Especially if you have metabolic syndrome …

Lycopene Lowers Mortality Risks
Also if you have rheumatoid arthritis, lupus, some cancers and possibly Alzheimer’s

By Will Block

The primary research upon which this article is based has not yet been traditionally published; i.e., it has not appeared in print. But it is scheduled for a future issue of Nutrition Research.1 Nevertheless, it is available electronically and its findings indicate that higher levels of serum lycopene are associated with reduced mortality.

Reduced Mortality Is a Life Extension Trend

Reduced mortality seems to be a growing trend for lycopene research. In fact, in this article there are three sidebars that amplify this connection. See the sidebar “Lycopene Reduces Rheumatoid Arthritis Mortality,” premised on an article to be published in the European Journal of Integrative Medicine. There are two other research papers not yet published, which feed two more sidebars: “Lycopene Reduces Lupus Mortality” and “Lycopene May Reduce Cancer Mortality.” That’s a total of four papers on the ability of lycopene to reduce mortality, all within a very tight publishing period!

These papers are available now. The first one powerfully provides evidence that there is a significantly lower risk of dying among metabolic syndrome patients who had higher levels of lycopene.

What is Lycopene?

Lycopene is a hydrocarbon phytochemical present in red fruit and vegetables (papayas, tomatoes, red peppers, watermelons, etc.) which belongs to the tetraterpene carotenoid family.

Ingestion of products containing cooked tomato accounts for about 80% of daily dietary intake of lycopene in the developed world. In the western world, there are significant individual differences, with average lycopene consumption falling between 5 and 7 mg/day.2

Lycopene is distinguished by its ability to neutralize free radicals, and consequently conferring measurable protection against cancer, atherosclerosis, diabetes, and some inflammatory diseases.

Moreover, there is a growing body of epidemiological evidence suggesting that lycopene consumption is associated with decreased risk of various chronic diseases, while lycopene also demonstrates significant antioxidant activity in a number of in vitro and in vivo systems.


Higher levels of serum lycopene
are associated with
reduced mortality.


The multiple biological effects of lycopene are determined by its unique chemical structure and biochemical properties.

What is Metabolic Syndrome?

Metabolic syndrome is a condition characterized by at least three of the following five metabolic criteria:

1) Abdominal obesity

2) Increased fasting glucose

3) High blood pressure

4) Increased plasma triglycerides

5) Reduced high-density lipoprotein (HDL) cholesterol concentrations


There is a significantly lower risk of
dying among metabolic syndrome
patients who had
higher levels of lycopene.


27% of Adults 20 Years or More Have Metabolic Syndrome

In the United States, metabolic syndrome affects as much as 27% of adults 20 years and older. Metabolic syndrome touches more than 86 million Americans—a huge number. Importantly, this syndrome is a risk factor for cardiovascular disease, type 2 diabetes mellitus, and stroke. Moreover, metabolic syndrome also increases the risk of mortality. Although the biological mechanisms by which metabolic syndrome increases the risk of mortality are varied and not entirely clear, among these mechanisms are increased oxidative stress and inflammation which may play an important role in the high mortality of individuals with metabolic syndrome.


Cooked tomato accounts for about
80% of daily dietary intake of
lycopene in the developed world.


In the new study,1 a team from the University of Nebraska Medical Center in Omaha evaluated data from 2,499 participants who enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2001-2006. NHANES is a program of studies designed to assess the health and nutritional status of adults and children in the United States. The survey is unique in that it combines interviews and physical examinations. Subjects were limited to those 20 years of age and older with metabolic syndrome. Blood samples collected upon enrollment were analyzed for serum lycopene concentrations.

Among subjects whose lycopene levels were among the top one-third of participants, the risk of dying over follow-up was 39% lower than those in the lowest group (the third tertile), and for those whose levels were in the middle third, the risk was 33% lower.


Metabolic syndrome touches
more than 86 million Americans—
a huge number.


First Study to Connect Serum Lycopene and Mortality Risk in Metabolic Syndrome

“To our knowledge, this is the first study to examine the association between serum lycopene and the risk of mortality in individuals with metabolic syndrome,” authors Guang-Ming Han and colleagues announce in their paper.1

Furthermore, they wrote, “Although the biological mechanisms by which metabolic syndrome increases the risk of mortality are not entirely clear, increased oxidative stress and inflammation may play an important role in the higher rate of mortality of individuals with metabolic syndrome.”


The mean survival time of people
with the highest serum lycopene
concentration was about 4 months
more than the medium group; they
lived about 13 months more than
people with the lowest serum levels.


