242 CNO REPORT 31 MAR 2017



CNO Report # 242

Release Date  31 MAR 2017

Draft Report Compiled by

Ralph Turchiano





In This Issue:

1.       Mayo discovers high-intensity aerobic training can reverse aging processes in adults

2.       Some veggies each day keeps the stress blues away

3.       ‘Harmless’ painkillers associated with increased risk of cardiac arrest

4.       Link between Vitamin D treatment and autism prevention

5.       Dietary anti-cancer compound may work by influence on cellular genetics

6.       Study: More than half of college football athletes have inadequate levels of vitamin D

7.       Alzheimer’s disease linked to the metabolism of unsaturated fats, new research finds

8.       UNSW scientists unveil a giant leap for anti-aging

9.       Infant vitamin B1 deficiency leads to poor motor function and balance

10.   Larger doses of vitamin C may lead to a greater reduction in common cold duration

11.   Sleep-inducing herb: The key component identified

12.   High doses of vitamin C to improve cancer treatment passes human safety trial



Public Release: 10-Mar-2017

Mayo discovers high-intensity aerobic training can reverse aging processes in adults

Mayo Clinic

ROCHESTER, Minn. — Everyone knows that exercise is good for you, but what type of training helps most, especially when you’re older — say over 65? A Mayo Clinic study says it’s high-intensity aerobic exercise, which can reverse some cellular aspects of aging. The findings appear in Cell Metabolism.

Mayo researchers compared high-intensity interval training, resistance training and combined training. All training types improved lean body mass and insulin sensitivity, but only high-intensity and combined training improved aerobic capacity and mitochondrial function for skeletal muscle. Decline in mitochondrial content and function are common in older adults.

High-intensity intervals also improved muscle protein content that not only enhanced energetic functions, but also caused muscle enlargement, especially in older adults. The researchers emphasized an important finding: Exercise training significantly enhanced the cellular machinery responsible for making new proteins. That contributes to protein synthesis, thus reversing a major adverse effect of aging. However, adding resistance training is important to achieve significant muscle strength.

“We encourage everyone to exercise regularly, but the take-home message for aging adults that supervised high-intensity training is probably best, because, both metabolically and at the molecular level, it confers the most benefits,” says K. Sreekumaran Nair, M.D., Ph.D., a Mayo Clinic endocrinologist and senior researcher on the study. He says the high-intensity training reversed some manifestations of aging in the body’s protein function. He cautioned that increasing muscle strength requires resistance training a couple of days a week.

The study’s goal was to find evidence that will help develop targeted therapies and exercise recommendations for individuals at various ages. Researchers tracked metabolic and molecular changes in a group of young and older adults over 12 weeks, gathering data 72 hours after individuals in randomized groups completed each type of exercise. General findings showed:

·         Cardio respiratory health, muscle mass and insulin sensitivity improved with all training.

·         Mitochondrial cellular function declined with age but improved with training.

·         Increase in muscle strength occurred only modestly with high-intensity interval training but occurred with resistance training alone or when added to the aerobic training.

·         Exercise improves skeletal muscle gene expression independent of age.

·         Exercise substantially enhanced the ribosomal proteins responsible for synthesizing new proteins, which is mainly responsible for enhanced mitochondrial function.

·         Training has little effect on skeletal muscle DNA energy transfer but promotes skeletal muscle protein expression with maximum effect in older adults.

Public Release: 15-Mar-2017

Some veggies each day keeps the stress blues away

Women who eat their veggies at lower risk of psychological stress

University of Sydney

Published today in the British Medical Journal Open, the longitudinal study of more than 60,000 Australians aged 45 years and above measured participants fruit and vegetable consumption, lifestyle factors and psychological distress at two time points, 2006-08 and 2010.

Psychological distress was measured using the Kessler Psychological Distress Scale, a 10-item questionnaire measuring general anxiety and depression. Usual fruit and vegetable consumption was assessed using short validated questions.

Key findings

People who ate 3-4 daily serves of vegetables had a 12 per cent lower risk of stress than those who ate 0-1 serves daily.

People who ate 5-7 daily serves of fruit and vegetables had a 14 per cent lower risk of stress than those who ate 0-4 serves daily.

