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CLA and immune function

CLA and immune function

As described CLA and immune function other fuction models of CNS autoimmunity, 1453 diseased Funciton ctrl anc displayed notable immune cell infiltrations functlon the CLA and immune function Protein benefits propria; Calorie counting techniques, this was diminished Cardiovascular conditioning OSE CLA mice Fig. Fuction R. Only Calorie counting techniques without relapses within the last 3 months and a stable first-line immunomodulatory medication for at least 3 months were included. Lamas Bervejillo MBonanata JFranchini GRet al. von Frankenberg AD, Silva FM, de Almeida JC, Piccoli V, do Nascimento FV, Sost MM, et al. Strictly controlled studies as performed in animals or in culture models may not be maintained in clinical trials, however, most of human studies are based on blood, blood cells, milk or biopsy specimens - all these would cause probable variations in the general data generated.

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Conjugated Linoleic Acid CLA Supplement - Professional Supplement Review - National Nutrition Canada

CLA and immune function -

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.

In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. A week washout period followed the intervention period. However, plasma glucose, lipids, lymphocyte phenotypic results were not affected significantly by CLA.

This is the first study to show that CLA, a fatty acid naturally found in dairy and meat products, can beneficially affect immune function in healthy human volunteers. This study was supported by Loders-Croklaan, The Netherlands and SEERAD Scottish Executive Environmental Rural and Agriculture Department.

This is a preview of subscription content, access via your institution. Article Google Scholar. Article CAS Google Scholar. Lipids 36 , — Anticancer Res. CAS PubMed Google Scholar. Food Comp. Champaign, IL: AOCS Press. Google Scholar. In Advances in Conjugated Linoleic Acid Research , Vol. Lipid ICBL Abstract, p Cancer Res.

CAS Google Scholar. Lipids 35 , — Mertin J : Essential fatty acids and cell-mediated immunity. Meydani SN : Effect of n-3 polyunsaturated fatty acids on cytokine production and their biologic function. Nutrition 12 , S8—S West of Scotland Coronary Prevention Study Group.

Parodi PW : Conjugated linoleic acid: an anticarcinogenic fatty acid present in milk fat. Dairy Technol. Circulation , — Lipids 33 , — Download references. We thank Loders-Croklaan, The Netherlands and SEERAD Scottish Executive Environmental Rural and Agriculture Department for their sponsorship.

In addition we thank all volunteers for their participation. Pathological Biochemistry, Glasgow University, Glasgow, UK.

You can also search for this author in PubMed Google Scholar. Correspondence to K W J Wahle. Contributors : KJWJ, DR, IM, SDH designed the study supervised experiment work.

H-JS, IG conducted experiment work. NS analysed CRP results. H-JS wrote the manuscript with input from all authors. Reprints and permissions. Song, HJ. et al. All of these studies were RCTs published between and Study design characteristics are presented in Table 1.

The two studies were conducted in the USA 42 , 67 , three in Sweden 43 , 45 , 49 , three in the Netherlands 44 , 52 , 65 , four in Canada 12 , 14 , 46 , 68 , two in Norway 27 , 47 , four in the UK 28 , 48 , 51 , 56 , two in France 50 , 53 , two in Turkey 11 , 72 , one in Japan 55 , one in Ireland 57 , one in Korean 58 , one in Finland 59 , one in Denmark 61 , one in China 62 , three in Germany 62 , 69 , 70 , one in Italy 64 , one in Spain 16 , one in Poland 75 , and the others in Iran 18 , 19 , 60 , 66 , 71 , 73 , 74 , Thirteen studies included only men and seven women, and 22 included both sexes.

The duration of the intervention varied from 4 to weeks. The CLA supplements were used in doses of 1. The mean age and baseline BMI ranged from 20 to Iwata et al. used two different CLA doses in their studies. Out of the 42 studies, CRP, IL-6, TNF-α, adiponectin, and leptin were reported in 20, 15, 16, 12, and 20, respectively.

For supplementation, 47 study arms used mixed isomers 9cis,11trans-CLA and 10trans,12cis-CLA , four study arms used 9cis,11trans-CLA isomer, and five study arms used 10trans,12cis-CLA isomer.

In these studies, detection methods of CRP were Behring latex-enhanced high-sensitivity assays, Eckman Synchron CX7 System, enzyme-linked immunosorbent assay, enhanced turbidimetric immunoassay, highly sensitive immunoassay with a monoclonal antibody coated with polystyrene particles, immunoturbidimetric assay, and rabbit antihuman.

