Ray Peat Email Advice Depository

[Beastmode]

Me: I’d like to research vaccines and wanted to ask about your general opinion since there is so much noise online. Do vaccines even work against the illness they are meant to work against? My impression is that science mixed up “inflammation” and “immune response” and that is why they are using dangerous adjuvants that trigger the inflammatory response. What is your view on that?

Ray: Have you seen Suzanne Humphries’ things on vaccination? Your comment about inflammation vs immune response describes the situation exactly. I think inflammation is often a sign that the body’s resistance is low. The body is designed to handle viral and bacterial infections entering through the respiratory and digestive systems, and antigens of introduced by injection don’t produce the same reactions that the normally acquired infections do. The 20th century medical model of the immune system introduced by Paul Ehrlich was designed to promote the sale of drugs, and is corrupt at its core. Jamie Cunliffe (“damage”) and Polly Matzinger (“danger”) have introduced more biological models of immunity, that I think should displace the Ehrlich model. Good oxidative metabolism, with optimal vitamin D and thyroid function, gets people through epidemics without getting sick, despite being exposed to the thing that made others sick.

Clin Transl Med. 2018 Jul 2;7(1):20.
Cancer; an induced disease of twentieth century! Induction of tolerance,
increased entropy and 'Dark Energy': loss of biorhythms (Anabolism v.
Catabolism).
Khatami M(1).
(1)Inflammation, Aging and Cancer, National Cancer Institute (NCI), National
Institutes of Health (NIH), Bethesda, MD, USA. [email protected].
Maintenance of health involves a synchronized network of catabolic and anabolic
signals among organs/tissues/cells that requires differential bioenergetics from
mitochondria and glycolysis (biological laws or biorhythms). We defined
biological circadian rhythms as Yin (tumoricidal) and Yang (tumorigenic) arms of
acute inflammation (effective immunity) involving immune and non-immune systems.
Role of pathogens in altering immunity and inducing diseases and cancer has been
documented for over a century. However, in 1955s decision makers in
cancer/medical establishment allowed public (current baby boomers) to consume
million doses of virus-contaminated polio vaccines. The risk of cancer incidence
and mortality sharply rose from 5% (rate of hereditary/genetic or innate disease)
in 1900s, to its current scary status of 33% or 50% among women and men,
respectively. Despite better hygiene, modern detection technologies and discovery
of antibiotics, baby boomers and subsequent 2-3 generations are sicker than
previous generations at same age. American health status ranks last among other
developed nations while America invests highest amount of resources for
healthcare. In this perspective we present evidence that cancer is an induced
disease of twentieth century, facilitated by a great deception of cancer/medical
establishment for huge corporate profits. Unlike popularized opinions that cancer
is 100, 200 or 1000 diseases, we demonstrate that cancer is only one disease; the
severe disturbances in biorhythms (differential bioenergetics) or loss of balance
in Yin and Yang of effective immunity. Cancer projects that are promoted and
funded by decision makers are reductionist approaches, wrong and unethical and
resulted in loss of millions of precious lives and financial toxicity to society.
Public vaccination with pathogen-specific vaccines (e.g., flu, hepatitis, HPV,
meningitis, measles) weakens, not promotes, immunity. Results of irresponsible
projects on cancer sciences or vaccines are increased population of
drug-dependent sick society. Outcome failure rates of claimed 'targeted' drugs,
'precision' or 'personalized' medicine are 90% (± 5) for solid tumors. We
demonstrate that aging, frequent exposures to environmental hazards, infections
and pathogen-specific vaccines and ingredients are 'antigen overload' for immune
system, skewing the Yin and Yang response profiles and leading to induction of
'mild', 'moderate' or 'severe' immune disorders. Induction of decoy or pattern
recognition receptors (e.g., PRRs), such as IRAK-M or IL-1dRs ('designer'
molecules) and associated genomic instability and over-expression of growth
promoting factors (e.g., pyruvate kinases, mTOR and PI3Ks, histamine, PGE2, VEGF)
could lead to immune tolerance, facilitating cancer cells to hijack anabolic
machinery of immunity (Yang) for their increased growth requirements. Expression
of constituent embryonic factors would negatively regulate differentiation of
tumor cells through epithelial-mesenchymal-transition and create "dual negative
feedback loop" that influence tissue metabolism under hypoxic conditions. It is
further hypothesized that induction of tolerance creates 'dark energy' and
increased entropy and temperature in cancer microenvironment allowing disorderly
cancer proliferation and mitosis along with increased glucose metabolism via
Crabtree and Pasteur Effects, under mitophagy and ribophagy, conditions that are
toxic to host survival. Effective translational medicine into treatment requires
systematic and logical studies of complex interactions of tumor cells with host
environment that dictate clinical outcomes. Promoting effective immunity
(biological circadian rhythms) are fundamental steps in correcting host
differential bioenergetics and controlling cancer growth, preventing or delaying
onset of diseases and maintaining public health. The author urges independent
professionals and policy makers to take a closer look at cancer dilemma and stop
the 'scientific/medical ponzi schemes' of a powerful group that control a
drug-dependent sick society before all hopes for promoting public health
evaporate.
Clin Transl Med. 2016 Dec;5(1):35.
Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint?
Khatami M(1).
(1)National Cancer Institute (NCI), the National Institutes of Health (NIH),
Bethesda, MD, USA. [email protected].
Longevity and accumulation of multiple context-dependent signaling pathways of
long-standing inflammation (antigen-load or oxidative stress) are the results of
decreased/altered regulation of immunity and loss of control switch mechanisms
that we defined as Yin and Yang of acute inflammation or immune surveillance.
Chronic inflammation is initiated by immune disruptors-induced progressive
changes in physiology and function of susceptible host tissues that lead to
increased immune suppression and multistep disease processes including
carcinogenesis. The interrelated multiple hypotheses that are presented for the
first time in this article are extension of author's earlier series of
'accidental' discoveries on the role of inflammation in developmental stages of
immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of
data on chronic diseases suggest that nearly all age-associated illnesses,
generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g.,
hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g.,
accelerated neurodegenerative and autoimmune diseases or site-specific cancers
and metastasis) are variations of hypersensitivity responses of tissues that are
manifested as different diseases in immune-responsive or immune-privileged
tissues. Continuous release/presence of low level histamine (subclinical) in
circulation could contribute to sustained oxidative stress and induction of
'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible
tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms
of cumulative delayed hypersensitivity responses that would induce immunological
chaos in favor of tissue growth in target tissues. Shared or special features of
growth from fetus development into adulthood and aging processes and
carcinogenesis are briefly compared with regard to energy requirements of highly
complex function of Yin and Yang. Features of Yang (growth-promoting) arm of
acute inflammation during fetus and cancer growth will be compared for consuming
low energy from glycolysis (Warburg effect). Growth of fetus and cancer cells
under hypoxic conditions and impaired mitochondrial energy requirements of
tissues including metabolism of essential branched amino acids (e.g., val, leu,
isoleu) will be compared for proposing a working model for future systematic
research on cancer biology, prevention and therapy. Presentation of a working
model provides insightful clues into bioenergetics that are required for fetus
growth (absence of external threat and lack of high energy-demands of Yin events
and parasite-like survival in host), normal growth in adulthood (balance in Yin
and Yang processes) or disease processes and carcinogenesis (loss of balance in
Yin-Yang). Future studies require focusing on dynamics and promotion of
natural/inherent balance between Yin (tumoricidal) and Yang (tumorigenic) of
effective immunity that develop after birth. Lawless growth of cancerous cells
and loss of cell contact inhibition could partially be due to impaired
mitochondria (mitophagy) that influence metabolism of branched chain amino acids
for biosynthesis of structural proteins. The author invites interested scientists
with diverse expertise to provide comments, confirm, dispute and question and/or
expand and collaborate on many components of the proposed working model with the
goal to better understand cancer biology for future designs of cost-effective
research and clinical trials and prevention of cancer. Initial events during
oxidative stress-induced damages to DNA/RNA repair mechanisms and inappropriate
expression of inflammatory mediators are potentially correctable, preventable or
druggable, if future studies were to focus on systematic understanding of early
altered immune response dynamics toward multistep chronic diseases and
carcinogenesis.

