NAD+ for fatigue?

[cmath]

Tirz seems to be depleting my energy quite a bit. I'm doing all the things like protein and water and exercising, etc. Does anyone have any success with NAD + either capsule or SQ? Open to other suggestions as well

 

[Calm Logic]

For some people at least, MOTS-c has more energy/feelz. But I haven't tried anything for energy yet.

 

[AndyPanda]

Tirz seems to be depleting my energy quite a bit. I'm doing all the things like protein and water and exercising, etc. Does anyone have any success with NAD + either capsule or SQ? Open to other suggestions as well

I have two cents! NAD+ has low bioavailability in the oral form. Subcutaneous is better, but infusion is the best. Some people swear by NAD+, while others don’t feel anything. Because it is a little pricey, I would suggest that you try a B-Complex injection first. Something like NEUROBION, or Polibion/Polybcon that is $0.50 or less per IM injection. B3 (nicotinamide) is a precursor to NAD+ anyway and with a lot of these peptides and supplements you won’t feel much of anything unless it is something you are deficient in. I think it’s why so many people go for Clenbutetol or stimulants. It isn’t natural and you can feel it working.

 

[Calm Logic]

Below is a table from Google (Gemini). It may be horribly wrong (had to correct it twice already), but the general idea I get is that NAD+ subq looks like it may be worth the greater cost (depending on age, tolerance to oral stimulants like clen, etc). Or trying oral NR supplements (or oral NAD+ and NMN (NMNH)), like on Amazon.

Rank	Method	Description	Potential NAD+ Impact	Key Considerations
1	NAD+ IV Therapy	Direct infusion into bloodstream.	Highest, Rapid	Medical procedure, Costly, Limited long-term data.
2	NAD+ Subq Injection	Injection under the skin.	Significant, Relatively Rapid	Requires sterile technique, Less human research than oral, Potential site reactions.
3	NR Supplements	Oral NAD+ precursor, well-studied.	Significant	Oral, Good bioavailability, Quality control important.
4	Oral NAD+ Supplements	Direct oral NAD+ delivery.	Potentially Significant (bioavailability dependent)	Oral, Bioavailability research ongoing, May require specific formulations for better absorption.
5	NMN Supplements	Oral NAD+ precursor, promising research.	Significant	Oral, Bioavailability research ongoing, Quality control important.
6	NMN Subq Injection	Injection of NMN under the skin.	Potentially Significant, May have better bioavailability than oral NMN	Requires sterile technique, Less human research than oral NMN/NR, Dosage protocols evolving.
7	High-Dose NAM	Oral Vitamin B3 precursor, high doses can inhibit sirtuins.	Moderate	Oral, Lower cost, High doses may have negative effects.
8	Sirtuin Activators	Compounds like Resveratrol, enhance NAD+ effects.	Indirect	Often dietary, Bioavailability varies, Efficacy under investigation.
9	Exercise	Regular physical activity.	Mild, Gradual	Numerous other health benefits, Sustainable.
10	Caloric Restriction/IF	Reduced calorie intake or eating windows.	Mild, Gradual	Requires planning, Not for everyone.
11	Dietary B3	Foods containing Niacin/Nicotinamide.	Minimal	Essential for health, Dietary intake alone has limited impact on boosting NAD+.

Ideally, for fatigue, I would combine approaches like something for NAD+ (subq NAD+, oral precursor, whatever), along with peptides/vitamins/supplements/TRT, and a low-dose stimulant for extra "support" as needed.

Regarding tirz fatigue specifically, more calories or carbs (even a daily potato 🥔 or glass of Fairlife chocolate milk) may give a boost (at least over time):

Post in thread 'Switching from sema to tiirz'

Apr 27, 2025

From what I remember hearing (on a Youtubed podcast), Dr. Seeds says that fatigue from peptides is your body healing (which sounds more like BS everyday but puts a positive spin on it).

