August 2000 Blog with Durk and Sandy

He alone is worthy of life and freedom
who each day does battle for them anew.

– Goethe, Faust


On April 20, 1999, the U.S. District Court for the District of Columbia issued the Pearson-decision mandate to the FDA, as directed by the court of appeals; the Pearson ruling was decided by the U.S. Court of Appeals for the District of Columbia Circuit on January 15, 1999 in Pearson & Shaw et al. vs. FDA et al. The mandate compelled the FDA to implement the First Amendment disclaimer process as described by the appeals court to the FDA’s health-claims approval process. The court ruled that the FDA could not prohibit health claims outright unless they were inherently misleading (i.e., no disclaimer or additional information could render the claim nonmisleading). If a health claim is only potentially misleading (that is, some consumers may misunderstand it), the FDA must first consider the use of disclaimers to correct any potential misleadingness. The constitutionally correct remedy for truthful, but inadequate, information is to provide more information, not to prohibit the truthful information.

In early June of 1999, after seeing that the FDA was doing nothing whatsoever to implement the court’s mandate, Jonathan Emord (representing the plaintiffs) wrote a series of letters to Commissioner Henney and CFSAN Director Levitt demanding that the Pearson decision be implemented immediately and asking the FDA to provide a date by which they would agree to rule on the issue of disclaimers for the four health claims that were at issue in Pearson, the prohibition of which had been ruled unconstitutional. For months, the FDA refused to set a certain date by which they would make a decision on the health-claim approvals with disclaimers. Finally, after we filed a request for injunctive relief against the FDA in the U.S. District Court for the District of Columbia, asking that the court block the FDA from continuing to enforce the unconstitutional ban on the four Pearson claims, the FDA has now agreed to issue a decision by October 24, 2000. We await the decision on our request for injunctive relief by the district court judge, Gladys Kessler, who ruled against us before in the Pearson case we then won at the appeals court level. We will appeal if Judge Kessler denies our motion.

In the meantime, we had filed three other petitions for health claims with the FDA. The agency denied all of them, including claims that vitamin E may reduce the risk of cardiovascular disease, that folic acid, vitamin B6, and vitamin B12 may reduce the risk of cardiovascular disease, and that saw palmetto may reduce the symptoms of benign prostatic hypertrophy. In the saw palmetto case, the FDA decided that the treatment of a disease was approvable only as a drug claim [flying in the face of the meaning of “dietary supplement” and of a supplement-disease relationship as defined in the Nutrition Labeling and Education Act (NLEA, 1991) and the Dietary Supplement Health and Education Act (DSHEA, 1994)]. We have filed suit against the FDA for denial of all three claims. These cases are now on stay pending FDA’s determination by May 24, 2000 on whether to allow the two vitamin claims with disclaimers and whether to evaluate the saw palmetto claim under the drug-approval process or the health-claims review standard. Please see for further information or to make a donation. Many thanks to all those who have sent in donations.

On April 27, 2000, the Grocery Manufacturers Association (GMA) filed a citizen petition with the FDA endorsing Pearson and demanding that the FDA immediately implement the constitutional mandate for free flow of information as decided in that case, both for dietary supplements and for conventional foods. The FDA has 180 days within which to respond to citizen petitions.

GMA is the world’s largest association of food, beverage, and consumer product companies, including such giants as Anheuser-Busch, Campbell Soup Company, Coca-Cola Company, General Mills, Nabisco, Nestle USA, PepsiCo, Procter & Gamble, Quaker Oats, and Unilever, with yearly American sales of $460 billion and with over 2.5 million employees in the U.S. GMA is a major political and legal threat to the FDA’s stonewalling on complying with the Pearson court decision.

We highly recommend that anyone interested in this case read the GMA’s press release, comments presented at the FDA’s recent Pearson compliance meeting, and citizen petition at their Web site, You will find none of the wishy-washy, compromising language that you usually find when an industrial trade group complains to a regulatory agency with which it is in bed or wishes to get in bed. The GMA attorneys clearly understand the First Amendment speech issue at stake and, in particular, recognize that the future of the food industry depends upon the communication of truthful health claims concerning foods.

