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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
March 2, 2013

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Nurse Observers Increase Polyp Detection
Technique to Magnify Motion on Video May Have Uses in Medicine
Job Strain Isn't Associated with Elevated Risk for Cancer
Time Magazine Cover Story Tackles High Cost of Healthcare
Nonsteroidal Anti-Inflammatory Drug-Associated Kidney Injury in Children
Fever Spike? Look at the Food Tray
Uptick in Advanced Breast Cancer Among Young Women
Novel Drug Approved for HER-2 Positive Advanced Breast Cancer
Estrogen-Like Drug Approved for Menopause-Related Vulvovaginal Atrophy
Mediterranean Diet Lowers Cardiovascular Events in People at Risk
Major Psychiatric Disorders Linked to Genes Involved with Brain's Calcium Balance
USPSTF: Postmenopausal Women Shouldn't Take Calcium and Vitamin D to Prevent Fractures
High Calcium Intake Is Associated with Earlier Mortality in Women
Vitamin D and Calcium Supplementation in Women: Making Sense of Conflicting Data
Vitamin D and Calcium: What Women Need at Midlife and After

MM: There is no question that an extra set of eyes will invariably find more irregularities. Just like it's usually a good idea to get a 2nd opinion when there is a difficult or controversial issue. The only downside to this is that more irregularities are being noticed but how many of these discoveries will lead to wasted efforts and added expense that yields no benefit in order to see a single life saved? One can use the argument that saving a life should not have a price tag attached to it but unfortunately reality steps in and says that in order to save the most lives, it may not be in society's best interest to discover every irregularity. In other words, can we truly afford it?
Am J Gastroenterol 2013 Feb; 108:166
Nurse Observers Increase Polyp Detection
Further evidence that two pairs of eyes are better than one during colonoscopy.
Several studies have suggested that performing colonoscopy with a second observer, such as an endoscopy fellow or nurse, increases polyp detection (Gastrointest Endosc 2011; 71:1223 and JW Gastroenterol Jan 13 2012), but others have found no association (Dis Colon Rectum 2009; 52:1337).
In the current study, 502 patients were randomized to undergo a screening colonoscopy by an endoscopist only (control group) or with the addition of an endoscopy nurse as a second observer. Nineteen endoscopy nurses with a mean of 8.2 years of experience participated. Sessile serrated polyps were categorized as adenomas.
The number of adenomas found in the nurse observer group was 0.82 per colonoscopy compared with 0.64 in the control group, representing a 28% increase in mean number of adenomas detected in the nurse observer group (P=0.02). The adenoma detection rate was also higher in the nurse observer group, but the difference was not significant (47.0% vs. 40.7%). Detection by polyp location (right vs. left colon) was similar between groups. Nurse-observed colonoscopies tended to detect higher proportions of nonpedunculated polyps and also both benign and advanced lesions. Nurses detected 40 individual lesions that had not been seen by the endoscopist.
Comment: Overall, the evidence suggests that two observers during colonoscopy are better than one, although this effect might turn out to be endoscopist-specific. The mechanisms by which two observers increase detection are still uncertain. Possibilities include better viewing of the screen by the observer or a more careful examination by the endoscopist, who might compete to avoid any embarrassment associated with missed lesions. Regardless, the effect appears to be a positive one for patient care.
Douglas K. Rex, MD Published in Journal Watch Gastroenterology March 1, 2013
Citation(s): Aslanian HR et al. Nurse observation during colonoscopy increases polyp detection: A randomized prospective study. Am J Gastroenterol 2013 Feb; 108:166.

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MM: This is one of those cool geek things that I love so much. Check out the video in the link from the New York Times
Technique to Magnify Motion on Video May Have Uses in Medicine
By Joe Elia
A new technique developed at MIT allows amplification of small motion and color changes on video images. This could enable the measurement of heart rates in newborn nurseries, for instance, without having to connect the patient to monitors.
As shown in a New York Times video, the technology allows the real-time manipulation of video data — both color and motion. The coursing of blood through the skin in rhythm with the pulse is apparent. The algorithm is available free for noncommercial use.
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/301/5#sthash.g9b5KvMm.dpuf
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MM: It has been argued that some stress is a good thing. Unfortunately many of us are under chronic, unrelenting stress and that (hopefully small) segment of the population very well may be at increased risk for cancer. This study looks at a substantial population but it fails to look at those who are under the most stress and compare that to the norm.
