The Landmark Dietary Supplement Study

Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study

Gladys Block, Christopher D Jensen, Edward P Norkus, Tapashi B Dalvi, Les G Wong, Jamie F McManus and Mark L Hudes.

Nutrition Journal 2007, 6:30doi:10.1186/1475-2891-6-30
Published 24 October 2007



Dietary supplement use in the United States is prevalent and represents an important source of nutrition. However, little is known about individuals who routinely consume multiple dietary supplements. This study describes the dietary supplement usage patterns, health, and nutritional status of long-term multiple dietary supplement users, and where possible makes comparisons to non-users and multivitamin/mineral supplement users.


Using a cross-sectional study design, information was obtained by online questionnaires and physical examination (fasting blood, blood pressure, body weight) from a convenience sample of long-term users of multiple dietary supplements manufactured by Shaklee Corporation (Multiple Supp users, n=278). Data for non-users (No Supp users, n=602) and multivitamin/mineral supplement users (Single Supp users, n=176) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and NHANES III 1988-1994. Logistic regression methods were used to estimate odds ratios with 95% confidence intervals.


Dietary supplements consumed on a daily basis by more than 50% of Multiple Supp users included a multivitamin/mineral, B-complex, vitamin C, carotenoids, vitamin E, calcium with vitamin D, omega-3 fatty acids, flavonoids, lecithin, alfalfa, coenzyme Q10 with resveratrol, glucosamine, and a herbal immune supplement. The majority of women also consumed gamma linolenic acid and a probiotic supplement, whereas men also consumed zinc, garlic, saw palmetto, and a soy protein supplement. Serum nutrient concentrations generally increased with increasing dietary supplement use. After adjustment for age, gender, income, education and body mass index, greater degree of supplement use was associated with more favorable concentrations of serum homocysteine, C-reactive protein, high-density lipoprotein cholesterol, and triglycerides, as well as lower risk of prevalent elevated blood pressure and diabetes.


This group of long-term multiple dietary supplement users consumed a broad array of vitamin/mineral, herbal, and condition-specific dietary supplements on a daily basis. They were more likely to have optimal concentrations of chronic disease-related biomarkers, and less likely to have suboptimal blood nutrient concentrations, elevated blood pressure, and diabetes compared to non-users and multivitamin/mineral users. These findings should be confirmed by studying the dietary supplement usage patterns, health, and nutritional status of other groups of heavy users of dietary supplements.

Author Affiliations:

  • Gladys Block
    PhD, School of Public Health, University of California, Berkeley, CA
  • Christopher D. Jensen
    PhD, MPH, School of Public Health, University of California, Berkeley, CA
  • Edward P. Norkus
    PhD, Department of Medical Research, Our Lady of Mercy Medical Center, Bronx, NY
  • Tapashi B. Dalvi
    MPH, School of Public Health, University of California, Berkeley, CA
  • Les G. Wong
    BS, Shaklee Corporation, Pleasanton, CA
  • Jamie F. McManus
    MD, Shaklee Corporation, Pleasanton, CA
  • Mark L. Hudes
    PhD, Nutritional Sciences, University of California, Berkeley, CA


Neuroscientists Fight Brain Damage with Gut Microbes

Neuroscientists from Cornell University have found that by tweaking the gut microbiota of mice it’s possible to reduce the amount of brain damage incurred following a stroke.

Their work, which is described in Nature Medicine, isn’t a readymade cure for brain damage, but it does shed new light on a very hyped topic in medicine—the relationship between the gut and brain—while offering some new hope to the some 800,000 Americans who will suffer a stroke in any given year.

A stroke is a medical emergency characterized by some variety of disrupted blood flow to the brain, either by way of blockage or by way of hemorrhage. Neurons are starved of their blood supply and very quickly die. The non-fatal result is usually a combination of impaired functioning—including but not limited to cognitive deficits, hearing and vision loss, emotional and psychological problems, and, very frequently, some degree of paralysis—and, thus, permanent disability.

Functioning can sometimes be regained, at least partially, but this is by no means a guaranteed outcome. Emergency stroke interventions mostly involve removing whatever blockage is causing the stroke in the first place (a clot), usually with drugs or sometimes surgery.