Lycopene Eases Oxidative Stress and Decreases Inflammation

“Lycopene has the potential to reduce the risk of mortality by alleviating oxidative stress and decreasing inflammation,” they proclaim.1 Also, “As expected, our study clearly demonstrated that higher serum lycopene level is significantly associated with higher survival time among participants with metabolic syndrome.”

Results showed that the mean survival time of people with the highest serum lycopene concentration was about 4 months more than the medium group, and about 13 months more than people with the lowest serum levels.

“Although the biological mechanisms by which metabolic syndrome increases the risk of mortality are not entirely clear, increased oxidative stress and inflammation may play an important role in the higher rate of mortality of individuals with metabolic syndrome,” wrote the researchers. “As a natural antioxidant, lycopene was found to alleviate oxidative stress and decrease inflammation.

“Also, animal experiments demonstrate that lycopene can significantly decrease the pro-inflammatory cytokines and chemokines expression by inhibiting tumor necrosis factor alpha (TNFalpha)-mediated activation of the NF-kappa B signaling pathway in vitro and in vivo. Therefore, lycopene has the potential to reduce the risk of mortality by alleviating oxidative stress and decreasing inflammation.”


Importantly, most of the clear
beneficial results have been found
when using a mixed ingredient
therapy supplement, containing
lycopene and other nutrients
found in whole tomatoes.


The Bountiful Dose

Importantly, most of the clear beneficial results have been found when using a mixed ingredient therapy supplement, containing lycopene and other nutrients found in whole tomatoes.. Truly, the mixed ingredient approach represents a harvest of nutrients.

As an antioxidant, lycopene as a mixed ingredient has been taken orally in doses of 6.5, 15, 30 mgs daily, along with other dose levels. Doses cited in the literature for reducing the risk of:

• Coronary artery disease
2 mg
6 months3
• Prostate cancer
15 mg
6 months4
• Brain tumors
8 mg
3 months5
• High blood pressure
250 mg
8 weeks6
• Gum disease
8 mg
2 weeks7
• Exercise-induced asthma
30 mg
1 week8
• Infertility
4 mg
3 months9
• Mouth sores
4-8 mg
3 months10
• Sun damaged skin
16 mg
12 weeks11

This list is not exhaustive.

Dose for Lowering Mortality

Returning to the initial article on lycopene and mortality,1 the question remains: how much lycopene can raise one from the lowest tertile (third) into the highest? Of the three groups, the mean levels were as follows:

1. First tertile group—lowest serum lycopene level, 0.204 μmol/L

2. Second tertile group—middle serum lycopene level 0.374 μmol/L

3. Third tertile group—highest serum lycopene level, 0.626 μmol/L

The results of the length of life for each group were: 120.6 months for the high serum lycopene group compared to 116.3 months for the middle group and 107.4 months for the lowest group. These were calculated by the date of death for participants. This means that those in the highest serum level tended to live 13.2 months longer—more than one year!

The good news is that in a Lyc-O-Mato (mixed ingredient) study, serum levels of lycopene increased from 0.28 (week 0) to 0.62 nmol/mL, with consumption of only one standard Lyc-O-Mato capsule containing 9.8 mg of lycopene.12

References

  1. Han GM, Meza JL, Soliman GA, Monirul Islam KM, Watanabe-Galloway S. Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome, Nutrition Research (2016), doi: 10.1016/j.nutres.2016.01.003.
  2. Wang XD. Lycopene metabolism and its biological significance. Am J Clin Nutr. 2012 Nov;96(5):1214S-22S.
  3. Misra R, Mangi S, Joshi S, Mittal S, Gupta SK, Pandey RM. LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial. J Obstet Gynaecol Res. 2006 Jun;32(3):299-304.
  4. Schwenke C, Ubrig B, Thürmann P, Eggersmann C, Roth S. Lycopene for advanced hormone refractory prostate cancer: a prospective, open phase II pilot study. J Urol. 2009 Mar;181(3):1098-103.
  5. Puri T, Goyal S, Julka PK, Nair O, Sharma DN, Rath GK. Lycopene in treatment of high-grade gliomas: a pilot study. Neurol India. 2010 Jan-Feb;58(1):20-3.
  6. Engelhard YN, Gazer B, Paran E. Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study. Am Heart J. 2006 Jan;151(1):100.
  7. Belludi SA, Verma S, Banthia R, Bhusari P, Parwani S, Kedia S, Saiprasad SV. Effect of lycopene in the treatment of periodontal disease: a clinical study. J Contemp Dent Pract. 2013 Nov 1;14(6):1054-9.
  8. Neuman I, Nahum H, Ben-Amotz A. Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant. Allergy. 2000 Dec;55(12):1184-9.
  9. Filipcikova R, Oborna I, Brezinova J, Novotny J, Wojewodka G, De Sanctis JB, Radova L, Hajduch M, Radzioch D. Lycopene improves the distorted ratio between AA/DHA in the seminal plasma of infertile males and increases the likelihood of successful pregnancy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Mar;159(1):77-82.
  10. Karemore TV, Motwani M. Evaluation of the effect of newer antioxidant lycopene in the treatment of oral submucous fibrosis. Indian J Dent Res. 2012 Jul-Aug;23(4):524-8.
  11. Rizwan M, Rodriguez-Blanco I, Harbottle A, Birch-Machin MA, Watson RE, Rhodes LE. Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol. 2011 Jan;164(1):154-62. doi: 10.1111/j.1365-2133.2010.
  12. Aust O, Stahl W, Sies H, Tronnier H, Heinrich U. Supplementation with tomato-based products increase lycopene, phytofluene, and phytoene levels in human serum and protects against uv-light-induced erythema. Int J Vitam Nutr Res. 2005 Jan;75(1):54-60.