In fact, as we noted in our latest article for Liberty magazine,* food companies could join the fast-growing high-tech companies in NASDAQ if truthful health claims could be made about their products. It would become profitable for food companies to invest much more money in research on the relationship between foods and disease. It would also become profitable to develop new foods (using genetic engineering), such as fruits and vegetables that make much more vitamin E and polyphenols, or cattle that make omega-3 fatty acids (like fish).1 Or how about a potato that contains slowly digested starch (sort of a time-release source of glucose) or undigestable polymers (soluble and insoluble fiber) rather than the rapidly digested starch now found in potatoes that can cause blood-sugar spikes, hyperinsulinemia, hyperlipidemias, and more weight gain?2And let’s engineer soybeans to produce 100 times as much alpha-tocopherol and omega-3 fatty acids as omega-6 fatty acids. Would you buy delicious yet low-calorie, low-glycemic-index, high-fiber French fries that are a true health food? The way to get public support for genetic engineering is by creating versions of popular foods that provide health benefits to consumers that are greater than those provided by conventional foods – and to communicate these benefits to consumers in labels and in advertisements.

* We highly recommend this publication for freedom lovers; PO Box 1181, Port Townsend, WA 98368, 1-800-854-6991, $29.50/12 issues (1 year).


  1. Some such work is already being done, but the future depends upon the ability of food companies to communicate to consumers the benefits of these new foods. For example, two genes for the enzyme isoflavone synthase, which catalyzes the first committed step in the biosynthesis of isoflavones, including genistein and daidzein, were isolated from soybeans and expressed in another plant that does not otherwise produce isoflavones. See Nature Biotechnology 18:208-212 (2000). Isoflavones have been shown to influence not only sex hormone metabolism and physiological activity, but also protein synthesis, malignant cell proliferation, differentiation, and angiogenesis. They are thought to be protective against some cancers. Yet many people do not like the taste of soybeans, a major dietary source of isoflavones. If consumers could get isoflavones from their favorite vegetables, it could be a tremendous benefit both for consumers, who could eat more palatable sources of healthful isoflavones, and the food companies developing and selling these new vegetables. (Don’t be surprised if there are still complaints and howls from such folks as farmers committed to raising the old-style plants, and ideologues who can’t stomach high tech or “tinkering” with Nature.)3
  2. Just before we sent this issue of our newsletter to “press,” the news arrived in our copy of the May 2000 Nature Biotechnology that a scientific group has now created by genetic engineering a potato producing very high amylose (slowly digested) starch by inhibiting two enzymes that would normally make the amylopectin type of starch that is rapidly digested. See Schwall et al., “Production of Very-High-Amylose Potato Starch by Inhibition of SBE A and B,” Nature Biotechnology 18:551-554 (2000).
  3. There may not be as much opposition to genetic engineering as has been suggested by public opinion polls run by environmental groups, according to a news note in the May 2000 Nature Biotechnology. A U.K. public information initiative “funded by, but not beholden to, industry” has announced poll results (from a poll conducted by professional polling organization NOP) that asked people if they “would personally eat food if they knew it was genetically modified or contained GM ingredients.” 46% of people polled said they would, as compared with 50% who said they would not. And this was in the UK, where opposition to GM foods is supposedly very high. So what is the problem now? The biggest one appears to be (surprise, surprise) the FDA, which (according to another news report in the same issue of Nature Biotechnology) is about to announce a new requirement that all foods containing GMOs must undergo premarket evaluation at the agency. Moreover, the FDA delegation representing the U.S. is not objecting to new regulations on international trade in GMOs being worked out by CODEX that are (says Henry Miller, a former U.S. FDA official and a senior fellow at the Hoover Institution, Stanford, California) “more appropriate to potentially dangerous drugs and pesticides than to gene-spliced tomatoes, potatoes, and strawberries.”


You’ve probably heard that R.J. Reynolds Tobacco Co. has developed a new type of cigarette, called Eclipse, in which the tobacco is heated, not burned. Though you still get nicotine, which has certain unhealthful effects (such as blood pressure increase), the carcinogenic effects of the smoke are reduced by 90%, which should dramatically reduce the smoker’s risk of mouth, throat, and lung cancers and also reduce the destruction of antioxidants in the smoker’s lungs and bloodstream. It would still be better not to use tobacco, but if you are going to do so, this is safer than traditional direct combustion smoking. R.J. Reynolds has decided to start off by selling the new cigarette online (, where they can provide information on the new product, such as what is different about it and how you use it.

