Flax seed can be a divisive topic. Some vegans will argue that flax seed oil is a good precursor source for EPA, an important omega-3 fatty acid (it isn't). Some say that the negative PCa-ALA (alpha linolenic acid) studies somehow don't apply when the ALA is from flax seed oil. My view is that the prudent position is to avoid anything that has been associated with aggressive PCa, even if studies have been mixed.
True flax seed believers are devoted to the morning ritual of grinding whole flax seed. When I hear of someone grinding two or three days supply at a time, can apostasy be far behind? ALA is unstable & the seeds should be ground, without heat, shortly before use. The amount of oil consumed is probably far less than by those who use Barlean's flax oil, and the benefit of the lignans may offset any harm, but why take the risk?
Flax seed hull products contain no fat & plenty of lignans, particularly secoisolariciresinol diglucoside [SDG].
The lignans are a class of plant polyphenols, some of which can be metabolized by gut microbes to produce mammalian lignans - enterodiol & enterolactone being of greatest interest.
100g flax seed can provide "300,000 µg (0.3 g)" lignans, including 165,000 µg (0.165 g) SDG. [1]
[2] (2005 - The Netherlands)
"Our study is the first pharmacokinetic study on enterodiol and enterolactone in humans consuming a single dose of purified SDG. A substantial part (at least 40%) of the metabolites of SDG, enterodiol and enterolactone, becomes available in the blood circulation and is subsequently excreted. Enterodiol and enterolactone are absorbed 8–10 h after consumption of SDG and eliminated slowly."
[3] (2013 - U.S.)
"We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of ... VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for ∼30 days."
"Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue .., and a near-significant inverse association was observed for enterodiol ... An inverse association was observed between enterolactone and VEGF .., although this did not reach statistical significance."
Note: "The Ki-67 protein ... is a cellular marker for proliferation. It is strictly associated with cell proliferation." (Wiki)
Note: "Vascular endothelial growth factor (VEGF) ... is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions." (Wiki)
This study used data from an earlier study that had four arms: (i) flax, (ii) low-fat (20%), (iii) flax+low-fat & (iv) controls. The low-fat variable is a distraction. Wendy D-M combined (i) with (iii) & (ii) with (iv) for comparison. I suppose that's reasonable, since the earlier study had shown no benefit in a 20% fat diet.
The study is one of those one-month pre-prostatectomy studies that raise interesting ideas but can't predict long-term effects.
From the original study paper: "Men ... were provided with ample ground flaxseed to last until their date of surgery. To reduce the variability in nutrient composition that could occur between crops, the flaxseed used for this study was obtained from ENRECO in one lot (150 kg) and was analyzed for nutrient content at two time points during the study period. Given its propensity for rancidity, the flaxseed was stored in whole-grain form under cold storage (4°C) and ground and packaged in daily dose (30 g) sealed opaque packets as needed"
"Men receiving flaxseed also were instructed to drink at least 64 ounces/d of fluids to reduce potential risk of colonic impaction or dehydration resulting from the increased fiber load and to keep their flaxseed packets under refrigeration (to retard spoilage)."
It's not clear how many packets were distributed at one time, but ALA is seriously unstable once exposed to oxygen in the air.
I don't know how 30 g of ground flax seed compares to 5 g of flax seed hulls (my dose), but the latter delivers 150-300 mg SDG. Study [2] used "a single dose of purified SDG (1.31 μmol/kg body wt)".
...
Much depends on gut bacteria (it can take 6 months to recover production after use of an antibacterial drug.) The most useful studies tested plasma levels of enterodiol & enterolactone. Epidemiological studies can be difficult to interpret, since some populations have very low levels of lignans in the diet. Exceptions are some parts of Finland & other areas with a high consumption of whole-grain rye bread. Rye bran is extraordinarily rich in lignans. (As a home bread baker I was not able to find a source of rye bran in the U.S. when I tried about 7 years ago. Making an edible loaf with 100% rye flour is beyond my skills, but I would like to experiment with the bran.)
