Long-term Treatment With Nicotinamide Induces Glucose Intolerance And Skeletal Muscle Lipotoxicity

[jyb]

He dosn't seem so concerned with SUFAs and says that they are healthful.

I never said the contrary (why would I? I live in Europe thriving on extra high fat diet.). However over the years he has followed and recommended different diets, one high and one low in fat. Niacinamide is to be taken in context of the low fat one and the citations above by Mitto. Niacinamide is well known to kill fatty acid oxidation - both pufa and sfa.

 

[Queequeg]

I never said the contrary (why would I? I live in Europe thriving on extra high fat diet.). However over the years he has followed and recommended different diets, one high and one low in fat. Niacinamide is to be taken in context of the low fat one and the citations above by Mitto. Niacinamide is well known to kill fatty acid oxidation - both pufa and sfa.

You are taking me out of context. My point on the SUFAs is that I have yet to see where Ray recommends Niacinamide only when on a low fat diet. That is your assertion, not Rays. I think Ray believes that Niacinamide's benefit is that it reduces FFA in the blood.
Here is just one of many quotes where he talks about this. If what you say is true he wouldn't recommend coconut oil while taking niacinamide and/or would say only take niacinamide while on a low fat diet. If you still believe otherwise then again please provide a quote from Ray that proves it.

"It's the stored PUFA, released by stress or hunger, that slow metabolism. Niacinamide helps to lower free fatty acids, and good nutrition will allow the liver to slowly detoxify the PUFA, if it isn't being flooded with large amounts of them. A small amount of coconut oil with each meal will increase the ability to oxidize fat, by momentarily stopping the antithyroid effect of the PUFA. Aspirin is another thing that reduces the stress-related increase of free fatty acids, stimulating metabolism. Taking a thyroid supplement is reasonable until the ratio of saturated fats to PUFA is about 2 to 1." RO

 

[whodathunkit]

This is simultaneously a great thread and a disturbing one. Sometimes I'm not the brightest light on the tree so the topic of niacin/niacinimide has been rather confusing for me as to why there's so much research that indicates it's beneficial, but it's such a dismal failure every time I try it. There's so much info scattered here and there that it's difficult to get to the pith of why it's supposed to be beneficial. This thread turned the light on for me and helped me understand it. So in that regard, it's great.

However it's disturbing because I now realize why it's such a failure for me and so many other people, and I believe it shouldn't be recommended as "easily" as it seems to be, without offering brief caveats on dosage and potential effects on metabolism. I'm trying to lose weight and am recovering my metabolism from crappy fat burning, which is why niacinimide isn't good for me. I see lots of enthusiasm over niacinimide, but not much about how bad it can be for people with some metabolic problems.

 

[whodathunkit]

"It's the stored PUFA, released by stress or hunger, that slow metabolism. Niacinamide helps to lower free fatty acids, and good nutrition will allow the liver to slowly detoxify the PUFA, if it isn't being flooded with large amounts of them. A small amount of coconut oil with each meal will increase the ability to oxidize fat, by momentarily stopping the antithyroid effect of the PUFA. Aspirin is another thing that reduces the stress-related increase of free fatty acids, stimulating metabolism. Taking a thyroid supplement is reasonable until the ratio of saturated fats to PUFA is about 2 to 1."

Thank you. More to think about. :)

 

[jyb]

Here is just one of many quotes where he talks about this. If what you say is true he wouldn't recommend coconut oil while taking niacinamide and/or would say only take niacinamide while on a low fat diet. If you still believe otherwise then again please provide a quote from Ray that proves it.

Notice he mentions a "small" amount of coconut oil. That is typically how he describes its use, it does not contribute much to beta oxidation for energy. Whereas your original list including fatty dairy and meat such as ice cream hints at a version of the diet where the fatty acids contribute to energy and are of a different nature (longer chains promote beta oxidation unlike short ones), serving a different purpose which seems at odds with that of niacinamide.

 

[Queequeg]

Notice he mentions a "small" amount of coconut oil. That is typically how he describes its use, it does not contribute much to beta oxidation for energy. Whereas your original list including fatty dairy and meat such as ice cream hints at a version of the diet where the fatty acids contribute to energy and are of a different nature (longer chains promote beta oxidation unlike short ones), serving a different purpose which seems at odds with that of niacinamide.

You are making the claim that Ray only recommends niacinamide for those on a low fat diet. I have yet to see anything close to him saying this and the above quote certainly doesn't say this. Again if you have some other info on this please provide it. I can't prove a negative.

 

[Tarmander]

Sometimes I'm not the brightest light on the tree so the topic of niacin/niacinimide has been rather confusing for me as to why there's so much research that indicates it's beneficial, but it's such a dismal failure every time I try it.

Ha this is like a description of every Peat Supplement I have tried, at least at first. Caffeine/B vitamins/ fat soluble vitamins/protein/calcium/raw carrot is great! I feel like crap on it!

