Conjugated linoleic acid (CLA) and diabetes

Here is another installment on the series of blogs about the health benefits of conjugated linoleic acid (CLA), a fatty acid or fat in plain English, found primarily in the foods of ruminant origin, such as the milk and meat products from cows, buffaloes, sheep, goat, etc. I was invited by Nova Science Publishers, Hauppauge, New York, to write a book chapter on CLA this past summer. Although I decided not to submit the book chapter eventually, here I discuss a few things about the potential relationship of CLA with diabetes. I apologize in advance for the content that may not be as palatable for blog readers as can be for a scientific audience.

The role of CLA in regulating type-2 diabetes, which is also linked to obesity, is not only complex and not well understood, but also conflicting at times. Since t-10, c-12 CLA is linked to decreased body fat, it is this isomer that is implicated as an antidiabetic. It has been shown that CLA was as equally effective as thiazolidinediones, a class of oral insulin sensitizing agents that improve glucose utilization without stimulating insulin release, in reducing fasting glucose in Zucker diabetic rats (Belury and Vanden Huevel, 1999). In a double blind study with human diabetics, Belury (2002b) showed a decreased blood glucose and plasma leptin in CLA supplemented patients. Belury et al. (2003) suggested that t-10, c-12 isomer may be the bioactive isomer of CLA that influences the body weight changes observed in subjects with type-2 diabetes. Although serum insulin was higher in CLA fed rats than thiazolidinediones treated rats, it was only half the amount observed in control rats (Belury and Vanden Huevel, 1999). Later, Henrickson et al. (2003) demonstrated that the improved glucose tolerance and insulin-stimulated glucose transport in the skeletal muscle of obese Zucker diabetic rats was due to t-10, c-12 isomer with no effect due to c-9, t-11 isomer. In contrast, t-10, c-12 isomer of CLA was shown to induce hyperinsulinemia and fatty liver in mice with no effect due to c-9, t-11 isomer (Clément et al., 2002). Similarly, t-10, c-12 isomer of CLA promoted insulin resistance, increased serum glucose and insulin concentrations, whereas c-9, t-11 isomer had ameliorative effect on lipid metabolism in ob/ob mice (Roche et al., 2002). Brown et al. (2003) demonstrated that t-10, c-12 isomer of CLA decreased insulin-stimulated glucose uptake and metabolism in differentiating human preadipocytes.

The initial proposition about the activation of PPARγ in modulating diabetes (Belury and Vanden Heuvel, 1999; Moya-Camarena et al., 1999) seems to be questioned with a new finding decreasing the expression of PPARγ by t-10, c-12 (but not c-9, t-11) in adipocytes, which could promote insulin resistance and oppose the hypoglycemic actions of thiazolidinediones in vivo (Brown and McIntosh, 2003; Brown et al., 2003). This could be the reason why Risérus et al. (2002) found an increased insulin resistance and glycemia in abdominally obese men when treated with 3.4g/d of t-10, c-12 isomer of CLA. Some of the concerns about insulin resistance in humans (Risérus et al., 2002) and mice (Roche et al., 2002) as well as fatty liver associated with CLA (Clément et al., 2002) could probably be eliminated with arginine-CLA (Kim et al., 2004), because arginine infusion is known to have a preventive role in the insulin resistance by decreasing total plasma homocysteine concentration (Cassone Faldetta et al., 2002). 

More recently, the use of moderate doses of an equimolar mix of the two main CLA isomers reduced body fat content, improved plasma lipid profile, maintained insulin sensitivity (despite a moderate degree of hyperinsulinaemia) without the promotion of inflammatory markers in adipose tissue of mice fed a high-fat diet (Parra et al., 2010). Supplementation with CLA exerted beneficial effects on BMI, total and trunk adipose mass, and lean tissue mass in obese postmenopausal women with type 2 diabetes (Norris et al., 2009). Furthermore, supplementation with these CLA may be beneficial for weight loss, glycemic control, or both.  Results from another experiment demonstrated that that t10c12CLA can improve liver carbohydrate and lipid metabolism in type I diabetic mice (Jourdan et al., 2009).

 

Put together, the effects of CLA on diabetes appear to be beneficial. However, further research on the effects, doses, and mechanisms of action of CLA is warranted.

Contact the author regarding complete details about the references or if you have any questions.

Conjugated linoleic acid (CLA) and bone health

This is another part of a series of blogs that I have written about the health benefits of conjugated linoleic acid (CLA), a fatty acid or fat in plain English, found primarily in foods of ruminant origin, such as the milk and meat products from cows, buffaloes, sheep, goat, etc. I was invited by Nova Science Publishers, Hauppauge, New York, to write a book chapter on CLA this past summer. Although I decided not to submit the chapter eventually, here I discuss a few things about the potential relationship of CLA with bone health. Therefore, I apologize in advance for the content that may not be as palatable for blog readers.

Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism and increase total body ash content. However, the effects on bone mass appear to be slightly inconsistent between animal and human studies. When CLA was consumed as a dietary supplement along with moderate treadmill exercise, a significant increase in bone mass was observed in middle-aged female mice (Banu et al., 2008). Extra calcium in the diet improved CLA's effects on bone mass, particularly in male mice; without extra dietary calcium there was no effect of CLA on bone mass (Park et al., 2008). This finding may help improve the efficacy of CLA to be used as a dietary supplement as part of an osteoporosis prevention strategy (Park et al., 2008). In a study on age-associated bone loss in C57BL/6 female mice, CLA was suggested to prevent the loss of bone and muscle mass by modulating markers of inflammation and osteoclastogenic factors (Rahman et al., 2007). Halade et al. (2010) investigated the ability of conjugated linoleic acid (CLA) and fish oil (FO), alone or in combination, to modulate bone loss using 12 months old C57Bl/6J mice fed 10% corn oil diet as control or supplemented with 0.5% CLA or 5% FO or 0.5% CLA+5% FO for 6 months. It was shown that CLA-fed mice had reduced body weight and body fat mass with enhanced hind leg lean mass and bone mineral density, which were associated with fatty liver and increased insulin resistance. However, when CLA was given with fish oil, mice exhibited reduced body weight, BFM, peroxisome proliferator-activated receptor gamma and cathepsin K expression in bone marrow with enhanced BMD and hind leg lean mass. Moreover, CLA with fish oil supplementation reduced liver hypertrophy and improved insulin sensitivity with remarkable attenuation of bone marrow adiposity, inflammation and oxidative stress in aging mice. Results suggested that CLA in combination with fish oil might be a novel dietary supplement to reduce fat mass and improve BMD. Dietary CLA prevented many of the growth- and bone-related side effects arising from 8 weeks of corticosteroid administration, which is used in many disease states, while resulting in greater increases in bone mineral content and bone mineral density, and can contribute to an improvement in some of the mechanical properties of bone (Roy et al., 2008). In a study with postmenopausal women, Brownbill et al. (2005) observed higher BMD in the forearm hip, lumbar spine and whole body. These findings indicated dietary CLA may positively benefit BMD in postmenopausal women. However, in a double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism (Doyle et al., 2005). More studies are warranted examining the relationship between dietary CLA and BMD. 

Watkins et al. (1996) found a higher rate of bone formation in chicks fed butterfat, which was suggested to be due probably to increased CLA intake. Dietary CLA led to differences in CLA enrichment of various organs and tissues, bone marrow and periosteum containing the highest concentrations of CLA and brain the lowest (Li and Watkins, 1998). Enrichment of chondrocytes with CLA affected collagen synthesis in a dose dependent fashion (Watkins et al., 1999). Reduced production of arachidonic acid and PGE₂ in the chondrocytes was suggested to be the possible mechanism (Watkins and Siefert, 2000). Such changes in bone biomarkers and bone formation rates in rats were associated with increased c-9, t-11 CLA in bone tissue lipids (Watkins et al., 2003). Furthermore, dietary beef fat and a CLA supplement were able to maintain synthetic activity of osteoblastic cells and CLA was even able to rescue the reduced bone formation rate in rats given a diet high in ώ-6 FA (Watkins et al., 2003). McDonald (2000) suggested increased ash content in CLA fed animals (Park et al., 1999) is due to protection of bone loss from cytokines. Further investigation is needed as to how bone metabolism is affected by CLA and mechanism of action related with it.

A significant reduction of high fat diet-induced bone marrow adiposity was observed in t-10, c-12 CLA fed mice as compared to that of corn oil and c-9, t-11 CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections (Rahman et al, 2010). Mice fed a t-10, c-12 diet maintained a significantly higher bone mineral density in femoral, tibial and lumbar regions than those fed corn oil and c-9, t-11 CLA diets.  In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t-10, c-12 CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c-9, t-11 CLA and linoleic acid treated cultures. It was suggested that t-10, c-12 CLA is the most potent CLA isomer and it exerted its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity (Rahman et al, 2010). In another experiment (Platt and El-Sohemy, 2009), c-9, t-11 CLA CLA inhibited osteoclast formation and activity from human cells, suggesting that this isomer may prevent bone resorption in humans. However, t-10, c-12 did not significantly reduce osteoclast formation, but reduced osteoclast activity and cathepsin K and RANK expression, suggesting that this isomer may also affect bone resorption. Similarly, c-9, t-11 CLA, but not t-10, c-12 isomer of CLA increased the formation of mineralized bone nodules using bone cells of human origin, providing evidence for isomer-specific effects of CLA on bone health (Platt et al., 2007). In contrast, commercially available CLA mixtures and single CLA isomers had no effect on bone mass in hyperinsulinemic, obese rats (Burr et al., 2007).

Contact the author regarding complete details about the references or if you have any questions.