Can restriction of carbohydrate and/or omega-6 fatty acids prevent breast cancer development – Dr Annadie Krygsman
Dr Annadie Krygsman
Dept of Physiological Sciences, University of Stellenbosch
Title of the project
Can simple dietary modification by restriction of carbohydrate and/or omega-6 fatty acids prevent breast cancer development in the urban South African context?
The Western diet is well-documented to induce obesity due the high glycemic load, combined with high saturated fat content, and most recently identified aberrant omega-6:omega-3 fatty acid (FA) ratio. Obesity is associated with an increased risk of hormone-related cancers, such as breast cancer, as excess body fat results in excess production of estrogen in the adipose stromal cells. In South Africa, change to an urban diet has led to an increase in diet-induced obesity in the black female population, and hence an increased incidence of breast cancer. The South African urban diet primarily consists of high glycemic load carbohydrates, such as white bread, pap and rice, accompanied by high saturated fat animal proteins such as chicken and high fat meat cuts. These foods are furthermore cooked in oils which are high in omega-6 FA (sunflower oil) which contributes to the high omega-6:omega-3 which has now been implicated in the pathogenesis of cancer, cardiovascular, inflammatory and autoimmune diseases.
The high glycemic load carbohydrate intake of the Western diet is proposed to upregulate the Insulin/IGF-1 pathway which, although important for post-natal growth, in adulthood is thought to be causative to breast-, and other cancers. IGF-1 is known for its mutagenic and proliferative activity, and high levels of IGF-1 are associated with a higher incidence of breast cancer through (amongst others) its action as a paracrine growth factor for cancer cells and hyperactivation of the IGF-Insulin receptor. Recently, a diet low in carbohydrates and high in protein has been shown to slow tumor growth and prevent cancer initiation in mice providing a potential means of preventing cancer development by dietary modification.
The role of dietary FA in breast cancer etiology has been met with controversy, but it was recently reported that women with a higher intake of omega-6 FA had an increased risk for breast cancer. A healthy omega-6:omega-3 ratio, associated with greatly reduced risk of disease, is regarded to be equal or less that 4:1, whereas the ratio in the South African Western Diet is in excess of 30:1. Very few studies have investigated the role of omega-3 as opposed omega-6 FA in the diet, and how dietary modulation of these FA can influence the development of breast cancer.
It is not clear which, or whether, single component/s of the Western diet causes these maladaptive pathophysiological consequences and current dietary guidelines are thus not sufficient to prevent breast cancer. Simple reduction of the intake of carbohydrates and/or omega-6 FA, could be a simple way to prevent breast cancer development and slow tumor growth. Using the obese Wistar rat as model, this would be effected by: 1. Restricting carbohydrate consumption; 2. restricting omega-6 fats in the diet, or 3. enhancing omega-3:omega-6 ratio through changing to high omega-3 fat sources (canola oil and low omega-6 spreads). This is proposed to occur through down regulation of the insulin/IGF-1 pathways, but is not yet documented. Important would be to conserve an isocaloric content of each proposed diet, so as to make it achievable for day-to-day implementation for the average person. The added positive effect, in addition to prevention of breast cancer, would be reduction in body weight, improvement of glucose intolerance/insulin resistance and thus reduction in overall diseases risk.
The project was divided into three phases:
Phase 1 consisted of the development of the metabolic model of the SA-obese rat. This entailed feeding the animals 6 different diets:
- High Fat / Low carbohydrate Sunflower (HF-SUN): containing a high/undesired ratio of omega-6:omega-3 fatty acids, and a reduced carbohydrate content
- Low Fat / High carbohydrate Sunflower (LF-SUN): containing a high/undesired ratio of omega-6:omega-3 fatty acids, and a high carbohydrate content
- High Fat / Low carbohydrate Canola (HF-CAN): containing a low/healthy ratio of omega-6:omega-3 fatty acids, and a reduced carbohydrate content
- Low Fat / High carbohydrate Canola (LF-CAN): containing a low/healthy ratio of omega-6:omega-3 fatty acids, and a high carbohydrate content
- High Fat / Low carbohydrate Sunflower + omega-3 (HF-SUN+n3): containing a reduced ratio of omega-6:omega-3 fatty acids due to omega-3 supplementation, and a reduced carbohydrate content
- Low Fat / High carbohydrate Sunflower + omega-3 (LF-SUN+n3): containing a reduced ratio of omega-6:omega-3 fatty acids due to omega-3 supplementation, and a high carbohydrate content but supplemented
Results from this phase indicated distinct differences in metabolic parameters, according to either oil type or carbohydrate content, as expected. The early results have shown a negative effect of canola oil on glucose tolerance, which is in line with recent studies published on both rodents and humans. This is problematic and will need further investigation.
The data available was presented with success at the Metabolism, Diet and Disease Conference in Georgetown, Washington DC, USA.
Phase 2 consisted of the induction of breast cancer in the model described above. Animals were injected with a homogeneic mammary cancer cell suspension after 12 weeks on each of the diets. Latency and progression of tumor development was followed for 14 days. Distinct differences in tumor latency and development was seen and these differed according to both oil type and carbohydrate intake. We saw a negative effect of both canola oil and fish oil (omega-3) supplementation on tumor progression and size, compared with sunflower oil. This led to further investigations into the oxidative status of the animals, which is directly influenced by the fat/oil type.
Phase 3 – plasma, tumor and tissue analyses are underway. The plasma analyses were completed with success, and yielded good data, again pointing to a negative outcome in canola oil. The tissue analysis is well underway, and fatty acid profile for pre-cancer liver as been completed. The post-cancer fatty acid analyses are planned to commence following the completion of the oxidative status analyses.
At this time the oxidative status analysis of the pre-cancer liver is underway and should be completed within the next 6 weeks. Following this, all data is complete for the first manuscript which will then be submitted soon after. The fatty acid and oxidative status analyses of the tumors and mammary fat pads will commence immediately following the completion of the pre-cancer liver oxidative status analysis.
Conferences, abstracts and poster
- Restriction of dietary omega-6 fatty acid and carbohydrate content differentially modulates metabolic syndrome traits in the South African-representative rat dietary model. Anneke M. Brand, Annadie Krygsman.
- Oral Presentation 6: Sunflower vs Canola oil differentially modulates metabolic traits and mammary tumor development in the South African-representative rat dietary orthotopic breast cancer model.
- PPT: Sunflower vs Canola oil modulation of metabolic traits and tumor development. Krygsman.
- Poster: Restriction of dietary omega-6 fatty acid and carbohydrate content differentially modulates metabolic syndrome traits in the South African-representative rat dietary model. Anneke M. Brand, Annadie Krygsman.