Cell Phone Use Affects Brain Glucose Metabolism

http://www.medscape.com/viewarticle/737860
Susan Jeffrey

February 23, 2011 — Use of a cell phone for as little as 50 minutes at a time appears to affect brain glucose metabolism in the region closest to the phone's antenna, a new study shows.

Investigators used positron emission tomography (PET) during cell phone use in the on and then off positions and found that although whole-brain metabolism was not affected, metabolism was increased in the orbitofrontal cortex and the temporal pole areas of the brain while the cell phone was on, areas that are close to where phone's antenna meets the head.

Dr. Nora Volkow

"We do not know what the clinical significance of this finding is, both with respect to potential therapeutic effect of this type of technology but also potential negative consequences from cell phone exposure," said lead study author Nora D. Volkow, MD, from the National Institute on Drug Abuse in Bethesda, Maryland, during a teleconference.

In the interim though, she recommends using hands-free devices or speaker-phone mode to avoid direct contact of the telephone with the head. Previous work suggests that if the phone is a foot or more away it is very unlikely to have any effects, she said. "So there are some very easy solutions that don't cost anything for those who want to play it safe."

Caution may be particularly necessary for children and adolescents whose neural tissue is still developing, Dr. Volkow noted. This is also a population who started their lives with cell phones and can expect to be exposed for years to come, she added.

Their report appears in the February 23 issue of the Journal of the American Medical Association.

Effect of Imaging Tools?

The proliferation of cell phone use has raised the question of the effects of radiofrequency-modulated electromagnetic fields (RF-EMFs), particularly carcinogenic effects. Epidemiologic studies looking at the relationship between cell phones and brain tumors have been inconsistent with some, but not all, studies finding increased risk, "and the issue remains unresolved," the study authors write.

Dr. Volkow is well known for her work in the area of addictions, not generally adverse effects of cell phone use, but this new study nevertheless stemmed from that research, she said. They have been studying whether imaging technologies, including PET and magnetic resonance imaging (MRI), that are used to study the brain can directly affect brain function. "For the past 15 years, we've done a series of studies to try to actually assess whether magnetic fields affect brain glucose metabolism," Dr. Volkow explained.

They found, for example, that the static magnetic field of a 4-T MRI does not affect brain metabolism, she said. However, when the magnetic fields were changed rapidly, which produces electrical currents, there was a significant increase in glucose metabolism in the brain. They wondered whether the RF-EMFs produced by cell phones might do the same thing.

The current study was a randomized, crossover study that enrolled 47 healthy, community-dwelling subjects. All underwent PET with (¹⁸F)fluorodeoxyglucose injection twice for 50 minutes at a time, once with a cell phone at each ear but only the right phone on, although it was muted, and once with both cell phones off.

They found that whole brain metabolism was not significantly different with the phone on vs off. However, metabolism in the regions closest to the antenna, the orbitofrontal cortex and temporal pole, was significantly higher when the cell phone was on.

Table. Brain Metabolism in Area Closest to Antenna With Cell Phone On vs Off

Endpoint	On Mode	Off Mode	Mean Difference (95% CI)	P
Metabolism in area closest to antenna, μmol/100 g per minute	35.7	33.3	2.4 (0.67 – 4.2)	.004

CI = confidence interval

The difference between off and on modes was about a 7% increase in glucose metabolism, within the range of physiologic activation during speaking, for example, she said.

The increases in activation also correlated significantly with the estimated electromagnetic field amplitudes for both absolute metabolism (R = 0.95) and for normalized metabolism (R = 0.89, P < .001 for both).

It's possible that the activation would be even higher in subjects who are actually talking on the phone, but in this study they did not want the subjects to talk during imaging, which might have activated other brain areas and confounded the cell phone's effects, she said.

Unfortunately, Dr. Volkow noted, these findings don't shed any light on the controversy of whether cell phone exposure produces or does not produce cancer. "What it does say to us is that the human brain is sensitive to this electromagnetic radiation," she said. Whether this has any negative consequences needs to be evaluated.

