Jump to content
Dean Pomerleau

Cold Exposure & Other Mild Stressors for Increased Health & Longevity

Recommended Posts

I'll chime in. Gordo is right. Don't eat more than a gram or two of cinnamon per day, if that. In fact I think I have have developed elevated liver enzymes for a while as a result of excess Saigon cinnamon.

 

If you're going to do lots of cinnamon, use Ceylon cinnamon. I buy mine from Nuts.com. They have either ground ($13.99/lb) or in sticks ($18.99/lb). I like the sticks.  The Ceylon is low in warfarin, which is what is in Saigon cinnamon that can trash your liver.

 

Of course, it's not entirely clear you get the same cinnamon benefits with Ceylon as Saigon, since must studies are done with Saigon cinnamon. This would (I presume) include this "stomach cooling" study referenced earlier.

 

--Dean

Share this post


Link to post
Share on other sites

All:
 

I'll chime in. Gordo is right. Don't eat more than a gram or two of cinnamon per day, if that.


Gordo and Dean are right ;) .
 

If you're going to do lots of cinnamon, use Ceylon cinnamon. ... [which] is low in warfarin ... Of course, it's not entirely clear you get the same cinnamon benefits with Ceylon as Saigon, since must studies are done with Saigon cinnamon.

 
Unfortunately, "Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance."(1) Yes, there is in vitro shit and rodents injected with extracts, but this human trial clearly trumps that.

 

A second trial, performed by employees of the manufacturer and of its hired Contract Research Organization, found that 1 g of a proprietary 10:1 water-ethanol extract of Ceylon cinnamon did lower the glucose curve following a standard meal "between 0 and 120 min by 14.8% (P = 0.15) and between 0 and 60 min by 21.2% (P < 0.05) compared to the placebo" in healthy subjects(2); assuming that's a real result, it's an open question whether and what level of straight-up Ceylon cinnamon would do the same job and if those levels would still wind up containing too much coumarin (the extract does not).

 

Reference

1: Wickenberg J, Lindstedt S, Berntorp K, Nilsson J, Hlebowicz J. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance. Br J Nutr. 2012 Jun;107(12):1845-9. doi: 10.1017/S0007114511005113. Epub 2011 Sep 20. PubMed PMID: 21929834.

 

2: Beejmohun V, Peytavy-Izard M, Mignon C, Muscente-Paque D, Deplanque X, Ripoll C, Chapal N. Acute effect of Ceylon cinnamon extract on postprandial glycemia: alpha-amylase inhibition, starch tolerance test in rats, and randomized crossover clinical trial in healthy volunteers. BMC Complement Altern Med. 2014 Sep 23;14:351. doi: 10.1186/1472-6882-14-351. PubMed PMID: 25249234; PubMed Central PMCID: PMC4246455.

Share this post


Link to post
Share on other sites

Thanks for the info on cinnamon. I had no idea. I drink a couple of cups of Harney and Son's cinnamon spiced tea everyday. (Usually their decaf version) I wrote to them to find out what type of cinnamon they use.

 

Thanks!

-Pea

Share this post


Link to post
Share on other sites

Greetings from Siberia!   This is a fantastic thread!   Brilliant work Dean!   Bravo  Gordo!   I’ve  read through all the posts and have now downloaded the PDF file so I can study it thoroughly.

 

About myself:   I moved  from California to Siberia six years ago with my Russian wife.  I practice mild CR (BMI 21), TRF (14-16hrs daily fast),  and follow a  "Nordic"-style vegetarian+ limited kefir &oily fish diet.

 

I’d been into taking cold showers and swimming in cool water for some time, but this thread inspired me to begin a program of cold baths.   The water is icy cold coming out of the tap year round where I live, which makes it easy.  I've been doing it four weeks so far--quite a step up from the showers.  I’m now really looking forward to the Siberian winter!  It’s already down to -5 C in the mornings

Share this post


Link to post
Share on other sites

SIbiriak,

 

Welcome to the CR forums! Wow, moving to Siberia - now that's taking cold exposure to a whole new level!

 

 I'm glad you've found this CE thread helpful. I'm impressed if you've really read it all. There are parts of this thread that even I've forgotten about! Speaking of cognitive performance, see my next post.

 

--Dean

Share this post


Link to post
Share on other sites

Cold Exposure and Cognitive Performance

 

I've reported recently that both chronic and acute cold exposure seems to make my brain work better. I was sorta joking at the time, likening it to a super-cooled quantum computer. But it does feel like a real phenomena. And I just stumbled across a possible mechanism.

 

It's long been known that cold exposure increases activity in the brain region known as the locus coeruleus [1], which is one of the main sources of norepinephrine (noradrenaline) that is the signalling molecule which tells brown and beige fat to generate heat. 

