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Cold Exposure & Other Mild Stressors for Increased Health & Longevity

Cold Exposure Exercise Fasting UCPs UCP1 UCP3 FGF21

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#61 Dean Pomerleau

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Posted 16 February 2016 - 01:18 PM

To even more thoroughly answer Mike's question about what it takes to activate BAT, below is the table from the full text of review article [1] showing the various cooling protocols used in human studies of BAT activity. 

 

For those of us who are Celcius impaired, here is a conversion for the various temperatures used:

 

°C     °F

16     61

17     63

18     64

19     66

20     68

 

The studies that were most effective at eliciting BAT activity in people used temperatures between 61 and 64°F (16-18 °C).

 

--Dean

 

 

F1.large.jpg?width=800&height=600&carous

 

 
-----------------
[1] Am J Physiol Regul Integr Comp Physiol. 2014 Jul 15;307(2):R103-13.
 
Cold-activated brown adipose tissue in human adults: methodological issues.
 
van der Lans AA, Wierts R, Vosselman MJ, Schrauwen P, Brans B, van Marken
Lichtenbelt WD.
 
 
The relevance of functional brown adipose tissue (BAT) depots in human adults was
undisputedly proven approximately seven years ago. Here we give an overview of
all dedicated studies that were published on cold-induced BAT activity in adult
humans that appeared since then. Different cooling protocols and imaging
techniques to determine BAT activity are reviewed. BAT activation can be achieved
by means of air- or water-cooling protocols. The most promising approach is
individualized cooling, during which subjects are studied at the lowest
temperature for nonshivering condition, probably revealing maximal nonshivering
thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using
the individualized cooling protocol. Currently, the most widely used technique to
study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose
([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging.
Dynamic imaging provides quantitative information about glucose uptake rates,
whereas static imaging reflects overall BAT glucose uptake, localization, and
distribution. In general, standardized uptake values (SUV) are used to quantify
BAT activity. An accurate determination of total BAT volume is hampered by the
limited spatial resolution of the PET image, leading to spillover. Different
research groups use different SUV threshold values, which make it difficult to
directly compare BAT activity levels between studies. Another issue is the
comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with
baseline values. This comparison can be performed by using the “fixed volume”
methodology. Finally, the potential use of other relatively noninvasive methods
to quantify BAT, like magnetic resonance imaging or thermography, is discussed.
 
PMID: 24871967

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#62 AlPater

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Posted 16 February 2016 - 02:20 PM

I'm not a bear for punishment and like to be comfortable.  But at the end of a day I take off my sweater and open top shirt buttons to prepare for sleep.  I enjoy sleeping in a cool room and need to have my hands and especially feet warm to go to sleep on average four times per night.

 

They say when doing such things as driving a vehicle, keep your feet coo and head warm.  For going to sleep, which you do not wnat to do when driving, do the opposite.

 

http://time.com/3602...om-temperature/

 

"Healthy men who spent a month sleeping in a cool (but not cold) 66-degree room increased their stores of metabolically active brown fat ... “Brown fat” may not sound very desirable, but it actually helps your body burn calories and dispose of excess blood sugar, he explains.?"

 

"In Celi’s brown fat experiment, the men slept under thin sheets. ... while the cold may be good for your metabolism and brown fat stores, you may be paying for those benefits with a night of fitful sleep."

 

"keeping your skin temperature “perfectly comfortable” is important when it comes to maintaining deep, restful slumber."

 

"the bottom line: keeping your head nice and cool is conducive to good sleep. To achieve that, set your thermostat somewhere around 65 degrees, research suggests. And layer up until you feel the Sandman creep closer."

 

 

http://healthland.ti...to-fall-asleep/

 

"Researchers from the University of Pittsburgh School of Medicine"

 

"When Buysse’s group gave 12 insomniacs a cap to wear that contained circulating water at cool temperatures, they were able to get them to fall asleep almost as easily as people without sleep disorders: using the caps, the insomniacs took about 13 minutes to fall asleep, compared with 16 minutes for the healthy controls, and they slept for 89% of the time they were in bed, which was similar to the amount of time the controls spent asleep."

 

"melatonin, one of the more effective medications to help people sleep, also works in part by lowering body temperature."

 

 

Brown adipose tissue--when it pays to be inefficient.
Celi FS.
N Engl J Med. 2009 Apr 9;360(15):1553-6. doi: 10.1056/NEJMe0900466. No abstract available.
PMID: 19357412 Free PMC Article
 
Figure 1
nihms147035f1.jpg
The Activation of Brown Adipose Tissue

Stimulation of β3-adrenergic receptors leads to the dramatic increase in the intracellular concentration of triiodothyronine (T3) by means of the type 2 5′ deiodinase (D2); T3 in turn stimulates the transcription of uncoupling protein 1 (UCP1), which causes the leakage of protons from the inner membrane of the mitochondria, hence dissipating energy in the form of heat. The abbreviation cAMP denotes cyclic adenosine monophosphate, CRE cAMP response element, T4 thyroxine, and TRE thyroid hormone response element.