Some info/advice from a future overlord (Google Gemini):

While fatigue is not listed as a common side effect of tirzepatide by the manufacturer, some individuals have reported experiencing it. Here's why tirzepatide might cause fatigue:

• Reduced Calorie Intake: Tirzepatide can significantly decrease appetite, leading to lower calorie consumption. This reduced energy intake can result in...

• Calm Logic

• 

 

[cmath]

Thank you for that! That's super helpful. I do already take quite a few supplements, including B vitamins, do you have any suggestions for stimulants for people that are pretty reactive to stimulants? I don't want to feel cracked out. 😬

Below is a table from Google (Gemini). It may be horribly wrong (had to correct it twice already), but the general idea I get is that NAD+ subq looks like it may be worth the greater cost (depending on age, tolerance to oral stimulants like clen, etc). Or trying oral NR supplements (or oral NAD+ and NMN (NMNH)), like on Amazon.

Rank	Method	Description	Potential NAD+ Impact	Key Considerations
1	NAD+ IV Therapy	Direct infusion into bloodstream.	Highest, Rapid	Medical procedure, Costly, Limited long-term data.
2	NAD+ Subq Injection	Injection under the skin.	Significant, Relatively Rapid	Requires sterile technique, Less human research than oral, Potential site reactions.
3	NR Supplements	Oral NAD+ precursor, well-studied.	Significant	Oral, Good bioavailability, Quality control important.
4	Oral NAD+ Supplements	Direct oral NAD+ delivery.	Potentially Significant (bioavailability dependent)	Oral, Bioavailability research ongoing, May require specific formulations for better absorption.
5	NMN Supplements	Oral NAD+ precursor, promising research.	Significant	Oral, Bioavailability research ongoing, Quality control important.
6	NMN Subq Injection	Injection of NMN under the skin.	Potentially Significant, May have better bioavailability than oral NMN	Requires sterile technique, Less human research than oral NMN/NR, Dosage protocols evolving.
7	High-Dose NAM	Oral Vitamin B3 precursor, high doses can inhibit sirtuins.	Moderate	Oral, Lower cost, High doses may have negative effects.
8	Sirtuin Activators	Compounds like Resveratrol, enhance NAD+ effects.	Indirect	Often dietary, Bioavailability varies, Efficacy under investigation.
9	Exercise	Regular physical activity.	Mild, Gradual	Numerous other health benefits, Sustainable.
10	Caloric Restriction/IF	Reduced calorie intake or eating windows.	Mild, Gradual	Requires planning, Not for everyone.
11	Dietary B3	Foods containing Niacin/Nicotinamide.	Minimal	Essential for health, Dietary intake alone has limited impact on boosting NAD+.

Ideally, for fatigue, I would combine approaches like something for NAD+ (subq NAD+, oral precursor, whatever), along with peptides/vitamins/supplements/TRT, and a low-dose stimulant for extra "support" as needed.

Regarding tirz fatigue specifically, more calories or carbs (even a daily potato 🥔 or glass of Fairlife chocolate milk) may give a boost (at least over time):

Post in thread 'Switching from sema to tiirz'

Apr 27, 2025

From what I remember hearing (on a Youtubed podcast), Dr. Seeds says that fatigue from peptides is your body healing (which sounds more like BS everyday but puts a positive spin on it).

Some info/advice from a future overlord (Google Gemini):

While fatigue is not listed as a common side effect of tirzepatide by the manufacturer, some individuals have reported experiencing it. Here's why tirzepatide might cause fatigue:

• Reduced Calorie Intake: Tirzepatide can significantly decrease appetite, leading to lower calorie consumption. This reduced energy intake can result in...

• Calm Logic

• 

Post in thread 'Switching from sema to tiirz'

Apr 27, 2025

From what I remember hearing (on a Youtubed podcast), Dr. Seeds says that fatigue from peptides is your body healing (which sounds more like BS everyday but puts a positive spin on it).

