Should you recommend CLA for Weight Loss? Linda Lizotte, R, D, CDN

What is CLA? CLA is made up of various fatty acid isomers =

compounds that share the same chemical formula but differ in chemical structure.

Related isomers can have very different effects: CLA c9-t11 Rumenic helps immune system while

t10-c12 helps weight loss

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CLA Research

Conjugated Linoleic Acid Reduces Body Fat Mass in Overweight and Obese Humans, J Nutr 2000 Dec;130(12):2943-8

Purpose: To investigate the dose-response relationships of CLA with regard to BFM in humans

Randomized, double-blind study including 60 OW or obese volunteers

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CLA Reduces Body Fat Mass

Subjects were divided into 5 groups They were given either olive oil (placebo), CLA

1.7g, 3.4g, 5.1 g, 6.8 g daily for 12 weeks. Body composition was measured Results: A Significantly higher reduction in BFM

was found in the CLA groups, compared with the placebo group

3.4 g (P= .05), 6.8 g (P= .02) These 2 doses got the best results.

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CLA Reduces Abdominal Obesity

Conjugated Linoleic Acid reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomized controlled trial.

Int J Obes Relat Metab Disord 2001 Aug;25(8):1129-35.

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Purpose: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic syndrome (X). – Subjects: 25 abdominally obese men between

39-64 y.o.– Double-blind randomized controlled trial for 4

weeks

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CLA research for Syndrome X

CLA Reduces Abdominal Obesity Results: After 4 weeks there was a

significant decrease in abdominal diameter, in the CLA group compared to placebo.

Authors’ conclusion: CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat.

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CLA’s effects on serum lipids and body fat Effect of supplementation with CLA on

human serum lipids and body fat. J Nutr Biochem 2001 Oct;12(10);585-594.

22 volunteers, divided in 2 groups Double-blind study Study group got .7g CLA for 4 weeks, then

1.4 g CLA for next 4 weeks. Control group received placebo.

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CLA’s effects on serum lipids and body fat Serum LDL cholesterol Triacylglycerols total cholesterol

all decreased significantly during the first period.

The sum of the thickness of 10 skinfolds Percentage body fat calculated from it and fat mass were all significantly reduced in the CLA

group during the second period.

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CLA’s effects on serum lipids and body fat The CLA content of all lipids checked

increased gradually with supplementation and doubled at the end of the study.

These data indicate that supplementation with .7 g - 1.4 g CLA daily for 4-8 weeks may modulate body fat and serum lipids as well as increase the CLA content of serum lipids in humans.

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Let’s analyze a negative CLA study Trial by Riserus in the Journal Circulation.

Diabetes Care 2002 Sep;25(9):1516-21

From this trial they report that dietary supplementation of CLA to men resulted in elevations both of oxidative stress ( free radical burden) and of the inflammation biomarker CRP.

We know C-reactive protein is a sensitive indicator linked to heart attack mortality.

This study also claims that blood glucose levels worsened on CLA.

Circulation. 2002 Oct 8;106(15):1925-9.

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Negative Research on CLA Riserus commented that the degree of elevation of

oxidative stress (F2 isoprostanes) from the single-isomer CLA mixture exceeded that attributable to heavy smoking.

Why were smokers included in a study that is measuring oxidative stress?  

Quote from Riserus: “Whether or not the CRP increase (41%) within the CLA mixture group, which was not significantly different from placebo, is clinically relevant is uncertain, but the strong link between elevated CRP and coronary risk might cause some concern.”

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Problems with this study

Why did the researchers include smokers when smokers are known to have elevated F2 Isoprostanes? The exact oxidative stress markers they looked at here

Why does this study show worsening of blood sugar when all other studies show the opposite?

Why did they study the 10-12 isomer alone when supplements are an equal mix of 9,11 and 10,12 more like nature provides in food?

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Is the title of this study deceiving? The title of the study is: “Supplementation with conjugated linoleic acid

causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.”

Isomer dependent means that only the t10-c12 CLA showed negative results

Why is this not clear in the title? Why do they start the title with “Supplementation

with CLA………….. DFH CLA is 50:50 c9-t11 and t10-c12, NEVER 10-

12 alone.

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Many positive diabetes studiesSource:Ohio State University, Journal of Nutrition Date:Jan 29,2003 Fat That May Benefit Diabetics Reduces Weight, Blood Sugar “Supplementing the diet with a certain fatty acid

may lead to better weight control and disease management in diabetics.”

“Diabetics who added an essential fatty acid called conjugated linoleic acid (CLA) to their diets had lower body mass as well as lower blood sugar levels by the end of the eight-week study.”

http://www.sciencedaily.com/releases/2003/01/030129080354.htm

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Studies are positive for diabetes

Quotes from Martha Belury, the senior author of the study and associate professor of human nutrition at Ohio State University:

"In previous work, we found that CLA delayed the onset of diabetes in rats”

"In this study, we found that it also helped improve the management of adult-onset diabetes in humans."

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Controversial research on CLA

The researchers asked 21 people with adult-onset diabetes to take either a supplement containing a mix of rumenic acid (9,11) and 10-12 isomer CLA or a safflower oil supplement as a control.

The group was divided roughly in half. Rumenic acid is the predominant isomer in foods

that contain CLA, while the 10-12 isomer is a little less abundant.

Participants were instructed to take their respective supplements every day for eight weeks.

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Controversial research on CLA At the end of the trial, the researchers took blood

samples from each participant to check CLA levels.

By then, fasting blood glucose levels had decreased in 9 of the 11 people taking the CLA supplement

but only in 2 of the 10 taking safflower supplements

Fasting blood glucose levels decreased nearly five-fold in patients taking CLA, compared to patients taking the safflower oil.

