Ray Peat Email Advice Depository

[Pointless]

From Jun 4, 2011
RP:
"I keep thinking about doing a newsletter about fructose, but I think the ideology behind the hatred of fructose is the real issue. The typical internet libertarian ideology thinks the killer ape doctrine of Konrad Lorenz, Robert Ardrey, and Desmond Morris is the essence of anthropology. For most of these people, hunter-gatherers were just hunters who found some seeds occasionally."

COMRADE PEAT CONFOIRMD

 

[Sheila]

In answer to a question about the anaemia of chronic disease and leukaemia....

"Estrogen is a stress and crisis hormone, so there’s a steady upward tendency in its effect with age, which is interrupted during the fertile years by progesterone. Progesterone decline usually starts around age 40 because of things interfering with thyroid function. Declining liver function and increasing pituitary activity influence the way problems develop. Oxygen tension is normally low in bone marrow, and stimulates constant cell proliferation, but when estrogen’s oxygen-wasting effect is added, it changes the balance of cell growth; its worst effect is to stimulate fibroblasts and collagen production in the marrow, displacing the red and white cells. Estrogen shifts cells from oxidative production of carbon dioxide to the glycolytic formation of lactic acid, tending to prevent normal differentiation of cell function. The effects of estrogen include the leakage of the lactic acid-forming enzyme LDH into the serum, and the increase of copper in the serum, and these are recognized as signs of CLL, but the genetic-clonal ideology of cancer prevents recognition of the metabolic pattern. Estrogen causes relative hyperventilation, reinforcing the cellular changes. CLL seems to be less common in people adapted to high altitude, where lactic acid formation is inhibited."

 

[Sheila]

And the papers he so kindly sent to go with this response/1

Eur J Appl Physiol Occup Physiol. 1994;69(5):402-7.
Hyperventilation-induced changes of blood cell counts depend on hypocapnia.
Stäubli M, Vogel F, Bärtsch P, Flückiger G, Ziegler WH.
Department of Medicine, University of Bern, Switzerland.
Voluntary hyperventilation for 20 min causes haemoconcentration and an increase
of white blood cell and thrombocyte numbers. In this study, we investigated
whether these changes depend on the changes of blood gases or on the muscle work
of breathing. A group of 12 healthy medical students breathed 36 l.min-1 of air,
or air with 5% CO2 for a period of 20 min. The partial pressure of CO2 decreased
by 21.4 mmHg (2.85 kPa; P < 0.001) with air and by 4.1 mmHg (0.55 kPa; P < 0.005)
with CO2 enriched air. This was accompanied by haemoconcentration of 8.9% with
air (P < 0.01) and of 1.6% with CO2 enriched air (P < 0.05), an increase in the
lymphocyte count of 42% with air (P < 0.001) and no change with CO2 enriched air,
and an increase of the platelet number of 8.4% with air (P < 0.01) and no change
with CO2 enriched air. The number of neutrophil granulocytes did not change
during the experiments, but 75 min after deep breathing of air, band-formed
neutrophils had increased by 82% (P < 0.025), whereas they were unchanged 75 min
after the experiment with CO2 enriched air. Adrenaline and noradrenaline
increased by 360% and 151% during the experiment with air, but remained unchanged
with CO2 enriched air. It was concluded that the changes in the white blood cell
and platelet counts and of the plasma catecholamine concentrations during and
after voluntary hyperventilation for 20 min were consequences of marked
hypocapnic alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

JNMA J Nepal Med Assoc. 2009 Jan-Mar;48(173):35-40.
Pattern of occurrence of leukemia at a teaching hospital in eastern region of Nepal - a six year study.
Kulshrestha R, Sah SP.
INTRODUCTION:
Pattern of leukemia is known to vary widely throughout the world. The characterization of distribution patterns of different subtypes of leukemia in Nepal needs further study. We wanted to study the leukemia pattern in our institute.
METHODS:
A retrospective study of 196 cases of leukemia, diagnosed at BPKIHS, between January 1997 to December 2002 was done. We analyzed the pattern of leukemia at BPKIHS by morphological subtype, gender, age at diagnosis, time period of diagnosis (seasonality), and geographic distribution.
RESULTS:
Morphological sub typing showed that 121 cases were of acute leukemia and 75 of chronic leukemia. Chronic myeloid leukemia constituted the single largest group comprising 35.2 % of all cases, followed by acute myeloid leukemia (28.57 %) and acute lymphoid leukemia (19.9 %). Maximum numbers of cases were from the lowlands while least number of cases were from the mountain districts. Results were compared with literature from Nepal and other countries. This is the second series of leukemia from Nepal.
CONCLUSIONS:
The data published in this study reflects the leukemia pattern in the eastern region of Nepal. The pattern and distribution of AML, CML, ALL was similar to that in the developed western countries while the lesser frequency of CLL was similar to that in Southeast Asian region.

 

[milk_lover]

I asked Peat about what he thinks of apple juice.

His answer: "Apple juice is very good nutritionally, apart from the risk of the fungal contaminant."

..........

[ moderator edit: related thread RP Email Advice Discussion: Fungal-Free Apple Juice ]

 

[milk_lover]

Follow up question on how to know if the apple juice is free of fungal contaminant.

Peat answered: "There are probably flavor indications, but I don’t know whether anyone has studied that."

 

[keith]

Asked about high blood pressure. I gave a few specifics about my particular situation (including being overweight), and noted that I previously tried high dose K2, and magnesium, and that I don't limit salt, so wanted to provide that context to his answer:

"Have you had a blood test for TSH and vitamin D? High TSH is often the main factor in high blood pressure, so it should be low. A deficiency of calcium or vitamin D can increase parathyroid hormone, increasing serum calcium and blood pressure. Drinking two quarts of low fat milk per day will help to lose weight and lower blood pressure.

Contrib Nephrol. 1991; 90: 206-11.
Calcium, parathyroids and aging.
Fujita T.
Department of Medicine, Kobe University School of Medicine, Japan.
Calcium is unique in its distribution in living organisms with an extremely high
hard and soft tissue and extra- intracellular concentration gradient. Calcium
deficiency through stimulating parathyroid hormone secretion tends to blunt such
a difference by paradoxically increasing the calcium concentration in the soft
tissue and intracellular compartment. Since aging is associated with the
progressive aggravation of calcium deficiency, such blunting also progresses
with aging. The dysfunction, damage and death of cells occurring in all diseases
is always associated with a blunting of the extra- and intracellular calcium
components. Calcium supplement especially with highly biologically available
active absorbable calcium, was associated with the suppression of parathyroid
hormone secretion and the normalization of a such blunting of intercompartmental
distribution of calcium examples in hypertension and diabetes mellitus with
evident improvement of clinical manifestations and laboratory tests.

