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Dean Pomerleau

Cold Exposure & Other Mild Stressors for Increased Health & Longevity

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21 hours 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. 🙂

The definition of 'pleasant' may be pretty subjective. Most of people here, me included, find it pretty pleasant to feel the cold and the adaptive response of the body to it.

Some people just won't tolerate it, but often it appears to be more of a mental issue or rejection.

Also as Dean says it's very advisable to approach CE with caution, starting with mildly cold or cool temperatures and short exposures. It's good to start from the fall, getting accustomed to the progressive decrease in air and water temperatures. And really cold water causes a sudden release of norepinephrine with the consequent spike in blood pressure. Exposure should not be sudden: first a foot, then the leg, then spraying the torso and so on...

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19 hours ago, Dean Pomerleau said:

Ron, 

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 

Thanks. I am still not convinced that exposure to cold has a significant long-term benefit in humans. For every other major factor, such exercise, diet, caloric restriction, we can find statistically significant trends in population studies.

For cold exposure, the trends are generally negatively associated with longevity. Here is another, larger study:

"Cold weather kills 20 times as many people as hot weather, according to an international study analyzing over 74 million deaths in 384 locations across 13 countries. ...

Around 7.71% of all deaths were caused by non-optimal temperatures, with substantial differences between countries, ranging from around 3% in Thailand, Brazil, and Sweden to about 11% in China, Italy, and Japan. Cold was responsible for the majority of these deaths (7.29% of all deaths), while just 0.42% of all deaths were attributable to heat." 
https://www.sciencedaily.com/releases/2015/05/150520193831.htm

I understand that such population studies have their shortcomings. But I will repeat that one would expect that if long-term cold exposure was of significant benefit to human longevity, we would see a higher proportion of extraordinary longevity in populations subjected to such exposure, yet, we see the opposite (regardless of income and healthcare access):

rXu5hZhl2n82cerd1bCoYlCw1RrM5jQ0-tPKtnidk3A.png.37af60bc0a1c22dc19d074c0ffd3efcd.png

 

Edited by Ron Put

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1 hour ago, Ron Put said:

For cold exposure, the trends are generally negatively associated with longevity. Here is another, larger study:

"Cold weather kills 20 times as many people as hot weather,

Dean pointed out that CE is a hormetic stressor similar to exercise.  To be beneficial the dose must be within ones tolerance.  If ones tolerance is poor as is common with advanced age and especially sickness then CE is a potentially fatal stressor.  Being able to control exposure is key.

 

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Ron,

By your same argument, one might expect to see extended longevity in countries with frequent food shortages, like South Sudan or Yemen, since many of its citizens be naturally subject to calorie restriction. Or we should expect to see extended longevity as a result of a high proportion of vegetarians in countries like India, as Todd Allen speciously tried to argue on another thread.

There are just too many confounders in human populations. Here is an interesting one. There is some evidence (e.g. [1]), that the circadian rhythm disruption resulting from living at higher latitudes or at certain positions within a (longitudinal) time zone is associated with cancer and all-cause mortality. If true, this could quite conceivably mask any benefits of extra (potential) cold exposure associated with living at a higher latitude.

Conversely, in the US, people living at more northern latitudes do live longer than southerners. Should I crow about this as evidence in favor of cold exposure? Clearly not. There are many more important causes of the north/south discrepancy in US longevity that any benefits of CE would be swamped in the data. This shows the silliness of looking to human population-level epidemiological data for evidence of longevity benefits of specific interventions like cold exposure. 

Moreover, the typical oldster who reaches 100 does so as a result of freakishly good genes (and possibly good healthcare), not because of their meticulous lifestyle choices, since so few people make the kind of comprehensive and sometimes challenging lifestyle choices we do and sticks with them for decades. So expecting to see statistical evidence to support longevity benefits of CE (or CR) in the tiny fraction of people who are lucky enough to make it to 100 is like looking for a needle in a haystack.

Plus, cold outdoor temperatures have very little correlation with the temperature people are exposed to for any length of time during the day, particularly well-educated people in affluent first world countries living at northern latitudes (with indoor heat and AC) who are likely to be the only ones with any chance of making the prerequisite good lifestyle choices and have access to good medical care to avoid the typical diseases of affluence that cut lifespan short before any benefits of CE (or CR) become manifest.