 

[Agent207]

So in theory NAM should be a nice add to a preworkout stack, right?

 

[haidut]

So in theory NAM should be a nice add to a preworkout stack, right?

Pre- or post-workout, both should help. If it does indeed upregulate androgen receptors and sensitivity, and also increases fast twitch fiber numbers then taking alone or in combination with DHEA, androsterone, or even progesterone should work like as if a much more powerful steroid was used and thus amplify perormance. Don't think it would be anabolic, but it should increase strength and endurance.

 

[chispas]

Not really, no. The study found no change in weight between NAM group and controls. It also said that the accumulation of fat in the muscle is the tradeoff between staying lean and insulin sensitivity. So, the mice on NAM stayed lean at the expense of decreased insulin sensitivity. It's in one of the quotes from the study I provided.

I was under the impression that type II fast twitch fibres are actually "fast" while the body is in a glycolitic state. Once muscles get hold of too much glucose as metabolism upregulates to an oxidative state, the slower type I fibres take precedence in doing the work. Over time, as the fascia structure of the muscle changes, type II fibres can even change to become slow as well. I can find you the research on this if you're interested.

If B3 is putting fat into the muscle and giving precedence to type II fast twitch fibres, is it sensible to infer that it is undesirable to try to make the body's muscles use glycogen? To my mind, this can only result in big, slow-twitch, powerlifter-style muscles.

 

[chispas]

... sorry, and the reason type I fibres would be less desirable is because they have less potential to contract with a high velocity. I understand powerlifters don't care about velocity, but Olympic weightlifters do.

 

[nathan10000]

I thought the main purpose to take niacinamide is to reduce lipolysis but the truth is it actually increase lipolysis and at the same time reduce oxidation in the muscle which is a dangerous combination. It is shifting your TG from adipose tissue to the muscle but not to the liver. So you are just buying more time, the liver will compensate for the increased lipolysis but eventually it lead to fatty liver.

Niacinamide is worse than high fat diet, at least in high fat diet muscle try to adapt by increasing fatty acid oxidation whereas niacinamide you have lower oxidation in the musle.
"HFD significantly enhanced FA oxidation (Fig. 5D), suggesting an active response to diets in skeletal muscle."

Look at the conclusion.
"the present results suggest that long-term treatment with NAM, although at lower dose, leads to glucose intolerance and skeletal muscle lipid accumulation in mice fed regular chow."

Is it fine to take a supplement which ruins your glucose control and increase lipid in your muscle?

 

[Wagner83]

Would you say a very low fat diet would be mandatory to supplement with it? I don't get the glucose intolerance part since it inhibits FA oxidation and is supposed to ***t the metabolism towards glucose .

 

[nathan10000]

Would you say a very low fat diet would be mandatory to supplement with it? I don't get the glucose intolerance part since it inhibits FA oxidation and is supposed to ***t the metabolism towards glucose .

low fat diet wont help. the lipolysis is from adipose tissue. carbohydrate is converted to fat by gluconeogenesis. It doesnt inhibit FA oxidation but reduce it. The reduction will cause more lipid accumulation unless you are fine with looking chubby and prediabetic. Dont forget niacinamide will increase FFA too.

 

[nathan10000]

So in theory NAM should be a nice add to a preworkout stack, right?

Nope, you are ruining the benefit of exercise as there is reduction in oxidation. You want a preworkout stack that increase lipolysis and increase oxidation.

 

[nathan10000]

I just started on Niacinamide and now am confused. Why again is it beneficial to lower fat oxidation? I can see that for athletes that this may be good for increased performance but for someone on a normal fat diet (limited PUFA) wouldn't niacinamide just increase fat deposits.

ya, exactly increase adipose tissue

 

[Wagner83]

Great, thanks.



3. Insulin resistance or diabetes induced by high-fat diet (HFD) are quite different than the what NAM did even though both approaches are characterized by elevated glucose levels. NAM seems to increase blood glucose simply by shifting preference to glucose oxidation while the HFD induced by reducing mitophagy and autophagy (which were actually drastically increased by NAM). It also suggests that NAM could be an anti-obesity agent, potentially at the expense of reduced "insulin sensitivity" but the definition of such sensitivity is obviously problematic and can be quite broad and arbitrary. Finally, high fat diet and resveratrol induced fatty acid oxidation much like the recent studied with cancer and HFD found as well.


TLDR: If there is sufficient amount of fat in your diet, taking the HED of 7.5mg/kg NAM may cause some lipid accumulation in muscle but NO such accumulation liver. High fat diets generally causes both muscle AND liver lipid accumulation and the effects on insulin resistance by HFD and NAM are quite different. Also, NAM inhibits SIRT1 pretty potently even at that low-ish dose and as a result dramatically inhibits fatty acid oxidation (FAO), which shifts the fuel preference over to sugar. The drug Mildronate, with many proven benefits and performance enhancing effects, has the same overall metabolic effects minus the SIRT inhibition. The inhibition by NAM of SIRT1, FAO, and raising of NAD/NADH levels is likely to be very beneficial for a number of degenerative conditions including CVD, neurological conditions, cancer, autoimmune conditions, wasting diseases, etc. NAM may be helpful even as a drug for obesity at the expense of mild lipid accumulation in muscle.

