D is for deficiency

Less exposure to sunlight leaves many Americans lacking key vitamin
By Gee Loeb Sharp McClatchy News Service
Posted: 03/28/2010 11:51:12 PM MDT

We have evolved into a society sorely lacking in vitamin D.

Countless research hours have been conducted to help spread the word on its benefits, debunk the myths associated with it and lay out a simple set of guidelines to follow for optimum usage.

According to Dr. Jay Mattingly, a full-time anesthesiologist working for University of Tennessee Medical Group who recently became certified by the American Board of Anti-Aging, more than 1 billion people worldwide are deficient in vitamin D.

Actually, vitamin D isn`t a vitamin at all, but a hormone with receptors in all organs of the body, including the brain, heart, breast, colon, prostate and pancreas.

According to the Vitamin D Council, vitamin D deficiency has been implicated as a major factor in the pathology of at least 17 varieties of cancer, as well as heart disease, stroke, hypertension, autoimmune diseases, diabetes, depression, chronic pain, osteoarthritis, osteoporosis and more.

A major reason for our evolutionary decrease in vitamin D is our avoidance of the sun`s rays. Ask any vitamin D enthusiast about the sun`s ultraviolet rays and you`ll hear about its benefits, and how the skin produces about 10,000 units of vitamin D in response to 20 to 30 minutes of summer sun exposure.

Agnes Green, owner of The Healer Within wellness center in Portland, Ore., and a functional nutritionist, says we lack enough exposure to the sun to allow our bodies to produce sufficient amounts of vitamin D.

“We`re involved in more indoor activities,” Green says. “We are on our computers or watching TV, especially children and young adults who play video games. Our sun supply is cut down by diminished exposure, and what little time we do spend outdoors is rendered useless by the UV protection we lather over ourselves. … UV sunglasses also rob us of vitamin D production. … Unless you live directly under a hole in the ozone layer, you have no need for this militant sun protection. On the contrary, you`re doing yourself and your kids a disservice.”

How much vitamin D should you take? Though the U.S. government recently increased its daily recommendation to 400 IU daily, other doctors and health care professionals recommend a much higher dosage.

“The dose I recommend is 800 to 1,000 IU daily, though many of my patients with osteoporosis are still deficient at that dosage,” says Dr. Catherine Robilio Womack, internist and associate professor of medicine at the University of Tennessee Health Science Center. “Many osteoporosis patients need 1,000 to 2,000 IU daily or a bigger weekly dosage. It doesn`t matter so much what you take daily; it is the cumulative dose that is important.”

Vitamin D in pill form can be toxic when taken in excess, so it is always important to have your levels checked after increasing your intake.

According to Mattingly, everyone needs differing amounts of vitamin D, just like anything else, but the average person needs 5,000 IU daily.

“There are no adequate dietary sources of vitamin D,” Mattingly says. “The average multi-vitamin has only 400 IU and an 8 oz. glass of milk supplies only 100 IU. Even supplements like Caltrate have only 600 to 800 IU.”

Vitamin and calcium supplements may reduce breast cancer risk

Public release date: 18-Apr-2010
http://www.eurekalert.org/pub_releases/2010-04/aafc-vac041210.php

Contact: Jeremy Moore
jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research

Vitamin and calcium supplements may reduce breast cancer risk

WASHINGTON, D.C. — Vitamins and calcium supplements appear to reduce the risk of breast cancer, according to findings presented at the American Association for Cancer Research 101st Annual Meeting 2010.

“It is not an immediate effect. You don’t take a vitamin today and your breast cancer risk is reduced tomorrow,” said Jaime Matta, Ph.D., professor in the Ponce School of Medicine in Puerto Rico. “However, we did see a long-term effect in terms of breast cancer reduction.”

Matta said the findings suggest that the calcium supplements are acting to enhance DNA repair capacity, a complex biological process involving more than 200 proteins that, if disrupted, can lead to cancer.

“This process involves at least five separate pathways and is critical for maintaining genomic stability,” said Matta. “When the DNA is not repaired, it leads to mutation that leads to cancer.”

The study included 268 women with breast cancer and 457 healthy controls. Women were more likely to have breast cancer if they were older, had a family history of breast cancer, had no history of breastfeeding and had lower DNA repair capacity.

