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What is Pre-Diabetes? #ShortsCLA and diabetes -
CRP is synthesized by liver in response to inflammation. Inflammations may be due to a variety of reasons such as cancer, diabetes, cardiovascular diseases, etc. Increased plasma concentration of CRP, a circulatory inflammation marker helps in predicting CVD [ ].
A mixture of 9- and CLA isomers with equal proportions also reported an increased CRP, but not of the other inflammatory markers, i.
Another study concluded that a mixture of 9- and CLAs had more adverse effects on CVD markers, while 9-CLA isomer appeared to be more neutral in healthy postmenopausal women.
Daily supplementation of 5. The CLA mixture at a dose of 3. High dose of CLA consumption 6. In contrast, CLA in the same composition ratio , but in lower dose i.
Outcome from some recent studies suggested that CLA did not increase the risk of CVD. Pfeuffer et al. It was observed that CLA did not impair endothelial function. Other parameters associated with metabolic syndrome and oxidative stress were not changed or slightly improved.
Interestingly, it was observed that oral supplementation of CLA along with calcium reduced the incidence of pregnancy-induced hypertension without changing the plasma levels of other circulatory markers such as PGF2α, CRP and IL-6 [ ].
Forty eight healthy primigravidas with a family history of preeclampsia and with diastolic notch were included in this double-blind and placebo-controlled non cross-over study. Participants were randomized to daily oral doses of elemental calcium 0.
The controversial beneficial and detrimental effects of CLA on heart health observed during clinical studied are summarized in Figure 2. All these studies were too randomized in dosage, composition and duration, which make difficult to conclude the positive effects of CLA on heart health.
Moreover, there is a complete lack of uniformity in assessing the effects CLA on heart health, i. Even though the isomeric mixture of 9- and 10 CLA was found to exert some positive effects, it is necessary to elucidate the mechanism of action to ascertain which of these isomers elicited the effect.
Different studies show that the effects of dietary CLA on immune functions in animal as well as human models are highly variable and inconsistent Table 4. For instance, a 93 d long study in 17 young women upon feeding with 3. Even after immunization with influenza vaccine, the delayed type hypersensitivity response and serum antibody titers were not altered during the intervention period.
These data suggest that short-term CLA supplementation in healthy volunteers was safe, but it showed no added benefit to their immune status [ ].
Moreover, short-term consumption of CLA produced no observable physiological change in blood coagulation and platelet function in healthy adult females [ 23 ]. CLA supplementation 3.
Although the overall effect was not significant, the results at least suggested that CLA might have a biologically relevant enhancing effect on the response to hepatitis B vaccination, which warrants further study [ ].
Contrary to this, supplementation with the 9- and CLA isomers blend, respectively significantly enhanced phyto-hemagglutinin PHA content, a T-cell mitogen-induced lymphocyte proliferator. Plasma IgA and IgM levels were found increased upon supplementation with 9- and CLAs , but decreased the levels of IgE, TNF-α and IL-1β.
In addition to these effects, delayed hypersensitivity response was decreased during CLA supplementation [ ]. CLA is reported to modify the inflammatory responses associated with allergic airway disease, primarily in animal models.
A prominent study in this regard came from the group of MacRedmond et al. However, daily supplementation of 4. One of the early studies in this direction measured the mean serum phospholipid esterified 9-CLA concentration in peripheral blood; observed it as significantly higher in 98 patients with chronic stable asthma, and 25 patients with acute severe asthma.
Thus the supposed role of oxygen-derived free-radical activity in inflamed lung tissue was envisaged [ ]. It shows that, some attempts were made to estimate the effect of CLA on immunity with reference to asthma, but none of them succeeded in reproducing the positive effects such as enhancement of immune function, down regulation of autoimmunity and increased proliferation of lymphocytes , consistently in clinical studies [ — ].
Furthermore, activation of peroxisome proliferator-activated receptors PPARs, a group of nuclear receptors , especially PPAR- γ in the human airway smooth muscle would be a possible strategy to treat airway diseases [ ]; therefore, targeting PPAR- γ , 9-CLA might show therapeutic value in alleviating airway disease by affecting epithelial and eosinophil functions [ ].
The interest on CLA mainly sprouted from the discovery of the anticancer property of CLAs [ 11 ]. Nevertheless, only a few studies have examined the isomers-specific effects of CLA in humans. In fact, no clinical studies have been conducted to relate CLA consumption with the incidence of cancer, but the data available in this regard are only from epidemiological studies.
Such data can be viewed as a collection of statistical tools used to elucidate the associations of CLA exposures to health outcomes. Regarding clinical studies on cancer, many researchers focused on human breast cancer; for instance, in an elaborate follow-up study using Cox proportional hazards models; Larsson et al.
Chajes et al. High-fat dairy food and CLA intake were examined in 60, women of age 40 to 76 Swedish mammography cohort study with It was found that women who consumed four or more servings of high-fat dairy foods per day including whole milk, full-fat cultured milk, cheese, cream, sour cream and butter showed half the risk of developing colorectal cancer, compared to women who consumed less than one serving per day [ ].
Concerning CLA intake, they found it was associated with an almost 30 percent reduction in the risk of colorectal cancer [ ]. Similarly, the possible role of CLA in preventing testicular cancer was depicted by the decreased CLA content in mitochondrial fractions of testicular cancer as against the normal testicular cells; and that CLA incorporation into nuclei and cytosol was significantly higher than its incorporation into plasma membranes and mitochondria [ ].
Tumors in estrogen receptor ER -negative epithelial cells in the breast are common among premenopausal women [ ]. McCann et al. Another epidemiological study the Netherlands cohort with 6. A few studies examined the relationship between dietary or serum CLA in women and the risk of breast cancer.
Such studies found an inverse association between dietary and serum CLA and risk of breast cancer in postmenopausal women [ ]. But in contrast, the adipose tissue extracts from a population of French patients with invasive breast carcinoma failed to reveal any positive correlation between adipose tissue CLA and the incidence of breast cancer [ ].
Since CLA accumulates in body fat stores, the adipose tissue of breast cancer obtained at the time of surgery could be used as a qualitative biomarker for CLA intake. Thus, the available human clinical studies could not ascertain the anti-cancer property of CLA. A major limitation in the epidemiological studies is the difficulty in obtaining accurate estimates of dietary CLA intake.
Most of the studies were carried out in small populations, where the diversity in food habits was less. Moreover, no clinical studies evaluated the effects of pure CLA preparations or individual isomers on the incidences of cancer.
It focuses that well-defined and controlled studies are required to fully understand the effects of CLA intake on the incidence of human cancer. The life style epidemics, diabetes and obesity are considered as the major causes of morbidity and mortality all over the world; and that obesity and weight gain are associated with an increased risk of diabetes [ ].
The hormone, insulin is responsible for regulating glucose concentration in blood. Insulin resistance is a state in which cells do not respond properly to insulin even if it is available in the blood , which leads to hyperinsulinemia high blood insulin.
Some animal studies demonstrated that CLA supplementation enhances insulin sensitivity; however, the mechanism underlying this effect is unclear [ , ]. Relatively few studies have examined the anti-diabetic properties of CLA in humans.
Supplementation of 3. The CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men [ 60 ].
Oxidative stress seems closely related to induced insulin resistance, which suggests a link between the FA-induced lipid peroxidation; these unfavorable effects of CLA might be of clinical relevance with regard to CVD [ 60 ].
Recently, Shadman et al. In non-diabetic abdominally obese men, 3. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular diseases. But, the isomeric mixture of 9- and CLA 3.
Sixteen individuals age, Clinical studies regarding the anti-diabetic effects of CLA are inconclusive. Rather, some of them speculated the reduction in insulin sensitivity; which attract immediate attention of the medical practitioners, because the increased consumption of CLA through dietary supplements might be ill-advised.
It seems that the use of weight-loss supplements containing 9-CLA, CLA or both as mixture is worrying, because most of the clinical studies presented in the previous sections provide mostly neutral or inconclusive results with very few favorable impacts Table 5.
In association with this, a few studies reported some adverse effects such as oxidative stress, insulin resistance, gastrointestinal irritation, etc. Many studies showed increase in the plasma concentration of CLA, which was directly proportional to the quantity of CLA consumed [ 23 , ].
Therefore, the immediate expected biological effect is oxidative stress. Oxidative stress is the reflection of an imbalance between the systemic manifestation of reactive oxygen species and the ability of the body system to readily detoxify them or to repair the resulting damage imparted to cell components like proteins, lipids and nucleic acids.
Prolonged oxidative stress may lead to cancer and heart diseases [ ]. Supplementation with CLA dramatically increased the rates of oxidative stress, to the levels considerably higher than that observed in heavy smokers [ 60 ]; it also enhanced the release of inflammatory biomarkers in obese men [ 60 ].
Long-term CLA supplementation studies lasting for one and two years have found to be well tolerated, but there was an increase in circulatory markers of inflammation such as CRP, TNFs, and ILs [ 59 , ].
Changes in these markers of inflammation and oxidative stress could be related to the increase in insulin resistance associated with the risk of cardiovascular disease [ 79 , ].
Administration of CLA 4. Insulin resistance is a physiological disorder, under which the cells fail to respond to the normal actions of the hormone insulin, though it is sufficiently produced by the body — this impairment leads to hyperglycemia i.
Decreased sensitivity or resistance towards insulin upon consumption of CLA was observed in some studies [ 60 , 65 ]. Furthermore, insulin resistance is closely related to the impairment decrease of the expression of glucose transporter-4 GLUT4 , a membrane transporter of glucose.
It was proven beyond doubt that CLA decreases the expression of GLUT4 [ ], which shows that indiscriminate use of CLA to treat obesity would lead to type 2 diabetes as the immediate side effect, this would further damage blood vessels and thereby increased risk of CVD [ ].
Moreover, unutilized insulin due to resistance in plasma can contribute to increased appetite especially for carbohydrates and sugary foods , which would add to the gravity of CVD. A few studies showed mild irritations of intestinal tract such as irritation [ 60 ], laxative effects and flatulence [ 47 ], gas bloating [ 20 ], indigestion, diarrhea and nausea [ 36 , 48 ] in subjects consumed CLA.
Most of these effects were considered as mild to moderate and were transient; and one may assume that these effects may be due to the capsule material or the oily nature of the substance or initial adaptive problem with the lipid nutrient. Consumption of commercial CLA reduced the fat content in cows [ ].
Since milk is the only source of nutrients for infants, decreased milk fat in lactating humans is another concern regarding the CLA consumption. Masters et al. However, another two human studies found no changes in milk fat or protein [ , ], but in these studies, the intervention period was too short about a wk to arrive at a conclusive result.
General view on CLAs is that the 10 - CLA exerts specific effects on adipocytes and liver, whereas both the 9- and CLAs appear to be active in inhibiting carcinogenesis [ 14 ]. It is likely that the inconsistent and often contradictory results on the effectiveness of CLA consumption in human health could be the outcome of a number of factors, including differences in subject groups, age, quantity and duration of CLA intake, composition of CLA mixture, purity of CLA, acceptance of the CLA by the body, food intake, gender and racial differences, genetic polymorphism and also the executed measurements parameters studied for assessing the effect.
Moreover, crucial factors that impact research outcomes include the nature of control supplement placebo , and study design cross-over vs. non cross-over designs , because, the efficacy of CLA supplements remains inconsistent in cross-over and non cross-over randomized clinical studies [ ].
