Sunday, December 30, 2012

HIV kills off girl's leukemia

US doctors say they have saved a seven-year-old girl who was close to dying from leukemia by pioneering the use of an unlikely ally: a modified form of HIV.
After fighting Emily Whitehead's disease with chemotherapy for almost two years and watching the young girl have two relapses, doctors at the Children's Hospital of Philadelphia said she "faced grim prospects". In February, they agreed to take her on in an experimental program that fought fire with fire.
Helped by a genetically altered HIV - stripped of the devastating properties that cause AIDS - doctors turned the girl's immune cells into a superior force able to rout the "aggressive" leukemia.
Emily was the first child and one of only a handful of people to be given what's officially known as CTL019 therapy.
The hospital stressed this could not yet be called "a magic bullet".
But in her case, at least, the success was dramatic.
First, millions of the girl's natural immune system cells were removed. Then the modified HIV was used to carry in a new gene that would boost the immune cells and help them spot, then attack, cancer cells that had previously been able to sneak in "under the radar".
Finally, the rebooted immune cells were sent back in to do their work. "The researchers have created a guided missile that locks in on and kills B cells, thereby attacking B-cell leukemia," the hospital said.

Monday, December 10, 2012

How to increase your testosterone level

14 ways to naturally Increase your testosterone

1. Get more Zinc
Zinc is very important for the production of natural testosterone
because Zinc prevents testosterone from being converted into estrogen (the female hormone) by making the enzyme aromatase not work (look at #3 below) plus…

Zinc itself turns estrogen into testosterone and Zinc helps produce healthier sperm and higher sperm counts so actually… Low levels of zinc can cause low testosterone levels.
Foods high in Zinc include oysters (a natural aphrodisiac), liver, seafood, poultry, nuts & seeds or you can supplement with at least 50-to-100mg of Zinc daily
2. Eat more healthy fats
Research has shown that men who ate diets rich in healthy fats like monounsaturated fats & Omega-3 fats had the highest testosterone levels so…
You can naturally raise your testosterone levels by adding more healthy fats by eating more nuts & seeds, fatty fish like salmon & tuna, avocados, olives, vegetable oils, and natural peanut butter and…
Eating a very low-fat diet can actually lead to lowered testosterone levels because your body needs healthy fats in order to produce testosterone but…
This doesn't mean you need to eat a REAL HIGH fat diet - Just make sure at least 20-to-30% of your total daily calories comes from healthy fats.
3. Lose body fat
The more overweight you are or the higher your body fat percentage is = The higher your estrogen levels will be because body fat contains an enzyme called aromatase that converts your 'manly' testosterone into 'womanly' estrogen making your testosterone levels drop so…
Look at these fat burning workouts to lower body fat, reduce estrogen and increase testosterone and…
Try not to Diet or cut too many calories when trying to lose body fat because you don't want your body going into starvation or survival mode which will cause your body to stop making testosterone so whenever you're trying to lose fat & increase testosterone at the same time…
Make sure you focus on losing 1-to-3 pounds of fat a week mainly thru fat loss workouts and a basic diet plan
4. Get rid of excess estrogen
To get rid of excess estrogen that makes you fatter & weaker so your body can naturally produce more testosterone…
5. Try to avoid Xenoestrogens
Xenoestrogens are man-made estrogens that are found in things like pesticides, artificial growth hormones & steroids, air fresheners and plastic containers and these xenoestrogens will increase your levels of the female hormone estrogen while lowering testosterone so…
  • Eat more organic fruits & vegetables that are free of pesticides and if you do buy your fruits & vegetables at a regular grocery store… Make sure you wash them to lower your chances of consuming any xenoestrogens and…
  • Eat more naturally raised meats instead of eating beef, chicken, pork and even milk that was raised using artificial growth hormones and steroids and…
  • Use glass products to store food & water instead of plastic since plastic products tend to produce xenoestrogens that'll get into your water & food especially when heated and… Even some canned foods contain plastic coatings that contain xenoestrogens and…
  • Don't use any perfumes, colognes, or air fresheners that have parabens listed as one of the ingredients. Parabens are xenoestrogens.
Please note: It'll be fairly hard for you to 100% completely avoid all xenoestrogens but if you follow the other tips on this page (especially tips #3 & #4) - You'll still be able to naturally increase your testosterone while getting rid of excess estrogen without having to worry so much about trying to avoid xenoestrogens and…

Also note: Since most xenoestrogens accumulate in your body fat - your best defense against xenoestrogens is to lose body fat (look at #3 again)
6. Get at least 6-to-8 hours of Sleep every night
A university of Chicago study showed that men who got little sleep had way lower testosterone levels than men who got 6-to-8 hours of sleep and… According to a University of North Carolina study… Your testosterone levels can drop down by as much as 40 PERCENT when you don't get enough sleep and generally…
Your testosterone levels are 30% higher in the morning than in the evening and this is why you may be more horny in the mornings and as a matter of fact…
A loss of morning erections or loss of sexual desire in the morning could be a sign that your testosterone is declining so you need to get 6-to-8 hours of sleep every night because while you're sleeping…
Your body produces the most testosterone and the better you sleep the more testosterone your body will produce while you sleep so if you're having trouble getting 6-to-8 hours of good quality 'testosterone producing' sleep every night - Look at 33 Secrets to a Good Night's Sleep
7. Stress Less
When you get stressed out - your body releases a "stress" hormone called cortisol that shuts down testosterone production…
Research led by Population Council endocrinologist Matthew Hardy found that stress hormones like cortisol overpower the enzymes responsible for ensuring that cells in the testes produce testosterone

Cortisol also makes you gain belly fat and you already know from #3 above that the fatter you are = you'll have more estrogen and less testosterone so…
You need to stop worrying about the little things, avoid overtraining, control your temper and look at these 100 ways to lower stress and Being more positive can reduce your stress levels and increase Testosterone…
A recent study found that fans of a losing team had 50 percent lower levels of testosterone after their team lost and fans had up to 100% higher levels of testosterone after their team won.
Taking a natural supplement like Ashwagandha can also help reduce cortisol.
8. Take 1000-to-1500mg of Vitamin C per day
Now if you have a hard time avoiding stress - you want to start taking 1000-to-1500mg of Vitamin C per day because…
  • Vitamin C has been shown to lower cortisol levels allowing your body to make more Testosterone and like Zinc…
  • Vitamin C reduces the armostase enzyme that converts your Testosterone into Estrogen.
9. Workout like a man
You can force your body to produce a lot of testosterone when you…
  • Do Compound exercises that train several large muscle groups like Power Cleans, Squats, Bench presses, Deadlifts, Chin-ups, Dips, and Military presses and you can still do isolation exercises like triceps extensions, bicep curls or chest flyes for definition but if trying to boost your Testosterone and build more muscle quickly - stick with compound exercises and…
  • According to a Swedish study… To get the biggest boost in testosterone when you do your compound exercises… Make sure you use heavy weights that will allow you to only do about 3-to-5 reps per set and you want to do about 5-to-8 sets of each compound exercise you do but…
  • You also want to limit your workout time on those compound exercises to 1-to-2 hours so just do only 1-to-2 compound exercises followed by a few optional isolation exercises twice a week (Mon. & Thur. for example) and as for burning fat…
  • Avoid 'sissy cardio' where you walk or run for long periods of time and start doing Manly Cardio workouts like Hill sprints and intervals 3-to-4 times a week and limit your long duration sissy cardio workouts to only 2 times a week and…
  • Make extra sure that you rest harder than you work out because overtraining leads to more cortisol and lower testosterone (see #7 again) and you may need to get 8+ hours of sleep to allow your body to recuperate and produce more testosterone after you workout like a man (see #6 again)and…
10. Try to get Sexually Stimulated as much as possible
If you're not getting sexual stimulated or sexual aroused very much right now (especially if you're over 40)…You can dramatically boost your testosterone levels by getting sexually stimulated more often so basically…
You need to start doing almost anything you can to get a sexually stimulating 'Viagra free' erection and German scientists even found that simply having an erection causes your levels of circulating testosterone to rise significantly and look at how these other 3 studies prove how much your testosterone can rise after getting sexual stimulated…

In a study done by Ludwig Boltzmann Institute for Urban Ethology in Vienna… 10 men viewed a 15 minute pornographic film and the men's testosterone levels increased 100 percent afterwards.