The Cornell work has to do with the gut-brain coupling imposed by the immune system. Following a stroke, pro-inflammatory compounds are produced in the intestines and travel to the brain, where they cause all sorts of inflammatory trouble and ultimately facilitate brain damage beyond normal blood deprivation.

The microbes in question here are known generally as commensal bacteria. Their whole commensal thing is chilling on the parts of your body exposed to the outside world (skin, respiratory tract, gastrointestinal tract), a group of surfaces known together as the epithelium, and living it up courtesy of your various forms of filth. While often thought of as “good bacteria,” their goodness is only provisional: Good bacteria can become bad bacteria very fast if the body’s immune system goes south.

Post-stroke MRI. Image: Wiki

This immune system is represented on epithelial surfaces by Gamma delta T cells (?? T cells), which are in their highest abundance within the mucosal membranes of the intestines. Their role seems to be as a sort of early-warning system for infections and they help direct the body’s inflammatory responses. The Gamma deltas are part of the immune system’s peripheral defenses, which includes all of the immune system outside of the brain.

But they can still have effects on the brain, which is still a bit mysterious. “The peripheral immune system, which involves both innate and adaptive immune cells, has an essential role in the pathophysiology of stroke and contributes to secondary neurodegeneration by releasing neurotoxic factors, including reactive oxygen and nitrogen species, as well as exopeptidases,” the current paper explains.

So, while a stroke has the obvious effect of starving neurons of blood, there’s this whole secondary wave of destruction, which comes courtesy of the gut-dwelling Gamma delta dudes. The neuroscientists found that these cells race to the meninges, the interface between the brain and spinal cord, following a stroke, and it would thus seem that immune cells have something of a gut-brain expressway (a gut-brain axis, properly) at their disposal.

The researchers tailored the gut bacteria in their experiments using both antibiotics and fecal transplants from other mice that had been treated with antibiotics. By doing so they were able to reduce the destructive Gamma deltas while also boosting the production and transport of anti-inflammatory immune cells called Treg cells. They found that after inducing these changes, fewer inflammatory cells made their way up to the meninges, which is obviously a good thing. Less inflammation occurs in the brain, and so less destructon.

There’s still a lot of work to do here. For one thing, it’s unknown how all of this scales to human bodies and whether the effects can be replicated. We’re still a long ways off from emergency room fecal transplants for stroke patients, but at the very least we’ve learned something interesting about the immune system’s role in bridging guts and brains.


Honey-Lavender Lemonade Recipe

5590Enjoy a refreshing twist on a classic beverage. This lemonade recipe includes honey and Lavender Vitality™ essential oil for an added touch of sophistication and depth.

Sophisticated, yes. Complicated, no. With just five simple ingredients, this is a warm-weather treat you can whip up in minutes. So throw on a sun hat, grab your favorite book, and find a sunny spot. This Honey-Lavender Lemonade is the perfect summer companion. You may even find yourself lifting your pinky finger as you sip.

Honey-Lavender Lemonade Recipe
Prep Time: 10 minutes

Total Time: 10 minutes

Yield: About 10 cups


  • 6 lemons, juiced
  • 1 lime, juiced
  • ½ cup honey
  • 2 drops Lavender Vitality essential oil
  • Ice water, about 10 cups
  • Lavender sprigs, optional


  1. Combine lemon juice, lime juice, honey, and Lavender Vitality in a large glass pitcher.
  2. Add water to taste.
  3. Stir until well mixed.
  4. Garnish with sprigs of lavender.

This blog was reprinted with permission from the Young Living website.

Vitamin D Shines Beyond Bone Health

Shaklee Health Sciences

Green grass and blue sky with sun

Do you know which nutrient is created in your skin when exposed to adequate sunlight, facilitates calcium absorption and is so important to humans that it is considered to be both a vitamin and a hormone? Many of you may have guessed vitamin D and you would be correct! Vitamin D has long been recognized for its essential role in bone health. Working in concert with a number of other vitamins, minerals and hormones, vitamin D helps promote bone mineralization (1). Your body is finely tuned to utilize Vitamin D in the incorporation of calcium and other minerals into supporting the very dynamic process of bone shaping and reshaping and without adequate intakes of vitamin D your bones can become brittle leading to an increased risk of bone fractures and osteoporosis. But there are a number of other functions Vitamin D plays in the body and research is finally beginning to uncover some exciting new health benefits of Vitamin D.

