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Cold Exposure & Other Mild Stressors for Increased Health & Longevity

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The author of that article,  K.A. Virtanen,  is co-author of the following article on BAT,  with full text available.  Some neat diagrams.   It's a pretty dense article--I'm hoping Mccoy can predigest it for me.

Brown Adipose Tissue Energy Metabolism in Humans

Edited by Sibiriak

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1 hour ago, Sibiriak said:

The author of that article,  K.A. Virtanen,  is co-author of the following article on BAT,  with full text available.  Some neat diagrams.   It's a pretty dense article--I'm hoping Mccoy can predigest it for me.

Brown Adipose Tissue Energy Metabolism in Humans

OK, a demonstration of copy/paste capabilities of the new forum software with some BAT porn:

image.thumb.png.8bd04b25290028f7fbce43d0a36aadf4.png

Figure 1. From: Brown Adipose Tissue Energy Metabolism in Humans.

Uncoupling protein 1 (UCP1)-mediated brown adipose tissue thermogenesis. Upper panel: Brown adipose tissue UCP1-mediated thermogenesis is activated by fatty acids produced via norepinephrine-induced intracellular triglyceride (TG) lipolysis during cold exposure. Middle panel: Acute pharmacological inhibition of intracellular TG lipolysis blunts brown adipose tissue thermogenesis via reduction of intracellular fatty acids availability. Lower panel: Genetic deletion-mediated inhibition of intracellular TG lipolysis in brown adipose tissues leads to increased reliance on circulating nonesterified fatty acids (NEFA) and triglyceride (TG)-rich lipoproteins to sustain UCP1-mediated thermogenesis. The mitochondrion illustration was obtained free of copyright from Pixabay (www.pixabay.com, 2018).

 

Figure 2

 
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The standard definition of brown adipose tissue in vivo in humans. Brown adipose tissue is currently defined in vivo in humans by the combination of two radiological features: (1) 18-fluorodeoxyglucose (18FDG) uptake above a set threshold higher than that usually observed in white adipose tissues using positron emission tomography (left panels); and (2) a radio-density that is compatible with the presence of adipose tissue using computed tomography (right panels). After intravenous (i.v.) injection of 18FDG, whole body (static) positron emission tomography scanning is performed, giving quantitative tissue bio-distribution of the tracer into brown adipose tissues. This tissue tracer uptake is co-registered with tissue radio-density measured using computed tomography. The middle left and right panels show positron emission tomography and computed tomography transverse views, respectively, of supraclavicular brown adipose tissue in a healthy individual during a standardized cooling protocol. Source of illustration: Shutterstock (www.shuterstock.com, 2018, no. 100687138).

 

Figure 3

 
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Whole body glucose uptake into brown adipose tissues and muscles during acute cold exposure. During mild cold exposure, glucose uptake is stimulated in brown adipose tissue, but also in several centrally-located skeletal muscles. Brown adipose tissue glucose uptake is ~8-fold higher than that of skeletal muscles, on average, per gram of tissue during mild cold exposure. However, total mass of brown adipose tissue is about 0.2% of that of skeletal muscles. Therefore, brown adipose tissue and skeletal muscle glucose uptake account for ~1 and 50%, respectively, of systemic glucose disposal. The figures presented were calculated from previously published data in young healthy individuals, before cold acclimation (39). BAT, brown adipose tissue; SUV, standard uptake value. Source of muscle illustration: Shutterstock (www.shuterstock.com, 2018, no. 404668558).

Figure 4

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Organ-specific glucose partitioning during acute cold exposure. The figures presented were calculated from a previously published study in young healthy individuals, before cold acclimation (39), based on calculations that we detailed previously (110). BAT, brown adipose tissue; WATsc, sub-cutaneous white adipose tissues; WATv, visceral white adipose tissue.

