Herbs & Dietary Supplements-Part I: St. John’s Wort

(12/8/08)- It looks like Gingko biloba has taken another hit, despite some individual's belief that it helps prevent cognitive decline. The results of the Ginkgo biloba Enhancement of Memory (GEM) research study indicated no difference between control and research groups. This study was a multisite, randomized control 6-year trial of Ginkgo biloba vs. placebo of 3019 community volunteers with a minimum age of 75. At baseline, each subject was given a neuropsychological battery and then randomized to either receive 120 mg BID of Ginkgo biloba or placebo.

Six months later they were reevaluated and those who showed some cognitive decline retook the neuropsychological battery. The battery and clinical reports were reviewed by an expert panel, blind to the study, and those individuals who showed decline were referred for a full neurological examination including MRI in order to confirm the diagnosis of dementia.

In all, 523 individuals developed dementia, with no statistical difference between control and experimental group. In the placebo group, 16.1% developed dementia, while in the Ginkgo group 17.9%. By the end of the study, 60.3% of the study group was still taking the medication.

The study can be found in JAMA 2008 Nov.19; 300:2253.

Note should be made that the authors of the study suggest a longer duration of G.biloba intake might be effective and they plan to analyze some subjects further. An editorial accompanying this article indicated that the investigators did not include data on overall cognitive decline or functional disability in their report.

This author wonders what if they included a third group of subjects who believed Gingko biloba really worked. Would the synergistic effect of belief and taking the dosage prove effective? What if a different dose was used?

(3/12/07)- Proponents of the use of vitamins have raised several questions with the results of the recent Danish study that we discuss in our item dated 3/7/07 below. Two large vitamin studies from China and Italy showed that antioxidant supplements did lower the mortality risk of the subjects in those studies.

The other issue raised by advocates of vitamin usage is that the studies were done on unhealthy individuals, whereas most vitamin users are healthy subjects. The figures from the Danish study are biased because very high dosages of the vitamins in question were used on the subjects.

A recent report, called the Women's Health Study, evaluated the use of 600 International Units (IU) of vitamin E every other day by nearly 40,000 healthy women. In that study, the vitamin users over 65 were 26% less likely to suffer a major cardiovascular event and 24% less likely to die during the study period.

The daily dietary reference intakes (DRI) set forth by health authorities are much lower than the vitamin dosages ingested by the subjects in the Danish study.

(3/7/07)- A group of Danish researchers have concluded, after reviewing the data from 47 different studies, that the ingestion of massive amounts of high dosages of antioxidants does more harm than it does good.

The review of the medical research studies into beta carotene, vitamin A and vitamin E concluded that supplement users had higher death rates during the various study periods compared with nonusers, according to the report that was published in a recent edition of the Journal of the American Medical Association (JAMA).

The investigators from Copenhagen University raise important questions about how best to study the health effects of vitamins and supplements. The vast majority of the research uses high doses of antioxidants to treat unhealthy people such as smokers or people with heart disease as opposed to healthy users of the supplements.

The results of the study showed that beta-carotene use increased mortality risk of mortality by 7%, vitamin A boosted risk by 16% and vitamin E boosted risk by 4%.

The study showed no increased risk with vitamin C and a potential benefit from Selenium that the researchers concluded required further studies.

(8/31/01)-The Food and Drug Administration (FDA) is seeking to provide consumers with more information about the side effects experienced when taking popular dietary supplements and other foods.

The agency intends to consolidate its outdated computer systems into one system that will be able to advise the consumer about the adverse-events reported to the agency. Last year there were about 7,000 adverse-events reported to the agency. Reporting of adverse-events re dietary supplements is not mandatory as is required for drug-related adverse events. Last year there were more than 250,000 reported drug related adverse-events. The system is not expected to be operative until the fall.

"I'll believe it when I see it," said Sidney Wolfe, director of Public Citizen's Health Research Group, a Washington based consumer-advocacy group. "Their record on this issue is abysmal." According to Mr. Wolfe the FDA hasn't added information to an important data-base on dietary-supplement adverse events for almost three years.