Vitamin supplements appeared to reduce the risk of breast cancer by about 30 percent. Calcium supplements reduced the risk of breast cancer by 40 percent. After controlling for the level of DNA repair capacity, calcium supplements were no longer as protective, but the link between vitamin supplements and breast cancer reduction remained.

“We’re not talking about mega doses of these vitamins and calcium supplements, so this is definitely one way to reduce risk,” said Matta.

Women who eat foods with high glycemic index may be at greater risk for heart disease

Public release date: 12-Apr-2010
http://www.eurekalert.org/pub_releases/2010-04/jaaj-wwe040810.php

Contact: Vittorio Krogh, M.D., M.S.
vittorio.krogh@istitutotumori.mi.it
JAMA and Archives Journals

Women who eat foods with high glycemic index may be at greater risk for heart disease

Consuming carbohydrates with high glycemic index—an indicator of how quickly a food affects blood glucose levels—appears to be associated with the risk of coronary heart disease in women but not men, according to a report in the April 12 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

High-carbohydrate diets increase the levels of blood glucose and of harmful blood fats known as triglycerides while reducing levels of protective HDL or “good” cholesterol, thereby increasing heart disease risk, according to background information in the article. However, not all carbohydrates have the same effect on blood glucose levels. The glycemic index is a measure of how much a food raises blood glucose levels compared with the same amount of glucose or white bread. A related measure, the glycemic load, is calculated based on the glycemic index of a given food and also on the total amount of carbohydrates it contains.

Sabina Sieri, Ph.D., of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, and colleagues studied 47,749 Italian adults—15,171 men and 32,578 women—who completed dietary questionnaires. Based on their responses, the researchers calculated their overall carbohydrate intakes as well as the average glycemic index of the foods they consumed and the glycemic loads of their diets. During a median (midpoint) of 7.9 years of follow-up, 463 participants (158 women and 305 men) developed coronary heart disease.

The one-fourth of women who consumed the most carbohydrates overall had approximately twice the risk of heart disease as the one-fourth who consumed the least. When these carbohydrates were separated into high– and low–glycemic index categories, increased intake from high–glycemic index foods was significantly associated with greater risk of coronary heart disease, whereas low–glycemic index carbohydrates were not. “Thus, a high consumption of carbohydrates from high–glycemic index foods, rather than the overall quantity of carbohydrates consumed, appears to influence the risk of developing coronary heart disease,” the authors write.

The one-fourth of women whose diet had the highest glycemic load had 2.24 times the risk of heart disease compared with the one-fourth of women with the lowest glycemic load.

Overall carbohydrate intake, glycemic index and glycemic load were not associated with heart disease risk in men. This could be because the adverse changes associated with carbohydrate intake, including triglyceride levels, are stronger risk factors for heart disease in women than in men, the authors note.

“We tentatively suggest that the adverse effects of a high glycemic diet in women are mediated by sex-related differences in lipoprotein and glucose metabolism, but further prospective studies are required to verify a lack of association of a high dietary glycemic load with cardiovascular disease in men,” they conclude.

How Many Calories Per Day for the Elderly?

All foods contain calories that provide the body with energy necessary for human function. Reading, sitting quietly, the pumping action of the heart and normal breathing all require calories. Caloric needs are greatest for young adults. As we age and our activity levels and muscle mass decrease, so does the amount of calories we need to consume.

Elderly Energy Needs

1. After we reach 50, recommended nutrient intake drops by 5 percent for each decade we age due to a decrease in the body’s active cells and loss of muscle tissue.

But determining ideal caloric intake for the elderly is not much different than calculating it for younger adults. It does, however, require some basic arithmetic.

The Harris-Benedict equation is a formula that determines basal metabolic rate then factors in physical activity to derive at the recommended daily caloric intake. The basal metabolic rate is the amount of calories burned at rest.

The formula to determine metabolic rate varies for elderly men and women.

