Omega-3 fatty acids likely NOT associated with prostate cancer

A weakly constructed study was reported recently that purportedly associated higher levels of omega-3 fatty acid blood levels and prostate cancer. See this CBS News report, for instance.

Lipid and omega-3 fat expert, Dr. William Harris, posted this concise critique of the study, exposing some fundamental problems:

First, the reported EPA+DHA level in the plasma phospholipids in this study was 3.62% in the no-cancer control group, 3.66% in the total cancer group, 3.67% in the low grade cancer group, and 3.74% in the high-grade group. These differences between cases and controls are very small and would have no meaning clinically as they are within the normal variation. Based on experiments in our lab, the lowest quartile would correspond to an HS-Omega-3 Index of <3.16% and the highest to an Index of >4.77%). These values are obviously low, and virtually none of the subjects was in “danger” of having an HS-Omega-3 Index of >8%. So to conclude that regular consumption of 2 oily fish meals a week or taking fish oil supplements (both of which would result in an Index above the observed range) would increase risk for prostate cancer is extrapolating beyond the data.

This study did not test the question of whether giving fish oil supplements (or eating more oily fish) increased PC risk; it looked only a blood levels of omega-3 which are determined by intake, other dietary factors, metabolism and genetics.


The authors also failed to present the fuller story taught by the literature. The same team reported in 2010 that the use of fish oil supplements was not associated with any increased risk for prostate cancer. A 2010 meta-analysis of fish consumption and prostate cancer reported a reduction in late stage or fatal cancer among cohort studies, but no overall relationship between prostate cancer and fish intake. Terry et al. in 2001 reported higher fish intake was associated with lower risk for prostate cancer incidence and death, and Leitzmann et al. in 2004 reported similar findings. Higher intakes of canned, preserved fish were reported to be associated with reduced risk for prostate cancer. Epstein et al found that a higher omega-3 fatty acid intake predicted better survival for men who already had prostate cancer, and increased fish intake was associated with a 63% reduction in risk for aggressive prostate cancer in a case-control study by Fradet et al). So there is considerable evidence actually FAVORING an increase in fish intake for prostate cancer risk reduction.

Another piece of the picture is to compare prostate cancer rates in Japan vs the US. Here is a quote from the World Foundation of Urology:


"[Prostate cancer] incidence is really high in North America and Northern Europe (e.g., 63 X 100,000 white men and 102 X 100,000 Afro-Americans in the United States), but very low in Asia (e.g., 10 X 100,000 men in Japan).”

Since the Japanese typically eat about 8x more omega-3 fatty acids than Americans do and their
blood levels are twice as high, you’d think their prostate cancer risk would be much higher...
but the opposite is the case.


Omega-3 fatty acids are physiologically necessary, normalizing multiple metabolic phenomena including augmentation of parasympathetic tone, reductions of postprandial (after-meal) lipoprotein excursions, and endothelial function. It would indeed make no sense that nutrients that are necessary for life and health exert an adverse effect such as prostate cancer at such low blood levels. (Recall that an omega-3 RBC index of 6.0% or greater is associated with reduced potential for sudden cardiac death.)

I personally take 3600 mg per day of EPA + DHA in highly-purified, non-oxidized triglyceride form (Ascenta Nutrasea liquid) that yields an RBC omega-3 index of just over 10%, the level that I believe the overwhelming bulk of data suggest is the ideal level for humans.

Comments (6) -

  • Jeff

    7/23/2013 10:56:11 PM |

    Can you advise where you get the Nutrasea Liquid that you mention you personally use above?.  I'm not finding any in the 3600mg range.  I couldn't find any where 2 doses equals that amount either.  Looking for high quality Omega 3's that are not sourced from Krill due to shell fish allergy.  Currently taking fish oil gel caplets of dubious quality.  Thanks in advance.

  • pickinthefive

    7/29/2013 5:58:45 PM |

    Hi Dr. Davis,
    A question I would have.  If you are at a known risk for prostate cancer, i.e. father or uncle's already have it, or in my case a reletively high PSA and symptoms of BPH, would it be wise to avoid the Omega 3's ?
    Thank you,
    Monty

  • Edwin

    8/14/2013 9:27:43 AM |

    So my eating a canned salmon sandwich for lunch most days which has about 1g of Omega3 (I take no supplements) should be safe?