BMJ 2013 Feb 7; 346:f165
Job Strain Isn't Associated with Elevated Risk for Cancer
No association was found for colorectal, lung, breast, or prostate cancer.
Psychological stress prompts physiological responses (e.g., release of stress hormones), which might trigger cancer-promoting effects. However, whether stress is associated with cancer is unclear. In this meta-analysis of 12 prospective European studies, researchers examined whether work-related stress is associated with cancer risk.
The analysis included 116,000 working adults (age range, 17–70) who were cancer-free at baseline. Self-reported job strain (defined as high demands and low control at work) was measured at baseline using a validated questionnaire. During a mean follow-up of 12 years, nearly 5% of participants developed cancer. In analyses adjusted for multiple confounders (including socioeconomic status, smoking, and alcohol use), job strain was not associated with overall cancer risk or with risk for colorectal, lung, breast, or prostate cancer. No combination of work demand (high vs. low) and control (high vs. low) was associated with overall cancer risk.
Comment: In this study, job strain was not associated with elevated risk for cancer. However, job strain is not entirely benign — the same investigators reported an association between job strain and risk for myocardial infarction and coronary death (Lancet 2012; 380:1491).
Paul S. Mueller, MD, MPH, FACP  Published in Journal Watch General Medicine February 28, 2013
Citation(s): Heikkilä K et al. Work stress and risk of cancer: Meta-analysis of 5700 incident cancer events in 116 000 European men and women. BMJ 2013 Feb 7; 346:f165.
- See more at: http://general-medicine.jwatch.org/cgi/content/full/2013/228/4?q=

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MM: As Americans, we tend to spend significantly more than any other society on healthcare. This shows its greatest skew in expenditure on those over 70. Yet, we tend to provide a lower overall quality of life and healthcare for our elderly when compared to what other societies are doing for their elderly. One of the big reasons for this lopsided expenditure is the huge number of tests and procedures that are performed at "end of life".
Time Magazine Cover Story Tackles High Cost of Healthcare
By Kelly Young
In Time magazine's cover story this week, author Steven Brill asks a question most patients have had to confront: "Why exactly are the bills so high?"
He notes that the U.S. spends more on healthcare than the next 10 biggest-spending nations combined.
Brill spent 7 months analyzing bills from hospitals, doctors, drug companies, and other healthcare firms. He delves into how a hospital's chargemaster sets prices for everything, like $1.50 for a single Tylenol tablet and $283 for a chest x-ray.
Meanwhile, one nonprofit hospital operates with a profit margin of 26%, and hospital CEOs often have higher salaries than the presidents of their affiliated universities.
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/228/2#sthash.aEfZ40p2.dpuf
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MM: For many years we have worked under the premise that we should alternate doses of NSAIDs like ibuprofen and acetaminophen (Tylenol(R)) in order to fight a fever in a child. This study indicates that this may not have been the best approach. Maybe a cool bath would be a better choice?
J Pediatr 2013 Jan 28
Nonsteroidal Anti-Inflammatory Drug-Associated Kidney Injury in Children
NSAIDS were associated with acute kidney injury even at recommended doses.
Many drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), can lead to serious kidney injury. To describe NSAID-associated acute kidney injury (AKI) in children, researchers in Indiana retrospectively reviewed medical charts of 1015 children (age, <18 years) who were admitted to a children's hospital with AKI (elevated serum creatinine and elevated glomerular filtration rate [eGFR] <75 mL/min/1.73 m2) in January 1999 through June 2010. NSAID-associated AKI excluded children with comorbid conditions, multifactorial AKI, or alternate cause of AKI.
In all, 27 children (2.7%) had NSAID-associated AKI; 67% had used ibuprofen, 78% had used NSAIDs for <7 days, and 75% had received recommended dosing. The most common presenting symptoms were vomiting, abdominal pain, and decreased urine output. A history of volume depletion (dehydration) was reported in 67%. Five children were admitted to the intensive care unit and four patients (all aged <5 years) required dialysis. Findings of kidney biopsies in 11 patients included acute interstitial nephritis, acute tubular necrosis, or both.
Comment: Nonsteroidal anti-inflammatory drugs are used frequently in children but exposure to these drugs increases risk for kidney injury, even at recommended doses. The risk is even higher when children are dehydrated.