This is the formula for women: BMR = 655 + (4.35 x weight in pounds) + (4.7 x height in inches) — (4.7 x age in years).
And here’s the formula for men: BMR = 66 + (6.23 x weight in pounds) + (12.7 x height in inches) — (6.8 x age in years)

Once the basal metabolic rate has been determined, you need to factor in activity levels. To account for activity, you multiply the BMR by a figure representing the appropriate activity level. For the elderly individual who participates in little or no activity, multiply the BMR by 1.2. For the person who is lightly active or participates in sports one to three times per week, multiply the BMR by 1.375. The moderately active elderly individual who exercises or participates in sports three to five days per week should multiply his or her BMR by 1.55. The exerciser who works out hard six to seven days per week should multiply the BMR by 1.725.

An example might be useful. Here are the step-by-step calculations you would use to determine the ideal caloric intake for a 79-year-old female who is 66 inches tall, weighs 130 pounds and who exercises one to three times per week.

First, you would determine basal metabolic rate:

BMR = 655 + (4.35 x 130) + (4.7 x 66) — (4.7 x 79)
BMR = 655 + (565.5) + (310.2) — (371.3)
BMR = 655 + 504.4
BMR = 1,159.4 Calories
Then, you would you would account for her activity level. This elderly woman participates in activity one to three times per week; therefore, her BMR is multiplied by 1.375.
Activity level = 1,159.4 x 1.375
Activity level = 1,594.175 calories

Therefore, the women should ideally consume about 1,595 calories per day.

Food Pyramids as a Guide

2. The U.S. Department of Agriculture created an interactive tool, mypyramid.gov, to address individual dietary needs for the American population. At the mypyramid.gov site, individuals can enter personal information such as age, weight, height and activity level to determine caloric needs.

How the elderly get their calories also is important.

Researchers at Tufts University have revised the food guide pyramid for the elderly to focus on specific nutrient needs.
A healthy diet for the elderly consists of three or more daily servings of brightly colored vegetables, two or more servings of deeply colored fruits, six or more servings of whole and fortified grains, three or more servings of low-fat dairy and two or more servings of protein-rich foods such as lean meats, eggs and legumes.

Hydration

3. Hydration is also a concern for the elderly due to their decreased sense of thirst. An adequate consumption of water is eight 8-ounce glasses of water, fruit juice, tea or coffee per day.

Source: www.ehow.com/ livestrong.com

The Benefits of Exercise in Postmenopausal Women At a Glance

A new study out of Australia shows significant benefits to bone mineral density among postmenopausal women who participate in a twice-weekly exercise program.

Read more about this research below.

A February 2010 research study from the University of New South Wales examined the effect of an aerobic weight-bearing exercise program on bone mineral density (BMD) in postmenopausal women. The purpose of the study was to examine what specific role – if any – regular exercise had on BMD.

30 postmenopausal women were divided into two groups for the study. The first group (19 women, mean age 66.4 years) was assigned a two-year exercise program consisting of twice-weekly aerobic weight-bearing exercises. The second group (11 women, mean age 65.4 years) did not participate in an exercise program. Before and after the two-year study period, bone density measurements were taken at the spine and hip of each study participant.

At the end of the study, women in the exercise group experienced less than one-fourth the spinal BMD loss compared to the control group (-0.8 compared to -3.8, 95% CI 0.3-5.7% difference.) Results were even more impressive for the hip measurement, where the exercise group saw a 9.6% improvement compared to a 4.4% loss in the controls (14.0% difference, 95% CI 4.6-23.5.)

The authors of the study concluded: “this study adds strong evidence that twice-weekly weight-bearing aerobic exercise has a protective effect on bone density in postmenopausal women as well as being associated with other measurable benefits.”

Caplan GA, Ward JA, Lord SR. The benefits of exercise in postmenopausal women. 2010. Australian Journal of Public Health 17(1):23-6.

How Red Wine May Shield Brain from Stroke Damage

Newswise — Researchers at Johns Hopkins say they have discovered the way in which red wine consumption may protect the brain from damage following a stroke.

Two hours after feeding mice a single modest dose of resveratrol, a compound found in the skins and seeds of red grapes, the scientists induced an ischemic stroke by essentially cutting off blood supply to the animals’ brains. They found that the animals that had preventively ingested the resveratrol suffered significantly less brain damage than the ones that had not been given the compound.

