Extreme Fatigue From Niacinamide- Lipolysis Dependence?

[Ben]

It should work in theory but I have tried absurd doses to no avail. Progesterone can down regulate your 5a reductase that takes a few weeks to recover. Experience with aromatase inhibitors in general usually shows that they elevate progesterone.

The surest way to reverse the palpable effects of estrogen in men is to use DHT, but I think it requires some sophistication on account of the user for androgens are suppressive and there is the problem of transfer risk to women and children.

I don't know of any supplements besides creatine that elevate DHT, and DHT itself is illegal in the US. Creatine elevates DHT very much, but many people say it reduces their sex drive. Do you have any idea of the mechanism behind it? DHT itself increases sex drive.

By the way, I read that zinc, copper, and vitamin B6 are all aromatase and prolactin inhibitors, but also inhibit 5-aR. I don't see what's wrong with minimizing 5-aR along with aromatase if progesterone is supplemented, since progesterone is a highly protective hormone, and supports a healthy metabolism by inhibiting lipolysis for example. I bet those vitamins/minerals also increase progesterone. Zinc and copper, and probably progesterone, also increase testosterone by reducing testosterone derivatives, which has positive effects.

Some posts about DHT:

viewtopic.php?f=3&t=2916&p=38306&hilit=creatine#p37649

When I took only T4, I was greatly dysfunctional. But then when I got only 10 mcg of T3 per day, everything improved. I similarly take 90 mcg of T3 per day, and I don't feel hyperthyroid. It's probably getting deactivated like you said. RP said a "slightly hyperthyroid" state can be pleasurable, but I don't understand how a person like me can reach that state.

So I guess it's at best it would be a waste of money on cynomel if it gets converted to reverse-T3, and at worse your theory would be correct about reverse-T3 impairing T3 from functioning as it should.

 

[haidut]

There are some ways to legally raise DHT, and just by searching Google it seems that the bodybuilding community is all over it, and people who managed to raise their DHT do report dramatically increased libido, without the issues high T causes through aromatization.
So, based on my research and the forums I read it seems that the most sensible way would be to take the herb Tribulus Terrestris, 10mg-15mg of DHEA and combine that with a strong aromataze inhibitor. Here are some studies:
http://www.ncbi.nlm.nih.gov/pubmed/18068966
http://www.libilov.com/en/clinical_stud ... d_1996.htm
http://suppversity.blogspot.com/2012/06 ... tical.html
http://www.ncbi.nlm.nih.gov/pubmed/16797178


If the above studies transfer correctly into humans, then you should be able to raise DHT by taking pregnenolone as well, since it also converts to DHEA and is safer to supplement than DHEA directly.
Thus, a reasonable approach seems to take 500mg+ (maybe even as high as 1g) pregnenolone daily combined with a strong AI like anastrozole or letrozole every other day (or twice a week). Alternatively, take 10mg-15mg of DHEA with the AI.
Finally, yet another option would be to take about 500mg extract of Tribulus and combine with the AI.
If you can't get your hands on pharma AI then taking about 3.5g of vitamin E daily should have similar effect to the AI as it has been shown to reduce E2 levels by 60%+ and act BOTH as estrogen "receptor" antagonist AND aromatase inhibitor.
I am actually tempted to try this myself

 

[unexamined_whimsy]

I am not sure the body converts the excess T3 into reverse T3. The things I read suggest that excess T4 is converted into reverse T3. That's why taking pure T4 is not advisable and why so many people being prescribed synthetic thyroid (usually thyroxine, which is pure T4) by their doctor feel like absolute s*** and report feeling worse than without taking anything at all. Overdosing on T3 is possible, and the people not reacting to T3 are probably estrogen dominant as suggested above. So, sorting out estrogen issues is good but I would not recommend anyone go on T4 only.

In my original quote, "Anything more than the slightest excess of exogenous T3 perceived by the body is quickly deactivated via the D3 deiodinase into reverse-T3. D3 also converts some of the T4 into T2." I had switched reverse-T3 for T2. To be clear, D3 converts T3 --> T2 and T4 --> reverse T3. The point remains that excess T3 can be deactivated.

