Foods/Supplements-Vitamins: Flaxseed hull lignans - Enterolactone

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...

[4f] ncbi.nlm.nih.gov/pubmed/209...

[5] en.wikipedia.org/wiki/Nordi...

8 Replies

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  • Well, I guess I will stop taking Flax Seed Oil to try to help with hot flashes. Although, the suggestion on the board was whole flax seeds ground so I was already not following instructions properly. How about the other suggestion at that time, Magnesium Citrate? Does anyone have studies that suggest that supplement is harmful? Does it have to be Citrate or will Magnesium as part of a vitamin/mineral block like Calcium/Magnesium/Vitamin D work? Has anyone actually found something off the shelf that helps with hot flashes? I'm willing to try anything without actually going the prescription route. The flashes are annoying but no so terrible that I want to risk other side effects with a new drug.

  • Your hot flashes are most likely from your Lupron injections--My Doc. Uses Vantas a Lupron implant gel--implanted under your arm and is good for a year. I take Casodex and Avodart on the side daily. This implant puts out a steady daily amount--so there are no ups or downs--and limited hot flashes. Actually I have none.

    As to Calcium Magnesium vitamin D3--I recommend to all my-------to buy Country Life's Calcium Magnesium Complex--which is in the form of an amino acid chelate. This is the best of the best for bone health Blood Pressure and other issues. Add Vitamin D3 separately--best place to buy is Vitacost.com--I am not a stockholder--just like low prices. The Cal-Mag complex is 2 tablets which gives 1000 mg Cal and 500 mg Magnesium--I take it twice a day after breakfast and dinner.

    Hope this helps.

    Nalakrats

  • So you don't take a multi-vitamin, right? Because then you'd be getting too much calcium. From what I've heard, some say 800 & some 1000, but both sides say not more than that.

  • No multi vitamin, as I regulate almost all supplements individually. It may be that my twice a day use is double of what is "recommended, or from what the I have heard crowd thinks", but my use has been the same for 21 years. And with the same products. The fact that I use the Amino Acid Chelate Form, of the minerals, allows for any excess supplementation to easily pass the Renal System without harm. My last Bone Density for a 73 year old came in in terms of age, of what would have been expected, of an "Athletic 25 year old"--was the words used, by the examiner. I am not about to change! My Pca did not come from excess Calcium use, it came from 2 Mutations in my Genome---BRCA-2 and PTEN. I.E, I can find just as to Vitamin D3 alone, that there are "those; from the what I have heard crowd" say 10,000 IU's is maximum and above this level would be considered toxic, and others say 40,000 IU's is the line not to cross, for daily use, as this is toxic". How could all these so called experts be 400% apart?

    The recommendation by the Food Science Community for not just Vitamin D3, but for plain old Vitamin D[both forms], goes back to the turn of the 19th to the 20th Century, when it was determined that a proper value of Vitamin D was 400 IU units per day. That is still the Government Daily Required Minimum[RDA]. Just look at any milk carton, or other food where D is provided. The Food industry, goes along, to get along.

    You know how 400 IU's has become the standard for over 100 years? It is the minimal amount needed per day by an individual to prevent the disease Rickets. "My God" we are still living in the dark ages! As a further example, of what I call "Traditional Stupidity"--is the normal body temperature of 98.6. This comes from also that same Era, and has never changed. As there may be an average, but it is not 98.6. This number came from the average of temperatures of 100 healthy people.

    Can you imagine, only 100 people were averaged. This would be in the Statistical Confidence Level of about 1%. My average temperature is 97.4--does this make me sick? Some Doctors have actually said to me, "my low temperature just means my metabolism runs slower, than normal people". "Normal People"?

    So in ending this reply, I will repeat--an 'old saw'---"each to their own". But in my case, my own comes from 50 years of use and experimentation on my own body. I first popped my first supplement in 1967. And I have been at it this long, with an incredible amount of changes as the real science of nutritional healing, and supplementation has evolved. It was not until 1995, that I changed my Calcium and Magnesium intake. Using these supplements not as supplements, but as drugs, to overcome Blood Pressure issues, and to then use them for Bone Density Enhancement.

    Nalakrats

  • Thank you, Nalakrats. Very interesting.