 

So I was fascinated to see this article today about a new paper [2] from Stanford researchers in the top neuroscience journal Neuron.

 

The researchers measured how integrated or coordinated the activity was between different brain regions when people were at rest and when doing cognitively challenging tasks. Not surprisingly, they found that brain regions were more integrated and working in a coordinated fashion when performing a cognitively demanding tasks compared to when they were resting. They also found that people whose brains were more integrated at rest performed better on the challenging cognitive task. 

 

But here is the kicker, and how it relates to cold exposure:

 

As a final step in their study, the researchers measured pupil size to try and tease out how the brain coordinates this change in connectivity. Pupil size is an indirect measure of the activity of a small region in the brainstem called the locus coeruleus that is thought to amplify or mute signals across the entire brain. Up to a certain point, increases in pupil size likely indicate greater amplification of strong signals and greater muting of weak signals across the brain.
 
The researchers found that pupil size roughly tracked with changes in brain connectivity during rest, in that larger pupils were associated with greater connectedness. This suggests that the noradrenaline coming from the locus coeruleus might be what drives the brain to become more integrated during highly complicated cognitive tasks, allowing a person to perform well on that task.

 

How about that for evidence to support my crazy theory about cold exposure boosts cognitive performance!?

 

Of course, CE probably needs to be chronic, so you overcome the perceived discomfort from acute cold exposure, and avoid the deleterious effects such stress and distraction would otherwise have on cognition.

 

But once you're cold acclimatized, it looks like your brain may indeed be turbocharged.

 

--Dean

 

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

[1] Neuroscience. 1997 Dec;81(4):1055-64.

 
Chronic cold stress alters the basal and evoked electrophysiological activity of 
rat locus coeruleus neurons.
 
Mana MJ(1), Grace AA.
 
Author information: 
(1)Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
 
In vivo extracellular single-unit recording techniques revealed that chronic cold
stress significantly alters both the basal and the evoked electrophysiological
activity of noradrenergic neurons in the locus coeruleus of the anaesthetized
rat. Following 17-21 days of chronic cold exposure (5 degrees C), the single-unit
activity of histologically-identified locus coeruleus neurons in chloral
hydrate-anaesthetized rats was recorded and analysed in terms of their basal
firing rate and pattern of spike activity, as well as their response to footshock
stimulation. There was no significant difference in the incidence of
spontaneously active cells/electrode track between cold-stressed rats and control
rats. However, the basal spike activity of locus coeruleus cells recorded from
cold-stressed rats differed significantly from that of control rats along two
dimensions: i) they displayed significantly higher basal firing rates (mean =
1.88 Hz vs 1.20 Hz, respectively); and ii) they frequently exhibited spontaneous 
burst-firing activity that was not observed in control rats (observed in 15/17
cold-stressed rats vs 1/26 control rats). The evoked spike activity of locus
coeruleus cells in cold-stressed rats also differed significantly from that of
control rats along two dimensions: i) they were more likely to respond to
footshock stimulation (mean = 90.3% vs 74.4%, respectively); and ii) these
responses were more likely to consist of multispike bursts of action potentials
(mean = 8 bursts/50 stimulations vs 1 burst/50 stimulations, respectively). These
results indicate that alterations in the electrophysiological activity of
noradrenergic locus coeruleus neurons may contribute to the phenomenon of
stress-induced sensitization of norepinephrine release that is thought to
underlie some of the neuropathological changes that accompany long-term stress.
 
PMID: 9330367
 
------------------
[2] Neuron. 2016 Sep 28. pii: S0896-6273(16)30577-3. doi:
10.1016/j.neuron.2016.09.018. [Epub ahead of print]
 
The Dynamics of Functional Brain Networks: Integrated Network States during
Cognitive Task Performance.
 
Shine JM(1), Bissett PG(2), Bell PT(3), Koyejo O(2), Balsters JH(4), Gorgolewski 
KJ(2), Moodie CA(2), Poldrack RA(2).
 
Higher brain function relies upon the ability to flexibly integrate information
across specialized communities of brain regions; however, it is unclear how this 
mechanism manifests over time. In this study, we used time-resolved network
analysis of fMRI data to demonstrate that the human brain traverses between
functional states that maximize either segregation into tight-knit communities or
integration across otherwise disparate neural regions. Integrated states enable
faster and more accurate performance on a cognitive task, and are associated with
dilations in pupil diameter, suggesting that ascending neuromodulatory systems
may govern the transition between these alternative modes of brain function.
Together, our results confirm a direct link between cognitive performance and the
dynamic reorganization of the network structure of the brain.
 
Published by Elsevier Inc.
 
