June 2000 Blog with Durk and Sandy
SAVING PEOPLE FROM THEMSELVES – DOES IT WORK?
Although more than 80 countries have laws that require motorists and their passengers to fasten their seat belts, there is little evidence that these laws are saving many lives, according to a report in the Jan. 29, 2000 Lancet.
The Lancet article notes that a report commissioned by the UK government’s Department of Transport and then surpressed by that agency noted that “available data for eight western European countries that introduced a seat-belt law between 1973 and 1976 suggest that it has not led to a detectable change in road deaths.” An editorial in The Lancet in 1986 reported that this failure was very disappointing in light of the 1000 lives saved per year that had been anticipated and despite 95% compliance with the law. In fact, surprisingly, in the 23 months that followed the introduction of the UK seat-belt law, the number of deaths among pedestrians, cyclists, and unbelted rear seat passengers rose by 8%, 13%, and 25%, respectively.
The authors suggest that people have an internally set amount of risk they are willing to incur and that, if risks are perceived to be lessened by, say, the enforced use of seat belts, then people increase other driving risks to again reach their preferred risk level. We agree. This is consistent with reports that have shown that legally required use of motorcycle helmets has been associated with an increased risk of motorcycle accidents.
The authors then question the effectiveness of condoms in reducing HIV infections. They cite a U.S. study finding no reduction in disease incidence in women insisting on condom use compared with non-condom users. If condom use increases (thus decreasing risk per sexual encounter) people might increase their casual sexual activity. The authors calculated that when baseline condom use is 50% and it is desired to decrease the number of unprotected sex acts, then condom use must increase to at least 67% if total sexual activity increases by 50%, and to at least 76% if total sexual activity doubles.
We would like to point out another example of this phenomenon: low nicotine, low-tar cigarettes were supposed to reduce people’s exposure to the toxic contents of tobacco smoke but this approach was thwarted by smokers taking larger puffs and holding the smoke in their lungs longer or smoking more cigarettes. The result of former FDA Commissioner David Kessler’s proposed “solution” to cigarette smoking was for FDA to take over the regulation of tobacco, to then reduce nicotine content of cigarettes over a period of a few years and finally to phase out the sales of cigarettes, would be a ludicrous failure, since people smoke as many cigarettes as needed to reach the desired intake level of nicotine. Fortunately, the U.S. Supreme Court has recognized and ruled (5-4) in late March that the FDA has no Congressionally granted authority to regulate cigarettes, though you can be sure there will be a major assault on the Congress by the Administration demanding that Congress give the FDA that authority.
Cigarettes could actually be made far safer by allowing the heating of the tobacco (rather than burning), which would deliver the desired nicotine without the accompanying carcinogenic tars, but FDA doesn’t seem interested in safer cigarettes. In fact, several years ago, the FDA threatened a tobacco company that was test marketing such devices with felony prosecution for marketing an FDA unapproved medical device and nicotine delivery system. Their view seems to be that you should have only two choices: do it their way or die.
Thus, the attempt to induce or coerce people to accept safety measures (to protect people from themselves) may not have the benefits touted for them. For example, since the creation of the Occupational Safety and Health Administration (OSHA), the century long decrease in workplace injuries has slowed. Do government programs enforcing the use of safety devices actually make people safer or are they just expensive feel-good programs that support large bureaucracies and attract government snoops into every aspect of our lives that contains some risk?
Richens et al, “Condoms and Seat Belts: the Parallels and the Lessons,” The Lancet 355:400-403 (2000).