Now there is really exciting new research indicating that vitamin D’s health benefits may shine well beyond bone health. Because vitamin D also plays an important role in maintaining a healthy immune system and regulating cell growth and differentiation (2, 3), the process that determines what a cell is destined to become, supplemental vitamin D may actually be helpful for cancer prevention, in particular prostate, breast and colon cancers (4, 5, 6, 7).

In 2005, Harvard researchers reported the results of a study involving 1029 men with prostate cancer and 1,300 healthy men. After analyzing the blood of these men, researchers found that men with the highest level of vitamin D had significantly lower overall risk (45%) of prostate cancer, including aggressive prostate cancer. In addition, men with a specific receptor that helps vitamin D work got greater protection if they also had high levels of vitamin D in their blood. Those men had a 55% lower risk of prostate cancer and 77% lower risk of aggressive cancer.

Just this year, researchers pooled data from two earlier studies, the Nurses Health Study and the St. George’s Hospital Study and found that women with the highest blood levels of the active form of vitamin D had the lowest risk of breast cancer. Researchers also reported that the level of vitamin D in the blood associated with a 50% reduction in risk could be maintained by taking 2000 IU of vitamin D3 daily plus spending as little as 10-15 minutes a day in the sun (8).

Vitamin D emerged as a protective factor against colon cancer in a study of over 3,000 adults (96% of whom were men) who underwent a colonoscopy between 1994 and 1997 to look for polyps or lesions in the colon. About 10% of the group was found to have at least one advanced cancerous lesion in the colon. However, there was a significantly lower risk of advanced cancerous lesions among men with the highest vitamin D intake.

Such study results have sparked further interest in the role of vitamin D for cancer prevention and more good news for vitamin D has just arrived. In the June 2007, issue of the American Journal of Clinical Nutrition, researchers at the Osteoporosis Research Center at Creighton University discovered that postmenopausal women taking calcium or calcium plus vitamin D for reducing the risk of bone fractures (the primary outcome of the study), got the added benefit of a significant reduction in the risk of cancer. In this study, 1179 healthy, post-menopausal women were randomly assigned to receive 1400-1500 mg of calcium, 1400-1500 mg of calcium plus 1100 IU of vitamin D3, or a placebo. After 4 years, women receiving calcium only reduced their risk of developing cancer by 47% and the women taking calcium plus vitamin D, had a 60% risk reduction!

The findings of such studies really do highlight the importance of achieving optimum vitamin D status. Eating a healthy diet including foods fortified with vitamin D, like reduced fat milk or soy milk is certainly a good place to start. However keep in mind that many dairy products made from milk (e.g. cheese, reduced fat ice cream) are not typically fortified with vitamin D and contain only small amounts. Some ready to eat cereals may be fortified but only a few commonly eaten foods are good sources of vitamin D, like cooked salmon, mackerel and tuna.

Sun exposure for about 10 to 15 minutes at least two times a week can help, but remember sunscreen use which helps reduce the risk of skin cancer, actually blocks vitamin D synthesis in the skin. And if you plan on being out in the sun, make sure you avoid the most dangerous time of the day, between the hours of 10 am to 2 pm.

And of course, one of the safest and most convenient ways to get adequate amounts of vitamin D is to take a multivitamin/mineral supplement and/or a calcium supplement with added vitamin D. Look for a supplement with at least 400 to 800 IU of vitamin D per serving and one that provides the most active form of vitamin D, Vitamin D3 also known as cholecalciferol.

Be well.