DOI: 10.1016/j.neuron.2016.09.018 
PMID: 27693256 

Share this post


Link to post
Share on other sites

Heat Shock Proteins Extend Lifespan & Preserves Cognition in Mice

 

Somehow in my post about heat shock proteins and cold exposure, I missed this study [1], which Fight Aging! pointed to on their blog this week.

 

In [1], researchers found that intranasal administration of Heat Shock Protein 70 (HSP70) increased both mean and maximum lifespan of mice when started either in old age (17 months) or middle age (12 months) and continued through the rest of life. Here are the survival curves for HSP70 started in old age (left) or middle age (right):

 

3yXLLQd.png

 

HSP70 treatment beginning at both ages also improved cognition, as measured by decreased time to find the platform after several days of learning in a Morris water maze. HSP70 treatment also made mice or curious and exploratory. HSP70 also preserved neuron and synapse density in the brain and especially in the hippocampus (important for memory), which tends to decline with age. Finally, HSP70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain.

 

It would obviously be nice to see these results replicated, but on the surface they are quite amazing, especially given the simplicity of the treatment (nasal mist).

 

Heat shock proteins like HSP70 serve as protein "chaperones" making sure they continue to fold correctly under stress conditions. They were originally believed to be heat-shock specific, but have since be found to be upregulated to protect against negative effects of a variety of environmental stresses, including cold exposure, as discussed in my previous post.

 

So it looks like upregulation of heat shock proteins is yet another way cold exposure potentially slow aging and improve cognition.

 

--Dean

 

----------

[1] Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):16006-11. doi:

10.1073/pnas.1516131112. Epub 2015 Dec 14.
 
Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.
 
Bobkova NV(1), Evgen'ev M(2), Garbuz DG(3), Kulikov AM(4), Morozov A(3), Samokhin
A(1), Velmeshev D(1), Medvinskaya N(1), Nesterova I(1), Pollock A(5), Nudler
E(6).
 
Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective
role in various neurodegenerative disorders often associated with aging, but its 
activity and availability in neuronal tissue decrease with age. Here we explored 
the effects of intranasal administration of exogenous recombinant human Hsp70
(eHsp70) on lifespan and neurological parameters in middle-aged and old mice.
Long-term administration of eHsp70 significantly enhanced the lifespan of animals
of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70
administration demonstrated improved learning and memory in old mice. Likewise,
the investigation of locomotor and exploratory activities after eHsp70 treatment 
demonstrated a significant therapeutic effect of this chaperone. Measurements of 
synaptophysin show that eHsp70 treatment in old mice resulted in larger
synaptophysin-immunopositive areas and higher neuron density compared with
control animals. Furthermore, eHsp70 treatment decreased accumulation of
lipofuscin, an aging-related marker, in the brain and enhanced proteasome
activity. The potential of eHsp70 intranasal treatment to protect synaptic
machinery in old animals offers a unique pharmacological approach for various
neurodegenerative disorders associated with human aging.
 
DOI: 10.1073/pnas.1516131112 
PMCID: PMC4702952
PMID: 26668376

Share this post


Link to post
Share on other sites

Nice find!  Too early to say for people of course, but with that effect size, quite interesting. I wonder whether high temperature  induced HSP ( Tim Ferris commentary here) may have the same effect.

 

Dean, I assume you mean cold exposure ( typo: old exposure).  Have not seen any direct comparisons of extent of HSP induction via cold versus heat but it may be noteworthy the relative magnitude of HSP induction via these two discrete mechanisms.  Fortunately they are not mutually exclusive and either or both can be pursued.

Edited by Mechanism

Share this post


Link to post
Share on other sites

Mechanism,

 

Thanks for catching the old → cold typo. I fixed it. Yes - hot temperatures are well-known to induce heat shock proteins, and is obviously where the name came from. As you said, the two aren't mutually exclusive, and are often employed together (going from hot sauna to cool pool). Just make sure you've got a good heart!

 

--Dean

Share this post


Link to post
Share on other sites

Long-Lived Ames Dwarf Mice have Increased BAT Function

 

A new study [1] of Ames dwarf mice evidence that BAT and thermogenesis may be important for longevity:

 

Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption (VO2) and heat production,...

 

Here, we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also utilize interscapular BAT (iBAT) removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Further, we show that Ames dwarf mice are able to compensate for loss of iBAT by utilizing their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature and remarkably extended longevity.

 

--Dean

 

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

[1] Endocrinology. 2016 Oct 14:en20161593. [Epub ahead of print]

Brown Adipose Tissue Function is Enhanced in Long-Lived, Male Ames Dwarf Mice.

Darcy J(1,)(2), McFadden S(1), Fang Y(1), Huber JA(1), Zhang C(1,)(3), Sun LY(4),
Bartke A(1,)(2).

