/31/12) Why do you emphasize orange juice over other fruit juices?

Ray Peat said:
A few other juices are good, for example watermelon. Some fruits contain things that affect the hormones.

Kasra said:
What are the other safe fruits?

Ray Peat said:
Corossol, lychee, longan, guaba, papaya, pawpaw, sapota, guanabana.

(Similar question by shaadoe)

Ray Peat said:
Some frozen and canned fruits are good; applesauce, corossol, guanabana, longans, and lychees for example.
 

bradley

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Re: Ray Peat Email Advice: Migraine

On aborting a migraine:

Lots of sugar, without coffee, would be quicker for restoring blood sugar. At least a quart of milk shake or ice cream can provide the needed sugar in a form that can be assimilated quickly. 100 mg of progesterone in oil can usually stop it, by stopping the wastage of glucose.
 

cliff

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Q: Do you think alkalized cocoa has any benefits over normal cocoa?
A:The idea is to remove the fat so that it mixes easily with milk.

Q:Someone told me you drink HFCS coke regularly? do you think it is not
that harmful if someone is healthy?
A:I prefer Mexican coke with real sugar (it tastes very different), but metabolically there isn't much difference.

Q: Does a protein deficiency lower liver detoxification due to increased
muscle breakdown which inhibits thyroid via amino acids which lowers
metabolic efficiency of liver?
A:Yes, I think that's at least part of how it works.

Q: Do you think any of the dessicated thyroid products are good?
A:I haven't seen anything that compares well with the original Armour.

Q: Do you think zinc oxide is the least harmful commercially available sunscreen?
A:Yes

Q:In mitochondria and mortality you mention pyruvate having similar effects of lactate. Isn't pyruvate necessary for oxidative metabolism? Is pyruvate only bad when mitochrondia can't fully metabolize it?
A:Yes

Q: Do you think pure USP B vitamins, like niacinamide or b1, are safe?
A:Because of individual sensitivities, each one should be tested carefully. Allergic reactions sometimes show up within a few minutes of contacting your mouth, other times it takes a couple of days to see a bad reaction. The worst one is B2, folic acid is next for allergies. B1, pantothenic acid, niacinamide and B6 are pretty safe.

Q: Does T3 act like caffeine in the way if you don't eat enough sugar you can get nervousness, heart skipping, headaches, etc?
A:Not like caffeine, but if too much is taken suddenly, a person who has been deficient in thyroid is likely to experience an excess of adrenaline. Since the body normally produces about 4 mcg of T3 in an hour, taking 10 or 20 mcg at once is unphysiological.

Q:Is it ok to eat baking soda with protein meals or does it buffer stomach acid?
A:It slows digestion down for a few minutes.

Q:When you say several effects of co2 shuts off glycolysis, do you mean anaerobic glycolysis or all glycolysis, if all glycolysis how does glucose enter mitochondria without breaking down to pyruvate?
A:Meaning the entry of lactate into the blood stream inappropriately, which would usually be called aerobic glycolysis, though you can't be sure how much oxygen is getting to the cells when CO2 is deficient, since its absence causes many problems in oxygen delivery and use.
Q:So when CO2 isn't deficient glycolysis, meaning glucose to pyruvate, is fine?
A:Yes, as part of oxidative metabolism, it's better than burning too much fat.

(asked him this question after paul jaminet claimed ray would agree with him to use O6 oil to help eczema...)
Q: Do you recommend someone try omega 6 supplementation from say safflower oil in an extreme case on eczema? Or will the omega 6 appear to heal the eczema because of lowered metabolism?
A:Slowing metabolism and causing inflammation are its two basic functions.

Q:My dad asked about what to do for his skin cancer
A:Yes, avoidance of unsaturated fats is the most important thing.
Aspirin, caffeine, and orange juice are protective.
Keeping the TSH low is important, because it stimulates melanoma growth.




