Evening Primrose Oil

Yesterday I had a patient who was taking evening primrose oil each day for leg weakness. Standing in front of this patient I wondered about the evidence behind the use of this supplement, so here we are, time to look at some scientific evidence!
Many people use evening primrose oil for treatment of scaly itchy rashes (atopic dermatitis), rheumatoid arthritis, and for relief of menopausal and premenstrual symptoms.
A Cochrane review published in 2012 showed that dietary supplements such as Vitamin D, primrose oil, hempseed oil, and sea buckthorn oil had no benefits in patient with eczema.
Studies that looked at using primrose oil for menopausal and premenstrual symptoms appear to show negligible results similar to participants who had been given a placebo.
A 2011 Cochrane review suggested that there was moderate evidence to support the use of oils containing gamma linoleic acid (in evening primrose, borage, or blackcurrant seed oil) in relieving symptoms of rheumatoid arthritis. However, the review also mentioned that further investigations into how effective these oils are and their side effects are warranted.

My 2 cents? Health Canada's review of evening primrose oil states that it is safe to consume 1300-1600mg/ day "for maintenance of good health." If your dose falls within these safe guidelines and you feel a benefit from its use, I'd suggest that it's likely safe to continue using it unless otherwise recommended by your health care providers.

Information Sources
http://www.ncbi.nlm.nih.gov/pubmed/22336810
http://www.ncbi.nlm.nih.gov/pubmed/22139538
http://www.ncbi.nlm.nih.gov/pubmed/21328257
Evening Primrose Oil Health Canada Monograph

Artificial Colors?

Even as a dietitian, food additives can confuse me. I often have patients who avoid foods that contain artificial colors. So what's the fuss, why are people avoiding this ingredient? The first thing to consider is processed food, and what type of foods are a part of your diet. If you eat a lot of packaged or pre-prepared meals, you're likely consuming a large amount of preservatives and additives. Often times, the scientific community is still unclear on how some of these additives affect our bodily functions

Artificial colors can be found in foods such as juices, soda, candy, condiments, icing, baked goods, cookies, cereals, yogurts, soups and even in some medications. Some are concerned that artificial colors have been linked to attention deficit hyperactivity disorder (ADHD) in children and allergic reactions.While others argue that the evidence supporting negative claims behind artificial colors is insufficient. The 2010 Food and Drug Association report stated that exposure to food additives and artificial colors may be associated with adverse behaviors in "susceptible" children with other behavior problems. However, to determine which child is "susceptible" and which is not is a whole other debate. Additionally, a 2011 study in the Journal of Clinical Pediatrics stated that a sub-group of children show significant symptom improvement when consuming a diet free of artificial colors

So whats the conclusion? The debate is still going! If your child is consuming common foods with no trouble, restricting their diet "just because" may not be the answer. However if you notice significant behavior changes with foods that contain artificial colors, a trial restriction of  artificial colors with the guidance of a physician or dietitian may be warranted in children who haven't responded to conventional treatments.

Information Sources
http://cpj.sagepub.com/content/50/4/279.short
http://www.huffingtonpost.ca/lisa-tsakos/artificial-food-colours-labels_b_1281843.html
http://www.healthcastle.com/which-food-additives-avoid
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261946/
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/FoodAdvisoryCommittee/UCM248113.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21127082

HealthTip: What to do About Gout?

If you are suffering from gout, the following suggestions may help limit painful gout attacks:

• If you are overweight, work with your friends, family, doctor and dietitian to try to reach a healthier weight.
• Drink 8-12 cups of fluid throughout the day to help flush uric acid out of the body and limit crystallization in joints.
• Pay attention to your meat, fish, and poultry intake. These foods are high in purines and decreasing portion sizes may help limit the amount of uric acid in the blood. Beans, peas, lentils, tofu, nuts, seeds, and low-fat dairy are other sources of protein that you may want to add to your diet.
• Pay attention to saturated fat. Saturated fat may decrease the body's ability to eliminate uric acid. Try choosing foods with lower amounts of saturated and trans fat and higher amounts of mono- or poly-unsaturated fat ...check out the nutrition label!
• Limiting or avoiding alcohol, especially beer, may limit gout attacks, as alcohol interferes with elimination of uric acid from the body.
• Fructose is a sugar that may increase uric acid. Read food labels to see if your juices, candies, or treats are sweetened with high-fructose corn syrup.
• Some studies suggest that low-fat dairy may decrease risk of gout. Try adding skim or 1% milk, yogurt, or low-fat cheese to your diet.
• Whole grains high in fiber, vegetables, and fruits add variety at meal time and may limit foods high in purines.