Figure 5

 
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Brown adipose tissue uptake of energy substrates. Total brown adipose tissue uptake of energy substrates is calculated from published quantitative, dynamic positron emission tomography or microdialysis experiments in humans, multiplied by a typical total brown adipose tissue mass reported in the literature. Data from (73, 108, 113), (108, 113, 114), (115), and (116) were used to calculate glucose, NEFA, dietary fatty acid, and glutamate BAT uptake, respectively. 18FDG, 18-fluorodeoxyglucose; BAT, brown adipose tissue; NEFA, nonesterified fatty acids; PET/CT, positron emission tomography coupled with computed tomography.

Figure 6

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Glucose metabolism in brown adipose tissue. Most of the glucose taken up by brown adipose tissue during cold exposure does not contribute to thermogenesis. Experimental data show that approximately half of the glucose molecules are excreted from brown adipose tissue as lactate. Most of the remaining glucose likely contributes to glycerol production (glyceroneogenesis) and/or fatty acid synthesis (de novolipogenesis) for intracellular triglyceride synthesis. The mitochondrion illustration was obtained free of copyright from Pixabay (www.pixabay.com, 2018).

Figure 7

 
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Intracellular triglyceride (TG) mobilization in brown adipose tissue during cold exposure. Left panel: Brown adipose tissue (BAT), white adipose tissue (WAT) and trapezius muscle change in radio-density during standardized acute cold exposure from previously published studies of our group (39, 73, 108, 109). Right panel: During cold-induced brown adipose tissue metabolic activation, up to 8 g of intracellular triglycerides can be mobilized within 2 h. The metabolic fate of the fatty acids that are mobilized is currently unknown. Although these fatty acids likely constitute most of the energy substrates driving brown adipose tissue thermogenesis, a fraction of them may also be released in circulation to be utilized by other tissues. NEFA, nonesterified fatty acids; UCP1, uncoupling protein 1. The mitochondrion illustration was obtained free of copyright from Pixabay (www.pixabay.com, 2018).

Figure 8

 
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Brown adipose tissue (BAT) oxidative metabolism and contribution to total body energy expenditure. Brown adipose tissue oxygen consumptions are from U Din et al. (143) and brown adipose tissue-containing adipose tissue (AT) mass range is from Leitner et al. (61). Calculations were made assuming energy expenditure of 4.801 kcal per liter of oxygen consumed (201) and an adipose tissue density of 0.925 g.ml−1 (202). AT, adipose tissue.

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3 hours ago, Sibiriak said:

.... It's a pretty dense article--I'm hoping Mccoy can predigest it for me.

I'm feeling pretty queasy in the stomach now, LOL

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J Therm Biol. 2018 Oct;77:137-144. doi: 10.1016/j.jtherbio.2018.08.016. Epub 2018 Aug 23.

Sex difference in cold perception and shivering onset upon gradual cold exposure.

Abstract

To maintain a thermal balance when experiencing cold, humans reduce heat loss and enhance heat production. A potent and rapid mechanism for heat generation is shivering. Research has shown that women prefer a warmer environment and feel less comfortable than men in the same thermal condition. Using the Blanketrol® III, a temperature management device commonly used to study brown adipose tissue activity, we tested whether the experimental temperature (TE) at which men and women start to shiver differs. Twenty male and 23 female volunteers underwent a cooling protocol, starting at 24 °C and gradually decreasing by 1-2 °C every 5 min until an electromyogram detected the shivering or the temperature reached 9 °C. Women started shivering at a higher TE than men (11.3 ± 1.8 °C for women vs 9.6 ± 1.8 °C for men, P = 0.003). In addition, women felt cool, scored by a visual analogue scale, at a higher TE than men (18.3 ± 3.0 °C for women vs 14.6 ± 2.6 °C for men, P < 0.001). This study demonstrates a sex difference in response to cold exposure: women require shivering as a source of heat production earlier than men. This difference could be important and sex should be considered when using cooling protocols in physiological studies.

