February 15, 2001 Research Update

James Bogash, D.C. Mesa, AZ
info@lifecarechiropractic.com
www.lifecarechiropractic.com

Immunomodulation May Benefit Patients With Chronic Fatigue

This is really an interesting approach to management of CFS. Immune cells from the patient's lymph node are removed, treated with interluekin-2 and injected back into the patient. The results are promising. Now, for those of you a little confused as to how this may work. I've discussed Th1:Th2 ratios previously (Th1=attack mode, too much linked to autoimmune...Th2=defense, too much linked to allergies and asthma). IL-2 is a cytokine in the body that shifts the balance towards a Th1 response. So, if chronic fatigue is related to the body overreacting to stimuli from the environment (constant, subacute allergic exposure and reaction), switching the balance back towards a Th1 state may help relieve symptoms. The downside to this is its seeming complexity and cost ($5,000). It is possible that zinc and transfer factor are two substances that may also stimulate a Th1 response.

(article) Immunomodulation using lymph node extraction and ex vivo cell culture, followed by autologous cell reinfusion, significantly improves the symptoms of chronic fatigue syndrome, according to the results of a phase 1 trial. The patients studied "had more restorative sleep and woke up rested, and their activity levels improved," Dr. Nancy G. Klimas, of the University of Miami in Florida, told Reuters Health. She presented the findings here at the American Association for Chronic Fatigue Syndrome Fifth International Conference. Dr. Klimas and colleagues obtained lymph nodes from 13 patients and cultured the cells for 10 to 12 days with anti-CD3 and interleukin-2. The cells were then infused back into the donors, who were monitored for 24 weeks. No adverse effects were noted, the researchers reported. The patients had significant improvement over the 24 weeks in tests of word retrieval fluency, and there was a trend toward significant change in speed of visual scanning. The most pronounced improvements were in cognitive function, but patients also reported less muscle pain, less lymph node pain, fewer sore throats and more physical stamina. Dr. Klimas said that the benefits began immediately and were seen throughout the trial. "Many clinicians are still having trouble even believing that this is an entity that deserves their attention or is 'real,'" she noted. "Studies like this, I think, should validate the severity of the biologic underpinnings of this illness and that they are amenable to therapy." Her group hopes to begin expanded clinical trials within the next 12 months. The trials will probably involve about four sites and as many as 100 patients. "I think [immunomodulation] does have the potential to be a new and novel form of therapy," Dr. Klimas said. She pointed out that it would only involve one injection and that if it proves successful in the long term, it could be cost effective. She estimated that if the therapy is approved for commercial use, it would cost about $5000 per patient. Several physicians attending the conference hailed the report as confirming that the immune system is important in causing the symptoms of chronic fatigue syndrome. Dr. Nelson Gantz, of Pinnacle Health Systems in Harrisburg, Pennsylvania, said, "Possibly by altering the cytokine balance we can decrease symptoms....This suggests that maybe other therapies directed at various cytokines may help some patients."

Some Manganese Supplements May Exceed Safe Intake Levels

When it comes to vitamins and minerals, most have a wide range of effective and safe doses. Manganese is one of the minerals that does not and can cause problems at high enough levels. High levels have been linked to Parkinson's like symptoms. Aslo, a few years back a research article was released that strongly tied hair manganese levels and persons incarcerated for violent behavior ( Entrez-PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1884602&dopt=Abstract). Of an interesting note--infant formulas have much higher levels of manganese than breast milk.