Furthermore, I said I don't expect CE alone to extend (maximum) lifespan, or help someone reach 100. I said that pretty strong evidence suggests that CR is effective in rodents only when coupled with CE.  As a corollary, it stands to reason that if serious CR can significantly extend human lifespan (which I seriously doubt BTW), it likely needs to be coupled with CE. It seems virtually certain that there no significant population anywhere in the world that practices significant CR with good nutrition and cold exposure, not to mention having access to good medical care, and engaging in exercise to maintain CV health, etc to test this hypothesis.

In summary, expecting to see support of the longevity benefits of CE (or CR, or CR+CE) in country-wide or "Blue Zone" epidemiological data is a fool's errand. At best you might hope to see support for benefits of the "low hanging fruit" when it comes to diet and lifestyle choices ( e.g. exercise, healthy diet - mostly plant-based, healthy weight, don't smoke, etc.), since those are the only interventions likely to be practiced by enough of the population to show up in the data.

Even then I wouldn't trust epidemiological evidence except as a hint to look for more direct evidence, due to presence of so much heterogeneity and confounders when studying large human populations. The only possible exception might be relatively homogeneous sub-populations which can serve as their own control group due to internal variability - like Californian Adventists, some of whom are vegetarian and others who aren't but who otherwise have relatively similar social, economic, and lifestyle characteristics.

--Dean

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

[1] Chronobiol Int. 2011 Mar;28(2):155-62. doi: 10.3109/07420528.2010.541312.

Latitude of residence and position in time zone are predictors of cancer incidence, cancer mortality, and life expectancy at birth.

Borisenkov MF(1). Author information: (1)Institute of Physiology, Komi Science Centre, Ural Branch of Russian Academy of Science, Syktyvkar, Russia. borisenkov@physiol.komisc.ru

Comment in Chronobiol Int. 2011 May;28(5):471-3; author reply p 473.

According to the hypothesis of circadian disruption, external factors that disturb the function of the circadian system can raise the risk of malignant neoplasm and reduce life span. Recent work has shown that the functionality of the circadian system is dependent not only on latitude of residence but also on the region's position in the time zone. The purpose of the present research was to examine the influence of latitude and time zone on cancer incidence, cancer mortality, and life expectancy at birth. A stepwise multiple regression analysis was carried out on residents of 59 regions of the European part of the Russian Federation (EPRF) using age-standardized parameters (per 100,000) of cancer incidence (CI), cancer mortality (CM), and life expectancy at birth (LE, yrs) as dependent variables. The geographical coordinates (latitude and position in the time zone) of the regions were used as independent variables, controlling for the level of economic development in the regions. The same analysis was carried out for LE in 31 regions in China. Latitude was the strongest predictor of LE in the EPRF population; it explained 48% and 45% of the variability in LE of women and men, respectively. Position within the time zone accounted for an additional 4% and 3% variability of LE in women and men, respectively. The highest values for LE were observed in the southeast of the EPRF. In China, latitude was not a predictor of LE, whereas position in the time zone explained 15% and 18% of the LE variability in women and men, respectively. The highest values of LE were observed in the eastern regions of China. Both latitude and position within the time zone were predictors for CI and CM of the EPRF population. Latitude was the best predictor of stomach CI and CM; this predictor explained 46% and 50% of the variability, respectively. Position within the time zone was the best predictor of female breast CM; it explained 15% of the variability. In most cases, CI and CM increased with increasing latitude of residence, from the eastern to the western border of the time zone, and with increasing level of economic development within the region. The dependence of CI, CM, and LE on the geographical coordinates of residence is in agreement with the hypothesis of circadian disruption. DOI: 10.3109/07420528.2010.541312 PMID: 21231877

 

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On 6/7/2019 at 3:44 PM, Dean Pomerleau said:

Ron,

By your same argument, one might expect to see extended longevity in countries with frequent food shortages, like South Sudan or Yemen, since many of its citizens be naturally subject to calorie restriction. Or we should expect to see extended longevity as a result of a high proportion of vegetarians in countries like India, as Todd Allen speciously tried to argue on another thread.

... There are just too many confounders in human populations. Here is an interesting one. There is some evidence (e.g. [1]), that the circadian rhythm disruption resulting from living at higher latitudes or at certain positions within a (longitudinal) time zone is associated with cancer and all-cause mortality. If true, this could quite conceivably mask any benefits of extra (potential) cold exposure associated with living at a higher latitude.