Some info/advice from a future overlord (Google Gemini):

While fatigue is not listed as a common side effect of tirzepatide by the manufacturer, some individuals have reported experiencing it. Here's why tirzepatide might cause fatigue:

• Reduced Calorie Intake: Tirzepatide can significantly decrease appetite, leading to lower calorie consumption. This reduced energy intake can result in...

• Calm Logic

• 

 

[Calm Logic]

Phentermine

 

[cmath]

Phentermine

Gah! Can't do it. Do you have a runner up? LOL

 

[Calm Logic]

A nice cup of tea, haha. I do like the V8 energy drinks, and (less so) a functional, low-acid coffee called Everyday Dose (which doesn't taste as good as plain coffee).

Maybe a very low dose of the phentermine, like a tablet cut in 4? Or a caffeine tablet, whole or cut in half.

 

[Calm Logic]

Since NAD+ has anti-inflammatory properties (from an article not about NAD+):

Frontiers | Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of f...

www.frontiersin.org

We argue that inflammation affects some of the biological systems underlying fatigue and that inflammation may therefore be one of the major driving forces for fatigue.

Of course, reducing inflammation over time is only one way NAD+ may help with fatigue:

NAD+ related supplements may help fight fatigue through several interconnected mechanisms:

• Boosting Energy Production: NAD+ is a crucial coenzyme involved in the process of converting nutrients from food into adenosine triphosphate (ATP), the primary energy currency of cells. By increasing NAD+ levels, supplements can enhance the efficiency of this process, leading to more available cellular energy and potentially reducing feelings of fatigue.
  
  
• Supporting Mitochondrial Function: Mitochondria are the powerhouses of cells, responsible for generating most of the ATP. NAD+ is vital for optimal mitochondrial function. Supplementation may help improve mitochondrial health and efficiency, thereby increasing energy production and combating fatigue associated with mitochondrial dysfunction.
  
  
• Enhancing DNA Repair: NAD+ is a necessary cofactor for enzymes like PARPs (poly(ADP-ribose) polymerases) that are involved in DNA repair. When DNA is damaged, PARPs consume NAD+ to facilitate the repair process. By ensuring sufficient NAD+ levels, supplements can support efficient DNA repair, which is essential for overall cellular health and energy maintenance. Excessive DNA damage and subsequent NAD+ depletion can contribute to fatigue.
  
  
• Activating Sirtuins: Sirtuins are a family of proteins that play a role in regulating cellular metabolism, inflammation, and aging. They are NAD+-dependent enzymes. By increasing NAD+ levels, supplements can enhance sirtuin activity, which may have indirect effects on energy levels by improving metabolic function and reducing cellular stress.
  
  
• Combating Oxidative Stress: NAD+ is also involved in the production of NADPH, another important molecule that helps protect cells from oxidative stress. By supporting healthy NAD+ levels, supplements may indirectly help reduce the energy drain caused by oxidative damage.

Types of NAD+ Precursors in Supplements:

Many supplements don't contain NAD+ directly, as it is not easily absorbed. Instead, they contain NAD+ precursors, which the body can convert into NAD+.

Common precursors include:

• Nicotinamide Riboside (NR): This form of vitamin B3 is considered an efficient precursor for NAD+ synthesis.
  
  
• Nicotinamide Mononucleotide (NMN): NMN is another precursor that has shown promise in increasing NAD+ levels.
  
  
• Nicotinic Acid (NA) (Niacin): Another form of vitamin B3, but it can cause flushing in some individuals.
  
  
• Nicotinamide (Nam) (Niacinamide): Another form of vitamin B3 that is also used by the body to produce NAD+.
  
  
• Tryptophan: An amino acid that can be converted to NAD+ through a less efficient pathway.

Important Considerations:

• Bioavailability: The effectiveness of NAD+ supplements can depend on the specific precursor used and its bioavailability (how well it is absorbed and utilized by the body).
  