Per, http://www.ncbi.nlm.nih.gov/pubmed/16131330 :

Type 3 iodothyronine deiodinase (D3) is the physiologic inactivator of thyroid hormones, catalyzing the inner ring deiodination of thyroxine (T(4)) to reverse triiodothyronine (rT(3)) and (T(3)) to 3, 3'-diiodothyronine (T(2)), both of which are biologically inactive.

Taken as a whole, studies on levothyroxine vs liothyronine are clearly quite equivocal. Those arguing staunchly in favor of T3, or adding T3, are cherry picking the research. I think individual requirements lie along a continuum between 100% T4 and 100% T3.

 

[unexamined_whimsy]

There are some ways to legally raise DHT, and just by searching Google it seems that the bodybuilding community is all over it, and people who managed to raise their DHT do report dramatically increased libido, without the issues high T causes through aromatization.
So, based on my research and the forums I read it seems that the most sensible way would be to take the herb Tribulus Terrestris, 10mg-15mg of DHEA and combine that with a strong aromataze inhibitor. Here are some studies:
http://www.ncbi.nlm.nih.gov/pubmed/18068966
http://www.libilov.com/en/clinical_stud ... d_1996.htm
http://suppversity.blogspot.com/2012/06 ... tical.html
http://www.ncbi.nlm.nih.gov/pubmed/16797178


If the above studies transfer correctly into humans, then you should be able to raise DHT by taking pregnenolone as well, since it also converts to DHEA and is safer to supplement than DHEA directly.
Thus, a reasonable approach seems to take 500mg+ (maybe even as high as 1g) pregnenolone daily combined with a strong AI like anastrozole or letrozole every other day (or twice a week). Alternatively, take 10mg-15mg of DHEA with the AI.
Finally, yet another option would be to take about 500mg extract of Tribulus and combine with the AI.
If you can't get your hands on pharma AI then taking about 3.5g of vitamin E daily should have similar effect to the AI as it has been shown to reduce E2 levels by 60%+ and act BOTH as estrogen "receptor" antagonist AND aromatase inhibitor.
I am actually tempted to try this myself

Both tribulus and fenugreek can be estrogenic (gyno inducing) according to anecdote. Fenugreek, is used to induce lactation in India and so may be prolactinogenic. Also, Protodioscin, per se, may be effective but I haven't found a source with a high concentration of it. I think tongkat ali would be a better option given that it has also been shown to be anti-estrogenic.

The deductive idea of using DHEA+AI idea has been tried by users now for over a decade, but no one has found success with it as far as i know. The DHEA itself is as effective as a mild-testosterone cycle if you are not prone to estrogen but makes matters much worse if you are very much like testosterone itself.

Pharmaceutical AIs have a very scary side-effect profile and you should only take them if you have exhausted all options.

I think vitamin E has excellent potential as an anti-estrogen, and have personally had an excellent experience for the said purpose. What source do you intend using such a high dose of?

 

[unexamined_whimsy]

I think you're more or less in good shape, except the insomnia. Do you know your prolactin level? A trial with a dopamine agonist may be helpful if your prolactin is around 10. Does vitamin b6 help with sleep?

I have lethargy in addition to insomnia, so I wouldn't consider myself in good shape - lethargy means during some of the day I can't do basic stuff like holding a conversation (and much worse if I can't have my Peat foods). It's pretty clear from my temperatures that I'm hypothyroid. I'll try vit6, but I don't know my prolactin level.

I see. Have you ever measured your cortisol levels?

 

[SAFarmer]

Thyroid, particularly any amount of supplemental T3, often adversely affects the androgen to estrogen ratio especially in males, primarily by increasing SHBG. The estrogen-dominant body deactivates much of the T3 via the D3 deiodinase and increases thyroid binding globulin rendering you functionally hypothyroid even when you are taking replacement doses of thyroid.

Hi

Could you please provide references/studies as basis for your statement/belief above ?

Thanks

 

[unexamined_whimsy]

Thyroid, particularly any amount of supplemental T3, often adversely affects the androgen to estrogen ratio especially in males, primarily by increasing SHBG. The estrogen-dominant body deactivates much of the T3 via the D3 deiodinase and increases thyroid binding globulin rendering you functionally hypothyroid even when you are taking replacement doses of thyroid.

