Fish oils may help prevent esophageal cancer
NORWICH, UNITED KINGDOM. Cancer of the esophagus has a poor prognosis and is increasing in frequency.
Esophageal cancer is usually preceded by a condition called Barrett's esophagus (BE) in which the normal
squamous (scale-like) epithelium in the lower esophagus is replaced with columnar epithelium. About 5% of
patients with BE progress to esophageal cancer. BE, in turn, is linked to gastroesophageal reflux disease (GERD)
with from 10-20% of GERD patients progressing to BE.
Research has shown that colon cancer is associated with an increased expression of the COX-2 enzyme in the
colon and that fish oil can reduce both the COX-2 level and the risk of colon cancer. There is also evidence that the
COX-2 enzyme is upregulated in Barrett's esophagus and esophageal cancer. British researchers therefore
reasoned that fish oil supplementation might also be beneficial in BE and thus, indirectly, lower the risk of
esophageal cancer.
Their clinical trial involved 46 patients with previously diagnosed BE. Twenty-seven of them were assigned to
receive 3 EPA (eicosapentaenoic acid) capsules daily providing a total EPA intake of 1.5 grams a day with the
remaining 19 patients serving as controls. Before the start of supplementation and at the end of the 6-month trial
period, all participants underwent endoscopy during which appropriate biopsy samples were obtained. Analysis of
the samples showed a significantly increased concentration of EPA and a significantly decreased level of COX-2
proteins in BE tissue in the supplement group, but not in the control group.
The researchers conclude that regular supplementation with relatively small doses of EPA results in significant
incorporation of metabolically active long-chain amoega-3 fatty acids into BE tissue and a concomitant, beneficial
decrease in COX-2.
Mehta, SP, et al. Effect of n-3 polyunsaturated fatty acids on Barrett's epithelium in the human lower
esophagus. American Journal of Clinical Nutrition, Vol. 87, 2008, pp. 949-56
Fatty fish reduces risk of kidney cancer in women
STOCKHOLM, SWEDEN. It is estimated that in the U.S. about 40,000 individuals will be diagnosed with kidney cancer in 2006 and about 13,000 will die from the disease. A recent study from Sweden provides evidence for a simple risk reduction strategy—eat fatty fish. This study was initiated in the late 1980s and involved 90,000 Swedish women who were questioned about their dietary habits and then followed for more than a decade. Women who consumed at least one portion of fatty fish each week during the study period ending in 2004 had a reduced risk of kidney cancer of 74% when compared to those who ate no fatty fish. However, eating lean non-fatty fish produced no protection. This result is based on a subgroup of 36,664 women who provided fish consumption information at baseline and again in 1997. There were 40 incident kidney cancer cases during the 1998-2004 follow-up. In this study, fatty fish included salmon, raw (pickled) herring, sardines and mackerel. Non-fatty fish included cod, tuna, fresh-water fish, shrimp and lobster.
The authors comment that these results support the hypothesis that the lower risk of kidney cancer is possibly due to the increased intake of fish oil rich in the two marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as vitamin D. They discuss the evidence for the biological plausibility of this hypothesis. The authors also point out that an explanation for the null results from earlier studies of the influence of fish consumption of cancer may have been the failure to distinguish fatty from not-fatty fish intake. As regards vitamin D, they discuss studies that found a connection between kidney cancer and vitamin D deficiency as measured by serum marker levels. This epidemiologic study, according to the authors, is the first to address this dietary association.
Wolk, A et al. Long-term Fatty Fish Consumption and Renal Cell Carcinoma Incidence in Women. Journal of the American Medical Association, 2006, Vol. 296, No. 11, pp. 1371-6
Fish oils in cancer prevention
STOCKHOLM, SWEDEN. Several test tube (in vitro) and animal experiments have clearly shown
that
the long-chain omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA), the main components of fish oil, help inhibit the promotion and progression
of
cancer. Their beneficial effect is particularly pronounced in hormone-dependent cancers such as breast
and
prostate cancer. Some, but not all, epidemiologic studies have also found a beneficial effect.
