Optimizing foods for special dietary use in Canada: key outcomes and recommendations from a tripartite workshop.

Many health conditions result in unique nutritional requirements (e.g., protein restriction, low energy, fortification) and the need to consume foods in nontraditional formats (e.g., liquid diets, supplements, tube feeding). In Canada, 45% of hospital patients are malnourished upon admission, resulting in prolonged hospital stays, increased health care costs, and higher mortality rates. Fortunately, advances in nutrition and food science enabled the development of products that provide nutritional support for individuals in hospital and at home. In Canada, these products are defined as Foods for Special Dietary Use (FSDUs). Canada's regulation of FSDUs (Division 24 of the Food and Drug Regulations) is particularly stringent and outdated, which results in products that do not meet current nutritional recommendations or allow application of current technologies, and lack harmonization with other countries. Many of these issues also apply to the Infant Food regulations in Canada. To provide vulnerable populations with optimal nutrition, experts have suggested modernization of Canadian FSDU regulations. A multi-stakeholder workshop established several recommendations and goals toward that end while ensuring the safety of consumers. These include (i) assessing other jurisdictions' regulations; (ii) tracking products currently on the market; (iii) temporary marketing authorizations to permit products on the market and collect data; (iv) use of incorporation by reference for compositional requirements; (v) support for research of FSDU and nutritional needs of special population; and (vi) better understanding accessibility to these products. Overall, the proposed vision is for a modern, safe, flexible, innovative, and health-driven regulatory framework for FSDU in Canada.

Research and regulatory gaps for the substantiation of protein content claims on foods.

Protein claims provide guidance to consumers seeking protein-rich foods. Protein claim regulations differ globally, and both Canada and the United States require protein quality assessments. A tripartite workshop identified the need to (i) harmonize, (ii) update existing amino acid composition and digestibility databases, (iii) develop non-animal bioassays, and (iv) evaluate the impact of protein claims on human health. The Protein-Digestibility Corrected Amino Acid Score method is recommended for current regulatory use in Canada.

Key attributes of global partnerships in food and nutrition to align research agendas and improve public health.

Partnerships among academia, government, and industry have emerged in response to global challenges in food and nutrition. At a workshop reviewing international partnerships, we concluded that to build a partnership, partners must establish a common goal, identify barriers, and engage all stakeholders to ensure project sustainability. To be effective, partnerships must synchronize methodologies and adopt evidence-based processes, and be led by governmental or nonprofit organizations to ensure trust among partners and with the public.

α-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways.

BACKGROUND: Diets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA). METHODS: The ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 µM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50-100 µM), alone and combined with TRAS (10 µg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined. RESULTS: ALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation. CONCLUSIONS: Together these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA-rich diets on HER2 signaling pathways.

α-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments.

Flaxseed, rich in α-linolenic acid (ALA), is a complementary breast cancer (BC) therapy; however ALA effectiveness and mechanism are unclear. Variation in cellular expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and estrogen (E2) levels may alter ALA effectiveness. This research determined the effect of ALA on growth, apoptosis, and phospholipid fatty acids of 4 BC cell lines with varying receptor expression ± E2. MCF-7 (ER+/PR+/HER2-), BT-474 (ER+/PR+/HER2+), MDA-MB-231 (ER-/PR-/HER2-) and MDA-MB-468 (ER-/PR-/HER2-) cells were incubated with ALA (50-200 µM) ± 1 nM E2 for 48-72 h. ALA dose-dependently reduced growth, measured by trypan blue exclusion, of all cells (55-80% with 75 µM), and this effect was not altered by E2. ALA (75 µM)+E2 induced apoptosis, measured by flow cytometry (up to 111.2%). Decreased growth and increased apoptosis is related to increased cell phospholipid % ALA (up to 25.1%), measured by gas chromatography. ALA is shown for the first time to reduce cell growth and induce apoptosis regardless of receptor expression and E2 environment, by incorporating into BC phospholipids, supporting the use of ALA and ALA-rich foods as a safe, inexpensive complementary therapy for a wide range of BC.

Growth and gene expression differ over time in alpha-linolenic acid treated breast cancer cells.

SCOPE: Heterogeneity of breast cancer (BC) subtypes makes BC treatment difficult. α-linolenic acid (ALA), rich in flaxseed oil, has been shown to reduce growth and increase apoptosis in several BC cell lines, but the mechanism of action needs further understanding. METHODS AND RESULTS: Four BC cell lines (MCF-7, BT-474, MDA-MB-231 and MDA-MB-468) were incubated with 75 µM ALA+1 nM 17-ß estradiol (E2) or 1 nM E2 only (control) for 24 h. MDA-MB-231 cells were additionally incubated at 6 and 12 h. Viable cell number was measured, and expression of genes related to BC (signaling pathways, cell cycle, apoptosis) was quantified by real-time PCR array. There was a reduction in growth of all ALA treated cell lines after 24 h, and in MDA-MB-231 cells this was time-dependent. Many genes were altered after 24 h, and these differed between cell lines. In MDA-MB-231 cells, several gene expression changes were time-dependent. CONCLUSIONS: ALA reduces growth of BC cell lines, by modifying signaling pathways, which differ between BC molecular subtypes. The ALA effect on gene expression is dynamic and changes over time, indicating the significance of incubation period in detecting gene changes.

17ß-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17ß-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.