16 Popular Nuts and Seeds + Their Health Benefits
This blog has not been approved by your local health department and is not intended to provide diagnosis, treatment, or medical advice.
In this article:
- Nuts and Seeds Health Benefits
- Popular Nuts and Seeds
- 1. Almonds
- 2. Black Seed
- 3. Brazil Nuts
- 4. Cashew Nuts
- 5. Chia seeds
- 6. Fenugreek seeds
- 7. Flaxseeds
- 8. Hempseeds
- 9. Macadamia Nuts
- 10. Pecans
- 11. Pine Nuts
- 12. Pistachios
- 13. Pumpkin seeds
- 14. Sesame Seeds
- 15. Sunflower seeds
- 16. Walnuts
Nuts and Seeds Health Benefits
It is incredible to realize the nutritional value that nuts and seeds provide. They are rich food sources of essential fatty acids, protein, vitamin E, and minerals. Nuts and seeds are also rich in dietary fiber and an array of important health-promoting phytochemicals, including carotenoids, phytosterols like beta-sitosterol, and polyphenol compounds such as flavonoids, proanthocyanidins, and resveratrol. In some nuts, roasting destroys many of these compounds. While in almonds and pistachios, roasting does little harm.
One of the interesting findings about nut and seed consumption is that despite their high-calorie content, studies indicate that frequent consumption of nuts and seeds is associated with lower rates of obesity and diabetes. Eating nuts and seeds promotes satiety, the feeling of being full. They also are associated with a lower risk for diabetes through improved blood sugar control.1
Many nuts and seeds are also a rich source of the amino acid arginine. One of arginine's essential functions is to form nitric oxide. This compound is very important in improving blood flow and preventing the formation of blood clots. Elevated nitric oxide levels are thought to be one of the key reasons frequent nut and seed consumption reduces the risk of heart disease and strokes.2
By increasing arginine and nitric oxide levels, the consumption of nuts improves blood flow, reduces blood clot formation, and improves blood fluidity (the blood becomes less viscous and, therefore, flows through blood vessels more quickly). The improvement offered by increased dietary arginine or supplementation can be significant due to improved nitric oxide levels.2,3
Nuts and seeds can be eaten whole as snacks, added to foods like salads, whole grain cereals, or yogurt, or made into nut butter with a food processor. Nuts and seeds are also familiar sources of oils for cooking, salad dressings, and skin care products. Here are some important nuts and seeds to consider adding to your diet.
Popular Nuts and Seeds
Eating healthy nuts and seeds is highly beneficial. For those who want to enjoy an abundance of flavors and health benefits, it's important to incorporate different varieties into a diet. Research shows that the health benefits of nuts and seeds play a vital role in disease prevention. Fortunately, there are ample varieties available.
Almonds are packed full of nutrients and health-promoting compounds. They also promote blood sugar control and satiety, making them an excellent snack, especially for those having difficulty controlling blood sugar levels.4 Like other nuts, almonds appear pretty helpful in fighting against heart disease. Almonds produce this benefit when raw, roasted or consumed as nut butter.5 Almonds also exert antioxidant and other benefits in protecting the cardiovascular system from damage.
2. Black Seed
Black cumin (Nigella sativa) is the source of a ripe fruit containing tiny black seeds that have historically been used in folk medicine in the Middle East to promote good health. This chemically diverse seed contains powerful amino acids, proteins, minerals, fiber, potassium, and sodium. The black seed is spicy and exudes a powerful aroma. Research has shown that black seed promotes vitality and supports the heart, vascular system, liver, kidneys, and immune function.6
3. Brazil Nuts
Brazil nuts come from a giant evergreen tree (Bertholletia excelsa) that native to Amazonian forests. Rich in nutrients, Brazil nuts are the primary food source of selenium worldwide. Research has shown that organic selenium from Brazil nuts supports antioxidant activity and offers considerable protection against aging, heart disease, and chronic disease.7 Other beneficial nutrients are thiamine, protein, minerals, and fiber, which aids in weight loss, boost immunity, and enhance digestive health. Brazil nuts can be eaten blanched or raw.
