NAD+ SUPPLEMENTS

NAD+ IV TREATMENT

Dr K is the man when it comes to NAD+ IVs.  His advanced technique can deliver 720 mg of NAD+ in an hour or less.  Not only is this far more convenient than the 4-8 hour slow drip others are using, but we find that the fast delivery has a much more pronounced effect. Finishing wth the warm flush from his patent pending FastVitaminIV makes the whole experience far superior and more effective.

The founder of Koniver Wellness has been practicing Performance Medicine for over 18 years. Not satisfied with the disease-based model of modern medicine, Dr. Koniver seeks to help his clients optimize their health and performance through time-tested, nutrient and science driven protocols that are the cutting-edge of medicine.

He is a frequent guest on popular podcasts like Ben Greenfield and Marcus Aubrey. The clip above is from a recent appearance on  the Perils and Promise of Medicine Podcast, listen here.

Koniver Wellness

Craig Koniver, MD

Dr. Koniver is the founder and creator of the patent-pending FastVitaminIV® as well as re-engineering the NAD+ IV protocols, now called Brain Refuel™.

Dr. Koniver’s client list includes Navy SEALs, NFL players, PGA golfers, Hall of Fame NHL players, world-class professional athletes, Fortune 100 Executives, well-known celebrities and TV personalities.

His clinic is located in beautiful Charleston, SC. In addition, Dr. Koniver offers a comprehensive training program of the Koniver Wellness Model to physician practices throughout the world.

Learn More

 Disclaimer:  Dr Koniver consults and helps design our NAD+ and NMN supplements

WHY SUBLINGUAL?

POOR BIOAVAILABILITY FOR NAD+, NMN, AND NR CAPSULES

All NAD+ supplements can restore NAD+ in the Liver but this does not solve NAD+ deficiency throughout the body.

This research shows that ALL NAD+, NMN and NR are metabolized by CD38 in the liver to NAM, and ONLY NAM is excreted to the rest of the body

“orally delivered NR and NMN are converted into NAM before reaching the systemic circulation“

“we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally“

“IV administration of either compound results in its detection within the circulation, proving that the route of delivery has a profound effect on the ability of these precursors to reach target tissues”

* the above are direct quotes from the research

Quantitative Analysis of NAD Synthesis-Breakdown Fluxes (Liu, 2018)

Providing NAD+ or its immediate precursor, NMN, directly to the bloodstream is much more effective than dropping large quantities of NAM or NR into the liver and trying to force it to produce more NMN and NAD to the bloodstream.

NAD+ SUPPLEMENTATION

The hypothalamus is the master regulator of metabolism which impacts the entire body,and is theorized to be a central clock that controls aging itself.

NAD+ crosses the blood brain barrier to increase NAD+ in the hypothalamus to increase energy expenditure and decrease hunger (more below).

Administration of LABELED NAD+ by IP and IV injection of just 1 mg/kg a day 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.

They also show that NR and NMN can not utilize the cd43 gap to cross the blood brain barrier.

This might explain why In humans, NAD+ clinics have found success treating addictions and other brain imbalances, but NR and NMN have not been used in similar fashion.

Below are some of the disease and illnesses that we believe NAD+ supplementation is more effective for than NMN.

  • Chronic fatigue
  • Weight control
  • Mood disorders
  • Alcohol and drug addiction

Research has also shown NAD+ supplementation to be effective for the following conditions (more here).

  • Protects against liver damage
  • Multiple Sclerosis autoimmune-related neurodegeneration
  • Heart disease
  • Heart damage from stroke
  • Brain damage from injury

 

 

NAD+ DOES CROSS THE BLOOD BRAIN BARRIER

 

There are claims that both NMN and NAD+ are "TOO LARGE", and cannot enter cells directly, but must first be broken down to NR.

We recently wrote this article refuting that theory.

On September 1 2018, more proof was published proving that NAD+ crosses the blood brain barrier, enters the hypothalamus INTACT, and raises NAD+ levels.

Even better, just 1 Mg/kg a day decreased hunger, increased energy expenditure and fat burning for up to 24 hours after dosage.

For reference, most research providing mice with NMN or NR in drinking water uses 300 to 400 Mg/kg a day.