Ames dwarf mice (Prop1(df/df)) are long-lived due to a loss of function mutation
resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone and
prolactin. Along with a marked extension of longevity, Ames dwarf mice have
improved energy metabolism as measured by an increase in their oxygen consumption
(VO2) and heat production, as well as a decrease in their respiratory quotient
(RQ). Along with alterations in energy metabolism, Ames dwarf mice have a lower
core body temperature (Tco). Moreover, Ames dwarf mice have functionally altered
epididymal white adipose tissue (eWAT) that improves, rather than impairs, their
insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine
secretion. Given the unique phenotype of Ames dwarf eWAT, their improved energy
metabolism and lower Tco, we hypothesized that Ames dwarf brown adipose tissue
(BAT) may function differently than that of their normal littermates. Here, we
use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT
function. We also utilize interscapular BAT (iBAT) removal to demonstrate that
BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it
is less important for their normal littermates. Further, we show that Ames dwarf
mice are able to compensate for loss of iBAT by utilizing their WAT depots as an
energy source. These findings demonstrate enhanced BAT function in animals with
GH and thyroid hormone deficiencies, chronic reduction of body temperature and
remarkably extended longevity.

DOI: 10.1210/en.2016-1593
PMID: 27740871

Share this post


Link to post
Share on other sites

Cold exposure boosts heart rate variability (HRV) which in turn is strongly correlated with longevity.  When I recently became interested in HRV at first I was expecting CE to actually lower HRV (since it is well documented in the literature that CE boosts the sympathetic nervous system, which by itself is an HRV lowering factor). But I heard anecdotes from others that track HRV saying CE actually boosted their HRV.  Then I began tracking my own HRV, and my observations confirmed this.  Over time I found that the more intense the CE, the higher my HRV goes.  I didn't remember seeing anything about this in any of the CE related studies I had read, so I did some digging and found this:

 

Autonomic nervous function during whole-body cold exposure before and after cold acclimation

 

What the researchers found was that cold-induced elevation in high frequency power became significant after cold acclimation, while other HRV parameters remained unchanged.  Cold exposure increased sympathetic activity, which was blunted after cold acclimation. Parasympathetic activity showed a minor increase in cold, which was enhanced after cold acclimation. In conclusion, cold habituation lowers sympathetic activation and causes a shift toward increased parasympathetic activity.

 

NOTE: Cold acclimation occurred after 10 days of subjects being exposed to 50 degree F temps (10C) for 2 hours a day.

 

My last measurement (from this morning):

CEHRV.png

 

 

For comparison purposes, here are HRV values from a large, healthy, physically active population:

6.png

 

 

Table 1 – Data from 10,308 Elite HRV users showing ln(rMSSD) and Elite HRV Score presented by age range and gender.

 

And here are values from elite olympians:

 

 

EnduranceVsPower-1080x510.png

 

 

In conclusion, I know how to win the $500,000 palo alto longevity prize, so if any of you has access to a lab and has the credentials to enroll, I'll gladly split it with you!  ;)

Edited by Gordo

Share this post


Link to post
Share on other sites

Rapamycin Impairs Glucose Metabolism in BAT

 

Two side effects of Rapamycin (Rap) prevent it from being a very good longevity drug - it suppresses the immune system and impairs glucose tolerance. In fact the former is the reason Rap is given to organ transplant patients, i.e. to suppress their immune system to keep it from rejecting their new organ. But many transplant patients given Rap develop what's known as "New Onset Diabetes After Transplant" (NODAT) because of Rap's negative effect on glucose metabolism. That is one reason that some people think a cocktail of Rap + Metformin might be a more promising longevity treatment that Rap or Metformin alone - since metformin helps improve glucose metabolism thereby overcoming one of Rap's negative side effects.

 

This new study [1] helps explain how Rap impairs glucose metabolism. They found Rap treatment both in vitro and in vivo (in rats) resulted in BAT cells with lower expression of several proteins related to thermogenesis and which are important for glucose (and fat) metabolism:

 

In vivo treatment of rats with rapamycin for three weeks ... inhibited norepinephrine (NE)-induced lipolysis, the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and uncoupling protein (UCP)-1 in brown adipocytes. Importantly, basal mitochondrial respiration, proton leak and maximal respiratory capacity were significantly decreased in brown adipocytes treated with rapamycin. In conclusion, we demonstrate, for the first time the important role of brown adipocytes as target cells of rapamycin, suggesting that insulin resistance in BAT might play a major role in NODAT development.

 

In short, rapamycin appears to suppress metabolic activity in BAT, which serves a major sink for glucose, thereby promoting glucose intolerance.

 

--Dean

 

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

[1] Biochim Biophys Acta. 2016 Sep 26;1861(12 Pt A):1929-1941. doi:

10.1016/j.bbalip.2016.09.016. [Epub ahead of print]
 
Rapamycin negatively impacts insulin signaling, glucose uptake and uncoupling
protein-1 in brown adipocytes.
 