4. Cashew Nuts
Cashews are the seed that adheres to the bottom of the apple of the cashew tree (Anacardium occidentale), native to northeastern Brazil. Cashews have a lower fat content and, as a result, a lower calorie density than other nuts. They are a good source of many minerals, especially magnesium, copper, potassium, iron, and zinc.
Like other nuts, the consumption of cashews (1.5 servings or 42 g per day) can positively affect blood cholesterol and glucose levels. The changes tend to be a little longer (12 weeks vs. 4 weeks).9,10
5. Chia seeds
Chia seeds (Salvia hispanica), are the the edible seeds of a flowering plant from the mint family plant native to Mexico and Central America. It became an important food crop in ancient Aztec, Mayan, and Mesoamerican cultures. Rich in many nutrients, Chia seed is exceptionally high in α-linolenic acid, an essential omega-3 fatty acid precursor to longer omega-3s like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that can be found in pre-formed in fish oil supplements. Chia seed consumption has shown an ability to promote improved blood sugar control and body weight in overweight adults. It has also been shown to improve endurance in distance runners.8 Like other nuts and seeds, chia seeds aid in blood pressure control and reduce other risk factors for cardiovascular disease.
6. Fenugreek seeds
Fenugreek (Trigonella foenum-graecum L.) is one of the world’s longest-used medicinal herbs. Modern investigations into fenugreek have established a basis for its health benefits. Fenugreek seeds contain 45 to 60% carbohydrates, including mucilaginous fiber, 20 to 30% protein high in the amino acids tryptophan and lysine, and 5 to 10% fat. While its nutritional profile is important, the real benefits appear to be from fenugreek’s rich supply of phytochemicals, especially alkaloids, flavonoids, and phenolic acids.11 Fenugreek has shown some benefits in improving blood sugar control and promoting weight loss in overweight individuals. An extract of fenugreek seeds having a unique 3:1 ratio for the compounds protodioscin to trigonelline has been shown to exert some beneficial effects in boosting testosterone levels in men and improving symptoms like hot flashes and depression in women going through menopause.12,
Flaxseeds are rich in omega-3 fatty acids, minerals, vitamins, fiber, and healthy protein. Since studies have shown that flaxseeds can help to promote regular bowel movements, prevent chronic disease, and lower cholesterol, they are healthy in many ways. Flaxseeds also come in yellow, dark brown, or golden varieties. They are flat in shape and have a nutty, sweet taste. The high fiber in flaxseeds helps with weight loss and appetite suppression.
Flax (Linum usitatissimum) is a plant native to the Mediterranean that has been used as a food item and for making linen cloth for over 5,000 years. Flaxseeds are small seeds a little larger than sesame seeds. They have a hard, smooth, and shiny shell that ranges in color from dark amber to reddish brown depending. Flaxseed has a nutty, sweet, and earthy taste. Flaxseeds are usually not consumed whole. Instead, they are ground to enhance nutrient absorption and health benefits.
Flaxseeds are rich in the essential omega-3 fatty acid alpha-linolenic acid (ALA). They are a very good source of dietary fiber, magnesium, and manganese. The primary health benefits focus on its ALA content and rich source of fiber components known as lignans. While ALA is an omega-3 fatty acids, it must be converted to the longer omega-3s in the body. Fish oils provide these longer-chain oils like EPA and DHA preformed. The conversion of ALA to EPA and DHA in the body is insufficient to meet the needs for these longer omega-3s.14 However, ALA has shown its health benefits, such as reducing the risk of heart disease and chronic disease.15
Flaxseeds are the most abundant sources of lignans. These fiber components exert many beneficial effects, primarily on breast health in women. Lignans increase the production of sex hormone-binding globulin, or SHBG. This protein binds sex hormones like estrogen and can help escort excess estrogen from the body. Much scientific evidence demonstrates that lignans have significant protective effects in both men and women. Ground flaxseeds also improve cardiovascular health by lowering cholesterol levels and exerting a mild effect in lowering blood pressure as well.16
Hempseeds are the highly nutritious seed of industrial hemp (Cannabis sativa). Hempseeds can be consumed whole and unhulled, but it is typically eaten by the “heart” or unhulled kernel. Hempseeds are also ground into flour or concentrated into protein powder. High in nutrition, hempseeds provide 25–35% fats that, like flaxseeds and chia, contain the essential omega-3 fatty acid, alpha-linolenic acid. It also contains 20–25% proteins and 20–30% carbohydrates, mainly dietary fiber. Hempseeds also provide a rich source of antioxidants and active phytochemicals. Hempseeds, like other nuts and seeds, are often eaten not only for their taste but also to help reduce inflammation, lower cholesterol and stabilize blood pressure.
