Lowcarb Bread - Fermentation radio chat BBC

My lowcarb bread + stuff arrived today, despite first discovering Atkins back in 2002'ish, this is the first time Ive actually tried any of the lowcarb food substitutes. Seems im "late" to the party lawl. Taste and texture are actually OK, quite close to normal bread, although they do not seem to contain significant fibre.

This stuff is fucking expensive though. Those activa cookies were advertised as lowcarb in the store however after checking the box they have 6g per cookie, seems a bit high tbh considering the cookies are quite small. The bread certainly gets a thumbs up however.




One of my colleagues sent me this BBC radio chat on the lost art of fermentation. I personally think fermented foods are a critical part of a good diet. There is one part in the radio chat where it is said that up until the 1960's most bread actually went through a more thorough fermentation process. Its not appreciated how fantastic vinegar/acetic acid foods are.

What if fat works like muscle?

This post probably wont make any sense, I am slightly psychotic, you know.

Myostatin is a negative regulator of muscle growth. Without Myostatin your muscles will grow huge, regardless of anything else you do. Another requirement of muscle growth is "activation". I.E. the old phrase, use it or lose it. Muscle activation commences by the nervous system, so the more nervous system stimulation you give to muscle, the more it will grow. There does seem to be one other factor though as EMS ( electrical muscle stimulation ) is not quite as effective as exercise by the host organism. I have no idea personally what the missing ingredient is though.

A clue to the mechanism of Myostatin control of muscle growth comes from this recent paper, it looks like myostatin deficiency allows for greater nervous system innervation of the muscle. This makes sense, because as stated above, the number 1 rule governing muscle mass is nervous system stimulation ( activation ).

Adipose tissue is also innervated by the nervous system, and this innervation ALSO seems to be critical for managing adipose tissue mass. Further, denervation of fat tissue increases fat pad mass and fat cell number ( 1 ). I didnt see anything mentioned about calories in calories out there btw....

Having recently brought myself up to date on the latest model we have for lipolysis, it seems that the current mainstream view of "insulin inhibits fat breakdown by stopping hormone sensitive lipase" is actually VERY crude and sketchy. The truth is its wwaaaayyyyy more complicated than that.

The latest model of lipolysis involves atleast 3 different enzymes. Triglyceride inside fat cells is trapped inside a lipid droplet. To begin lipolysis, the triglyceride is first acted on by an enzyme called adipose triglyceride lipase ( ATGL ) , this converts it to diglyceride, which is 2 fatty acid molecules attached to glycerol. Once its a diglyceride, ATGL becomes useless and we next have to make use of our old friend hormone sensitive lipase.

HSL is responsible for further chopping the diglyceride into monoglyceride, after which it is acted on by another enzyme to finally break it down into fatty acids + glycerol. The twist in the tale is that HSL is actually under neuroendocrine control. HSL activity is low until stimulation of the fat cell by the nervous system. And norepinephrine is the signal molecule acting via the nervous system.

So basically, HSL is not only negatively regulated by insulin, it is also positively regulated by norepinephrine. And surprise surprise, obese people have low rates of HSL activity via norepinephrine stimulation ( 2 ). By the way, women with PCOS also have reduced HSL activity, although it doesnt appear to be as bad as in obesity.

But this brings us back to the serum FFA paradox, if obese people have low rates of lipolysis via low nervous system stimulation of HSL, why do they have increased circulating FFA?

As I said, its a paradox.

The bottom line and point im trying to make here is that, fat tissue mass is principally controlled by nervous system stimulation just as is muscle tissue mass. I also personally speculate that, just like muscle tissue mass will grow to extreme levels without negative feedback from Myostatin, fat tissue mass will also grow to extreme levels without negative feedback from X.

What is X? fuck knows lol. Let the so called medical industry figure it out, its not my job, im just an average guy who works in I.T.

But, if you really want my opinion, I think that MC4R is a big part of X.

MC4R also acts on fat cells via the nervous system ( 3 ). It was slightly painful to read in that paper that "pale skin" was associated with mutations in the neuroendocrine system, as I have been "slightly" chubby my entire lift and also suffer from pale skin. It is very white, and I NEVER EVER tan in the sun, no matter how long I spend in it.

Insomnia & Ketosis revisited

Sleepiness after a meal or postprandial somnolence as its called, is interesting. I have always lamented at how if I could just get that deep sleepiness feeling right when im suppose to go to bed, things would be ssooooo fucking awesome!

Everyone knows that "carby" meals make you sleepy, but it doesnt work with 100% consistency. Sometimes carby meals dont have any affect on me at all. What I have noticed is that usually for a meal to make me sleepy, it needs to be 1) large & carby , and 2) the first meal of the day, breaking an extended fast.

Theres been a number of studies showing that exercise in the morning helps one sleep at night. And theres an interesting thing on that wikipedia article about the large neutral amino acid transporter. Wikipedia says that one of the possible explanations for postprandial somnolence is insulin stimulating BCAA uptake into skeletal muscle, but NOT tryptophan, thereby leaving tryptophan as the more abundant amino acid in the blood, giving it exclusive access to the transporter. ( apparently under basal conditions all the amino acids 'compete' for transport into the brain )

The result of more insulin is more tryptophan into the brain -> more seretonin -> more melatonin in the brain.

