BLUEBERRY STUDY PRESENTATIONS AT AMERICAN AGING ASSOCIATION ANNUAL MEETINGS:
THE 2002 BLUEBERRY HEALTH STUDY: DAILY BLUEBERRIES IMPROVE DECISION-SPEED AND AGE-RELATED HEALTH INDICATORS
R. Martin, MMT Corp., Sherman, CT 06784, R.J. Coppings, Lane College, Jackson, TN 38301, K.E. Gerstmann, NY, NY 10014, J.A. Joseph, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, A.C. Kokesh, Charleston, WV 25301, B. Kristal, Weill Medical College-Cornell University Medical Center, NY, NY 10021 and Burke Medical Research Institute, White Plains, NY 10605, D. Mathew, New Fairfield, CT 06812, B. Sachs, HR Herbs, Sherman, CT 06784, A. Pruchnicki, Mount Sinai Medical Center, NY, NY 10029, R. Schnoll, Brooklyn College, Brooklyn, NY 11210, and A. Wetherell, Defence Science & Technology Laboratory, UK. Contact email: BlueberryStudy@aol.com
Joseph and collaborators reported in 1999 that blueberry diet supplementation significantly reduced cognitive decline in older laboratory rats. Our research group observed decision-speed improvement during a pilot study with thirteen multiple sclerosis patients (2001). The 2002 Blueberry Health Study was then conducted to determine if blueberries provide health benefits to a larger number of adults, aged 60 and over.
The 2002 study was a sixteen-week randomized, multicenter, crossover trial involving 100 participants and positive and placebo controls. The protocol included four 4-week steps: baseline measurement, treatment period 1, treatment period 2, and post-treatment follow-up.
To begin the study, Connecticut residents were invited to public meetings at the New Fairfield and Mansfield Senior Centers, and to the study web site at BlueberryStudy.com. Recruitment ended approximately 30 days after newspaper, radio and television announcements were made.
Participants were randomly assigned to receive individually quick frozen wild Maine blueberries (1 cup/day or 10 lbs/month), rice powder (500 mg/day), coenzyme Q10 (30-mg/day) or an antioxidant mixture containing mixed tocopherols (500 IU total/day) plus lipoic acid (25 mg/day). To equalize blueberry and control group expectations, participants were sent email messages citing evidence of health benefits from vitamin E, lipoic acid and our other control supplements. Participants conducted weekly measurements of single-choice decision speed, provided estimates of their aches and pains, energy-level, mood, sharpness, peacefulness, sleep quality, and overall health, and made three separate decision-speed predictions each week to allow expectations and motivation to be measured. Errors and decision speed were recorded before and also after predictions during each measurement session, to provide additional measures of participant expectations and motivation.
Ninety seven participants completed the protocol. Among those receiving wild blueberries, significant improvement occurred in decision speed (t-test p = 0.024) and self-reported aches and pains (p = 0.017), energy level (p = 0.002), sharpness (p = 0.001), sleep quality (p = 0.017), mood (p = 0.010), peacefulness (p = 0.005) and overall health (p = 0.001). Blueberry group response times improved by 4.2%, decreasing from 39.96 to 38.27 centiseconds, more than twice the improvement in the control group. Actual decision speeds were not displayed during the study so speed improvement could not influence self-reported health. Adjustments to balance decision speed predictions, error rates and within-measurement decision-speed improvement (our measures of expectation and motivation) in blueberry and control groups did not significantly change these results. Two blueberry recipients reported hearing improvement that was confirmed by an independent observer, and three reported their prostate serum antigen level declined. Significant changes were not observed in any control group.
Results of this study indicate that blueberries consumed regularly for four weeks can improve a number of health indicators related to aging, including decision speed, aches and pains, and energy level.
We greatly appreciate assistance provided by Bill Holme, Phil Fichandler, Kathy Hull, Marilyn Gerling and many others at the New Fairfield and Mansfield Senior Centers.
Citations: Joseph et al. (1999) J Neurosci. Sep 15;19(18): 8114-21. Pappas et al. (2001) 30th Ann. Mtg. Amer. Aging Assoc., Abstr. 106.
SENIOR CENTERS CAN ADMINISTER AND INCREASE THE STATISTICAL POWER OF LONGEVITY STUDIES.