WE MOVE AGAINST THE FDA AGAIN AND AGAIN AND AGAIN
We, along with our coplaintiffs, have now filed three new suits against the FDA. You can download all the briefs, which clearly explain the issues involved, from www.emord.com. The first suit challenges, as a violation of the First Amendment, of the Dietary Supplement Health and Education Act, and of the court’s mandated disclaimer approach to health claims in Pearson v. Shalala (U.S. Court of Appeals for the District of Columbia, Jan. 15, 1999), the FDA’s rejection and prohibition of two petitioned health claims (one that vitamins B6, B12, and folic acid may reduce the risk of vascular disease, and the other that vitamin E may reduce the risk of cardiovascular disease*). The second suit challenges, as a violation of the First Amendment, the Dietary Supplement Health and Education Act (DSHEA), and the court’s ruling in Pearson v. Shalala, the denial by FDA of a health claim that saw palmetto may reduce the symptoms of benign prostatic hypertrophy. (The FDA wouldn’t even consider this proposed health claim, saying that it should be considered a drug claim rather than a health claim, even though the claim and the herb met all the provisions of the DSHEA.) The third suit asks that the court hold the FDA and its responsible officers in contempt of court for their failure to permit the four health claims ruled in Pearson v. Shalala to have been denied by the FDA in violation of the First Amendment.
By this time, we shall also have filed a petition with the U.S. District Court for the District of Columbia for an injunction to prevent the FDA from enforcing its prohibition on the use of the four claims held in Pearson v. Shalala to have been denied in violation of the First Amendment. We ask the court to note that a year was held to be too long in complying with the Supreme Court’s ruling against “separate but equal” schools for blacks in Brown v. the Board of Education. The First Amendment is certainly as much of a core civil right as the 14th Amendment.
All this fun stuff can be downloaded at www.emord.com! If you would like to help us pay our share of the mounting legal bills, please send your donation (checks should be made out to Emord & Associates, with the memo section noting that they are for the Pearson & Shaw Litigation Fund) to: Emord & Associates, 5282 Lyngate Court, Burke, VA 22015. Don’t be helpless. Be part of the action by fighting back. Thank you!
* For our health claim submission, we commissioned a review of the literature on vitamin E and cardiovascular disease by William A. Pryor, Ph.D., a leading scientist studying the relationship between antioxidants and free radical disorders; he is also co-Editor-in-Chief of the highly respected Free Radicals in Biology and Medicine. Dr. Pryor has edited and done some rewriting of that review and has published it in Free Radicals in Biology and Medicine 28(1):141-164 (2000). This is an excellent review. In the abstract, Dr. Pryor notes: “There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is ‘complete.’ At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.”
LIVING LONGER AND BETTER THROUGH CHEMISTRY: DO IT YOURSELF GENE MICROARRAYS
The most promising development to date in the pursuit of longer and better human lifespans is the DNA chip or microarray. These devices consist of wafers, usually made of glass, etched with hundreds of thousands of microscopic wells, each of which contains a short stretch of DNA or RNA. These can bond with any matching strands in a sample, the matches being identified using fluorescent tags. This allows one to identify whether and to what extent various genes are turned on or off under particular conditions, thus quickly permitting the identification of anti-aging methods that work (compared, for example, to the gene changes induced by caloric restriction in rats, mice, fruit flies, and other organisms).
A group of California scientists has now developed a do-it-yourself kit for building a DNA microarray1 less expensively than those commercially available and has made the information freely available on the Web http://cmgm.stanford.edu/pbrown/mguide/. Using the website, a researcher can build a microarray for an estimated $30,000, about half the current cost of a commercial device. You’ll also need a scanner to analyze the chips. A “freeware” database designed for microarray data has now been made available by the group to allow users to store, sort and analyze genetic data (see http://www.microarrays.org). When mass produced as consumer home health test devices, these gene arrays will probably cost only a few dollars.
Now all we have to do is make sure that government agencies like the FDA, claiming that their regulations will (among other things) protect us from ourselves, prevent the results of research from being converted into actual gene therapy to put it to practical use.
Eternal vigilance is the price of liberty and of longer lifespans.
- Dalton, “DIY Microarrayers Promise DNA Chips with Everything” Nature 403:234 (2000)
HOW THE GOVERNMENT PROTECTS THE CONFIDENTIALITY
OF YOUR MEDICAL RECORDS
When Congress passed the Health Insurance Portability and Accountability Act of 1996, it gave itself until August 1999 to enact comprehensive medical privacy legislation. If it missed the deadline, then another provision of the bill empowered the Department of Health and Human Services (DHHS) to issue such regulations. The Congress has chosen to save itself a lot of work and political hassle by irresponsibily handing the job off to DHHS.