Diamonds represent pooled estimates from random-effects analysis. WMD, weighted mean difference; CI, confidence interval; CLA, conjugated linoleic acid; CRP, C-reactive protein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-alpha.

Overall, 24 effect sizes from 20 studies for CRP were included in the analysis. In the other subgroups, the effect of CLA supplementation on serum concentrations of CRP was not significant Table 3.

Table 3 Subgroup analyses of CLA supplementation on inflammatory cytokines and adipokines. In the other subgroups, the effect of CLA supplementation on serum concentrations of IL-6 was not significant Table 3. In the other subgroups, the effect of CLA supplementation on serum concentrations of TNF-α was not significant Table 3.

The present study conducted a nonlinear dose—response regression to analyze the dose—response relationship between CLA supplementation and inflammatory cytokines and adipokines.

Meta-regression analyses were performed to assess whether inflammatory cytokines and adipokines were affected by CLA supplementation doses and intervention duration.

WMD, weighted mean difference; CI, confidence interval; CRP, C-reactive protein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-alpha. The sensitivity analysis demonstrated that no study had a significant impact on the overall findings.

Although the overall result of studies reporting data on TNF-α was sensitive to the study by Song et al. In the case of CRP, some studies had an impact on the overall effect size, including that of Whigham et al.

It was shown that the exclusion of every individual study by the sensitivity analysis could not change the direction of the correlation but eliminated the significant effect of CLA on CRP. Table 4 displays the Grading of Recommendations Assessment, Development, and Evaluation GRADE profile of CLA supplementation on inflammatory cytokine and adipokine variables together with the certainty in outcomes.

For CRP, because of serious limitations in inconsistency, the quality of evidence was moderate. In the case of IL-6, because of very serious limitations in inconsistency and for TNF-α because of very serious limitations in inconsistency ad serious limitations for publication bias, the quality of evidence was low.

For both outcomes, including leptin and adiponectin, because of very serious limitations in inconsistency and serious limitations in imprecision, the quality of evidence was very low. Table 4 GRADE profile of CLA supplementation for inflammatory cytokines and adipokines.

Using the GRADE methodology, which was previously outlined, the total degree of evidence certainty across the studies was evaluated and summarized In this review, an analysis of pooling 42 studies indicated that CLA supplementation increased CRP concentrations, decreased IL-6 and TNF-α values, and had no effect on adiponectin and leptin levels.

Taking CLA decreased IL-6 in male individuals and unhealthy subjects if the trial duration was less than 12 weeks and when a mixture of two isomers was used. However, in subgroup analyses based on isomer type, 10trans12cis- CLA isomer significantly increased TNF-α.

Supplementation with CLA reduced adiponectin in women. It also decreased leptin in women and unhealthy adults but increased in those with normal baseline BMI. Moreover, the results of the meta-regression analysis showed that there was no significant linear association between intervention doses and duration of supplementation with inflammatory cytokines and adipokines.

The majority of studies included in this meta-analysis used supplements consisting of mixed amounts of CLA isomers. Therefore, since CLA isomers have shown different effects on inflammation 30 , 78 , it is suggested that this issue be considered in research.

It is also important to consider the contents of the placebo used in studies. Some included RCTs have used vegetable oils as a placebo, such as safflower and olive oils. One study has indicated the reduced effect of safflower oil on CRP levels compared to CLA Another study has elucidated the anti-inflammatory effect of olive oils through the prevention of lipooxygenase and enzymes that synthesize leukotriene In other words, prescribing these vegetable oils as a placebo might misinterpret results.

Diet and physical activity can play an important role in inflammatory conditions It is better to consider the effects of these two factors in the result of the present meta-analysis.

Although, in some studies, the confounding variables of physical activity and diet were controlled, in some trials, these factors were not considered. Diet is an important regulatory factor in the immune response. Malnutrition leads to suppression of the immune system, whereas overnutrition leads to immune activation.

Some foods have anti-inflammatory effects, and there are still controversies about others Also, a high-fat diet causes excessive body fat accumulation and impairs the immune system.

On the other hand, it has been reported that trans and saturated fatty acids are significantly associated with the inflammatory state Although ruminant trans fatty acids have different effects than industrial trans fatty acids, several studies show that industrial trans fatty acids promote inflammation, whereas ruminant trans fatty acids have been reported to be harmless or even beneficial to health, as well as also having anti-inflammatory properties One study reported that sedentary subjects had higher levels of inflammatory factors such as IL-6 and TNF-α compared to subjects with higher physical activity Other confounding factors that can affect inflammatory markers are sleep duration and sleep quality.