Hi

Could you please provide references/studies as basis for your statement/belief above ?

Thanks

Regarding estrogen stimulating D3 expression:

http://www.ncbi.nlm.nih.gov/pubmed/16935842

Our data suggest that estradiol may be one of the factors contributing to the induction of D3 activity in the pregnant uterus and that in addition to gene-specific regulatory elements, more distant common regulatory elements also may be involved in the regulation of D3 expression.

joe.endocrinology-journals.org/content/209/3/273.full.pdf

Estrogens and progesterones independently upregulate D3 expression in the uterus, and sex hormones upregulate D3 in the adult ovary and developing testis, all tissues that express modest amounts of D3 activity.

Regarding estrogen and hyperthyroidism:

http://jcem.endojournals.org/content/38/2/207.abstract

The contribution of testosterone and androstenedione to plasma estrone and estradiol (product of conversion ratio and plasma concentration of precursor) was significantly increased in the men and women with hyperthyroidism. Thus, the increased estrogen levels in spontaneous hyperthyroidism results in large part, from increased peripheral conversion rather than by direct glandular secretion.

http://www.ncbi.nlm.nih.gov/pubmed/1166483
http://www.ncbi.nlm.nih.gov/pubmed/23276903

Also, http://www.ncbi.nlm.nih.gov/pubmed/9062479 suggests that in experimentally-induced mild hyperthyroidism the net nitrogen balance is negative (roughly, a catabolic state).

 

[SAFarmer]

Thanks.
Before I read those studies (and hoping they are full text) though, are they the source of your opinion regarding the statements above, ie is that what your beliefs are based on?

 

[haidut]

I took Niacinamide right before and after a flu sickness, and was very weak for a long time although my symptoms of it were gone. I ran out of it and thought I got well finally. I couldn't have guessed it was Niacinamide, but I took it again, and I'm extremely weak again. Everyday tasks take a lot of effort in this crippling state, and once again like before, I can't put my arm up completely.

My best guess about the mechanism is that the lipolysis inhibition from niacinamide brings on a state of fatigue because my body is used to burning fatty acids, and that source of energy isn't there. I'm lazy in my default state, which I wonder about the mechanism of, but this effect from niacinamide is physicalfatigue. I can easily go up stairs normally if I need/want to, but with niacinamide it would be such a drag. It's worth stating that tianeptine (anti-serotonin drug) gives me physical energy, and when I took big doses, going without it would give me physical fatigue. When I took them together, tianeptine put me into a pleasant dreamy state.

So I took niacinamide for a couple of months last time and didn't get used to it. There is probably a basic problem with dependence on fatty acids for fuel, but I don't know what I can do about it. I've been taking thyroid for a while and have been eating RP way for 2 years, but I still have some estrogen-related health problems visible at the surface (acne, dandruff, rosacea, blood pooling in veins and orthostatic hypotension), and probably fatty acid dependence for fuel. What can I do so my body consumes glucose better so I don't have to have lipolysis to have energy?

The extreme fatigue attributed to niacinamide may be caused by something else. There is a drug called Mildronate that works very similarly to niacinamide in terms of fatty acid oxidation inhibition and it has the exact opposite effect of what is being described here.
http://en.wikipedia.org/wiki/Mildronate
Not only does it not cause fatigue but it is used to treat it, as well as reduce it onset in athletes and other people under stress.
How much niacinamide are you taking? Keep in mind that in higher doses of (500mg+) niacinamide works EXACTLY like a benzodiazepine drug (Valium, Xanax, etc) and those drugs are not exactly known for their anti-fatigue effects, but rather the exact opposite. I posted some studies on niacinamide/benzo connection so if you are interested just search the forum.

