DHA Supplements and Prostate Cancer

A study was released this month that correlated a higher percentage of omega-3 fatty acids in the blood, especially DPA and DHA, with an increased risk for prostate cancer. This made big news and the merits of the study have been debated and people have been asking me if it would make me change my recommendations for taking DHA.

The study by Braskey et al (1) was funded by the National Cancer Institute and was a case-control analysis. It was also an offshoot of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). There were numerous statistically significant findings with the strongest being for DHA. A DHA percentage of >3.62 was associated with a 39% increased risk of prostate cancer when compared to a DHA percentage of < 2.33 (1.39, 1.06-1.82). The finding was stronger for low-grade prostate cancer while insignificant for high-grade.

Interestingly, ALA levels were not associated with an increased risk of prostate cancer and the omega-6 fatty acid, linoleic acid (LA), was slightly associated with a reduced risk.

Additionally, the researchers performed a meta-analysis of 7 similar studies and again found that DHA was associated with an increased risk of prostate cancer (1.16, 1.03-1.31). In the 5 studies that separated low-grade versus high-grade, both low (1.20, 1.04-1.38) and high (1.48, 1.10-1.99) were associated with an increased risk.

As I see it, the strengths of the study are:

– Percentage of fatty acids in the blood is possibly a better indicator of actual intake (or absorption) than a food frequency questionnaire.

– The follow-up was about 8 years, which seems long enough to eliminate the possibility of reverse causation in which DHA levels might be elevated due to the prostate cancer.

The potential weaknesses of the study are:

– Measuring fatty acids as a percentage rather than an absolute amount could be misleading. One person might have a higher percentage of DHA, but a lower total amount of DHA. For example, if you eat a very low-fat diet but with a bit of fish, then your DHA will be high as a percentage, but could possibly be lower, in total, than someone who eats a large amount of fat including fish. In other words, it could be that people with a higher percentage of DHA actually have a lower absolute amount of DHA. I don’t know how likely this is, but it doesn’t seem to be out of the question if many fish-eaters are on low-fat diets. Given some of the findings from other studies I’m about to discuss, this might be plausible.

– The whole project of associating the percentage of various fatty acids with various cancers has been fraught with null, inconsistent, and weak findings. When this is the case, it’s a good indication, in my opinion, that there is nothing really there.

This study was criticized by Dr. Michael Murray in his July 22, 2013 article, Does Fish Oil Really Boost Prostate Cancer? One interesting point he makes is that the omega-3 levels in those with prostate cancer were not very high. Those without cancer had an average DHA level of 2.91% (95% CI: 2.86-2.96) while those with cancer had a level of 3.01% (95% CI: 2.95-3.08). People taking fish oil supplements tend to have amounts quite a bit higher than that.

I will go a step further than Dr. Murray and suggest that the differences between the two groups, while statistically significant, are so minor as to be practically meaningless: a DHA level of 2.91% is pretty much the same as 3.01%. Even when you add EPA + DPA + DHA together, the difference is hardly anything (4.48% for the no cancer group vs. 4.66% for the cancer group).

What about studies measuring intake?

A 2006 meta-analysis of 7 cohort studies found no significant association with the incidence of prostate cancer and intake of EPA or DHA (2). A 2010 meta-analysis of fish consumption and prostate cancer, which included most of the studies from the 2006 meta-analysis plus many more, found no association between fish consumption and prostate cancer incidence, and a reduced risk for prostate consumption mortality (3).

Speaking of fish, there is a question as to whether the association between omega-3 percentage and prostate cancer found in Braskey et al could be explained by mercury contamination of fish. While I found a study indicating that mercury levels in humans are correlated with fish consumption (4), I could not find any examining an association between mercury and prostate cancer. I did find two sources which indicate that if mercury causes prostate cancer, no one seems to know about it yet (5, 6).

So where does this leave us? I have a friend who pointed out that the mere idea that DHA could cause prostate cancer is ridiculous given what an important component of brain tissue DHA is. That’s an interesting perspective, though something good for the brain is not necessarily good for the prostate. I do think his point should increase the burden of proof needed before concluding that DHA causes prostate cancer.

One final point is that vegans who do not supplement with DHA tend to have DHA levels around 1%. As I reported recently, we have an anecdotal report of a 60-year old vegan man who raised his DHA levels from 1.0% to 4.8% using 320 mg of DHA plus 130 mg of EPA per day. My recommendations are for vegetarians 60 and under to supplement with 200-300 mg every other day and for vegans over 60 to supplement with that much every day. If you are someone who is at high risk for prostate cancer, I can see supplementing on the lower side of these recommendations (though I cannot tell any given individual what amount they personally need) to keep your levels below the 3.6% cutoff in Braskey et al.

In summary, I’m skeptical that DHA causes prostate cancer, but if you are at high risk, it might be prudent to stick to the lower end of the daily recommendations until more is known.

Support JackNorrisRd.com

Please share and/or like my posts! Thanks!

