Niacinamide for Testosterone, DHT and being Alpha

Niacinamide, the key for high NAD+, testosterone, DHT and sexual function…

Are NMN and NR ripoffs if you could just use niacinamide?

Let’s talk about the benefits of niacinamide!

What I’ll be showing you

• Why do we want to be an alpha energy male?
• Niacinamide on testosterone
• Niacinamide on androgen receptors
• Niacinamide increases DHT
• Niacinamide on cortisol
• Niacinamide for stronger erections
• Niacinamide inhibits estrogen signaling
• Niacinamide improves sleep
• Niacinamide on dopamine, serotonin and mood
• Summary

Niacinamide on testosterone

At least 3 steroidogenic enzymes use NAD+. This includes CYP450scc (cholesterol side chain cleavage enzyme), 3β-HSD and 17β-HSD3.

• CYP450scc is the enzyme that converts progesterone to pregnenolone and uses NADPH as a cofactor (R). Boosting NAD levels will help with NADPH creation.
• 3β-HSD uses NAD as a cofactor. Low NAD can lead to low 3β-HSD activity and low steroids (in the tear duct for example and cause dry eyes) (R).
• 17β-HSD3, which converts androstenedione to testosterone (activation) preferentially uses NADP as a cofactor (NADP is created from NAD). On the flip side, 17β-HSD2 which converts testosterone to androstenedione (inactivation) uses NAD as a cofactor.

Supplementing rats with niacinamide reduced ROS (reactive oxygen species), increased ATP production and restored LH, FSH and testosterone levels (R).

As you can see in this graph in the tweet, the increase in LH, FSH and testosterone correlates with the increase in NAD+.

There is a possible correlation with NAD levels of testosterone.

According to this study, niacinamide increased testosterone, likely by increasing NAD levels.
The dose was quite large, at roughly 6g for a 100kg guy. pic.twitter.com/DGivumgj8k

— Hans Amato (@HansAmato) July 8, 2023

The ideal niacinamide dose was 400mg/kg, translating to 64.86mg/kg for a human (6486.49mg for a 100kg person). Yes close to 6g of niacinamide is a high dose.

Niacinamide on androgen receptors

Testosterone and DHT bind to androgen receptors (AR) to exert their effects.

SIRT1 activation (think resveratrol) reduces AR expression. SIRT1 antagonists (i.e. niacinamide) induce endogenous AR expression and enhance DHT-mediated AR expression (R). 

Niacinamide itself enhances DHT-induced AR expression, indicating that nicotinamide can modulate androgen hormone-dependent signaling (R).

Niacinamide increases DHT

DHT is extremely important for mood, sexual function (libido, erections, semen production), insulin sensitivity, muscle strength, and more.

5 alpha reductase (5AR) uses NADPH and using niacinamide to boost NAD and NADPH production (R, R). Additionally, ribose stimulates NADPH production through the pentose phosphate pathway, which can then be used to boost 5AR.

Niacinamide + ribose synergistically help to boost NAD and NADPH and should be able to increase DHT.

Niacinamide on cortisol

Niacinamide can help to lower excess cortisol, thus making you more stress resilient.

Niacinamide might help to lower excess cortisol.

Just 240mg of niacinamide (as RiaGev) daily dramatically lowered salivary cortisol (the free fraction). pic.twitter.com/wCS3lQrQ10

— Hans Amato (@HansAmato) July 26, 2023

Low ATP, NAD+ and glutathione, can stimulate the sympathetic nervous and increase cortisol secretion. Niacinamide, by increasing ATP, NAD+ and glutathione, can lower cortisol (R).

Cortisol exists in multiple forms and is deactivation by 2 main enzymes; 11β-HSD2 and 5-alpha reductase.

11β-HSD2 deactivates cortisol to cortisone and uses NAD to do so. 11β-HSD1 activates cortisol again. Niacinamide inhibits 11β-HSD1 while boosting 11β-HSD2 (R, R).

