DHA and Angiogenesis: The Bottom Line

So I thought I’d finish up the series on DHA and angiogenesis by discussing 2 issues:

1.      First, an assertion: The pathway by which oxidized DHA drives angiogenesis may be really important for human health.

2.      Second, the $64,000 question: Is there evidence that high levels of dietary DHA promotes diseases of pathological angiogenesis? What about other dietary factors bearing on DHA oxidation?

Significance of the Oxidized DHA Link to Angiogenesis

The papers discussed in Friday’s post about a major angiogenesis pathway stimulated by oxidized DHA (Omega-3s, Angiogenesis and Cancer: Part II, April 29, 2011) may not seem important to many readers. But to cancer researchers and pharmaceutical companies, this is blockbuster work.

A tumor is, in the words of Hal Dvorak, “a wound that never heals.” [1] To support growth, cancers invoke the wound healing process – especially, creation of new blood vessels, or angiogenesis. But the tumor prevents the wound healing process from completing. If it ever did complete, then the tumor itself would be healed. It would cease to grow and become benign.

It’s been recognized for decades that an ability to block angiogenesis would effectively constitute a cure for cancer. The William Li video explains why: nearly everyone gets microscopic tumors that never develop the ability to induce angiogenesis. Life-threatening cancer is the result of tumors that can induce angiogenesis. No angiogenesis, and no one would die of cancer.

But existing anti-angiogenic cancer therapies have produced disappointing results. Avastin, an anti-angiogenic drug targeting VEGF (vascular endothelial growth factor), has been estimated to extend colon cancer patient lifespan by only 6 weeks.  (Nevertheless, Avastin generated $7.3 billion in revenue last year. Imagine how much money there would be in an anti-angiogenic therapy that worked!)

The work I discussed last Friday suggests a reason for that failure. Recall these pictures:

If only the VEGF pathway is blocked (upper right), there is almost as much angiogenesis and wound healing as in a normal wound (upper left). But when both the VEGF and TLR-2 angiogenic pathways are blocked (lower right), there is no wound healing.

If these are the operative pathways in cancer also, then blocking the TLR-2 angiogenesis pathway might be the key to cancer therapy.

But cancer is not the only disease of pathological angiogenesis. Others include:

  • Age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity – three common causes of blindness.
  • Atherosclerosis, which often features angiogenic vessels in thickened arterial walls.
  • Vascular malformations and tumors.
  • Obesity. Adipose tissue utilizes angiogenic pathways, and angiogenesis inhibition prevents the deposition of fat.
  • Rosacea, psoriasis, and some other skin conditions.
  • Endometriosis, uterine fibroids, and some other causes of female infertility.
  • Rheumatoid arthritis.
  • Crohn’s disease.
  • Preeclampsia.

It may be that the TLR-2 pathway is key to these diseases as well, and that a treatment that inhibits this pathway can cure or improve all of these diseases.

Add up the size of these markets and a pharmaceutical company executive would swoon.

Luckily, we’re not pharmaceutical company executives. But we can still get excited over possibilities to improve these diseases through diet and anti-microbial medicine.

Infections as Contributing Causes of These Diseases

TLR-2 is stimulated by other things besides oxidized DHA. In particular, TLR-2 is an immune molecule which is stimulated by pathogen proteins. As Wikipedia notes:

TLR-2 recognizes many bacterial, fungal, viral, and certain endogenous substances.

This tells us that many pathogens may stimulate angiogenesis through the TLR-2 pathway. As a result, anti-microbial medicines might help treat some diseases of pathological angiogenesis.

Some antibiotics, including doxycycline and minocycline, are known to exercise anti-angiogenic effects independent of the antibiotic effects. [2]

Diet-Induced Angiogenesis

Many foods affect angiogenesis. In fact, cancer studies have identified dozens of plant foods, from garlic to tomatoes to leeks, that possess anti-angiogenic properties.

However, foods can also promote angiogenesis. Let’s stick to the oxidized DHA pathway and see if there’s evidence that foods drive it.

You’ll recall the recipe was:

DHA + oxidative stress + retinyl protein = TLR-2 driven angiogenesis

If this pathway is important in human disease, then we should expect diseases of angiogenesis to be worsened by adding the ingredients on the left.