Researchers at Sweden’s famous Karolinska Institutet have just published a comprehensive review of the
current knowledge regarding the role of PUFAs in carcinogenesis. They conclude that omega-3 PUFAs
are
protective against cancer progression, while omega-6 PUFAs, notably arachidonic acid and its
derivatives, help
promote the growth of cancer. They believe the n-3 PUFAs exert their beneficial effects in several
different
ways:
- They suppress the synthesis of pro-inflammatory eicosanoids from arachidonic acid and thus produce
an
overall anti-inflammatory effect.
- They positively affect gene expression or the activities of signal transduction molecules involved in the
control of cell growth, differentiation apoptosis, angiogenesis and metastasis.
- They suppress excessive production of nitrogen oxide (NO) during chronic inflammation and thereby
help
prevent DNA damage and impaired DNA repair.
- They decrease estrogen production and thus reduce the estrogen-stimulated growth of hormone-
dependent
cancer cells.
- Fish oils improve insulin sensitivity and cell membrane fluidity and may help prevent metastasis
through
these effects.
Free radicals and reactive oxygen species produced in cells may attack PUFAs resulting in the formation
of
more free radicals, specifically hydroperoxides. The hydroperoxides, in turn, may damage DNA ultimately
leading to cancer. These effects have indeed been observed in some in vitro experiments, but not
in
actual human beings. Many studies have shown that fish oils actually retard aging and suppress so-
called free
radical diseases such as atherosclerosis and cancer. Other studies have shown that a daily EPA + DHA
intake
in excess of 2.3 grams decreases the production of superoxide, a potent cancer promoter.
At least one in vitro and one animal experiment have observed that EPA + DHA kill human breast
cancer
cells via the formation of hydroperoxides, but that this effect is strongly inhibited by vitamin E. Thus, at
this point,
it is not entirely clear whether EPA + DHA exert part of their beneficial effect through an increase or a
decrease
in the production of free radicals and reactive oxygen species. The researchers recommend more work
in this
area, but emphasize that the major benefits of fish oils probably are associated with their ability to inhibit
the
synthesis of arachidonic acid-derived, pro-inflammatory eicosanoids. The Swedish researchers also
confirm that
fatty, cold-water fish are the best sources of EPA and DHA and that the conversion rate of alpha-linolenic
acid
(flaxseed oil) to EPA is very low, even in healthy humans – probably in the order of 2-5%.
Larsson, SC, et al. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential
mechanisms.
American Journal of Clinical Nutrition, Vol. 79, June 2004, pp. 935-45
Editor’s comment: There would appear to be a growing body of evidence to the effect that long-
chain
omega-3 fatty acids, in particular EPA and DHA, help prevent the promotion and progression of certain
cancers,
notably hormone-dependent ones. Some of the mechanisms involved in this protective effect are well
understood. While others, notably the role of free-radical formation, clearly need more work. Of some
concern
is the uncertainty surrounding vitamin E. Both vitamin E and fish oils have been found to help prevent
hormone-
dependent cancers, so taking both for cancer prevention is probably desirable. The situation is much less
clear
when it comes to slowing down an existing cancer and preventing it from spreading. Should one just rely
on
vitamin E (particularly the succinate form) or place one’s faith in fish oils, or is the combination of the two
the
best way to go? Clearly more research in this area is urgently required.
Fish consumption reduces lung cancer risk
NAGOYA, JAPAN. Lung cancer is the leading cause of cancer deaths in Japan even though the
incidence and mortality is still less than two-thirds of that found in the USA and the UK. Japanese
researchers have just completed a study aimed at determining the association between lung cancer and
diet. Their study involved 748 men and 297 women aged 40 to 79 years who had been diagnosed with
lung cancer and 2964 male and 1189 female cancer-free controls.
The researchers found that both men and women who ate cooked or raw fish five times a week or more
had half the incidence of lung adenocarcinoma when compared to participants who ate cooked or raw fish
less than once a week. Women who consumed tofu (soybean curds) five times a week or more were
found to have half the risk of adenocarcinomas, as compared to women who consumed tofu less than
once a week. Frequent consumption of carrots was found to be beneficial for women, but detrimental for
men especially smokers. Green vegetables were found to be highly beneficial for men, but not
statistically so for women. There was also some evidence that increased coffee consumption is
associated with an increased risk of squamous cell and small cell lung carcinomas in men. Increased
consumption of dried or salted fish was not beneficial for men or women. The researchers speculate that
this is because the processing destroys the healthy omega-3 oils (eicosapentaenoic acid and
docosahexaenoic acid) present in raw and cooked fish.