In a nutshell, these recommendations are very similar to the recommendations of a healthy diet rich in whole grains, low-fat dairy, vegetables, fruit, and protein from plant and animal sources. These changes would likely not be a replacement for prescribed medications in those with severe gout, but they may help limit the frequency and severity of gout attacks. Speak with your doctor and dietitian about what changes you can make on your own!

Information Sources
http://www.mayoclinic.com/health/gout-diet/MY01137
www.mayoclinic.com/health/gout/DS00090
http://www.nejm.org/doi/full/10.1056/NEJMoa035700

HealthTip: What Is Gout?

Gout is an complex form of arthritis which involves sudden, severe attacks of pain, redness and tenderness in joints, often in the big toe.  It occurs when high levels of uric acid in the blood accumulate and form crystals around a joint. The body produces uric acid when it breaks down purines. Purines can be found in common foods such as meats (especially organ meats), anchovies, herring, asparagus, sardines, mushrooms, and beer. A 2004 study from the New England Journal of Medicine suggested that higher consumption of meat and seafood was associated with increased risk of gout, while a high intake of dairy was associated with a decreased risk of gout. The study also suggested that high intake of purine-rich vegetables did not increase the risk of developing gout. Other studies find that those who are overweight or obese are also at increased risk.
If you suffer from gout, speak with your family physician about what diet changes and medications may be right for you. For more information on small changes you can make to help with gout attacks see my following post.

Information Sources
http://www.mayoclinic.com/health/gout-diet/MY01137
www.mayoclinic.com/health/gout/DS00090
http://www.nejm.org/doi/full/10.1056/NEJMoa035700

HealthTip: Hemoglobin

Continuing on with my explanation of blood tests, today I will discuss hemoglobin.
Hemoglobin is a protein found in red blood cells, responsible for carrying oxygen away from the lungs to the body's tissues. A blood test for hemoglobin measures the amount of this protein in the blood. Low hemoglobin levels could be related to anemia, over-hydration, bleeding, red blood cell destruction, iron deficiency, folate deficiency, vitamin B12 deficiency, and/ or vitamin B6 deficiency. In addition, certain diseases and infections may cause hemoglobin levels to drop.

A low hemoglobin may be normal in some people and not be a sign of any deficiency.  However, if you experience symptoms such as:

• Fatigue
• Faster than normal heartbeat during exercise or activity
• Shortness of breath
• Pale skin and gums
• Lack of energy

you may want to speak with your physician about having your hemoglobin and iron levels checked.

Information Sources:
http://www.nlm.nih.gov/medlineplus/ency/article/003645.htm
http://www.mayoclinic.com/health/low-hemoglobin/MY01183

HealthTip: Childhood Egg Allergy

Eggs are a healthy and affordable source of protein. However, egg is a common allergy which may trigger serious allergic reactions in some children. In the past, the avoidance of eggs and egg products in those with serious allergic reactions would be recommended; but new research suggests children may grow out of allergies they experienced as infants. For example, ~70% of infants allergic to cows milk may grow out of this allergy by the age of 5-6 years.
In a new study from the New England Journal of Medicine, researchers wanted to find out if exposing children with egg allergy to small but increasing doses of egg would desensitize them. Egg white powder or a placebo was first given to 55 children between the ages of 5-11 years. Those who tolerated the egg white powder were given cooked egg. If no allergic reactions were observed, eggs were re-introduced into the diet and the children were evaluated after 6 and 12 months. Results showed that 28% of the children in the study were able to eat eggs successfully.
These new studies suggest that exposing children to small amounts of their food allergen may help build up tolerance. However, if your child has a life threatening response to a certain food, trialing the food should always be discussed and planned with a physician to ensure the safety of your child.