This study found both IV and IP injections had similar results. The results with 1-3 Mg/Kg by IP is extremely promising, as we note that sublingual delivery can be even more effective than IP delivery.

NAD+ DOES ENTERS CELLS INTACT

Once in the bloodstream NAD+ was thought to be too large to cross the cell membrane, making it ineffective at restoring the NAD+ contents inside the cells of many tissues. In this article we show that is not true for heart and brain, and perhaps other tissues.

In fact, this research published in March 2018 shows NAD+ is able to cross the blood brain barrier and quickly increases levels of NAD+ in the hypothalamus, while NR and NMN do not.

Administration of 1 mg/kg of NAD+ reduced hunger and weight gain, and increases energy expenditure and fat burning in mice (r).

Elevating NAD+ levels the hypothalamus has great impact throughout the body, as it regulates hunger and energy expenditure.

Restoring NAD+ levels in the hypothalamus to those of a young animal is very likely to have a positive impact on organs and tissues throughout the body.

(more about the importance of hypothalamus as master regulator of metabolism below)

Even more tantalizing are the possible implications for aging itself.
That the hypothalamus as master aging clock, is a credible theory on aging.

Hypothalamus controls energy metabolism

Hypothalamic circuits regulating appetite and energy homeostasis:  pathways to obesity
The hypothalamus in particular has emerged as an integrating, superordinate master regulator of whole-body energy homeostasis.
In summary, the hypothalamus plays a key role in the regulation of appetite and food intake both in humans and rodents.
Hypothalamic inflammation impairs the effects of insulin and leptin, contributing not only to hyperphagia and obesity development but also to the associated dysregulation of glucose homeostasis.
Brain regulation of appetite and satiety
Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem.
Brain Regulation of Energy Metabolism (Roh, 2016)
The hypothalamus is the region of the brain that controls food intake and body weight.
Leptin and insulin signal the status of body energy stores to the hypothalamus.
Hypothalamic regulation of energy homeostasis (Sainsbury, 2002)
These peripheral hormones influence their effects on energy homeostasis either by activating or inhibiting the activity of the orexigenic or anorexic peptides within the hypothalamus.
 

 

NMN and NAD+ enter tissues directly

Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic Connexin 43 (Roh, 2018)

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.

Exogenous NAD Blocks Cardiac Hypertrophic Response via Activation of the SIRT3-LKB1-AMP-activated Kinase Pathway (Pillai, 2009)

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

Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo (Fermenting, 2009)

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 NAD

leading 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+ administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA 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

Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice (Wang, 2016)

NAD(+) could be an effective and promising agent to treat multiple sclerosis

Prevents heart disease

Exogenous NAD Blocks Cardiac Hypertrophic Response via Activation of the SIRT3-LKB1-AMP-activated Kinase Pathway (Pillai, 2009)

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

Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model (Zhang, 2016)

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

Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia (Ying,2007)

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

 

Importance of Hypothalamus for Energy Metabolism

Hypothalamic circuits regulating appetite and energy homeostasis:  pathways to obesity
The hypothalamus in particular has emerged as an integrating, superordinate master regulator of whole-body energy homeostasis.
In summary, the hypothalamus plays a key role in the regulation of appetite and food intake both in humans and rodents.
Hypothalamic inflammation impairs the effects of insulin and leptin, contributing not only to hyperphagia and obesity development but also to the associated dysregulation of glucose homeostasis.
Brain regulation of appetite and satiety
Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem.
Brain Regulation of Energy Metabolism (Roh, 2016)
The hypothalamus is the region of the brain that controls food intake and body weight.
Leptin and insulin signal the status of body energy stores to the hypothalamus.
Hypothalamic regulation of energy homeostasis (Sainsbury, 2002)
These peripheral hormones influence their effects on energy homeostasis either by activating or inhibiting the activity of the orexigenic or anorexic peptides within the hypothalamus.

Hypothalamus as master aging clock

Building the Case that Aging is Controlled from the BrainIs there an Aging Clock in the Hypothalamus?Hypothalamic programming of systemic ageing involving IKK-b, NF-kB and GnRH (Zhang, 2014)