 
 
N Engl J Med. 2009 Apr 9;360(15):1518-25. doi: 10.1056/NEJMoa0808949.
Functional brown adipose tissue in healthy adults.
Virtanen KA1, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P.
PMID: 19357407
 
Abstract
 
Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.
 
 
N Engl J Med. 2009 Apr 9;360(15):1509-17. doi: 10.1056/NEJMoa0810780.
Identification and importance of brown adipose tissue in adult humans.
Cypess AM1, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR.
PMID: 19357406 Free PMC Article
 
Abstract
BACKGROUND:
 
Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans.
 
METHODS:
 
We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery.
 
RESULTS:
 
Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007).
 
CONCLUSIONS:
 
Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.
 
 
N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718.
Cold-activated brown adipose tissue in healthy men.
van Marken Lichtenbelt WD1, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ.
PMID: 19357405 Free full text
 
Abstract
 
BACKGROUND:
 
Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism.
 
METHODS:
 
We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry.
 
RESULTS:
 
Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation.
 
CONCLUSIONS:
 
The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.


#63 Dean Pomerleau

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Posted 16 February 2016 - 06:11 PM

This is my daughter Kendall. It seems cold tolerance runs in the family. :-)

 

--Dean

 

6cHsZGQ.png


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#64 Zeta

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Posted 17 February 2016 - 07:58 AM

Wow, very cool thread. The sleep angle is of particular interest to me. I'd already lowered my bedroom from 23° to 20°, without noticing an effect on sleep, but after reading the above, I think I'll push it down further, and see what happens. Even if I don't sleep better, it sounds like I might end up improving my health.
 
Dean, judging by the footwear it looks like your daughter is doing ballet in the snow!
 
Zeta

 

P.S. Only now noticed my unintentional pun.



#65 Dean Pomerleau

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Posted 17 February 2016 - 09:21 AM

Good eyes Zeta,

Yes, my daughter is a dancer (mostly ballet) and wanted some dramatic poses in snow for her portfolio. That is just one of many she and I took yesterday, and one of the less aerobatic ones.

I too sleep with very light covers in a cool room (~18C = 64F). I find I've gotten used to it and seem to be sleeping quite soundly lately. But it does take some acclimatization / getting used to.

--Dean
There will never be peace in the world while there are animals in our bellies.

#66 Zeta

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Posted 17 February 2016 - 09:55 AM

"Bait-and-switch", "acclimatization"? This is clearly our day for puns!

 

Back to the cool thread: I may not feel comfortable enough if my body is much colder/exposed. If I'm not, I might try to fashion a head-cooling cap of some kind, sort of like the cooling vest, but for my head. I see from a quick Google search that such things exist and can actually be purchased. (What can't, these days!)

 

Zeta



#67 Dean Pomerleau

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Posted 17 February 2016 - 11:21 AM

Zeta,

 

"Bait-and-switch", "acclimatization"? This is clearly our day for puns!

 

I actually didn't intend to use acclimatization as a pun in the context of sleeping in cool conditions. I meant it to suggest literal adaptation to the cold - via building up more BAT!

 

But for "bait-and-switch" comment on the Fish & PCBs thread, that was was definitely me trying to be clever :-).

 

Cooling headgear might do the trick, but if you want to cool your head and keep your body warm(er), why not just turn down the thermostat and use more covers to compensate, but leave your head exposed? That has the added benefit of saving on your heating bill in the process. Are you in a warm climate, or are there others in your household whose comfort you need to consider?

 

--Dean


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#68 Saul

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Posted 17 February 2016 - 11:50 AM

Hi ALL!

 

As I've indicated before, I consider this a very interesting topic -- I hope that there will be a talk at CR IX on the effects of cold exposure, and perhaps also on the very interesting effects of the protein FGF21.

 

  -- Saul



#69 Zeta

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Posted 17 February 2016 - 12:08 PM

Why not just turn down the thermostat and use more covers to compensate, but leave your head exposed?

 

The heating system in my building (apt. complex) is such that there's no way to lower the temperature in my bedroom below around 16-17° or so. And once summer comes, the head cooler will of course be far more efficient.



#70 Saul

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Posted 17 February 2016 - 07:27 PM

Also, you have a lovely daughter, Dean!

 

:)xyz

 

  -- Saul



#71 Dean Pomerleau

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Posted 18 February 2016 - 03:37 AM

Also, you have a lovely daughter, Dean!
 