Women who ate 3-4 daily serves of vegetables had an 18 per cent lower risk of stress than women who ate 0-1 serves daily.

Women who ate 2 daily serves of fruit had a 16 per cent lower risk of stress than women who ate 0-1 serves daily.

Women who ate 5-7 daily serves of fruit and vegetables had a 23 per cent lower risk of stress than women who ate 0-1 serves daily.

At the start of the study, characteristics associated with higher stress included: being female, younger, having lower education and income, being overweight/obese, a current smoker and being physically inactive.

Fruit consumption alone had no significant association with a lower incidence of stress.

There was no significant association between higher levels of fruit and vegetable intake (greater than 7 daily serves) and a lower incidence of stress.

“This study shows that moderate daily fruit and vegetable consumption is associated with lower rates of psychological stress,” said Dr Melody Ding of the University of Sydney’s School of Public Health.

“It also reveals that moderate daily vegetable intake alone is linked to a lower incidence of psychological stress. Moderate fruit intake alone appears to confer no significant benefit on people’s psychological stress.”

These new findings are consistent with numerous cross sectional and longitudinal studies showing that fruit and vegetables, together and separately, are linked with a lower risk of depression and higher levels of well-being assessed by several measures of mental health.

“We found that fruit and vegetables were more protective for women than men, suggesting that women may benefit more from fruit and vegetables,” said first author and University of Sydney PhD student, Binh Nguyen.

The investigators say further studies should investigate the possibility of a ‘threshold’ between medium and higher levels of fruit and vegetable intake and psychological stress.

This research was based on data from the Sax Institute’s 45 and Up Study.

Public Release: 15-Mar-2017

‘Harmless’ painkillers associated with increased risk of cardiac arrest

Researchers advise avoiding diclofenac and limiting ibuprofen to 1200 mg per day

European Society of Cardiology


Sophia Antipolis, 15 March 2017: Painkillers considered harmless by the general public are associated with increased risk of cardiac arrest, according to research published today in the March issue of European Heart Journal – Cardiovascular Pharmacotherapy.1

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide and some, including ibuprofen, are available over the counter.

“Allowing these drugs to be purchased without a prescription, and without any advice or restrictions, sends a message to the public that they must be safe,” said author Professor Gunnar H. Gislason, professor of cardiology at Copenhagen University Hospital Gentofte, Denmark. “Previous studies have shown that NSAIDs are related to increased cardiovascular risk which is a concern because they are widely used.”

The current study investigated the link between NSAID use and cardiac arrest. All patients who had an out-of-hospital cardiac arrest in Denmark between 2001 and 2010 were identified from the nationwide Danish Cardiac Arrest Registry. Data was collected on all redeemed prescriptions for NSAIDs from Danish pharmacies since 1995. These included the non-selective NSAIDs (diclofenac, naproxen, ibuprofen), and COX-2 selective inhibitors (rofecoxib, celecoxib).

A case-time-control design was used to examine the association between NSAID use and cardiac arrest. Each patient served as both case and control in two different time periods, eliminating the confounding effect of chronic comorbidities. Use of NSAIDs during the 30 days before cardiac arrest (case period) was compared to used of NSAIDs during a preceding 30 day period without cardiac arrest (control period).

Information was not obtained on over-the-counter drugs. Ibuprofen is the only over-the-counter NSAID in Denmark and is limited to small packages of 200 mg dosages. As patients were their own control, any underestimation of ibuprofen use should be equally distributed between the case and control periods.

A total of 28 947 patients had an out-of-hospital cardiac arrest in Denmark during the ten year period. Of these, 3 376 were treated with an NSAID up to 30 days before the event. Ibuprofen and diclofenac were the most commonly used NSAIDs, making up 51% and 22% of total NSAID use, respectively.

Use of any NSAID was associated with a 31% increased risk of cardiac arrest. Diclofenac and ibuprofen were associated with a 50% and 31% increased risk, respectively. Naproxen, celecoxib and rofecoxib were not associated with the occurrence of cardiac arrest, probably due to a low number of events.