I greatly appreciate donations of any amount and it allows me to spend more time on nutrition (click here).

Amazon.com Gift Cards – E-mail Delivery

Vegan for Life: Everything You Need to Know to Be Healthy and Fit on a Plant-Based Diet from Amazon.com

References

1. Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst. 2013 Jul 10. [Epub ahead of print] | link

2. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA. 2006 Jan 25;295(4):403-15. Review. Erratum in: JAMA. 2006 Apr 26;295(16):1900. | link

3. Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010 Nov;92(5):1223-33. doi: 10.3945/ajcn.2010.29530. Epub 2010 Sep 15. | link

4. Yoshizawa K, Rimm EB, Morris JS, Spate VL, Hsieh CC, Spiegelman D, Stampfer MJ, Willett WC. Mercury and the risk of coronary heart disease in men. N Engl J Med. 2002 Nov 28;347(22):1755-60. (I only read the abstract.) | link

5. Landrigan PJ. Occupational and community exposures to toxic metals: lead, cadmium, mercury and arsenic. West J Med. 1982 Dec;137(6):531-9. | link

6. Järup L. Hazards of heavy metal contamination. Br Med Bull. 2003;68:167-82. | link

27 Responses to “DHA Supplements and Prostate Cancer”

  1. Tyler Says:

    ” I have a friend who pointed out that the mere idea that DHA could cause prostate cancer is ridiculous given what an important component of brain tissue DHA is.”

    This would be like saying that the mere idea that cholesterol could cause heart disease is ridiculous given what an important component cholesterol is throughout the body.

    Also, people with low-fat intakes don’t necessarily have low blood levels of fats and I imagine the people in the study had fairly similar fat intakes to begin with.

  2. Andreas Says:

    “It is further possible that a large part of the electrophysiological effects attributed to n-3 PUFAs may be dependent on their oxidation. An interesting study led by Sébastien Judé of Nutrition, Croissance et Cancer in France showed that the electrophysiological effects of DHA on the transient outward current in cardiomyocytes were only present when the DHA was oxidized with a small amount of hydrogen peroxide; DHA on its own was much less effective.10 This finding led the authors to speculate that perhaps it is oxidized derivatives of DHA that are responsible for many of the electrophysiological effects of DHA observed to date—primarily in culture dishes, where DHA is exposed to room air and thus likely to be oxidized.”

    LINK: http://www.the-scientist.com/?articles.view/articleNo/32901/title/Omega-3s–Fishing-for-a-Mechanism/

    http://www.ncbi.nlm.nih.gov/pubmed/12813005

  3. Dan Says:

    Jack, your reading on this is concise and explanatory.

    However, I distrust most associational studies in nutritional epidemiology and pharmacoepidemiology, given the number of studies I have seen linking healthy user bias with outcomes.

    Having said that, I had thought that %FFA (e.g. %DHA in phospholipid membranes) is the STANDARD measurement for DHA levels in a person.

    I wonder if Dr. Michael Murray has pre-existing views and opinions on omega-3’s that cause him to distrust any new, negative research on the subject. I certainly am initially disinclined to distrust research that comes out and contradicts what I previously thought – ie my preconceptions and views.

    Having said that, given my own family history of prostate cancer, and my father’s disease in a pesco-vegetarian setting with lots of DHA/EPA on board, I am stopping my vegan DHA supplement after this bottle runs out. I also agree with Tyler’s comment.

    Andreas, I enjoyed the fishing for a mechanism article; and I thank you for bringing it to my attention. The scientists seem to suggest that exposure to omega-6 at high levels as they are found in a typical western diet is a classic example of hormesis, i.e. inducing ‘immunity’ based on subtoxic levels of a substance by boosting antioxidant genes and other protective pathways. I wonder if the same can be said of vegan cadmium levels.

    “It has long been known that 4-hydroxynonenal, an aldehyde formed from the oxidation of n-6 PUFAs (primarily found in corn and vegetable oils and a huge part of our diet), can both help and harm the heart. At subtoxic concentrations (≤10µM), 4-hydroxynonenal exerts a beneficial “hormetic” effect that activates antioxidant response gene pathways. At higher concentrations, however, 4-hydroxynonenal causes cell death. Yan Zhang of the Keio University School of Medicine in Tokyo and colleagues recently showed that treating cardiomyocytes with small, subtoxic doses (5µM) of 4-hydroxynonenal offers protection from subsequent exposure to toxic doses (≥20µM).7 This group further showed the physiological relevance of this effect by pretreating mice with 4-hydroxynonenal prior to restriction of their coronary blood supply, and showed that treated mice fared better: less of the ventricular tissue died following the simulated heart attack.”

  4. Andreas Says:

    Dan,

    I dont think the scientists are suggesting exposure of omega 6 at high levels causes harm. Excess non-oxidized omega 6’s & 3’s are stored in adipose tissue. along with other fatty acids.