P.D. Fichandler, H.A. Raphaelson, and M.A. Gerling, Mansfield Senior Center, Mansfield, CT 06268, K. Hull, New Fairfield Senior Center, New Fairfield, CT 06812, R.J. Coppings, Lane College, Jackson, TN 38301, K.E. Gerstmann, NY, NY 10014, William Holme, Bethel, CT 06801, J.A. Joseph, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, A.C. Kokesh, Charleston, WV 25301, D. Mathew, New Fairfield, CT 06812, B. Sachs, HR Herbs, Sherman, CT 06784, A. Pruchnicki, Mount Sinai Medical Center, NY, NY 10029, R. Schnoll, Brooklyn College, Brooklyn, NY 11210, A. Wetherell, DERA Chemical and Biological Defence Sector, UK and R. Martin, MMT Corp., Sherman, CT 06784. Contact email: BlueberryStudy@aol.com
Today's modern senior centers have networked computers, computer classes and volunteer teachers who can train and assist study participants. They have regular meetings that greatly speed recruitment. And they have a corps of reliable study participants and professional volunteers who can work with scientists to implement study protocols.
Our experience conducting the 2002 Blueberry Health Study at the New Fairfield and Mansfield Senior Centers suggests that large-scale studies of the kind described over 30 years ago by Alex Comfort (1969) can be conducted, at virtually no cost, if scientists work with senior center leaders. Their skill, dedication and willingness to perform tasks required during human studies -- reminding participants to provide weekly reports, assisting with computer tasks, typing answers for those who are unable, communicating regularly with scientists -- tie everyone's efforts together and lead to a level of reliability that is more than sufficient for high-quality studies.
Recruitment at both centers required approximately 1 month, rather than six to twelve months typical for this kind of study. The baseline period dropout rate was 25% when PF worked with Mansfield participants, and 60% for all other participants. Overall test-retest reliability for decision speed was 0.92, far higher than the average reported reliability of 0.67 for other cognitive studies. The final confidence limit for decision-speed improvement during the blueberry study was 0.025. Without data from senior center participants, the confidence limit would have been 0.077.
The formula we found successful included (1) public meetings at each center, at the start, middle and end of the study, (2) weekly email messages to participants and center leaders, who posted and announced them for those without email, (3) formation of a review committee so that the leaders and participants could review and amend each weekly draft message before it was released, (4) weekly phone conversations between scientists and center leaders, to respond rapidly to problems and questions, and (5) involvement of both the center director and one or two leaders, including the individual in charge of computer instruction.
Dr. Comfort published his research plans, repeatedly, but could not implement them (Kirkwood, 2001). Today's senior centers appear to have the hardware and human talent and dedication needed to carry out studies of the kind he so eloquently described. Scientists and Senior Center members who wish to join our research group are invited to contact us at BlueberryStudy.com.
Citations: Comfort, A. (1969) Lancet: Dec 27;2(7635):1411-4. Kirkwood, TB Exp Gerontol 1998 Jan-Mar;33(1-2):135-40.
Acknowledgments: We thank Phil Fichandler, Howard Raphaelson, William Holme, Marilyn Gerling, Kathy Hull and Catherine Pappas for inventing their roles as leaders/scientists and enabling the 2002 Blueberry Health Study to be completed. We thank also the MMT Corp. for contributing the study software, Capsugel Inc., for donating all capsules for the study, the Wild Blueberry Association of North America for providing all blueberries, and the Danbury A&P Superfoodmart, Sherman IGA Supermarket, Mansfield Big Y Supermarket, Happy Rainbows Herbs and the New Fairfield and Mansfield Senior Centers for serving as our regular blueberry distribution centers.
