Hypericin: the active ingredient in Saint John's Wort

by A.Y. Oubre

Hypericin, a photochemical extracted from St. Johns Wort (Hypericum perforatum) and related species, has been shown to have potent, broad spectrum antimicrobial activity. This compound is an aromatic polycyclic anthrone, a class of colored or pigmented chemical substances which have photosensitizing activity. In both in vitro (laboratory) and in vivo (animal) studies, low, non-toxic doses of hypericin significantly inhibited the replication of several viruses, including HIV, influenza A, cytomegalovirus (CMV), Herpes simplex 1 and 2 (HSV-1 and HSV-2), and Epstein-Barr virus (EBV). Hypericin and its chemical relative, pseudohypericin, produce antiviral activity through a different mechanism of action than do AZT and other nucleoside antiviral agents. Hypericin does not appear to directly alter the activity of reverse transcriptase although it does block the formation of HIV synctium. Recent findings have shown that the antiretroviral action of this compound disrupts uncoating of the lipid envelope of both DNA and RNA viruses, thus preventing infected cells from releasing HIV copies. Theoretically, hypericin and AZT, in combination, may have synergistic antiviral effects against HIV. On the other hand, hypericin actually may increase the toxicity of antiretroviral nucleosides such as AZT, ddI, or ddC.

Traditionally, extracts of St. Johns Wort (which contain hypericin) have been used as an antidepressant, possibly by acting as a MAO inhibitor. The psychotropic effects attributed to hypericin in St. Johns Wort extract suggest that the pigment compound can cross the blood brain barrier (possibly treating neuropsychological symptoms such as dementia). Laboratory investigations indicate that hypericin may be beneficial as an HIV therapy. However, its administration should be carefully monitored by a physician. The levels of hypericin found in most commercially available extracts of St. Johns Wort generally are not sufficient to be therapeutically effective against viral infections.

Liver function should be tested periodically in persons taking hypericin. Also, extreme photosensitivity has been observed in a few cases of people taking this high doses (in excess of 10 mg per day) of this compound. Finally, there is a very small possibility that adverse reactions could occur on occasion between hypericin and other foods or drugs which interfere with MAO inhibitors.

Active principles in St. Johns Wort

The quantity and quality of active principles in Hypericin species vary according to geographical locale, climate, time of day, and time of year. St. Johns Wort contains dianthrone derivatives, mainly in the form of hypericin and pseudo-hypericin as well as flavonoids. Small amounts of coumarins, phenolic carboxylic compounds, phloroglucinol derivatives, monoterpenes, sesquiterpenes, n-alkanes, n-alkanols, carotenoids, and beta-sitosterol are present. The roots contain zanthones. Practitioners and consumers should note that St. Johns Wort extracts, whether standardized or not, consist of other active ingredients in addition to hypericin and pseudohypericin.

Pre-clinical studies

Both in-vitro (test tube) and in-vivo (animal) pre-clinical studies suggest that hypericin (and, to a lesser extent, pseudo-hypericin) may have therapeutic benefits for HIV infection and other retroviral diseases. Certain compounds other than hypericin extracted from Hypericum species have antibiotic activity. marked antiretroviral effects, however, have been reported primarily for hypericin which is isolated mainly from Hypericum perforatum. However, synthetic hypericin has been used in recent studies.

In in-vitro and in-vivo studies, both hypericin and pseudohypericin (extracted from Hypericum triquetifolium) had antiviral activity against several retroviruses. In one experiment, mice were simultaneously injected with low doses of the compounds and with Friend leukemia virus (FV). This aggressive retrovirus normally causes rapid splenomegaly (swelling of the spleen) and acute erythroleukemia in mice. However, these symptoms were effectively suppressed by the addition of hypericin. Splenomegaly had not occurred ten days after infection at the close of the study. No infectious virus could be recovered from the spleen. Also, viremia normally associated with FV was absent. Mice treated with hypericin and pseudohypericin survived a much longer time than mice treated with a toxic antiviral (N3dthd). Unlike most antiretroviral drugs, hypericin (given in a single dose of low concentration) was effective without being cytotoxic. Even when it was administered after viral infection had already started, it still inhibited the onset of disease.

