Nam
Posted: 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.
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https://sci-hub.se/10.1007/s11306-019-1604-43.6 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.