The FDA monitors the dietary supplement industry in a less rigorous way than it does the prescription drug industry as result of a law passed by Congress in 1994. Under the 1994 law manufacturers do not need governmental approval before marketing their product. See our article on Drug Evaluation. Supplementary products can come and go as long as they are cautious in their claims. One can never be sure of how pure they are or the exact dosage of the active ingredient or the dosage that provides therapeutic effect. This, however, does not mean that they will not have a beneficial effect.

Copies of the second Annual Bibliography of Significant Advances in Dietary Supplement Research may be downloaded from the ODS website at

According to a report from Michael F. Mangano, acting inspector general of the Health and Human Services Department, manufacturers of dietary supplements, the supplements themselves and their ingredients should be registered with the government. According to the report the Food and Drug Administration lacks the most basic information needed to analyze reports of illness and injury associated with dietary supplements and sports nutritional products. Dietary supplement manufacturers do not have to report "adverse events" to the FDA, as makers of prescription drugs must do.

The report further stated that investigators oftentimes could not determine the active ingredients in the dietary supplement or locate the maker of products suspected of harming users. The magnitude of the problem is reflected from the fact that according to the report 100 million Americans are taking dietary supplements, and they spent $15 billion on them last year.

It has been determined that some of the dietary supplements have increased risks associated with their usage. Ginko biloboa, which is often taken to enhance memory, "can lead to excessive bleeding and in some cases, stroke" according to the report. High doses of vitamin A during pregnancy can lead to birth defects. Herbal remedies that contain Aristolochia, also known as Virginia snakeroot, can cause kidney damage and cancers of the urinary tract.

The FDA can seize products, issue warnings, request recalls and order manufacturers to put more information on product labels. From January 1994 to June 2000, investigators reported that only 31 actions were taken to protect users of dietary supplements. A spokesman for the American Herbal Products Association, a trade group for the industry, said it opposed mandatory reporting of injuries and illnesses because there was "no public health need" to do it.

The report went on to further state that the FDA had not established "good manufacturing practices" to control ingredients used in dietary supplements. Thus a user of dietary supplements "cannot assume the products contain what is listed on the labels, in the quantities listed."

The most popular psychotropic herb presently on the shelves is St. John’s Wort. From 1990 to 1997, the use of St. John’s Wort grew by 2600% as contrasted with Gingko Biloba, which grew 142%. It has been around as a medicinal herb for approximately two thousand years. Two recent studies however have indicated that there may be negative interactions between St. John's Wort and a drug used in transplants, and also interference with a drug used in AIDS cocktails.

There is even some evidence that at one point many years ago St. John's Wort was used as a topical salve or balm for burns and skin wounds. During the Renaissance, the writings of Paracel suggested its use in a variety of conditions including psychological maladies, but not specifically as an antidepressant. The first specific reference to use of St. John’s Wort as a treatment for depression occurred about 350 years ago when a Chemist, Angelo Sala, pointed out its use in treating melancholia.

A revised interest in St. John’s Wort began in the early part of the twentieth century, a period of rejuvenation in "natural" treatments for disease. (A novel by T. Corghesian Boyle entitled Road to Wellness touches on an interesting sidelight in the history of "natural cures" at the turn of the century and during 1930’s.)

Peterson's Field Guide to Medicinal Plants (1990 edition) describes its uses: "Fresh flowers in tea tincture, or olive oil, once popular domestic medicine for treatment of external ulcers, wounds (especially those with severed nerve tissue), sores, cuts, bruises etc. Tea is a folk remedy for bladder ailments, depression, dysentery, diarrhea, and worms. Experimentally it may be used as a sedative, anti-inflammatory, or antibacterial agent. It contains the biological active compounds choline, pectin, rutin, sitosterol, hypericin, and pseudohypericin." It goes on to warn that if applied externally, it may cause skin burns when exposed to sun.

Recently, phytobiologists and chemists as well as psychopharmacologists who have studied St. John’s Wort report it is effective in mild to moderate depression and in dysthymia as well as seasonal affective disorders. On a molecular level, it effects gamma amino butyric acid (GABA) and causes reuptake inhibition of serotonin, norepinephrine and dopamine.

