By Benjamin V. Treadwell, Ph.D.

On a daily basis, we are exposed to potentially harmful compounds. They may include the drugs we take (cold medications, antihistamines, antidepressants, etc.), as well as toxic chemicals in our environment. Luckily, these harmful compounds can be acted on and removed or neutralized by cellular enzymes in the tissues of our bodies.

Enzyme Education
There are two major biological pathways and two classes of cellular enzymes — referred to as Phase I and Phase II — that are largely responsible for detoxification. The Phase I enzymes are first in acting on (metabolizing) the toxic compound, producing a product (metabolite) that is then passed on to the Phase II enzymes for further modification.

This system protects us against relatively new or foreign-to-nature (xenobiotic) drugs as well as the carcinogens present in our industrialized environment. But how did it evolve? It is unlikely that caveman or cavewoman had access to any of today’s medications. Nor were they exposed to modern carcinogens. In other words, many of today’s toxic compounds were not present during man’s evolution.

A compound our distant ancestor might have encountered (tar, smoke, toxic chemicals in certain foods) does, however, have some similarity to our high-tech drugs. Because the enzymes are inherently flexible, the same enzymes that acted on early-man-encountered substances can also twist into a conformation to wrap around and act on more modern-day compounds.

Enzymes and Aging
Often, though, the product of the Phase I enzymes is highly reactive and, if not immediately acted upon by the Phase II enzymes, can cause tissue damage, cancer and other diseases. Research is demonstrating an association between aging and a decline in Phase II enzyme activity, which may at least partly explain the increase with age of cancer, musculoskeletal disease and neurodegenerative diseases. The question is, how can we reverse, or at a minimum attenuate, the gradual decline in this important class of detoxifying enzymes?

Plant + Enzyme Chemistry
Recent discoveries have identified a number of different chemical compounds, contained in certain plants, that have the unique property of activating the Phase II enzymes. Some of these plants and their enzyme-activating compounds include: garlic (allicin), turmeric (curcumin), cruciferous vegetables (sulforaphane), grapes (resveratrol), and green tea (catechins).

Most of the work demonstrating Phase II enzyme activation with these compounds has been carried out in cell culture or animal studies, rather than with human subjects. However, a 2007 study of people taking a green tea extract produced significant results.

Green Tea for Phase II
Forty-two men and women were asked to take capsules containing green tea extract (800 mg/day) for a period of four weeks. The protocol involved taking blood from each of the subjects before they began taking the extract, then again at the end of the four weeks. The white blood cells were isolated from the pre- and post-extract blood samples to measure the level of glutathione S-transferase (GST), an important member of the detoxifying Phase II enzymes (there are over 200). The results? A 20% average increase in GST.

Biochemical Balance
The next obvious question is whether or not there is risk of over-activating the Phase II enzymes, creating a biochemical imbalance, by taking compounds like green tea extract on a regular basis. The 2007 study appears to indicate that this is not the case.

Although there was a 20% mean increase in the GST Phase II enzyme level, what is perhaps more remarkable are the different rates of increase, relative to baseline levels, when the subjects were divided into three groups. Those with the lowest baseline GST showed an 80% increase in GST. For those at mid baseline level, the increase was 20%, and those with the highest baseline GST showed a slight decrease.

In other words, it appears the enzyme system is self-regulated to the extent that some mechanism exists to prevent over-production of the Phase II enzymes.

A new clinical study has demonstrated the positive effects of an extract of green tea on stimulating the production of a group of enzymes that protects tissues from disease-producing toxins.

Researchers from the University of Arizona and the National Cancer Institute examined the level of an enzyme, glutathione S-transferase (GST) as a representative of  a family of enzymes involved in cellular detoxification – Phase II Enzymes - in white blood samples taken from test subjects before (baseline) and after a four-week treatment with an extract of green tea.

Factors affecting baseline enzyme activity include genetic profile, diet, contact with environmental toxins and age. Those subjects with the lowest baseline levels had the largest increase in the production of GST in response to daily treatment with 800 mg green tea extract capsules. 

These results are consistent with epidemiological studies showing that areas of the world with higher consumption of green tea and related plant compounds have a lower incidence of certain diseases, including cancer. They may also help to identify one of mechanisms involved in reducing the incidence of cancer and other disease states by increasing intake of plants containing polyphenolic compounds.   

Details and methodology appeared in the August 2007 issue of Cancer Epidemiology, Biomarkers and Prevention, published by the American Association for Cancer Research.

To read the abstract, click here.
"Modulation of Human Glutathione S-Transferases by Polyphenon E Intervention"
Cancer Epidemiology Biomarkers & Prevention 16, 1662-1666, August 1, 2007.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

QUESTION:   Could you please tell me the recommended daily dosages of vitamins K and D? How much of these vitamins should be in our multi-vitamin? I am in my fifties. Thank you. — R.

ANSWER: To obtain optimum health, the amount of vitamin D can be up to 2,000 international units (IU) per day. However, I believe 800 to 1,000 IU per day is sufficient. As for vitamin K, the results are not in just yet, but I think that taking a supplement containing 100 to 200 micrograms per day is a reasonable amount.

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Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.