We previously reported that safflower oil supplementation for 16 weeks decreased fat mass in the trunk region, and CLA decreased total body fat mass and body weight10
. As a result of these findings, in the present study we hypothesized that safflower oil would improve measures of glycemic control, blood lipids and inflammatory markers, and CLA would have no effect on these parameters. Additionally, we hypothesized that any metabolic effects of safflower oil and CLA would become evident after there was an increase in serum linoleic acid and CLA, respectively.
Although CLA caused a reduction in both body weight and fat mass10
, CLA did not improve markers of glycemic control, insulin sensitivity, inflammation or blood lipids. This may be due to an inadequate loss of body weight or body fat in the 16 week treatment period. CLA induced a 1.1 kg, or 1.1% body weight loss and a 1.3 kg, or 3.2% fat mass reduction2
, which is smaller than the 5% body weight loss recommended for improved glycemic control4
. In another study which resulted in no detectable changes in body composition, supplementation with 3.0 grams of mixed-isomer CLA for 8 weeks worsened markers of insulin sensitivity in people with type 2 diabetes17
. This difference of results with our study may be due to the length of supplementation. The pre-determined steps statistical model utilized in our study first tests whether a difference exists between weeks 0 and 16 of supplementation. If there is no difference, earlier weeks are not analyzed. However, it is possible that fasting glucose and QUICKI were worsened with CLA supplementation at earlier time points (weeks 4, 8, and 12) and normalized by 16 weeks.
Contrary to CLA, SAF supplementation improved numerous metabolic endpoints including HbA1c, fasting glucose, insulin sensitivity estimated by QUICKI, HDL cholesterol, CRP, and adiponectin. The dramatic physiological effect of SAF was unexpected because the intake of linoleic acid typically consumed in the American diet is adequate when compared to dietary recommendations. Women in our study reported an average linoleic acid intake of 6.8% (or ~12.6 g/d) of total energy. Adding linoleic acid consumed from the supplements, average intake increased to 9.8% of energy. The Dietary Reference Intake Report has set the acceptable macronutrient distribution range at 5–10% of energy from n-6 PUFA11
. Accordingly, subjects in our study were not consuming a sub-optimal amount of linoleic acid before supplementation, nor did supplementation increase linoleic acid consumption beyond what is recommended for a healthy diet. The SAF treatment, consisting primarily of linoleic acid (18:2n6), was a minor amount of added oil (8 g or ~1 2/3 tsp), making this addition to the diet achievable on a daily basis. These results provide evidence that a small change in dietary behavior to alter the fatty acid content of the diet may improve metabolic parameters in people already consuming what is currently considered to be an adequate amount of dietary linoleic acid.
The health effects of n-6 PUFA intakes in the range of 5–10% of energy include decreased risk for heart disease through the improvement of multiple risk factors such as blood lipid profile and inflammatory status11
. However, it is difficult to determine from intervention studies whether increased PUFA alone is responsible for these effects, because increasing dietary PUFA is typically accomplished by decreasing intake of another macronutrient such as saturated fat or carbohydrate11
. In the present study, subjects consumed 8 g of oil containing 72 kcal per day. Although subjects were aware of the energy content of the supplements, they were not given specific guidelines for reducing energy intake to avoid weight gain. Consequently, there were no significant differences in the macronutrient content of the diet throughout the study10
, and the supplement likely changed macronutrient distribution primarily by increasing total polyunsaturated fat intake. The evidence from our study supports an independent effect of increasing intake of a linoleic acid-rich oil on the endpoints measured in this study.
In the pre-determined steps statistical analysis, it was determined that significant effects of SAF treatment became evident after either 12 or 16 weeks of supplementation. The minimum time at which an increase in serum linoleic acid could be detected was after four weeks of supplementation. It can be inferred then, that the biological activity of linoleic acid may depend on a certain level of its accumulation in the body. However, from this study we cannot determine mechanistically how linoleic acid or other components of safflower oil are acting to induce biological effects. In addition, we cannot determine if safflower oil as a whole or linoleic acid specifically is inducing the effects seen in this study. In particular, tocopherals are naturally present in safflower oil. Although both the CLA and SAF treatments contained tocopherals, the distribution of isomers and the total tocopherol content was different. Future studies with safflower oil should measure serum tocopherol accumulation.
Previously, we reported that SAF supplementation reduced trunk fat by 6.3%10, which may explain some of the beneficial metabolic effects detected in the current analyses. Metabolic syndrome5
, insulin resistance18
, and elevations in CRP19 are positively correlated with visceral adipose tissue, and some of these factors appear to have even stronger associations in women than men5
. Although not a marker for visceral fat mass, adiponectin, an insulin sensitizing adipocytokine that was increased with SAF supplementation, has a weak negative association with visceral adipose mass20
. We analyzed body composition with DEXA, which is unable to differentiate between the loss of subcutaneous and visceral fat in the trunk region. However, it is likely that some of the trunk fat lost can be attributed to decreased visceral fat because of the association between visceral fat and several metabolic markers that were improved with SAF. In support of this, abdominal subcutaneous fat has not been found to have consistent deleterious effects as has visceral fat21
Subjects in this study were post-menopausal, obese women with type 2 diabetes who had low HDL cholesterol and elevated CRP and HbA1c. This metabolic profile is associated with an increased risk of cardiovascular disease22
. HDL cholesterol was less than the 1.3 mmol/L value recommended by the American Heart Association as the minimum desirable level. SAF treatment for 16 weeks increased HDL by an average of 0.12 mmol/L, bringing HDL levels to 0.82 mmol/L in Supplementation Period 1 and 1.0 mmol/L in Supplementation Period 2. Although this increase did not raise HDL to 1.3 mmol/L, it has been estimated that a 0.026 mmol/L increase in HDL is associated with a 1.9%–2.9% decrease in cardiovascular disease risk23
, making the increase seen in our study clinically meaningful. CRP is an independent risk factor for cardiovascular disease24
and in this study the average baseline CRP levels fell into the “high risk” category (> 3 mg/L) as defined by the American Heart Association. Therefore the average decrease of CRP by 17.5% observed after 16 weeks of SAF supplementation is also a clinically relevant change. The average decrease in HbA1c was 0.64% after 16 weeks of SAF supplementation. Additionally, fasting glucose and QUICKI were improved. In a meta-analysis, intensive treatment of type 2 diabetes over 5 years resulted in a 0.9% decrease in HbA1c. This corresponded to a 17% decrease in non-fatal myocardial infarction and a 15% decrease in events of coronary heart disease5
. From the present study we are unable to determine long-term effects of SAF supplementation, but it is possible that risk of cardiovascular outcomes may be decreased in this high-risk group if the changes seen in our study are maintained.
In conclusion, daily supplementation with 6.4 g of mixed-isomer CLA for 16 weeks did not improve markers of glycemic control, inflammation, or blood lipids in obese, post-menopausal women with type 2 diabetes. On the contrary, daily supplementation of 8 grams of safflower oil for 16 weeks improved fasting glucose, HbA1c, QUICKI, CRP, HDL cholesterol, and adiponectin,. Inclusion of a small amount of readily available and inexpensive safflower oil into the diet may have meaningful effects on clinically important risk factors in the management of diabetes and prevention of diabetes-related complications.