Determination of a normal CLA content in the blood plasma could help in estimating if a person consumes satisfactory amounts of CLA with the diet, and thus takes advantage of its potential beneficial effects on health. The only CLA isomer that appears in higher percentage than the detection limit 0.
The duration of this study was 6 months, and in the last group who consumed CLA supplement, the average CLA content in plasma was 0. The blood samples were collected for analysis in the morning in the fasted state after a 12 h restriction for meal and drinks.
Thus, individuals who have 9-CLA levels in their blood plasma within the range up to 0. In most of the clinical studies, vegetable oils such as sunflower oil, olive oil, safflower oil and soybean oil Table 2 have been used as placebo in the form of capsules or pills [ 49 , 66 , 90 ]. In fact, the proportion of MUFA and PUFA, especially LA present in these placebo oils for instance, the predominantly used sunflower and olive oils are not properly addressed by the researchers.
According to WHO Codex International food standards , sunflower oil, soybean oil, olive oil and safflower oil contained significant levels of MUFA and PUFA, which include OA, LA and ALA Table 6 [ , ].
It was thought that VA is the only precursor of CLA in humans. However, non-ruminal bacteria inhabiting human gastro-intestinal GI tract like Lactobacillus acidophilus and L.
casei isolated from intestine [ ], Bifidobacterium bifidum and B. breve isolated from the fecal matter of neonates [ ], and Ruberia spp. isolated from intestine [ ] could efficiently produce 9-CLA from LA, probably though the mediation of VA in tissues or hydroxy octadeceinoic acid [ ], as occurring in ruminal biohydorgenation.
In addition to 9-CLA, Lactobacillus spp. also synthesizes CLA and trans -9, trans- CLA [ ]. From this, it is evident that a portion of LA in placebo oil would be biohydogenated by the bacteria residing in GI tract as in rumen into CLA through the mediation of VA. Irrespective of this fact, most of the clinical studies use the aforesaid vegetable oils as placebo, neglecting their effects on human health; especially their supposed supplementary and complementary effects.
The dietary intake of the precursor VA was found to have some major effects on heart health, blood lipid profile and immunity, and also protective against fatal ischemic heart disease [ — ]. This would lead to the misinterpretation of the results, i.
Therefore, during clinical studies, the composition of FA in placebo and its effects on human health need to be addressed with due respect, and independently for getting reliable results.
The clinical studies with CLA lack a common protocol for selecting the subjects. Description of the subjects including gender and age, medical treatments given prior to intervention are the critical factors to be considered while selecting the subjects.
Medical history of the subjects should also be recorded before concluding the safety and efficacy concerns of CLA consumption. In most of the studies, the subjects selected were categorized and designated as normal, healthy obese, with metabolic syndrome, with insulin resistance, etc.
This arbitrary classification for the convenience of the investigator poses a question i. Is it with the designation normal, obese, immune-compromised subjects with metabolic syndrome or with other diseases?
Another factor to be considered in clinical studies is the continental, racial and gender differences among the subjects; for instance, literature shows that most of the clinical studies on CLA were performed in North America and Europe.
The reproducibility of such results in racially and continently separated populations all over the world, especially in Asia, Africa and South America is another point of concern, which has to be verified before accepting the nutritional status of CLA in modulating biological functions.
Other factors of concern are the composition, dosage and duration of CLA consumption. If not otherwise stated, composition and purity of CLA are meant for 9- and 10 CLAs. Generally, human studies use a CLA mixture about of 9- and CLAs; and proportion of CLA isomers depends mainly on the nature of substrate, mode of synthesis production , physico-chemical parameters involved in synthesis, and purification strategies adopted [ , ].
Most of clinical studies evaluated the effects of CLA consumption for a short period, usually of 4—12 wk. But Gaullier et al. Generally, in these studies, CLA isomer or mixture dosages varied from 0.
The dosage of CLA administration in humans is also very low, compared to animal studies in terms of body weight ; thus the results in pre-clinical animal studies high dose may not be comparable with the real clinical studies.
Therefore, CLA dose intake may be considered based on energy percentage. Two people with the same body weight may have a very different body composition e. men; body builder vs. obese person , which in turn impacts the metabolism differently.
Another crucial question is the retention of the so-called good effects for a long time; of course, one might expect that CLA should be consumed as if drugs are taken for chronic diseases. Unlike in mechanistic in vitro studies, the criss-crossed signaling pathway through which CLA induce its effects has to be elucidated clearly in clinical studies.
Moreover, the biological effects of individual CLA isomers, mainly 9- and CLA, their synergistic interactions and even the possible opposition between the isomers have to be unveiled. Effect of CLA consumption along with various adjuncts is another area of clinical research that has to be studied evidently.
Some studies showed the positive health benefits of CLA are related to heart health and body fat reduction on consumption along with calcium, VA, whey proteins and oryzanol [ 49 , 68 , ].
CLA consumption along with other PUFA was found to have protective effect against renal carcinoma [ ]. Therefore, an effective combination of CLA along with other supplements or with ω -3 FAs has to be addressed to reveal the possible real effects of CLA consumption on human health. As far as the voluminous literature on CLA is concerned, only a few studies to date examined the effects of CLA in humans in vivo.
However, results of these studies do not reflect the dramatic and consistent data demonstrated in animal studies. Thus, these disappointing results in humans demand more precise experimentations with humans.
The interest in CLA research still persists, and hence, many questions related to the safety and efficacy on the consumption CLA have to be answered scientifically. Hence, it is imperative to critically evaluate and consolidate prominent findings on human consumption of CLA, i.
One of the major limitations in human studies is that most of the studies depend only on the blood cells or plasma, and fat deposition. Thus, majority of the clinical studies failed to provide conclusive evidences for the effectiveness of CLA on human health, except for anti-obesitic properties which offered a little hope to prevent body weight regain though fat deposition, nevertheless increased oxidative stress and insulin resistance due to such over-consumption of CLA poses contradictory concerns.
Moreover, age, gender, genetic polymorphism and immune status of the subject, role of other nutrients present in the diet, and extend of absorption of individual isomers to different tissues have to be well addressed during the intervention period — so as to evaluate the safety and efficacy of CLA consumption on human health.
As far as human consumption of CLA is concerned, a definite conclusion for safety and efficacy has not been reached yet. At this context, we strongly recommend the need for more precise and well-designed long-term intervention studies with controlled food intake and activity level to assess the effectiveness of CLA on human health.
Moreover, such studies need to be duplicated in other laboratories giving emphasis to men and women, age group, ethnic background, food style, continental and even national uniqueness, cultural and geographic barriers, etc.
without comparing data from animal studies — i. In toto , clinical evidences indicate a possible link of supplemental CLA per se toward negative or inconclusive outcomes; thus, inclusion of CLA in the Codex Alimentarius Book of Food — which describes internationally recognized standards of food — may be considered.
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Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated. Home Health Information Library Conjugated Linoleic Acid. Conjugated Linoleic Acid. Uses Conjugated linoleic acid CLA is a slightly altered form of the essential fatty acid linoleic acid.
What Are Star Ratings? This supplement has been used in connection with the following health conditions: Used for Why 2 Stars. Although the evidence is conflicting, the majority of the evidence shows CLA can help people lose body fat, and may promote a small amount of weight loss.
Conjugated linoleic acid CLA is a group of polyunsaturated fatty acids found mainly in dairy products. In numerous randomized controlled trials lasting from 12 weeks to two years, CLA supplementation has been found to reduce body fat in people with overweight and obesity.
Although some trials have reported weight loss attributable to CLA, others have found no effect of CLA on body weight. A meta-analysis of seven placebo-controlled trials lasting six months or longer concluded CLA use is associated with small increases in weight loss and fat loss.
Importantly, conflicting evidence has emerged regarding the impact of CLA on oxidative stress and insulin resistance. Therefore, the use of CLA by people with type 2 diabetes or signs of insulin resistance should be carefully monitored.
Conjugated linoleic acid may play a role in reducing body fat. Research has reported that CLA supplementation produces minor gains in muscle size and strength in weight-training men. Preliminary research suggests that CLA might reduce breast cancer risk.
Preliminary and test tube studies indicate that CLA may reduce the risk of colon cancer. Preliminary research suggests that CLA might reduce the risk of cancers at several sites, including breast, prostate, colorectal, lung, skin, and stomach. Omega-6 fatty acids found in sunflower seed oil a source of linoleic acid may be beneficial.
Studies have reported that linoleic acid reduced relapse severity and length and decreased disability due to MS. How It Works How to Use It Most studies in humans have used 1.
Where to Find It CLA is found mainly in dairy products and also in beef and poultry, eggs, and corn oil. Possible Deficiencies No deficiencies of CLA are reported or believed to occur, since it is not an essential nutrient.
Interactions with Medicines As of the last update, we found no reported interactions between this supplement and medicines. It is possible that unknown interactions exist.
Many scientists believe that high leptin levels may play a role in obesity, one of the biggest risk factors for adult-onset diabetes. 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. In the current study, the researchers found that one particular CLA isomer, t10cCLA the ' isomer' helped control both body weight and leptin levels. The researchers asked 21 people with adult-onset diabetes to take either a daily supplement containing a mix of rumenic acid and isomer or a safflower oil supplement as a control, for the eight-week period.
The group was divided roughly in half. Rumenic acid is the predominant isomer in foods that contain CLA, while the isomer is less abundant. CLA can be found in foods such as beef, lamb and dairy products. At the end of the trial, the researchers took blood samples from each participant to check CLA levels.
Conjugated linoleic acid CLA is a slightly altered form of Fueling for peak performance essential fatty diabeetes linoleic CA. While there is no way diabetse predict whether a Diabeets, mineral, or herb will successfully Maintaining a balanced gut or Brown rice products associated health conditions, our unique ratings tell Brown rice products how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people. For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being. For a supplement, little scientific support. CLA is a slightly altered form of the essential fatty acid linoleic acid.CLA and diabetes -
Leptin levels decreased in the CLA group, and rose slightly in the safflower group. A study conducted by the Diabetes Prevention Program Research Group found that a modest reduction in body weight resulted in a 58 percent reduction in the incidence of diabetes in a group of people at high risk for developing the disease.
Belury conducted the study with Annie Mahon of the department of foods and nutrition at Purdue University and Sebastiano Banni of the department of experimental biology at the University of Cagliari, Italy.
The research received support from Pharmanutrients, Inc. Although Belury has consulted for both companies in the past, she was not a paid consultant during the time of this study. Contact: Martha Belury, ; Belury. edu Written by Holly Wagner; ; Wagner. Lane Ave. Columbus, Ohio OHIO.
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Metrics details. This comprehensive review critically evaluates whether supposed health benefits propounded upon human consumption of conjugated linoleic acids CLAs are clinically proven or not.
With a general introduction on the chemistry of CLA, major clinical evidences pertaining to intervention strategies, body composition, cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated.
Supposed adverse effects such as oxidative stress, insulin resistance, irritation of intestinal tract and milk fat depression are also examined. It seems that no consistent result was observed even in similar studies conducted at different laboratories, this may be due to variations in age, gender, racial and geographical disparities, coupled with type and dose of CLA supplemented.
Thus, supposed promising results reported in mechanistic and pre-clinical studies cannot be extrapolated with humans, mainly due to the lack of inconsistency in analyses, prolonged intervention studies, follow-up studies and international co-ordination of concerted studies.
Briefly, clinical evidences accumulated thus far show that CLA is not eliciting significantly promising and consistent health effects so as to uphold it as neither a functional nor a medical food.