Takezaki, T., et al. Dietary factors and lung cancer risk in Japanese with special reference to fish
consumption and adenocarcinomas. British Journal of Cancer, Vol. 84, No. 9, May 4, 2001, pp. 1199-
1206
Fish oils and the immune system
OXFORD, UNITED KINGDOM. Animal studies have shown that an increase in fat intake can decrease
the number of natural killer (NK) cells found in the blood and spleen. NK cells are an integral part of the
natural immune response to virus infections and certain types of cancer. Researchers at Oxford
University now report that fish oil significantly decreases NK cell activity in healthy human subjects.
Their clinical trial involved 48 men and women aged 55 to 75 years. The participants were randomized to
receive one of six supplements for 12 weeks. The supplements were all provided in the form of capsules,
three of which were to be taken with each meal. The nine capsules (daily intake) contained either a total
of 2 g alpha-linolenic acid, 770 mg gamma-linolenic acid (from evening primrose oil), 680 mg arachidonic
acid, 720 mg docosahexaenoic acid (DHA), 720 mg eicosapentaenoic acid (EPA)+ 280 mg DHA (fish oil)
or a placebo (an 80:20 mix of palm and sunflower oils). All the participants had blood samples taken four
weeks before start of supplementation, immediately before start of supplementation, and then every four
weeks during the trial as well as after a four-week washout period. The researchers found no changes in
killer cell activity except in the group taking fish oil. Here they observed an average decline of 20 per cent
after 8 weeks and 48 per cent after 12 weeks. The decline was completely reversed after the washout
period. The fact that no decline was observed with pure DHA strongly suggests that EPA was
responsible. The researchers conclude that an excessive EPA intake could have adverse effects for
people at risk of viral infections and some cancers. Editor’s Note: The British researchers’
speculation about fish oils perhaps affecting the effectiveness of NK cells in killing cancer cells is at odds
with the results of many other studies. There are at least a dozen studies that show a clear protective
effect of fish or fish oil against breast, colon, and prostate cancer. NOTE: This study was partly funded by
Unilever. [54 references]
Thies, Frank, et al. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3
or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 years.
American Journal of Clinical Nutrition, Vol. 73, March 2001, pp. 539-48
Docosahexaenoic acid halts melanoma
We do not usually report on animal or test tube experiments, but found the results of this study so
intriguing that we decided to make an exception.
VALHALLA, NEW YORK. The incidence of cutaneous malignant melanoma is growing rapidly among
persons with fair skin. It is estimated that one in 75 Americans will develop melanoma within their
lifetime. Melanoma has a pronounced tendency to spread to other organs (metastasis) and the 5-year
survival rate for metastatic melanoma is less than 10%. There is growing evidence that diet can influence
the risk of developing melanoma. It is now believed that a high intake of omega-6 fatty acids stimulates
the growth of melanoma and other cancers whereas omega-3 fatty acids suppress the growth of cancer
cells.
Researchers at the New York Medical College and the American Health Foundation have just released
the results of a laboratory experiment which clearly shows that docosahexaenoic acid (DHA), a main
component of fish oil, is highly effective in inhibiting the growth of human melanoma cells. The
researchers treated 12 different human metastatic melanoma cell cultures (in vitro) with DHA and found
that more than 50% of them stopped growing. They urge further testing of their findings in full-scale
clinical trials involving patients with melanoma. They conclude that “if DHA is capable of suppressing cell
and tumor growth and metastatic potential in in vivo models of melanoma, a clinical trial of DHA would be
warranted as an adjuvant to current surgical and chemotherapeutic interventions”.