Dr. Jamie McManus MD, FAAFP

Chairman, Medical Affairs, Health Sciences and Education


Deluca HF and Zierold C. Mechanisms and functions of vitamin D. Nutr Rev 1998;56:S4-10.
Hayes CE, Hashold FE, Spach KM, Pederson LB. The immunological functions of vitamin D endocrine system. Cell Mol Biol 200;49:277-300.
Holick MF. Evolution and function of vitamin D. Recent Results Cancer Res. 2003;164:3-28.
Martinez ME and Willet WC. Calcium, vitamin D and colorectal cancer: a review of epidemiologic evidence. Cancer Epidemiol. Biomark. Prev 1998;7:163-68.
Garland C et al. Dietary vitamin D and calcium and risk of colorectal cancer: a 19 year prospective study in men. Lancet 1985;1:307-9.
H. Li, M. Stampfer, E. Giovannucci et al. Prediagnostic plasma vitamin D levels, vitamin D receptor gene polymorphisms, and susceptibility to prostate cancer. 2005 Prostate Cancer Symposium.
Leiberman D, et al. Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 2003;290:2959-67.
Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. AJCN 2007;85:1586-91.

Essential Oil Spotlight: Blue Cypress

Blue-Cypress2-121x300Are you familiar with Blue Cypress essential oil? Surprisingly, many of our members are not yet acquainted with this amazingly versatile oil. Let me introduce you!

Sometimes referred to as Blue Gold, Blue Cypress is a beautiful, cobalt blue and is the only naturally blue essential oil that comes from a tree. Other blue essential oils such as German Chamomile and Blue Tansy are from flowers. So distinctive and beloved is this tree’s aroma that it was chosen as the official fragrance of the Sydney 2000 Olympics.

Young Living’s Blue Cypress essential oil is steam distilled from the leaves and wood of the rare Northern Cypress Pine, native only to Australia’s Northern Territory. The scientific name of Blue Cypress, Callitris intratropica, is derived from the Greek calli (beautiful) and treis (three), which references the tree’s triangular leaves that are arranged in spirals of three.

Blue Cypress has been used for thousands of years by Australian aboriginal people in a variety of household and personal applications. Here are a few ways you can use Blue Cypress:

Blue-Cypress-2-300x1991. Support muscles. Blue Cypress is great to use post-workout. Just add a few drops to V-6 Vegetable Oil ComplexOrtho Ease® Massage Oil, or Ortho Sport® Massage Oil and rub it on muscles after physical workouts.

2. Moisturize skin. Blue Cypress has excellent beneficial properties for the skin. Use Blue Cypress alone or blend it with Sacred Frankincense, Lavender, and Royal Hawaiian Sandalwood essential oils and apply topically to hydrate the skin after time outside.

3. Soothe skin while shaving. Add a drop or two of Blue Cypress to shaving cream, soap, or aftershave to help prevent razor burn.

4. Use in household cleaning. Add Blue Cypress to Thieves® Household Cleaner for extra cleaning power or include it in a custom blend of Lemon and Clove essential oils mixed in water to create your own all-purpose cleaner for kitchens, bathrooms, desktops, and other surfaces.

This blog was written by Young Living International and Portfolio Brand Manager Heidi Jeanfreau, and reprinted with permission from the Young Living website.

Essential Smoothies: Ingredients and Recipes to Power Your Day

green-smoothie-300x199Smoothies are a great way to satisfy your hunger, while easily adding in your daily fruits and vegetables. Here are some of the best ingredients for smoothies, and a few recipes that you’ll love.


High Protein Ingredients: Pack your smoothie full of protein with these ingredients, which will provide you with the energy you need to keep your day going:

  • Nonfat or low-fat plain yogurt or Greek yogurt
  • Nonfat or low-fat plain milk
  • Nonfat or low-fat plain kefir
  • Tofu
  • Natural peanut butter
  • Almond butter
  • Plain soymilk
  • Almond milk
  • Young Living Pure Protein Complete: Vanilla Spice or Chocolate Deluxe

Greens: Get in your daily dose of vegetables by adding spinach, kale, or celery to your smoothies. Since they will be grounded down into a drinkable form, these foods will be a lot easier to consume. Plus, your body needs them and they will boost your energy.