F. Bruder Stapleton, MD  Published in Journal Watch Pediatrics and Adolescent Medicine February 27, 2013
Citation(s): Misurac JM et al. Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children. J Pediatr 2013 Jan 28; [e-pub ahead of print].
- See more at: http://pediatrics.jwatch.org/cgi/content/full/2013/227/1?q=etoc_jwpeds#sthash.BWsdSOC1.dpuf
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J Hosp Med 2012 Nov/Dec; 7:702
Fever Spike? Look at the Food Tray
Febrile hospitalized patients with normal food intake have a low likelihood of bacteremia.
Fever in hospitalized patients is a nonspecific finding that can have many causes including infection, inflammatory diseases, malignancy, thromboembolism, endocrine disorders, and drug reactions. Predicting the presence of bacteremia based on clinical examination is unreliable, so evaluation typically involves blood cultures, which have relatively low yield and a high false-positive rate from bacterial contamination. Might food consumption be a useful adjunct for predicting bacteremia?
Researchers in Japan performed an observational study in approximately 1200 consecutive patients (age, ≥6 years) who underwent blood cultures primarily for evaluation of fever (axillary temperature >37.5–38.0°C). Patients who were not on regular diets and those with anorexia-inducing conditions (e.g., gastrointestinal disease, cancer with chemotherapy) were excluded. Nurses assessed patients' food consumption at each meal as low (<50% consumed), moderate (50%–80% consumed) or high (>80% consumed). On the basis of food consumption from the meal immediately preceding each blood culture, bacteremia was related inversely to food consumption: 18% of patients in the low-consumption group, versus 4% and 1.5% of patients in the moderate- and high-consumption groups, respectively, had blood cultures that identified bacteremia. The negative predictive value of high consumption for excluding bacteremia was 98%.
Comment: This study is limited because the findings cannot be generalized across different patient populations, and we don't know whether food consumption can be assessed reliably. If the results are validated in various clinical settings, normal food consumption could be helpful in ruling out bacteremia and deciding whether to provide empirical antibiotics to febrile patients.
Neil H. Winawer, MD, SFHM  Published in Journal Watch Hospital Medicine February 15, 2013
Citation(s):  Komatsu T et al. Predicting bacteremia based on nurse-assessed food consumption at the time of blood culture. J Hosp Med 2012 Nov/Dec; 7:702.
- See more at: http://hospital-medicine.jwatch.org/cgi/content/full/2013/215/2?q=etoc_jwid#sthash.u9MA5H73.dpuf
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MM: Could this uptick in breast cancer be associated with the increasing trend of obesity and the concomitant trend in lower vitamin D levels and the persistent trend towards lower Iodine levels in the body? It appears that there may be several contributing factors that have real solutions available. The HCG metabolic syndrome and weight management program could be a very good starting point to stymieing this rise in breast cancer. Combine this with increased vitamin D levels, a daily oral Iodine supplement such as Iodoral (R) along with perhaps the use of Low Dose Naltrexone (LDN) and you suddenly have a program that may be quite beneficial to modulating the immune system and possibly battling cancer risk.
Uptick in Advanced Breast Cancer Among Young Women
By Joe Elia
Breast cancer with remote metastases is occurring with increasing frequency among young U.S. women, a study of federal cancer data published in JAMA shows.
Researchers examined data from the Surveillance, Epidemiology, and End Results (SEER) program. They found the incidence of advanced breast cancer (i.e., with metastases to bone, brain, lung) among 25- to 39-year-olds rose from 1.53 per 100,000 in 1976 to 2.90 in 2009. Rates were higher among blacks, non-Hispanic whites, and those with estrogen receptor–positive tumors.
The authors say that more-sensitive diagnostic tools are unlikely to have caused this uptick, which is continuing and may even be increasing. They urge confirmation of their findings and remind readers that the increase is occurring "in an age group that already has the worst prognosis, no recommended routine screening practice, the least health insurance, and the most potential years of life."
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/227/2#sthash.kboTmOpG.dpuf
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MM: The monoclonal antibody drugs (MAB's) such as those discussed in this article have amazing potential but they almost always carry significant risk. Recent studies have indicated that many people who are "cured" of their cancer and survive are then attached by another unrelated cancer within a few years. Many of these subsequent cancers are due to the treatments that they have received for the original cancer. We need to weigh the risks of all drugs and treatments, irrespective of what they are being used for. Not all ailments require emergency treatment.
