NAD+ for fatigue?

cmath

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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
 
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.
 
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.

RankMethodDescriptionPotential NAD+ ImpactKey Considerations
1NAD+ IV TherapyDirect infusion into bloodstream.Highest, RapidMedical procedure, Costly, Limited long-term data.
2NAD+ Subq InjectionInjection under the skin.Significant, Relatively RapidRequires sterile technique, Less human research than oral, Potential site reactions.
3NR SupplementsOral NAD+ precursor, well-studied.SignificantOral, Good bioavailability, Quality control important.
4Oral NAD+ SupplementsDirect oral NAD+ delivery.Potentially Significant (bioavailability dependent)Oral, Bioavailability research ongoing, May require specific formulations for better absorption.
5NMN SupplementsOral NAD+ precursor, promising research.SignificantOral, Bioavailability research ongoing, Quality control important.
6NMN Subq InjectionInjection of NMN under the skin.Potentially Significant, May have better bioavailability than oral NMNRequires sterile technique, Less human research than oral NMN/NR, Dosage protocols evolving.
7High-Dose NAMOral Vitamin B3 precursor, high doses can inhibit sirtuins.ModerateOral, Lower cost, High doses may have negative effects.
8Sirtuin ActivatorsCompounds like Resveratrol, enhance NAD+ effects.IndirectOften dietary, Bioavailability varies, Efficacy under investigation.
9ExerciseRegular physical activity.Mild, GradualNumerous other health benefits, Sustainable.
10Caloric Restriction/IFReduced calorie intake or eating windows.Mild, GradualRequires planning, Not for everyone.
11Dietary B3Foods containing Niacin/Nicotinamide.MinimalEssential 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):

 
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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.

RankMethodDescriptionPotential NAD+ ImpactKey Considerations
1NAD+ IV TherapyDirect infusion into bloodstream.Highest, RapidMedical procedure, Costly, Limited long-term data.
2NAD+ Subq InjectionInjection under the skin.Significant, Relatively RapidRequires sterile technique, Less human research than oral, Potential site reactions.
3NR SupplementsOral NAD+ precursor, well-studied.SignificantOral, Good bioavailability, Quality control important.
4Oral NAD+ SupplementsDirect oral NAD+ delivery.Potentially Significant (bioavailability dependent)Oral, Bioavailability research ongoing, May require specific formulations for better absorption.
5NMN SupplementsOral NAD+ precursor, promising research.SignificantOral, Bioavailability research ongoing, Quality control important.
6NMN Subq InjectionInjection of NMN under the skin.Potentially Significant, May have better bioavailability than oral NMNRequires sterile technique, Less human research than oral NMN/NR, Dosage protocols evolving.
7High-Dose NAMOral Vitamin B3 precursor, high doses can inhibit sirtuins.ModerateOral, Lower cost, High doses may have negative effects.
8Sirtuin ActivatorsCompounds like Resveratrol, enhance NAD+ effects.IndirectOften dietary, Bioavailability varies, Efficacy under investigation.
9ExerciseRegular physical activity.Mild, GradualNumerous other health benefits, Sustainable.
10Caloric Restriction/IFReduced calorie intake or eating windows.Mild, GradualRequires planning, Not for everyone.
11Dietary B3Foods containing Niacin/Nicotinamide.MinimalEssential 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):

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

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.
Google Gemini said:
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.
 
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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.
 
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:

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

Also, regarding energy/fatigue/performance:


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.
 

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