Conjugated linoleic acids CLAs encompass a group of positional and geometric isomers of octadecadienoic acids — naturally occurring polyunsaturated fatty acids or PUFA- synthesized in the rumen of cattle, deer, sheep and goat by microbial biotransformation of forage-derived fatty acids FAs such as oleic acid OA , linoleic acid LA and α -linolenic acid ALA ultimately into saturated stearic acid SA [ 1 , 2 ].
Although CLA is formed as an intermediate during ruminal biohydrogenation of OA, LA and ALA, its primary source in vivo is endogenous de novo synthesis by the activity of Δ 9 -desaturase from the monounsaturated FA MUFA , the vaccenic acid trans ,; VA , another intermediate in ruminal biohydrogenation [ 3 ].
It is also synthesized endogenously in humans from dietary VA by the activity of Δ 9 -desaturase [ 4 , 5 ] Figure 1. The Δ 9 -desaturase also referred to as stearoyl-CoA desaturase; EC 1.
Thus, VA is the pivotal precursor of 9-CLA in ruminants probably in mammals too ; therefore, an essential FA in humans. Major ω fatty acids with their common names, structures and systemic names. Therefore, the primary focus of all mechanistic, preclinical and clinical studies pertaining to CLA were on 9- and CLAs — especially a mixture of both or rarely one of these two isomers with others isomers as impurities [ 8 , 9 ].
During the past couple of decades, hundreds of reports - principally based on in vitro , microbial, animal, and of late clinical studies on humans - have been accumulating with the highlights of contrasting biological activities of CLA isomers, especially of 9- and CLAs [ 9 , 10 ].
The supposed health benefit of CLA was discovered nearly three decades ago, i. As the biomedical studies with CLA expanded, it became apparent that CLA showed a range of positive health effects in experimental animal models.
Such supposed beneficial health effects were attributed to suppressing cancer, reducing body fat accretion, delaying the onset of type II diabetes, retarding the development of atherosclerosis, improving the mineralization of bone and modulating the immune system [ 12 — 14 ].
Therefore, CLA-rich foods may be considered as functional foods a food offers an additional function in the form of health-promotion or disease prevention in combination with some supporting ingredients ; and that CLAs per se are neither a food nor a functional food but a FA class with some bioactive properties.
In the light of the aforesaid background, this review critically examines whether the health benefits attributed to CLA on humans are clinically proven or not. Keeping this in mind, this review is categorized into different sections with appropriate illustrations wherever necessary.
Very often, the CLAs are erroneously classified as omega -6 abbreviated as ω -6 or n -6 FAs. In fact, CLA is a class of FAs comprising as many as 56 isomers with conjugated juxtaposed or neighboring double bond pairs i.
Regarding geometric isomers, the cis and trans configurations unequivocally indicate the steric relations around a given double bond; however, instead of cis and trans, the symbols Z from German zusammen, means together and E from German entgegen , means opposite , respectively are used in some classifications.
It should not be confused with the counting of carbon position from ω -CH 3 or —COOH terminus along the acyl chain; the former is used in ω classification, while the latter in systemic nomenclature. From this, it is evident that only the isomers with the conjugated double bonds on carbon positions starting at 10 from —COOH terminus have indeed their first C-C double bond at the ω -6 position, while counting from the methyl -CH 3 terminus i.
from the last or omega -C in the acyl chain Figure 1. Thus, trans , cis CLA designated as CLA is a typical ω -6 CLA; while the biologically active and predominantly natural occurring 9 - CLA is a typical ω -7 FA [ 8 ].
Though, VA the principal precursor of 9-CLA is devoid of conjugated double bonds; it is also an ω -6 FA, while counting from the methyl terminus on the acyl chain Figure 1. Clinical studies are generally of two categories: the cross-over and non cross-over parallel or between patients designs; in the former, the subjects are randomized into two groups of which the first receive X e.
In cross-over study, the influence of covariates is reduced as each cross-over patient serves as her or his own control; while in non cross-over study, the treatment groups may be unbalanced on certain covariates [ 16 ]. Unlike non cross-over study, cross-over studies are statistically efficient, and hence fewer subjects are required for the study.
In fact, in non cross-over design, the placebo effect will not be mixed up with the effect of the test material. Thus, both methods have some advantages and disadvantages in different situations, and hence, selection of study design depends on the situation of the study.
Generally, the clinical studies on the efficacy of CLA are randomized, double-blind and placebo-controlled designs comprising two groups, i. In such experiments, neither the researcher nor the subjects know whether they received CLA or the placebo designed for the purpose i.
Such types of clinical studies ensure that the personal expectations of neither the researcher nor the subjects influence the results, making it more dependable, and thus eliminate possible treatment bias. Nevertheless, in case of some life-threatening diseases like cancer, analyses of the implications on the direct supplementation of CLA seem to be difficult.
In such cases, epidemiological studies were performed in which intake data derived from a validated food-frequency questionnaire are linked to an existing or freshly established nutrient databases containing analytical data of specific FA [ 16 — 18 ].
These studies may be limited by the variability of CLA in the food supply as well as the difficulty of assessing the intake of these minor dietary FAs, the CLA.
Some of the commercially available CLA preparations, commonly used for clinical studies are detailed in Table 1. Most of the clinical studies monitored the effect of commercially available CLA supplements, which usually contain a mixture of 9- and CLAs at approximately ratio, whereas some other researchers used naturally CLA-enriched dairy products for evaluating the biological activities.
Feeding animals with plant oils rich in LA or ALA such as sunflower, soybean or linseed oil is shown to enhance the 9-CLA content in the milk fat, which can subsequently be used to make CLA-enriched dairy products [ 31 ], i.
For instance, the CLA content could be enhanced up to 2. Naturally CLA-enriched in situ dairy products such as butter, cheese, etc.
were incorporated in a variety of recipes such as those used for making muffins, cakes, sauces, and very often used as spreads. Overweight or obesity - one of the typical syndromes of lifestyle diseases - is referred to as the excessive fat accumulation that impacts health.
The occurrence of overweight and obesity has been augmented as the most common health issue of modern food style. Obesity is considered as a cause for many health problems such as heart diseases, infertility and insulin resistance [ 35 ].
With a view to lose weight and improve the body composition i. Among them, CLAs draw more attention, since many pre-clinical studies in animal models proved its inverse relationship with obesity.
The significant clinical studies investigating the effect of CLA on body composition and their intervention strategies are shown in Table 2. In clinical studies, several methods or techniques were applied to measure the body composition.
The simplest method is that, to measure the thickness of subcutaneous fat in multiple places on the body such as abdominal area, arms, sub-scapular region large triangular muscle near shoulder bone , buttocks and thighs [ 25 , 51 , 52 ].
Other commonly used measures are bioelectrical impedance analysis [ 39 ], hydrodensitometry and dual-energy X-ray absorptiometry DEXA [ 53 — 55 ].
Among them, DEXA is the most widely used method in clinical studies to assess body composition due to CLA consumption.
In fact, DEXA measures total body composition and fat content with a high degree of accuracy and is considered as the gold standard for measuring the body composition, since one can get an image of the entire body [ 56 ]. Another commonly used method is the measurement of body mass index, i.
According to World Health Organization [ 57 ], a BMI greater than or equal to 25 is overweight, and a BMI greater than or equal to 30 is considered as obesity. In fact, BMI is not necessarily a good measure, especially in terms of body composition; for instance, individuals like athletes with strong bone and greater muscle lean mass have a higher BMI than non-athletes, and hence different BMI classifications of overweight is warranted while assessing obesity in terms of body girth [ 58 ].
Some of the clinical studies suggested a positive association of the intake of 3. In another study, supplementation of 4.
In a different study comprising 60 overweight or obese volunteers including men and women who received 3. Steck et al. They concluded that lean body mass LBM increased by the higher dose after 12 wk of intervention.
Supplementation of 9- and CLAs at a dosage of 1. Interestingly, CLA was found to be effective in reducing the weight gain associated with psychiatric medications - one of the major side effects in psychological treatments. Consumption of CLA at a dosage of 3. A possible explanation for this effect is that green tea extract high in pigallocatechin-gallate can directly inhibit gastric and pancreatic lipases, thereby increasing the thermogenesis and possibly prevent the enzymatic degradation of catechol O-methyltransferase, an enzyme which plays a role in the respiration rate of brown adipose tissue [ 62 ].
Due to overeating and sedentary life, the incidence of weight gain during holiday season i. For instance, supplementation of CLA 3. On the contrary, an inverse relationship between CLA and body composition has been demonstrated. One of the first studies demonstrating negative effects of CLA was performed with 71 subjects including obese men and women of 20 to 50 yr of age.
Body was measured by hydrodensitometry, but the results did not show any effect on body composition [ 64 ]. In sedentary young women, intake of 2.
Likewise, consumption of 4. Some of the studies observed gender specific effects of CLA intake. Riserus et al.
The small sample size and short duration were the major limitations of this study; thus, the effects of CLA in abdominal obesity need to be investigated further in larger studies with longer duration.
Long-term 1 yr supplementation daily dose of CLA was 3. In this double-blind placebo-controlled study, female and male 31 volunteers with BMI of 25—30 were included. In a bicentric study conducted simultaneously at Clermont-Ferrand, France and Maastricht, The Netherlands , eighty-one middle-aged, overweight, healthy men and women were enrolled, and all subjects consumed a drinkable dairy product containing 3 g of high OA sunflower oil daily for 6 wk, the run-in period [ 46 ].
Volunteers were then randomized over five groups receiving daily either 3 g of high OA sunflower oil, 1. Percentage BFM, fat and LBM were assessed at the end of the run-in and experimental periods by DEXA.
Dietary intake was also recorded. It was concluded that, a daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 wk had no significant effect on body composition in overweight, middle-aged men and women [ 46 ].
A study from Greece reported that CLA administered first at 0. Raff et al. This study gained more importance, as it was reported in children aged between 6 and 10 yr, who were overweight or obese, but otherwise healthy [ 67 ] ]. It is known that the γ -oryzanol is a phytochemical having several biological activities like anti-oxidant activity, anti-atherogenic effect, lowering triglycerides and improves LBM [ 68 ].
This report also indicates that CLA per se was less efficient to improve BFM; for instance, a recent non cross-over clinical study conducted on 66 non-trained healthy male students for 2 month showed that CLA supplementation had no effect on LBM, BFM, trunk and visceral fats, and waist circumference [ 69 ].
Some clinical studies suggested that administration of CLA might be the most effective strategy in controlling regionalized reduction of fat mass rather than its constitutional reduction, i. For instance, administration of 3. Waist-to-hip ratio also decreased significantly in healthy, overweight and obese men, compared with placebo group.
Interestingly, these effects were produced independent of diet and specific lifestyle. Exercising individuals often add nutritional supplements to their diet to accelerate the increase in muscle mass and strength from heavy resistance-exercise training.
Some short- and long-term studies employing high doses of CLA in healthy and obese, sedentary and exercised adults have shown beneficial effects of CLA in reducing fat mass and increasing LBM. A daily supplementation of 1. In this study, physical exercise was standardized as 90 min in gym, three times a wk; and concluded that CLA reduces the deposition of fat.
These results seem to be encouraging, because much lower dose of CLA produced the expected results - when compared to other studies - wherein comparatively 2 to 4 folds higher concentrations of CLA were used. Effect of CLA Clarinol A supplementation in conjunction with 6 wk of aerobic exercise training on 33 untrained to moderately trained men average age CLA showed no ergogenic benefits on neuromuscular fatigue, and field tests of muscular endurance and power.