Lycopene Reduces Rheumatoid Arthritis Mortality

Increased oxidative stress and/or chronic inflammation may play important roles in the high mortality of individuals with rheumatoid arthritis (RA).1 As a natural antioxidant, lycopene can alleviate oxidative stress and decrease inflammation. Therefore, the researchers hypothesized that lycopene has a potential to reduce the risk of mortality in individuals with RA.

694 RA participants aged 20 years and older, drawn from the third National Health and Nutrition Examination Survey (NHAMES III), were divided into three groups by the tertile rank method according to their serum concentration of lycopene.

These participants were followed-up from the date of interviews (1988–1994) to December 31, 2011 for mortality. Mortality, survival functions and hazard ratios of mortality were compared between these three groups.

The mortality of participants was significantly lower for the third tertile group compared to the first tertile group and the second tertile group among participants with RA. There was a significant survival difference between the third tertile group and the first tertile group. And when adjusted for demographic and other risk factors, RA participants in the third tertile group had a significantly reduced hazard ratio for all-cause mortality—a 36.9 risk hazard reduction compared to RA participants in the first tertile group.

These findings indicate that serum lycopene has a significant inverse association with long-term all-cause mortality in individuals with RA. RA is an autoimmune disease, characterized by excessive production of oxidative stress and/or chronic inflammation that leads to functional joint impairment and increased mortality.

The mortality in patients with RA has decreased over past decades due to earlier diagnosis, and more aggressive and efficient therapies. Nevertheless, it still remains higher in patients with RA compared to the general population.

Although the reasons for the high mortality are not entirely clear, accumulating epidemiologic evidence indicates that increased oxidative stress and/or chronic inflammation may play important roles in the high mortality of individuals with RA. Lycopene reduces RA mortality.



  1. Han GM, Han XF. Serum lycopene is inversely associated with long-term all-cause mortality in individuals with rheumatoid arthritis: Result from the NHANES III. Eur J Integr Med. 2015 463. Available online 23 October 2015.

Lycopene Reduces Lupus Mortality

Persistent inflammation and oxidative stress are the main mechanisms that increase the risks of cardiovascular disease-related morbidity and mortality in systemic lupus erythematosus (SLE).1 As a natural antioxidant, lycopene can alleviate oxidative stress and suppress inflammation. The authors of a recent study hypothesized that lycopene had the potential to reduce mortality in SLE.

Thirty-seven participants with SLE from the NHANES III study were divided into two groups (higher level group and lower level group) according to serum lycopene levels. These participants were followed-up from the date of interview (1988-1994) to 31 December 2006 for mortality. Mortality rate and survival function were compared between the two SLE groups.


Higher serum lycopene has the
protective effect on mortality in SLE.


The mortality rate was significantly lower in the higher-level group (5.3%) than in the lower level group (33.3%). There was a significant survival difference between the higher-level group and the lower level group. Additionally, cardiovascular disease-related mortality was dramatically lower in the higher-level group than that in the lower level group.

These findings from nationally representative samples (NHANES III) indicate that higher serum lycopene has the protective effect on mortality in SLE.



  1. Han GM, Han XF. Lycopene reduces mortality in people with systemic lupus erythematosus: A pilot study based on the third national health and nutrition examination survey. J Dermatolog Treat. 2016 Jan 14:1-6. [Epub ahead of print]

Lycopene May Reduce Cancer Mortality

Another new analysis was conducted to evaluate the association between plasma beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, total carotenoids, retinol, alpha-tocopherol and subsequent mortality.1


All-cause mortality was the
primary outcome while cause-
specific mortality was the
secondary outcome.