Conversely, in the US, people living at more northern latitudes do live longer than southerners. Should I crow about this as evidence in favor of cold exposure? ...

Even then I wouldn't trust epidemiological evidence except as a hint to look for more direct evidence, due to presence of so much heterogeneity and confounders when studying large human populations. The only possible exception might be relatively homogeneous sub-populations which can serve as their own control group due to internal variability - like Californian Adventists, some of whom are vegetarian and others who aren't but who otherwise have relatively similar social, economic, and lifestyle characteristics.

...

Actually, there are a number of appropriate population studies which correlate both calorie/protein restriction and plant diets, with lower mortality/longevity. In addition to Okinawa and Sardinia, there are also other examples of populations which experienced significant caloric restriction, without malnutrition:

"During World War 1 in 1917, Danish men and women were forced to reduce food consumption for 2 years, but with a well-planned and adequate consumption of whole grain cereals, vegetables, and milk. The result of this undesired experiment was an impressive 34% reduction in death rates (Hindhede, 1920). Similarly, in Norway during World War 2, the citizens of Oslo underwent a forced 20% CR without malnutrition (i.e. Norwegians were provided with adequate intake of fresh vegetables, potatoes, fish and whole cereals) for approximately 4 years (1941-45). In this forced experiment, mortality dropped by 30% compared to the pre-war level in both men and women (Strom and Jensen, 1951)". https://www.draisistoledo.com/wp-content/uploads/Calorie-restriction-in-humans-An-update.pdf

I am not aware of any similar population results showing correlation with cold exposure.

As to some of the examples above, we must differentiate between caloric restriction and malnutrition. Just as we must take into account regional lifestyle, education, diet and access to healthcare (all of these are generally worse in the southern US).

Anyway, while I am aware of the lab results, I still remain skeptical of long term benefits in humans.

If someone enjoys cold showers and ice dunks, that's a different matter, of course. :)

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11 hours ago, Ron Put said:

... there are also other examples of populations which experienced significant caloric restriction, without malnutrition:

"During World War 1 in 1917, Danish men and women were forced to reduce food consumption for 2 years, but with a well-planned and adequate consumption of whole grain cereals, vegetables, and milk. The result of this undesired experiment was an impressive 34% reduction in death rates (Hindhede, 1920). Similarly, in Norway during World War 2, the citizens of Oslo underwent a forced 20% CR without malnutrition (i.e. Norwegians were provided with adequate intake of fresh vegetables, potatoes, fish and whole cereals) for approximately 4 years (1941-45). In this forced experiment, mortality dropped by 30% compared to the pre-war level in both men and women (Strom and Jensen, 1951)."

Ron, 

It's interesting that the two examples you give of populations that benefited from forced CR during wartime (Denmark and Norway) are two of the northernmost countries in Europe. In fact, the city of Oslo which you cite as evidence for the benefits of CR is one of the top 10 coldest cities in Europe, with a year round average high temperature of 49F (10C) and low of 36F (2C).

So I take it back. It appears there is epidemiology evidence that human longevity benefits may result from the combination of CR and CE. I still don't think such evidence is worth very much, but thanks for pointing it out. 

Dean 

 

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Quote

Ron Put: 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

 

Btw,  I'm from California but live in Siberia now which has long, severe winters,  and I can assure you,  the average Siberian is exposed to warmer average temperatures than an average Californian. 

Edited by Sibiriak

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4 hours ago, Dean Pomerleau said:

... So I take it back. It appears there is epidemiology evidence that human longevity benefits may result from the combination of CR and CE. I still don't think such evidence is worth very much, but thanks for pointing it out. 

Dean 

 

Haha. Of course, these studies compare the same population in restricted calories state and in free feeding state. And restricting calories appears to be beneficial in terms of lower mortality rates.

However, the longevity of the Scandinavians is still lower than that of the Mediterraneans, as per my post above. Cold exposure, higher incomes and better access to more advanced healthcare up North notwithstanding.

Edited by Ron Put

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Cold Exposure and Glucose Revisited

A couple posts ago on this thread I said that the evidence in favor of cold exposure for glucose control, and therefore avoidance of type 2 diabetes was "incontrovertible." Here are a couple recent papers supporting this conclusion.

The first [1] represented the kind of epidemiology evidence that Ron might appreciate :-).

