This study published Sept 26 2018 gave obese mice 1 mg/kg of NAD+ by inter peritoneal injection for 4 weeks, which restored NAD+ levels in the hypothalamus to normal levels.
The hypothalamus is the master regulator of metabolism. Decreased levels of NAD+ are found in hypothalamus with obesity, disease, and the normal aging process.
In this study, supplementation with NAD+ :
- Restored NAD+ levels to normal
- Increased Energy Expenditure
- Increased metabolism rate
- Decreased Blood glucose levels
- Decreased Cholesterol levels
- Improved sleep patterns
- Improved weight control
NAD+ Controls energy metabolism
This research confirms and extends earlier research on the importance of NAD+ levels on energy metabolism and the effectiveness of NAD+ supplementation to restore vigor. I covered this more fully in this article.
What is notable in this study is that a dose of only 1 mg/kg per day was able to achieve all these results over a short period of 4 weeks. As the authors note, this is a 100x smaller dosage than required for NAD+ precursors NMN and NR to achieve some of the same results.
It is notable that supplementation with NAD by itself, at a 100-times lower dose compared with those of its precursors NMN and NR (25,26), caused a beneficial metabolic effect
Restores NAD+ levels
Decreased Blood Glucose Levels
Relevance: The improvements in metabolism from supplementation with NR or NMN are most likely the result of those precursors being metabolized to NAD+ in the liver. Supplementation with NAD+ provides the same benefits for metabolism through a more direct route and requiring much smaller dosages to achieve the desired results.
The increased efficiency of NAD+ supplementation vs NMN or NR in restoring metabolism is also seen in this study published August 29, 2018.
Researchers were able to trace labeled NAD+ to prove it does enter the hypothalamus directly, without conversion to NR or NMN as many had previously supposed.
They also show that NR and NMN are NOT ABLE to cross the blood brain barrier to the hypothalamus.
Read more about that study here
Importance of Hypothalamus for Energy Metabolism
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.
Energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brainstem.
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.
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.