Amino Acids. 2007 Jan;32(1):95-100. Epub 2006 May 15.
Enhancement of transglutaminase activity and polyamine depletion in B16-F10
melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of
the in vivo metastatic potential.
Lentini A, Forni C, Provenzano B, Beninati S.
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin
(HP) on the proliferation rate of highly metastatic murine B16-F10 melanoma cell
were investigated. NG or HP treatment of melanoma cells produced a remarkable
reduction of cell proliferation, paralleled with both the lowering of the
intracellular levels of polyamine, spermidine and spermine and the enhancement of
transglutaminase (TGase, EC 2.3.2.13) activity. Orally administered NG or HP in
C57BL6/N mice inoculated with B16-F10 cells affected the pulmonary invasion of
melanoma cells in an in vivo metastatic assay. The number of lung metastases
detected by a computerized image analyzer was reduced, compared to untreated
animals, by about 69% in NG-treated mice and by about 36% in HP-treated mice.
Survival studies showed that 50% of the NG-treated animals died 38 +/- 3.1 days
after tumor cell injection (control group: 18 +/- 1.5 days) and HP-treated mice
died 27 +/- 2.3 days after cell inoculation. Taken together, these findings
provide further evidences for the potential anticancer properties of dietary
flavonoids as chemopreventive agents against malignant melanoma.

Biosci Biotechnol Biochem. 2000 Sep;64(9):1813-20.
Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells.
Iwashita K, Kobori M, Yamaki K, Tsushida T.
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
moldive@nfri.affrc.go.jp
We investigated the growth inhibitory activity of several flavonoids, including
apigenin, luteolin, kaempherol, quercetin, butein, isoliquiritigenin, naringenin,
genistein, and daizein against B16 mouse melanoma 4A5 cells. Isoliquiritigenin
and butein, belonging to the chalcone group, markedly suppressed the growth of
B16 melanoma cells and induced cell death. The other flavonoids tested showed
little growth inhibitory activity and scarcely caused cell death. In cells
treated with isoliquiritigenin or butein, condensation of nuclei and
fragmentation of nuclear DNA, which are typical phenomena of apoptosis, were
observed by Hoechst 33258 staining and by agarose gel electrophoresis of DNA.
Flowcytometric analysis showed that isoliquiritigenin and butein increased the
proportion of hypodiploid cells in the population of B16 melanoma cells. These
results demonstrate that isoliquiritigenin and butein inhibit cell proliferation
and induce apoptosis in B16 melanoma cells. Extracellular glucose decreased the
proportion of hypodiploid cells that appeared as a result of isoliquiritigenin
treatment. p53 was not detected in cells treated with either of these chalcones,
however, protein of the Bcl-2 family were detected. The level of expression of
Bax in cells treated with either of these chalcones was markedly elevated and the
level of Bcl-XL decreased slightly. Isoliquiritigenin did not affect Bcl-2
expression, but butein down-regulated Bcl-2 expression. From these results, it
seems that the pathway by which the chalcones induce apoptosis may be independent
of p53 and dependent on proteins of the Bcl-2 family. It was supposed that
isoliquiritigenin induces apoptosis in B16 cells by a mechanism involving
inhibition of glucose transmembrane transport and promotion of Bax expression. On
the other hand, it was suggested that butein induces apoptosis via
down-regulation of Bcl-2 expression and promotion of Bax expression. This
mechanism differs from the isoliquiritigenin induction pathway.

Endocr Relat Cancer. 2006 Dec;13(4):1269-77.
Human melanoma cells express functional receptors for thyroid-stimulating
hormone.
Ellerhorst JA, Sendi-Naderi A, Johnson MK, Cooke CP, Dang SM, Diwan AH.
Department of Experimental Therapeutics, Unit 362, University of Texas, MD
Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA.
jaellerh@mdanderson.org
We have reported a high prevalence of hypothyroidism in the cutaneous melanoma
population, suggesting that the pathologic hormonal environment of hypothyroidism
promotes melanoma growth. The objective of this study was to test the hypothesis
that TSH, which circulates at elevated levels in hypothyroid individuals,
stimulates the growth of melanoma cells. Our results show that TSH receptors
(TSHR) are expressed by virtually all cutaneous melanocytic lesions, including
benign nevi, dysplastic nevi, and melanomas, with higher expression found in
malignant and pre-malignant lesions. The finding of TSHR expression by human
tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR
expression is demonstrated by immunofluorescent staining, western blotting, and
reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the
ability of TSH to induce the formation of cAMP and to activate the
mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not
melanocytes, are induced to proliferate at a physiologically relevant
concentration of TSH. Taken together, these data support the hypothesis that TSH
is a growth factor for human melanoma. Our findings have broad clinical
implications for the prevention of melanoma and the management of established
disease.

