Not an easy subject, so apologies up-front.
[1] If you have smelled rancid butter, you will be familiar with the smell of butyric acid. It can even be detected, at much lower levels, in freshly-bought butter. Butyric acid is a short-chain fatty acid found in butter in triglyceride form. With rancidity, the glyceride connection is broken & the odor becomes discernable. Butter is 3-4% butyric acid - the name comes from the Latin for butter.
Butyrate is simply an ester or salt of butyric acid. Cells lining the human colon rely on butyrates for energy. Colon cell health depends - not on butter consumption - but on the cooperation of bacteria in the gut. It also depends on fuel for the bacteria. This is fermentable fiber such as pectin, which can be digested by the bacteria, with butyrates being part of the "waste products". Carbohydrate in - fatty acids out!
Pectins are polysaccharides - carbohydrate chains of monosaccharides. Glucose & fructose are examples of monosaccharides. Another class of polysaccharides includes the fructans, which includes the inulins.
Inulin is marketed as a prebiotic (not probiotic). The theory is that it is an ideal food for "preferred" bacteria. Of course, one cannot predict which colonies will grow & which will wither, in any individual. You have to start with some preferred bacteria. But the idea - one of them - is that more butyrates will be produced if beneficial colonies are restored.
Anyway, butyrate is therefore a naturally occurring substance - arguably more natural to the body than any supplement, apart from vitamin D.
The butyrate of interest in the studies is sodium butyrate:
easylivinghealth.com/E-Lyte...
Oral sodium butyrate takes a hit in the liver (first pass), so dosage is a bit high. Tributyrin, which has a nasty taste, might be an alternative, I suppose, but hard to come by.
[2] Sodium butyrate is a HDAC inhibitor. As such, it can reverse epigenetic changes in PCa. It is well tolerated.
Histones are the proteins that facilitate efficient DNA binding into a tiny tight ball for storage. Acetylase is the enzyme that loosens histones, allowing access to DNA coding instructions. PCa triggers the generation of deacetylases that counter acetylase & prevent access to DNA areas responsible for anti-cancer genes. Over-expression of histone deacetylases [HDACs] is an epigenetic change - no mutations are involved. Epigenetic changes can, in theory, be reversed. Sodium butyrate is a natural HDAC inhibitor. **
** For a nice, albeit more technical, explanation, see "DNA Accessibility", beneath the study links.
[2a] (2016 - U.S.) "The histone H2B of the prostate cancer cell line DU-145 was found to have hypoacetylation ... as compared to the non-malignant prostatic cell line RC170N/h."
"H2B regained acetylation ... in the DU-145 cells after sodium butyrate treatment."
[3] Sodium butyrate & androgen receptor coregulators.
[3a] (2013 - Czech Republic) The Abstract makes a point that I have long thought missing in discussions of the androgen receptor [AR]. When androgen binds to the AR, there is no obligation for it to zip along to the nucleus & initiate cell division. What happens next depends on context - specifically, the AR coregulators - not only coactivators, but also corepressors.
Sodium butyrate has an effect on at least two coregulators in cancer cells, with minimal effect on normal cells.
[4] Sodium butyrate induces cellular senescence in prostate cancer cells.
[4a] (2011 - Germany) "Cellular senescence leads to an irreversible block of cellular division capacity both in cell culture and in vivo. The induction of an irreversible cell cycle arrest is very useful for treatment of cancer. Histone deacetylases (HDACs) are considered as therapeutic targets to treat cancer patients. HDAC inhibitors repress cancer growth and are used in various clinical trials. Here, we analyzed whether sodium butyrate (NaBu), an inhibitor of class I and II HDACs, induces cellular senescence in neuroblastoma and prostate cancer (PCa) including an androgen-dependent as well as an androgen-independent human PCa cell line."
"The data underline that tumor cells can be driven towards cellular senescence by HDAC inhibitors, which may further arise as a potent possibility for tumor suppression."
[5] Sodium butyrate - cell cycle arrest &/or cell death (apoptosis).
[5a] (2012 - China) "Histone deacetylase inhibitors (HDACis) have shown significant antiproliferative and apoptotic properties in various types of cancer cells, including prostate cancer cells, and are therefore being evaluated as a treatment modality. However, the mechanism by which sodium butyrate(SB) induces apoptosis is not completely understood. We focused on SB which exists in the intestine and is therefore expected to have less adverse effects."
"SB induces {cell cycle} arrest {&} potently induced apoptosis"
[6] Sodium butyrate & the Androgen Receptor [AR]
[6a] (2007 - South Korea) What is facinating about this LNCaP cell study, is that:
"Sodium butyrate induced the expression of AR after 48 h treatment. In addition, immunofluorescence assay revealed the nuclear localization of the AR after sodium butyrate treatment."
"... sodium butyrate effectively inhibited cell proliferation and induced apoptosis of human prostate cancer cells by altering the expression of cell cycle regulators and AR."
So, rather than suppressing AR, Sodium butyrate seems to have restored its traditional role as a regulater of growth. Seemingly by reversing epigenetic changes:
"The expression levels of acetylated histone H3 and H4 increased significantly after 48 h treatment with sodium butyrate."
[7] Sodium butyrate versus Tributyrin.
[7a] (2004 - Germany) "Butyrates are naturally occurring short-chain fatty acids leading to differentiation of numerous cell types... The potential clinical utility of butyric acid is mainly limited by a short half-life in vivo as plasma concentrations decrease within minutes below the concentration needed for effects in vitro... To circumvent the problem of fast metabolism of butyrate monomers, analogues have been tested... Tributyrin is a readily available trimer of butyric acid and is cleaved intracellular by lipases into three molecules of butyric acid."
"The tumour size was significantly less increasing in the treated animals with no significant difference between sodium butyrate or tributyrin applied with equal final plasma concentration."
"In this study, we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. These two HDACs have shown a strong cell growth-inhibitory and proapoptotic activity.
[8] For those who are now eager to try Tibetan butter tea, which is made with rancid (yak) butter:
theglobeandmail.com/life/tr...
-Patrick
[2a] ncbi.nlm.nih.gov/pmc/articl...
[3a] ncbi.nlm.nih.gov/pubmed/235...
[4a] ncbi.nlm.nih.gov/pubmed/259...
[5a] ncbi.nlm.nih.gov/pubmed/219...
[6a] ar.iiarjournals.org/content...
[7a] ncbi.nlm.nih.gov/pmc/articl...
DNA Accessibility
In mammalian cells, the genome is tightly packed into chromatin units called nucleosomes, which consist of ∼147-base-pair segments of DNA wrapped around a core of eight histones (two each of H2A, H2B, H3, and H4).39,40 Electrostatic forces between positive-charged lysine residues on the histone proteins and negative-charged phosphates on the DNA backbone allow the nucleosome to adopt a highly condensed three-dimensional structure that limits access to the DNA segment by transcription factors and other DNA-seeking chemicals. For example, for a segment of DNA to be read by the cell's transcriptional machinery, the DNA must first be made accessible. One means by which this is achieved in the cell is through acetylation by HAT36 of the lysine residues on the histone tails protruding from the nucleosome cores.24,40 This neutralizes the positive charges on the histone tails (relieving electrostatic forces that keep the histone–DNA pair bound closely together) and exposes the DNA.39 Once transcription has been completed, HDAC enzymes remove the N-acetyl groups from the acetylated lysine residues, which restores positive charge to the histone and draws the DNA back into its protected, less-accessible tertiary structure.5