In addition, a study on healthy subjects reported that higher IL-6 levels were associated with lower sleep quality Here, we showed CLA consumption increased CRP concentrations, decreased IL-6 and TNF-α, and did not change adiponectin and leptin levels.

There are some meta-analyses that have investigated the effect of CLA on the abovementioned markers. For example, Derakhshandeh-Rishehri et al. A meta-analysis conducted by Haghighatdoost et al. Another meta-analysis conducted on 19 RCTs demonstrated that CLA intake had a small but not significant decline in plasma leptin.

However, it significantly decreased leptin in obese individuals, with trials lasting for less than 24 weeks A study carried out by Mazidi et al. By combining previous and current results, it can be acknowledged that except for the effect of CLA in increasing CRP levels, there is no consensus on other markers i.

Moreover, it is noteworthy to state that exercise, dietary intake, sleep duration, and sleep quality can alter the effects of CLA. Therefore, further well-designed studies may clarify the role of CLA on the abovementioned markers.

In the present study, the gender-dependent impact of CLA has also been shown in the reduction of IL-6, TNF-α, adiponectin, and leptin. Based on evidence, CLA can induce testosterone biosynthesis 91 , and subsequently, testosterone is able to decrease IL-6 expression It has also been stated that circulating CLA concentrations are greater in women than in men Therefore, the aforementioned evidence can justify the different effects seen between men IL-6 and TNF-α reduction and women adiponectin and leptin reduction after taking CLA.

The effect of CLA on inflammatory responses has generated inconsistent results. This may be due to isomers and tissue-specific responses of CLA. Moreover, across the included RCTs, administration doses of CLA varied from 1. Health characteristics, inflammation status, and even gut microbiome composition of the recruited individuals were also different These variations in the studies can influence the results and interpretations.

For example, in relation to isomer and tissue-specific response, 9cis,11trans-CLA isomer exerts its anti-inflammatory effect by activating the peroxisome proliferator-activated receptor-γ PPAR-γ -dependent pathway and ultimately reducing the production of proinflammatory cytokines such as TNF-α and IL-6 However, the 10trans,12cis-CLA isomer has been reported to have a proinflammatory effect in adipose tissue, in contrast to its effects on innate immunity and vascular cells.

In addition, in adipose tissue, activation of PPAR­γ is contrary to the physiological effects of 10trans,12cis-CLA in vitro and in vivo This isomer downregulates PPAR-γ gene expression and increases TNF-α, IL-6, and CRP production in adipose tissue 78 , It seems that the reason for this inconsistency is cytokines secreted from adipocytes, which in turn alter PPAR­γ expression and activity in the fat cell.

Therefore, inconclusive results regarding the anti-inflammatory properties of CLA are likely due to the subtle proinflammatory effects of the 10trans,12cis-CLA isomers in specific tissues 30 , Overall, it appears that CLA can elicit both anti-inflammatory and proinflammatory features.

Some proposed mechanisms for the effects of CLA isomers on inflammation include the following: 1 Modulation of eicosanoid signaling. This means that CLA reduces the production of inflammatory eicosanoids derived from arachidonic acid AA through the inhibition of several steps in the AA cascade.

Also, it suppresses the expression of the inducible NO synthase iNOS gene, which leads to a decrease in IL-6 production. This meta-analysis has some limitations that should be addressed.

Most of the included studies had a relatively small sample size, which can cause an overestimation of the results. Observation of publication bias for TNF-α findings suggests overestimation of CLA efficiency on TNF-α.

Moreover, TNF-α, IL-6, and CRP results were sensitive to some studies. In conclusion, it is suggested that CLA supplementation can have both proinflammatory and anti-inflammatory roles. It can enhance CRP concentrations while reducing TNF-α and IL-6 levels.

Furthermore, CLA is able to decrease adiponectin and leptin in women. It can also decrease leptin in unhealthy adults and increase it in subjects with a normal baseline BMI. Finally, in order to improve the quality of studies, future clinical trials are encouraged to carefully consider CLA-isomer-specific regulation of inflammatory markers and take notice of the contents of the placebo used in their control groups.

It is also important to keep in mind the gender-dependent impact of CLA. Further inquiries can be directed to the corresponding authors. OA and SR contributed to the conception and design of the study. DA-L, MZ, and GS contributed to data extraction.