Cancer Lett. 1995 Aug 16;95(1-2):221-5.
Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by
polyphenolic compounds.
Menon LG, Kuttan R, Kuttan G.
Amala Cancer Research Centre, Thrissur, Kerala, India.
Several polyphenolic compounds were tested for the inhibition of lung metastasis
induced by B16F10 melanoma cells in mice. Oral administration of polyphenols such
as curcumin and catechin at concentrations of 200 nmol/kg body weight were found
to inhibit the lung metastasis maximally as seen by the reduction in the number
of lung tumor nodules (80%). Other polyphenols which inhibited the lung tumor
nodule formation were rutin (71.2%), epicatechin (61%), naringin (27.2%) and
naringenin (26.1%). The polyphenols which did not inhibit lung tumor nodule
formation were quercetin, morin and ellagic acid. Consequent to the inhibition of
the lung tumor nodules, the life span of animals treated with polyphenols was
also found to be increased. Curcumin (143.85%), catechin (80.81%) and rutin
(63.59%) had maximal increase in life span. The results indicate a possible use
of these compounds in arresting the metastatic growth of tumor cells.

Chem Biodivers. 2011 Jun;8(6):1152-62. doi: 10.1002/cbdv.201000311.
In vitro Cytotoxic Activity of Extracts and Isolated Constituents of Salvia
leriifolia Benth. against a Panel of Human Cancer Cell Lines.
Tundis R, Loizzo MR, Menichini F, Bonesi M, Colica C, Menichini F.
Department of Pharmaceutical Sciences, Faculty of Pharmacy and Nutrition and
Health Sciences, University of Calabria, I-87036 Rende (CS) (phone:
+39-0984-493246; fax: +39-0984-493298). tundis@unical.it.
In the course of recent efforts to identify new potential antiproliferative
active principles, Salvia leriifolia extracts and isolated constituents were
evaluated for their cytotoxic activity against a panel of human cancer cell
lines, including renal adenocarcinoma (ACHN), amelanotic melanoma (C32),
colorectal adenocarcinoma (Caco-2), lung large cell carcinoma (COR-L23),
malignant melanoma (A375), lung carcinoma (A549), and hepatocellular carcinoma
(Huh-7D12) cells. The hexane and CH(2) Cl(2) extracts showed the strongest
cytotoxic activity against the C32 cell line with IC(50) values of 11.2 and
13.6 μg/ml, respectively, and the AcOEt extract was the most active extract
against the COR-L23 cell line (IC(50) of 20.9 μg/ml). Buchariol, a sesquiterpene
obtained by biofractionation of the CH(2) Cl(2) extract, exhibited a higher
activity than the positive control vinblastine against the C32 and A549 cell
lines (IC(50) values of 2.1 and 12.6 μM, resp.). Interesting results were also
obtained for naringenin, a flavonoid isolated from the AcOEt extract, which
exhibited a strong cytotoxic activity against the C32, LNCaP, and COR-L23 cell
lines (IC(50) values of 2.2, 7.7, and 33.4 μM, resp.), compared to vinblastine
(IC(50) values of 3.3, 32.2, 50.0 μM, resp.). None of the tested compounds
affected the proliferation of skin fibroblasts (142BR), suggesting a selective
activity against tumor cells.

Biosci Biotechnol Biochem. 2006 Jun;70(6):1499-501.
Stimulation of melanogenesis by the citrus flavonoid naringenin in mouse B16
melanoma cells.
Ohguchi K, Akao Y, Nozawa Y.
Gifu International Institute of Biotechnology. kohguchi@giib.or.jp
Naringenin is a naturally occurring citrus flavanone. In this study, we examined
the effect of naringenin on melanogenesis in mouse B16 melanoma cells. Melanin
contents and tyrosinase activities were strongly increased by naringenin.
Naringenin was found to cause marked increases in the expression levels of
melanogenic enzymes.

J Exp Clin Cancer Res. 2001 Jun;20(2):287-92.
Effect of Caffeine, a xanthine derivative, in the inhibition of experimental lung
metastasis induced by B16F10 melanoma cells.
Gude RP, Menon LG, Rao SG.
Chemotherapy & Stem Cell Biology Division. Cancer Research Institute, Parel,
Mumbai, India. cri@soochak.ncst.ernet.in
Caffeine, a methyl xanthine derivative, was studied to assess the effect on
B16F10 melanoma induced experimental metastasis. Caffeine was administered at a
dose of 100 and 50 mg/kg body weight by both routes, to tumour bearing animals.
Solid tumour reduction studies with Caffeine showed a significant reduction in
tumour volume for 100 mg/kg dose by both oral and i.p. routes. The Caffeine
treated metastatic tumour bearing animals significantly (p<0.001) inhibited lung
tumour nodules. Serum sialic acid levels and lung hydroxyproline contents in the
treated groups were significantly (p<0.001) low, when compared with the untreated
control animals. In the present study, our results suggest that Caffeine inhibits
solid tumour development and pulmonary experimental metastasis induced by B16F10 melanoma cells, in murine model.