He's on a role with his vaccine responses. Unfortunately, The U.S government knows nothing about supporting "supportive" science for optimal health.

 

[Beastmode]

Vaccine emails continued:

Me:
My wife was recommend Liposomal or Lypospheric vitamin c before and after getting mandatory vaccines by the government. Also take magnesium and a zinc supplement as soon as possible.

After the vaccinations, to take an Advanced TRS and Sun chlorrella.

Are you familiar with any of these substances?

Not sure if they'll do more harm than good.

Ray:
Magnesium and zinc supplements are usually safe, but milk, eggs, seafood, meat, fruit, etc., usually provide enough. The other suggestions sound like a supplement salesman’s ideas, and could be harmful.

Me:
Any specific type of magnesium or zinc supplement ingredients/qualities to look for?

My wife drinks a few cups of coffee per day (safe chelator of metals I believe.)

Would charcoal and/or cascara be useful in situation like this?

Ray:
Magnesium glycinate is usually safe; zinc supplements shouldn’t be more than 10 mg. Coffee is protective of the immune system, reducing inflammation. Your usual fibrous foods are helpful, because stress increases the absorption of endotoxin and bacteria. Cascara has antiinflammatory effects that should be helpful; I don’t think charcoal would.

 

[Beastmode]

Me:
Are you familiar with a safe way to make jello for kids? My toddler is wanting different types of foods she sees, but they’re all filled with harmful material.

Ray:
I mix Great Lakes (or similar) gelatin with sugar, add some water, and warm it in a microwave until it’s clear, then add frozen orange juice concentrate, or lime, lemon, or grape juice.

 

[member 2106]

Me: Do you know what factors influence the deepness of a person's voice?
The tone of my voice varies in a way which I can't explain coherently, although there does seem to be a correlation between anxiety and a slightly higher pitch.

Ray: The basic pitch gets lower as the larynx grows under the influence of androgen, but nervous tension, tightening the muscles, increases the pitch. Swelling of the vocal cords affects the sound quality, too.

 

[Beastmode]

Me:
When might testosterone be a worthy level to check for a 40 year old male?

Is there such a thing as "free" levels that are worth checking over total?

Ray:
I don’t think it’s worth the bother, unless there are problems that seem related.

 

[schultz]

Me:
It is said hyperglycemia is bad because it can cause damage to nerves, blood vessels, organs. Do you think the sugar itself can cause damage if its level is kept high in the
blood stream for an extended period? There is a lot going on when the body is in a state of hyperglycemia, so it seems a little bit weird to blame any damage that is caused entirely on the sugar itself. Could it just be something else that happens to be high like FFA, insulin, lactic acid, or even an absence of something, like sugar (being utilized) or CO2?