Information Source:
http://www.nlm.nih.gov/medlineplus/videos/news/egg_allergy_071912.html

HealthTip: Serum Albumin

Often times we get our blood work done but have no idea of what the values or tests mean. I will be posting an explanation of common blood tests conducted over the next few days, and today I will begin with serum albumin.
Albumin is a protein made by the liver that helps transport molecules such as calcium, bilirubin and progesterone (hormone) through the blood. Albumin also helps keep fluid in the blood from leaking out into the body's tissues.
A blood test for serum albumin measures the amount of this protein in the clear portion of blood. This test can help screen for liver disease, kidney disease, or if the body is not absorbing enough protein.
It is important to note that albumin levels can be affected with hydration (albumin may be low when there is too much fluid in the body, or high when the body is dehydrated), inflammation, and during infections. Therefore, it may not be reliable to screen for liver or kidney disease, or protein malnutrition with serum albumin when patients are suffering from infection or are over-hydrated or dehydrated.

Information Sources:
http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm

Update

Just an update to those who check this blog. It has been a few very busy months of completing my dietetics internship and beginning my new job! I will be working as a clinical dietitian at multiple acute care sites and will also be working at a cancer agency. I hope to now have a bit more time to blog and get back into the flow of posting updates more often. I have been using twitter to drop a few short and sweet tips a few times a week, so please follow me there if you're interested. If you've got any questions of your own, feel free to post on this blog and I'll get back to you as soon as possible.

Thanks for following,
The New R.D.

HealthTip: The Strength of Optimism

This post is dedicated to a man who defied medical logic; My wonderful grandfather lived  for 86 years. He had diabetes, hypertension (high blood pressure), high cholesterol, and showed no significant symptoms of disease until the last ~6 months of his life. The reason for this? Did he have a healthy diet low in excess sugar and fat; high in fiber, fruits and vegetables? No. Did he exercise everyday? No.
What was his secret?
Optimism!
Studies suggest that positive feelings reduce the risk of heart disease, heart attack, and stroke. In a review of 200 studies, the Harvard School of Public Health found that "optimism, life satisfaction and happiness are associated with reduced risk of cardiovascular (heart) disease regardless of factors such as age, socioeconomic status, smoking status or body weight."
Opa was the happiest man I knew. He was always smiling, laughing, loving his family, and saw everything as a positive learning experience.
The most optimistic participants in the Harvard study had a ~50% reduced risk of experiencing an initial cardiovascular event compared to less optimistic participants. This doesn't necessarily mean that healthy lifestyle doesn't matter, because those who exercised, ate a balanced diet, and got enough sleep showed benefit through normalized blood pressure, cholesterol, and weight.

So, what do you take away from this? Although diet, exercise, and lifestyle are important, an optimistic view on life and family support may do more for our bodies than we initially thought. My Opa is proof of this theory! So why not try to take a positive view on life, enjoy each experience, limit stress over small "hiccups," and love your family; I don't think it would hurt!!

Information Source:
http://www.nlm.nih.gov/medlineplus/news/fullstory_124222.html

HealthTip: Iron

Our bodies require iron in order for red blood cells to carry oxygen to our tissues, supply oxygen to working muscles, and take part in biochemical reactions. Iron is needed for normal growth and development; low iron can result in fatigue, decreased immunity, poor performance, and even irritability.
Iron is found in two forms in our diet: heme and non-heme. Heme iron is in hemoglobin, a protein in red blood cells. This type of iron comes from animal foods that originally contained hemoglobin e.g. red meats, poultry, and fish.
Iron found in food such as lentils, beans, broccoli, is non-heme iron. Heme iron is better absorbed by our bodies than non-heme iron. Therefore, it is recommended to have non-heme iron sources with Vitamin C (e.g. glass of orange juice) to promote iron absorption in the body.

Examples of foods with heme iron include:

• Chicken liver; Chicken
• Oysters
• Beef liver; Beef
• Turkey
• Tuna

Examples of foods with non-heme iron include:

• Iron fortified cereal
• Instant fortified oatmeal
• Beans
• Lentils
• Tofu
• Spinach

The absorption of non-heme iron is decreased by tannins found in tea, calcium, polyphenols and phytates found in whole grains and legumes. Not eating non-heme iron with foods that decrease its absorption and eating it with meat protein and vitamin C will maximize its absorption.
For more information about iron sources or recommended daily amounts, please see the information sources listed below.