This combined strategy showed that supervised resistance exercise training is safe and effective for increasing strength in older adults, because aging is associated with lower muscle mass and an increase in body fat. Similarly, in another double blind and placebo controlled resistance-training study, no decrease in visceral adipose tissue was observed; however a significant reduction in the cross-sectional area of visceral adipose tissue was noticed in the placebo group [ 22 ].
In this study, 30 overweight and moderately obese, but otherwise healthy middle-aged 35 to 55 yr male subjects received 3. Pinkoski et al. Thus, some of the studies showed the effectiveness of CLA in fat mass reduction in subjects during resistance-training program.
Contrary to this, no CLA-specific effects were observed on body composition, energy expenditure or appetite in non-obese, regularly exercising individuals comprising 25 men and 27 women , who received either 3. It suggests that CLA supplementation may promote testosterone synthesis through a molecular pathway that should be investigated in detail.
Furthermore, this study becomes much relevant, since the correlation between the production of testosterone and body building still remains a controversy. Some pre-clinical studies showed that CLA reduces fat uptake into adipocytes by lowering the activities of lipoprotein lipase and Δ 9 -desaturase, instead of enhancing lipolysis [ 14 , 74 , 75 ].
Based upon this background, a few clinical investigations were made on the effect of CLA on fat-mass regain after weight loss - with an assumption that CLA could block body fat gain. To check this, overweight adults were administered a very low-calorie diet for 3 wk, followed by CLA supplementation at a dosage of either 1.
Subjects took CLA in either dose showed increased regain of fat-free mass and resting metabolic rate, thereby lowering the regain of body fat relative to the control subjects. Interestingly, they concluded in later findings that the measures of appetite hunger, satiety and fullness favorably and dose-independently affected by the same dose of CLA but had no effect on energy intake at breakfast or improved body-weight maintenance after weight loss [ 76 ].
Apart from a few studies that investigated the effects of CLA supplementation in humans, there were some experiments designed to supplement CLA-enriched dairy products.
Consumption of dairy products such as ultra-heat treated milk, butter, and cheese enriched with 1. Another experiment compared the effects of the consumption of a modified butter, naturally enriched with CLA 4. Consumption of a drinkable dairy product containing up to 3 g of CLA isomer for 18 wk did not result in any significant effect on body composition in overweight, middle-aged men and women [ 46 ].
Venkatramanan et al. More precisely, consumption of CLA-enriched milks in either form failed to alter TAG concentrations in the blood; body weight or fat composition [ 51 ]. Thus, in general, dairy products enriched with either of 9- or CLA isomers or its mixture failed to establish a consistent effect on body composition.
The question of inconclusive results on efficacy and effectiveness of CLA on body composition and obesity may answer from long-term intervention studies. Effects of any dietary supplement or food ingredient on body composition should be assessed over an extended period of time to conclude the results, because crash diet procedures seem inappropriate.
In most of the studies, the intervention period lasted only for a few wk, and long-term studies were very few. In a study, subjects including men and women were supplemented with 3.
During the first 12 month, significant reduction in BFM and leptin levels was reported. These changes in body composition were not related to diet and exercise. Most of the effects on BFM were observed during the first 6 month of CLA supplementation and the extension study concluded that CLA may be beneficial in preventing weight regain and long-term maintenance of BFM and LBM.
These studies seem to be important as most of weight loss studies in overweight and obese subjects have demonstrated that most subjects will regain the lost weight within the next 1 to 2 yr [ 43 , 80 ]. Gaullier et al. Energy expenditure, substrate utilization and dietary fat oxidation were measured before and after 6 month of CLA supplementation, which showed that fat oxidation and energy expenditure increased during sleep in subjects received CLA, in comparison to placebo [ 81 ].
Supplementation of CLA 6. Such long-term studies have to be conducted in a cross-over design by including men and women of different age groups to generalize the beneficial effects of CLA.
However, all of them failed to reproduce the dramatic results reported in animal and in vitro models, especially mice. The extensive controversies in clinical studies limit from proposing a definite statement regarding the beneficial effects of CLA on body composition, so as to address the increasing concerns of health professionals, body builders and athletes.
Hyper-triacylglycerolemia and elevated plasma cholesterol are suggested as the major risk factors for atherosclerosis and cardio-vascular diseases CVD , and that blood lipid profile, blood pressure, BMI and blood sugar are generally considered as the indicators of heart health.
The lipid profile is a panel of blood tests performed on the patient to determine the risk of CVD. These tests are good indicators of whether someone is likely to have a heart attack or stroke caused by blockage of blood vessels or hardening of the arteries atherosclerosis.
The lipid profile typically includes the baseline measurements of total cholesterol; high density lipoprotein cholesterol HDL-C , often called good cholesterol; low density lipoprotein cholesterol LDL-C , called bad cholesterol; and TAG in plasma [ 82 ]. Normal cholesterol levels vary by age and sex.
LDL-C is the major cholesterol carrier in the blood, and if too much it is in circulation, it can slowly build up in the walls of the arteries of heart and brain leading to arteriosclerotic vascular diseases.
According to American Heart Association, a high TAG level combined with low HDL-C or high LDL-C increases the risk of CVD [ 83 ]. The major circulatory markers associated with heart health are C-reactive protein CRP , tumor necrosis factor- α TNF- α , keto -dihydro prostaglandinF2 PGF2 , 8- iso- prostaglandinF2- α PGF2α , leptin, interleukin IL -6, plasma alanine transaminase, and total bilirubin [ 45 ].
Variations in the concentration of these markers in blood plasma from the normal level indicate dysfunctions of human system. The major circulatory markers associated with heart health and their normal levels in blood are listed in Table 3.
Some animal studies suggest the health benefits anti-CVD effects of CLA such as anti-sclerotic and improvements in blood lipid profile, hypolipidaemic and anti-oxidative effects [ 84 — 86 ].
Two different isomers of CLA i. The CLA is pro-atherogenic and induces pathways involved in the development of insulin resistance, whereas 9-CLA is associated with reduced risk of CVD [ 87 — 89 ].
Epidemiological studies showed that plasma HDL-C concentrations have an inverse relationship with the risk of CVD, and it is anticipated that raising plasma HDL-C levels might protect against atherosclerosis [ 83 ].
Supposed effects of CLA supplementation on blood lipid profile also remains inconclusive. Supplementation of an isomeric blend of CLA 9- and CLAs in ratio for 12 wk 1. Similarly, a dose of 0.
In this study, 22 volunteers were enrolled and they were divided into study and control groups in a doubly blind design; the study group received 0.
Diet was controlled, and no significant differences in energy or macronutrient intake were found between the two groups. A significant reduction of HDL-C was observed when 6.
But 2. In contrast, CLA 9- and CLA in ratio in a dose of 3. And the ratio of LDL-C to HDL-C was significantly reduced in subjects with stable, diet-controlled type 2 diabetes [ 90 ].
In this non cross-over double-blind, placebo-controlled and randomized study, 51 normolipidaemic subjects were enrolled. These results further suggested that CLA supplementation significantly improved the lipid profile in human subjects without any adverse effects on body weight, plasma glucose and insulin concentrations; and thus indicates the supposed cardio-protective effects of CLA.
Contrary to this, the opposing effects 9- and CLAs were observed by Tricon et al. It showed that CLAincreased the ratios of LDL-C to HDL-C and total to HDL-C, whereas 9 - CLA decreased them, suggesting the beneficial effects of CLA on blood lipid profile [ 93 ].
But, later, the same group showed that dairy products enriched with 9-CLA 1. Some studies observed neither a beneficial nor an adverse effect of an isomeric blend of 9- and CLA in a ratio other than A 93 d long study in 17 healthy female volunteers to observe the effect of dietary CLA on blood lipids, lipoproteins, and tissue FA composition showed that daily supplementation of 3.
Furthermore, no adverse effect of CLA supplementation was reported in this study, though plasma concentration of CLA was increased during the intervention period, i. Some studies investigated the effect of dairy products on lipid profile.
However, human studies with the supplementation of CLA-enriched dairy products in situ enrichment produced contradictory results. Intake of 1. However, levels of CLA and VA in human milk can be modulated if breastfeeding mothers replace conventional dairy and meat products with organic dairy products enriched by natural feeding [ 95 ].
Recently, Penedo et al. Furthermore, sheep cheese naturally enriched in VA, CLA and ALA improved the lipid profile and reduced anandamide an endogenous cannabinoid neurotransmitter and obesity marker in adults with diagnosed mildly hypercholesterolaemia [ 97 ].
CRP is synthesized by liver in response to inflammation. Inflammations may be due to a variety of reasons such as cancer, diabetes, cardiovascular diseases, etc.
Increased plasma concentration of CRP, a circulatory inflammation marker helps in predicting CVD [ ]. A mixture of 9- and CLA isomers with equal proportions also reported an increased CRP, but not of the other inflammatory markers, i.
Another study concluded that a mixture of 9- and CLAs had more adverse effects on CVD markers, while 9-CLA isomer appeared to be more neutral in healthy postmenopausal women.
Daily supplementation of 5. The CLA mixture at a dose of 3. High dose of CLA consumption 6. In contrast, CLA in the same composition ratio , but in lower dose i.
Outcome from some recent studies suggested that CLA did not increase the risk of CVD. Pfeuffer et al. It was observed that CLA did not impair endothelial function.
Other parameters associated with metabolic syndrome and oxidative stress were not changed or slightly improved. Interestingly, it was observed that oral supplementation of CLA along with calcium reduced the incidence of pregnancy-induced hypertension without changing the plasma levels of other circulatory markers such as PGF2α, CRP and IL-6 [ ].
Forty eight healthy primigravidas with a family history of preeclampsia and with diastolic notch were included in this double-blind and placebo-controlled non cross-over study.
Participants were randomized to daily oral doses of elemental calcium 0. The controversial beneficial and detrimental effects of CLA on heart health observed during clinical studied are summarized in Figure 2. All these studies were too randomized in dosage, composition and duration, which make difficult to conclude the positive effects of CLA on heart health.
Moreover, there is a complete lack of uniformity in assessing the effects CLA on heart health, i. Even though the isomeric mixture of 9- and 10 CLA was found to exert some positive effects, it is necessary to elucidate the mechanism of action to ascertain which of these isomers elicited the effect.
Different studies show that the effects of dietary CLA on immune functions in animal as well as human models are highly variable and inconsistent Table 4. For instance, a 93 d long study in 17 young women upon feeding with 3.
Even after immunization with influenza vaccine, the delayed type hypersensitivity response and serum antibody titers were not altered during the intervention period. These data suggest that short-term CLA supplementation in healthy volunteers was safe, but it showed no added benefit to their immune status [ ].
Moreover, short-term consumption of CLA produced no observable physiological change in blood coagulation and platelet function in healthy adult females [ 23 ]. CLA supplementation 3. Although the overall effect was not significant, the results at least suggested that CLA might have a biologically relevant enhancing effect on the response to hepatitis B vaccination, which warrants further study [ ].
Contrary to this, supplementation with the 9- and CLA isomers blend, respectively significantly enhanced phyto-hemagglutinin PHA content, a T-cell mitogen-induced lymphocyte proliferator. Plasma IgA and IgM levels were found increased upon supplementation with 9- and CLAs , but decreased the levels of IgE, TNF-α and IL-1β.
In addition to these effects, delayed hypersensitivity response was decreased during CLA supplementation [ ].
