N-Nitrosation: A Positive Epidemiological Relationship between Red Meat Intake and Colorectal Cancer

[Guest guest]

N-Nitrosation: A Positive Epidemiological Relationship between Red Meat intake

and Colorectal Cancer

JoAnn Guest

Jun 18, 2005 13:22 PDT

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Hughes R, Pollock JR, Bingham S.

Dunn Human Nutrition Unit, Medical Research Council, Cambridge CB2 2XY,

UK.

 

 

 

 

Red meat increases colonic N-nitrosation, and this may explain the

positive epidemiological relationship between red meat intake and

colorectal cancer risk.

 

 

Vegetables, tea, and soy have been shown to block N-nitroso compound

(NOC) formation and are associated with protection against colorectal cancer.

 

To determine whether these supplements affect fecal NOC

excretion during consumption of a high red meat (420 g/day) diet, 11

male volunteers were studied over a randomized series of 15-day dietary periods.

Seven of these subjects completed a further dietary period to test the effects

of soy (100 g/day).

 

Soy significantly suppressed fecal apparent total NOC (ATNC)

concentration (P = 0.02), but supplements of vegetables (400 g/day as

134 g broccoli, 134 g brussels sprouts, and 134 g petits pois) and tea

extract (3 g/day) did not affect mean levels of fecal ATNC, nitrogen and

ammonia excretion, and fecal water genotoxicity.

 

However, fecal weight was increased (P < 0.001) and associated with

reduced transit time (r = 0.594, P < 0.0001), so that contact between

ATNC, nitrite, and ammonia and the large bowel mucosa would have been

reduced. Longer transit times were associated with elevated fecal ATNC

concentrations (r = 0.42, P = 0.002). Fecal nitrite was significantly

suppressed during the tea supplement compared with the meat-only (P =

0.0028) and meat + vegetables diets (P = 0.005 for microgram NO2/g).

 

Nutr Cancer 2002;42(1):70-7 PMID: 12235653 [PubMed - in process]

 

 

Effect of vegetables, tea, and soy on endogenous N-nitrosation, fecal

ammonia, and fecal water genotoxicity during a high red meat diet in

humans.

 

Oncol Rep, 12/02

 

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Introduction Testicular cancer accounts for <2% of malignant neoplasms

in men but is the most common tumor in young adult men aged 15-44 years

in the United States.[1] The only well-established risk factor for

testicular cancer is cryptorchidism (nondescent of the testes into the

scrotum at birth) (reviewed in Reference 2).

 

An ecological study of per capita fat consumption and testicular cancer

rates[3] and a case-control study have been suggestive of increased

testicular cancer risk with a high-fat diet.[4]

 

Diets high in red meat and milk and low in fruits and green vegetables

have been associated with elevated risk of testicular cancer.[4-6]

 

Although testicular cancers can be divided clinically into slow-growing

seminomas, rapidly growing nonseminomas, and mixed germ cell tumors

(those with seminomatous and nonseminomatous elements), only one study

has analyzed diet in relation to histology.[4]

 

To evaluate the association of dietary factors with risk of testicular

cancer, we conducted a hospital-based case-control study at The

University of Texas M. D. Anderson Cancer Center.

 

Specifically, we examined whether testicular cancer risk increased with

a high dietary intake of fats, meat, and milk and low consumption of

fruits and vegetables. We also assessed whether the dietary factors

associated with risk varied by testicular cancer histopathology.

 

Methods We identified men with testicular cancer who registered at M. D.

Anderson Cancer Center (Houston, TX) between January 1990 and October

1996 through the M. D. Anderson Tumor Registry and the M. D. Anderson

Genitourinary Oncology Clinic. Potential cases were defined as men who

were alive during the data collection phase of the investigation, were

between the ages of 18 and 50 years at the time of diagnosis, and lived

in Texas, Louisiana, Arkansas, or Oklahoma.

 

The age restriction was chosen because testicular cancer occurs most

often between 18 and 50 years, and we restricted the region to the

south-central United States so that the cases and controls would be from

a defined geographic area. All men diagnosed with testicular cancer were

eligible for inclusion, regardless of their ethnicity, tumor stage, and

histology.

 

To identify controls, we asked each case to nominate healthy friends who

had never had cancer and were of the same ethnicity, age (±5 yr), and

state of residence as the case. We chose friend controls, because the

cases arose from an undefined population, which is a common concern with

hospital-based case-control studies. We assumed friends of cases, had

they developed testicular cancer, would have been more likely to have

come to M. D. Anderson Cancer Center than a population-based control

group. Cases and controls completed self-administered questionnaires

eliciting information on demographics; lifestyle habits; medical

history, including history of cryptorchidism, family history of cancer,

body size, and shape; and diet.

 

To assess diet, we used a modified and revised version of the National

Cancer Institute's (NCI's) Health Habits and History Questionnaire

(HHHQ), which contained 152 foods and beverages[7,8] and has been

validated in a range of populations.[9,10] The time period assessed by

the questionnaire was the year before cancer diagnosis for cases and the

previous year for controls.

 

From the information we calculated food consumption and nutrient intake

by using DietSys (version 4.0), the nutrient analysis program developed

for the NCI's HHHQ.[11] To adjust for total energy intake, all dietary

factors were analyzed per 1,000 kcal dietary intake according to the

nutrient density adjustment method described by Willett,[12] and we also

used total daily calories in multivariable modeling.