:)xyz
 
  -- Saul


Thanks Saul. She takes after her mother :-)

--Dean
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#72 Gordo

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Posted 18 February 2016 - 10:56 PM

I've been doing quite a lot of self experimentation lately with cold exposure.  I've also reconfigured the techkewl vest by putting 2 of the PCM packs over my shoulders like football shoulder pads, while the other two cover my ribs (Dean you asked about this earlier - the cooling packs go from the top of the logo all the way to the bottom of the vest and almost as wide as the vest (you can see the seams if you look closely):

techkewlovershoulder.jpg

 

A vest more specifically designed to target BAT might be a better option.

Like others, I also have a pretty long commute, so I've been trying cold exposure then as well, down to the goose bump level, tee shirt all week, no heat or coats.  Its really interesting how quickly you can become cold adapted.  My tolerance for cold has greatly increased during my experimentation.  I am also certain I have activated my BAT.  I think this is probably even more obvious to CR practitioners.  I kept my diet, caloric intake, and exercise the same as it has been for a long time, but the cold exposure has caused me to become ravenously hungry during my normal evening fast period.  Last night I broke the usual fast and ended up eating a tomato, handful of walnuts, an entire pint of blueberries, a clementine, and a pickle (odd that I had a strong craving for pickles like a pregnant woman).  Despite the extra eating, I have lost weight (not something I was shooting for).  So all of this is very interesting, but its also going to cost me $ and some would argue, waste food.  I guess if there are significant health/longevity benefits it might be worth it.  I tried to amp up my regular meals more today, which helped although I'm still hungry this evening as I chill, haha.  I'll have to compensate even more for the extra calories burned by BAT when I'm doing this.



#73 Dean Pomerleau

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Posted 19 February 2016 - 05:02 PM

Gordo,

Thanks for the update. Pretty clever of you to shift the cooling packs to the shoulders. I'm not surprised about increased hunger and the extra calorie needs. It's amazing how much extra energy a little brown fat can burn when you are cold. 

 

--Dean


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#74 Dean Pomerleau

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Posted 20 February 2016 - 05:23 PM

All,

 

Saul wrote:

As I've indicated before, I consider this a very interesting topic -- I hope that there will be a talk at CR IX on the effects of cold exposure, and perhaps also on the very interesting effects of the protein FGF21.

 

I don't think I've pointed to all the evidence that exercise is yet one more way to increase brown fat. Here is a good paper [1] (and press release) on it. This is the graphical abstract from the paper:

 

Image%20%5B7%5D.png

 

So from the full text, and from this diagram, it appears that non-shivering thermogenesis (like several of us are experimenting with via cold exposure) increases FGF21, which in turn causes an increase in brown fat levels. Exercise appears to mimic shivering thermogenesis, which creates more brown fat via another pathway, specifically by increasing another hormone, Irisin, which turns white fat to brown fat. So for those following along, here is the latest list of things that appear to increase and/or activate brown fat:

  • Cold exposure - by far the best BAT activator
  • Metformin
  • Green Tea
  • Caffeine
  • Capsaicin
  • Low protein diet
  • Exercise

I'll note once again that all of these are thought to be health-promoting and/or life-extending. Could the fact that they all increase levels of brown fat have something to do with it? I seems like a strong possibility....

 

--Dean

 

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

[1] Cell Metab. 2014 Feb 4;19(2):302-9. doi: 10.1016/j.cmet.2013.12.017.

Irisin and FGF21 are cold-induced endocrine activators of brown fat function in
humans.

Lee P(1), Linderman JD(1), Smith S(1), Brychta RJ(1), Wang J(1), Idelson C(1),
Perron RM(1), Werner CD(1), Phan GQ(2), Kammula US(2), Kebebew E(3), Pacak K(4),
Chen KY(1), Celi FS(5).

Full text: http://dx.doi.org.sc...met.2013.12.017

Rediscovery of cold-activated brown adipose tissue (BAT) in humans has boosted
research interest in identifying BAT activators for metabolic benefits. Of
particular interest are cytokines capable of fat browning. Irisin, derived from
FNDC5, is an exercise-induced myokine that drives brown-fat-like thermogenesis in
murine white fat. Here we explored whether cold exposure is an afferent signal
for irisin secretion in humans and compared it with FGF21, a brown adipokine in
rodents. Cold exposure increased circulating irisin and FGF21. We found an
induction of irisin secretion proportional to shivering intensity, in magnitude
similar to exercise-stimulated secretion. FNDC5 and/or FGF21 treatment
upregulated human adipocyte brown fat gene/protein expression and thermogenesis
in a depot-specific manner. These results suggest exercise-induced irisin
secretion could have evolved from shivering-related muscle contraction, serving
to augment brown fat thermogenesis in concert with FGF21. Irisin-mediated
muscle-adipose crosstalk may represent a thermogenic, cold-activated endocrine
axis that is exploitable in obesity therapeutics development.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID: 24506871


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#75 Dean Pomerleau

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Posted 20 February 2016 - 05:44 PM

All,

 

As observed in the previous post, non-shivering thermogenesis appears to upregulate FGF21, which boosts levels of brown fat. We also saw earlier in this thread (in this post), perhaps not coincidently as I've argued, that elevated FGF21 is associated with lifespan extension, at least in mice (PMID 23066506).