It looked at ~5000 Spanish adults, correlating their rate of pre-diabetes, diabetes and insulin resistance (measured by an oral glucose tolerance test) with the mean annual temperature of their hometown. There was a pretty dramatic direct correlation, even after accounting for a host of potential confounders, including "multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation." They found that rate of diabetes was 39% lower in people who lived in the coldest part of Spain compared with the warmest. The authors concluded there result are:

Quote

...consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

The second study [2], was interventional. The authors exposed 15 healthy men to both thermoneutral conditions (72F, 22C) and cold exposure (64F, 18C) via a whole body suit. They found that cold exposure improved glucose uptake and insulin sensitivity by 20% without increasing insulin secretion from the pancreas. They conclude:

Quote

These data support the concept that human BAT metabolism significantly contributes to whole body glucose and lipid utilization in a coordinated manner.

Avoiding diabetes is important in its own right, given how prevelant it has become in western society. But improved glucose metabolism also may explain why it appears important to combine CR with CE to achieve longevity benefits. One of the most important ways CR seems to boost lifespan (in rodents, where it has been demonstrated) is by downregulating insulin and the pro-aging insulin signaling pathway, thereby shifting the organism into a metabolic mode which emphasizes maintenence and repair rather than growth and reproduction. 

But without much insulin around, glucose has a tendency to get stuck in the bloodstream unable to enter cells, an effect some of us have experienced first hand. Elevated circulating glucose has negative long-term health and longevity consequences as illustrated by the ravages of diabetes. 

Adding cold exposure on top of CR may overcome this potential Achille's heal of CR alone by boosting metabolically-active brown/beige adipose tissue (BAT) to serve as a sink for circulating glucose.

--Dean 

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[1] Eur J Endocrinol. 2019 May 1;180(5):273-280. doi: 10.1530/EJE-18-0818.

Ambient temperature and prevalence of diabetes and insulin resistance in the Spanish population: Di@bet.es study.

Valdés S(1)(2), Doulatram-Gamgaram V(1), Lago A(1)(2), García Torres F(3), Badía-Guillén R(1), Olveira G(1)(2), Goday A(4), Calle-Pascual A(2)(5), Castaño L(2)(6)(7), Castell C(8), Delgado E(9), Menendez E(9), Franch-Nadal J(2)(10), Gaztambide S(2)(11)(7), Girbés J(12), Gomis R(2)(13), Ortega E(13)(14), Galán-García JL(15), Aguilera-Venegas G(15), Soriguer F(1)(2), Rojo-Martínez G(1)(2). 

Objective: The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population (Di@bet.es study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (β: 0.087, P < 0.001), 2 h plasma glucose (β: 0.049, P = 0.008) and HOMA-IR (β: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose.

Conclusions: Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

DOI: 10.1530/EJE-18-0818

PMID: 30840583

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

[2] J Clin Endocrinol Metab. 2017 Nov 1;102(11):4226-4234. doi: 10.1210/jc.2017-01250.

Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men.

Iwen KA(1), Backhaus J(1), Cassens M(1), Waltl M(1), Hedesan OC(2), Merkel M(3), Heeren J(4), Sina C(5), Rademacher L(1), Windjäger A(1), Haug AR(6), Kiefer FW(2), Lehnert H(1)(7), Schmid SM(1)(7).

Context: Mounting evidence suggests beneficial effects of brown adipose tissue (BAT) activation on glucose and lipid metabolism in humans. It is unclear whether cold-induced BAT activation affects not only insulin sensitivity but also insulin secretion. Likewise, the role in clearing circulating fatty acids (FAs) has not been fully explored. Objective: Exploring the effects of cold-induced BAT activation on insulin sensitivity and secretion, as well as on plasma FA profiles. Design: Fifteen healthy men participated in a cross-balanced repeated within-subject study with two experimental conditions. Subjects were exposed to thermoneutrality (22°C) and to moderate cold (18.06°C, shivering excluded) by use of a water-perfused whole body suit. Cold-induced BAT activation was quantified by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography in a subset of volunteers. A Botnia clamp procedure was applied to determine pancreatic first phase insulin response (FPIR) and insulin sensitivity. Hormones and metabolites, including 26 specific plasma FAs, were sampled throughout the experiment. Results: Cold exposure induced BAT activity. Plasma noradrenaline and dopamine concentrations increased in response to cold. Peripheral glucose uptake and insulin sensitivity significantly improved by ∼20%, whereas FPIR remained stable. Lignoceric acid (C24:0) concentrations increased, whereas levels of eicosanoic acid (C20:1n9), nervonic acid (C24:1n9), and behenic acid (C22:0) decreased. Conclusions: Cold-exposure induces sympathetic nervous system activity and BAT metabolism in humans, resulting in improved glucose metabolism without affecting pancreatic insulin secretion. In addition, BAT activation is associated with altered circulating concentrations of distinct FAs. These data support the concept that human BAT metabolism significantly contributes to whole body glucose and lipid utilization in a coordinated manner. Copyright © 2017 Endocrine Society