CLA is reported to modify the inflammatory responses associated with allergic airway disease, primarily in animal models. A prominent study in this regard came from the group of MacRedmond et al.
However, daily supplementation of 4. One of the early studies in this direction measured the mean serum phospholipid esterified 9-CLA concentration in peripheral blood; observed it as significantly higher in 98 patients with chronic stable asthma, and 25 patients with acute severe asthma.
Thus the supposed role of oxygen-derived free-radical activity in inflamed lung tissue was envisaged [ ]. It shows that, some attempts were made to estimate the effect of CLA on immunity with reference to asthma, but none of them succeeded in reproducing the positive effects such as enhancement of immune function, down regulation of autoimmunity and increased proliferation of lymphocytes , consistently in clinical studies [ — ].
Furthermore, activation of peroxisome proliferator-activated receptors PPARs, a group of nuclear receptors , especially PPAR- γ in the human airway smooth muscle would be a possible strategy to treat airway diseases [ ]; therefore, targeting PPAR- γ , 9-CLA might show therapeutic value in alleviating airway disease by affecting epithelial and eosinophil functions [ ].
The interest on CLA mainly sprouted from the discovery of the anticancer property of CLAs [ 11 ]. Nevertheless, only a few studies have examined the isomers-specific effects of CLA in humans. In fact, no clinical studies have been conducted to relate CLA consumption with the incidence of cancer, but the data available in this regard are only from epidemiological studies.
Such data can be viewed as a collection of statistical tools used to elucidate the associations of CLA exposures to health outcomes. Regarding clinical studies on cancer, many researchers focused on human breast cancer; for instance, in an elaborate follow-up study using Cox proportional hazards models; Larsson et al.
Chajes et al. High-fat dairy food and CLA intake were examined in 60, women of age 40 to 76 Swedish mammography cohort study with It was found that women who consumed four or more servings of high-fat dairy foods per day including whole milk, full-fat cultured milk, cheese, cream, sour cream and butter showed half the risk of developing colorectal cancer, compared to women who consumed less than one serving per day [ ].
Concerning CLA intake, they found it was associated with an almost 30 percent reduction in the risk of colorectal cancer [ ]. Similarly, the possible role of CLA in preventing testicular cancer was depicted by the decreased CLA content in mitochondrial fractions of testicular cancer as against the normal testicular cells; and that CLA incorporation into nuclei and cytosol was significantly higher than its incorporation into plasma membranes and mitochondria [ ].
Tumors in estrogen receptor ER -negative epithelial cells in the breast are common among premenopausal women [ ]. McCann et al. Another epidemiological study the Netherlands cohort with 6. A few studies examined the relationship between dietary or serum CLA in women and the risk of breast cancer.
Such studies found an inverse association between dietary and serum CLA and risk of breast cancer in postmenopausal women [ ]. But in contrast, the adipose tissue extracts from a population of French patients with invasive breast carcinoma failed to reveal any positive correlation between adipose tissue CLA and the incidence of breast cancer [ ].
Since CLA accumulates in body fat stores, the adipose tissue of breast cancer obtained at the time of surgery could be used as a qualitative biomarker for CLA intake.
Thus, the available human clinical studies could not ascertain the anti-cancer property of CLA. A major limitation in the epidemiological studies is the difficulty in obtaining accurate estimates of dietary CLA intake.
Most of the studies were carried out in small populations, where the diversity in food habits was less. Moreover, no clinical studies evaluated the effects of pure CLA preparations or individual isomers on the incidences of cancer.
It focuses that well-defined and controlled studies are required to fully understand the effects of CLA intake on the incidence of human cancer.
The life style epidemics, diabetes and obesity are considered as the major causes of morbidity and mortality all over the world; and that obesity and weight gain are associated with an increased risk of diabetes [ ].
The hormone, insulin is responsible for regulating glucose concentration in blood. Insulin resistance is a state in which cells do not respond properly to insulin even if it is available in the blood , which leads to hyperinsulinemia high blood insulin.
Some animal studies demonstrated that CLA supplementation enhances insulin sensitivity; however, the mechanism underlying this effect is unclear [ , ]. Relatively few studies have examined the anti-diabetic properties of CLA in humans.
Supplementation of 3. The CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men [ 60 ]. Oxidative stress seems closely related to induced insulin resistance, which suggests a link between the FA-induced lipid peroxidation; these unfavorable effects of CLA might be of clinical relevance with regard to CVD [ 60 ].
Recently, Shadman et al. In non-diabetic abdominally obese men, 3. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular diseases. But, the isomeric mixture of 9- and CLA 3.
Sixteen individuals age, Clinical studies regarding the anti-diabetic effects of CLA are inconclusive. Rather, some of them speculated the reduction in insulin sensitivity; which attract immediate attention of the medical practitioners, because the increased consumption of CLA through dietary supplements might be ill-advised.
It seems that the use of weight-loss supplements containing 9-CLA, CLA or both as mixture is worrying, because most of the clinical studies presented in the previous sections provide mostly neutral or inconclusive results with very few favorable impacts Table 5.
Secondary objectives were modifications of anthropometric and metabolic parameters. Moreover, medication safety and tolerability were important outcomes. The participation of MET and CLA on the insulin signaling pathway was explored with muscles biopsies from the vastus lateralis performed under local anesthesia after 16 weeks of intervention.
An incision with a no. RNA concentration was determined using a NanoDrop spectrophotometer Thermo Scientific, Waltham, MA. Integrity was evaluated by agarose gel electrophoresis using a vertical chamber Enduro Labnet International, Edison, NJ and the UltraSlim LED Illuminator SLB Maestrogen, Las Vegas, NV.
The genetic expression patterns of IRS1, IRS2, and IRS4 were studied in 14 and 17 muscular tissue biopsies obtained from the MET and CLA groups, respectively.
Quantitative reverse transcription polymerase chain reaction array human insulin signaling pathway, RT 2 Profiler, PAHSZ, Qiagen was performed. Normalization was computed with ACTB, B2M, GAPDH, HPRT1, and RPLP0. Descriptive statistics for all numerical variables are reported as the mean and standard deviation and standard error of the mean SEM for contrasts as indicated in the text or figures.
Contrast among treatment groups was assessed by analysis of variance and analysis of covariance ANCOVA for adjustment by confounding variables. χ 2 Analyses were also executed to evaluate differences in proportion among groups. SPSS software version 22 IBM, Armonk, NY was used to conduct the statistical analyses.
Enrollment occurred from August to July Fifty patients completed the week intervention; 1 external outlier was identified and excluded during the analysis PLB group. In 1 case, EHCT performance was technically impossible CLA group. For this reason, we report the results of 48 executed clamps Fig.
Throughout the study, 1 patient was eliminated when a preexisting lipoma was surgically removed without notifying the research team PLB group ; a second patient with psychosocial anomalies and suspected pregnancy was eliminated as well PLB group.
Pubertal development Tanner stage 1, defined as prepubertal; Tanner stages 2 to 3, defined as early puberty; and Tanner stages 4 to 5, defined as late puberty was assessed after a clinical inspection of the mammary glands, testes volume, and pubic hair.
Demographic and baseline characteristics were similar among the groups Table 1. Flowchart representing the number of subjects at study enrollment and study termination. Fourteen clamp studies were conducted in the PLB group, 17 in the MET-treated group, and 17 in the CLA-treated group.
No significant differences were observed in baseline anthropometric and metabolic parameters or insulin resistance measured by surrogate indexes of insulin resistance fasting insulinemia, HOMA-IR, and QUICKI. The overall impact of the intervention showed a positive effect on weight, height, BMI, and waist circumference, as well as on surrogated indexes of insulin resistance and physical fitness score in all of the groups Table 2.
No statistically significant differences were observed in these parameters between treatment groups. No differences were evident when comparing surrogate indices of insulin resistance during the postintervention phase among the groups. Overall Impact of Intervention Regarding Anthropometric, Metabolic, and Insulin Resistance Outcomes in All Patients.
The P values were determined by a paired-samples Student t test. Data are expressed as mean SEM. The primary outcome, insulin sensitivity, calculated as the Rd value, showed significant difference between the CLA group compared with PLB 6.
Moreover, fasting insulinemia Fig. When ANCOVA was executed and the aforementioned variables were controlled, no statistically significant differences were found between the three groups with regards to Rd value.
However, these effect sizes were not clinically relevant. Fasting insulin serum concentrations were significantly lower in the CLA-treated group at study termination, whereas no differences were found in the MET-treated patients or in the PLB group.
The error bars show SEM. HOMA-IR was significantly lower in the CLA-treated group at study termination compared with initial values. No differences were found in the MET-treated and control groups.
We analyzed the changes between initial and final serum triglycerides and high-density lipoprotein HDL cholesterol by ANCOVA. For these particular variables, no Tanner or change in BMI modified postintervention levels. Furthermore, HDL cholesterol and triglyceride baseline levels did show an influence over the final levels.
Patients in the CLA group had a statistically significant increase in serum triglycerides when compared with MET Moreover, HDL levels were lower in the CLA group when compared with MET The main differences favoring MET treatment over the lipid profile were evident only when compared with CLA.
Nonserious adverse events most commonly reported were abdominal pain, diarrhea, dizziness, headache, nausea, and gastritis. The analyses of IRS1, IRS2, and IRS4 revealed that only IRS2 was modulated in the CLA group, showing a 3. The rest of the genes did not show statistically significant differences.
These data support the fact that CLA has a critical effect in the molecular insulin pathway through the upregulation of ISR2. This mechanism might be related to optimal glucose uptake observed in CLA-treated patients. This study supports that CLA improves insulin sensitivity, as measured by EHCT in a group of obese children, and exceeds LIP benefits.
Recent studies have revealed that MET has important effects on insulin sensitivity when compared with PLB, and its use in nondiabetic, obese individuals has been massively extended 6, 20, A systematic review conducted by Brufani et al.
Nonetheless, when these outcomes were evaluated by frequently sampled intravenous glucose tolerance test 22 or hyperglycemic clamp technique 23 , no significant differences were reported. Wiegand et al. We found in our study a significant improvement in all anthropometric parameters, including weight, BMI, waist circumference, and body composition fat mass and fat-free mass, data not shown ; nonetheless, these results were not significantly different among the treatment groups.
To our knowledge, no randomized PLB-controlled trial using EHCT had been executed for the evaluation of MET benefits on insulin sensitivity in children. These data could be consistent with the final results of the Diabetes Prevention Program Research Group 24 that showed that diabetes incidence was better reduced in a LIP group compared with PLB.
Several studies have proposed beneficial effects of CLA isomers on body composition, inflammation, and insulin sensitivity, promoting differentiation, lipid metabolism regulation, and apoptotic mechanisms in adipocytes 10— Interestingly, evidence has suggested that the trans , cis isomer of CLA might induce insulin resistance, whereas the CLA mixture has beneficial effects on body composition and insulin sensitivity.
Risérus et al. No differences were observed when comparing PLB and CLA mixture-treated individuals. The confounding variables included in the ANCOVA model showed a decline on group differences. Among these adjustments, Tanner stage was the main variable that modified insulin sensitivity, and despite our small sample size, the effect size of CLA on the Rd value remained.
Despite the fact that several CLA isomers might have deleterious effects on insulin sensitivity and resistance, certain mixtures may neutralize negative effects and even induce a synergistic positive response on these parameters, as well as on metabolic and anthropometric values.