 

We contacted by mail 335 eligible men diagnosed with testicular cancer,

and 101 (30.1%) agreed to participate. We also approached 155 more men

in the outpatient Genitourinary Oncology Clinic, of whom 86 (55.5%)

agreed to participate. Of these 187 men, 25 were excluded because their

HHHQs were not completed and two were excluded because they reported

eating too many foods daily, leaving 160 cases for analysis.

 

We contacted 202 healthy potential controls by mail. Of these, 148 men

(73.3%) returned the questionnaires. Eleven controls were excluded

because they did not complete the HHHQ and one was excluded for

consuming too many food items per day, leaving 136 healthy controls for

analysis.

 

Because there were multiple cases who would be excluded in the analysis

of matched data because they did not have a friend control, we evaluated

the effect of dissolving the match on our crude and adjusted results. To

do so, we compared the unconditional and conditional logistic regression

point estimates for all cases and controls, regardless of matching.

Because the point estimates in both of these analyses were essentially

the same (data not shown), we presented the results with the matching

dissolved.

 

For descriptive analyses, we tested the differences in the means and

distributions of cases and controls by using Student's t-test and the X2

test.

 

Using unconditional logistic regression modeling, we adjusted for the

potential confounders of age, education, income, ethnicity, history of

cryptorchidism, and total daily caloric intake.

 

Age, years of education, and total daily calories were entered as

continuous variables, income as a scaled variable, and ethnicity and

history of cryptorchidism as categorical variables.

 

The quartile cut points used for dietary intake were based on the

consumption distribution among the controls. Multivariable trend tests

were calculated by entering the dietary component as a scaled variable

in the model. The model building strategy used stepwise backward

elimination, and the models were compared by using the likelihood ratio

test.[13] All significance tests were two-sided and the a was set at

0.05.

 

Results In Table 1 we present selected demographic characteristics for

cases and controls grouped by histopathological type. There were 82 men

diagnosed with nonseminoma tumors, 46 men diagnosed with pure seminomas,

and 32 men diagnosed with mixed germ cell tumors. The ethnic

distribution of men with nonseminoma, seminoma, and mixed germ cell

tumors was generally similar to that of controls.

 

The controls tended to be older, had more education, and had higher

incomes than the cases, although not all these factors were

statistically significant across all histological groups. Although we

tried to match on age, the cases tended to identify friend controls that

were older than themselves. For this reason, in our analyses we

consistently controlled for age as a confounder.

 

History of cryptorchidism was significantly more common in all

histological groups than in the controls. As shown in Table 2, there

were many differences in dietary intake between controls and cases (all

histopathological types combined).

 

The cases had significantly higher daily total energy, total fat,

saturated fat, and meat intake than controls (p = 0.0001, 0.0002,

0.0001, and 0.006, respectively). Although lower in cases than controls,

milk consumption (including whole, 2%, and skim) was not significantly

different. Dietary fiber intake was significantly lower in cases than

controls (p = 0.006), as was fruit consumption (p = 0.05). Consumption

of vegetables and dark green and deep yellow fruits and vegetables was

lower in cases than controls, but the difference was of borderline

statistical significance (p = 0.09 and 0.08, respectively).

 

Dietary intake further varied by the cases' histology. Men diagnosed

with nonseminoma testicular cancer consumed significantly more fats and

meats and significantly less dietary fiber and vegetables than controls.

 

 

The men with seminomas had significantly higher intakes of fats and meat

than controls but fiber, fruits, and vegetable intake similar to

controls. Men diagnosed with mixed germ cell tumors consumed more fats

and less fruit than controls.

 

Multivariable logistic regression analyses of individual dietary

components (comparing lowest with highest quartiles of consumption)

adjusting for age, education, income, ethnicity, cryptorchidism, and

total daily calories.

 

Increasing total fat, saturated fat, meat, and cholesterol consumption

were associated with increasing risk of nonseminoma testicular cancer,

with odds ratios (ORs) of 6.3, 2.3, 5.3, and 4.6 for the highest

quartiles, respectively. An inverse relation was observed for calcium

and dietary fiber intake and nonseminoma cancer risk and no consistent

trend was observed for milk, fruit, vegetable, or dark green and deep

yellow fruit and vegetable consumption.

 

Risk for seminoma testicular cancer increased with increasing intake of

meat and total cholesterol (the ORs for the highest vs. the lowest

quartiles were 3.6 and 3.1, respectively). Increased total and saturated

fat intakes were marginally associated with increased seminoma risk (the

ORs for the highest vs. the lowest quartiles were 1.9 and 2.1,

respectively). Higher total fat consumption was nearly significantly

related to increased mixed germ cell tumor risk (the OR for the highest

vs. the lowest quartile was 4.2).

 

When multivariable regression analysis with backward elimination was

used to assess the independent effects of multiple dietary components,

only saturated fat remained in the model for nonseminoma testicular

cancer (Table 3). In multivariable regression analyses for seminoma and

mixed germ cell tumor risk, the only dietary variables that remained in

each of the models were cholesterol and total fat, respectively (Table

3).

 

Discussion There are few published studies of the relation between diet

and testicular cancer. The results of our case-control analysis provide

evidence that dietary habits, particularly high total fat and saturated

fat intake, may increase risk of testicular cancer.

 

We also found an association with increased meat intake and increased

seminoma risk.

 

This agrees with an investigation in Uruguayan men in which higher red

meat consumption and total fat intake were associated with increased

risk of seminomas.[4]

 

In that study, no associations were observed for nonseminoma tumors, but

the results were based on a limited number of cases (30 seminoma and 28

nonseminoma cancers).[4]

 

We found an inverse association between dietary fiber and testicular

cancer risk that has not been previously reported. Our findings are

weakly supportive of previous studies in which higher intakes of fruits

and vegetables were associated with decreased risk of testicular cancer.