García-Casarrubios E(1), de Moura C(2), Arroba AI(3), Pescador N(4),
Calderon-Dominguez M(5), Garcia L(1), Herrero L(5), Serra D(5), Cadenas S(6),
Reis F(7), Carvalho E(8), Obregon MJ(1), Valverde ÁM(9).
 
 
New onset diabetes after transplantation (NODAT) is a metabolic disorder that
affects 40% of patients on immunosuppressive agent (IA) treatment, such as
rapamycin (also known as sirolimus). IAs negatively modulate insulin action in
peripheral tissues including skeletal muscle, liver and white fat. However, the
effects of IAs on insulin sensitivity and thermogenesis in brown adipose tissue
(BAT) have not been investigated. We have analyzed the impact of rapamycin on
insulin signaling, thermogenic gene-expression and mitochondrial respiration in
BAT. Treatment of brown adipocytes with rapamycin for 16h significantly decreased
insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated
protein kinase B (Akt) phosphorylation. Consequently, both insulin-induced
glucose transporter 4 (GLUT4) translocation to the plasma membrane and glucose
uptake were decreased. Early activation of the N-terminal Janus activated kinase 
(JNK) was also observed, thereby increasing IRS1 Ser 307 phosphorylation. These
effects of rapamycin on insulin signaling in brown adipocytes were partly
prevented by a JNK inhibitor. In vivo treatment of rats with rapamycin for three 
weeks abolished insulin-mediated Akt phosphorylation in BAT. Rapamycin also
inhibited norepinephrine (NE)-induced lipolysis, the expression of peroxisome
proliferator-activated receptor γ coactivator 1α (PGC-1α) and uncoupling protein 
(UCP)-1 in brown adipocytes. Importantly, basal mitochondrial respiration, proton
leak and maximal respiratory capacity were significantly decreased in brown
adipocytes treated with rapamycin. In conclusion, we demonstrate, for the first
time the important role of brown adipocytes as target cells of rapamycin,
suggesting that insulin resistance in BAT might play a major role in NODAT
development.
 
Copyright © 2016 Elsevier B.V. All rights reserved.
 
DOI: 10.1016/j.bbalip.2016.09.016 
PMID: 27686967

Share this post


Link to post
Share on other sites

Sthira,

 

In this long thread has cryotherapy been addressed? I'm wondering if it's worth the money.

 

Yes - it has in this post, titled Cryostimulation Reduces Inflammation, Speeds Exercise Recovery, Burns Fat and Improves Serum CholesterolThe treatment was 3min exposure to -166 °F. Pretty chilly. It's not clear such acute CE works better (or is worth the money) relative to more modest, extended CE like the 45 min run I just did in the wind and rain at 59 °F. 

 

--Dean

Share this post


Link to post
Share on other sites

Rutin-Rich Foods Boost BAT Activity

 

It's been a while since I've added to the list of BAT & thermogenesis boosting substances and interventions. But here is a new one, published today - rutin. In a new study [1] (popular press) mice on a regular diet that was supplemented with rutin in their drinking water (1mg/ml) resulted in 

 

reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both the genetically obese mice and the mice with diet-induced obesity.

 

Mechanistically, it's clear that the rutin was acting as a cold mimetic:

 

Specifically, the researchers found that rutin directly binds to and stabilizes SIRT1 (NAD-dependent deacetylase sirtuin-1), leading to hypoacetylation of PGC1α protein, which stimulates Tfam transactivation and eventually augments mitochondrial number and UCP1 activity in BAT. Rutin functions as a cold mimetic through activating a SIRT1-PGC1α-Tfam signaling cascade and increasing mitochondrial number and UCP1 activity in BAT. Rutin also induced brown-like (beige) adipocyte formation in subcutaneous adipose tissue in both obesity mouse models.

 

They used mulberry extract in [1], but according to a few sources (1, 2, 3), the best source of rutin appears to be buckwheat, followed by apple peels, citrus fruit, mulberries, aronia berries, cranberries, peaches, rooibos tea, amaranth leaves, and figs.

 

I get buckwheat groats from Nuts.com, which I boil and mixed into my starch mix. I've also purchased dried mulberries from Nuts.com in the past too. I include rooibos tea in my "witches brew" beverage. I grow amaranth in my garden, and of course each apples, citrus, cranberries and peaches.

 

I've updated the list of BAT foods and treatments below.

 

--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 - 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]  The FASEB Journal, 2016; 

 

Rutin ameliorates obesity through brown fat activation.

