Flaxseed Increases Animal Lifespan and Reduces Ovarian Cancer Severity by Toxically Augmenting One-Carbon Metabolism.

William C Weston,Karen H Hales,Dale B Hales

doi:10.3390/molecules26185674

William C Weston, Karen H Hales + Show 1 more

Open Access

https://doi.org/10.3390/molecules26185674

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Abstract

We used an LC-MS/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as “1-amino d-proline”) induced at least 15-fold elevated plasma cystathionine. Surprisingly, plasma homocysteine (Hcy) was stable in flaxseed-fed hens despite such highly elevated cystathionine. To explain stable Hcy, our data suggest accelerated Hcy remethylation via BHMT and MS-B12. Also supporting accelerated Hcy remethylation, we observed elevated S-adenosylmethionine (SAM), an elevated SAM:SAH ratio, and elevated methylthioadenosine (MTA), in flaxseed-fed hens. These results suggest that flaxseed increases SAM biosynthesis and possibly increases polyamine biosynthesis. The following endpoint phenotypes were observed in hens consuming flaxseed: decreased physiological aging, increased empirical lifespan, 9–14% reduced body mass, and improved liver function. Overall, we suggest that flaxseed can protect women from ovarian tumor metastasis by decreasing omental adiposity. We also propose that flaxseed protects cancer patients from cancer-associated cachexia by enhancing liver function.

Highlights

Our laboratory utilizes the White Leghorn laying hen as a pre-clinical animal model for the study of ovarian cancer
The diets that we used are abbreviated in our study as follows: control diet (CTL), 10% defatted flaxseed meal (DFM), 15% whole flaxseed (WFX), 5% flaxseed oil (FXO), 5% corn oil (CRN), and 5% fish oil (FSH)
This study indicated that flaxseed, via the anti-B6 effect of 1-amino D-proline (1ADP), redirects carbon flux through one-carbon metabolism in a manner that increases lifespan and reduces ovarian cancer severity in laying hens

Summary

Introduction

Our laboratory utilizes the White Leghorn laying hen as a pre-clinical animal model for the study of ovarian cancer. Laying hens spontaneously develop “biologically natural” ovarian tumors starting at around two years of age This is the age when the hen will have ovulated as frequently as a woman who is approaching menopause [1,2,3,4,5]. We are the first lab to elucidate a one-carbon metabolic phenomenon that allows flaxseed to shift cancer into a disease that animals can “survive with” instead of “die from”. This speaks highly about flaxseed’s potential as an anti-cancer food, especially considering ovarian cancer’s reputation as a highly lethal carcinoma [12]

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