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CLA lowers Leptin Levels

The researchers also studied the impact each isomer had on changes in body weight and levels of the hormone leptin.

It was the 10-12 isomer that was linked to a reduction in body weight and leptin levels.

Leptin levels decreased in the CLA group, and rose slightly in the safflower group.

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CLA worked without dieting

While the average weight loss among patients taking CLA supplements was small (about 3.5 pounds), they had been asked to not change their normal caloric intake during the study.

The group taking safflower supplements neither lost nor gained weight.

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Trans10, cis12 conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator.Granlund L, Juvet LK, Pedersen JI, Nebb HI.

A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 and trans10, cis12 CLA. A crude mixture of these isomers has in animal studies been shown to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the trans10, cis12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which trans10, cis12 CLA affects lipid accumulation in adipocytes. We have shown that trans10, cis12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 and 25 micromolar, respectively. Trans10, cis12 CLA fails to activate peroxisome proliferator-activated receptor gamma (PPARgamma), but selectively inhibits thiazolidinedione-induced PPARgamma activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with trans10, cis12 CLA alone, or in combination with Darglitazone, down regulate the mRNA expression of PPARgamma, as well as its target genes fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.

CLA worsens CRP and IRS??

CONCLUSIONS: Weight loss in morbidly obese patients induces a significant decrease of CRP and IL-6 concentrations in association with an improvement of the Insulin Resistance Syndrome.

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CLA for immune system

• Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta. 2002 Apr 15;1581(3):89-99

• Conjugated linoleic acid (CLA) is a dietary fatty acid that has received considerable attention due to its unique properties in rodent models including anti-cancer, anti-atherogenic and anti-diabetic effects.

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CLA’s immune benefits

• CLA decreased the production of PGE(2), TNFalpha and the inflammatory agent nitric oxide (NO) in RAW cells treated with IFN gamma.

• Other pro-inflammatory cytokines: IL-1 beta and IL-6 were similarly decreased by CLA treatment.

• Taken together, these results suggest that CLA has anti-inflammatory properties that are mediated, at least in part, by the nuclear hormone receptor PPAR gamma.

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Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men.Albers R, van der Wielen RP, Brink EJ, Hendriks HF, Dorovska-Taran VN, Mohede IC.Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, The Netherlands.

Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. DESIGN: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: 71 healthy males aged 31-69 y received one of the following treatments: (1). mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2). mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3). sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11+t10,c12) (50:50) or 1.6 g (c9,t11+t10,c12) CLA (80:20) per day in treatment groups for 12 weeks. RESULTS: Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA 50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-alpha, IL1-beta, IL6, IFN-gamma, IL2, IL4, and PGE(2), were not affected. CONCLUSION: This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group.

What does this study tell us?

It supports the benefits, anti-inflammatory, of CLA that is a 50:50 mix of 9,11 and 10,12.

DFH CLA is exactly this: 50:50 mix of 9,11 and 10,12 isomers.

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Conjugated linoleic acid (CLA) is a dietary fatty acid that has received considerable attention due to its unique properties in rodent models including anti-cancer, anti-atherogenic and anti-diabetic effects. The effects of CLA are similar to those seen with ligands for peroxisome proliferator-activated receptor (PPARs), most notably of the PPAR gamma subtype. With the recent observation of a role for PPAR gamma in regulation of immune responses, we suspected that CLA could affect immune function, in particular macrophage activity. The goal of our study was to examine whether this dietary fatty acid has anti-inflammatory properties similar to those reported for PPAR gamma activators such as 15-deoxy prostaglandin J(2) (PGJ(2)). CLA decreased the interferon-gamma (IFN gamma)-induced mRNA expression of mediators of inflammation including COX2, inducible NOS (iNOS), and tumor necrosis factor alpha (TNFalpha). Reporter assays also demonstrated reduced IFN gamma-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 IFN gamma. Other pro-inflammatory cytokines such as IL-1 beta 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. This differentiation process, as well as the regulation of iNOS and COX2 by 15dPGJ(2), is believed to involve PPAR gamma. Taken together, these results suggest that CLA has anti-inflammatory properties that are mediated, at least in part, by the nuclear hormone receptor PPAR gamma.

Study summaries: CLA reduces the following inflammatory biomarkers: IL1 and IL6, TNF alpha, COX2, iNOS, PGE2 and nitric

oxide

Food for thought: CLA reduces all inflammation pathways yet increases

CRP, an inflammatory biomarker for heart disease?? This nutrient helps weight loss and diabetes yet is bad for

the heart? There are many studies showing CLA’s anti-cancer

benefits.

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Dietary CLA decreased weight loss and extended survival following the onset of kidney failure in NZB/W F1 mice.Yang M, Cook ME.Lipids. 2003 Jan;38(1):21-4 Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

In an earlier study, we showed that feeding CLA immediately after weaning prolonged survival of NZB/W F1 mice after onset of proteinuria. In the present study, the feeding of CLA was delayed until mice had developed proteinuria. Thirty NZB/W F1 mice were fed a regular rodent chow after weaning. Urine samples were collected to detect proteinuria. Once a mouse was proteinuria positive, it was then randomly assigned to a 0.5% CLA supplement semipurified diet or a control diet (supplement 0.5% corn oil). The next proteinuria positive mouse was then assigned to the opposite diet to which the first mouse was assigned. Mice fed the control diet lost 25% more body weight (13.0 g) than mice fed the CLA diet (9.7 g). Moreover, CLA-fed mice survived an average 1.7-fold longer (148 d) than mice fed the control diet (89 d) after the onset of proteinuria. This follow-up study confirmed that dietary CLA had a beneficial effect in the autoimmune NZB/W F1 mouse. In summary, the cachectic symptom of systemic lupus erythematosus was decreased by dietary CLA and survival days were increased over control group.