Intrinsa

Intrinsa is designed to support stomach, small intestine, and colon health using three well-researched ingredients. Butyrate has potent epigenetic influences, with considerable interest in its ability to influence gene silencing via its effects on histone acetylation. Usable by all ABO blood types.

Butyric Acid (from Magnesium Butyrate).  Also called n-Butanoic acid, or normal butyric acid, is a carboxylic acid with structural formula CH3CH2CH2-COOH. It is notably found in rancid butter or parmesan cheese and has an unpleasant odor and acrid taste, with a sweetish aftertaste (similar to ether). Butyric acid can be detected by mammals with good scent detection abilities (e.g. dogs) at 10 ppb, while humans can detect it in concentrations above 10 ppm.

Normal butyric acid or fermentation butyric acid is found in butter, as an hexyl ester in the oil of Heracleum giganteum (cow parsnip) and as an octyl ester in parsnip (Pastinaca sativa); it has also been found in the fluids of flesh and in perspiration. It may be prepared by the hydrolysis of ethyl acetoacetate or by passing carbon monoxide over a mixture of sodium acetate and sodium ethylate at 205 °C. It is ordinarily prepared by the fermentation of sugar or starch, brought about by the addition of putrefying cheese, with calcium carbonate being added to neutralize the acids formed in the process. The butyric fermentation of starch is aided by the direct addition of Bacillus subtilis.

Butyric acid is a short chain fatty acid (SCFA), which supports the health and healing of cells in the small and large intestine. Many research studies have demonstrated that butyric acid impedes the ability of cancer cells to proliferate in the colon, and therefore is protective of colon cancer. SCFAs have also been associated with helping to maintain healthy blood lipid and sugar levels.

Larch Arabinogalactan.  Larch is a polysaccharide produced from the bark of the Larch tree. Arabinogalactans are found throughout nature and are found in other plants with immunostimulatory activity, including echinacea. Larch arabinogalactan is thought to have immunostimulatory effects by increasing release of interferon gamma, tumor necrosis factor alpha, interleukin-1 and interleukin-6 and stimulating phagocytosis and natural killer cell activity. Larch arabinogalactan is a fibrous product which ferments in the gut. It increases gut microflora, e.g. Lactobacillus, increases short-chain fatty acid production and minimizes ammonia production and absorption. These effects suggest it may be beneficial as a dietary fiber supplement for improving gastrointestinal health and as an adjunct for treating hepatic encephalopathy. Larch arabinogalactan has been shown to concentrate in the liver. Some people think it might block hepatic receptors for metastatic cells and decrease liver metastases. (1,2)

Caprylic acid (from Magnesium Caprylate).  Caprylic acid is the common name for a medium-chain 8-carbon saturated fatty acid known by the systematic name octanoic acid. It is an oily liquid with a slightly unpleasant rancid taste that is minimally soluble in water. It is found naturally in sweat, fusel oil, the milk of cows and goats, coconuts, breast milk and palm and coconut oil.

Caprylic acid is absorbed from the intestine and, in contrast with long-chain fatty acids, immediately enters into the portal circulation. It is carried by blood lipids. Most ingested caprylic acid undergoes beta-oxidation in the liver. Caprylic acid is known to have anti-fungal properties and is often recommended by nutritionists for the treatment of candidiasis. Caprylic acid is excellent for dealing with candida in the intestines, which are frequently colonized by candida; but, being a medium-chain fatty acid, it has more difficulty in penetrating fatty cell wall membranes. Therefore, caprylic acid works synergistically with butyric acid – a short chain fatty acid—so that it that can more easily penetrate tissues in the body such as muscles, joints, and sinuses. Caprylic acid is also used in the treatment of some bacterial infections.