BLUEBERRY STUDY WEB SITES FOR COGNITIVE PERFORMANCE MEASUREMENT APPEAR SUFFICIENTLY PRECISE TO DETECT A 0.1% CHANGE IN PERFORMANCE DURING AGING
R.J. Martin, MMT Corp., M.E. Luzi and T.J. Millard, Sherman IGA Supermarket and B.S. Sachs, HR Herbs, Sherman, CT 06784, R.J. Coppings, Lane College, Jackson, TN 38301, K.E. Gerstmann, NY, NY 10003, William H. Holme, Bethel, CT 06801, K. Hull, New Fairfield Senior Center, New Fairfield, CT 06812, J.A. Joseph, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, A.C. Kokesh, Charleston, WV 25301, B.S. Kristal, Weill Medical College-Cornell University Medical College, NY, NY 10021 and Burke Medical Research Institute, White Plains, NY 10605, A. Pruchnicki, Mount Sinai Medical Center, NY, NY 10029, H.A. Raphaelson, Mansfield Senior Center, Mansfield, CT 06268, R. Schnoll, Brooklyn College, Brooklyn, NY 11210, and A. Wetherell, Defence Science & Technology Laboratory, UK. Contact email: BlueberryStudy@aol.com
To evaluate methods for reducing age-associated cognitive decline during 2-year to 3-year study periods, measurement precision should detect with 95% confidence differences of 0.1% or more between treatment and control groups having ~1% average annual decline. To develop such high precision for our 2000, 2002 and 2004 blueberry studies, self-calibrating web sites were developed for online measurement of 4-choice and 2-choice decision speed and immediate and delayed word recall (patent no. 6,712,615). These sites enable participants to measure their performance repeatedly and thereby obtain very precise average measures of these aspects of cognition. Annual test-retest reliability values for decision speed during 2000-2004 ranged from 0.95 to over 0.99. Results collected from these sites were used to develop computer simulations which indicate that both our blueberry study design, with two major types of performance measurement (decision speed and recall), and Alex Comfort's (1969, 1979) approach to measuring human aging, with 60 different types of physiological and performance measurement, are capable of identifying agents that can reduce a 1% annual decline to 0.95% if 10,000 or more participants complete required measurements. The major problem of accurately monitoring food and supplement intake over long study periods can be solved in part with supermarket purchase logs and food sharing and spoilage reports. Purchase logs received to date indicate that 18 participants purchased 2,845 items at the Sherman IGA Supermarket with electronic discount cards that provide automatic "health discounts" of ~40% on blueberries and 35 other health-related foods. Automatic discount cards can significantly aid recruitment and retention and provide a high-density data stream to help examine whether local advertising campaigns or health news reports cause unbalanced diet or health supplement shifts in either treatment or control groups. Blueberrystudy.com measurement and diet-tracking software are expected to be available to other research groups later this year.
Comfort A. Test-battery to measure ageing-rate in man. Lancet. 1969. Dec 27;2(7635):1411-4 and The Biology of Senescence. 1979. Elsevier Press, New York, 3rd ed.
MEMORY SCORE IMPROVEMENT OBSERVED DURING TWO-YEAR BLUEBERRY STUDY
H.A. Raphaelson, Mansfield Senior Center, Mansfield, CT 06268, R.J. Coppings, Lane College, Jackson,TN 38301, K.E. Gerstmann, NY, NY 10003, William H. Holme, Bethel, CT 06801, K. Hull, New Fairfield Senior Center, New Fairfield, CT 06812, J.A. Joseph, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, A.C. Kokesh, Charleston, WV 25301, B.S. Kristal, Weill Medical College-Cornell University Medical College, NY, NY 10021 and Burke Medical Research Institute, White Plains, NY 10605, A. Pruchnicki, Mount Sinai Medical Center, NY, NY 10029, R. Schnoll, Brooklyn College, Brooklyn, NY 11210, A. Wetherell, Defence Science & Technology Laboratory, UK, and M.E. Luzi, Sherman IGA Supermarket, B.S. Sachs, HR Herbs, Teas and Gifts, and R.J. Martin (P), MMT Corp. of Sherman, CT 06784. Contact: Blueberrystudy@aol.com.
This research was conducted in Sherman, New Fairfield, Danbury, Bethel and Mansfield, Connecticut with coordination provided by the MMT Corp. and members of the Mansfield Senior Center.
Following the 1999 report by Joseph et al. of cognitive improvement among blueberry-fed rats and our 2000 and 2002 pilot human trials showing decision speed improvement during 1 month of 1-cup/dy blueberry consumption, we commenced a long-term exploratory study to determine whether memory decline could be reduced or reversed by blueberry consumption over 2 years.