Sylvain Doré, Ph.D., an associate professor of anesthesiology and critical care medicine and pharmacology and molecular sciences at the Johns Hopkins University School of Medicine, says his study suggests that resveratrol increases levels of an enzyme (heme oxygenase) already known to shield nerve cells in the brain from damage. When the stroke hits, the brain is ready to protect itself because of elevated enzyme levels. In mice that lacked the enzyme, the study found, resveratrol had no significant protective effect and their brain cells died after a stroke.

“Our study adds to evidence that resveratrol can potentially build brain resistance to ischemic stroke,” says Doré, the leader of the study, which appears online in the journal Experimental Neurology.

www.functionalfoods.com

‘Epigenetic’ concepts offer new approach to degenerative disease

Public release date:
28-Apr-2010http://www.eurekalert.org/pub_releases/2010-04/osu-co042810.php

Contact: Rod Dashwood
rod.dashwood@oregonstate.edu
541-737-5086
Oregon State University

‘Epigenetic’ concepts offer new approach to degenerative disease

ANAHEIM, Calif. – In studies on cancer, heart disease, neurological disorders and other degenerative conditions, some scientists are moving away from the “nature-versus-nurture” debate and are finding you’re not a creature of either genetics or environment, but both – with enormous implications for a new approach to health.

The new field of “epigenetics” is rapidly revealing how people, plants and animals do start with a certain genetic code at conception. But the choice of which genes are “expressed,” or activated, is strongly affected by environmental influences. The expression of genes can change rapidly over time, they can be influenced by external factors, those changes can be passed along to offspring, and they can literally hold the key to life and death.

Some of the newest work in this field was outlined today by researchers from the Linus Pauling Institute at Oregon State University, speaking at experimental Biology 2010, a professional conference in Anaheim, Calif.

According to Rod Dashwood, a professor of environmental and molecular toxicology and head of LPI’s Cancer Chemoprotection Program, epigenetics is a unifying theory in which many health problems, ranging from cancer to cardiovascular disease and neurological disorders, can all be caused at least in part by altered “histone modifications,” and their effects on the reading of DNA in cells.

“We believe that many diseases that have aberrant gene expression at their root can be linked to how DNA is packaged, and the actions of enzymes such as histone deacetylases, or HDACs,” Dashwood said. “As recently as 10 years ago we knew almost nothing about HDAC dysregulation in cancer or other diseases, but it’s now one of the most promising areas of health-related research.”

In the case of cancer, tumor suppressor genes can cause cancer cells to die by acting as a brake on unrestrained cell growth. But too much of the HDAC enzyme can “switch off” tumor suppressor genes, even though the underlying DNA sequence of the cell – its genetic structure – has not been changed or mutated. If this happens, cells continue to replicate without restraint, which is a fundamental characteristic of cancer development.

The good news – for cancer and perhaps many other health problems – is that “HDAC inhibitors” can stop this degenerative process, and some of them have already been identified in common foods. Examples include sulforaphane in broccoli, indole-3-carbinol in cruciferous vegetables, and organosulfur compounds in vegetables like garlic and onions. Butyrate, a compound produced in the intestine when dietary fiber is fermented, is an HDAC inhibitor, and it provides one possible explanation for why higher intake of dietary fiber might help prevent cancer.

“Metabolism seems to be a key factor, too, generating the active HDAC inhibitor at the site of action,” Dashwood said. “In cancer cells, tumor suppressors such as p21 and p53 often become epigenetically silenced. HDAC inhibitors can help turn them on again, and trick the cancer cell into committing suicide via apoptosis.

“We already know some of the things people can do to help prevent cancer with certain dietary or lifestyle approaches,” Dashwood said. “Now we’re hoping to more fully understand the molecular processes going on, including at the epigenetic level. This should open the door for new approaches to disease prevention or treatment through diet, as well as in complementing conventional drug therapies.”

OSU scientists recently received an $8.5 million grant from the National Cancer Institute to explore these issues, making the LPI program one of the leaders in the nation on diet, epigenetics, and cancer prevention. The positive findings of laboratory research are already being converted to placebo-controlled human intervention trials on such health concerns as colon and prostate cancer, which are among the most common cancers in the United States.

