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Dean Pomerleau

Cold Exposure & Other Mild Stressors for Increased Health & Longevity

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I didn't see this old study posted here, which seems very promising:

 

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Uric acid and glutathione levels during short-term whole body cold exposure.
 
Siems WG, van Kuijk FJ, Maass R, Brenke R.
Abstract
Ten healthy subjects who swim regularly in ice-cold water during the winter (winter swimming), were evaluated before and after this short-term whole body exposure. A drastic decrease in plasma uric acid concentration was observed during and following the exposure to the cold stimulus. We hypothesize that the uric acid decrease can be caused by its consumption after formation of oxygen radicals. In addition, the erythrocytic level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione also increased following cold exposure, which supports this hypothesis. Furthermore, the baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of nonwinter swimmers. This can be viewed as an adaptation to repeated oxidative stress, and is postulated as mechanism for body hardening. Hardening is the exposure to a natural, e.g., thermal stimulus, resulting in an increased tolerance to stress, e.g., diseases. Exposure to repeated intensive short-term cold stimuli is often applied in hydrotherapy, which is used in physical medicine for hardening.
 
It looks like cold exposure acts as an exercise for defense system against oxidative stress. You lose some of your endogenous anti oxidants, but improve your overall capacity in the long run. 
Edited by Burak

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Thanks Burak.

 

Full-text link: 

https://www.researchgate.net/publication/15136440_Uric_acid_and_glutathione_levels_during_short-term_whole_body_cold_exposure

 

Members swim at least once per week for about 5 min in ice-cold water.

 

I've been swimming in the icy-cold Yenisei river.  But no way I can stay in for five minutes!     Way too cold for that.    I go in and out multiple times.  Air temperature has been quite hot, but the water is still ice cold.

 

13_10.jpg?alias=standard_900x600nc

Summer float board yoga on the Yenisei.

Nice to swim out to them and say hello!

Edited by Sibiriak

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Very nice picture, which triggers two questions:

 

  1. Would you have the breath to say hello after a swim in the Yenisei? I sure wouldn't, I have remained breathless/paralyzed in much warmer waters
  2. Is resistance to cold regarded as manly in Siberia? Does it cause admiration in gals?

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Would you have the breath to say hello after a swim in the Yenisei? I sure wouldn't, I have remained breathless/paralyzed in much warmer waters

 

I haven't found breathing to be a problem.  But after about 15 seconds I start feeling  increasingly intense bodily pain.    So, to be honest, I really wouldn't be able to swim out and have a relaxed chat with the yoga girls.  The last time I went to the river it was   hot and sunny and there was no breeze at all;  it was 34C,  baking, and the water was glistening, inviting, cool and dark and potentially deadly--I just couldn't resist going in.   Around 30 seconds.  In and out 4 or so times.  Felt great.      Once, though,  I stayed in a bit too long and was chilled for hours.

 

I've been doing ice-cold showers and baths (I mean really  cold) methodically for several years now,  and less methodically for much longer.    I believe this has helped reduce my level of "cold shock response".   Plus I do do some cold water ocean swimming when I get the chance.

 

See:  A physiological trip through cold water exposure

 

http://scienceofsport.blogspot.ru/2008/01/exercise-in-cold-part-ii.html

 

The cold-shock response - the biggest challenge to survival in the cold

 

One of the first things you experience when submerging yourself in cold water is something called the "cold-shock response." This is characterized by an uncontrollable gasp for air, followed by a prolonged period of hyperventilation - more rapid breathing. In fact, this response is one of the most likely causes of death in most cold-water immersions such as when one falls out of a boat into icy water. It's not difficult to see that if the timing of that "gasp" is slightly wrong, you'll take in a huge lungful of air, and one or two gasps while underwater is all it takes to drown.

 

The other big 'killer' is a heart attack, which can result when the temperature of the blood returning to the heart is suddenly cooled - this can affect the electrical conduction within the heart, causing fibrillation. So it is these two possibilities - drowning and cardiac arrest that are most likely the cause of death. However, as we said, most times, people blame hypothermia for death, when in fact the body temperature does not need to fall for an unlucky 'swimmer' to perish in the cold.