Another study published by Psychoneuroendocrinology used sexually arousing films on 9 males and testosterone levels increased within 10 minutes of sexually arousal.

In a study published in the Archives of Sexual Behavior… Testosterone was measured every 15 min for 3 hours in 8 men before, during, and after the showing of a sexually explicit movie and there was an average increase of 35% in testosterone so…
Not getting sexual stimulated or aroused for long periods of time can actually decrease your testosterone levels so if you find it hard to get sexually stimulated… You can do all the other 12 things on this page to increase your testosterone which will increase your sex drive or libido making you get sexually stimulated much easier and/or…
You can take a supplement like Horny Goat Weedto make you get sexually stimulated more easier to ramp up your testosterone levels.
11. Make sure you're getting enough Vitamin A, B & E
Vitamins A , B & E (along with Vitamin C & zinc) are all essential in the production of testosterone and not getting enough A, B, & E Vitamins will lead to lower testosterone levels but…If you're eating plenty of fruits & veggies, lean meats and nuts then you shouldn't have to worry too much about supplementing with any extra A, B, & E Vitamins.
12. Don't overheat your testicles (your balls) Your testicles need to be 94-to-96 degrees or about 2 degrees cooler than your body temperature to function at it's best and produce the most testosterone so…
If you're wearing tight underwear, tight pants, take long HOT baths or do anything thing else to overheat your testicles… You may inhibit your testosterone production so it's best to wear looser clothes like boxers to prevent overheating your balls and did you also know that…
Carrying around excess fat also overheats your testicles so look at #3 again for how to burn fat.
13. Don't Drink any Alcohol & Don't eat any Grapefruit

Even if you had only 2 drinks a day… Alcohol makes it hard for your liver to breakdown estrogen making you have more estrogen & less testosterone which will cause you to become more woman-like by making you loose facial & pubic hair, get man boobs and become impotent and…
Alcohol decrease zinc levels in your body (look at #1 again) an just like alcohol - Grapefruits can also make it hard for your liver to breakdown estrogen.
14. Boost Testosterone 40% with D-Aspartate
D-Aspartate is an amino acid that's produced in your pituitary gland and your testicles (or your balls) and it boosts the production of testosterone plus…
D-Aspartate also increases sperm production and the Journal of Reproductive Biology and Endocrinology reported that men taking 3 grams of D-Aspartate every morning increased their testosterone by 40%

Monday, December 3, 2012

Fighting heart disease

The wonderpill takes advantage of the live micro-organisms in “friendly” bacteria

The wonderpill takes advantage of the live micro-organisms in “friendly” bacteria
Wednesday November 21,2012

By Jo Willey

PEOPLE at risk from cholesterol could soon take a simple pill which controls levels and protects sufferers.
Scientists are hailing the treatment as a new fat-buster because of the way it helps to prevent the clogging up of patients’ arteries.

The wonderpill takes advantage of the live micro-organisms in “friendly” bacteria many people already take in the form of a yogurt drink or dietary supplement.

Just two capsules packed with healthy bacteria every day slashed cholesterol in the body.

In the study presented to the American Heart Association, the team from McGill University in Montreal, Canada, said the treatment made use of probiotics, the live micro-organisms present in the gut.

Dr Mitchell Jones, the study’s lead author said such treatments are drawing increasing medical attention as researchers unravel how supplementing gut bacteria with probiotics can play a role in health and chronic conditions such as heart disease.

Scientists are hailing the treatment as a new fat-buster because of the way it helps to prevent the clogging up of patients’ arteries

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Previous studies found that a formulation of the bacteria known as lactobacillus reuteri has lowered blood levels of “bad” cholesterol.

Dr Jones’s team investigated whether this same probiotic could cut blood levels of the molecules of cholesterol attached to fatty acids, a potent combination linked to the risk of cardiovascular disease.

Researchers tracked these molecules of cholesterol which were bound to saturated fat and have been linked to dangerous arterial plaque build-up and occur at higher levels in coronary artery disease patients.

For the first time, the research showed that the probiotic formulation can cut the molecules of cholesterol linked to fat – known as cholesterol esters – “and in particular reduce the cholesterol esters associated with ‘bad’ saturated fatty acids in the blood,” said Dr Jones.

“Good” cholesterol and blood triglycerides, a dangerous form of fat in the blood, were unchanged. The scientists say that lactobacillus bacteria alone may have an impact on cholesterol levels in several ways, including breaking apart molecules known as bile salts.

Dr Jones said: “Most dietary cholesterol management products require consumption between 2 to 25g a day.”

Patients appear to tolerate the probiotic well and it has a long history of safe use, he said.

Victoria Taylor of the British Heart Foundation said: “This is a relatively small piece of research and it’s still some way off before we could recommend probiotic supplements to help people with high cholesterol.

“In the meantime, reducing levels of saturated fat as part of a healthy, balanced diet is an important part of controlling cholesterol and cutting your risk of heart disease.”

Obesity kills at least 30,000 people a year in England alone and it is predicted that by 2025, half of men and a third of women in the UK will be obese, raising the risk of diabetes, heart disease, stroke and cancer.

Previous research has hailed the health benefits of regularly taking probiotics.

Researchers at the University of East Anglia and Norwich Research Park found that a yogurt drink containing the bacteria lactobacillus casei shirota (LcS) could help bring relief to millions of hayfever sufferers by changing their immune system.

They found that yoghurt drinks containing LcS helped the immune system in responding to pollen.

Researchers at the Irish Agriculture and Food Development Authority engineered a strain of “friendly” live bacteria called lactobacillus to produce a fatty acid called conjugated linoleic acid, or CLA, which is linked to lower body fat in humans.

Also On E

Saturday, December 1, 2012

Stem cells being made from blood


Related Stories

A patient's own blood has been used to make personalised stem cells, which doctors hope will eventually be used to treat a range of diseases.

The team at the University of Cambridge says this could be one of the easiest and safest sources of stem cells.

In a study, published in the journal Stem Cells: Translational Medicine, the cells were used to build blood vessels.

However, experts cautioned that the safety of using such stem cells was still unclear.

Stem cells are one of the great hopes of medical research. They can transform into any other type of cell the body is built from - so they should be able to repair everything from the brain to the heart, and eyes to bone.

Start Quote

It's a hell of a lot easier to get a blood sample than a high quality skin sample so that's a big benefit”
End Quote Prof Chris Mason University College London

One source of stem cells is embryos, but this is ethically controversial and they would be rejected by the immune system in the same way as an organ transplant.

