Mahatma Gandhi, India’s "Father of Naturopathy"

Michael Cronin, ND

AANP President 

The entrance to S-VYASA's Prashanti Kutiram Campus

I am writing this from the Swami Vivekananda Yoga Anusandhana Samsthanain University (S-VYASA) near Bangalore, India in the state of Karnataka. I was invited (with 4 weeks notice) to give a presentation on the evolution of the naturopathic profession and naturopathic education in North America at the first International Conference on Yoga, Naturopathy and Arogya (ICYN) in Bangalore, known as the Silicon Valley of India. Naturopathy as a healthcare profession is considered to include Yoga, and there are 12 universities across the country offering a degree in Naturopathy and Yogic Sciences, as well as numerous inpatient facilities. Mohandas (often referred to as Mahatma, meaning “great soul”) Gandhi revived naturopathy in India and is often referred to as the "Father of Naturopathy." Gandhi's birthday, October 2nd, is to be celebrated here by the profession as Yoga and Naturopathy Day.

The ICYN was sponsored by the state government of Karnataka’s Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH). They see Naturopathy as an intrinsic part of the healthcare system and just this week announced that 10% of the state's overall healthcare budget would be dedicated to patients receiving AYUSH care. There is an epidemic of non-communicable disease in India, including diabetes, and cardiovascular diseases are the country’s leading cause of death. There are also other provisions in the works to improve the public access to Naturopathy care, including adding outpatient naturopathic services in all municipal hospitals. 

The scope of practice in Naturopathy includes hydrotherapy, fasting, diet therapy, massage, Acupuncture and Yoga. It does not include medicine administered orally, Homeopathy or Botanical Medicine. Steps are being taken to bridge this divide in order to use evidence-based practices, following the established principles of Naturopathy. Historically, Homeopathy, Ayurveda, and Unani (Persian herbal medicine, widely practiced in Southern Asia) have existed as separate branches of traditional knowledge systems in India and traditional Chinese medicine is not practiced.

The Jindal NatureCure Center

Most naturopathic care is currently delivered through inpatient services. Patients frequently stay for two to four weeks if not longer. The patients fast and juice and afterwards eat natural organic foods, massage, hydrotherapy and learn therapeutic yoga as well as relaxation and meditation techniques for their specific health condition. I just visited the Jindal NatureCure Institute, a beautiful 275-bed, 100-acre inpatient naturopathic and yogic hospital/sanatorium, established as a charitable trust. 

Naturopathic evidence-based research is alive and well in India. At S-VYASA, where we are staying, they have Ph.D. candidates in Yoga who are focusing on many aspects of naturopathy. One Ph.D. candidate I spoke with is researching hydrotherapy for hypertension, another on diabetes and a third on migraines. There is much published work on the physiologic effects of meditation as well as work towards understanding which specific yoga asanas (postures), breathing, relaxation and meditative techniques are best for specific conditions.   

An international working group on naturopathy and yoga convened the day after the conference with participants from over 20 countries. There were four subgroups established, including education, research, clinical practice and regulatory advocacy. Participants from the United States included representatives from Harvard Medical School, the Department of Defense, the Samueli Institute and the AANP. The working group is being funded by the State government of Karnataka’s Department of AYUSH. The government perceives the promotion of Naturopathy and Yoga as not only good for public health, but also an economic engine, separate from their conventional medical tourism. The state has 3 colleges and many hospitals/sanatoriums including, one 275-bed facility and another 200-bed facility. There is clearly dynamic development of Karnataka’s medical tourism capacity and naturopathy is seen as an important component. 

The Indian educational system offers a Science pre-university “stream” in what would be considered an American 11^th and 12^th grade. They have a four-year academic program and a fifth year of internship. They have also established a two-year advanced degree program offering an MD in Naturopathy. 

Learning about India’s unique relationship with Naturopathy was very exciting, but the enthusiasm of the students, doctors, educators and officials was by far the best part. They are all so pleased to connect with the North American profession, as we are to connect with them!

Namaste,

Michael Cronin, ND

Courtesy: http://www.physicianswholisten.blogspot.in/

Posted on: Thursday, February 16, 2012

Wellness versus illness: An Article by Dr. B M Hegde

The ghost of Adverse Drug Reactions staring at our face as the biggest cause of death in modern medicine, couldbe avoided if we follow the holistic management of illnesses to bring man back to his/her state of wellness

“The secret of getting things done is to act!”— Dante Alighieri

Wellness is the overall well being of human beings. Illness is a state where one does not feel well. While quantum physics has opened a new vista in the field of human physiology of wholeness in place of our reductionist, mechanistic, biochemistry based human physiology, the world has now come to realise that the conventional definition of health by the World Health Organisation (WHO) needs change. In this context the IOM, the audit body of US medical establishment, in their February 2010 meeting, had accepted the new definition of Whole Person Healing (WPH) as the future illness care system.

Wellness (conventionally called health) is now defined as “enthusiasm to work and enthusiasm to be compassionate.” Interestingly, this fits in with the time honoured definition of health in Indian Ayurveda, the mother of all medical wisdoms in the world, almost from the time of the Vedas; the latter being timeless. We have now come one full circle in the so called scientific medicine with a down to earth do-able definition of health while the WHO definition of health as a state of physical, psychological, spiritual, emotional, social etc wellbeing, according to Richard Smith, the former editor of the British Medical Journal, is attainable only under two circumstances—after death and during the height of orgasm, which lasts only for a few seconds, anyway!

