This is not intended to be medical advice, consult an independent physician for advice before dieting or supplementing guys.
A methionine restricted, leucine reduced, malnutrition-free diet which is ketogenic by virtue of MCT supplementation, could be the ultimate life-extension diet. It takes advantage of three known LE pathways - reduced mTOR and reduced IGF-1, low methionine cancer control, and elevated BHB ketosis for fat loss, brain energy and reduced inflammation.
NAD+ levels are important in any diet, but may be especially important for ketosis. It has been hypothesized that elevated BHB levels can only by be controlled when high affinity nicotinic acid G-protein coupled receptors are maintained at adequate levels via NAD. It has been observed that NAD deficiency may be pathogenic in schizophrenics, which may be why niacin works as a treatment. Elevated BHB levels may also explain their elevated Kynurenic Acid levels.
Since we now know that NAMPT levels decrease with age, NR may be more adequate for restoring NAD+ (NR->NMN->NAD+). The niacin flush may serve as a biomarker for NAD+ levels as well; people who do not experience much flush may have low levels (see bellow).
In any case I suspect that for anyone on a ketogenic diet, whether low carb or via MCTs, niacin/NR supplementation may need to be considered to keep BHB levels in check. Wouldn't niacin also help to keep LDL levels in check if one were using unrefined red palm oil instead of an MCT supplement?
W. Todd Penberthy, PhD, JOM Volume 27, Number 1, 2012
"Explanations for the Simultaneous Recovery from Acute Schizophrenia and the Niacin-Flush Response
Hoffer observed that treatment with high doses of the non-flush NAD precursor, nicotinamide, also frequently resulted in recovery from acute schizophrenia similar to recovery from pellagra dementia. While restoration of the nicotinic acid-mediated flush response does correlate with niacin-mediated recovery from schizophrenia, it does not necessarily mean that this effect was primarily the result of the flush response.It seems much more likely that the restoration of NAD levels is central to recovery, where NAD as NAD+, NADP+, NADH, and/or NADPH, may be restoring prostaglandin- flush pathways by one or a combination of the >450 reactions that require NAD for ac- tivity. There are several possible explanations for the observed reduced flush response. In this section we give consideration to each explanation and ultimately come to the conclusion that the reduced flush response is firstly an NAD deficiency, where PUFA reductions are likely to be secondary to this effect. This analysis concludes that schizo- phrenia is most likely not an essential fatty acid deficiency disease, but more of a NAD deficiency disease.
Firstly, the reduced niacin flush response observed in schizophrenia likely involves nia- cin receptor ligand mediated desensitization. A metabolic study of schizophrenia indicates a general increase in PUFA catabolism.31 Beta-hydroxybutryate levels were found to be elevated 2.6 fold. Beta-hydroxybutyrate is proposed to be the naturally occurring endogenous ligand for the high affinity nicotinic acid G-protein coupled receptor.32 Decreased levels of the GPR109a protein are observed in the brains of schizophrenics, as are increased GPR109a transcripts.33 Such ligand dependent receptor down-regulation (a.k.a., receptor desensitization) is a common theme with the G-protein coupled receptor protein superfamily. Thus, NAD may be simply restoring PUFA metabolism such that the levels of the beta-hydroxybutyrate ligand for the high affinity nicotinic acid G- protein coupled receptor are returned to normal levels. The GPR109a protein may then be expressed at correct levels, thus restoring the niacin-flush response to normal as well. This general alteration is surely a major contributor to the reduced flush response seen in schizophrenics."
[...]
"Glutamine is required for the last step in the conversion of niacin to NAD when starting from either tryptophan or nicotinic acid/niacin. [...] Glutamine is the most abundant amino acid in the body. To date glutamine studies have mostly focused on treating severely burned patients, those experiencing cancer cachexia, or undergoing chemotherapy.63 Therapeutic benefits were observed for all of these situa- tions. The most effective doses were seen after administration of 10-15 g three times each day with the biggest responses seen closer to the 45 g per day dosage.[...] In sum- mary, 3-10 g of arginine three times each day, and 10-15 g of glutamine three times each day may additionally provide therapeutic benefit to the schizophrenic."
Edited by LexLux, 01 June 2014 - 03:16 PM.
