Prolonged fasting 're-boots' immune system

Results of a new study on mice and a phase 1 trial of humans suggest that prolonged cycles of fasting - for 2-4 days at a time - not only protect against toxic effects of chemotherapy, but also trigger stem cell regeneration of new immune cells and clearing out of old, damaged cells.

The study, by researchers from the University of Southern California (USC) in Los Angeles, and published in the journalCell Stem Cell, is the first to show that a natural intervention can trigger regeneration of an organ or system throughstem cells.

The team believes the findings could benefit people with immune system damage, for example if they have receivedchemotherapy treatment for cancer. It could also benefit the elderly whose immune systems are weakened through aging, making them more susceptible to disease.

The scientists say prolonged fasting appears to shift stem cells of the immune system from a dormant state to an active state of self-renewal.

Results from experiments with mice and a phase 1 human clinical trial showed that long periods of fasting significantly lowered levels of white blood cells. In the mice, it flipped a switch that changed the signaling pathways of hematopoietic stem cells - a group of stem cells that generate blood and immune systems.

"We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system," says Valter Longo, a professor of Gerontology and the Biological Sciences at the USC Davis School of Gerontology, and director of the USC Longevity Institute.

He says that when you stop eating, the body uses up stored glucose, fat and ketones, and also recycles worn out and damaged immune cells.

"What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting," he explains. "Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?"

In mice, prolonged fasting replenished worn out immune cells with new ones

The researchers found that fasting for 2-4 days reduced PKA, an enzyme that is involved in extending lifespan in simple organisms.

In mice, prolonged periods of fasting - repeated cycles of 2-4 days with no food - over the course of 6 months, killed older and damaged immune cells and generated new ones.

During each fasting cycle, the drop in white cell levels triggered a stem-cell based regeneration of new immune cells. In particular, prolonged fasting reduced PKA, an enzyme that the team had previously discovered is involved in extending lifespan in simple organisms.

Other studies have also linked PKA to the control of stem cell self-renewal and pluripotency - the extent to which they can become different cell-types.

Prolonged fasting also led to a drop in IGF-1, a growth factor hormone linked to aging, cancer and tumor progression.

Switching off the gene for PKA is the key step that triggers the stem cells to shift to regeneration, Prof. Longo says. "It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system."

And the good news, he adds, is that the body also rids itself "of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system."

Three-day fast protected cancer patients from toxic chemo effects

In a clinical trial involving a small group of cancer patients, the team also found that fasting for 3 days before receiving chemotherapy protected them from its toxic effects.

While chemotherapy saves lives, it also causes significant damage to the immune system, and the team hopes their findings show that fasting may help to minimize some of that harm.

Meanwhile, there is no suggestion that people should try to get these same effects by prolonged fasting, which should only be done under medical supervision.

More clinical studies are now needed to test the effectiveness of the approach in humans and also examine the side effects.

Prof. Longo says they are now investigating whether these same regeneration effects work with other systems and organs as well as the immune system. His lab is already planning further animal studies and clinical trials.

Funds from the National Institute of Aging of the National Institutes of Health (NIH), the V Foundation and the National Cancer Institute of the NIH helped finance the study.

Meanwhile, Medical News Today recently reported how stem cells show potential for brain damage repair. Research from Australia suggests by manipulating cell-surface proteins it may be possible to get bone marrow stem cells to differentiate into brain cells. If the method proves viable, it could lead to ways of generating new brain cell populations for repairing brain damage.

Written by Catharine Paddock PhD

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Caffeine: how does it really affect our health?

When we wake up in the morning, many of us reach for a coffee to kick-start our day. According to the International Coffee Organization, approximately 1.6 billion cups of coffee are consumed worldwide every day.

The US Food and Drug Administration (FDA) state that the average amount of caffeine consumed in the US is approximately 300 mg per person per day - the equivalent to between two and four cups of coffee. This is considered to be a moderate caffeine intake, which according to many studies, can promote a variety of health benefits.