During my "socially defiant" days when im doing a more high-carb diet, I notice that I sleep much more deeper and longer than compared to when im on ketosis and lowcarbing. Also, now and then, I watch some of durianriders videos for a good laugh, and one thing he boasts often about is how he gets 12hrs of sleep at night followed by some gibberish mumble that "carbs = brain seretonin". Another thing that durianrider is fanatic about is dates. I couldnt help but notice wikipedia has this little gem on its tryptophan page "It is particularly plentiful in dried dates"

hhhhhhmmmmmmmmmmmmmmm

This could all be rubbish as im speculating here, but when lowcarbing, the only time you spike insulin is with protein heavy meals. But heres the crux, during such a meal, you also spike plasma amino acids. So when lowcarbing, you always spike insulin and plasma BCAA together, thereby never giving tryptophan a selective advantage at getting into the brain via the large neutral amino acid transporter.

Besides, how exactly does tryptophan get into the brain anyway?

What if the large neutral amino acid transporter is the only way it can get in?

Does that mean on a lowcarb diet, tryptophan is ALWAYS fighting with the other amino acids for entry, because your always spiking insulin and plasma amino acids simultaneously? Is it even worse if your never exercising and never making your muscles more insulin sensitive?

Here is exactly where the exercise anecdote comes in, exercise makes your muscle insulin sensitive, and insulin only drives tryptophan's competitors into muscle, not tryptophan itself! This explains why exercise in the morning is affective for sleep, because if you exercise in the morning, its generally before any food intake. So if you exercise in the morning, you get insulin sensitive muscles ready for the next meal to suck up all those serum BCAA, leaving tryptophan alone in the blood to enter the brain uninhibited.

Ofcourse, exercise need not be necessary, the other spin-off to this argument is that while lowcarbing, it might be good now and then to spike insulin without spiking plasma amino acids. And what better way to do this than a bag of dried dates? ( since dried dates are a good source of tryptophan ). Another good thing about dates is that they do not contain any starch, its mostly more complex carbs like sucrose/fructose, so the assault on your blood sugar will be more timid.

So heres my conclusion, if your lowcarbing and having difficulty sleeping, try having a bag of dried dates now and then, have them ON THIER OWN, not with any other food. Dried dates are not hyper-palatable, I can usually only get through about 130grams ( 88g carbs ) of them before my body tell me "hey fat dude, thats enough!" and I push the bag away. And im usually a big eater aswell.

Epic Obesity Rant

Following on from our "basal energy expenditure failing to predict obesity" post, it seems the same author has written what I can only describe as an epic rant towards the medical industry. It makes for a fantastic read and is well worth 1-2 hours of your time, however towards the end it becomes slightly disappointing as the author converges to the solution of obesity being a "low-fat" diet since his argument is that the body strives to maintain substrate balance and not energy balance per se.

This is because of the observations made in carbohydrate overfeeding studies whereby they generally do not produce significant increases in de novo lipogenesis, and it is therefore wrongly concluded that only dietary fat can contribute to adiposity. Ofcourse, this presents a paradox, as the thing we measure, de novo lipogenesis, does not translate into the phenotype we observe, adiposity, because many people following a ~5% fat vegen diet still manage to produce significant increases in adiposity. This is the fallacy of the above overfeeding study, I can only wonder what the above study would have shown if they had measured changes in adiposity.

Problems in applying the energy balance concept

The author makes the argument that the energy balance theory...

Energy Balance = Energy Intake – Energy Expenditure

fails to consistently predict not only changes in adiposity for every individual, but fails to explain the level of adiposity at which they become weight stable. Most obese people are actually weight stable, but it is at a higher level of adiposity. It should be obvious that, like most things in biology, adiposity is trapped in and regulated by a negative feedback loop ( 1 , 2 ). The only way to successfully change adiposity levels is to change the equilibrium or "middle" point that the feedback loop operates around.

A good analogy is seen with water and drinking. Drinking more water may increase our short-term water balance, but in the long-run we just end up pissing it all out again. And it works in the same way in the negative direction too. For how long can you dehydrate(calorie restrict) yourself for?, before thirst(hunger) becomes overwhelming? - thanks for this notion sidereal :P

The misleading emphasis on the importance of low resting metabolic rates

As we saw previously, BMR does not predict adiposity, the author also makes the point that stature ( height ) which is positively correlated with energy expenditure also does not predict adiposity. This is quite blatently true, I know many tall people who struggle with bodyfat as much as anyone, and I know just as many small people who remain skinny while eating junk food diets.

The author also mentions that things like futile cycles and uncoupling proteins do not make significant contributions to energy wastage that can change levels of adiposity. I personally have seen first hand hundreds of rodent studies showing all sorts of manipulations with UCP's, and various other enzymes/proteins that produce dramatic changes in adiposity, however none of it seems actionable or practical for humans.

News Addiction

I found this on housepricecrash.co.uk

1.News is predominantly negative. Which headline gets your attention: “Another blissful day” or “Murderous rampage on the subway”? In order to keep you plugged in, news has to shock you out of your complacency. In practice that means it usually has to scare or worry you. News’ primary marketing method is fear.

2.News is addictive. If you’re a daily news junkie, try giving it up for 30 days, and you’ll see what I mean. Even when I just planned to quickly scan the headlines, I’d often get sucked into reading sensationalized articles that provided no real value.