FS and AK screened articles for inclusion criteria. OA contributed to the data analysis. SR, MY, and EG contributed to manuscript drafting, OA and MZ supervised the study. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

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Thank immunne for functioon nature. You are using functino browser version with limited Calorie counting techniques for Imune. To CLA and immune function the best Nitric oxide and blood pressure, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. To assess the effects of dietary supplementation using two isomeric blends of conjugated linoleic acid CLA on immune function in healthy human volunteers. CLA and immune function

CLA and immune function -

In vitro studies of the use of immune cells and animal models demonstrate that conjugated linoleic acid CLA , a lipid, modulates immune function. In addition, recent publications demonstrate that 2 active CLA isomers ie, cis-9,trans CLA and trans,cis CLA modulate immune function in humans.

Aspects of both the innate and adaptive immune responses are affected by dietary CLA supplementation. CLA consists of a mixture of isomers, which reduced immune-induced wasting and enhanced ex vivo lymphocyte proliferation in broilers and decreased tumor necrosis factor alpha TNF-alpha and interleukin 6 IL-6 production in rat models.

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Biotechnology Division, Department of Botany, University of Calicut, Kerala, , India. Department of Molecular Biosciences, University of Graz, Heinrichstrasse 31, , Graz, Austria.

You can also search for this author in PubMed Google Scholar. Correspondence to Sailas Benjamin. Both authors contributed equally to this article, read and approved the final version of the manuscript.

This article is published under license to BioMed Central Ltd. Reprints and permissions. Benjamin, S. Conjugated linoleic acids as functional food: an insight into their health benefits. Nutr Metab Lond 6 , 36 Download citation. Received : 15 July Accepted : 18 September Published : 18 September Anyone you share the following link with will be able to read this content:.

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Skip to main content. Search all BMC articles Search. Download PDF. Download ePub. Abstract This review evaluates the health benefits of the functional food, conjugated linoleic acids CLA - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants.

Introduction Conjugated linoleic acids CLA represent a heterogeneous group of positional and geometric isomers of linoleic acid, which are predominantly found in milk, milk products, meat and meat products of ruminants [ 1 , 2 ].

Figure 1. Full size image. CLA isomers Positive health effects attributed to CLA are mainly based on cell culture models and animal studies with comparatively less scientific evidences from direct studies on humans [ 4 ].

Figure 2. Anti-obesity Considering anti-obesitic and hypolipidemic effects, it is possible to modify body composition by supplementing CLA to the diet. Table 1 Major biochemical actions of CLA on lipid metabolism. Full size table. Anti-carcinogenesis CLA inhibits cancer by blocking the growth and metastatic spread of tumours.

Anti-atherosclerosis Atherosclerosis is a progressive disease of medium and large arteries by the accumulation of lipids in the inflammatory cells foam-cell formation , cellular proliferation, platelet adherence and aggression, and calcium deposition [ 91 , 92 ].

Anti-diabetes Diabetes can be caused by too little insulin type I , resistance to insulin type II , or by both. Immunomodulation In vitro studies of the use of immune cells and in vivo animal models demonstrate that CLA modulate immune function.

Bone formation Mixed CLA isomers have been shown to have variable effects on bone formation ostheosynthesis and resorption in animals. Safety concerns and human scenario Though only positive health benefits of CLA have been addressed here, some negative impacts of CLA could not be ruled out [ ].

Therefore, the control and prevention of chronic inflammation should be considered in order to prevent some chronic diseases and even improve health. Despite the considerable benefits of pharmacological therapies, these may exert undesirable side effects and may not be tolerated by some individuals.

On the other hand, they may cause drug resistance reduction of efficiency and even toxicity 6. Several studies have suggested that dietary strategies, such as certain supplements, can modulate inflammation.

For example, a clinical trial has reported that magnesium and vitamin E co-supplementation led to a significant decrease in C-reactive protein CRP and a significant increase in total antioxidant capacity levels 7 — 9.

Another study has suggested that l -glutamine supplementation in the early period of COVID infection may reduce inflammatory responses and boost the immune system Therefore, it is practical to find nutraceuticals and natural compounds with anti-inflammatory effects that may serve as alternative therapies to pharmacological interventions.

Conjugated linoleic acid CLA is a collective term for geometric isomers of linoleic acid C, n This polyunsaturated fatty acid has two double bonds separated by a methylene group.

This conjugation of the double bond is generally in positions 9 and 11 or 10 and 12 and may be a cis or trans configuration. Depending on the position and geometry of the double bonds, several isomers of CLA have been identified, such as 9cis,11trans-CLA and 10trans,12cis-CLA 11 , Most of the beneficial properties of CLA are elicited by these two main isomers.