They powered the study to detect even small effects, Dr. Volkow added. If they had not seen any effect after 50 minutes of exposure, "it would have been much easier to dismiss any concern about potential negatives of cell phones," she said. "But the fact that we are observing changes really highlights the need to do the studies to be properly able to answer the question of whether cell phone exposure can have harmful effects or not."

It's also possible that if there may be beneficial effects, she speculated. "Could one use, for example, this type of technology to activate areas of the brain that may not be properly activated and explore potential therapeutic applications of this type of technology? But that would require that one show there are no untoward effects."

Add to the Concern

In an editorial accompanying the publication, Henry Lai, PhD, from the Department of Bioengineering at the University of Washington, Seattle, and Lennart Hardell, MD, PhD, from the Department of Oncology at University Hospital, Orebro, Sweden, point out that this is the first investigation in humans of glucose metabolism in the brain after cell phone use.

"The results by Volkow et al add to the concern about possible acute and long-term health effects of radiofrequency emissions from wireless phones, including both mobile and cordless desktop phones," they write.

"Although the biological significance, if any, of increased glucose metabolism from acute cell phone exposure is unknown, the results warrant further investigation."

The effects are unlikely to be mediated by the substantial increase in temperature seen with cell phones given the activation was "quite distant" from where the cell phone made contact, they speculate. Further, since the subjects were only listening rather than talking on the phone, "the effect observed could thus potentially be more pronounced in normal-use situations."

The study was supported by the Intramural Research Program of the National Institutes of Health and by infrastructure support from the US Department of Energy. The researchers and editorialists have disclosed no relevant financial relationships.

JAMA. 2011;305:808-814, 828-829.

Vitamin D and Calcium Supplementation Reduces Fracture Risk

http://www.medscape.com/viewarticle/755764?src=mpnews&spon=34

Joe Barber Jr, PhD

December 19, 2011 — Combined supplementation with vitamin D and calcium can reduce the risk for fracture, according to the findings of a meta-analysis.

Mei Chung, PhD, MPH, from Tufts Medical Center in Boston, Massachusetts, and colleagues published their findings in the December 20 issue of the Annals of Internal Medicine.

The authors mention that active forms of vitamin D participate in a number of biological processes in addition to their indirect effects on bone mineralization. "For example, as recently noted, 1,25-(OH)2D inhibits parathyroid hormone secretion and promotes insulin secretion, inhibits adaptive immunity and promotes innate immunity, and inhibits proliferation and stimulates differentiation of cells," the authors write. "These functions suggest a possible role of vitamin D in cancer prevention."

In this meta-analysis, the authors included 137 studies to address 4 questions regarding the effects of vitamin D supplementation on fracture and cancer risk. Compared with placebo, combined vitamin D and calcium supplementation reduced the risk for fracture (pooled relative risk ratio, 0.88; 95% confidence interval [CI], 0.78 - 0.99), although vitamin D supplementation alone did not reduce this risk (pooled relative risk ratio, 1.03; 95% CI, 0.84 - 1.26). The effect of combined vitamin D and calcium supplementation was significantly stronger in the institutional setting than in the community setting (institutional setting: relative risk ratio, 0.71 [95% CI, 0.57 - 0.89]; community setting: relative risk ratio, 0.89 [95% CI, 0.76 - 1.04]; P = .07).

The authors searched the MEDLINE and Cochran Central Register of Control Trials databases through July 2011 for studies limited to human participants, published in English-language journals. The search terms included vitamin D, 25-hydroxyvitamin D, calcium, and text terms and Medical Subject Heading terms related to cancer or neoplasms, fracture, and bone mineral density.

Compared with placebo, randomized controlled trials reported hazard or risk ratios for the incidence and mortality of colorectal, breast, or total cancer ranging from 0.55 to 1.09. Among randomized controlled trials evaluating combined vitamin D and calcium supplementation vs placebo regarding cancer risk, a trend of no effect of supplementation was identified, although one smaller study reported that combined vitamin D and calcium supplementation reduced the incidence of total cancer by 60% (95% CI, 18% - 80%).