Blood samples were collected from 259 participants in a chemoprevention trial aimed at the prevention of second cancers of the oral cavity, pharynx, or larynx. High performance liquid chromatography (HPLC) was used to analyze for selected micronutrients. All-cause mortality was the primary outcome while cause-specific mortality was the secondary outcome.


Only plasma lycopene
was significantly associated
(inversely) with total mortality in
the full study population.


61 deaths occurred over a follow-up time of 90 months. In models adjusted for age, plasma cholesterol, time-dependent smoking, treatment arm, study site and gender, only plasma lycopene was significantly inversely associated with total mortality.

Smoking status modified plasma nutrient associations with total mortality. Lycopene, alpha-carotene and total carotenoids were inversely associated with mortality in non-smokers, while plasma retinol and alpha-tocopherol were positively associated with mortality in smokers. Smoking modifies associations between nutrients and mortality.

Again, only plasma lycopene was significantly associated (inversely) with total mortality in the full study population.



  1. Mayne ST, Cartmel B, Lin H, Zheng T, Goodwin WJ Jr. Low plasma lycopene concentration is associated with increased mortality in a cohort of patients with prior oral, pharynx or larynx cancers. J Am Coll Nutr. 2004 Feb;23(1):34-42.

Lycopene Lowers Renal Cell Carcinoma

The February 2015 issue of the journal Cancer reported a finding among participants in the Women's Health Initiative (WHI) of a lower risk of renal cell carcinoma in association with greater intake of lycopene.1

Cathryn Bock, PhD, MPH, and colleagues analyzed data from 96,196 postmenopausal women enrolled in the WHI from 1993 to 1998, and were followed through July, 2013. Dietary questionnaires completed upon enrollment were analyzed for the intake of lycopene and other antioxidants, and supplement use was ascertained in subject interviews.

Two hundred-forty women were diagnosed with renal cell carcinoma over follow-up. Among women whose intake of lycopene was among the top 25%, there was a 39% lesser risk of the disease in comparison with those whose intake was among the lowest 25%.


Among women whose intake of
lycopene was among the top 25%,
there was a 39% lesser risk of the
disease in comparison with those
whose intake was among
the lowest 25%.


Scary Cancer of the Kidneys

Kidney cancer is the eighth-most common cancer in women. One particularly scary fact about this cancer is that by the time it is spotted, it has often progressed to an advanced stage. This makes prevention especially key when it comes to this illness.

“Lycopene from food sources has also been associated with decreased risk of breast and prostate cancers, and a diet high in vegetables and fruits are generally well-accepted for promoting good health,” noted Dr. Bock, who is an associate professor of Oncology at Wayne State University's School of Medicine.

“Kidney cancer is a relatively rare cancer, so focusing only on reducing risk of this disease would be short-sighted,” she remarked. “Rather, a diet focused on one's own personal risk factors, such as family history, would be more beneficial.”



  1. Ho WJ, Simon MS, Yildiz VO, Shikany JM, Kato I, Beebe-Dimmer JL, Cetnar JP, Bock CH. Antioxidant micronutrients and the risk of renal cell carcinoma in the Women's Health Initiative cohort. Cancer. 2015 Feb 15;121(4):580-8. doi: 10.1002/cncr.29091. Epub 2014 Oct 9.

Lycopene Lowers Risk of Alzheimer’s Mortality

Oxidative stress is implicated in the cause of Alzheimer’s disease (AD). Amassing evidence shows that antioxidant-rich food and antioxidant supplements reduce the risk of AD by inhibiting oxidative stress. A recent study found that serum levels of carotenoids are associated with the risk of AD mortality in a nationally representative sample of US adults.1

Using data from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File, 6,958 participants, older than 50 years, were included in this study.

The researchers found that high serum levels of lycopene and lutein + zeaxanthin at baseline were associated with a lower risk of AD mortality after adjustment for potential covariates. The reduction in the mortality risk was progressively raised by increasing serum lycopene and lutein + zeaxanthin levels. In contrast, no associations with AD mortality were observed for other serum carotenoids, including alpha-carotene, beta-carotene, and beta-cryptoxanthin.

It was concluded that high serum levels of lycopene and lutein + zeaxanthin are associated with a lower risk of AD mortality in adults. These findings suggest that a high intake of lycopene- or lutein + zeaxanthin-rich food may be important for reducing the AD mortality risk. Supplements should be able to achieve similar results.



  1. Min JY, Min KB. Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer's disease mortality in older adults. Dement Geriatr Cogn Disord. 2014;37(3-4):246-56. doi: 10.1159/000356486. Epub 2013 Nov 15.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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