Ray Peat Email Advice Depository

[raypeatclips]

I know a few people besides myself who have had very good results from swallowing a little lidocaine; absorbing it through the skin works too, if you use enough.

 

[Peatit]

Dear Ray,

I've been suffering from insomnia since childhood (difficulties falling asleep at night even felling my body tired and very light sleep) and even though I'm very closely following your advices for 3 years now, nothing seems to improve regarding this issue.
I know that you consider that sleep quality is correlated with high resting energy state of the brain but, despite the fact I've brought back my thyroid function to an adequate level (cynomel+NDT leading to highish body temperature and HR) and that I have a very good diet, my sleep hasn't improved.
I tried pregnenolone, salt, sugar, sodium bicarbonate, bag breathing, carrot salad, low dose DHEA (1-2mg), aspirin, sunlight exposure, red light etc. and nothing seems to help.
I also tried valerian and surprisingly, it has a stimulating effect on me. The only thing that sometimes knocks me out is cyproheptadine (only 0,5 mg) but I wake up in a very bad mood.
I might also specify that this problem isn't affected by my psychological stress level (which is low, most of the time).

Do you think that there might exist other important factors that I'm missing out?

Best regards,
------------------------------------------------------------------------------------

Histamine and serotonin promote wakefulness, and cyproheptadine blocks those, but its other effects aren’t very pleasant. Have you tried diphenhydramine? Endotoxin from intestinal bacteria increases histamine and serotonin; poor digestion is probably the most common cause of insomnia. Avoiding starches is often helpful. Small amounts of some excipients in supplements, and allergens in some foods, can increase the nighttime absorption of endotoxin. The antimicrobial/antiinflammatory effects of cascara can improve sleep; an antibiotic such as tetracycline can reduce the intestinal inflammation.

 

[raypeatclips]

Q. I know you advise the usual carrot/bamboo/mushrooms for fibers. I saw a comment of yours that commented about potato fiber being protective against bowel cancer, I wondered if there were any other fibers that you don't often talk about, that protect against bowel cancer in a similar way?

In general, cellulose fibers do protect against bowel cancer, but a few plant fibers that contain lignin or that are fermentable increase cancer. Wheat bran is the only common cereal fiber that’s protective.

Cancer Res. 1986 Apr;46(4 Pt 1):1727-34.
Relationship between colonic luminal pH, cell proliferation, and colon
carcinogenesis in 1,2-dimethylhydrazine treated rats fed high fiber diets.
Jacobs LR, Lupton JR.
The comparative effects of different fibers on colonic luminal pH, crypt cell
proliferation, and colon carcinogenesis were studied in 120 male Sprague-Dawley
rats. The animals were divided into five equal groups and fed either a basal
fiber free diet or the basal diet supplemented with 10% pectin, cellulose or
guar, or 20% oat bran for up to 30 weeks. 1,2-Dimethylhydrazine was given at 20
mg/kg body weight as a weekly s.c. injection for 12 weeks. Food intake and weight
gain were similar in all diet groups. At sacrifice, in vivo pH measurements
showed that compared to fiber free rats, all fibers significantly acidified large
bowel luminal contents (P less than 0.05). In the guar group 62.5% of rats
developed colonic tumors compared to 33.4% of the fiber free rats (P less than
0.05). The yield of proximal colonic adenocarcinomas in the oat bran, pectin, and
guar groups was increased by 4.5 to 5 times over the fiber free level (P less
than 0.05-0.025). Pectin and guar provided the greatest stimulus to cell
proliferation. A lower luminal pH was associated with a higher tumor yield and
increased epithelial cell proliferation. Thus, acidification of colonic contents
by high fiber diets failed to inhibit rat colon carcinogenesis, while the
consumption of soluble fibers, such as oat bran, pectin, and guar, was associated
with enhancement of proximal colon carcinogenesis.

Proc Soc Exp Biol Med. 1986 Dec;183(3):299-310.
Relationship between dietary fiber and cancer: metabolic, physiologic, and
cellular mechanisms.
Jacobs LR.
The relationships between fiber consumption and human cancer rates have been
examined, together with an analysis of the effects of individual dietary fibers
on the experimental induction of large bowel cancer. The human epidemiology
indicates an inverse correlation between high fiber consumption and lower colon
cancer rates. Cereal fiber sources show the most consistent negative correlation.
However, human case-control studies in general fail to confirm any protective
effect due to dietary fiber. Case-control studies indicate that if any source of
dietary fiber is possibly antineoplastic then it is probably vegetables. These
results may mean that purified fibers alone do not inhibit tumor development,
whereas it is likely that some other factors present in vegetables are
antineoplastic. Experiments in laboratory animals, using chemical induction of
large bowel cancer, have in general shown a protective effect with supplements of
poorly fermentable fibers such as wheat bran or cellulose. In contrast, a number
of fermentable fiber supplements including pectin, corn bran, oat bran,
undegraded carageenan, agar, psyllium, guar gum, and alfalfa have been shown to
enhance tumor development. Possible mechanisms by which fibers may inhibit colon
tumorigenesis include dilution and adsorption of any carcinogens and/or promoters
contained within the intestinal lumen, the modulation of colonic microbial
metabolic activity, and biological modification of intestinal epithelial cells.
Dietary fibers not only bind carcinogens, bile acids, and other potential toxins
but also essential nutrients, such as minerals, which can inhibit the
carcinogenic process. Fermentation of fibers within the large bowel results in
the production of short chain fatty acids, which in vivo stimulate cell
proliferation, while butyrate appears to be antineoplastic in vitro. Evidence
suggests that if dietary fibers stimulate cell proliferation during the stage of
initiation, then this may lead to tumor enhancement. Fermentation also lowers
luminal pH, which in turn modifies colonic microbial metabolic acidity, and is
associated with increased epithelial cell proliferation and colon carcinogenesis.
Because dietary fibers differ in their physiochemical properties it has been
difficult to identify a single mechanism by which fibers modify colon
carcinogenesis. Clearly, more metabolic and physiological studies are needed to
fully define the mechanisms by which certain fibers inhibit while others enhance
experimental colon carcinogenesis.