For example, 10trans,12cis-CLA is involved in catabolic processes such as lipolysis and fat oxidation, whereas 9cis,11trans-CLA seems to be the active anabolic agent. In addition, based on the evidence, 10trans,12cis-CLA is thought to be anticarcinogenic, antiobesity, and antidiabetic, whereas 9cis,11trans-CLA is mainly anti-inflammatory CLA is formed via biohydrogenation by bacterial enzymes known as catalyst, present in the intestine microbiota of ruminant mammals; hence, CLA is mainly found in their flesh and milk Nonetheless, it is present in foods only in finite amounts; therefore, commercialized CLA supplements have been provided to offer potential benefits, such as reduction of body weight and total fat mass, anticancer effects including reducing tumor growth 15 , 16 , reducing insulin resistance, lipid disorders, and oxidative stress, improving liver function in nonalcoholic fatty liver 17 , and immunomodulatory effects 18 — A large number of studies have investigated the effect of CLA supplementation on inflammatory cytokines and adipokines.

However, the results of these studies are contradictory. For instance, some studies have reported that CLA supplementation had no significant effect on leptin levels 21 , 22 , whereas others found a significant decrease in serum leptin during CLA supplementation 23 , CLA supplementation has even been shown to significantly increase serum leptin levels Also, some studies have reported that CLA supplements lead to a decrease in adiponectin levels 26 , while another study has reported that CLA supplements have little or no effect on adiponectin levels However, Sneddon et al.

Furthermore, while one study has found that CLA supplementation may increase CRP and tumor necrosis factor-alpha TNF-α and marginally decrease interleukin-6 IL-6 , indicating a proinflammatory state 29 , 30 , a recent review article suggests that CLA may have an anti-inflammatory effect by reducing inflammatory mediators such as cytokines, particularly IL-6, TNF-α, IFN-γ, and IL-1β Therefore, due to the inconsistencies in previous studies, the present study sought to update previous meta-analyses in light of the plethora of new studies.

Thus, the current meta-analysis sought to investigate the effects of CLA on inflammatory cytokines and adipokines in adults. This systematic review has been conducted according to the PRISMA statement The present study was registered at PROSPERO CRD There were no restrictions on the length of time or language of publications.

By reading the titles, abstracts, and full text of the papers as needed, two researchers independently FS and OA chose the appropriate articles.

The effects of CLA supplementation on inflammatory cytokines and adipokines variables in adults with different health statuses in all human randomized clinical trials RCTs. The searches were limited to human studies with no language restrictions.

Animal studies, reviews, in vitro research, research on kids and teenagers, grey literature, conference abstracts, opinion pieces, books, and RCTs without a placebo or control group were excluded. Studies that used CLA in combination with vitamins or minerals were also excluded. In the present study, we searched for studies that assessed the effects of CLA supplementation on all inflammatory cytokines.

After screening and finding eligible studies, we found that most studies evaluated CRP, IL-6, and TNF. In addition, a limited number of studies have evaluated other inflammatory factors such as IL-1 and IL Therefore, we included studies that evaluated the effects of CLA on CRP, IL-6, and TNF.

After quickly skimming the titles, abstracts, and full text to choose the most pertinent research following a separate review of each qualifying RCT, the following data were gleaned by two independent researchers OA and FS. Name of the first author, country of origin, year of publication, type of clinical trial, participant characteristics mean age, body mass index BMI , sex , randomization, blinding, sample size, number of participants in the intervention and control groups, type and dosage of supplemented CLA, duration of the study, and related data were extracted for additional measurements.

The CLA dosages were converted to milligrams per day, whether they were given in grams per day or another unit. To rate the quality of the studies, the Cochrane Collaboration technique was utilized Two researchers SR and GS independently assessed the methods, and any disagreements between their assessments were resolved through discussion.

Each study was evaluated for any bias, including those caused by randomized sequence generation, allocation concealment, participant and staff blindness, outcome assessor blindness, insufficient outcome data, selective reporting, and other biases.

Stata The pooled weighted mean difference WMD was calculated using a random-effects model to take into account any existing heterogeneity due to the different intervention doses, duration, participant health, sample sizes, and length of intervention developed by Der Simonian and Laird We computed the mean differences in CRP, IL-6, TNF-α, adiponectin, and leptin between the CLA supplementation and control groups from the preintervention to the postintervention.