“The findings are a stark reminder that NSAIDs are not harmless,” said Professor Gislason. “Diclofenac and ibuprofen, both commonly used drugs, were associated with significantly increased risk of cardiac arrest. NSAIDs should be used with caution and for a valid indication. They should probably be avoided in patients with cardiovascular disease or many cardiovascular risk factors.”

NSAIDs exert numerous effects on the cardiovascular system which could explain the link with cardiac arrest. These include influencing platelet aggregation and causing blood clots, causing the arteries to constrict, increasing fluid retention, and raising blood pressure.

Professor Gislason said: “I don’t think these drugs should be sold in supermarkets or petrol stations where there is no professional advice on how to use them. Over-the-counter NSAIDs should only be available at pharmacies, in limited quantities, and in low doses.”

“Do not take more than 1200 mg of ibuprofen per day,” he continued. “Naproxen is probably the safest NSAID and we can take up to 500 mg a day. Diclofenac is the riskiest NSAID and should be avoided by patients with cardiovascular disease and the general population. Safer drugs are available that have similar painkilling effects so there is no reason to use diclofenac.”

Professor Gislason concluded: “The current message being sent to the public about NSAIDs is wrong. If you can buy these drugs in a convenience store then you probably think ‘they must be safe for me’. Our study adds to the evidence about the adverse cardiovascular effects of NSAIDs and confirms that they should be taken seriously, and used only after consulting a healthcare professional.”

Public Release: 16-Mar-2017

Link between Vitamin D treatment and autism prevention

University of Queensland

Giving vitamin D supplements to mice during pregnancy prevents autism traits in their offspring, University of Queensland researchers have discovered.

The discovery provides further evidence of the crucial role vitamin D plays in brain development, said lead researcher Professor Darryl Eyles, from UQ’s Queensland Brain Institute.

“Our study used the most widely accepted developmental model of autism in which affected mice behave abnormally and show deficits in social interaction, basic learning and stereotyped behaviours,” Professor Eyles said.

“We found that pregnant females treated with active vitamin D in the equivalent of the first trimester of pregnancy produced offspring that did not develop these deficits.”

In human studies, QBI researchers recently found a link between pregnant women with low Vitamin D levels and the increased likelihood of having a child with autistic traits.

Autism — or autism spectrum disorder — describes lifelong developmental disabilities including difficulty or inability to communicate with others and interact socially.

Sun exposure is the major source of vitamin D — which skin cells manufacture in response to UV rays — but it is also found in some foods.

Dr Wei Luan, a postdoctoral researcher involved in the study, said vitamin D was crucial for maintaining healthy bones, but the active hormonal form of vitamin D cannot be given to pregnant women because it may affect the skeleton of the developing foetus.

“Recent funding will now allow us to determine how much cholecalciferol – the supplement form that is safe for pregnant women — is needed to achieve the same levels of active hormonal vitamin D in the bloodstream,” said Dr Luan.

“This new information will allow us to further investigate the ideal dose and timing of vitamin D supplementation for pregnant women.

It was previously thought vitamin D had a protective anti-inflammatory effect during brain development, but the study didn’t find this to be the case.

New funding from the National Health and Medical Research Council will allow researchers to continue to study how vitamin D protects against autism.


The study was published in Molecular Autism and included key collaborators from the Swiss Federal Institute of Technology.

Public Release: 16-Mar-2017

Dietary anti-cancer compound may work by influence on cellular genetics

Oregon State University

CORVALLIS, Ore. – Researchers have discovered one of the reasons why broccoli may be good for your health.

They found that sulforaphane, a dietary compound from broccoli that’s known to help prevent prostate cancer, may work through its influence on long, non-coding RNAs. This is another step forward in a compelling new area of study on the underlying genetics of cancer development and progression.

The findings were published by researchers from Oregon State University in the Journal of Nutritional Biochemistry.

The research provides more evidence for how these lncRNAs, which were once thought to be a type of “junk DNA” of no particular value or function, may instead play a critical role in triggering cells to become malignant and spread.

Growing evidence shows that lncRNAs, which number in the thousands, have a major role in cell biology and development, often by controlling what genes are turned on, or “expressed” to carry out their genetic function. Scientists now believe that when these lncRNAs are dysregulated they can contribute to multiple disease processes, including cancer.

