The World’s Healthiest Substance?

An Update on the Health Effects of Lycopene

Categorized under Supplements

Lycopene is a red plant pigment (a carotenoid) that’s most famously found in tomatoes but also occurs in watermelon, pink grapefruit, papaya, and gac fruit, whatever the hell that is.

Biotest included it in its prostate support and vascular sexual health supplement, P-Well™, because lycopene loves the prostate. The evidence is overwhelming:

  • A meta analysis of 26 studies with over 560,000 participants found an inverse relationship between lycopene levels and prostate cancer.
  • A study of almost 50 thousand men found those with higher intakes of lycopene were less likely to develop prostate cancer.
  • Another meta analysis of 17 studies found that men with increased tomato product consumption (as stated, a primary source of lycopene) correlated with a 15 to 20% lower rate of prostate cancer.

There’s also a bunch of research showing how lycopene inhibits prostate growth, otherwise known as benign prostatic hypertrophy, or BPH….

You know, I just had a thought. Rather than drone on about how lycopene does what it does and force you to wallow in biochemical esoterica, I’m just going to list a series of lycopene factoids that illustrate just how important this carotenoid is to human health.

Later on in the article, if you want, you can continue reading and I’ll give you some more background intel.

Lycopene for 500, Alex (or Whoever’s Taking His Place)

  • Among all the carotenoids (over 600 of them), lycopene has the highest free-radical scavenging ability.
  • When men suffering from infertility took 2 milligrams of lycopene twice a day for three months, 66% of the men showed improved sperm concentration while 73% showed improved sperm motility (when sperm are more active, you’re more likely to slide an impregnating puck through the egg’s net).
  • In addition to showing promise in fighting prostate cancer, lycopene has also shown promise against bladder, cervical, oral, esophageal, pancreatic, and rectal cancers, in addition to leukemia and cancers of the colon, lung, and breast.
  • Levels of lycopene are inversely related with plasma glucose levels and fasting insulin levels. (That means it makes you more insulin sensitive, thus thwarting Type II diabetes and inefficient carbohydrate metabolism in general.)
  • As little as 5 to 7 mg. a day of lycopene is thought to reduce the risk of cardiovascular disease, but in the cases of existing cardiovascular disease, doses of 35 to 75 mg. per day might be needed.
  • Lycopene seems to protect the skin against UV-B induced sun damage.
  • Lycopene can inhibit platelet-derived growth factor, which inhibits the growth, invasion, and metastasis of melanoma.
  • In hairless mice, lycopene improved the visual appearance of skin, made the skin moister, and even increased skin thickness. (When animals age, their skin gets thinner, allowing for more wrinkles.)
  • Increased lycopene levels may be associated with a lower risk of age-related macular degeneration.
  • Lycopene can activate the adaptive immune response (the T-cells and B-cells that produce antibodies that attack specific infections).
  • Lycopene is thought to have promise in combating some neurodegenerative diseases.
  • A meta analysis of 12 studies found that 25 mg. of lycopene taken daily reduced LDL (the “bad” cholesterol) and high blood pressure.
  • An observational study of 6,000 people found that eating tomatoes protected against digestive cancers (those of the throat, stomach, and colon).
  • Taking up to 3 grams of lycopene per kilogram of bodyweight has no adverse effects. In other words, it’s extremely safe.

Lycopene

How It Do What It Do?

Lycopene is, of course, a hugely powerful antioxidant, which explains a lot of its beneficial effects (reducing fasting blood glucose, improving sperm quality and quantity, reverting tumor initiation, etc.).

But lycopene is also a potent anti-inflammatory agent, has hypocholesterolemic action (prevents plaque in arteries), exhibits strong immune modulation (protects against bacterial infection), displays anti-angiogenesis properties (prevents blood vessels from “feeding” tumors), and has significant abilities to modulate phase I and phase II enzymes (allowing it to protect cells and tissues in general).