In in-vitro studies, mouse cell lines were infected with radiation leukemia virus (Rad LV) and then incubated with hypericin. The activity of reverse transcriptase in these cells was suppressed through indirect mechanisms. In contrast to nucleoside analogues, polycyclic diones such as hypericin interfere directly with the viral replication cycle during stages in which virions are assembled or intact virions are shedded from immature cores. Alternatively, these aromatic compounds may directly inactivate mature retrovirus that contains normal, assembled cores. Other findings indicate that hypericin is able to inactivate virions and block viral release from infected cells by interacting with the cell membrane.

Unpublished data show that hypericin disrupts the formation of synctia in HIV disease as well as in de novo infection of cells. In in-vitro studies, hypericin showed selective activity against HIV and modest inhibition of reverse transcriptase. In vitro research also revealed that hypericin lowered viral activity in whole human blood taken from HIV infected persons. “Wild” strains of HIV taken directly from infected patients are sometimes more resistant to antiviral agents than are viral strains bred in the laboratory.

Other investigations indicate that the antiviral effects of hypericin on murine cytomegalovirus (MCMV), Sindbus virus (SV), and HIV are enhanced by exposure to fluorescent light. Hypericin and to some degree, pseudohypericin, were effective against FV and HSV-1 when the viruses were first incubated with the compounds for one hour at 37 degrees C before mice were infected. Pre-incubation for one hour at 4 degrees C, however, produced no antiviral effects. The authors of this study (who are scientists at Lilly Research Laboratories) reported that hypericin and pseudohypericin were effective in vitro against enveloped viruses such as HSV and influenza when the cultures were pre-incubated with these agents at 37 degrees C. They also correctly showed that hypericin and its analogue inhibit DNA and RNA viruses, but not viruses which lack a lipid envelope. The Lilly researchers, who call AZT a preferred therapy for HIV, however, claim that single dose administration of hypericin is not efficacious. Human clinical trials are needed to evaluate the appropriate dose ranges at which hypericin is therapeutic but nontoxic, and to assess the differences, if any, between natural and synthetic hypericins. In animal studies, natural sources of hypericin (in combination with its analogue, pseudohypericin), showed greater antiviral activity that did synthetic hypericin. Preliminary findings thus far strongly indicate that the wide spectrum antiviral properties of hypericin, its experimental effectiveness at low concentrations, and its unconventional mechanisms of antiviral action make it a promising candidate for a new class of HIV therapies.

Mechanisms of action

Hypericin and pseudohypericin had no effect on purified reverse transcriptase alone. They did not alter levels of intracellular viral mRNA. Instead, hypericin lowers the number of mature viral particles without suppressing intracellular levels of viral mRNA. The concentrations of viral antigens on the cell surface were also unaffected by hypericin. These findings, as a whole, imply that the compounds interfere with viral assembly, budding, shedding or stability at the level of the cell membrane When hypericin was added to viral-infected cell cultures, red fluorescence appeared at localized areas on the lipid surface membrane.

Unlike nucleoside analogues, polycyclic diones such as hypericin have no effects on transcription, translation, or transport of viral proteins to the cell membrane. They are not directly active against reverse transcriptase even though reverse transcriptase activity was reduced in infected cells that had first been incubated with hypericin. Cells treated with hypericin form immature or abnormally assembled cores. This indicates that hypericin may block the processing of gag-encoded precursor polypeptides. Hypericin, whether in the intracellular medium or bounded to the membrane, is thought to lower the activity of reverse transcriptase by interfering with protein synthesis. (It is noteworthy that the antiviral effects of harmine, a photoactive alkaloid, involve disrupted kinase activity in enveloped RNA viruses.)

Viral particles are not formed when gag-related polyproteins fail to be cleaved or synthesized. Gag-related polyproteins, therefore, may play a decisive role in the virucidal actions of hypericin. Reverse transcriptase within the core of the assembled virus probably takes the form of an inactive enzyme or proenzyme. Mechanisms involving viral-encoded proteases or kinases might be required to activate reverse transcriptase. These mechanisms could transform the enzyme from a nonfunctional to a functional state. Both hypericin and pseudohypericin are thought to influence protease activity. In turn, altered protease activity could disrupt the cleavage or synthesis of gag-related polyproteins. As a result, immature viral cores would be formed. Alternatively, by selectively binding to viral polyproteins, hypericin could interfere with the gag and gag-pol polyproteins needed for viral assembly. Thus, hypericin could block the process whereby RNA packages encapsulated viral particles.