Researchers have shown that skin cells taken from an adult can be tricked into becoming stem cells, which the body should recognise as part of itself and would not reject.

The team at Cambridge looked in blood samples for a type of repair cell that whizzes through the bloodstream repairing any damage to the walls of blood vessels. These were then converted into stem cells.

Dr Amer Rana said this method was better than taking samples from skin.

"We are excited to have developed a practical and efficient method to create stem cells from a cell type found in blood," he said.

"Tissue biopsies are undesirable - particularly for children and the elderly - whereas taking blood samples is routine for all patients."

Dr Rana told the BBC the cells also appeared to be safer to use than those made from skin.

"The fact that these appeared to be fairly stable is very promising," he said.

"The next stage obviously is to say, 'OK if we can do all this, let's actually make some clinical grade cells,' we can then move this technology into the clinic for the first time."

Prof Chris Mason, an expert on regenerative medicine at University College London, said there was some "beautiful work" coming out of the lab in Cambridge.

"It's a hell of a lot easier to get a blood sample than a high quality skin sample, so that's a big benefit," he said.

"However, induced pluripotent stem cells [those converted from adult cells] are still very new, we need far more experience to totally reprogram a cell in a way we know to be safe."

The British Heart Foundation said these cells had "great potential".

Monday, July 30, 2012

smoothie thar flaten belly

6 drinks that shrink your belly

Published July 13, 2012
| Prevention Magazine
That ice-cold lemonade may hit the spot on a 90-degree day, but it’s not doing your waistline any favors. A 20-ounce Minute Maid Lemonade contains 250 calories and 68 g of sugar. Fortunately, there are plenty of refreshing summer drinks that you can drink without guilt—and they may actually help you lose weight. Here are six ways to quench your thirst without packing on pounds.
6 Super Smoothie Recipes
Flat Belly Drink: Flavored Water
Staying hydrated is important when you’re trying to lose weight. Drinking plenty of water helps your body maintain proper fluid balance, stops water retention (a big cause of bloated bellies), and even increases the feeling of fullness so you eat less overall. But if plain water bores you, spruce it up with fresh herbs, citrus fruits, and other low-cal flavor enhancers (sliced cucumbers work well too) to encourage you to drink up. Try our Sassy Water recipe from the Flat Belly Diet!
Get the full Sassy Water Recipe
Flat Belly Drink: Watermelon Smoothie
As long as they’re made without sugary mixers like sherbet, smoothies are a guilt-free way to hydrate—and watermelon is a terrific, low-cal smoothie base. Not only is it a natural hydrator because of its water content, watermelon is also loaded with nutrients, including cancer-fighting lycopene, as well as an amino acid known as arginine. A study in the Journal of Nutrition found that arginine can decrease body fat and increase lean muscle mass, so whip up this 56-calorie metabolism booster and sip away!
Try This Watermelon Smoothie Recipe
Flat Belly Drink: Iced Peppermint Tea
This minty thirst quencher is super refreshing on a hot summer day, but it’s also a super-effective belly flattener. Peppermint helps your stomach process fat, ensuring even high-fat foods like burgers and steaks are digested quickly, which helps prevent bloat.
7 Healing Herbal Teas
Flat Belly Drink: Pineapple Frappe
This blended pineapple drink tastes like a beach vacation in a glass—and it packs in two belly-flattening ingredients. A tablespoon of flaxseed oil adds monounsaturated fatty acids (MUFAs), proven belly flatteners, and pineapple itself contains bromelain, an enzyme that helps break down protein, ease digestion, and banish bloat.
Try This Pineapple Smoothie Recipe
Flat Belly Drink: Green Tea
Besides reducing your risk of cancer and heart disease, green tea benefits the whole body and contains catechins, antioxidants that studies show can help reduce belly fat. If you sip green tea before a workout, these compounds can also increase your fat burn during aerobic exercise.
Discover dozens of other foods that can help blast belly fat in The Flat Belly Diet Cookbook!
Flat Belly Drink: Dark Chocolate Shake
Really? Yes, really. Chocolate—especially the dark kind—helps you slim you down because it decreases appetite and lessens food cravings overall. However, at nearly 400 calories, this shake is more of a meal than a snack. Try it for a quick breakfast to keep your appetite tamed for hours.
Get The Belly-Flattening Smoothie

Read more:

Saturday, July 28, 2012

light lifting, big muscles

Light lifting, big muscles?

Study runs contrary to common wisdom and finds that substantial growth can come without all the grunting and bulging associated with heavy weights. The key? Repetitions.

By James Fell, Special to Tribune Newspapers

7:19 PM CDT, July 25, 2012

Click here to find out more!

Attention fans of heavy lifting: Grab your torches and pitchforks! Someone is questioning your long-held beliefs told by preachers of the hard-core gospel and published ad nauseam in magazines with the word "muscle" in the title.
Here goes: Lifting near your maximum weight is not necessary to build muscle mass and gain strength.
"Consistent practice combined with good nutrition and practicing good form and working to fatigue — no matter what the load — is what makes up the majority of results," says Stuart Phillips, a professor of kinesiology at McMaster University in Hamilton, Ontario.
It's that "no matter what the load" part that has people up in bulging, veiny arms. "Load" is how heavy the weight is, and "heavy = huge" has been preached since Schwarzenegger wore short pants.
"At the risk of inviting death threats," Phillips told me, "I think a lot of the variables in a resistance training program — rest, sets, loads and other variables — are largely redundant in their capacity to bring about strength and (bigger muscles)." More important to Phillips is that you, "Get to the weight room, consistently practice, work to fatigue — this is 80 percent of the job."
And Phillips has some science to back up his claims.
The study
Phillips and his team studied 18 college-age men for 10 weeks. Published in April in the Journal of Applied Physiology, the research examined the results on three weight-lifting routines:
Three sets at 30 percent of maximum (with 100 percent being the maximum amount of weight they could lift for one repetition).
One set of 80 percent of maximum.
Three sets of 80 percent of maximum.
The study focused on leg-extension exercises, and participants were allocated to two of the three routines (a different routine for each leg). The findings fly in the face of current recommendations and state that the lighter-weight routine had the same muscle growth results as the three sets of heavy weights routine. It also showed that the number of sets is important, because lifting three sets to fatigue at the lighter load made muscles bigger than did a single set of much heavier weight.
How is this possible? Traditional thinking is that only heavy lifting works the larger, "fast-twitch" muscle fibers that are more responsive to gaining size, and that lighter weights only engage the smaller "slow-twitch" fibers that are for muscular endurance.
But Phillips says traditional thinking isn't on target. His main reason: fatigue. Even with lighter weights, when you do enough reps to tire the muscle — so that no further lifts can be made while maintaining good form — then both fast- and slow-twitch muscle fibers are recruited and muscles grow in size.
Size vs. strength
But though your muscle grows and you do get stronger with the lower-weight routine, your muscles won't be as strong as those of people doing the heavier-lifting routine, the study showed.
Ten weeks into these routines, when strength was measured by seeing how much a test subject could lift for one rep, those lifting light weights to fatigue were 20 percent stronger, but those lifting heavier weights were almost 40 percent stronger. Those doing the single-set routine were about 30 percent stronger.
No small potatoes.
Phillips suggests the difference lies in neural adaptations that enable these greater strength capabilities, perhaps coupled with extra confidence from having practiced with heavier weights.
And the proof was in subsequent isometric testing — where test subjects tested their strength against a fixed resistance, so without any movement. The results were just a few percentage points apart.
Phillips sees isometrics as a truer measure of strength gains because none of the participants was practiced at it.
The most important disclaimer to make in all of this is to reveal that these participants, while recreationally active, did not engage in regular weight lifting over the last year. They were "untrained" subjects.
"We'll have to do another study with trained subjects or I'll never hear the end of it," Phillips said. However, as people do become trained, even with intense efforts, strength and size results slow down dramatically.
Not everyone's sold
"When you're just starting off, almost everything should work," said William Kraemer, a professor of kinesiology at the University of Connecticut and editor of the Journal of Strength and Conditioning Research. Kraemer says there is a lot of literature to support the model of lighter weights for improving endurance, heavier for gaining size, and heaviest for strength. He also promised new studies coming soon to back this up further.
Kraemer also disagrees with Phillips that it's possible for lighter lifting — even to fatigue — to stimulate all of the muscle. "It's because of the basic size principle. The more weight you lift, the more motor units are recruited. You're also better training connective tissues: bones and ligaments."
I mentioned that most people just aren't willing to work that hard, but Kraemer doesn't like "better than nothing" thinking. He's sees it as "betraying the optimal for the minimal."
Plus, "strength gains are the money-maker with the general population," extols Boston-based Eric Cressey, a sought-after strength coach who trains professional and Olympic athletes.
"Strength is a crucial foundation for power, which is what we lose as we get older." He sees the value in a lighter approach for novice populations, but says lighter loads also can raise potential for over-use injuries. At lighter loads, you must increase repetitions to achieve fatigue, and this can lead to strains. (Phillips counters that heavy loads come with their own dangers of injury, especially for older populations.)
The size plateau
In the end: "Few experienced lifters can make gains for more than a few years without anabolic steroids," says Phillips. "Everybody has a genetic plateau."
"Everything works, nothing works forever," Cressey said. (He's also a competitive power lifter and holds several state, national and world records.)
And though, for now, high-intensity lifting is the default recommendation by most trainers, the heavy versus light argument is far from over.
Kraemer is in favor of starting light to develop comfort, but insists on the need for progression. Regular heavy training is critical for long-term success, he maintains.
Phillips, on the other hand, wants weight lifting more inclusive, so that even the novice and the nervous can get substantial health, strength (and vanity) benefits from it without having to go too far from their comfort zone.
Either way, lifting can do a body good. You win no matter how heavy you go.
Fell is a certified strength and conditioning specialist