Biochim Biophys Acta. 2000 Dec 11;1499(1-2):1-10.
Influence of pentoxifylline, A-802710, propentofylline and A-802715 (Hoechst) on
the expression of cell cycle blocks and S-phase content after irradiation damage.
Bohm L, Theron T, Binder A.
Department of Radiation Oncology, Faculty of Medicine, University of
Stellenbosch, P.O. Box 19063, 7505, Tygerberg, South Africa. elb@gerga.sun.ac.za
The toxicity of the five methylxanthine derivatives, caffeine, pentoxifylline,
A802710, propentofylline and A802715, was determined against the two human
melanoma lines, Be11 and MeWo, and against the two human squamous cell carcinoma
lines, 4197 and 4451, by vital dye staining assay. Pentoxifylline and A802710
emerge as the least toxic showing TD(50) (toxic dose of 50%) levels of 3.0-4.0
mM. Propentofylline and caffeine take an intermediate position. A802715 has a
TD(50) of 0.9-1.1 mM and is the most toxic. Subtoxic concentrations (<TD50)added
after irradiation at maximum expression of the G2/M block show that
pentoxifylline and A802710 effectively abrogate the G2/M block, whereas A802715
and propentofylline prolong the G2/M block or remain ineffective depending on the
p53 status of the cell line. In p53 wt cells BrdU incorporations show that the
irradiation-induced suppression of S-phase entry is marginally enhanced by
pentoxifylline but strongly enhanced by propentofylline and A802715. This effect
was not seen in p53 mutant cells. Since propentofylline and A802715 prolong the
G2/M block and effectively suppress BrdU incorporation these two drugs emerge as
antagonists to pentoxifylline, caffeine and A802710. Common structural features
of propentofylline and A802715 are a propyl substituent at the N7 position in
contrast to pentoxifylline, caffeine and A802710 where the N7 substituent is a
methyl group. The results document the effectiveness of four methylxanthines in
influencing cell regulation and damage response in human tumor cells.

Melanoma Res. 1998 Apr;8(2):131-7.
Inhibition of melanoma pulmonary metastasis by methylxanthines due to decreased
invasion and proliferation.
Lentini A, Kleinman HK, Mattioli P, Autuori-Pezzoli V, Nicolini L, Pietrini A,
Abbruzzese A, Cardinali M, Beninati S.
Department of Biology, II University of Rome Tor Vergata, Italy.
Theophylline- and caffeine-treated B16-F10 cells exhibited low adhesion to
laminin/collagen type IV and reduced invasion through Matrigel in an in vitro
assay. In contrast, theobromine appeared ineffective. When young adult C57BL/6
mice were injected intravenously with theophylline-treated B16-F10 cells, the
number of surface lung tumours was markedly reduced. Densitometric analyses
performed on digitalized microscopic images of histological sections of lung were
used to estimate the frequency (number of lung foci; NLF) and the size (average
area of metastatic foci; AMF) of the resulting tumour foci. These parameters were
correlated to the proliferation (AMF) and invasion (NLF) of melanoma cells in
vivo. The data showed a similar theophylline-induced decrease in the AMF and NLF
values (71%, P < 0.01). Caffeine treatment produced a more pronounced decrease in
the AMF (61%, P < 0.01) than in the NLF (25%, P < 0.01). To our knowledge, this
is the first demonstration that theophylline and caffeine possess the capacity to
inhibit not only cell proliferation, but also the metastatic behaviour of
melanoma cancer cells.

