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Conjugated Linoleic Acid (CLA)

6/5/02 CLA and Cancer LEF Magazine, April 2000
6/5/02 The Benefits of CLA - Too Good To Be True? LEF Magazine June 1999
6/5/02 Fatty Acid Basics Research documents CLA’s growing number of potential health benefits. Animal studies have found that CLA has beneficial effects on several types of cancer, atherosclerosis and diabetes; immune function; energy; and weight and muscle mass. The results of human studies with CLA presented at the August 2000 national meeting of the American Chemical Society indicate that the substance may help overweight adults lose weight and fat, maintain weight loss, retain lean muscle mass and control adult-onset diabetes. “Because of the human studies, the strongest evidence is for the use of CLA in weight management, but we are going into — and have patents for — diabetes and joint health,” says Rockway.
6/5/02 CLA May Help to Inhibit Proliferation of Colon,Prostate Cancer, Study Suggests Lake Bluff, Illinois, January 8, 2001 In a recent study published in Cancer Letters, an international scientific journal, researchers at Harvard Medical School have identified molecular components in the dietary supplement conjugated linoleic acid (CLA) as potentially influential in the reduction of colorectal and prostatic cancer cells. A naturally occurring fatty acid found primarily in milk, beef and dairy products, CLA is part of the omega-6 fatty acid family. Its mechanism of action, however, mimics that of omega-3 fatty acids such as fish oil, which have been proven to have significant health benefits. Mounting scientific evidence now suggests that some omega -6 dietary fatty acids, such as CLA, can inhibit tumor growth and proliferation of human cancer cells.
6/5/02 Pharmanutrients.com Source of CLA One
6/5/02 Experimental and Unconventional Search on Lenoleic
6/5/02 Mechanisms of Reduced Metastasis by Conjugated Linoleic Acid Kent L. Erickson University of California, Davis Thus, CLA can be an important chemo-protective agent in breast cancer and that one mechanism may involve alteration of proteins that are known to enhance tumorigenesis. This study provides additional evidence to support a phase I clinical trial of CLA since CLA at this level does not appear to be harmful to humans
6/5/02 References on CLA
6/5/02 The Battle of the Bulge Natural Supplements that Aid Weight and Fat-Loss Conjugated linoleic acid (CLA) is an omega-3 that may be useful for reducing fat through improving insulin resistance. According to Susie Rockway, Ph.D., director of scientific and clinical affairs for Lake Bluff, Ill.-based Pharmanutrients CLA is appropriately used for weight maintenance and fat loss. She directed a small pilot study using Pharmanutrients' proprietary CLA ingredient, CLA One™, that involved six people who took 3 g/d of the ingredient (225 mg CLA) for six weeks, while incorporating diet and exercise into their regimen. "We saw fat loss, increase in lean body mass, significant difference in cholesterol and triglycerides, weight circumference--all the parameters you want to see in people who should be losing weight and gaining muscle,"
6/5/02 The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 2002 Mar 28;177(2):163-72 PMID: 11825663 The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer
6/5/02 Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPARgamma-dependent mechanism. Biochim Biophys Acta 2002 Apr 15;1581(3):89-99 PMID: 12020636 CLA decreased the interferon-gamma (IFNgamma)-induced mRNA expression of mediators of inflammation including cyclooxygenase 2 (COX2), inducible NOS (iNOS), and tumor necrosis factor alpha (TNFalpha). Reporter assays also demonstrated reduced IFNgamma-stimulated transcriptional activity of the iNOS and COX2 promoters by CLA. Consequently, CLA decreased the production of PGE(2), TNFalpha and the inflammatory agent nitric oxide (NO) in RAW cells treated with IFNgamma. Other pro-inflammatory cytokines such as IL-1beta and IL-6 were similarly decreased by CLA treatment of RAW cells. In addition, various CLA isomers induced HL60 cell differentiation along the monocytic lineage as assessed by measuring expression of the cell surface marker CD14
6/5/02 Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats: a possible mechanism of the anticarcinogenic effect by CLA. Br J Nutr 2001 Nov;86(5):549-55 PMID: 11737953 However, dietary CLA decreased mucosal levels of prostaglandin E2, thromboxane B2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis
6/5/02 Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF-7 and SW480 cancer cells Lipids 2001 Oct;36(10):1161-8 PMID: 11768161 These data indicate that the growth-promoting effects of LA in the SW480 cell line may be associated with enhanced conversion of AA to PGE2 but that the growth-suppressing effects of CLA isomers in both cell lines may be due to changes in AA distribution among cellular lipids and an altered prostaglandin profile
9/9/01 TITLE: Conjugated linoleic acid and other anticarcinogenic agents of bovine milk fat SOURCE: J Dairy Sci; 82(6):1339-49 1999 UI: 99314099 AUTHOR: Parodi PW Prevention is an important strategy for conquering cancer. Milk fat contains a number of components, such as conjugated linoleic acid, sphingomyelin, butyric acid, ether lipids, beta-carotene, and vitamins A and D that have anticancer potential. Conjugated linoleic acid inhibits the growth of a number of human cancer cell lines and suppresses chemically-induced tumor development at a number of sites in animal models.