9. Macadamia Nuts
The macadamia tree (Macadamia integrifolia) is native to the subtropical rainforests of Australia and is native to southern Queensland and northern New South Wales. Macadamia nuts are loved for their flavor, which owes primarily to a higher fat content (72%) and lowers protein content (8%) compared to other nuts. Macadamia nuts are a good source of many nutrients, including magnesium, potassium, niacin, thiamine, copper, and zinc.
Several studies with macadamia nut consumption have shown significant health benefits in lowering cholesterol. For example, in one study, macadamia nut consumption (40-90 g/d), lowered LDL cholesterol concentrations by 5.3%, respectively, raising protective HDL cholesterol levels by 7.9%.18
Pecans are versatile and edible nuts that grow on a majestic tree that is a type of hickory (Carya illinoensis) native to North America, specifically along the Mississippi River Valley. Like macadamia nuts, pecans also have a high-fat content, with most of the fat in the form of heart-healthy monounsaturated oleic acid, the main fat of olive oil. A 30 g serving of pecans supplies 190 calories, 19.5 grams of fat, 2.6 grams of protein, only 3.93 grams of carbohydrate, and 2.72 grams of dietary fiber. Pecans are an excellent source of many nutrients, especially B vitamins and minerals. A 30 g serving of pecans meets 71% of the recommended daily intake (RDI) for manganese, 38% of the RDI for copper, and almost 20% of the RDI for zinc.
Pecans provide significant amounts of plant sterols (95 mg per 100 g) that lower cholesterol levels. The chief sterol in pecans is beta-sitosterol, which represents 90% of the total sterols.
Beta-sitosterol and other sterols block cholesterol absorption from the intestine and can lower LDL cholesterol concentrations by 10-14%. Beta-sitosterol has also shown beneficial effects in supporting prostate health.19 In one double-blind study of 200 men with prostate enlargement, those taking beta-sitosterol (60mg daily) increased the maximum urine flow rate by 40%. It decreased the mean residual urine volume in the bladder after urination from 66 ml to 30 ml. A 100 g daily intake of pecans would provide approximately 90mg of beta-sitosterol.
Clinical studies have shown pecan consumption to lower LDL cholesterol. And even with subjects eating 100 g of pecans daily, delivering 459 calories and 44 grams of fat, they did not gain weight.20 Many people avoid nuts because they think these high-calorie foods will lead to weight gain, but this study and others show that does not appear to be the case (especially for raw nuts).
11. Pine Nuts
Pine nuts are the seeds of various species of pine trees, with those from the Mediterranean (Pinus pinea), Mexico (Pinus cembroides), and the Southwest United States (Pinus edulis) being the most widely available.
Like other nuts, pine nuts are rich in nutrients. But pine nuts provide more protein than any other nut as 100 g of pine nuts yields 24 g of protein. Pine nuts are a particularly rich source of the essential amino acid arginine. As stated in the Introduction, arginine is used to produce nitric oxide, a key compound for vascular health.
Pistachios are peanut-sized seeds of a small tree (Pistacia vera) native to the Middle East and western Asia that looks a bit like an apple tree. California is now one of the world’s largest producers of pistachios.
Pistachios are similar in nutritional profile to other nuts. It has a high-fat content (72%) and supplies reasonable levels of many B vitamins, such as B6, thiamin, and niacin. It is also an excellent source of trace minerals like zinc, copper, and manganese.