Specifically, cancer, AMD, rosacea, and so forth should be worsened by high doses of DHA, high doses of vitamin A, and low doses of antioxidant minerals like zinc or selenium.

Is there any evidence for that pattern?

Cancer Studies

First, let me give my bottom line on the Brasky study that kicked off this series. High tissue levels of DHA were associated with increased risk of high-grade prostate cancer, and the oxidized DHA angiogenesis pathway provides a mechanism for this association. What’s not clear is why tissue DHA levels were high. EPA levels were also elevated in the high-grade prostate cancers, but not by nearly as much as DHA levels. EPA and DHA appear together in fish and fish oil, so this suggests that fish consumption contributed to but was not the primary cause of the elevated tissue DHA. The drug finasteride greatly raised risk of high-grade prostate cancer, but the paper did not break down the DHA-cancer association between the finasteride and placebo arms. The most likely explanation, in my view, is that finasteride increases conversion of EPA to DHA and creates artificially high tissue DHA levels. The high DHA levels combined with oxidative stress drive cancer through the TLR-2 angiogenesis pathway.

A clever but unlikely alternative explanation was suggested by Peter at Hyperlipid: perhaps extra dietary fish oil raises testosterone levels. Prostate cancer is a hormone-dependent cancer and can be promoted by testosterone, just as breast cancer is promoted by estrogen. Possible supporting evidence comes from a paper showing an inverse association between metabolic syndrome / diabetes and prostate cancer. The trouble with this idea is that (a) this effect should have been strongest in the low-grade cancers, since diabetes reduced the incidence of low-grade cancers, but in the Brasky study DHA had no association with low-grade cancers, (b) fish oil lowers testosterone levels in rats, (c) in the Brasky study high-grade prostate cancers were strongly associated with obesity and the obese generally have low testosterone levels, and (d) surprisingly, high-grade prostate cancers are associated with low testosterone, not high. So one could argue that fish oil might promote high-grade prostate cancer by lowering testosterone!

A unified explanation along this line would be: Finasteride raises DHA levels, and DHA lowers testosterone. Low testosterone reduces incidence of low-grade prostate cancers but makes it much more likely they will progress to high-grade. Thus, finasteride reduces prostate cancer incidence but increases high-grade prostate cancer incidence and overall prostate cancer mortality. Fits all the facts. Could be.

My bottom line: the Brasky study is weak evidence for anything, but it does raise a whiff of evidence that high dietary fish oil intake might encourage a transition from low-grade to high-grade cancer.

What about other ingredients in the recipe? Does increasing retinyl levels raise cancer risk?

Retinyl palmitate (vitamin A) has been tested in clinical trials for its effect on cancer risk. The trials had to be cut short when it was found that vitamin A increased cancer mortality:

The Carotene and Retinol Efficacy Trial (CARET) was a multicenter randomized, double-blind placebo-controlled chemoprevention trial testing whether daily supplementation with 30 mg β-carotene + 25,000 IU retinyl palmitate would reduce lung cancer risk among 18,314 heavy smokers, former heavy smokers and asbestos-exposed workers. The intervention ended 21 months early in January, 1996 when interim analysis found evidence that the supplements increased the risk of lung cancer and total mortality in this high-risk population by 28% and 17%, respectively (10). [3]

After the study ended participants were tracked for years afterward. Those who had received vitamin A during the trial, but especially those in the vitamin A arm who took additional supplements (mainly multivitamins which are rich in A, but possibly also fish oil), had more high-grade prostate cancers:

As a proportion of the total prostate cancer cases, more men who were randomized to the active arm developed high-grade prostate cancer (Gleason 7-10) than in the placebo arm (44.6% vs. 40.1%, respectively)….

For aggressive prostate cancer, men in the CARET intervention arm who used additional supplements had a relative risk for aggressive prostate cancer (Gleason >or=7 or stage III/IV) of 1.52 (95% CI, 1.03-2.24; P < 0.05), relative to all others. [3]

Interestingly, in the placebo arm taking multivitamins and other supplements reduced cancer risk.

Other studies have found similar results.

Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P(trend) = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. [4]

Carotenoids, which can generally be converted to vitamin A, are also associated with higher cancer risk. There is one exception – lycopene:

Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. [5]

What’s special about lycopene? Wikipedia explains:

Lycopene may be the most powerful carotenoid quencher of singlet oxygen,[18] being 100 times more efficient in test tube studies of singlet-oxygen quenching action than vitamin E … The absence of the beta-ionone ring structure for lycopene increases its antioxidant action….