OSU scientists have published a number of studies on these topics in professional journals such as Cancer Research, Cancer Prevention Research, Carcinogenesis, and Seminars in Cancer Biology. Among the most recent findings is that naturally occurring organoselenium compounds in the diet might prevent the progress of human prostate and colon cancer through an HDAC inhibition mechanism.

“Some therapeutic drugs already used for cancer treatment in the clinical setting probably work, at least in part, because they are acting as HDAC inhibitors,” Dashwood said. “And what’s most intriguing is that HDAC inhibition may affect many degenerative health issues, not just cancer. Heart disease, stroke, bipolar disorder, and even aging may all have links to HDAC/histone alterations.

“In the future, a single HDAC inhibitor conceptually could have benefits for more than one degenerative disease problem.”

Rhodiola Extract Improves Burnout Fatigue, Attention, and Cortisol Response

The Journal of the American Botanical Council

Issue: 82 Page: 28-29

Rhodiola Extract Improves Burnout Fatigue, Attention, and Cortisol Response

HerbalGram. 2009;82:28-29 American Botanical Council

Reviewed: Olsson EMG, von Scheele B, Panossian AG. A randomized, double-blind, placebo-controlled, parallel-group study of the standardized extract SHR-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009;75:105-112.

Psychological stress can induce fatigue syndrome, which is characterized by long-term exhaustion, physical weakness, depression, lack of drive, poor concentration, and difficulty sleeping. Consumers often treat stress-related fatigue with stimulants. Rhodiola (Rhodiola rosea, Crassulaceae) root extract has stimulant and stress-protective (or adaptogenic) properties. The objective of this study was to determine whether daily intake of a proprietary rhodiola extract would produce any positive effects on attention, quality of life, and symptoms of fatigue and depression in subjects with stress-related fatigue.

Sixty men and women (20-55 years) living in and around Stockholm, Sweden, responded to an advertisement to participate in this randomized, double-blind, placebo-controlled study. Included subjects had “fatigue syndrome” as classified by the World Health Organization’s International Classification of Diseases. The project was approved by the Swedish Medical Product Agency and the University of Uppsala. The subjects had daily symptoms of fatigue, enduring for at least 2 weeks, related to a specific stressor that had been present for at least 6 months, and their daily functioning was negatively affected by stress. The symptoms could not be related to substance abuse or psychiatric or other primary disorders.

The diagnosis of fatigue syndrome differs from that of chronic fatigue syndrome. Fatigue syndrome requires the identification of specific stressors while chronic fatigue syndrome focuses on the immune system and symptoms of pain in the lymph nodes, joints, and muscles.

Subjects were given 120 placebo or identical-appearing tablets of a proprietary Rhodiola rosea root extract (576 mg extract/day, SHR-5, Swedish Herbal Institute, Gothenburg, Sweden). The extract was a 4:1 concentrate made by using a 70% ethanol solvent; it contained 4.0 mg/tablet of rhodioloside along with quantified but unspecified amounts of tyrosol, rosavin, and triandrin.

The primary endpoint was a reduction in fatigue symptoms assessed according to the Pines’ burnout scale. Attention was evaluated by the Conners’ computerized continuous performance test II (CCPT II) for features such as omissions, commissions, variability, and response reaction time standard error (Hit RT SE). The reduction in depressive symptoms was estimated using the Montgomery-Asberg depression rating scale (MADRS), quality of life was measured using the SF-36 questionnaire, and the cortisol (a stress hormone) response to awakening was determined from saliva samples. Saliva sampling was chosen because it is a simple, non-invasive, non-stressful method that participants could do at home. Saliva samples were collected using Salivette cotton rolls, which participants were instructed to place in the mouth for at least 1 minute or until the cotton roll was soaking wet, at 0, 15, 30 and 60 minutes after awakening.