The man who led the movement for WPH was late Professor Rustum Roy, one of the greatest scientists the world ever had. He was one of the founder members of the IOM. “Over forty? It is time to fix a date for mammogram and the cost has come down for this holiday season from Rs3,950 to just Rs1,750,” reads the prominent headline advertisement in The New Indian Express dated 9 October 2011 in Chennai.  This kind of disease mongering efforts is at the root of all our problems in medicine. They are based on the wrong science of reductionism. Cancer is not a disease in the true sense. Cancer cells are a bunch of “jobless, directionless, wandering, rogue cells” which remain in the human system for years before they show up as clinical cancer only when their numbers have swollen to many millions. Therefore, the so called early diagnosis of cancer and cancer screening in the apparently healthy populations are only myths, although they make good business sense for the cancer industry.

While I have been writing about this for years, the US government has issued a circular that screening for prostate cancer using PSA test is unscientific and unreliable. Mammogram is not far from that truth. In fact, in many places routine mammograms have been given up as mammograms themselves could help generate cancers to grow faster from those wandering cells which otherwise would have died a natural death before they become clinical cancers. Cancer research is an area where the “so called” cancer researchers can tap from a bottom less pocket of the research funds. The research has gone too far from reality into vivisectionist research from reductionism.

This year’s Nobel Prize is an example of that last statement. The three people that succeeded in finding out the small receptor on human immune cells have got the prize. That receptor or its ligand (for making a drug) will not solve any problem. The immune system works as a whole and in association with the other systems of the human being. This has been proven time and again but we do not seem to learn our lessons from our own mistakes. Our cloning efforts, our genetic engineering efforts, our stem cell (exogenous) research have all come to naught. In fact, we conveniently forget the efforts of those researchers who have shown us the right path for stem cells research.

Way back in the early 1950s Professor Robert Becker of the New York University Medical School, a great brain in orthopaedic surgery, had shown how the body cells, wherever they are, under stress and urgent need, could transform themselves into pluripotent stem cells. That is really the body's own efforts to produce endogenous stem cells. He demonstrated that the red blood cells at a fracture site under the periosteum of the broken bone could slowly change into nucleated cells and then put out pseudopodia to become real powerful pluripotent endogenous stem cells which know what to do to heal the bone.

Whereas the stem cells produced by us in the laboratory from any source, when introduced into the human body, need the help of the environment to do what we intend them to do, endogenous stem cells are born with the message to do what is needed. The internal environment for the exogenous stem cells includes not just the body as we see it but the mind. In fact, human body is the human mind seen as a solid body according to quantum physics! The exogenous stem cells could even harm the human system as happened with the first attempts to treat childhood cancers with this method. The original cancer died but a new cancer cropped up! Dolly, the first cloned animal died prematurely as she was as old as her mother (from whom the original cell was used for cloning) and suffered from old age diseases like cancer and joint damage even in infancy! Eric Drexler’s efforts to produce self replicating nanobots which do not require father and mother died a premature death before it took off. Mr Drexler made billions from his company share holders when he claimed that human beings could be made in the laboratory!  Venture capitalists poured millions into his kitty without any returns at the end of the day.

AIDS research in another example. While the protean causes of that syndrome are still very vague, researchers make hay when the research funds pour into the area in plenty. They are still going after that poor virus, the HIV, whose original sin was that it was discovered in the bone marrow of that first young homosexual in San Francisco who died of the syndrome in 1981. In retrospect, we now know that any germ could be found in such patients as their immune guard is very weak. The original paper of this association between HIV and AIDS in the prestigious journal Science was only a case history. Based on that case report the author, Luc Montaigner, got his Nobel Prize recently.

Time has come to think afresh in this area of repetitive research in preference to that of holistic refutative research. When we once understand wellness and the real definition of health, we would quickly realise that all illness management has to be holistic where the body, mind and environment of the patient are taken into consideration. The era of disease and diagnosis will replace the era of understanding the suffering human being (the patient) in trying to make him whole again. That is called healing. Research must be true “outcomes” research and not research to better surrogate end points as we do now. One example will be in order here. All the studies of cholesterol-lowering efforts with reductionist chemicals starting with the original choestyramine to the present statins have only shown the effect of their lowering the blood report of cholesterol levels while they all showed higher death rates in the treated group at the end of the day. Death is the real outcome while lowered blood report is a surrogate end point. The story seems to be similar with our efforts to lower many of the fluctuating biological levels which we have been labelling as “diseases”.

Chemical reductionist molecular therapeutics will have to give place to energy therapeutics as the human body is a bundle of jumping leptons and correction of such errors will have to use energy scientifically. Many proven methods of energy treatment have been in vogue for eons even in many alternate systems. One more reason why energy methods are better is the speed with which one gets results with energy healing methods. Whereas chemical message transmission happens at a rate of one centimetre per second, energy healing transmission happens at a rate of 1,86,000 miles per second!  Most, if not all, reductionist chemical molecules are alien to the human system and they are rejected by the liver in the first place. (The first pass effect that we teach medical students in pharmacology means that the body is trying to destroy as much of the drug as possible) .