Lycopene is not modified to vitamin A in the body

So lycopene does not increase retinyl levels, but does act as an extraordinarily powerful antioxidant, thus reducing oxidative stress! If you wanted a good food for stopping the DHA – angiogenesis pathway, you’ve found it: tomatoes.

Hmmm, tomatoes go well with salmon …

That gets us to the third part of the recipe, oxidative stress. If oxidized DHA drives angiogenesis, then antioxidants should be preventative for these diseases.

The evidence here is rather mixed, because with the exception of the negative effects of vitamin A, most antioxidants seem to have little effect on cancer. Nevertheless, I’ll give some studies. Selenium is a antioxidant mineral due to its role in glutathione peroxidase:

Serum selenium was inversely associated with risk of prostate cancer (comparing highest to lowest quartiles, OR = 0.71, 95% CI 0.39-1.28; p for trend = 0.11), with similar patterns seen in both blacks and whites. [6]

Zinc is an antioxidant due to its role in zinc-copper superoxide dismutase. Prostate cancer is associated with low tissue levels of zinc. [7, 8] High dietary intake of zinc is associated with lower rates of prostate cancer. [9]

N-acetylcysteine is an antioxidant supplement that is a precursor to glutathione. N-acetylcysteine has been shown to prevent angiogenesis and has been proposed as a likely cancer preventative, but this is as yet untested. [10]

Other Diseases of Angiogenesis

I’ll skip those for now, other than to note that fish oil is a well-known trigger of rosacea. Is it possible that the mechanism is via TLR-2 activation by oxidized DHA?


At the moment there’s some puffs of smoke but no fire. Observational studies weakly link high DHA, high vitamin A, and low antioxidant status to diseases of angiogenesis such as cancer.

This pattern would be consistent with the idea that the natural pathway used in wound healing to trigger angiogenesis – DHA oxidation and combination with retinyl protein to trigger TLR-2 pathways – is also important for cancer progression.

It suggests a strategy of reduced fish oil and vitamin A consumption and increased intake of certain antioxidants (such as lycopene, zinc, selenium, or NAC) may be helpful against cancer.

However, this idea needs testing. No study in animal cancer models has tested this dietary combination.

Given the many proven benefits of moderate amounts of fish oil, I don’t see a reason yet to alter our recommendation that healthy people should eat a pound of fish per week. That said, I do think very high intakes of fish or fish oil are ill advised. And I’m intrigued by the idea that dietary changes may have the potential to play a powerful role in recovery from diseases of angiogenesis such as cancer.


[1] Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650-9. http://pmid.us/3537791.

[2] Yao JS et al. Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration. Neurochem Int. 2007 Feb;50(3):524-30. http://pmid.us/17145119.

[3] Neuhouser ML et al. Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2202-6. http://pmid.us/19661078.

[4] Mondul AM et al. Serum retinol and risk of prostate cancer. Am J Epidemiol. 2011 Apr 1;173(7):813-21. http://pmid.us/21389041.

[5] Vogt TM et al. Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites. Am J Epidemiol. 2002 Jun 1;155(11):1023-32. http://pmid.us/12034581.

[6] Vogt TM et al. Serum selenium and risk of prostate cancer in U.S. blacks and whites. Int J Cancer. 2003 Feb 20;103(5):664-70. http://pmid.us/12494476.

[7] Sarafanov AG et al. Prostate cancer outcome and tissue levels of metal ions. Prostate. 2011 Jan 26. doi: 10.1002/pros.21339. [Epub ahead of print] http://pmid.us/21271612.

[8] Costello LC, Franklin RB. Zinc is decreased in prostate cancer: an established relationship of prostate cancer! J Biol Inorg Chem. 2011 Jan;16(1):3-8. http://pmid.us/21140181.

[9] Epstein MM et al. Dietary zinc and prostate cancer survival in a Swedish cohort. Am J Clin Nutr. 2011 Mar;93(3):586-93. http://pmid.us/21228268.

[10] Noonan DM et al. Angiogenesis and cancer prevention: a vision. Recent Results Cancer Res. 2007;174:219-24. http://pmid.us/17302199.

Leave a comment ?