Another even less conventional type of cigarette, called Premier, was made available by a tobacco company several years ago, but FDA’s then Commissioner David Kessler claimed it was a nicotine delivery system and, hence, an unapproved medical device and that the FDA had regulatory authority over it. That and marketing problems knocked Premier out of the market. This time, apparently, they waited until the FDA had been determined by the US Supreme Court not to have authority over tobacco before releasing the new cigarette. (Remember that regulatory agencies such as the FDA get their legitimate authority only from the Congress and subject to Constitutional limits on government action. FDA’s authority can be changed at any time by Congress, of course, which can give FDA authority over interstate commerce in tobacco, if it wishes.)


A new paper1 reports that extended longevity in Drosophila melanogaster (fruit fly) is correlated with large changes in antioxidant defense system (ADS) gene expression, accumulation of copper-zinc superoxide dismutase (CuZnSOD) protein, and an increase in ADS enzyme activities, that are not observed in 17 other (metabolic) enzymes. Thus, they suggest, longevity is associated with resistance to oxidative stress rather than being the result of some non-specific and general metabolic reorganization of the organism.

In an earlier study, the group had created several long-lived strains of Drosophila by artificial selection and reported that the only factor that robustly separated out all long-lived strains from all normal lived strains was paraquat resistance. Since paraquat increases oxidative stress, the results suggest that enhanced resistance to oxidative resistance might play a role in the Drosophila enhanced longevity phenotype. Chromosomal studies reportedly showed that it was the 3rd chromosome, and particularly the proximal portion of the left arm (3L), that was necessary for the expression of the extended longevity. The structural genes for both CuZnSOD and catalase are located on chromosome 3L.

The gene expression and protein changes were followed in a normal lifespan progenitor strain (Ra) and in an extended longevity (La) strain produced by selecting for late reproducers in the Ra strain and an La strain reverse selected (using early reproducers) for reduced lifespan, the (RevLa) strain. They then measured the levels of antioxidant and non-antioxidant gene and enzyme expression in the Ra, La, and RevLa strains, to see what changes fostered longevity. The La strain was distinguished from Ra by 1) a significantly enhanced expression of certain antioxidant defense system (ADS) mRNAs such as CuZnSOD, MnSod, and to a lesser extent catalase; 2) an enhanced level of the CuZnSOD protein; 3) a significantly increased activity of the corresponding CuZnSOD and catalase enzymes; and 4) a significantly enhanced resistance of the organism to the biological damage caused by oxidative stress. The RevLa strain differed from the La strain in having 1) a significantly decreased expression of these same ADS mRNAs; and 2) a significantly decreased activity of the corresponding ADS enzymes. The authors report that “The large and statistically significant changes in the ADS enzyme activities associated with both forward and reverse selection are specifically restricted to those ADS enzymes and are not observed in 17 other ‘ordinary’ metabolic enzymes…”

For example, selection for extended longevity resulted in a 4.2% overall increase in the general metabolic activities, whereas reverse selection for shortened longevity resulted in a 10.5% overall decline in these same values. On the other hand, CuZnSOD showed a 49.1% increase in its specific activity for the selected extended longevity, with a 25.6% decrease in the animals selected for shortened longevity.

As evidence that it is the resistance to oxidative stress rather than resistance to stress in general that is the operative factor, the authors cite their earlier study in which they developed from the Ra strain a new strain (PQR) that was extraordinarily resistant to paraquat, but rather than having higher levels of ADS, they had elevated P450 enzyme levels and depressed ADS enzyme activity levels. (Apparently these animals used the P450 enzyme system to detoxify the paraquat by converting it to another chemical species rather than increasing antioxidant defense systems to prevent oxidative damage by the paraquat.) The PQR animals had a normal longevity indistinguishable from that of Ra. Hence, the authors, conclude, it is the oxidative stress resistance that made the difference in longevity.