The ghost of Adverse Drug Reactions, (ADRs) staring at our face as the biggest cause of death in modern medicine, could be avoided if we follow the holistic management of illnesses to bring man back to his/her state of wellness as defined above. Long live mankind on this planet in good health and happiness. Medical profession is always needed as the doctor is not just a drug vendor but a real friend, philosopher and guide in illness. In addition, science has now shown that all the drugs or surgical methods that we use work mainly because of the faith the patient has in the doctor, the so called placebo effect, also called the expectation effect (EE).  A good doctor, humane and human, full of empathy, will be God to patients at all times. Basically, a good doctor should be a good human being.

“If you want others to be happy, practice compassion. If you want to be happy, practice compassion" — The Dalai Lama.

Prof. Dr. B M Hegde is former Chancellor of Manipal University.
(Professor  BM Hegde can be contacted at hegdebm@gmail.com)

Appeared in: Moneylife, November 16, 2011.

Lycopene's Effects on Health and Diseases

A comprehensive review of the literature

V. Kalai Selvan, MPharm, PhD; A. Vijayakumar, MPharm, PhD; K. Suresh Kumar, MPharm; Gyanedra Nath Singh, MPharm, PhD

Abstract

Lycopene is present in many fruits and vegetables, with tomatoes and processed tomato products being among the richest sources. This review highlights the scientific documentation of lycopene as a therapeutic agent. Lycopene may alleviate chronic diseases such as cancer and coronary heart disease. Lycopene has also been found effective in the treatment of eye diseases, male infertility, inflammation, and osteoporosis. Experimental, clinical, and epidemiological studies have also established its role in the management of diabetes and hepatoprotection. Uses of lycopene have been studied extensively through epidemiological and biochemical investigations of its properties and its bioavailability from tomato-based diets. No adverse events have been reported in association with the consumption of lycopene-containing foods. The present review article supports the therapeutic efficacy of lycopene; however, more multicenter clinical trials are warranted to confirm its efficacy.

Introduction

Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables. It is a red, fat-soluble pigment found in certain plants and microorganisms, where it serves as an accessory light-gathering pigment and protects them from ultraviolet B radiation. Gac fruit (Momordica cochinchinensis); tomatoes (Lycopersicon esculentum); and tomato products, including ketchup, tomato juice, and pizza sauce, are the more bioavailable sources of lycopene.¹ Gac fruit contains 2,227 mcg/g lycopene; tomato contains 31 mcg/g.² Lycopene is also found in watermelon, papaya, pink grapefruit, and pink guava (Figure 1). Lycopene is more bioavailable in processed and cooked tomato products than in fresh tomatoes.^3,4

Figure 1: Amount of lycopene present in different fruits

Lycopene is synthesized by plants and microorganisms, but not by animals. It is a red open-chain unsaturated carotenoid, acyclic isomer of beta-carotene, and longer than any other carotenoid (Figure 2). This highly unsaturated hydrocarbon contains 11 conjugated and 2 unconjugated double bonds, predisposing lycopene to isomerization and degradation upon exposure to light, excessive heat, and air. This results in color loss and renders tomato extract ineffective as a food or pharmaceutical coloring agent.^5,6

Figure 2: Chemical Structure of Lycopene

Lycopene, also known as psi-carotene, is very sensitive to heat and oxidation and is insoluble in water. Because of the abundance of double bonds in its structure, there are potentially 1,056 different isomers of lycopene, but only a fraction are found in nature.^4,7 In a study cis-isomers of lycopene were shown to be more stable, having higher antioxidant potential compared to the all-trans lycopene.⁸

This review summarizes the background information about lycopene and presents the most current knowledge with respect to its role in human health.

Bioavailability and Pharmacokinetics

The mechanism of absorption of lycopene is still being determined. Lycopene ingested in its natural trans form (eg, in raw tomatoes) is poorly absorbed; heat processing tomatoes and tomato products induces isomerization of lycopene from all-trans to cis configuration, in turn increasing its bioavailability.⁹ Also, because lycopene is a fat-soluble compound, absorption into tissues is improved when it is consumed with oil. Its concentration in body tissues is higher than all other carotenoids.^10,11 In one study, serum concentrations of lycopene increased after consumption of heated tomato juice mixed with oil, with a peak at 24–48 h after ingestion.^12,13 Heating tomato juice resulted in trans-to-cis isomerization of lycopene, and on ingestion of this juice, the cis isomers of lycopene appeared to predominate in human serum over the all-trans isomers.¹² The exact functions and relative activities of these different isomers are yet to be studied.

Lycopene is incorporated into lipid micelles in the small intestine. These micelles are formed from dietary fats and bile acids and help to solubilize the hydrophobic form of lycopene and allow it to permeate the intestinal mucosal cells by a passive transport mechanism. In blood plasma, lycopene is eventually distributed into the very low– and low-density lipoprotein fractions.¹² Lycopene is mainly distributed to fatty tissues and organs such as the adrenal glands, liver, and testes (Figure 3). In contrast to other carotenoids, lycopene’s serum values are not regularly reduced by smoking or alcohol consumption, although levels decrease with increasing age.¹⁰