Fruit: Use fresh fruit or frozen fruit. If your fruit is frozen, your smoothie will end up more thick. The best fruits for smoothies are:

  • Berries (strawberries, blueberries, raspberries, and blackberries)
  • Mango
  • Pineapple
  • Peach
  • Banana
  • Apple
  • Melon
  • Cherries
  • Apricot

Essential Oils: Pack your smoothie with energy and flavor with essential oils. Some of the best essential oils for smoothies include Orange, Lime, Lemon, Grapefruit, and Tangerine. Be sure to consult individual product labels before using any essential oils in smoothies.

NingXia Red: With the combination of the wolfberry superfruit, pure Lemon, Orange, Yuzu, and Tangerine essential oils, along with blueberry, aronia, cherry, pomegranate, and plum juices, NingXia Red has tons of awesome ingredients you will love. Add 1-2 ounces to your smoothie or add a NingXia Red Singles packet.

NingXia Nitro: Give your smoothie an energy boost with NingXia Nitro! This product combines 100 percent pure, therapeutic-grade essential oils with powerful ingredients such as Green tea extract, Korean ginseng, and several fruit juices.

Smoothie Recipes

Try any of these delicious smoothie recipes to power your morning, afternoon, or evening.

Green Banana Smoothie


  • 1 cup water
  • 1 cup spinach
  • ½ cup kale
  • 1 banana
  • 1-2 drops of each essential oil of your choice
  • 1 cup ice


Put ingredients into a blender. Blend until smooth.

Pure Protein Green Smoothie


  • 1 cup water
  • 1 cup spinach
  • 1 scoop Young Living Pure Protein Complete
  • 1-2 tablespoons peanut or almond butter
  • 1-2 drops of each essential oil of your choice
  • 1 cup ice


Put ingredients into a blender. Blend until smooth.

Strawberry Banana Power Smoothie


  • 1 cup water
  • ½ cup frozen strawberries
  • 1 banana
  • 1 scoop Vanilla Spice Pure Protein Complete
  • 1-2 drops of each essential oil of your choice
  • 1 cup ice


Put ingredients into a blender. Blend until smooth.

Chocolate Protein Delight Smoothie


  • I cup water
  • 1 banana
  • 1 scoop Chocolate Deluxe Pure Protein Complete
  • 1-2 tablespoons peanut or almond butter
  • 1-2 drops of each essential oil of your choice
  • 1 cup ice


Put ingredients into a blender. Blend until smooth.

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ADD/Concentration (12 yrs+) High Blood Pressure
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Adrenal Glands Hayfever
Allergies Immune System Booster
Anxiety & Panic Attack Incontinence
Arthritis, Rheumatism Kidneys
Asperger’s Syndrome Liver
Asthma Memory Problems
Autism Menopause Relief
Bad Breath Motion Sickness
Bladder Infection, UTI Muscle Pain Relief
Bruising, Healing Obsessive Compulsive Disorder
Candida, Yeast Infection Premenstrual Syndrome (PMS)
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Thiamine ‘reverses kidney damage

Doses of vitamin B1 (thiamine) can reverse early kidney disease in people with type 2 diabetes, research shows.
The team from Warwick University tested the effect of vitamin B1, which is found in meat, yeast and grain, on 40 patients from Pakistan.
The treatment stopped the loss of a key protein in the urine, the journal Diabetologia reports.
Charity Diabetes UK called the results “very promising” – but said it was too early for any firm conclusions.
The latest findings build on earlier work by the Warwick University team, showing that many diabetes patients have a deficiency of thiamine.
According to the researchers, this cheap and readily available supplement could benefit most people with diabetes – both type 1 and type 2 – as between 70% and 90% of people with diabetes are thiamine deficient.
In diabetes the small blood vessels in the body can become damaged.
We would not advise that people look to vitamin supplements to reduce their risk of kidney complications at this stage
Dr Iain Frame of Diabetes UK
When the blood vessels that supply blood to the kidneys are involved, the kidneys stop working correctly and important proteins, such as albumin, are lost from the blood into the urine.
A third of the patients in the study saw a return to normal urinary albumin excretion after being treated with high dose (300mg) thiamine taken orally each day for three months.
The experts say thiamine works by helping protect cells against the harmful effects of the high blood sugar levels found in diabetes.
Lead researcher Professor Paul Thornalley said: “This is the first study of its kind and suggests that correcting thiamine deficiency in people with diabetes with thiamine supplements may provide improved therapy for early-stage kidney disease.”
They plan more work to confirm their findings.
Dr Iain Frame of Diabetes UK said: “Diabetes UK hopes a large clinical trial will be possible as results so far are very promising.
“However, we would like to stress that it’s still too early to come to any firm conclusions about the role of vitamin B1 and we would not advise that people look to vitamin supplements to reduce their risk of kidney complications at this stage.”
A person should be able to get all the thiamine they need from a normal healthy diet.