 

 

Gallagher and co-workers[6] conducted a large Canadian population-based

study and reported that green vegetable consumption had a protective

relative risk of 0.5 (95% confidence interval = 0.3-0.9) in the highest

compared with the lowest quartile.

 

In a case-control study in England, Davies and colleagues[5] collected

data on fresh fruit and vegetable consumption in adolescence. Although

cases tended to have eaten fewer oranges, apples, and vegetable and

fruit salads than the population controls, the difference was not

statistically significant.[5] The weak associations found in our study

with fruit and vegetables were not consistent across testicular cancer

histologies in the multivariable analysis, despite reports that these

foods reduce the risk of many cancers (reviewed in Reference 14).

 

We did not find an association between milk intake and testicular cancer

risk, which is in contrast to the results of Davies and colleagues,[5]

who found that for every increased quarter pint of milk consumed per day

during adolescence the relative risk was 1.39 (95% confidence interval =

1.19-21.9). However, the results of the British study should be viewed

somewhat cautiously, inasmuch as it was unclear whether consumption of

milk itself or some component in the milk (such as saturated fat or

calcium) increased risk. In our study, we found dietary calcium intake

to have a significant inverse dose-response gradient with risk of

nonseminoma testicular cancer.

 

To our knowledge, no other previous study has reported an association

with calcium intake and testicular cancer.

 

 

The association with dietary fat should be interpreted cautiously,

because spurious associations with cancer in case-control studies have

been reported (reviewed in Reference 12). We observed a higher reported

total daily caloric intake in the cases than in the controls. To

possibly explain this, we examined weight, body mass index, and crude

estimators of physical activity (in adolescence, age 20, and adulthood)

and found them to be similar between cases and controls (data not

shown).

 

There has been considerable controversy over whether increased total

caloric intake itself increases cancer risk or whether a dietary

component (such as saturated fat) is the factor that increases risk. For

example, Slattery and co-workers[19] reported that colon cancer risk was

not associated with dietary fat, protein, or carbohydrate intake after

adjustment for total energy intake.

 

Certainly, the finding that caloric restriction in mice reduces the

incidence of sporadic and induced tumors supports the hypothesis that

higher caloric intake increases cancer risk.[20] However, to conclude

that higher saturated fat intake is associated with increased risk of

testicular tumors or to speculate on possible biologic mechanisms would

be premature.

 

Although we report many interesting associations, there are several

limitations in our study. Because cases reported diet for the year

previous to diagnosis and controls reported diet for the previous year,

we were concerned that the discrepancy in reporting years could affect

our results. We therefore introduced a term for year of diagnosis into

the model to evaluate the impact on the point estimates, but that had

little effect.

 

We also split the case group by stratifying on the year of the case's

diagnosis (i.e., 1990-93 and 1994-96) and compared these results with

those of our analysis for all cases and controls combined; again there

were no differences in the point estimates. Of greater concern is the

potential for bias in dietary recall inherent in case-control studies,

although Willett[12] suggests that diet can be adequately recalled for

up to 10 years with acceptable levels of misclassification.

 

In comparisons of prospectively and retrospectively collected diet data,

Wilkens and co-workers[21] reported that fat intakes were overreported

by colon cancer cases compared with controls but not by prostate or

breast cancer cases. However, a prospectively designed study for a rare

tumor (such as testicular cancer) would be inefficient. It is therefore

impossible to determine the extent and direction of recall bias among

the testicular cancer patients and controls, although this remains a

possible explanation for our observations.

 

We used friends of cases as controls, because we thought

population-based controls would not reflect the population from which

the cases arose, despite the problem that friends might be too " similar "

to cases. We do not believe " over-matching " occurred, because our

controls were significantly older and better educated than our cases.

However, this implies that the associations found between diet and

testicular cancer may be spurious because of the inclusion of more

highly educated controls.

 

For example, the more educated controls may be more conscious of fat

intake and methods to reduce dietary fat consumption. Also,

participation in this study was less than ideal, particularly for cases.

The effect of the low response on the associations found with diet is

difficult to predict but remains a concern in this investigation.

 

There were several limitations to our study, but it did reveal specific

dietary components that were associated with testicular cancer risk.

Because high total and saturated fat and meat intakes were found to be

consistently and significantly associated with risk of testicular

cancer, more dietary studies addressing this issue are needed.

 

Cholesterol intake, although likely correlated with meat consumption,

should also be examined. Future research should include an evaluation of

dietary calcium and fiber, inasmuch as we found higher intakes reduced

risk. Clarification of the role of genetic and early life exposures in

the etiology of testicular cancer and the identification of other risk

factors (including diet) could provide further insights into this cancer

that occurs at a relatively young age.

 

Acknowledgments and Notes

 

The authors thank all the men who participated in the study, Dr. Maureen

Goode (Dept. of Scientific Publications, The University of Texas M. D.

Anderson Cancer Center) for editing the manuscript, and Dr. Philip

Beckett (Texas Children's Hospital, Baylor College of Medicine) for

helpful comments. This work was supported by The University of Texas M.

D. Anderson Cancer Center Education Program in Cancer Prevention, which

is supported by National Cancer Institute Grant R25-CA-57730.