 

Now I've come across an interesting fact about curcumin, which nearly everyone believes to be health promoting, except apparently Michael who seems (seemed?) to think evidence in favor of curcumin to be rank nonsense :-).

 

Study [1] found that curcumin, like cold exposure, elevates the apparent lifespan-extending protein FGF21, both in vitro in liver cells from normal C57BL/6 mice and in vivo in a mice model of insulin resistance. Since we saw above (PMID 24506871) that FGF21 boosts brown fat levels, now it appears we can add curcumin to the list of brown fat increasing/activating interventions (i.e. curcumin -> increased FGF21 -> increased brown fat). So here is the latest full list of brown fat inducers:

  • Cold exposure - by far the best BAT inducer/activator
  • Metformin
  • Green Tea
  • Caffeine
  • Capsaicin
  • Curcumin
  • Low protein diet
  • Exercise

--Dean

 

 

----------

[1] J Nutr. 2015 Oct;145(10):2300-7. doi: 10.3945/jn.115.216853. Epub 2015 Sep 2.

Short-Term Curcumin Gavage Sensitizes Insulin Signaling in Dexamethasone-Treated
C57BL/6 Mice.

Tian L(1), Zeng K(2), Shao W(3), Yang BB(4), Fantus IG(5), Weng J(6), Jin T(7).

BACKGROUND: Long-term dietary curcumin (>12 wk) improves metabolic homeostasis in
obese mice by sensitizing insulin signaling and reducing hepatic gluconeogenesis.
Whether these occur only secondary to its chronic anti-inflammatory and
antioxidative functions is unknown.
OBJECTIVE: In this study, we assessed the insulin sensitization effect of
short-term curcumin gavage in a rapid dexamethasone-induced insulin resistance
mouse model, in which the chronic anti-inflammatory function is eliminated.
METHODS: Six-week-old male C57BL/6 mice received an intraperitoneal injection of
dexamethasone (100 mg/kg body weight) or phosphate-buffered saline every day for
5 d, with or without simultaneous curcumin gavage (500 mg/kg body weight). On day
7, insulin tolerance tests were performed. After a booster dexamethasone
injection and curcumin gavage on day 8, blood glucose and insulin concentrations
were measured. Liver tissues were collected on day 10 for quantitative polymerase
chain reaction and Western blotting to assess gluconeogenic gene expression,
insulin signaling, and the expression of fibroblast growth factor 21 (FGF21).
Primary hepatocytes from separate, untreated C57BL/6 mice were used for testing
the in vitro effect of curcumin treatment.
RESULTS: Dexamethasone injection impaired insulin tolerance (P < 0.05) and
elevated ambient plasma insulin concentrations by ~2.7-fold (P < 0.01).
Concomitant curcumin administration improved insulin sensitivity and reduced
hepatic gluconeogenic gene expression. The insulin sensitization effect of
curcumin was demonstrated by increased stimulation of S473 phosphorylation of
protein kinase B (P < 0.01) in the dexamethasone-treated mouse liver, as well as
the repression of glucose production in primary hepatocytes (P < 0.001). Finally,
curcumin gavage increased FGF21 expression by 2.1-fold in the mouse liver (P <
0.05) and curcumin treatment increased FGF21 expression in primary hepatocytes.
CONCLUSION: These observations suggest that the early beneficial effect of
curcumin intervention in dexamethasone-treated mice is the sensitization of
insulin signaling, involving the stimulation of FGF21 production, a known insulin
sensitizer.


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#76 Kenton

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Posted 22 February 2016 - 11:34 PM

Currently, I'm cold most of the time, always wear a scarf, and even wear a girdle around my waist to try to stay warm.  I surely cannot subject my 5'9" 105lb body to cold as described in this thread w/o snuffing out my QOL and ability to be productive.  Interestingly, for the first 10 yrs of my CR I surfed in the very cold Pacific Ocean for an hour a day.  I seem to be much healthier now for the past two years without the cold water exposure (it's complicated--I'm just saying).  I do eat lots of curcumin.  Great work on the research.  I've always been intrigued and wondered about human CR and cold exposure, too.


Edited by Kenton, 22 February 2016 - 11:34 PM.


#77 Dean Pomerleau

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Posted 23 February 2016 - 03:27 AM

Hi Kenton - Nice to hear from you!

You wrote:

I surely cannot subject my 5'9" 105lb body to cold...


