Effect of Low-Fat Diets on Plasma Levels of NF-κB–Regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer

Abstract

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.

Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer

“…There also was a suggestion that higher enterolactone was associated with hindered tumor angiogenesis by lower tumor expression of VEGF. Conversely, we observed no association between enterolignans and reduced activation of inflammatory pathways in the prostate as manifested by NFjB activity, a finding consistent with a study by Heymach et al 21 Therefore, these study findings support that enterolignans, and specifically enterolactone, are likely to exert chemoprotective effects by hindering cell proliferation and possibly reduced tumor angiogenesis.…”

“…As previously described elsewhere, 17,21 immunohistochemistry was used to determine the proliferation index (Ki67; Biocare, Walnut Creek, CA, USA), VEGF (Santa Cruz Biotechnology, Santa Cruz, CA, USA), and activation of NFjB (Abcam, Cambridge, MA, USA) from tissue sections cut from formalin-fixed paraffin-embedded prostatic tumor blocks. Slides were reviewed and scored by two independent pathologists who were blinded to randomization status.…”

“…Slides were reviewed and scored by two independent pathologists who were blinded to randomization status. 17,21 To compare the effects of a diet high in lignans against a diet not supplemented with a source of dietary lignan on urinary levels of enterolignans, we combined both flaxseed groups, that is, flaxseed alone and flaxseed/low-fat diet, into one group (Flaxseed) and combined the two groups that did not receive flaxseed, that is, control and low-fat diet (No Flaxseed). Differences in the baseline characteristics between the two study groups (Flaxseed vs. No Flaxseed) were determined using t-tests.…”

Flax Seeds In Prostate Cancer A Case report- self experienced.

“…flaxseeds and low fat diet in combination might often benefits to some men with cancer prostate. Two vitrostudies also support that enterolactone merabolite of flaxseeds reduce prostate cancer development and proliferation (9,10).…”

Designing a broad-spectrum integrative approach for cancer prevention and treatment

“…Trials of diets enriched in whole grains, low-glycemic diets, and both low-fat diets and Mediterranean diets enriched in olive oil and almonds reduced levels of inflammation as measured by CRP [155–158]. Low fat diets, weight loss and supplements (anthocyanins and fish oil) have been observed in randomized trials to reduce cytokines and signaling molecules [159–162]. Mind-body interventions have emphasized immune targets, with findings of interventional trials including activation of T cells and lymphokine-activated killer cells and increased natural killer cell activity [163,164].…”