Conjugated Linoleic Acid & Safflower Oil: A Medical Approach

Conjugated linoleic acid (CLA) is a well- known weight loss aid. Mainly used for its capability to reduce body fat levels, CLA came into the spotlight once with the emergence of numerous studies conducted on its chemical composition.

The milk and meat products of ruminants are its main sources. It can also be found in the eggs of chicken fed with it and in some mushroom species such as the white button mushrooms^[1]. Recent research found another plant-based source, one that specialists claim to be the richest of all, namely the safflower. Evidence suggests safflower-based CLA might have potent antitumor properties, and could successfully individual trying in the treatment of diabetes patients.

CLA Safflower Oil – The Better Alternative?

Deemed as the richest source of conjugated linoleic acid, the safflower came to the public’s attention rather recently. However, knowing of its multiple benefits, the studies conducted on its chemical structure can only lead to a good outcome. Moreover, given that there are enough vegetarians and vegans interested in dietary supplementation, a plant-based source is more than welcomed.

Safflower: The Emergence of Herbal Oils

Safflower is an annual plant, belonging to the Asteraceae family^[2]. It is native to the Middle Eastern regions but has high growth rates on the European and North American continents as well. It thrives in arid environments with seasonal rain. The plant’s height varies from 1 to 4 feet tall. The inflorescence has a globular shape and can be either yellow, orange or red.

Thanks to its pigmentation, it has been successfully used as a dye for centuries by the people inhabiting the banks of the Nile or those living close to the Ganges. However, with the passing of time, due to relatively weak pigments, it lost this role to the detriment of other plants such as saffron.

The production increased once people started using another of its major by-products, the seeds, to obtain oil. Safflower seed oil has similar functions to the sunflower one in that it can be used as a cooking oil or base for margarine. It is also employed in beauty products.

Experts have studied its composition and deemed it as safe for general use.

Safflower oil might be more beneficial than other herbal oils in that it contains, aside from the monounsaturated fatty acids, a large amount of polyunsaturated fatty ones as well (linoleic acid). The presence in safflower seed oil of omega-9 fatty acids improves the immune system’s function. In one study, thirty-five obese women with type 2 diabetes were given an eight-gram dose of safflower oil for sixteen consecutive weeks. At the end of the project, it was shown that all subjects registered a decrease in C-reactive protein levels, a molecule with role in the inflammation process.

Data confirms its involvement in treatments for cancer patients. More randomized-controlled trials, as well as case-control studies, should be conducted to indicate whether safflower is truly the more reliable CLA source of them all.

Safflower is a good source of iron, phosphorus, and magnesium. Throughout the ages, people have used it in treatments for anemia and muscle spasm. Safflower seed oil can also provide relief from headaches and nausea.

What is Conjugated Linoleic Acid?

Conjugated Linoleic Acid is the general name given to the family of 28 isomers of the linoleic acid. The isomers known to the date are derivatives of the three fatty acids synthesized in the rumen of ruminants such as goats, sheep or cows as follows: the oleic, linoleic and alpha-linoleic acid.

In vivo studies show that, in people, CLA is the by-product of vaccenic acid’s (VA) endogenous synthesizing. VA is the main trans-fatty acid present in human milk, with lipogenesis and roles in heart and liver health as well as immunity. Upon conversion into CLA, it has anticarcinogenic properties in human models.

In 2008, experts from the University of Alberta conducted a study on a group of obese rats fed VA supplements for a 3-week period. The project led to the conclusion that the CLA-converted vaccenic acid decreased both cholesterol and triglyceride levels. Although there is a lack of information concerning the exact effect of CLA in humans, supplementation in animal models shows numerous benefits. The positive health effects in experimental subjects might have contributed to CLA’s recognition as generally safe by the U.S. FDA.

Chemical Structure of CLA

From a chemical point of view, CLA is a mixture of isomers which makes it an unsaturated fat. However, it stands out among others of its kind by being a trans fatty acid and a cis fatty acid at the same time. By bonding in two different ways with the molecules it interacts with, the conjugated linoleic acid has two different manners of action as well as two distinct ways of influencing the body.

The former does not enjoy a good reputation at the present moment. Most studies show side effects and a bad overall influence in tested subjects. Aside from lowering the ‘good’ cholesterol levels, it is also harmful to the heart, something easily understandable if we take into account that the majority of its sources are processed (hydrogenated oils, margarine). The latter, however, is regarded as generally healthy, due to its mostly natural sources (avocado, hazelnuts, macadamia nuts).