(article) ConsumerLab.com issued an alert on Monday that that some glucosamine and chondroitin products, used for osteoarthritis, exceed newly established upper intake levels for manganese. According to the Institute of Medicine's newly-released guidelines, the tolerable upper intake level (UL) for manganese in adults is 11 milligrams per day. Neurologic adverse effects, similar to symptoms caused by Parkinson's disease, have been observed in individuals who have consumed high amounts of manganese, and iron absorption by the gut may be inhibited.Two products evaluated in ConsumerLab.com's Glucosamine and Chondroitin Product Review last year claim to contain, respectively, 25 mg and 30 mg of manganese per suggested daily serving. These amounts far exceed the recommended UL of 11 mg per day, which includes all dietary and supplement intake. One of these products had already failed ConsumerLab.com's initial testing for not having its claimed amount of chondroitin. The other product initially passed the review, but has now been removed from ConsumerLab.com's list of Quality Approved Products in light of the new recommendations. Manganese is an essential nutrient involved in bone formation and in protein, fat, and carbohydrate metabolism. Nuts, legumes, tea, and whole grains are rich sources of manganese. The recommended adequate intake of manganese for adults is approximately 2 milligrams per day, which is similar to the intake levels from typical American diets.

Pulmonary Function, Waist Circumference And Antioxidants

With several studies now pointing to the benefit of antioxidants on lung function, why are they not standard recommendations for asthmatics? vitamin C is known to inhibit the release of histamine from mast cells, possibly effecting the level of bronchoconstriction in response to an allergen. This article also indentifies an association with waist circumference and lung function. Greater circumference equals poorer function. The authors theorize that this may be due to a direct mechanical effect on the diaphragm and chest well. I would rather look as increased waist circumference as a marker for other lifestyle habits (increased stress, poor glycemic control) that would also have an effect of lung function.

Am J Epidemiol 2001;153:157-163 Waist circumference is inversely associated with lung function, according to the results of a new study. The findings also suggest that vitamin C intake is directly associated with pulmonary function in men. The researchers also determined that when waist circumference and other factors were taken into account, "vitamin C and beta-carotene were significantly positively associated with lung function in men and that beta-carotene also seemed to be positively associated with FVC in women." But Dr. Chen's team did not detect a significant association between pulmonary function and retinol or vitamin E in either sex. The investigators found that "the odds ratio of airway obstruction increased significantly with waist circumference but decreased with vitamin C intake" in both sexes. The researchers also detected an association between lung function and beta-carotene, but not between lung function and retinol or vitamin E. The cause of the inverse association between girth and pulmonary function is uncertain, but one possible explanation, according to the researchers, is that a large waist circumference may affect the movement of the diaphragm and chest wall.

Long-Term Safety, Efficacy of a Cholesterol-Lowering Diet in Children

This is interesting. I never once considered a diet low in total fat intake (28%), saturated fat and cholesterol as being potentially harmful. But it appears that some researchers and clinicians were concerned enough to perform a research study. Risk factors for heart disease such as high cholesterol levels and fatty streaks found in the arteries are becoming more common in our children. We have to re-evaluate what we are feeded our kids. Keep your eyes open for a research study evaluating the "safety" of a diet low in refined carbs...

Pediatrics 2001 Feb; 107(2):256-264 Diets reduced in fat and cholesterol are recommended for children over 2 years of age, yet long-term safety and efficacy are unknown. This study tests the long-term efficacy and safety of a cholesterol-lowering dietary intervention in children. Methods. Six hundred sixty-three children 8 to 10 years of age with elevated low-density lipoprotein cholesterol (LDL-C) were randomized to a dietary intervention or usual care group, with a mean of 7.4 years' follow-up. The dietary behavioral intervention promoted adherence to a diet with 28% of energy from total fat, <8% from saturated fat, up to 9% from polyunsaturated fat, and <75 mg/1000 kcal cholesterol per day. Serum LDL-C, height, and serum ferritin were primary efficacy and safety outcomes. Results. Reductions in dietary total fat, saturated fat, and cholesterol were greater in the intervention than in the usual care group throughout the intervention period. At 1 year, 3 years, and at the last visit, the intervention compared with the usual care group had 4.8 mg/dL (.13 mmol/L), 3.3 mg/dL (.09 mmol/L), and 2.0 mg/dL (.05 mmol/L) lower LDL-C, respectively. There were no differences at any data collection point in height or serum ferritin or any differences in an adverse direction in red blood cell folate, serum retinol and zinc, sexual maturation, or body mass index. Conclusion. Dietary fat modification can be achieved and safely sustained in actively growing children with elevated LDL-C, and elevated LDL-C levels can be improved significantly up to 3 years. Changes in the usual care group's diet suggest that pediatric practices and societal and environmental forces are having positive public health effects on dietary behavior during adolescence.