 

X. Yuan, G. Wei, Y. You, Y. Huang, H. J. Lee, M. Dong, J. Lin, T. Hu, H. Zhang, C. Zhang, H. Zhou, R. Ye, X. Qi, B. Zhai, W. Huang, S. Liu, W. Xie, Q. Liu, X. Liu, C. Cui, D. Li, J. Zhan, J. Cheng, Z. Yuan, W. Jin. 

 

Abstract

Increasing energy expenditure through activation of brown adipose tissue (BAT) is a critical approach to treating obesity and diabetes. In this study, rutin, a natural compound extracted from mulberry and a drug used as a capillary stabilizer clinically for many years without any side effects, regulated whole-body energy metabolism by enhancing BAT activity. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both genetically obese (Db/Db) and diet-induced obesity (DIO) mice. Rutin also induced brown-like adipocyte (beige) formation in subcutaneous adipose tissue in both obesity mouse models. Mechanistically, we found that rutin directly bound to and stabilized SIRT1, leading to hypoacetylation of peroxisome proliferator-activated receptor γ coactivator-1α protein, which stimulated Tfam transactivation and eventually augmented the number of mitochondria and UCP1 activity in BAT. These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorder.

PMID: unavailable

DOI: 10.1096/fj.201600459RR

Share this post


Link to post
Share on other sites

Buckwheat porridge (kasha) is a staple in Russia.  It's easy to make at home and available in any столовая (ubiquitous cafeteria-style eateries).  I consume it daily.  Often beans and buckwheat instead of rice.

Edited by Sibiriak

Share this post


Link to post
Share on other sites

Breakthrough in Understanding Diabetes Shows Why Cold Exposure Beneficial - Lower Ceramides

 

This new article [1] (full text, popular press) in Cell Metabolism claims to show why some people get diabetes and others don't. The authors say:

 

Accumulation of a toxic class of fat metabolites, known as ceramides, may make people more prone to type 2 diabetes.

"Ceramides impact the way the body handles nutrients," says the study's senior author Scott Summers, Ph.D., also chairman of the University of Utah Department of Nutrition and Integrative Physiology. "They impair the way the body responds to insulin, and also how it burns calories."

In the study, published on Nov. 3 in Cell Metabolism online, the researchers show that a buildup of ceramides prevents the normal function of fat (adipose) tissue.

How do these deleterious ceramides form? It looks like dietary saturated fat, but not PUFA, increases ceramide levels in muscle cells. From [2]:

The ceramide content did not change in any muscle from PUFA diet group but increased in the SAT diet group by 46% and 52% in the soleus and red section of the gastrocnemius, respectively. 
 
So that makes sense in the context of diabetes - high dietary saturated fat leads to increased ceramide accumulation which results in "gumming up" the bodies ability to use insulin to metabolize glucose.
 
Where does cold exposure come in? The new paper [1] found that ceramides also interfere with the balance between beige and white fat, and that cold exposure or beta-adrenergic agonists decrease ceramide concentration in the whole body and particularly in fat deposits, leading to improvements in glucose metabolism.
 
Here is the graphical highlights, showing that injecting mice with an compound that inhibits the synthesis of ceramide (a type of sphingolipid) causes lower ceramide concentration in fat tissue, which in turn results in the browning/beiging of fat, resulting in better insulin sensitivity and increased energy expenditure (through thermogenesis):
 
n9CmKUT.png
 
 
They tested the linkage between cold and ceramide levels directly in mice, by measure the ceramide levels in various adipose tissues before and after 5-days of cold exposure. Here is the graph of what they found:
 
t6BOMK7.png
 
As you can see, ceramide levels in BAT is low to begin with, but drops by almost 50% in both visceral and subcutaneous fat deposits as a result of cold exposure. The authors inteprete this and associated energy expenditure tests they conducted as suggesting "sphingolipid depletion may be an important means of increasing the thermogenic properties of white adipose depots."
 
In summary:
 
cold exposure (or low SFA diet) → lower ceramides → beiging of white fat → improved glucose metabolism → lower diabetes risk
 
--Dean
 
---------------
[1] Cell Metabolism (2016), http://dx.doi.org/10.1016/j.cmet.2016.10.002
 
Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
 
Bhagirath Chaurasia,1,14,15,16,
* Vincent Andre Kaddai,1,14 Graeme Iain Lancaster,1 Darren C. Henstridge,2
Sandhya Sriram,3 Dwight Lark Anolin Galam,4 Venkatesh Gopalan,5 K.N. Bhanu Prakash,5 S. Sendhil Velan,5
Sarada Bulchand,6 Teh Jing Tsong,7 Mei Wang,7 Monowarul Mobin Siddique,8 Guan Yuguang,4
Kristmundur Sigmundsson,4 Natalie A. Mellet,9 Jacquelyn M. Weir,9 Peter J. Meikle,9 M. Shabeer Bin M. Yassin,10
Asim Shabbir,11 James A. Shayman,12 Yoshio Hirabayashi,13 Sue-Anne Toh Ee Shiow,10 Shigeki Sugii,3,4
and Scott A. Summers1,1
 
SUMMARY Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/ deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulinsensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism.
 