Holy cow Kenton! That's a BMI of 15.5. That's pretty darn low. Be careful. I can certainly see why cold exposure (or cold water surfing) is not an appealing or viable option for you, at that level of CR. I just wonder if being that low is wise. But if you're feeling good (physically & psychologically), more power to you!

P.S. Do you plan to be at the CR Conference? I'd love to finally meet you in person!

--Dean
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#78 Gordo

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Posted 25 February 2016 - 09:19 PM

Dean, I think you could do a TED talk called "The unifying theory of longevity!" Haha.  To add to your list, "women have more BAT and live longer" and "lean people have better BAT activation than overweight people, and live longer".

 

Regarding the last 2 posts, I suspect that extreme low BMIs will end up being counter productive and life shortening.  Research has shown that brown fat activation is muted or non-existent in humans with extremely low BMIs.  Then you have the bone and muscle loss problems, and the studies of centenarians which suggest very low bmi does not result in longevity for humans.



#79 Dean Pomerleau

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Posted 26 February 2016 - 01:33 PM

Gordo,

 

You are right about women and naturally lean people having more BAT, and overweight/obese people having less. But in this post we saw that leanness as a sole result of severe calorie deficit (i.e anorexia) did not lead to BAT expression. So it requires more than just "getting lean" to increase one's BAT. Unfortunately being a woman or being naturally lean are not modifiable lifestyle factors that one can engage in to increase BAT. Another non-modifiable factor that is (inversely) associated with increased BAT expression is age. This study [1] measured the BAT levels in 4000 Chinese men and women. In addition to finding more BAT in women than men, and more BAT in thin than overweight/obese people, it found that BAT was quite rare in older individuals. Here is a graph of the percent of people with detectable BAT as a function of age (left) and BMI (right):

 

zkYojML.png     iGF0xON.png

 

As you can see, it's really uncommon for adults over 50 or with a BMI > 25 to express BAT, at least in among the Chinese subjects in this study.  They also found that people with detectable BAT were much less likely to suffer from markers for metabolic syndrome - visceral fat accumulation, high triglycerides & cholesterol and high fasting glucose, but it's not clear whether extra BAT expression causes improvements in metabolic syndrome risk factors, either directly (e.g. by burning triglycerides) or indirectly (e.g. by preventing obesity via increased calorie expenditure), or is simply correlated with reduced risk factors (i.e. increased BAT and improved risk factors both resulting from reduced obesity). 

 

Finally, this graph was interesting, in that it demonstrates that presumably unintentional cold exposure is associated with increased BAT expression. It compares the percent of subjects with detectable BAT as a function of outdoor temperature on the day of the scan - a proxy for the season (winter vs. summer) in Shanghai where the study was conducted. Note the 4000 subjects were scanned over the course of an entire year, providing a good distribution of ambient temperatures:

 

NoaISN5.png

 

As you can see, if it is was winter / cool outside (< 68 °F) people were much more likely to express BAT. And it wasn't that subjects were simply colder during the scan when it was done in the winter, since they were all kept at thermoneutral conditions (75 °F) for at least an hour prior to and during the scan. More evidence that folks who live in warm climates might be at a disadvantage relative to BAT expression.

 

Speaking of climate - there is also evidence that the climate of one's ancestors influences BAT expression. Study [2] compared BAT levels in "Dutch nationals with south Asian ancestry and matched Caucasian participants". They found that caucasians had 50% more BAT than people with south asian ancestors, despite all of them living in the same (northern) city in the Netherlands. Picking up on this observation, the same group of researchers suggest in [3] that the unusual high rate of cardiovascular disease among south asian populations may be a result of lower BAT expression:

 

A contributing factor that may underlie the development of this disadvantageous
metabolic phenotype is the presence of a lower amount of brown adipose tissue
(BAT) in South Asian subjects, resulting in lower energy expenditure and lower
lipid oxidation and glucose uptake. As it has been established that the increased
prevalence of classical risk factors in South Asians cannot fully explain their
increased risk for CVD, other non-classical risk factors must underlie this
residual risk.

 

More evidence that one's ancestry may play a significant role in BAT expression comes from this oldie but goodie from 1957 [4]. Researchers subjected healthy men of Caucasian, Inuit or African descent to an air temperature of 17°C. They found the Inuits had the highest baseline thermogenesis and that cold exposure resulted in twice the increase in thermogenesis in the Caucasian and Inuit men relative to the men with African ancestry:

 

After 55 minutes of exposure, both the Caucasian and Eskimo subjects demonstrated an average rise in metabolism of 22 Cal/hr/m2 above control levels of 40 and 55 Cal/hr/m2, respectively. Negro subjects showed an increase in body heat production of only 10 Cal/hr/m2 after 85 minutes in the cold room. Although the absolute levels of heat production differed for the Eskimo and Caucasian groups, these subjects responded in a similar fashion to the standard cold stress.