Prostaglandins. 1996 Jan;51(1):1-17.
Identification of arachidonic acid pathways required for the invasive and
metastatic activity of malignant tumor cells.
Reich R, Martin GR.
Department of Pharmacology, Hebrew University of Jerusalem, Israel.
Metastasis is a complex process, almost a cascade, involving multiple steps and
activities. However, an important factor is that malignant cells are able to
penetrate through the multiple basement membrane barriers surrounding tissues,
blood vessels, nerves and muscle that would otherwise block their dissemination.
Penetration of malignant tumor cells through basement membrane is an active
process requiring proteolysis. We report here that inhibitors of both the
cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism convert
mouse melanoma and human fibrosarcoma cells to a non invasive state by reducing
the production of MMP-2, an enzyme required for the degradation of basement
membranes. Specific metabolites of each pathway, i.e. PGF2 alpha and 5-HPETE, are
able to transcend the block and restore collagenase production, invasiveness in
vitro and metastatic activity in vivo. These studies indicate a key role for
arachidonic acid metabolites in metastasis and suggest novel therapeutic
approaches for inhibiting the spread of cancer.

Chemotherapy. 2003 May;49(1-2):71-5.
Potentiation of lipid peroxidation in B16F10 and B16F1 melanoma cells by
caffeine, a methylxanthine derivative: relationship to intracellular glutathione.
Shukla V, Gude RP.
Chemotherapy Division, Cancer Research Institute, Tata Memorial Centre, Mumbai,
India.
BACKGROUND: Caffeine has shown an inhibitory role in invasion and proliferation
in melanoma pulmonary metastasis as well as in high-grade tissue sarcoma.
However, little is known about its mechanism and possible role in metastatic cell
lines.
MATERIALS AND METHODS: B16F10 and B16F1 cell lines of high and low metastatic
potential were treated with caffeine at different time intervals with different
doses. Reduced glutathione, glutathione S-transferase and lipid peroxides were
estimated to evaluate the effect of caffeine.
RESULTS: Caffeine treatment showed glutathione depletion and increased lipid
peroxidation with higher glutathione S-transferase activity in both B16F10 and
B16F1 cell lines. However the effect of caffeine was dependent on the time factor
as well as on the dose.
CONCLUSIONS: Caffeine was an effective inhibitor of metastatic activity.
Glutathione depletion in conjunction with increased lipid peroxidation was a
potent indicator in the regulation of metastatic behavior of B16F10 and B16F1
melanoma cell lines.

Mol Cell Biochem. 2008 Jan;308(1-2):193-200. Epub 2007 Oct 12.
Caffeine inhibits UV-mediated NF-kappaB activation in A2058 melanoma cells: an
ATM-PKCdelta-p38 MAPK-dependent mechanism.
Ravi D, Muniyappa H, Das KC.
Department of Pathology, University of Arkansas for Medical Sciences, 4301 W
Markham Street, Slot # 845, Little Rock, AR 72205, USA.
Mammalian ultraviolet (UV) radiation response is a gene induction cascade
activated by several transcription factors, including NF-kappaB. Although
NF-kappaB is induced by UV radiation, the signal transduction mechanism remains
relatively unclear. In the present study, we show that UV-induced NF-kappaB
activation is mediated by the activation of Ataxia telangiecia mutated (ATM) and
protein kinase C (PKC). We also show that caffeine specifically inhibits
UV-mediated NF-kappaB activation, but not TNFalpha-mediated NF-kappaB activation.
In addition, our study shows that ATM, but not ATM-Rad3-related (ATR) or
DNA-dependent protein kinase (DNA-PK) is involved in UV-induced NF-kappaB
activation. Because SB203580 (a p38 MAPK inhibitor), or Calphostin C or rottlerin
(PKC inhibitors) was able to inhibit UV-mediated NF-kappaB activation, we
evaluated whether caffeine could inhibit p38 MAPK or PKC activity. Caffeine or
rottlerin inhibited UV-induced phosphorylation of p38 MAPK, but not
anisomycin-induced phosphorylation of p38 MAPK, suggesting that p38 MAPK is
downstream of PKC. Additionally, caffeine could effectively inhibit UV-induced
increases in PKC activity. Taken together, our study demonstrates that caffeine
is a potent inhibitor of UV-induced NF-kappaB activation. Additionally, this
inhibition occurs due to the inhibitory action of caffeine on ATM and PKC,
resulting in the inhibition of p38 MAPK activation.