[4] Plasma enterolactone & PCa.
[4a] (2009 - Europe - EPIC (European Prospective Investigation into Cancer and Nutrition)) Using data from "Denmark, Germany, Greece, Italy, the Netherlands, Spain, Sweden and the United Kingdom".
"No statistically significant associations were observed for circulating concentrations of ... enterolactone or enterodiol in relation to overall risk for prostate cancer."
Median enterolactone in cases was 3.8 ng/mL (=12.7 nmol/L if my conversion is correct - seems high) - about the same as the controls.
[4b] (2007 - Scotland)
"A total of 433 cases and 483 controls aged 50-74 years were asked to complete a validated FFQ and provide a non-fasting blood sample. ... analysis found significant inverse associations with increased serum concentrations of enterolactone (adjusted OR 0.40 ...)"
[4c] (2004 - Sweden)
"There was no significant association between quartiles of plasma enterolactone and risk of prostate cancer. Odds ratios for prostate cancer, ... for increasing concentrations of enterolactone in quartiles were 1.00 (referent), 0.81 .., 1.03 ..., and 1.22 {!!!} ..."
"Men with very low enterolactone levels, however, had significantly higher risk of prostate cancer, odds ratio for bottom decile versus all other deciles was 1.68" Implying that the benefit occurs at lowish levels, but not beyond.
[4d] (200= - Finland - ATBC (α-Tocopherol, β-Carotene Cancer Prevention Study))
"Enterolactone concentrations were measured ... in serum collected at baseline ... from 214 men with prostate cancer diagnosed during a 6-year follow-up and from 214 controls matched by age, date of baseline blood collection, intervention group, and local study area. Mean serum enterolactone concentration (in nmol/liter) did not differ significantly between case and control subjects"
The ATBC study involved only smokers & ex-smokers.
It's possible that average Enterolactone levels are much higher in Finns than in many populations, due to whole grain rye bread consumption. If so, it would be an unsuitable population for such a study. Mean serum enterolactone in cases was 15.9 nmol/liter, versus 16.9 nmol/liter in controls.
This ties in with the 2nd finding in [4c].
[4e] (2002 - Finland, Sweden & Norway)
Median (of the two inner quartiles - i.e. the 25-75th percentile range) serum enterolactone (nmol/liter) in cases was versus controls"
- Finland: 15.6 v. 15.5
- Sweden: 13.6 v. 13.8
- Norway: 7.2 v. 6.6
(This can probably be explained by the breads favored by each country [5].)
"In Finland, the lowest incidence of prostate cancer is observed in the northeast part of the country, a region where the consumption of rye bread is particularly high."
The PCa risk factor by quartile (quartile 1 being the reference point, & set to 1.00):
- Finland: 1.00 0.94 0.93 1.02
- Sweden: 1.00 0.66 0.75 0.87
- Norway: 1.00 1.29 1.35 1.21
So, Norwegians, who don't have much enterolactone, compared to Finns & Swedes, had more protection at the lowest levels. "... in the Norwegian subgroup with a lagtime of more than 19 years between sampling and diagnosis, the risk was significantly increased in the second and third quartiles of enterolactone levels compared to the bottom quartile. Speculatively, the levels of enterolactone in our study may have been too low for a protective effect, but even in the evaluation of very high levels of enterolactone by analysis of the upper octile, no protective effect was observed."
Go figure!
[4f] (2010 - Jamaica)
Bad news: "Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85 ...) as well as high-grade disease (OR, 2.46 ...)"
I wonder what the sources of enterolactone are in the Jamaican diet?
-Patrick
[1] en.wikipedia.org/wiki/Lignan
[2] jn.nutrition.org/content/13...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4a] ncbi.nlm.nih.gov/pmc/articl...
[4b] ncbi.nlm.nih.gov/pubmed/174...
[4c] ncbi.nlm.nih.gov/pubmed/158...
[4d] cebp.aacrjournals.org/conte...
[4e] onlinelibrary.wiley.com/doi...