If you've noticed that you have decreased energy levels, and may have a low iron intake through food, speak with your doctor about a blood test determine the level of iron stored in your body. If lab tests show that your iron is low, explore increasing your iron intake through food and/or supplements with your doctor, dietitian, or pharmacist!

Information Sources:
http://ods.od.nih.gov/factsheets/iron-HealthProfessional/
http://www.dietitians.ca/getattachment/130db3ca-3a27-4147-90ae-ae27a543b09b/FactSheet-Iron.pdf.aspx

HealthTip: Wanting What You "Can't Have"?

They say you always want what you can't have.
In the past, or maybe even still today, dietitians have been known as the "food police." I'm here to inform you that, we in fact are not the food police, and if you meet an RD who makes you feel like they are, maybe you're not talking to the right dietitian.
Sometimes specific diets are required in acute medicine to allow the body to heal, but if we're talking about the everyday, regular person who is trying to stay healthy, you don't have to cut out the foods you love.
Pasta, chocolate, cake, ice cream,  soda, burgers, pizza...sounds like a list of foods that may be called "guilty pleasures," but do you really need to feel guilty about eating something you enjoy? How is that guilt serving you?

Get away from the guilt:

• Plan ahead: try to consciously include high fibre carbohydrates, protein, dairy, and vegetables at meals. When all these food groups are present at meal time, you may find yourself feeling fuller and wanting less dessert.
• Have the foods you enjoy but control the amount/ frequency.
  Separate a few pieces of dark chocolate from the whole bar; give yourself 1 scoop of icecream instead of two; instead of having dessert everyday, try having it every other day and alternate with fruit or yogurt.
• If salt is your vice, start looking at nutrition facts tables. As a guideline, try comparing snacks you enjoy and look for those with 15% or less of the daily value of sodium per serving.
• Love your soda? Changing to a diet variety could be an idea. Flavoring for water, such as Crystal Lite is available if you want to try something new to get away from the sugar and calories in soda.
• Try making some favorite foods at home instead of purchasing fast food. Burgers and pizza made at home can be much lower in saturated fat and sodium. Home made burgers also freeze well for easy access when you're in a rush!
• Think before you eat. Are you hungry? Are you eating because you're bored? Are you feeling guilty? If so, stop and ask yourself why and make a thoughtful choice. If you're going to have a certain food and you recognize a negative feeling, consider how much you plan to eat, consider what would get rid of that feeling, make your choice and make it count! 

Enjoy your food, add variety, try new things, balance meals with 3-4 food groups, recognize when associating negative feelings with specific foods, and try to consider why those feelings may be arising.

Mindful, guilt-free, balanced eating is the goal. All foods can fit as long as you consider what you're choosing, how much, and how often!

HealthTip: Glycemic Index

If you have diabetes, you may have heard of glycemic index. Glycemic index (GI) was determined by comparing different foods to how white sugar breaks down in the body. Foods are categorized into high, medium, or low GI foods. Low GI foods take longer to break down and digest, resulting in lower blood glucose increases over a longer period of time(important for people with diabetes). High GI foods break down quickly and result in higher blood sugar spikes.
If you're a diabetic and have trouble controlling your blood glucose after meals, consider adding low GI foods to your diet and see the link below!

Information Source
http://www.diabetes.ca/files/glycemicindex_08.pdf

HealthTip: Carbohydrates

Foods that break down into sugar in our body are considered to be carbohydrates. It would be important for those with diabetes to know which types of foods include carbohydrates because these foods can result in increased blood sugars.

Carbohydrates include:

• Starches and Grains: e.g. pasta, rice, pita, tortillas, cereal, bread, oatmeal, potatoes, corn, legumes
• Milk: milk contains lactose, a naturally occurring milk sugar
• Fruit: e.g. bananas, apples, pears, oranges, grapes, berries, mango
• Juice: contains large amounts of concentrated sugar

Our bodies require carbohydrates to break down into glucose and be used as an energy source. Since our brains cannot function without glucose, it is important to know that it is not necessary to cut out carbohydrates from your diet.

If weight or blood sugar management are a personal concern, start by considering the type of carbohydrates your choosing and the portion of food groups at meal times.