Some effects of the trans , cis isomer promote a blunted glucose uptake that depends on decreased expression of glucose transporter 4 GLUT-4 Moreover, decreased incorporation of free fatty acids into the cells may be induced by CLA, a mechanism that could be related to diminished expression of peroxisome proliferator-activated receptor- γ in adipocytes CLA has been proposed as an apoptotic accelerator of adipocytes in mammals that liberates and increases fatty acid oxidation elsewhere in the body Evidence of deleterious effects has mainly been reported in animal models, in which administered doses of CLA are superior to those used in humans 0.
These effects, if present in humans, could be hyperglycemia and hyperlipidemia, which may predispose an individual to diabetes and nonalcoholic fatty liver disease 30, However, few studies have been published regarding the molecular mechanisms of CLA in skeletal muscle that could explain increased glucose uptake in our treated patients.
On this matter, Vaughan et al. Furthermore, animal models have shown the beneficial effects of CLA on insulin sensitivity and overexpression of peroxisome proliferator-activated receptor- γ and GLUT-4 in the muscle of supplemented rats In the present study we were able to demonstrate that postintervention IRS2 expression in the skeletal muscle was significantly upregulated in CLA-treated patients.
To our knowledge, no studies have been published regarding the effects of CLA or CLA—isomer mixtures on insulin receptor substrate molecules. Xu et al. The insulin-sensitizing effects of MET have been mainly described in liver tissue. Although CLA effects have been mainly focused on adipose tissue modeling, the present study demonstrates that molecular mechanisms, particularly IRS2 upregulation, might mediate insulin-sensitizing effects on skeletal muscle.
This phenomenon could explain the increased glucose infusion rate tolerability in our patients treated with CLA throughout the EHCT. Moreover, significant HOMA-IR improvement observed only in CLA-treated patients denotes a significant performance in skeletal muscle that promotes a lower pancreatic insulin secretion.
A recently published meta-analysis demonstrated that the deleterious effects of CLA consumption might be negligible, whereas its benefits, although subtle, seem to be clinically relevant regarding weight and fat mass loss In our study, BMI improvement was significant in all groups, although not significantly different among them.
Racine et al. In the CLA group, we noticed a decline in the HDL cholesterol concentration that was not statistically significant when compared with PLB. The strength of this study is supported by its own design. For example, inclusion and, particularly, elimination criteria were strictly applied.
Baseline characteristics of participants were similar regarding anthropometric and metabolic condition, particularly those related to subrogated indexes of insulin resistance. Additionally, the main outcome was evaluated by the gold standard EHCT, and the benefits of the overall LIP were evident and similar, regardless of treatment allocation.
Although the withdrawal of participants was high in our study, the elimination was random and homogeneous in all groups. The current study demonstrates the benefits of an LIP and additional effect of CLA over the gold standard EHCT.
Lifestyle intervention, independent of any treatment, showed effects on the main outcome variables, specifically weight, height, BMI, waist circumference, surrogate indexes of insulin resistance, and fitness condition, in all of the groups.
IRS2 upregulation was evident in CLA-treated patients; this mechanism might be involved in insulin-sensitizing effects on skeletal muscle.
Finally, the incidence of hypertriglyceridemia and hypo- α -lipoproteinemia in CLA-treated patients might be a concern and may be related to the types of CLA isomers used in this study. Further research to evaluate the benefits of different mixtures of CLA isomers may be warranted.
This study was supported by Grant SALUD from Consejo Nacional de Ciencia y Technología Mexico and by funding from Laboratorio Silanes S.
Clinical trial registry: ClinicalTrials. NCT registered 12 February Gutiérrez J , Rivera-Dommarco J , Shamah-Levy T , Villalpando-Hernández S , Franco A , Cuevas-Nasu L , Romero-Martínez M , Hernández-Ávila M. Encuesta Nacional de Salud y Nutrición. Morelos, Mexico : Instituto Nacional de Salud Pública Google Scholar.
Google Preview. Utzschneider KM , Van de Lagemaat A , Faulenbach MV , Goedecke JH , Carr DB , Boyko EJ , Fujimoto WY , Kahn SE. Insulin resistance is the best predictor of the metabolic syndrome in subjects with a first-degree relative with type 2 diabetes. Obesity Silver Spring.
Garner DM , Wooley SC. Confronting the failure of behavioral and dietary treatments for obesity. Clin Psychol Rev. Mauro M , Taylor V , Wharton S , Sharma AM. Barriers to obesity treatment.
Diqbetes Ohio State University. COLUMBUS, Ohio — Supplementing the diet with a certain annd acid diabwtes lead to BIA impedance vector analysis Brown rice products control and disease management in diabetics, a new study suggests. Diabetics Diabefes added Enhance skin texture 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. Hyperglycemia, or high blood sugar, is a hallmark of diabetes. Researchers also found that higher levels of this fatty acid in the bloodstream meant lower levels of leptin, a hormone thought to regulate fat levels. Scientists think that high leptin levels may play a role in obesity, one of the biggest risk factors for adult-onset diabetes. Metrics details. This Continuous glucose monitoring accuracy review critically evaluates whether supposed health benefits propounded upon human Diabeets of conjugated ad acids CLAs are clinically proven diabetws not. With a general introduction on the Brown rice products of CLA, major ane CLA and diabetes pertaining to intervention strategies, body composition, cardio-vascular health, immunity, asthma, cancer and diabetes are evaluated. Supposed adverse effects such as oxidative stress, insulin resistance, irritation of intestinal tract and milk fat depression are also examined. It seems that no consistent result was observed even in similar studies conducted at different laboratories, this may be due to variations in age, gender, racial and geographical disparities, coupled with type and dose of CLA supplemented.Conjugated linoleic acid CCLA is a diqbetes of different isomers, or chemical dabetes, of linoleic acid. Linoleic diwbetes is an essential fatty acid—a type of fat that Energy management techniques for athletes body needs for optimum nad.
Based on preliminary evidence, CLA has ddiabetes promoted as a diabetss supplement and as a treatment for diabetes. However, there is little evidence Lower cholesterol naturally it works and diabftes evidence that CLA might diabetew worsen blood sugar control in people who are overweight.
Although linoleic acid itself is dabetes important nutritional source of essential fatty CLA and diabetes, there is no evidence that you need to get conjugated linoleic acid in diaetes diet. CLA does occur in food, amd it would be very difficult to get the recommended dose that way.
Diabeets are the only practical source. The typical dosage of Anr ranges from 3 diabehes 5 diabetew daily. As with all supplements taken at this high a dosage, it aand important to diabeyes a reputable brand, Brown rice products, as diabbetes very small diabetex of CA toxic contaminant could diabtees add up.
While Brown rice products is often Cayenne pepper appetite suppressant for aiding weight dlabetes or improving body diiabetes ratio of muscle to fatevidence from studies is conflicting. Note : Some, but not all studies have raised concerns that use Diabetic retinopathy treatment options CLA by CLA and diabetes people could raise Enhance skin texture resistance and therefore increase risk of diabetes.
Diqbetes addition, Healthy vitamin suppliers might increase cardiovascular diabettes in other ways, as described in the Safety Issues.
One Brown rice products failed to find that CLA-enriched milk Natural fat burner for appetite control helpful for metabolic Enhance skin texturea condition Brown rice products with increased risk of heart disease.
Diqbetes week, double-blind, placebo-controlled study of 40 subjects anv CLA as a treatment for people with allergies to birch pollen duabetes common cause of xiabetes feverand found some evidence of benefit. A CCLA double-blind trial found weak qnd that Ahd might be useful for high cholesterol.
Some animal and test znd studies suggest that CLA might help prevent cancerbut the dianetes is preliminary and inconsistent.
Diiabetes study diabehes to diabeted that CLA can enhance immune anv. CLA appears an be a generally dizbetes nutritional substance. During diabrtes course of diabeets into its effect on fat, CLA adn found aand act somewhat similarly to some oral medications diaetes for diabefes. This led Enhance skin texture research diabetees the possible usefulness of CLA diabrtes a diabetez for diabetes.
In one study, CLA reduced blood sugar levels in diabetic rats as effectively as a standard diabetes treatment. The Smoking cessation strategies indicated that CLA improved insulin responsiveness in people with type 2 adult onset diabetes.
However, several subsequent studies found opposite and rather alarming results: Use of CLA by people with diabetes may worsen blood sugar control; in overweight people without diabetes, CLA might decrease insulin sensitivity, creating a prediabetic state. One study found that CLA impairs endothelial function and another that it increases levels of C-reactive protein; both of these effects suggest a possible increase in cardiovascular risk.
Concerns have also been raised regarding use of CLA by nursing mothers. A double-blind, placebo-controlled study indicates that use of CLA reduces the fat content of human breast milk. Maximum safe dosages of CLA for young children, pregnant women, or those with severe liver or kidney disease have not been determined.
A pilot study with the aim of studying the efficacy and tolerability of CLA Tonalin on the body composition in humans. Liilestrom, Norway: Medstat Research Ltd.
Reduced body fat with conjugated linoleic acid feeding in the mouse. FASEB J. Effects of conjugated linoleic acid CLA supplementation during resistance training on body composition and strength [abstract]. J Strength Cond Res.
Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr. Paper presented at: th ACS National Meeting; August; Washington, DC. Abstract AGFD Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats.
Conjugated linoleic acid and the risk of breast cancer. Conjugated linoleic acid supplementation in humans—metabolic effects. Wadstein J, Gudmundsen O.
Conjugated linoleic acid reduces body fat in healthy exercising humans. J Int Med Res. Conjugated linoleic acid CLA reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial.
Int J Obes Relat Metab Disord. Conjugated linoleic acid and disease prevention: a review of current knowledge. J Am Coll Nutr. Maternal supplementation with CLA decreases milk fat in humans. The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects.
Br J Nutr. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans.
Am J Clin Nutr. The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects.
Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects. Eur J Clin Nutr. Efficacy and safety of dietary supplements containing conjugated linoleic acid CLA for the treatment of obesity-evidence from animal and human studies.
J Lipid Res. Effects of two conjugated linoleic acid isomers on body fat mass in overweight humans. Obes Res. Safety profile of conjugated linoleic acid in a month trial in obese humans. Food Chem Toxicol. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus.
Supplementation with trans10 cisconjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain.
Conjugated Linoleic Acid Impairs Endothelial Function. Arterioscler Thromb Vasc Biol. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans.
The effect of CLA on body composition in humans: systematic review and meta-analysis. Asia Pac J Clin Nutr. The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers.
The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes. The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Int J Obes Lond. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.
Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Chromium picolinate and conjugated linoleic acid do not synergistically influence diet- and exercise-induced changes in body composition and health indexes in overweight women.
J Nutr Biochem. Effects of milk supplementation with conjugated linoleic acid isomers cis-9, trans and trans, cis on body composition and metabolic syndrome components.
Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep. Immunological and metabolic effects of cis-9, transconjugated linoleic acid in subjects with birch pollen allergy.