Ray:
"In tissue culture experiments, very high glucose has harmful effects, but those conditions don’t reflect what happens in the whole organism. Glucose in the blood is increased adaptively to protect against something that’s damaging the tissues, and that’s usually a hormone imbalance that is interfering with the ability to oxidize glucose. The “glycation” that’s usually blamed on high glucose is mostly caused by lipid peroxidation from polyunsaturated fats, and the glycerol that’s liberated by lipolysis, and metabolized to methylglyoxal. The fats block glucose metabolism for energy, and more glucose is produced to overcome that."

 

[theLaw]

Me:
If someone ate a carrot with each meal, would that have a significant effect on vitamin/mineral absorption of that meal?

Ray:
It slows absorption, and the carotene should be taken into account nutritionally.

 

[DaveFoster]

Me:
I have a question about infections. Since bacterial or viral infections, such as, for the latter, the cold or flu, can elevate the pulse and temperature, would a person with a fever and tachycardia need to lower their thyroid dosage until the infection passes?

Dr. Peat:
The stress of infection lowers T3, and I think small supplements probably help with recovery.

Me:
That's interesting. I wondered about the overlapping symptoms with hypothyroidism, such as chills and hyperventilation.

 

[Gadsie]

Dear mr Peat,

Currently there are multiple companies working on developing chemicals that (re)generat hair cells in the inner ear. Do you think the body is somehow capable of restoring (noise) damaged hearing without these new pharmaceutical chemicals?

Ray peat:
I think they, and other stem cells such as in the pancreas, are always being regenerated, but are being killed by unfavorable conditions in the body, such as reductive stress and inflammation.

 

[member 2106]

I wanted to know whether Ray ever read fiction, and what his thoughts were on the urge to invent stories and characters, etc.

Ray: I wrote poetry occasionally in my late teens, once sold a sonnet for 10 pesos; as an English major I read some novels, but almost always dislike such involvement in someone’s personal view of things, and prefer orientation toward reality.

 

[meatbag]

via @pinacolada from Weight Loss: Starch And Trytophan Are What Are Stopping You
-----
I once emailed peat about alpha males and he had an interesting reply.

I think it’s a projection of the social darwinist ideology of capitalism. As the religious justification for poverty was fading, middle of the 19th century, the hierarchic world view began seeing itself in animals, and then that became the “scientific basis” for justifying social stratification. The schools have been important for indoctrinating the ideology. The idea of a “pecking order” in chickens was similar to the idea of an alpha male in apes, and—disregarding the actual studies—became “common knowledge” by the middle of the last century. The pecking order develops in domestic chickens only under certain circumstances in flocks of a certain size, and in ape families the dominant male role is much more flexible, subtle, and situational than the genetic determinists have trained people to believe. When I was in the biology department at the U. of Oregon, 1968-72, professors were using Desmond Morris’s book The Naked Apeas a text book—a projection of Tory social ethics/militarism onto archeologic samples, and then an argument from that to “human nature.” It was as if Ayn Rand’s books were being used in sociology and philosophy courses.

 

[cardochav]

Ray on CBD: “I think the effects of CBD probably depend on how much polyunsaturated fat the person’s tissues have; the endogenous cannabinoids can increase inflammation, so the plant analog can be antiinflammatory by reducing that effect.”

 

[RayPeatFan777]

I was hoping you could answer a couple of questions that I havent been able to find answers for.

Many blogs and books have written about eating carbohydrates alone on an empty stomach leading to the shuttling of more tryptophan to the brain.
I know fructose wont spike insulin but I am wondering if the glucose and sucrose in a pint of orange juice eaten alone on an empty stomach would be enough to raise brain serotonin?

Secondly, do you think the amount of sugar in a coke is enough to support the metabolic boost from the caffeine in most people?

I think the ratio of sugar to caffeine in coke is right, for most people. Most of the beliefs about tryptophan, serotonin, and sugar are wrong. Free fatty acids bind to albumin more strongly than tryptophan, and so make it available to the brain. Sugar generally inhibits lipolysis, so it would decrease brain tryptophan and serotonin. I think that accounts for some of sugar’s anti-stress effect.

Med Sci Sports Exerc. 1997 Jan;29(1):58-62.
Effects of acute physical exercise on central serotonergic systems.
Chaouloff F(1).
(1)Génétique du Stress, INSERM CJF 94-05, Université Bordeaux II, France.
This paper reviews data concerning the effects of acute physical exercise
(treadmill running) in trained rats. Works from the 1980's have established that
acute running increases brain serotonin (5-hydroxytryptamine: 5-HT) synthesis in
two ways. Lipolysis-elicited release of free fatty acids in the blood compartment
displaces the binding of the essential amino acid tryptophan to albumin, thereby
increasing the concentration of the so-called "free tryptophan" portion, and
because exercise increases the ratio of circulating free tryptophan to the sum of
the concentrations of the amino acids that compete with tryptophan for uptake at
the blood-brain barrier level, tryptophan enters markedly in the brain
compartment. However, this marked increase in central tryptophan levels increases
only to a low extent brain 5-HT synthesis, as assessed by the analysis of
5-hydroxyindoleacetic acid levels, thereby suggesting that exercise promotes
feedback regulatory mechanisms. Indirect indices of 5-HT functions open the
possibility that acute exercise-induced increases in 5-HT biosynthesis are
associated with (or lead to) increases in 5-HT release. Lastly, the hypothesis
that training and/or acute exercise triggers changes in 5-HT receptors has been
examined in several studies; actually, both positive and negative results have
been reached. Taken together, all these data support the need for future studies
on the functional effects of exercise on 5-HT, including those related to the
hypothesis that the positive mood effects of exercise rely (partly or totally) on
central serotonergic systems.