The health benefits of pistachios are like other nuts, and many clinical studies have been conducted showing cholesterol-lowering effects, heart and vascular health effects, improved blood sugar control, and weight loss-promoting effects. But pistachio intake has shown other health benefits that may be related to the unique phytochemical composition of pistachios. Pistachio consumption appears to exert significant anti-inflammatory and antioxidant effects due to its phytochemical composition, e.g., the high proanthocyanidin content. In clinical trials where human subjects consume or do not consume pistachios, those consuming pistachios show increased antioxidant activity in their blood and a decrease in inflammation and other oxidative markers.21
13. Pumpkin seeds
Pumpkins are a variety of winter squash that were celebrated by Native Americans for their dietary and medicinal properties. Like many of the other food treasures of the “New World,” the cultivation of pumpkins has spread throughout the world. Pumpkin seeds, also known as pepitas, are flat, dark green seeds. Some are encased in a yellow-white husk, although some varieties of pumpkins produce seeds without shells. Pumpkin seeds have a malleable, chewy texture and a subtly sweet, nutty flavor. They are a great simple snack. Pumpkin seeds are also a key ingredient in the recipes of many cuisines worldwide, especially common to traditional Mexican cuisine.
Pumpkin seeds are nutritious and excellent sources of essential fatty acids, plant sterols like beta-sitosterol, protein (29%), and magnesium, iron, zinc, manganese, and copper.
Pumpkin seeds have long been used to support prostate health. The prostate requires many of the nutrients in nuts and seeds to function properly, especially those pumpkin seeds that are rich in such as essential fatty acids, plant sterols, and zinc. The benefits of beta-sitosterol prostate enlargement is described above in the pecan description. While pecan is higher in beta-sitosterol (90% of the sterols in pecans are beta-sitosterol), pumpkins as a more than 2.5 times higher total sterol content than pecans (265 mg per 100 g for pumpkin seeds versus 95 mg per 100 g for pecans).21 The rich, unique phytosterol content of pumpkin seeds and their total nutritional profile make them stand out as a potentially valuable functional food in modern times compared to other nuts and seeds.22
14. Sesame Seeds
Sesame (Sesamum indicum) was one of the first cultivated food crops. Originating in India, sesame spread throughout the Middle East and world. Unhulled sesame seeds are very small, flat oval seeds that come in many colors, including white, yellow, red, and black. Hulled sesame seeds have a bitter taste, while unhulled sesame seeds are characterized as having a buttery, nutty taste and a delicate crunch. Sesame seeds are the main ingredients in Middle Eastern foods, tahini, and halvah.
Sesame seeds contain a 50% fat content, mainly monounsaturated fat. It has a 25% protein content with a favorable amino acid profile. Sesame seeds are high in the sulfur-containing amino acids methionine and cysteine. Many vegetarian protein sources such as soy, pea, peanuts, and other legumes lack sufficient levels of these important amino acids. Sesame seeds help to make these foods a complete protein. Sesame seeds are a good source B vitamins and minerals like magnesium, calcium, iron, and copper.
Sesame seeds are a rich source of sesamin, a lignin found only in sesame. Lignins are larger and more complex molecules lignans (see flaxseed above) with different health benefitsesamin has demonstrated some impressive antioxidant effects and are probably responsible for why sesame seed oil does not easily go rancid. has demonstrated remarkable antioxidant effects. In addition to providing antioxidant benefits to sesame products, sesamin is also responsible for the increased antioxidant capacity in the blood produced by sesame seed ingestion (40 g per day).23 Eating 40 g of sesame seeds daily also showed significant benefit in promoting joint health in a study in subjects with knee osteoarthritis.24
15. Sunflower seeds
Sunflowers provide antioxidant-rich seeds that have ample phytosterol levels. These heart-healthy snacks also contain calcium, niacin, protein, copper, selenium, magnesium, and fiber. Since sunflower seeds provide great flavor with low calories, they are used in a variety of meals. Sunflower seeds can be shelled or unshelled. They are also a great source of vitamin E.
Sunflower seeds are from Helianthus annuus, the beautiful and well-known sunflower. The grayish sunflower seeds are encased in tear-dropped shaped gray or black shells but can also have black and white stripes. Highly nutritious, sunflower seeds were a staple of the Native Americans for over 5,000 years. Rich in essential fatty acid linoleic acid, sunflower seeds are also a great source of vitamin E and many other nutrients, including thiamine, magnesium, selenium, vitamin B6, folate, and dietary fiber.