    To my undestanding, they are saying that “4-hydroxynonenal” is formed in the body as a consequence of oxidative stress and its also produced when omega 6 fatty acids are exposed to air, light and oxygen during the production of oils. Basically, the high exogenous amounts of 4-hydroxynonenal found in oils are absorbed and cause cell death as they indicate.

    http://en.wikipedia.org/wiki/4-Hydroxynonenal

    linoleic acid hydroperoxides produced from linoleic acid during oil production are other problematic molecules.
    http://www.ncbi.nlm.nih.gov/pubmed/18293301

    Cadmium inducing oxidative stress.
    http://www.ncbi.nlm.nih.gov/pubmed/19236887
    http://www.ncbi.nlm.nih.gov/pubmed/20361350
    http://www.ncbi.nlm.nih.gov/pubmed/16507456

    Cadmium and production of inflammatory eicosanoid, TXA2.
    http://www.ncbi.nlm.nih.gov/pubmed/12495261
    http://openagricola.nal.usda.gov/Record/IND23279376
    — My understanding is that the researchers from these studies used very high levels of cadmium and I don’t know if we could get high levels of cadmium like those in these studies from eating food.

  5. Jack Norris RD Says:

    Andreas (or anyone who knows),

    One thing I’m not clear on is what becomes of an oxidized fatty acid, and whether any (or all) oxidized fatty acids are counted when someone’s blood level of that fatty acid is measured. My understanding is that oxidation can either remove a hydrogen, in which case the molecular structure is the same except that it becomes negatively charged [wrong -- see below]. Or it can add an oxygen, in which case the molecular structure is changed by one oxygen (or the addition of an entire molecule attached to that oxygen?).

    If I am correct in this understanding, does anyone know if, at the very least, the negatively charged version of the molecules would show up in the measurement of the fatty acid?

  6. Andreas Says:

    Jack,

    My understanding is that oxidized fatty acids are lipid radicals, lipid peroxyl radicals and lipid peroxides/hydroperoxides.
    Here: http://en.wikipedia.org/wiki/Lipid_peroxidation

    Simple lectures on the topic:
    http://naldc.nal.usda.gov/download/25421/PDF
    http://class.fst.ohio-state.edu/fst605/605p/LipidOxidation.pdf

    Exogenous antioxidants prevent the production of lipid radicals in the body by preventing free radicals from damaging the fatty acids in the cell membranes.
    http://www.sciencedirect.com/science/article/pii/S0003986100920356
    http://www.ncbi.nlm.nih.gov/pubmed/10958813

    I am mainly referring to the oxidized fatty acids found in PUFA oils that we absorb and not the oxidized fatty acids that are produced by free radicals oxidizing the fatty acids in cell membranes and lipoproteins.

    Free radicals, oxidants, that induce lipid peroxidation in the body:
    http://www.ncbi.nlm.nih.gov/pubmed/17713644
    http://www.ncbi.nlm.nih.gov/pubmed/23559632
    http://www.ncbi.nlm.nih.gov/pubmed/21517278

  7. Jack Norris RD Says:

    > My understanding is that oxidation can either remove a hydrogen, in which case the molecular structure is the same except that it becomes negatively charged.

    I misspoke. If you lose an electron through losing an entire hydrogen, it would become a different structure. If you lose an electron only, it would become positively charged but with the same structure.

  8. Dan Says:

    Regarding cadmium and veganism, wouldn’t it be better to ask one’s physician to test either blood or urine cadmium levels and confirm they are elevated beyond the normal range, prior to starting someone on lifelong daily zinc supplementation (which has costs, inconvenience, unknown benefits, and potential risks)?

    Saying every vegan should take low-dose zinc is like saying every vegan should take an iron supplement, just to prevent anemia in a few people. I prefer targeted, tailored, personalized approaches to health prevention, rather than blanket recommendations. There are probably some people who do have very high levels of cadmium who could benefit from either chelation or oral zinc supplements; the key is identifying them, not treating the entire population of vegans with zinc.

    JMHO.

  9. Jack Norris RD Says:

    Dan,

    From the reading I did, chelation therapy doesn’t work for cadmium – it’s better to be proactive. I am not giving any “official” recommendations for zinc for vegans, but given that vegans’ zinc intakes are low, that zinc is less absorbed from plant foods, and that vegans’ cadmium levels are higher than omnivores and increase over time, I don’t see the harm in suggesting the amount of zinc I have suggested.

    It’s my honest opinion and that’s what my reader’s want from me. But no one is bound by it.

    Suggesting that every vegan should go out and get their cadmium levels tested seems a bit much to me, but if someone wants to, more power to them. I just don’t see the dangers of a bit of extra zinc to warrant that.

  10. Dan Says:

    Hi Jack,
    There is an interesting series of letters in JAMA this week speculating that the benefit in the recent TACT randomized trial on chelation in patients with coronary artery disease was due to reduction in total body cadmium levels.

    Also of note is that the Adventist Health Study-2 showed large protective associations on renal mortality for vegetarianism in the U.S. Given that the main toxicity of cadmium is kidney disease, and progression to renal failure, if vegans had higher cadmium burdens and toxicity thereof, wouldn’t it show up as an increased signal of harm in AHS-2? I am also interested to know if EPIC replicated this finding.