Figure 3: Amount of lycopene distribution in various body tissues and organs

Effect of Lycopene on Free Radical– and Nitric Oxide–Scavenging Properties

Oxidative stress is an important contributor to the risk of chronic diseases. Antioxidants scavenge free radicals, otherwise known as reactive oxygen species (ROS), and prevent the damage they can cause. Free radicals have been associated with pathogenesis of various disorders and diseases such as cancer, cardiovascular disease, osteoporosis, diabetes, and cataracts.¹⁴ In one study, lycopene significantly restored the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR); reduced glutathione (GSH); and decreased levels of the lipid peroxide malondialdehyde (MDA) in hypertensive patients.¹⁵ In another study, lycopene was found to have a favorable effect in reducing MDA levels and increasing GSH levels in coronary artery disease in postmenopausal women.¹⁶

The protective effect of lycopene on ischemic brain injury in rat brain homogenates has also been established. In one study, lycopene (5 µM and 10 µM) inhibited iron-catalyzed lipid peroxidation and nitric oxide production by about 31% and 61% respectively.¹⁷

The generation of nitric oxide gives rise to several other reactive species, including peroxynitrite (ONOO–), which is capable of inflicting tissue damage.¹⁸ Lycopene at the concentration of 0.31-10 µM prevented the 3-morpholinosydnonimine stress-induced DNA damage in Chinese hamsters; the protective effect is due to the scavenging of intracellular reactive oxygen and/or nitrogen species, reducing the amounts 47.5% and 42.4% respectively.^19,20

Effect of Lycopene on the Management of Diabetes

A recent study demonstrated that administration of lycopene (90 mg/kg body weight) to streptozotocin-induced hyperglycemic rats caused a decrease in glucose levels, an increase in insulin concentration, a decrease in H2O2 and thiobarbituric acid reactive substances levels, increased total antioxidant status, and increased antioxidant enzyme activities (ie, catalase, superoxide dismutase, glutathione peroxidase) with improvement in serum lipid profile.²¹ Kuhad et al reported that lycopene at doses of 1, 2, and 4 mg/kg has significant, dose-dependent antidiabetic action in streptozotocin-induced diabetic rats.²² In a clinical study investigating the role of lycopene in diabetic patients (N=133), lycopene reduced the risk of diabetic retinopathy.²³

Role of Lycopene in Atherogenesis

Inflammatory mediators such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-8 enhance binding of low-density lipoprotein to endothelium and up-regulate expression of leukocyte adhesion molecules on endothelium during the process of atherogenesis.²⁴ A study found that lycopene inhibited TNF-α-induced NF-κB activation, ICAM-1 expression, and monocyte-endothelial interaction in human umbilical endothelial cells. A further analysis revealed that lycopene attenuated TNF-α-induced IκB phosphorylation, NF-κB expression, and NF-κB p65 translocation from cytosol to nucleus.²⁵ In a placebo-controlled, double-blind, crossover study on healthy human volunteers, 5.7 mg of lycopene for 26 days significantly restricted TNF-α production.²⁶ In one rodent study, lycopene significantly inhibited paw edema formation and attenuated liver injury induced by ischaemia-reperfusion at doses of 25 and 50 mg/kg.²⁷ It also exhibited antiatherogenic effects by inhibiting the expression of inflammatory mediators in hyperhomocysteinemic rats.²⁸

Diet is believed to play a major role in the development of cardiovascular diseases.²⁹ Ingestion of oxidizable lipids and iron catalysts for peroxide decomposition can lead to extensive formation of potentially toxic lipid peroxides, which are implicated in the process of atherosclerosis. Research is focused on preventing cardiovascular diseases through dietary changes. Primarily epidemiological studies, as well as some in vitro and limited in vivo experiments, support the hypothesis that carotenoids, including beta-carotene and lycopene, may protect lipoproteins and vascular cells from oxidation. In particular, lycopene is known to be an efficient scavenger of ROS, including singlet oxygen and other excited species.^30,31Lycopene has demonstrated reduction in oxidative DNA damage in cell culture and in rodent models.^32,33In addition, clinical studies demonstrate that a lycopene-rich diet (including tomato sauce-based pasta dishes for 3 weeks) protects against oxidative DNA damage in human leukocytes in vitro and prostate tissue in vivo.^34,35 In another rodent study, the efficacy of lycopene on myocardial injury after ischemia and reperfusion was explored. In histopathological examinations, myocardial damage was significantly reduced in the lycopene-treated group. Lycopene treatment resulted in preservation of the myocardial antioxidant status and altered hemodynamic parameters as compared to control.³⁶

Clinical studies demonstrate that a lycopene-rich diet (including tomato sauce-based pasta dishes for 3 weeks) protects against oxidative DNA damage.

A single-blind placebo controlled clinical trial found tomato extract (250 mg per day) for 4 weeks reduced blood pressure in patients with grade-1 hypertension.³⁷ The hypocholesterolemic effect of lycopene was also demonstrated in an in vitro study in which it inhibited the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase—the rate-limiting enzyme in cholesterol biosynthesis.³⁸

Effect of Lycopene on Hepatoprotection

Liver damage is associated with cellular necrosis, increase in tissue lipid peroxidation, and depletion of tissue GSH levels. In addition, serum levels of many biochemical markers like serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, triglycerides, cholesterol, bilirubin, and alkaline phosphatase are elevated when liver damage is present.³⁹ The hepatoprotective effect of lycopene was evaluated against galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatitis in rats. Lycopene at a dose of 10 mg/kg (intraperitoneal) significantly reduced the levels of cholesterol, triglycerides, and free fatty acids, followed by a decrease in the levels of phospholipids in the serum and the liver.⁴⁰ Another study demonstrated lycopene significantly restored antioxidant liver enzymes, such as glutathione peroxidase, glutathione-s-transferase, against N-methyl-N′-nitro-N-nitrosoguanidine, and saturated sodium chloride (S-NaCl)-induced gastric carcinogenesis.⁴¹