Niacinamide for stronger erections

Quick background on erections before I show you how niacinamide can improve them.

In order to get an erection, the smooth muscle cells of the penis (corpus cavernosum) need to relax so that blood can flow in. The more blood can flow in, the better the outflow of blood (vein) can be pinched closed.

Calcium in the cell excites it to contract. To get an erection, the calcium needs to be transported out; then the corpus cavernosum can properly relax.

Oxidative stress, inflammation and low nitric oxide damage the corpus cavernosum and vasculature, which impairs this whole process.

Quick background on BH4 for erections

In order to create NO, eNOS uses BH4. BH4 is an anti-oxidant and is reduced when oxidative stress is high.

Men with ED have significantly lower BH4 and NO.

When BH4 gets “used”, it turns to BH2. The enzyme that converts BH2 back into BH4, uses NADH (created from NAD+).

Back to niacinamide

Niacinamide can improve erections via a variety of mechanisms, namely:

• Lowering inflammation (less damage to penile tissue)
• Suppress calcium inflow by inhibiting ADP-ribose cyclase (aka CD38), thus allowing for better relaxation (R)
• Boosting NAD+ which enhances eNOS function (R, R).
• Increasing BH4, which is a cofactor for eNOS to create NO
• Inhibiting PARP (R). PARP is a DNA repair enzyme that uses NAD+. PARP inhibitors restore erectile function and significantly reversed all molecular and histological alterations induced by oxidative stress.
  • PARP inhibition allows for better smooth muscle relaxation (R).
  • PARP inhibition in the corpus cavernosum improves cavernosal endothelial function and restores abnormalities of the NO/cGMP pathway (R).
  • PARP inhibition increases NAD and ATP, which allows for better calcium export (R).
  • Part inhibition increases GAPDH, which increases NADPH production (to be used to lower oxidative stress) (R)
  • PARP inhibition lowers superoxide (a free radical) production (R).

Niacinamide inhibits estrogen signaling

Excess estrogen contributes to weight gain around the hip and pec area, gynecomastia, erectile dysfunction, cancer, water retention, aggression, mood disorders and so on.

Niacinamide has anti-estrogenic effects by reducing estrogen receptor alpha (ERα) expression and signaling.

You might have heard of histone deacetylases (HDACs). Inhibition of HDACs has been shown to have many benefits such as inhibiting cellular damage and even cancer.

Histone acetyltransferases and class I and class II HDACs cause posttranscriptional modification of histone proteins that participate in ERalpha signaling.

SIRT1, a class III HDAC, regulates ERα expression and inhibition of SIRT1 activity suppresses ERα expression (R).

Niacinamide can be a great tool to reduce excess estrogen signaling.

Niacinamide improves sleep

Good quality sleep is key for high testosterone.

Sleep tends to get worse with age as NAD drops and oxidative stress increases. As we age, light sleep goes up and deep sleep down. It’s that kind of sleep that when you wake up, you don’t feel rested.

Sirtuins use NAD+ and play a crucial role in regulating sleep-wake cycles. Since oxidative stress increases with age and NAD+ drops, and this can negatively impact people’s circadian rhythms, leading to sleep disturbances

In this study, boosting NAD+ with NMN (360mg daily) dramatically increased deep sleep and reduced light sleep. Interestingly, most of the sleep benefits only became prominent after 7 weeks (R).

Also, daytime fatigue is caused by oxidative stress, DNA damage and low NAD. PARP activation, due to DNA damage, promotes sleep/slumber (so that repair can take place) (R).

Niacinamide on dopamine, serotonin and mood

Dopamine

Dopamine is involved in mood, memory, focus, and more. High dopamine runs hand in hand with high testosterone.

Dopamine can be created from phenylalanine, tyrosine and L-dopa.

The rate-limited enzyme for dopamine is tyrosine hydroxylase (TH), which uses BH4 as a cofactor.