9/9/01 TITLE: Milk and dairy products in cancer prevention: focus on bovine lactoferrin . AUTHOR: Tsuda H, Sekine K, Ushida Y, Kuhara T, Takasuka N, Iigo M, Han BS, Moore MA SOURCE: Mutat Res; 462(2-3):227-33 2000 UI: 20232002 It has been proposed that whereas fats in general could promote tumor development, individual milk fats like conjugated linoleic acid could exert inhibitory effects Whey protein may also be beneficial, as shown by both animal and human studies, and experimental data have demonstrated that the major component bovine lactoferrin (bLF), inhibits colon carcinogenesis in the post-initiation stage in male F344 rats treated with azoxymethane (AOM) without any overt toxicity. The incidence of adenocarcinomas in the groups receiving 2% and 0.2% bLF were thus 15% and 25%, respectively, in contrast to the 57.5% control value (P<0.01 and P<0.05, respectively). Results in other animal models have provided further indications that bLF might find application as a natural ingredient of milk with potential for chemoprevention of colon and other cancers.
9/9/01 TITLE: Site-dependent modulating effects of conjugated fatty acids from safflower oil in a rat two-stage carcinogenesis model in female Sprague-Dawley rats. AUTHOR: Kimoto N, Hirose M, Futakuchi M, Iwata T, Kasai M, Shirai T SOURCE: Cancer Lett; 168(1):15-21 2001 UI: 21261653 Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis
9/9/01 TITLE: Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells. AUTHOR: Roche HM, Terres AM, Black IB, Gibney MJ, Kelleher D SOURCE: Gut; 48(6):797-802 2001 UI: 21257926 Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects
9/9/01 TITLE: Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression AUTHOR: Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL SOURCE: Diabetes; 50(5):1149-57 2001 UI: 21232237 Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator-activated receptor (PPAR)-gamma response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism
9/9/01 TITLE: Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells. AUTHOR: O'Shea M, Devery R, Lawless F, Murphy J, Stanton C SOURCE: Anticancer Res; 20(5B):3591-601 2000 UI: 21014300 The relationship between growth and the antioxidant enzyme defence system in human MCF-7 (breast) cancer cells treated with bovine milk fat enriched with conjugated linoleic acid (CLA) was studied. The data indicate that milk fat triglyceride-bound CLA, consisting primarily of the c9, t11 isomer, was cytotoxic towards MCF-7 cells.
9/9/01 TITLE: Conjugated linoleic acid: implications for human health SOURCE: Pharmacol Res; 42(6):503-10 2000 UI: 20514444 AUTHOR: Whigham LD, Cook ME, Atkinson RL Conjugated linoleic acid (CLA) is being sold as a panacea that has the capability of reducing or eliminating cancer, preventing heart disease, improving immune function, and altering body composition to treat obesity or build lean body mass. Unfortunately, there has been very little published human research on CLA. This review will examine the literature on CLA and discuss the animal research on which the above claims are made. The limited human studies will be presented with an evaluation of the potential uses of CLA for human health and disease
9/9/01 TITLE: Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice. AUTHOR: Petrik MB, McEntee MF, Johnson BT, Obukowicz MG, Whelan J SOURCE: J Nutr; 130(10):2434-43 2000 UI: 20472859 These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.
