Posted 7/19/2013 4:42 PM (GMT 0)
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Material posted here is intended for educational purposes only, and
must not be considered a substitute for informed medical advice from
your own physician.
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From: Stephen Strum, MD, FACP
Board-Certified Medical Oncologist
Specializing in Prostate Cancer since 1983
To: MB URSUS
On Jul 15, 2013, at 3:04 PM, Ursus MB wrote:
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Material posted here is intended for educational purposes only, and
must not be considered a substitute for informed medical advice from
your own physician.
**********
MB URSUS:
Dear Dr. Strum,
about 3 years ago, I sent you a note asking for
your advice concerning my effort to reduce the
odds that I will get prostate cancer.
My father died of prostate cancer, and my psa has
been above typical levels for my age (1.4 at age
40, up to 1.7 by age 44, but then down to 1.5,
where it has stayed pretty constant, using the
Beckman-Coulter hybritech assay).
STRUM: and this TREND is a key that is often
ignored yet it is highly important. Cancer cells
make substances that mark their growth. These
are called biological markers or biomarkers.
A biomarker is a distinctive biological or
biologically derived indicator of a process,
event, or condition. And PSA, despite its
limitations, and at least for me, is a darn good biomarker.
Provisos, however, are always part of life. The
lab analysis should be the same type from one
study to the next. No interferences by
conditions that can raise the biomarker and give
a false impression should exist. Therefore, to
be sure, no ejaculation within 48 hours before
testing for the PSA. And although controversial,
test the same time of the day e.g., morning or
afternoon because many of these tests have a DIURNAL rhythm.
Realize that BPH plays a big part in the
production of PSA. Know what your gland volume
is. Some physicians are very good at estimating
the gland (prostate) volume. I was usually
accurate to within 10 cc of the gland volume
determined by ultrasound or dedicated MRI. The
rule of thumb I used and that seemed at least for
me in my 30 years of PC (prostate cancer)
experience to work is gland volume x 0.067 =
benign related PSA. Therefore a gland volume of
40 cc would equate with 2.68 ng/ml of PSA. In
your case, that would exceed your TOTAL PSA
determination. At age 44, a gland volume of
25-30 cc would be healthy. If 25cc then expected
PSA of 1.675. Realizing this is a CALCULATION,
it would indicate that you do not have
significant EXCESS PSA. In other words, YOUR
total PSA - calculated benign PSA = Excess
PSA. Excess PSA could be attributed to PC.
An example. PSA total is 3.9. Gland volume is
25 cc. Calculated benign PSA is 1.675. Total - benign-related PSA = 2.225.
Given that most PC's today are Gleason score of
6, and knowing that the PSA leak of a GS 6 is
4.26, you would divide the EXCESS PSA of 2.225 by
the PSA leak of 4.26 to get 0.522, which would be
the CALCULATED TUMOR VOLUME. 0.5 cc tumor volume
is the upper level of what could well be
"insignificant PC". The above is a routine
calculation I have used in my practice for a long
time; it has been very helpful and is often
confirmed by those men going for a RP (radical prostatectomy).
Table 1: PSA Leak vs Weighted Gleason Grade
Gleason Grade (Weighted) PSA leak Rounded Off (exact)
5 1 (0.93)
4.5 1.5 (1.36)
4 2 (1.99)
3.5 3 (2.92)
3 4 (4.26)
2.5 6 (6.23)
2 10 (9.12)
1.5 15 (13.33)
1 20 (19.49)
In your case, I have no sense of any risk based
on what you have presented so far. You may have
elements of BPH and also of prostatitis. Most
often, in the setting of PC, and with the
provisos mentioned, the PSA history is one of an
inexorable rise in value over time.
MB URSUS:
Your suggestions included the following:
"Make your diet one that is a CRD (Carbohydrate-restricted diet) &
read The Anti-inflammation Zone by Barry Sears to understand why this
is important. Reduce inflammation further by
obtaining an Essential Fatty Acid
(EFA) profile or Comprehensive Fatty Acid (CFA) profile via the MAYO
MEDICAL LABs. See
<<http://bit.ly/1AtZ7>http://bit.ly/1AtZ7>http://bit.ly/1AtZ7.
Calculate the ratios of
omega 6 to omega 3 and of arachidonic acid to EPA and aim for
1.5. Use a refined fish oil product like Eicosamax Liquid containing
EPA 1500mg, DHA 1200mg per tsp and titrate the dose to respectable
ratios as noted above. Eicosamax is made by Prothera. Most patients
require only 1 tsp to 1.5 tsp to achieve the above Biological End
Point (BEP). So think BEP in all issues of biology--from your health
to that of the environment."
I did these things, though I used a different
brand of fish oil (Nordic Naturals Ultimate
Omega). With supplementation, my EPA was around
350 mnol/mL, DHA around 290 nmol/mL, and AA:EPA ratio around 2.3 to one.
STRUM: that ratio is very acceptable, and most
Americans have ratios of 20:1 up to 40:1 due to
high ingestion of arachidonic acid (ARA) and
little consumption of cold water fish.
MB URSUS:
Should I be concerned that my EPA level is so
much higher than the lab's reference range of 40-100 nmol/mL?
STRUM: In my opinion, and despite the recent
article by Brasky et al, I have never seen the
use of omega-3 fatty acids cause any unexpected behavior.