Int J Cardiol. 1992 Jun; 35(3): 303-10.
Parathyroid hormone and genetic hypertension.
Schleiffer R.
Biologie Cellulaire & Physiopathologie Digestives, INSERM U61, Strasbourg,
France.
Recent research provides evidence that parathyroid hormone is implicated in the
pathogenesis of genetic hypertension. Abnormalities in calcium metabolism in
genetic hypertension have been reported. These include hypercalciuria, depressed
serum ionized calcium associated with enhanced serum parathyroid hormone levels.
Calcium supplement resulted in normalization of calcium metabolism and reduction
in blood pressure. In addition, removal of parathyroid glands attenuated the
rise in blood pressure in genetic hypertensive rat. This review focuses on the
links between calcium metabolism and calcium endocrine system abnormalities and
the etiology of experimental genetic hypertension. The mechanisms by which
dietary supplement and parathyroidectomy lower genetic hypertension are also
discussed. Although the causality of raised parathyroid hormone in genetic
hypertension is not yet fully understood, we conclude that this hormone may play
a permissive effect in the development of hypertension.

Eur J Endocrinol. 2001 Apr;144(4):339-46.
Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients.
Diekman MJ, Harms MP, Endert E, Wieling W, Wiersinga WM.
Department of Endocrinology, Academic Medical Centre, University of Amsterdam,
The Netherlands.
OBJECTIVE: Total peripheral vascular resistance (TPR) decreases in thyrotoxicosis
and increases in hypothyroidism. Several mechanisms may be involved, including
adaptation to changes in heat production and direct non-genomic effects of
tri-iodothyronine (T3) on vascular smooth muscle cells. The aim of this study was
to see if changes in TPR are related to changes in plasma concentrations of the
endothelial hormones adrenomedullin and endothelin-1 as well as other hormones
affecting vasculature. DESIGN: A prospective study. SUBJECTS: Eleven hypothyroid
patients (pretreatment: thyroid-stimulating hormone (TSH) 68 (38-201) mU/l, T3
0.7 (0.35-1.5) nmol/l, fT4 3.0 (2.0-5.9) pmol/l, median (range)) and 14 with
hyperthyroidism (pretreatment: TSH 0.02 (<0.01-0.06) mU/l, T3 6.4 (2.3-13.0)
nmol/l, fT4 56.1 (22.9-70.0) pmol/l) were studied before treatment and 3 months
after reaching the euthyroid state. Blood collection was carried out
simultaneously with the recording of finger arterial pressure (FINAP). Cardiac
output and TPR were derived from stroke volume computations by modelling flow
from the FINAP signal. RESULTS: Thyroid-function tests of hypothyroid and
thyrotoxic patients did not differ after restoration of the euthyroid state. TPR,
expressed in arbitrary units (AU), decreased after correction of hypothyroidism
(from 1.32+/-0.65 to 0.96+/-0.36 AU, P=0.04) and increased after correction of
hyperthyroidism (from 0.75+/-0.18 to 1.10+/-0.35 AU, P=0.007). Adrenomedullin
concentrations did not change during the transition from the hypothyroid state
3.2(0.9-11.0) pmol/l to the euthyroid state 4.9(0.9-8.6) pmol/l, but decreased
after treatment of hyperthyroidism, from 5.2(0.9-11.0) pmol/l to 2.2(0.9-5.4)
pmol/l. Plasma endothelin-1 was undetectable in all samples. Changes in TPR upon
treatment correlated with log DeltafT4 (r=-0.65, P=0.001), log DeltaT3, (r=-0.57,
P=0.006), Delta noradrenaline (r=0.54, P=0.02) and Delta ANP (atrial natriuretic
peptide) (r=-0.59, P=0.004). Multiple linear regression analysis indicated that
only T3 was an independent determinant of TPR. Changes in T3 accounted for 46% of
the variability in the changes in TPR. CONCLUSIONS: TPR is reduced in
thyrotoxicosis and increased in hypothyroidism. Restoration of the euthyroid
state normalizes TPR. Changes in TPR are not related to plasma adrenomedullin
concentrations, but 46% could be explained by changes in T3. Altered ANP
secretion and adrenergic tone may contribute to the T3-induced changes in TPR.
Clinical Trial

Ann Ital Med Int. 1997 Apr-Jun;12(2):94-7.
[Hypothyroidism with pseudo-ischemic and hypertensive clinical presentation: physiopathological and diagnostic considerations]
[Article in Italian]
La Brocca A.
Divisione di Medicina Interna, Ospedale Civile di Giaveno (TO), Azienda Regionale
U.S.L. 5 di Torino.
Serious primary hypothyroidism, disclosed fortuitously through routine thyroid
function test derangements, was found in a 40-year-old woman admitted to the
hospital with a tentative diagnosis of ischemic heart disease. The clinical
picture and electrocardiographic alterations of pseudo-ischemic heart disease
associated with hypertension, particularly diastolic, may be the only significant
manifestations of hypothyroidism. Substitutive hormone replacement therapy
enables a good prognosis for children and young adults. A diagnosis of
hypothyroidism should be considered during the initial evaluation of
pseudo-ischemic, hypertensive and hypercholesterolemic patients, even when no
other signs or clinical symptoms of hormonal deficiency are evident. Particular
attention should be paid to female patients, as they are much more frequently
affected by thyroid pathologies.

J Hum Hypertens. 1998 Feb;12(2):79-82.
Hypertension and hypothyroidism.
Fletcher AK, Weetman AP.
University of Sheffield, Department of Medicine, Northern General Hospital, UK.
Correction of the causes of secondary forms of hypertension usually restores
blood pressure to normal. Hypothyroidism is a potentially important but
overlooked cause of hypertension and restoration of euthyroidism with thyroxine
therapy usually results in a substantial reduction in both systolic and diastolic
blood pressure, especially in younger subjects. The mechanism of hypertension in
hypothyroidism is not completely understood: changes in circulating
catecholamines, their receptors and the renin-angiotensin-aldosterone system have
all been implicated. Effective treatment with thyroxine is readily available and
inexpensive.

Clin Endocrinol (Oxf). 1980 Oct;13(4):339-42.
Reversible hypertension and hypothyroidism.
Bing RF, Briggs RS, Burden AC, Russell GI, Swales JD, Thurston H.
Six patients with hypothyroidism and hypertension whose blood pressure fell to
normal when treated with thyroxine (172 +/- 7.2/112 +/- 2.1 to 140 +/- 3.2/84+/-
1.6 mmHg, P < 0.001) are described. Plasma renin activity (1.76 +/- 0.63 ng
angiotensin I.ml-1.h-1) was low before treatment. Hypertension with low plasma
renin is consistent with sodium retention. Hypertension in the hypothyroid
patient only requires further evaluation if it persists after adequate treatment
with thyroxine.

Fukuoka Igaku Zasshi. 1983 Sep;74(9):658-62.
[2 cases of hypothyroidism associated with hypertensive cerebral hemorrhage]
[Article in Japanese]
Yao H, Nishimura Y, Morita E, Watanabe A.