One person dropped out of the treatment group; each group had 3 men. The placebo group had much better compliance than the rhodiola group (P = 0.07). The number of tablets remaining in the container was 0-75 tablets in the rhodiola group and 0-29 tablets in the placebo group. There was a significant improvement in fatigue symptoms, quality of life, depression, and attention in both groups. The authors state that these improvements could be due to a placebo effect, a general effect of taking the tests twice, or a regression towards the mean. However, the rhodiola group benefited more than the placebo group on assessment of fatigue symptoms (P = 0.047) and attention (omissions—not responding when a response is required [P = 0.02], variability [P=0.005], and Hit RT SE [P=0.001] that indicate a more stable work pace). The cortisol response to awakening stress (awakening is a mild stressor) was reduced significantly following 28 days of treatment with the rhodiola extract in comparison with the control group (P = 0.038). No adverse events occurred during the study, and no major side effects that could be clearly linked to the rhodiola preparation were reported by any of the subjects.

The authors conclude that repeated administration of rhodiola extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome. According to the authors, this study is the first to show that this proprietary rhodiola extract benefits patients with chronic stress-induced fatigue. Additionally, this study is the first to suggest clinically that Rhodiola rosea root benefits stress-induced disorders by modulating cortisol. There are data suggesting that the inhibitory effect of Rhodiola rosea on the increased basal level of cortisol results in an improvement in cognitive function. This proposal is consistent with other studies suggesting that optimal corticosteroid levels are a requirement for efficient cognitive function, as significant changes (up or down) in circulating levels of corticosteroids correlate with cognitive impairment.1 Modulation of cortisol content is believed to be a key mechanism of action of phytoadaptogens.

The authors suggest that the reason a potential effect on depressive symptoms was lacking—as has been documented in a previous trial designed to measure the effect of this specific rhodiola extract on depressed patients2—may have been due to the inadequate duration and because subjects with depression as a major symptom were excluded from this trial. The authors do not hypothesize why the rhodiola group had poorer compliance or whether the findings would have been more robust if compliance were improved. It should be noted that the effects seen in this study may be specific to the proprietary rhodiola product used and the specific dose.

—Heather S. Oliff, PhD

References

1. Herbert J, Goodyer IM, Grossman AB, et al. Do corticosteroids damage the brain? J Neuroendocrinol. 2006;18:393-411.
2. Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmstrom C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J. Psyc. 2007;61:343-348.

Source: http://cms.herbalgram.org/herbalgram/issue82/article3409.html

American Botanical Council, 6200 Manor Rd, Austin, TX 78723
Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

COLD-fX® Special Extract from American Ginseng Root Shown Safe for Children with Upper Respiratory Tract Infections

The Journal of the American Botanical Council

Issue: 81 Page: 30-31

COLD-fX® Special Extract from American Ginseng Root Shown Safe for Children with Upper Respiratory Tract Infections

HerbalGram. 2009;81:30-31 American Botanical Council

Reviewed: Vohra S, Johnston BC, Laycock KL, et al. Safety and tolerability of North American ginseng extract in the treatment of pediatric upper respiratory tract infection: a phase II randomized, controlled trial of 2 dosing schedules. Pediatrics. Aug 2008;122(2): e402-e410.

Upper respiratory tract infections (URIs) are more common in children than in adults, and parents often treat their children’s symptoms with herbs and other natural health products (NHPs, the regulatory term used in Canada for vitamins, minerals, herbs, homeopathic remedies, etc.). One of the most popular products used for enhancing immunity and preventing and treating URIs in Canada is a special, patented extract of American ginseng root (Panax quinquefolius, Araliaceae) called COLD-fX® (CV Technologies, Inc., Edmonton, Alberta, Canada) consisting of only the saccharide fraction of the root (i.e., furanyl-, oligo- and polysaccharides). Unlike conventional ginseng extracts, this preparation does not contain ginsenosides, the characteristic active triterpene glycosides in various species of the genus Panax that are the subject of most chemical and pharmacological research on this highly-researched genus.

In Canada, COLD-fX is approved by the Natural Health Products Directorate of Health Canada for the prevention and treatment of URIs related to cold and flu, based on a previous review of published clinical trials and laboratory research. Although the safety and efficacy of COLD-fX has been studied for the treatment and prevention of URIs in adults, the authors of this phase II randomized, double-blind, dose-finding, 3-arm clinical trial claim that it is the first to examine safety, dose, and efficacy in children.