3.News is myopic. News provides the illusion of completeness, but in truth its coverage is ridiculously narrow. There are many fascinating happenings in the world that never make the news. After getting your daily update on current events, you think you know what’s going on in the world. But with billions of people on this planet, you’re sorely mistaken. You don’t have a clue.

4.News is marketing. Think this; don’t think that. Fear this; worry about that. Yes, yes, we’re all gonna die. Make me feel afraid, so then I’ll buy the sponsors’ products to feel better. Global warming won’t seem so bad when I’m driving my new car and popping my anti-depressants. Pump me full of fear; then sell me the cure.

5.News is shallow. Complex topics are reduced to sound bites and simplistic platitudes. Even the “in-depth” stories are unbelievably shallow. Skip the news and read books instead.

6.News is untrustworthy. Start looking for the political and corporate agendas behind the stories, and you’ll see them oozing out of every nook and cranny.

7.News is thought conditioning. Here’s how to think, so you’ll fit in like a good little human.

8.News is trivia. What passes for important is actually far from it. How much of today’s news will you remember next year? Can you even remember last month’s news? Your brain discards the news because it’s trivial; what you internalize is the fear-based conditioning.

9.News is redundant. Most news stories are repetitive, redundant, and say the same things twice. Very few stories are actually fresh and new. News should really be called “olds.”

10.News is irrelevant. How many news stories are relevant to you personally? Virtually none.

11.News isn’t actionable. How many news stories are actionable for you right now? Less than none.

12.News is problem-obsessed. The news loves to report problems. It will tell you all the things that are wrong in gory detail. How many of those problems have you actually solved? Which ones are you hard at work solving right now? The news conditions you to worry about problems but not to actually solve them. That’s because you’re encouraged to worry about unsolvable problems and then buy the sponsors’ products to assuage your fears. Drop the news for a while, and you’ll find you naturally spend more time solving problems than worrying about them.

13.News is a waste of time. Try to quantify your real gain from news consumption compared to other activities, and you’ll see just how worthless it really is. 10 minutes of news checking per day = 61 hours per year. Over a 50-year period, that’s huge. If you consume 30 minutes of daily news, it’s 183 hours per year – about 23 eight-hour days. That’s a full working month out of every year. Yikes! Was your last year of news consumption worth that much to you? How about a month long vacation instead?

Stevia - can it help with Hepatic IR?

A recent study has put forward the proposal through experimental verification that indeed Stevia may help with hepatic IR by lowering the enzymes responsible for glucose production.

The main enzymes involved in hepatic glucose production are....

• Glucose 6-phosphatase ( G6Pase )
  
• Phosphoenolpyruvate carboxykinase ( PEPCK )
• Pyruvate carboxylase
• Fructose-1,6-bisphosphatase

The last one, Fructose-1,6-bisphosphatase ( FBPase ), seems to be a strong likely suspect for increased hepatic glucose production. Claims have been made that the first 2 enzymes on our list, G6Pase and PEPCK are not responsible for the increased hepatic glucose production seen in diabetes and hepatic IR.

Further incrimination comes from a 2001 study looking at Metformin's actions on the above 4 enzymes. They found that metformin decreased both endogenous glucose production and alanine gluconeogenesis, there was a strong association bewteen alanine gluconeogenesis and FBPase levels, and metformin was able to reduce hepatic FBPase levels by a whopping 50%! Importantly, they did not record any significant changes in the other gluconeogenic enzymes.

So..... it looks like all fingers are pointing firmly at --> Fructose-1,6-bisphosphatase <--

Evil bitch!

Sadly I dont have access to the full text of the stevia study so I cant really disect the meaningfulness of thier conclusions, but if stevia works by Fructose-1,6-bisphosphatase reduction that could be good news. Not only is FBPase involved in hepatic glucose production however, it may even have an affect on adiposity.

Right now I cant help but think that increased hepatic glucose production leads to increased fasting glucose oxidation and thus gets in the way of fat oxidation in the fasting state. This was somewhat alluded to in the gnolls.org post here.

This study looking and respiratory quotients brings up an interesting conclusion....

a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

That "independent of low energy expenditure" part is interesting, something we learnt about in the last post. About how basal energy expenditure is not related to adiposity, well, that seems to agree with the independent thing mentioned above.

Does basal energy expenditure predict obesity?

The answer appears to be a resounding, NO. What we can clearly see from the below picture is that there is no obvious relationship between adiposity and basal energy expenditure.

It can be concluded that relatively high or relatively low rates of BEE do not influence body weights and adiposity in a statistically identifiable manner. This contradicts and challenges the widely held view that low resting metabolic rates promote the development of obesity

Back to the brain again!

I feel like this whole metabolic syndrome thing is going around in circles sometimes! This paper touches on some of the key points that Lustig makes in his speech's, the paper is very information dense so I have highlighted the important points below.