Prev Med. 1987 Jul;16(4):566-71.
Effect of dietary fiber on colonic cell proliferation and its relationship to
colon carcinogenesis.
Jacobs LR.
The addition of specific fiber supplements to semipurified diets has been shown
to stimulate large bowel cell proliferation in laboratory rodents. Relatively
insoluble fibers such as cellulose, which is poorly fermented, the more-soluble
oat bran, and inert bulking agents such as kaolin produce little or no effect on
cell growth. On the other hand, wheat bran, pectin, guar gum, and degraded
carageenan all stimulate large bowel cell proliferation, the greatest growth
response tending to occur in the cecum or proximal colon. The proximal large
bowel is also the major site for the intestinal fermentation of dietary fiber and
any other nonabsorbed carbohydrates. The fermentation of fiber by colonic
microorganisms results in the production of short-chain fatty acids and a lower
pH of large bowel contents, metabolic events known to be associated with
increased epithelial cell growth. In general, factors that stimulate cell growth
also enhance tumor development, a concept that holds true in the colon even for
dietary fibers such as pectin and guar gum. Wheat bran can also stimulate colon
carcinogenesis when fed only during carcinogen exposure. Oat bran and corn bran
may stimulate colon carcinogenesis by increasing fecal bile acid excretion, a
feature of many soluble fibers, while the acidification of large bowel contents
is associated with an increased frequency of chemically induced colonic cancers.
A greater understanding of colonic metabolism and cell physiology is needed to
define fully the mechanisms by which dietary fibers modify colon cancer
development.

J Nutr. 1997 Nov;127(11):2217-25.
Wheat bran diet reduces tumor incidence in a rat model of colon cancer
independent of effects on distal luminal butyrate concentrations.
Zoran DL, Turner ND, Taddeo SS, Chapkin RS, Lupton JR.
Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471, USA.
To investigate the effects of dietary fibers in colonic luminal physiology and
their role in the prevention of colon cancer, a study was conducted using two
diet groups and two treatment groups in a 2 x 2 factorial design. The two diets
differed only in the type of dietary fiber, wheat bran and oat bran, and the two
treatments were injection with the colon-specific carcinogen azoxymethane, or
saline, as a control. There were 34 rats in the carcinogen-injected groups and 11
saline-injected rats per diet group. The goal of the study was to determine if a
moderate consumption (6 g/100 g diet) of wheat bran or oat bran would alter the
development of colonic tumors in this rat model of colon cancer, and if the
differences in tumor incidence were correlated to luminal butyrate
concentrations, luminal pH or fecal bulk. Short-chain fatty acid concentrations
(SCFA) were measured in feces during the first half of the study (the promotion
phase of tumor development) and again at the end of the study. Rats consuming oat
bran had greater body weights (P < 0. 002), produced much larger concentrations
of all SCFA, including butyrate, in both the proximal and distal colon (P <
0.0001), had more acidic luminal pH values (P < 0.0001), but also had
significantly more development of colon tumors (P < 0.03). Alternatively, rats
consuming wheat bran produced more typical molar ratios of the SCFA (65:10:20),
had a relatively greater concentration of butyrate than propionate, and produced
a larger volume (P < 0.05) and more bulky stool than the rats fed oat bran. The
results of this study support other evidence that an acidic luminal pH is not
protective in and of itself, and that diets containing wheat bran are protective
against colon cancer development. In addition, these data show that large luminal
butyrate concentrations in the distal colon alone, as were present in the rats
consuming oat bran diets, are not protective of tumor development.