DOI: 10.1210/jc.2017-01250

PMID: 28945846

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Personally I think the evidence for CE is more compelling than the evidence for serious CR.  As Dean pointed out, "To summarize, in species that span a wide range of latitudes, the within-species longevity is pretty strongly correlated with how far north (or south in the southern hemisphere) an individual lives. That is, cooler environments → increased lifespan across a huge range of land, freshwater and marine species."   Humans on the other hand, live in climate controlled environments, so no matter where they live, they rarely get any cold exposure.  And yet we can, and have, observed positive physiological changes in humans as a result of cold exposure.  I summarized a lot of the findings here.

As for Okinawans - for MEN, the longevity increase was less than one year compared to mainland Japanese men, oh, and also less favorable compared to the CA adventists who don't do CR (but do for the most part eat a plant based whole food diet and some fish).  The lack of junk food, strong community, and lower stress living probably mean a lot more for longevity than restricting calories.

Speaking of men and longevity, it is interesting to note that for MEN, the top 2 countries in the world for life expectancy are Switzerland and Iceland.

I enjoyed this article: 

Type in the latitude and longitude for longevity, and you’ll arrive at Iceland. Here’s why.

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That graphic about the economies with the biggest percentage of centenarians is an example of data that is meaningless. The primary reason is the most fundamental - the integrity of the data is abysmal. Even in a highly developed country, with presumably excellent records - like Japan. Here is the Japanese scam with regard to centenarians:

https://www.bbc.com/news/world-asia-pacific-11258071

Executive summary: vast numbers of centenarians in Japan are fictional - people's deaths are not recorded so that families may continue to draw pension benefits. I wouldn't trust longevity statistics coming out of Japan, period.

The other countries are just ludicrous if you know anything about the realities on the ground - Uruguay, Dominican Republic, Chile - LOL. The records over there are worth exactly nothing, with vast numbers of people whose birth records are approximate at best, so good luck trying to establish age based on such. You can't base any kind of age analysis on records this poor. Places like Vietnam, that have experienced war and displacement on a vast scale, have seriously distorted demographic numbers due to people dying, emigrating and being displaced. When you have people fleeing in vast numbers, it's almost never the very old, so what is left behind is a distorted age group - they are not a consistent cohort who have gone through all the natural stages of birth and death in their natural numbers. Such stats are meaningless. 

With the possible exception of Scandinavian countries (Finland too is iffy, on account of WWII), you should not place too much faith in the age-distribution of the population as saying much of anything about longevity factors. 

And when it comes to supercentenarians the situation grows even worse due to the tiny numbers. You are left with essentially anecdotes. Jeanne Calment is a wild outlier with no one even coming close - and now serious questions have been raised as to how legitimate her age actually was (see the thread I started about this). And what conclusion should you reach about DIET when the oldest man (112+ yo) for a while was a Jewish immigrant to Israel who lived through years of ghetto starvation and concentration camps - how good do you suppose his diet was during that years long time? Btw. his profession was a candymaker - do you suppose he ever dipped into his own production? Or maybe you want to reach conclusions about COLD and geographic lattitude based on this fellow, who spent decades in one of the hottest spots on earth, Israel. 

Put me down as deeply suspicious of the whole hype about Blue Zones. Because I think it's a natural human tendency to try to find and believe in good news. I am very, very skeptical about the integrity of statistics and demographic data coming from any of these places, including Okinawa which saw extreme WWII action, and whose pension system (and all its weaknesses and temptations) is Japanese. 

But that's just me. I suppose I'm cursed by an aversion to hype. 