Some investigators, however, propose that hypericin lyses infectious virion by interacting directly with the viral envelope instead of disrupting gag-encoded precursor polyproteins or modifying other proteins. In any case, the antiviral properties of hypericin appear to involve its interactions with the cell membrane or cell surface recognition sites. Molecular modifications at or near the surface provide a model for rationally designing a new class of anti-HIV agents. Such therapies may be able to block HIV-encoded protease located in the gag-pol region. Importantly, drugs of this type would not be toxic like AZT and other agents whose pharmacological actions are based on direct inhibition of reverse transcriptase.

The aromatic, ringed structure encircled by six phenolic hydroxy groups seems critical to the antiviral activity of the hypericin molecule. Quinone groups, which often have antiviral properties, also exert photodynamic effects. Hypericin is thought to generate singlet oxygen. However, free radical quenchers can interfere with singlet oxygen reactions involving hypericin thereby reducing its antiviral properties.

Hypericin has a unique molecular structure in which one-half of the molecule is hydrophilic (water loving) while the other half is hydrophobic (water repelling). The top, bottom and side (non-polar) of the hypericin molecule which contains the methyl groups are hydrophobic. It is thought that the molecule might bond to the outer surface of the cell membrane. Presumably, the hydrophobic side would be immersed in fat Singlet oxygen, though less reactive than triplet oxygen, binds with two-electron targets, including, for example, the double bonds found in polyunsaturated fatty acids. The hydrophilic sides, in contrast, could hydrogen-bond to the aqueous media.

Discrepancies between in vivo findings from different studies on the antiretroviral effects of hypericin and pseudo-hypericin may be due partly to variations in light. However, differences in hypericin isolation methods and in the strains of mice used also could account for variable findings in several investigations. The antiviral effects of hypericin are largely but not completely, attributed to its photodynamic properties. In the presence of light, hypericin completely inhibited infection of cell cultures of equine infectious anemia virus (EIAV). On exposure to fluorescent light, hypericin inactivated MCMV, Sindbis virus (SV), and HIV-1. Both membrane virions and virus-infected cells were more strongly inactivated by visible light. (Polyacetylene phenylheptatriyine (PHY), a substance purified from the plant, Bidens pilosa, also shows antiviral activity against membrane-bound viruses such as MCMV. The antiviral effects, which involved interactions between PHY and membrane, occurred in the presence of long wave ultraviolet light). Significant advances in photobiological research have been made in recent years. New findings demonstrate clearly that photodynamic action accounts for the antiviral properties of several natural product derivatives, including hypericin.

Light is required for the photosensitization of hypericin. The compound absorbs light quanta and generates it in the form of singlet oxygen. In so doing, hypericin triggers the photo-oxidation of cellular components, including, for example, the photohemolysis of red blood cells. The underlying mechanism of photodynamic reactions is not fully understood. It is thought to involve interactions between oxygen and light as well as sensitizing pigment which binds to the cell membrane.

In photodynamic reactions mediated by hypericin, singlet oxygen serves as the main oxidant. Singlet oxygen has a strong affinity for pi electron-systems found in compounds such as polycyclic diones. The pi electrons, responsible for the photoactive properties of hypericin, absorb visible and ultraviolet light and then reemit it within the range of green and red light. The two hydroxy groups and the two methyl groups flanking each side of hypericin’s eight ringed structure do not lie within the same plane. Instead, they repel each other, placing strain on the benzenoid structure. This causes the hypericin molecule to twist and become unstable. Hypothetically, the steric strain could increase the energy state of the pi electrons. This would allow them to form temporary bonds with singlet oxygen which, at a later point, could be released to disrupt mechanisms of viral replication. Pi electrons therefore, seem to play a major role in the antiviral activity of hypericin.