Still, there is evidence that might interfere with the supposed health benefits of CLA. In one randomized, double-blind study, 25 obese men were given either CLA or placebo (olive oil) for a 3-month period. At the end of the project, the group that was offered the acid-based substance showed decreased insulin sensitivity, and a negative alteration of the oxidative stress and inflammation markers. The result was attributed to the two main CLA  isomers, c9 and t11, whose behavioral patterns were different, and even opposed to a certain extent. It is unsafe to assume whether the substance affects other bodily processes in the absence of additional studies.

Later research indicates that CLA can also be obtained by means of bacterial action, especially that of those inhabiting the gastrointestinal tract. Moreover, in vitro projects aiming to produce additional quantities by using the propionibacteria, bifidobacteria and lactic acid bacteria strains have been a success.

Safflower-based Conjugated Linoleic acid

There is no clear evidence to show that safflower-based CLA is more effective than the animal-based one. The available pieces of information state the substance is just as beneficial, no matter its source. Whether it is obtained from a herb or the byproducts of ruminants, CLA shows the same anti-obesity and anti-inflammatory properties when given to living models. However, producers say the plant has more potent from thanks to a higher oil concentration. Also, its efficacy might be the result of a faster absorption by the body because of an easier digestion process. Whether this is only a marketing strategy or the truth, we have yet to find out.

CLA Usage in The Medical System

CLA is currently employed in an array of medical treatments for patients with obesity or diabetes. Specialists are also conducting trials as to assess the acid’s role in the carcinogenic cell inhibition process. Older research projects on animal subjects point towards effectiveness in immunomodulation while later ones suggest it might be helpful in people with bone problems.

CLA’s Effect on Obesity

CLA safflower oil enjoys its current popularity thanks to various studies pinpointing its anti-obesity properties. Today’s society glorifies the body’s health but is equally true that it also puts a lot of emphasis on the way people look. No surprise there are so many dietary supplements nowadays, from the weight loss aids to the muscle building ones.

We live in a culture where the way our bodies look and feel are ahead of other factors. CLA might be more useful than other oils in that it links with the PPAR receptors alpha and beta, involved in the fat burning process. Still, it also interacts with the PPAR-gamma receptor, connected to an increase in adipose tissue. In vivo and in vitro studies show conflicting results.

In one randomized study, a group of lower weight, overweight and middle-aged adults were given CLA for a period of 7 to 13 weeks. Results indicated a decrease in body fat level in all the participants in spite of different physical conditions.

Interests in the conjugated linoleic acid as a weight loss aid increased once the specialists discovered its action on cyclic AMP^[3]. The main derivative of adenosine triphosphate, cAMP is involved in lipolysis, a process by means of which the body uses fat instead of carbohydrates as the main energy source.

Another in vivo study conducted on male and female mice showed that CLA supplementation led to a decrease of up to 60% in the body fat mass of all subjects. Although food intake was not significantly reduced, medium and high doses had the highest success rate. Low doses did not show important modifications.

Reports state that only the 10, 12 CLA isomer have, as well as conjugated linoleic acid, anti-obesity effects. Decreased lipogenesis and adipocyte apoptosis have been noticed. In addition, the 9, 11 isomers have alleged anti-inflammatory properties, but might promote weight gain, as shown in a trial performed on rodents.

One research project has reported that in most cases CLA consumption is paired with decreased energy intake and increased energy expenditure in animal subjects. However, this does not seem to always be the case with human models. Evidence indicates no change in the body fat mass or lean mass of subjects given a 3.9-gram CLA supplementation per day for twelve weeks. Another human study demonstrated shifts in the basal metabolic rate but without any particular effect on the adipose tissue.

Conjugated linoleic acid might target the body fat mass reduction by inducing pre-adipocyte apoptosis. It can also sustain the weight loss process by suppressing appetite.

Conflicting conclusions are resurfacing more and more nowadays. Scientists have yet to know for sure why CLA seems to work in some subjects, while others are immune to its action. Public data points towards three factors that could be responsible for the inconclusive results:

CLA in Diabetes Patients

Interest in the omega-type fatty acids has grown over the past few years. Given their presence in CLA’s chemical composition, it was only natural for the acid to gain more attention.

In spite of insufficient data, there is evidence according to which safflower-based omega-9 fatty acids might play an active role in the insulin sensitivity process in diabetes patients. Evidence exhibits the existence of obesity as an onset for the medical condition. Inflammation seems to be another underlying cause.

Studies suggest a strong relationship between inflammation and obesity due to the existence of the inflammatory cytokine in the adipose tissue.

Trials conducted on animal subjects (mice) or humans have shown the impact of inflammatory modulators on insulin action in overweight models. Gene expression in the metabolic pathway resembles the one in the inflammatory one. Discussions on the theme of cytokine impact on insulin resistance have been led, and the conclusions are quite striking. Experts mention that glucose metabolism in obese patients is increased in comparison to that of normal-weight people. This leads to the inhibition of insulin-signaling receptors which in turn causes weaker liver and muscle mass activity.