KEYWORDS:

Cold temperature; Sex characteristics; Shivering; Skin temperature; Thermogenesis; Thermosensing

PMID:
 
30196892
 
DOI:
 
10.1016/j.jtherbio.2018.08.016
 
____________________________________________________________
FYI: I noticed there are quite a few used Blanketrol machines on eBay (sort by distance) some are quite cheap.  It would be fun to have one of those!

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An interesting look at cold induced cognitive impairment (and how to prevent it).  Unclear what type of cinnamon was used, but they also used green tea extract which performed better than either pepper or cinnamon when it comes to markers of BAT activation:

 

Int J Hyperthermia. 2018 Sep 13:1-10. doi: 10.1080/02656736.2018.1511835. [Epub ahead of print]

Pepper and cinnamon improve cold induced cognitive impairment via increasing non-shivering thermogenesis; a study.

Study Link

 

Abstract

Despite an understanding that a major effect of cold exposure is a fall in core body temperature which is responsible for the observed decrements in the performance, it is surprising that thermogenic supplements are seldom evaluated to verify if they can aid in improving the performance during cold exposure. Following evidence from our previous study indicating the ability of pepper and cinnamon to improve coldendurance, we investigated further here if the improved endurance had advantages in real time where they could positively affect cognitive performance (assessed by Novel object test) when exposed to cold in albino wistar rats. In order to delineate if the observed improvement if any, was due to their cognitive enhancing ability or thermogenic potential, distinctive room temperature (RT) and cold temperature (CT) groups were used. Cold exposure impaired cognitive performance which improved following treatment with both the spices. We noted an increased rate of cold adaptive thermogenesis in CT treated group as evidenced by an elevated norepinephrine, free fatty acid levels in blood, increased expression of UCP1 in brown adipose tissue, the net effect being a decreased fall in the core body temperature. Absence of any notable effect in these parameters in the RT treated group ascertained that at least in the current experimental set up the observed improvement in performance in CT treated group is due to the thermogenic potential of the spices alone. In conclusion, our results demonstrate that the cognitive impairment caused by exposure to cold can be effectively countered by agents with thermogenic potential.

KEYWORDS:

Spices; cold stress; learning and memory; non-shivering thermogenesis; novel object test

PMID:
 
30208750
 
DOI:
 
10.1080/02656736.2018.1511835
 
 

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This wasn't the focus of the study, but these researchers discovered a synergy in mice between calorie restriction and BAT stimulation for beneficial health outcomes.  I guess this is not surprising since we know BAT activation is hampered by obesity.

Lab Invest. 2018 Sep 26. doi: 10.1038/s41374-018-0120-x. [Epub ahead of print]

Activation of brown adipose tissue enhances the efficacy of caloric restriction for treatment of nonalcoholic steatohepatitis.

Abstract

Nonalcoholic steatohepatitis (NASH) is the form of nonalcoholic fatty liver disease that can evolve into cirrhosis. Lifestyle modifications achieving 10% weight loss reverse NASH, but there are no effective approved drug treatments. We previously identified defective adaptive thermogenesis as a factor contributing to metabolic syndrome and hepatic steatosis. We have now tested whether increasing nonshivering thermogenesis can improve preexisting NASH in mice. In high-fat diet-fed foz/foz mice with established NASH, treatment with β3AR agonist restored brown adipose tissue (BAT) function, decreased body weight, improved glucose tolerance, and reduced hepatic lipid content compared to untreated counterparts, but had no impact on liver inflammation or on nonalcoholic fatty liver disease activity score (NAS). Similarly, β3AR agonist did not alter liver pathology in other steatohepatitis models, including MCD diet-fed diabetic obese db/db mice. Caloric restriction alone alleviated the hepatic inflammatory signature in foz/foz mice. Addition of a β3AR agonist to mice subjected to caloric restriction enhanced weight loss and glucose tolerance, and improved liver steatosis, hepatocellular injury, and further reduced liver inflammation. These changes contributed to a significantly lower NAS score such as no (0/9) animals in this group fulfilled the criteria for NASH pathology compared to eight out of ten mice under caloric restriction alone. In conclusion, β3AR agonist counteracts features of the metabolic syndrome and alleviates steatosis, but does not reverse NASH. However, when coupled with weight loss therapy, BAT stimulation provides additional therapeutic advantages and reverses NASH.