Cancer Res. 1989 Aug 15;49(16):4629-35.
Biochemical epidemiology of colon cancer: effect of types of dietary fiber on
fecal mutagens, acid, and neutral sterols in healthy subjects.
Reddy B, Engle A, Katsifis S, Simi B, Bartram HP, Perrino P, Mahan C.
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla,
New York 10595.
Several epidemiological studies suggest an inverse relationship between fiber
intake and colon cancer risk. Animal model studies indicate that this inhibitory
effect depends on the source of dietary fiber. Because of the potential
significance of certain colonic mutagens and secondary bile acids in the
pathogenesis of colon cancer, the effect of types of supplemental fiber on fecal
mutagens and bile acids was studied in human volunteers. Seventy-two healthy
individuals consuming high-fat/moderately low-fiber diets were screened for fecal
mutagenic activity using the Ames Salmonella typhimurium/microsomal assay system.
Twenty-one of them were found to excrete high levels of mutagens, and 19 of them
were recruited for the diet intervention study. All participants provided two
24-h stool specimens and a 4-day food record while consuming their normal
(control) diet. They were then asked to consume the control diet plus 10 g of
dietary fiber from wheat bran, oat fiber, or cellulose for 5 wk. After each fiber
period, they were asked to consume their control diet. At the end of each fiber
and control diet period, each subject provided two 24-h stool specimens. Stool
samples were analyzed for bile acids and mutagens using the Ames strains TA98 and
TA100 with or without S9 (microsomal) activation. The concentrations of fecal
secondary bile acids (deoxycholic acid, lithocholic acid, and 12-ketolithocholic
acid) and of fecal mutagenic activity in TA98 and TA100 with and without S9
activation were significantly lower during the wheat bran and cellulose
supplementation periods. Oat fiber supplementation had no such effect on these
fecal constituents. Thus, the increased fiber intake in the form of wheat bran or
cellulose may reduce the production and/or excretion of mutagens in the stools
and decrease the concentration of fecal secondary bile acids in humans.

Prev Med. 1987 Jul;16(4):540-4.
Fiber, stool bulk, and bile acid output: implications for colon cancer risk.
McPherson-Kay R.
Dietary fiber has direct effects on stool bulk and bile acid output that may be
of relevance in the etiology of colon cancer. Most types of fiber increase the
total volume of stool and reduce the concentration of specific substances,
including bile acids, that are in contact with the bowel wall. However, fibers
differ in their effect on stool bulk, with wheat fiber being a more effective
stool bulking agent than fruit and vegetable fibers. In addition, the extent to
which a specific fiber reduces bile acid concentration will be modified by its
concomitant effects on total fecal sterol excretion. Whereas wheat bran reduces
fecal bile acid concentration, pectin, lignin, and oat bran do not. These three
fibers significantly increase total bile acid output. Bile acids act as promoters
of colonic tumors in mutagenesis assay systems and in various animal models.
Human epidemiological studies show a relationship between various dietary
variables, including fat and fiber intake, fecal concentration of bile acids, and
colon cancer risk.

 

[HDD]

I'm posting this since Ray Peat is recommending an antihistamine (ketotifen)that, as far as I know, is new in his recommendations.

"Have you tried other types of antihistamine, such as ketotifen, diphenhydramine, or cyproheptadine?"

 

[member 2106]

For hay fever: "Coffee, aspirin, and pregnenolone are usually helpful; Benadryl works for some people, though its excipients can be allergenic."

 

[Dan W]

Some orange juice e-mails:

Are you concerned about frozen concentrate packaging?

Yes, but I weigh it against the alternatives.

What are the problems of the reconstituted or fresh commercial juices nowadays? Unripeness, enzymes, flavor packs?
The CostCo Kirkland brand seems clean, and comes in a HDPE plastic bottle, but I haven't tried it.

The fresh ones shouldn't have any problems, but some of the pasteurized kind seem to have been processed in other ways. I just use the kinds that taste o.k. and don't produce bad reactions.

In a past email exchange, you've stated that you started getting allergic reactions (due to the enzymes used to liquefy the pulp) to frozen concentrate OJ, but lately, you've said you use it when good fruit is scarce. Has the process of its production changed, or are some products OK, without the liquefied pulp?

All the major companies now say that they aren't using the pulp-melting enzymes; I think they were afraid of getting sued.

 

[Wagner83]

Hi Ray!

In a previous discussion you said :" For topical use (T3), I think about a tenth of a microgram per milliliter is effective."
Do you mind sharing why such a dilution is necessary?

I think that was referring to its use as eye drops, where it’s extremely well absorbed.

Ok , do you think on other body parts T3 is pretty useless or needs a much higher concentration to have an effect?
I have found information on how the skin deactivates or transforms thyroid hormones but not sure about T3, certain forms of T2 have their use.

Spoiler: References

References:

Expression of Hypothalamic–Pituitary–Thyroid Axis Related Genes in the Human Skin
"Actual transformation of T4 to T3, and of T3 to T2 have been demonstrated in cultured epidermal keratinocytes (Kaplan et al, 1988), although the pattern of expression of the corresponding genes has not been evaluated in human skin."

Acute downregulation of Type II and Type III iodothyronine deiodinases by photoperiod in peripubertal male and female Siberian hamsters. - PubMed - NCBI
"whereas DIO3 both catabolizes T3 into diiodothryonine (T2) "

Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats. - PubMed - NCBI

"3,3'-T2 did not affect GH levels whatever the dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum TSH and GH levels in rats."

3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro. - PubMed - NCBI
"These data confirm that T2 has significant thyromimetic activity, and that this activity is selective both in vivo and in vitro. However, there are no data to support a selective central effect, T2 being relatively more potent in stimulating hepatic ME mRNA than in suppression of TSH in vivo. The basis for this differential thyromimetic activity is not selective affinity of the different TR isoforms for T2, or divergent properties of T2 in competitive binding and functional assays in vitro."