The lncRNAs are also of special interest, researchers say, because they are so highly cell- and tissue-specific.

Unlike many chemotherapeutic drugs that affect healthy cells as well as malignant ones and can cause undesired side effects, the control of lncRNAs may offer a new way to specifically prevent or slow the progression of malignant cells.

“This could be a turning point in our understanding of how cancer may be triggered and spreads,” said Emily Ho, the endowed director of the Moore Family Center for Whole Grain Foods, Nutrition and Preventive Health at OSU, a professor in the College of Public Health and Human Sciences and principal investigator with the Linus Pauling Institute.

“It’s obviously of interest that this dietary compound, found at some of its highest levels in broccoli, can affect lncRNAs. This could open the door to a whole range of new dietary strategies, foods or drugs that might play a role in cancer suppression or therapeutic control.”

In particular, this research showed that one lncRNA, called LINC01116, is upregulated in a human cell line of prostate cancer, but can be decreased by treatment with sulforaphane. The data “reinforce the idea that lncRNAs are an exciting new avenue for chemoprevention research, and chemicals derived from diet can alter their expression,” the scientists wrote in their study.

“We showed that treatment with sulforaphane could normalize the levels of this lncRNA,” said Laura Beaver, a research associate in the Linus Pauling Institute and College of Public Health and Human Sciences, and lead author on the study. “This may relate to more than just cancer prevention. It would be of significant value if we could develop methods to greatly slow the progress of cancer, help keep it from becoming invasive.”

The impact of diet on lncRNA expression has been largely unknown until now, the researchers said. In this study, they identified a four-fold decrease in the ability of prostate cancer cells to form colonies when LINC01116 was disrupted.

Among men, prostate cancer is the second most frequently diagnosed cancer globally, and the second leading cause of cancer-related deaths in the United States. Worth noting, the researchers said, is that an increased consumption of cruciferous vegetables such as broccoli, which are high in sulforaphane, appears to be associated with a lower risk of developing prostate cancer.

That same lncRNA, they noted, is also overexpressed in studies of several other types of cancer, including brain, lung and colon cancer. Some other lncRNAs have been found at higher levels in breast, stomach, lung, prostate cancer and chronic lymphocytic leukemia.

In other research, a knockout of the gene that encodes one type of lncRNA in mice conferred some resistance to obesity caused by a high-fat diet.

“Taken together, this literature and our own study begin to paint a picture of the important and previously unappreciated role of lncRNAs in the body’s response to diet,” the researchers wrote in the study. “These discoveries illustrate that lncRNAs can play important roles in cancer development and may be useful targets for cancer prevention, detection and treatment.”


This research was supported by the National Institutes of Health. The work included collaborators from Texas A&M Health Science Center.

Public Release: 17-Mar-2017

Study: More than half of college football athletes have inadequate levels of vitamin D

Vitamin D deficiency linked to muscle injuries

Hospital for Special Surgery

More than half of college football athletes participating in the NFL Combine had inadequate levels of vitamin D, and this left them more susceptible to muscle injuries, according to a study at Hospital for Special Surgery (HSS).

“Vitamin D has been shown to play a role in muscle function and strength,” said Scott Rodeo, MD, senior investigator and co-chief emeritus of the Sports Medicine and Shoulder Service at HSS. “While most prior studies have focused on the aging population as the group most likely to experience the harmful effects of inadequate vitamin D, few reports have looked at the impact on muscle injury and function in the high performance athlete.”

Dr. Rodeo and colleagues set out to determine if there was a relationship between serum vitamin D levels and lower extremity muscle strains and core muscle injury, or “sports hernia,” in college football players. The study included athletes participating in the National Football League Scouting Combine, where coaches, general managers and scouts evaluate top college football players hoping to make it into the big leagues.

The study, presented at the American Academy of Orthopaedic Surgeons Annual Meeting on March 16, included 214 college athletes who took part in the 2015 combine. Baseline data was collected, including age, body mass index (BMI), injury history, and whether they had missed any games due to a lower extremity muscle strain or core muscle injury.