Novel Drug Approved for HER-2 Positive Advanced Breast Cancer
By Kristin J. Kelley
Ado-trastuzumab emtansine, an antibody-drug conjugate marketed as Kadcyla, has been approved by the FDA to treat HER2-positive metastatic breast cancer. The drug — known as T-DM1 during clinical trials — is indicated for patients who didn't respond to treatment with the anti-HER2 agent trastuzumab plus chemotherapy.
In a randomized trial of nearly 1000 patients, progression-free survival was longer with T-DM1 than with lapatinib plus capecitabine (9.6 vs. 6.4 months). T-DM1 patients also had fewer grade 3 or 4 adverse events.
The drug will have a boxed warning about the potential risks for heart toxicity, liver toxicity, death, and life-threatening birth defects. Common treatment side effects include constipation, elevated liver enzymes, fatigue, muscle or joint pain, nausea, and thrombocytopenia.
The approval has been "eagerly anticipated," says Journal Watch Oncology and Hematology Editor-in-Chief Dr. William Gradishar. He says he expects that the drug will become "the preferred treatment" in eligible patients.
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/225/1#sthash.OpUeoog1.dpuf
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Estrogen-Like Drug Approved for Menopause-Related Vulvovaginal Atrophy
By The Editors
The FDA has approved ospemifene (Osphena) to treat moderate-to-severe dyspareunia — painful intercourse due to vulvar and vaginal atrophy during menopause.
The drug, to be taken as a pill once a day with food, will carry a boxed warning that it can cause thickening of the endometrium. Women will be advised to consult with a clinician if they experience bleeding. Risks for stroke and deep venous thrombosis are reportedly lower with ospemifene than those seen with estrogen therapy.
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/227/5#sthash.1v4ymDQZ.dpuf
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Mediterranean Diet Lowers Cardiovascular Events in People at Risk
By Cara Adler
A Mediterranean diet, compared with a low-fat control diet, lowered the risk for major cardiovascular events by 30% in people at high risk for cardiovascular disease, according to a New England Journal of Medicine study.
Some 7500 people in Spain with risk factors for cardiovascular disease were randomized to a Mediterranean diet supplemented with extra-virgin olive oil (1 liter per week), a Mediterranean diet supplemented with mixed nuts (30 g per day), or a low-fat diet. Dietitians counseled all participants about how to follow their diet, and compliance was good in all three groups.
After a median follow up of 4.8 years, each of the two Mediterranean diet groups showed a 30% relative reduction in the rate of the primary outcome — myocardial infarction, stroke, or cardiovascular mortality — compared with the control group. Reductions in stroke accounted for most of the benefit.
The authors conclude that their results "support the benefits of the Mediterranean diet for the primary prevention of cardiovascular disease."
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/226/1#sthash.wIRGhXzc.dpuf
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Major Psychiatric Disorders Linked to Genes Involved with Brain's Calcium Balance
By Joe Elia
Five major psychiatric illneses — autism, ADHD, bipolar disorder, depression, and schizophrenia — seem related to calcium-signaling pathways in the brain, according to a Lancet study.
Researchers performed genome-wide analyses on some 30,000 patients with the disorders and a roughly equal number of controls. They identified four genetic variants — all related to calcium signaling — that were significantly associated with the presence of one of the five disorders.
Commentators, noting the importance of calcium signaling to nerve growth and development, conclude that the results could help identify new targets for psychotropic drugs.
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/228/4#sthash.XRiE9zQG.dpuf
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USPSTF: Postmenopausal Women Shouldn't Take Calcium and Vitamin D to Prevent Fractures
By Kelly Young
Postmenopausal women should not take supplementary calcium (1000 mg or less) and vitamin D (400 IU or less) to prevent fractures, the U.S. Preventive Services Task Force says in a new recommendation published in the Annals of Internal Medicine.
The task force says that supplementation at these doses doesn't reduce primary fracture risk, while it does pose a small increased risk for renal stones.
The group concluded that there is not enough evidence to make recommendations for or against higher doses of calcium and vitamin D or for men or premenopausal women.
Marion Nestle and Malden Nesheim conclude in an editorial: "While we wait for the results of further research, the USPSTF's cautious, evidence-based advice should encourage clinicians to think carefully before advising calcium and vitamin D supplementation for healthy individuals."