Every tissue of the body that has been tested for it has the enzymes needed to metabolize thyroxine; toxins, such as lipid peroxides, can affect some tissues more than others, making a T3 supplement more valuable for them. Systemic changes, such as in calcium, phosphate, vitamin D, and sugar, can affect them, and a higher-than-normal concentration of hormone on the skin, can sometimes overcome those regional defects. One researcher found that T3 is normally converted into 3,5-T2 by functional mitochondria.

 

[Wagner83]

So if T3 is converted into T2 by healthy mitochondria then topical T3 does not sound like it would have negative effects besides the possibility of taking too much at once . Would the threshold be quite lower than for an oral dose since the effects are regional?

Ray said:

If it penetrates about half a centimeter into the skin before it’s greatly diluted by the blood, the local concentration could be high with moderate absorption. People have had good results using a solution with 10 mcg in 100 ml. on skin rashes.

 

[raypeatclips]

Q. Any dangers on taking magnesium when prolactin is high?

Correcting a magnesium deficiency can help to correct excessive prolactin, but I haven’t heard warnings related to prolactin. When an excess of magnesium is taken up very quickly it can cause profound anesthesia, but the kidneys soon excrete enough to correct it.

 

[Elderflower j58]

Hello Dr Peat '
I hope you can point me in the right direction regarding
Retrieving some sort of smile that I desperately need.

I have only 3 teeth left in my mouth,started losing my teeth one by one
About 12 years ago,before that gum disease, loose teeth , teeth breaking off at
Gum line. I was told I had a calcium problem years ago and to drink more milk

Lost one tooth each on my first two pregnancies ,two on third
Mostly stayed away from dentists after traumatic painfull removal
Of two wisdom teeth in my teens,never went back for other two

I thought I was doing the right thing holding on to my remaining teeth stumps
As I had lots of bone loss and the bone wouldn't diminish as much if I kept my stumps.
Now it seems I've been holding on to toxic teeth that most probably have caused cavitations. I m just frozen as to what options are open to me.I have no pain in my mouth
Last abscess about 2 years ago ,oil pulling I found great for abscesses

The big worry for me is deep silent toxic infection in my jawbone,plus the connection
With heart disease which I have since age 39, 6 or 7 stents ,heart attack in 2015 which resulted in 3 stents back to back, torturous angioplasty almost 3 hours long ,dissection,
But recovered well.

I don't take any heart meds ,I eat quite healthy no obvious puffa's
I take vit AEDK ,taurine magnesium ,progesterone Brewers yeast.

I'm awaiting genetic test results from lipid clinic regarding my very high cholesterol
Total cholesterol.::: last summer--10.1, Christmas--7.4,--- may this year---6.3
No statin I think taurine lowered it nicely,not too worried about it


I desperately need a smile of some sort, I feel so guilty ,I promised my husband
I would get my teeth fixed,he sadly passed away in February .
I need to feel whole again

All your advice greatly appreciated

Dr peats answer

I think you’re right about keeping the roots to reduce bone loss; rinsing the mouth with coconut oil reduces bacteria. Dental abscesses probably originate with digestive problems; a dentist I knew discovered that he no longer had to treat his patients’ periodontal disease surgically when he prescribed laxatives for them. I think the “silent infection” doctrine is mostly an excuse for expensive treatments. The association between jaw abscesses and heart disease is probably by way of a more general problem involving low vitamin D, a low ratio of calcium to phosphate in the diet, intestinal inflammation, and chronic activation of the renin-angiotensin system.

 

[raypeatclips]

Q. What do you think about applying fat soluble vitamins or hormones such as pregnenolone in oil bases to the testicles?

With pure vitamin E as a solvent it might be o.k., but I think it’s risky to alter the lipids in the environment of the gonads.

 

[milk_lover]

Q. What is your opinion about swimming in public swimming pools? Are the chlorine and human urine a concern since our skins are live large organs that can interact with the environment? My hair becomes really weird after swimming.

I don’t think it’s something that a person should spend a lot of time doing.

 

[ecstatichamster]

I asked Ray about his ideas on vegetarianism and how key that is to the Gerson diet outcomes.
----

The ratio of potassium to sodium, and the avoidance of polyunsaturated oils, were basic principles of Gerson’s. I think his objection to milk and cheese was based on their high fat content, and the addition of salt to cheese. The nutritional composition of milk from grass fed animals is very similar to that of the grass they ate, apart from the saturation of the fatty acids. The current ideas of the Gerson diet don’t accurately reflect Gerson’s ideas; for example, the book his daughter published about 20 years after his death advocated using linseed oil, on the pages where he had warned in capital letters against using any oil, and she claimed that she had found information in his office indicating admiration for Johanna Budwig’s ideas, including the use of linseed oil.

 

[milk_lover]

Q. Does Coke have any advantage over Pepsi nutritionally or allergy wise?

That has been my impression, but I haven’t seen any organized tests of it.