 

Swimming in the cold - a problem of breathing and muscle weakness

 

Once you've overcome that problem, however, the next thing to worry about is swimming. And again, the hyperventilation that happens in the cold has a profound effect on the ability to swim in an efficient manner.   The graph below, from a paper published by Eglin and Tipton in 2005 (EJAP) shows the breathing response of a swimmer exposed to cold water.  [ETC.]

 

 

Next problem - the "DiCaprio" problem - a cold muscle, and cold skin, equal a weak muscle

 

The next problem is equally significant - when the muscle and the skin are cooled, the muscle becomes weaker! So the cold water on the skin will make a powerful swimmer incapable of swimming, simply because his skin is cooled. There is evidence from studies that shows that the ability of the muscle to produce force is as much as 25% lower immediately after exposure to water at 10 degrees celsius - this would only drop in even colder water.  [ETC.]

 

So that is the bad news. . .but the good news is that humans are adaptable organisms, and just like we make adaptations to things like marathon training, we also make adaptations to stressors such as cold-water immersion. The data show that exposures to cold water as short as three minutes in a 10 C shower will attenuate the cold-shock response by as much as 20-30%.
Edited by Sibiriak

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I love any article with "unexpected" in its title.  This looks really interesting to me, I hope someone can get the full text.  Bing also has an image for it in the search results that I'd love to see in full resolution.

 

An unexpected role for bile acid synthesis in adaptation to low temperature

Enhanced conversion of dietary cholesterol to bile acids through the alternative pathway leads to cold-associated, metabolically beneficial changes in the intestinal microbiome and to elevated bile acid levels that contribute to adaptive thermogenesis.

 

coldbile1.jpgcoldbile2.jpg

PMID:   28697185       I noticed that my body seems to work very well without a gallbladder, no downside whatsoever (digestion works much better now actually).  I'm wondering if this article offers some explanation for my experience in that regard. Either way, a fascinating topic..  

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Cf. Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice

 

http://www.sciencedirect.com/science/article/pii/S0021915011005624

 

In the present study, we tested the hypothesis that voluntary wheel running ameliorates atherosclerosis possibly by modulating cholesterol metabolism. By using hypercholesterolemic LDLR-deficient mice on a western-type diet, we were able to show for the first time that voluntary wheel running provokes specific changes in cholesterol metabolism, particularly by promoting its conversion into bile acids likely contributing to reduced plasma lipid levels, and that these alterations coincide with a reduction in atherosclerosis.

 

Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis

http://www.nature.com/nm/journal/v23/n7/full/nm.4357.html

 

Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production. Genetic and pharmacological interventions that targeted the synthesis and biliary excretion of bile acids prevented the rise in fecal bile acid excretion, changed the bacterial composition of the gut and modulated thermogenic responses. These results identify bile acids as important metabolic effectors under conditions of sustained BAT activation and highlight the relevance of cholesterol metabolism by the host for diet-induced changes of the gut microbiota and energy metabolism.

 

(Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.

https://www.crsociety.org/topic/11488-cold-exposure-other-mild-stressors-for-increased-health-longevity/page-3?do=findComment&comment=15106)

Edited by Sibiriak

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One note on berberine. I have always wondered why LEF isn't selling a supplement with it, particularly since they have been heavily hyping metformin in their magazine in the past few years, and berberine seems to act in a similar fashion. By googling the LEF website I did find this note in one of their articles:

 

http://www.lifeextension.com/Protocols/Skin-Nails-Hair/Acne/Page-07

 

 

Although berberine has been studied in human clinical trials and shown to have several metabolic benefits, concerns about long-term use of berberine have been raised on the basis of certain preclinical studies (Kysenius 2014; Mikes 1985; Mikes 1983). Some evidence suggests that long-term berberine use, especially at high doses, may impair particular aspects of cellular metabolism in specific types of cells. The implications of this preclinical research are yet to be determined by long-term human clinical trials, therefore Life Extension currently recommends short-term use of berberine.

 

 

That was a good pickup BrianA.  I recently looked into berberine as Peter Attia listed it as one of his supplements in a podcast Q&A follow-up on the Tim Ferris podcast ( about 19 minutes into this: http://podbay.fm/show/863897795/e/1426120736?autostart=1 ). He expressed enthusiasm over the similarities between berberine and metformin AMP kinase activators, and as well as berberine's unique role of PCSK9 inhibition which metformin does not do.  Apparently PCSK9 is overexpressed in about 10-15% of individuals, and its inhibition may reduce LDL particle number.