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Btw., if someone wants to see the kind of considerations involved in validating demographic data wrt. age, especially centenarians, here's an interesting read:

https://www.demogr.mpg.de/books/odense/6/12.htm

I think it shows pretty comprehensively why you should exercise extreme caution in taking statistics coming out of most countries at face value. 

Bottom line: disregard most such comparisons between countries.

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This study [1] looks like the best evidence yet that chronic consumption of tea catechins, perhaps in combination with caffeine, activates brown adipose tissue and more than doubles cold-induced thermogenesis, even in people who have little BAT to start with. 

--Dean

Am J Clin Nutr. 2017 Apr;105(4):873-881.  Epub 2017 Mar 8.

Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans.

Yoneshiro T(1), Matsushita M(2), Hibi M(3), Tone H(3), Takeshita M(3), Yasunaga K(3), Katsuragi Y(3), Kameya T(4), Sugie H(4), Saito M(5).

Background: The thermogenic effects of green tea catechin have been repeatedly reported, but their mechanisms are poorly understood.

Objective: The aim of this study was to investigate the acute and chronic effects of catechin on brown adipose tissue (BAT), a site specialized for nonshivering thermogenesis, in humans.Design: Fifteen healthy male volunteers underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity. To examine the acute catechin effect, whole-body energy expenditure (EE) after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine (catechin beverage) was measured. Next, to investigate the chronic catechin effects, 10 men with low BAT activity were enrolled. Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C, which is proportional to BAT activity, was examined. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies.Results: A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 ± 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 ± 2.68 kcal). The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups. Multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (β = 0.496, P = 0.003). Daily ingestion of the catechin beverage [in people with low BAT activity to start with - DP] elevated mean ± SEM CIT (from 92.0 ± 26.5 to 197.9 ± 27.7 kcal/d; P = 0.009), whereas the placebo beverage [containing caffeine only - DP] did not change it. Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering CIT, probably because of the recruitment of BAT, in humans. 

© 2017 American Society for Nutrition.

DOI: 10.3945/ajcn.116.144972

PMID: 28275131

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Ginger Triggers Fat Browning

Here is another medicinal herb to add to the long list of interventions that trigger the formation and/or activation of brown adipose tissue: ginger root.

The new study [1] found that 16 weeks of ginger supplements prevented high-fat diet-induced obesity in mice at least in part by converting white adipose tissue to metabolically active brown/beige adipose tissue (BAT).

Yet another example of a food with recognized health benefits having at least part of its positive effects through boosting BAT.

--Dean

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 - ginger root, 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]

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

[1] J Nutr Biochem. 2019 May 21;70:105-115. doi: 10.1016/j.jnutbio.2019.05.001. [Epub ahead of print]

Ginger prevents obesity through regulation of energy metabolism and activation of browning in high-fat diet-induced obese mice.

Wang J(1), Li D(2), Wang P(2), Hu X(1), Chen F(3). 

Numerous natural herbs have been proven as safe anti-obesity resources. Ginger, one of the most widely consumed spices, has shown beneficial effects against obesity and related metabolic disorders. The present study aimed to examine whether the antiobesity effect of ginger is associated with energy metabolism. Mice were maintained on either a normal control diet or a high-fat diet (HFD) with or without 500 mg/kg (w/w) ginger supplementation. After 16 weeks, ginger supplementation alleviated the HFD-induced increases in body weight, fat accumulation, and levels of serum glucose, triglyceride and cholesterol. Indirect calorimetry showed that ginger administration significantly increased the respiratory exchange ratio (RER) and heat production in both diet models. Furthermore, ginger administration corrected the HFD-induced changes in concentrations of intermediates in glycolysis and the TCA cycle. Moreover, ginger enhanced brown adipose tissue function and activated white adipose tissue browning by altering the gene expression and protein levels of some brown and beige adipocyte-selective markers. Additionally, stimulation of the browning program by ginger may be partly regulated by the sirtuin-1 (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway. Taken together, these results indicate that dietary ginger prevents body weight gain by remodeling whole-body energy metabolism and inducing browning of white adipose tissue (WAT). Thus, ginger is an edible plant that plays a role in the therapeutic treatment of obesity and related disorders.

Copyright © 2019. Published by Elsevier Inc.