But what DHHS has now proposed as medical records confidentialty rules is – surprise, surprise – a complete fraud. First, the proposed regulations would abolish the established principle that a patient’s consent is required before his or her medical information can be released to third parties. One provision says, “Under our proposal, most uses and disclosures of an individual’s protected health information would not require explicit authorization by the individual.” The proposed new rules allow, for example, access to patients’ medical information under the categories of “treatment, payment, and health care operations” without patients’ knowledge, consent, or even ability to track who received the information. An attorney in a litigation could obtain a patient’s medical records “with a written statement certifying that the protected health information requested concerns a litigant to the proceeding and that the health condition of such litigant is at issue in such proceedings.”
Specified medical information could be disclosed (though disclosure would not be compelled) to the police at their request to help them identify suspects, fugitives, witnesses, and missing persons, or even to determine whether a crime had occurred! (Disclosure for these purposes may not be compelled, but who is going to say “no” and run the risk of being investigated themselves? Any doctor is always at risk for being accused of prescribing too many controlled-substance painkillers.)
Moreover, incredibly, if a physician wanted to provide greater protection to his or her patients’ medical records than that provided in the DHHS regulations, it would be illegal for him or her to do so.
Agencies at almost any level of government, or private entities acting on their behalf, would have broad access to personally identifiable medical data. Release would be permitted without the patient’s consent, knowledge, or notification “for inclusion in a governmental health data system that collects health data for analysis in support of policy, planning, regulatory, or management functions authorized by law.” This includes literally hundreds of government databases.
The only disclosures that actually require patient consent are those for private activities such as sales, rental, bartering or marketing, enrollment decisions in a health plan, or use for fundraising purposes. These uses, which do require patient consent, are being touted by DHHS as a basis for their claim that these regulations “protect” medical information confidentiality. Of course, if you believe, as we do, that government is a far greater danger to privacy than these private sector entities, you know better, but watch out, they may try to tar folks who oppose these “protective” regulations as antigovernment extremists.
See Appelbaum, “Threat to the Confidentiality of Medical Records – No Place to Hide,” JAMA 283(6):795-796 (2000); for regulations, see Standards for privacy of individually identifiable health information, 64 Federal Register 59918-60065 (1999) at su_docs/aces/aces140.html.
VITAMIN C SUPPLEMENTS INCREASE PROGRESS OF ATHEROSCLEROSIS, SAYS NEW STUDY
There has been some concern about the implications of a press release sent out by the University of Southern California on March 2nd [contact: Paul Dingsdale, (323) 442-2830]. In that press release, the results are reported of a study presented at the American Heart Association’s 40th Annual Conference on Cardiovascular Disease Epidemiology and Prevention in San Diego, Calif. on March 2, 2000. The results are said to show that in people taking 500 mg a day of vitamin C (both smokers and nonsmokers), a greater progression of atherosclerosis (measured as increases in carotid artery wall thickness) occurred compared to those not taking vitamin C. Over 18 months, nonsmokers taking 500 mg a day of vitamin C had a reported 2.5-times greater increase in carotid wall thickness compared to those not taking vitamin C, while smokers taking 500 mg a day of vitamin C had a 5-fold increase in carotid wall thickness.
There are a number of problems with this study, the first of which is that it has not yet been peer-reviewed and published in a scientific journal. Hence, the raw data are not available and it is not possible to determine how the study was done, characteristics of the controls and subjects, how measurements were made, the statistical analyses, and so forth. The paper was presented as a poster at the above-mentioned conference. One generally does not send out press releases to tout the results of a study presented in a poster session at a conference and not peer-reviewed and published.