• WAT dysfunction is characterized by the inability of WAT to store lipids or restrain lipolysis in the fed state, and results in elevated circulating FFAs
• insulin and leptin are the main endocrine adiposity signals in mammals
• The hypothalamus orchestrates nutrient partitioning and appetite depending on the signals it gets from leptin and insulin
• diabetic patients started on insulin tend to gain weight
• leptin administration reduces adiposity in leptin deficient rodents and humans
• Whole body insulin receptor knockout produces a significantly lower level of fat mass than adipocyte insulin receptor knockout only
• brain insulin signaling plays a pivotal role in preserving fat mass and retaining FFAs in WAT
• effects of leptin are mediated primarily via signaling in the brain
• Re-constitution of neuronal leptin receptors completely reverses the lipotoxic, dysmetabolic phenotype of leptin receptor deficient db/db mice. Conversely, deletion of the peripheral leptin receptor in mice but not the brain results in no obvious dysmetabolic phenotype or alterations in adiposity indicating that brain leptin signalling is the only important thing when considering fat mass

Brain regulation of WAT mass by leptin and insulin

• reducing neuronal leptin receptor levels by 50% in mice results in increased fat mass, while food intake seems not to be affected [56]. ( so much for calories in calories out )
• leptin stimulates lipolysis by increasing sympathetic nervous system outflow to WAT
• chronic intracerebroventricular insulin infusion can increase fat mass in mice without affecting food intake
• insulin infusion into the mediobasal hypothalamus acutely restrains lipolysis in rats, as assessed by WAT triglyceride hydrolase activity and HSL activation state, by reducing sympathetic nervous system outflow to WAT

Lipolytic flux from WAT drives hepatic gluconeogenesis

• FFA levels closely correlate with hepatic glucose production, independent of systemic insulin or glucose levels
• combined knock-out of leptin receptors in Agrp and Pomc neurons has an additive effect resulting in an approximately 30% increase in adiposity despite equal food intake
• brain leptin signaling in both Pomc and Agrp neurons plays an important role in the regulation of adiposity
• only Agrp insulin receptor knock-out mice, but not Pomc, fail to suppress hepatic glucose production during hyperinsulinemia ( hmm interesting! )

Protein and Insulin secretion / AUC

A study looking at the various affects of different protein sources on insulin and blood glucose. The protein sources were Tuna, Egg white, Turkey, Whey.

Whey was very effective in lowering blood glucose, with fish a very close second. The sharp drop in blood glucose would almost certainly be accompanied by a strong surge in glucagon. Not surprisingly, Whey also produced the most vicious insulin spike, much higher than all the other protein sources. However at 180 mins after the meal all insulin levels were essentially back to baseline for all the protein sources.

In a buffet meal following the protein test meal, the subjects consuming the whey protein consumed the LEAST calories in the buffet, and the whey protein group reported the highest degree of satiation. Egg white was the least satiating protein, and compared to whey, it actually produced a slight rise in blood glucose before causing it to dip, unlike whey which seemingly only produced a strong dip in blood glucose.

This study was done in lean healthy people, but what it highlights yet again is that calories DO NOT COUNT.

Whats counts is HORMONES

If calories were all that mattered, the test subjects should have all consumed roughly the same amount of calories at the buffet.

U.S. government buys Hollow Point Bullets by the millions!

This is one of the more scary stories to come out, that is related to the impending economic apocalypse. The article makes a very good point, why is the US government buying 450 million of these expensive bullets? You dont buy expensive weaponary unless you *feel* as though there made be a need for it.

The article also mentions record firearm sales across all of america. As if everyone knows about the coming apocalypse and is preparing for it. Is the US government aware of the mess it has created? The mess whereby they have allowed many women to breed large dysfunctional families because it has supported them with welfare ( by money printing ) in hopes for a return in the future by getting extra votes? The whole situation stinks.

With this mass bullet purchase, does the US government now prepare to *put down* the wild animal it has helped raise?

Daily I have my eye on the financial markets and everytime I see Gold surging up I get slightly worried. Its only a matter of time before the government starts printing more money to fuel thier grand welfare scheme. 50% of the working peoples taxes goes to welfare!!!!! fifty fucking percent!!!!! Politicians will ultimately only do what protects themselves, not the rest of us. Trust is fragile in the free market, this is such a valuable lesson I learnt from playing in PvP realms in World Of Worldcraft. Strike first and strike hard.

Urgh, maybe I should lay off the Cabergoline, it just makes me a anxious nervous wreck.

Serum FFA paradox

This paper makes for a good read summarizing all the FFA stuff.

For whatever reason, high serum FFA promotes insulin resistance, BUT.... and heres the important point, NO-ONE knows why this is currently. This is highlighted in the paper, at present, we have ONLY theories as to why it happens. If you ask me, its certainly nothing to do with "energy excess".

As I understand it, cells are ALWAYS in energy excess, they always have far more substrate floating around than what can actually be used. IF this was NOT true, then it would not be possible to fatally overdose on Dinitrophenol.

Something strange I have observed is that while taking Niacin, during the initial phase when my serum FFA drops, I actually feel VERY energetic.

But this is counter intuitive, if Serum FFA drops, I should in theory have less energy because I have less substrates for making energy. But this is complete opposite to what happens, when serum FFA drops, I feel MORE energetic, not less, thus that theory seems to be wrong. Lowering serum FFA increases insulin sensitivity aswell.

Further, 80 minutes after the niacin oral dose, when serum FFA shoots up and peaks, I actually start to feel tired and subdued!. Sometimes its so bad I have to lay down and take a nap! All the while I have MORE substrate available.........This is the paradox.

The only conclusion here is that high serum FFA reduces energy expenditure. THIS is also able to explain why we get insulin resistant during high serum FFA. Ofcourse one could argue that perhaps its the affect of Niacin acting on the GPR109A receptor. I also get very energetic in deep ketosis, which is associated with activation of this receptor.

Niacin Scam?

This review offers alot of good information about Nicotinic Acid aka Niacin.