DOI: 10.1016/j.jnutbio.2019.05.001

PMID: 31200315

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This new study [1] found that in mice, lifelong moderate CR (20%) coupled with a cool housing temperature* preserves brown adipose tissue in middle age (12m). This combination of CR + chronic cold exposure also greatly boosts markers of BAT activity in the CRed mice when they were exposed to cold (39F or 4C), as illustrated in the graph below (fig. 5d from [1]).

The dashed horizontal line is the baseline level of each marker (normalized to 1) as measured in 3 month old mice at normal room temperature. When such young mice were exposed to cold, the levels of most of the BAT activity markers rose modestly (light bars) relative to baseline. In contrast, markers of BAT activity remained almost unchanged relative to baseline in AL-fed, middle-aged mice (grey middle bars). But in the modestly CR'ed, middle-aged mice (black bars), the markers of BAT activity shot up when they were exposed to cold.

ex2xx7m.jpg

This aligns nicely with evidence I've presented previously that moderate CR boosts BAT and BAT activity in the presence of modest lifelong cold exposure (i.e. housing rodents at normal room temperature).

The authors suggest this BAT boost is one important mechanism by which CR prevents the metabolic dysfunction associated with aging, especially inflammation and insulin resistance. They conclude:

"In brief, our study identifies the contribution of scWAT [subcutaneous White Adipose Tissue - DP] impairment to age-associated metabolic dysfunction and identifies browning in response to food restriction, as a potential therapeutic strategy to prevent the adverse metabolic effects in middle-aged animals."

--Dean

* The mice were housed at 70F (20C), which is about 10F below mouse's thermoneutral temperature of ~81F (27C). 

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

[1] Aging Cell. 2019 Jun;18(3):e12948. doi: 10.1111/acel.12948. Epub 2019 Mar 28.

Long-term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity.

Corrales P(1), Vivas Y(1), Izquierdo-Lahuerta A(1), Horrillo D(1), Seoane-Collazo P(2)(3), Velasco I(1), Torres L(1), Lopez Y(1), Martínez C(1), López M(2), Ros M(1)(4), Obregon MJ(4)(5), Medina-Gomez G(1)(4). 

Age-related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR. To elucidate the role of CR in delaying early signs of aging, young (3 months), middle-aged (12 months), and old (20 months) mice fed al libitum and middle-aged and old mice subjected to early-onset CR were used. We show that impaired plasticity of subcutaneous WAT (scWAT) contributes to IR, which is already evident in middle-aged mice. Moreover, alteration of thyroid axis status with age is an important factor contributing to BAT dysfunction in middle-aged animals. Both defects in WAT and BAT/beige cells are ameliorated by CR. Accordingly, CR attenuated the age-related decline in scWAT function and decreased the extent of fibro-inflammation. Furthermore, CR promoted scWAT browning. In brief, our study identifies the contribution of scWAT impairment to age-associated metabolic dysfunction and identifies browning in response to food restriction, as a potential therapeutic strategy to prevent the adverse metabolic effects in middle-aged animals.

© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

DOI: 10.1111/acel.12948

PMCID: PMC6516146

PMID: 30920127

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Berries Boost BAT

One prominent category of healthy foods that hasn't previously made the long list of interventions that influence brown adipose tissue is berries.

In this sixteen week study [1], researchers spiked the drinking water of obesity/diabetes-prone mice with Cyanidin-3-glucoside (C3G), one of the important anthocyanins found in everyone's favorite dark blue/black/red fruits and particularly berries. Here is a full list of the most C3G-rich foods.

They found that:

"C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function."

They conclude:

"Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity."

It should come as no surprise that berries and other anthocyanin-rich foods boost BAT given how many other known health-promoting interventions have been shown to also increase BAT. 

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
  •  Anthocyanin-rich foods - Blackberries, cherries, blueberries, raspberries, plums 
  • 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 - ginger root, 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]

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

[1] Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700261. Epub 2017 Aug 28.

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function.

You Y(1)(2)(3), Yuan X(4), Liu X(5)(6)(7), Liang C(2)(8), Meng M(5), Huang Y(5)(6), Han X(2), Guo J(2), Guo Y(2), Ren C(2), Zhang Q(2), Sun X(2), Ma T(2)(9), Liu G(3), Jin W(5)(6), Huang W(1)(2), Zhan J(1)(2). 

SCOPE: Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. METHODS AND RESULTS: Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. CONCLUSION: Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI: 10.1002/mnfr.201700261

PMID: 28691397

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