Can Vitamin D Treat Pain?

Women with dysmenorrhea who take a single high dose of vitamin D suffer much less menstrual pain and have no need of pain medications for any reason for up to 2 months, a new study has found.

“To our knowledge, this is the first study investigating the effect of a single high dose of vitamin D in primary dysmenorrhea,” wrote the study authors, led by Antonino Lasco, MD, from the Department of Internal Medicine, University of Messina, Italy.

“Our data support the use of cholecalciferol in these patients, especially when exhibiting low plasmatic levels of 25(OH)D [25-hydroxyvitamin D],” they write.

The study is published February 27 in the Archives of Internal Medicine.

Pain Trigger

Dysmenorrhea affects almost one half of menstruating women. The pelvic pain is believed to be triggered by excessive uterine production of prostaglandins, synthesized from omega-6 fatty acids before menses, that control vasoconstriction and uterine contractions.

According to the study authors, vitamin D may act as an anti-inflammatory and may regulate the expression of key genes involved in the prostaglandin pathway, causing decreased biological activity of prostaglandins.

The study included 40 women aged 18 to 40 years who had experienced at least 4 consecutive painful menstrual periods in the past 6 months and had a 25(OH)D serum level below the upper limit of the lowest quartile (<45 ng/mL). They were not taking calcium, vitamin D, oral contraceptives, or other medications, and they had not used an intrauterine contraceptive device during the previous 6 months.

The participants could use other means of birth control, however. They were also allowed to use nonsteroidal anti-inflammatory drugs (NSAIDs) as needed, but they had to record their use of these agents.

The women were randomly assigned to receive a single oral dose of 300,000 IUs of vitamin D (cholecalciferol) or placebo 5 days before the time they expected to begin their next menstrual period.

The primary outcome was intensity of menstrual pain as measured by a visual analog scale. The secondary outcome was use of NSAIDs.

After 2 months, baseline pain scores decreased 41% among women in the vitamin D group; there was no difference in scores among women taking placebo (P < .001). The greatest reduction in pain was among women in the vitamin D group who had the most severe pain at baseline (r = -0.76; P < .001)

During the study, none of the women in the vitamin D group needed NSAIDs to manage pain at 1 and 2 months, whereas 40% of those taking placebo used an NSAID at least once (P = .003).

Implications for Chronic Pain?

In an accompanying commentary, Elizabeth R. Bertone-Johnson, ScD, from the Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, and JoAnn E Manson, MD, from the Division of Preventive Medicine, Department of Epidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, said the study provides support for larger randomized trials of vitamin D for treating pain-related conditions in women.

Chronic widespread pain and fibromyalgia syndromes are more prevalent in women, "likely owing to the influence of sex steroid hormones," they write.

This future research, they write, must address several key issues.

"First, it is important to know how long reductions in pain associated with a single high-dose vitamin D therapy would persist and how often treatment would need to be repeated," the editorialists write. They point out that each dose would need to be effective for a lengthy period for average daily intake to remain below recommended upper limits.

Because many women will experience dysmenorrhea for several years until menopause, follow-up of participants in vitamin D trials must be extended to better evaluate adverse effects and to compare risks and benefits, they note.

The editorialists also note that it remains unknown whether vitamin D would improve dysmenorrhea pain in women with higher 25(OH)D levels.

"If these findings are confirmed in future randomized trials, vitamin D supplementation may become an important new treatment option for women who experience menstrual pain disorders," they conclude. "In the meantime, encouraging all women to obtain the recommended dietary allowance for vitamin D (≥600 IU/d for women of reproductive age), as well as screening for low serum 25(OH)D levels among women with other risk factors for vitamin D deficiency, would be a rational interim approach."

Pain Site

Approached for comment, Clifford Lo, MD, PhD, Director, Harvard Human Nutrition Program, and Medical Education Coordinator, Harvard Medical School Division of Nutrition, said that although the numbers were small, there was a convincing difference between the placebo and vitamin D groups in the study.

However, although it is plausible that vitamin D affects prostaglandins, the study did not specify which prostaglandin or which pain site might be involved, said Dr. Lo, whose research interests include vitamin D metabolism.

The study proposes an interesting possible mechanism, "but that's certainly not good enough for me to say that this is a good treatment for pain," said Dr. Lo. "It's very premature to say it's something we should use."