The average age of the athletes was 22. Their vitamin D levels were determined with a blood test. Levels were defined as normal (? 32 ng/mL), insufficient (20 – 31 ng/mL), and deficient (< 20 ng/mL).

A total of 126 players (59%) were found to have an abnormal serum vitamin D level, including 22 athletes (10%) with a severe deficiency. Researchers found a significantly higher prevalence of lower extremity muscle strain and core muscle injury in those who had low vitamin D levels. Fourteen study participants reported missing at least one game due to a strain injury, and 86% of those players were found to have inadequate vitamin D levels.

“Our primary finding is that NFL combine athletes at greatest risk for lower extremity muscle strain or core muscle injury had lower levels of vitamin D. This could be related to physiologic changes that occur to muscle composition in deficient states,” Dr. Rodeo explained. “Awareness of the potential for vitamin D inadequacy could lead to early recognition of the problem in certain athletes. This could allow for supplementation to bring levels up to normal and potentially prevent future injury,” Dr. Rodeo notes.

While the findings are significant for high performing athletes, there may be a message for the general population as well, according to Dr. Rodeo. Adequate vitamin D is essential for musculoskeletal structure, function and strength. But by some estimates, more than 40 percent of the U.S. population is deficient in vitamin D.

Sometimes called the “sunshine vitamin,” it is produced by the skin when exposed to sunlight. Sun avoidance and the use of sunscreen may in part account for low vitamin D levels in the population. Milk and fortified foods, including orange juice and some cereals, can also provide vitamin D, but one would need to consume a large amount of these foods. When individuals are found to have a deficiency, vitamin D supplements are usually prescribed.

“Although our study looked at high performance athletes, it’s probably a good idea for anyone engaging in athletic activities to give some thought to vitamin D,” Dr. Rodeo says. “Indeed, adequate levels of vitamin D are important to maintain good muscle and bone health in people of all ages.”

Public Release: 22-Mar-2017

Alzheimer’s disease linked to the metabolism of unsaturated fats, new research finds

King’s College London

A new study published in PLOS Medicine‘s Special Issue on Dementia has found that the metabolism of omega-3 and omega-6 unsaturated fatty acids in the brain are associated with the progression of Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disorder, which causes impaired memory, executive function and language. It accounts for 60 – 80% of total dementia cases worldwide, with over 46 million people suffering from the disease worldwide. The number of patients is estimated to rise to 131.5 million by 2050.

Currently it is thought that the main reason for developing memory problems in dementia is the presence of two big molecules in the brain called tau and amyloid proteins. These proteins have been extensively studied and have been shown to start accumulating in the brain up to 20 years prior to the onset of the disease. However, there is limited information on how small molecule metabolism in the brain is associated with the development and progression of Alzheimer’s disease.

In this study, researchers from King’s College London and the National Institute on Aging in the United States looked at brain tissue samples from 43 people ranging in age from 57 to 95 years old. They compared the differences in hundreds of small molecules in three groups: 14 people with healthy brains, 15 that had high levels of tau and amyloid but didn’t show memory problems and 14 clinically diagnosed Alzheimer’s patients.

They also looked at three different areas in the brain, one that usually shows little tau and amyloid, one that shows more tau and another that shows more amyloid. The main molecules that were different were six small fats, including omegas, which changed in abundance in different regions of the brain.

They found that unsaturated fatty acids were significantly decreased in Alzheimer’s brains when compared to brains from healthy patients.

Co-lead author of the study, Dr Cristina Legido Quigley from King’s College London said: “While this was a small study, our results show a potentially crucial and unexpected role for fats in the onset of dementia. Most surprisingly we found that a supposedly beneficial omega3, DHA, actually increased with the progression of the disease.

“It is now important for us to build on and replicate these findings in a larger study and see whether it corroborates our initial findings.”

Public Release: 23-Mar-2017

UNSW scientists unveil a giant leap for anti-aging

University of New South Wales

UNSW researchers have made a discovery that could lead to a revolutionary drug that actually reverses ageing, improves DNA repair and could even help NASA get its astronauts to Mars.