  1. I would not be too afraid of fish consumption just yet.
    Aren’t cultures with high fish consumptions generally pretty healthy?
    Also don’t most fish like sardines, salmon, mackerel et al provide decent amounts of selenium?

  2. Paul,

    Well, you may have forgotten, but not all anti-angiogenic cancer drugs have produced disappointing results!

    LDN (low dose naltrexone) is one drug that has produced great results with cancer. Ian Zagon is a great researcher in this area:


  3. Hi utility73,

    Yes, and yes. I’m also not too afraid of fish consumption – I’m maintaining our book recommendations – but I think cancer patients might want to be careful to do moderate fish oil only.

    Hi Mario,

    Thank you for reminding me that I need to write about LDN!

    I didn’t know LDN was anti-angiogenic. It’s a little wonder drug – good against everything.

    You know you can do a guest post on it anytime …

    Best, Paul

  4. This DHA thing reminds me of T Colin Campbell stating casein causes cancer and we shouldn’t consume milk because of this. Whey is cancer protective and also happens to be in milk. Makes me wonder if something in whole fish may balance out this possible issue with DHA.

  5. Hi chuck,

    The balance of EPA with DHA may be important in inflammatory pathways, and upsetting that balance could be one reason finasteride is harmful.

    Also, foods high in DHA tend to be high in antioxidants like vitamin E and selenium, so that would help moderate the oxidative pathway.

    In general I think real foods are the way to go!

  6. I’m wondering about liver which is high in vitamin A. Is that potentially an issue or is something else in it balancing out the high amounts of vitamin A.

  7. Hi Jon,

    Liver is very nutritious but should be eaten in moderation. We eat about 1/4 pound per week beef liver. I wouldn’t go above 1/2 pound per week beef liver because of the risk of too much copper. If you take a multivitamin I wouldn’t go above 1/2 pound liver from all animals per week due to vitamin A; if you don’t take a multivitamin a bit more liver is possible.

  8. No mention of vitamins A, D and K interaction in these studies. Ignorance or by design?

    Just like the recommendations to supplement with large quantities of fish oil to reduce inflammation, often without mentioning that it is primarily the excess of omega-6 (in the SAD) causing the problem.

  9. Hi Paul,

    DHA + oxidative stress + retinyl protein = TLR-2 driven angiogenesis

    How would fasting enter into the above equation? DHA and retinyl would be low, oxidation stress possibly higher, but would the timeframes involved – 16 hours to extended days be long enough to cut off angiogenesis to cancer cells or do you think this is a much longer undertaking?

    Thank You.

  10. Hi Peter,

    Probably both. Most scientists are ignorant of A,D,K interactions. And they have to design papers to be focused. It’s not easy to explore all the issues in a paper’s space limitations – look at how sprawling my last 3 posts have been.

    The bigger defect is not discussing the interaction of finasteride with DHA. This group has done papers on finasteride and prostate cancer risk and on DHA and prostate cancer risk, but nowhere do they discuss the interaction.

    Maybe it’s coming in a future paper … and this is just milking the study for as many papers as possible. Or maybe it’s concealing an inconvenient finding.

    Hi Perry,

    That’s a good question. I don’t know. Fasting might increase tissue DHA levels, since DHA isn’t easily burned for energy. It would also deplete antioxidant levels over time, unless they were supplemented. I’m not sure I’d count on fasting as an anti-angiogenic therapy. It’s a good research question.

    Best, Paul

  11. Paul, I’ve been suspicious of the benefits of fish oil beyond what’s required to balance n-6. Of course, the question still remains: how is it that the Inuits, Southeast Asians, Okinawans and others living in maritime regions who ate fish in large quantity enjoyed such vitality and was apparently cancer-free?

    Well, according to one source (http://fanaticcook.blogspot.com/2010/07/traditional-okinawan-diet-sweet.html), the Okinawans circa 1950 didn’t eat as much fish as we thought; their staple diet was really sweet potatoes — presumably those purple sweet potatoes indegenous to the island. Fish was limited to 15g per day (~1% of their 1800 total calories), while sweet potatoes accounted for 850g or 70% of total calories. This was a carb-rich diet (85%), with limited proteins (9%) and fat (6%). Note, also that their PUFA intake of 4.8% was about half of what the mainland Japanese ate.

