Notes on HMB; Leucine as a Supposedly-Ketogenic Amino Acid

This article [Kuhara et al., 1982: (http://www.ncbi.nlm.nih.gov/pubmed/7116632)] describes leucine as being a "potent ketogenic amino acid," and I guess there can be a significant contribution of leucine-derived branched chain organic acids, such as HMB/3-hydroxyisovalerate, to ketogenesis. About 5 percent of leucine normally is converted into HMB, apparently. The only other thing I thought of is that the slight elevation in plasma branched-chain amino acids (Holocek et al., 2009) [Holecek et al., 2009: (http://www.ncbi.nlm.nih.gov/pubmed/19056452)] might conceivably produce tryptophan (TRP) and tyrosine (TYR) and phenylalanine (PHE) depletion from the brain, in my opinion, but it looks like the effect is probably not even as pronounced as the increase in the plasma BCAA (leucine+isoleucine+valine)/(TYR+TRP+PHE) ratio from a high-protein meal. In dietary protein, 20-30 percent of the amino acids are BCAA's, if memory serves, and this causes the plasma BCAA/(TYR+TRP+PHE) ratio to increase progressively as the dietary protein intake increases [Fernstrom et al., 1979: (http://www.ajcn.org/cgi/reprint/32/9/1912.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/573061)]. There's the potential that that effect, to the extent that it could occur in response to the mild, apparent "leucine-sparing" effect of HMB (Holocek et al., 2009), could, in my opinion, produce transient worsening of mood or other psychiatric complications in people. Although some of those trials with HMB suggest that the opposite effect would occur, I can't really put a lot of faith in some of these articles on the effects of BCAAs on the brain. They're used as neuroprotectives and as a treatment for mania (leucine and other BCAAs), and I doubt HMB would have the same effects. It's not an amino acid and wouldn't be expected to compete with tyrosine, tryptophan, and phenylalanine for entry into the brain. But I can't be sure about that, and it's obviously something a person would want to discuss with one's doctor. It's possible that the supposed neuroprotective effects of leucine and BCAAs, as in spinocerebellar degeneration, etc., are not mediated by glutamine or 2-oxoglutarate sparing or whatever mechanism has been suggested but are the result of a ketogenic effect of leucine in astrocytes (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=BCAA+spinocerebellar). The authors of those BCAA-as-neuroprotective articles view the BCAAs as being energy substrates or as being capable of decreasing glutamate, though, I think. I don't know what the proposed mechanisms are, besides those mechanisms. HMB can also act as a precursor of fatty acids and could conceivably cause problems in people with liver disease, but those old articles show that it's, evidently, preferentially incorporated into cholesterol. I discussed the BCAA issues in a past posting (http://hardcorephysiologyfun.blogspot.com/2009/02/potential-psychiatric-pitfalls-in.html).