Sunflower seeds, like other seeds, are great simply as a health-promoting snack. Sunflower seeds can promote satiety and provide protein with a very good amino acid profile. Like other ancient seeds (chia, pumpkin, hemp, etc.), sunflower seeds are being investigated and promoted as a possible answer to curbing the rise in diseases of modern living, such as obesity, cardiovascular disease, and diabetes.25
Walnuts are the fruit of large, long-lived walnut trees. These large, oblong to round nuts are usually 3.75 to 6.25 cm in and surrounded by an outer, leathery husk that houses the wrinkled meat that resembles the human brain. The state of California in the United States provides more than half of walnuts produced commercially. Walnuts are an excellent source of health-promoting fats. About 13% of its fat content is from alpha-linolenic acid, the essential omega-3 fatty acid (see above discussion on Flaxseeds). Walnuts are a good source of many minerals, including manganese, magnesium, and copper.
Walnuts have proven to be a "brain food." It seems nature helped provide us with this clue because of its shell and meat's wrinkled, brain-like appearance. The benefits are not only due to its nutritional profile but, perhaps more importantly, to the phytochemicals the nut provides. It is rich in ellagic acid, which is converted to compounds by gut bacteria that protect cells and fight aging, especially in the brain and cardiovascular system.26
Human clinical trials have shown walnut consumption improves both cognitive performance and memory. Many underlying biochemical mechanisms are responsible for these effects, including reducing oxidative damage, increasing antioxidant defense, and decreasing inflammation within the brain. The effects of walnut consumption are so encouraging that many researchers suggest an early and walnut-enriched diet to help prevent and improve age-related brain function and memory loss.27
Walnuts are also very important in promoting cardiovascular health. The high alpha-linolenic acid and phytochemical content are a big part of this effect, but walnuts also contain relatively high arginine levels (see Introduction above). Numerous studies have shown walnuts produce heart-health benefits, including studies showing regular walnut consumption produces an additive protective effect of the heart-healthy Mediterranean diet. The walnut-rich Mediterranean diet produced lower levels of total cholesterol, LDL cholesterol, and Lp(a).28
- Ros E. Health benefits of nut consumption. Nutrients. 2010 Jul;2(7):652-682.
- Ros E. Nuts and novel biomarkers of cardiovascular disease. Am J Clin Nutr. 2009 May;89(5):1649S-56S.
- Mariotti F. Arginine supplementation and cardiometabolic risk. Curr Opin Clin Nutr Metab Care. 2020 Jan;23(1):29-34.
- Palacios OM, Maki KC, Xiao D, Wilcox ML, Dicklin MR, Kramer M, Trivedi R, Burton-Freeman B, Edirisinghe I. Effects of Consuming Almonds on Insulin Sensitivity and Other Cardiometabolic Health Markers in Adults With Prediabetes. J Am Coll Nutr. 2020 Jul;39(5):397-406.
- Kalita S, Khandelwal S, Madan J, Pandya H, Sesikeran B, Krishnaswamy K. Almonds and Cardiovascular Health: A Review. Nutrients. 2018 Apr 11;10(4):468.
- Hannan MA, Rahman MA, Sohag AAM, etal. Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety. Nutrients. 2021 May 24;13(6):1784.
- Cardoso BR, Duarte GBS, Reis BZ, Cozzolino SMF. Brazil nuts: Nutritional composition, health benefits and safety aspects. Food Res Int. 2017 Oct;100(Pt 2):9-18.
- Parker J, Schellenberger AN, Roe AL, Oketch-Rabah H, Calderón AI. Therapeutic Perspectives on Chia Seed and Its Oil: A Review. Planta Med. 2018 Jul;84(9-10):606-612.
- Mah E, Schulz JA, Kaden VN, Lawless AL, Rotor J, Mantilla LB, Liska DJ. Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial. Am J Clin Nutr. 2017 May;105(5):1070-1078.