But some studies claim otherwise, even suggesting that one or two cups of coffee a day may negatively impact our health. So, what are we to believe?

We analyze the potential health benefits, as well as the negative side effects of caffeine consumption.

A natural stimulant

The main ingredient in coffee is caffeine - a compound that naturally derives from over 60 different plant sources, including coffee beans, tea leaves, cacao seeds and cola nut seeds.

Caffeine acts as a stimulant by activating the central nervous system. It can combat tiredness and improve concentration and focus.

According to the University of Michigan Health Service, the stimulating effects of caffeine can start as early as 15 minutes after consumption and last up to 6 hours.

Other than coffee, caffeine is commonly consumed through tea, soft drinks - particularly energy drinks - and chocolate. It is also found in some prescription and non-prescription drugs, such as cold, allergy and pain medication.

The potential health benefits

As well as its stimulating effects, caffeine has been heralded for providing an array of health benefits.

Some studies have suggested that drinking three or four cups of coffee a day may reduce the risk of liver, mouth and throatcancer.

Last year, Medical News Today reported on a study suggesting that consuming three cups of coffee a day may reduce the risk of liver cancer by 50%, while another study suggests that drinking four cups a day could halve the risk of mouth and throat cancer.

Caffeine consumption has also been associated with positive effects on the brain.

Last year, a study from the Harvard School of Public Health suggested that drinking between two and four cups of coffee a day may reduce suicide risk in adults, while more recent research found that ingesting 200 mg of caffeine each day may boost long-term memory.

Other studies have also suggested that caffeine intake may protect against type 2 diabetes, Parkinson's disease, cardiovascular disease and stroke.

Caffeine: the 'socially acceptable psychoactive drug'

With so much research claiming that caffeine consumption can benefit our health, and considering the number of products that contain the stimulant, it is no wonder caffeine consumption is so widespread.

But Steven E. Meredith, postdoctoral research fellow at The Johns Hopkins University School of Medicine, told Medical News Today that, perhaps due to widespread consumption, many of us forget that caffeine is a psychoactive substance - a drug that crosses the blood-brain barrier to stimulate the central nervous system.

He said:

"Unlike most other psychoactive substances, caffeine use is socially acceptable, and the drug is widely used. In fact, caffeine is the most commonly used psychoactive substance in the world.

Moreover, the vast majority of caffeine consumers use the substance regularly without apparent harm. These factors likely contribute to the perspective that caffeine is a benign substance that everyone can use without suffering any negative consequences."

The negative effects of caffeine consumption

But of course, there can be negative consequences from caffeine consumption, particularly if ingested in high doses.

The Mayo Clinic state that consuming more than 500-600 mg of caffeine a day may lead to insomnia, nervousness, restlessness, irritability, an upset stomach, a fast heartbeat and even muscle tremors.

However, previous research has linked even moderate amounts of caffeine to negative health effects.

Last year, Medical News Today reported on a study suggesting that consuming 300 mg of caffeine a day during pregnancy may increase the risk of low birth weight babies, while other research suggests that drinking four cups of coffee a day may increase the risk of early death.

Effects of caffeine vary from person to person

But Meredith told us that the effects of caffeine can vary in each individual, which may explain why there are mixed messages surrounding whether caffeine is good or bad for us.

For example, he said that individuals with anxiety disorders are more susceptible to the anxiogenic effects of the compound.

Cigarette smokers can metabolize caffeine twice as fast as non-smokers.

"Caffeine can also metabolize at different rates among individuals for various reasons. For example, cigarette smokers metabolize caffeine twice as fast as non-smokers," he added.

"However, caffeine metabolism is slower among infants, pregnant women and individuals with liver disease. In addition, some medications slow caffeine metabolism, which may increase the risk for caffeine intoxication. But the effects of caffeine also vary simply because we're all different."