For example, the brief summation in the press release claims that the vitamin consumers in the study had the same general health characteristics and health habits as those who did not use vitamin pills. Without seeing the data, how is one to know? Moreover, it is said that about 30% of the 573 participants used vitamin supplements regularly, ranging from about 30 mg to 1000 mg of vitamin C or more a day. It is important to see how many people took how much and how they were segregated according to the dose ingested. There may have been differences in general health characteristics and health habits between those taking the larger doses of vitamin C compared to the smaller doses, even if the characteristics and health habits were similar for vitamin C users as a whole compared to non-vitamin users. For example, people with greater risk because of having higher cholesterol levels may have been more likely to take larger amounts of vitamin C. Without this information, it is not possible to assess the reported results for the study.
As Dr. Jeffrey Blumberg, Chief of the Antioxidants Research Laboratory at the U.S. Department of Agriculture’s Human Nutrition Research Center on Aging at Tufts University commented, “This is a preliminary epidemiological study, and it is important to put the reported findings in the context of all the available information. This is the first report of any negative effect of vitamin C on the arteries, in contrast to the totality of data about vitamin C and health. A number of other studies suggest a positive effect of vitamin C on arterial health, and the USC researchers offered no plausible mechanism by which vitamin C could have the adverse effect observed in this study.” Dr. Balz Frei, professor and director of the Linus Pauling Institute, noted that “The results from the study presented last week, in fact, are in direct conflict with a study published in 1995 in the American Heart Association journal Circulation. That research found a significant reduction in carotid artery wall thickness in people over 55 who consumed about 1000 mg or more of vitamin C a day, compared to those consuming less than 88 mg a day.” Frei said the new vitamin C report did not put its findings in the proper context of hundreds of existing studies demonstrating the health benefits of vitamin C.
Meanwhile, the USC press release states that the study’s lead author, James H. Dwyer, Ph.D., “suggests that anyone interested in vascular health and vitamins should look to the American Heart Association to learn about the respected group’s dietary recommendations.” The American Heart Association is one of the groups that filed an amicus curiae brief on the (losing) side supporting the FDA in Pearson v. Shalala; in other words, the AHA supported FDA’s unconstitutional restrictions on the communication of truthful information (with disclaimers if necessary to prevent consumer misunderstanding) concerning the relationship between dietary supplements and cardiovascular disease. While this is not a scientific argument against the credibility of the vitamin C study, it is a good reason to look long and hard at the claimed results. When you mix politics with science, you rarely get good science.
Council for Responsible Nutrition press release; contact Cyndie S. Sirekis, (202) 263-1002.
PERSISTENCE OF MEMORY
A new study has vindicated the views on memory of William James. As James said on p. 659 of his 1890 book, The Principles of Psychology, “Memory being . . . altogether conditioned on [the ability to excite] brain-paths, its excellence in a given individual will depend partly on the number and partly on the persistence of these paths.” He maintained that memory could be improved by establishing a large network of memories with many cross-connections that would make it easier to make associations with and access a new memory.
The new study examined the effect on memory of knocking out NMDA receptors only within the CA1 region of the hippocampus in mice. It is well known that the hippocampus is important as part of the memory system, especially in mediating connections with diverse and interconnected regions of the cerebral cortex. However, the hippocampus is only a part of this process since, for example, it is not necessary for the recall of long-term memories.
A previous study had found that CA1-NMDA knockout mice had severely impaired spatial learning and memory. The new study found that their mice with the same defect were severely impaired across a broad range of nonspatial learning tests. The researchers tested James’ hypothesis by exposing the impaired mice to an enriched environment (lots of toys and other things to explore) that would presumably help establish many memory interconnections. Examination by electron microscopy showed that the number of synaptic connections in the brain was increased under conditions of enrichment in normal mice, but also in the mutant mice without CA1-NMDA receptors. Incredibly, the enrichment almost eliminated the memory defects observed in the NMDA knockout mice, as well as (as expected) increasing learning performance in normal mice. One possible explanation is that increased connectivity in the neocortex, which retained its normal NMDA receptors, could compensate for a hippocampus lacking its NMDA receptors.