What makes you say high blood glucose would be a normal consequence of shifting metabolism towards glucose oxidation rather than fat (even in muscles)?
How reducing fatty acids oxidation and increasing fat content in muscles would result in an "anti obesity" agent?

Again, at low doses niacinamide caused lipid accumulation and potently reduced FAO , so unless someone is lean and switches to a no fat diet I don't see why it would be beneficial to supplement with it.

To me it looks like a powerful tool that shouldn't be messed with unless someone has a very specific condition.

low fat diet wont help. the lipolysis is from adipose tissue. carbohydrate is converted to fat by gluconeogenesis. It doesnt inhibit FA oxidation but reduce it. The reduction will cause more lipid accumulation unless you are fine with looking chubby and prediabetic. Dont forget niacinamide will increase FFA too.

Ok but if it shifts the metabolism towards more glucose oxidation, your liver works well to store glycogen , and overall your body uses glucose efficiently I don't see why would you put on fat. It also sounds like FFA acids would increase if one consumes fat while supplementing with NAM

 

[chispas]

I thought the main purpose to take niacinamide is to reduce lipolysis but the truth is it actually increase lipolysis and at the same time reduce oxidation in the muscle which is a dangerous combination. It is shifting your TG from adipose tissue to the muscle but not to the liver. So you are just buying more time, the liver will compensate for the increased lipolysis but eventually it lead to fatty liver.

Niacinamide is worse than high fat diet, at least in high fat diet muscle try to adapt by increasing fatty acid oxidation whereas niacinamide you have lower oxidation in the musle.
"HFD significantly enhanced FA oxidation (Fig. 5D), suggesting an active response to diets in skeletal muscle."

Look at the conclusion.
"the present results suggest that long-term treatment with NAM, although at lower dose, leads to glucose intolerance and skeletal muscle lipid accumulation in mice fed regular chow."

Is it fine to take a supplement which ruins your glucose control and increase lipid in your muscle?

As I asked above, I'm not sure how much oxidation really happens in muscle compared to the rest of the body's metabolism. It stands to reason that fast twitch fibres should work in a reduced energy state, because they are not endurance muscles, they have brief but high rates of contractile output.

If your muscles needed sugar constantly, all strength would be lost as soon as glycogen was depleted. This evidently is not the case.

Niacinamide seems to be aiding the effect of getting more from less, by keeping the muscle in a reduced state where it starts to actually store fat for fast twitch contractions. I did not realise this was even possible. I thought the common explanation was that you had to train the fibres to become bigger in order to hold more glycogen and thereby become stronger. Perhaps this is actually inefficient.

I have witnessed first hand a friend resolve their advanced NAFL disease with 500mg niacinamide/day. I do not think it creates liver problems, research indicates the complete opposite.

 

[Wagner83]

If your muscles needed sugar constantly, all strength would be lost as soon as glycogen was depleted. This evidently is not the case.

Niacinamide seems to be aiding the effect of getting more from less, by keeping the muscle in a reduced state where it starts to actually store fat for fast twitch contractions.

Wouldn't the high blood glucose be explained by that need and the absence of glycogen in muscles?

Where did you get the idea that fat was used for the fast twitch contractions?

 

[chispas]

Wouldn't the high blood glucose be explained by that need and the absence of glycogen in muscles?

Where did you get the idea that fat was used for the fast twitch contractions?

I don't understand your first question, sorry.

The following quote is from an athletics website:

"Fast-twitch fibers are good for rapid movements like jumping or sprinting that require fast muscle contractions of short duration. Unlike slow-twitch fibers, fast twitch-fibers rely on anaerobic respiration (glycolysis alone) to produce two molecules of ATP per molecule of glucose. While much less efficient than aerobic respiration, it is ideal for rapid bursts of movement since it is not rate limited by need for oxygen. Lactic acid, a byproduct of anaerobic respiration, accumulates in the muscle reducing the pH (making it more acidic, and producing the stinging feeling in muscles when exercising). This inhibits further anaerobic respiration. While this may seem counter-intuitive, it is a feedback cycle in place to protect the muscles from over-exertion and resultant damage."

And:

"As fast-twitch fibers generally do not require oxygenation, they contain fewer blood vessels and mitochondria than slow-twitch fibers and less myoglobin, resulting in a paler colour. Muscles controlling eye movements contain high numbers of fast-twitch fibers (~85% fast-twitch)."



Source: Boundless. “Slow-Twitch and Fast-Twitch Muscle Fibers.” Boundless Anatomy and Physiology Boundless, 27 Sep. 2016. Retrieved 12 Feb. 2017 from Slow-Twitch and Fast-Twitch Muscle Fibers