    Those 15g of fish is less than 1/4 of what the mainland Japanese ate (60g): ~4% of total calories or about 150mg of n-3 FA. Compare that to the 1 tsp of n-3 most people supplement these days: 1.6k mg. That’s about 10x what the Japanese ate. I don’t know if the math is right, but it seems that 1 tsp of fish oil is tantamous to eating 600g of fish. Clearly no Japanese could have eaten that much fish per day. Not even the Inuits!

    I believe you cite these studies in your series, but check out this link for further arguments against taking fish oil as a dietary supplement.


    I think the key to the Okinawans’ longevity was the sweet potato, not fish oil! In othe words, the safe starch and their limited protein (as well as caloric) intake!

  12. Hey Paul,

    Interesting post. The adverse effects of carotenes were also seen the ATBC trial, without any preformed vitamin A. Tufts researchers followed it up with ferrets. Their studies suggested that large, but not small, doses of beta-carotene lead to apocarotenal formation that leads to the oxidative destruction of retinoic acid, leading to a cellular deficiency of vitamin A in lung tissue, and that this is responsible for the pro-cancerous effects. So I don’t really think, in that case, it was the vitamin A that was the problem.

    I wrote about this a long time ago here:



  13. I should add that I was probably overstating the case against carotenes in that article. The Tufts research suggested that 30 mg/d, which is really only obtainable from supplements, is harmful, but that 6 mg/day, which would be obtainable from a vegetable-rich diet, was not harmful and might be beneficial.


  14. “The William Li video explains why: nearly everyone gets microscopic tumors that never develop the ability to induce angiogenesis.”

    This comment is probably based on observations of people on the Western diet. Possibly, people who don’t eat the Western diet don’t generate tumors (or don’t generate them in any significant numbers). Possibly, something in our Western diet initiates tumorigenesis, and then all bets are off regarding supposedly healthy foods (a la Campbell’s aflatoxin/casein studies).

    I.e. maybe “DHA + oxidative stress + retinyl protein = TLR-2 driven angiogenesis” is Step 2.

    Also, the equation could also exhibit saturable kinetics or have an important rate-limiting step.

    Thought-provoking stuff as always, Paul.

    Oh, Natty, I think what constitutes a prototypical Okinawan diet is in the eye of the beholder. What I’ve gathered from my foray into this is that Okinawan’s used an aweful lot of lard in their cooking, so that 6% value for fats looks quite absurd from this point of view. But who knows? Your source may be correct. The important point is, I believe, cancer in this population likely only became evident after the adoption of the Western diet (or parts of).

  15. Hi natty,

    A key thing to keep in mind is that only cold-water fish have large amounts of omega-3. So Kitavans, living in warm waters, would have gotten modest omega-3 no matter how much fish they ate.

    Something else to keep in mind is that during World War II and for several decades afterward, Okinawans were very poor. Meat was rarely available. Many people ate near starvation diets.

    My understanding is that the true traditional Okinawan diet was high in fat. This is mentioned in the book.

    Thanks for the link to Bix’s post, I also read her site.

  16. Hi Chris,

    Thanks much for the link and insight.

    Another factor to consider is that many carotenoids bind to the same receptors, so too much beta-carotene can mean less of the rest, which may have been more beneficial. Also, there may be competition between carotenoids and retinoids.

    In general I think mixed carotenoids from real foods, and a mix of carotenoids and moderate amounts of preformed A from foods, fare pretty well in the literature. But high doses of one, or imbalances due to supplementation of one species, may be detrimental.

    To be honest I’m almost ready to assert the view that we should drop multivitamins, instead take a multimineral supplement and supplement C/D/K as necessary and get all other vitamins from food!

    Vitamin A-rich foods may be much healthier than vitamin tablet A, and the multivitamin A may increase risk of an excess or force eating suboptimal amounts of nutritious vitamin A-rich foods.

  17. Hi Poisonguy,

    All true. It would be interesting to see how prevalent those microtumors are on other diets, but who knows when that research will be done. Not until large numbers of people are eating other diets.

  18. I take 1 teaspoon a day of fermented cod liver oil (from a glass bottle, not capsules), which the Weston A. Price Foundation recommend as being a traditional food rather than a supplement. I’d be grateful for your view on this, Paul.

  19. Hi Elima,

    In isolation, the fermented cod liver oil is a very nutritious food. However, in the context of a whole diet, it can easily provide too much fish oil and vitamin A.