 

My search found the following - bit dated - but useful summary of some of the potential concerns regarding berberine toxicity esp. with long-term use:

 

https://diabetesupdate.blogspot.com/2013/08/berberine-works-but-may-very-well-be.html

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https://medicalxpress.com/news/2017-09-bad-body-fat-good.htmlsays, in rhodents, "The researchers found that blocking the activity of a specific protein in white fat triggered the fat to begin to brown into beige fat, a type of fat in between white and brown. Blocking the protein to create beige fat caused the fat cells to heat up and burn calories."

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https://medicalxpress.com/news/2017-09-bad-body-fat-good.htmlsays, in rhodents, "The researchers found that blocking the activity of a specific protein in white fat triggered the fat to begin to brown into beige fat, a type of fat in between white and brown. Blocking the protein to create beige fat caused the fat cells to heat up and burn calories."

Good find but it's also unclear from that overview what they actually did, seems like standard CE:

 

"When we put the mice into a cold environment, levels of the protein also decreased in white fat, allowing that fat to behave more like brown fat. Cold induces brown and beige fats to burn stored energy and produce heat."

 

Nice to know Washington University is active in this research area though...

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https://medicalxpress.com/news/2017-09-bad-body-fat-good.htmlsays, in rhodents, "The researchers found that blocking the activity of a specific protein in white fat triggered the fat to begin to brown into beige fat, a type of fat in between white and brown. Blocking the protein to create beige fat caused the fat cells to heat up and burn calories."

Good find but it's also unclear from that overview what they actually did, seems like standard CE:

 

"When we put the mice into a cold environment, levels of the protein also decreased in white fat, allowing that fat to behave more like brown fat. Cold induces brown and beige fats to burn stored energy and produce heat."

 

Nice to know Washington University is active in this research area though...

 

It's clear from Kenton's quote that they didn't just do CE: ""The researchers found that blocking the activity of a specific protein in white fat triggered the fat to begin to brown into beige fat." Even in your quote, it says "When we put the mice into a cold environment, levels of the protein also decreased in white fat".

 

The press story does cite the scientific paper:

Lodhi IJ, Dean JM, He A, Park H, Tan M, Feng C, Song H, Hsu FF, Semenkovich CF. PexRAP inhibits PRDM16-mediated thermogenic gene expression. Cell Reports, Sept.19, 2017.

 

... which you can find on their website.

 

 

PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation [via either inducibly knocking out the gene for the protein or by using small hairpin RNA] promoted adipocyte browning. [This is based on mRNA for UCP1, which is not the most convincing way to document this, but here it is:

 

gr1.jpg

The data of interest are UCP1 relative mRNA in Figs. 1(h) and (i)]. Body composition analysis by EchoMRI indicated that PexRAP-iKO had significantly reduced adiposity when subjected to high fat feeding (Figure 1B). The decreased adiposity was observed despite hyperphagia (Figure S2A). Indirect calorimetry indicated that the knockout mice have elevated energy expenditure (Figure 1C). Histologic analysis showed that white adipocytes were smaller in PexRAP-iKO mice, and brown adipocytes had marked depletion of lipid droplets (Figure 1D). Morphometric analysis of the gonadal adipose depot confirmed that adipocyte size and number were significantly decreased in PexRAP-iKO mice compared with control animals (Figures S2B and S2C). ...

 

[see, by comparison, "Gene expression in iWAT of control and PexRAP-AKO female mice following 3 day cold exposure (n = 3)" in Fig. F]

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PexRAP inactivation [via either inducibly knocking out the gene for the protein or by using small hairpin RNA] promoted adipocyte browning.

Pharmacological inhibition of PexRAP function in adipose tissue may be an appropriate strategy for treating obesity.

 

http://www.cell.com/cell-reports/fulltext/S2211-1247%2817%2931219-6

 

Not particularly  relevant to CR/CE practitioners?

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Not particularly  relevant to CR/CE practitioners?

 

If you mean treating obesity is not relevant, yes.  If you mean optimal health and longevity - go buy some small hairpins  ;)

Thanks for digging into that article Michael.