The “impressive light-mediated antiviral activities” of hypericin have been shown in several studies. Sindbus virus (SV), for example, was 99% inhibited in the presence of light. In the dark, however, the antiviral effects of hypericin were reduced by more than two orders of magnitude. On exposure to light (650-700nm.), hypericin undergoes type II photosensitization in which singlet oxygen and other reactive molecular species are produced. Though not as destructive as free radicals (which are generated in Type I photosensitization, singlet oxygen could damage viral membranes, thereby interfering with proteins and nucleic acids. Nonetheless, hypericin also has some degree of virucidal activity in the dark, though much less so than in light. It is thought that the antiviral effects produced in the absence of light take place through a different mode of action than light-mediated virucidal activity. Protein kinase C, for example, may represent an alternative target for hypericin’s antiviral action in the absence of light.

One of the therapeutic advantages of hypericin is that it works by multiple steps. Hypericin is probably able to interrupt various phases in the replication of enveloped retroviruses. These stages include polyprotein cleavage and protein alterations as well as assembly, budding and shedding of viral components. The compound’s disadvantages as an anti-HIV agent involve its potential toxicity when patients are exposed to sunlight. Also, it has been reported that in humans, hypericin is more effective in suppressing HSV-1 and HSV-2 than HIV. Future research is required to elucidate the mechanisms through which hypericin generates and reacts with singlet oxygen in triggering antiviral effects.


Clinical trials were conducted the early 1990’s by Dr. Bihari in New York City recommending the following regimen. For the first two weeks, patients take 10 mg once a day for two weeks. During the second two weeks, the dosage alternates between 10 mg per day on the first day, 20 mg on the second day, 10 mg on the third day, and so forth. The ultimate dosage is given during the fifth and sixth weeks when patients are given 20 mg per day.

It has been proposed that beta-carotene, a known free radical quencher, be administered in combination with hypericin. Theoretically, this might reduce any toxic side-effects associated with hypericin’s generation of free radicals. Some investigators, however, have warned that quenchers also may lessen the anti-viral properties of hypericin. The role of beta-carotene and other free-radical scavengers in hypericin therapy deserves further clarification.


Hypericin, a pigment molecule with photodynamic activity, has dramatic antiviral activity, especially in the presence of light. Like several other plant derived substances, hypericin only inhibits viruses with membranes. It has antiviral effects against a wide range of retroviruses, including HSV-1, HSV-2, (murine) CMV, and HIV-1. In contrast to nucleoside agents such as AZT, hypericin and its chemical relative, pseudohypericin, do not directly affect the activity of reverse transcriptase. Rather, these agents seem to disrupt various stages of viral replication, including assembly, budding, shedding and possibly protein synthesis, all of which depend on the integrity of the viral membrane.

Hypericin and related compounds, with their alternative targets for virucidal activity, comprise a new class of potential anti-HIV drugs. It is not yet known how effective hypericin will be in human AIDS. Preliminary findings, however, strongly suggest that this compound is one of the most promising, new anti-HIV prototype molecules currently under investigation.

Pregnenolone, the feel-good hormone

PillManPregnenolone is a steroid precursor hormone produced in the adrenal glands, liver, skin, brain, testicles, ovaries and retina of the eyes. It is made in the body from the bad-rap guy, cholesterol. Naturally, to get pregnenolone, we need adequate amounts of cholesterol plus other nutrients, including vitamin A, thyroid hormone and enzymes. If any of these are inadequate, you will have a less than desired supply of pregnenolone.

In a healthy person, the conversion of cholesterol to pregnenolone occurs inside the mitochondria, nicknamed “the lungs of the cell” because of their role in cell respiration. Once produced, pregnenolone leaves the mitochondria, so it cannot inhibit its own synthesis. In fact, both progesterone and pregnenolone stimulate their own synthesis so that if you take them, the body’s ability to synthesize them is not suppressed. Sometimes short term therapy restores the body’s ability to produce adequate amounts. In the cytoplasm, enzymes convert pregnenolone into either progesterone or DHEA, depending on the tissue and the need.