 

[Wagner83]

"Hi Ray,

[...]
These compounds have been used to treat worms: thiabendazole, levamisole (doesn't look safe), albendazole, mebendazole , pranziquatel and niclosamide. Are any of these better to use? What about flowers of sulphur, garlic and coconuts?"

The last three are safe.

 

[Dan W]

Response to a question about whether sourdough that hasn't been fermented long is better than normal dough that has been fermented for 24-32 hours:

It’s the time of soaking that lets the enzymes break down the gluten, so I think the longer time is probably better, but I haven’t had experience with longer than about 16 hours. The nature of the starter makes a difference, and adding sugar is a way to prevent the development of a bad taste. It’s essential to use flour that hasn’t been heat treated.

 

[paymanz]

what are your thoughts on eating ruminant animal's brain? lightly cooked.

for its hormones and cholesterol content.

The steroids are probably valuable; although I’m skeptical of the mad cow disease theory, I don’t eat ruminant brains.

 

[aquaman]

Q: Is Arimidex or another estrogen inhibitor safe to use, or would it have other hormonal consequences?

I think the (liver, brain) toxicity of the commercial aromatase inhibitors is too great except for treating cancer. A diet, with good thyroid function, that corrected the bloating should gradually shift the fat distribution. Hypothyroidism would greatly increase the toxicity.

Brain Res. 2007 Aug 24;1165:21-9.
Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic
neuronal death in mixed mouse cortical cultures.
Orlando R, Caruso A, Molinaro G, Motolese M, Matrisciano F, Togna G, Melchiorri
D, Nicoletti F, Bruno V.
Department of Human Physiology and Pharmacology, University of Rome La Sapienza,
Italy.
The use of anabolic-androgenic steroids (AASs) in the world of sport has raised a
major concern for the serious, sometimes life-threatening, side effects
associated with these drugs. Most of the CNS effects are of psychiatric origin,
and whether or not AASs are toxic to neurons is yet unknown. We compared the
effect of testosterone with that of the AASs, 19-nortestosterone (nandrolone),
stanozolol, and gestrinone, on excitotoxic neuronal death induced by
N-methyl-d-aspartate (NMDA) in primary cultures of mouse cortical cells. In the
most relevant experiments, steroids were applied to the cultures once daily
during the 4 days preceding the NMDA pulse. Under these conditions, testosterone
amplified excitotoxic neuronal death only at very high concentrations (10 muM),
whereas it was protective at concentrations of 10 nM and inactive at intermediate
concentrations. Low concentrations of testosterone became neurotoxic in the
presence of the aromatase inhibitors, i.e. anastrozole and aminoglutethimide,
suggesting that the intrinsic toxicity of testosterone was counterbalanced by its
aromatization into 17beta-estradiol. As opposed to testosterone, nortestosterone,
stanozolol and gestrinone amplified NMDA toxicity at nanomolar concentrations;
their action was insensitive to aromatase inhibitors, but was abrogated by the
androgen receptor antagonist, flutamide. None of the AASs were toxic in the
absence of NMDA. These data suggest that AASs increase neuronal vulnerability to
an excitotoxic insult and may therefore facilitate neuronal death associated with
acute or chronic CNS disorders.

 

[Wagner83]

Hi Ray,


I wonder if the agaritine and other toxic compounds in mushrooms are actually extracted in the broth rather than being mostly destroyed, the mushrooms themselves look safe after thorough cooking, but given the quotes below I'm not sure the broth is:


1)
Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom. - PubMed - NCBI
"
[...]. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure."

2)

"
Also, Schulzová et al. (2002) studied the effect of boiling on the content of agaritine in the cultivated mushroom. Sliced fruit bodies of A. bitorquis, containing 360 mg agaritine/kg, were boiled in closed jars in steam. Similar results as shown in Figure 8 were obtained, when whole mushrooms were used instead of sliced mushrooms. As can beseen in Figure 8, boiling resulted in a significant progressive decrease of agaritine in solid mushrooms, whereas the concentration in the aqueous solution increased during the first 15 minutes. No further increase in the agaritine content of the boiling water was observed thereafter. The most pronounced changes occurred during the first minute of boiling. The solid mushrooms had lost 55% of their agaritine after 5 minutes of boilingand about 90% after 60-120 minutes of boiling. The total amount of agaritine in the system was also reduced during cooking, being about 75% of the original amount after 5 minutes and about 60% of the original amount after 60 minutes of boiling."


By the way:

"
Table 7 summarises published measurements on agaritine content of canned Agaricus bisporus. It is evident that relatively low agaritine levels are found in canned products, usually less than 10 % of the agaritine level detected in fresh mushrooms (Liu et al., 1982; Stijve et al., 1986; Hajslŏvá et al., 1998; Andersson et al., 1999). "

Information extracted from this interesting pdf: https://www.google.ch/url?sa=t&rct=...01.pdf&usg=AFQjCNHtqlUrZHxXWmUW5xLubHgE444C6A :

Boiling sliced mushrooms for three hours extracts most of the beneficial things into the water, and I think the balance is favorable.

