Whistleblowers unite in roundtable
The concerns of a gathering of medical whistleblowers who attended a roundtable on May 15 were reported in the July 2005 issue of PLoS Medicine (http://medicine.plosjournals.org) by investigative journalist Jeanne Lenzer, who concluded that the pharmaceutical industry’s synchrony with the U.S. health care industry may be compromising medicine’s integrity.
Roundtable attendee David Graham, of the US Food and Drug Administration summed up his position by stating "The pharma-FDA complex has to be dismantled, and the American people have to insist on that, otherwise we're going to have disasters like Vioxx that happen in the future."
Other members of the gathering included Allen Jones, formerly of the Pennsylvania office of the Inspector General; Stefan Kruszewski, formerly of the Bureau of Program Integrity in the Pennsylvania Department of Public Welfare, Kathleen Slattery-Moschkau, who wrote and directed the film Side Effects, and an anonymous pharmaceutical industry researcher.
Jones reported that he filed a civil rights lawsuit in 2002 "to preserve my job and my right to speak out,” on his discovery of an account into which pharmaceutical companies were making deposits that was accessible by state officials responsible for writing guidelines for the treatment of patients in the state system. The officials "were given unrestricted educational grants that were deposited into an off-the-books account," according to Jones, who was removed from his position for talking to the press.
Stefan Kruszewski was also terminated from his position after uncovering abuse and fraud in the Pennsylvania Department of Public Welfare Bureau of Program Integrity.
In Kathleen Slattery-Moschkau’s film, she presented a fictionalized account of her experiences as a pharmaceutical representative, a job she resigned from after witnessing disturbing marketing practices.
In an editorial in the same issue of PLoS Medicine, the authors called the picture that emerged “deeply troubling" and voiced the hope that the report will encourage discussion.
Brain arachidonic acid associated with depression
Writing in the June 2005 Journal of Lipid Research, Pnina Green of Tel Aviv University and colleagues reported that a line of rats that exhibit signs of depression have higher brain levels of arachidonic acid, an omega-6 fatty acid, than normal mice.
Recent research has shown that a deficiency of omega-3 fatty acids may be a culprit in depression, as depressed patients have been found to have lower omega-3 blood levels than non-depressed individuals. Dr Green explained, "The ‘phospholipid hypothesis’ of depression postulates that decreased omega-3 fatty acid intake, and hence, perhaps decreased brain omega-3 fatty acid content, could be responsible for the disease. In humans, because of high dietary variability and the obvious inability to examine brain tissue, the theory is backed up mainly by indirect evidence."
In the current study, Dr Green and colleagues found that the brains of rats bred to exhibit characteristics of depression had similar levels of omega-3 fatty acids, but higher levels of the omega-6 fatty acid arachidonic acid. Arachidonic acid was 21 percent higher in the hypothalamus than in the brains of control rats, 24 percent higher in the nucleus accumbens, 31 percent higher in the prefrontal cortex, and 23 percent higher in the striatum. The discovery suggests that the balance between omega-3 and omega-6 fatty acids may be altered in depression.
"The finding that in the depressive rats the omega-3 fatty acid levels were not decreased, but arachidonic acid was substantially increased as compared to controls is somewhat unexpected," Dr. Green stated. "But the finding lends itself nicely to the theory that increased omega-3 fatty acid intake may shift the balance between the two fatty acid families in the brain, since it has been demonstrated in animal studies that increased omega-3 fatty acid intake may result in decreased brain arachidonic acid."
Inefficient metabolism within blood vessels proposed as atherosclerosis mechanism
In a letter published in the May 26 2005 issue of Nature (www.nature.com) researchers at Washington University School of Medicine in St. Louis suggest that an underlying cause of atherosclerosis could be problems with the mitochondria of the cells in the vessel walls. Mitochondria are the cells' energy producing organs, which also create a signficant amount of oxidative stress. The presence of cardiovascular disease in individuals in whom risk factors such as high cholesterol are lacking has motivated scientists to investigate other mechanisms of the disease.
