Low-dose niacinamide has striking anti-obesity effects

Jam

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Just double checked the study, and it appears that the NAM dose is 37.5mg/g not kg, for the mice… that would indicate a much higher dosage than 2.5mg/kg for humans. Right? I think @mevcit is right
No.

The formula, for an arbitrary animal of arbitrary weight, is:

HED mg/kg = animal dose (mg/kg) * ((animal weight (kg) / human weight (kg)) ^ 0.33)

Thus, for a human weighing 70kg:

37.5 * ((0.02 / 70) ^ 0.33) = 2.54mg/kg
 

EvanHinkle

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Further:

“male mice were fed high fat diet (Research Diets, D12492, with 60 kcal% fat) for 8 weeks, and then randomized into two groups: one fed normal water and the other fed water with NAM (Sigma-Aldrich, N0636) supplementation (18.75g NAM/ 100ml water as a clear solution) which was corresponding with 37.5mg/ g BW/ day”

So they were given 18 grams of NAM/day? Yikes, that’s quite a dose!
 

EvanHinkle

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No.

The formula, for an arbitrary animal of arbitrary weight, is:

HED mg/kg = animal dose (mg/kg) * ((animal weight (kg) / human weight (kg)) ^ 0.33)

Thus, for a human weighing 70kg:

37.5 * ((0.02 / 70) ^ 0.33) = 2.54mg/kg
I may be confused, but in the study it says the mice were given 37.5mg/g not 37.5mg/kg. This would affect the conversion equation right because g need to first be converted to kg
 

mevcit

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It just amazes me that people still do not know that mg/g = g/kg. The dose given to mice was 37.5 mg/g BW. @EvanHinkle, yes, I'm right.
 

Jam

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I may be confused, but in the study it says the mice were given 37.5mg/g not 37.5mg/kg. This would affect the conversion equation right because g need to first be converted to kg
Interesting. Even though it's getting past my bed time, let's take a look, FWIW:

Animal rooms were maintained at 20–22℃ with 30–70% relative humidity and a 12-hour light/dark cycle. 4-week C57BL/6J male mice were fed high fat diet (Research Diets, D12492, with 60 kcal% fat) for 8 weeks, and then randomized into two groups: one fed normal water and the other fed water with NAM (Sigma-Aldrich, N0636) supplementation (18.75g NAM/ 100ml water as a clear solution) which was corresponding with 37.5mg/ g BW/ day [17].

Let's see... anyone know how much water an adult rat drinks?? Aha:


Under these conditions, daily food intake, expressed per 100 g body weight (b.w.), is about 20 g at 5 weeks of age, decreases during early life and stabilizes for adult rats at a level of about 6–8 g. Correspondingly daily water intake decreases to a level of 9–12 ml per 100 g body weight.

10ml per 100g body weight is 2ml for a 20g rat. 18,750mg / 50 = 375mg. That's 18.75mg/g. So I guess the NAM rats are drinking double the water. Must be all that NAM making them extra thirsty. An insane amount of NAM by any standards.

However, from the conclusion:

This study has evaluated the function and mechanism of high-dose NAM on obesity and concluded that high-dose NAM ameliorated obesity after 2 weeks. In OLETF rats, 4-week supplementation of 100 mg NAM/kg BW/day increased NAD+ and improved glucose metabolism [14]. However, in mice, 8-week supplementation of 100 mg NAM/kg BW/day induced glucose intolerance and skeletal muscle lipotoxicity [25].

Now they're on mg/kg, which is more like it. This to me indicates a typo in the amount of NAM (18.75g per 100ml water). The solubility of NAM in water is given by Merck to be 500 g/L (at 25 °C) (MERCK INDEX (1996)). I suspect an 18g/100ml solution would be quite cloudy, and very bitter, but I'm not certain.

Where are they pulling that 100mg from, though? Rounding 37.5mg to 100mg seems a bit much, but ok.
 
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Mauritio

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37mg/g isnt that 37000mg/kg?