In a paper published in Science today, the team identifies a critical step in the molecular process that allows cells to repair damaged DNA.

Their experiments in mice suggest a treatment is possible for DNA damage from ageing and radiation. It is so promising it has attracted the attention of NASA, which believes the treatment can help its Mars mission.

While our cells have an innate capability to repair DNA damage ? which happens every time we go out into the sun, for example – their ability to do this declines as we age.

The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair.

Treating mice with a NAD+ precursor, or “booster,” called NMN improved their cells’ ability to repair DNA damage caused by radiation exposure or old age.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School Boston.

Human trials of NMN therapy will begin within six months.

“This is the closest we are to a safe and effective anti-ageing drug that’s perhaps only three to five years away from being on the market if the trials go well,” says Sinclair, who maintains a lab at UNSW in Sydney.

What it means for astronauts, childhood cancer survivors, and the rest of us:

The work has excited NASA, which is considering the challenge of keeping its astronauts healthy during a four-year mission to Mars.

Even on short missions, astronauts experience accelerated ageing from cosmic radiation, suffering from muscle weakness, memory loss and other symptoms when they return. On a trip to Mars, the situation would be far worse: five per cent of the astronauts’ cells would die and their chances of cancer would approach 100 per cent.

Professor Sinclair and his UNSW colleague Dr Lindsay Wu were winners in NASA’s iTech competition in December last year.

“We came in with a solution for a biological problem and it won the competition out of 300 entries,” Dr Wu says.

Cosmic radiation is not only an issue for astronauts. We’re all exposed to it aboard aircraft, with a London-Singapore-Melbourne flight roughly equivalent in radiation to a chest x-ray.

In theory, the same treatment could mitigate any effects of DNA damage for frequent flyers. The other group that could benefit from this work is survivors of childhood cancers.

Dr Wu says 96 per cent of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer.

“All of this adds up to the fact they have accelerated ageing, which is devastating,” he says.

“It would be great to do something about that, and we believe we can with this molecule.”

An anti-ageing pill could be on the horizon:

For the past four years, Professor Sinclair and Dr Wu have been working on making NMN into a drug substance with their companies MetroBiotech NSW and MetroBiotech International.

The human trials will begin this year at Brigham and Women’s Hospital, in Boston.

The findings on NAD+ and NMN add momentum to the exciting work the UNSW Laboratory for Ageing Research has done over the past four years.

They’ve been looking at the interplay of a number of proteins and molecules and their roles in the ageing process.

They had already established that NAD+ could be useful for treating various diseases of ageing, female infertility and also treating side effects of chemotherapy.

In 2003, Professor Sinclair made a link between the anti-ageing enzyme SIRT1 and resveratrol, a naturally occurring molecule found in tiny quantities in red wine.

“While resveratrol activates SIRT1 alone, NAD+ boosters activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

Public Release: 29-Mar-2017

Infant vitamin B1 deficiency leads to poor motor function and balance

Lack of vitamin has long-term consequences for children’s health, Tel Aviv University researchers say

American Friends of Tel Aviv University

A new Tel Aviv University study published in Maternal and Child Nutrition found that infantile Vitamin B1 (thiamine) deficiency severely affected the motor function of preschoolers who were fed faulty formula in the first year of their lives. The conclusions were based on a retrospective study of children who received Remedia, an Israeli formula brand completely lacking in Vitamin B1, in 2004.

The study was conducted by Prof. Aviva Fattal-Valevski of TAU’s Sackler School of Medicine and the director of the Pediatric Neurology Unit at Tel Aviv Sourasky Medical Center, and her master’s student Yael Harel.

Prof. Fattal-Valevski followed the development of 39 five- to six-year-old children who had been exposed to a thiamine-deficient formula as infants. She compared their motor performance with 30 age-matched healthy children with unremarkable infant nutritional history.

The participants’ motor function was evaluated with the Movement Assessment Battery for Children and the Zuk Assessment. Both tests revealed statistically significant differences between the exposed and unexposed groups for gross and fine motor development. The differences were especially noteworthy with regards to balance-control functioning and fine motor skills. Both assessments concurred on the high rate of children exhibiting motor function difficulties in comparison to the unexposed group.