Niacin was something I had to re-visit in my quest to unlock the secrets of bile acids on metabolism. Niacin has long been reported to have positive affects on cholesterol,

whats that?

No Im not talking about those stupid numbers you get from lab blood test results that are suppose to be some kind of predictor of cardiovascular mortality risk, no. Im talking about this Cholesterol. Look at the molecular structure of Cholesterol for a second, notice something fishy? Its looks a bit like the sex hormone estrogen. Or, what about the sex hormone testosterone? EH? What about bile acids? AHHHHH, wait a second, they do all look familiar!

Yes, its because Cholesterol, sex hormones, bile acids, and probably many other important signalling molecules are all actually built from the same backbone, the molecule of steroid. It seems that molecules built from this same steroidal backbone are used by many organisms as hormonal signalling molecules, including plants and fungi. Infact the stuff in Holy Basil, Ursolic acid and Oleanolic acid also have the steroid backbone, so that means they are most likely plant hormones.

BTW, does this mean bile acids are infact hormones? YES!, ( if you ask me. )

Anyway, back to Niacin. So what does it do exactly? It blocks lipolysis, and it makes your skin burn bright red. AKA, the niacin flush. It also lowers LDL, vLDL, the blood test numbers that put the shits up doctors arses.

But perhaps more importantly, it raises HDL. Im not gonna be talking about the LDL stuff today. Its boring.

HDL, or High-density lipoprotein is not actually Cholesterol, it is a lipoprotein as its name suggests, its used to carry lipids in the blood because the blood is water-soluble and not fat-soluble. The function of HDL is to carry Cholesterol to the liver for conversion into bile acids! Bingo!, So to increase our bile acid pool size, having a high HDL number is probably something we want. A large bile acid pool size increases our incretin affect. All this is good stuff you know.

But HDL also takes Cholesterol to the ovaries/testes for conversion into sex hormones! More good stuff! Estrogen is something that girls want, and testosterone is something boys want. So having a high HDL is likely to support our sex hormone production. Ofcourse just because we are delivering more Cholesterol to the sex glands, it doesnt automatically mean our sex hormone production will be higher.

However, here is something to think about, Health, Sexual Attractiveness, and Fertility, are all intimately linked. Healthy people are also generally more sexually attractive. And probably more fertile too. I cant help but wonder if HDL is a good predictor of the hip:waist ratio in women, the hip:waist ratio that men use to decide female sexual attractiveness. Perhaps the same is also true for men, women display a preference for the V torso shape in men, that is, wide broad shoulders and chest, along with a lean robust waist.

In both cases, waist health/slenderness is a pretty good predictor of sexual attractiveness. IS that because waist health is also a good predictor of HDL?

Ok back to the review paper. How does Niacin block lipolysis? It acts on the GPR109A receptor. So atleast 50% of the good stuff that niacin does is mediated by this receptor. But as mentioned previously, this receptor has a natural endogenous ligand, beta-hydroxybutyrate. Yes thats right, the stuff you get on a ketogenic diet, ketone bodies. So chances are, anything good that niacin does through receptor GPR109A binding is probably also done by beta-hydroxybutyrate.
The good stuff includes lowering LDL, raising HDL, and treating atherosclerosis.

But why would beta-hydroxybutyrate block lipolysis? Well, its part of the negative feedback loop between liver ketone production and lipolysis. This has to be controlled within a tight range to avoid ketoacidosis. When serum ketones are high, GPR109A blocks lipolysis to avoid further increases in serum ketones, which would result in acidification of the blood. Meanwhile, when serum ketones are low, GPR109A binding is low, allowing significant lipolysis for ketone production.

Opps, whats that your saying? We cant make ketones? Why? Oh , because we have high insulin?! Yes, we have hyperinsulinemia, WHY? Oh I see. Damn that paleo baked potato. Throw it in the bin next time Jim.

This bring me to another point, a certain blogger by the name of C***S*** has been fond of promoting the theory that high levels of circulating FFA is a significant contributer to whole body insulin resistance. And when you look at the pubmed papers, this is mostly true. The blogger in question mentions that this is because lipolysis is high, indicating that insulin is failing to do its job of surpressing lipolysis and trapping FFA in fat cells. The implication is made that high levels of dietary fat promotes high circulating FFA levels and thus promotes whole body insulin resistance and consequently glucose intolerance.

But who says that supression of lipolysis should fall solely to the role of insulin? Did you ask your fat cells this? Did they reply with "yeh, im only suppose to listen to insulin dude".

How the fuck do you know what natures design is? Maybe, just MAYBE, serum ketones AND insulin are suppose to work together to suppress lipolysis? MAYBE the problem of high circulating FFA promoting whole body insulin resistance IS because lipolysis in fat cells is too high, but maybe its also because we've been stuffing too many healthy low reward potato's down our throats, and raising insulin so much that liver ketone production vanishes into a myth, whispered only by fools.

This leaves little old insulin on its own to suppress fat cell lipolysis. And it seems without big brother beta-hydroxybutyrate to back him up, hes just a push-over.

BTW, the resolution of this is not to lower fat intake and eat more carbs. MAYBE Insulin is a wimp on his own. Getting more wimps into the fray aint gonna help you.

No

The resolution is to stop eating insulinogenic foods, let insulin come down, and let the liver finally breath some fresh air and make some ketones! Let it churn out the big bad boy in town, beta-hydroxybutyrate.