Int J Sports Med. 2001 Oct;22(7):482-97.
Physiology and pathophysiology of the serotonergic system and its implications on
mental and physical performance. Part II.
Strüder HK(1), Weicker H.
(1)Institute of Theory and Practice of Training and Movement, German Sport
University, Cologne, Germany. [email protected]
As shown in the first part of this review, well equilibrated neurotransmission in
which 5-HT plays a dominant role is important for proper neuromodulation and
adjustment of neuronal network elements. Adequate 5-HT system function supports
regulation of intercommunicative neuronal transmission in the brain, which
optimizes behavioral neuromodulation during and after different forms of
exertions, thereby preventing transient dysregulation. Impairment of
neuromodulation and neuronal network in the brain with transient dysfunctions or
permanent substantial deficits at manifestation of various types of depression
results from prevalent impairment of 5-HT neurotransmission and its central
interaction with other neurotransmitter systems. Exercise-induced increase of
free tryptophan (TRP) in blood occurs due to liberation from albumin, which is
caused by adrenergically induced lipolysis of free fatty acids and results in
higher free TRP uptake into the brain. Consecutively enhanced serotonin (5-HT)
biosynthesis does not per se initiate mood impairment or central fatigue. It is
suggested that in overtrained athletes central fatigue, mental deficiency and
behavioral alterations with depressive mood are probably not primarily caused by
metabolic and neuromuscular alterations. The primary trigger of these transient
behavioural alterations might instead be initiated by a central exhaustive
exercise stress which elicits impairment of complex neuromodulation, also
afflicting the interaction of central neurotransmitters or hypothalamic
neuropeptides and releasing factors. In a consecutive correction of the
variation, the implication of the serotonergic system on the central neuromodular
disturbance might improve or prevent the progressive course both in transient and
in permanent mental disorders. However, an unsuccessful attempt to improve the
depressive symptomatology leads mostly to an overproportional exaggeration of the
behavioral changes.

Braz J Med Biol Res. 2017 Oct 19;50(12):e6432.
Physical exercise-induced fatigue: the role of serotonergic and dopaminergic
systems.
Cordeiro LMS(1), Rabelo PCR(1), Moraes MM(1), Teixeira-Coelho F(1)(2), Coimbra
CC(3), Wanner SP(1), Soares DD(1).
(1)Laboratório de Fisiologia do Exercício, Escola de Educação Física,
Fisioterapia e Terapia Ocupacional, Universidade Federal de Minas Gerais, Belo
Horizonte, MG, Brasil.
(2)Centro de Formação de Professores, Universidade Federal do Recôncavo da Bahia,
Amargosa, BA, Brasil.
(3)Laboratório de Endocrinologia e Metabolismo, Instituto de Ciências Biológicas,
Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling
that leads to reduced intensity or interruption of physical exercises, thereby
regulating performance. The present review aims to present advances on the
understanding of fatigue, which has recently been proposed as a defense mechanism
instead of a "physiological failure" in the context of prolonged (aerobic)
exercises. We also present recent advances on the association between serotonin,
dopamine and fatigue. Experiments with rodents, which allow direct manipulation
of brain serotonin and dopamine during exercise, clearly indicate that increased
serotoninergic activity reduces performance, while increased dopaminergic
activity is associated with increased performance. Nevertheless, experiments with
humans, particularly those involving nutritional supplementation or
pharmacological manipulations, have yielded conflicting results on the
relationship between serotonin, dopamine and fatigue. The only clear and
reproducible effect observed in humans is increased performance in hot
environments after treatment with inhibitors of dopamine reuptake. Because the
serotonergic and dopaminergic systems interact with each other, the
serotonin-to-dopamine ratio seems to be more relevant for determining fatigue
than analyzing or manipulating only one of the two transmitters. Finally,
physical training protocols induce neuroplasticity, thus modulating the action of
these neurotransmitters in order to improve physical performance.

Dan Med J. 2016 Feb;63(2). pii: B5204.
Modulation of motoneuron activity by serotonin.
Perrier JF(1).
(1)[email protected].
Serotonin is a major neuromodulator in the central nervous system involved in
most physiological functions including appetite regulation, sexual arousal, sleep
regulation and motor control. The activity of neurons from the raphe spinal
tract, which release serotonin on motoneurons, is positively correlated with
motor behaviour. During moderate physical activity, serotonin is released from
synaptic terminals onto the dendrites and cell bodies of motoneurons. Serotonin
increases the excitability of motoneurons and thereby facilitate muscle
contraction by acting on several parallel intracellular pathways. By activating
5-HT1A receptors, serotonin inhibits TWIK-related acid-sensitive potassium
channels and small conductance calcium-activated potassium channels. In parallel,
serotonin binds to 5-HT2 receptors, which promotes the low-threshold L-type
Ca(2+) channels. During intense physical activity, more serotonin is released.
The reuptake systems saturate and serotonin spills over to reach extrasynaptic
5-HT1A receptors located on the axon initial segment of motoneurons. This in turn
induces the inhibition of the Na(+) channels responsible for the initiation of
action potentials. Fewer nerve impulses are generated and muscle contraction
becomes weaker. By decreasing the gain of motoneurons, serotonin triggers central
fatigue.