And maybe, most interestingly, or at least most interestingly to me, lycopene fosters something known as “gap junctional communications,” which is another way of saying that it allows exchange of signaling molecules and nutrients between neighboring cells. This is important because one of the characteristics of cancer is the loss of gap junctional communications.

Why Not Just Eat Tomatoes?

Tomatoes generally contain relatively large amounts of lycopene (roughly 31 mcg. per gram). However, getting adequate or therapeutic amounts of lycopene isn’t as easy as chomping on a tomato every day.

The frustrating thing is that the lycopene molecules in a fresh tomato are all in the trans configuration. Trans literally means “the other side of” in Latin and it refers to the condition when atoms or functional groups are on opposing sides of an imaginary line drawn down the middle of a molecule. The problem with that is the trans configuration prevents much of the lycopene from being absorbed.

What we need to do is “flip” the functional groups to a cis configuration (“this side of”). We can do this by processing the tomatoes, i.e., exposing them to heat, acid, or light, or pureeing them.

But even if we do manage to flip the lycopene, things like age, gender, hormonal status, smoking, alcohol, how well we chew or masticate the tomato, and how much fiber we eat with it (fiber reduces absorption) affect how much lycopene our digestive system extracts from a tomato.

So while eating tomato paste or stewed tomatoes is, in theory at least, a much more viable way to get adequate amounts of lycopene, it’s still problematic. As is true with most fruits (and vegetables), the content of any specific carotenoid like lycopene (or any phytochemical) varies enormously due to tomato variety, soil quality, length of growing season, and environmental factors.

Then there’s the issue of dosage. Estimates of how much we need for optimal health run to 25 mg. a day or more, making it extremely difficult to get that much from natural sources.

That leaves us with two options: 1) Eat a lot of tomato paste every day, thereby giving yourself a fighting chance of getting enough lycopene, or 2), take lycopene in supplement form.

Enter P-Well™

As mentioned, Biotest included lycopene in its P-Well™ formulation and it’s pretty easy to see why.

Together with punicaligan (the workhorse polyphenol in pomegranate) and cranberry extract, lycopene and its partners not only support prostate health, but they might also allow you to enjoy a better sex life by allowing more blood to flow into the penis (by improving the elasticity of the blood vessels in the penis and throughout the body).

But beyond all that, it’s pretty clear that lycopene is a hugely potent natural substance that everyone, man and woman alike, should arguably consider taking to improve overall health.

Buy p-Well Here

Each serving of P-Well™ contains 30 mg. of lycopene from natural tomato fruit extract, along with 180 mg. of punicaligan from pomegranate whole fruit extract and 50 mg. of cranberry whole fruit concentrate. Take P-Well™ for prostate support, vascular sexual health, and urinary tract health, or take it just for the health of it.

You can read more about P-Well™ here.