Albino, Anthony P., et al. Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid:
association with decreased pRb phosphorylation. Cancer Research, Vol. 60, August 1, 2000, pp. 4139-
45
Fish oils combat weight loss in cancer patients
EDINBURGH, UNITED KINGDOM. Cachexia (abnormal weight loss) is a major problem in many types of
cancer especially cancer of the pancreas. Preliminary research has shown that supplementing the diet
with fish oils, about 2.2 grams of EPA (eicosapentaenoic acid) and 1.4 grams of DHA (docosahexaenoic
acid) daily, will stabilize weight in patients with inoperable pancreatic cancer. Now researchers at the
Royal Infirmary of Edinburgh report that patients with pancreatic cancer can actually gain weight by
consuming a nutritional supplement fortified with fish oils. The experiment involved 20 patients with
inoperable pancreatic cancer (aged 18 to 80 years). The participants were asked to ingest two cans of
fish oil-enriched nutritional supplement per day in addition to their normal food intake. The nutritional
supplement provided 310 kcal per can and contained 16.1 g protein, 49.7 g carbohydrate, 6.5 g fat, 1.09
g EPA, 0.46 g DHA, and 28 essential vitamins and minerals.
After three weeks the patients had gained an average (median) of 1 kg in weight and at seven weeks an
average of 2 kg. A significant improvement in performance status and appetite was also noted after three
weeks on the supplement. Other research has shown that EPA inhibits the growth of pancreatic cancer
cells in vitro. It is therefore of interest to note that the average survival time among the patients
was over eight months. This compares very favourably with the normal survival time of 4.1 months and is
at least as good as the survival time that can be obtained with aggressive chemotherapy.
The researchers conclude that a fish oil-enriched nutritional supplement has the potential to be a safe and
effective means of preventing weight loss in cancer patients and may even increase survival time in
patients with cancer of the pancreas. NOTE: This study was partially funded by Abbott Laboratories, the
maker of the nutritional supplement.
Barber, M.D., et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with
pancreatic cancer. British Journal of Cancer, Vol. 81, No. 1, September 1999, pp. 80-86
Fish oils improve survival of cancer patients
PATRAS, GREECE. Chemotherapy and other conventional medical treatments have proven ineffective
in improving quality of life and survival of patients with end stage cancer. Now Greek medical
researchers report that fish oil supplementation markedly increases the survival time for cancer patients
with generalized malignancy. Their study involved 60 patients with generalized solid tumors. The
patients were divided into two groups with one group receiving 18 grams/day of fish oil (six capsules of
MAXEPA three times daily containing 170 mg eicosapentaenoic acid [EPA] and 115 mg
docosahexaenoic acid [DHA] per capsule) and the other group receiving a placebo. The fish oil group
also received 200 mg of vitamin E daily to compensate for the oxidative effect of the fish oil. Each group
included 15 well-nourished and 15 malnourished patients. None of the well-nourished patients suffered
from cancer cachexia (abnormally low weight and general weakness). The researchers measured the
level of T cells, natural killer cells, and the synthesis of interleukin and tumor necrosis factor before the
start of the supplementation and on day 40 of the trial. The study followed all patients until they died.
Malnourished patients were found to have a considerably impaired immune function and a decreased
production of tumor necrosis factor; both parameters were restored through fish oil supplementation.
Malnourished patients overall had a much shorter survival time than well-nourished ones (mean of 213
days versus 481 days). Both malnourished and well-nourished patients who received fish oil and vitamin
E survived significantly longer than did patients on placebo. The researchers speculate that fish oils exert
their beneficial effect by decreasing the body's production of prostaglandin E2 which is believed to play an
important role in the initiation and progression of cancer. They conclude that supplementation with
dietary omega-3 polyunsaturated fatty acids, specifically fish oils with an antioxidant such as vitamin E
may offer significant palliative support to cancer patients with end stage metastatic disease.
Gogos, Charalambos A., et al. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore
immunodeficiency and prolong survival for severely ill patients with generalized malignancy. Cancer, Vol.
82, January 15, 1998, pp. 395-402
Fat consumption and cancer
LONDON, UNITED KINGDOM. Several major epidemiologic studies have found a clear association
between a high dietary fat intake and the risk of developing breast and colon cancer. The correlation is
particularly strong in the case of animal fats. One study found that a high fish or fish oil consumption is
protective against later stage colon cancer in men, but has no effect on mortality from breast cancer.