There were 2 dosing arms and a placebo arm. The objectives were to document the safety and efficacy of weight-based dosing schedules and to determine the treatment effect of COLD-fX on the severity and duration of pediatric URIs. Children aged 3-12 years old were recruited between November 2005 and February 2006 from 2 teaching hospitals at the University of Alberta (Edmonton, Alberta, Canada). A computerized random number generator was used for randomization.

Parents of the subjects contacted the study nurse upon the onset of symptoms. If the study nurse determined that the symptoms were those of a URI, then the pharmacy was contacted and the study medications (COLD-fX or placebo) were dispensed and sent by courier. The weight-based COLD-fX standard dose (n=13) was 26 mg/kg on day 1, 17 mg/kg on day 2, and 9 mg/kg on day 3. Children who received the standard adult dose (600 mg on day 1, 400 mg on day 2, and 200 mg on day 3) weighed over 45 kg. The weight-based COLD-fX low-dose group (n=14) received 13 mg/kg on day 1, 8.5 mg/kg on day 2, and 4.5 mg/kg on day 3. Children in the low dose group also weighed less than 45 kg. The placebo group (n=15) received a liquid solution similar in appearance to the COLD-fX formulation. The placebo or COLD-fX formulations were dispensed into 3 equal portions to be taken 3 times daily for 3 days. The children received other medications and tests as determined by their physicians. The severity and duration of the URIs were measured using the Canadian Acute Respiratory Infection Flu Scale (CARIFS) score, a validated 18-item scale that covers 3 domains: symptoms, function, and parental impact. The severity and duration of the treatment effect was measured as the average length of time in days from treatment onset to resolution of symptoms, defined as a 25% decrease from the baseline CARIFS score.

No serious adverse events were reported. A total of 31 subjects reported 51 adverse events. Out of these, 8 were classified as moderate: 2 in the low-dose group (fever and secondary bacterial throat infection), 6 in the placebo group, and none in the standard dose group. In addition, 11 adverse events were classified as possibly related to the intervention. Those receiving the standard dose had fewer of these adverse events than either those receiving low-dose or placebo, but there was no statistically significant between-group difference.

The severity and duration of treatment effect was 1.5 days for the standard dose group, 1.9 days for the low dose group, and 1.9 days for the placebo group. This is all-the-more impressive given that those in the standard dose group were the sickest group at the outset. Nevertheless, the study group was too small for this trend to reach statistical significance. From this information, however, the authors were able to calculate that repeating the study with 48 children in each treatment arm could confirm whether COLD-fX shortens the duration of colds in children. The use of antipyretics (fever-reducing medications) was highest in the low-dose group (P=0.48). Otherwise, there was no significant difference in the use of cold and flu remedies, antibiotics, or asthma medications among the groups.

The authors conclude that the standard weight-based dose of COLD-fX used in this study is safe and well-tolerated in children and appropriate for larger, phase III clinical trials. The difference in the use of NHPs and asthma medication was not significant among the treatment arms, but the authors recommend that future investigators caution subjects not to use other NHPs during the study and to include a specific measure of asthma status. The authors also recommend rigorous stepwise clinical trials from phase I to phase III on NHPs, which could help to avoid expensive negative phase III trials. Future research on the efficacy of COLDfX in the treatment of pediatric URIs is warranted. In addition, the authors recommend studies evaluating daily use of COLD-fX in children for preventing URIs.

In February 2007 the American Botanical Council published an extensive clinical monograph on COLD-fX (also known by the name of its extract, CVT-E002), available on the ABC Web site at http://cms.herbalgram.org/herbclip/306/review44663.html.

—Marissa Oppel, MS

Source: http://cms.herbalgram.org/herbalgram/issue81/article3372.html

American Botanical Council, 6200 Manor Rd, Austin, TX 78723
Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

Biological Activity of Curcuminoids from Turmeric Assessed in Patients with Advanced Pancreatic Cancer

The Journal of the American Botanical Council

Issue: 81 Page: 23

Biological Activity of Curcuminoids from Turmeric Assessed in Patients with Advanced Pancreatic Cancer

HerbalGram. 2009;81:23 American Botanical Council

Reviewed: Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491–4499.