Hypertension. 1983 Jan-Feb;5(1):112-5.
Hypothyroidism as a cause of hypertension.
Saito I, Ito K, Saruta T.
To study whether there is an association between hypertension and hypothyroidism,
measurements of blood pressure and thyroid function were determined in 477 female
patients with chronic thyroiditis. Based on the blood levels of thyroxine (T4)
and thyroid stimulating hormone (TSH), 308 patients were considered euthyroid and
169 were hypothyroid [T4 = 2.9 +/- 0.1 micrograms/dl and TSH = 105.8 +/- 6.8
microU/ml (mean +/- SEM)]. Diastolic, but not systolic, blood pressure in
hypothyroid patients over 50 years was higher than in euthyroid patients of
corresponding age groups. The prevalence of hypertension was higher in
hypothyroid patients when hypertension was defined as the systolic and/or
diastolic blood pressure above 160/95 mm Hg (14.8% vs 5.5%; p less than 0.01).
Correlations between diastolic, but not systolic, blood pressure and either the
blood level of triiodothyronine (T3) or T4 was significant (r = - 0.174, p less
than 0.01, and r = 0.208, p less than 0.01, respectively) when data from both
euthyroid and hypothyroid patients were combined. Adequate thyroid hormone
replacement therapy for an average 14.8 months in 14 patients resulted in a
normalization of thyroid function and a reduction of blood pressure (p less than
0.01). In four who showed no change in thyroid function due to inadequate
replacement therapy, blood pressure remained elevated. These results suggest a
close association between hypertension and hypothyroidism.

Clin Exp Hypertens A. 1985;7(11):1499-514.
Hypertension in hypothyroidism: arterial pressure and hormone relationships.
Richards AM, Nicholls MG, Espiner EA, Ikram H, Turner JG, Brownlie BE.
To investigate the regulation of arterial pressure and vasoactive hormones in
hypothyroidism associated with hypertension, we measured intra-arterial pressure
and hourly venous hormones (renin, angiotensin II, aldosterone, catecholamines
and cortisol) for 24 hours in five hypertensive patients with primary
hypothyroidism before commencing treatment, and again after three to six months
of thyroxine replacement therapy. Arterial pressure fell significantly after
thyroxine replacement in four patients. Thyroxine treatment was associated with a
fall in plasma norepinephrine levels together with a decline in slopes of
norepinephrine/arterial pressure regression lines which suggests that the
sympathetic system may contribute to the hypertension in hypothyroidism.
Variability of heart rate, blood pressure and plasma norepinephrine fell with
thyroxine replacement consistent with impaired damping of swings in sympathetic
activity in the untreated state. Reciprocal changes in arterial pressure and
renin-angiotensin-aldosterone system activity suggested that this system was not
the mediator of hypertension in hypothyroidism.

Hypertension. 1988 Jan;11(1):78-83.
Effects of thyroid function on blood pressure. Recognition of hypothyroid hypertension.
Streeten DH, Anderson GH Jr, Howland T, Chiang R, Smulyan H.
Department of Medicine, SUNY-Health Science Center, Syracuse 13210.
Hypothyroidism has been known to be associated, at times, with diastolic
hypertension. We have found in 40 thyrotoxic patients that the induction of
hypothyroidism by radioiodine therapy significantly increased diastolic blood
pressure, raising it above 90 mm Hg in 16 (40%) of the patients. Restoration of
euthyroidism with thyroxine administration significantly reduced the systolic and
diastolic blood pressures in these patients, with a fall in diastolic pressure
below 90 mm Hg in nine of 16 patients. The prevalence of hypothyroidism was
determined by measurements of serum thyroxine and thyrotropin concentrations in
688 consecutive hypertensive patients, referred for evaluation and therapy of
their hypertension. Hypothyroidism was found in 25 (3.6%) of the patients.
Restoration of normal serum thyroxine and thyrotropin levels with thyroid hormone
replacement therapy lowered diastolic blood pressure to levels below 90 mm Hg in
32% of these patients who could be followed up after withdrawal of all
antihypertensive drug therapy when euthyroidism had been restored (i.e., 1.2% of
the 688 patients). It is concluded that diastolic hypertension resulting from
hypothyroidism is a relatively common disorder, present in 1.2% of our referred
hypertensive patients, that should be sought and treated.

Can J Physiol Pharmacol. 1994 Sep;72(9):1066-74.
A role for thyroid hormones in cold-induced elevation of blood pressure and cardiac hypertrophy.
Fregly MJ, Rossi F, Cade JR.
Department of Physiology, University of Florida, College of Medicine, Gainesville
32610-0274.
The systolic blood pressures of two groups of rats that were exposed to cold (5
degrees C) for 4 weeks were elevated significantly above that of warm-acclimated
controls maintained at 24 degrees C. At this time these groups were given the
antithyroid drug aminotriazole in their food at 0.3 g/kg. At the same time, one
group was given 15.8 micrograms thyroxine (T4)/kg body mass per day, while the
second received 31.6. The doses were chosen as replacement (15.8 micrograms/kg)
and twice replacement (31.8 micrograms/kg) for the rats. The results of the study
revealed that both groups receiving aminotriazole and T4 had reductions in blood
pressure within 1 week of initiation of treatment. Blood pressures reached
control level after 5 weeks. Cardiac hypertrophy accompanying cold-induced
hypertension was reduced with the lower dose of T4 and prevented with the higher
dose. Serum concentrations of T4 and triiodothyronine (T3) in the two treated
groups were reduced, while serum thyroid-stimulating hormone concentration and
thyroid mass were increased above that of the warm-acclimated control group. This
suggests that the rats were hypothyroid relative to the warm-acclimated control
group. However, the treated rats grew at the same rate as nontreated,
cold-exposed controls and had similar food and water intakes, a similar
dipsogenic response to acute administration of isoproterenol, and similar colonic
temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)"

 

[paymanz]

about tea , and if there is any concern in regard of its estrogen and tannin content...

The addition of lemon or milk to tea reduces the reactivity of the tannins. In recent years, the tea industry has very commonly been adulterating the product. Pu erh is one that still seems to be o.k.

 

[Simonsays]

I asked Ray whether it is possible for someone to start using T3 who has been running on adrenaline for so long without it making it worse.

He replied:

When T3 is used in small doses, such as 3 or 4 mcg at a time, it can be very effective for lowering adrenalin by letting glucose be more fully oxidized. It’s helpful to keep a chart of your waking and midday temperature and pulse rate to watch the cumulative effects of the T3, so you can adjust the dose. A dose at bedtime typically makes it possible to go to sleep quickly; it should be supported by things like orange juice, cheese, and milk. A natural desiccated thyroid product, in the long run, is a convenient way to keep your metabolic rate where it should be. Cytomel is the only T3 product that I’m confident of, at present.