British medical researchers now report that fish and fish oils not only protect against colon cancer in men,
but also against colon and breast cancer in women. This protective effect, however, is only apparent in
countries where the intake of animal fats is high. In other words, a high intake of fish or fish oils
counteracts the detrimental effects of a high animal fat consumption.
The study compared cancer mortality rates in 24 European countries, Canada and the USA with fish
consumption and the intake of animal fats. In countries where the animal fat intake was high the
researchers found a clear inverse correlation between the ratio of fish fat to animal fat and the risk of
developing breast cancer in women and colon cancer in both men and women. A similar correlation was
found between cancer risk and the ratio of fish fat to total fat intake.
The researchers conclude that a 15% decrease in animal fat intake combined with a 3-fold increase in
fish oil intake could possibly reduce male colon cancer risk by as much as 30% in countries with a high
animal fat intake. A 3-fold increase in fish oil intake could be achieved by eating fish three times a week
or by taking two standard fish oil capsules daily.
Caygill, C.P.J., et al. Fat, fish, fish oil and cancer. British Journal of Cancer, Vol. 74, No. 1, July 1996,
pp. 159-64
Colon cancer progression associated with fatty acid status
BADALONA, SPAIN. Several epidemiological studies have shown that high fat diets are associated with
an increased risk of colon cancer. Other studies have shown that diets rich in fish and fish oils are
protective against colon cancer. Spanish medical researchers have just released the results of a major
study aimed at determining if and how polyunsaturated fatty acids play a role in the progression of
adenomas (benign polyps) to full-blown colon cancer. The study involved 27 patients with sporadic
benign polyps of the rectum or colon, 22 patients with cancer of the colon or rectum, and 12 subjects with
a normal colon. The researchers measured the fatty acid profile of blood plasma and biopsy samples of
the lining of the colon from both diseased and normal areas. They found no differences between polyp
patients and patients with a normal colon as far as plasma profile and normal colon lining profile was
concerned. However, there was a significant difference between the fatty acid profile of normal colon
tissue and diseased colon tissue in adenoma patients. Diseased lining tissue was found to have higher
levels of linoleic acid, dihomogammalinolenic acid, and eicosapentaenoic acid (EPA) and lower levels of
alpha-linolenic and arachidonic acids. There was also a very significant stepwise reduction in EPA
content of diseased colon lining from the benign polyp stage to the most severe colon cancer stage.
The researchers conclude that there are significant changes in the levels of n-3 and n-6 fatty acids early
on in the sequence leading from benign polyps to colon cancer and speculate that these changes might
participate in the progression to colon cancer. They recommend further work to investigate the benefits
of long-term dietary manipulation in view of the finding that low-dose fish oil supplementation normalizes
the cell proliferation pattern in patients with sporadic polyps.
Fernandez-Banares, F., et al. Changes of the mucosal n3 and n6 fatty acid status occur early in the
colorectal adenoma-carcinoma sequence. Gut, Vol. 38, 1996, pp. 254-59
Fish oils help patients with pancreatic cancer
EDINBURGH, UNITED KINGDOM. Cachexia (abnormally low weight, weakness, and general bodily
decline) is common in patients suffering from pancreatic cancer. Cachexia makes patients more prone to
infections, can shorten their survival, and reduce their mobility.
Researchers at the Royal Infirmary of Edinburgh have released the results of a study which clearly shows
that fish oil supplementation can halt and even reverse cachexia in patients with pancreatic cancer. The
study involved 18 patients with inoperable pancreatic cancer (9 had stage IV tumors). The patients were
started out on 2 grams/day of fish oils (containing 360 mg of eicosapentaenoic acid and 240 mg of
docosahexaenoic acid). The dose was subsequently increased by 2 grams/day every week until the
patients’ body tolerance was reached. The average final intake was 12 grams/day. Prior to entering the
trial the average (mean) weight loss among the patients was 2.9 kg (6.3 lbs) per month. After 3 months
of fish oil supplementation an average weight gain of 0.3 kg/month was observed among the patients.