  • Stephen in Anaheim

    8/15/2013 5:29:38 AM |

    I have to say that this is a great thing to read! In most dietary articles that I stumble across nowadays, I can find at least a paragraph or more on why people should be adding more Omega-3 fatty acids to your diet. In fact, I have read that Omega-3 can be quite beneficial for a number of medical conditions ranging from childhood asthma to fibromyalgia. It is scary to think that it could associated with a higher risk of prostate cancer, even though the underlying study was not well constructed.

  • Edward

    8/16/2013 3:08:29 AM |

    Dr. Davis,
    I take fish oil from a brand called "Carlson fish oil" it contains omega 3 fish oil 1,600. What would be the highest safest amount a person can take in Omega 3 in your experience from your patients and practice? What are your thoughts on the Linus Pauling Heart therapy which calls for a person taking at least 10 grams of vitamin C and 3-5 grams of Lysine in order to reverse plaque and heart disease? I have read the two time Nobel prize winner's books and his writings on heart disease are compelling. I would love the insight from an actual cardiologist with a practice to confirm what works and doesn't work.

  • Edward

    8/16/2013 1:19:06 PM |

    Dr. Davis,
    How much fish oil would you consider the highest and safest dosage for a person to take for heart disease and would the dosage a person who is healthy or heart problems differ?

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Interview with Jimmy Moore of Livin' La Vida Low-Carb

Interview with Jimmy Moore of Livin' La Vida Low-Carb

Here's my podcast interview with Jimmy Moore, host of the Livin' La Vida Low-Carb Show. (If you want to fast forward to the interview, go to time marker 41:20 on the slidebar.)



In the podcast, I talk about how the Track Your Plaque program and its focus on lipoprotein testing, along with the need to reverse the incredible epidemic of diabetes and pre-diabetes, led to elimination of all wheat from the diet and the book, Wheat Belly.

Comments (11) -

  • Might-o'chondri-AL

    9/8/2011 1:03:32 AM |

    To Pedro  (posted here since Server blocked),
    Journal Biological Chemistry 2003,278:54-63  "A Type 1 Diabetes-related Protein from Wheat" that refers to globulin (a storage molecule of wheat) being antigenic for autoimmune problems was where I saw wheat genome estimated in 2002 to be 16.5 gigabase. I read that article when tried to track down Doc's reason to declare wheat implicated in Type 1 diabetes. Full article at www. jbc.org/content/278/1/54.full

    A 2010 reference to wheat genome is in journal Cytogenic and Genome Research, Vol. 129, No. 1-3, 2010 abstract's 1st sentence refers to wheat genome as 1C-17Gbp. English abstract at http://content.karger.com/
    produktedb/produkte.asp?doi=313072

    As I understand it 1 giga-base   =  109 base pairs, and mega-base =  106 base pairs; it's not a formula like that used to compare computer bytes of giga-bytes and mega-bytes.

    You might have research use for the Harvard Gene Index Project's Computational Biology & Functional Genomics Laboratory; if use link below look at top of page and see a category for "Gene Indices", click there to then choose from subjects "Plants", "Animal" or several other indices.
    http://compbio.dfci.harvard.edu/tgi

  • Might-o'chondri-AL

    9/8/2011 1:06:38 AM |

    To Pedro  (Server blocked elsewhere),
    Journal Biological Chemistry 2003,278:54-63  "A Type 1 Diabetes-related Protein from Wheat" that refers to globulin (a storage molecule of wheat) being antigenic for autoimmune problems was where I saw wheat genome estimated in 2002 to be 16.5 gigabase. I read that article when tried to track down Doc's reason to declare wheat implicated in Type 1 diabetes. Full article at www. jbc.org/content/278/1/54.full

  • otterotter

    9/8/2011 2:35:31 AM |

    Dr.Davis,

    Just listened to the podcast, that's fantastic !

    I have been diagnosed with TD2 last Sept, and since then being on the very low carb. Everything went well except my total cholesterol went out of control, and in January it was 400.