Brain function, including mood, memory and thinking:

Depressed patients were found to have low levels of pregnenolone in their cerebro-spinal fluid. This fluid circulates throughout the spinal column and brain, any major change in its chemistry is reflected in this spinal fluid. Because the brain concentration decreases from its peak value at age thirty to only 5% of peak value at 90, the need for supplemental pregnenolone increases as we age. In fact, the older and/or sicker you are, the more likely you are to feel an effect from pregnenolone.

Pregnenolone may help restore impaired memory, according to neurobiologist Eugene Roberts of the City of Hope Medical Center in Los Angeles, and his colleagues, biologist James F. Morley, of the St. Louis VA Medical Center. These researchers tested pregnenolone and other steroids on mice. They found that pregnenolone is several hundred times more potent than any memory enhancer that had been tested before. Their report, in the March 1992 Proceedings of the National Academy of Sciences, says that pregnenolone restores normal levels of memory hormones which decline during aging. Roberts noted that pregnenolone was used in the late 1940’s to treat rheumatoid arthritis but fell into disuse when cortisone was discovered. But, says Roberts, pregnenolone was never found to have adverse side effects whereas the toxic effects of cortisone are many and severe.

Pregnenolone also acts on NMDA (N-methyl-D-aspartate) receptors which affect learning and memory by regulating the function of the synapses on our neurons. Dr. Flood of the Geriatric Research Education and Clinical Center in St. Louis writes “Pregnenolone is the most potent memory enhancer yet reported”.

Alzheimer’s, Parkinson’s and other forms of dementia and mental deterioration that occurs with everyone as we age may benefit from pregnenolone supplementation.

Cholesterol-lowering drugs:

Drugs that are used by patients to lower their cholesterol levels inadvertently also block the production of pregnenolone which may lead to impaired brain function. Pregnenolone has a unique ability to repair the enzymes in the cytochrome P-450 system which are responsible for converting cholesterol into pregnenolone. Therefore, pregnenolone supplementation should be considered essential for anyone using cholesterol lowering drugs. Other enzymes in the P-450 system are vital to certain detoxification processes which are also stabilized by pregnenolone.

Pregnenolone doesn’t affect the rate of synthesis of these enzymes, but it stabilizes them against the normal proteolytic enzymes, increasing their activity. This stabilizing action is a general feature of these steroids.

Protection from cortisone toxicity:

The classic effects of toxic levels of cortisol include daytime euphoria, insomnia plus hot flashes at night, osteoporosis, brain aging, atrophy of the skin plus other signs of premature aging and adrenal atrophy (shrinking). Two injections of cortisone can destroy the beta cells of the pancreas in dogs, causing diabetes. Peat believes that stress-inducing elevation in cortisone can cause diabetes in people as well.

Peat reports that pregnenolone can be used to withdraw from cortisone therapy over a one month period without developing “Addison” disease symptoms (from adrenal atrophy), because of its normalizing effects on the adrenal gland. In female patients, progesterone therapy may also be indicated.

Reduced exophthalmia in Graves’ disease patients:

In the 1950’s pregnenolone was tested on patients with exophthalmis (bulging eyes) from Graves’ disease. It was reported that their eyes quickly receded to a more normal position in their sockets. Peat gave pregnenolone to a desperate woman with seriously bulging eyes. After using pregnenolone for just a few weeks, she telephoned him and said that her eyes were completely normal.

Since pregnenolone is a precursor of both progesterone and DHEA, it is a much safer therapy. Peat recommends it for everyone past the age of 40 and even younger, if persistent health problems occur. This includes even the juvenile diabetic. Why? Because pregnenolone was shown to rejuvenate the beta cells of the pancreas in diabetic animals. If it works on animals, its worth a try in humans.

List of essential minerals

An “essential mineral” is a chemical element that is required by organisms for survival or at least for health. The elements carbon, hydrogen, nitrogen, and oxygen, however, are excluded from the list because they are so omnipresent that they were never recognized as minerals.

The well-established essential minerals are:

  • calcium
  • chlorine
  • chromium
  • cobalt
  • copper
  • iodine
  • iron
  • magnesium
  • manganese
  • molybdenum
  • phosphorus
  • potassium
  • selenium
  • silicon
  • sodium
  • sulfur
  • zinc

In addition, the following elements are suspected to be essential minerals:

  • boron
  • nickel
  • tin
  • vanadium

Circumstantial evidence suggests that the following elements might also be essential, despite the reputation many of them have for being merely toxic 1:

  • aluminum
  • arsenic
  • bromine
  • cadmium
  • germanium
  • lead
  • lithium
  • rubidium


PillMan“I’ve heard of it,” said a friend of mine. “That’s skin pigment, isn’t it?”