 

[raypeatclips]

https://raypeatforum.com/community/...otoxin-my-experience.12803/page-3#post-177029

"Her taste for starches and sweet pastry is probably because she isn’t able to store glycogen efficiently, with stress hormones causing her to metabolize glucose quickly and wastefully. In hypothyroidism, chronically high free fatty acids interfere with the production of energy needed to stop the stress that keeps the fatty acids high. The starches are probably contributing to inflammation and the production of serotonin. Small doses of an antibiotic such as tetracycline or erythromycin can sometimes lower intestinal serotonin production, but it’s best to find an antiseptic food that can be used daily—well cooked mushrooms and bamboo sprouts are alternatives to raw carrot. Finding alternative foods for the starches might be possible—cakes can be made with powdered milk instead of flour, with eggs; salty meats (puffed pork rinds, or bacon fried in coconut oil, for example, can be used to make finely shredded carrots tasty); chewy gelatin with various flavors; and things like cream-puffs or yorkshire pudding, that minimize the use of flour, might help to lower her serotonin. I don’t think anesthesia should be combined with cyproheptadine, but I think dentists are too aggressive in treating deciduous teeth; the important thing is to improve her digestion and hormones as her permanent teeth are developing. The so-called temporary fillings, made of zinc oxide and eugenol, are very easy to put in, and are antiseptic and mildly anesthetic topically. (I had them in wisdom teeth, and they lasted for years.) X-rays, anesthesia, and drilling into invisible cavities have their place in especially problematic adult teeth, but seem inappropriate for teeth that will soon be gone."

 

[Velve921]

[moderator edit: related thread RP Email Advice Comment: Lung Cancer]

Dr. Peat wrote me this regarding lung cancer:

Lung cancer cells produce increased amounts of some things that promote abnormal growth, and some of these can be inhibited by common harmless materials. The effects of adenosine and (leaked) ATP are inhibited by caffeine, prostaglandins are inhibited by aspirin and pregnenolone, estrogen by progesterone, aromatase inhibitors, orange juice and cooked mushrooms, histamine and serotonin by antihistamines, cyproheptadine, nitric oxide by tetracycline, progesterone, agmatine, etc. Emodin, in cascara, blocks various things in lung cancer, and its laxative effect helps to lower nitric oxide, histamine, and serotonin.

1. Front Immunol. 2016 Mar 29;7:109.
A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment.
Ohta A(1).
(1)Center for Drug Discovery, Northeastern University , Boston, MA , USA.
Within tumors, some areas are less oxygenated than others. Since their home
ground is under chronic hypoxia, tumor cells adapt to this condition by
activating aerobic glycolysis; however, this hypoxic environment is very harsh
for incoming immune cells. Deprivation of oxygen limits availability of energy
sources and induces accumulation of extracellular adenosine in tumors.
Extracellular adenosine, upon binding with adenosine receptors on the surface of
various immune cells, suppresses pro-inflammatory activities. In addition,
signaling through adenosine receptors upregulates a number of anti-inflammatory
molecules and immunoregulatory cells, leading to the establishment of a
long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine,
tumors can discourage antitumor immune responses no matter how the response was
induced, whether it was spontaneous or artificially introduced with a therapeutic
intention. Preclinical studies have shown the significance of adenosine in tumor
survival strategy by demonstrating tumor regression after inactivation of
adenosine receptors, inhibition of adenosine-producing enzymes, or reversal of
tissue hypoxia. These promising results indicate a potential use of the
inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.

Adenosine A2A Receptor: A Prognosis Marker For Lung Cancer
Tech ID: 08-11
Summary
The role of angiogenesis in tumor survival and metastasis is now well recognized. Hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha are both known to induce angiogenesis by upregulating a common set of cytokines, including VEGF, but only the activation of HIF-2alpha has been associated with poor prognosis in lung cancer. However, since HIF-2alpha is highly labile, it is a poor candidate for a biomarker.
Scientists at National Jewish Health have discovered that the receptor Adenosine A2A (ADORA2A) is expressed only in response to HIF-2alpha activation and more importantly that the expression of ADORA2A is increased in later stage lung tumors.
This receptor could therefore be used as a prognosis marker for lung cancer as well as a potential new target for an anti-angiogenic approach to treating lung cancer.
Potential Applications
A biomarker for HIF-2alpha activation and therefore for poor prognosis in lung cancer.
A target for anti-angiogenic therapy in lung cancer

Cancer Biol Ther. 2013 Sep;14(9):860-8.
Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth.
Mediavilla-Varela M1, Luddy K1, Noyes D1, Khalil FK2, Neuger AM3, Soliman H4, Antonia SJ5.
Recently it has become clear that the cost associated with the Warburg effect, which is inefficient production of ATP, is offset by selective advantages that are produced by resultant intracellular metabolic alterations. In fact tumors may be addicted to the Warburg effect. In addition these alterations result in changes in the extracellular tumor microenvironment that can also produce selective advantages for tumor cell growth and survival. One such extracellular alteration is increased adenosine concentrations that have been shown to impair T cell mediated rejection and support angiogenesis. The expression of the A2A receptor in non-small cell cancer (NSCLC) tissues, cell lines and cancer associated fibroblasts (CAF) was determined by performing immunohistrochemistry and immunoblot analysis. The efficacy of the A2A receptor antagonists in vivo was evaluated in a PC9 xenograft model. To determine the mode of cell death induced by A2A receptor antagonists flow cytometry, immunoblot, and cytotoxic analysis were performed. We found that a significant number of lung adenocarcinomas express adenosine A2A receptors. Antagonism of these receptors impaired CAF and tumor cell growth in vitro and inhibited human tumor xenograft growth in mice. These observations add to the rationale for testing adenosine A2A receptor antagonists as anticancer therapeutics. Not only could there be prevention of negative signaling in T cells within the tumor microenvironment and inhibition of angiogenesis, but also an inhibitory effect on tumor-promoting, immunosuppressive CAFs and a direct inhibitory effect on the tumor cells themselves.
Biochim Biophys Acta. 2011 Jun;1807(6):726-34.

Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and
increases reactive oxygen species resulting in ATP depletion and cell death in
human glioblastoma cells.
Pike LS(1), Smift AL, Croteau NJ, Ferrick DA, Wu M.
(1)Seahorse Bioscience, North Billerica, MA 01862, USA.
Normal differentiated cells rely primarily on mitochondrial oxidative
phosphorylation to produce adenosine triphosphate (ATP) to maintain their
viability and functions by using three major bioenergetic fuels: glucose,
glutamine and fatty acids. Many cancer cells, however, rely on aerobic glycolysis
for their growth and survival, and recent studies indicate that some cancer cells
depend on glutamine as well. This altered metabolism in cancers occurs through
oncogene activation or loss of tumor suppressor genes in multiple signaling
pathways, including the phosphoinositide 3-kinase and Myc pathways. Relatively
little is known, however, about the role of fatty acids as a bioenergetic fuel in
growth and survival of cancer cells. Here, we report that human glioblastoma
SF188 cells oxidize fatty acids and that inhibition of fatty acid β-oxidation by
etomoxir, a carnitine palmitoyltransferase 1 inhibitor, markedly reduces cellular
ATP levels and viability. We also found that inhibition of fatty acid oxidation
controls the NADPH level. In the presence of reactive oxygen species scavenger
tiron, however, ATP depletion is prevented without restoring fatty acid
oxidation. This suggests that oxidative stress may lead to bioenergetic failure
and cell death. Our work provides evidence that mitochondrial fatty acid
oxidation may provide NADPH for defense against oxidative stress and prevent ATP
loss and cell death.