Complex carbohydrates take longer to break down in the body, are often higher in fiber, and help you feel full for longer. For example, 1 slice of white bread may have 1g of fiber; 1 slice of sprouted whole grain bread may have 5g of fiber. The whole grain bread will be more filling, results in a lower blood glucose rise, and promotes regular bowel health.

For more information about complex carbohydrates see: http://www.nlm.nih.gov/medlineplus/ency/article/002469.htm

HealthTip: Neilson Milk Recall

For any of those who drink Neilson Milk, the Canadian Food Inspection Agency requested a recall this morning, as some batches of milk may be contaminated with a cleaning solution. The recalled products have the UPC code 066800 00404 4 and a best before date of Feb. 12, 2012.
The contaminated milk might not look or smell any different, but drinking it may cause nausea, upset stomach or vomiting. If you know anyone who drinks Neilson milk, please advise them of this product recall.

Information Source:
http://www.cbc.ca/news/health/story/2012/01/27/saputo-milk-recall.html

HealthTip: Marketing to Children

Have you ever wondered where and how your children are being marketed to? Have you taken a moment to consider the world of commercialism and marketing you and your children live in? Children are exposed to marketing through TV, radio, internet, games, at malls, through flyers, billbords, coupons, in grocery stores, and even at school. If you're interested, take 5 minutes to watch the trailer for "Consuming Kids: The Commercialism of Childhood" : http://www.youtube.com/watch?v=HKH4YGKnOSs

Part 1 of this series from the Media Education Foundation can be found at: http://www.youtube.com/watch?v=jPlTrgiE2sc&feature=related

HealthTip: Kale Chips Anyone?

Do you find yourself having cravings for the satisfying crunch of chips or salty crackers. A healthier way to give into your craving may be to try making kale chips!
Kale is a leafy, green (or purple) vegetable from the brassica family. This family also contains vegetables such as cabbage and brussel sprouts, so if you find that these vegetables commonly cause bloating, kale chips may not be your best option. Kale is a commonly referred to as a "super-food" because it is a high source of potassium, fiber, calcium, Vitamin K, Vitamin C, Vitamin A, and beta-carotene.
To bake kale chips, you'll need kale, olive oil, salt, and garlic powder (optional). You can season the kale any way you like, so be creative!

• Wash kale
• Remove the leafy part of the kale from its stem
• Tear kale leaves into bite size pieces and place in a bowl with the olive oil (start with 1-2tbsp), salt, and garlic powder
• Toss the kale to ensure its thoroughly coated with the oil and seasonings (this will ensure that it becomes crispy when baked)
• Place torn leaves separately on a baking sheet and bake at ~300F for 10-15 minutes or until kale becomes crispy 

It may take you a few tries to get the exact crispiness you want, so don't give up if your first batch isn't perfect! After reading this post maybe you'll consider this vitamin and mineral packed snack option the next time you're tempted to buy that bag of high-fat, nutrient-lacking chips?

Information Sources:
http://www.healthcastle.com/video-week-making-kale-chips
http://www.nal.usda.gov/fnic/foodcomp/cgi-bin/list_nut_edit.pl
http://www.hc-sc.gc.ca/fn-an/nutrition/reference/table/ref_vitam_tbl-eng.php

HealthTip: Fish For Your Brain

Regularly consuming fish may help keep your mind sharp later in life!
Researchers asked 260 mentally healthy participants what foods they normally ate. Through MRI brain scans the researchers measured the amount of grey matter in the brain. A high volume of grey matter suggests a healthy brain. When this volume decreases, it suggests that brain cells are shrinking. Participants who ate baked or broiled fish weekly showed to have more grey matter in the brain and less complications related to trouble thinking or Alzheimer's disease. Those who consumed fried fish did not show the same benefits.
So, if you're a fan of fish, you may want to consider making it a weekly dinner option; it may be a piece of the puzzle that helps you stay sharp for longer!

Information Source:
http://www.nlm.nih.gov/medlineplus/videos/news/cook_it_120111.html

HealthTip: Trying to Cut Chocolate Cravings?