Rob M. Van Dam, adjunct associate professor of the Department of Nutrition at the Harvard School of Public Health, told Medical News Today that the effects of caffeine are dependent on each person's genetic characteristics and lifestyle factors.

"Thus, some people may have difficulty sleeping or experience tremors or stress with relatively low caffeine intakes and it is useful to be aware of these symptoms and reduce caffeine intake if these occur," he added.

Caffeine addiction and withdrawal

Given the positive effects caffeine can have as a stimulant, Meredith told Medical News Today that for some people, this can result in caffeine addiction:

"Caffeine activates many of the same behavioral and neuropharmacological mechanisms that are activated by other reinforcers, including other drugs of abuse.

And, like many other reinforcers, caffeine is associated with various positive subjective effects like increased wellbeing, sociability, and feelings of energy and alertness. For this reason and others, a small percentage of the population develops caffeine use disorder."

He said that some people can become physically dependent on caffeine, with absence or reduction of coffee consumption in these individuals resulting in caffeine withdrawal.

This can trigger symptoms such as headache, fatigue, drowsiness, depression, irritability, concentration difficulties, nausea and vomiting.

"Dependence can become so strong for some individuals that they're unable to reduce consumption despite knowledge of recurrent physical or psychological problems associated with continued use," Meredith added.

Kids and adolescents 'should avoid caffeine consumption'

Meredith said that based on the negative side effects caffeine consumption can have, doctors should be discussing caffeine use with their patients to determine whether they are ingesting safe levels of the stimulant.

Furthermore, he warned that this is particularly important for children and adolescents.

Pediatricians recommend that children should steer clear from caffeine, often found in soft drinks.

The majority of pediatricians recommend that this population should avoid caffeine consumption, particularly since it is unknown as to how excessive caffeine intake impacts the developing brain.

"Notably, caffeine interferes with sleep, and sleep plays a critical role in learning. Some laboratory research suggests that caffeine interferes with sleep and learning among adolescent rodents, which, in turn, hinders normal neurological development that is noticeable into adulthood," said Meredith.

"Some psychologists are also concerned that a pattern of caffeine use or abuse among young people may lead to subsequent problematic drug and alcohol use."

The FDA clearly hold a similar view to pediatricians. In May last year, the organization announced it would beinvestigating the safety of caffeine in food products, particularly products aimed at children and adolescents.

The FDA are concerned that many food and drink products, such as jelly beans, waffles, syrup and chewing gum, now have caffeine added to them to enhance their stimulating effect.

Michael R. Taylor, deputy commissioner for foods and veterinary medicine at the FDA, said:

"We're particularly concerned about children and adolescents and the responsibility FDA and the food industry have to protect public health and respect social norms that suggest we shouldn't be marketing stimulants, such as caffeine, to our children."

Meredith told us that studies have shown high caffeine intake may also produce negative side effects in pregnant women and individuals with heart conditions or anxiety disorders.

However, he added that the majority of us consume caffeine in moderation without any harmful side effects, so healthy adults should not be overly concerned.

"But we should be mindful that when we consume caffeine, we are consuming a psychoactive substance that can cause or exacerbate some health problems," he cautioned.

Written by Honor Whiteman

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Lose the weight, not the potatoes

Research published this week in the Journal of the American College of Nutrition demonstrates that people can eat potatoes and still lose weight.

The study, a collaborative effort between the University of California at Davis and the Illinois Institute of Technology, sought to gain a better understanding of the role of calorie reduction and the glycemic index in weight loss when potatoes are included in the diet.

"Some people have questioned the role of potatoes in a weight loss regimen because of the vegetable's designation as a high glycemic index food," explained Dr. Britt Burton-Freeman, PhD, the lead investigator of the study. "However, the results of this study confirm what health professionals and nutrition experts have said for years: it is not about eliminating a certain food or food groups, rather, it is reducing calories that count," said Burton-Freeman.