    Lastly, I wouldn’t suggest every vegan get tested, but if they’ve been vegan for more than about 5-6 years, which seemed to be the breakpoint in the Slovak study (perhaps my memory is not best here), it might be reasonable to get a cadmium test done. As per the monograph I sent you, cadmium intake is much lower in the US than in some other areas like Japan and Belgium.

    Regarding whether there would be any harm from extra zinc, we just don’t know. I prefer not to play around with heavy metals, or unproven dietary supplements. In the massive Heart Protection Study (20,586 patients), a cocktail of antioxidants including zinc showed absolutely no benefit on cancer or cardiovascular disease after 11 years of follow-up. We know from some supplementation trials (folic acid, vitamin E, vitamin A), that these things do sometimes cause unexpected and unanticipated toxicity. I try to stay well within the RDI set by the IOM and other sources, and minimize supplementation to the bare minimum. It is not all that hard to get zinc from a whole plant foods diet.

  11. Dan Says:

    I must correct myself. The upper limit for zinc intake in adults (age>18) is 40 mg/d. Adding a supplement of 10 mg per day is unlikely to exceed this.

    Humans are apparently able tolerate to intake of approximately 110 mg/d (100 mg supplement plus 10 mg dietary intake), at least for 9 months (http://ajpregu.physiology.org/content/263/5/R1162.reprint).

    Very high zinc intakes (>150 mg/d) can lead to copper deficiency (http://jama.jamanetwork.com/article.aspx?articleid=362186).

    Approximately 45% of the general population may have dietary zinc deficiency:

    http://jn.nutrition.org/content/130/5/1367S.long

    Thus I can’t see any harm with adding zinc at a dose of 10 mg/d. On the other hand, I think the benefit remains highly theoretical, and I am not sure the expense and inconvenience would be justified, except perhaps in long-term vegans living in cadmium-contaminated countries (e.g. Japan and Belgium):

    “The daily intake of cadmium through food varies in part by geographic region. As an example, intake is reported to be approximately 8 to 30 mcg in Europe and the United States, versus 59 to 113 mcg in various areas of Japan [8]. There is also a wide individual variation in cadmium intake based upon the type and amount of food consumed. Since this variation follows a log-normal distribution, most individuals ingest between 4 and 60 mcg per day (eg, ±2 SD) if the average individual intake is 15 mcg per day [6,9].

    Since the average gastrointestinal absorption is five percent, the net absorbed amount of cadmium is approximately 1 to 2 mcg per day in Europe and the United States, and up to 5 mcg in “non-polluted” areas in Japan. A slight degree of iron deficiency markedly enhances the absorption of dietary cadmium (and iron) from the gastrointestinal tract; this phenomenon is one reason why women constitute a risk group for environmental cadmium exposure.”

  12. Andreas Says:

    “We know from some supplementation trials (folic acid, vitamin E, vitamin A), that these things do sometimes cause unexpected and unanticipated toxicity.”

    Synthetic supplements* There is whole food supplements.

    Regarding cadmium,

    Dr Gregor did this video(http://www.youtube.com/watch?v=_E1FXNGswoU) on phosphorus and he cited a study where vegans were able to clear more phosphorus out from the blood than omnivores.

    Maybe those who consume animal products have higher tissue levels of cadmium and lower levels of cadmium in the urine. Maybe we vegans can clear cadmium in urine because of our higher antioxidant intake.

    Here is an interesting 2013 review on cadmium and antioxidants that I haven’t read completely: http://www.eurjchem.com/index.php/eurjchem/article/view/739

    Jack, is there any study which compares the blood and “urine” omnivores and vegans? – You pointed out urine cadmium on the cadmium page, end of the chart, but I didn’t see the study. Is there a study?

  13. Jack Norris RD Says:

    Andreas,

    No, urine cadmium levels were not measured in the study.

  14. Dan Says:

    Andreas, urine cadmium levels reflect cumulative exposure burden simply because cadmium is bioconcentrated in the kidney tissue. Blood levels (and I presume hair levels) reflect more recent, acute exposures. There is a paper from 1992 that I posted here showing that 3 months on a lacto-vegetarian diet lowered hair cadmium levels by approximately 27% (p<0.0001). The authors speculated that the co-absorption of calcium in the dairy foods was what blocked cadmium uptake in that diet.

    I don't know of any data to suggest that antioxidants are effective for ameliorating cadmium toxicity. According to what I have read, the treatment is purely supportive (e.g. dialysis), and actually largely aimed at prevention of ongoing exposure.

    It would be nice to have an animal study showing that zinc intake modulates cadmium uptake, but I don't know of any (haven't checked though). I am not too concerned because I do not live in a heavily-cadmium contaminated country (e.g. Japan, Belgium). I do however eat soybeans from China every day. I might stop buying those but I believe that cadmium levels in legumes are not particularly high (especially as compared with grains, e.g. wheat, rice and seed oils).