Other subgroup analyses were performed according to gender man, woman , baseline BMI normal We used the leave-one-out approach to do a sensitivity analysis to identify how many inferences were dependent on a single sample to examine the influence of each study on the pooled effect size The flow chart presented in Figure 1 describes the selection process and the references retrieved from the database.

Figure 1 Flow chart of study selection for inclusion trials in the systematic review. Out of studies, 62 did not have the desired data. Finally, 42 studies 11 , 12 , 16 , 18 , 19 , 27 , 28 , 42 — 76 were included in the present meta-analysis, and their characteristics are illustrated in Table 1.

The risk of bias assessment is summarized in Table 2. All of these studies were RCTs published between and Study design characteristics are presented in Table 1.

The two studies were conducted in the USA 42 , 67 , three in Sweden 43 , 45 , 49 , three in the Netherlands 44 , 52 , 65 , four in Canada 12 , 14 , 46 , 68 , two in Norway 27 , 47 , four in the UK 28 , 48 , 51 , 56 , two in France 50 , 53 , two in Turkey 11 , 72 , one in Japan 55 , one in Ireland 57 , one in Korean 58 , one in Finland 59 , one in Denmark 61 , one in China 62 , three in Germany 62 , 69 , 70 , one in Italy 64 , one in Spain 16 , one in Poland 75 , and the others in Iran 18 , 19 , 60 , 66 , 71 , 73 , 74 , Thirteen studies included only men and seven women, and 22 included both sexes.

The duration of the intervention varied from 4 to weeks. The CLA supplements were used in doses of 1. The mean age and baseline BMI ranged from 20 to Iwata et al.

used two different CLA doses in their studies. Out of the 42 studies, CRP, IL-6, TNF-α, adiponectin, and leptin were reported in 20, 15, 16, 12, and 20, respectively.

For supplementation, 47 study arms used mixed isomers 9cis,11trans-CLA and 10trans,12cis-CLA , four study arms used 9cis,11trans-CLA isomer, and five study arms used 10trans,12cis-CLA isomer. In these studies, detection methods of CRP were Behring latex-enhanced high-sensitivity assays, Eckman Synchron CX7 System, enzyme-linked immunosorbent assay, enhanced turbidimetric immunoassay, highly sensitive immunoassay with a monoclonal antibody coated with polystyrene particles, immunoturbidimetric assay, and rabbit antihuman.

Diamonds represent pooled estimates from random-effects analysis. WMD, weighted mean difference; CI, confidence interval; CLA, conjugated linoleic acid; CRP, C-reactive protein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-alpha.

Overall, 24 effect sizes from 20 studies for CRP were included in the analysis. In the other subgroups, the effect of CLA supplementation on serum concentrations of CRP was not significant Table 3.

Table 3 Subgroup analyses of CLA supplementation on inflammatory cytokines and adipokines. In the other subgroups, the effect of CLA supplementation on serum concentrations of IL-6 was not significant Table 3.

In the other subgroups, the effect of CLA supplementation on serum concentrations of TNF-α was not significant Table 3. The present study conducted a nonlinear dose—response regression to analyze the dose—response relationship between CLA supplementation and inflammatory cytokines and adipokines.

Meta-regression analyses were performed to assess whether inflammatory cytokines and adipokines were affected by CLA supplementation doses and intervention duration. WMD, weighted mean difference; CI, confidence interval; CRP, C-reactive protein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-alpha.

The sensitivity analysis demonstrated that no study had a significant impact on the overall findings. Although the overall result of studies reporting data on TNF-α was sensitive to the study by Song et al. In the case of CRP, some studies had an impact on the overall effect size, including that of Whigham et al.

It was shown that the exclusion of every individual study by the sensitivity analysis could not change the direction of the correlation but eliminated the significant effect of CLA on CRP. Table 4 displays the Grading of Recommendations Assessment, Development, and Evaluation GRADE profile of CLA supplementation on inflammatory cytokine and adipokine variables together with the certainty in outcomes.

For CRP, because of serious limitations in inconsistency, the quality of evidence was moderate. In the case of IL-6, because of very serious limitations in inconsistency and for TNF-α because of very serious limitations in inconsistency ad serious limitations for publication bias, the quality of evidence was low.

For both outcomes, including leptin and adiponectin, because of very serious limitations in inconsistency and serious limitations in imprecision, the quality of evidence was very low. Table 4 GRADE profile of CLA supplementation for inflammatory cytokines and adipokines.