Pain associated with dysmenorrhea is generally subjective and not easily measured, he added. It is difficult to make conclusions about the effect an agent will have on pain when there is "no convincing biomarker" for the pain, as was the case with this study, said Dr. Lo.

The 300,000 IU dose of vitamin D used in the study is probably harmless if taken every month or 2, and even perhaps every week, but it could cause hypercalcemia if taken daily, said Dr. Lo. The typical vitamin D dose is 400 to 1000 IU/day.

Dr. Lo pointed out that because the participants in the study had vitamin D levels below 45 ng/mL, they were not exactly deficient in vitamin D to begin with. "Most people would say that you're not deficient until you're below 20 ng/ml," he said. "I would say that half the American population is below 30 ng/mL."

Arch Intern Med. 2012;172:366-367, 367-369.

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Istilah migren berasal dari pemakaian kata hemicrania oleh Galen sekitar 200 M, untuk melukiskan suatu kelainan periodik yang terdiri atas nyeri hemikranial yang paroksimal serta mengganggu penglihatan, vomitus fotofobia, berulang dengan interval teratur dan mereda ketika keadaan sekeliling tenang.^{1, 2,} 

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   Epilepsi merupakan masalah penting baik dipandang dari sudut ilmu kedokteran maupun sosial, diperkirakan bahwa diseluruh dunia terdapat lebih dari dua puluh juta orang dengan epilepsi, akan tetapi hanya sebagian kecil para penderita tersebut yang telah dapat menikmati pengobatan secara optimal.

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Flavanones in Citrus Fruit May Lower Stroke Risk

High intake of flavanones, a subclass of flavonoids found in the greatest concentrations in oranges and grapefruit, is associated with a 19% lower risk for ischemic stroke in women, a new analysis from the Nurses’ Health Study has shown. 

Although oranges are the best source of flavanones, North Americans tend to drink the juices of these fruits, lead author Aedín Cassidy, PhD, professor, nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom, told Medscape Medical News.

However, because commercial juices often contain sugar that may increase diabetes risk, she said, "our advice would be to eat more of the citrus fruits as opposed to product made from the citrus fruits."

Much of the recent evidence has focused on vitamin C, Dr. Cassidy added. "What we’re showing here is that there are other bioactive constituents in citrus fruits that may be responsible for this cardioprotective effect."

The results are published online February 23 in Stroke.

Cumulative Intake

This analysis used data from the Nurses’ Health Study on 69,622 participants who completed food-frequency questionnaires (FFQs) every 4 years. The 1990 FFQ was used as a baseline and included dietary intake data collected over the next 14 years.

Researchers used a state-of-the-art food database to examine 6 commonly consumed flavonoids: flavanones (including eriodictyol, hesperetin, and naringenin), anthocyanins, flavan-3-ols, flavonoid polymers, flavonols, and flavones. To arrive at intakes of individual compounds, they multiplied the sum of the consumption frequency of each food by the content of the specific flavonoid of a specified portion size. They averaged the intake for the current and preceding FFQ to determine the cumulative intakes (energy adjusted) for a given questionnaire cycle.

A diagnosis of stroke was confirmed from medical records. Researchers categorized strokes into ischemic, including embolic or thrombotic; hemorrhagic, including subarachnoid or intraparenchymal stroke; and unknown. Over the course of the study, 1803 strokes occurred; 943 of these were ischemic, 253 were hemorrhagic, and 607 were of unknown type.

The baseline median intake of total flavonoids (quintile 3) was 232 mg/d; the lowest intake (quintile 1) was 96.8 mg/d, and the highest (quintile 5) was 761.2 mg/d.

Tea was the main contributor to total flavonoid intake, with apples and oranges/orange juices also contributing significant amounts. Blueberries were the main source of anthocyanins, and oranges and orange juice were the main contributors to flavanone and flavone intake.

The study found that flavanone intake was inversely related to the risk for ischemic stroke. After adjustment for stroke risk factors, such as age, body mass index, physical activity, alcohol consumption, menopausal status, smoking, and history of type 2 diabetes, women in the top quintile of flavanone intake had a relative risk of 0.81 (95% confidence interval [CI], 0.66 - 0.99; P for trend = .04) compared with women in the bottom quintile. Further adjustment for calcium or magnesium intakes did not greatly alter the results.

Highest intake of citrus fruits/juices, which represent the main dietary source of flavanones, also tended to be associated with a reduced risk for ischemic stroke, with a relative risk of 0.90 (95% CI, 0.77 - 1.05).