Friday, July 27, 2012

first person cured of hiv

Berlin Patient, first person cured of HIV, may soon have company

By Erin Loury

Los Angeles Times

2:26 PM PDT, July 27, 2012

Washington, D.C.


The Berlin Patient, the only person considered cured of HIV, may soon have some company.
Researchers at the International AIDS Conference in Washington, D.C., made presentations Thursday on two HIV-positive men from Boston who developed lymphoma. In both cases, their treatment included a bone marrow transplant, which results in a new immune system. The bone marrow donors did not have HIV.
The patients were conditioned for their transplants with a reduced-intensity protocol that allowed them to maintain enough strength to continue taking antiretroviral drugs to keep their HIV in check. These drugs are usually too toxic for HIV-positive cancer patients to handle.
So far, it appears that their new immune systems have remained HIV-free. Seventeen months after the transplants, researchers could not detect any HIV genetic material in the patients’ blood. They say the credit for this goes to the antiretroviral drugs the patients are taking.
Still unclear is whether the virus still lurks in the patients’ tissues. “It is possible that there is still other residual HIV material, “said study author Dr. Timothy Henrich of Harvard University and Brigham and Women's Hospital. If doctors became convinced that all trace of the virus is gone, the patients could stop taking the antiretroviral drugs and be considered cured.
But they’re not there yet.
“We’re being very carful to refer to our patients as not being functionally cured,” said study author Daniel Kuritzkes, also of Harvard University and Brigham and Women's Hospital. Only when these patients can successfully stop their medication can they be considered cured of HIV.
The only person in that category right now is the Berlin Patient, a.k.a. Timothy Brown. He had a bone marrow transplant to treat acute myeloid leukemia. In his case, the bone marrow donor was not only HIV-negative, but had a rare genetic mutation that blocks HIV from entering cells. That effectively makes Brown immune to the virus, and his body has remained HIV-free even without taking antiretroviral drugs.
The two patients in Boston received their bone marrow transplants from people who did not have the rare genetic variant, which is why they are still taking their drugs.
Researchers are working on potential cures that involve transferring that genetic mutation to HIV-positive patients without taking on the significant risks of a bone marrow transplant.
Another study presented Thursday reported on 12 French HIV-positive patients who received early treatment and have acquired an ability to naturally control HIV. These patients offer hope that it may be possible to “functionally” cure the disease – enabling people to tolerate HIV without completing ridding their bodies of the virus.
The patients started taking antiretroviral medication within 10 weeks of their HIV infections and stopped about three years later. Now, nearly seven years after ending treatment, these patients still have very low levels of the virus in their bodies. They appear similar to a small group of people known as “elite controllers” who naturally suppress HIV to low levels and do not get sick from the virus.
Reservoirs of dormant HIV can occur throughout the body. This sleeping HIV can periodically wake up and re-infect a person, which is why people with HIV usually have to take medication for life.
The French patients still have very low reservoirs of virus in their bodies, and researchers wondered if their ability to manage the virus related to how these remaining patches of HIV were distributed among a type of white blood cells called memory T cells. Pockets of HIV usually build up in long-lived types of memory T cells. However, researchers found that this rare cohort had dormant HIV primarily in shorter-lived memory T cells – similar to elite controllers – so their infected cells don’t persist as long.
The results provide further evidence that antiretroviral therapy should be started soon after infection, researchers said.
To wipe out all traces of HIV, scientists must find a way to wake up reservoirs of sleeping virus and target them with drugs. Jerome Zack, director of the UCLA Center for AIDS Research, made a presentation about this approach.
Zack and his colleagues outfitted little lipid bubbles called liposomes with antibodies that specifically match up with CD4 cells, the type of white blood cell that HIV usually attacks. The liposomes deliver two drugs to the cell – one, called bryostatin, switches on cell activity, and the other, a protease inhibitor, prevents HIV virus from assembling more virus once it starts to reproduce.
These liposomes didn’t target or otherwise activate another type of white blood cells called CD8 cells. As a result, the treatment didn’t trigger toxic inflammation. However, scientists still need to figure out how to design liposomes that identify only the CD4 cells that are infected with dormant HIV.
Bryostatin is a useful molecule, but also exorbitantly expensive – a single gram can cost $1 million.
Zack and his colleagues published a paper in Nature Medicine last week that described a number of synthetic products that mimic bryostatin, and cost only about $2,000 per gram to manufacture. Zack said that a few of these compounds also outperform their natural counterpart in switching on latent HIV while triggering less inflammation.