NCCAM Director Foresees Slowdown in Alternative Medicine Grants

$89.1 million is 2001 budget the National Advisory Council for Complementary and Alternative Medicine to be given out for research grants. Compare this budget to NIH's overall budget. Not much of a dent. So we have a small percentage of money going to CAM research and now reduced approval of incoming grants. And mainstream medicine loves to comment on how there is no research on CAM therapies. That's because there's pennies for reasearch compared to the money that the pharmaceuticals can produce for researching their products. But we do have, in some cases, thousands of years of experience....

(article) After an initial few years of budget growth and an increase in grant awards, the National Center for Complementary and Alternative Medicine (NCCAM) will cut the number of new grants for fiscal 2001, center director Stephen Straus said on Monday. "We're going to slow down the pace of new initiatives," said Straus, whose center is a division of the National Institutes of Health (NIH). Outlining the state of the NCCAM to the National Advisory Council for Complementary and Alternative Medicine here, Straus explained that despite a generous increase in its budget for the fiscal year, which began on October 1, the center's previous grant commitments mean that there will be less room for new awards. The NIH gave NCCAM $89.1 million for fiscal year 2001 compared to $68.3 million in 2000. In terms of awards, about 35% of the budget will go toward research grants, 23% to designated centers of excellence — which are organized to study specific disease states or categories — and 10% to training current providers and educating new providers. The remainder will be allocated toward administration and other initiatives. In 1999, the year NCCAM was founded, it was easy to award grants, said Straus, noting they were usually "low-hanging fruit" and of high caliber. Almost half of the 23 applications that year were awarded, he said. In fiscal year 2000, 31% of 144 applications were granted, which was in line with the overall NIH average that approved 26% of 33,000 applications in that fiscal year. This year, the NCCAM estimates it will receive 212 applications, but will likely support only 18%, partly because of budget constraints held over from funds granted in 1999 and 2000, but also because of quality concerns, Straus said.

Celebrex Has No Safety Advantage Over NSAIDs, Panel Says

Celebrex's manufacturer's are not going to like this. The new selective COX-2 inhibitors where designed to be safer on the stomach (don't forget that NSAIDs can also damage the liver, kidneys, GI tract other than the stomach, as well as the joints themselves...). But post-marketing studies do not support the advocacy of safer stomachs, primarily with concomitant use of aspirin. And remember, the population that is most likely to be continued users of "arthritis drugs" will also be more likely to be taking an aspirin a day for heart disease prevention.

(article) A postmarket study of celecoxib, conducted by the drug firm Pharmacia, failed to establish the drug's safety superiority to nonsteroidal anti-inflammatory drugs (NSAIDs), an advisory panel to the US Food and Drug Administration (FDA) determined on Wednesday. The Arthritis Advisory Committee met here to discuss whether findings from Pharmacia's extensive Celecoxib Long-term Arthritis Safety Study (CLASS) trial proved that celecoxib is safer than ibuprofen and diclofenac, and whether COX-2 inhibitors taken with aspirin may pose a health risk that warrants further study. The panel agreed that Pharmacia had not established a "clinically meaningful" safety advantage over NSAIDs and that data from the CLASS study would not support a superiority claim at present. According to the committee, the ability of the CLASS study to demonstrate a better safety profile was hindered by one compelling factor: concomitant aspirin use. Although the trial showed an overall twofold reduction in gastrointestinal complications in celecoxib-treated patients, that trend was reversed among subjects who took also low-dose aspirin. Among aspirin takers, celecoxib did not demonstrate safety superiority over ibuprofen or over pooled NSAIDS da