Then again, maybe I'm an ignorant moron who doesnt know anything.

Now, where was I? Ok, on the topic of GPR109A. IT seems with an oral dose of Niacin, the resulting suppression of lipolysis is SO strong that serum levels of FFA fall significantly that they actually sharply rebound some 80 minutes later, the rebound is so strong that serum FFA shoots up and peaks at about 40% above its initial starting level. It then slowly falls off and gradually returns to its baseline level after about 4 hours. If , during this period, some clown attempts to make you drink a solution of free glucose molecules for an OGTT ( oral glucose tolerance test ), you will, ofcourse, fail.

This is an affect of high serum FFA promoting IR and is why Niacin supplementation is associated with blood sugar disturbances. WELL, its only associated with blood sugar disturbances if you like cereal for breakfast, sandwhichs for lunch, and potato's for dinner.

Us ketogenic diet practitioners wont be having any disturbances, my friend. ( ok seriously, if your gonna supplement Niacin, dont eat any carbs for atleast 4 hours after, youll be largely glucose intolerant during this time )

And why do serum FFA sharply rebound? Its because of the negative feedback loop thing again. I found out several years ago that things that cause rapid drops in serum FFA also cause rapid bursts of human growth hormone secretion. Amoung the many things growth hormone does, is increase lipolysis. The growth hormone spike after an oral Niacin dose is infact well documented.

OK OK, so what am I getting at?? is Niacin supplemention worthless if your on a ketogenic diet? Well, not completely. It seems that atleast 50% of the benefits of Niacin supplementation comes from the effects of the skin flushing. So all you wimps out there taking your slow release formula's are missing a good portion of the important stuff. It seems the skin flushing has the added benefit of producing endogenous ligands for PPARγ. By the way, when someone mentions PPAR, you need to sit up and pay attention, these receptors are important. Have a look at the Clinical relevance section in the wikipedia article linked there.

I couldnt help but laugh when searching pubmed for Niacin, most of the researchers and medical people are pretty much coming straight out in thier papers and saying that Niacin supplementation is an incredibly effective treatment for atherosclerosis, but its not a "practical treatment" because your glucose tolerance is reduced ( solved by low-carbing ) and that people exhibit poor compliance because of the skin flushing ( solved by not being a wimp ).

No, it seems people are much happier sitting in thier corners, stuffing thier faces with carbohydrates all day and handing out thier money to the drug companies. In a most sickening display, reading the pubmed papers it seems all of the researchers appear to be literally falling over themselves looking for Niacin mimicking drugs and agonists that do the same function, but that dont cause skin flushing and allow you to still have bagels for breakfast.

You see, the medical establishment is not interested in your health, they are interested in making a drug discovery, selling it to the drug companies, then living a life of luxury in Thailand shagging young thai girls. Thats what researchers dream of at night.

They are interested in emptying your bank accounts! Not saving your life.

They cant just come out and tell everyone, "hey, go low-carb, take niacin, and man up when flushing". Theres no profit to be had there!

Now just to be legal, I am not offering medical advice here, BUT if I had a problem with atherosclerosis, I would first, read the paper I linked in the beginning of the article, make my own conclusions, then I PROBABLY would go low-carb, supplement 700mg niacin 5x per week ( the flushing type only ), and make sure I get plenty of K2 Mk-4 in my diet from egg yolks, grass fed dairy fat, beef liver. I would also try to lose some weight, visceral fat is a good place to start.

Lastly, I think theres some good things to be had from raising HDL, the research paper mentions that high HDL is a far far better thing to have when trying to avoid heart attacks, then just simply lowering your LDL, ( if that has even any benefit at all )

Things to increase your HDL

• Go low-carb
• Niacin supplementation
• Weight loss
• Mild to moderate alcohol intake ( one has to wonder if this only works because ethanol is metabolised into ketones )
• Consumption of omega-3 fatty acids
• Stay away from vegetable oils
• exercise
• Magesium supplementation
  

Metabolic Syndrome Solved?

The study I found in the previous post has really got me thinking, if triglyceride accumulation in tissues is not the cause of insulin resistance, then what is? I had to go back and re-read Peters LIRKO posts aswell as all the comments. After reading it all again it suddenly hit me, Hepatic IR is almost certainly the "cause" of metabolic syndrome. If insulin cannot suppress hepatic glucose production during an oral carbohydrate load, then you are diabetic.

There is a strong trend between obese/diabetic people that they preferentially continue oxidising fat even in the face of an oral glucose load, and this ties in with IR. Insulin resistance is basically the cells way of saying that it is not interested in accepting glucose for oxidation at this point in time. Sorry, but its busy oxidising fat. Guess what though, peripheral IR and hepatic glucose production are also associated with something else. The fasting state.

Call me crazy, but it almost looks like the problem is that obese/diabetic people simply have an issue with transitioning from the fasted state into the fed state. More on this in a bit.

So what CAUSES hepatic IR? Most people would jump on the fatty liver bandwagon at this point, the study in the previous post is very good evidence that it is NOT the cause however.

Still not convinced?

Well have a look here, the authors of this paper manipulated malonyl-CoA to allow enhanced fatty acid oxidation at the mitochondrial level, and this was sufficient to reverse IR without any significant change in fatty liver. So now it looks like IR is mediated by something going on at the mitochondrial level. Also, look here, The title almost says it all....Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis

So obesity/diabetes just means you have fucked up Liver mitochondria? I don't believe that. The fact that we have many rodent studies showing alleviation of IR with various interventions hints that perhaps the mitochondria are not on their last leg, but rather, they just aint getting the correct messages. Theres just a simple breakdown in communication somewhere. Perhaps.