She was thinking of melanin, the dark color in skin and hair. Since that conversation I’ve encountered many people who confuse the two words. Melatonin is a natural molecule made by the pineal gland, which is located in the brain. Since 1993, melatonin supplements have been available in many health food and drug stores, and through mail order catalogs.

Melatonin is made from an amino acid called tryptophan. Tryptophan is an essential amino acid, that is, the body cannot make it; we need to get it through the foods we eat. Tryptophan is found in a wide variety of foods. As we consume tryptophan during the day, the body converts it into serotonin, an important brain chemical involved with mood. Serotonin, in turn, is converted into melatonin. This conversion occurs most efficiently at night.

Melatonin helps to set and control the internal clock that governs the natural rhythms of the body. Each night the pineal gland produces melatonin which helps us fall asleep. Research about this molecule has been going on since it was discovered in 1958, but it has only been in the last few years that there has been such attention paid to melatonin. Close to a thousand articles about melatonin were published worldwide in 1994. One reason for this growing interest is that we are realizing that deep sleep is not the only byproduct of melatonin. We are learning that it has a significant influence on our hormonal, immune, and nervous systems. Research is accumulating about melatonin’s role as a powerful antioxidant, its possible anti-aging benefits, and its dream-enhancing properties. It is an effective tool to prevent or cure jet lag, an ideal substance to reset the biological clock in shift workers, and a great supplement for those who have insomnia. Melatonin also may have roles to play in the treatment of prostate enlargement, as an addition to cancer treatment, in lowering cholesterol levels, in influencing reproduction, and more. A delightful bonus is that melatonin can increase lifespan.

Melatonin and longevity

A few years ago researchers in Switzerland gave male mice melatonin in their drinking water (Maestroni, 1988). Another group of mice received plain water. At the start of the study all the mice were 19 months old (equivalent to about 60 years in humans) and healthy.

The researchers were surprised when the mice on melatonin showed such a striking improvement in their health, and most remarkably, lived so much longer! And after 5 months on melatonin, astonishing differences in the fur quality and vigor of the two groups became evident. The mean survival time of the untreated group was 25 months (78 years in humans) versus 31 months (98 years) in the melatonin-treated mice!

A similar experiment was repeated in 1991 by Pierpaoli and colleagues. The results confirmed the earlier study. Melatonin, when given regularly to middle-aged mice, increased their life span by 20%.

How would melatonin administration do in the young? To find out, Pierpaoli and colleagues gave melatonin every night to young, female mice (strain C3H/He) starting at age 12 months until death. (There are various strains of laboratory mice and the effect of a particular substance may be different on each strain. That’s why it’s important to mention which one.) These mice had not yet reached menopause. The average lifespan in this strain of mice is about 24 months. The age of 12 months (pre-menopause) would correspond roughly to age 35 in humans. To the surprise of everyone, melatonin shortened survival by 6%. A common reason was the high rate of ovarian cancer in these young mice. Apparently there are cells in the ovaries, in this strain, that overgrow when stimulated by melatonin, causing tumors. Another strain of young, female mice (NZB) was also given melatonin nightly starting at age 12 months. They lived longer. Another group of NZB strain female mice was given melatonin at 5 months of age (Pierpaoli, 1994). They also lived longer. Therefore, there is a difference in response to melatonin by different mouse strains.

How did melatonin effect mice who had already reached menopause? In an additional study, when 18 month old postmenopausal female mice (strain C57BL/ 6) were given melatonin nightly, ovarian cancer was not detected and they lived 20% longer than mice of the same age who were not given melatonin.

How can we interpret these studies in order to make practical recommendations for us humans? First we have to realize that rodents and humans may respond differently to the same medicine. We have seen that different strains of mice respond differently. However, we know by experience in countless other studies and with various other medicines that there is often a similarity between the effects of a substance on rodents and that on humans. It is also possible that if the younger, female mice had been given a lower dose of melatonin, they may have fared better. Based purely on a weight ratio, the amount of melatonin given the mice was many times the dose a human would normally use at night for sleep.