Continuing effects of vitamin deficiency in infancy

Infant deaths caused 13 years ago by the Remedia formula brand in Israel brought to light the potentially devastating impact of vitamin B1 deficiency. The infants were hospitalized with cardiac and neurological symptoms caused by the lack of vitamin B1, which is usually found in their formula.

“At first it was a mystery,” said Prof. Fattal-Valevski. “It was like an epidemic. But after the grandmothers discussed the situation in the waiting room, it became clear that the infants, all under a year old, had consumed the same formula.

“After a food technician from the Health Department confirmed the total lack of vitamin B1 in the formula, we immediately provided the infants with supplements. Some recovered quickly, but three infants died and about 20 infants were left with severe disabilities and epilepsy.”

The need for awareness

“The body’s capacity for storing Vitamin B1 is limited,” said Prof. Fattal-Valevski. “Unlike vitamin B12, vitamin B1 is only stored in the body for three weeks. It needs to be frequently replenished. It is critical to be aware of how important this vitamin is for child development. Even healthy babies might be at risk for B1 deficiency. If your infant is suffering from virus after virus, you must intervene with extra vitamins. But it’s a vicious cycle, because one of the first symptoms of lack of B1 in the system is an absence of appetite.

“We’ve proven that B1 deficiency in infancy has long-term implications on gross and fine motor function and balance skills in childhood,” said Prof. Fattal-Valevski. “Our study emphasizes the importance of proper infant feeding and regulatory control of breast milk substitutes.”

The researchers are now focused on the link between infant B1 deficiency and later learning disabilities.

Public Release: 30-Mar-2017

Larger doses of vitamin C may lead to a greater reduction in common cold duration

University of Helsinki

The relationship between vitamin C dosage and its effects on the duration of the common cold symptoms may extend to 6-8 grams per day.

Dozens of animal studies using different animal species have found that vitamin C significantly prevents and alleviates infections caused by diverse bacteria, viruses, and protozoa. Given the universal nature of the effect of vitamin C against various infections in different animal species, it also seems evident that vitamin C influences the susceptibility to, and the severity of infections in humans. However, the practical importance of vitamin C in human infections is not known.

The common cold is the most extensively studied infection regarding the effects of vitamin C. The majority of controlled trials have used a modest dosage of only 1 g per day of vitamin C. The pooled effect of all published studies has shown a statistically highly significant difference between the vitamin C and placebo groups, which indicates a genuine biological effect. However, the optimal doses and the maximal effects of vitamin C on the common cold are unknown. The trials that used doses higher than 1 g per day usually found greater effects than trials with exactly 1 g per day, which suggests a dose dependent effect. Nevertheless, definitive conclusions cannot be made from such a comparison because of numerous confounding differences between the trials. The most valid examination of dose-response is therefore within a single trial that has randomly selected trial groups with different vitamin C doses, so that exposure to viruses is similar and the outcome definition is identical in the study groups.

Dr. Harri Hemilä from the University of Helsinki, Finland, analyzed the findings of two randomized trials each of which investigated the effects of two vitamin C doses on the duration of the common cold. The first trial administered 3 g/day vitamin C to two study groups, 6 g/day to a third group, and the fourth group was administered a placebo. Compared with the placebo group the 6 g/day dose shortened colds by 17%, twice as much as the 3 g/day doses did. The second trial administered 4 g/day and 8 g/day vitamin C, and placebo to different groups, but only on the first day of the cold. Compared with the placebo group, the 8 g/day dose shortened colds by 19%, twice as much as the 4 g/day dose did. Both studies revealed a significant dose-response relationship between the vitamin C dosage and the duration of the common cold. The dose-response relationship in these two trials was also quite linear up to the levels of 6-8 g/day, thus it is possible that even higher doses may lead to still greater reductions in the duration of common cold. Dr. Hemilä notes that there have been proposals that vitamin C doses should be over 15 g/day for the best treatment of colds, but the highest doses that have so far been investigated in randomized trials have been much lower.