I think now we can see why low-carb is so effective and important for metabolic syndrome sufferers, it bypasses most of the hepatic IR problem. I.E. it avoids dietary induced hyperglycaemia. It avoids exposing your periphery to an onslaught of glucose from both the Liver and the digesting meal. In addition, the more glucose you have flooding into your blood from the Liver and the digesting meal, the more insulin you will be secreting to deal with that glucose.

You see, beta cells secrete insulin in response to glucose exploding in their cytosol, Peter@Hyperlipid has already told us that the Liver is the main destination for dietary glucose, aswell as the main site for insulin degradation. So my guess is that having an even slightly IR liver could cause MAJOR increases in blood sugar and serum insulin, both from an inability to suppress hepatic glucose production and because insulin degradation in the liver is reduced.

Enter the fat cell!

With all the excess blood sugar and insulin swimming around, it has to go somewhere. Either it doesnt go anywhere, and you are therefore diabetic, or your fat cells suck it all up, and your not a diabetic. The ability of your fat cells to suck up all the excess insulin and glucose will determine how fat you can ultimately get, and ofcourse at what weight you will develop diabetes.

If your fat tissue is happy to expand and remain insulin sensitive forever, you will never get diabetes but each carbohydrate meal that you chug down will put you one step closer to entering the guinness book of records as the worlds most obese human. Alternatively, if your fat tissue is not happy with expanding much, youll get diabetes while being still relatively thin.

I am not sure what exactly determines fat tissue expansion capabilities precisely, certainly genetics will play a role. Oh and, in addition, ItsTheWooo pointed out in a comment in one of the Peter's post that hyperinsulinemia not only blocks fat breakdown, it also slows fat oxidation, so now we also see why obese people are lazy and tired.

I think now I finally understand why I have such a problem with tubers/rice VS fruit/honey. Simple carbohydrate meals containing lots of generic glucose molecules as opposed to other forms of more complex saccharide will storm past the insulin resistant liver just minutes after ingestion and cause incredible insulin secretion, and my fat cells will be more then happy to mop it all up. Cheers. So yes people, Glycemic Index MATTERS!

Phew, still with me so far? Ok, just a bit more....

Before I was talking about how obese/diabetic people appear as though they simply have difficulty transitioning into the fed state from the fasted state. Whats the difference between these two states? Remember, there is no receptor for calories. The difference is the Incretin affect! The incretin affect is the FIRST way that your body reacts hormonally to the food that you eat. All subsequent hormonal affects should just be downstream of the incretin affect, so if the incretin affect is not working as it should, chances are the rest of your metabolism wont be either.

We have already seen how obese people secrete less GLP-1 in response to carbs than lean people, they also secrete less bile acids than lean people. Opps, us fatties are not doing so good so far!

Its worth noting that one of the most effective treatments for morbid obesity is the roux-en-y gastric bypass, which significantly enhances both GLP-1 secretion and bile acids. Further, this surgery is able to almost completely reverse diabetes very shortly after operation, before any significant weight loss is achieved. However at this point this fact should NOT be surprising because as we established earlier in the post, cellular triglyceride content does not have any impact on insulin resistance.

Wouldn't it be nice if we could fine some link between GLP-1 and hepatic function? Well, if incretins and GLP-1 are so effective, why dont roux-en-y patients completely reverse their whole obesity and diabetes and return to being normal lean healthy people? The incretin system seems to play more of a role in post-prandial energy expenditure is the most likely explanation. In that study, they noted mice were able to consume significantly more food ( 25%-70% ) and yet not gain excess weight.

In this review , they talk about the first wave of incretins being released before any significant digestion or absorption of calories is done, indicating that the nervous system is likely key player in the incretin response. This brings me to this paper, it seems GLP-1 is present in the brain aswell as the gut, and brain GLP-1 signalling may be the most important of all.

Activation of central GLP-1Rs contributes substantially to the inhibition of endogenous glucose production

Ah Ha! Inhibition of hepatic glucose production! Thats EXACTLY what we want after eating a potato.

Lastly, heres one last and recent study confirming that GLP-1 signalling in the brain improves hepatic insulin sensitivity.

Summary

• Metabolic syndrome is primarily hepatic insulin resistance
• Fatty liver does not significantly contribute to hepatic IR
• Mitochondrial dysfunction seems to precede hepatic IR and fatty liver
• The more hepatic IR you have, the more glucose intolerant you are
• Obese/diabetics have difficulty transitioning from the fasted state to the fed state, which seems to be mainly driven by a poor incretin response.
• If you have hepatic IR, fat tissue keeps you out of diabetes if it has the ability to expand and make you obese.
• Insulin performs the same function in fat as it does in muscle, i.e. it makes them bigger.
• Low-carb is effective for Metabolic Syndrome because it reduces postprandial glucose momentum into the blood
• In Metabolic Syndrome, the worse foods are those containing large amounts of simple glucose molecules that enter the blood stream quickly. I.E. high glycemic index foods.
• Hyperinsulinemia doesnt just reduce fat breakdown, it inhibits fat oxidation
• The CAUSE of hepatic IR has not yet been pinpointed, although it currently looks like either mitochondrial garble or insufficient incretin action via the nervous system.