 

I can't get the full text of [4] to see whether the men were all from the same region, to eliminate possible effects of cold acclimation between the three sets of subjects. But the results generally seem to support the notion that one's genetic heritage may influence BAT expression.

 

While several of the factors discussed above (like gender, age and ethnicity) are non-modifiable, I think you are right that it's worth listing them. Here is the latest full list of modifiable and [non-modifiable] factors associated with increased BAT expression:

  • Cold exposure - by far the best BAT inducer/activator
  • Metformin
  • Green tea
  • Caffeine
  • Capsaicin
  • Curcumin
  • Exercise
  • Low protein diet
  • Avoid obesity/overweight
  • [Being naturally thin - high metabolic rate]
  • [Being younger]
  • [Being female]
  • [Ethnicity - having cold-climate ancestors]

 

I think you could do a TED talk called "The unifying theory of longevity!" Haha.

 

It is striking how many of these BAT-inducers are known (or thought) to be associated with increased health & longevity. Of course correlation is not causation, but the fact that all of these disparate interventions/characteristics result in increased BAT and better health/longevity is certainly suggestive of a causal chain with BAT in the middle, mediating the benefits.

 

--Dean
 
-----------
[1] PLoS One. 2015 Apr 20;10(4):e0123795. doi: 10.1371/journal.pone.0123795.
eCollection 2015.
 
Brown adipose tissue activation is inversely related to central obesity and
metabolic parameters in adult human.
 
Wang Q(1), Zhang M(2), Xu M(1), Gu W(1), Xi Y(2), Qi L(3), Li B(2), Wang W(1).
 
Author information: 
(1)Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai
Jiao-Tong University School of Medicine, Shanghai, China; Department of Endocrine
and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic
Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine,
Shanghai, China. (2)Department of Nuclear Medicine, Rui-Jin Hospital, Shanghai
Jiao-Tong University School of Medicine, Shanghai, China. (3)Department of
Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States 
of America.
 
 
BACKGROUND: Recent studies have shown that adult human possess active brown
adipose tissue (BAT), which might be important in affecting obesity. However, the
supporting evidence on the relationship between BAT and central obesity and
metabolic profile in large population based studies is sparse.
 
METHODOLOGY/PRINCIPAL FINDINGS: We studied 4011 (2688 males and 1323 females)
tumor-free Chinese adults aged 18-89 for BAT activities, visceral/subcutaneous
fat areas (VFA/SFA), waist circumferences (WC) and metabolic parameters. We found
that the prevalence of BAT was around 2.7% in our study participants, with a
significant sexual difference (5.5% in the females vs. 1.3% in the males;
p<0.0001). BAT detection was increased in low temperature and declined in elderly
subjects. The BAT positive subjects had lower BMI (P<0.0001), less SFA (P<0.01), 
VFA (P<0.0001), WC (P<0.0001), lower fasting glucose and triglyceride levels
(both P<0.01) and increased HDL cholesterol concentrations (P<0.0001), compared
with the BAT negative subjects. Robust logistic regression revealed that after
adjustment for covariates (including age, sex, BMI, VFA, SFA and WC), age and BMI
in the males (0.92 [95%CI, 0.88-0.96] and 0.84 [95% CI, 0.75-0.96], both P
≤0.008) while age and VFA in the females (0.87 [95%CI, 0.83-0.91] and 0.98
[95%CI, 0.97-0.99], respectively, P<0.05) were independently associated with
detectable BAT.
 
CONCLUSIONS/SIGNIFICANCE: Our data suggest that decreased amount of active BAT
might be associated with accumulation of visceral fat content and unfavorable
metabolic outcomes.
 
PMCID: PMC4403996
PMID: 25894250
 
------------------
[2] Lancet Diabetes Endocrinol. 2014 Mar;2(3):210-7. doi:
10.1016/S2213-8587(13)70156-6. Epub 2013 Nov 12.
 
Brown adipose tissue volume in healthy lean south Asian adults compared with
white Caucasians: a prospective, case-controlled observational study.
 
Bakker LE(1), Boon MR(2), van der Linden RA(1), Arias-Bouda LP(3), van Klinken
JB(4), Smit F(3), Verberne HJ(5), Jukema JW(6), Tamsma JT(1), Havekes LM(7), van 
Marken Lichtenbelt WD(8), Jazet IM(1), Rensen PC(9).
 