PLoS One. 2009 Sep 15;4(9):e7033.
Oxygen consumption can regulate the growth of tumors, a new perspective on the
Warburg effect.
Chen Y(1), Cairns R, Papandreou I, Koong A, Denko NC.
(1)Division of Radiation and Cancer Biology, Department of Radiation Oncology,
Stanford University School of Medicine, Stanford, California, USA.
BACKGROUND: The unique metabolism of tumors was described many years ago by Otto
Warburg, who identified tumor cells with increased glycolysis and decreased
mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per
glucose molecule than mitochondrial oxidative phosphorylation, so in terms of
energy production, it is unclear how increasing a less efficient process provides
tumors with a growth advantage.
METHODS/FINDINGS: We carried out a screen for loss of genetic elements in
pancreatic tumor cells that accelerated their growth as tumors, and identified
mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells
decreased mitochondrial activity, and increased glycolysis, but paradoxically,
decreased cellular growth in vitro. Following Warburg's observations, this
mutation causes decreased mitochondrial function, compensatory increase in
glycolysis and accelerated growth in vivo. Likewise, knockdown of either
mitochondrial ribosomal protein L12 (MRPL12) or cytochrome oxidase had a similar
effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1)
increased oxygen consumption and decreased tumor growth. Finally, treatment of
tumor bearing animals with dichloroacetate (DCA) increased pyruvate consumption
in the mitochondria, increased total oxygen consumption, increased tumor hypoxia
and slowed tumor growth.
CONCLUSIONS: We interpret these findings to show that non-oncogenic genetic
changes that alter mitochondrial metabolism can regulate tumor growth through
modulation of the consumption of oxygen, which appears to be a rate limiting
substrate for tumor proliferation.

Acta Pharmacol Sin. 2016 May 2.
Dexamethasone suppresses the growth of human non-small cell lung cancer via
inducing estrogen sulfotransferase and inactivating estrogen.
Wang LJ(1), Li J(1), Hao FR(1), Yuan Y(1), Li JY(1), Lu W(2,)(1), Zhou TY(2,)(1).
(1)Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking
University, Beijing 100191, China. (2)State Key Laboratory of Natural and
Biomimetic Drugs, Peking University, Beijing 100191, China.
AIM: Dexamethasone (DEX) is a widely used synthetic glucocorticoid, which has
shown anti-cancer efficacy and anti-estrogenic activity. In this study we
explored the possibility that DEX might be used as an endocrine therapeutic agent
to treat human non-small cell lung cancer (NSCLC).
METHODS: The viability and proliferation of human NSCLC cell lines A549 and H1299
were assessed in vitro. Anti-tumor action was also evaluated in A549 xenograft
nude mice treated with DEX (2 or 4 mg·kg(-1)·d(-1), ig) or the positive control
tamoxifen (50 mg·kg(-1)·d(-1), ig) for 32 d. The expression of estrogen
sulfotransferase (EST) in tumor cells and tissues was examined. The intratumoral
estrogen levels and uterine estrogen responses were measured.
RESULTS: DEX displayed mild cytotoxicity to the NSCLC cells (IC50 >500 μmol/L)
compared to tamoxifen (IC50 <50 μmol/L), but it was able to inhibit the cell
proliferation at low micromolar ranges. Furthermore, DEX (0.1-10 μmol/L)
dose-dependently up-regulated EST expression in the cells, and inhibited the cell
migration in vitro. Triclosan, a sulfation inhibitor, was able to diminish
DEX-caused inhibition on the cell viability. In A549 xenograft nude mice, DEX or
tamoxifen administration remarkably suppressed the tumor growth. Moreover, DEX
administration dose-dependently increased EST expression in tumor tissues, and
reduced intratumoral estrogen levels as well as the volumes and weights of uteri.
CONCLUSION: DEX suppresses the growth of A549 xenograft tumors via inducing EST
and decreasing estradiol levels in tumor tissues, suggesting that DEX may be used
as anti-estrogenic agent for the treatment of NSCLC.

Am J Transl Res. 2016 Jan 15;8(1):81-97. eCollection 2016.
Prognostic significance of aromatase and estrogen receptor beta expression in
EGFR wild-type lung adenocarcinoma.
Tanaka K(1), Shimizu K(1), Kakegawa S(1), Ohtaki Y(1), Nagashima T(1), Kaira
K(2), Horiguchi J(1), Oyama T(3), Takeyoshi I(1).
(1)Department of Thoracic and Visceral Organ Surgery, Graduate School of
Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
(2)Department of Medicine and Molecular Science, Graduate School of Medicine,
Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
(3)Department of Division of Diagnostic Pathology, Graduate School of Medicine,
Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
OBJECTIVES: Based on recent findings of aromatase and estrogen receptor beta
(ERβ) expression in non-small-cell lung cancer, we assessed the
clinicopathological and prognostic significance of aromatase and ERβ expression
and their relationship to epidermal growth factor receptor (EGFR) mutation in
lung adenocarcinoma.
MATERIALS AND METHODS: We evaluated 150 resected primary lung adenocarcinoma
specimens. Expression of aromatase, ERα, ERβ, progesterone receptor (PR), and
human epidermal growth factor receptor 2 (HER2) was evaluated by immunostaining,
and EGFR and KRAS mutations were analyzed. Overall survival (OS) and
recurrence-free survival (RFS) were calculated using the Kaplan-Meier method.
RESULTS: Expression of aromatase, ERα, ERβ, PR, and HER2 was detected in 88.0%,
1.3%, 79.3%, 2.7%, and 39.3% of specimens, respectively. In patients with EGFR
wild-type lung adenocarcinoma, high aromatase expression was an independent
predictor of poor OS (hazard ratio

---

=2.638; 95% confidence interval [CI],
1.173-5.936; P=.019) and RFS (HR=2.505; 95% CI, 1.154-5.434; P=.020). Positive
ERβ expression was also an independent predictor of poor RFS (HR=4.013; 95% CI,
1.219-13.207; P=.022). Furthermore, high aromatase expression was a significant
predictor of poor survival only in females (OS, P=.010; RFS, P=.007), whereas
positive ERβ expression was an important predictor of poor survival only in males
(OS, P=.073; RFS, P=.051). No prognostic significance was observed in patients
with EGFR mutations.
CONCLUSIONS: Our findings suggest that EGFR wild-type lung adenocarcinoma is an
estrogen-dependent carcinoma, and aromatase expression and ERβ expression are
potent prognostic markers for EGFR wild-type lung adenocarcinoma.