  15. Dan Says:

    I spoke too soon. I found this interesting paper:

    Environ Res. 2009 Oct;109(7):914-21. doi: 10.1016/j.envres.2009.07.006. Epub 2009 Jul 31. Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women–a prospective cohort study. Kippler M, Goessler W, Nermell B, Ekström EC, Lönnerdal B, El Arifeen S, Vahter M. Source Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
    Abstract
    Experimental studies indicate that zinc (Zn) and calcium (Ca) status, in addition to iron (Fe) status, affect gastrointestinal absorption of cadmium (Cd), an environmental pollutant that is toxic to kidneys, bone and endocrine systems. The aim of this study was to evaluate how various nutritional factors influence the uptake of Cd in women, particularly during pregnancy. The study was carried out in a rural area of Bangladesh, where malnutrition is prevalent and exposure to Cd via food appears elevated. The uptake of Cd was evaluated by associations between erythrocyte Cd concentrations (Ery-Cd), a marker of ongoing Cd exposure, and concentrations of nutritional markers. Blood samples, collected in early pregnancy and 6 months postpartum, were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Ery-Cd varied considerably (range: 0.31-5.4microg/kg) with a median of 1.1microg/kg (approximately 0.5microg/L in whole blood) in early pregnancy. Ery-Cd was associated with erythrocyte manganese (Ery-Mn; positively), plasma ferritin (p-Ft; negatively), and erythrocyte Ca (Ery-Ca; negatively) in decreasing order, indicating common transporters for Cd, Fe and Mn. There was no evidence of Cd uptake via Zn transporters, but the association between Ery-Cd and p-Ft seemed to be dependent on adequate Zn status. On average, Ery-Cd increased significantly by 0.2microg/kg from early pregnancy to 6 months postpartum, apparently due to up-regulated divalent metal transporter 1 (DMT1). In conclusion, intestinal uptake of Cd appears to be influenced either directly or indirectly by several micronutrients, in particular Fe, Mn and Zn. The negative association with Ca may suggest that Cd inhibits the transport of Ca to blood.

    …and this…

    Toxicol Appl Pharmacol. 1996 Feb;136(2):332-41. Bioavailability of cadmium from shellfish and mixed diet in women. Vahter M, Berglund M, Nermell B, Akesson A. Source Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Abstract
    Dietary intake and uptake of cadmium (Cd) were studied in nonsmoking women, 20-50 years of age, consuming a mixed diet low in shellfish (N = 34) or with shellfish once a week or more (N = 17). Duplicate diets were collected during 4 consecutive days for the determination of Cd content. The women kept detailed dietary records, and the intake of energy and various nutrients was calculated. The shellfish diets (median 22.3 micrograms Cd/day) contained twice as much Cd as the mixed diets (median 10.5 micrograms Cd/day; p < 0.0001). Cadmium in feces corresponded to 100 and 99% of that in duplicates of shellfish diets and mixed diets, respectively, indicating a low average absorption of the dietary Cd. In spite of the differences in the daily intake of Cd, there was no statistically significant difference in the concentrations of Cd in blood (B-Cd, shellfish group 0.25 micrograms/liter, mixed diet group 0.23 micrograms/liter) or urine (U-Cd, 0.10 micrograms Cd/liter in both groups). This indicates a lower absorption of Cd in the shellfish group than in the mixed diet group or a difference in the kinetics. A higher gastrointestinal absorption of Cd in the mixed diet group could partly be explained by lower body iron stores as measured by the concentrations of serum ferritin (S-fer, median 18 micrograms/liter, compared to 31 micrograms/liter in the shellfish group). In the mixed diet group, S-fer was negatively correlated with B-Cd and the main determining for B-Cd besides U-Cd in the multiple regression analysis, indicating an increased absorption of Cd at low body iron stores. When women with S-fer exceeding 20 micrograms/liter were compared, the higher dietary intake of Cd in the shellfish group compared to the mixed diet group (24 versus 10 micrograms/day) resulted in higher B-Cd (0.26 versus 0.16 micrograms/liter), although not in proportion to the difference in Cd intake. Thus, there seems to be differences in the bioavailability and/or kinetics of dietary Cd related to the type of diet. This is, to our knowledge, the first study where the influence of various types of diets and nutritional factors on the intake and uptake of cadmium in human subjects has been studied.

    …and similarly…

    Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. M Berglund, A Akesson, B Nermell, and M Vahter. Abstract

    Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Dan Says:

    …the part that was missing…

    UCd was mainly correated with age, fiber intake, cadmium intake, and serum ferritin, besides BCd. Age and fiber intake explained 22% of the variation in UCd. The results of the present study indicate that BCd may reflect body burden at long-term, low-level cadmium exposure.

  17. Andreas Says:

    Thanks Jack for taking a look.

    Dan,

    Interesting studies you’ve linked however its too bad the study that measured urine cadmium levels is not free. I would of liked to take an actual look at the paper.