- See more at: http://firstwatch.jwatch.org/cgi/content/full/2013/226/2#sthash.u0UUXYMu.dpuf
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BMJ 2013 Feb 13; 346:f228
High Calcium Intake Is Associated with Earlier Mortality in Women
Higher death rates occurred with daily intakes exceeding 1400 mg.
Oral calcium supplementation is associated with elevated risk for adverse cardiovascular (CV) events such as myocardial infarction (e.g., JW Gen Med May 12 2011). Moreover, in a recent study (JW Gen Med Feb 26 2013), high-dose calcium supplementation was associated with excess CV-related mortality in men. In this prospective cohort study, Swedish investigators assessed the associations between long-term calcium intake and all-cause and CV-related death in 61,000 women born between 1914 and 1948.
Researchers estimated dietary, supplemental, and total calcium intake from food-frequency questionnaires that were completed at baseline (1987–1990) and in 1997. Median follow-up was 19 years. Compared with dietary calcium intakes of 600 to 999 mg daily, daily intakes of ≥1400 mg were associated with significantly higher rates of death from all causes (multivariate adjusted hazard ratio, 1.4), CV disease (AHR, 1.5), and ischemic heart disease (AHR, 2.1), but not from stroke. Similar results were obtained for total calcium intake. Vitamin D intake did not modify the associations.
Comment: In this study, high calcium intake was associated with excess risk for all-cause and CV-related mortality but not from stroke-related death. Although these results do not prove causality, they — along with the results of prior studies — suggest that people avoid excessive calcium intake (i.e., ≥1400 mg daily) and that high calcium intake should be reserved for situations in which benefits clearly outweigh risks.
Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine February 28, 2013
Citation(s): Michaëlsson K et al. Long term calcium intake and rates of all cause and cardiovascular mortality: Community based prospective longitudinal cohort study. BMJ 2013 Feb 13; 346:f228.
- See more at: http://general-medicine.jwatch.org/cgi/content/full/2013/228/2?q=etoc_jwgenmed#sthash.ToCvXkn7.dpuf
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Vitamin D and Calcium Supplementation in Women: Making Sense
of Conflicting Data

Most women should strive to eat a diet rich in these nutrients and consider supplements only if necessary to meet the RDA.
Many clinicians are confused about the benefits and risks of vitamin D and calcium supplementation for midlife and older women. We offer guidance on the appropriate use of these supplements.
VITAMIN D: Long recognized as important for skeletal health, vitamin D has garnered recent interest for its possible nonskeletal benefits. This vitamin is synthesized in the skin in response to sunlight and can also be ingested as vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Natural dietary sources of vitamin D are few and include fatty fish and egg yolks. Vitamin D is also commonly added to milk and some other dairy products, cereals, and orange juice. Vitamin D is hydroxylated in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating metabolite, and is then further converted to 1,25-dihydroxyvitamin D (calcitriol).
A recent evidence-based Institute of Medicine (IOM) report1,2 provides guidelines about the amount of vitamin D that most North American women should consume. The IOM's review confirmed that vitamin D clearly confers bone benefits, but found that current data are insufficient to conclude that it lowers risk for nonskeletal diseases (e.g., cardiovascular disease [CVD], diabetes, cancer); thus, the IOM based its recommendations only on the amount required for bone health:

Because the IOM assumed little to no sun exposure, these guidelines apply even to individuals living in northern latitudes during the winter.
The IOM also reviewed safety data on high-dose vitamin D supplements and set the tolerable upper level of daily intake at 4000 IU (previously 2000 IU). Extremely high intakes can lead to hypercalcemia, thereby damaging the kidneys and heart, but data are lacking about the long-term safety of intakes above the RDA. Several ongoing randomized trials should clarify the benefit-risk balance of such doses. For example, in the large, 5-year VITamin D and OmegA-3 TriaL (VITAL), researchers are testing 2000-IU daily supplemental vitamin D3 for primary prevention of cancer and CVD.3
The IOM's recommendations reflect a population-level, public-health orientation and are intended to complement but not replace individualized clinical decision making. Clinical guidelines that combine both perspectives are useful.4 Per the IOM, most healthy individuals should do their best to meet the aforementioned RDAs and do not need routine 25(OH)D testing. However, for individuals with risk factors for, or clinical conditions associated with, vitamin D insufficiency (e.g., malabsorption, osteoporosis), 25(OH)D measurement is prudent. If the level is <20 ng/mL, two approaches to vitamin D therapy are as follows:

Roughly speaking, 25(OH)D increases by 6 to 10 ng/mL for each additional 1000 IU daily of supplemental vitamin D3.4 Reassessing 25(OH)D is necessary about 3 months after a dose change to check that the target level has been attained. Some organizations recommend maintenance levels >30 ng/mL for "at-risk" individuals. The IOM recommends avoiding 25(OH)D levels >50 ng/mL, as some research suggests excess risk for CVD,1 pancreatic cancer,5 all-cause mortality,6 and even fractures7 at these levels.