 

 

 

http://store..net/annieappleseedproject/tesdietistex.html

 

 

Nutr & Cancer, 3/03

 

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FLAXSEED OIL (ALA) & PROSTATE CANCER

 

Witch Hunt or Cause for Concern? By Udo Erasmus

 

Background, and Abbreviations used in this Article:

 

EFAs: Essential Fatty Acids are substances from fats that must be

provided by foods because the body cannot make them, and yet must have

them for health. EFAs exist in two families: omega-3 (n-3) and omega-6

(n-6). From these two, the body can make several derivatives, hormones,

and other active substances.

 

N-3: omega-3 fatty acids include

 

1. ALA (alpha-linolenic acid; abundant in flax, and present in smaller

quantities in hemp, walnut, soybean, and canola); given enough ALA to

start with, the body converts ALA into SDA, EPA, and DHA in various

tissues, according to need; 2. SDA (stearidonic acid; present in a few

exotic seeds);

 

3. EPA (eicosapentaenoic acid; parent of Series 1 eicosanoid hormones;

found in snake and fish oils);

 

4. DHA (docosahexaenoic acid; the major brain n-3; found in fish oils).

 

ALA: Alpha-Linolenic Acid is the (n-3) EFA. It is sometimes shortened to

LNA. Others shorten it to ALNA.

 

ALA is very fragile to destruction by light, oxygen (air), and heat, and

must therefore be protected from these destructive influences. If this

is not done, ALA molecules are changed from natural and beneficial, to

unnatural and toxic. ALA is destroyed about 5 times faster than LA, the

n-6 EFA.

 

ALA is deficient in the diets of most people in affluent societies. Its

intake has decreased to less than 20% of what was present in common

diets 150 years ago, mainly due to decreased use because of its

fragility.

 

N-6: omega-6 fatty acids include

 

1. LA (linoleic acid; abundant in safflower, sunflower, and corn;

present in medium quantities in soybean, sesame, pumpkin seed, and

almond; present in small quantities in canola, peanut, and olive); given

enough LA to start with, the body converts LA into GLA, DGLA, and AA in

various tissues, according to need;

 

2. GLA (gamma-linolenic acid; present in evening primrose oil);

 

3. DGLA (dihomogamma-linolenic acid; parent of Series 1 eicosanoid

hormones);

 

4. AA (Arachidonic acid; the major brain n-6; parent of Series 2

eicosanoid hormones;

 

found in meat, eggs, and dairy products).

 

LA: Linoleic Acid is the omega-6 (n-6) EFA.

 

LA is abundant in the diets of most people in affluent societies, its

intake having doubled during the past 100 years due to increased use of

corn and safflower oils. LA is sensitive to destruction by light, oxygen

(air), and heat, and should be protected from these destructive

influences. If this is not done, LA molecules can change from natural

and beneficial, to unnatural and toxic.

 

Introduction

 

In their frenzy to boost sales, manufacturers of flax oil have greatly

promoted (perhaps even over-promoted) its benefits but have not

addressed the down side of flax oil. Flax oil has benefits, but it also

has shortcomings. Overlooked, these can lead to serious health problems.

What are these shortcomings, and what are the problems that can stem

from excessive use of flax oil?

 

Context

 

A recent review article points out that prostate cancer is increasing,

and is the second leading cause of cancer deaths in the Western world.

The etiology of prostate cancer remains unclear, course and progression

are unpredictable, and definite treatment is not yet established.

 

Lifestyle and diet could contribute to the progression from small,

latent, non-metastatic tumors to clinically significant, invasive,

metastatic lesions.1

 

Research on the involvement of fats and fatty acids in prostate cancer

has been inconsistent. Most of the information available comes from

epidemiological studies. Data from animal and human studies are

limited.1

 

There is the further problems that results from animal studies,

especially rats, cannot be automatically generalized to humans, because

rats and humans metabolize fats quite differently. Also, rats don’t fry

steaks, don’t use salad dressings and mayonnaise made with oils that

have been highly processed, and don’t eat butter that has been exposed

to light and air, sometimes for weeks. The reason I make this point will

become clear a little later.

 

Studies done on cell cultures do not take into account the effects of

fats on other organs that can affect tumor development and growth. In

particular, some fatty acids up- or down-regulate the functions of

genes, and it appears that some fatty acids also change the

effectiveness of hormones even if they don’t change hormone levels

present in tissues.

 

A One-side View

 

Within this context, the suggestion has been made in published

literature that flax oil should not be used because it can increase

prostate cancer. The Prostate Forum2 lists six studies showing positive

correlation between ALA (in serum, adipose tissue, and red blood cell

membranes) and prostate cancer.

 

Of the six studies, one showed no correlation.3 One found a small (not

statistically significant) positive correlation.4 Four studies found a

strong positive correlation between ALA and prostate cancer.5,6,7,8 At

least two other studies have also shown a correlation of alpha-linolenic

acid with increased prostate cancer.9,10

 

According to Prostate Forum, several labs have found that ALA is one of

the most powerful growth stimulants for human prostate cancer cells.2

 

The Prostate Forum has recommended against the use of flax oil by men

with prostate cancer. Since flax oil is the richest readily available

food source of ALA, the reasoning goes, this oil should cause the most

prostate cancer.

 

Sources of ALA Used Studies that Support One-Sided View The ‘ALA’ in

population (epidemiologic) studies comes from two main sources:

vegetable oil, and red meat animal products. Both were shown to

correlate with similar increases in prostate cancer.

 

In cell studies, chemically ‘pure’ fatty acids are usually used. The

sources of ALA, the n-3 EFA that is 5 times more easily destroyed by

light, oxygen, and heat than LA (the n-6 EFA), come from foods that have

been treated with great carelessness. Let me illustrate this point.