Do you find yourself sitting at your desk with the sudden craving for chocolate, cookies, or other festive sweets. This would be a daily occurrence in my case!
U.K. researchers conducted a study with 78 participants who were regular chocolate-eaters at work but had gone 2 days without chocolate. One group took a 15 minute walk on a treadmill and was then given a task during cravings, while the other group rested before being given a task. All participants had a bowl of chocolate on their desk. Results showed that the group that took a 15 minute walk ate approximately half of the chocolate when compared to those who rested before their task.
Snacking on high calorie foods can become a mindless task at work while sitting in front of a computer screen. If you feel a craving coming on, try going for a short walk. If the craving is still strong after the walk, try loading your desk area with healthier snacks such as sliced apples with caramel dip, yogurt with fresh berries and granola, a high fiber low sugar granola bar (that contains a bit of chocolate ovcourse), or a handful of roasted nuts. At this time of year it can be difficult to not give into cravings, but before you pick up that extra brownie, try to take a moment to determine if you're actually hungry; if you're not hungry but still really want the brownie, why not just take half? There are ways to have your chocolate and eat it too!

Information Source:
http://www.nlm.nih.gov/medlineplus/news/fullstory_119668.html

HealthTip: Iron Deficiency Anemia

Anemia can result from many different health complications. Iron deficiency, vitamin deficiencies, or even chronic (long-term) illness may result in anemia.
Vegetarians, pregnant women, and female endurance athletes may be at an increased risk of iron-deficiency anemia. In iron deficiency anemia, the body doesn't have enough iron. Without enough iron, the body can't make enough hemoglobin (the protein in red blood cells that allows them to deliver oxygen to our tissues); The result is fewer, smaller red blood cells with a decreased ability to carry oxygen. This type of anemia can often be corrected with iron supplementation and adding iron-rich foods to your diet. Foods rich in iron include:

• Meat, fish, poultry
• Beans
• Dark green, leafy vegetables e.g. spinach
• Bright orange vegetables e.g. peppers, tomatoes
• Dried fruit 
• Iron fortified cereals, breads, and pasta

Our bodies absorb more iron from animal (meat) sources than other sources. Adult males (19-49yrs) commonly need 8mg iron/day while non-pregnant adult females need 18mg iron/day. Vegetarians are often recommended to have a little less than double these amounts because plant sources of iron are less absorbed in our bodies (therefore we need more to meet our needs). Also, as mentioned before, you can increase the absorption of iron in your body by having your iron-rich foods/ supplements with vitamin C containing foods such as orange juice or kiwi.

Stay tuned, other types of anemias are still to come!

Information Sources:
http://www.pennutrition.com.ezproxy.library.ubc.ca/KnowledgePathway.aspx?kpid=403&trcatid=43&trid=911http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001586/
http://www.mayoclinic.com/health/anemia/DS00321

HealthTip: What is Anemia?

Anemia occurs when we don't have enough healthy red blood cells in our body. Red blood cells contain a red, iron-rich protein called hemoglobin. Hemoglobin gives red blood cells their color and allows them to carry oxygen to the body's tissues. To produce hemoglobin and red blood cells, the body needs iron, vitamin B-12, folate and other nutrients from food. Those with anemia may experience symptoms such as:

• Fatigue
• Pale skin
• Irregular heart beat
• Shortness of breath
• Chest pain
• Dizziness
• Cold hands and feet

Many of us take iron supplements because we consider ourselves to be anemic, but what if your anemia isn't related to an iron deficiency? If you experience these symptoms, see a physician to organize a blood test to determine if you have anemia, and what type.
If you do take an iron supplement, a few good tips to consider would be:

• The upper limit (the most you can have without taking an overdose) is 40 mg/ day for infants and 45mg/ day for adults
• These is good evidence to suggest that taking iron supplements with a meal including vitamin C (e.g. a glass of orange juice) will increase the absorption of iron supplement in the body
• Currently, no scientific evidence supports the thought that iron absorption is decreased if taken with milk

So, if supplements are the route that you choose to take, utilize your health-care team of physicians, pharmacists, and dietitians to make the best and safest choices for you.

Stay tuned for my next post about the different types of anemia's!

Information Sources:
http://www.mayoclinic.com/health/anemia/DS00321/DSECTION=causes
http://www.pennutrition.com.ezproxy.library.ubc.ca/KnowledgePathway.aspx?kpid=403&trid=1961&trcatid=42
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001586/