The research team, led by Professor of Medicine Clay F Semenkovich, MD, engineered mice to express uncoupling protein-1 in the aorta wall, anticipating that the protein could protect the animals from high blood pressure and atherosclerosis based on findings from previous research. Uncoupling protein converts energy from calories into heat and creates a similar effect as exercise in skeletal muscle. Expression of the protein was induced by administration of an antibiotic that causes atherosclerosis in mice.
Because mitochondria generate free radicals during the production of energy, the researchers believed that with less energy there would be less damage. However, rather than being protected, the mice developed hypertension and atherosclerosis. Dr Semenkovich explained, "The cells in the blood vessel wall apparently were trying to compensate for their less powerful mitochondria. It is possible that the decreased energy stores induced by the uncoupling protein caused cells to move more oxygen through the system. But the increased flux of oxygen through the blood vessel wall caused oxidative damage, high blood pressure and atherosclerosis."
Dr Semenkovich hypothesized that the same process may occur in aging humans, and that a deficiency of essential fatty acids could cause the changes in blood vessel wall metabolism. "It would be interesting to figure out how to take essential fatty acids, get them into the vessel wall and see if you could treat atherosclerosis that way," he stated.
Small prostate glands, obesity increase risk of aggressive prostate cancer
At the annual meeting of the American Urological Association, held in May, Martha K Terris, MD, of the Veterans Affairs Medical Center in Augusta, Georgia reported that being obese or having a small prostate gland increase the risk of developing an aggressive form of prostate cancer.
Dr Terris and her colleagues evaluated the association between body mass index and prostate cancer in 787 men whose prostate glands were biopsied. They found that obesity was associated with a greater risk of prostate cancer, and also increased the risk of developing an aggressive cancer. The finding is controversial, because the hormone changes that occur with obesity decrease the hormone testosterone, which fuels prostate cancer growth. A reduction in testosterone would theoretically decrease prostate cancer risk. However, it appears that there is an association between obesity and aggressive cancers that are not testosterone-dependent.
In another study, Dr Terris’ team analyzed data from 1,106 men with prostate cancer who had their prostate glands removed, and found that those whose glands were smaller had a greater risk of aggressive disease. Dr Terris explained, “If you have a large prostate, cancer can grow to a fairly large size before it outgrows the surrounding prostate and spreads out into other areas of the body. However, if the prostate containing the cancer is small, the cancer does not have to grow very much before it is big enough to spread outside the gland.” She added, “Similar to the findings in obese men with prostate cancer, the explanation may be differences in hormone levels. If you have estrogen or less testosterone in your system, your prostate will not be as large as a man with a high testosterone because these hormones affect both benign prostate growth and cancer. As a result, the same hormone balance that result in a small prostate gives hormone insensitive tumors more chance to grow.”
Vitamin D therapy boosts drug's effect on prostate cancer survival
Tocotrienols lower cholesterol
JAMA meta-analysis concludes vitamin D supplementation lowers fracture risk
Diets high in folate linked with lower risk of prostate cancer
The current study utlized data from a case-control study of prostate cancer conducted between 1991 and 2002 in which 1,294 patients with prostate cancer were compared with 1,451 patients without cancer who were admitted to the same network of hospitals. Dietary information gathered from interviews during which the participants were asked about their intake of 78 different foods during the two years prior to their diagnosis or hospital admission was analyzed for folate and other nutritional levels.
Analysis of the data determined that folate intake was inversely related to prostate cancer risk. Men in the top one-fifth of folate consumption had a 34 percent lower risk of prostate cancer than that experienced by men whose folate intake was in the lowest fifth. This relathionship was consistent among men of all ages. When men whose intake of folate was high and alcohol consumption was low were compared to those whose intake of folate was low and alcohol consumption high, they were found to have a 54 percent lower risk of the disease.
The authors discuss two mechanisms which explain low folate's relationship to an increase in cancer. First, a deficiency of the vitamin decreases S-adenosylmethionine (SAMe), which can lead to DNA hypomethylation and increase the activation of genes that promote cancer. The other explanation for folate's benefit is that a deficiency can cause an error in DNA synthesis that results in breaks in the chromosomes which increase cancer risk.
Higher vitamin B6 means lower colorectal cancer risk for women
A study published in the May 4 2005 of the Journal of the National Cancer Institute found that having a relatively high intake of vitamin B6 or having high levels of the vitamin in the blood was associated with a lower risk of deveveloping colorectal cancer.