CALCIUM: The IOM also conducted a parallel assessment of calcium and concluded that this nutrient provides critical bone benefits.1,2 The Women's Health Initiative (WHI), a randomized trial of the benefits and risks of daily calcium (1000 mg) and low-dose vitamin D (400 IU) supplements in 36,282 postmenopausal women (age range, 50–79), showed that treatment led to significantly less bone loss at the hip and a 12% reduction in hip fracture rate.8 Although the latter figure was lower than expected and not statistically significant, it was one of the findings that led to the influential U.S. Preventive Services Task Force's 2013 assertion that this treatment is ineffective for fracture prevention at midlife and beyond.9 However, among WHI participants aged ≥60 — the age group most likely to sustain osteoporotic fractures — the intervention was associated with a larger, statistically significant 21% reduction in hip fracture rate.8 Moreover, among participants who took their study pills regularly and were not already taking supplements, the intervention was associated with a still larger, statistically significant 30% reduction in hip fracture rate.8 Participants with intakes ≥1200 mg/daily at baseline did not clearly benefit from the intervention, suggesting that "more is not necessarily better." The evidence as a whole points to the need for sufficient calcium to ensure bone health and prevent fractures.1,2,10
The IOM set the current RDA for calcium (from food plus supplements) at 1000 mg for women aged ≤50 and 1200 mg for those aged >50. Many women are consuming unnecessarily high doses of supplemental calcium. Instead, they should aim to meet the RDA by eating calcium-rich foods (e.g., milk, yogurt, cheese, and other dairy foods; fish such as sardines or salmon; tofu; calcium-fortified juice and cereals; broccoli, collard greens, and kale) and consider supplements only if their diet does not provide the recommended amount of calcium. Given that the median daily dietary calcium intake of midlife and older women is about 700 mg1 (equivalent to 2–3 servings of the above foods), many women need no more than about 500 mg daily in calcium supplements to meet the RDA.10
Calcium from food does not seem to raise CVD risk (indeed, observational data suggest that the opposite may be true11), but calcium supplements may raise blood calcium levels more rapidly than dietary calcium, thereby boosting risk for heart disease. This hypothesis, however, remains unproven.10 In the WHI, no overall elevation in myocardial infarction (MI) or stroke risk occurred,12 although a 22% increase in MI risk was noted among participants who first began taking calcium supplements as part of the trial (but not among those already taking them at baseline).13 However, the supplements did not increase coronary artery calcification at trial's end.14 Also, a review of randomized trials showed that, compared with placebo, calcium supplements (whether alone or with vitamin D) were not linked to CVD risk.11 Nevertheless, striving to obtain calcium from food rather than from supplements — while ensuring adequate concurrent vitamin D intake — is wise.
Regarding other clinical outcomes in the WHI, a significant 17% increase in risk for kidney stones was noted,8 but the background intake of calcium was high. Total mortality was reduced by 9% (a finding of borderline statistical significance),15 and risk for total, colorectal, or breast cancer was unaffected.16 Overall, the findings suggest that calcium supplementation to bring the total intake of this nutrient to the RDA level — but not to exceed it — can lower risk for hip fracture without raising risk for CVD or other major adverse events.10
CONCLUSION: To maintain bone health, current recommendations for daily vitamin D intake call for 600 IU for women aged ≤70 and 800 IU for those aged >70, and recommendations for daily calcium intake are 1000 mg for women aged ≤50 and 1200 mg for those aged >50. The benefit–risk balance of long-term supplementation with doses of vitamin D and/or calcium that exceed the RDA is the subject of ongoing research. Most women should endeavor to eat a diet rich in these nutrients and consider supplements only if necessary to meet the RDA.