 

In one of the epidemiologic studies,5 the sources of ALA were listed.

 

 

They include red meat and bacon, salad dressing and mayonnaise [made

from soybean and/or canola oils which have been destructively processed

by degumming, refining, bleaching, and deodorizing (so-called ‘RBD

oils’)],

 

and butter (which is poorly protected from light and air between the

time the cow is milked until the butter is consumed).

 

In addition, beef and butter contain trans- fatty acids, and these

correlate with increased cancers including prostate cancer.

 

One of these trans- fatty acid is Conjugated Linoleic Acid (CLA) which

is also sold as a supplement in capsules (see article on CLA on

www.udoerasmus.com ).

 

Some Other Views

 

Interestingly, a study done with flax grain has shown that flax inhibits

the growth of prostate cancer.6 Another study showed that prostatic

alpha-linolenic acid was lower in cancerous prostate glands that

exhibited perineural invasion, seminal vesicle involvement, and stage T3

tumors.7

 

In a review article on n-3 fatty acids and cancer, the author makes the

observation that the effect of n-3 polyunsaturated fatty acids (PUFAs)

on cancer depends on “background levels of n-6 PUFAs and antioxidants,

and this could account for previously inconsistent results in

experimental carcinogenesis.”

 

He also makes the observation that “n-3 PUFAs appear to be excellent

substrates for lipid peroxidation in situations where an oxidative

stress is involved, such as in the action of several cytotoxic agents in

the treatment of cancer,”8

 

Other researchers found that the ratio of n-3/n-6 PUFAs decreased in the

following order: normal, benign prostatic hyperplasia, and prostate

cancer. This indicates that n-3 inhibit prostate problems. They conclude

that the ratio of n-3/n-6 may have an important association with the

benign and malignant statue of prostatic disease.9

 

Yet other researchers suggest that among fatty acids, the n-6 derivative

arachidonic acid (AA), delivered in larger than normal quantities to

prostate cancer cells in tissue culture by LDL cholesterol via

over-expression of its receptor (LDLr), increases the activity of the

cancer-related genes c-fos and cox-2.10

 

In 1994, one review suggested that for prostate cancer, fat consumption

should be decreased to 15% of calories. The antioxidants selenium and

vitamin E should be supplemented, and a soy product should be used.11

 

Another study shows that the same n-6 derivative AA, stimulates growth

and division of prostate cancer cells (both hormone-sensitive and

hormone-insensitive) by increasing lipoxygenase enzyme activity

(increasing inflammation).

 

The researchers show that if you block this enzyme, the prostate cells

self-destruct (apoptose) very rapidly.

This could be achieved by inhibitor molecules, by decrease of AA in the

medium (or diet), and by increase of n-3 fatty acids that inhibit the

production of AA.

 

One further study showed a positive association between prostate cancer

and animal fat, as well as the n-3 EFA (ALA). It also showed an inverse

association between the antioxidant vitamin C and prostate cancer.13

 

A study in 1985 showed that GLA, ALA, AA, and EPA all killed prostate

cancer cells in tissue culture, but did not affect the normal cells with

which they were cultured. The latter continued to grow normally. When

essential fatty acids were not present, the prostate cancer cells

overgrew the normal cells.14

 

In 1991, the view from research was that diets containing high levels of

n-6 fatty acids enhance tumorigenesis in animals, and that diets with

equivalent levels of n-3 fatty acids diminish tumorigenesis.15

 

A 1999 publication concludes that the combination of fatty acids makes a

difference. In this study, GLA, ALA, and EPA increase the death of

prostate cancer cells. A slight increase of cancer cell death was

obtained when ALA was combined with AA, OA, or GLA. But ALA with LA or

EPA had no effect or even decreased prostate cancer cell deaths.16

 

A study with another prostate cancer cell line reports that GLA and EPA,

which inhibit an important enzyme in carcinogenesis (urokinase-type

plasminogen activator [uPA]), suppress cell proliferation (growth and

division). Low EPA and high uPA levels have been reported in cancer.

ALA, LA, and AA also suppressed cell proliferation in this study.17

 

Another study found that rats grow faster when vitamin E is given along

with linseed oil (which is refined, bleached, deodorized flax oil), grow

slower if linseed oil was given without vitamin E, and grow even slower

in the presence of pro-oxidant.18

 

A study in women found that only ALA, but not saturates,

monounsaturates, or long chain polyunsaturates n-3 or n-6, had a

protective effect on breast cancer.19

 

A 1999 study found that mutation of the androgen receptor (AR) gene as a

cause of prostate cancer is rare, and that over-expression of the AR

gene seems to be the most common alteration in hormone-refractory

prostate cancer.20 The question left unanswered is what causes this

over-expression.

 

A study published in 2001 concludes that a high intake of both red meat

and dairy products is associated with a two-fold increase in risk of

prostate cancer. The reason for the association with red meat remains

unexplained.21 Another 2001 study found that a short term (3 month) low

fat, fish oil (EPA and DHA) enriched diet increased the n-3/n-6 ratio in

plasma and adipose tissue. Also, cyclooxygenase (COX-2) expression

decreased in 4 of 7 patients.22 COX-2 produces inflammation, which is

involved in cancer.

 

Finally, a study found that DHA and EPA decreased expression of several

genes that are up-regulated by androgen in LNCaP prostate cancer cells.

They thereby reduced androgen-mediated cell growth of this prostate

cancer cell line. DHA increased the proto-oncoprotein c-jun.23

 

Science has become so technical that we’re nearing the Tower of Babble,

where everyone talks and no one understands. We get lost in a sea of

details, lose our common sense, and only drug manufacturers, whose

products suppress symptoms without effecting cure, benefit from the

confusion.