  
• Individual Response: Responses to NAD+ supplementation can vary between individuals.
  
  
• Further Research: While research is promising, the long-term effects and optimal dosages of NAD+ supplements in humans are still being investigated.
  
  
• Consult a Healthcare Professional: It is always advisable to consult with a healthcare provider before starting any new supplement, especially if you have underlying health conditions or are taking other medications. They can provide personalized advice based on your individual needs.

In summary, NAD+ related supplements, by boosting NAD+ levels, can potentially help fight fatigue by supporting energy production at the cellular level, optimizing mitochondrial function, aiding in DNA repair, activating beneficial enzymes, and combating oxidative stress. However, it's important to choose supplements wisely and consult with a healthcare professional.

Oxidative stress and inflammation are often intertwined. Oxidative stress can trigger and exacerbate inflammation, and conversely, inflammatory processes can lead to increased ROS production and oxidative damage. NAD+ plays a role in managing both of these processes, and its effects on one can indirectly impact the other.

 

[PickleRN]

I’ve also experienced significant fatigue on Reta. Working in a science-based profession, I naturally lean toward the fatigue being ketoacidosis. While this can be the case, I am already taking a stimulant in the form of Vyvanse. Throughout the day, I find no fatigue using this medication. But about 1630 I am utterly fatigued. Vyvanse is a drug prescribed by your physician for ADHD. Your physician would have to prescribe this for you.
So the use of a stimulant medication seems to be enough to get through a working day, but not into the evening. However, on the bright side, I have been sleeping much better since I started this process back in February 2025.

 

[Calm Logic]

That is an interesting stimulant:

https://en.wikipedia.org/wiki/Lisdexamfetamine

According to a 2019 systematic review, lisdexamfetamine was the most effective treatment for adult ADHD.

A rare case of ketoacidosis in someone without diabetes on tirz:

Tirzepatide-Induced Ketoacidosis in Non-Diabetic Patients - PMC

Tirzepatide is a novel glucagon-like peptide 1/glucose-dependent insulinotropic peptide (GLP-1/GIP) receptor agonist. It was recently approved for diabetes control and weight reduction in non-diabetic patients. We report the first case of ...

pmc.ncbi.nlm.nih.gov

Ketoacidosis was not reported in obese non-diabetic patients receiving dual-acting GLP-1 agonists aimed at weight reduction. This is the first case report of ketoacidosis being induced by tirzepatide. The most likely mechanism underlying ketoacidosis is starvation ketoacidosis. The main mechanisms causing starvation ketoacidosis are vomiting, nausea, diarrhoea and poor caloric intake induced by dual-acting GLP-1 agonists. In addition, dual-acting GLP-1 agonists can suppress appetite, prolong gastric emptying and decrease calorie intake. Obese patients with limited calorie intake, sometimes less than 500 calories, are at risk of ketosis.

 

[Peloma]

Tirz seems to be depleting my energy quite a bit. I'm doing all the things like protein and water and exercising, etc. Does anyone have any success with NAD + either capsule or SQ? Open to other suggestions as well

Capsules are a waste of money, based on the available research. Mots-c, and maybe Semax might a good option.

Maybe a couple of bumps of Colombian bam bam can get ya going... ❄️ 😆

 

[Skidude]

I started TMG when I started NAD+ based on other's recommendations.
I read the following to convince me-

Taking TMG (trimethylglycine) with NAD+ (nicotinamide adenine dinucleotide) supplements, or NAD+ precursors like NMN, is beneficial because TMG acts as a methyl donor, which helps maintain healthy methylation processes. Methylation is crucial for DNA function, gene expression, and various bodily processes. While NAD+ metabolism, including that of precursors like NMN, can deplete methyl groups, TMG helps replenish them, ensuring optimal methylation levels.