Overall, 11 patients (61%) gained weight, 3 became weight-stable, and 4 continued to lose weight, but at
a significantly reduced rate. The concentration of eicosapentaenoic acid in plasma phospholipids
increased from 0 to 5.3% of total fatty acids after 1 month of supplementation while the concentration of
docosahexaenoic acid increased to 6.6% from a base level of 3.5%. The researchers conclude that fish
oil supplementation arrests weight loss in cancer patients with cachexia.
Wigmore, Stephen J., et al. The effect of polyunsaturated fatty acids on the progress of cachexia in
patients with pancreatic cancer. Nutrition (suppl), Vol. 12, No. 1, 1996, pp. S27-S30
Fish consumption and colon cancer
LONDON, UNITED KINGDOM. British researchers have published a major epidemiologic study dealing
with the association between fish consumption and the incidence of breast and colon cancer, The
researchers gathered data concerning the consumption of fish in 25 European countries for the periods
1961-63, 1974-76 and 1984-86. They also determined the standardized mortality rates for breast and
colon cancer for the period 1983-87 for the same 25 countries. A statistical evaluation of the data
showed a strong inverse correlation between recent fish consumption and colon cancer in men. The
correlation was somewhat weaker for fish consumption 10 years earlier and non-existent for consumption
23 years earlier. A similar pattern was found for women, but the correlations were not statistically
significant. The researchers found no correlation between breast cancer mortality and fish consumption
at any time. They conclude that the consumption of fish and fish oils helps protect against colon cancer
in its later stages, but does not affect the initiation stage. They believe fish oils exert their protective
effect by inhibiting the formation of prostaglandin PGE2 which has been associated with the development
and progression of colon cancer.
Caygill, C.P.J. and Hill, M.J. Fish, n-3 fatty acids and human colorectal and breast cancer mortality.
European Journal of Cancer Prevention, Vol. 4, 1995, pp. 329-32
Fish oil supplementation helps prevent colon cancer
ROME, ITALY. The presence of benign polyps (adenomas) is a significant risk factor for full-blown colon
or rectal cancer. Animal studies have shown that the omega-3 polyunsaturated fatty acids,
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the development of colon cancer
and epidemiological studies have shown that fish consumption is inversely proportional with the incidence
of colon cancer. Encouraged by these findings, researchers at the Catholic University of Rome set out to
determine if fish oil supplementation would inhibit the development of benign polyps, the precursors of
colon cancer.
Their study involved 34 men and 26 women who had just undergone surgery to remove benign polyps
from their colon. The patients were divided into 4 groups. Group 1 was supplemented with 1.4 grams of
EPA and 1.1 grams of DHA per day, group 2 with 2.7 grams of EPA and 2.4 grams of DHA, group 3 with
4.1 grams of EPA and 3.6 grams of DHA while group 4 received placebo capsules containing mainly olive
oil. Biopsy samples from the lower part of the colon lining and blood samples were taken and analyzed at
the start of the trial and 30 days later at the end of the supplementation period. Overall, patients in the
fish oil groups experienced a significant decline in the number of abnormal cells in their colon lining as
compared to members of the placebo group. Further analysis showed that the reduction in the number of
abnormal cells was limited to patients who had a large number of abnormal cells at the beginning of the
trial. The researchers also noted a very significant increase in EPA and DHA levels and a significant drop
in arachidonic acid level in the biopsy samples from the fish oil supplemented patients.
A separate 6-month trial involving 15 patients taking 1.4 grams per day of EPA and 1.1 grams per day of
DHA also showed a significant drop in the number of abnormal colon lining cells. The researchers
conclude that low-dose supplementation with fish oils inhibit the proliferation of abnormal cells (a
precursor to polyps) in patients at risk for colon cancer and that this effect can be maintained with long-
term treatment. They caution that it may be advisable to increase vitamin E intake during fish oil
administration.
Anti, Marcello, et al. Effects of different doses of fish oil on rectal cell proliferation in patients with
sporadic colonic adenomas. Gastroenterology, Vol. 107, December 1994, pp. 1709-18