 

It is not difficult to see that these various findings by researchers

must leave most people confused. The problem with these studies is the

isolation in which they are carried out.

 

In Nature, n-3 and n-6 EFAs are undamaged because they have not been

destructively processed, and are accompanied by by many other

oil-soluble substances, including antioxidants, mineral, vitamins,

phytosterols, lecithin, and more. Many of these substances have

anti-cancer or immune-enhancing effects in the body. In the lab,

substances are isolated into chemically pure forms, which are easier to

manage, but in their effects on the body are far different from whole

foods with their thousands of synergistic ingredients.

 

We should address the contradictory findings of the studies by applying

some common sense. That is what we will attempt to do next.

 

N-3 related Causes of Prostate Cancer: Common Sense EFAs are chemically

very active molecules. They are required for vital functions in all

cells and tissues. We cannot live withut them. They must be provided by

foods.

 

The big question that begs to be answered is why substances that are

absolutely required for health can at the same time give you cancer and

kill you. It doesn’t make sense. So there must be other issues that are

being ignored when professionals (untrained in nutrition), in this case

of ALA and flax oil, issue an edict against their use.

 

Here are my thoughts on the issues that must be considered in trying to

find out what is happening in the effects of EFAs in prostate cancer,

and how to avoid or fix it.

 

1. Processing damage of ALA, the most fragile of essential nutrients,

must be considered as a possible cause of increased prostate cancer. As

ALA consumption increases, so does the amount of damaged, toxic

breakdown products of ALA resulting from careless treatment of this

essential nutrient.

 

Unless care is taken to protect ALA from being damaged and thus made

toxic by light, air, and heat, health problems based on the toxicity of

altered molecules of ALA should be expected to accompany ALA intake.

 

2. Pro-oxidants. According to one of the above studies, which compared

high and low intakes of ALA in humans,5 the strongest risk factor was

the consumption of red meat. Red meat is rich in iron, which along with

other metal elements such as copper, has strong pro-oxidant action that

can speed up the damage done to EFAs by light, oxygen, and heat. That’s

true outside the body as well as inside the body.

 

Because of ALA’s far higher fragility, we should expect ALA to be

damaged far more extensively than LA. As a result, far more toxicity

should come from diets with higher ALA intake in association with

pro-oxidants that lead to free radical formation and oxidation products.

 

 

Related information shows that red meat consumption correlates with

increased cancer in general. White meats from chicken and turkey, which

contain as much ALA as red meat does, show less of a correlation with

cancer than red meat.

 

High fat fish, which contains more n-3 than red meat, and in the form of

EPA and DHA, that are even more fragile to damage done by light, air,

and heat, lowers cancer risk factors. And raw high fat fish, in the form

of Japanese sushi or sashimi, correlates with the least cancer.

 

These findings do not provide proofs, but the trend is obvious. It

suggests that ALA or the other n-3 do not increase prostate cancer, but

that the n-3 molecules damaged during commercial processing and food

preparation-cooking, frying, and especially barbecuing-may well be the

reason for the increased cancer seen in some of the studies.

 

A question that is not often discussed is the effect of cytotoxic

(cell-toxic) chemicals used in the treatment of cancer. Some of these

appear to be able to damage (oxidize) n-3 fats when both are given to a

cancer patient.

 

3. Antioxidant depletion. Research has consistently shown that increased

intake of EFAs increases the need for antioxidants.(31) EFAs are

high-energy fuel. In the body, they build a strong fire. A strong fire

throws more sparks than a weak one. Those who fear the EFAs suggest that

we should lower intake. That means, turn down the fire.

 

Taken to its logical conclusion, that would mean that we should put the

fire out, because if there’s no fire (i.e. we are dead), there’ll be no

sparks that can do damage. Then we need no more antioxidant spark

control, because the fire's out. What would be the point of that?

 

A more viable solution is to make the strongest possible fire of energy

(life), and to make sure that there’s good spark control. Antioxidant

protection should accompany our increased intake of EFAs. N-3 fatty

acids, being more chemically active than n-6, probably require a higher

antioxidant intake for spark control. But higher n-6 intake too,

requires more antioxidants.

 

The richest source of antioxidants is fresh green vegetables. They make

hundreds of different kinds of antioxidants. The seeds themselves are

also rich sources of antioxidants for their own (and if we eat them,

our) protection. Oils made with health in mind contain natural

antioxidants appropriate for their EFA content. Oils made with shelf

life in mind have had these antioxidants removed. That's why synthetic

antioxidants (BHA, BHT, and others) are added to replace the natural

antioxidants that were removed by refining, bleaching and deodorizing.

 

And research has shown that 400-800mg of vitamin E daily reduce

cardiovascular risk by over 75%,(32) while 200ug of selenium daily

reduce cancer risk by over 50%.(33) These two powerful antioxidants, as

well as zinc, manganese, vitamin C, vitamin A (or carotene),

sulfur-containing amino acids, alpha-lipoic acid, garlic, and onions,

all provide antioxidant protection to the body.(33b) Certain herbs, and

mushrooms also help.()

 

4. Lack of Phytosterols. Phytosterols have been shown to inhibit many

cancers. One of the pioneers in natural treatments of cancer, Dr.

Emanuel Revici, worked from the hypothesis that lack of EFAs, and lack

of (phyto)sterols cause cancer. He successfully reversed cancer with

EFAs and/or sterols. His methods reversed the cancers of many patients,

and Revici himself was a testimony to his own methods. He died a few

years ago at the age of 102.