Divided by 12 for HED conversion =
3083mg/kg HED

Which comes down to about 247g per day for a 80kg human.

Something doesn't add up here.
 

Jam

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Interesting. Even though it's getting past my bed time, let's take a look, FWIW:



Let's see... anyone know how much water an adult rat drinks?? Aha:




10ml per 100g body weight is 2ml for a 20g rat. 1,8750mg / 50 = 375mg. That's 18.75mg/g. So I guess the NAM rats are drinking double the water. Must be all that NAM making them extra thirsty. An insane amount of NAM by any standards.

However, from the conclusion:



Now they're on mg/kg, which is more like it. This to me indicates a typo in the amount of NAM (18.75g per 100ml water). The solubility of NAM in water is given by Merck to be 500 g/L (at 25 °C) (MERCK INDEX (1996)). That means 50g/100ml. That means 33g in 100ml of saturated NAM solution. 18.75g is roughly half that. I suspect the solution would be quite cloudy, and very bitter, but I'm not certain.

Where are they pulling that 100mg from, though? Rounding 37.5mg to 100mg seems a bit much, but ok.
Ps. In ref. 17 (Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice) a high dose of NAM is defined as 1.0g/kg.
 

Mauritio

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Now they're on mg/kg, which is more like it. This to me indicates a typo in the amount of NAM (18.75g per 100ml water). The solubility of NAM in water is given by Merck to be 500 g/L (at 25 °C) (MERCK INDEX (1996)). That means 50g/100ml. That means 33g in 100ml of saturated NAM solution. 18.75g is roughly half that. I suspect the solution would be quite cloudy, and very bitter, but I'm not certain.

Where are they pulling that 100mg from, though? Rounding 37.5mg to 100mg seems a bit much, but ok.
I also suspect it might be a typo, that would make the most sense.

The 100mg/kg are not referring to this study, but other ones with higher doses that didn't show benefits.
I guess they wanted to highlight the contrast between their 37mg/kg dose and the 100mg/kg dose used in other studies.
 

EvanHinkle

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I shot a query over to science direct. I’ll update the thread if I get an answer. Thanks everyone!
 

mevcit

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I shot a query over to science direct. I’ll update the thread if I get an answer. Thanks everyone!
You should directly ask the corresponding author(s) if you have a question regarding the details of the study. There are two corresponding authors (the last two names) on this paper.

I do not believe that a low dose such as the one mentioned on this forum would have such effect. Also, nicotinamide is extremely soluble in water, it won't form a cloudy solution at that concentration haha. On the other hand, the LD50 of nicotinamide in mice is 2.5 g/kg BW. So, one should pay attention to the LD50 in mice and question how the mice survived this treatment. If there is indeed a typo, the corresponding authors should be able to clarify their mistake.

Lastly, this is not a high impact factor journal, all the authors are Chinese, and the study was conducted in China. So, don't take anything for granted until you see other studies with similar outcomes. People may call me racist but this is the bitter truth in the scientific world.
 

Inaut

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You should directly ask the corresponding author(s) if you have a question regarding the details of the study. There are two corresponding authors (the last two names) on this paper.

I do not believe that a low dose such as the one mentioned on this forum would have such effect. Also, nicotinamide is extremely soluble in water, it won't form a cloudy solution at that concentration haha. On the other hand, the LD50 of nicotinamide in mice is 2.5 g/kg BW. So, one should pay attention to the LD50 in mice and question how the mice survived this treatment. If there is indeed a typo, the corresponding authors should be able to clarify their mistake.

Lastly, this is not a high impact factor journal, all the authors are Chinese, and the study was conducted in China. So, don't take anything for granted until you see other studies with similar outcomes. People may call me racist but this is the bitter truth in the scientific world.
I appreciate your perspective
 
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You should directly ask the corresponding author(s) if you have a question regarding the details of the study. There are two corresponding authors (the last two names) on this paper.