Role of Lycopene in the Treatment of Hepatitis C

Hepatitis C virus infection and hepatocellular carcinoma are growing health problems around the globe. In vitro, animal, and clinical studies suggest that lycopene may attenuate liver injury and possibly prevent the development of hepatocellular carcinoma.⁴²

Role of Lycopene in the Prevention of Cancer

There have been a few experimental studies on the role of lycopene in preventing or treating cancer.⁴³Some evidence suggests that cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix could be reduced with increased lycopene intake.^44,45

Lycopene supplementation in mice reduces experimental tumor metastasis in vivo induced by the human hepatoma cell line SK-Hep-1; the same study suggests that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.⁴⁶ An in vitro cell culture study showed that lycopene inhibited the growth of human colon cancer HT-29 cells even at low concentration. The inhibitory effects of lycopene on cell proliferation of human colon cancer HT-29 cells were, in part, associated with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.⁴⁷ Lycopene inhibited platelet-derived growth factor-BB–induced signaling and cell migration in human cultured skin fibroblasts through a direct binding to platelet-derived growth factor-BB.⁴⁸

The antiproliferative and apoptotic effect of lycopene on various cell lines, such as human colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human erythroleukemia (K562), and Raji, a prototype of Burkitt lymphoma cell line, was evaluated. Lycopene 4 µM/ml reduced the proliferation capacity.⁴⁹

Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. One study of 404 patients in China, 130 of whom had prostate cancer, suggested that those who had the highest intakes of green tea or lycopene, independently, had an inverse association with developing prostate cancer. In addition, those ingesting both green tea and lycopene had an even greater inverse association (P<0.01), suggesting there may be synergistic effects.⁵⁰ In vitro studies with lycopene have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines.⁵¹ The data also suggest that lycopene and soy isoflavones may delay progression of both hormone-refractory and hormone-sensitive prostate cancer.⁵¹ In a clinical investigation of elderly men, lycopene (15 mg/day) inhibited progression of benign prostate hyperplasia.⁵² At less than 1 μM concentration, lycopene was shown to inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression, specifically in prostate cancer cells, without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin 43, whose expression is up-regulated by lycopene, allowing direct intercellular gap junction communication (GJC). GJC is deficient in many human tumors, and its restoration or up-regulation is associated with decreased proliferation.⁵³ A recent analysis of the evidence to date stated that there is insufficient evidence to conclude lycopene reduces tumor progression or improves overall survival in patients with existing prostate cancer.⁵⁴

In cell cultures, lycopene has been found to inhibit breast cancer tumors more efficiently when compared to alpha- and beta-carotene.^55,56 In one study, samples taken from the Breast Cancer Serum Bank in Columbia, Mo., were analyzed to evaluate the relationship of types of carotenoids, lycopene, selenium, and retinol with breast cancer. Only lycopene was found to be associated with a reduced risk for developing breast cancer.⁵⁷

Effect on Eye Diseases

Cataracts are a multifactorial disease. Osmotic stress, together with weakened antioxidant defense mechanisms, is attributed to the changes observed in human diabetic cataract (Figure 4). Epidemiological studies provide evidence that nutritional antioxidants slow down the progression of cataracts and age-related macular degeneration.⁵⁸ An experimental study found lycopene can protect the human retinal pigment epithelium cell line ARPE-19. ARPE-19 protects against H2O2-induced oxidative stress in vitro.⁵⁹Lycopene decreases the serum and lipoproteins in age-related macular degeneration patients.⁶⁰ The potential role of lycopene in the prevention of cataracts is also established. It prevents sugar-induced morphological changes and modulates antioxidant status of human lens epithelial cells in vitro; 200 mg/kg significantly delayed the onset and progression of 30% galactose-induced cataract on rats; the protective effect was found to be due to the antioxidant potential.^61,62

Lycopene and Bone Health

Among the many factors involved in bone health, oxidative stress induced by ROS is one that is associated with osteoporosis.⁶³ Lycopene has an effect on proliferation and differentiation of osteoblasts (human osteoblast-like osteosarcoma SaOS-2 cells), the cells responsible for bone formation.⁶⁴ In a cross-sectional study, 33 postmenopausal women aged 50–60 years were administered lycopene for 7 days. Serum samples were used to measure serum lycopene, lipid peroxidation, protein thiols, bone alkaline phosphatase, and cross-linked N-telopeptides of type-I collagen (NTx). Higher intake of lycopene decreased the level of NTx and also protein oxidation (P<0.05). Similarly, groups with higher serum lycopene had lower protein oxidation (P<0.05).⁶⁵ Carbonyl levels, which are the product of protein oxidation, lead to oxidative stress and osteoporosis.⁶⁶ Hence the possible mechanism of action of lycopene for the treatment of osteoporosis may be by reducing carbonyl levels.