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: CLA and diabetes| Department of Surgery | Some of the studies done on diabetes were performed using a purified isomer whereas others use a mixture of CLA isomers. This makes interpretation difficult. Should we encourage consumption of dairy products or are we talking about a dietary supplement? We need more research to address all of these issues. Vanden Heuvel said that his work has generated interest from industry, with CLA supplement makers, Pharmanutrients and Natural said to be keen, while the National Cattlemen's Beef Association were said to have funded some of the initial research. Content provided by Corbion Jan Insight Guide. The good news is that most bun quality Content provided by ADM: Innovation that Feeds the Future Oct Case Study. Today, a unique challenge faces food producers. As plant-based awareness grows, consumers are becoming more conscientious of what they eat and how it fuels Content provided by Cargill Oils Oct White Paper. To say bakery fats are Content provided by Angel Yeast — Yeast and Baking Ingredients Oct White Paper. An innovative solution used to slow down the aging process, extend the shelf life of bread, and solve the problem of "flavor loss"! Mazidi M, Karimi E, Rezaie P, Ferns GA. Effects of conjugated linoleic acid supplementation on serum C-reactive protein: A systematic review and meta-analysis of randomized controlled trials. Cardiovasc Ther. Medina EA, Horn WF, Keim NL, Havel PJ, Benito P, Kelley DS, et al. Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Mądry E, Malesza IJ, Subramaniapillai M, Czochralska-Duszyńska A, Walkowiak M, Miśkiewicz-Chotnicka A, et al. Body fat changes and liver safety in obese and overweight women supplemented with conjugated linoleic acid: A week randomised, double-blind, placebo-controlled trial. Mirzaii S, Mansourian M, Derakhshandeh-Rishehri S-M, Kelishadi R, Heidari-Beni M. Association of conjugated linoleic acid consumption and liver enzymes in human studies: A systematic review and meta-analysis of randomized controlled clinical trials. Morvaridzadeh M, Estêvão MD, Morvaridi M, Belančić A, Mohammadi S, Hassani M, et al. The effect of Conjugated Linoleic Acid intake on oxidative stress parameters and antioxidant enzymes: a systematic review and meta-analysis of randomized clinical trials. Suksatan W, Putera HD, Abdulkadhim AH, Hammid AT, Ismailov JA, Jannat B, et al. The effect of conjugated linoleic acid supplementation on oxidative stress markers: A systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN. Haghighat N, Shimi G, Shiraseb F, Karbasi A, Nadery M, Ashtary-Larky D, et al. The effects of conjugated linoleic acid supplementation on liver function enzymes and malondialdehyde in adults: A GRADE-assessed systematic review and dose-response meta-analysis. Pharmacol Res. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions, version 5. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Joseph SV, Jacques H, Plourde M, Mitchell PL, McLeod RS, Jones PJ. Conjugated linoleic acid supplementation for 8 weeks does not affect body composition, lipid profile, or safety biomarkers in overweight, hyperlipidemic men. Moloney F, Yeow T-P, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Zhao W-S, Zhai J-J, Wang Y-H, Xie P-S, Yin X-J, Li L-X, et al. Conjugated Linoleic Acid Supplementation Enhances Antihypertensive Effect of Ramipril in Chinese Patients With Obesity-Related Hypertension. Am J Hypertens. Shadman Z, Rastmanesh R, Hedayati M, Taleban F, Saadat N, Tahbaz F, et al. Effects of Conjugated Linoleic Acid on Insulin Sensitivity and Diabetes Markers in Type 2 Diabetic Patients. Iran J Endocrinol Metab. Shadman Z, Taleban FA, Saadat N, Hedayati M. Effect of conjugated linoleic acid and vitamin E on glycemic control, body composition, and inflammatory markers in overweight type2 diabetics. J Diabetes Metab Disord. Abedi R, Aref-Hosseini S-R, Khoshbaten M, Ebrahimi-Mameghani M, Laleh HJ, Jalalypour F, et al. The effect of conjugated linoleic acid CLA on inflammatory factors in Non-Alcoholic Fatty Liver Disease NAFLD : A randomized controlled clinical trial. Prog Nutr. CAS Google Scholar. Ebrahimi-Mameghani M, Jamali H, Mahdavi R, Kakaei F, Abedi R, Kabir-Mamdooh B. Conjugated linoleic acid improves glycemic response, lipid profile, and oxidative stress in obese patients with non-alcoholic fatty liver disease: a randomized controlled clinical trial. Croat Med J. Eftekhari MH, Aliasghari F, Babaei-Beigi MA, Hasanzadeh J. Effect of conjugated linoleic acid and omega-3 fatty acid supplementation on inflammatory and oxidative stress markers in atherosclerotic patients. ARYA atherosclerosis. Norris LE, Collene AL, Asp ML, Hsu JC, Liu LF, Richardson JR, et al. Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus. Carvalho RF, Uehara SK, Rosa G. Microencapsulated conjugated linoleic acid associated with hypocaloric diet reduces body fat in sedentary women with metabolic syndrome. Vasc Health Risk Manag. RISerus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans 10 cis 12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Naumann E, Carpentier YA, Saebo A, Lassel TS, Chardigny J-M, Sébédio J-L, et al. Cis-9, trans and trans, cis conjugated linoleic acid CLA do not affect the plasma lipoprotein profile in moderately overweight subjects with LDL phenotype B. Schmitt B, Ferry C, Daniel N, Weill P, Kerhoas N, Legrand P. Oléagineux, Corps gras, Lipides. Mensah GARG, Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: and Beyond. J Am Coll Cardiol. Tune JD, Goodwill AG, Sassoon DJ, Mather KJ. Cardiovascular consequences of metabolic syndrome. Transl Res. Funck LG, Barrera-Arellano D, Block JM. Conjugated linoleic acid CLA and its relationship with cardiovascular disease and associated risk factors. Arch Latinoam Nutr. DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB. Am J Physiol. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Larsen TM, AstrupAJJolr. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Grimble RF, et al. Effects of cis-9, trans and trans, cis conjugated linoleic acid on immune cell function in healthy humans. Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, et al. Opposing effects of cis-9, trans and trans, cis conjugated linoleic acid on blood lipids in healthy humans. Noto A, Zahradka P, Yurkova N, Xie X, Truong H, Nitschmann E, et al. Dietary conjugated linoleic acid decreases adipocyte size and favorably modifies adipokine status and insulin sensitivity in obese, insulin-resistant rats. Shim WS, Kim SK, Kim HJ, Kang ES, Ahn CW, Lim SK, et al. Decrement of postprandial insulin secretion determines the progressive nature of type-2 diabetes. Eur J Endocrinol. De Roos B, Rucklidge G, Reid M, Ross K, Duncan G, Navarro MA, et al. Divergent mechanisms of cis9, transand trans10, cisconjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach. FASEB J. de Almeida MM, de Souza YO, Luquetti SCPD, Sabarense CM, do Amaral Corrêa JO, da Conceição EPS, et al. Cis-9, trans and trans, cis CLA mixture does not change body composition, induces insulin resistance and increases serum HDL cholesterol level in rats. Eyjolfson V, Spriet LL, Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc. Viladomiu M, Hontecillas R, Bassaganya-Riera JJEJoP. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol. Aslani MR, Matin S, Nemati A, Mesgari-Abbasi M, Ghorbani S, Ghobadi H. Effects of conjugated linoleic acid supplementation on serum levels of interleukin-6 and sirtuin 1 in COPD patients. Avicenna J Phytomed. Shahmirzadi FE, Ghavamzadeh S, Zamani T. The effect of conjugated linoleic acid supplementation on body composition, serum insulin and leptin in obese adults. Arch Iran Med. Wang JY, Lu KC, Lin YF, Hu W-M. Correlation of serum leptin concentrations with body composition and gender in Taiwanese hemodialysis patients without diabetes. Ren Fail. Haghighatdoost F, Hariri M. Effect of conjugated linoleic acid supplementation on serum leptin concentration: a systematic review and meta-analysis. Asbaghi O, Shimi G, Shiraseb F, Karbasi A, Nadery M, Ashtary-Larky D, et al. Pharmacological Research. Kadegowda AK, Connor EE, Teter BB, Sampugna J, Delmonte P, Piperova LS, et al. Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice. Wang Y, Jones PJ. Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes. Eder K, Ringseis R. Mol Nutr Food Res. Metabolism and actions of conjugated linoleic acids on atherosclerosis-related events in vascular endothelial cells and smooth muscle cells. DeClercq V, Taylor CG, Wigle J, Wright B, Tworek L, Zahradka PJTJoNB. Conjugated linoleic acid improves blood pressure by increasing adiponectin and endothelial nitric oxide synthase activity. J Nutr Biochem. Jiang S, Chen H, Wang Z, Riethoven J-J, Xia Y, Miner J, et al. Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes. Stringer DM, Zahradka P, DeClercq VC, Ryz NR, Diakiw R, Burr LL, et al. Modulation of lipid droplet size and lipid droplet proteins by trans, cis conjugated linoleic acid parallels improvements in hepatic steatosis in obese, insulin-resistant rats. Biochim Biophys Acta. Andreoli MF, Illesca PG, González MA, Bernal CAJL. Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profile during protein repletion in rats. Download references. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences TUMS , Tehran, Iran. Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Community Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran. Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Department of Cellular and Molecular Nutrition, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. You can also search for this author in PubMed Google Scholar. and G. contributed in conception, data collection and manuscript drafting. contributed in data collection and manuscript drafting. revised the manuscript. All authors reviewed the manuscript. Correspondence to Ghazaleh Shimi or Omid Asbaghi. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Ghodoosi, N. et al. The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose—response meta-analysis. Published: Received: May 28, Available on J-STAGE: June 28, Accepted: June 16, Advance online publication: - Revised: -. Download PDF K Download citation RIS compatible with EndNote, Reference Manager, ProCite, RefWorks. Article overview. References Related articles 0. Figures 0. Content from these authors. Supplementary material 0. Result List. Previous article Next article. |
| CLA Targets Diabetes | Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Several studies have acknowledged the beneficial effects of CLA isomers on body composition 9, 10 , immune response 11 , bacterial-induced colonic inflammation 12, 13 , as well as improvements in insulin sensitivity and lipid metabolism in experimental animals and humans 9. Increased malondialdehyde levels in coronary heart disease. PubMed PubMed Central Google Scholar Rubin D, Herrmann J, Much D, Pfeuffer M, Laue C, Winkler P, et al. No significant differences were observed in baseline anthropometric and metabolic parameters or insulin resistance measured by surrogate indexes of insulin resistance fasting insulinemia, HOMA-IR, and QUICKI. Abel Jalife. |
| Fat That May Benefit Diabetics Reduces Weight, Blood Sugar | Non-linear dose—response relations between CLA supplementation and absolute mean differences. On the other hand, the overall quality of the evidence showing the influence of CLA supplementation on Insulin, AST, IL-6, and CRP was upgraded to moderate. Most of clinical studies evaluated the effects of CLA consumption for a short period, usually of 4—12 wk. Descriptive statistics for all numerical variables are reported as the mean and standard deviation and standard error of the mean SEM for contrasts as indicated in the text or figures. Medicine and Health. |
| Conjugated Linoleic Acid – Health Information Library | PeaceHealth | Anx to our Endurance running shoes, Aslani et al. J Int Brown rice products Resdlabetes 5 : —6. Br J Nutr94 5 : —5. References 1. Am J Clin Nutr. Jiang S, Chen H, Wang Z, Riethoven J-J, Xia Y, Miner J, et al. |