    We generally prefer whole foods and tend to think that salmon as a source of fish oil, beef liver and egg yolks as a source of vitamin A, and a bit more sunshine for D will be better overall by providing many other nutrients in addition to the EPA/DHA/A/D.

    We favor vitamin K2 supplements so we don’t need the fermented fish oil for that.

    If you took the cod liver oil with the salmon, beef liver, and eggs, we’d fear too much A and fish oil, especially if combined with a multivitamin.

    If you do take the cod liver oil I wouldn’t take a multivitamin, only a multimineral.

    Best, Paul

  20. > To be honest I’m almost ready to assert the view that we should drop
    > multivitamins, instead take a multimineral supplement and supplement C/D/K
    > as necessary and get all other vitamins from food!

    I have not been taking a multivitamin after Chris pointed out the problems with choline. But I do take many of your other recommendations, but based largely on your book and website. For example, I take the optional B’s. If you change your view, could you be explicit about it?

  21. Hi Jeremy,

    Yes, of course, we’ll do blog posts and alerts with any changes in recommendations.

    I see replacing a multivitamin with a multimineral as a relatively minor tweak – it is probably an improvement for those eating very healthy home-cooked nutritious foods, and may be a loss for those eating less nutritious foods.

    I’m also starting to lean toward including more vegetables, which also reduces the argument for a multivitamin. I’ll be blogging about that in months ahead.

  22. I’ve noticed there are substantial differences in the amount of Vitamin A in various multis. I’ve been using the Centrum Silver, which has 2500 IUs. The other multi you have listed, Rainbow Light, has 5000. I’ve seen some as high as 7000. I eat 14 eggs per week, as well as approximately 1/3 lb of beef liver, which according to fitday adds up to 47,547 IUs of Vitamin A per week from food. Guess I might be getting enough from food alone!

  23. Hi Kate,

    Yes, I think that is enough from food alone, and you are doing very well to eat so much eggs and liver!

    I think you might do well to just take a multimineral tablet, not a multivitamin, and let the food supply the vitamins.

    I’ll put up some multimineral suggestions on the supplements page soon.

    Best, Paul

  24. Here are some multi mineral possibilities. All are available on Amazon. A lot of multi mins seem to be formulated with either a lot of calcium or a lot of copper (which clearly would not work with liver consumption), and most have iron. This looks like a good possibility with iron:


    These are the best I could find without iron:



  25. Thanks, Kate! I appreciate you sharing your research.

  26. “Finasteride raises DHA levels, and DHA lowers testosterone”

    What is the evidence for this? In fact, finasteride raises testosterone levels slightly(PMID:14624915). Perhaps you have DHT and DHA confused?

  27. Hi yoyo,

    The evidence is internal to the Brasky study. While finasteride may not raise DHA much for the median person, a fraction of persons developed very high DHA but not EPA levels on finasteride but not on placebo. So finasteride may raise testosterone for most users, but possibly (and hopefully the study authors will address this issue some day) finasteride leads to lower testosterone for the minority who develop high DHA.

    However, this is not what I think the mechanism for trouble from DHA is. I think it’s the angiogenesis mechanism. I spelled out the testosterone possibility as a way of rescuing Peter’s idea, and acknowledging that other mechanisms were possible.

    Best, Paul

  28. Paul —

    Great series. I tried my best to keep up.

    Recently someone I know had metastatic melanoma discovered in her lungs. Fairly dim prognosis, sadly.

    She’s adopted the “Budwig Diet,” which is apparently a popular anti-cancer approach: no “sugar,” no salad oils, but heavy in flaxseed oil, fruit, cottage cheese, all nuts (except peanuts), and a fair amount of grains. No to low meat, butter, sat fat in general.

    http://imgur.com/acODs has a graphic, and you can read more about here: http://www.cancure.org/budwig_diet.htm

    My initial response was alarm — given what I view to be curious inconsistencies (no sugar but heavy fruit… no salad oils but any nuts…) and high omega-3, but then I had pointed out that flaxseed at least on the surface doesn’t provide direct DHA. It was at that point I realized I was in over my head.

    Any thoughts on this vis-a-vis this latest series? I also thought it interesting to look at a fairly common anti-cancer diet. thanks as always!

  29. Hi John,

    I’ve had several requests for cancer advice so I’ll do that this week.