Finding May Solve Riddle of Fatigue in Muscles

One of the great unanswered questions in physiology is why muscles get tired. The experience is universal, common to creatures that have muscles, but the answer has been elusive until now.
Scientists at Columbia say they have not only come up with an answer, but have also devised, for mice, an experimental drug that can revive the animals and let them keep running long after they would normally flop down in exhaustion.
For decades, muscle fatigue had been largely ignored or misunderstood. Leading physiology textbooks did not even try to offer a mechanism, said Dr. Andrew Marks, principal investigator of the new study. A popular theory, that muscles become tired because they release lactic acid, was discredited not long ago.
In a report published Monday in an early online edition of Proceedings of the National Academy of Sciences, Dr. Marks says the problem is calcium flow inside muscle cells. Ordinarily, ebbs and flows of calcium in cells control muscle contractions. But when muscles grow tired, the investigators report, tiny channels in them start leaking calcium, and that weakens contractions. At the same time, the leaked calcium stimulates an enzyme that eats into muscle fibers, contributing to the muscle exhaustion.
In recent years, says George Brooks of the University of California, Berkeley, muscle researchers have had more or less continuous discussions about why muscles fatigue. It was his work that largely discredited the lactic-acid hypothesis, but that left a void.
What did make muscles tired?
The new work in mice, Dr. Brooks said, “is exciting and provocative.” It is a finding that came unexpectedly from a very different line of research. Dr. Marks, a cardiologist, wanted to discover better ways to treat people with congestive heart failure, a chronic and debilitating condition that affects an estimated 4.8 million Americans.
Its hallmark is a damaged heart, usually from a heart attack or high blood pressure. Struggling to pump blood, the heart grows, sometimes becoming so large that it fills a patient’s chest. As the disease progresses, the lungs fill with fluid. Eventually, with congested lungs and a heart that can barely pump, patients become so short of breath that they cannot walk across a room. Half die within five years.
In his efforts to understand why the heart muscle weakened, Dr. Marks focused on the molecular events in the heart. He knew the sequence of events. As the damaged heart tries to deal with the body’s demands for blood, the nervous system floods the heart with the fight or flight hormones, epinephrine and norepinephrine, that make the heart muscle cells contract harder.
The intensified contractions, Dr. Marks and his colleagues discovered, occurred because the hormones caused calcium to be released into the heart muscle cells’ channels.
But eventually the epinephrine and norepinephrine cannot stimulate the heart enough to meet the demands for blood. The brain responds by releasing more and more of those fight or flight hormones until it is releasing them all the time. At that point, the calcium channels in heart muscle are overstimulated and start to leak.
When they understood the mechanisms, the researchers developed a class of experimental drugs that block the leaks in calcium channels in the heart muscle. The drugs were originally created to block cells’ calcium channels, a way of lowering blood pressure.