    Neal

  • Well I have been taking Flax seed oil together with a Highly concentrated Fish Oil together twice daily, for 22 years--and I do not think it has given me Pca--or ruined my Health. Cold pressed Flax Seed Oil, and the newer extraction techniques of sub-critical and super critical extractions, that can give you an incredible profile.

    I take as to profile--Linum usitatissimum 3000mg per day

    Alpha Linolenic Acid[Omega -3] 1500mg per day

    Oleic acid[Omega-9] 400 mg per day

    Linoleic Acid[Omega-6] 375 mg per day

    Each to their own--don't need a big study--it is like butter will kill you--must eat Oleo.

    Nalakrats

  • Nalakrats,

    I am astonished!

    The connection between alpha linolenic acid [ALA] & PCa was first reported by Giovannucci in 1993 [1]:

    ALA was "associated with advanced prostate cancer risk; ... the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43 ...)"

    I too used flax oil for a number of years - until I read the ALA papers, post-diagnosis.

    What do you think the ALA does for you?

    What is meant by "Highly concentrated Fish Oil"? That there is a high concentration of EPA/DHA? If so, they may protect against ALA. (I doubt that many use flax oil for ALA & also take in marine omega-3.)

    Same with linoleic acid [LA]. Giovannucci later reported that the men with high ALA & low LA were at greatest risk. In that instance it's because of competition for enzymes. In the case of ALA & EPA/DHA, it would be lipid raft uptake competition, IMO.

    Why do you supplement with LA? For most Americans, there is too much LA in the diet.

    & Oleic acid? I know it is the main fatty acid in olive oil, but a high oleic: stearic fatty acid ratio is associated with advanced disease.

    -Patrick

    [1] ncbi.nlm.nih.gov/pubmed/810...

  • Patrick, don't be astonished! In the 1950's, Butter was no good for you because it caused heart disease, so the world had to change to the new kid on the block Margarine. About that time, around 1960, eggs were no good for you, for you would surely die of the same dreaded heart disease. You were warned, by Doctors, to not eat more than 2 or was it 4 eggs in a week. Then the experts said eggs were OK, then they were again not OK, now they are OK. As a member of the Food Science Community[Retired], I can write a book on how this all came to be driven by Food Consortiums, and cleaver advertising, to even have our Doctors, who at that time, took a total of 3 required credits, in Med school on the subject of Diet and Nutrition.

    We now know from a study, done on Cadavers of Women at Sloan Memorial, in NYC. that dissection of breast material of those dying of Breast Cancer, had not just high but enormous amounts of Partially Hydrogenated Fat deposited in their, breasts. Undigested, PHF. The type most prominently found in Margarine. SMH, then published side by side, not only the reports of the deposited fats of the Cadavers, but a report showing how with the increase use of Margarine, the increase of Breast Cancer followed. They graphed it on a simple X,Y axis graph, and the use of Margarine increase followed exactly the increase of Breast Cancer.

    Now some unknown partying mad cap Scientist in 1964 wrote a paper. Titled, "Is Partially Hydrogenated Fat a Food Polymer"? The premise of the paper in short was that the body recognizes Saturated Fat, and it recognizes Unsaturated fat and metabolizes these fats according to each individuals Metabolic Digestion Factors. And that further, the Partially Saturated Fats[PHF], would not be metabolized, in a normal way, as the body would not recognize it as a food ingredient, but a foreign substance, because according to the Nature of God, this Chemical[Food Polymer], did not and does not exist in nature. Just like eating newspapers would surely not be considered food by the body.

    The point being, that Flax seed Oil from Flax Seed, both exist in Nature, and was meant by our Creator to be eaten. Granted the Oil in todays Supplemental Capsules is highly concentrated, but that which makes up the composition of the oil are not foreign chemicals or substances, but natural ingredients that exist in other foods/meats, and in Nature. Now it has been proved that drinking too much distilled water can kill you. As I said in another post, my Pca, comes from 2 Gene Mutations, BRCA-2 and PTEN. I do not think my use of Flax Seed Oil caused my Mutations. As an Ashkenazi Jew, the mutations are typical for us Jews. 18% of Ashkenazi's who get Pca, have the same sequencing aberrations, as I have. I do not think Flax Seed or Oil has anything whatsoever to do with, Pca. And I know the person who wrote that paper. He writes here often, when he can, and he may have been too far ahead of his time.

    Nalakrats