There are pieces of information according to which safflower-based CLA might decrease insulin sensitivity in diabetes patients.

In one study, scientists from the Clinical Research Center at The Ohio State University Medical Center have discovered a decreased adipose mass in obese, postmenopausal women with type 2 diabetes. During the 16-week trial, thirty-five women were divided into two groups. One was given safflower oil while the other was supplemented with CLA extract. The conclusions at the end of the project were the following:

Safflower oil seemed to have a better effect than animal-based CLA in all subjects after only four weeks of supplementation. Moreover, supplementation for sixteen weeks showed improved markers of glycemic control as well as a fasting effect on adiponectin^[4] (which reduces appetite).

This aspect might lead people into thinking that conjugated linoleic acid extracted from safflower seeds might be more effective than the one obtained from an animal source.

In mouse scientific procedures, the animals saw an improvement in liver function after supplementation with a CLA mixture. The 10,12 isomer of the conjugated linoleic acid reduced triglyceride production, and also had a beneficial effect on adipose lipid metabolism.

However, there is evidence according to which CLA might trigger hepatic steatosis. The 9,11 isomer could be behind this process. In spite of this, a few projects indicate that the isomer promotes insulin sensitivity, and protects the body against oxidative stress via mitochondrial antioxidant enzyme activation.  More studies are to be conducted for a better understanding of the whole process.

Atheroprotective Effects of CLA

Administration of CLA isomers 9,11 and 10,12 has shown inhibitory properties in models with atherosclerosis. The acid’s atheroprotective effects on inflammation might be the reason behind the process.

Atherosclerosis is a complex medical condition characterized by arterial wall damage via lipid plaque accumulation. Currently, the underlying cause and mechanism of action remain uncertain. Most experts study it because of the major complications it produces both in the heart and the brain. It is present in most adults over the age of fifty, with a higher incidence in men. People with diabetes and overweight individuals are more likely to suffer from it than the rest of the population. Heart attack and stroke are usually the endpoints of the condition.

In one experiment, atherosclerotic lesions via cholesterol administration have been produced in a group of rabbits. In most cases, the process was triggered by the deposition of lipids on the vascular wall which in turn led to damage to the connective tissue.

In a randomized study, experts gave a group of overweight children and adults a blend of CLA isomers consisting of 50% 9,11 isomer and 50% 10,12 isomer. It was registered a decrease in LDL levels, an increase in HDL levels, and a lower risk of developing atherosclerosis in adult men. In another 8-week project, 51 healthy male volunteers took a CLA mixture; the specialists have concluded that the conjugated linoleic acid led to a lower concentration of triacylglycerol, known for the role it plays in ischaemic heart disease development.

In animal models, including rodents and rabbits, anti-atherogenic effects have been registered following CLA administration. They include:

There is, however, a controversy surrounding CLA’s side effects, some of which might cause severe damage to the heart. The cardiolipotoxicity process upon CLA administration has been carefully observed in one research project.

A number of twelve mice were put into three different groups and given meals comprising of low-fat chow, sucrose-enriched olive oil, and corn oil. Results showed no change in the body fat mass after short-term fat feeding in any of the subjects. However, the group fed olive oil (which contains linoleic acid) exhibited signs of diastolic dysfunction and impaired left the ventricular function. Cardiac stiffening noticed in the group fed a high-fat diet has been attributed to an excess of n-6 polyunsaturated fatty acids found in CLA.

Positive Effects on High Blood Pressure

Experts state conjugated linoleic acid successfully reduces blood pressure in obese, diabetic rodents. It is uncertain whether it has the same effect in human subjects due to a lack of studies in this regard. However, existing evidence points towards a connection between CLA isomers and adiponectin production. Specialists have noticed a decreased risk of obesity-related hypertension in animal figures fed a CLA mix.

Dosage is a key factor in most studies involving the 9,11 and 10,12 isomers. In the majority of experiments conducted on rodents, the success was due to the ingested amount; the 10,12 isomer was more beneficial in regards to heart health in spite of a lower quantity in CLA’s overall composition.

Recent data shows that, when paired with Ramipril, it enhances its effect on high blood pressure. In one Chinese study, eight obese adults were divided into two groups. The first was given a daily dose of CLA and Ramipril and the second a combination of Ramipril and placebo. At the end of the eight-week period, the results were the following:

The exact mechanism of action in people with high blood pressure remains unknown. Additional studies are a necessity in this regard.

Anti-Carcinogenic Properties of CLA

The first time CLA came to public attention was for its anti-carcinogenic effects. The isomer mixture 10,12 seems to be the factor responsible for this property, although present-day data remains inconclusive. Whereas equally crucial in the process of burning fat and atherosclerosis regression, the presence of conjugated linoleic acid in cancer treatments deserves to be documented.