Dr. Marks and his colleagues altered the drugs to make them less toxic and to rid them of their ability to block calcium channels. They were left with drugs that stopped calcium leaks. The investigators called the drugs rycals, because they attach to the ryanodine receptor/calcium release channel in heart muscle cells. The investigators tested rycals in mice and found that they could prevent heart failure and arrhythmias in the animals. Columbia obtained a patent for the drugs and licensed them to a start-up company, Armgo Pharma of New York. Dr. Marks is a consultant to the company.
It hopes to start testing one of the drugs for safety in patients in the spring, but the tests will not be at Columbia because of the university and investigators’ conflicts of interest. In the meantime, Dr. Marks wondered whether the mechanism he discovered might apply to skeletal muscle as well as heart muscle. Skeletal muscle is similar to heart muscle, he noted, and has the same calcium channel system. And heart failure patients complain that their muscles are extremely weak.
“If you go to the hospital and ask heart failure patients what is bothering them, they don’t say their heart is weak,” Dr. Marks said. “They say they are weak.”
So he and his colleagues looked at making mice exercise to exhaustion, swimming and then running on a treadmill. The calcium channels in their skeletal muscles became leaky, the investigators found. And when they gave the mice their experimental drug, the animals could run 10 to 20 percent longer.
Then, collaborating with David Nieman, an exercise scientist at Appalachian State University in Boone, N.C., the investigators asked whether the human skeletal muscles grew tired for the same reason, calcium leaks.
Highly trained bicyclists rode stationary bikes at intense levels of exertion for three hours a day three days in a row. For comparison, other cyclists sat in the room but did not exercise.
Dr. Nieman removed snips of thigh muscle from all the athletes after the third day and sent them to Columbia, where Dr. Marks’s group analyzed them without knowing which samples were from the exercisers and which were not.The results, Dr. Marks said, were clear. The calcium channels in the exercisers leaked. A few days later, the channels had repaired themselves. The athletes were back to normal.
Of course, even though Dr. Marks wants to develop the drug to help people with congestive heart failure, hoping to alleviate their fatigue and improve their heart functions, athletes might also be tempted to use it if it eventually goes to the market.
The odds are against this particular drug being approved, though, cautions Dr. W. Robb McClellan, a heart disease researcher at U.C.L.A.
“In heart failure, there are three medications that improve mortality, but there have probably been 10 times that many tested,” he said.
Even if the first drug that prevents calcium leaks does not work in patients, Dr. McClellan added, the important advance is to understand the molecular events underlying fatigue. “Then,” he said, “you can design therapies.”
So the day may come when there is an antifatigue drug.
That idea, “is sort of amazing,” said Dr. Steven Liggett, a heart-failure researcher at the University of Maryland. Yet, Dr. Liggett said, for athletes “we have to ask whether it would be prudent to be circumventing this mechanism.”
“Maybe this is a protective mechanism,” he said. “Maybe fatigue is saying that you are getting ready to go into a danger zone. So it is cutting you off. If you could will yourself to run as fast and as long as you could, some people would run until they keeled over and died.”