Mycopathologia. 1984 Mar 15;85(1-2):75-9.
Lack of carcinogenicity of agaritine by subcutaneous administration in mice.
Toth B, Sornson H.
Agaritine (A), an ingredient of the cultivated mushroom of commerce Agaricus
bisporus, was administered by subcutaneous injection to two groups of randomly
bred Swiss mice. In the first group the animals of both sexes were treated at a
100 micrograms/g body weight basis five times at weekly intervals, while in the
second group the mice received a single A treatment of 100 micrograms/g body
weight for females and 50 micrograms/g body weight for males. The administration
of the compound resulted in no detectable carcinogenic effect in the animals.
Since some of the breakdown products of A were shown to be carcinogenic in mice
and the mushroom itself was found to be mutagenic, the field is discussed in the
light of the obtained results.

J Toxicol Environ Health. 1981 Jul-Aug;8(1-2):1-9.
Studies of the tumorigenic potential of 4-substituted phenylhydrazines by the
subcutaneous route.
Toth B, Nagel D.
4-Methylphenylhydrazine hydrochloride (4-MPH) was administered to randomly bred
Swiss mice as 26 weekly sc injections of 140 microgram per gram of body weight
and N'-acetyl-4-(hydroxymethyl)phenylhydrazine (AMPH) as 26 weekly sc injections
of 500 microgram/g. As a solvent control, physiological saline was also given as
26 weekly sc injections of 0.01 ml/g. The 4-MPH treatment induced a significant
incidence (24%) of fibrosarcomas in males. In the 4-MPH-treated females and some
AMPH-treated male mice, a few soft-tissue tumors were observed; however, their
appearance could not be related to treatment. 4-MPH is formed under special
experimental conditions from 4-hydroxymethylphenyl-hydrazine, which is an in
vitro breakdown product of agaritine, an ingredient of the cultivated mushroom
Agaricus bisporus. The implications of the findings are discussed.

Anticancer Res. 1981;1(5):255-8.
Attempted tumor induction with agaritine in mice.
Toth B, Raha CR, Wallcave L, Nagel D.
Agaritine, a constituent of the cultivated mushroom of commerce Agaricus
bisporus, was administered at concentrations of 0.0625 and 0.03125% in drinking
water daily for life to randomly bred Swiss mice. Consumption of the chemical
resulted in no detectable carcinogenic action under the experimental conditions.
During the course of the experiment, however, a substantial number of animals
developed convulsive seizures.

Biochim Biophys Acta. 2010 Jul;1800(7):669-73.
Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity
against leukemic cells.
Endo M(1), Beppu H, Akiyama H, Wakamatsu K, Ito S, Kawamoto Y, Shimpo K, Sumiya
T, Koike T, Matsui T.
(1)Department of Biology, Faculty of Medical Technology, Fujita Health University
School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
BACKGROUND: Mushrooms of the genus Agaricus are a common folk remedy against
carcinoma. The active ingredients, polysaccharides and protein-polysaccharide
complexes containing beta-glucan, have been isolated and shown to have indirect
tumor-suppressing activity via an immunological activation.
METHODS: The diffusible fraction of a hot-water extract of Agaricus blazei
Murrill (ABM) powder was fractionated by HPLC based on the anti-tumor activity
against leukemic cells in vitro. The structure of the anti-tumor substance was
determined by NMR and MS analyses.
RESULTS: We purified a tumorcidal substance from the diffusible fraction of ABM
and identified it as agaritine, beta-N-(gamma-l(+)-glutamyl)-4-(hydroxymethyl)
phenylhydrazine, having a molecular mass of 267 Da. This compound inhibited the
proliferation of leukemic cell lines such as U937, MOLT4, HL60 and K562 with
IC(50) values of 2.7, 9.4, 13.0, and 16.0 microg/mL, respectively, but showed no
significant effect on normal lymphatic cells at concentrations up to 40
microg/mL. Although agaritine has been suspected of having genotoxic or
carcinogenic properties, agaritine did not activate the umu gene of Salmonella,
which reacts to carcinogens.
GENERAL SIGNIFICANCE: The results indicate that agaritine from ABM has direct
anti-tumor activity against leukemic tumor cells in vitro. This is in contrast to
the carcinogenic activity previously ascribed to this compound. Our results also
show that this activity is distinct from that of beta-glucan, which indirectly
suppresses proliferation of tumor cells.

Food Chem Toxicol. 1998 Nov;36(11):971-4.
Covalent binding of agaritine to DNA in vivo.
Shephard SE(1), Schlatter C.
(1)Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
14C-Ring-labelled agaritine was administered orally to eight C57BL/6 mice at a
chemical dose of 7.5 mg and radioactive dose of 1.2 x 10(9) dpm/kg body weight.
After 24 hr, the animals were killed and DNA from stomach, liver and kidneys was
purified by a phenol-free method involving proteinase K digestion of chromatin
and coprecipitated proteins, followed by hydroxylapatite chromatography, dialysis
and precipitation with ethanol. An increase in radioactivity was found in DNA of
all three organs examined. Stomach DNA had the highest levels: 160 and 30 dpm/mg
DNA in males and females, respectively. Liver and kidney DNA both showed levels
of approximately 1 dpm/mg, with no measurable gender differences. Expressed in
the units of the covalent binding index (CBI), agaritine has a potency of 42 in
mouse stomach in males and 8 in females. The CBI of agaritine in liver and kidney
was 0.2-0.3 in both sexes. The genotoxic activity of agaritine is thus very weak.
The cumulative lifetime cancer risk of agaritine consumption in mushrooms is
estimated to lie at approximately 10(-5).