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Fall approaching or just beginning in non-tropical northern hemisphere, I'm looking forward to start a new cycle of CE and upregulate mTOR in BAT through the NE receptors. The advantage of alternating seasons is that we can expose gradually. Last summer it hit over 40°C and I also practiced sun exposure (vitamin D3 galore) so no way I could feel a minimal hint of cold. But maybe I activated some HSPs (Heath shock Proteins).

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Hi folks,

 

I had to post this one [1], a new study shared by Al Pater (thanks Al!) that intermittent fasting (IF) triggers the browning of white fat in mice. They fed the IF mice for two days and then fasted them for one day, continuing this 3-day cycle for several months. By the end, the IF mice weighed less than the AL mice, even when they were pair-fed (i.e. received the same amount of calories over each 3 day cycle). The IF mice also were metabolically much more healthy, with much better glucose tolerance (28% better) when the mice were fed a high-fat diet. The researchers tracked the improvement down to a browning of white fat, an increase in BAT and an increase in expression of UCP1 in BAT. 

 

Most fascinating of all, the metabolic benefits of IF was greatly attenuated when the mice were housed at thermoneutrality (30 degC instead of the normal 22 degC). Rather than being 28% better at the glucose tolerance test, IF mice were only 9% better than AL mice when both were housed at the warmer temperature. This, despite the fact that the thermoneutral IF mice showed an increase expression of UCP1 in BAT.

 

In other words, intermittent fasting gave mice the potential to burn more glucose in their BAT and therefore avoid glucose intolerance, but it wasn't activated when they were housed in thermoneutral conditions. The IF mice housed in thermoneutral conditions didn't garner much in the way of glucose-metabolizing benefits of intermittent fasting because they weren't cold enough to trigger thermogenesis.

 

+1 for the combination of intermittent fasting and cold exposure.

 

--Dean

 

-------------------------------------

[1] Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.
Kim KH, Kim YH, Son JE, Lee JH, Kim S, Choe MS, Moon JH, Zhong J, Fu K, Lenglin F, Yoo JA, Bilan PJ, Klip A, Nagy A, Kim JR, Park JG, Hussein SM, Doh KO, Hui CC, Sung HK.
Cell Res. 2017 Oct 17. doi: 10.1038/cr.2017.126. [Epub ahead of print]
PMID: 29039412
http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2017126a.html
https://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2017126a.pdf (https://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2017126a.pdf)
Abstract
Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

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Nice study.  FYI: I just started a new practice of "forest bathing" (OK, really just spending more time in the woods, but the woo-woo people call it forest bathing now, haha, but all kidding aside, there are now numerous peer reviewed studies showing the multiple benefits including immune function enhancement).  I've been doing my (information technology) work from the woods, without shirt, while sipping ice water, lately this has been getting me just slightly above the shivering threshold.  Very much enjoying working out there with curious squirrels coming to visit and all the birds and insects singing continuously.  I don't know why I didn't start doing this years ago?  I've taken several conference calls so far from the woods and no one noticed, haha.

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That's funny Gordo, I too have taken to spending a lot of time in the forest lately. In fact, I lived in a tent in the woods near my home for much of July and half of August, coming home for a few hours each day to eat and spend time with the family.

 

Maybe Costa Rica and/or the ayha ceremony we enjoyed affected us in the same way. :-)

 

Dean

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You guys might be interested in this. Although it's been somewhat contentious, the evidence seems to be that pigs have no brown adipose tissue, an ancestor of theirs having lost functional UCP1 tens of millions of years ago: "An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence." Chinese scientists recently reported reconstituting the pig UCP1 using mouse UCP1, in a kind of intragenetic version of the Jurassic Park trick:

 

 

Pigs (Artiodactyl family Suidae) lack a functional UCP1 gene, resulting in poor thermoregulation and susceptibility to cold, which is an economic and pig welfare issue owing to neonatal mortality. Pigs also have a tendency toward fat accumulation, which may be linked to their lack of UCP1, and thus influences the efficiency of pig production.

 

Here, we report application of a CRISPR/Cas9-mediated, homologous recombination (HR)-independent approach to efficiently insert mouse adiponectin-UCP1 into the porcine endogenous UCP1 locus. The resultant UCP1 knock-in (KI) pigs showed an improved ability to maintain body temperature during acute cold exposure, but they did not have alterations in physical activity levels or total daily energy expenditure (DEE). Furthermore, ectopic UCP1 expression in white adipose tissue (WAT) dramatically decreased fat deposition by 4.89% (P < 0.01), consequently increasing carcass lean percentage (CLP; P < 0.05).