Front Biosci (Landmark Ed). 2009 Jan 1;14:2285-92.
Expression of aromatase CYP19 and its relationship with parameters in NSCLC.
Oyama T(1), Kagawa N, Sugio K, Uramoto H, Hatano O, Harada N, Kaneko K, Kawamoto
T, Yasumoto K.
(1)Second Department of Surgery and Department of Environmental Health,
University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
[email protected]
Human aromatase (CYP19) responsible for the conversion of androgens to estrogens
is expressed not only in gonads and adrenals but also in many other tissues,
including normal lungs and lung cancers. To investigate the involvement of CYP19
in lung cancer development, purified CYP19 protein and antibody are required. In
this study, we have developed an efficient expression method of human aromatase
in E. coli (>1000 nmol/L culture). The protein purified from E. coli was used to
raise an antibody against the human CYP19 in rabbits. The resulting antibody
showed a high titer judged by ELISA, which allowed us to determine the expression
of CYP19 in non-small cell lung cancer (NSCLC). Of 78 NSCLC specimens from
Japanese patients, 50 (64%) NSCLC aberrantly expressed CYP19. This CYP19
expression in NSCLC was independent of any clinical and pathological parameters
as well as the expression of other P450s, except tumor stage. The results suggest
that the aromatase inhibitors might be useful for the management of non-small
cell lung cancer in postmenopausal women.

Ann N Y Acad Sci. 2009 Feb;1155:194-205.
Targeting aromatase and estrogen signaling in human non-small cell lung cancer.
Márquez-Garbán DC(1), Chen HW, Goodglick L, Fishbein MC, Pietras RJ.
(1)University of California School of Medicine, Department of Medicine, Division
of Hematology-Oncology, Los Angeles, California 90095-1678, USA.
[email protected]
Lung cancer has become increasingly common in women, and gender differences in
the physiology and pathogenesis of the disease have suggested a role for
estrogens. In the lung recent data have shown local production of estrogens from
androgens via the action of aromatase enzyme and higher levels of estrogen in
tumor tissue as compared with surrounding normal lung tissue. High levels of
aromatase expression are also maintained in metastases as compared with primary
tumors. Consistent with these findings, clinical studies suggest that aromatase
expression may be a useful predictive biomarker for prognosis in the management
of non-small cell lung cancer (NSCLC), the most common form of lung malignancy.
Low levels of aromatase associate with a higher probability of long-term survival
in older women with early stage NSCLC. Treatment of lung NSCLC xenografts in vivo
with an aromatase inhibitor (exemestane) alone or combined with standard
cisplatin chemotherapy elicits a significant reduction in tumor progression as
compared to paired controls. Further, lung cancer progression is also governed by
complex interactions between estrogen and growth factor signaling pathways to
stimulate the growth of NSCLC as well as tumor-associated angiogenesis. We find
that combination therapy with the multitargeted growth factor receptor inhibitor
vandetanib and the estrogen receptor antagonist fulvestrant inhibit tumor growth
more effectively than either treatment administered alone. Thus, incorporation of
antiestrogen treatment strategies in standard antitumor therapies for NSCLC may
contribute to improved patient outcome, an approach that deserves to be tested in
clinical trials.

Acta Pharmacol Sin. 2004 Jun;25(6):812-6.
Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis.
Xiang Y(1), Ma B, Li T, Gao JW, Yu HM, Li XJ.
(1)Department of Pharmacology, School of Basic Medical Sciences, Peking
University, Beijing 100083, China.
AIM: To study effects of acetazolamide on aquaporin-1 (AQP(1)) protein expression
and angiogenesis.
METHODS: Establishing Lewis-lung-carcinoma model, the localization of AQP(1) in
tumor tissues was investigated by immunohistochemical methods; The biological
activity of acetazolamide was detected by endothelial cells proliferation test
(MTT) assay and chorioallantoic membrane (CAM) vascular inhibition test.
RESULTS: Immunohistochemical localization of AQP(1) in mice tumor was labeled in
capillaries, post capillary venules endothelial cells. After being treated with
acetazolamide, the number of capillaries and post capillary venules was
significantly decreased in tumor tissue. Acetazolamide showed significant
inhibitory effect on angiogenesis in CAM and endothelial cell proliferation.
CONCLUSION: Acetazolamide might be identified and developed as one of potential
lead compounds for a new therapeutic intervention in inhibiting cancer
angiogenesis.

1. Inflammopharmacology. 2014 Apr;22(2):127-34.
Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through
inducing apoptosis.
Li WY(1), Ng YF, Zhang H, Guo ZD, Guo DJ, Kwan YW, Leung GP, Lee SM, Yu PH, Chan
SW.
(1)Department of Applied Biology and Chemical Technology, The Hong Kong
Polytechnic University, Hong Kong, China.
This study investigated the mechanism of the cytotoxic effect of emodin, an
active anthraquinone, on human lung adenocarcinoma A549 cells. In vitro growth
inhibition and suppression on colony forming were used to evaluate the effects of
emodin on A549 cells. Emodin's ability in changing the expressions of
apoptosis-related genes was studied by real-time RT-PCR. Emodin could
significantly inhibit the growth of A549 cells with IC50 = 16.85 μg/ml (~60 μM).
It also concentration dependently inhibited the colony-forming ability of A549
cells with IC50 = 7.60 μg/ml (~30 μM). Hallmarks of apoptosis, such as
single-strand DNA breakage and DNA fragmentation, were observed in A549 cells
treated with emodin. Emodin (72 h) treatment could up-regulate the gene
expression of FASL (p < 0.05) and down-regulate the gene expression of C-MYC (p <
0.01), but induce no significant changes in the gene expressions of MCL1, GAPDH,
BAX and CCND1. These results suggest that emodin could induce growth inhibition
and apoptosis in A549 cells through modifying the extrinsic apoptotic pathways
and the induction of cell cycle arrest.

2. Cancer Lett. 2013 Dec 1;341(2):139-49. doi: 10.1016/j.canlet.2013.08.023. Epub
2013 Aug 17.
Targeted abrogation of diverse signal transduction cascades by emodin for the
treatment of inflammatory disorders and cancer.
Shrimali D(1), Shanmugam MK, Kumar AP, Zhang J, Tan BK, Ahn KS, Sethi G.
(1)Department of Pharmacology, Yong Loo Lin School of Medicine, National
University of Singapore, Singapore 117597, Singapore.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural occurring
anthraquinone derivative isolated from roots and barks of numerous plants, molds,
and lichens. It is found as an active ingredient in different Chinese herbs
including Rheum palmatum and Polygonam multiflorum, and has diuretic,
vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory,
and anti-cancer effects. The anti-inflammatory effects of emodin have been
exhibited in various in vitro as well as in vivo models of inflammation including
pancreatitis, arthritis, asthma, atherosclerosis and glomerulonephritis. As an
anti-cancer agent, emodin has been shown to suppress the growth of various tumor
cell lines including hepatocellular carcinoma, pancreatic, breast, colorectal,
leukemia, and lung cancers. Emodin is a pleiotropic molecule capable of
interacting with several major molecular targets including NF-κB, casein kinase
II, HER2/neu, HIF-1α, AKT/mTOR, STAT3, CXCR4, topoisomerase II, p53, p21, and
androgen receptors which are involved in inflammation and cancer. This review
summarizes reported anti-inflammatory and anti-cancer effects of emodin, and
re-emphasizes its potential therapeutic role in the treatment of inflammatory
diseases and cancer.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

3. Immunopharmacol Immunotoxicol. 2013 Apr;35(2):307. doi:
10.3109/08923973.2013.766802.
Emodin: inhibitory effects on growth in malignant tumors.
Kapoor S.
Comment on
Immunopharmacol Immunotoxicol. 2012 Oct;34(5):768-78.