Vitamin C

In this analysis, the addition of vitamin C to the statistical model did not substantially change the relationship between flavanones and ischemic stroke risk. "That’s not to say vitamin C isn’t important," stressed Dr. Cassidy. "We know that vitamin C may be one of the constituents responsible for the effect, but here’s some evidence that suggests that perhaps there are other components in citrus fruits that also may be responsible."

Animal and in vitro experiments have shown that the flavanones naringenin and hesperetin have anti-inflammatory and neuroprotective effects. "Some of these compounds can cross the blood-brain barrier so they are actually getting to the brain," said Dr. Cassidy.

There’s growing interest in the protective qualities of flavonoids, and with it progressively more sophisticated food databases that cover the wide range of flavonoids in the diet.

"About 5 years ago, people would have been publishing on flavonoids, but only on 2 or 3 of the subclasses," Dr. Cassidy noted. "Here we have an as-good-as-we-can-get database on 6 different subclasses. If you do large population-based study like this one, this can really help to generate hypotheses."

Using such a database can help further the understanding of possible mechanisms, dose effects, and optimal sources of various flavonoids, she added. The study found only a modest, and nonsignificant, inverse association between a higher intake of flavones and anthocyanins and the risk for total and ischemic stroke. There was no evidence of a link between flavones and stroke risk.

The lack of association between some flavonoids and stroke was somewhat surprising because there is evidence that dark chocolate, which contains these compounds, has positive effects on blood pressure, blood flow, and vascular and heart function, said Dr. Cassidy. "We assumed that they also may well have had effect on stroke risk, but we didn’t find that in these data sets."

The study found no association between any of the flavonoids and hemorrhagic stroke.

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Diet Soda Tied to Heart Attack, Stroke Risks

Diet soda may benefit the waistline, but a new study suggests that people who drink it every day have a heightened risk of heart attack and stroke.

The study, which followed almost 2,600 older adults for a decade, found that those who drank diet soda every day were 44% more likely than non-drinkers to suffer a heart attack or stroke.

Of course, the findings, reported online January 27 in the Journal of General Internal Medicine, don't prove that the sugar-free drinks are actually to blame.

There may be other things about diet-soda lovers that explain the connection, researchers say.

"What we saw was an association," said lead researcher Dr. Hannah Gardener, of the University of Miami Miller School of Medicine. "These people may tend to have more unhealthy habits."

She and her colleagues tried to account for that, Gardener told Reuters Health.

Daily diet-soda drinkers did tend to be heavier and more often have heart risk factors like high blood pressure, diabetes and unhealthy cholesterol levels.

That all suggests that people who were trying to shed pounds or manage existing health problems often opted for a diet soda over the sugar-laden variety.

But even after the researchers factored in those differences -- along with people's reported diet and exercise habits -- they found that daily diet soda was linked to a 44% higher chance of heart attack or stroke.

Nevertheless, Dr. Gardener said, it's impossible for a study to capture all the variables that could be at work.

The findings do build on a few recent studies that also found diet-soda drinkers are more likely to have certain cardiovascular risk factors, like high blood pressure or high blood sugar.

This is the first study, Dr. Gardener said, to look at actual vascular events.

The findings are based on 2,564 New York City adults who were 69 years old, on average, at the outset. Over the next decade, 591 men and women had a heart attack, stroke or died of cardiovascular causes.

That included 31% of the 163 people who were daily diet-soda drinkers at the study's start. In contrast, 22% of people who rarely or never drank diet soda went on to have a heart attack or stroke.

There was no increased risk linked to less-than-daily consumption. Nor was regular soda tied to heart attacks and strokes.

If diet soda, itself, somehow contributes to health risks, it's not clear how, Dr. Gardener said.

There's research in rats suggesting that artificial sweeteners can end up boosting food intake and weight. But whether results in rodents translate to humans is unknown.

"I don't think people should change their behavior based on this study," Dr. Gardener said. "And I wouldn't advocate drinking regular soda instead."

Regular soda is high in calories, and for people who need to shed pounds, experts often suggest swapping regular soda for the diet version.

A study out this month found that the advice may be sound. Obese people who were randomly assigned to drink water or diet drinks in place of sugary ones lost about five pounds over six months.

Dr. Gardener said that further studies such as hers are still needed to confirm a connection between diet soda and cardiovascular trouble.