The active ingredient hypericin in St. John’s Wort has been shown to inhibit the enzyme monoamine oxidase A & B and may increase capillary blood flow as well as having antiviral and anti-inflammatory actions. Another component of St. John’s Wort is hyperforin, which has many neurochemical properties and may play a role in the antidepressant activity. See our 2-part article on Aging and Depression. Please also see our article Nutraceuticals and the Elderly

These active ingredients appear to have long half-lives which indicate that a once daily dosing would be effective. The Psychiatric News (1999; 34:27) states "clinicians should start patients at 900 milligrams per day, but may boost dose to 1800 milligrams daily if necessary…If the drug is going to help…results will become evident in one to three weeks." They also reported that the side effects of St. John's Wort are "much less" than antidepressants.

As far as we have researched, there are no qualified placebo-control, randomized studies showing robust results for St. John’s Wort. It is actively used in Germany and clinicians throughout the United States report success with it.

In a recent study conducted by the National Institutes of Health under the leadership of Dr. Stephen Piscitelli an inter-reaction was noted between St.John's Wort and the AIDS drug, indinaver, sold by Merck & Company under the name Crixivan. According to Dr. Judith Falloon of the National Institute of Allergy and Infectious Diseases " Most people taking medications to treat H.I.V. infections should avoid St. John's Wort".

According to a study done at the University Hospital in Zurich it was ascertained that St. John's Wort interfered with the drug cyclosporine, which is used to keep transplant patients from rejecting their new organs.

We advise our readers to check with their treating physicians to determine possible synergistic effects with other medications. There are many psychopharmacological medications on the market that have been shown to be effective in treating 60 to 80 percent of the individuals with depression. It may be that St. John’s Wort will join this category. Only time will tell. Presently, Cavaet emptor (Let the buyer beware).

Prevention is a very complex factor that is still not very well understood. Synergistic effects may enhance or inhibit specific reactions. Sharing information with your treating physician is a necessary step in helping deal with any medical condition. This means informing the physician of all supplements or alternative medicines being taken. It also is important that the treating physician be aware of the role of complimentary medicines on health.

Doctors need to be especially aware of any potential interaction variables that may contraindicate use of supplements or herbal medications and the positive role of certain of these treatments. Research on these topics is in progress. Everyone awaits the results of these studies. At present, the hype for vitamins and herbal supplements have caught on as reflected in the amount of money spent on these products, especially by those over 60 years of age. They must be used with caution. Anti-aging is still a concept that remains beyond our reach, even though many of us would like to see it happen.

A survey that appeared in the Journal of the American Medical Association (JAMA) in November of 1998 indicated that total spending for alternative treatment for psychiatric disorders rose from 14.6 billion in 1990 to 21.2 billion in 1997. This total included herbs, dietary supplements, acupuncture, chiropractor visits, homeopathy and energy healing. It was estimated that alternative practitioner visits rose from 427 million in 1990 to 629 million in 1997. Contrast this with the total visits to primary care physicians which went from 388 million in 1990 to 386 million in 1997. During this period the use of herbal medicine rose 380%. 

One could only speculate on the reasons for the rise in herbal medication use. Unless there is a dramatic change in the perception or, for that matter, primary care treatment, these numbers will continue to hold but at a slower rate of growth as researchers tell us more about its activity and look at long term results. Reasons for the increase in usage range from fewer side effects, rising cost of primary care, or lack of confidence in the medical profession. An aging population tends to use more complementary and cheaper medical treatment. The sense of using "natural products" enhances the feeling of health.

In addition there is the greater advertising blitz and the growth of large stores dedicated to vitamins and supplementary products. The increase use of the internet with its capacity to spread data rapidly may put people in possession of not so robust information from all over the world, especially where herbal medicine is strong i.e. Germany and China.

Please See:
St. John’s Wort -Herbs and Dietary Supplements-Part II-Ephedra
Phytomedicine or Herbalist-What is It?-Part III
Herbal Medicine and Botanical Supplements Caveat-Part IV
Treating Osteoarthritis with Dietary Supplements-Part V
St John's Wort: Does It Help Treat Depression-Part VI
Herbal Products: Use With Caution-Part VII
Kava: Safety Alert-Part VIII
Herbal Usage for Hormone Replacement Therapy-Part IX
Latest Research Questions the Effectiveness of Herbal Supplements-Part X



Harold Rubin, MS, ABD, CRC, Guest Lecturer
Updated December 8, 2008

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