 

Unfortunately, much of his work is now lost.(34a) Phytosterols are found

in the membranes of all cells of all plants, in seeds and in unrefined

oils, but they are not found in animals. They inhibit sterol reactions:

cholesterol, and the male and female steroid hormones androgen

(testosterone), estrogens (estradiol, estriol, progesterone), and

corticosteroids (aldosterone, cortisol, and others).

 

They therefore slow down the growth of steroid hormone-specific cancers,

including some types of prostate cancer.

 

5. Too much ALA in relation to LA is another factor that needs to be

addressed. N-3 and n-6 EFAs compete in the body for space on the enzymes

that convert them into derivatives and eicosanoid hormones. Hence the

ratio between them must be such that adequate amounts of both are

converted.

 

A ratio of 2: 1 of n-3 to n-6 will do this. So will a ratio of 1: 4. In

healthy people, a wide range of ratios is able to maintain health. In

people with degenerative conditions, emphasis on n-3 seems to be more

effective. That’s because n-3 intake has dropped to 1/6th of what people

obtained in their diet 150 years ago, while n-6 intake has doubled over

the past 100 years.

 

This problem can be caused by flax oil. Flaxseed, used as the exclusive

source of fats in the diet, will eventually lead to n-6 deficiency. Both

flax and flax oil have an n-3: n-6 ratio of 3.5 or even 4: 1. Using such

a ratio will result in the n-6 EFA being crowded out from the enzymes.

And that will lead to n-6 deficiency symptoms.

 

The list of n-6 symptoms is long but, relevant here, is the fact that

n-6 deficiency leads to deterioration of immune function, which in turn

can lead to increased cancer growth.24

 

A comprehensive list of n-3 and n-6 deficiency symptoms is found in the

book Fats That Heal Fats That Kill. High n-3 with low n-6 can also be

seen in other cancers. I have seen a reference in that regard for breast

cancer.(35)

 

6. Other toxic materials that accompany EFAs can also affect cancers.

For instance, antibiotics used in feeds end up in meat. These

antibiotics can inhibit immune function.(36) Hormones and pesticides

contained in meat, butter, and other dairy products can also affect

cancer outcome.

 

In vegetable oils, the packaging can also be an issue. Plastics, which

contain fillers, plasticisers, stabilizers, mould releasers, and other

industrial chemicals may be able to dissolve in oils, and then have an

effect on the body that accompanies the oil. Packaging oils in clear

glass or plastic, especially those that contain n-3 (canola and soybean)

is an antiquated and inadvisable method, because it exposes the oils to

the destructive influence of light.

 

In some plastics, heavy metals like lead have been found. Carbon Black,

a cousin of soot used to make some plastics opaque to light, contains

PAHs (Polycyclic Aromatic Hydrocarbons) that form when carbon reacts

with itself in a situation of incomplete burning. PAHs are

carcinogenic.(37)

 

Oxidative stress from cell-killing (cytotoxic) chemicals-industrial

(e.g. pesticides) or even pharmaceutical (e.g. drugs used to treat

cancer and other conditions) can affect the action of n-3 (and other

nutrients) in the body. Since n-3 are natural and essential, and drugs

are unnatural and toxic, preference should be given to natural

treatments whenever possible.

 

The practice of " complementary medicine " , in which natural as well as

unnatural treatments are combined, in such cases becomes " contradictory

medicine " . To be healthy, we must not poison our genetic program and its

work, and we must give that genetic program the building blocks it needs

to build a healthy body.

 

If we give our genetic program the building blocks it needs but poison

it at the same time, we should not expect good health outcomes, because

these two approaches contradict each other. We cannot poison our way to

health.

 

The Cause of the Increase in Prostate Cancer: Research Authors of

published studies have suggested several possibilities to explain the

correlation of ALA with prostate cancer.

 

These include:

 

1. Oxidation products of ALA formed during cooking of meat;

 

2. Damage done to ALA molecules during processing;

 

3. Low ratio of LA: ALA (too little LA, which leads to breakdown of

immune system function and therefore to increased cancer growth;

 

4. Lack of balancing molecules such as phytosterols and antioxidants,

which are found in seeds, but are removed or damaged during processing

and cooking practices;

 

5. Free radical formation from fatty acid oxidation.

 

6. ALA-based free radicals (resulting from processing) that can damage

genetic material (DNA) and lead to tumor formation;

 

7. Decrease in the level of antioxidants, because they are used up to

deal with ALA-based free radicals produced in the body;

 

8. Alterations in eicosanoid synthesis;

 

9. Changes in cell membrane composition, affecting permeability and

receptor activity;

 

10. Interference with 5-alpha-reductase activity;

 

11. EFAs may increase steroid hormone production that is important in

androgen sensitive growth. (Actually, EFAs decrease steroid hormones.

Apparently they make hormones work better, and therefore smaller amounts

of hormones are needed to get their normal job done.

 

Differences between Oils Made Without or With Health in Mind

 

I learned about the highly sensitive n-3 ALA in 1983. I have emphasized

since that time that ALA should never be subjected to the destructive

influences of light, oxygen, and high temperatures.

 

One or more of these destructive influences is involved during

 

1. Commercial and home frying;

 

2. Processing (deodorization) involved in the production of the cooking

(RBD) oils that line the shelves of grocery, convenience, and health

food stores;

 

3. Hydrogenation, a process used to make margarine and shortening; and

 

4. Partial hydrogenation of oils to make shelf stable convenience foods.

 

 

Damage done to ALA molecules by light, air, and heat can produce highly

toxic unnatural molecules.24 ALA forms more toxic breakdown products due

to processing damage than does the n-6 EFA.24

 

Destructive processing is likely the cause of some of the changes that

lead to increased prostate cancer.