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Practice Guideline Effective in Community-Acquired Pneumonia

Use of a clinical practice guideline (CPG) for community-acquired pneumonia (CAP) led to increased use of ampicillin, which is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP, according to the results of a retrospective study reported in an article published online February 20 in Pediatrics. 

"[CAP] is a common pediatric illness caused by Streptococcus pneumoniae," write Ross E. Newman, DO, from the Department of Pediatrics, University of Missouri–Kansas City School of Medicine, Children's Mercy Hospitals and Clinics, and colleagues. "New pediatric Infectious Diseases Society of America CAP guidelines are now available recommending ampicillin as empirical treatment of children hospitalized with uncomplicated CAP."

The study goal was to assess the effect of implementing a CPG on antibiotic treatment of children hospitalized with CAP. The study sample consisted of patients admitted to a children's hospital from July 8, 2007, through July 9, 2009, and discharged with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code for pneumonia (480–486). This period began 12 months before and ended 12 months after introduction of the CAP CPG. The investigators used 3-stage least squares regression analyses to evaluate the effect of their institution's antimicrobial stewardship program (ASP) and other hypothesized simultaneous associations.

Of 1033 patients included in the final analysis, 530 (51%) were admitted before CPG implementation, and 503 (49%) were admitted after CPG implementation. The most commonly prescribed antibiotic before CPG implementation was ceftriaxone (72%), followed by ampicillin (13%); ampicillin was the most commonly prescribed antibiotic after CPG implementation (63%).

The effect of the CPG was associated with a 34% increase in ampicillin use, and the combined effect of the CPG and ASP was associated with a 12% increase in amoxicillin use at hospital discharge and a 16% decrease in cefdinir and amoxicillin/clavulanate use (P < .001 for all). During both study periods, treatment failure was infrequent (1.5% before CPG implementation and 1% after CPG implementation).

"A CPG and ASP led to the increase in use of ampicillin for children hospitalized with CAP," the study authors write. "In addition, less broad-spectrum discharge antibiotics were used. Patient adverse outcomes were low, indicating that ampicillin is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP."

There was less compliance with other guideline recommendations, however. Obtaining blood cultures in all hospitalized children, for example, was recommended by the CPG, but the rate of blood culture draws in this population remained the same before and after the CPG (56% vs 54%; P = .4).

Limitations of this study include retrospective chart review, use of ICD-9 codes to identify patients with suspected uncomplicated CAP, and failure of the analysis to capture patients who experienced treatment failure and sought care at other institutions or had primary care physicians expand antimicrobial coverage for continued symptoms.

"Because CAP is a common pediatric condition, the use of a narrow-spectrum agent is important in preventing the further development of antibiotic resistance," the study authors conclude. "Second, although providers were willing to follow CPG recommendations for empirical antibiotic choices, other recommendations were not followed, including length of therapy and obtaining blood cultures. Finally, CPGs should be continually monitored and evaluated to ensure successful implementation, utilization, and revisions when required."

Three of the study authors were supported by a grant from the Agency for Healthcare Research and Quality.

 

Pediatrics. Published online February 20, 2012. Abstract

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Hipertensi Ensefalopati

Latar Belakang

Hipertensi sampai saat ini merupakan masalah penting dalam dunia kesehatan karena prevalensinya yang tinggi dan komplikasi jangka panjang yang diakibatkannya. Budi Darmojo dalam laporan penelitiannya menyatakan bahwa 1,8–28,6% penduduk yang berusia di atas 20 tahun adalah penderita hipertensi, dan umumnya prevalensi hipertensi berkisar sekitar antara 8,6–10%. Dari penelitian yang ada terlihat kecenderungan bahwa masyarakat perkotaan lebih banyak menderita hipertensi dibanding masyarakat pedesaan. Jika dibanding antara wanita dan pria ternyata wanita lebih banyak menderita hipertensi. ^{( 1 )}

Hipertensi apabila tidak ditangani dengan baik akan menyebabkan berbagai macam komplikasi. Apabila tekanan darah meningkat dengan cepat dapat terjadi kerusakan pada target organ yaitu otak, mata, jantung, ginjal, dan pembuluh darah lainnya yang dapat mengancam jiwa penderita, maka keadaan ini dikenal sebagai kegawat daruratan hipertensi atau hipertensi krisis. ^{( 2, 3 )}

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