Monday, 9 April 2012
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
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