More importantly, should I be concerned by high
omega 3 levels, in light of the recent and much
publicized study from doctors at the Hutchinson
Cancer Research Institute, which seemed to link
high levels of serum EPA and DHA to an increased
risk of prostate cancer and of aggressive prostate cancer?
STRUM: the medical literature on issues of fish
oil and selenium, lycopene, etc swings back and
forth every decade. Much of what we conclude of
these days is weighted heavily by the statistical
analyses. A paper written by my group in LA on
the value of MCP (modified citrus pectin) showed
some statistically significant but not impressive
ability to prolong PSA doubling time (PSADT) in
men with established PC. Just this past year,
Glen Tisman, using a different analytic method to
study our results said that the authors' results
UNDERstated the value of MCP. So in this case,
our publication, using a statistical analysis,
APPEARS to have given a lower value to MCP than another statistical method.
MB URSUS:
I realize you typically advise people who already
have prostate cancer, rather than those trying to
avoid it. But an ounce of prevention is worth a
pound of cure, or something like that, and I
appreciate any advice you might offer.
STRUM:
I believe that due diligence requires not merely
reading a tabloid or email article but the full
PDF of the Brasky et al report from 2013 and the
publications relating to the same topic. For me,
I have used the Mayo Medical Labs Comprehensive
Fatty Acid (CFA) profile for over ten
years. This reports fatty acid content by actual
measurement in millimoles per ml and not by
"weight" as in the Brasky article. I wish the
authors would have also submitted their samples
to another lab. I also would have wanted to know
who were the pathologists who read the Gleason
score. As an ex-pathologist who at one time was
an expert in the pathology of Hodgkin's disease
(HD), I realize the KEY significance of the
designation "expert". Some so-called experts at
academic institutions are given that label due to
political (old boy's club) reasons. As one of
the charter members of the Society of
Hematopathologists, there were 2 physicians in
that elite group that the rest of the charter
members often chuckled about in relation to their
ineptness. But due to political reasons, nothing
could be done about this. I recall this because
I was the youngest of the charter members and was
astounded that in such an outstanding grouping of
pathology experts on HD that two could be
included for this reason. I have seen huge
differences in the GS (Gleason score)
interpretations, and therefore I am amazed that
the pathologist(s) of record are not listed in
the text of the 2013 article by Brasky et al.
I have emailed Dr. Brasky asking him the name(s)
of the pathologist(s) and also commenting that I
have not found analyzing fatty acids by weight
percentage as helpful as actually millimole per
ml measurement, as done with the Mayo Medical
Labs test called Comprehensive Fatty Acid (CFA)
profile (see <http://bit.ly/1AtZ7>http://bit.ly/1AtZ7).
Others have commented negatively on this study by
Brasky et al ( D'Amico in an interview). The CMO
of Thorne Research had this to say in his criticism of the article:
The data came from what is referred to as a
retrospective, nested, case-control study. The
data was extracted from another, much larger,
previously conducted trial that was not
originally intended to examine the relationship
between omega-3 fatty acid levels and prostate
cancer. In other words, the original study was
not designed to determine any of the conclusions
reached in the analysis contained in the article.
The study's results conflict with the results
from other studies that do suggest that omega-3
fatty acids offer a protective benefit against
prostate cancer; and these other studies were, in
fact, designed to analyze that very outcome. (See
link)
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629172/>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629172/
Identifying one particular physiologic marker in
a group of individuals with a given condition -
in this case, an elevated omega-3 level in men
with prostate cancer - does not prove causation,
especially when that marker can be influenced by
diet or behavior and is only measured at a single point in time.
It is also hugely important to realize that the
authors of this study did not assess any of the
participants' dietary intake of fatty fish or
omega-3 nutritional supplements - the study's
conclusions are based wholly on the results of a single blood test.
The omega-3 index, which measures both EPA and
DHA within red blood cells, is a much more
accurate indicator of long-term omega-3 intake
and tissue status than is the plasma omega-3
level, which is subject to significant day-to-day variability.
A number of confounding risk factors might have
influenced the purported outcomes in the study,
despite attempts by the investigators to account for them:
1.53 percent of the subjects with prostate cancer were smokers.
2.64 percent of the cancer subjects regularly consumed alcohol.
3.30 percent of the cancer subjects had at least
one first-degree relative with prostate cancer.
4.80 percent of the cancer subjects were overweight or obese.
Considering the extensive body of literature
that supports the anti-inflammatory effects of
omega-3 fatty acids, there is no credible
biological mechanism, nor is one suggested in the
article, that would explain why these essential
fatty acids might increase tumorigenesis.
Summary: Given the inconsistent data
attributable to omega-3 fatty acids and prostate
cancer, and acknowledging the broad range of
health benefits that are almost universally
accorded to omega-3 fatty acid consumption, it
would be premature to stop eating fish or to
discontinue taking omega-3 nutritional supplements on the basis of this study.
Robert Rountree, MD
Chief Medical Officer
Thorne Research, Inc.
I hope the above gives you better perspective. I
know it is not a definitive response.
Stephen B. Strum, MD, FACP
Board Certified: Internal Medicine, Medical Oncology
Specialist in Prostate Cancer since 1983
Member: ASCO, AUA, ASTRO, Member: International
Strategic Cancer Alliance (ISCA)
Ashland, OR 97520