    What I don't understand is my Lp(a) is close to 0 ( less than 5.0 mg/dL as it was reported).

    Here is my latest direct measurements from SPECTRACELL LAB in Huston.

    VLDL Particels: 122 nmol/L (needs to be < 85)
    Total LDL Particles : 1271 nmol/L (needs to be < 900)
    Non-HDL Particles: 1394 nmol/L (needs to be < 1000)
    RLP(Remnant Lipoprotein) 205 nmol/L (needs to be < 150)
    Small Dense LDL III: 552 nmol/L (needs to be < 300, marked as very high risk right now)
    Small Dense LDL IV: 96 nmol/L (needs to be  7000)
    Large Buoyant HDL 2b: 2045 nmol/L (needs to be > 1500)

    Apo B-100: 127 mg/dL (needs to be < 80)
    Lp(a) : less than 5 mg/dL (needs to be < 30)
    C-Reactive Protein-hs : 0.2 mg/L (needs to be < 1)
    Insulin: less than 4.0 uIU/mL (needs to be < 35)
    Homocycteine: 12.3 umol/L (needs to be < 11)

    Total Cholesterol: 259 mg/dL
    LDL: 159 mg/dL
    HDL: 59 mg/dL
    Triglycerides: 118 mg/dL
    Non-HDL-Chol : 200 mg/dL


    I already removed the cheese and eggs from the diet, I suspect I am APOE 4.

    Any comments on my pattern ?

    thanks!

    otterotter

  • Might-o'chondri-AL

    9/8/2011 2:53:25 AM |

    To DCMarc  (server blocked where belongs),
    Benfotiamine, a synthetic thiamine used in diabetic neuropathy, increases enzyme trans-keto-lase inside a cell. The use in diabetics and neuro-degeneration may (?) require professional consideration in cancer cases. Trans-keto-lase spurs cells to go into aerobic glycolysis (aerobic here refers to cell performing glycolysis despite oxygen being around for performing normal mitochondrial oxidative phosphorylation) for processing cells glucose; this aerobic glycolysis is the  famous Warburg effect and experimentally administering trans-keto-lase augments cancer cell proliferation (likewise experimentally spiking up thiamin increases trans-keto-lase).

    Trans-keto-lase works for diabetics & in neuro-degeneration because  it pushes cell's glucose (via transcription once cAMP binds to it)  into the hexose mono-phosphate shunt ( of D-glucose-6p to D-glucono-lactone 6P to D-glycr-aldhehyde-3-phosphate) called the Pentose  Pathway (where hexose forms into pentose). This  process generates NADPH which boosts anti-oxidant glutathione ( & thioredoxin) production inside the cell. Also NADPH brings on the  activation of  the cell's endoplasmic reticulum's Unfolded Protein Response which helps the endoplasmic reticulum (ER) tolerate dangerous endoplasmic reticulum stress (ER stress is significant in diabetes and neuro-degeneration).

    ER stress, with protein folding complications, sees NADP+ accumulate and so augmenting trans-keto-lase pushes quicker output of NADPH to keep pace; this  triggers the Unfolded Protein Response to induce Cu,ZnSOD expression that then alleviates the ER stress (ie: helps ER tolerate demanding conditions).  This helps in that it  keeps the stressed ER  ( a state that coincides with more local super-oxide O--),  from seeding the dangerous (and largely un-neutralizable) hydroxyl radicals (hydroxyl radicals come about when super-oxide related hydrogen peroxide  provokes Fenton  & Haber/Weiss reactions reducing Cu++ or Fe+++ ). This is similarly how trans-keto-lase also benefits cancer cells ( rampant cancer cell growth demands protein folding that formally stresses the ER); the prevention against reactive oxygen species means cancer cells don't suffer apoptosis (cell death).

    Diabetics use of Befotiamine ( a dynamic fat soluble thiamine trans-keto-lase booster) will  help them similarly with their ER stress . In  their case the shift to using their regularly high glucose in the Pentose Pathway will mean quicker degradation of that glucose than if cells used mitochondrial oxidative phosphorylation. This also means the glycation (Doc warns against this from high glucose)  and thus tissue cells levels of advanced glycation end products (AGE) will be less; blunting the amount of AGE messing with monocytes and less endothelial dysfunction  amount to less inflammation, less diabetic oxidative stress and likewise less alteration of the vascular tissue such as atherosclerosis.

