DR. PHYLLIS J. MULLENIX, Ph.D. is a pharmacologist and toxicologist by training... In the 1980s, Dr. Mullenix was Head of the Toxicology Department at the Forsyth Dental Center, a world renowned dental research institution affiliated with the Harvard Medical School. She was invited to start Forsyth's Toxicology Department because of her expertise in neurotoxicology. She is presently a Research Associate in Psychiatry at the Children's Hospital Medical Center in Boston. Dr. Mullenix's academic appointments, professional positions held, teaching experience, awards, honors and many published scientific research articles to her name are numerous.

The first test Dr. Mullenix was asked to perform at the Forsyth Dental Center was a test related to neurotoxicity of fluoride. The person who asked her to perform this test was Dr. Harold C. Hodge, one of the founders of the Society of Toxicology. Since that time, Dr. Mullenix has conducted additional research related to fluoride including one study which is about to be published. She is considered one of the foremost experts on the neurotoxicity of fluoride compounds..

Please join me in welcoming Dr. Mullenix to the ADD-Holistic list! Don't forget to post your questions after Dr. Mullenix' first post on Monday.

Best Wishes,
- Mark
mgold@tiac.net

September 14, 1998

Statement from Phyllis Mullenix, Ph.D.

It was 1982 when fluoride was first brought to my attention as a substance in need of investigation. At that time, I was in the Departments of Psychiatry at Boston's Children's Hospital and Neuropathology at the Harvard Medical School. My studies focused on detection procedures for neurotoxicity, and they typically considered a variety of environmental and therapeutic agents, i.e., radiation, lead, amphetamine, phenytoin, nitrous oxide. Dr. John Hein, then Director of Forsyth's Dental Infirmary for Children in Boston, was interested in neurotoxicity studies and invited me to continue this research at Forsyth and to apply it to substances used in dentistry. Fluoride was prominent on his list.

Five years lapsed before our investigations of fluoride began. The delay was due to time spent on technological improvements, specifically development of a computer pattern recognition system for the objective quantification of behavior in an animal model. In early June of 1986, the Forsyth Dental Center was noted for this achievement in the Wall Street Journal and the Boston Herald, and applications of our research grew. The new technology enabled us to study the clinically recognized neurotoxicity associated with the treatment for childhood leukemia. Simultaneously, we started investigations of fluoride, the "safe and effective" treatment for dental caries.

Initially, the fluoride study sparked little interest, and in fact we were quite anxious to move on to something academically more exciting. Using an animal model developed for the study of dental fluorosis, we expected rats drinking fluoride-treated water would behave the same as matching controls. They did not. The scientific literature led us to believe that rats would easily tolerate 175 ppm fluoride in their drinking water. They did not. Reports in the literature indicated that fluoride would not cross the blood brain barrier. But it did. Prenatal exposure to fluoride was not supposed to permanently alter behavioral outcome. It did. Like walking into quicksand, our confidence that brain function was impervious to fluoride was sinking.

Our 1995 paper in Neurotoxicology and Teratology was the first laboratory study to demonstrate in vivo that central nervous system (CNS) function was vulnerable to fluoride, that the effects on behavior depended on the age at exposure and that fluoride accumulated in brain tissues. The behavioral changes common to weanling and adult exposures were different from those after prenatal exposure. Whereas prenatal exposure dispersed many behaviors as seen in drug-induced hyperactivity, weanling and adult exposures led to behavior-specific changes more related to cognitive deficits. Brain histology was not examined in this study, but we suggested that the effects on behavior were consistent with interrupted hippocampal development (a brain region generally linked with memory).

Establishing a threshold dose for effects on the CNS, in rats or humans, was not the intent of this initial investigation. Yet, one fact relevant to human exposure emerged quite clear. When rats consumed 75-125 ppm and humans 5-10 ppm fluoride in their respective drinking waters, the result was equivalent ranges of plasma fluoride levels. This range is observed with some treatments for osteoporosis, and it is exceeded ten times over, one hour after children receive topical applications of some dental fluoride gels. Thus, humans are being exposed to levels of fluoride we know alters behavior in rats.

We concluded that the rat study flagged potential for motor dysfunction, IQ deficits and/or learning disabilities in humans. Confident as we were, the data were only one piece of the puzzle, the overall picture was still emerging. Soon thereafter we learned of two epidemiological studies (Fluoride, 1995-1996) from China showing IQ deficits in children over-exposed to fluoride via drinking water or soot from burning coal. A recent review (International Clinical Psychopharmacology, 1994) listed case reports of CNS effects in humans excessively exposed to fluoride, information that spans almost 60 years. A common theme appeared in the reported effects: impaired memory and concentration, lethargy, headache, depression and confusion. The same theme was echoed in once classified reports about workers from the Manhatten Project. In all, our rat data seem to fit a consistent picture.

Information linking fluoride and CNS dysfunction continues in 1998.