I do not believe that a low dose such as the one mentioned on this forum would have such effect. Also, nicotinamide is extremely soluble in water, it won't form a cloudy solution at that concentration haha. On the other hand, the LD50 of nicotinamide in mice is 2.5 g/kg BW. So, one should pay attention to the LD50 in mice and question how the mice survived this treatment. If there is indeed a typo, the corresponding authors should be able to clarify their mistake.

Lastly, this is not a high impact factor journal, all the authors are Chinese, and the study was conducted in China. So, don't take anything for granted until you see other studies with similar outcomes. People may call me racist but this is the bitter truth in the scientific world.
There are human studies like the one I mentioned earlier in the thread(Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy )that can be referenced for human doses. They started with 250 mg and worked up to 1 g. And although the goal of the study was somewhat different, the results were similar in humans at these dosages compared with the original study post by Haidut.
 

EvanHinkle

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You should directly ask the corresponding author(s) if you have a question regarding the details of the study. There are two corresponding authors (the last two names) on this paper.

I do not believe that a low dose such as the one mentioned on this forum would have such effect. Also, nicotinamide is extremely soluble in water, it won't form a cloudy solution at that concentration haha. On the other hand, the LD50 of nicotinamide in mice is 2.5 g/kg BW. So, one should pay attention to the LD50 in mice and question how the mice survived this treatment. If there is indeed a typo, the corresponding authors should be able to clarify their mistake.

Lastly, this is not a high impact factor journal, all the authors are Chinese, and the study was conducted in China. So, don't take anything for granted until you see other studies with similar outcomes. People may call me racist but this is the bitter truth in the scientific world.
I honestly thought many of these same thoughts. It’s why I was initially more inclined to contact science direct vs the authors, (hoping it’s just a transcription typo). I’ll go the extra mile if I don’t get the information I’m looking for, but considering I was gonna take the results with a grain of salt anyway, I wasn’t really inclined to do the extra legwork at the outset.
 
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Chris Masterjohn has a series on youtube on Niacin. It was helpful to me. However, he says that Niacin can give some people diabetes. Does anyone know if there is any validity to this assertion? I wonder what the mechanism might be and if it could be mitigated. I would like to try using the Niacinamide but want to understand what possible problems might occur. It seems like it is important to get enough protein while taking Niacinamide because it can deplete methionine. And possibly it can deplete Choline? So would making sure you are getting both those help with any problems? Does anyone have any insight on this? Or has anyone tried it?
 

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Chris Masterjohn has a series on youtube on Niacin. It was helpful to me. However, he says that Niacin can give some people diabetes. Does anyone know if there is any validity to this assertion? I wonder what the mechanism might be and if it could be mitigated. I would like to try using the Niacinamide but want to understand what possible problems might occur. It seems like it is important to get enough protein while taking Niacinamide because it can deplete methionine. And possibly it can deplete Choline? So would making sure you are getting both those help with any problems? Does anyone have any insight on this? Or has anyone tried it?
If you take niacin in unphysiological doses, it will mess up your substrate balance. Initially, niacin will significantly depress free fatty acids and enhance glucose oxidation. If you take too much niacin with regards to your current metabolic situation, there will be a rebound of free fatty acids to supranormal levels. If you repeat this to an extreme you'll compromise your ability to oxidize glucose and end up with chronically elevated free fatty acids. You basically end up with the exact opposite of what you wanted to achieve by taking niacin in the first place.

1654382100148.png


 

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If you take niacin in unphysiological doses, it will mess up your substrate balance. Initially, niacin will significantly depress free fatty acids and enhance glucose oxidation. If you take too much niacin with regards to your current metabolic situation, there will be a rebound of free fatty acids to supranormal levels. If you repeat this to an extreme you'll compromise your ability to oxidize glucose and end up with chronically elevated free fatty acids. You basically end up with the exact opposite of what you wanted to achieve by taking niacin in the first place.

View attachment 37540


That is interesting, bearing in mind the dosages here for example (I think I originally saw the link here)

 

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