Med Sci Sports Exerc. 1997 Jan;29(1):45-57.
Possible mechanisms of central nervous system fatigue during exercise.
Davis JM(1), Bailey SP.
(1)Department of Exercise Science, School of Public Health, University of South
Carolina, Columbia 29208, USA.
Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively
little attention has been placed on the role of the central nervous system (CNS)
in fatigue during exercise despite the fact that the unwillingness to generate
and maintain adequate CNS drive to the working muscle is the most likely
explanation of fatigue for most people during normal activities. Several
biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have
been developed for several neurotransmitters including serotonin (5-HT;
5-hydroxytryptamine), dopamine, and acetylcholine. The most prominent one
involves an increase in 5-HT activity in various brain regions. Good evidence
suggests that increases and decreases in brain 5-HT activity during prolonged
exercise hasten and delay fatigue, respectively, and nutritional manipulations
designed to attenuate brain 5-HT synthesis during prolonged exercise improve
endurance performance. Other neuromodulators that may influence fatigue during
exercise include cytokines and ammonia. Increases in several cytokines have been
associated with reduced exercise tolerance associated with acute viral or
bacterial infection. Accumulation of ammonia in the blood and brain during
exercise could also negatively effect the CNS function and fatigue. Clearly
fatigue during prolonged exercise is influenced by multiple CNS and peripheral
factors. Further elucidation of how CNS influences affect fatigue is relevant for
achieving optimal muscular performance in athletics as well as everyday life.

Neuroscience. 2017 May 4;349:27-34.
Serotonin regulation in a rat model of exercise-induced chronic fatigue.
Liu Z(1), Wu Y(2), Liu T(3), Li R(4), Xie M(5).
(1)Department of Neurology, Beijing Friendship Hospital, Capital Medical
University, Beijing 100050, China. Electronic address: [email protected].
(2)Centers for Disease Control and Prevention, Atlanta 30329, USA.
(3)Liver Research Center, Beijing Friendship Hospital, Capital Medical
University, Beijing 100050, China.
(4)Department of Pharmacy, Beijing Friendship Hospital, Capital Medical
University, Beijing 100050, China.
(5)China Institute of Sports Medicine, 2-A Sidegate, Tiyuguan Road, Dongcheng
District, Beijing 100061, China.
This study investigated the mechanisms underlying regulation of the serotonin
system in the rat brain during exercise-induced chronic fatigue. High-performance
liquid chromatography-mass spectrometry (HPLC-MS) was performed to measure serum
tryptophan of the fatigued rat. HPLC was conducted to measure 5-hydroxytryptamine
(5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex and
hippocampus. In addition, 5-HT1A receptor and 5-HT transporter (5-HTT) mRNA
expressions were measured at the same locations using real-time PCR. The results
demonstrated a significant reduction in the serum tryptophan level in rats with
exercise-induced chronic fatigue. Moreover, increased 5-HT and decreased 5-HIAA
levels were detected in the frontal cortex and hippocampus, and these alterations
were significant. Further, 5-HTT expression was significantly increased and
5-HT1A receptor expression was significantly decreased. These results indicate
that the 5-HT system plays an important role in the development of
exercise-induced chronic fatigue. The 5-HT levels in different parts of the brain
increased simultaneously, especially at synapses, and these alterations were
associated with changes in 5-HTT and 5-HT1A mRNA expressions.
Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain Res. 2017 Nov 15;1675:116-126.
Tryptophan circuit in fatigue: From blood to brain and cognition.
Yamashita M(1), Yamamoto T(2).
(1)Department of Neuroscience, Psychology and Behaviour, University of Leicester,
Lancaster Road, Leicester LE1 9HN, United Kingdom. Electronic address:
[email protected].
(2)Department of Psychology, Tezukayama University, 3-1-3, Gakuenminami,
Nara-shi, Nara 631-8585, Japan. Electronic address: [email protected].
Brain tryptophan and its neuroactive metabolites play key roles in central
fatigue. However, previous brain function analysis targets may have included both
glia and neurons together. Here, we clarified the fatigue-cognitive circuit of
the central-peripheral linkage, including the role of glial-neuronal interaction
in cognition. Using a rat model of central fatigue induced by chronic sleep
disorder (CFSD), we isolated presynaptic terminals and oligodendrocytes. Results
showed that compared to control group, presynaptic levels of tryptophan,
kynurenine, and kynurenic acid, but not serotonin, in the CFSD group were higher
in the hypothalamus and hippocampus. Moreover, CFSD group had higher
oligodendrocytic levels of tryptophan, and impaired spatial cognitive memory
accuracy and increased hyperactivity and impulsivity. These findings suggest that
dynamic change in glial-neuronal interactions within the hypothalamus-hippocampal
circuit causes central fatigue, and increased tryptophan-kynurenic acid pathway
activity in this circuit causes reduced cognitive function. Additionally, CFSD
group had 1.5 times higher plasma levels of tryptophan and kynurenine.
Furthermore, in rats undergoing intraperitoneal administration of kynurenine
(100mg/kg) versus vehicle, kynurenine-treated rats showed enhanced production of
kynurenic acid in the hippocampus, with suppressed recall of retained spatial
cognitive memory. The study revealed that uptake of periphery-derived kynurenine
and tryptophan into the brain enhances kynurenic acid production in the brain,
and the three factors produce amplification effect involved in the role of
central-peripheral linkage in central fatigue, triggering cognitive dysfunction.
Copyright © 2017 Elsevier B.V. All rights reserved.