Using the GRADE methodology, which was previously outlined, the total degree of evidence certainty across the studies was evaluated and summarized In this review, an analysis of pooling 42 studies indicated that CLA supplementation increased CRP concentrations, decreased IL-6 and TNF-α values, and had no effect on adiponectin and leptin levels.

Taking CLA decreased IL-6 in male individuals and unhealthy subjects if the trial duration was less than 12 weeks and when a mixture of two isomers was used. However, in subgroup analyses based on isomer type, 10trans12cis- CLA isomer significantly increased TNF-α.

Supplementation with CLA reduced adiponectin in women. It also decreased leptin in women and unhealthy adults but increased in those with normal baseline BMI. Moreover, the results of the meta-regression analysis showed that there was no significant linear association between intervention doses and duration of supplementation with inflammatory cytokines and adipokines.

The majority of studies included in this meta-analysis used supplements consisting of mixed amounts of CLA isomers. Therefore, since CLA isomers have shown different effects on inflammation 30 , 78 , it is suggested that this issue be considered in research.

It is also important to consider the contents of the placebo used in studies. Some included RCTs have used vegetable oils as a placebo, such as safflower and olive oils. One study has indicated the reduced effect of safflower oil on CRP levels compared to CLA Another study has elucidated the anti-inflammatory effect of olive oils through the prevention of lipooxygenase and enzymes that synthesize leukotriene In other words, prescribing these vegetable oils as a placebo might misinterpret results.

Diet and physical activity can play an important role in inflammatory conditions It is better to consider the effects of these two factors in the result of the present meta-analysis. Although, in some studies, the confounding variables of physical activity and diet were controlled, in some trials, these factors were not considered.

Diet is an important regulatory factor in the immune response. Malnutrition leads to suppression of the immune system, whereas overnutrition leads to immune activation. Some foods have anti-inflammatory effects, and there are still controversies about others Also, a high-fat diet causes excessive body fat accumulation and impairs the immune system.

On the other hand, it has been reported that trans and saturated fatty acids are significantly associated with the inflammatory state Although ruminant trans fatty acids have different effects than industrial trans fatty acids, several studies show that industrial trans fatty acids promote inflammation, whereas ruminant trans fatty acids have been reported to be harmless or even beneficial to health, as well as also having anti-inflammatory properties One study reported that sedentary subjects had higher levels of inflammatory factors such as IL-6 and TNF-α compared to subjects with higher physical activity Other confounding factors that can affect inflammatory markers are sleep duration and sleep quality.

In addition, a study on healthy subjects reported that higher IL-6 levels were associated with lower sleep quality Here, we showed CLA consumption increased CRP concentrations, decreased IL-6 and TNF-α, and did not change adiponectin and leptin levels.

There are some meta-analyses that have investigated the effect of CLA on the abovementioned markers. For example, Derakhshandeh-Rishehri et al. A meta-analysis conducted by Haghighatdoost et al. Another meta-analysis conducted on 19 RCTs demonstrated that CLA intake had a small but not significant decline in plasma leptin.

However, it significantly decreased leptin in obese individuals, with trials lasting for less than 24 weeks A study carried out by Mazidi et al.

By combining previous and current results, it can be acknowledged that except for the effect of CLA in increasing CRP levels, there is no consensus on other markers i. Moreover, it is noteworthy to state that exercise, dietary intake, sleep duration, and sleep quality can alter the effects of CLA.

Therefore, further well-designed studies may clarify the role of CLA on the abovementioned markers. In the present study, the gender-dependent impact of CLA has also been shown in the reduction of IL-6, TNF-α, adiponectin, and leptin. Based on evidence, CLA can induce testosterone biosynthesis 91 , and subsequently, testosterone is able to decrease IL-6 expression It has also been stated that circulating CLA concentrations are greater in women than in men Therefore, the aforementioned evidence can justify the different effects seen between men IL-6 and TNF-α reduction and women adiponectin and leptin reduction after taking CLA.

The effect of CLA on inflammatory responses has generated inconsistent results. This may be due to isomers and tissue-specific responses of CLA. Moreover, across the included RCTs, administration doses of CLA varied from 1. Health characteristics, inflammation status, and even gut microbiome composition of the recruited individuals were also different These variations in the studies can influence the results and interpretations.

For example, in relation to isomer and tissue-specific response, 9cis,11trans-CLA isomer exerts its anti-inflammatory effect by activating the peroxisome proliferator-activated receptor-γ PPAR-γ -dependent pathway and ultimately reducing the production of proinflammatory cytokines such as TNF-α and IL-6 However, the 10trans,12cis-CLA isomer has been reported to have a proinflammatory effect in adipose tissue, in contrast to its effects on innate immunity and vascular cells.