Monday, July 23, 2012

milk doesn't do a body good

5 ways milk doesn't do a body good
Got milk? Not so fast. The All-American beverage of choice is high in calories, saturated fat, and unnatural chemicals that can cause a range of health problems
Published July 19, 2012, at 7:42 AM
According to The Department of Agriculture people should drink three 8-ounce glasses of milk per day, which weighs in at around 1.5 pounds. Photo: ThinkStock/
Milk was once christened "nature's perfect food," says Mark Bittman at The New York Times. The Department of Agriculture recommends three 8-ounce glasses of the stuff a day (which equals about 1.5 pounds). After all: It builds strong bones, is packed with nutrients, and helps kids grow taller. But drinking dairy can be problematic, and its most notorious ingredient, lactose, is indigestible by a significant percentage of Americans. Here, five reasons milk actually doesn't do a body good:
1. It's high in calories and saturated fat
Ounce for ounce, milk has about "the same calorie load as soda," Neal Barnard, president of the Physicians Committee for Responsible Medicine, tells The New York Times. Lactose is still a sugar, and contributes about 55 percent of skim milk's calories. Plus, milk and other dairy products are big sources of saturated fat, "and there are very credible links between dairy consumption and both Type 1 diabetes and the most dangerous form of prostate cancer." One serving of 2 percent milk has even been found to have the same saturated fat count as a serving of french fries.
2. A lot of people can't drink it
In the United States, as many as 50 million people are lactose intolerant: Roughly 90 percent of Asian-Americans can't drink milk, and 75 percent of all African-Americans, Mexican-Americans, and Jewish-Americans are similarly lactose intolerant. Recent studies suggest soy milk might not be much better: An article published in the Journal of Dentistry suggests that soy milk encourages bacteria in our mouth to produce five to six times more acid than usual, leading to plaque, tooth decay, and cavities.
3. Milk is often full of chemicals
"Commercial milk is disgusting," says Deborah Dunham at Blisstree. The mass-produced stuff is filled with growth hormones and antibiotics used to make cows lactate unnaturally. These additives may make the milk appear white and creamy-looking, but "all of this has been blamed for skin problems, acne, allergies, inflammation of the body," and much more. "Not to mention the fact that drinking cow's milk is simply unnatural — no other species drinks milk from another species except us."
4. Many people are allergic
Sure, the peanut allergy is the number one food allergy in the country. But did you know that the second most common type is "milk allergy"? It affects an estimated 3 million children in the United States. Like peanut allergy, the severity of milk allergy can range from mild reactions to being life-threatening.
5. You don't need milk for strong bones
"You don't need milk, or large amounts of calcium, for bone integrity, says the Times' Bittman. Not only are fracture rates the highest in milk-drinking countries, but it turns out that the biggest two factors contributing to bone strength are "lifelong exercise and vitamin D, which you could get from sunshine." All of this isn't to say that milk doesn't have its health benefits, says Adam Dachis at Lifehacker. But now there seems to be a likelihood that "dairy is a food you should eat because you enjoy it and not for its claims of better health."

Friday, July 13, 2012

'Beige Fat' Cells Could Help Fight Obesity

Newly Identified 'Beige Fat' Cells Could Help Fight Obesity
Newly Discovered Fat Appears to Burn Calories, Researchers Say
Looking to slim down? Then beige is your color, at least as far as fat is concerned.
Scientists at Dana-Farber Cancer Institute have isolated a new type of energy-burning cell known as "beige fat," which they say may have therapeutic potential for aiding weight loss and treating obesity in adults.
According to a new report published in the journal Cell, beige fat is scattered in pea-size deposits beneath the skin near the collarbone and along the spine. But rather than storing excess calories in the form of jiggly thighs and a jelly belly as blubbery-and-prolific white fat does, this type of fat is a calorie burner.
Sweating and Freezing
"During exercise, muscles release the hormone irisin, which then converts ordinary white fat cells into beige ones – and those beige cells burn up extra calories," explains Bruce Spiegelman, the senior author of the paper.
It's long been known that the calories burned during exercise exceed the number used during the actual activity. Beige fat could be responsible for torching these extra calories. However, because the muscles also release irisin when the body is cold, Spiegelman speculates that the beige fat mechanism might have evolved as a response to shivering, which, like exercise, is a neuromuscular activity.
Spiegelman doesn't necessarily believe the conversion of cells to beige is permanent. "It's an adaptive process," he says. "They probably increase or decrease depending on physiological conditions such as age, sex and obesity."
This could be why more brown fat and perhaps more beige fat is present in people who are fit and physically active versus those who are slothful couch potatoes. An attractive hypothesis to be sure, but Spiegelman cautions there's not yet enough evidence to prove it.
Beige Versus Brown
Beige fat appears to be genetically distinct from "brown fat" another type of fat found in small amounts in the necks and collarbones of adults and in larger amounts in rodents and human infants. It's distinct from the white fat that plagues anyone who struggles to lose weight. Both brown and beige fat have an abundance of mitochondria, the tiny power plants of the cell that convert food into energy and generate heat. Both types contain iron, which gives them their distinctive brown and beige hues.
But the two fats differ in a number of ways. One key difference is that brown fat cells express high levels of UCP1, a protein required by mitochondria that burns calories and generates heat, whereas beige cells normally express low levels of it. Beige cells can, however, turn on high levels of UCP1 in response to cold or the release of irisin, enabling beige fat to burn calories nearly as effectively as brown fat. Also, brown fat cells appear to arise from stem cells precursors that also produce muscle cells, while beige fat forms within deposits of white fat cells from beige cell precursors.
The discovery of irisin, and its ability to transform white fat to brown fat was originally announced in another paper by Spiegelman that his team published earlier this year. This latest Cell report confirms that irisin specifically stimulates white fat to produce beige fat.
Dr. Dazid Katz, director of the Yale University Prevention Research Center, said the existence of a middle ground between white and brown fat makes sense.
We already knew that exercise could induce a transformation of white fat to brown," he said. "This simply characterizes the intermediate state. The functional significance of this 'beige fat' appears to be what we already knew: exercise, and cold, can raise energy expenditure in part through the activation of brown fat."
The hope, of course, is that the beige fat cells might one day lead to new treatments for obesity and diabetes. Dana-Farber has licensed both discoveries to Ember Therapeutics, a biotech company founded by Spiegelman. Keith Ayoob, associate clinical professor of pediatrics at the Albert Einstein College of Medicine, said that this research will be crucial in determining whether anything useful can come from this discovery.
"We need to know more about how much is there, why some people may have a greater or lesser proportion of it, and to see if it can be of use in helping people lose weight," Ayoob said. "There may be a way -- probably via a drug -- to stimulate either the production of beige or brown fat over white fat, or to increase fat breakdown.
Would such a drug be a good idea? Katz said he remains skeptical, saying that he believes the finding means "that the quest for a magical means of tickling both brown and beige fat into burning more calories ... without the ... inconvenience of actually exercising or eating better will continue in earnest.
"To date, our efforts to tickle the metabolic engine in this selective manner have reaped a whirlwind of unintended consequences, and frankly, I see that peril around this corner as well."
As for using cold and shivering as an alternative to exercise – some diet gurus are already recommending this – Spiegelman says forget about it.
"Anyone can write a book to say it works, but this demands serious research and clinical trials," he said. "We've never done the experiments before, and it would be a pretty uncomfortable therapy, so realistically I don't think it's a good road to travel down."

Friday, June 29, 2012

rooibos tea


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Scientific classification
Species:A. linearis
Binomial name
Aspalathus linearis
(N.L.Burm.) R.Dahlgr.
Rooibos (Anglicized pronunciation: play /ˈrɔɪbɒs/ ROY-bos;[1] Afrikaans pronunciation: [rɔːibɔs], "red bush"; scientific name Aspalathus linearis) is a broom-like member of the legume family of plants growing in South Africa's fynbos.
The generic name comes from the plant Calicotome villosa, aspalathos in Greek. This plant has very similar growth and flowers to the redbush. The specific name linearis comes from the plant's linear growing structure and needle-like leaves.
The plant is used to make a herbal tea called rooibos tea, bush tea (esp. Southern Africa), redbush tea (esp. UK), South African red tea, or red tea. The product has been popular in Southern Africa for generations and is now consumed in many countries. It is sometimes spelled rooibosch in accordance with the old Dutch etymology.