Lycopene Therapy in Male Infertility

Excessive ROS-containing free-oxygen radicals have been identified as one of the causes of male infertility.⁶⁷ Lycopene is a component of the human redox defense mechanism against free radicals. It is found in high concentrations in the testes and seminal plasma (Figure 3), and decreased levels have been demonstrated in men suffering from infertility.⁶⁷ Oral administration of lycopene (2 mg twice a day for 3 months) to men with infertility significantly improved the sperm concentration in 66% of cases and motility in 73% of cases.⁶⁷

Table 1. Summary of the pharmacological actions of lycopene at various dose levels

S. No	Pharmacological action	Experimental study	Effective doses
1	Nitric oxide scavenging	In vitro5	5 and 10 µM
2	TNF-α inhibition26	Clinical	5.7 mg/kg
3	Anti-inflammatory27	In vivo	25 and 50 mg/kg
4	Anti-diabetic21	Animal	90 mg/kg
5	Hepatoprotection40	In vivo	10 mg/kg
6	Anti-apoptotic49	In vitro	4 µM
7	Anti-cataract62	In vivo	200 mg/kg
8	Treatment of male infertility67	Clinical	2 mg twice/day

Drug and Food Interactions

Cholesterol-lowering drugs like Probucol decrease the absorption of lycopene.⁶⁸ Food substances such as mineral oil, red palm oil, fat substitutes, and pectin may also decrease the absorption of lycopene, whereas beta-carotene, medium-chain triglycerides, and dietary oils such as olive oil may enhance its absorption.^69,70 Antioxidant effects are increased when lycopene is combined with lutein, and the growth of cancer cells is decreased when it is combined with vitamin D or E.

Toxicity Profile

A sub-chronic toxicity study on lycopene was conducted by oral administration at dietary concentrations of 0.25, 0.50, and 1.0% to rats for a period of 90 days. The results from this study do not show any evidence of toxicity of lycopene at dietary levels up to 1.0% as demonstrated by the findings of clinical observations, neurobehavioral observations, motor activity assessment, body weight and food consumption measurements, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, or histopathology.⁷¹ Another study also demonstrated that intake of lycopene (75 mg/day) did not causes any adverse events in humans.⁷² A phase I clinical trial conducted on healthy adult male subjects found no significant hepatic or renal toxicity attributable to lycopene doses ranging from 10 to 120 mg, though minimal gastrointestinal toxicity was observed.73

Scientific evidence for lycopene use in pregnancy is not available; however, no adverse events have been reported in association with the consumption of lycopene-containing foods during pregnancy.

Recommended Intake Levels of Lycopene

Due to the variation of lycopene content in food sources, it has been difficult to estimate optimal daily intake. Ranges of 3.7 to 16.15 mg have been reported for the United States.⁷⁴ Reported values for Finland, the United Kingdom, and Germany have been 0.7, 1.1, and 1.3 mg, respectively.⁷⁵ A survey in Canada showed daily intake of lycopene to be 25.2 mg.⁷⁶ However, a recent study in which healthy human subjects ingested lycopene from tomato ketchup and supplements at levels of 5, 10 and 20 mg daily for 1 week found that doses of 5–10 mg significantly increased serum lycopene levels (P<0.05) and also significantly reduced lipid and protein oxidation (P<0.05).⁷⁷ This level of intake can easily be achieved by ingesting several dietary sources of lycopene.

Summary and Conclusions

Lycopene, as an antioxidant, reduces oxidative stress. It may play a significant role in many health concerns, including cardiovascular disease, diabetes, cancer, osteoporosis, liver disease, cataracts, and male infertility. The appropriate dose and duration of lycopene supplementation remains to be determined. Some of the studies on lycopene have included other food supplements, making it difficult to discern lycopene’s individual effects.

References

1. Arab L, Steck S. Lycopene and cardiovascular disease. Am J Clin Nutr. 2000;71(6):1691S-1695S.

2. Betty K, Charlotta T, Mary CH, McKeon Thomas A. Fatty acid and carotenoid composition of Gac (Momordica cochinchinensis Spreng) fruit. J Agri Food Chem. 2004;52:274-279.

3. Gartner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr. 1997;66:116–122.

4. Rao AV, Agarwal S. Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: a review. Nutr Res. 1999;19(2):305-323.

5. Lee MT, Chen BH. Stability of lycopene during heating and illumination in a model system. Food Chem. 2002;78;425-432.

6. Yang K, Lule U, Xiao-Lin D. Lycopene: Its properties and relationship to human health. Food Rev International. 2006;22:309-333.

7. Woodall AA, Britton G, Jackson MJ. Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: relationship between carotenoid structure and protective ability. Biochim Biophys Acta.1997;1336(3):575-586.

8. Chasse GA, Mak ML, Deretey E, et al. An ab initio computational study on selected lycopene isomers. J Mol Struct.2000;571(1-3):27-37.

9. Micozzi MS, Brown ED, Edwards BK, et al. Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am J Clin Nutr. 1992;55(6):1120-1125.

10. Gerster H. The potential role of lycopene for human health. J Am Coll Nutr. 1997;16(2):109-126.

11. Stahl W, Junghans B, De Boer B, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett. 1998;427(2):305-308.

12. Stahl W, Sies H. Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans. J Nutr. 1992;122(11):2161-2166.

13. Clinton SK. Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev. 1998;56(2 pt 1):35-51.

14. Ratnam DV, Ankola DD, Bharadwaj V, Sahana DK, Kumar MN. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release. 2006;113(3):189-207.