— JoAnn E. Manson, MD, DrPH, and Shari S. Bassuk, ScD - Dr. Manson is Professor of Medicine and Chief, Division of Preventive Medicine, Harvard Medical School and Brigham and Women's Hospital; and a WHI principal investigator. Dr. Bassuk is an epidemiologist and science writer at Brigham and Women's Hospital.
Published in Journal Watch Women's Health February 28, 2013
Citation(s): 1. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. The National Academies Press; 2011.
2. Ross AC et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know. J Clin Endocrinol Metab 2011 Jan; 96:53.
3. Manson JE et al. The VITamin D and OmegA-3 TriaL (VITAL): Rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials 2012 Jan; 33:159.
4. Szmuilowicz ED and Manson JE. How much vitamin D should you recommend to your nonpregnant patients? OBG Management 2011 Jul; 23:45.
5. Stolzenberg-Solomon RZ et al. Serum vitamin D and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial. Cancer Res 2009 Feb 15; 69:1439.
6. Melamed ML et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008 Aug 11; 168:1629. (http://dx.doi.org/10.1001/archinte.168.15.1629)
7. Sanders KM et al. Annual high-dose oral vitamin D and falls and fractures in older women: A randomized controlled trial. JAMA 2010 May 12; 303:1815.
8. Jackson RD et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006 Feb 16; 354:669.
9. U.S. Preventive Services Task Force. Vitamin D and Calcium Supplementation to Prevent Fractures in Adults: U.S. Preventive Services Task Force Recommendation Statement.
10. Manson JE and Bassuk SS. Calcium supplements: Do they help or harm? North American Menopause Society (NAMS) Practice Pearl September 6 , 2012.
11. Wang L et al. Calcium intake and risk of cardiovascular disease: A review of prospective studies and randomized clinical trials. Am J Cardiovasc Drugs 2012 Apr 1; 12:105.
12. Hsia J et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007 Feb 20; 115:846.
13. Bolland MJ et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ 2011 Apr 19; 342:d2040.
14. Manson JE et al. Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative. Menopause 2010 Jul; 17:683.
15. LaCroix AZ et al. Calcium plus vitamin D supplementation and mortality in postmenopausal women: The Women's Health Initiative calcium-vitamin D randomized controlled trial. J Gerontol A Biol Sci Med Sci 2009 May; 64:559.
16. Manson JE et al. Vitamin D and prevention of cancer — ready for prime time? N Engl J Med 2011 Apr 14; 364:1385.
See more at: http://womens-health.jwatch.org/cgi/content/full/2013/228/1?q=etoc_jwwomen#sthash.JIF0rBSw.dpuf
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Vitamin D and Calcium: What Women Need at Midlife and After
Both nutrients are important for bone health.
With conflicting nutritional information available from multiple sources, it's hard to decide not only what to eat, but what, if any, supplements to take. It's commonly recommended that women — especially as they get older — should take calcium and vitamin D supplements to help strengthen bones and protect against future fractures (broken bones). However, the U.S. Preventive Services Task Force (USPSTF) recently concluded that there isn't enough proof that taking these supplements before or after menopause prevents fractures in women who never had fractures before, and that the possible harm supplements may cause is unknown.
So what should you do? Here's what we know right now about calcium and vitamin D for midlife and older women.
What It Is: Vitamin D is not a true vitamin. It's considered a "prohormone," a substance from which hormones are made. It comes in two forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). If you are buying a vitamin D supplement, you may see both forms on the shelf. Unlike other vitamins, vitamin D can be made by the body: Your skin manufactures it when exposed to sunlight.
What It Does: Vitamin D works in the small intestine to help absorb calcium into the bloodstream, so that the calcium can help build bone. Vitamin D also helps strengthen muscles and the immune system and helps reduce inflammation. The bone-health benefits of vitamin D have been clearly shown. Some studies have suggested that vitamin D plays a role in preventing cardiovascular disease or some cancers. However, there is not yet enough information to prove that any dose of vitamin D can protect against these conditions, and its use for this purpose is not recommended.