| Key concepts: cla, conjugated linoleic acid, body fat, type-2 diabetes | Med Sci Sports Exerc ; Thom E. A pilot study with the aim of studying the efficacy and tolerability of Tonalin CLA on the body composition in humans. Lillestrom, Norway: Medstat Research Ltd. Learn more about TraceGains, the company. The information presented by TraceGains is for informational purposes only. It is based on scientific studies human, animal, or in vitro , clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Information expires December PeaceHealth endeavors to provide comprehensive health care information, however some topics in this database describe services and procedures not offered by our providers or within our facilities because they do not comply with, nor are they condoned by, the ethics policies of our organization. This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated. Home Health Information Library Conjugated Linoleic Acid. Conjugated Linoleic Acid. Uses Conjugated linoleic acid CLA is a slightly altered form of the essential fatty acid linoleic acid. What Are Star Ratings? This supplement has been used in connection with the following health conditions: Used for Why 2 Stars. Although the evidence is conflicting, the majority of the evidence shows CLA can help people lose body fat, and may promote a small amount of weight loss. Conjugated linoleic acid CLA is a group of polyunsaturated fatty acids found mainly in dairy products. In numerous randomized controlled trials lasting from 12 weeks to two years, CLA supplementation has been found to reduce body fat in people with overweight and obesity. Although some trials have reported weight loss attributable to CLA, others have found no effect of CLA on body weight. A meta-analysis of seven placebo-controlled trials lasting six months or longer concluded CLA use is associated with small increases in weight loss and fat loss. Importantly, conflicting evidence has emerged regarding the impact of CLA on oxidative stress and insulin resistance. Therefore, the use of CLA by people with type 2 diabetes or signs of insulin resistance should be carefully monitored. Conjugated linoleic acid may play a role in reducing body fat. Research has reported that CLA supplementation produces minor gains in muscle size and strength in weight-training men. Preliminary research suggests that CLA might reduce breast cancer risk. Preliminary and test tube studies indicate that CLA may reduce the risk of colon cancer. Preliminary research suggests that CLA might reduce the risk of cancers at several sites, including breast, prostate, colorectal, lung, skin, and stomach. Omega-6 fatty acids found in sunflower seed oil a source of linoleic acid may be beneficial. Studies have reported that linoleic acid reduced relapse severity and length and decreased disability due to MS. How It Works How to Use It Most studies in humans have used 1. Where to Find It CLA is found mainly in dairy products and also in beef and poultry, eggs, and corn oil. Possible Deficiencies No deficiencies of CLA are reported or believed to occur, since it is not an essential nutrient. Interactions with Medicines As of the last update, we found no reported interactions between this supplement and medicines. It is possible that unknown interactions exist. If you take medication, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist. The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist. Side Effects Side Effects Overweight volunteers who took 4. Related Information. References 1. Next Section: How It Works ». Previous Section: « Uses. Next Section: Interactions ». Previous Section: « How It Works. Next Section: Side Effects ». The confounding variables included in the ANCOVA model showed a decline on group differences. Among these adjustments, Tanner stage was the main variable that modified insulin sensitivity, and despite our small sample size, the effect size of CLA on the Rd value remained. Despite the fact that several CLA isomers might have deleterious effects on insulin sensitivity and resistance, certain mixtures may neutralize negative effects and even induce a synergistic positive response on these parameters, as well as on metabolic and anthropometric values. Some effects of the trans , cis isomer promote a blunted glucose uptake that depends on decreased expression of glucose transporter 4 GLUT-4 Moreover, decreased incorporation of free fatty acids into the cells may be induced by CLA, a mechanism that could be related to diminished expression of peroxisome proliferator-activated receptor- γ in adipocytes CLA has been proposed as an apoptotic accelerator of adipocytes in mammals that liberates and increases fatty acid oxidation elsewhere in the body Evidence of deleterious effects has mainly been reported in animal models, in which administered doses of CLA are superior to those used in humans 0. These effects, if present in humans, could be hyperglycemia and hyperlipidemia, which may predispose an individual to diabetes and nonalcoholic fatty liver disease 30, However, few studies have been published regarding the molecular mechanisms of CLA in skeletal muscle that could explain increased glucose uptake in our treated patients. On this matter, Vaughan et al. Furthermore, animal models have shown the beneficial effects of CLA on insulin sensitivity and overexpression of peroxisome proliferator-activated receptor- γ and GLUT-4 in the muscle of supplemented rats In the present study we were able to demonstrate that postintervention IRS2 expression in the skeletal muscle was significantly upregulated in CLA-treated patients. To our knowledge, no studies have been published regarding the effects of CLA or CLA—isomer mixtures on insulin receptor substrate molecules. Xu et al. The insulin-sensitizing effects of MET have been mainly described in liver tissue. Although CLA effects have been mainly focused on adipose tissue modeling, the present study demonstrates that molecular mechanisms, particularly IRS2 upregulation, might mediate insulin-sensitizing effects on skeletal muscle. This phenomenon could explain the increased glucose infusion rate tolerability in our patients treated with CLA throughout the EHCT. Moreover, significant HOMA-IR improvement observed only in CLA-treated patients denotes a significant performance in skeletal muscle that promotes a lower pancreatic insulin secretion. A recently published meta-analysis demonstrated that the deleterious effects of CLA consumption might be negligible, whereas its benefits, although subtle, seem to be clinically relevant regarding weight and fat mass loss In our study, BMI improvement was significant in all groups, although not significantly different among them. Racine et al. In the CLA group, we noticed a decline in the HDL cholesterol concentration that was not statistically significant when compared with PLB. The strength of this study is supported by its own design. For example, inclusion and, particularly, elimination criteria were strictly applied. Baseline characteristics of participants were similar regarding anthropometric and metabolic condition, particularly those related to subrogated indexes of insulin resistance. Additionally, the main outcome was evaluated by the gold standard EHCT, and the benefits of the overall LIP were evident and similar, regardless of treatment allocation. Although the withdrawal of participants was high in our study, the elimination was random and homogeneous in all groups. The current study demonstrates the benefits of an LIP and additional effect of CLA over the gold standard EHCT. Lifestyle intervention, independent of any treatment, showed effects on the main outcome variables, specifically weight, height, BMI, waist circumference, surrogate indexes of insulin resistance, and fitness condition, in all of the groups. IRS2 upregulation was evident in CLA-treated patients; this mechanism might be involved in insulin-sensitizing effects on skeletal muscle. Finally, the incidence of hypertriglyceridemia and hypo- α -lipoproteinemia in CLA-treated patients might be a concern and may be related to the types of CLA isomers used in this study. Further research to evaluate the benefits of different mixtures of CLA isomers may be warranted. This study was supported by Grant SALUD from Consejo Nacional de Ciencia y Technología Mexico and by funding from Laboratorio Silanes S. Clinical trial registry: ClinicalTrials. NCT registered 12 February Gutiérrez J , Rivera-Dommarco J , Shamah-Levy T , Villalpando-Hernández S , Franco A , Cuevas-Nasu L , Romero-Martínez M , Hernández-Ávila M. Encuesta Nacional de Salud y Nutrición. Morelos, Mexico : Instituto Nacional de Salud Pública Google Scholar. Google Preview. Utzschneider KM , Van de Lagemaat A , Faulenbach MV , Goedecke JH , Carr DB , Boyko EJ , Fujimoto WY , Kahn SE. Insulin resistance is the best predictor of the metabolic syndrome in subjects with a first-degree relative with type 2 diabetes. Obesity Silver Spring. Garner DM , Wooley SC. Confronting the failure of behavioral and dietary treatments for obesity. Clin Psychol Rev. Mauro M , Taylor V , Wharton S , Sharma AM. Barriers to obesity treatment. Eur J Intern Med. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. Eur J Endocrinol. Brufani C , Crinò A , Fintini D , Patera PI , Cappa M , Manco M. Systematic review of metformin use in obese nondiabetic children and adolescents. Horm Res Paediatr. Conjugated linoleic acid. Anim Health Res Rev. Christie WW , Dobson G , Adlof RO. A practical guide to the isolation, analysis and identification of conjugated linoleic acid. Eyjolfson V , Spriet LL , Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc. Effect of conjugated linoleic acid on body fat accretion in overweight or obese children. Am J Clin Nutr. Song H-J , Grant I , Rotondo D , Mohede I , Sattar N , Heys SD , Wahle KWJ. Effect of CLA supplementation on immune function in young healthy volunteers. Eur J Clin Nutr. Hontecillas R , Wannemeulher MJ , Zimmerman DR , Hutto DL , Wilson JH , Ahn DU , Bassaganya-Riera J. Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. J Nutr. Bassaganya-Riera J , Reynolds K , Martino-Catt S , Cui Y , Hennighausen L , Gonzalez F , Rohrer J , Benninghoff AU , Hontecillas R. Activation of PPAR γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Larsen TM , Toubro S , Astrup A. Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res. American Diabetes Association. Diabetes Care. World Health Organization. Energy and protein requirements. World Health Organ Tech Rep Ser. Treviño RP , Marshall RM , Jr , Hale DE , Rodriguez R , Baker G , Gomez J. Diabetes risk factors in low-income Mexican-American children. DeFronzo RA , Tobin JD , Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. Morrison JA , Friedman LA , Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Catoira N , Nagel M , Di Girolamo G , Gonzalez CD. Pharmacological treatment of obesity in children and adolescents: current status and perspectives. Expert Opin Pharmacother. Quinn SM , Baur LA , Garnett SP , Cowell CT. Treatment of clinical insulin resistance in children: a systematic review. Obes Rev. Freemark M , Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Yanovski JA , Krakoff J , Salaita CG , McDuffie JR , Kozlosky M , Sebring NG , Reynolds JC , Brady SM , Calis KA. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. Risérus U , Arner P , Brismar K , Vessby B. Treatment with dietary trans 10 cis 12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Brown JM , McIntosh MK. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. Conjugated linoleic acid supplementation enhances insulin sensitivity and peroxisome proliferator-activated receptor gamma and glucose transporter type 4 protein expression in the skeletal muscles of rats during endurance exercise. Iran J Basic Med Sci. Zhai JJ , Liu ZL , Li JM , Chen JP , Jiang L , Wang DM , Yuan J , Shen J-G , Yang D-P , Chen J-Q. Different mechanisms of cis -9, trans and trans , cis conjugated linoleic acid affecting lipid metabolism in 3T3-L1 cells. J Nutr Biochem. Whigham LD , Watras AC , Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Clément L , Poirier H , Niot I , Bocher V , Guerre-Millo M , Krief S , Staels B , Besnard P. Dietary trans,cis conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. Tsuboyama-Kasaoka N , Takahashi M , Tanemura K , Kim HJ , Tange T , Okuyama H , Kasai M , Ikemoto S , Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Vaughan RA , Garcia-Smith R , Bisoffi M , Conn CA , Trujillo KA. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis. J Endocrinol. Onakpoya IJ , Posadzki PP , Watson LK , Davies LA , Ernst E. The efficacy of long-term conjugated linoleic acid CLA supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Subjects and Methods. Journal Article. Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial. Nayely Garibay-Nieto , Nayely Garibay-Nieto. Oxford Academic. Gloria Queipo-García. Flor Alvarez. Mayra Bustos. Erendira Villanueva. Fernando Ramírez. Mireya León. Estibalitz Laresgoiti-Servitje. Ravindranath Duggirala. Teresa Macías. Sergio Cuevas , Sergio Cuevas. Abel Jalife. Miguel Fonseca-Sánchez. Fabiola Serratos. Juan Carlos López-Alvarenga. PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Abstract Context:. Figure 1. Open in new tab Download slide. Table 1. Participant Characteristics at Randomization. Age, y |
Welche bemerkenswerte Frage
Wacker, mir scheint es die prächtige Idee
Etwas so wird nicht erhalten
Dieses schon besprachen vor kurzem
Sie sind recht, es ist genau