[edit] Production

Green rooibos tea
Rooibos Tea in a glass
A Rooibos-infused liqueur and Rooibos tea
Rooibos is grown only in a small area in the region of the Western Cape province of South Africa.[2] Generally, the leaves are oxidized, a process often, inaccurately, referred to as fermentation by analogy with tea-processing terminology. This process produces the distinctive reddish-brown colour of rooibos and enhances the flavour. Unoxidized "green" rooibos is also produced, but the more demanding production process for green rooibos (similar to the method by which green tea is produced) makes it more expensive than traditional rooibos. It carries a malty and slightly grassy flavour somewhat different from its red counterpart.

[edit] Use

In South Africa it is common to prepare rooibos tea in the same manner as black tea, and add milk and sugar to taste. Other methods include a slice of lemon and using honey instead of sugar to sweeten.
Several coffee shops in South Africa have recently begun to sell "red espresso", which is concentrated rooibos served and presented in the style of ordinary espresso. This has given rise to rooibos-based variations of coffee drinks such as red lattes and red cappuccinos. Iced tea made from rooibos has recently been introduced in South Africa, Australia, and in the United States. A variant of a London Fog, known as a Cape Town Fog, can also be made using Rooibos steeped in steamed milk with vanilla syrup.

[edit] Nutritional and health benefits

Rooibos is becoming more popular in Western countries, particularly among health-conscious consumers, due to its high level of antioxidants such as aspalathin[3] and nothofagin, its lack of caffeine, and its low tannin levels compared to fully oxidized black tea or unoxidized green tea leaves.[4] Rooibos also contains a number of phenolic compounds, including flavanols, flavones, flavanones, and dihydrochalcones.[5]
Rooibos is purported to assist with nervous tension, allergies and digestive problems.[6] Rooibos tea has been shown to inhibit in vitro activity of xanthine oxidase, yet an in vivo study has not been conducted. Xanthine oxidase (XO) plays a role in conversion of purine to uric acid in humans and reducing the activity of XO could limit uric acid production, which would aid in treatment of gout. In in vitro tests only, for the specific concentration tested, the tea was shown to be less than half as effective as allopurinol, which is the drug typically prescribed to inhibit XO activity in treating gout.[7]
Two rooibos flavonoids, quercetin and luteolin have been known to have cancer fighting qualities.[8] Rooibos does not contain the antioxidant Epigallocatechin-3-gallate (EGCG).[9]
Traditional medicinal uses of rooibos in South Africa include alleviating infantile colic, allergies, asthma and dermatological problems.[10][11]

[edit] Scientific study

Monday, June 18, 2012



The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
N Engl J Med 2006; 354:1567-1577April 13, 2006


In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease.


We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke.


Mean plasma homocysteine levels decreased by 2.4 μmol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 μmol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49).


Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. ( number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.)

Media in This Article

Figure 1Mean (+SD) Plasma Levels of Total Homocysteine, Folate, Vitamin B6, and Vitamin B12.
Figure 2Kaplan–Meier Estimates of the Proportion of Patients with the Composite Primary Outcome of Death from Cardiovascular Causes, Myocardial Infarction, or Stroke.
Numerous studies suggest that homocysteine may be a modifiable risk factor for cardiovascular disease. In experimental studies, homocysteine causes oxidative stress, damages endothelium, and enhances thrombogenicity.1-3 In general, epidemiologic studies show an independent and graded association between homocysteine levels and cardiovascular risk.4-8 The observational data suggest that even mild-to-moderate elevations in homocysteine increase cardiovascular risk; this observation is important, because such increases are common and can easily be corrected with safe and inexpensive therapy. Folic acid is the most important dietary determinant of homocysteine; daily supplementation with 0.5 to 5.0 mg typically lowers plasma homocysteine levels by about 25 percent. Vitamin B12 supplementation of at least 0.4 mg daily further lowers levels by about 7 percent, and vitamin B6 supplements may be particularly important in lowering homocysteine after methionine loading.9,10
We report the results of the Heart Outcomes Prevention Evaluation (HOPE) 2 study, a large, prospective, randomized clinical trial designed to determine whether prolonged administration of folic acid combined with vitamins B6 and B12 reduces the risk of major vascular events in persons at high cardiovascular risk.


Study Design

HOPE-2 was a randomized, double-blind, placebo-controlled trial evaluating whether therapy with homocysteine-lowering B vitamins reduces the risk of major vascular events in a high-risk population. The trial design has been described previously.11 The study was coordinated by the Population Health Research Institute at McMaster University in Hamilton, Ontario, and sponsored by the Canadian Institutes of Health Research. Study drug and matching placebo were provided by Jamieson Laboratories, Canada. The study sponsors were not involved in the design, execution, analysis, or reporting of the trial results. An independent data and safety monitoring board monitored the safety of the participants and the overall quality and scientific integrity of the study. The study was approved by the ethics review boards of all participating institutions, and all patients provided written informed consent.

Study Population

Men and women 55 years of age or older who had a history of vascular disease (coronary, cerebrovascular, or peripheral vascular) or diabetes and additional risk factors for atherosclerosis were enrolled, irrespective of their homocysteine levels, from countries with mandatory folate fortification of food (Canada and the United States) and countries without mandatory folate fortification (Brazil, western Europe, and Slovakia). Patients who were taking vitamin supplements containing more than 0.2 mg of folic acid per day were excluded. Detailed eligibility criteria have been published previously11 and are provided in the Supplementary Appendix (available with the full text of this article at

Study Intervention

Patients were randomly assigned to receive a combined pill containing 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 (active treatment) or matching placebo daily. The study used central telephone randomization. The randomization code was generated with the use of a fixed block size of four, stratified according to center. All study investigators, personnel, and participants were unaware of the randomization procedure and the treatment assignments.

Follow-up and Laboratory Evaluation

After randomization, patients were evaluated every six months to determine their adherence to treatment (by interview and pill count) and identify adverse events and clinical outcomes. Blood samples were collected at randomization, at two years, and at the end of the study in a randomly selected subgroup of patients after an overnight fast, with proportional representation from countries with folate fortification of food and countries without folate fortification and with expected significant differences in dietary habits.
Plasma levels of folate (Roche chemiluminescence method, Roche Diagnostics), vitamin B6 (Chromsystems kit, Instruments and Chemicals), and vitamin B12 (Immulite 2000 Analyzer, Diagnostic Products) were measured at randomization and at two years. Total plasma homocysteine levels were measured (Abbott IMX immunofluorescence method, Abbott) at randomization, at two years, and at the end of the study (average, five years).