Nutrients. 2018 Jan 25;10(2). pii: E119.
Effects of Glutamine and Alanine Supplementation on Central Fatigue Markers in
Rats Submitted to Resistance Training.
Coqueiro AY(1), Raizel R(2), Bonvini A(3), Hypólito T(4), Godois ADM(5), Pereira
JRR(6), Garcia ABO(7), Lara RSB(8), Rogero MM(9), Tirapegui J(10).
(1)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(2)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(3)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(4)Department of Nutrition, Faculty of Public Health, University of São Paulo,
Avenida Doutor Arnaldo 715, São Paulo SP 01246-904, Brazil.
[email protected].
(5)Faculty of Nutrition, Federal University of Mato Grosso, Avenida Fernando
Correa 2367, Cuiabá MT 78060-900, Brazil. [email protected].
(6)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(7)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(8)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
(9)Department of Nutrition, Faculty of Public Health, University of São Paulo,
Avenida Doutor Arnaldo 715, São Paulo SP 01246-904, Brazil. [email protected].
(10)Department of Food and Experimental Nutrition, Faculty of Pharmaceutical
Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, São Paulo
SP 05508-000, Brazil. [email protected].
Recent evidence suggests that increased brain serotonin synthesis impairs
performance in high-intensity intermittent exercise and specific amino acids may
modulate this condition, delaying fatigue. This study investigated the effects of
glutamine and alanine supplementation on central fatigue markers in rats
submitted to resistance training (RT). Wistar rats were distributed in: sedentary
(SED), trained (CON), trained and supplemented with alanine (ALA), glutamine and
alanine in their free form (G + A), or as dipeptide (DIP). Trained groups
underwent a ladder-climbing exercise for eight weeks, with progressive loads. In
the last 21 days, supplementations were offered in water with a 4% concentration.
Albeit without statistically significance difference, RT decreased liver
glycogen, and enhanced the concentrations of plasma glucose, free fatty acids
(FFA), hypothalamic serotonin, and ammonia in muscle and the liver. Amino acids
affected fatigue parameters depending on the supplementation form. G + A
prevented the muscle ammonia increase by RT, whereas ALA and DIP augmented
ammonia and glycogen concentrations in muscle. DIP also increased liver ammonia.
ALA and G + A reduced plasma FFA, whereas DIP increased this parameter, free
tryptophan/total tryptophan ratio, hypothalamic serotonin, and the
serotonin/dopamine ratio. The supplementations did not affect physical
performance. In conclusion, glutamine and alanine may improve or impair central
fatigue markers depending on their supplementation form.

J Neural Transm. 1986;65(3-4):219-32.
Peripheral and central short-term effects of fusaric acid, a DBH inhibitor, on
tryptophan and serotonin metabolism in the rat.
Chaouloff F, Laude D, Merino D, Serrurrier B, Elghozi JL.
Fusaric acid (FA) administration to the rats promoted one hour later a large
decrease in plasma total tryptophan (TRP), without affecting either plasma free
TRP or lipolysis, as measured by plasma non esterified fatty acid concentration.
The previous change was associated with hypoinsulinemia, hyperglycemia and
increased plasma corticosterone level. Regression analysis revealed a significant
correlation between brain TRP and the percentage of plasma TRP which was free
(i.e. unbound to albumin), both increased by FA injection. The increase in brain
TRP promoted an increased brain serotonin synthesis, as measured by the enhanced
brain and CSF 5-HIAA levels. Valine pretreatment, which blocks TRP entry into the
brain, completely prevented FA-induced brain TRP and brain 5-HIAA increases.
These results suggest that the increased brain serotonergic turnover following FA
treatment was due to a peripheral action of the drug upon TRP disposition. The
latter effect may be caused (i) by in vivo peripheral alterations in
catecholaminergic metabolism and (ii) by FA chemical structure since in vitro
experiments revealed that FA was able to displace TRP binding to albumin, thus
increasing the plasma free TRP pool.

Front Psychiatry. 2018 Nov 16;9:589.
Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue
Syndrome.
Noda M(1), Ifuku M(2), Hossain MS(2), Katafuchi T(2).
(1)Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences,
Kyushu University, Fukuoka, Japan.
(2)Department of Neuroinflammation and Brain Fatigue Science, Graduate School of
Medical Sciences, Kyushu University, Fukuoka, Japan.
Fatigue is commonly reported in a variety of illnesses and has major impact on
quality of life. Chronic fatigue syndrome (CFS) is a debilitating syndrome of
unknown etiology. The clinical symptoms include problems in neuroendocrine,
autonomic, and immune systems. It is becoming clear that the brain is the central
regulator of CFS. For example, neuroinflammation, especially induced by
activation of microglia and astrocytes, may play a prominent role in the
development of CFS, though little is known about molecular mechanisms. Many
possible causes of CFS have been proposed. However, in this mini-review, we
summarize evidence for a role for microglia and astrocytes in the onset and the
maintenance of immunologically induced CFS. In a model using virus mimicking
synthetic double-stranded RNA, infection causes sequential signaling such as
increased blood brain barrier (BBB) permeability, microglia/macrophage activation
through Toll-like receptor 3 (TLR3) signaling, secretion of IL-1β, upregulation
of the serotonin transporter (5-HTT) in astrocytes, reducing extracellular
serotonin (5-HT) levels and hence reduced activation of 5-HT1A receptor subtype.
Hopefully, drug discovery targeting these pathways may be effective for CFS
therapy.