Giving Disorganized Boys the Tools for Success

LOS ALTOS, Calif. — “Can we take a look at your backpack?”
Ana Homayoun repeats that question countless times a day. No, she does not screen airline passengers or work security at a basketball arena.
Ms. Homayoun is a tutor. She helps teenagers with subjects like math and science, but she particularly specializes in teaching boys how to become more organized.
One afternoon in her cozy office suite in this affluent suburb south of San Francisco, she asked John Ferrari, 14, to go through a two-inch stack of papers he pulled from his backpack. He sorted through the papers, placing them in separate piles — writing, spelling, vocabulary, tests — to bring order to his loose-leaf binder.
“Oh, here’s my class schedule, what a relief,” said John, an eighth grader.
A moment later, he stumbled across something even more valuable. “I have to turn this in tomorrow,” John said. “It’s the name I want on my diploma.”
With girls outperforming boys these days in high school and college, educators have been sparring over whether there is a crisis in the education of boys. Some suggest the need for more single-sex schools, more male role models or new teaching techniques. Others are experimenting with physical changes in classrooms that encourage boys to move around, rather than trying to anchor them to their seats.
But as they debate, high-priced tutors and college counselors have jumped into the fray by charging as much as $100 an hour and up to bring boys to heel.
The tutors say their main focus is organizational skills because boys seem generally to have more difficulty getting organized and multitasking than girls do.
And so private counselors in places as diverse as Chicago, New York City, Sarasota, Fla., and Bennington, Vt., who guide juniors and seniors in applying to college, have devised elaborate systems — from color-coded, four-month calendars that mark dozens of deadlines to file boxes that students must take to each session.
Donna Goldberg began working with students in Manhattan on how to get organized 17 years ago. Her inspiration was her own son, then in seventh grade. Mrs. Goldberg was astonished to learn that he had not been turning in any homework.
“He opened his backpack, which was really a black hole, and he said, ‘Here it is,’ ” she said. He had not understood that in seventh grade he was responsible for handing in his homework, instead of waiting to be asked.
Some educators think the tutors are on the right track, whether or not there is science to back them up. “The guys just don’t seem to develop the skills that involve organization as early,” said Judith Kleinfeld, a psychology professor at the University of Alaska and founder of the Boys Project, a coalition of researchers, educators and parents to address boys’ problems.
Mrs. Goldberg, Ms. Homayoun and other private tutors say boys must learn not only how to organize, but also how to manage their time and even how to study.
Robert Gittings, a sixth grader, has been coming weekly to work with Ms. Homayoun since September. He, too, is asked to empty his backpack, and on one visit, cheerfully removed a vast collection of textbooks, binders, workbooks, paperback books and hardcover library books.
Most of the binders were orderly and reasonably neat. But there was a stack of papers from science, nearly an inch thick, that needed to be sorted.
“Do you have homework for tonight?” Ms. Homayoun asked.
He replied, “We have a work sheet.” But it was not in the homework section of the science binder or in his daily planner.
Then Robert remembered where he put it. From a side pocket of his backpack, he pulled a sheet of paper that has been folded into a tiny rectangle.
Ms. Homayoun laughed and said gently, “Maybe we should put that in the homework section?”
Ms. Homayoun opened her business, Green Ivy Educational Consulting, not long after graduating from Duke University in 2001. She created her organizational system — basically an elaboration of the ways she studied in high school — after she began tutoring six years ago.
“I would ask, What’s the class that troubles you the most?” she said. “I would ask to see the binder, and it would always be the messiest.”
She requires her clients to have a three-ring, loose-leaf binder for each academic subject, to divide each binder into five sections — notes, homework, handouts, tests and quizzes, and blank paper — and to use a hole puncher relentlessly, so that every sheet of school-related paper is put into its proper home.
Students must maintain a daily planner; they are required to number the order in which they want to do each day’s homework and draw a box next to each assignment, so it can be checked off when completed.
Homework must be done in a two-hour block in a quiet room, with absolutely no distractions: no instant messaging, no Internet, no music, no cellphone, no television.
While some girls need help getting organized, at least three-quarters of her students are boys, Ms. Homayoun said. Girls usually adopt her methods more quickly.
“Girls pick up on this much faster,” said Ms. Homayoun, 28, who has a relaxed but firm manner and a gift for diplomacy with teenagers and their parents. “Boys, you still have to be on them for a while. They’re not going to pick up on it immediately. You have to roll with it.”
Two seniors arrived for weekly appointments, expecting to complete their college applications and file them online. But the tutor discovered that one boy left out sections of basic personal information on his application, while the other missed a requirement for three short essays by the University of Virginia. Each was disappointed that there was more work to do.
“Sorry,” she consoled one. “It’s like thinking you’ve finished a marathon and finding out you have three miles left.”
With guidance and constant follow-up, boys can make significant progress, Ms. Homayoun said. Ernie McMillan, 17, a high school senior who has been working with her since the summer before his junior year, is one example. He created orderly binders, kept on top of his daily planner, took notes while reading and even agreed to eliminate distractions during homework.
In the spring of his sophomore year, Mr. McMillan had a 2.8 grade-point average, a B-minus. After working with Ms. Homayoun, he raised his average to 3.1 in the first semester of his junior year. Last spring, he brought it up to 3.5, a B-plus.
“I was really happy about that,” he said. “I always thought I could do it, and I didn’t understand why I couldn’t. I just needed that backing, that structure. I was turning in my assignments on time. I was working ahead on my classes. I was organized in a way I never had been before.”
Mr. McMillan stopped for a moment, before adding, “She totally reworked my backpack, too.”
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