 

[haidut]

There are some ways to legally raise DHT, and just by searching Google it seems that the bodybuilding community is all over it, and people who managed to raise their DHT do report dramatically increased libido, without the issues high T causes through aromatization.
So, based on my research and the forums I read it seems that the most sensible way would be to take the herb Tribulus Terrestris, 10mg-15mg of DHEA and combine that with a strong aromataze inhibitor. Here are some studies:
http://www.ncbi.nlm.nih.gov/pubmed/18068966
http://www.libilov.com/en/clinical_stud ... d_1996.htm
http://suppversity.blogspot.com/2012/06 ... tical.html
http://www.ncbi.nlm.nih.gov/pubmed/16797178


If the above studies transfer correctly into humans, then you should be able to raise DHT by taking pregnenolone as well, since it also converts to DHEA and is safer to supplement than DHEA directly.
Thus, a reasonable approach seems to take 500mg+ (maybe even as high as 1g) pregnenolone daily combined with a strong AI like anastrozole or letrozole every other day (or twice a week). Alternatively, take 10mg-15mg of DHEA with the AI.
Finally, yet another option would be to take about 500mg extract of Tribulus and combine with the AI.
If you can't get your hands on pharma AI then taking about 3.5g of vitamin E daily should have similar effect to the AI as it has been shown to reduce E2 levels by 60%+ and act BOTH as estrogen "receptor" antagonist AND aromatase inhibitor.
I am actually tempted to try this myself

Both tribulus and fenugreek can be estrogenic (gyno inducing) according to anecdote. Fenugreek, is used to induce lactation in India and so may be prolactinogenic. Also, Protodioscin, per se, may be effective but I haven't found a source with a high concentration of it. I think tongkat ali would be a better option given that it has also been shown to be anti-estrogenic.

The deductive idea of using DHEA+AI idea has been tried by users now for over a decade, but no one has found success with it as far as i know. The DHEA itself is as effective as a mild-testosterone cycle if you are not prone to estrogen but makes matters much worse if you are very much like testosterone itself.

Pharmaceutical AIs have a very scary side-effect profile and you should only take them if you have exhausted all options.

I think vitamin E has excellent potential as an anti-estrogen, and have personally had an excellent experience for the said purpose. What source do you intend using such a high dose of?

I agree about fenugreek, but none of my studies mention it so not sure why it comes up??
Tribulus may be estrogenic in certain individuals but the AI should be able to take care of that. If you don't what to take pharma AI, three capsule of this product a day should do the trick:
http://www.swansonvitamins.com/swanson- ... l-30-sgels

 

[Ben]

The extreme fatigue attributed to niacinamide may be caused by something else. There is a drug called Mildronate that works very similarly to niacinamide in terms of fatty acid oxidation inhibition and it has the exact opposite effect of what is being described here.
http://en.wikipedia.org/wiki/Mildronate
Not only does it not cause fatigue but it is used to treat it, as well as reduce it onset in athletes and other people under stress.
How much niacinamide are you taking? Keep in mind that in higher doses of (500mg+) niacinamide works EXACTLY like a benzodiazepine drug (Valium, Xanax, etc) and those drugs are not exactly known for their anti-fatigue effects, but rather the exact opposite. I posted some studies on niacinamide/benzo connection so if you are interested just search the forum.

Interesting speculation. While I read your posts and some study on niacinamide and treating anxiety, I didn't know benzos can cause fatigue. A quick search can show that Xanax and others can indeed cause "extreme" fatigue in people. If your speculation is correct, I wonder how benzos and niacinamide can cause physical fatigue by working on benzo receptors. Maybe they also work on the spinal cord and PNS, reducing one's strength.

 

[haidut]

The extreme fatigue attributed to niacinamide may be caused by something else. There is a drug called Mildronate that works very similarly to niacinamide in terms of fatty acid oxidation inhibition and it has the exact opposite effect of what is being described here.
http://en.wikipedia.org/wiki/Mildronate
Not only does it not cause fatigue but it is used to treat it, as well as reduce it onset in athletes and other people under stress.
How much niacinamide are you taking? Keep in mind that in higher doses of (500mg+) niacinamide works EXACTLY like a benzodiazepine drug (Valium, Xanax, etc) and those drugs are not exactly known for their anti-fatigue effects, but rather the exact opposite. I posted some studies on niacinamide/benzo connection so if you are interested just search the forum.

Interesting speculation. While I read your posts and some study on niacinamide and treating anxiety, I didn't know benzos can cause fatigue. A quick search can show that Xanax and others can indeed cause "extreme" fatigue in people. If your speculation is correct, I wonder how benzos and niacinamide can cause physical fatigue by working on benzo receptors. Maybe they also work on the spinal cord and PNS, reducing one's strength.