J Pediatr. 1983 Mar;102(3):426-32.
Influence of free fatty acids and glucose infusion on serum bilirubin and
bilirubin binding to albumin: clinical implications.
Ostrea EM Jr, Bassel M, Fleury CA, Bartos A, Jesurun CA.
We studied the risk of a large group of jaundiced neonates for bilirubin
encephalopathy by serial assessment of their reserve serum albumin binding
capacity as measured by the saturation index test. In 1271 infants with serum
bilirubin concentration greater than 10 mg/dl, 12% had a saturation index (SI) of
7% or greater and therefore were clinically at or near risk for bilirubin
encephalopathy. Treatment with glucose infusion (1 gm/kg over one hour) was
highly effective in lowering the SI (delta = -3.7%. P less than 0.001). In none
of the infants did SI rebound to 7% or greater within 24 hours after the
infusion. In a detailed study of 19 infants who received glucose, the highly
significant (P less than 0.001) fall in SI (delta = -3.7%) was accompanied by an
equally significant rise in serum values for insulin (delta = +21.6 mcu/ml) and
fall in serum free fatty acids (delta = -0.51 mEq/L). Many factors in the study,
such as prematurity, hemolysis, acidosis, and hypoxemia, could have predisposed
the infants to the risk of bilirubin encephalopathy. However, the facility by
which most (93%) of the infants with high SI, including those who were premature
or had evidence of hemolysis or respiratory insufficiency, responded to infusion
of glucose indicates that serum free fatty acids may be the principal factor
contributing to the high saturation index and therefore an underestimated factor
in bilirubin binding to albumin.

 

[milk_lover]

Me: I’ve been recently into this fascination of smelling good perfumes and buying some of them if money allows. The perfumes are of top quality and from niche houses. I know some of them could induce allergy, affect hormones, or dater people away from you but I can’t stop enjoying them. I enjoy the notes of vanilla, rose, agarwood, ambergris, tobacco, honey, and many more notes. What are your opinions about those fragrances? I heard they are some notes that can arouse women, which can be inappropriate if you work at a company with many ladies around you. Also, I heard some fragrances can increase androgens and make you more masculine.

Ray Peat: The same steroid metabolite increases attraction of women, and confidence in men. Have you read Luca Turin’s work, or heard his google lecture?

Me: I watched some of Luca Turin's youtube videos and they were definitely fascinating to me, especially when he talked about the vibrations of smell molecules, as opposed to their shapes and the shapes of receptors, being responsible for creating the fragrance. Andersterone is a pheromone that is sold in many perfume essential oils online stores from Thailand and south east Asia countries.
Unrelated matter.. I see my little nephews and nieces sleeping and most of them sleep on their stomachs. Children have a higher metabolism than us and that’s why they can be really smart. Do you think sleeping on the stomach is healthier than other sleeping positions (right side, left side, on the back etc.,)? I read somewhere that sleeping on the stomach helps you avoid excessive loss of CO2.

Ray Peat: I think the position is better for the function of the viscera.

 

[haidut]

The risk of cancer incidence
and mortality sharply rose from 5% (rate of hereditary/genetic or innate disease)
in 1900s, to its current scary status of 33% or 50% among women and men,
respectively. Despite better hygiene, modern detection technologies and discovery
of antibiotics, baby boomers and subsequent 2-3 generations are sicker than
previous generations at same age.

I am glad Ray also provided a study corroborating the drastically lower average health of last 2 generations compared to the previous ones, despite improvements in sanitation, "health" care, food processing, etc.

 

[Miso]

On Deuterium Depletion:

“Hi Dr Peat,
I'm currently diving into Deuterium research and fascinated by it; on the one hand, high Deuterium appears to impact metabolism overtime by "jamming" ATP synthase- so it would be prudent to keep deuterium content in body low.
I recall in one of your interviews you mentioned deuterium depleted water, and I want to give it a try (there's a new USA based supply offering 25ppm at better price than the ones from EU suppliers).
In terms of Deuterium content in foods, there's a push for Ketogenic type diets to help deplete it, Center of Deuterium Depletion in CA recommends reducing intake of carbohydrates, specially fruits as they believe that's where Deuterium gets pushed into. Short of moving into high altitude regions, is there any legitimate concerns about reducing carbs to avoid excess Deuterium?
On the flip side, there's investigation around using Deuterated PUFAs to prevent lipid peroxidation damage from propagating. Looks like a drug is under development using D-PUFAs against neurodegenerative conditions. What are your thoughts on using D-PUFAs as a weapon against oxidative stress? Also, would be interesting if Deuterium played a beneficial role during mead acid production.”

Dr Peat
“I think beet sugar from areas east of the Rockies is likely to be low deuterium, since more will be rained out enroute from the ocean. I think a similar process of reducing deuterium is likely to be involved in producing fruit and milk, since the aging organism accumulates deuterium; young tissues are better than old tissues. I think LG Boros talks nonsense.”

 

[RayPeatFan777]

Hello Ray. Do you think amoxicillin is one of the safer antibiotics?

RP:
I would call it one of the less risky.

 

[milk_lover]

Me: "A friend of mine is asking about the safety of working with an airline company as a steward."

RAY: "I don’t know what the current situation is, but contamination of the air conditioning has been a serious health problem."

 

[Amazoniac]

What exactly is wrong with vitamin C supplements?

- Me:

"Hello, Ray.

You've expressed your concerns with vitamin C supplementation many times before. In spite of the potential problems, it's common to find people reporting a good experience.

Can you be more specific about what is wrong with the industrial process and how it could be made great again? Someone shared a diagram sent by you, but there was no comment included. It's valuable to have it clarified so that users demand the improvement.

Also, do you have an opinion on freeze-dried fruits rich in it?

Let me know in case you don't want an eventual reply to be shared elsewhere."​

- Raj:

"What diagram do you refer to? Are you thinking of some particular freeze dried fruits?"​

- Me:

"It's Figure 2 from the following publication, but the message was vague.
- Microbial Reactions for the Synthesis of Vitamin C (l-Ascorbic Acid)

From your 'Bean Syndrome' article:
- Oxyradicals and multivitamin tablets
How do you think that the traditional (good) product would have performed?
A complicator is the fast absorption of vitamin C in relation to the length of the experiment.