 

Mechanism studies indicated that the loss of fat upon UCP1 activation in WAT was linked to elevated lipolysis. UCP1 KI pigs are a potentially valuable resource for agricultural production through their combination of cold adaptation, which improves pig welfare and reduces economic losses, with reduced fat deposition and increased lean meat production.

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That's funny Gordo, I too have taken to spending a lot of time in the forest lately. In fact, I lived in a tent in the woods near my home for much of July and half of August, coming home for a few hours each day to eat and spend time with the family.

 

Maybe Costa Rica and/or the ayha ceremony we enjoyed affected us in the same way. :-)

 

Dean

 

Always good to see Dean posting. Could you explain your motivation behind your July/August routine?

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I believe this thread should be made a sticky.

 

I've been pondering this a while but the proper term to describe the hormetic effects of CE is probably: cryohormesis. Actually, I didn't search if this has been previously used. Google doesn't carry the term.

 

A summary:

 

  • Xenohormesis: hormesis by phytochemicals produced by plants in response to various stressors (ingestion of phenolic compounds, terpenes and other phytochemicals)
  • Mitohormesis: hormesis by increased formation of ROS within the mitochondria (physical exercise)
  • Cryohormesis: hormesis by increased hormonal and metabolic reaction to cold environments (scientific cold exposure).

When people see me in shirt or T-shirt and start asking, I've started to answer citing cryohormesis and its effects. Must review the thread. Going to be a pretty lenghty answer.

Edited by mccoy

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If you are working on a classification scheme,  you may want to find a category that would cover heat exposure as well.  Saunas, for example.

 

 

Btw,  I was in California for almost a month.  I went ocean swimming almost everyday.  The water was rather cool and invigorating.  I enjoyed it immensely.   A few days before leaving, though, I swam out and talked to a couple of guys on paddle boards.  We chatted for about twenty minutes.  Toward the end of the conversation one of the guys remarked on the  large increase in Great White shark sightings and attacks.   That was news to me!    I wasn't certain if the guy was joking.  But I later checked on the net, and sure enough, he was right.  Of course, the odds of an attack where I was swimming were still very low,  but the imagination easily runs wild, and the thought of Great Whites in the waters dampened my swimming enjoyment just a bit.   Did spur me to swim faster though.

 

Now I'm back in Siberia.  Temperatres below -20 C.  New opportunities  for cold exposure!

Edited by Sibiriak

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If you are working on a classification scheme,  you may want to find a category that would cover heat exposure as well.  Saunas, for example.

 

That's easy, it's thermohormesis.  

 

 

 

Btw,  I was in California for almost a month.  I went ocean swimming almost everyday.  The water was rather cool and invigorating.  I enjoyed it immensely.   A few days before leaving, though, I swam out and talked to a couple of guys on paddle boards.  We chatted for about twenty minutes.  Toward the end of the conversation one of the guys remarked on the  large increase in Great White shark sightings and attacks.

 

Congrats for swimming in the Pacific, that's surely not for wimps (I consider myself within the wimps).

 

I know about Kimberly Chambers, the marathon swimmer who swims routinely in cold waters infested by white sharks. She bought a garden inflatable pool and filled it with water an ice to practice cold exposure.

 

 

A very interesting podcast with her on Rich Roll's, describign among other things her swim in the dark in the sharks area (they feed on sails which abound in the aquatic park).

 

http://www.richroll.com/podcast/kimberley-chambers/

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Mccoy,  thanks for the video!

 

Toward the end Chambers talks about a real treasure that's found at that edge where you are most uncomfortable, most fearful.    Fear-hormesis?  Thrill-hormesis?   I think Gordo is into that!

 

Congrats for swimming in the Pacific, that's surely not for wimps

 

To be honest, I grew up surfing in the Pacific,  so swimming in it  comes naturally to me.

Edited by Sibiriak

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This time I started practicing CE since fall and results are being good, the body withstands low temps pretty well.

The collateral effect though is that my hunger skyrocketed, especially the hunger for simple sugars. I know I'm guilty of blasphemy here, but I'm enjoying lots of hot cocoa drinks with dark muscovado and honey. Wonder if you guys suffer the same predicament.

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