 
BACKGROUND: Individuals of south Asian origin have a very high risk of developing
type 2 diabetes compared with white Caucasians. We aimed to assess volume and
activity of brown adipose tissue (BAT), which is thought to have a role in energy
metabolism by combusting fatty acids and glucose to produce heat and might
contribute to the difference in incidence of type 2 diabetes between ethnic
groups.
METHODS: We enrolled Dutch nationals with south Asian ancestry and matched
Caucasian participants at The Rijnland Hospital (Leiderdorp, Netherlands).
Eligible participants were healthy lean men aged 18-28 years, and we matched
groups for BMI. We measured BAT volume and activity with cold-induced
(18)F-fluorodeoxyglucose ((18)F-FDG) PET CT scans, and assessed resting energy
expenditure, non-shivering thermogenesis, and serum parameters. This study is
registered with the Netherlands Trial Register, number 2473.
FINDINGS: Between March 1, 2013, and June 1, 2013, we enrolled 12 participants in
each group; one Caucasian participant developed hyperventilation after (18)F-FDG 
administration, and was excluded from all cold-induced and BAT measurements.
Compared with Caucasian participants, south Asian participants did not differ in 
age (mean 23.6 years [SD 2.8] for south Asians vs 24.6 years [2.8] for
Caucasians) or BMI (21.5 kg/m(2) [2.0] vs 22.0 kg/m(2) [1.6]), but were shorter
(1.74 m [0.06] vs 1.85 m [0.04]) and lighter (65.0 kg [8.5] vs 75.1 kg [7.2]).
Thermoneutral resting energy expenditure was 1297 kcal per day (SD 123) in south 
Asian participants compared with 1689 kcal per day (193) in white Caucasian
participants (difference -32%, p=0.0008). On cold exposure, shiver temperature of
south Asians was 2.0°C higher than Caucasians (p=0.0067) and non-shivering
thermogenesis was increased by 20% in white Caucasians (p<0.0001) but was not
increased in south Asians. Although the maximum and mean standardised uptake
values of (18)F-FDG in BAT did not differ between groups, total BAT volume was
lower in south Asians (188 mL [SD 81]) than it was in Caucasians (287 mL [169];
difference -34%, p=0.04). Overall, BAT volume correlated positively with basal
resting energy expenditure in all assessable individuals (β=0.44, p=0.04).
INTERPRETATION: Lower resting energy expenditure, non-shivering thermogenesis,
and BAT volumes in south Asian populations might underlie their high
susceptibility to metabolic disturbances, such as obesity and type 2 diabetes.
Development of strategies to increase BAT volume and activity might help prevent 
and treat such disorders, particularly in south Asian individuals.
FUNDING: Dutch Heart Foundation (2009T038) and Dutch Diabetes Research Foundation
(2012.11.1500).
 
Copyright © 2014 Elsevier Ltd. All rights reserved.
 
PMID: 24622751
 
------------
[3] Crit Rev Clin Lab Sci. 2015;52(3):150-7. doi: 10.3109/10408363.2014.1003634. Epub
2015 May 8.
 
High prevalence of cardiovascular disease in South Asians: Central role for brown
adipose tissue?
 
Boon MR(1), Bakker LE, van der Linden RA, van Ouwerkerk AF, de Goeje PL, Counotte
J, Jazet IM, Rensen PC.
 
Author information: 
(1)Department of Endocrinology and Metabolic Diseases and.
 
Cardiovascular disease (CVD) is the leading cause of death in modern society.
Interestingly, the risk of developing CVD varies between different ethnic groups.
A particularly high risk is faced by South Asians, representing over one-fifth of
the world's population. Here, we review potential factors contributing to the
increased cardiovascular risk in the South Asian population and discuss novel
therapeutic strategies based on recent insights. In South Asians, classical
('metabolic') risk factors associated with CVD are highly prevalent and include
central obesity, insulin resistance, type 2 diabetes, and dyslipidemia. A
contributing factor that may underlie the development of this disadvantageous
metabolic phenotype is the presence of a lower amount of brown adipose tissue
(BAT) in South Asian subjects, resulting in lower energy expenditure and lower
lipid oxidation and glucose uptake. As it has been established that the increased
prevalence of classical risk factors in South Asians cannot fully explain their
increased risk for CVD, other non-classical risk factors must underlie this
residual risk. In South Asians, the prevalence of "inflammatory" risk factors
including visceral adipose tissue inflammation, endothelial dysfunction, and HDL 
dysfunction are higher compared with Caucasians. We conclude that a potential
novel therapy to lower CVD risk in the South Asian population is to enhance BAT
volume or its activity in order to diminish classical risk factors. Furthermore, 
anti-inflammatory therapy may lower non-classical risk factors in this population
and the combination of both strategies may be especially effective.
 
PMID: 25955567
 
--------------
[4] J Appl Physiol. 1958 Jan;12(1):9-12.
 
Racial variations to a standardized cold stress.
 
ADAMS T, COVINO BG.
 