Disease Prevention and Protection

• Butyric acid changes the structure of chromatin through its effects on post-translational modification, with key modifications being acetylation and phosphorylation of the nuclear histones. Butyric acid can also modify the differentiation state of cells and, in the case of cancerous colonic cells, overcomes their resistance to normal pre-programmed death. Thus, the activities of this fermentation product of dietary fiber may contribute substantially to the decreased incidence of bowel cancer that has been associated with fiber intake. (3) Butyric acid has been shown to help impede the ability of cancer cells to proliferate in the colon and therefore may be protective of colon cancer.
• Butyrates effects occur in normal and neoplastic colonic cells. In normal cells, butyrate induces proliferation at the crypt base, while inhibiting proliferation at the crypt surface. In neoplastic cells, butyrate inhibits DNA synthesis and arrests cell growth in the G1 phase of the cell cycle.
• Larch arabinogalactan increases gut microflora, e.g. Lactobacillus, increases short-chain fatty acid production and minimizes ammonia production and absorption. These effects suggest it may be beneficial as a dietary fiber supplement for improving gastrointestinal health and as an adjunct for treating hepatic encephalopathy.
• Larch arabinogalactan has been shown to concentrate in the liver. Some research shows it might block hepatic receptors for metastatic cells and decrease liver metastases. (1,2)
   

Amelioration of Symptoms of Ulcerative Colitis

• Butyric acid helps support the health and healing of cells in the small and large intestine.
• Butyrate plays an important role in the colonic mucosal growth and epithelial proliferation.
• A reduction in the colonic butyrate level induces chronic mucosal atrophy.
• Butyrate, and also to a lesser degree propionate, are substrates for the aerobic energy metabolism, and trophic factors of the colonocytes. (4)
   

Antifungal /Antiviral/ Antibacterial

• Caprylic acid was reported many years ago to have some antifungal activity in vitro. Other in vitro studies showed some activity against some viruses and bacteria.
• Caprylic acid may affect the fluidity of viral and fungal cell membranes.
• Immunostimulatory: larch arabinogalactan is thought to have immunostimulatory effects by increasing release of interferon gamma, tumor necrosis factor alpha, interleukin-1 and interleukin-6 and stimulating phagocytosis and natural killer cell activity.
   

Epigenetic Effects: Histone Modification

• Epigenetic influences are post-translational modifications of the histone proteins associated with the DNA strand or agents that can alter the methylation pattern of the genome.
• Histone modification results from changes to chromatin-containing acetylated histones. When histones are open, chromatin is accessible to transcription factors and genes are potentially active. When closed, chromatin is condensed and unavailable for reading. Butyrate has bee shown to be a potent inhibitor of the de-acetylation of histones. (5,6) 
   

Histone deacetylase inhibitors

• These enzymes remove an acetyl group from histones, which allows histones to bind DNA and inhibit gene transcription. HDAC inhibitors disrupt the cell cycle and/or induce apoptosis via activation of genes such as P21 and BAX. Cancer cells appear to be more sensitive than non-transformed cells HDAC inhibitory compounds.

• Natural products involved in inhibition of histone deacetylase (7):
  • Sulforaphane (broccoli sprouts)
  • Sodium butyrate
  • Diallyl disulfide (garlic)
  • Calorie restriction (SIRTUIN family of deacetylases)
  • Quercetin has a cooperative effect

1. D’Adamo P. Larch arabinogalactan. J Naturopath Med 1996;6:33-7.
2. Kelly GS. Larch arabinogalactan: Clinical relevance of a novel immune-enhancing polysaccharide. Alt Med Rev 1999;4:96-103.
3. Crit Rev Food Sci Nutr. 1998 May;38(4):259-97.
4. Int J Colorectal Dis. 1999 Nov;14(4-5):201-11.
5. Entin-Meer M, Rephaeli A, Yang X, Nudelman A, VandenBerg SR, Haas-Kogan DA. Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas. Mol Cancer Ther. 2005 Dec;4(12):1952-61.
6. Komata T, Kanzawa T, Nashimoto T, Aoki H, Endo S, Kon T, Takahashi H, Kondo S, Tanaka R. Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells. Int J Oncol. 2005 May;26(5):1345-52.
7. D’Adamo PJ. Lecture ‘Variation: A Central Concept in Naturopathic Medicine” NTANP Conference 10/2006 New York, NY