Eur J Cancer Clin Oncol. 1989 Oct;25(10):1413-7.
Early presence of activated ('exhausted') platelets in malignant tumors (breast
adenocarcinoma and malignant melanoma).
Mannucci PM, Cattaneo M, Canciani MT, Maniezzo M, Vaglini M, Cascinelli N.
A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy.
To evaluate whether or not the finding of platelet activation in patients with
tumors is related to the stage of malignancy, a study of biochemical markers
indicative of the presence of circulating activated ('exhausted') platelets was
carried out in 95 untreated patients with breast adenocarcinoma or malignant
melanoma, localized or spread to regional lymph nodes with no detectable distant
metastasis. These tumors were chosen as examples of tumors which can be
accurately staged for localization or spread, and as examples of mucin-secreting
tumors (breast adenocarcinoma) or neuroectodermic tumors (malignant melanoma).
Results were compared with those for 26 patients with benign breast disease, 23
blood donors and 50 hospital workers. The most frequent abnormalities were low
levels of intraplatelet ADP and 5-hydroxytryptamine and high ATP/ADP ratios.
Although these abnormalities occurred with both types of tumor, they were more
frequent and marked for melanomas and breast carcinomas spread to regional lymph
nodes. Our data indicate that the presence of exhausted platelets is an early
finding in patients with malignant tumors.

Br J Cancer. 1999 Nov;81(5):918-23.
Oral contraceptive use and risk of melanoma in premenopausal women.
Feskanich D, Hunter DJ, Willett WC, Spiegelman D, Stampfer MJ, Speizer FE,
Colditz GA.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School,
Boston, MA 02115, USA.
Melanoma has been increasing in white populations. Incidence rates rise steeply
in women until about age 50, suggesting oestrogen as a possible risk factor.
Oestrogens can increase melanocyte count and melanin content and cause
hyperpigmentation of the skin. We examined prospectively the association between
oral contraceptive (OC) use and diagnoses of superficial spreading and nodular
melanoma among 183,693 premenopausal white women in the Nurses' Health Study
(NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six
cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases
were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure,
sunburn history, mole counts, hair colour, family history of melanoma, parity,
height and body mass index were also assessed and included in logistic regression
models. A significant twofold increase in risk of melanoma (relative risk (RR) =
2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users
compared to never users. Risk was further increased among current users with 10
or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated
among past OC users, even among those with longer durations of use, and risk did
not decline linearly with time since last use. In conclusion, risk of
premenopausal melanoma may be increased among women who are current OC users,
particularly among those with longer durations of use. Further research is needed
to determine whether low-dose oestrogen pills in particular are associated with
an increase in risk and to describe possible interactions between OC use and sun
exposure or other risk factors for melanoma.

Oncol Rep. 2005 Apr;13(4):559-83.
Comment in:
J Urol. 2005 Aug;174(2):787-8.
Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer
prevention: a critical review of non-selective COX-2 blockade (review).
Harris RE, Beebe-Donk J, Doss H, Burr Doss D.
College of Medicine and Public Health, The Ohio State University, 320 West 10th
Avenue, Columbus, OH 43210-1240, USA. harris.44@osu.edu
We comprehensively reviewed the published scientific literature on non-steroidal
anti-inflammatory drugs (NSAIDs) and cancer and evaluated results based upon
epidemiologic criteria of judgment: consistency of results, strength of
association, dose response, molecular specificity, and biological plausibility.
Sufficient data from 91 epidemiologic studies were available to examine the dose
response of relative risk and level of NSAID intake for ten human malignancies.
Dose response curves were fitted by exponential regression. Results showed a
significant exponential decline in the risk with increasing intake of NSAIDs
(primarily aspirin or ibuprofen) for 7-10 malignancies including the four major
types: colon, breast, lung, and prostate cancer. Daily intake of NSAIDs,
primarily aspirin, produced risk reductions of 63% for colon, 39% for breast,
36% for lung, and 39% for prostate cancer. Significant risk reductions were also
observed for esophageal (73%), stomach (62%), and ovarian cancer (47%). NSAID
effects became apparent after five or more years of use and were stronger with
longer duration. Observed protective effects were also consistently stronger for
gastrointestinal malignancies (esophagus, stomach, and colon). Results for
pancreatic, urinary bladder, and renal cancer were inconsistent. Initial
epidemiologic studies of malignant melanoma, Hodgkin's disease, and adult
leukemia also found that NSAIDs are protective. A few studies suggest that
ibuprofen has stronger anticancer effects than aspirin, particularly against
breast and lung cancer. Overexpression of cyclooxygenase-2 (COX-2) and increased
prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most
anatomic sites. Preclinical investigations provide consistent evidence that both
selective and non-selective NSAIDs effectively inhibit chemically-induced
carcinogenesis of epithelial tumors. This review provides compelling and
converging evidence that regular intake of NSAIDs that non-selectively block
COX-2 protects against the development of many types of cancer.
 