References

  1. Melanie Caseiro, et al. Lycopene in Human Health, LWT – Food Science and Technology, 29 March, 2020. An overview of the effects of lycopene on humans and lab animals.
  2. V. Kalai Selvan, et al. Lycopene’s Effects on Health and Diseases, Natural Medicine Journal, March 2011 Vol. 3 Issue 3. An overview of the effects of lycopene on humans and lab animals.
  3. Ping Chen, et al. Lycopene and Risk of Prostate Cancer A Systematic Review and Meta-Analysis, Medicine (Baltimore). 2015 Aug;94(33): 31260. This study demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa.
  4. J Athen Lane, et al. ProDiet: A Phase II Randomized Placebo-controlled Trial of Green Tea Catechins and Lycopene in Men at Increased Risk of Prostate Cancer, Cancer Pres Res. 2018 Nov;11(1): 687-696. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0-2.95 ng/mL or 3.0-19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. All interventions were acceptable and well tolerated although men preferred the capsules. Dietary prevention is acceptable to men at risk of prostate cancer. This intervention trial demonstrates that a chemoprevention clinical trial is feasible.
  5. Ying Wang, et al. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort, Int J Cancer, 2016 June 15;138 (12):2846-55. Among men with high-risk cancers (T3-T4 or Gleason score 8-10, or nodal involvement), consistently reporting lycopene intake ≥ median on both post diagnosis surveys was associated with lower prostate-cancer specific mortality.
  6. Ping Chen, et al. Lycopene and Risk of Prostate Cancer A Systematic Review and Meta-Analysis, Medicine (Baltimore). 2015 Aug;94(33): 31260. This study demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa.
  7. J Athen Lane, et al. ProDiet: A Phase II Randomized Placebo-controlled Trial of Green Tea Catechins and Lycopene in Men at Increased Risk of Prostate Cancer, Cancer Pres Res. 2018 Nov;11(1): 687-696. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0-2.95 ng/mL or 3.0-19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. All interventions were acceptable and well tolerated although men preferred the capsules. Dietary prevention is acceptable to men at risk of prostate cancer. This intervention trial demonstrates that a chemoprevention clinical trial is feasible.
  8. Ying Wang, et al. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort, Int J Cancer, 2016 June 15;138 (12):2846-55. Among men with high-risk cancers (T3-T4 or Gleason score 8-10, or nodal involvement), consistently reporting lycopene intake ≥ median on both post diagnosis surveys was associated with lower prostate-cancer specific mortality.
  9. Rebecca E Graff, et al. Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression, Am J Clin Nutr. 2016 Mar;103(3): 851-860 – This study aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype. Their study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. During 23 years of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥ 2 servings/wk compared with < 1 serving/mo; multivariable HR: 0.70; 95% CI: 0.52, 0.95; P-trend = 0.002). With respect to molecular subtypes, cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease (HR: 0.54; 95% CI: 0.37, 0.81; P-trend = 0.004) but not with ERG-negative disease (HR: 0.96; 95% CI: 0.62, 1.50; P-trend = 0.10) (P-heterogeneity = 0.04). The conclude that, in particular, tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease.
  10. JL Rowles, et al. Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis, Prostate Cancer Prostatic Dis. 2017 Dec;20(4):361-377 – The data demonstrate that higher dietary and circulating lycopene concentrations are inversely associated with PCa risk. This was accompanied by dose-response relationships for dietary and circulating lycopene. However, lycopene was not associated with a reduced risk of advanced PCa.
  11. Jinyao Chen, et al. Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies, J Nutr Sci Vitaminol, 2013,59(3):213-23 – Eleven cohort studies and six nested case-control studies were identified through searching of international journal databases and reference lists of relevant publications. Two reviewers independently assessed the study quality and extracted data from each identified study; only studies with sufficient quality were included in the review. The main outcome of interest was incidence of prostate cancer. Compared with consumers of lower raw tomato intake, the odds ratio (OR) of incidence of prostate cancer among consumers of higher raw tomato intake was 0.81 [95% confidential interval (CI) 0.59-1.10]; for consumers of higher level of cooked tomato intake versus lower cooked tomato intake, this OR was 0.85 (95% CI 0.69-1.06); the OR of higher lycopene intake versus lower lycopene intake for prostate cancer was 0.93 (95% CI 0.86-1.01) and the OR for higher level of serum lycopene versus lower serum lycopene level was 0.97 (95% CI 0.88-1.08).
  12. Yulan Wang, et al. Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies, PLoS One. 2015;10(9) – α-carotene and lycopene, but not β-carotene, were inversely associated with the risk of PCa.