15. Bose KS, Agrawal BK. Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease. Singapore Med J. 2007;48(5):415-420.

16. 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. Obstet Gynecol.2006;32(3):299-304.

17. Hsiao G, Fong TH, Tzu NH, Lin KH, Chou DS, Sheu JR. A potent antioxidant, lycopene, affords neuroprotection against microglia activation and focal cerebral ischemia in rats. In Vivo. 2004;18(3):351-356.

18. Varma SD, Kavita RH. Susceptibility of the ocular lens to nitric oxide: implications in cataractogenesis. J Ocul pharmacol Th. 2007;23(2):188-195.

19. Muzandu K, Ishizuka M, Sakamoto KQ, et al. Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol Appl Pharmacol. 2006;215(3):330-340.

20. Jamshidzadeh A, Baghban M, Azarpira N, Bardbori AM, Niknahad H. Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem Toxicol. 2008;46(12):3612-3615.

21. Ali MM, Agha FC. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scand J Clin Lab Invest. 2009;69(3):371-379.

22. Kuhad A, Sethi R, Chopra S. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Science.2008;83(3-4):128-134.

23. Suzuki K, Ito Y, Nakamura S, Ochiai J, Aoki K. Relationship between serum carotenoids and hyperglycemia: a population-based cross-sectional study. J Epidemiol. 2002;12(5):357-366.

24. Wu WB, Chiang HS, Fang JY, Hung CF. Inhibitory effect of lycopene on PDGF-BB-induced signaling and migration in human dermal fibroblasts: a possible target for cancer. Biochemistry Society Transactions. 2007;35(5):1377-1378.

25. Hung CF, Huang TF, Chen BH, Shieh JM, Wu PH, Wu WB. Lycopene inhibits TNF-alpha-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion. Eur J Pharmacol. 2008;586(1-3):275-282.

26. Riso P, Visioli F, Grande S, Guarnieri S, Gardana C. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agr Food Chem. 2006;54(7):2563-2566.

27. Leticia B, Joao R, Bruno S, et al. Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia-reperfusion in the rat. Br J Nutr. 2009;102:126-133.

28. Liu X, Qu D, He F, Lu Q, Wang J, Cai D. Effect of lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats. Asia Pacc J Clin Nutr. 2007;16(Suppl 1):244-248.

29. Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. J Nutrition Biochem. 2006;17(6):365-373.

30. Pavia SAR, Russell RM. ß-Carotene and Other Carotenoids as Antioxidants. J Am College of Nutrition.1999;18(5):426-433.

31. Stahl W, Junghans B, De Boer ES, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. Fed Eur Biochem Soc Lett.1998;427(2):305-308.

32. 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. Amer Heart J. 2006;151(1):100e1-100e6.

33. Blum A, Monir M, Wirsnsky I, Ben-Arzi S. The beneficial effects of tomatoes. Eur J Intern Med. 2005;16(6):402-404.

34. Matos HR, Capelozzi VI, Gomes OF, Mascio PD, Medeiros MH. Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Arch Biochem Biophys 2001;396(2):171-177.

35. Matos HR, Mascio PDI, Medeiros MH. Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in cell cultures. Arch Biochem Biophys. 2000;383(1):56-59.

36. Pool-Zobel BL, Bub A, Müller H, Woollowski L, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis.1997;18(9):1847-1850.

37. Bowen P, Chen I, Stacewicz-Sapuntzakis M, et al. Tomato sauce supplementation and prostate cancer: Lycopene accumulation and modulation of biomarkers of carcinogenesis. Experiment Biol Med. 2002;227(10):886-893.

38. Bansal P, Gupta SK, Ojha SK, et al. Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury. Mol Cell Biochem. 2006;289(1-2):1-9.

39. Sharma A, Shing RT, Sehgal V, Handa SS. Antihepatotoxic activity of some plants used in herbal formulations.Fitoterapia. 1991;62:131-138.

40. Shivashangari KS, Ravikumar V, Vinodhkumar R, Sheriff SAA, Devaki T. Hepatoprotective potential of lycopene on D-alactosamine/lipopolysaccharide induced hepatitis in rats. Pharmacology Online. 2006;2:151-170.

41. Velmurugan B, Bhuvaneswaria V, Balasenthila S, Nagini S. Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutr Res.2001;21(8):1117-1124.

42. Seren S, Mutchnick M, Hutchinson D, et al. Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma. Nutr Cancer. 2008;60(6):729-735.

43. Doyle C, Kushi LH, Byers T, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. Canc J Clinicians. 2006;56:323-353.

44. Giovannuccci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Canc Inst. 1999;91(4):317-331.

45. Vrieling A, Voskuil DW, Bonfrer JM, Korse CM, Van Doorn J, Cats A. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. Am J Clin Nutr. 2007;86(5):1456-1462.

46. Huang CS, Liao JW, Hu ML. Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice. J Nutr. 2008;138(11):538-543.

47. Tang FY, Cho HJ, Pai MH, Chen YH. Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem. 2009;20(6):426-434.

48. Wu WB, Chiang HS, Fang JY, Hung CF. Inhibitory effect of lycopene on PDGF-BB-induced signaling and migration in human dermal fibroblasts: a possible target for cancer. Biochem Soc Trans. 2007;35(Pt 5):1377-1378.