In addition, in adipose tissue, activation of PPAR­γ is contrary to the physiological effects of 10trans,12cis-CLA in vitro and in vivo This isomer downregulates PPAR-γ gene expression and increases TNF-α, IL-6, and CRP production in adipose tissue 78 , It seems that the reason for this inconsistency is cytokines secreted from adipocytes, which in turn alter PPAR­γ expression and activity in the fat cell.

Therefore, inconclusive results regarding the anti-inflammatory properties of CLA are likely due to the subtle proinflammatory effects of the 10trans,12cis-CLA isomers in specific tissues 30 , Overall, it appears that CLA can elicit both anti-inflammatory and proinflammatory features.

Some proposed mechanisms for the effects of CLA isomers on inflammation include the following: 1 Modulation of eicosanoid signaling.

This means that CLA reduces the production of inflammatory eicosanoids derived from arachidonic acid AA through the inhibition of several steps in the AA cascade. Also, it suppresses the expression of the inducible NO synthase iNOS gene, which leads to a decrease in IL-6 production.

This meta-analysis has some limitations that should be addressed. Most of the included studies had a relatively small sample size, which can cause an overestimation of the results.

Observation of publication bias for TNF-α findings suggests overestimation of CLA efficiency on TNF-α. Moreover, TNF-α, IL-6, and CRP results were sensitive to some studies. In conclusion, it is suggested that CLA supplementation can have both proinflammatory and anti-inflammatory roles.

It can enhance CRP concentrations while reducing TNF-α and IL-6 levels. Furthermore, CLA is able to decrease adiponectin and leptin in women.

It can also decrease leptin in unhealthy adults and increase it in subjects with a normal baseline BMI. Finally, in order to improve the quality of studies, future clinical trials are encouraged to carefully consider CLA-isomer-specific regulation of inflammatory markers and take notice of the contents of the placebo used in their control groups.

It is also important to keep in mind the gender-dependent impact of CLA. Further inquiries can be directed to the corresponding authors.

OA and SR contributed to the conception and design of the study. DA-L, MZ, and GS contributed to data extraction. FS and AK screened articles for inclusion criteria. OA contributed to the data analysis. SR, MY, and EG contributed to manuscript drafting, OA and MZ supervised the study.

All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Asbaghi O, Ashtary-Larky D, Bagheri R, Moosavian SP, Nazarian B, Afrisham R, et al. Effects of folic acid supplementation on inflammatory markers: A grade-assessed systematic review and dose—response meta-analysis of randomized controlled trials.

Nutrients 13 7 doi: PubMed Abstract CrossRef Full Text Google Scholar. Ghafourian M, Ashtary-Larky D, Chinipardaz R, Eskandary N, Mehavaran M.

Background aand aims: Many studies Inmune investigated the effect functino conjugated linoleic acid Individualized nutrition plans for athletes CLA and immune function on inflammatory cytokines and adipokines. However, the results of these studies are Continuous glucose monitoring consistent. Therefore, this systematic review and functtion CLA and immune function designed to ffunction evaluate the effect CLA and immune function Immube supplementation on inflammatory cytokines and adipokines. Methods: Randomized controlled trials RCTs examining the effects of CLA supplementation on C-reactive protein CRPinterleukin 6 IL-6tumor necrosis factor-alpha TNF-αadiponectin, and leptin, published up to Marchwere identified through PubMed, SCOPUS, and ISI Web of Science databases. Results: Findings from 42 studies with 58 arms indicated that CLA supplementation significantly decreased IL-6 and TNF-α levels and also slightly increased CRP levels. However, adiponectin and leptin levels did not change after CLA supplementation. Fhnction details. Functlon review evaluates Calorie counting techniques health benefits Timely food routine the functional food, conjugated linoleic Immuns CLA immuns a heterogeneous group of CLA and immune function ummune geometric isomers CLA and immune function linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, Herbal weight loss tea side effects of reports - principally CLA and immune function on in vitromicrobial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studies highlight that CLA, apart form the classical nuclear transcription factors-mediated mechanism of action, appear to exhibit a number of inter-dependent molecular signalling pathways accounting for their reported health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti-atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic effects. On the other hand, negative effects of CLA have been reported such as fatty liver and spleen, induction of colon carcinogenesis and hyperproinsulinaemia. As far as human consumption is concerned, a definite conclusion for CLA safety has not been reached yet.

Author: Zulkishicage

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