--------------
[2] J Cell Physiol. 2010 Nov;225(3):786-91. doi: 10.1002/jcp.22283.

 
Effect of high fat diet enriched with unsaturated and diet rich in saturated
fatty acids on sphingolipid metabolism in rat skeletal muscle.
 
Blachnio-Zabielska A(1), Baranowski M, Zabielski P, Gorski J.
 
Author information: 
(1)Department of Physiology, Medical University of Bialystok, Bialystok, Poland. 
blacha@umwb.edu.pl
 
Consumption of high fat diet leads to muscle lipid accumulation which is an
important factor involved in induction of insulin resistance. Ceramide is likely 
to partially inhibit insulin signaling cascade. The aim of this study was to
examine the effect of different high fat diets on ceramide metabolism in rat
skeletal muscles. The experiments were carried out on rats fed for 5 weeks: (1) a
standard chow and (2) high fat diet rich in polyunsaturated fatty acids (PUFA)
and (3) diet enriched with saturated fatty acids (SAT). Assays were performed on 
three types of muscles: slow-twitch oxidative (soleus), fast-twitch
oxidative-glycolytic, and fast-twitch glycolytic (red and white section of the
gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT), 
neutral and acid sphingomyelinase (n- and aSMase), and neutral and alkaline
ceramidase (n- and alCDase) was examined. The content of ceramide, sphinganine,
sphingosine, and sphingosine-1-phosphate was also measured. The ceramide content 
did not change in any muscle from PUFA diet group but increased in the SAT diet
group by 46% and 52% in the soleus and red section of the gastrocnemius,
respectively. Elevated ceramide content in the SAT diet group could be a result
of increased SPT activity and simultaneously decreased activity of nCDase.
Unchanged ceramide content in the PUFA diet group might be a result of increased 
activity of SPT and alCDase and simultaneously decreased activity of SMases. We
conclude that regulation of muscle ceramide level depends on the diet and type of
skeletal muscle.
 
© 2010 Wiley-Liss, Inc.
 
DOI: 10.1002/jcp.22283 
PMID: 20568228

Share this post


Link to post
Share on other sites
CLINICAL IMPLICATIONS OF BASIC RESEARCH

Elizabeth G. Phimister, Ph.D., Editor

Wasting Energy to Treat Obesity

Paul Lee, M.B., B.S., Ph.D.

N Engl J Med 2016; 375:2298-2300 December 8, 2016 DOI: 10.1056/NEJMcibr1610015


The concept of enzyme therapy dates back to at least the 19th century, when pancreatic enzymes were offered to patients who had exocrine pancreatic insufficiency.1 In 1964, Christian de Duve suggested enzyme treatment as a therapeutic strategy for lysosomal disorder: three decades later, glucocerebrosidase replacement became the standard of treatment for Gaucher’s disease.2 Recently, Long et al.3 described experiments that were designed to probe enzymatic activity that generates a class of amino acids capable of short-circuiting the flow of mitochondrial energy, akin to but independent of the uncoupling protein 1 (UCP1) of brown adipose tissue. Mice that are treated with the enzyme or its metabolites lose weight as a result of uncoupled “energy wastage” in cells other than brown adipocytes. These findings raise the possibility of fighting obesity through supplementation with this enzyme or its biochemical products.

Creating a negative energy balance to lose weight is easy in principle but difficult in practice in a sedentary society. Indeed, achieving a sustained increase in energy expenditure through regular exercise is extremely difficult for most if not all overweight or obese persons. Chemical uncoupling is therefore an attractive strategy for the dissipation of excess energy, because surplus calories are “wasted” (in the form of heat) through biochemically futile cycling of metabolic substrates without the need for physical mechanical effort. This strategy is not new: the pharmacologic uncoupler 2,4-dinitrophenol was widely used as a weight-loss agent during the previous century, but its use was discontinued because of its systemic toxic effects.4

In studies in rodents, Long and colleagues identified a previously unstudied enzyme, known as peptidase M20 domain–containing 1 (PM20D1), that has uncoupling and fat-burning actions. This enzyme meets some of the criteria for an antiobesity enzyme therapy. First, it is secreted, detectable in plasma, and endogenously produced. Moreover, PM20D1 that is generated from a viral vector is resistant to degradation in the blood. Second, experimentally elevated levels of PM20D1 effect fat catabolism in animals, resulting in weight loss and glycemic improvement without compensatory orexigenic adaptation. Third, unlike uncoupling that is mediated by brown adipose tissue, which requires cold activation, PM20D1-induced weight loss occurs without cold exposure and therefore is suited to a thermoneutral environment 

(Figure 1FIGURE 1 Wasting Energy to Lose Weight.).