Esther K. Wei, ScD, from Brigham and Women's Hospital and Harvard Medical School, and colleagues examined data from women who participated in the Nurse's Health Study, which followed 121,700 nurses between the ages of 30 and 55 upon enrollment. The current study analyzed blood samples drawn in 1989 from 32,826 women in 1989 and food frequency questionnaires completed in 1980, 1984, 1986 and 1990. The blood samples were assayed for pyridoxal 5'-phosphate, the main circulating form of vitamin B6, which is necessary for DNA synthesis and methylation--processes that can be involved in the development of colorectal cancer.
From 1989 to 2000, 194 cases of colorectal cancer were diagnosed. Women whose vitamin B6 levels were in the top one-fourth of participants had a 44 percent lower risk of colorectal cancer than those whose levels were in the lowest quarter. The risk of colon cancer specifically was even lower, with a 58 percent reduction experienced by women in the highest quarter of plasma B6. Dietary intake of vitamin B6 was also inversely associated with the risk of developing colorectal cancer. Thirty-three cases of colorectal cancer were identified among women whose intake was in the top 25 percent compared to 59 in the lowest -fourth.
Vitamin B6 is involved in over 100 physiologic processes, including the conversion of homocysteine to cysteine and the regeneration of a form of folic acid involved in DNA synthesis, both which can be involved in the development of cancer.
Vitamin C offsets damage to unborn caused by smoking
Eliot Spindel, MD, PhD and colleagues at the Oregon National Primate Research Center, Oregon Health & Science University gave daily doses of nicotine to monkeys during pregnancy and supplemented some of them with 250 milligrams vitamin C per day. An additional group of monkeys received neither nicotine nor vitamin C. Dr Spindel, who is the study's senior author, explained the outcome: "We found that animals exposed to nicotine prior to birth had reduced air flow in the lungs compared to animals that were given nicotine and vitamin C. In fact, the nicotine plus vitamin C group had lung air flow close to that of a normal animal."
Although vitamin C appeared to protect the lungs, it did not protect against other effects of fetal nicotine exposure such as reduced body weight and abnormal brain development. Dr Spindel noted, "The findings of this research are highly applicable to humans. The sad reality is that approximately 11 percent of pregnant mothers continue to smoke during pregnancy -- this translates to about a half a million American women a year . . . While this research finding may assist the babies of these mothers, it does not make smoking during pregnancy more acceptable. It would only become a last resort treatment when an expectant mother is unwilling to stop smoking."
Fiber supplement improves lipids
The American Heart Association's Sixth Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology was the site of a presentation by Peter J. Verdegem, PhD on April 30, 2005 of his team's findings that supplementing with fiber can lower low-density lipoprotein (LDL) cholesterol and raise high-density lipoprotein (HDL) in diabetics. Diabetes is associated with the development of cardiovascular disease, for which disordered lipids are a risk factor. Research has shown that increasing the amount of fiber in the diet can help reduce cholesterol. The current study is among the first to evaluate fiber's effect diabetics' cardiovascular risk reduction for type 2 diabetes.
Seventy-eight individuals with type 2 diabetes received 5 grams of a supplement containing soluble and insoluble fiber before two to three meals per day for ninety days. The supplement consisted of guar gum, gum arabic, locust bean gum, pectin and oat fiber dispersed in calcium carbonate. Total, LDL and HDL cholesterol and triglycerides were measured at the beginining and end of the study.
At the study's conclusion, the participants' average total cholesterol had declined by 14.4 and triglcyerides were similarly reduced. While LDL cholesterol dropped by 28.7 percent to an average of 92 milligrams per deciliter, HDL rose by 21.8 percent to 55 mg/dL. Dr Verdegem, who is the chief science officer at Unicity International in Orem, Utah, explained, "The product was designed to fill that gap between the real intake and the advised intake. When it is in the intestines, the fiber decreases reabsorption of cholesterol from a meal."
He concluded,"The remarkable observation is that this works on two sides: It decreased LDL and increased HDL by significant amounts at 90 days. This approach is virtually free of side effects. It opens up an alternative treatment option."