Cancer Lett. 1997 Nov 25;120(1):79-85.
Failure of the cultivated mushroom (Agaricus bisporus) to induce tumors in the
A/J mouse lung tumor model.
Pilegaard K(1), Kristiansen E, Meyer OA, Gry J.
(1)Institute of Toxicology, National Food Agency of Denmark, Søborg.
We studied whether the cultivated mushroom (Agaricus bisporus) or
4-(carboxy)phenylhydrazine (CP) induce lung adenomas in the A/J mouse lung tumor
model. For 26 weeks female mice were fed a semisynthetic diet where 11 or 22% of
the diet was replaced by freeze-dried mushrooms. The intake of the mushroom diets
was equivalent to an intake of agaritine, the major phenylhydrazine derivative
occurring in the mushroom, of 92 or 166 mg/kg body weight per day. The intake of
CP was 106 mg/kg body weight per day. Neither the freeze-dried mushroom nor CP
induced statistically significant increased numbers of lung adenomas in female
A/J mice in the administered dosages.

Food Chem Toxicol. 1995 Apr;33(4):257-64.
Genotoxicity of agaritine in the lacI transgenic mouse mutation assay: evaluation
of the health risk of mushroom consumption.
Shephard SE(1), Gunz D, Schlatter C.
(1)Swiss Federal Institute of Technology, Schwerzenbach.
The mutagenic potency of the common mushroom Agaricus bisporus and crude
agaritine extracted from mushrooms was determined in vivo using a new mutagenesis
assay with lacI transgenic mice (Big Blue mice). Pairs of female lacI mice were
fed one of three diets for 15 wk: (1) fresh mushrooms 3 days/wk followed by
normal lab chow for 4 days/wk; (2) freeze-dried mushrooms mixed at 25% (w/w) into
powdered chow; or (3) a mushroom extract containing 30% agaritine (w/w) mixed
into powdered chow. The corresponding daily doses of agaritine were 30 (averaged
over the whole week), 80 and 120 mg/kg body weight, respectively. Positive
control animals received N-nitrosodimethylamine, N-nitrosomethylurea or urethane,
mixed into powdered chow at concentrations corresponding to daily doses of 0.3, 3
and 130 mg/kg body weight, respectively. DNA of the forestomach, kidney, liver,
lung and glandular stomach of the lacI mice was examined for increases in mutant
frequency (MF). Control MFs ranged from 5 x 10(-5) to 10 x 10(-5). Positive
control substances induced a two- to seven-fold increase in MF in their
respective target organs. Of the mushroom diets, significant effects were seen
only with the crude agaritine extract: it induced an increase in MF of 100% in
the kidney and 50% in the forestomach. The other two A. bisporus diets, with
lower agaritine doses, showed slightly but not significantly, raised MF values in
the kidney alone. Thus, agaritine was weakly genotoxic in vivo; no genotoxic
activity other than that attributable to agaritine was detected in A. bisporus.
Substances or processes that might influence carcinogenicity by means of
non-genotoxic mechanisms (e.g. increase in fibre, or decrease in calorie intake)
are not detected in the lacI assay. Using a previously derived quantitative
correlation between mutagenicity in the lacI test and carcinogenic potency, the
carcinogenicity of agaritine in mushrooms was estimated: the average Swiss
mushroom consumption of 4 g/day would be expected to contribute a lifetime
cumulative cancer risk of about two cases per 100,000 lives.

Naunyn Schmiedebergs Arch Pharmacol. 2016 Feb;389(2):131-49.
Natural compounds for pediatric cancer treatment.
Ferrucci V(1)(2), Boffa I(1)(3), De Masi G(1)(3), Zollo M(4)(5)(6).
(1)Department of Molecular Medicine and Medical Biotechnology, 'Federico II'
University of Naples, Via Pansini 5, Naples, Italy.
(2)European School of Molecular Medicine (SEMM), Milan, Italy.
(3)Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
(4)Department of Molecular Medicine and Medical Biotechnology, 'Federico II'
University of Naples, Via Pansini 5, Naples, Italy. [email protected].
(5)European School of Molecular Medicine (SEMM), Milan, Italy.
[email protected].
(6)Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
[email protected].
There is a tremendous need in clinics to impair cancer progression through
noninvasive therapeutic approaches. The use of natural compounds to achieve this
is of importance to improve the quality of life of young patients during their
treatments. This review will address the "status of the art" related to the
potential of natural compounds that are undergoing investigation in combination
with standard therapeutic protocols in preclinical and clinical studies and their
importance for pediatric cancer treatment. The early studies of drug discovery of
these natural compounds discussed here include the main targets, the cellular
signaling pathways involved, and the potential modes of action. We also focus on
some promising natural compounds that have shown excellent results in vitro and
in vivo: Chebulagic acid, Apigenin, Norcantharidin, Saffron/Crocin, Parthenolide,
Longikaurin E, Lupeol, Spongistatin 1, and Deoxy-variolin B. Additionally, we
introduce the effects of several compounds from nutraceutical and functional
foods, to underline their potential use as adjuvant therapies to improve
therapeutic benefits. For this purpose, we have selected several compounds:
Agaritine, Ganoderma and GL6 peptide, Diallyl trisulfide and Ajoene from garlic,
Epigallocatechin gallate from green tea, Curcumin, Resveratrol, and Quercetin.