    Flaxseed is probably beneficial for cancer patients, in moderation. Getting rid of salad oils / omega-6-rich oils is also good. Getting rid of sugars is good.

    Grains are not good.

    Dietary influences upon cancer is a very complicated issue, but I think there’s a fair amount of evidence at this point.

  30. Steve Brecher

    consumerlabs.com just updated their review of fish oil supplements with a brief discussion of the Brasky paper and of their recent communication with him about it. They report him as saying that his paper did not reflect supplement use; that a forthcoming study by him shows no association between fish oil supplement use and prostate cancer risk; and other research (http://www.ncbi.nlm.nih.gov/pubmed/20844069) has shown supplementation to be associated with a large reduction in late-stage and fatal prostate cancer risk.

    consumerlabs.com is a paid membership site.

  31. Steve Brecher

    In my previous comment, make the two references to a web site: consumerlab.com

  32. Thanks, Steve. I was just emailed that by another reader.

    It looks like it probably is the case that finasteride, not fish oil consumption, was driving the high tissue DHA levels.

    It will be very interesting to see the data on fish oil consumption vs cancer.

  33. For the men on Finasteride, there is another possibility: It has been shown that 5-Alpha Reductase Over-Inhibition by Finasteride reduces DHT and can cause higher grade prostate cancer. See http://meridianvalleylab.com/5-alpha-reductase-over-inhibition/

    “…While 5?-DHT has been implicated in male pattern baldness and benign prostatic hypertrophy, the real concern is prostate cancer. As early as 1986, it was suspected by some that 5?-DHT might be the main contributing factor to prostate cancer growth.4 However, recent studies have correlated low levels of DHT with decreased survival in prostate cancer patients.5,6,7

    Over-inhibition of 5-alpha reductase also results in decreased amounts of the metabolites of DHT, which include 3beta-Adiol (5alpha-androstane-3beta,17beta-diol), an anti-proliferative hormone that may help prevent prostate cancer. 10”

  34. Thanks, ron. Great find!

  35. sorry, I made a mistake with the link above. The correct link is

  36. Thanks, ron, I’ve corrected the link in your earlier comment. It is a very interesting piece.

  37. Re: Rosacea

    When you say high dose fish oil is a well known trigger for rosacea — does that caveat also apply to food sources such as cod liver oil, tinned sardines, poached wild salmon etc?

    I’ve experienced bouts of rosacea since hitting middle age. The rest of my body skin tans easily and is not sensitive — but my facial skin now is prone to bouts of redness plus blepharitis. The adding carbs did nothing for me and as I’ve written before, so many middle aged women do not follow low carb diets and yet they too suffer from these skin and eye changes when they hit mid life. I eat oily fish in the form of sardines 4 to 5 times per week plus 1-2 meals of wild salmon. I have not noticed extra flushing on those days. Pollen and sunlight seem to be triggers or some unknown allergy — but it’s really a nuisance — little red veins staying after the flushing. Not pretty.

    After a bout the past few days — I tried something that gave me relief. I took 1/4 teaspoon of ascorbic acid and mixed with 1/4 cup water and applied to face with cotton pad. It stung a tad. I waited several hours to see if any bad reactions would occur. No problems and my face actually appeared a little less red. Feeling adventurous, I then took 1/2 teaspoon of ascorbic acid and mixed with 1 tablespoon water. I applied this to my face — even under eyes — it stung a little but this stopped after a few minutes. Once dried, I added a thin layer of aloe vera gel (I was out of the plant so unfortunately had to use a commercial product that contains chemical preservatives and went to bed. The next morning — my red, itchy inflamed face was totally clear — completely clear. I know vitamin c is supposed to alleviate allergies but taking it internally did not stop the skin inflammation the way this did.

    I am also looking into trying an astoxanthin supplement for the blepharitis that often accompanies the facial flushing.

  38. Hi Annie,

    Very interesting result! Thanks for sharing.

    You might try the same thing internally, using a vitamin C and water toothpaste and brushing the inside of your cheeks and gums with it.

    I would expect the blepharitis to disappear shortly. That’s been my experience.