  13. Rhona A Beynon, et al. Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial, Int J Cancer. 2019 Apr 15;144(8):1918-1928 – Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. This study investigated the effect of factorial randomization to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analyzed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomization, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.
  14. Ke Zu, et al. Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era, J Natl Cancer Inst. 2014 Feb;106(2):dt430 – Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor.
  15. Li Nang, et al. Lycopene exerts anti-inflammatory effect to inhibit prostate cancer progression, Asian J Androl. 2019 Jan-Feb;21(1):8085 – The aim of this study was to investigate the efficacy of lycopene in inhibiting prostate cancer. Cell viability assays indicated the dose- and time-dependent toxicity of lycopene in prostate cancer cells. Annexin V/propidium iodide double-staining assays revealed the strong apoptotic effects of lycopene. The levels of inflammatory factors, including interleukin-1 (IL1), IL6, IL8, and tumor necrosis factor-α (TNF-α), in lycopene-treated cells were also reduced by lycopene treatment. With the increasing dose of lycopene, the survival of mice bearing prostate cancer xenografts was significantly improved (P < 0.01), and the tumor burden was significantly reduced (P < 0.01). Their results indicate that lycopene is a promising chemotherapy drug, which inhibits prostate cancer progression by suppressing the inflammatory response.
  16. Mohhamed M. Rafi, et al. Lycopene modulates growth and survival associated genes in prostate cancer, Journal of Nutritional Biochemistry, Vol 24, Issue 10, October 2013, Pages 1724-1734 – Flow cytometry analyses showed that lycopene, in combination with chemotherapeutic agents and PPARγ agonists, induced modest cell cycle arrest with significant increase in cell death by apoptosis and necrosis on prostate cancer. Gene array and quantitative reverse transcription polymerase chain reaction analyses showed that lycopene alters the expression of growth and apoptosis associated biomarkers in PC-3 cells. These findings highlight that lycopene attenuates prostate cancer by modulating the expression of growth and survival associated genes.
  17. S. Ellinger, et al. Tomatoes and lycopene in prevention and therapy–is there an evidence for prostate diseases? Akutelle Urol. 2009 Jan;40(1):37-43 – Tomatoes are discussed to have an important role in the prevention of and therapy for prostate cancer (PCA). This review summarizes the results of original contributions with a focus on interventional studies. Whereas epidemiological studies on BPH prevention provide no evidence for a preventive potential of tomatoes and tomato products, the majority of interventional trials points to an increased DNA resistance against oxidative-induced damage. Even though their effect on a surrogate marker of the IGF pathway cannot be evaluated so far due to insufficient data, the consumption of tomatoes and tomato products may probably protect from PCA–at least when considering low-grade PCA. Thus, regular consumption of these foods can be recommended for the prevention of PCA. Tomato products might also be useful in the therapy for BPH and PCA.
  18. L Chen, et al. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention, J Natl Cancer Inst. 2001 Dec 19;93(24):1872-9 – Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P < .001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P < .001), respectively. Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/10(5) dG [95% CI = 0.55 to 0.96 8-OHdG/10(5) dG]) than in the randomly selected patients (1.06 8-OHdG/10(5) dG [95% CI = 0.62 to 1.51 8-OHdG/10(5) dG]; P =.03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P < .001). These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.
  19. Danbin Li, et al. MicroRNA-let-7f-1 is induced by lycopene and inhibits cell proliferation and triggers apoptosis in prostate cancer, Molecular Medicine Reports, February 2, 2016 – The results of the current study indicate that miR let 7f 1 is involved in the anticancer effects of lycopene and serves an important role in the inhibition of prostate cancer progression through the downregulation of AKT2.
  20. Ingvild Paur, et al. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA, Clin Nutr 2017 Jun;36(3):672-679 – Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.
  21. T Bureyko, et al. Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro, Br J Nutr. 2009 Apr;10(7):990-7 – Malignant cell lines exhibited lower expression of alpha2beta1 with the addition of lycopene to culture media. Supplemental fish oil reduced alpha2beta1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins alphavbeta3 and alphavbeta5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.
  22. Lei Wan, et al. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis, Cancer Prev Res. 2014 Dec;7(12):1228-39 – Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk.
  23. Nayan Kumar Mohanty, et al. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia, Urol Oncol. Nov-Dec 2005;23(6):383-5 – A total of 40 patients with prostate cancer were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year. Results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction. They concluded that lycopene is an effective chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia, with no toxicity and good patient tolerance.