    Experimentally induced diabetes is often done by feeding a very high  fat diet. Much of the fat in a very high fat diet  acts to drive down the level of trans-keto-lase due to a transcription adaptationum within 8 weeks in rodents. For humans thiamine (B1) is often recommended to diabetics; cauliflower is a nice thiamine source to make into trans-keto-lase.

  • Might-o'chondri-AL

    9/8/2011 6:26:09 AM |

    To  B. Smith (Server won't post where belongs ),
    Glutamine, an amino acid, is used by cancer cells to keep apoptosis (cell death) from happening in several ways. One way is how glutamine keeps the cell nucleus from condensing and stops the capsase 3 & capsase 8 cascades from starting apoptosis. The other way is how there is an increase in the  anti-oxidant glutathione synthesis when glutamine elevates NADPH (see comment above for ER stress).

    Tumor Necrosis Factor alpha (TNF) works to destroy a cancer cell by running down that cell's mitochondrial glutathione level; this needs to be replenished with glutathione from that cell's cytosol. Once there is a 35% plunge in mitochondrial glutathione that  alters the mitochondrial membrane so that it stops bringing in glutathione to the mitochondria and starts leaking out cytochrome c into that cell's cytosol (which can jump start an apoptosis program). Cancer cells' rapid growth strains the normal oxidative stress limits of a cell, so cancer cells draw in lots of glutamine to boost the level of ready glutathione inside that cell; then the cytosol can continually shore up the mitochondrial glutathione levels to prevent one of the apoptosis scenarios from starting .

    A cancer cell at some point has to "transform" to progress and needs lots of DNA at that stage; glutamine is needed for synthesis of cellular RNA & DNA. The bio-synthesis of nucleotides utilizes glutamine; and having lots of de-oxy-ribo-nucleotides around favors DNA replication at that cancer's key "transformation" stage (ie: S-phase). The use of glutamine by a cancer cell for converting into energy to run on, like some normal cells do, is not why cancer cells take up so much glutamine.

  • Galina L.

    9/8/2011 4:25:13 PM |

    @ Might-o'chondri-AL
    Dear Might, do you mind to tell what do you think about that cancer research result?
    l http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117136/?tool=pubmed

  • Peter Silverman

    9/8/2011 6:58:08 PM |

    My cardiologist said, "look, I don't know about nutrition.  If you want to talk about nutrion, go talk to a nutritionist"

  • Might-o'chondri-AL

    9/9/2011 12:32:19 AM |

    Hi GalinaL,
    Cancer undergoes several oncongenic processes wherein the so-called epithelilial pheno-type cell (epithelial cells are +/-85% of cancer substrate cells) gets it's cell nucleus histones acetylated, which creates what is called "stemness"  (the ability of that cell to renew itself with potency, like our stem cells). This leads to a phase called epithelial-mesenchymal transition (where the morphing cell can go either way, either back to benign epithelial pheno-type or onward to dangerous mesenchymal pheno-type). It is when the enzyme histone acetyl-transferase no longer keeps that epithelial histone acetylated ( a sort of  limbo) that the epithelial cell's genetic expression gets knocked down permitting the further shift into full mesenchymal pheno-type .

    What is important to realize about cancer cell's taking over a cell's nuclear DNA is that when the pheno-type goes from epithelial to mesenchymal the cancer cell's mesenchymal pheno-type somehow still retains the ability to perform the stem cell "stemness" of indefinite replication. Your cited authors point out that keotones boost tumor growth (+/-2.5 times) and lactate boosts tumor metastasis (+/- 10 times); and  also that their metabolic use raises a cell's Acetyl-CoA and this increases the acetylation of histones causing more gene expressio. And so authors report limiting ketones and lactate in cancer seem to be the "achilles heel" to cut off in order to stop cancer's "stemness" (ie: inherent potential); their extrapolation from this is interesting as a theory..