Stuffed with fat and insulin Resis..........Er Sensitive!

I havent seen this paper discussed before. You know all those theories floating about how stuffing cells full of fat makes them insulin resistant, well its obvious why! Because of excess energy availability! Duh.

Wrongggggg!

Once again we see a perfect example of how humans are just in general wrong. Much more often than not. The more you observe and measure something, the more likely you are to be wrong, atleast in mind and theory. Is there any wonder why trading is so hard, the more you look at the charts the more likely you are to be wrong.

Anyway, in this paper the researchers deleted the Adipose triglyceride lipase gene in mice, this is an important enzyme for the breakdown of triglyceride, and without it, your FAT!.

These fat greedy little beasties had reduced energy expenditure, and massive stores of ectopic fat, I.E. massive stores of fat in other places other than adipose tissue, aswell as increased circulating free fatty acids ( compared to mutant ATGL -/- mice that were fed a low-fat diet ). This is certainly what most top doctors would call a "lipotoxic environment", and these greedy fat mice should be intensely diabetic. Theres just one problem...

They aint.

Nope, no siree! Infact they are more insulin sensitive than thier skinny chow fed litter-mates! Funny that. So, where are they more insulin sensitive exactly? Well, in the Liver, Adipose tissue, and heart.

Importantly, the researchers make the point that skeletal muscle was more insulin sensitive in vivo than ex vivo, suggesting that some circulating factor helps contribute to insulin sensitivity in skeletal muscle ( most likely Adiponectin ).

Here is the real kicker....

In fact, ATGL−/− mice fed a high-fat diet were more insulin sensitive than Wt mice fed a low-fat diet.

Thats it folks. Throw out all your biology and physiology text books. Thier all wrong.

Estrogen metabolism regulation

Given I am male and not a practicing doctor I generally know alot more about the androgens than the female hormones but I came across this study which made for a good read, I have bullet-pointed some of the more interesting quotes from the paper below.

The diversity of sex steroid action: regulation of metabolism by estrogen signaling.

• Estrogen is a major effector for the regulation of energy balance, body weight, fat distribution, and appetite (in mice )
• Ovariectomized mice display an increase in food consumption, decreased running wheel activities, and increased fat mass, which can be reversed with estrogen replacement
• Energy homeostasis and feeding behavior in the hypothalamus also follows the menstrual cycle, and food intake in women varies across the cycle with lowest daily food intake during the peri-ovulatory period when estrogen levels are maximum
• After puberty, estrogen modulates leptin synthesis and secretion
• In addition, raised levels of estrogens have been associated with increased leptin sensitivity in the brain
• Premenopausal women are more insulin sensitive with associated improved glucose tolerance, are more resistant to develop IR compared with men, and display increased expression of GLUT4
• Importantly, men with aromatase deficiency, who cannot synthesize estrogen hormones, display impairment in glucose metabolism and IR
• female mice have increased lipogenic capacities in adipocytes compared with male mice
• When circulating levels of estrogen are raised above the physiological range, adipose tissue metabolism is altered resulting in reduced lipogenic rates and fat depot size.
• This is further supported by epidemiological observations that serum triglyceride levels increase in postmenopausal women and that the level of LPL activity is reduced by estrogen treatment
• 17β-estradiol treatment suppressed the expression of lipogenic genes, i.e. fatty acid synthase (Fasn), stearoyl-coenzyme A desaturase 1 (Scd1), and glycerol-3-phosphate acyltransferase (Gpam), in livers of leptin-deficient Ob/Ob mice
• 17β-estradiol suppresses lipogenesis and TG accumulation in adipose tissue and liver in high-fat diet (HFD) fed and leptin-deficient female mice

Holy Basil - Gall Bladder Surgery - Weight Gain

Feeling much better and stronger now im back on Holy basil. I think its a under-rated fat loss supplement.

Holy basil contains the bile acid analogues oleanolic acid and ursolic acid which are potent agonists of the TGR5 receptor located in the small intestine. Activation of this receptor appears to be crucial for glucose tolerance, post-prandial thermogenesis and increased thyroid hormone T3.

Bile acids secreted by the Gall Bladder are not just things that help you digest fat, bile acids themselves are important signalling molecules, and are a critical part of the incretin affect. Serum bile acids are reported to be higher in Roux-en-Y surgery and could potentially assist in weight loss. The way its suppose to work is that after ingestion of food, bile acids from the gall bladder are secreted and help digest fats but some bile acids also go on to bind to the TG5R receptor help informing your body that youve been fed increasing post-prandial energy expenditure, ultimately helping you stay weight stable.

A search on google for weight gain after gall bladder removal yields many results and personal testamonials of people expericing rapid weight gain after surgery especially in the abdominal region. This is no surprise once you understand the science and the importance of the bile acid receptors.

I have blogged before on how obese people tend to have poor bile acid secretion after a meal, and a possible reason once again may be our old friend and foe, insulin. Insulin suppreses Cholesterol 7 alpha-hydroxylase which is apparantly is the rate-limiting step for bile acid synthesis from cholesterol.

Lastly, I briefly read somewhere before how the some strains for gut flora have the ability to modify and change the structure of post-meal bile acids. That probably needs more investigation though but it could just be another way the gut flora influence adiposity.

I would try to avoid having your Gall Bladder removed if you can help it.