PMID:
 
30258096
 
DOI:
 
10.1038/s41374-018-0120-x
Edited by Gordo

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https://www.cell.com/cell/fulltext/S0092-8674(18)31500-9?fbclid=IwAR1xelMsqAYbATAbpdvgS1IwqtRGMSmdHrFvZmWF-d8b9nOJZO8vs3AEZmk

Secretin: An Old Hormone with a Burning Secret

Most theories of meal-induced thermogenesis involve a gut-brain-brown adipose tissue axis driving sympathetic nervous system-mediated thermogenesis. Li et al. demonstrate that secretin released by the gut after a meal binds to abundant receptors in brown adipose tissue to stimulate thermogenesis, inhibiting food intake and thereby suggesting a novel role for secretin regulating satiety.

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Medical News Today has the results of the effect of cold on different strains of Rotifers.  The most striking finding was that low temperature was not always positive."

"The change in the median lifespan of each strain ranged from a decrease of 6 percent to an increase of 100 percent.

The team also observed "differences in maximum and relative lifespan extension and in mortality rate."

It also saw that in most strains, low temperature extended the "reproductive period and shortened the post-reproductive period, suggesting an extension of healthspan in most strains."

It ends with the following
"This means we really need to pay more attention to genetic variability in thinking about responses to aging therapies. That is going to be really important when we try to move some of these therapies into humans."

 

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My spontaneous reaction to the rotifers study is that those animals are not exactly similar to humans. But then, Valter Longo became world famous by publishng papers on yeast...

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I'm wondering about glucose homeostasis and cold exposure. I read the summary of the article on rats, glucose tolerance seems to improve after 14 weeks of exposure but I don't know if that's applicable directly to humans and the difference in figures.

Also, I wonder if there is a short term effect after an acute exposure, I never tried to measure blood glucose before and after a cold shower.

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I was just too curious about CE and glucose homeostasis so I had to do proceed with the experiment.

Instrumentation: Accucheck portable set. following units in mg/dL

Just After waking, I put myself under the cold shower for 7 minutes, that's what I usually do, full jet, full cold.

Blood glucose before the shower: 92; 98 (two measurements)

Blood glucose5 minutes after the shower: 88; 97 (two measurements).

The variability in the data is pretty high, so the experiment has not been conclusive. The intervals may suggests a slight drop in blood glucose after an acute exposure, but of course it has to be repeated.

Also my fasting BG was pretty high, that happens sometimes, maybe due to low fasting insuline.

One single measurement I made the day of Christmas, after a lunch with starches and cakes, resulted in an unexpectedly low peak of 110 mg/dL.

From the above and previous measurements it would seem that I tend to have good tolerance to glucose and tend to be sensitive to insuline, although fasting glucose is sometimes above the median of the general population. something to check regularly.

 

 

Edited by mccoy

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image.png.782943e3a5a2c1242ffea993183d54f1.png 

 

10 MARCH

CRYOPHILE CLUB

7/1 Otdykha Island

Beginning: 14:00. Free admission

The Krasnoyarsk Cryophile Club invites anyone who feels like it to take part in the Winter Bather Day. The city on the banks of the Yenisei offers unique opportunities for an extreme conditioning activity — ice swimming. The river that never freezes over within the bounds of the city allows for swimming in the icy cold water all year round. During the Winter Universiade Krasnoyarsk 2019, the water temperature is expected to be 0.2 ͦ С to +4 ͦ С, which is a stark contrast to that in the club’s saunas and banyas that are normally heated up to 120 ͦ С. If you want to feel the heat of the cold water and hospitality of Siberian people, take along a bathing suit, water shoes and a towel, and you are welcome!