49. Salman H, Bergman M, Djaldetti M, Bessler H. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother. 2007;61(6):366-369.

50. Jian L, Lee AH, Binns CW. Tea and Lycopene protect against prostate cancer. Asia Pac J Clin Nutr. 2007;16(Suppl 1):453-457.

51. Vaishampayan U, Hussain M, Banerjee M, et al. Lycopene and soy isoflavones in the treatment of prostate cancer.Nutr Cancer. 2007;59(1):1-7.

52. Schwarz S, Obermuller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008;138(1):49-53.

53. Heber D, Lu QY. Overview of mechanisms of action of lycopene. Exp Biol Med. 2002;227(10):920-923.

54. Perabo FG, Von Low EC, Siener R, Ellinger J, Muller SC, Bastian BJ. A critical assessment of phytotherapy for prostate cancer. Urologe A. 2009;48(3):270-283.

55. Zhang S, Tang G, Russell RM, et al. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr. 1997;66(3):626-632.

56. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta carotene. Nutr Cancer. 1995;24(3):257-266.

57. Dorgan JF, Sowell A, Swanson CA, et al. Relationships of serum carotenoids, retinal, alpha-tocopherol and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control. 1998;9(1):89-97.

58. Fernandez MM, Afshari NA. Nutrition and the prevention of cataracts. Curr Opin Ophthalmol. 2008;19(1):66-70.

59. Chichili GR, Nohr D, Frank J, et al. Protective effects of tomato extract with elevated beta-carotene levels on oxidative stress in ARPE-19 cells. Br J Nutr. 2006;96(4):643-649.

60. Cardinault N, Abalain JH, Sairafi B, et al. Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients. Clin Chim Acta. 2005;357(1):34-42.

61. Mohanty I, Joshi S, Trivedi D, Srivastava S, Gupta SK. Lycopene prevents sugar-induced morphological changes and modulates antioxidant status of human lens epithelial cells. Br J Nutr. 2002;88(4):347-354.

62. Gupta SK, Trivedi D, Srivastava S, Joshi S, Halder N, Varma SD. Lycopene attenuates oxidative stress induced experimental cataract development: an in vitro and in vivo study. Nutrition. 2003;19(9):794-799.

63. Rodriguez MS, Ramos MR, Munoz EC, Munez VM. Oxidative stress as a risk factor for osteosporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskeletal Disorders. 2007;8:124.

64. Kim L, Rao AV, Rao LG. Lycopene II—effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. J Med Food. 2003;6(2):79-86.

65. Rao LG, Mackinnon ES, Josse RG, Murray TM, Strauss A, Rao AV. Lycopene consumption decreases oxidative stress and bone resorption markers in postmenopausal women. Osteoporosis Int. 2007;18(1):109-115.

66. Korucuoglu U, Ciftci B, Gulbahar O, et al. Assessment of protein oxidation in women using raloxifene. Mol Cell Biochem. 2006;290(1-2):97-101.

67. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol. 2002; 34(3):369-372.

68. Elinder LS, Hadell K, Johansson J, et al. Probucol treatment decreases serum concentrations of diet-derived antioxidants. Arterioscler Thromb Vasc Biol. 1995;15(8):1057-1063.

69. Riedl J, Linseisen J, Hoffmann J, Wolfram G. Some dietary fibers reduce the absorption of carotenoids in women. J Nutr. 1999;129(12):2170-2176.

70. Johnson EJ, Qin J, Krinsky NI. Ingestion by men of a combined dose of beta-carotene and lycopene does not affect the absorption of beta-carotene but improves that of lycopene. J Nutr. 1997;127(9):1833-1837.

71. Jonker D, Kuper CF, Fraile N, Estrella A, Rodriguez Otero C. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats. Regul Toxicol Pharmacol. 2003;37(3):396-406.

72. Shao A, Hathcock JN. Risk assessment for the carotenoids: lutein and lycopene. Regul Toxicol Pharmacol. 2006;45(3):289-298.

73. Gustin DM, Rodvold KA, Jeffery A, et al. Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects. Cancer Epidemiol Biomarkers Prev. 2004;13(5):850-860.

74. Porrini M, Riso P. What are typical lycopene intakes? Nutr. 2005;135:2042S-2045S

75. Rao V, Heber D. Future directions and intake recommendations. Caledonian Science Press, Scotland U.K., 2001;43.

76. Rao AV, Fleshner N, Agarwal S. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer. 1999;33(2):159-164.

77. Rao AV, Shen HL. Effect of low dose lycopene intake on lycopene bioavailability and oxidative stress. Nutr Res.2002;22(10):1125-1131.

About the Lead Author

V. Kalai Selvan, MPharm, PhD, is senior scientific officer for the Indian Pharmacopoeia Commission, Government of India (Ministry of Health and Family welfare), in Ghaziabad. He has about 11 years of experience as a scientist and teacher in pharmaceutical sciences. He obtained his Bachelor of Pharmacy and Masters of Pharmacy from The Tamil Nadu Dr. M G R Medical University, Chennai, and his PhD from Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi. Dr. Selvan has published 16 research papers in peer reviewed national and international journals.

Accessed from: http://NaturalMedicineJournal.com - A Publication of American Association of Naturopathic Physicians.