    There are other processes beyond histone modification which show oncongenesis is not lineal. When the cancer cell is still just an epithelial pheno-type cell unit micro RNA (miRNA) of the miRNA-200 family group is un-methylated; and thus holds the epithelial pheno-type steady, because un-methylated miRNA isn't reactive enough for messenger RNA (mRNA) transcription. A 2nd stage is seen once hyper-methylation  occurs, while at the same time less miRNA is put out; this morphs the cancer cell into the mesenchymal pheno-type and at that stage metastasis is possible. While an advanced 3rd stage comes about when miRNA resurges somewhat; this is what makes extensive metastasis of cancer cells that have migrated start happening. (Lineal thinking about cancer is a trap, since it is methylation that lets cancer cells get going but later de-methylation that let's them thrive and patient outcome worsen).

    Warburg effect is suggested, by cited study, to be almost a lineal concept; which they propose to re-define as desireable if it simply limits lactate and ketone production in a cell. This theory has it's own trap because in the Warburg effect +/-60% of the carbon from glucose undergoing aerobic glycolysis in cancer cells is actually being used by cancer cells as a carbon scaffolding for "de novo" fatty acid synthesis to feed into fatty acid oxidation. In other words the elevated amount of cancer cell's aerobic glycolysis (Warburg effect) is really fostering fatty acid oxidation; and fatty acid oxidation increases cancer resistance.

    The cancer cells uncouple the mitochondria oxidative phosphorylation of glucose so that the a lot of the processing of glucose doesn't go all the way to normal completion of ATP production; instead cancer cells use the initial steps that perform oxidation of glucose to cleave off the carbon atoms from that glucose to use. In other words it is the mitochondrial uncoupling protein up-regulated by that cancer cell's genetic  transcription which, down the line, forces that cell to continue to escalate Warburg's aerobic glycolysis in order to keep up with energy demands as carbon skeletons get used up.

    Metaformin's use in cancer treatment was suggested by study's authors to support their "reverse Warburg" theory : that it is by forcing Warburg's aerobic glycolysis to occur, due to Metaformin,  which accounts for cancer control seen. This seems too lineal an interpretation of the events; especially with regard to preceding paragraph's explanation of how Warburg relates to unpredictable carbon molecule usage. Metaformin reliably does inhibit the mitochondrial complex 1; and this will stymie glucose (and also glutamate, which cancer cells prodigiously take in ) from going on to produce ATP. I would suggest that this also stops the oxidizing of glucose molecules and thus sparse carbon skeletons are available to make into fatty acids for burning.

    In addition Metaformin inhibiting mitochondrial complex 1 will also reduce fatty acid oxidation; this is because  NADH oxidation at that complex needs to happen in fatty acid oxidation. NAD+ is a crucial rate limiter in  fatty acid oxidation , but unless NADH can subsequently be re-oxidized as a molecule in the mitochondrial complex 1 it can't keep on driving fatty acid oxidation by lending out NAD+.  Metaformin use in cancer is even more complicated, because if the cancer has p53 then when glucose supply is low it manages to actually use more fatty acids to run on and then use auto-phagy house cleaning to avoid apoptosis death. Whereas, if a cancer does not have much p53 then Metaformin seems to be more effective in treating cancer.

  • Dr. William Davis

    9/9/2011 2:25:55 AM |

    Yup, and the nutritionist hawks the usual "cut your fat, eat more whole grains" line.

    It's a comedy of misinformation with advice from agencies paid for by your tax dollars.

  • Dr. William Davis

    9/9/2011 2:29:21 AM |

    Hi, otter--

    Obviously, I can provide only limited advice in a blog post.

    But I agree: Apo E4 is a prime consideration. However, keep in mind that small LDL remains the most atherogenic (plaque-causing) of all your patterns and still deserves the primary focus. Also, if this blood sample was drawn with ongoing weight loss, this alone can provide substantial distortions.

  • Galina L.

    9/9/2011 2:48:25 AM |

    Wow! I don't know who else would dissect that article like you did! I really, really appreciate you decision to replay on my question. Looks like  Metaformin could be healthful in more than one way in treating cancer.

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