    Antioxidants ameliorating cadmium (and lead):
    http://www.eurjchem.com/index.php/eurjchem/article/view/739
    http://www.ncbi.nlm.nih.gov/pubmed/20021251
    http://www.ncbi.nlm.nih.gov/pubmed/10969995
    http://www.ncbi.nlm.nih.gov/pubmed/17873360
    http://www.hindawi.com/journals/vmi/2011/457327/

    Role of diet in absorption and toxicity of oral cadmium-A review of literature
    http://www.ajol.info/index.php/ajb/article/download/77756/68178

    Lutein and Zeaxanthin are other very potent antioxidants that cure cancer and are found mainly in leafy greens.
    http://www.ncbi.nlm.nih.gov/pubmed/21128180
    http://www.jacn.org/content/23/suppl_6/567S.full

    I don’t agree with you that cadmium is bioaccumulated in the kidney/liver tissue of everyone. (http://www.ncbi.nlm.nih.gov/pubmed/21455421) I’ve seen MAJOR changes in my health from drinking freshly squeezed carrot juice and ingesting an abundance of raw freshly picked leafy greens by chewing them well without condiments.

    Have you ever heard of The Gerson Therapy? And not the misleading information on the wikipedia page of Max Gerson to hide the truth.
    http://www.youtube.com/watch?v=U7Ck9D45OT4

  18. Dave Says:

    What are your thoughts on prostate supplements like:

    http://www.MasterProstate.com

    While they don’t make any claims about cancer, it does have a rather robust ingredient list include 500mg beta sitosterol.

    I’m curious what the experts have to say about these types of pills.

  19. Jack Norris RD Says:

    Dave,

    > What are your thoughts on prostate supplements like:

    I’m afraid I’m not an expert on this.

  20. Dan Says:

    Back to DHA for a bit.

    I hope you don’t mind my attempts to draw debate and discussion from you and your other readers on these important health topics. This is not a game but a matter of great import. Before I recommend a drug or a supplement to someone, I want to be sure that benefit will exceed harm (at least in most cases) – i.e. the benefit of the doubt does not belong with the drug or supplement, it belongs to not prescribing it. In other words, if there is uncertainty, ideally we should not be opting to take or recommend it, because unanticipated toxicity (as seen in so many large randomized trials) can often arise.

    Here are the questions I would ask re: DHA supplementation for vegans.

    1) Are there level 1 randomized trials supporting provision of DHA for improving health (cognitive, cardiovascular, cancer) either in a) vegans; b) non-vegans; c) patients with serious disease?

    2) Barring this, are there strong, prospective, longitudinal cohort studies (ideally with blinded adjudication of outcomes and measurement of DHA levels) associating DHA status with improved health in vegans? Are the results consistent between multiple cohort studies, and is the association strong and independent of measured confounders?

    3) Does taking a DHA supplement have the same physiological and health benefits as consuming intact oily fish? In vegans or non-vegans? Could other fatty acids be involved in the benefit?

    4) Could there be unanticipated side effects or toxicity of taking long-term DHA supplements? (as we have seen for magnesium, folic acid, vitamin E, beta carotene, retinoic acid – just to name a few). What about the risk of prostate cancer in the latest report; and malignancies in females seen in the SU.FOL.OM3 RCT?

    5) Does the benefit of taking long-term DHA justify the price? Vegan DHA is very expensive (at least here in Canada). A 60 capsule bottle of 250 mg of microalgal DHA costs $30 plus 13% taxes. This gets into a discussion of cost-effectiveness.

    I should point out that the last 5 large randomized trials of EPA/DHA supplementation were all negative – OMEGA, ALPHA-OMEGA, RAPS, SU.FOL.OM3, and ORIGIN. Analyses included DHA levels and by baseline fish intake.

    The lack of data proving the benefit of DHA in non-vegans is concerning, although vegans could certainly be more deficient at baseline.

    Have the anecdotal reports you have been receiving on DHA and cognition been published in peer-reviewed journals? I have not been able to find any published case reports on DHA in vegans/vegetarians, and case reports represent the lowest standard of evidence in (human) evidence-based medicine (animal studies are considered lower than human case reports, which is not saying much).

    I would love to take DHA to treat my own probably non-existent DHA status, but won’t chance it until there is some standard of evidence to support it.

  21. Jack Norris RD Says:

    Dan,

    > Have the anecdotal reports you have been receiving on DHA and cognition

    Dr. Fuhrman told me about patients he’s seen, but I personally have not had anyone come to me with this situation.

    http://jacknorrisrd.com/dha-supplements-a-good-idea-especially-for-older-vegan-men/

    Once again, I’m just going to point you to my article on Omega-3s:

    http://veganhealth.org/articles/omega3

    Clearly, it seems that you do not find that evidence to be enough to suggest supplementing with DHA in vegans. I think reasonable people can disagree on that and and although I question it, myself, I always come back to the conclusion that it would be irresponsible of me not to recommend it.