The results of these experiments are consistent with Dr. Denham Harman’s free radical theory of aging. If oxidative stress resistance is the key factor in longevity, an important practical question is: until we can genetically upregulate our ADS systems by a means more acceptable than caloric restriction, what is the optimum way to take exogenous antioxidants and free radical stress signaling agents to mimic that effect? The lead author of this paper, Dr. Robert Arking, was interviewed in the Journal of Anti-Aging Medicine (Vol. 3 No. 1, pp. 9-13, Spring 2000)2 and directed his remarks largely to the results of this study. He notes that in upcoming experiments, he and his colleagues will be using a microarray to look at simultaneous changes in 7,000 fly genes.


  1. Arking et al, “Forward and Reverse Selection for Longevity in Drosophila is Characterized by Alteration of Antioxidant Gene Expression and Oxidative Damage Patterns,” Experimental Gerontology 35:167-185 (2000)
  2. In commenting on why he chose Drosophila as an aging model animal, Dr. Arking notes: “Flies age, and in some ways, they age differently than humans. Very few humans, as has been written, die because they drown in mashed bananas. However, the factors that make a fly weak so that it falls into the food and drowns are not dissimilar from the factors that make a human being weak – and these include free radicals.”


In our 1986 bestseller, The Life Extension Weight Loss Program (Doubleday), we included a chapter on how eating low-glycemic-index foods might help get rid of excess body fat and help maintain normal weight, as well as help prevent the aging damage that results from processes (such as glycosylation) brought on by chronic high insulin and high glucose levels.1 Lately, the glycemic index seems to have been rediscovered in popular weight-loss books. A pretty good guide to the glycemic index of foods, including an updated list of food measurements, is contained in The Glucose Revolution(Marlowe & Co., 1999). The authors are Jennie Brand-Miller, Ph.D., Thomas M. S. Wolever, M.D., Ph.D., Stephen Colagiuri, M.D., and Kaye Foster-Powell, M. Nutr. & Diet. We are familiar with some of Dr. Wolever’s original research in the field of glycemic-index nutrition.

The most interesting and practical piece of information we found in The Glucose Revolution is that you can slow down gastric emptying (and hence the rate of digestion) by adding acid foods to your diet. For example, the book suggests vinegar, lemon juice, acidic fruits, and sourdough bread. The book states (pg. 43) that “Within the last few years, several reports in the scientific literature have indicated that a realistic amount of vinegar or lemon juice in the form of a salad dressing consumed with a mixed meal has significant blood sugar lowering effects.” Although the book contains quite a few references, the authors have, unfortunately, provided no references for this statement. They go on to say that as little as 4 teaspoons of vinegar in a vinaigrette dressing (4 teaspoons vinegar and 2 teaspoons oil) taken with an average meal lowered blood sugar by as much as 30 percent. If so, this is a very remarkable effect.

More research on the glycemic index is appearing in the literature. For example, a 1999 study2 reports that in a survey of the dietary habits of 2000 British adults between the ages of 16 and 64, the 1420 participants with complete data showed a significant negative relation between serum HDL-cholesterol concentration and the glycemic index of the diet for both men (-0.00724, 95% CL -.0101 to -0.00434, p=0.02) and women (-0.01326, 95% CL -0.0162 to -0.0102, p<0.0001). (Low glycemic index was associated with higher HDLs.) The authors found no other dietary variable, including fiber, total sugar, total starch, total carbohydrates, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, or cholesterol, that was significantly related to serum HDL-cholesterol concentration.

In another recent study,3 researchers used a randomized crossover design in ten moderately overweight young men to compare the effects of a high-glycemic-index (high-GI) and a low-glycemic-index (low-GI) energy-restricted diet. The high-GI diet was 67% carbohydrate, 15% protein, and 18% fat, while the low-GI diet was 43% carbohydrate, 27% protein, and 30% fat. The amount of weight lost during the 6 days of the calorie-restricted diet was not different. However, leptin levels fell further during this period on the low-GI diet, as compared to the high-GI diet. This is interesting, since higher leptin levels in the overweight are often associated with leptin resistance. A new paper4 suggests that leptin is responsible for high blood pressure in the obese. The dietary study is also interesting because the leptin levels fell more in those eating a much higher-fat diet. (As you will recall, leptin is a hormone released largely by fat cells.) Still, this is a difficult study to interpret, since it is a very short-term study with only a few subjects and with very different macronutrient compositions of the two diets.