The mechanism of action in cancer patients remains unclear. It was shown that CLA isomers interact with the anti-inflammatory receptors responsible for triggering the medical condition. However, recent data suggests it might be the fact that they induce tumor apoptosis (programmed cell death). In the 1999 edition of the Journal of Nutrition was presented one study revealing potent anti-cancer properties. The project showed how female mice figures fed a CLA blend in their youth period had lower chances to develop breast cancer.

A similar study, this time conducted on mouse mammary tumor cells indicated that treatment with conjugated linoleic acid-induced cancer cell apoptosis. In addition, high concentrations led to an inhibition of G1-S progression of mammary tumor cells. However, experts acknowledged the existence of side effects as well. It seems that the 10,12 isomer sustains the tumorigenesis and metastasis of female mice suffering from breast cancer. It is believed that this applies only to those models that exhibited an excess in the epidermal growth factor receptor erbB2.

In another clinical trial, human gastric adenocarcinoma cells were incubated for 24 hours with different CLA concentrations. The results indicated a decreased cell attachment on fibronectin and laminin, two protein types with role in cell adhesion and migration. This might mean lowered risks of metastatic tumor occurrence.

Other Benefits of CLA Safflower Oil

The health benefits of safflower oil and its seed-based extract, the conjugated linoleic acid, are numerous. Aside from the already mentioned ones, it is also effective in hair and skin care, menstrual disorders, injuries or breathing problems. CLA is possibly helpful in treatments for children. One study showed potential benefits in adolescents with allergic asthma. Another one suggested the compound provided relief in children with HPV-induced laryngeal papillomatosis.

Due to its oily structure, it might help people with chronic constipation.

CLA supplementation has supposed benefits in patients with inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis. It does so by activating the PPAR-gamma receptor that has therapeutic value in this kind of medical conditions. Studies on rodents are usually more successful but not necessary the more reliable. In vivo studies conducted on animal and human gastric cells showed conflicting results. Moreover, the dosage used in animals was higher when it came to the CLA/ weight ratio.

Studies on CLA’s ability to reduce appetite have shown mixed results. One research project indicated that supplementation with 3.6 grams daily affected the process by interacting with oleoylethanolamide, a well-known appetite suppressant. The oil might make people feel full for longer. A few other trials had negative results.

Side Effects of CLA Safflower Oil

There is no concluding data showing side effects of CLA. Studies suggest general safety upon oral administration. Experts state supplementation is well-received by the majority of individuals, regardless of weight and age. There is, however, evidence that indicates possible side effects in people with diabetes and atherosclerosis following an excess in dosage. Also, the 9,11 isomer, as well as the 10,12 one, might play an active role in cancer pathogenesis in spite of alleged benefits.

Safflower oil might slow blood clotting, and could interfere with blood-clotting medication.

Specialists advise pregnant women to avoid CLA and any other safflower compound. The plant can increase general blood flow and induce contractions to the uterus, which could cause miscarriage. Supplementation while breastfeeding should be avoided.

Higher doses might lead to accumulation of liver fat. There is information according to which CLA present in supplements might have a different structure than that found in foods. The majority of side effects take place within the first week of administration. As in the case of most supplements, they tend to lose from intensity once the body accommodates to the daily dose.

How to Take Safflower Oil?

CLA safflower oil should be taken as any other herbal oil, that is by mouth. Whether one chooses it as an alternative to the more popular olive and corn oil or tries supplementation, conjugated linoleic acid has roughly the same effect. There is no recommended portion for all people. Rather, every individual trying it should match the dosage to his or her actual weight, age, and medical condition.

In the case of supplementation, the dosing ranges between 2 and 5 grams per day. For general health, 1 gram daily seems to be the optimal dose. However, in case one suffers from certain medical conditions or knows little about the required dosage, it is for the best to consult with a doctor beforehand.

Summing-up

CLA safflower oil is a dietary supplement used for an array of medical conditions ranging from obesity to diabetes and even cancer. People’s interest has grown with the passing of time and seems to have reached a peak in the recent years. Studies conducted on its chemical composition show a multitude of health-related benefits. Evidence suggests potent anti-inflammatory, anti-obesity and anti-carcinogenic effects in animal and human subjects alike. Some have more conclusive results than others.

It seems that success rate is ensured by the CLA dosage used in each study. Moreover, it appears that the oil works better in clinical trials involving animal figures. The outcomes of numerous studies are sometimes controversial in that not all results are similar in spite of the same substance and dosage being used. However, new pieces of information are promising. Safflower oil, as well as the conjugated linoleic acid, have good chances of becoming of higher importance in the near future.