How does PM20D1 induce weight loss? Long et al. found that this enzyme stitches lipids onto amino acids to generate N-acyl amino acids. These newly synthesized lipidated metabolites turn on uncoupling in cells that lack UCP1, including white adipocytes and muscle cells. Although the underlying mechanisms await further elucidation, preliminary results have revealed binding of N-acyl amino acids to mitochondrial transporters (such as the SLC25 family), which may fuel proton shunting and thereby mimic UCP1 function. Remarkably, the treatment of mice with N-acyl amino acids increased energy expenditure and lowered glucose, thus recapitulating the metabolic benefits observed in mice that overexpress PM20D1. Therefore, the supplementation of these fat-burning N-acyl amino acids also represents a plausible experimental therapeutic strategy.

PM20D1 is not found in white fat cells and is found only in UCP1-expressing adipocytes. These include classic interscapular brown and beige adipocytes; the latter are “brown fat–like” cells that are induced within inguinal white fat after cold exposure. Although brown adipose tissue diminishes after infancy, a considerable abundance of adipocytes — which can be induced to become beige adipocytes — reside within the neck and subcutaneous white fat of adult humans.5 The expression of PM20D1 in thermogenic UCP1-expressing adipocytes may be a hint regarding its evolutionary origin. On hypothermic threat, nonshivering (mediated by brown adipose tissue) and shivering (muscle-mediated) thermogenesis are progressively recruited to defend core temperature. Shivering disadvantages hunting and gathering efficiency and survival in the cold, and therefore selection may have favored the expression of an enzyme secreted by brown adipose tissue that ignites thermogenesis in other tissue types (such as white fat and muscle) — representing, as it were, an on-call hypothermia rescue corps — until inducible white adipocytes are “beiged” over time.

Furthermore, although plasma levels of PM20D1 are unchanged in cold-acclimated mice, cold exposure increases circulating levels of many N-acyl amino acids. From a diagnostic perspective, the PM20D1 enzyme–substrate–metabolite milieu may harbor a surrogate that is indicative of the whole-body “brown–beige” reserve. A plasma “cold-exposed” N-acyl amino acid metabolomic signature may be exploitable as a trackable biomarker of thermogenic capacity in humans.

There are, of course, many issues to consider before PM20D1 or its products could be considered as candidates for antiobesity drugs. The physiological characteristics of PM20D1 need to be fully explored in humans, and the off-target toxic effects need to be scrutinized in preclinical models, as underscored by the fatalities caused by 2,4-dinitrophenol. However, the study by Long et al. has illuminated uncharted research territory in the antiobesity therapeutics arena and provides a welcome — albeit tentative — context for the many N-acyl amino acids that have been discovered in mammals and the biologic significance of which has remained largely unknown.

>>>>>>>>>>>>>>>>>>>>>>>

The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

Long JZ, Svensson KJ, Bateman LA, Lin H, Kamenecka T, Lokurkar IA, Lou J, Rao RR, Chang MR, Jedrychowski MP, Paulo JA, Gygi SP, Griffin PR, Nomura DK, Spiegelman BM.

Cell. 2016 Jul 14;166(2):424-35. doi: 10.1016/j.cell.2016.05.071.

PMID: 27374330


Abstract

Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.

Comment in

METABOLISM. The quest to burn fat, effortlessly and safely.

Fan W, Evans R.

Science. 2016 Aug 19;353(6301):749-50. doi: 10.1126/science.aah6189. No abstract available.

PMID: 27540151


Edited by AlPater

Share this post


Link to post
Share on other sites

Rose hip supplementation increases energy expenditure and induces browning of white adipose tissue

Published: 6 December 2016

 

Although no differences in energy intake were found compared to the CTR group, rose hip prevented body weight gain and lowered blood glucose, insulin and cholesterol levels. Indirect calorimetry showed that rose hip-fed mice have significantly higher energy expenditure during the dark phase, despite comparable voluntary activity. Moreover, when challenged with treadmill running, rose hip-fed mice exhibited higher metabolic rate. Therefore, we hypothesized that rose hip could stimulate the brown adipose tissue (BAT) thermogenic capacity or may induce browning of the white adipose tissue (WAT).

 

 

Also:

Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

Published: 6 December 2016

 

 

Finally a new review paper on 

Chili pepper as a body weight-loss food

(BAT activation with chili peppers)  Note there seems to be a glaring typo in the abstract where they say "chili directly reduces energy expenditure by activating Brown Adipose Tissue" (reduces should be increases?). Actual article body states the opposite numerous times.

Edited by Gordo

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now

×