1) A recent study in Brain Research demonstrated that chronic exposure to fluoride in drinking water of rats compromised neuronal (hippocampal) and cerebrovascular integrity (blood brain barrier) and increased aluminum concentrations in brain tissues.

2) Masters and Coplan have reported (International Journal of Environmental Studies, in press) that silicofluorides in fluoridated drinking water increased levels of lead in children's blood, a risk factor that predicts higher crime rates, ADD and learning disabilities.

3) Luke at the International Society for Fluoride Research (ISFR) meeting in August reported that fluoride accumulated in the human pineal gland, as much or more so than in bones and teeth, and the pineal gland's melatonin biosynthesis pathway is affected by fluoride.

4) Also at the ISFR meeting, I reported that the fluorinated steroid (dexamethasone) disrupts behavior in rats to a greater degree than does the nonfluorinated steroid (prednisolone). This finding matched results just completed in a study of children receiving steroids as a part of their treatment for childhood leukemia. Dexamethasone, compared to prednisolone, further reduced IQ, specifically impairing reading comprehension, arithmetic calculation and short-term working memory.

Exposure to fluoride goes well beyond that in our drinking water, toothpastes and mouth rinses. Fluoridation of water dictates that it is in food and processed beverages. Pesticides such as cryolite also increase fluoride content of foods. The trend toward fluorinating pharmaceuticals increases fluoride exposure via medication. Fluoride, in various compounds, plays a heavy role in occupational exposures and for people living in close proximity to industry, i.e., aluminum, steel, brick, glass, petroleum, etc. With exposure so common, we can no longer afford to ignore potential CNS consequences of fluoride.

I would be happy to answer questions about any of the above material.

Phyllis J. Mullenix, Ph.D.

The following are responses from Dr. Mullenix to questions asked by Mark Gold.

September 17, 1998

Response to Questions from Mark Gold

Hi Mark,

Thank you for the questions and interest in our work. The following are responses to your questions.

1) You have the dose for the Brain Research paper correct. It was essentially 1 ppm fluoride in the drinking water for 52 weeks (not an equivalent dose). This was indeed a very low dose, but one close (or even lower) to that consumed by humans. Note that our study in rats included higher doses, but for shorter periods of time (6 or 20 weeks duration). We realized at the time that the duration of exposure was just as critical as the dose. We proposed studies looking at much lower doses with longer durations, but that was where our research was cut off. Hmmm, indeed.

2) There is no question that fluoride crosses the blood brain barrier, and it is also likely that some neurological effects can be reversed. The key variables to reversibility may involve: 1) the age at exposure- the earlier in brain development when exposed, the more likely changes will not be reversible. 2) the dose and duration of exposure. There are more than one mechanism by which fluoride could be causing problems for the brain. Repeated peak exposures to fluoride for a short duration of time may be a problem if the peaks occur during critical periods of brain development. The mechanism to be suspicious of here is fluoride's ability to interfere with the G2 phase of the cell cycle. In other words, it can interfere with brain development the same way that x-irradiation does. In contrast, low steady doses of long duration can still be a problem for the brain, even if the brain is well developed. However, the mechanism to be suspicious of here is the accumulation of fluoride. This situation is more likely to be reversible, but the problem is stopping the exposure to allow the body time to rid itself of the deposits so that the brain can recoup. Remember, there are major storage sites for fluoride in the body (bones, teeth and the pineal gland). Every time bones remodel, they kick out fluoride which can then be recirculated and go back into other soft tissues, including the brain. Ridding the body of fluoride can take years, even if you accomplished the difficult task of stopping all sources of fluoride exposure.

3) There are ways to restrict fluoride exposure:
a) drink distilled water or bottled water with known low fluoride content (i.e., Evian)
b) avoid drinking processed beverages made with fluoridated water- colas, etc.
c) avoid drinking tea
d) avoid foods sprayed with cryolite- used often on potatoes (outer peel may have as much as 20 ppm fluoride)
e) avoid foods that labs have confirmed as being high in fluoride- some cereals (fruit loops, wheaties), vegetables grown next to industries- spinach, celery
f) whenever possible, switch from fluorinated to nonfluorinated medications. Besides steroids, antibiotics, anesthetics (methoxyflurane) and antidepressants (prosac and paxil) contain fluorine in chemical structure. When metabolized, they may contribute to fluoride levels in blood.
g) get plenty of calcium in diet (magnesium can help some too).

4) The link of fluoride with fibromyalgia has not been explored in any depth. The new data showing fluoride's impact on melatonin biosynthesis, and the high concentrations in the human pineal gland, should be a real eye opener for many. I am ill at ease with this enzyme poison (fluoride) being that close to the hypothalamic-pituitary-axis functions in the body. Research is needed immediately, but will it happen for this politically sensitive subject?

I'm sorry if these answers are long, but there is much to say and learn.

Phyllis J. Mullenix, Ph.D.

Read another interview with Dr. Phyllis Mullenix at:
www.fluoridealert.org/mullenix-interview.htm