Trial Outcomes

The primary study outcome was the composite of death from cardiovascular causes, myocardial infarction, and stroke. Secondary outcomes were total ischemic events (defined as the composite of death from cardiovascular causes, myocardial infarction, stroke, hospitalization for unstable angina, and revascularization), death from any cause, hospitalization for unstable angina, hospitalization for congestive heart failure, revascularization, the incidence of cancer, and death from cancer. Other outcomes included transient ischemic attacks, venous thromboembolic events, and fractures. All primary and secondary outcomes were centrally adjudicated.
Deaths classified as due to cardiovascular causes were unexpected deaths presumed to be due to ischemic cardiovascular disease and occurring within 24 hours after the onset of symptoms without clinical or postmortem evidence of another cause, deaths from myocardial infarction or stroke within 7 days after the event, deaths associated with cardiovascular interventions within 30 days after cardiovascular surgery or within 7 days after percutaneous interventions, and deaths from congestive heart failure, arrhythmia, pulmonary embolism, or ruptured aortic aneurysm. Deaths from uncertain causes were presumed to be due to cardiovascular causes.
Myocardial infarction was diagnosed when two of the following three criteria were met: typical symptoms, increased cardiac-enzyme levels, and diagnostic electrocardiographic changes.12 Stroke was defined as a focal neurologic deficit lasting more than 24 hours. Computed tomography or magnetic resonance imaging was recommended to identify the type of stroke (ischemic or hemorrhagic). When these tools were not available, the stroke was classified as of uncertain type. Cancers (except basal-cell skin cancer) were diagnosed on the basis of pathological (or cytologic) findings or, when pathological data were not available, on the basis of clinical summaries, results of imaging, levels of serum markers, and other diagnostic procedures. Cancers were classified according to the International Classification of Diseases, 9th Revision.

Statistical Analysis

The study was designed to enroll 5000 patients and to average five years of follow-up to allow the detection of a proportional reduction in the risk of the primary outcome of 17 to 20 percent, with a statistical power of 80 percent and 90 percent, respectively, given an annual event rate of 4 percent in the placebo group and a two-tailed α value of 0.05. This enrollment target was also estimated to provide over 80 percent power to detect a 15 percent reduction in the risk of total ischemic events.
All analyses were performed according to the intention to treat and included all randomized patients. Survival curves were estimated according to the Kaplan–Meier procedure and were compared between treatment groups with the log-rank test. Prespecified subgroup analyses involving Cox models were used to evaluate outcomes in patients from regions with folate fortification of food and regions without folate fortification, according to the baseline plasma homocysteine level and the baseline serum creatinine level. Additional exploratory subgroup analyses were conducted to evaluate the consistency of the study results.


Characteristics of the Patients

Between January and December 2000, 5522 patients were recruited at 145 centers in 13 countries: 3982 (72.1 percent) were from countries with folate fortification of food, and 1540 (27.9 percent) were from countries without folate fortification. Of these patients, 2758 were randomly assigned to active treatment with folic acid and vitamins B6 and B12 and 2764 were assigned to placebo. Baseline characteristics are shown in Table 1Table 1Baseline Characteristics of the Patients. and were generally well balanced between the study groups.

Adherence, Adverse Events, and Follow-up

Among those assigned to the active-treatment group, 95.5 percent were still taking the study drug at one year, 94.0 percent were doing so at two years, 92.5 percent at three years, 91.4 percent at four years, and 90.8 percent at five years. The respective figures for the placebo group were 96.0 percent, 93.4 percent, 92.3 percent, 89.9 percent, and 88.5 percent. Use of open-label folic acid supplements ranged from 2.3 to 4.5 percent in the active-treatment group and from 2.2 to 5.5 percent in the placebo group. There were no serious adverse events related to study treatment. The most common reasons for permanently or temporarily discontinuing treatment at any time were the patient's decision (11.1 percent in the active-treatment group, vs. 12.6 percent in the placebo group), physician's advice (1.6 percent vs. 2.0 percent), hospitalization (1.0 percent vs. 0.8 percent), and general malaise (1.0 percent vs. 0.7 percent).
Follow-up averaged five years. A total of 37 patients, 21 in the active-treatment group and 16 in the placebo group, did not complete the study (21 declined to continue, and 16 were lost to follow-up). The vital status of 99.3 percent of patients was ascertained at the end of the study. All patients who declined to continue the study or were lost to follow-up completed at least two clinic visits and were included in the final analysis, with data censored at the time of the last follow-up visit.

Effects of Supplementation on Vitamin and Homocysteine Levels

Plasma vitamin levels and homocysteine levels for the subgroup of patients in whom they were measured are shown in Figure 1Figure 1Mean (+SD) Plasma Levels of Total Homocysteine, Folate, Vitamin B6, and Vitamin B12.. At randomization, there were no significant differences between the two groups in plasma levels of folate (27.6 nmol per liter [12.2 ng per milliliter] in the active-treatment group and 27.1 nmol per liter [12.0 ng per milliliter] in the placebo group), vitamin B6 (pyridoxal) (61.9 nmol per liter [10.3 ng per milliliter] and 58.1 nmol per liter [9.7 ng per milliliter], respectively), or vitamin B12 (322.2 pmol per liter [436.6 pg per milliliter] and 314.5 pmol per liter [426.1 pg per milliliter], respectively). Mean total plasma homocysteine levels were also similar in both groups (12.2 μmol per liter [1.6 mg per liter] in both). As expected, there were regional differences, with lower folate and higher homocysteine levels in patients from regions that did not require folate fortification of food than in patients from regions that required folate fortification.
Values obtained two years after randomization showed that plasma folate and vitamin B12 levels had approximately doubled and vitamin B6 levels had approximately quadrupled in the active-treatment group, with no significant changes in the placebo group (Figure 1). In the active-treatment group, the mean homocysteine level had decreased to 9.9 μmol per liter (1.3 mg per liter) at two years (a decrease of 2.2 μmol per liter [0.3 mg per liter] from baseline) and to 9.7 μmol per liter (1.3 mg per liter) at the end of the study (a decrease of 2.4 μmol per liter [0.3 mg per liter] from baseline). In the placebo group, the mean homocysteine level had increased to 13.2 μmol per liter (1.8 mg per liter) at two years (an increase of 1.1 μmol per liter [0.1 mg per liter] from baseline) and to 12.9 μmol per liter (1.7 mg per liter) at the end of the study (an increase of 0.8 μmol per liter [0.1 mg per liter] from baseline) (Figure 1). As a result, there was a difference of 3.3 μmol per liter (0.4 mg per liter) in the change from baseline in homocysteine levels between the treatment groups at two years and a difference of 3.2 μmol per liter (0.4 mg per liter) at the end of the study. These differences were greater in the regions that did not require folate fortification (3.7 μmol per liter [0.5 mg per liter] at two years and 4.1 μmol per liter [0.6 mg per liter] at the end of the study) than in regions that required folate fortification (3.2 μmol per liter at two years and 2.9 μmol per liter [0.4 mg per liter] at the end of the study).

Primary Outcomes and Deaths from Any Cause

In the active-treatment group, 519 patients (18.8 percent) died of cardiovascular causes or had a myocardial infarction or stroke, as compared with 547 patients (19.8 percent) in the placebo group (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41) (Figure 2Figure 2Kaplan–Meier Estimates of the Proportion of Patients with the Composite Primary Outcome of Death from Cardiovascular Causes, Myocardial Infarction, or Stroke. and Table 2Table 2Outcomes.). When each of the components of the primary composite outcome was analyzed separately, there were no significant differences between the groups in the rates of death from cardiovascular causes or myocardial infarction (Table 2 and the Supplementary Appendix). Fewer patients in the active-treatment group than in the placebo group had a stroke (111 [4.0 percent] vs. 147 [5.3 percent]; relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97; P=0.03). The risk of death from any cause was similar in the active-treatment group and the placebo group (relative risk, 0.99 with active treatment; 95 percent confidence interval, 0.88 to 1.13; P=0.94).

