Foods/Supplements-Vitamins: Lycopene ... - Advanced Prostate...

Advanced Prostate Cancer

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Foods/Supplements-Vitamins: Lycopene - Tomatoes

8 years ago•4 Replies

"Lycopene is the pigment principally responsible for the characteristic deep-red color of ripe tomato fruits and tomato products." [2c]

As of Aug 29, 2016, there are 434 PubMed hits for <prostate lycopene>.

[1] This all started in 1995, with Giovannucci's first paper on the subject, so I'll review his PubMed hits together, since he has been in the thick of it for over twenty years.

[1a] (1995 - U.S. - Health Professionals Follow-up Study)

"Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four--tomato sauce .., tomatoes .., and pizza .., but not strawberries--were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65 ... for consumption frequency greater than 10 versus less than 1.5 servings per week ...)"

Very impressive. All but one of the products are tomato-based - & there isn't the confounding issue of "healthy" lifestyle.

[1b] (1999 - U.S. - Review)

"Four cohort studies ... report data on the relationship between tomato or lycopene consumption and prostate cancer risk. In a cohort of 14, 000 Seventh-day Adventist men, only tomato intake and intake of beans, lentils, and peas were statistically significantly related to lower prostate cancer risk in a multivariate analysis. In a larger, more comprehensive dietary study, intake of the carotenoids β -carotene, α-carotene, lutein, and β-cryptoxanthin was not associated with risk of prostate cancer, but high lycopene intake was related to a statistically significant 21% reduction in risk. High intake of tomatoes and tomato products, which accounted for 82% of lycopene, reduced risk of total prostate cancer by 35% and aggressive prostate cancer by 53%. Tomato sauce had the strongest inverse association with prostate cancer risk (RR = 0.66 ...), and weaker inverse associations were observed with tomatoes and pizza, but none with tomato juice. Preliminary results from two other cohort studies also support this finding."

"One case-control study conducted in Minnesota found an inverse association between tomato intake and risk of prostate cancer that was not statistically significant. In another case-control study conducted in a multiethnic population in Hawaii, no association was found with consumption of “tomatoes.” However, the intake levels were not indicated, and it did not appear that tomato-based products such as tomato sauce were specifically addressed. A case-control study conducted in the U.K. found no association between raw or cooked tomatoes and risk of prostate cancer. Of note, the strongest dietary association found in that study was for baked beans (RR = 0.52 ...); the authors suggest that tinned baked beans may provide highly bioavailable lycopene from the tomato sauce.

"Three studies have examined serum carotenoids using prediagnostic samples in relation to prostate cancer risk. The first study, which was based on serum obtained in 1974 from 25,802 persons in Washington County, MD, found a 6.2% lower median lycopene level in prostate cancer case subjects diagnosed during 13 years compared with age- and race-matched control subjects. The estimated RR was 0.50 between high and low quartiles of lycopene. No other carotenoid was associated with prostate cancer risk. Preliminary results from the Physicians' Health Study (70), which was based on 581 case subjects, found a statistically significant RR of 0.56 when comparing high quintile with low quintile of plasma lycopene.

"A serum-based study conducted during the period from 1971 through 1993 in a Japanese-American population in Hawaii did not detect any association between serum lycopene levels and risk of prostate cancer. However, several characteristics of the study may have contributed to the lack of an association, including use of a single assessment of serum lycopene to characterize follow-up for up to a 22-year period (only 14 cases occurred within the first 5 years of follow-up), inclusion of “low virulence” disease (28% were diagnosed incidentally during surgery for benign prostatic hyperplasia), and very low serum lycopene levels [the median serum concentration among control subjects was only 134 ng/mL, compared with 320 ng/mL in the study by Hsing et al. and 424 ng/mL in the sample of 121 health professionals]. Ethnic differences in prostate cancer etiology may also be important, inasmuch as men of Asian descent may have an inherently low susceptibility to prostate cancer."

[1c] (1999 - U.S. - Physicians' Health Study)

"Subjects included 578 men who developed prostate cancer within 13 years ..."

"Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls ... The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75 ...); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56 ...)"

[1d] (2002 - U.S. - Health Professionals Follow-up Study)

"Results for the period from 1992 through 1998 confirmed our previous findings---that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84 ..."

"... intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77 ...), especially for extraprostatic cancers (RR = 0.65 ...)."

[1e] (2002 - U.S.)

"... the accumulated data suggest that the benefit may be most pronounced in the protection against more advanced or aggressive prostate cancer."

