Effect of Oral Docosahexaenoic Acid (DHA) Supplementation on DHA Levels and Omega-3 Index in Red Blood Cell Membranes of Breast Cancer Patients.

Alessio Molfino

doi:10.3389/fphys.2017.00549

Abstract

Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition.Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P-value < 0.05 was considered statistically significant.Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group), 12 patients with familiar positive history for BC (F group), 10 patients with sporadic BC (S group), and 10 healthy controls (C group). DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls (P < 0.001). No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (β = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as “good seafood consumers” showed at baseline DHA and omega-3 index higher with respect to “low seafood consumers” (P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in “low seafood consumers” with respect to “good seafood consumers” (P < 0.0001).Conclusion: DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy controls, seem to be associated with greater ability of DHA incorporation. Larger samples of BC patients are necessary to confirm our observation.

Highlights

Breast cancer (BC) is the most common cancer in women, with an incidence greater than 1 million of new cases per year worldwide (Bougnoux et al, 2009, 2010)
The sample size was determined based on a previous study conducted in BC patients observing changes of docosahexaenoic acid (DHA) levels before and after DHA oral supplementation (Bougnoux et al, 2009)
We observed a significant increase in DHA levels and omega-3 index in “good seafood consumers” (P < 0.001) (Table 4), as well as in “low seafood consumers” (P = 0.002 and P = 0.006, respectively) (Table 4)

Summary

Introduction

Breast cancer (BC) is the most common cancer in women, with an incidence greater than 1 million of new cases per year worldwide (Bougnoux et al, 2009, 2010). Diets with a high content in omega-6 polyunsaturated fatty acids (PUFAs), and relatively low omega-3 PUFAs (Molfino et al, 2014), are associated with increased risk to develop BC and its relapse (Chlebowski et al, 2006; de Lorgeril and Salen, 2012; Laviano et al, 2013). The lipid environment of cancer cells (i.e., the lipid component of cell membranes) may influence tumor sensitivity to chemotherapeutic agents. The membrane lipids of cancer cells are similar to those of storage lipids in terms of fatty acids composition, suggesting that DHA levels may potentially influence the activity of anti-tumor agents (Bougnoux et al, 1999, 2010). The possibility of recognizing “low-incorporator” patients would identify patients who might significantly increase the intake of DHA to increase the sensitivity of the tumor to cancer therapies. It could be hypothesized that “low-incorporators” may have an increased susceptibility to develop BC or a tumor recurrence

Methods

Results

Conclusion