These findings are consistent with reports on the improved maintenance of learning and memory in aging individuals with self-selected enriched environments; for example, highly educated people seem to be less likely to suffer from Alzheimer’s dementia, perhaps by maintaining synaptic connections, by having more to begin with, having larger numbers of memory interconnections, and running out the clock.
The effectiveness of an enriched environment in improving learning and memory continues to impress. And at the same time, it helps to vindicate the prescient author of a 110-year-old hypothesis concerning how memory works.
Eichenbaum and Harris, “Toying with Memory in the Hippocampus,” Nature Neuroscience 3(3):205-206 (2000); Rampon et al., Nature Neurosci 3:238-244 (2000).
RETURN TO LEPTIN AS A TREATMENT FOR OBESITY
We have written in earlier newsletters on the potential of the hormone leptin as a treatment for obesity. Leptin is released largely by fat cells (adipocytes), but recent research indicates that it can be released by muscle cells as well. When leptin levels are low, it is a signal of inadequate fat stores (food intake is low), and it increases the release of neuropeptide Y, among other things, to increase eating, as well as promoting a number of metabolic changes to conserve energy. Decreased leptin levels may be a part of the mechanism for changes induced by caloric restriction. Higher leptin levels signal plenty of stored body fat, and they decrease food intake and increase energy output, as well as increasing fat use for energy.
Though leptin levels are generally higher in obese people because of much greater fat mass, these higher leptin levels are often ineffective in obese individuals in reducing appetite, increasing metabolic rate, increasing the use of fat for energy, and increasing physical activity. This is called leptin resistance (analogous to the insulin resistance associated with high insulin levels in the obese), perhaps caused by the downregulation of leptin receptors.
Leptin injections have recently been tried as a treatment for obesity. Although for most experimental subjects, leptin did induce some weight loss, it was not too impressive. A letter in a recent Journal of the American Medical Association suggests some reasons why this may be so.
The authors state that leptin is characterized by what is called nyctohemeral rhythms, with serum leptin concentrations being highest around midnight. They note that this resembles the circadian rhythmicity of many other hormones, such as thyrotropin and prolactin. The leptin peak concentration precedes the peak concentrations of cortisol and growth hormone. In other words, just as there are physiological variations in growth hormone, with peaks appearing at specific times (such as 90 minutes after falling asleep), leptin concentrations vary such that giving exogenous leptin at one time may not produce the same results as giving it at another time.
Furthermore, the authors say, total circulating leptin levels exhibit a pattern indicative of pulsatile release, as is the case for other hormones, such as insulin. The pulse pattern for leptin shows a duration of approximately 30 minutes and is inversely related to rapid fluctuations in plasma cortisol and adrenocorticotropic hormone levels. (This is consistent with an earlier report that glucocorticoids are counterregulatory to leptin.) The authors believe that the pulsatile release of leptin is crucial for the attainment of its biological effects and may help explain the not too impressive effects of leptin treatments for obesity in recent clinical trials. (This is also consistent with reports for insulin in which pulsatile administration of a certain amount of insulin results in a larger biological effect than administration of the same amount of insulin in a nonpulsatile fashion.)
As with growth hormone administration, the physiological features of endogenous hormone release provide a pattern for administering exogenous hormone in order to get optimal biological effects without undesirable side effects. Perhaps leptin treatment may turn out to be more useful than studies have so far found.
Fruhbeck et al., “Chronobiology of Recombinant Leptin Therapy,” JAMA 283(12):1567 (2000); also, see Licinio et al., “Human Leptin Levels are Pulsatile and Inversely Related to Pituitary-Adrenal Function,” Nature Medicine 3:575-579 (1997); Gura, “Leptin Not Impressive in Clinical Trial,” Science 286:881-882 (1999); Zakrzewska et al., “Glucocorticoids as Counterregulatory Hormones of Leptin: Toward an Understanding of Leptin Resistance,” Diabetes 46:717-719 (1997).