  22. Dan Says:

    Hi Jack,

    Your synopsis is excellent – I just re-read it. There are indeed a lot of observational studies suggesting these long-chain omega-3 polyunsaturated fatty acids are associated with improved health outcomes, but I have always wondered (and continue to wonder) if PUFA levels are simply serving as a marker of a high quality diet. I have personally found in my clinical practice that poorer patients and less educated patients simply detest eating fish – and smoking, obesity, and a myriad of other factors track strongly with socioeconomic status and educational achievement – not all of these factors can be adjusted for.

    It’s a bit like the vitamin D story. There’s observational data suggesting it is associated with every possible health outcome under the sun (no pun intended) ranging from depression and suicide risk to heart disease to cancer to multiple sclerosis, etc. When you consider the type of person who may have low vitamin D status – someone who is relatively sedentary, institutionalized, may have a poor diet, etc – then you begin to wonder whether it’s all just a marker of that type of person’s ‘protoplasm’.

    We need a clinical trial to sort this out, but it is unlikely to happen with vegans. Since many non-vegans are also low in DHA, I will take all the clinical trials that have been conducted in the last 7-8 years (i.e. the statin era) and suggest that they are not showing any benefit for largely non-vegan populations, including in analyses where they stratified by baseline DHA levels and fish intake.

    And with respect to people older than 60 who have been long-time vegans and have very low DHA levels and cognitive issues, I think that anyone who has been a long-time vegan and doesn’t supplement with DHA will end up with low DHA; moreover, cognitive issues become very common after the age of 60 (including mild cognitive impairment eventually leading to dementia in some cases); and there doesn’t seem to be any measurement of DHA in older vegans without cognitive issues — if their DHA status was normal, that would tend to support the theory. Thus a comparison (control) group is needed.

    Here is what UpToDate says on DHA and cognition, in terms of prevention of dementia:

    Omega-3 fatty acids — The potential healthful affects of dietary intake of fish and omega-3 fatty acids on the risk of dementia as well as cardiovascular disease and other health conditions have been studied as well. The findings have been mixed, but most large, longitudinal studies have shown a benefit for higher fish consumption on the risk of dementia, cognitive decline, or the accumulation of white matter abnormalities on brain MRI [31,34-38], with some exceptions [33]. Interest has focused on specific omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the Framingham study, individuals with the top quartile levels of DHA measured at baseline had lower rates of incident dementia over nine years of follow-up [39]. Another prospective study associated higher plasma levels of EPA (but not DHA) with lower rates of hippocampal atrophy over four years of follow-up [40]. In a cross-sectional study, higher levels of ω-3 polyunsaturated fatty acid intake (as assessed through dietary surveys) were associated with lower levels of plasma beta-amyloid, a biomarker of AD [41].

    However, the above-mentioned studies are observational and subject to bias. It is possible that any apparent protective effects of dietary fish intake are due to residual confounding from factors such as education and economic status or due to the effects of fish intake on other processes such as vascular disease. No randomized study has examined the effect of dietary intake of fish and omega-3 fatty acids on the risk of dementia. A meta-analysis of three trials which studied the impact of omega-3 supplementation on cognitive performance found no effect of treatment after 6 to 40 months of supplementation [42].

    Moreover, DHA supplementation did not appear to be helpful in the treatment of patients with mild to moderate AD in one randomized trial [43]. (See “Treatment of dementia”, section on ‘Omega-3 fatty acids’.)

    Here is what UpToDate says about omega-3’s and treatment of dementia:

    Omega-3 fatty acids — Observational studies have suggested a possible association between dietary intake of fish and omega-3 fatty acids and a lower risk of dementia. (See “Prevention of dementia” and “Prevention of dementia”, section on ‘Low cholesterol and low fat diets’.)

    However, clinical trials have not supported a therapeutic role for omega-3 fatty acid supplementation in the treatment of AD:

    An 18-month trial of docosahexaenoic acid (DHA) supplementation in 295 patients with mild to moderate Alzheimer disease found no effect of active supplementation compared to placebo on the rate of cognitive and functional decline [54].

    In a randomized, double-blind trial, 204 patients with mild to moderate AD received omega-3 fatty acid supplements (430 mg docosahexaenoic acid and 150 mg eicosapentaenoic acid, four times daily) or placebo [55]. No significant differences in cognitive decline in the two groups were observed at 12 months.

  23. Jack Norris RD Says:

    Dan,

    If these DHA supplement trials were done on people with DHA levels as low as typically seen in vegans, then I would give them more weight, but my sense is that these people do not have such low DHA levels. By no means would I ever say that the average person’s dementia was caused by a lack of DHA. It could be that only 1% of dementia in the omnivorous population is caused by DHA deficiency and so there would be no way for there to be a benefit in a trial giving DHA to your average dementia patient. That still doesn’t mean that it’s healthy for vegans to have extremely low levels.

    But I hear what you’re saying.