 

 

image.png.0952f2714f5e13ef7e3e39a2cda971f0.png

Edited by Sibiriak

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On 3/4/2019 at 12:18 AM, Sibiriak said:

 the club’s saunas and banyas that are normally heated up to 120 ͦ С. If you want to feel the heat of the cold water and hospitality of Siberian people, take along a bathing suit, water shoes and a towel, and you are welcome!

120C = 248F, wow that's hot, wouldn't that kill people?

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On 3/4/2019 at 6:18 AM, Sibiriak said:

image.png.782943e3a5a2c1242ffea993183d54f1.png 

 

1If you want to feel the heat of the cold water and hospitality of Siberian people, take along a bathing suit, water shoes and a towel, and you are welcome!

 

 

image.png.0952f2714f5e13ef7e3e39a2cda971f0.png

The gracious hospitality of Siberian people in this case would probably kill most non -Siberians !

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16 hours ago, mccoy said:

Lots of people at the event !!

Looks like a lot of fun, Wim is really growing the guru retreat thing, haha.  

Quote

 

Professor Peter Pickkers, of Radboud University Medical Centre in the Netherlands, who conducted the E coli tests, told me: “We found that [his method] results in major changes in oxygen and CO2 levels and an increase in adrenaline to really high levels – higher than observed in people who bungee-jump for the first time.

“Higher adrenaline results in the production of the anti-inflammatory cytokine IL-10 and this inhibits the inflammatory response. We were really surprised that we found these results. The fact that you can influence your immune response willingly with these techniques is of interest, especially for patients with autoimmune diseases.”

 

 

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Over on the thread about olive leaves, Kenton wrote:

Quote

Are you still wearing the ice vest? I went through that and then, even better, cold-water surfing, and currently am (1) sleeping in 60F air unclothed with a sheet and a thin yarn blanket and (2) upon waking each day spending the first 30-60 min of putzing around (e.g., doing daily chores, fixing food, etc) still unclothed. Feel free to reply in the CRS CE thread.

Hi Kenton, nice to hear from you!

I too have stopped wearing my cold vest and switched to more naturalistic cold exposure opportunities, including: sleeping in a cold room, exercising and walking the dog in the cold with little clothing, and a daily cold shower.

Dean 

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On 3/6/2019 at 4:04 AM, mccoy said:

The gracious hospitality of Siberian people in this case would probably kill most non -Siberians !

Haha, it actually seems to kill the Siberians, too.

Siberia has an average life expectancy of close to a full decade shorter than the rest of Russia. And Russia already has the shortest life expectancy in Europe.

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19 hours ago, Ron Put said:

Haha, it actually seems to kill the Siberians, too.

Siberia has an average life expectancy of close to a full decade shorter than the rest of Russia.

I'm surprised you are attributing decreased life expectancy to the cold.  I expected you to blame their diet although there are other possibilities that may dwarf cold, the lack of fresh veggies and the abundance of alcohol.  The variation in summer/winter day length surely takes its toll as it does in other cities of the extreme north.  And the largest cities of Siberia such as Novosibirsk, Omsk and Chelyabinsk have a lot of heavy industry and many smaller cities are based on resource extraction such as metals mining in Norilsk and oil in Nizhnevartovsk.  Hard to guess the impact of environmental degradation but it surely is relevant since most of the population lives in cities versus a small minority living in pristine wilderness.

 

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My post was actually in jest :)

On a more serious note, while I understand the underlying theories, I am not convinced that intermittent cold exposure does anything of great significance to slow down aging in humans. IMO, there is certainly much less evidence for it than for the impact of CR, fasting, low protein or plant-based diets.

I did a cursory search and found this interesting, if not exactly rigorous overview: https://joshmitteldorf.scienceblog.com/2013/02/25/cold-temperature-and-life-span-its-not-about-the-rate-of-living/

Note the disparity in income (and presumably access to advanced healthcare) and the average lifespan.