[1f] (2002 - U.S. - Review)

"Recent epidemiologic studies have suggested a potential benefit of this carotenoid against the risk of prostate cancer, particularly the more lethal forms of this cancer. Five studies support a 30% to 40% reduction in risk associated with high tomato or lycopene consumption, three are consistent with a 30% reduction in risk, but the results were not statistically significant, and seven were not supportive of an association."

"The reasons for these inconsistencies are unclear, but in three of the seven null studies, tomato consumption or serum lycopene level may have been too low to observe an effect. Because the concentration and bioavailability of lycopene vary greatly across the various food items, dietary questionnaires vary markedly in their usefulness of estimating the true variation in tissue lycopene concentrations across individuals."

[1g] (2004 - U.S. - Health Professionals Follow-up Study)

"We matched 450 incident prostate cancer cases diagnosed from 1993-1998 to 450 controls by age, time, month, and year of blood donation."

"The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older (OR, 0.47 ...) and without a family history of prostate cancer (OR, 0.48 ...)."

[1h] (2004 - U.S. - Third National Health and Nutrition Examination Survey, 1988-94)

"Greater circulating concentrations of vitamin E, lycopene, and selenium, antioxidant micronutrients that are supported in published reports as protecting against prostate cancer, were observed also to be inversely associated with LUTS."

[1i] (2005 - U.S. - another review)

By 2005, it was perhaps frustrating that some studies showed great benefit, while others showed none. Here, Giovannucci discusses study design aspects that might yield "maximally informative" results.

[1j] (2007 - J Natl Cancer Inst)

Here, Giovannucci suggests the recent (as of 2007) null studies are the result of contamination due to PSA screening. i.e. the older studies used pre-PSA data, when every PCa case represented serious disease, whereas in the PSA era, many cases have lesser disease, & there are indications that lycopene is more important in protecting against advanced disease.

[1k] (2011 - in Cancer Causes Control)

"A recent analysis in the Prostate Cancer Prevention Trial (PCPT) appeared to show no association between serum lycopene and prostate cancer risk, but the unique study design of the PCPT and the complexity of prostate cancer epidemiology suggest an alternative interpretation of the reported findings."

That's all you can get without paying, but it shows Edward in damage control mode.

[1l] (2012 - "A Review and Reassessment in the PSA Screening Era")

Giovannucci expands on his defense of lycopene:

"An alternative possibility is that the earlier studies were conducted largely before the onset of PSA screening, where diagnosis of prostate cancer usually implied a period of increasing aggressive behavior leading to the diagnosis. Thus, the exposure was linked to the development of aggressive behavior in cancers with biologic potential to progress. In the PSA era, 1992–1998 with peak in 1992 following FDA approval as a screening test for prostate cancer, the diagnosis of prostate cancer is not typically linked to aggressive behavior ..." & so on.

[1m] (2014 - U.S. - Health Professionals Follow-up Study)

"Among 49,898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010."

"Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72 ...)."

"In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47 ...)."

"Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential."

[1n] (2015 - U.S./U.K./Spain/Germany/Netherlands/France/Australia/Finland/ Sweden/Norway/Denmark/Greece - pooled analysis of 15 studies)

"Data were available for up to 11,239 cases (including 1,654 advanced stage and 1,741 aggressive) and 18,541 controls from 15 studies."

"risk of aggressive prostate cancer was inversely associated with lycopene"

("OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65")

[2] Lycopene & biochemistry.

There are two parts to this:

(i) Lycopene, as with other carotenoids, require fat for uptake. (There is no point in having a salad bar meal with a no-fat dressing. It's perverse.)

(ii) Heat treatment alters the structure of lycopene. This has an important effect in the body.

[2a] (2004 - U.S.)

"Essentially no absorption of carotenoids was observed when salads with fat-free salad dressing were consumed."

"... the appearance of the carotenoids in plasma chylomicrons was higher after the ingestion of salads with full-fat than with reduced-fat salad dressing ..."

[2b] (1992 - Germany)

"We studied the uptake of lycopene from processed (boiled with 1% corn oil for 1 h) and unprocessed tomato juice in humans. Lycopene concentrations in human serum increased only when processed tomato juice was consumed. Lycopene uptake varied with individuals, but peak serum concentrations were always reached between 24 and 48 h. The carotenoid was eliminated from serum with a half-life of 2-3 d."