 

A more comprehensive story of how EFAs are damaged is found in the book

Fats That Heal Fats That Kill.

 

What Should we Do to Protect our Prostate Gland?

 

Born in 1942, I’m in the age group of men that should pay attention to

the condition of their prostate gland. I cannot give you medical advice

or make decisions for you, but I can tell you what I do.

 

I do not use, and recommend against the use of flax oil except in

combination with other, n-6 richer oils. It is a great source of n-3 but

a very poorly balanced oil, deficient in the equally necessary n-6.

 

I abhor the use of plastics for packaging liquids (water, oil, milk,

juices, alcohol, tinctures, etc.). Liquids move all the time, and

continually wash the inside of their container. You can taste plastic in

water. You won’t likely taste plastic in oils, but they are even more

likely to drift into oils than into water, because oils swell plastics.

 

I do use and recommend an oil blend containing flax with sunflower and

sesame oils from organically grown seeds, made with health in mind, and

in the right n-3: n-6 ratio to prevent n-6 deficiency.

 

I do insist that my oil blend is packed in brown glass and further

protected by a box to keep out all light.

 

I also use and recommend zinc, antioxidants, phytosterols, saw palmetto,

broccoli and other cruciferous vegetables, anti-inflammatory herbs, and

maitake extracts or mushrooms as part of a prostate nourishing

nutritional program.

 

I use and recommend optimum intake of all components of health: 20

minerals, 13 vitamins, 8-11 amino acids, and 2 fatty acids; detoxifying

fiber, digestive enzymes, and friendly bowel microorganisms;

antioxidants; herbs (phytonutrients); filtered water; clean air;

sunlight; and fuel.

 

I engage in and recommend physical activity (work or exercise) to stay

fit.

 

I indulge myself in and recommend rest; recreation; the passionate

pursuit of worthwhile goals; time spent with friends; a sense of humor;

good balance between work and play; heart-felt gratitude; and faith in

the grand scheme of things.

 

I don’t worry about ALA causing me prostate cancer. I use ALA on a daily

basis, balanced with LA in my oil blend, as part of my program for

health, along with lots of fresh organic green foods, proteins, support

for digestion, and carbohydrate intake limited to the amount I burn.

 

ALA, after all, is essential for life and for health.

 

 

http://store./annieappleseedproject/flaxoilcaner.html

 

 

 

LINK to 'the' expert on fats

 

--

 

 

Diet, Activity, and Lifestyle Associations With p53 Mutations in Colon

Tumors

=============================================

 

http://store./annieappleseedproject/dietaclifasw.html

Slattery ML, Curtin K, Ma K, et al.

 

The association between the p53 tumor suppression gene mutation, which

is a common event in the development of colon cancer, and dietary and

lifestyle factors was evaluated as part of a multicenter case-control

study.

 

The p53 mutational status was determined for a total of 1458 cases of

colon cancer using single strand conformational polymorphism/sequencing

of exons 5-8. The associations between those with mutations and those

without were compared with a population-based group of controls (n =

2410). Comparisons were also made between cases with p53 mutations

compared with cases without p53 mutations.

 

Subjects with a p53 mutation were more likely to consume a Western-style

diet compared with controls than were cases who were p53 wild type.

 

Specific components of the diet were also found to be most strongly

associated with p53 mutations, including a diet with a high glycemic

load as well as foods high in red meat, fast food, and trans-fatty acid

(mutation vs control, odds ratio = 1.92 95% CI = 1.47-2.50).

 

Diets with a high glycemic load relative to the lowest intake were found

to be significantly associated with missense mutations (OR = 1.69; 95%

CI = 1.23-2.33, comparing p53+ to controls, and OR = 1.72; 95% CI =

1.19-2.50, comparing cases p53+ to cases of p53 wild type).

 

Similar findings were seen with diets high in red meat, fast food and

trans-fatty acid.

 

The authors conclude that components of the Western diet -- namely, red

meat and foods that increase glycemic load -- play an important role in

the process of the p53 disease.

 

Clinical Commentary: This important study shows a clear association

between specific features of the Western diet and the p53 tumor

suppressor gene. Inactivation of the p53 tumor suppressor gene is a

common event in the development of colon cancer.

 

The strength of this study lies in the number of subjects studied and

the case-control study design, although little information is provided

on the dietary methodology used and the quality of the dietary data

collected (eg, what was the extent of under-reporting?). It is important

to note that the conclusions of the study need to be treated with some

caution, i.e. that components of the Western-style diet are associated

with the p53 disease pathway.

 

This study provides no indication of the mechanisms involved in this

association and the number of confounding factors controlled for were

limited.

 

Specific nutrient components, such as total fat intake and levels of

particular vitamins and minerals, also were not investigated. This is a

useful 'hypothesis-generating' study, and further research is certainly

warranted in this area, particularly the role of fruit and vegetables

(and other food components) as possible protective factors.

 

Cancer Epidemiology, Biomarkers and Prevention. 2002;11(6):541-548

 

Medscape Journal Scan, 9/02

_________________

_________________

JoAnn Guest

mrsjo-

DietaryTi-

www.geocities.com/mrsjoguest/Genes

 

 

 

 

AIM Barleygreen

" Wisdom of the Past, Food of the Future "

 

http://www.geocities.com/mrsjoguest/Diets.html

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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