NAD
NAD+ Supplements – Research and Benefits
Nicotinamide Adenide Dinucleotide (NAD+) and its immediate precursor Nicotinamide Mononucleotide (NMN) have both been shown to quickly elevate levels of NAD+ in various tissues and organs throughout the body.
NMN and NAD+ enter tissues directly
In conclusion, our results demonstrate that exogenous NAD is effectively imported into the hypothalamus and increases hypothalamic NAD content. Therefore, NAD supplement can constitute a therapeutic method for metabolic disorders characterized by hypothalamic NAD depletion in humans.
In this study published in September 2018, administration of LABELED NAD+ by IP and IV injection demonstrated that exogenous NAD+ crosses the blood brain barrier to enter the hypothalamus INTACT, reduces hunger and weight gain, and increases energy expenditure and fat burning in mice.
This study also shows that NR and NMN can not utilize the cd43 gap to cross the blood brain barrier!
This might explain why NAD+ clinics have found success treating addictions and other brain imbalances, but NR and NMN have not been used in similar fashion.
Bruzzone et al. (21) have shown that connexin 43 (Cx43) channels are permeable to extracellular NAD
Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis.
“Taken together, our findings strengthen the hypothesis that eNAD crosses the plasma membrane intact”
“In the present study we report that exposure to eNAD substantially increases the dinucleotide cellular pool, suggesting plasma membrane permeability”
Nicotinamide adenine dinucleotide is transported into mammalian mitochondria (Baur, 2018)
Here we present evidence that mitochondria directly import NAD
Taken together, our experiments confirm that despite the lack of any recognized transporter, mammalian mitochondria, like their yeast and plant counterparts, are capable of importing NAD
at least two studies have previously reported evidence for uptake of NAD, leading the authors to propose that intact NAD crosses the plasma membrane and subsequently enters the mitochondria directly
This observation suggests that a mitochondrial transporter for NMN may also await discovery
In summary, we show that mammalian mitochondria are capable of directly importing NAD (or NADH). This finding strongly suggests the existence of an undiscovered transporter in mammalian mitochondria
evidence that intracellular NMN contents promptly increase when the nucleotide is added to the culture media indicates that plasma membrane is permeable to this nucleotide
Pharmacological Effects of Exogenous NAD on Mitochondrial Bioenergetics, DNA Repair and Apoptosis
Although the canonical view considers NAD unable to permeates lipid bilayers (Di Lisa and Ziegler, 2001), several studies report evidence for exogenous NAD (eNAD) uptake by different cells “
These findings are at odds with the hypothesis that eNAD increase iNAD contents because of extracellularly-formed NAD precursors
Nicotinamide adenine dinucleotide is transported into mammalian mitochondria
mitochondria do not synthesize NAD at all, but rather take it up intact from the cytosol, which in turn, can take up NAD from the extracellular space
While mammalian mitochondria are generally considered to be impermeable to pyridine nucleotides (32,33), at least two studies have previously reported evidence for uptake of NADleading the authors to propose that intact NAD crosses the plasma membrane and subsequently enters the mitochondria directly
Increases energy and metabolism
Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic Connexin 43
In this study, administration of LABELED NAD+ by IP and IV injection demonstrated that exogenous NAD+ crosses the blood brain barrier to enter the hypothalamus INTACT, reduces hunger and weight gain, and increases energy expenditure and fat burning in mice.
This study shows that NAD+ levels in the blood have a direct effect on the levels of metabolic activity in the body.
They also show that NR and NMN can not utilize the cd43 gap to cross the blood brain barrier.
This might explain why NAD+ clinics have found success treating addictions and other brain imbalances, but NR and NMN have not been used in similar fashion.
In mice, exogenous NAD may be transported to the hypothalamus via Cx43 at the blood-brain barrier [48] thereby increasing hypothalamic NAD content and decreasing food intake and weight gain.
The study below also showed injecting just 1 mg/kg for 4 weeks weighed less and had more energy
Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice
Chronic NAD supplementation significantly attenuated weight gain in obese mice fed a high-fat diet. Furthermore, NAD treatment recovered the suppressed rhythms in the diurnal locomotor activity pat- terns in obese mice.
Mice that received NAD+ weighed less, were more active, and had better glucose control than mice that received placebo
Protects against age-related damage
Increased NAD+ levels protects against mitochondrial and age-related disorders (Srivastava,2016)
Reduced NAD+/NADH ratio is strongly implicated in mitochondrial disorders and, age-related disorders including diabetes, obesity, neurodegeneration and cancer [26, 53, 60, 71].
NAD+ levels also decline during aging in multiple models including worms, rodents and human tissue [17, 45, 67, 72].
Increasing evidence suggests that boosting NAD+ levels could be clinically beneficial, as it activates the NAD+/sirtuin pathway which yields beneficial effects on multiple metabolic pathways
Protects against liver damage
NAD+ at the doses of 100 or 200 mg/kg was also injected intraperitoneally 1 h before the DOX administration.
NAD(+) is capable of increasing the antioxidation capacity of tissues.
NAD(+) can significantly decrease DOX-induced liver damage
can also selectively decrease tumor cell survival, NAD(+)
Multiple Sclerosis autoimmune neurodegeneration
NAD(+) could be an effective and promising agent to treat multiple sclerosis
Prevents heart disease
Mice were simultaneously treated with NAD at 1 mg/kg/day for 2 weeks
NAD treatment was capable of maintaining cellular NAD levels
Exogenous supplementation of NAD restores the intracellular levels of NAD and blocks the cardiac hypertrophic response.
These results indicated that NAD treatment prevented the development of cardiomyocyte hypertrophy
NAD treatment restored the cellular NAD levels
NAD treatment may become a panacea for prevention and cure of many diseases in the future
Prevents heart damage from Stroke
NAD+ produced 85% decrease in the infarct size
NAD+ is one of the drugs that have greatest capacity to decrease myocardial ischemia
NAD+ dose dependently decreased infarct formation
Decreased brain damage
The profound protective effects of the intranasal NAD+ administration were also observed at 72 hrs after ischemia.
intranasal administration with 10 mg / kg NAD+, but not with 5 mg / kg NAD+, significantly attenuated the ischemia / reperfusion-produced neurological deficits
NAD+ administration can profoundly decrease brain damage under certain pathological conditions