Nutr Cancer. 2000;37(1):55-64.
Fate of the mushroom hydrazine agaritine in the rat and mouse.
Walton K(1), Coombs MM, King LJ, Walker R, Ioannides C.
(1)School of Physical Sciences, University of Surrey, Guildford, UK.
The fate of the mushroom hydrazine [14C]agaritine was investigated in the mouse
and rat strains previously employed in carcinogenicity studies with the edible
mushroom Agaricus bisporus. Agaritine was rapidly absorbed in both species,
achieving higher blood levels in the mouse, but with similar area under the
curve. Covalent binding of agaritine material to proteins was detected only in
the liver and kidney, but the extent of binding was the same in the rat and
mouse. Most of the radioactivity was excreted during the first 24 hours in both
animal species: in the rat it was distributed equally between urine and feces,
whereas in the mouse more of the radioactivity was excreted in the urine. No
qualitative differences in the metabolic profile were evident, but quantitative
differences were observed. Treatment of the urine with deconjugating enzymes did
not reveal the presence of any conjugates. Agaritine,
N'-acetyl-4-(hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzene
diazonium ion were not detected in the urine or in the plasma of either species.
No mutagens or promutagens were detected by the Ames mutagenicity assay in
the urine of either species after exposure to agaritine. Repeated administration of
agaritine to rats and mice did not alter the urinary metabolic profile and
excretion of radioactivity. Similarly, feeding mice a raw mushroom diet,
according to the protocol employed in the carcinogenicity studies, did not
modulate the excretion of radioactivity or the urinary metabolic pattern. No
major species differences in the fate of agaritine in rat and mouse were noted
that could provide a rationale for the carcinogenicity of A. bisporus in the
mouse, but not in the rat.

Biochim Biophys Acta. 2011 May;1810(5):519-25.
Agaritine from Agaricus blazei Murrill induces apoptosis in the leukemic cell
line U937.
Akiyama H(1), Endo M, Matsui T, Katsuda I, Emi N, Kawamoto Y, Koike T, Beppu H.
(1)Department of Clinical Hematology, Fujita Health University School of Health
Sciences, Toyoake, Aichi 470-1192, Japan. [email protected]
BACKGROUND: Agaricus blazei Murrill (ABM) has been shown to exhibit
immunostimulatory and anti-cancer activities; however, its mechanism of action is
poorly understood. We recently found that the diffusible fraction of hot-water
extract of ABM exhibits anti-tumor activity toward leukemic cells, and identified
it as agaritine, a hydrazine-containing compound. In the present study, we
examined the morphological and cytochemical effects of agaritine on U937 cells to
elucidate the tumoricidal mechanism of agaritine.
METHODS: Surface expression of phosphatidylserine (evaluated by annexin V
binding), Fas antigen, DNA cleavage using TUNEL staining, changes in caspase
activities and cytochrome c release, before and after treatment with agaritine,
were examined using U937 cells.
RESULTS: Nuclear damage, DNA fragmentation, was observed by Wright-Giemsa, TUNEL
staining and agarose gel electrophoresis when U937 cells were incubated with
10μg/mL of agaritine for 48h. Flow cytometric analysis indicated that agaritine
augments the proportion of annexin V-positive U937 cells without significant
change in Fas antigen expression. Activities of caspase-3, -8 and -9 were
gradually increased after the addition of agaritine. In the presence of caspase-3
or granzyme B inhibitor, except for the caspase-8 inhibitor, annexin V expression
was significantly decreased, suggesting that mainly caspase-3 and -9 participate
in the apoptotic pathway. Furthermore, cytochrome c release was detected by
western blotting analysis after agaritine treatment.
CONCLUSIONS: These results strongly suggest that the ABM constituent agaritine
moderately induces apoptosis in U937 leukemic cells via caspase activation
through cytochrome c release from mitochondria.
GENERAL SIGNIFICANCE: This is the first report suggesting that the anti-tumor
effect of agaritine is mediated through apoptosis. The present results might
provide helpful suggestions for the design of anti-tumor drugs toward leukemia
patients.

 

[Wagner83]

Same conversation as above:

Thanks for the references, it looks like agaritine in particular could be beneficial rather than toxic/carcinogenic. I have felt really strong anti-aromatase effects from the broth, but do you know if the lanosterol and proteins somehow end up in the broth? My guess was that what is left in the mushrooms (solid) may not be absorbable.

I think it’s best to grind them, because the fibrous material isn’t digestible; steroids will be emulsified with the various lipids.