Also, see the review in the September 1999 Nutrition Reviews on glycemic index, cardiovascular disease, and aging5 and a recent article in Science News.6


  1. For example, see Fukagawa et al., “Aging and High Concentrations of Glucose Potentiate Injury to Mitochondrial DNA,” Free Rad. Biol. Med. 27(11/12):1437-1443 (1999).
  2. Frost et al., “Glycaemic Index as a Determinant of Serum HDL-Cholesterol Concentration,” The Lancet 353:1045-1048 (1999).
  3. Agus et al., “Dietary Composition and Physiologic Adaptations to Energy Restriction,” Am. J. Clin. Nutr. 71:901-7 (2000).
  4. Aizawa-Abe et al., “Pathophysiological Role of Leptin in Obesity-Related Hypertension,” J. Clin. Invest. 105(9):1243-1252 (2000).
  5. Morris and Zemel, “Glycemic Index, Cardiovascular Disease, and Obesity,” Nutrition Reviews 57(9):273-276 (1999).
  6. Raloff, “The New GI Tracts,” Science News 157:236-238 (2000).


Nitric oxide reduces the severity of pulmonary vascular disease in rats. So do elastase inhibitors. Elastase inhibitors are, in fact, used in humans to treat emphysema and ameliorate the disease by slowing or preventing the destruction of elastin. The authors of a new study1 now propose that nitric oxide itself reduces elastase activity in vascular smooth muscle cells. This is very exciting because elastin destruction in arterial walls plays a major role in the loss of elasticity that takes place with aging and in hardening of the arteries.

Impaired production of nitric oxide is associated with a variety of disorders, including atherosclerosis, pulmonary hypertension, restenosis (reblockage) after angioplasty, and coronary arteriopathy after experimental heart transplantation. The changes that take place in these conditions includes smooth muscle cell proliferation, migration, and accumulation of extracellular matrix glycoproteins, such as collagen, fibronectin, and tenascin. Beneficial effects of nitric oxide in these conditions are due to its vasodilating effect plus effects on tissue remodeling (such as decreased smooth muscle cell proliferation in atherosclerotic plaques) and possibly nitric oxide’s role as an intracellular signaling molecule. Vascular remodeling that is part of the pathological processes in the above disorders includes heightened activity of proteolytic enzymes, such as elastases and matrix metalloproteinases.

The authors report that inhibition of elastase activity not only prevents the progression of vascular disease, but also appears to induce regression.

To test the effect of nitric oxide in modulating the induction of elastase in cultured smooth muscle cells, the researchers added the NO donor S-nitro-N-acetylpenicillamine (SNAP). SNAP did not suppress basal levels of elastase, but inhibited the greater-than-threefold induction of smooth muscle cell elastase elicited by serum-treated elastin (STE). Another NO donor also suppressed induction of smooth muscle cell elastase, as did a cyclic GMP mimetic. The researchers report that the suppression of STE-induced elastase activity occurred as a result of NO suppression of the signaling mechanism required for the transcription of elastase and that the effect is mediated by cyclic GMP.

The semi-essential amino acid arginine is the normal nitric oxide donor in animals, and some animal studies with arginine have shown atherosclerosis-regressing effects.


  1. Mitani et al., “Nitric Oxide Reduces Vascular Smooth Muscle Cell Elastase Activity Through cGMP-Mediated Suppression of ERK Phosphorylation and AML1B Nuclear Partitioning,” FASEB J. 14:805-814 (2000).


Two new studies published in the April 20, 2000 New England Journal of Medicine1have delivered negative news about the ability of dietary supplements to prevent disease, in this case the ability of a high-fiber cereal supplement or a low-fat, high-fiber diet to prevent the recurrence of colorectal adenomas.

Somehow the results of these two studies are being interpreted by some media people and even some supposed dietary “experts” to bear upon the question of whether a low-fat, high-fiber diet or a high-fiber cereal supplement may reduce the risk of developing colorectal cancer. They don’t.