9/9/01 TITLE: Antimutagenic and some other effects of conjugated linoleic acid SOURCE: Br J Nutr; 83(5):459-65 2000 UI: 20409830 AUTHOR: Kritchevsky D Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated, i.e. contiguous. CLA was identified as a component of milk and dairy products over 20 years ago. Two isomers predominate in the synthetic preparation, c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin, stomach, mammary or colon tumours in mice and rats. The inhibition of mammary tumours in rats is effective regardless of type of carcinogen or type or amount of dietary fat. CLA has also been shown to inhibit cholesterol-induced atherosclerosis in rabbits
9/9/01 TITLE: Conjugated linoleic acid and disease prevention: a review of current knowledge SOURCE: J Am Coll Nutr; 19(2 Suppl):111S-118S 2000 UI: 20220887 AUTHOR: MacDonald HB Conjugated linoleic acid (CLA), a derivative of a fatty acid linoleic acid (LA), has been reported to decrease tumorigenesis in animals. CLA is unique because unlike most antioxidants which are components of plant products, it is present in food from animal sources such as dairy foods and meats In vitro results suggest that CLA is cytotoxic to MCF-7 cells and it inhibits the proliferation of human malignant melanoma and colorectal cancer cells. In animal studies, CLA has inhibited the development of mouse epidermal tumors, mouse forestomach cancer and rat mammary cancer. Hamsters fed CLA collectively had significantly reduced levels of plasma total cholesterol, non-high-density lipoprotein cholesterol, (combined very-low and low-density lipoprotein) and triglycerides with no effect on high-density lipoprotein cholesterol, as compared to controls. Dietary CLA modulated certain aspects of the immune defense but had no obvious effect on the growth of an established, aggressive mammary tumor in mice. It is now thought that CLA itself may not have anti-oxidant capabilities but may produce substances which protect cells from the detrimental effects of peroxides. There is, however, insufficient evidence from human epidemiological data, and very few of the animal studies have shown a dose-response relationship with the quantity of CLA feed and the extent of tumor growth. Further research with tumor models is needed to test the efficacy and utility of CLA in cancer and other disease prevention and form the basis of evaluating its effect in humans by observational studies and clinical trials
9/9/01 TITLE: Early detection and prevention of colorectal cancer (review). SOURCE: Oncol Rep; 6(2):277-81 1999 UI: 99148148 AUTHOR: Dashwood RH The ACF can also be used as an end-point to screen for potential inhibitors of colorectal cancer; using this approach, we identified conjugated linoleic acids, indole-3-carbinol, chlorophyllin, and tea polyphenols as promising inhibitors in the colon. These compounds can be added to a growing list of natural and synthetic agents that might be effective against colorectal cancer, including selenium, calcium, and nonsteroidal anti-inflammatory agents
9/9/01 TITLE: Recent advances in conjugated linoleic acid research. AUTHOR: Sebedio JL, Gnaedig S, Chardigny JM SOURCE: Curr Opin Clin Nutr Metab Care; 2(6):499-506 1999 UI: 20142148 New results on the physiological properties of conjugated linoleic acid have been published by several working groups, especially showing the effects of single conjugated linoleic acid isomers on carcinogenesis and body composition. Recently, other studies have shown that conjugated linoleic acid has an influence on diabetes mellitus, platelet aggregation and the immune system. Conjugated linoleic acid was found to modify prostaglandin metabolism and delta9-desaturase activity and influence apoptosis
8/3/02 Inhibition of angiogenesis by the cancer chemopreventive agent conjugated linoleic Acid Cancer Res 2002 Aug 1;62(15):4383-9 PMID: 12154044 Both cis-9, trans-11 and trans-10, cis-12 CLA isomers were effective in inhibiting angiogenesis in vitro in a dose-dependent fashion. The ability of CLA to inhibit angiogenesis may contribute to its efficacy as a chemopreventive agent.

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