- Mohan V, Gayathri R, Jaacks LM, et al. Cashew Nut Consumption Increases HDL Cholesterol and Reduces Systolic Blood Pressure in Asian Indians with Type 2 Diabetes: A 12-Week Randomized Controlled Trial. J Nutr. 2018 Jan 1;148(1):63-69.
- Visuvanathan T, Than LTL, Stanslas J, Chew SY, Vellasamy S. Revisiting Trigonella foenum-graecum L.: Pharmacology and Therapeutic Potentialities. Plants (Basel). 2022 May 29;11(11):1450.
- Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a andomized Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind andomized clinical study. Aging Male. 2016 Jun;19(2):134-42.
- Khanna A, John F, Das S, Thomas J, Rao J, Maliakel B, Im K. Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study. J Food Biochem. 2020 Dec;44(12):e13507.
- Burdge GC. Α-linolenic acid interconversion is sufficient as a source of longer chain ω-3 polyunsaturated fatty acids in humans: An opinion. Lipids. 2022 Nov;57(6):267-287.
- Yuan Q, Xie F, Huang W, Hu M, Yan Q, Chen Z, Zheng Y, Liu L. The review of alpha-linolenic acid: Sources, metabolism, and pharmacology. Phytother Res. 2022 Jan;36(1):164-188. doi: 10.1002/ptr.7295. Epub 2021 Sep 22. PMID: 34553434
- Parikh M, Maddaford TG, Austria JA, Aliani M, Netticadan T, Pierce GN. Dietary Flaxseed as a Strategy for Improving Human Health. Nutrients. 2019 May 25;11(5):1171.
- Farinon B, Molinari R, Costantini L, Merendino N. The seed of industrial hemp (Cannabis sativa L.): Nutritional Quality and Potential Functionality for Human Health and Nutrition. Nutrients. 2020 Jun 29;12(7):1935. d
- Garg ML, Blake RJ, Wills RB. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men. J Nutr. 2003 Apr;133(4):1060-3.
- Berges RR, Windeler J, Trampisch HJ. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.
- Rajaram S, Burke K, Connell B, Myint T, Sabate J. A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women. J Nutr. 2001;131(9):2275-9.
- Mateos R, Salvador MD, Fregapane G, Goya L. Why Should Pistachio Be a Regular Food in Our Diet? Nutrients. 2022 Aug 5;14(15):3207.
- Phillips KM, Ruggio DM, Ashraf-Khorassani M. Phytosterol composition of nuts and seeds commonly consumed in the United States. J Agric Food Chem. 2005 Nov 30;53(24):9436-45.
- Alasalvar C, Chang SK, Bolling B, Oh WY, Shahidi F. Specialty seeds: Nutrients, bioactives, bioavailability, and health benefits: A comprehensive review. Compr Rev Food Sci Food Saf. 2021 May;20(3):2382-2427.
- Gouveia Lde A, Cardoso CA, de Oliveira GM, Rosa G, Moreira AS. Effects of the Intake of Sesame Seeds (Sesamum indicum L.) and Derivatives on Oxidative Stress: A Systematic Review. J Med Food. 2016 Apr;19(4):337-45.
- Eftekhar Sadat B, Khadem Haghighian M, et al. Effects of sesame seed supplementation on clinical signs and symptoms in patients with knee osteoarthritis. Int J Rheum Dis. 2013 Oct;16(5):578-82.
- Kakkar S, Tandon R, Tandon N. The rising status of edible seeds in lifestyle related diseases: A review. Food Chem. 2023 Feb 15;402:134220.
- Sánchez-González C, Ciudad CJ, Noé V, Izquierdo-Pulido M. Health benefits of walnut polyphenols: An exploration beyond their lipid profile. Crit Rev Food Sci Nutr. 2017 Nov 2;57(16):3373-3383.
- Chauhan A, Chauhan V. Beneficial Effects of Walnuts on Cognition and Brain Health. Nutrients. 2020 Feb 20;12(2):550.
- Zambon D, Sabate J, Munoz S, Campero B, Casals E, Merlos M, Laguna JC, Ros E. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial. Ann Intern Med 2000;132(7):538-46.