Pancreatic cancer is almost always lethal, and most patients die within 1 year of diagnosis. The only drugs approved by the Food and Drug Administration that are currently available for treatment are gemcitabine and erlotinib. Both of these drugs elicit responses in only a small percentage of patients (less than 10%), and their effect on survival is measured in weeks. Thus, effective treatments are urgently needed. Many studies have shown that nuclear transcription factor-κB (NF-κB) is activated in patients with pancreatic cancer; therefore, an agent that targets NF-κB may prove effective in the treatment of this disease.

Previous laboratory research has shown that curcuminoids, a group of compounds derived from the traditional herb and spice turmeric (Curcuma longa, Zingiberaceae), suppress NF-κB activation, cell growth associated with apoptosis (programmed cell death), and the growth of human pancreatic cancer xenografts in mice. These curcumoinds are curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin. Phase I human clinical trials of curcuminoids have shown that they are safe at doses up to 8 g/day but that their oral bioavailability may be poor. Thus, this phase II clinical trial was undertaken to determine whether orally administered curcuminoids have biological activity in patients with advanced pancreatic cancer.

Twenty-five patients (13 men, 12 women; aged 43-77) with histologically confirmed pancreatic cancer and a Karnofsky performance score greater than 60 were enrolled in this nonrandomized, open-label, phase II trial, which was conducted at the University of Texas

M.D. Anderson Cancer Center in Houston, Texas. As controls, cytokine levels were measured in 48–62 healthy volunteers depending on the cytokine assessed. The patients ingested a daily dose of 8 g of curcuminoids in capsule form (1 capsule = 1 g curcuminoids [900 mg curcumin, 80 mg desmethoxycurcumin, and 20 mg bisdesmethoxycurcumin]; Sabinsa Corp., Piscataway, NJ). Concomitant chemotherapy or radiotherapy was prohibited, but supportive care was allowed. Disease staging, a physical examination, and blood sampling were performed at baseline and at 4 and 8 weeks. Blood samples were used to measure the following values: cytokine concentrations (interleukin-6, -8, -10, and interleukin-1 receptor antagonist), carcinoembryonic antigen concentrations, and peripheral blood mononuclear cell expression of NF-κB and cyclooxygenase-2 (COX-2). The adverse events were assessed on the basis of the National Cancer Institute Expanded Common Toxicity Criteria (http://ctep.cancer.gov/forms/CTCAEv3.pdf), and tumor response was evaluated on the basis of the Response Evaluation Criteria in Solid Tumors.

Twenty-four patients were available for the toxicity evaluation, and 21 patients were available for evaluation of the response to treatment with curcuminoids. Circulating concentrations of curcumin in blood serum were low, which indicated poor oral bioavailability. However, 2 patients exhibited a favorable response to curcuminoids. Pancreatic cancer remained stable in 1 of these patients for greater than 18 months. “Marked” tumor regression (73%) and significant (P < 0.05) increases in serum interleukin-6, -8, and -10 and in interleukin-1 receptor agonist were observed in the other patient. NF-κB activation decreased with curcuminoids treatment, but not significantly compared with the healthy controls. COX-2 expression decreased significantly (P < 0.03) with curcumin treatment. Blood concentrations of curcumin peaked at 22–41 ng/mL and remained relatively constant over the first 4 weeks of the study. Carcinoembryonic antigen concentrations decreased gradually over 1 year in 1 patient, which indicated an improvement in cancer status. No treatment-related toxicity was observed. The results of this study indicate that orally administered curcuminoids are tolerated well at doses of 8 g/day for up to 18 months and have “biological activity in some patients with pancreatic cancer.” Although curcumin was poorly absorbed, biological activity (i.e., tumor regression and increase in cytokine concentrations) was evident at steady-state. Because curcumin is hydrophobic (i.e., not water soluble), it cannot be administered intravenously unless encapsulated in a liposome, which would presumably result in higher circulating concentrations of curcumin in the blood. The authors intend to conduct clinical trials in pancreatic cancer patients with the use of liposomal curcuminoids, which they hope will result in more consistent blood concentrations of curcumin and a better pharmacologic effect. —Brenda Milot, ELS Source: http://cms.herbalgram.org/herbalgram/issue81/article3376.html American Botanical Council, 6200 Manor Rd, Austin, TX 78723 Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

« Previous Page — Next Page »