    I look at it like this: There is a lot of evidence suggesting that DHA *might* be an important nutrient for brain functioning. Vegans have much lower levels of DHA. Let’s get vegan’s levels up to about what omnivores have just in case.

  24. Dan Says:

    I hear you. The problem with the ‘let’s get the DHA levels up to omnivore amounts’ has been made for many supplements that have proven harmful in the long run. My favorite example is oral magnesium given to survivors of heart attacks. It is well known that low magnesium is a predictor of coronary disease and in acute heart attacks, many patients have low magnesium levels. When this concept was tested in a clinical trial published in the BMJ in 1993, there was actually a large increase in cardiac events (http://www.bmj.com/content/307/6904/585) – totally the opposite of what would have been expected based on the biomarker studies, the observational data and the pathophysiology.

    We are just not smart enough to figure it all out without controlled clinical trials. Otherwise we would still be recommending vitamin A to male smokers (which killed them), anti-arrhythmics to patients with acute heart attacks (which caused more deaths than all soldiers killed in the Vietnam war, cumulatively), vitamin E (which led to hemorrhagic strokes and heart failure), hormone replacement therapy, etc,

    I do like your argument that if 1% of dementia is related to DHA status, this could be a real problem in vegans, given our very low DHA levels – and that this would be quite difficult to tease out in a clinical trial in a relatively uns*lected MCI population (mild cognitive impairment) with higher DHA levels at baseline. Erring on the side of safety and caution, to prevent this from occurring, one could recommend DHA.

    But I assume you have discounted the cancer findings from SU.FOL.OM3 randomized trial, which I will excerpt here (should we be discounting a >5-fold increase in cancer deaths in women by saying omega-3 are benign?):

    “Results with the full sample and by sex (P = .02 for interaction) are summarized in Table 4. The sex- and age-adjusted full-sample models revealed a lack of effect of the n-3 fatty acids on cancer incidence (HR, 1.17 [95% CI, 0.87-1.58]) or cancer mortality (HR, 1.47 [95% CI, 0.87-2.48]). Among men, there were 72 cancer cases in the n-3 fatty acids group and 73 cases in the comparison group. Allocation to n-3 fatty acids did not have an effect on overall cancer incidence or cancer mortality in men. Among women, there were 21 cases in the n-3 fatty acids group and 8 cases in the comparison group. Positive associations were noted between n-3 fatty acid supplementation and cancer incidence (HR, 3.02 [95% CI, 1.33-6.89]) and mortality (HR, 5.49 [95% CI, 1.18-25.97]).”

    And finally I think there are a host of meat/fish-derived molecules that are probably much lower in vegans (someone else pointed this out earlier I believe). Likely not all have been studied in observational data but I’m sure one day some will be. We’ve picked out DHA (and EPA) because that’s where a huge amount of attention has gone to – careers have been made, dissertations published, grants won. Yet distilling 1-2 servings of oily fish per week down to one or two key molecules daily and expecting the same benefit – not so sure about that. It hasn’t panned out well when applied to other paradigms (vitamin C, vitamin E, vitamin A, etc).

  25. Jack Norris RD Says:

    Dan,

    Weren’t the doses of beta-carotene from the lung cancer study much higher than what someone would typically get in the diet? And how high was the dosage in the SU.FOL.OM3 trial? I suspect much higher than my recommendation of 200-300 mg per day (or every other day for people under 60). Since a few servings of fish per week doesn’t seem to be killing people due to the high omega-3 intake, and I’m suggesting about what someone would get from a few servings of fish per week, I don’t think there is much cause for concern.

  26. Dan Says:

    SU.FOL.OM3 used eicosapentaenoic and docosahexaenoic acid, 600 mg, in a ratio of 2:1; they also used B vitamins in another arm; as well as placebo (it was 2 x 2 factorial).

    Your point about safety is well taken, since DHA is in fish, which eat algae (how they get their DHA – it moves up the food chain from algae to pelagic fish, apparently). So giving DHA should be similar to giving that one component of fish. I do wonder, if one is going to follow the recommendation, whether consuming every 2-3 days would be as beneficial as consuming every day, if there is indeed a benefit to getting the same levels as pesco-omnivores and pesco-vegetarians. If you want to restore normal physiology, get to the same levels.

    By the way, Inuit Greenlanders have some of the highest EPA/DHA levels in the world from marine food. They are typically well protected from thrombotic events like ischemic heart disease, but have a very high rate of hemorrhagic stroke. This was noted back in the 1970s by two intrepid Danish nutritionists. Not that we would be achieving those levels, but it is interesting that it is possible if you eat a massive amount of oily fish to get a hemorrhage.

  27. Richard Wiseman Says:

    this article I found on scholar.google supports your doubts about EPA and DHA (and in fact appears to refute the notion that they elevate the odds of prostate cancer). I am neither a doctor nor a statistician but having had prostate cancer (and prostatectomy) I found it of interest since I am about to take EPA & DHA supplements.

    http://ajcn.nutrition.org/content/80/1/204.short

Leave a Reply

*