Here's a more detailed explanation:

• TMG as a Methyl Donor:
  .Opens in new tab
  TMG provides methyl groups, which are essential building blocks for DNA and other cellular processes.
  
  
• NAD+ and Methylation:
  .Opens in new tab
  NAD+ is involved in numerous metabolic pathways, and its metabolism, particularly the breakdown of its precursors like NMN, can deplete the body's supply of methyl groups.
  
  
• Synergistic Effect:
  .Opens in new tab
  By combining TMG with NAD+ or NMN, you ensure a balanced methylation cycle, which is important for DNA integrity, gene regulation, and overall cellular health.
  
  
• Maintaining Methylation:
  .Opens in new tab
  TMG helps replenish methyl groups, preventing potential imbalances caused by NAD+ metabolism and ensuring optimal methylation levels for various bodily functions.

 

[StonePny]

Gah! Can't do it. Do you have a runner up? LOL

@Calm Logic beat me to it, but I was going to say, espresso ☺️. We're both in CA, my machine is on.
I'm also starting to get T fatigue. I was INVINCIBLE at the beginning, now getting tired at higher dose.

 

[Calm Logic]

I started TMG when I started NAD+ based on other's recommendations.
I read the following to convince me-

Also, regarding energy/fatigue/performance:

https://www.sciencedirect.com/science/article/pii/S0022316624010186

Betaine [TMG] may enhance exercise performance through 3 mechanisms. First, it promotes the biosynthesis of creatine, accelerating adenosine triphosphate regeneration, which is particularly beneficial for short, high-intensity activities. Second, betaine supplementation elevates blood nitric oxide levels, potentially increasing muscle blood flow and improving nutrient delivery and waste extraction. Third, betaine acts as an osmoprotectant, regulating cellular hydration and fluid balance, which could enhance performance in dehydrated or hot conditions [65].

The only concern: a moderate increase in total cholesterol and LDL at higher doses above 4g/day.

 

[Skidude]

Also, regarding energy/fatigue/performance:

https://www.sciencedirect.com/science/article/pii/S0022316624010186

The only concern: a moderate increase in total cholesterol and LDL at higher doses above 4g/day.

I just take a 750mg 1x a day, was like 15$ for bottle

 

[Calm Logic]

By the way, regarding the stimulants mentioned in this thread:

Let's compare the half-lives of clenbuterol, phentermine, caffeine, and Vyvanse:

• Clenbuterol: Has a relatively long half-life, typically ranging from 25 to 39 hours. This means it takes a significant amount of time for the body to eliminate half of the drug.
  
  
• Phentermine: The half-life of phentermine is generally around 20 hours. However, this can be influenced by urine pH. In acidic urine, the half-life can be shorter, around 7 to 8 hours.
  
  
• Caffeine: Has a much shorter half-life, averaging around 5 hours in healthy adults. This can vary significantly between individuals (from 1.5 to 9.5 hours) due to factors like genetics, liver function, age, and other medications.
  
  
• Vyvanse: Vyvanse (lisdexamfetamine) itself has a short half-life of less than 1 hour. However, it is a prodrug that is converted in the body to dextroamphetamine, which has a half-life of around 12 hours. Therefore, the effects and detectability of Vyvanse are related to the half-life of dextroamphetamine.

In summary:

Clenbuterol has the longest half-life among these four substances. Phentermine has a slightly shorter but still relatively long half-life. Vyvanse's active component (dextroamphetamine) has a moderate half-life, while caffeine has the shortest half-life. This means that clenbuterol will stay in your system for the longest duration, followed by phentermine, then Vyvanse, and finally caffeine being eliminated the quickest.

 

[Calm Logic]

Another option regarding tirz fatigue is changing the frequency from weekly to a lower dose every four days or so:

Instead of the peaks and troughs associated with weekly dosing, a more frequent schedule could lead to more stable levels of the medication, which some individuals might find better tolerated.