Mediterranean, average

29,360

82.8

Scandinavia, average:

65,934

82.2

One curious item: "... the same gene, TRPA-1 that is activated by cold in worms and mammals can also be triggered by eating Japanese horseradish (wasabi)" A much more pleasant way to activate it, IMO. I'll try it at dinner tonight. :)

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Ron,

Quote

On a more serious note, while I understand the underlying theories, I am not convinced that intermittent cold exposure does anything of great significance to slow down aging inhumans. IMO, there is certainly much less evidence for it than for the impact of CR, fasting, low protein or plant-based diets.

If you read the 500+ pages of this thread carefully 🙂 (or this post for a very, long yet still only partial summary), you'll learn that the (or my) major argument is that the lifespan benefits of CR only manifest when coupled with cold exposure. Some of the most important evidence is that virtually all of the successful CR experiments (in rodents) have also been accompanied by housing temperatures well below the rodents' thermoneutral temperature and when this wasn't the case (i.e. CR + thermoneutral or warm housing), the benefits of CR were either completely erased or greatly attenuated.

A secondary, related argument is that a net calorie deficit (rather than a low calorie intake per se) is sufficient to trigger the CR effect, especially if the calorie deficit is created by burning calories via brown/beige fat thermogenesis.

At the very least, the evidence is incontrovertible that CE improves glucose regulation in rodents and humans (here is just one of many posts discussing the evidence), which has been an issue observed in several of the most serious human CR practioners (including me) in the past, and that is generally a good thing for healthspan and disease avoidance, and likely (average) lifespan. 

1 hour ago, Ron Put said:

One curious item: "... the same gene, TRPA-1 that is activated by cold in worms and mammals can also be triggered by eating Japanese horseradish (wasabi)" A much more pleasant way to activate it, IMO. I'll try it at dinner tonight. :)

There are many discussions embedded in this thread discussing alternatives methods of triggering thermogenesis and boosting brown/beige adipose tissue, including spicy foods like wasabi. Here is the most up-to-date list (from this post) :

Quote

Here is the latest full list of modifiable and [nonmodifiable] factors associated with increased brown/beige adipose tissue and/or thermogenesis, with the factors mentioned in this post highlighted in red:

  • Cold exposure - by far the best BAT inducer/activator
  • Spicy / pungent foods, herbs & supplements - capsaicin / chilli peppers, curcumin / turmeric root, menthol/mint/camphor, oregano, cloves, mustard, horseradish/wasabi, garlic, onions
  • Sulforaphane-rich foods - Broccoli, brussels sprouts, cabbage
  • Nitrate-rich foods - beets, celery, arugula, and spinach
  • Arginine-rich foods - Good vegan sources include seeds (esp. sesame, sunflower & pumpkin), nuts (esp. almonds and walnuts) and legumes (esp. soy, lupin & fava beans and peas)
  • Citrulline-rich foods - Highest by far in watermelon, but also some in onions, garlic, onions, cucumber, other melons & gourds, walnuts, peanuts, almonds, cocoa, chickpeas
  • Luteolin-rich foods - Herbs (thyme, parsley, oregano, peppermint, rosemary), hot peppers, citrus fruit, celery, beets, spinach, cruciferous veggies, olive oil, carrots. 
  • Rutin-rich foods - Buckwheat, apple peels, citrus fruit, mulberries, aronia berries, cranberries, peaches, rooibos tea, amaranth leaves, figs
  • Healthy Fats - DHA / EPA / fish-oil, MUFA-rich diet,  Extra Virgin Olive Oil
  • Fiber - Especially cereal fiber (wheat and oat fiber)
  • Olive Polyphenols - Extra Virgin Olive Oil / Olive Leaf Extract / Olive Leaf Tea
  • Other foods - Apples / apple peels / ursolic acid; Citrus fruit / citrus peels / limonene; Honey / chrysin
  • Beverages - green tea, roasted coffee, red wine, cacao beans / chocolate
  • Low gluten diet
  • Methionine restriction - Reduce animal protein. Soy is low in methionine and high in arginine, but also high in leucine.
  • Leucine restriction - Reduce animals protein. Leucine is highest in beef, fish, eggs, cheese and soy.
  • Low protein diet
  • Drugs / Supplements - metformin, berberine, caffeine, creatine, nicotinamide riboside (NAD), resveratrol, melatonin
  • Medicinal Herbs - ginseng, cannabidiol / hemp oil / medicinal marijuana, balloon flower root (Platycodon Grandiflorus)
  • Time Restricted Feeding - most calories at breakfast
  • Exercise & elevated lactate / lactic acid
  • Acupuncture - locations Zusanli (foot - ST36) and Neiting (lower leg - ST44) 
  • Whole body vibration therapy
  • Avoid obesity/overweight
  • Low testosterone / castration in mice (and men?)
  • [being naturally thin - high metabolic rate]
  • [being younger]
  • [being female]
  • [Ethnicity - having cold-climate ancestors]
  • [being of genotype TT for rs1800592, TT for FTO SNP rs1421085 and AA for rs4994 as reported by 23andMe]