Ninety overweight men and women were randomly assigned to one of three groups: (1) reduced calorie/high GI, (2) reduced calorie/low GI, (3) control group with no calorie or GI restrictions. All three groups were provided potatoes, healthful recipes and instructions to consume 5-7 servings of potatoes per week. At the end of the 12-week study period, the researchers found that all three groups had lost weight and there was no significant difference in weight loss between the groups.

"There is no evidence that potatoes, when prepared in a healthful manner, contribute to weight gain. In fact, we are seeing that they can be part of a weight loss program," said Burton-Freeman.

Interestingly, even the control group reduced their caloric intake and lost weight despite not being provided with a specific calorie restriction. "The fact that all groups, even the control group, lost weight is a curious finding and provides cause for future research," said co-investigator Dr. Tissa Kappagoda, MD, PhD.

The study results are good news for potato lovers and any consumer who craves the satisfaction of wholesome yet healthy meal options. One medium-size (5.3 ounce) skin-on potato contains just 110 calories per serving, boasts more potassium (620g) than a banana, provides almost half the daily value of vitamin C (45 percent), and contains no fat, sodium or cholesterol.

This study was funded by the United States Potato Board.

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Fruit juice 'as bad' as sugary drinks, say researchers

Two medical researchers writing in one of The Lancet journals argue that because of its high sugar content, fruit juice could be just as bad for us as sugar-sweetened beverages like carbonated drinks and sodas.

Naveed Sattar, professor of Metabolic Medicine, and Dr. Jason Gill, both of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow in Scotland, call for the UK government to change the current "five a day" guideline to exclude a portion of fruit juice from the list of fruits and vegetable servings that count toward it.

In their paper, published in the The Lancet Diabetes & Endocrinology, they propose that including fruit juice as one of the five a day is "probably counter-productive," because it leads people to consider fruit juice as a healthy food that does not need to be limited, as is the case with less healthy foods.

They also urge food companies to improve container labeling of fruit juices to inform consumers they should drink no more than 150 ml a day of the product.

Fruit juice has come under the spotlight since medical experts recently started looking more closely at the link between high sugar intake and the risk for heart disease.

In 2012, researchers at Harvard reported in the journal Circulation that daily consumption of sugary drinks raised heart disease risk in men. Two years earlier, researchers presenting at an American Heart Association conference said Americans' higher consumption of sugary drinks has led to more diabetes and heart disease over the past decade.

Fruit juice is not a low-sugar alternative to sugar-sweetened drinks

Dr. Gill says "there seems to be a clear misperception that fruit juices and smoothies are low-sugar alternatives to sugar-sweetened beverages."

Prof. Sattar explains:

"Fruit juice has a similar energy density and sugar content to other sugary drinks, for example: 250 ml of apple juice typically contains 110 kcal and 26 g of sugar; and 250 ml of cola typically contains 105 kcal and 26.5 g of sugar."

He says research is beginning to show that unlike solid fruit intake, for which high consumption appears linked either to reduced or neutral risk for diabetes, high fruit juice intake is linked to raised risk for diabetes.

"One glass of fruit juice contains substantially more sugar than one piece of fruit."

"One glass of fruit juice contains substantially more sugar than one piece of fruit; in addition, much of the goodness in fruit - fibre, for example - is not found in fruit juice, or is there in far smaller amounts," he adds.

Also, although fruit juices contain vitamins and minerals that are mostly absent in sugar-sweetened drinks, the levels of nutrients in fruit juices many not be enough to offset the unhealthy effect that excessive consumption has on metabolism, says Dr. Gill.

In their paper they refer to a trial where participants drank half a liter of pure grape juice every day for 3 months. And the results showed that despite grape juice's high antioxidant properties, it led to increased insulin resistance and bigger waists in overweight adults.

Poor public awareness about the amount of sugar in fruit juice

The researchers also report an online poll of over 2,000 adults that tested public awareness of the sugar content of fruit juices. Respondents were asked to look at pictures of containers filled with non-alcoholic drinks and estimate how many teaspoons of sugar each contained.