4. J Appl Toxicol. 2014 Jan;34(1):95-104. doi: 10.1002/jat.2838. Epub 2012 Dec 5.
Exploration of effects of emodin in selected cancer cell lines: enhanced growth
inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like
conditions.
Masaldan S(1), Iyer VV.
(1)Centre for Bio-Separation Technology, VIT University, Vellore, 632014, Tamil
Nadu, India.
This study explores the link between the antiproliferative activity of emodin
through the generation of reactive oxygen species (ROS) in various cancer cell
lines and the expression of the androgen receptor (AR) in the prostate cancer
cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as
the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in
the above prostate cancer cells and the nonprostate cell lines A549 (lung),
HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among
all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549.
The mechanism of cytotoxicity of emodin was postulated to be the widely reported
ROS generation, based on the observations of poor in vitro radical-scavenging
activity and increased growth inhibition of emodin by ascorbic acid (AA)
pre-treatment owing to the additive effects of ROS generation by emodin and
pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and
hypoxia-like conditions (simulated by CoCl(2)) and LRP1 under normoxia. Emodin
upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even
more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP
and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like
conditions along with growth inhibition by emodin, suggests that emodin may be a
useful therapeutic option against androgen-sensitive prostate cancer and other
such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels
to allow the uptake of emodin and/or any other accompanying therapeutic agents by
LRP1.
Copyright © 2012 John Wiley & Sons, Ltd.



5. Asian Pac J Cancer Prev. 2012;13(4):1505-10.
Effects of emodin extracted from Chinese herbs on proliferation of non-small cell
lung cancer and underlying mechanisms.
He L(1), Bi JJ, Guo Q, Yu Y, Ye XF.
(1)Department of Pathology, Institute of Neuroscience, Chongqing Key Laboratory
of Neurobiology, Chongqing Medical University, Chongqing, China.
To aim of this was to observe emodin-mediated cytotoxicity and its influence on
Rad51 and ERCC1 expressionin non-small cell lung cancer (NSCLC). NSCLC cells were
cultured in vitro with emodin at various concentrations (0, 25, 50, 75 and 100
μmol/L) for 48 h and the proliferation inhibition rate was determined by the MTT
method. Then, NSCLC were treated with emodin (SK-MES-1 40 μmol/L, A549 70 μmol/L)
or 20 μmol/L U0126 (an ERK inhibitor) for 48 h, or with various concentrations of
emodin for 48 h and the protein and mRNA expressions of ERCC1 and Rad51 were
determined by RT-PCR and Western blot assay, respectively. Emodin exerted a
suppressive effect on the proliferation of NSCLC in a concentration dependent
manner. Protein and mRNA expression of ERCC1 and Rad51 was also significantly
decreased with the dose. Vacuolar degeneration was observed in A549 and SK-MES-1
cell lines after emodin treatment by transmission electron microscopy. Emodin may
thus inhibited cell proliferation in NSCLC cells by downregulation ERCC1 and
Rad51.


6. Immunopharmacol Immunotoxicol. 2012 Oct;34(5):768-78. doi:
10.3109/08923973.2012.654494. Epub 2012 Feb 3.
Emodin inhibits invasion and migration of prostate and lung cancer cells by
downregulating the expression of chemokine receptor CXCR4.
Ok S(1), Kim SM, Kim C, Nam D, Shim BS, Kim SH, Ahn KS, Choi SH, Ahn KS.
(1)College of Oriental Medicine and Institute of Oriental Medicine, Kyung Hee
University, Seoul, Republic of Korea.
Comment in
Immunopharmacol Immunotoxicol. 2013 Apr;35(2):307.
Emodin (ED), an anthraquinone derivative, has been found to inhibit
proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and
enhance chemotherapy. However, the detailed mechanism of ED related to the
regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects
cellular migration and invasion in prostate and lung cancer cells are not fully
understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in
promoting invasion and metastasis in tumors. Thus, novel agents that can
downregulate CXCR4 expression have therapeutic potential in repressing cancer
metastasis. Among ED and its derivatives, it is found that ED downregulated the
expression of both CXCR4 and HER2 without affecting cell viability in tumor
cells. The suppression of CXCR4 expression by ED was found to correlate with the
inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells.
Besides, neither proteasome inhibition nor lysosomal stabilization had any effect
on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms
unveiled that the downregulation of CXCR4 was at the transcriptional level, as
indicated by downregulation of mRNA expression and suppression of NF-κB
activation. Overall, our findings suggest that ED is a novel blocker of CXCR4
expression and, thus, has enormous potential as a powerful therapeutic agent for
metastatic cancer.

 

[Amazoniac]

My Question to Peat:
"Is there any difference between the crystal and the powder form of acetylsalicylic acid (ASA), particulary with regard to stability and Absorption?

What would be a reasonable dose of ASA if you are healthy (no cancer etc.) and have a good diet but only have some problems with falling into sleep and getting up in the morning?

Do you think its an good idea to take some ASA every day, in generell e.g. to prevent cancer?"

My Answer from Peat:

"I think a little aspirin, regularly if not daily, is good prevention, if you are sure to get enough vitamin K, to prevent excess bleeding. The amount depends on how you react to it, and can change as your metabolism adjusts. Taking some at bedtime can be very helpful for sleeping; sometimes I take about 500 mg at night, but other times just a little. I think the crystals are more stable, but I keep the big container (a multi-year supply) in the freezer, and keep out enough for a couple of months. The powdered forms developed an acetic acid smell with time, the crystals don't."

 

[milk_lover]

I asked Peat about what deodorant can be used because the deodorants in the market have nasty stuff.

His answer: "A topical aspirin solution might slightly reduce odors. Women with low thyroid, high estrogen, are over-sensitive to odors."

 

[allblues]

Asked Ray about forskolin;

Since it seems to be widely used in experiments, i'm guessing you would be familiar with the compound forskolin - do you have any opinion on using this herb extract as a supplement? ... The increase in cAMP levels seem interesting... some seem to find it helpful for weightloss.

I think coffee is much safer for similar purposes.

 

[goodandevil]

Q:"Hi ray hope you're well. Started my uncle on caco3 for kidney problems. He was on lasicks, saw lasicks inhibits carbonic anhydrase but like to get him off it because of past hypovolemia crises. Besides the caco3 and coconut oil i was thinking of urea internally, what do you think about that? Appreciatevely,"

R: "Urea is safe, but progesterone, pregnenolone, and thyroid are often curative for chronic kidney disease. Has his vitamin D been checked? When it’s low, parathyroid hormone rises, and it’s one of the “uremic toxins.”