In order for us to know for certain what melatonin will do in humans when given for a lifetime, we will need to follow at least a few hundred or thousand people receiving melatonin for a few decades. Multiple groups would be needed to try different dosages. The volunteers would be advised not to take any other supplements or medicines. Such a comprehensive study is not under way at this time. And the results of such a study would not be available until well into the 21st century. What are we to do in the meantime?

We have to make an intelligent decision based on the available information. There is no right or wrong answer at this time as to whether middle-aged and older people should or should not take melatonin regularly to increase their lifespan. Chronic and high dose melatonin use in the young is strongly discouraged at this time.

Different scientists familiar with these studies may endorse different courses of action. One scientist may caution, “Let’s wait a few more years before making any recommendations.” Another scientist may advocate, “If we wait, we’ll have to wait a few decades. I personally do not want to risk waiting that long; I may be 6 feet under by then. I’m 65 now and I’m having trouble sleeping at night. Melatonin provides me with great sleep. In addition to the obvious advantages of restful sleep, there’s the added bonus that it could extend my life span.” Who will eventually be proved right? No one can predict for sure at this time.

There are additional studies that support the role of melatonin and the pineal gland in life extension. It has been known for a few decades that when rodents had their pineal gland removed, they died sooner. When the pineal glands of young mice were transplanted into older mice, the older- mice lived longer and aging symptoms were postponed (Lesnikov, 1994). When young mice received the pineal gland from older mice, they died sooner.

The pineal gland releases substances other than just melatonin. These other substances, one such example is epithalamin, have a role to play in longevity; in fact, epithalamin and other pineal gland extracts have similarly produced life extension in mice (Anisimov, 1994).

The pineal gland has the means of communicating with every cell of the body through its primary hormone, melatonin. Most hormones need a receptor on the cell membrane before they can enter the cell. Not so for melatonin. As the pineal gland releases melatonin, it quickly goes into the local bloodstream and then to the rest of the body’s blood circulation. From there, melatonin finds its way to every body fluid and tissue. Because it is readily soluble in fat, melatonin has the unusual capacity to permeate into tissues and enter practically every cell of the body. (Most cell membranes are surrounded by a layer of fatty acids.) When melatonin enters the cells, it has the further ability to go directly to the DNA. Researchers speculate that the amount of melatonin reaching the DNA of every cell informs it as to which proteins to make. In November of 1994, the Journal of Biological Chemistry published a fascinating article where researchers Becker-Andre and colleagues found a specific receptor for melatonin right in the nucleus of cells. They conclude, “A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effects of this hormone.”

During infancy and childhood there is a high peak of melatonin reaching every cell. The high peak lets the cells know that the organism is young. The amount of melatonin released each night is less in middle age and even less still in old age. Therefore, as we advance in years, a lesser melatonin peak reaches the DNA in our cells. Some researchers think the pineal gland functions as the “aging clock.” The reasons for the decline in melatonin levels was discussed in chapter two. One possibility is the failure of the pineal cells. They may get overworked through the years and not function as efficiently. Perhaps supplementation with melatonin may allow the pineal gland to work less hard and preserve its optimal functions for many more years.

The decline of melatonin peak levels provides a signal to inform all cells in the body of their age i.e. it’s time to call it quits, call a lawyer to write a living will, and make the down payment for a plot at the cemetery (or cryonics arrangements for futurists). Melatonin supplementation could trick the DNA into thinking, “Maybe I miscalculated. I must be younger than I thought.”

We should not think of melatonin as the only influence on aging. In a complex organism such as the human body there are innumerable factors that are involved in the aging process. The pineal gland is only one of these factors, albeit an important one.

Some of the ways melatonin could prolong life span include it’s ability to be an antioxidant, enhance the immune system, provide deep sleep, and regulate hormonal levels. Another interesting correlation is between diet and melatonin. It is known that food restriction in rodents causes an increase in melatonin production (Stokkan, 1991). Food restriction also leads to life extension. It is too early to tell whether the increase in melatonin due to food restriction is one of the factors that leads to this longevity.