NAD+ is used to recycle BH4, therefore, niacinamide can boost BH4 and dopamine production.

It's not good to use tyrosine alone to increase dopamine, you want to use it with niacinamide.

Niacinamide increases NAD+, which increases BH4, which is a cofactor for tyrosine hydroxylase.

With tyrosine and niacinamide combo, dopamine release is much greater. pic.twitter.com/zpH8SAfrHs

— Hans Amato (@HansAmato) July 26, 2023

Using the dipeptide tyrosine-tryptophan was better at increasing dopamine than tyrosine alone. This is because NAD is created from tryptophan (R). It doesn’t have much tyrosine you supplement, if you don’t have enough NAD to recycle BH4, you’re not going to be making dopamine.

The dopaminergic peptide in whey

Whey contains a tetrapeptide (β-Lactolin) containing the tyrosine-tryptophan dipeptide.

β-Lactolin is very well-absorbed and delivered to the brain where it was associated with a dopamine level increase, resulting in improved spatial and object memory, verbal fluency and attention (R, R).

Not only does this peptide boost dopamine by providing the precursors, but also by inhibiting MAO-B (the enzyme that breaks dopamine down) (R).

Niacinamide increases BDNF which has been shown to:

• Increase tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis and promote the release of dopamine in the mesolimbic dopamine system (R, R).
• Increase the dopamine D3 receptor (R).

In summary, niacinamide can help to put you in a more dopaminergic state.

Serotonin

Even a small amount of niacinamide (100mg) can increase serotonin by 65% due to decreasing betaine and reducing COMT activity (R).

On the other hand, niacinamide in large doses is anti-serotonergic (R). In mice, 43mg of niacinamide gave 50% protection against 1mg of hydroxytryptophan (5-HTP).

A few symptoms of high serotonin include:

• Agitation or restlessness.
• Insomnia.
• Confusion.
• Rapid heart rate and high blood pressure.
• Dilated pupils.
• Loss of muscle coordination or twitching muscles.
• High blood pressure.
• Muscle rigidity.

If you have some/most of these symptoms, perhaps start at 3g niacinamide per day (1g over 3 doses) and work up from there as needed.

GABA

Niacinamide has tranquil, anti-anxiety and nootropic effects. It’s been shown to make you calmer and less aggressive (R).

A case report demonstrated that the use of 2500mg of niacinamide per day ameliorated severe anxiety in a 34-year-old male patient (R).

The exact mechanism is not entirely clear, but niacinamide’s GABAergic effects as well as its ability to increase ATP and BDNF and lower excess cortisol play a role (R, R, R).

Summary

In summary, niacinamide can help you be more Alpha by:

• Increasing testosterone and DHT
• Enhancing androgen signaling
• Reducing estrogen signaling
• Enhancing sleep
• Reducing anxiety and depression
• Improving erections

A few other benefits of niacinamide include:

• Improves skin health (when used topically)
  • Reduces fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing), increases elasticity and modulates skin sebum (decreases it when it’s too much and increases it when it’s too dry). (R, R)
• Helping at reducing/preventing migraines at doses of 500mg (R).
• Helping with arthritis and joint pain at doses of 900 to 4000 mg/day (R). A daily dosage of about 1g per 50 lb. body weight is ideal. Any trial should run for at least one month (R).

Use betaine with niacinamide

Niacinamide lowers methyl donors, such as betaine, which can slow down methylation.

This could lead to elevated homocysteine and reduced detoxification (of dopamine, estrogen, histamine, etc.).

One way to prevent a reduction in methyl donors when using high-dose niacin or niacinamide would be to use betaine anhydrous with it. A 1:1 ratio of betaine to niacinamide is a good starting point.

A good starting dose for niacinamide is 100-500mg daily. Higher doses can be used for the anti-anxiety and anti-depressant benefits.

• Niacinamide
• Betaine anhydrous