  39. Thanks Paul. Are you not concerned that the ascorbic acid will destroy your tooth enamel?

  40. Not really. It’s only for a brief period each day. Saliva will dilute it. Teeth if they’re well mineralized should stand up to weak acids. Since vitamin C in blood prevents tooth decay (http://www.ncbi.nlm.nih.gov/pubmed/8016554, http://www.ncbi.nlm.nih.gov/pubmed/2676112), and vitamin C is needed for collagen formation, oral vitamin C will promote enamel repair as well as erosion.

  41. Hi all,
    does anyone have any info (&/or links) on the fatty acid ratios in healthy human skin cells?

    trying to find some info on (optimal, ideal) omega content & type, 3,6,9 etc… LA/GLA/EPA/DHA etc….


  42. Thanks for the link Paul.

    I know you cover dietary & supplemental intake of Fatty Acids in great detail in your book & also in some great posts here.
    Have you any posts that cover fatty acid intake (absorption) through the skin; i’m talking oils.

    i want to start putting some good natural organic oil on my skin, mainly where i have dry skin; on my face & lower legs. Of course i don’t want to put anything on my skin that could potentially harm.

    I’m wondering if what may be beneficial to put on the skin, differs from what is beneficial in the diet.
    From the link you sent above, the fatty acid composition of skin in 21-33yr olds looks to be something approx like;
    Oleic (mono) 34%
    Palmitic (safa) 24%
    Linoleic (pufa) 15%
    Stearic (safa) 7.5%
    ETA (pufa) 7.5%
    Palmitoleic (mono) 5%
    I assume leaving approx 7% for others.
    There was no mention DHA or EPA.

    So, is it too simplistic to think that any oil you put on your skin should try & match the above fatty acid profile.

    Some natural oils i have seen in the local shops are;
    Grape Seed oil, Apricot Kernel oil, Emu Oil, Hemp Seed oil.
    & i’ve tried these two;
    EPO: a bit too sticky & greasy for the face & has an odd smell.
    Walnut: absorbs well & smell is okay (not strong).

    This site http://www.essentialoils.co.za/lipids.htm has the fatty acid analysis of quite a few oils.

    Emu Oil is probably the most expensive, the ‘sales pitch’ reads “emu oil and human skin are almost identical in fatty acid levels”.

  43. Darrin, coconut oil is an excellent skin oil. Use the same extra virgin coconut oil you use for food. A Google search will give you lots of tips on using coconut oil as a skin oil, particularly for dry skin or eczema. Coconut oil and shea butter are the two best skin oils available.

  44. Thanks Gary,

    I’ll take a look in to the Shea butter.

    I can’t stand the smell of coconut oil, so i’ll stick to eating it; I’ve tried 5 or more different brands, all organic extra virgin etc, in the search for for a no or less smell, but they all smell to strong for me.

    tho, i did try mct oil on the skin, which has no odour.

  45. Darrin, try expeller pressed coconut oil. It has much less taste and odor as compared to extra virgin coconut oil (and is also cheaper).

  46. Ah, Paul, you broke my heart in your reply to Jon W above when you recommended limiting consumption of liver. 😉

    Beef and chicken livers are about the only organ meats I find readily available, and they make me feel like a million bucks. I have been eating way more per week than your recommended limit. If I could buy cow brains (as discussed in Emily’s great “Zombieland” post) to diversify my organ meats, believe me, I would.

    I worry that if I significantly reduce my consumption of liver and fish — alas, I’ve also been eating more than 1 lb of fish per week (mostly salmon and sardines) — I’ll get stuck eating mostly muscle meats for protein. I eat egg yolks regularly, but am prone to developing food allergies, and therefore wary of eating more. Shellfish are great, but a bit too expensive to be a staple.

    Should I be worried about consuming mostly muscle meats for protein? Do you and Shou-Ching eat a lot of organ meats, or mostly muscle meat? Am I overlooking some obvious alternatives?

    Thanks again for all of the great advice and insights you provide.


  47. Hi Vincent,

    Chicken liver is low in copper and the vitamin A upper limit for those who get plenty of vitamin D and K2 is obscure. So if the chicken liver is significant you may be OK there. Re fish, lots of fish are low in omega-3, so if you diversify from omega-3-rich salmon and sardines to other fishes as well, you can eat as much fish as you like.

    If you’re feeling great, change as little as possible.

    We do eat a fair amount of muscle meats, but shellfish, salmon, liver, and eggs add up to more than half our protein, and collagen from bone broth adds maybe 10% or a bit more.

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