If you believe in cell "receptors", the current explanation is that niacinamide (as well as the pharma benzos) work as full GABAa receptor agonists, and partial GABAb receptor agonists. Taurine is claimed to have a very similar agonist profile, and if you take a big dose of taurine I guarantee that you will feel extreme "fatigue" and fall asleep pretty quickly.
Btw, any GABA-like agent in general will produce symptoms of "fatigue" or drowsiness, and a lot of the substances that Ray recommends are inhibitory in nature (i.e. act through GABA). He calls it "protective inhibition". Niacinamide, magnesium, progesterone, taurine, glycine, beta alanine, histamine antagonists, dopamine agonists, serotonin antagonists (cypro), etc are all Peat-friendly substances and they all happen to be quite sedative in higher doses. A lot of them work through or similarly to GABA, so their effects are not surprising to me.

 

[Wilfrid]

@ haidut,

I think that the research regarding tribulus terrestris therapeutic validity in humans are very scarce not to mention probably inconclusive.
It seems to be more a russian roulette than a potent therapeutic approach.
The studies made on rodents or other small animals seems promising but I'm not sure how to give any credit to this plant when it comes to human.


http://examine.com/supplements/Tribulus+terrestris/

I like the above site because the authors focus on human studies only (excluding animal/petri-dish studies).

 

[haidut]

@ haidut,

I think that the research regarding tribulus terrestris therapeutic validity in humans are very scarce not to mention probably inconclusive.
It seems to be more a russian roulette than a potent therapeutic approach.
The studies made on rodents or other small animals seems promising but I'm not sure how to give any credit to this plant when it comes to human.


http://examine.com/supplements/Tribulus+terrestris/

I like the above site because the authors focus on human studies only (excluding animal/petri-dish studies).

Agreed, I am just suggesting it as a possible route to raise DHT. If I was doing it I would be doing routine hormone tests as well to track effects. If it ends up being estrogenic then I'd obviously discontinue.

 

[haidut]

@ haidut,

I think that the research regarding tribulus terrestris therapeutic validity in humans are very scarce not to mention probably inconclusive.
It seems to be more a russian roulette than a potent therapeutic approach.
The studies made on rodents or other small animals seems promising but I'm not sure how to give any credit to this plant when it comes to human.


http://examine.com/supplements/Tribulus+terrestris/

I like the above site because the authors focus on human studies only (excluding animal/petri-dish studies).

Btw, there are quite a few studies with Tribulus on primates and results were impressive. I believe the consensus is that if something is working on a primate it should translate more or less directly to humans. The link I posted above discusses those primate studies.

 

[SAFarmer]

I am not sure the body converts the excess T3 into reverse T3. The things I read suggest that excess T4 is converted into reverse T3. That's why taking pure T4 is not advisable and why so many people being prescribed synthetic thyroid (usually thyroxine, which is pure T4) by their doctor feel like absolute s*** and report feeling worse than without taking anything at all. Overdosing on T3 is possible, and the people not reacting to T3 are probably estrogen dominant as suggested above. So, sorting out estrogen issues is good but I would not recommend anyone go on T4 only.

That's my take also and the reason why I questioned his "statement of fact" or view of T3 being converted into RT3 and asked for references. It seems he misinterpreted things a bit.

 

[SAFarmer]

In my original quote, "Anything more than the slightest excess of exogenous T3 perceived by the body is quickly deactivated via the D3 deiodinase into reverse-T3. D3 also converts some of the T4 into T2." I had switched reverse-T3 for T2. To be clear, D3 converts T3 --> T2 and T4 --> reverse T3. The point remains that excess T3 can be deactivated.

Per, http://www.ncbi.nlm.nih.gov/pubmed/16131330 :

Type 3 iodothyronine deiodinase (D3) is the physiologic inactivator of thyroid hormones, catalyzing the inner ring deiodination of thyroxine (T(4)) to reverse triiodothyronine (rT(3)) and (T(3)) to 3, 3'-diiodothyronine (T(2)), both of which are biologically inactive.