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charlie

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Re: Ray Peat Email Advice: Concerns of Fluoride in Gelatin

Regarding concerns of fluoride in gelatin:

Ray Peat said:
"The only analysis of gelatin that I have seen showed very little fluoride. Since most of the fluoride in an animal is concentrated in the bones, and gelatin is made from skin, it probably doesn't contain much."
 

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Re: Ray Peat Email Advice: Oral Health

Regarding oral health:

Ray Peat said:
"Besides keeping phosphates low, getting a lot of vitamin K, and maybe rubbing some onto the gums, might help; it's antiinflammatory. Some people have reverse gingivitis by "rinsing" with coconut oil twice a day, swishing it around for a couple of minutes."
 

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Re: Ray Peat Email Advice: Ray Peat Thoughts on Fluoride/Bro

Anon said:
"Dear Dr. Peat,
would you please state you thoughts on fluoride and bromide. Unfortunately they are being used a lot in the US in forms we cannot avoid, such as from air and water (bathing/showering), even if eating mostly organic. I have been using iodine to displace these elements which are bad not only for the thyroid but also other organs.I know you are against iodine supplements. How do we protect ourselves from the detriments of fluoride and bromide that we can't avoid? Especially if one cannot eat organic much of the time. We have been discussing this in the facebook group and I would love to share what you have to say
Thank you so much"

Ray Peat said:
"It's good to avoid fluoridated water as far as possible.
Certain forms of bromine, including bromate and polybrominated biphenyls, are definitely toxic, but simple bromide isn't very toxic; it took large amounts of Bromo-Seltzer used for a long time to produce harmful effects, hundreds of milligrams per day. Seawater contains bromide, so all seafood contains a lot; milk and meat naturally contain it, because soil generally contains a moderate amount. A few of the promoters of large iodine supplements--Abraham, Flechas, and Brownstein--are giving a wrong impression of bromine.

Exp Biol Med (Maywood). 2004 Jun;229(6):473-8.
Iodine toxicity and its amelioration.
Baker DH.
Department of Animal Sciences and Division of Nutritional Sciences, 290 Animal
Sciences Laboratory, University of Illinois, 1207 West Gregory Drive, Urbana,
Illinois 61801, USA. dhbaker@uiuc.edu
Iodine (I) toxicity is rare in animals and humans, but nuclear explosions that
give off radioactive I and excessive stable I ingestion in parts of the world
where seaweed is consumed represent specialized I toxicity concerns. Chronic
overconsumption of I reduces organic binding of I by the thyroid gland, which
results in hypothyroidism and goiter. Bromine can replace I on position 5 of both
T(3) and T(4) with no loss of thyroid hormone activity. Avian work has also
demonstrated that oral bromide salts can reverse the malaise and growth
depressions caused by high doses of I (as KI) added as supplements to the diet.
Newborn infants by virtue of having immature thyroid glands are most susceptible
to I toxicity, whether of stable or radioactive origin. For the latter, the 1986
Chernobyl nuclear accident in Belarus has provided evidence that KI blockage
therapy for exposed individuals 18 years of age and younger is effective in
minimizing the development of thyroid cancer. Whether bromide therapy has a place
in I toxicity situations remains to be determined."

Anon said:
"What about the fluoride in showering/bath water? Is that of concern?

Also, should one eat only eat organic foods to avoid getting fluoride in the body to interfere with thyroid function? If one cannot do so, what do you suggest if iodine supplementation is not a good idea?"


Ray Peat said:
"I don't think it's a problem. The soaps and shampoos people use are worse problems. Just washing the skin with pure soap alters the skin's endocrine function for days. and doing it every day is an "endocrine disrupter," even if there are no toxic additives in the soap."
 

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Re: Ray Peat Email Advice: Regarding Taking Thyroid

Regarding taking thyroid:

Ray Peat said:
".....a starting dose of about 1 mcg can produce a noticeable effect, and can be repeated at intervals according to the effect. 5 mcg with a meal is another way to start it. Thyroid tends to lower cholesterol by converting it into pregnenolone and other steroids, and yours is high enough to easily improve your steroid hormone balance."
 