Despite the findings of this meta-analysis, the authors mention that challenges remain in confirming the benefits of vitamin D supplementation in the general population. "No methods are currently available to quantify the contribution of endogenous vitamin D synthesis resulting from sun exposure on an individual or a group, and serious limitations remain in accurately estimating dietary vitamin D intake because of the incompleteness of nutrient databases for both vitamin D–fortified food and vitamin D supplements," the authors state.

"Future study is needed to evaluate the appropriate dose and dosing regimens of vitamin D supplementation for bone health outcomes."

The study and several authors were supported by the Agency for Healthcare Research and Quality. The authors have disclosed no relevant financial relationships.

Ann Intern Med. 2011;55:827-838.

First Data to Show Antihypertensive Therapy Prolongs Life

http://www.medscape.com/viewarticle/755802?src=mpnews&spon=34
Lisa Nainggolan

December 20, 2011 (New Brunswick, New Jersey) — The first long-term data from a high-blood-pressure study, the Systolic Hypertension in the Elderly Program (SHEP), show that each month of chlorthalidone-based therapy was associated with approximately one day of extension in life, free from cardiovascular death [1].

"The main findings are that after 22 years of follow-up, when about 60% of the participants in SHEP were dead, we saw a prolonged life expectancy in those who took the active treatment for 4.5 years, and that is the first time this has been reported in studies of hypertension, because you have to wait a long time to find out differences in life expectancy," lead author Dr John B Kostis (UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ) told heartwire . "In hypertension trials, by the time everybody dies, the investigators have died," he added.

In hypertension trials, by the time everybody dies, the investigators have died.

The study "is a strong message that may result in increased patient adherence to drug therapy and decrease the degree of therapeutic inertia by healthcare providers," he and his colleagues say in their paper in the December 21, 2011 issue of the Journal of the American Medical Association.

Kostis cautions, however, that the gains relate primarily to CVD avoidance and that "everyone has to die from something," but he points out that other benefits of antihypertensive treatment, such as preventing strokes, could arguably be even more important than prolonging life.

SHEP Participants Were 72, on Average, When They Entered the Trial

The SHEP trial was conducted between March 1985 and January 1988, and just over 4700 patients aged, on average, 72 years were randomized to active treatment with chlorthalidone--with atenolol added if antihypertensive control was not sufficient--or placebo for 4.5 years. After this time, all patients were asked to go on active therapy.

At 22 years later, life-expectancy gain--expressed as the area between the active and placebo survival curves--was 105 days for all-cause mortality and 158 days for cardiovascular death.

The active-treatment group had higher survival free from cardiovascular death vs the placebo group (hazard ratio 0.89; p=0.03), but similar survival for all-cause mortality (HR 0.97; p=0.42).

There were 1416 deaths (59.9%) in the active-treatment group and 1435 in the placebo group (60.5%). But cardiovascular death was lower in the active-treatment group--669 deaths (28.3%) vs 735 deaths (31.0%) in the placebo group (p=0.03).

Time to 70^th-percentile survival was 0.56 years longer in the active-treatment vs the placebo group for all-cause mortality and 1.41 years for survival free from CV death.

Stroke Prevention One of Key Messages

Kostis stresses, therefore, that the gains in life expectancy relate mainly to CVD. "If you do not die from CVD then you have more chance to die from other conditions. We found the CVD benefit was much higher than the overall benefit, because non-CV causes [of death] were more common in people treated [with antihypertensive therapy] at the beginning of SHEP.

If you start therapy early and live 20 more years, you will be productive and enjoy life.

"We all die, and if you don't die from heart disease you have the opportunity of dying from something else. Immortality hasn't been achieved yet in humans," he noted.

But, he believes, "it's better to live an extra year, then die from cancer." And he points out that other benefits of antihypertensive therapy, such as preventing strokes, are perhaps even more important. "Preventing one stroke has many implications other than life expectancy; stroke is a terrible thing."

Another key message from this trial is that the earlier therapy is started the better, says Kostis. "These patients happened to be elderly; they were 72, on average, when they were enrolled in this trial. But if you start treatment earlier you would have even better benefit. If you start therapy early and live 20 more years, you will be productive and enjoy life."

Kostis reported receiving grant support and travel to meetings from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Aging (NIA). Disclosures for the coauthors are listed in the paper.