So, you were wrong and I don't have to read all those references you gave ?

Taken as a whole, studies on levothyroxine vs liothyronine are clearly quite equivocal. Those arguing staunchly in favor of T3, or adding T3, are cherry picking the research. I think individual requirements lie along a continuum between 100% T4 and 100% T3.

So are you saying those supplementing T3 are cherry picking research ? I beg to differ.
I am doing very well supplementing only with a bit of T3 and can feel the warmth going into my feet after a dose of T3. T4 does not do this for me. But that's just my experience and I'd like to see the research you claim that prove T3 on it's own is detrimental. So what if a bit of extra T3 gets converted into T2. Is T2 bad for you?

 

[SAFarmer]

Also, http://www.ncbi.nlm.nih.gov/pubmed/9062479 suggests that in experimentally-induced mild hyperthyroidism the net nitrogen balance is negative (roughly, a catabolic state).

This is an interesting study for several reasons, even though the number of test subjects were only 7. Here is the full text, http://press.endocrine.org/doi/full/10. ... .82.3.3827 , and is well worth a read.

We know Ray Peat like to be in a state of mild hyperthyroidism and says it feels very good. In this study they define "mild hyperthyroidism" as above a certain serum T3 level they think should be hyperthyroid, ie not based on symptoms per se. This is problematic for the same reasons as the definition of euthyroid based on the range for TSH. It would probably be best to go with temps and pulse rather than serum T3 levels imo.

Further it is intersting that TSH fell "abrubtly" and T4 more gradually as T3 rose. According to Ray Peat a low TSH is good, the lower the better.

Thyroid hormone administration caused significant changes in serum lipoprotein levels. Total cholesterol fell from 4.29 ± 0.09 to 2.99 ± 0.14 mmol/L (P = 0.0001) due to a decrease in both high density lipoprotein (1.12 ± 0.06 vs. 0.96 ± 0.09 mmol/L; P = 0.03) and low density lipoprotein (2.81 ± 0.10 vs. 1.74 ± 0.09 mmol/L; P = 0.0001) fractions.

This is again in line whit what Broda Barnes and Ray Peat is saying. So why would anyone take statins if T3 works so good ?

They also used a dose of 75 ug T3 taken in 5 doses throughout the day every 4 hours. Although they say they had to decrease it a bit in some patients, it again was done based on a desired serum level of T3 and not hyper symptoms. It is also very interesting to note that later unpublished data from their lab showed that they got the same serum T3 levels with a single 100 ug dose supplemented with another 50ug later in the day. This is very much in line with Dr John Lowe who used that kind of single dose of T3 for more than 20 years without any problems.

It is also interesting that although there were initial negative Nitrogen balances in the first 3 weeks, this disappeared after 6-9 weeks, and promoted fat loss. These were also healthy young men, and it would be interesting to do these kinds of tests in hypo men.

 

[SAFarmer]

Further data on sex hormones after T3 supplementation by same authors of previous study.
This study is here, http://www.ncbi.nlm.nih.gov/pubmed/9439537

There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L.

So it seems T3 is good for the libido too ! (and no need to worry about estrogen increases)

 

[Mittir]

We know Ray Peat like to be in a state of mild hyperthyroidism and says it feels very good.

Nice summary on their studies.
IIRC RP used the term "slightly hyperthyroid" state in terms of pulse and heart rate.
In the study, the definition of "mildly hyperthyroid" looks like a medical definition.
They raised the total T3 level by 340 percent from baseline. Average people have
total T3 level around 130 ng/dL and in the study their target was 400 ng/dL.
That is 3 times the average and twice the value of upper limit of normal T3.
I do not think anyone tries to target 400. But study clearly shows even at 400 level
over all result is beneficial. I am curious to know if anyone here manage to have
total T3 level above 200 with supplementation.

Here is an interesting quote on N balance from this study

Although both lean and fat mass
were decreased by T3 treatment, as has been seen previously,
N balance showed an initial decline, but returned to
neutral and, in some individuals, even positive N balance
by 9 weeks. This finding is similar to that of Wilson and
Lamberts (17), who reported that T3 treatment in obese
patients, while promoting weight loss, did not cause a
deterioration in N balance.