METHODS: Flash-frozen high-antioxidant Maine wild blueberries were delivered every 3 months and stored without thawing in participant freezers. An average of 50 participants aged 50-84 recruited principally at the New Fairfield and Mansfield (Connecticut) Senior Centers consumed 10 lbs/month (1 cup/day) of uncooked blueberries while completing health reports and conducting optional memory measurements. Measurements were not required to enable noncomputer-savvy participants to take part and contribute monthly reports and physical exam results. To measure word memory, 20 words were presented, each after a 2-second delay for rehearsal. These words were then presented in forward and reverse order with incorrect choices interspersed to test recognition of those presented previously. This and other measurements are available online for use by other researchers at BlueberrryStudy.com/measurements.
RESULTS: Five long-term recall data sets were obtained. These included three spanning two years and two with baseline and post-blueberry results. All five data sets showed improvement over time with average errors declining by 12% (p < 0.05). Initial results were excluded to reduce the possibility that practice effects caused this improvement. Some participants also reported mood, sharpness, energy and hearing improvement, stronger fingernails and lower PSA levels.
CONCLUSION: Memory improvement over two years, when decline was expected, may be due to a previously undocumented year-to-year practice effect, to changes in determination to achieve high scores, or to cognitive enhancement by blueberries or other health factors. A randomized, controlled trial is needed to determine whether blueberries or other causes led to observed improvements.
2002-2007 BLUEBERRY HEALTH STUDY ANNUAL REPORT: INDIVIDUAL DATA SETS ARE NOW REACHING THE 95% CONFIDENCE LEVEL FOR MEMORY SCORE IMPROVEMENT.
Rolf J. Martin, MMT Corp., Sherman, CT and Burke-Cornell Medical Research Institute, White Plains, NY 10605, Richard J. Coppings, Jackson State Community College, Jackson, TN 38301, David Doiron, Mansfield Center, CT 06250, Kathy Hull, New Fairfield Senior Center, New Fairfield, CT 06812, James A. Joseph, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, Amy C. Kokesh, Charleston, WV 25301, Bruce S. Kristal, Weill Medical College-Cornell University Medical College, NY, NY 10021 and Burke Medical Research Institute, White Plains, NY 10605, Alec Pruchnicki, St. Vincent's Hospital, NY, NY 10014, Howard A. Raphaelson, Mansfield Senior Center, Mansfield, CT 06268, Barrie S. Sachs, HR Herbs, Teas and Gifts and Kurt Gerstmann, Sherman, CT 06784, Roseanne Schnoll, Health & Nutrition Sciences, Brooklyn College, Brooklyn, NY 11210 and Anthony Wetherell, Defence Science & Technology Laboratory, UK (retired). Contact: Blueberrystudy@aol.com. Web site: Blueberrystudy.com
BACKGROUND: Since 1999, blueberry extracts have been reported to increase hippocampal neurogenesis and plasticity, improve survival of transplanted nerve cells, improve rotarod and maze performance, reduce Alzheimer's-like changes, decrease tumorigenesis, and increase longevity in different animals. A critical question is whether blueberries can provide similar benefits to humans.
METHODS: To investigate cognitive effects of regular blueberry consumption over a 5-year period, we conducted an open label exploratory investigation of word memory and other performance changes that occur when people (median age ca. 70) consume 1 cup of high-antioxidant frozen wild Maine blueberries daily. Word memory was measured with random selections from a bank of 400 familiar nouns that did not change during the 5 year study period. Measurements were generally conducted during a single 20-40 minute measurement session once each week via the Internet using home or senior center computers. Two participants elected to conduct daily measurements and nine are conducting 4 measurements each week so that their individual data sets can reach the 95% level of confidence.
RESULTS: Errors during memory measurement decreased by 9.5% on average. Score improvements are now large enough to exceed the 95% confidence level for three of the 8 longest individual data sets (two-tailed t-test p < 0.02). As a partial control for practice effects, three new web pages were posted during 2007 for measurements with verbs, proper names, and uncommon nouns to determine if weekly practice with the initial word bank might have caused score improvement. Scores were equally high or higher for the three new (unpracticed) word sets.
(1) Regular blueberry consumption and/or weekly practice apparently improve ability to recall practiced words and also words that have not been practiced. Determining the relative contributions of practice and blueberries requires a much larger randomized, controlled study.
(2) Individual participants are able to generate data sets that reach 95% confidence for year-to-year changes that occur during aging or that may be produced by foods which stimulate neurogenesis.