 

It is hard to miss the fact that almost all of the interventions that boost thermogenesis/BAT listed above are considered healthy / beneficial in their own right.  My argument is that at least some of their ability to promote health stems from increased thermogenesis/BAT.

--Dean

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Dean, thanks for the great summary. I don't disagree with the lab research and the result indicating benefits such as increases brown fat levels.

I just don't see the trend in any population study I am aware of, as higher concentrations of centenarians are generally found in temperate or warm climates. You can find significant dietary trends affecting longevity, for example, but the relationship between cold exposure and longevity is, if anything, reversed. Yet it is an easy argument that in places with long, severe winters, the average resident is exposed, over a lifetime, to lower temperatures for longer periods than someplace like Costa Rica or Sardinia. If cold exposure had a significant beneficial effect, it would likely manifest in large population studies, methinks.

And here is something to ponder, too:

"In this large population-based cohort in Ontario, we found that short-term exposure to cold temperatures significantly increased the daily rates of hospitalisations for CHD, AMI and stroke. High temperatures were associated to a lesser degree with the hospitalisations for these conditions. ...

There are several biological mechanisms through which exposure to ambient temperatures can affect the cardiovascular system. Cold exposure are known to increase in blood pressure, heart rate, plasma fibrinogen, platelet viscosity and peripheral vasoconstriction.25 Cold may also increase cardiac load through raised inflammatory markers and coagulation parameters.26 Additionally, cold temperatures may trigger higher haemoglobin A1c levels in people with type 2 diabetes, which is a major risk factor for cardiovascular disease.27 Similarly, exposure to heat can elevate heart rate, blood pressure, blood viscosity and coagulability, weaken core temperature regulation and heighten the risk of coronary events and stroke.28https://heart.bmj.com/content/104/8/673#DC1

 

As to "a net calorie deficit (rather than a low calorie intake per se) is sufficient to trigger the CR effect," I agree. I posted a study on the subject elsewhere, which found similar of better markers in a group which increased energy expenditure by 12.5% while reducing calories by 12.5%, compared to a group which reduced calories by 25%, without increased energy expenditure.

Edited by Ron Put

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Ron, 

8 minutes ago, Ron Put said:

I just don't see the trend in any population study I am aware of, as higher concentrations of centenarians are generally found in temperate or warm climates

Read this post for a response to your skepticism.

Regarding the potential negative effects of acute cold exposure, the benefits of CE require acclimatization, and shouldn't be undertaken by the anyone at risk of cardiovascular events. Similar to strenuous exercise. 

Dean 

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Ron, 

P. S. The "27" referenced study (from 2005) mentioned in your quote on cold exposure and A1c levels is very out of date and counter to more recent large scale epidemiology evidence showing A1c levels improve during cold winter months. See this post.

 Dean

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