J

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Re: Ray Peat Email Advice: Related to Intestinal Bacteria

I mentioned to Ray Peat that I have some issues which I think are related to intestinal bacteria. He replied that travelers often pick up bacteria that can take a long time to change.

Ray Peat said:
A daily raw carrot (shredded, with olive oil and vinegar, for example) can gradually change the ecology. Sometimes very small amounts of an antibiotic can do it.

Then I asked him about which antibiotics one could use.

Ray Peat said:
Aspirin has a mild germicidal effect. Sometimes 30 to 50 milligrams of tetracycline or penicillin can help. Flowers of sulfur, a pinch a day for a few days will often establish a new flora.
 

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Ray Peat Email Advice: Severe Sleep Apnea

Anon said:
I have severe sleep apena. Which I take CPAP therapy for and have done so for 4 years.

Are there any alternate methods (foods, supplements, breathing) to manage or even "cure" sleep apnea? What causes Sleep Apnea?

I would be interested of any alternate methods you may recommend.

Thanks!

Ray Peat said:
Several things have been very effective, for example the drug Diamox, acetazolamide, stimulates respiration by changing CO2 and pH; caffeine, thyroid, and progesterone are the more natural things that stimulate respiration.

Anon said:
Thank You for your helpful recommendations.

Do your recommendations work for obstructive sleep apnea? That is what I have not central sleep apnea.

Does the Buteyko method have any merit for OSA?

Ray Peat said:
Thyroid is the main regulatory and adaptive substance for respiration. I think it's common to call the apnea "obstructive" when someone is fat, but it's probably essentially the same condition, filtered through the mechanical medical mind.
 

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Re: Ray Peat Email Advice: Blood Test Results

viewtopic.php?f=56&t=1060&p=10015#p10007

Ray Peat said:
High parathyroid hormone will increase calcium and lower phosphate. I regularly use at least two quarts of milk per day, in the past I have averaged a gallon a day, high calcium intake helps to compensate for low vitamin D, but both vitamin D and calcium in the diet tend to lower parathyroid hormone, and the serum calcium level. Quite a few people are now recommending from 2000 to 6000 i.u. of vitamin D3 daily during the winter.

Ray Peat said:
If your vitamin D was very low for a long time, I think your parathyroid glands probably enlarged, and might take some time to normalize under the influence of a generous amount of vitamin D and calcium.
 

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I asked him about circumcision and he said it was almost exclusively negative unless their was some abnormalities with the foreskin i.e too tight.
 

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Re: Ray Peat Email Advice:Regarding medications being ototox

mdrsports31 said:
Dear Dr. Peat,

I have read about certain medications being ototoxic and causing tinnitus. Are you are of this side effect with any particular medications. I am concerned because I am considering taking Claritin D (loratadine and pseudoephedrine), however, I have read that this can contribute to hearing damage.

Thank
-On Nov 29, 2012, at 1:43 PM

Ray Peat said:
Too much pseudoephedrine increases stress hormones, loratadine isn't good for the liver, and anything that irritates the intestine can cause tinnitus by increasing endotoxin absorption.
 

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Re: Ray Peat Email Advice: Mushrooms

viewtopic.php?f=2&t=165

Ray Peat said:
"Since reading about the chemicals in mushrooms I stopped eating them, but using them occasionally is o.k., probably better than many vegetables."
 

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Re: Ray Peat Email Advice: Regarding Magnesium Salicylate

Ray Peat said:
"I haven't tried magnesium salicylate, but most magnesium compounds have been seriously irritating to my intestine; I have mixed baking soda with salicylic acid, and it seems similar to aspirin. If the magnesium doesn't cause irritation, it would be a good form of salicylate. Magnesium salicylate is popular for arthritis, and it releases salicylic acid in the intestine and blood."
 

charlie

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:hattip Anon over at Peatarian.com.

http://www.peatarian.com/?qa=7292/long- ... m-and-pufa

Anon said:
Dr. Peat,

You have mentioned that exercise could bring about hypothyroidism. I
imagine long distance running is included. I wonder though, if they
become hypothyroid due to release of PUFAs to the bloodstream induced
by exercise. Do you think a person who doesn't eat PUFAs and runs long
distance is less likely, or a lot less likely, to become hypothyroid?

Ray Peat said:
Yes, a person relatively free of PUFA will be likely to recover very
quickly from prolonged stress.
 
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