Other NAD+ BoostersNam

p75213
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Joined: Wed Sep 11, 2019 12:04 am

Nam

Post by p75213 » Sat Sep 28, 2019 5:45 am

Why is NAM so unpopular compared to NMN and NR? I know of the toxicity to the liver at high doses. But from what I've read that's over 3 grams per day.


Fred
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Location: Sweden

Re: Nam

Post by Fred » Sat Sep 28, 2019 6:52 am

Nicotinamide (NAM) has some salutary effects in mice but not as impressive as NR/NMN. Perhaps because of inhibitory effects on the SIRT1 protein. At least NAM doesn´t SHORTEN life even if it doesn´t prolong life as NR/NMN did in some studies.

Both Charles Brenner and David Sinclair were involved in this NAM-study:

Nicotinamide improves aspects of healthspan but not lifespan in mice

" Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan...

Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways.

Though neither hepatic NAD+ nor NADP+ were boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854409/
Fred
Registered dietitian, Sweden.
p75213
Posts: 72
Joined: Wed Sep 11, 2019 12:04 am

Re: Nam

Post by p75213 » Sat Sep 28, 2019 3:43 pm

That's disappointing considering the price of NAM.
Fred
Posts: 442
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Re: Nam

Post by Fred » Fri Oct 11, 2019 4:07 am

NAM and how it applied topically prevents pre-malignant lesions, brightens, decrease inflammation in rosacea and eczema, treats wrinkles and acne and strengthens the skin barrier via cholesterol, fatty acid and ceramide synthesis.

From the review:

Diverse therapeutic efficacies and more diverse mechanisms
of nicotinamide.
(5th of October 2019)
3.6 Skin protection and effects against skin disorders

The effects of NAM on skin are promptly and prominently visible. Inflammatory or autoimmune skin diseases, such as acne vulgaris (Collins et al. 1991; Shalita et al. 1995), bullous pemphigoid (Fivenson et al. 1994), and atopic dermatitis (Soma et al. 2005), have been treated or ameliorated with NAM possibly through the aforementioned anti-inflammatory effects.

Wound healing in model animals was accelerated as well (Collins et al. 1991). Furthermore, NAM reduced new incidence of actinic keratosis as well as non-melanoma skin cancer in clinical trials (Chen et al. 2015); when topically applied, it relieves immunosuppression caused by UV-radiation damage while downregulating inflammation in the irradiation-damaged skin (Monfrecola et al. 2013). These effects against skin tumorigenesis led to a suggestion that NAM be added to sunscreen (Damian et al. 2008).

In addition, NAM has excellent cosmetic and anti-ageing effects on the skin. It increases skin hydration by improving skin-barrier function with enhanced levels of sphingolipids, free fatty acids, and cholesterol, key components of the epidermal permeability barrier in the stratum corneum (Tanno et al. 2000).

Molecular mechanisms responsible for these changes are poorly understood, but one in vitro study showed that NAM treatment increased mRNA level of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid synthesis, in keratinocytes (Holleran et al. 1990). Nicotinic acid administration is also effective in increasing ceramide synthesis, suggesting that its effects are mediated through the NAD + supply. Therefore, increased NADPH level could contribute to this effect since NADPH is a cofactor in the synthesis of fatty acids, cholesterol, and ceramides (Singh 1983).

Additionally, NAM increased synthesis of collagen, filaggrin, and involucrin, components of the dermal matrix that lead to an improvement in density, moisture retention, and elasticity of human skin (Oblong 2014). NAD + is a cofactor of UDP-glucose dehydrogenase, which plays a key role in the synthesis of glycosaminoglycans (GAGs) (Kalckar et al. 1956), important moisture factors in the dermis whoselevel decreases during intrinsic skin aging (Lee et al. 2016).

Another prominent effect of NAM is skin whitening, as it reduces melasma, a dark pigmentation of the skin caused by sun exposure, skin irritation, or genetic predisposition (Navarrete-Solis et al. 2011). This effect has largely been suggested to be associated with suppression of the migration of melanosomes from melanocytes to neighboring keratinocytes (Hakozaki et al. 2002).

How these various effects are mediated at the molecular level remains largely unknown. Keratinocytes and dermal fibroblasts undergo senescence upon aging or external stresses such as sun exposure (Orioli and Dellambra 2018). Levels of NAD + and SIRT1 activity also decrease in aging skin (Massudi et al. 2012).

Meanwhile, NAM treatment significantly increases the replicative life span of keratinocytes and fibroblasts (Kang et al. 2006) and expands the capacity of proliferation and differentiation of human stem cells (Ok et al. 2018), which may protect against epidermal thinning during aging. These are shown to be accompanied with an improvement of mitochondria quality. And, SIRT1 overexpression attenuates fibroblast senescence (Huang et al. 2008) while inhibiting the expression of matrix-metalloproteinases (MMP) thereby preserving the epidermal ECM (Ohguchi et al. 2010).

An involvement of SIRT6 activity can also be possible since low SIRT6 activity was shown to be involved in decreased collagen 1 expression and increased MMP-1 secretion (Baohua and Li 2012). However, the involvement of sirtuin proteins in the cosmetic effects of NAM has not yet been proven.
https://sci-hub.se/10.1007/s11306-019-1604-4
Fred
Registered dietitian, Sweden.
Drdavid
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Re: Nam

Post by Drdavid » Fri Oct 11, 2019 7:07 am

This will be the next big thing in cosmetics
Fred
Posts: 442
Joined: Tue Aug 13, 2019 3:17 pm
Location: Sweden

Re: Nam

Post by Fred » Fri Oct 11, 2019 7:56 am

I´ve been using niacinamide topically daily for 16 years. PROCTER & GAMBLE (Olay, SK-II) launched the first commercial 4% niacinamide moisturiser in 2003. It is still a big thing though because it works.

All major cosmetic companies include some products with niacinamide these days. NIA24 have a proprietary fat-soluble version called myristyl nicotinate. But niacinamide is the most well-researched.

CERAVE is a drugstore brand that is affordable and of very good quality. They have 4% niacinamide in their AM and PM moisturisers and several body products. I use the Cerave PM, light and very good.

OLAY Regenerist fragrance-free is very good and contains 2-4% niacinamide. They won´t tell the exact percentage, but their patents do.

LA ROCHE POSAY (Lóreal) have the LIPIKAR range with body lotions and balms with 4% niacinamide. I use them too on body, lips and around the eye area.

What will probably come now though is topical NR and NMN and their derivatives. Procter & Gamble had a licensing deal with Chromadex for use of NR in a cream. Nothing has materialised from that though. NUCHIDO, UNILEVER and P&G is working on topical senolytic/NAD/SIRT1-activating anti-aging products as we speak.
Fred
Registered dietitian, Sweden.
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