[2c] (2000 - Canada)

"Lycopene in fresh tomato fruits occurs essentially in the all-trans configuration. The main causes of tomato lycopene degradation during processing are isomerization and oxidation. Isomerization converts all-trans isomers to cis-isomers due to additional energy input and results in an unstable, energy-rich station." "Heat induces isomerization of the all-trans to cis forms. The cis-isomers increase with temperature and processing time." "The bioavailability of cis-isomers in food is higher than that of all-trans isomers."

[2d] (2007 - U.S.)

"Lycopene is present mainly as cis-isomers in human serum and tissues whereas all-trans-lycopene predominates in tomato products, suggesting that all-trans-lycopene is isomerised in the body or is less bioavailable."

"Healthy adult subjects (n 12) were recruited for this randomised cross-over trial. Each intervention was preceded by a 2-week washout period. Two tomato sauces, one rich in all-trans-lycopene (32.5 mg total lycopene/100 g sauce; 5 % cis-isomers), the other high in cis-lycopene (26.4 mg total lycopene/100 g sauce; 45 % cis-isomers), were produced by different heat-processing techniques. Each sauce (150 g) was served in a standardised meal at 08.00 hours after overnight fasting."

"The present study demonstrates significant lycopene bioavailability from cis-lycopene-rich tomato sauce and highlights the importance of considering isomer-distribution for lycopene bioavailability."

[2e] (2010 - Belgium)

"... thermal processing as such can improve the in vitro bioaccessibility of lycopene in tomato pulp, but the improvement was only significant upon treatments at temperatures of 130 and 140 °C. At such intense process conditions, one should be aware of the negative effect on other quality and nutrient parameters. Possibilities of thermal processing as such to improve the nutritional value of tomato pulp (without the addition of other ingredients) thus looks rather limited."

Mention is made of "the rather high thermal stability of lycopene".

In early Giovannucci studies, he cites lycopene as an example of the importance of consuming fruits & vegetables. It's what most believe, but it's not a scientific observation, & is complete nonsense in the context of lycopene.

Putting on my cook's hat (not a toque), I could make a quick tomato sauce with fresh tomatoes & very little processing, & get no lycopene benefit at all. Alternatively, I could make a pasta sauce, starting with canned Italian San Marzano tomatoes (already heat treated) &, due to the prolonged cooking time, maximize cis lycopene content. The olive oil in the sauce would ensure uptake of the lycopene. Nothing natural about it - & anathema to raw foodists.

[2f] (1996 - U.S. - prostatectomy analysis)

"All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues."

[2g] (2015 - U.S.)

Basically, confirms the preferred cis accumulation in prostate tissue reported almost 20 years earlier.

[3] Supplements.

One has to go out of one's way to find a lycopene product that isn't repackaged Lyc-O-Mato, e.g. [3].

I seem to recall that soon after the initial interest in lycopene, BASF produced a synthetic: LycoVit. Perhaps had high hopes for it. But see [4b].

There is variation in uptake rates. Even at the 10 mg dose, IMO, there will be an increase in plasma levels. It might take weeks, however, to reach the plateau where greater uptake is not possible. A higher dose (20 mg or 30 mg, say) will get there faster, but a maintenance dose of 30 mg is probably a waste of money - 10 mg might be enough. This is just opinion based on readings of years ago. & people are different.

I have no idea how high blood levels should be to ensure PCa saturation. Benign & malignant prostate cells readily take up lycopene. By why?

[4] Clinical Trials (25 hits).

Mostly of little interest. Not clear what these two Docetaxel trials hope to achieve.

[4a] "Docetaxel Plus Lycopene in Castration Resistant, Chemotherapy-Naïve Prostate Cancer Patients" Lyc-O-Mato Recruiting. University of California, Irvine

[4b] "Docetaxel and Lycopene in Metastatic Prostate Cancer" LycoVit Ongoing Medical University of South Carolina

...

My view is (a) that there is probable benefit, (b) Lyc-O-Mato is cheap, (c) side effects are unlikely & (d) drug interactions have not been reported. So why not supplement?

Alternatively, move in with a nice Italian girl who will feed you variations on pasta & tomato sauce every day. LOL

-Patrick

[1a] ncbi.nlm.nih.gov/pubmed/747...

[1b] jnci.oxfordjournals.org/con...

[1c] cancerres.aacrjournals.org/...

[1d] jnci.oxfordjournals.org/con...

[1e] ncbi.nlm.nih.gov/pubmed/121...

[1f] ncbi.nlm.nih.gov/pubmed/124...

[1g] cebp.aacrjournals.org/conte...

[1h] ncbi.nlm.nih.gov/pubmed/153...

[1i] jn.nutrition.org/content/13...

[1j] jnci.oxfordjournals.org/con...