Depending on the quality of the solution, its stability can be acceptable in conditions encountered daily:
- Oxidative decomposition of vitamin C in drinking water

If consumed with a juice that has plant nutrients with chelating properties, undesirable interactions with metals might be minimized.


Max Gerson supplemented his patients with 400 mg/d, but now they have increased to 1000-1500 mg/d. His book was published in 1958.

- Industrial Fermentation of Vitamin C

"After the discovery of Asc, a demand for pure Asc began to be seen, which triggered the development of industrial production processes in the early 1930s (Pappenberger and Hohmann, 2014). Between 1933 and 1934, not only Haworth and fellow British chemist Edmund Hirsthad synthesised Asc, but also, independently, the Polish chemist Tadeus Reichstein (Figure 7.2), succeeded in synthesising the vitamin in bulk, making it the first vitamin to be artificially produced (Stacey and Manners, 1978). The latter process made possible the cheap mass-production of semi-synthetic Asc, which was quickly marketed. Haworth was awarded the 1937 Nobel Prize in Chemistry in part for this work, but the Reichstein process, a combined chemical and bacterial fermentation sequence still used today to produce vitamin C, retained Reichstein’s name (Boudrant, 1990; Bremus et al., 2006). In 1934, Hoffmann–La Roche, which bought the Reichstein process patent, became the first pharmaceutical company to mass-produce and market synthetic vitamin C, under the brand name Redoxon (Bächi, 2008).

In the late 1960s and early 1970s, a two-step microbial fermentation process was developed in China (Yin et al., 1980). Compared to the Reichstein process, the new fermentation process provides a clear cost benefit: it requires not only less chemicals and energy but also significantly low investment in production equipment (Xu et al., 2004). Therefore, the two-step fermentation process substituted the classical Reichstein process and was widely applied by Chinese manufacturers that produced more than 80% of vitamin C in theworld market (Pappenberger and Hohmann, 2014). Currently, more than 100,000 t vitamin C are produced every year in the world and have been widely used in the food, beverage, animal feed and pharmaceutical industries (Bremus et al., 2006; Mandlaa, 2014)."​

I don't know if they're making up for ineffectiveness, but synthetic ascorbic acid must still have more positives than negatives. If it's a matter of trying to stick to the original protocol, being more comfortable including than excluding elements, it doesn't explain the increase in amount, they're dealing with some people in critical conditions.


There are those who are supplementing, deriving benefit from it and will keep taking regardless of what is presented to them, which is why it would be helpful if you could specify what's wrong with the industrial process nowadays and how it can be made reliable. What to look and ask for?

In case synthetic options are out of question, there are alternatives such as acerola or camu-camu powder. Do you have an opinion on these? Have you ever recommended them?

Check out Table 3 below, it's useful for comparison with metal contamination of synthetic products on the market:
- Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria dubia) pulp​

- Me:

"Ray, your thoughts on those points would be valuable. I could now access the publication and it's actually Figure 6 that was shared:

Spoiler

Is it familiar? Do you mind giving your opinion on what was commented below?"​

- Raj:

"There have been several major process changes. I don’t know of any tests that have found crystalline ascorbic acid so free of catalysts that it didn’t produce intense free radicals. Much of the concern about vitamin C supplementation is based on missing the DHA in many foods."​

- Me:

"After you mentioned this in one of your interviews by Patrick Timpone, I tried to search for the content and wasn't much impressed:

• Ascorbic acid and dehydroascorbic acid content of foods-as-eaten
• A Procedure for the Separation and Quantitative Analysis of Ascorbic Acid, Dehydroascorbic Acid, Isoascorbic Acid, and Dehydroisoascorbic Acid in Food and Animal Tissue
• Electrochemical Determination of Ascorbic Acid and Isoascorbic Acid in Ground Meat and in Processed Foods by High Pressure Liquid Chromatography

If it remains relatively stable depending on the water quality (as linked), I suppose that it must not be extremely contaminated. It could interact with minerals from a meal, but people usually take it away from it or with juices that have the chelating plant compounds that might prevent an interaction with free minerals. Once it gets to the site of absorption, it should behave just like food ascorbic acid. Am I missing something?

From the 'Bean Syndrome' link:

"In the absence of food in the stomach, hydroxyl radicals will react with the mucosal lining, pepsin, and pepsinogen. A well-characterized hydroxyl radical scavenger, 1.0 M ethanol, greatly reduced the rate of formation of dihydroxybenzoates (see Fig. 1)."​

I don't use it and probably won't, but find it curious that it's not rare to come across people who treat it as their favorite and most beneficial supplement in spite of these issues, so it's difficult to think of it doing more harm than good. I guess that they wouldn't be responding well to it if their diets were providing enough.

Do you have an opinion on food-based alternatives (dry acerola, camu-camu, gubinge, rose hips, etc)? I'm not a vendor, but would be nice if I was because there has to be safe options out there so that users reap the benefits without having to deal with the detrimental effects. I emphasize empathize with the struggle to find a reliable way to increase its intake, sometimes needs are very high."​

In case he replies later, I'll edit. I would've tried to keep it shorter if it was some personalized advice. Similar parts were to recapitulate since he must go through piles of emails a day; repeated ones are just crutches.

 

[theLaw]

Me: Hey Dr. Peat,

Is there a maximum amount of calcium from eggshells that someone can digest without problems in a single sitting?

Also, is it better to space out eggshell calcium intake throughout the day, or does it matter?

Ray: I’ve known people who took a tablespoonful with good results, but some people have digestive discomfort with that amount.