Post in thread 'Thoughts on dose increase vs spacing out'

Apr 6, 2025

I agree. It's a very individual experience and it's nice to have the flexibility of a compound or grey over the standard name brand dosing - which I didn't like at all.

Currently what's working for me - with the main goal to mitigate tirz fatigue - is lowering the amount of tirz in my system at any given time. This shows by switching to every 4 days the levels don't go above the 9mg weekly dose which is what I was looking for at this time.
Back in March they were climbing over 9mg when I was split dosing weekly.

Using 4.5 every 4 days -
I'm eating more and have more energy while still...

• Valerie

• 

 

[Abeebee]

Tirz seems to be depleting my energy quite a bit. I'm doing all the things like protein and water and exercising, etc. Does anyone have any success with NAD + either capsule or SQ? Open to other suggestions as well

I started taking 50mg NAD on Monday and Friday over two weeks ago and it has helped me tremendously. I just bumped up to 75mg my last pin. I actually feel awake during the day now. It doesn’t affect my sleep I can still definitely take a nap during the day if I try but the NAD I feel has really helped me be a functional human again 🤣

 

[eboseki]

my life sucks. I am chronically sleepy during the day, I take adderall, NAD, zip fizz x 2, mot-c, semax, got cerebrolysin on the way to try, yet typing this now my eyes are heavy. oh god why

 

[Calm Logic]

Some questions, feel free to pick and choose:

Are you also on a GLP1 medication? Which one and what is the dose? How long have you been on it?

How long have you been on the Adderall? I only ask since I wonder if you are taking a high enough dose or have gotten too used to it.

What do you think may be causing the fatigue? When did it start? Has anything you are taking helped?

Have you had bloodwork to rule out things? If you have seen a doctor, did they suggest anything?

 

[Kjm1960]

my life sucks. I am chronically sleepy during the day, I take adderall, NAD, zip fizz x 2, mot-c, semax, got cerebrolysin on the way to try, yet typing this now my eyes are heavy. oh god why

Could be the NAD, I definitely felt really sleepy from it, until I made sure I took TMG. And what is zip fizz?

 

[Calm Logic]

It's an energy drink powder with a lot of B-12.

 

[Jtjones416]

NAD+ made me extremely tired. I'm not a napper and couldn't stay awake. It was recommended to take SS-31. I just stop altogether and now back to myself.

 

[eboseki]

someone also recommended to me SS-31. Not the cheapest of peptides I see, I have some on the way sounds promising. how frustrating it is to take something for energy only for it to have the opposite effect. I’ll cut the NAD out for now too

 

[Skidude]

someone also recommended to me SS-31. Not the cheapest of peptides I see, I have some on the way sounds promising. how frustrating it is to take something for energy only for it to have the opposite effect. I’ll cut the NAD out for now too

I dose TMG (trimethylglycine ) with NAD+

Yes, it is generally recommended to take trimethylglycine (TMG) with nicotinamide mononucleotide (NMN).

Here's why:

• Methylation:
  NMN is a precursor to NAD+, a vital coenzyme that requires methyl groups for its synthesis. Taking TMG, a methyl donor, alongside NMN ensures an adequate supply of methyl groups for this process.
  
  
• Synergy:
  TMG and NMN work synergistically to enhance the benefits of both supplements. They support cellular methylation, improve mitochondrial function, and promote healthy aging.
  
  • Prevents Depletion:
    High doses of NMN can deplete methyl groups in the body. Taking TMG with NMN helps to replenish these groups and prevent potential side effects.
    

Dosage:

The recommended ratio of TMG to NMN is 1:1. For example, if you take 500mg of NMN, you can also take 500mg of TMG.

Note:

It's important to consult with a healthcare professional before taking any supplements, including TMG and NMN. They can advise you on the appropriate dosage and ensure that these supplements are safe for you.

 

[eboseki]

I dose TMG (trimethylglycine ) with NAD+

Got some on the way, thanks 🙏