Abstract
 
Healthy, male, Negro, Caucasian and Eskimo subjects were subjected nude to an air temperature of 17°C. Rectal, average skin and extremity temperatures, body metabolism, sweating rates and electromyograms were obtained at 5-minute intervals throughout the duplicate exposure periods for each individual. After 55 minutes of exposure, both the Caucasian and Eskimo subjects demonstrated an average rise in metabolism of 22 Cal/hr/m2 above control levels of 40 and 55 Cal/hr/m2, respectively. Negro subjects showed an increase in body heat production of only 10 Cal/hr/m2 after 85 minutes in the cold room. Although the absolute levels of heat production differed for the Eskimo and Caucasian groups, these subjects responded in a similar fashion to the standard cold stress.
 
Submitted on July 24, 1957
 
PMID: 13502249

There will never be peace in the world while there are animals in our bellies.

#80 Dean Pomerleau

Dean Pomerleau
  • Lifetime Member
  • 2,491 posts

Posted 26 February 2016 - 03:46 PM

In my previous post, I said it was unclear from the study of 4000 Chinese people whether the association between BAT and better cardiovascular risk factors was a causal relationship, or just a correlation. This study [1] from last month suggests that the relationship may be causal. It found:

 

BAT activity negatively correlated with arterial inflammation (r=-0.178, p<0.01), a relationship that persisted after correcting for age and BMI (r=-0.147, p<0.01). Using either high sensitivity or high accuracy thresholds (from receiver operating curve analyses) to define elevated BAT, high BAT was associated with a reduced risk of CVD events (P = 0.048) even after correcting for age (P = 0.037).

 

So arterial inflammation and cardiovascular events were lower in people who had higher amounts of BAT, independent of age and BMI. The 'survival' curves (actually curves for 'time free from CVD events') during the 4.5 years of follow-up for people with high BAT activity (green) and low BAT activity (blue), for two different BAT-activity thresholds, are shown below:

 

rvCkcAm.png

 

Remarkably, the graph on the right shows that people with high BAT activity had zero CVD events vs. 30 CVD events (~10% of population) in the low-BAT group, during the 4.5 years of followup, the authors said:

 

Further, no [CVD] events were observed in subjects with high BAT activity,
raising the possibility that BAT could have an important role in vasoprotection. 

 

In short, these results suggests that BAT isn't just associated with reduced risk of cardiovascular disease, via its impact on body weight / adiposity. Instead having increased BAT activity may cause a reduction in CVD risk, independent of age and body weight.

 

--Dean

 

-----------

[1] J Nucl Med. 2016 Jan 21. pii: jnumed.115.166025. [Epub ahead of print]

 
Supraclavicular Brown adipose tissue FDG uptake and cardiovascular disease.
 
Takx R(1), Ishai A(2), Truong QA(3), MacNabb MH(2), Scherrer-Crosbie M(2),
Tawakol A(2).
 
Author information: 
(1)Utrecht University Medical Center, Netherlands; (2)Massachusetts General
Hospital, United States; (3)Weill Cornell College of Medicine.
 
 
RATIONALE: Pre-clinical data suggests a negative correlation between brown
adipose tissue (BAT) and the degree of coronary atherosclerosis. We sought to
evaluate the relationship between (18)F-FDG uptake in supraclavicular BAT in
relation to: 1) arterial inflammation and 2) subsequent cardiovascular disease
(CVD) events in humans.
METHODS: Individuals who underwent (18)F-FDG PET/CT for clinical indications, but
who did not have either cancer or known atherosclerotic disease at time of
imaging were included. While blinded to clinical data, (18)F-FDG uptake was
measured within BAT (in supraclavicular region) as well as in subcutaneous
adipose tissues (SAT). Tissue density was evaluated using CT (Hounsfield units). 
Arterial inflammation was assessed by measuring of arterial FDG uptake and
calculating target to background ratio (TBR). Cardiovascular disease (CVD) events
were independently adjudicated by blinded cardiologists. Thereafter, the
relationship between BAT activity and CVD events was evaluated.
RESULTS: A total of 443 patients (age, 43% male, body mass index (BMI) 26
(23-31)) were included and 34 experienced a cardiovascular event during a median 
follow-up of 4 years. BAT activity negatively correlated with arterial
inflammation (r=-0.178, p<0.01), a relationship that persisted after correcting
for age and BMI (r=-0.147, p<0.01). Using either high sensitivity or high
accuracy thresholds (from receiver opereating curve analyses) to define elevated 
BAT, high BAT was associated with a reduced risk of CVD events (P = 0.048) even
after correcting for age (P = 0.037).
CONCLUSION: Our results suggest that increased supraclavicular BAT activity is
inversely associated with arterial inflammation, independently of age and BMI.
Additionally, increased BAT may be associated with fewer cardiovascular events.
 
Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
 
PMID: 26795284

There will never be peace in the world while there are animals in our bellies.





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