How Much You Need: If you are regularly exposed to sunlight even for a short amount of time (as little as 15–30 minutes twice a week), you might have enough vitamin D. However, as you age, your body may be less efficient at making vitamin D; also, many women avoid sun exposure to protect against skin cancer and wrinkling. The recommended daily amount of vitamin D is:

A blood test can determine if you are getting an adequate amount of vitamin D (or too much). This test is not routinely recommended but can be helpful if you have malabsorption (decreased ability to absorb nutrients), osteoporosis, fractures, or another condition that makes having adequate vitamin D especially important. Your clinician (doctor, nurse practitioner, nurse midwife, or physician assistant) might have an individualized recommendation about vitamin D for you if you have certain health conditions.
How Much Is Too Much: Very high doses of vitamin D can increase calcium levels in the blood, causing kidney and heart damage. Unlike many other vitamins, D can build up in the body over time. Some ongoing studies are looking at exactly how much vitamin D is too much; for now, it is recommended that you not use supplements over 4000 IU for an extended period. If you are taking several different dietary supplements, check the labels on all of them to be sure you are not overdoing it. Don't worry about getting too much vitamin D from sun exposure or foods; that's not likely to happen.
How to Get It: Vitamin D occurs naturally in very few foods: egg yolks, fatty fish (mackerel, salmon, tuna), and beef liver. Some foods are fortified with vitamin D (and say so on the label): milk and other dairy products, cereals and grains, orange juice. If you can't get enough vitamin D from sunshine and your diet, many forms of nonprescription vitamin D supplements are available in various doses; some calcium supplements have vitamin D added as well. Many regular daily multiple vitamin supplements contain the recommended amounts of vitamin D, so check the label. As with all vitamins, inexpensive generic vitamin D supplements purchased at a pharmacy or grocery store work just as well as expensive name-brand ones advertised as "natural" or in some way superior. Look for "USP verified" on the label. Manufacturers of supplements are not required to follow the same strict guidelines as for prescription drugs. However, they may choose to have the USP agency check their products. "USP verified" means the supplement actually contains the ingredients on the label, does not contain harmful chemicals, will be released into the body in a specified amount of time, and has been manufactured according to strict guidelines.
For your body to absorb vitamin D well, take it with a meal that contains some fat — preferably "good fats" found in avocados, olive oil, fatty fish, or nuts.
What It Is: Calcium is a mineral that is essential to health in many ways.
What It Does: Calcium makes up most of your bones and teeth. It also plays a role in clotting blood and helping nerves, muscles, and the heart to work properly. Getting an adequate amount of calcium is necessary for bone health. Some studies have suggested that calcium, like vitamin D, may play a role in preventing some cancers or cardiovascular disease, but it's too early to say whether this is true.
How Much You Need: The recommended daily amount of calcium from food and — if necessary — supplements, is:

How Much Is Too Much: Taking too much calcium from supplements can cause kidney stones and heart disease. Don't worry about getting too much calcium from your diet, though; this does not seem to be a health problem and in fact might be beneficial. If you're using supplements, don't take more than the recommended amount.
How to Get It: Calcium is found in many foods, such as dairy products (milk, yogurt, cheese), some fish (such as sardines and salmon), tofu, calcium-fortified juices, and some dark green vegetables. If you eat three to four 8-ounce servings of dairy products a day, you are probably getting enough calcium from your diet. If you don't get enough dietary calcium, consider a supplement only to bring the total amount up to the recommended level. Supplements are available in various forms, including tablets, capsules, liquids, and candy-like chews. Some calcium supplements also contain vitamin D. As with vitamin D, inexpensive generic supplements are just as effective as expensive, well-advertised name brands, but look for the term "USP verified" on the label.
IN CONCLUSION: Vitamin D and calcium are essential to bone health. If possible, get adequate amounts from your diet and, for vitamin D, from sun exposure. Talk with your clinician or a nutritionist about supplements and bone health. If you have health problems that affect your ability to absorb nutrients, to get sun exposure, or to eat foods containing calcium and vitamin D — or if you are taking medications that affect your bone health or you have already had a fracture — different guidelines may apply to you.
And, of course, don't forget that a healthful diet, regular exercise, and good habits such as avoiding or quitting smoking and excessive alcohol also contribute to your overall wellbeing.
Food Sources of Vitamin D and Calcium
U.S. Preventive Services Task Force Information on Vitamin D and Calcium
Choosing and Using Supplements
Diane E. Judge, APN/CNP Published in Journal Watch Women's Health February 28, 2013
- See more at: http://womens-health.jwatch.org/cgi/content/full/2013/228/2?q=etoc_jwwomen#sthash.634W9cgX.dpuf

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