Secondary and Other Outcomes

Among the prespecified cardiovascular secondary outcomes, total ischemic events occurred in 900 (32.6 percent) patients in the active-treatment group and in 890 patients (32.2 percent) in the placebo group (relative risk, 1.03; 95 percent confidence interval, 0.94 to 1.13; P=0.57) (Table 2). A total of 268 patients (9.7 percent) in the active-treatment group were hospitalized for unstable angina, as compared with 219 (7.9 percent) in the placebo group (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49; P=0.02). There were no significant differences between the treatment groups in hospitalization for heart failure and revascularization.
There were no significant differences in incident cancers and deaths from cancer. There were also no significant differences in the rates of transient ischemic attack, venous thromboembolism, or fracture.

Subgroup Analysis

There were no significant treatment benefits with respect to the primary outcome in any of the prespecified or exploratory subgroups evaluated (Figure 3Figure 3Effect of Folic Acid and Vitamins B6 and B12 on the Primary Outcome in Prespecified and Exploratory Subgroups.). Of particular interest was the treatment effect among patients with high baseline levels of homocysteine. In the top third of the baseline homocysteine distribution (homocysteine ≥12.7 μmol per liter [1.7 mg per liter]), 23.9 percent of the patients in the active-treatment group and 24.0 percent of the patients in the placebo group had a primary-outcome event. Primary event rates also did not differ significantly between the treatment groups among patients in the upper fifth of the baseline homocysteine distribution (≥19.7 μmol per liter [2.7 mg per liter]).
We further explored the effect of treatment on stroke. Most strokes (185, or 71.7 percent) were ischemic, 19 (7.4 percent) were hemorrhagic, 48 (18.6 percent) were classified as of uncertain type, and 6 (2.3 percent) were classified as occurring after surgery or an invasive cardiovascular intervention. Ischemic stroke occurred in 81 patients (2.9 percent) in the active-treatment group and 104 (3.8 percent) in the placebo group (relative risk, 0.78; 95 percent confidence interval, 0.58 to 1.04; P=0.10). There were no significant differences in the rates of hemorrhagic stroke. Fewer patients in the active-treatment group than in the placebo group had a nonfatal stroke (84 vs. 117; relative risk, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.02). The incidence of fatal stroke was low and not significantly different between the treatment groups. The apparent effect of treatment on stroke did not differ significantly between regions with mandatory folate fortification of food and regions without mandatory folate fortification and between patients with higher as compared with lower baseline total homocysteine levels (upper vs. middle or lower third of the baseline homocysteine distribution).
The baseline homocysteine level (as a continuous measure) was a predictor of cardiovascular events in analyses adjusted for age, sex, and treatment assignment. Hazard ratios for these analyses were 1.03 for the primary outcome (95 percent confidence interval, 1.02 to 1.04), 1.04 for death from cardiovascular causes (95 percent confidence interval, 1.02 to 1.05), 1.02 for myocardial infarction (95 percent confidence interval, 1.01 to 1.04), and 1.03 for stroke (95 percent confidence interval, 1.02 to 1.05).


In our study, daily administration of the combination of folic acid, vitamin B6, and vitamin B12 lowered homocysteine levels significantly but did not reduce the incidence of the primary outcome — the composite of death from cardiovascular causes, myocardial infarction, and stroke — during a mean follow-up period of five years. In subgroup analysis, there was no heterogeneity of treatment effects among patients from regions with mandatory fortification of food with folate and regions without mandatory folate fortification and among patients with higher as compared with lower baseline homocysteine levels.
Our findings are consistent with those of the Norwegian Vitamin (NORVIT) trial, reported elsewhere in this issue of the Journal.13 The NORVIT trial evaluated 3749 patients with recent myocardial infarction from Norway, a country without folate fortification of food, and found no significant beneficial effect of combined treatment with folic acid and vitamin B12, with or without vitamin B6, in spite of adequate homocysteine lowering. Similarly, there was no treatment benefit in the Vitamin Intervention for Stroke Prevention (VISP) study14 and in a smaller trial conducted in 593 patients with stable coronary heart disease in the Netherlands.15
On the basis of epidemiologic studies conducted before our study was initiated, many of which were retrospective, our trial was adequately powered to allow the detection of a proportional reduction in the risk of the primary outcome of 17 to 20 percent. More recent prospective observational studies and a meta-analysis of these studies found the magnitude of the association between homocysteine and cardiovascular risk to be lower. After adjustment for known cardiovascular risk factors and regression dilution bias, a 25 percent decrease in the homocysteine level (about 3 μmol per liter [0.4 mg per liter]) was associated with an 11 percent decrease in the risk of coronary heart disease and a 19 percent decrease in the risk of stroke.8 Our findings cannot definitively exclude the possibility that B vitamin supplements have a very small beneficial effect on coronary heart disease, of a magnitude similar to these more recent estimates of the strength of the epidemiologic association (for example, a reduction in risk of 10 percent or less). However, this appears unlikely, considering the consistency of our findings across various coronary heart disease outcomes and subgroups, the lack of effect of treatment on total ischemic events — for which the trial was well powered to detect even a 13 percent reduction in risk — and the concordant findings of the NORVIT and VISP trials. The apparent increase in the rate of unstable angina in the active-treatment group is inconsistent with the neutral findings for all other coronary heart disease outcomes evaluated and may be related to the difficulty in establishing this diagnosis and to the play of chance.
With regard to the risk of stroke, we observed an absolute reduction of 1.3 percentage points and a relative reduction of 24 percent among patients assigned to the active-treatment group. However, these results must be interpreted with caution. The number of strokes in our study was much lower than the number of coronary events, the confidence intervals around the estimated risk reduction are wide, and the results are not adjusted for the multiplicity of outcomes compared. Also, we found no effect of treatment on transient ischemic attacks. From a biologic perspective, a treatment benefit restricted to stroke would be difficult to explain. Furthermore, the two other large trials of homocysteine-lowering vitamins that have been completed did not show a beneficial effect of treatment on stroke.13,14 Therefore, we believe that the apparent beneficial effect of B vitamin supplements on stroke in our trial may represent either an overestimate of the real effect or a spurious result due to the play of chance. Ongoing trials and a meta-analysis of all homocysteine-lowering trials16 should be able to clarify this issue.
The discordance between the epidemiology of homocysteine and the results of the clinical trials completed to date is similar to that noted for antioxidant vitamins17 and estrogen18 and may be related to inherent limitations of observational studies. Indeed, homocysteine levels are related to renal dysfunction, smoking, elevated blood pressure, and other cardiovascular risk factors and are higher in people with atherosclerosis than in those without.4 Therefore, homocysteine could be a marker, but not a cause, of vascular disease, and the epidemiologic data could be the result of residual confounding that cannot be fully adjusted for, of reverse causality, or of both. Our findings may also relate to exposure to folate-fortified food in over 70 percent of the study patients. This exposure probably reduced the number of patients with substantially increased homocysteine levels, the subgroup that might be most likely to benefit from B vitamin supplementation. Several large trials are further exploring these questions.16
In conclusion, combined daily administration of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 for five years had no beneficial effects on major vascular events in a high-risk population with vascular disease. Our results do not support the use of folic acid and B vitamin supplements as a preventive treatment