 

[goodandevil]

Q:"Hi ray, been giving my cat aspirin for motility problems (10mg/day), along with collagen, coconut oil, and 100mg CaCO3 per 3 oz canned fish catfood. Would you foresee any problems with aspirin? Thank you again for your time."

R: "That seems like a safe dose. I think some of the studies confuse the effects of the stress of intravenous treatment with the effects of aspirin."


Gastroenterology. 1976 Nov;71(5):754-9.
Gastric mucosal lesions produced by intravenous infusion of aspirin in cats.
Bugat R, Thompson MR, Aures D, Grossman MI.
Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the "broken barrier."

J Vet Intern Med. 2003 Jan-Feb;17(1):73-83.
Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and
long-term management with low-dose aspirin in 24 cases.
Smith SA, Tobias AH, Jacob KA, Fine DM, Grumbles PL.
Department of Small Animal Clinical Sciences, University of Minnesota, St Paul,
MN 55108, USA.
Records of 127 cats with arterial thromboembolism (ATE) were reviewed.
Abyssinian, Birman, Ragdoll, and male cats were overrepresented. Tachypnea (91%),
hypothermia (66%), and absent limb motor function (66%) were common. Of 90 cats
with diagnostics performed, underlying diseases were hyperthyroidism (12),
cardiomyopathy (dilated [8], unclassified [33], hypertrophic obstructive [5],
hypertrophic [19]), neoplasia (6), other (4), and none (3). Common abnormalities
were left atrial enlargement (93%), congestive heart failure (CHF, 44%), and
arrhythmias (44%). Of cats without CHF, 89% were tachypneic. Common biochemical
abnormalities were hyperglycemia, azotemia, and abnormally high serum
concentrations of muscle enzymes. Of 87 cats treated for acute limb ATE, 39 (45%)
survived to be discharged. Significant differences were found between survivors
and nonsurvivors for temperature (P < .00001), heart rate (P = .038), serum
phosphorus concentration (P = .024), motor function (P = .008), and number of
limbs affected (P = .001). No significant difference was found between survivors
and nonsurvivors when compared by age, respiratory rate, other biochemical
analytes, or concurrent CHE A logistic regression model based on rectal
temperature predicted a 50% probability of survival at 98.9 degrees F (37.2
degrees C). Median survival time (MST) for discharged cats was 117 days. Eleven
cats had ATE recurrences, and 5 cats developed limb problems. Cats with CHF (MST:
77 days) had significantly shorter survival than cats without CHF (MST: 223 days;
P = .016). No significant difference was found in survival or recurrence rate
between cats receiving high-dose aspirin (> or = 40 mg/cat q72h) and cats
receiving low-dose aspirin (5 mg/cat q72h). Adverse effects were less frequent
and milder for the lower dosage.

Rom J Gastroenterol. 2002 Dec;11(4):309-12.
Salycylate--induced pancreatic injury in the cat: a preliminary study.
Mentes A, Batur Y, Bayol U.
Department of Surgery, Aegean University Faculty of Medicine, Bornova, 35100
Yzmir, Turkey.
The effect of intravenous aspirin on the exocrine pancreatic secretion was
investigated in a feline isolated pancreaticoduodenal preparation. The study
group received a 500 mg/kg bolus dose of aspirin intravenously. Duodenal washouts
were collected for six hours. The serum and perfusate aspirin content increased
significantly after aspirin administration (p = 0.01). However, the pH,
bicarbonate, sodium, potassium and calcium content in the duodenal outflow did
not show significant changes between 0 and 6 hours. A significant difference in
the perfusate calcium content was present between ASA treated and control cats
starting at the end of the first hour of the experiment (p=0.005).
Histopathological examination of the pancreas revealed marked erythrocyte
extravasation in the ASA treated animals. It is suggested that the ASA- related
increase in the calcium secretion of the pancreas should be regarded as an
indication of aspirin induced pancreatic damage.

Farmakol Toksikol. 1986 May-Jun;49(3):50-2.
[Effect of a course of dosages of acetylsalicylic acid and sodium salicylate on
the indices of the tonus of vessels of differing functional importance in cats]
[Article in Russian]
Riabkov AN, Kolobaev AV.
The experiments on 42 adult male and females cats showed that acetylsalicylic
acid and sodium salicylate (daily orally in 7-day and 14-day courses in a dose of
100 mg/kg) increase the tension of some visceral (of the myocardium, liver,
stomach) and major (of the abdominal aorta, femoral and carotid) arteries, sodium
salicylate effect being more pronounced. The maximum changes were noted in the
vessels of the gastric mucosa and submucous layer.

 

[goodandevil]

Me: "Is lactic acid a long-term concern with kefiran?" "I'm a sjorgen's-like state because if digestive issues. Kefiran seems to help my rls, the effect is quite noticable, but i believe i feeel anxious or depressed after a week of use. My hypothesis is that though the lactobacilli may have a short-term antiinflammatory benefit, longer term lactic acid production may be detrimental. I heard you comment recently on the antiinflammatory action of lactobacilli, what do gou think of kefiran? Thx"

Ray: "Even dead lactobacilli have an antiinflammatory effect in the intestine, so it’s probably something in their cell wall coat, and kefiran might have a physical effect of that sort."

 

[goodandevil]

Per email:

I:"For someone taking a supplement, how many times a week should a 200mcg pill be taken to restore t4 conversion, presuming adequate protein?"

Ray:"During the first week, every day would be o.k., then I think once or twice a week is enough."

Pure encapsulations has a good selenium: just selenomethionine and cellulose, plus an ascorbyl salt.

 

[keith]

I asked Ray about a recurring skin infection. I asked about using povidone iodine (he answered) and chlorhexidine gluconate (he didn't address). I briefly also mentioned having high blood pressure, which is the reason he mentions that at the end:

"It isn’t good to repeatedly cover a very large skin area with iodine, but it’s safe to use on small areas. 10% sulfur soap is another safe disinfectant that works on various types of infection. There are some nutritional deficiencies that can cause recurring infections. Vitamin D deficiencies are very common, and predispose to all sorts of immunity problems. Hypothyroidism and vitamin A deficiencies sometimes lead to prolonged infections, and increased TSH is very closely involved with high blood pressure."

 

[nograde]

Dear Dr. Peat,

silicone-sheets are still considered the "gold-standard" for reducing hypertrophic scars. What do you think is the mechanism behind this effect? Maybe CO2 trapping or silicone acting as irritant causing "tissue remodeling"? Do you have experience with other methods for reducing scars?

Answer:

I had a good experience with reducing a scar by coating it with viscous vitamin E. I think trapping CO2 is probably the main effect of the silicone.

 

[unexamined_whimsy]

Dear Dr. Peat,

Are there any concerns regarding the regular use of umami boosting ingredients such as soya sauce and fish sauce?

Answer:

No.