I know a number of individuals who have started to take melatonin nightly at doses ranging from 1 mg to 10 mg. They do not take melatonin necessarily for sleep, but primarily for its potential health and longevity benefits. Four of these individuals have been taking it for over two years, without apparent side effects. Some organizations involved in seeking ways for life extension are recommending to their members to use melatonin regularly.

A few pineal gland researchers have started to take melatonin for its potential health benefits. Russel Reiter, a neuroendocrinologist and foremost pineal gland researcher, is quoted in Vogue magazine, February 1995, “I’ve been taking it for years for jet lag. When we made the discovery about its antioxidant potential, I started taking it regularly.” (He takes about 1 mg nightly.)

We don’t know for certain the long-term, positive or negative, effects of melatonin use in humans then again we hardly know for certain the long-term effects of many common medicines or supplements, including aspirin and vitamins.

Coenzyme Q10

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a lipoidal vitamin-like substance similar in structure to vitamin K. CoQ10 resembles a vitamin but is unique in that it is not only present in many human foods, but also can be biosynthesized within mammalian tissue. Two other vitamins having similar properties, including the ability to be synthesized within mammalian tissue, are nicotinamide and vitamin C.

CoQ6 through CoQ10 are the most common forms of this coenzyme and occur in a wide range of microorganisms. However, CoQ10 is found only in mammals. Studies have shown that, although other CoQ  – homologues – are found in human tissue, only CoQ10 is functional. The homologues occur in such trace amounts as to be functionally insignificant.

Coenzyme Q10 has captured the imagination of medical scientists since it was discovered in 1957 and isolated in 1960. Thereafter, researchers found it to be essential in cell respiration, electron transfer and the control of oxidation reactions (redox reactions). What this may mean therapeutically will be discussed later.

Coenzyme Q10 can be found human heart tissue. Its importance to humans is illustrated by the fact the heart may cease to function as coenzyme Q10 levels fall.

Coenzyme Q10 – method of action

Dr. F. L. Crane and colleagues first isolated and extracted Coenzyme Q10 from mammalian tissue in 1957. Their initial research concluded CoQ10 was able to add or remove oxygen from a biologically active molecule. The importance of this becomes clear when it is realized that a lack of oxygen can produce a decline in cellular energy, while an overabundance will result in the formation of toxic substances.

CoQ10 is found in the myocardium and is particularly concentrated in the inner membranes of the mitochondria and of the Golgi apparatus. Mitochondria manufacture adenosine triphosphate (ATP).

CoQ10 plays a critical role in pumping protons across the mitochondrial membrane, hence providing the body with enough energy to stay alive. It serves the same function as the cylinders in an automobile engine where the gasoline is ignited and explodes to drive the piston. Without CoQ10 the cell is like a dead engine; there is no spark or ignition. CoQ10 also appears to exert regulatory effects on mitochondrial enzymes. CoQ10 functions in redox reactions in Golgi membranes. The role of CoQ10 as a redox carrier in the respiratory chain is well established based on the evidence of reconstitution data and kinetic evidence.

Research on CoQ10-depleted or replenished submitochondrial particles demonstrates that this coenzyme is essential to the redox component between NADH and succinate dehydrogenase and cytochrome. It also has regulatory effects on the succinate dehydrogenase and NADH dehydrogenase and cyctochrome b-C1 complex.

These findings are important therapeutically, for they provide insight as to how CoQ10 can benefit those with congestive heart failure, for example, where correction of deficiencies and improved bioenergetics occur following treatment with CoQ10.

Oral administration elevates plasma CoQ10 levels. CoQ10 passes quickly from plasma into the tissue, reaching levels higher in tissue than would occur solely due to equilibration. CoQ10 is absorbed mainly into the liver and to a lesser degree into other tissues.

A carefully designed study compared CoQ10-containing vesicles with beta-carotene containing vesicles. The study raised the possibility that the observed CoQ10 antioxidant effect could be to scavenge singlet oxygen and to affect the structure of the lipid bilayer so as to inhibit the decomposition of hydrogen peroxide and the release of harmful free radicals.