The results showed that even though all the drinks had a similar sugar content, on average the respondents underestimated the sugar content of fruit juices and smoothies by 48%, and overestimated that of carbonated drinks by an average of 12%.

Prof. Sattar says there are strong public health reasons for taxing or targeting sugary drinks in some way, so as to reduce consumption. But he and Dr. Gill do not go as far as to advocate children should not drink fruit juice at all, which is what some have been calling for in the US.

They do, however, urge public health policymakers to include fruit juice when they debate the issue of sugar-sweetened drinks.

Written by Catharine Paddock PhD

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Arthritis drug helps bald man grow full head of hair

There is no cure or treatment for alopecia universalis, an uncommon autoimmune disease that causes loss of hair over the entire scalp and body. Now doctors at Yale University in New Haven, CT, report how they successfully restored hair on the head and other parts of the body in a 25-year- old man with the disease that had left him nearly completely hairless all over.

They write about the treatment and the results in the Journal of Investigative Dermatology and say it is the first reported case of a successfully targeted treatment for this rare form of alopecia areata, which occurs when the immune system mistakenly attacks the hair follicles.

After the treatment, which uses an FDA-approved drug for rheumatoid arthritis called tofacitinib citrate, the patient regained a full head of hair, eyebrows and eyelashes, plus facial, armpit, groin and other hair, none of which he had when he first sought medical help.

Senior author Brett A. King, assistant professor of dermatology at Yale University School of Medicine, says the results were exactly what they hoped for, and represent a "huge step forward" in treating patients with the condition. He adds:

"While it's one case, we anticipated the successful treatment of this man based on our current understanding of the disease and the drug. We believe the same results will be duplicated in other patients, and we plan to try."

As well as alopecia universalis, the patient had also been diagnosed with another condition called plaque psoriasis, which causes scaly red areas to develop on the skin. The only hair he had on his body was in the psoriasis plaques on his head.

His doctor referred him to Yale's dermatology unit for treatment of the psoriasis - he had never received treatment for alopecia universalis.

Tofacitinib had already been used successfully in humans to treat psoriasis - and in lab mice, it has been shown to reverse a less extreme form of alopecia called alopecia areata. So it made sense, the researchers thought, to see if the drug could tackle the alopecia universalis as well as the psoriasis.

"There are no good options for long-term treatment of alopecia universalis," Prof. King explains, "The best available science suggested this might work, and it has."

Hair growth visible after 2 months of treatment

To begin with, the team put the patient on a 5 mg twice daily dose of tofacitinib. After 2 months, his psoriasis began to improve, and he had hair on his scalp and face - for the first time in 7 years.

From then on, the researchers increased the dose to 15 mg a day. After another 3 months, the patient had a full head of hair, and had also grown eyebrows and eyelashes, and hair on his face, in his armpits, and other areas.

The patient was administered a 5 mg twice daily dose of tofacitinib. After 2 months, his psoriasis began to improve, and he had hair on his scalp and face - for the first time in 7 years.

After 8 months of treatment, all his hair had regrown, say the researchers, adding that they saw no lab abnormalities and the patient reported feeling no side effects.

Prof. King suggests the drug - which is designed to treat the autoimmune disease rheumatoid arthritis - stops the immune system attacking the hair follicles.

He has already proposed a trial using a cream form of the medicine as a treatment for alopecia areata.

According to the National Organization for Rare Disorders, there are about 2.5 million Americans with alopecia areata, which affects both males and females equally and can surface at any age, but most typically during childhood.

The study follows one Medical News Today reported in September 2011, also by a team at Yale, that found molecular signals that trigger hair growth in mice. Writing in the journal Cell, the researchers described how they found molecular signals from stem cells under the fatty layer of the skin were important for bringing about hair growth.

Another study, reported by Medical News Today in August 2014, revealed how a bone marrow disease drug helped restore hair growth in alopecia areata patients.

Written by Catharine Paddock PhD

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