Colorectal adenomas are a type of tumor that can develop into a malignant cancer (up to two-thirds of all colorectal carcinomas arise from adenomas). Hence, the diet and supplement were tested in these two studies not for their ability to reduce the risk of colorectal cancer developing from normal tissue, but for their ability to reduce the risk of recurrence of an already developed tumor. These patients already had genetically damaged colon cells. While it is known, for example, that a high-fiber diet or supplement can reduce the mutagenicity of colon contents, and this mechanism might plausibly contribute to a reduction in the risk of developing colon cancer, there is no mechanism, to our knowledge, whereby a low-fat, high-fiber diet or dietary fiber supplement can reverse the genetic damage that has already occurred and has caused a colorectal lesion to develop. A fiber supplement or low-fat, high-fiber diet might reduce the risk of developing colon cancer from normal tissue and yet fail to reduce the risk of developing colon cancer from an adenoma.

It is really unfortunate that these misinterpretations of the fiber studies have been published widely in the popular press. It does a serious disservice to consumers, who may now believe that these studies prove that they cannot reduce their risk of getting colorectal cancer by eating more fiber.


  1. Schatzkin et al., “Lack of Effect of a Low-Fat, High-Fiber Diet on the Recurrence of Colorectal Adenomas,” N. Engl. J. Med. 342(16):1149-1155 (2000); Alberts et al., “Lack of Effect of a High-Fiber Cereal Supplement on the Recurrence of Colorectal Adenomas,” N. Engl. J. Med. 342(16):1156-1162 (2000); Byers, “Diet, Colorectal Adenomas, and Colorectal Cancer” [editorial], N. Engl. J. Med. 342(16):1206-1207 (2000).


In another remarkable demonstration of the healthful effects of an enriched environment (in this case, a cage with lots of novel and frequently changing elements to explore), mice expressing the huntingtin gene took much longer to reach the onset of their disease, a fatal neurodegenerative mouse version of Huntington’s disease, when exposed to an enriched environment as compared to the usual routine care.1 The huntingtin gene is the same gene as the one in Huntington’s disease patients that has an expanded CAG repeat encoding an extended polyglutamine segment, which causes the disease.

Animals were tested for motor coordination every week by being placed at the end of a suspended, horizontal wooden rod. At the end of the testing at 22 weeks, only one of the environmentally enriched HD mice (14%) had failed the wooden rod test, while all those under routine care had failed.

A late component of the disease is seizures. At the end of 22 weeks, two of the nonenriched mice had them, but none of the enriched mice had them.


  1. van Dellen et al., “Delaying the Onset of Huntington’s in Mice,” Nature 404:721-722 (2000).


A study of the relationship between muscle strength at midlife and long-term mortality in a group of 6040 healthy men aged 45 to 68 years at baseline has reported an association with all-cause mortality, independent of BMI (body mass index).* Maximal hand-strength tests and BMI assessments were made at baseline in 1965 to 1970, and then the group was followed for mortality for 30 years(!).

The death rates per 1000 person-years were 24.6 in those with BMI < 20, 18.5 in the middle BMI category, and 18.0 in those with BMI > 25. For grip-strength tertiles, the mortality rates were 24.8 in the lowest, 18.5 in the middle, and 14.0 in the highest third. For all BMIs, the mortality rate was lower, the greater the grip strength. The lowest relative risk (RR) of mortality over 30 years was 1.0 (reference to which all other RRs were compared) for a combination of BMI 20-24.9 and in the highest tertile for grip strength. One reason for the moderate effect of BMI on mortality in this study is that the authors removed from the analysis all subjects with documented diseases at Exam 1, as well as all deaths that happened during the first 3 years after Exam 1. For example, they removed the men with cardiovascular disease, many of whom might have been expected to have a higher BMI.

The researchers note that muscle strength depends upon both muscle and nerve function, which is why it is such a good marker for mortality.

* Body mass index is (weight in kg)/(height in meters)2.


  1. Rantanen et al., “Muscle Strength and Body Mass Index as Long-Term Predictors of Mortality in Initially Healthy Men,” J. Geront: Medical Sci. 55A(3):M168-M173 (2000).

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