Dr. Hemilä concludes that “given the consistent effect of vitamin C on the duration of colds, and its safety and low cost, it would be worthwhile for individual common cold patients to test whether therapeutic 8 g/day vitamin C is beneficial for them. Self-dosing of vitamin C must be started as soon as possible after the onset of common cold symptoms to be most effective.” Dr Hemilä also states that further therapeutic trials should be carried out to investigate the dose-response relation in the region of over 8 g/day of vitamin C.

Public Release: 30-Mar-2017

Sleep-inducing herb: The key component identified

Can’t sleep? Your sleep problems may be improved if you try an Indian herb, Ashwagandha. Researchers in the sleep institute in Japan found that an active component of Ashwagandha leaves significantly induces sleep.

Ashwagandha (Withania somnifera) is a central herb in Ayurveda, the traditional home medicine native to India. As signified by its Latin name somnifera, meaning sleep-inducing, it has been recommended for sound sleep through centuries. Even though scientific studies also support that crude powder of Ashwagandha promotes sleep, the active component with sleep-inducing property remains unknown.

The research group led by Mahesh K. Kaushik and Yoshihiro Urade of the International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, investigated the effect of various components of Ashwaganda on sleep in mice by recording electroencephalogram and electromyography. The water extract of Ashwaganda leaf containing rich in triethylene glycol (TEG) promoted non-rapid eye movement (NREM) sleep significantly and changed rapid eye movement (REM) sleep slightly, while the alcoholic extract containing active withanolides showed no effect on sleep. The sleep induced by TEG was similar to normal sleep. Furthermore, commercially available TEG also increased the amount of NREM sleep. They thus concluded that TEG is the active component that induces physiologically sound sleep.

Sleeplessness and other sleep disorder such as restless leg syndrome are common complaints among the middle-aged population. Insomnia is one of the most common neuropsychiatric disorders, with an estimated incident of 10-15% in general population and 30-60% in elderly population. It is closely linked with certain other diseases including obesity, cardiovascular diseases, depression, anxiety, mania deficits etc. Currently available synthetic drugs often show severe side effects. On the other hand, Ashwagandha crude powder including the significant amount of TEG can be consumed for better sleep without any side effects. The findings in this study could revolutionize the natural plant-based therapies for insomnia and sleep related disorders.

However, the clinical application of TEG to treat insomnia is still in the immature status, because the TEG is primarily used for industrial purpose and very little is known about its applicability and toxicity to the biological systems. Further studies will thus be needed to confirm the safety of TEG.

According to the authors, they are currently evaluating the effect of TEG administration on stress, because Ashwagandha is believed to mitigate stress and correct imbalance of various nervous systems. Future studies also include the identification of target brain area of TEG, its BBB permeability and the mechanism through which TEG induces sleep.

Public Release: 30-Mar-2017

High doses of vitamin C to improve cancer treatment passes human safety trial

Clinical trials found that it is safe to regularly infuse brain and lung cancer patients with 800 — 1000 times the daily recommended amount of vitamin C as a potential strategy to improve outcomes of standard cancer treatments. In a work presented March 30, 2017 in Cancer Cell, University of Iowa researchers also show pathways by which altered iron metabolism in cancer cells, and not normal cells, lead to increased sensitivity to cancer cell death caused by high dose vitamin C.

“This paper reveals a metabolic frailty in cancer cells that is based on their own production of oxidizing agents that allows us to utilize existing redox active compounds, like vitamin C, to sensitize cancer cells to radiation and chemotherapy,” says co-author Garry Buettner, who was one of the first to propose that cancer cells might have a vulnerability to redox active compounds over 40 years ago. Buettner, along with study senior authors Bryan Allen and Douglas Spitz, are faculty members at the University of Iowa’s Department of Radiation Oncology, Free Radical and Radiation Biology Program, in the Holden Comprehensive Cancer Center.

The 11 evaluable patients enrolled in the brain cancer safety trial received three infusions of vitamin C a week for 2 months followed by two infusions per week for 7 months while receiving standard care radiation and chemotherapy. The goal of each infusion was to raise the concentration of vitamin C in a patient’s blood to 20,000 μM, as compared to a blood level of about 70 μM found in most adults. The high dose is necessary because vitamin C has a half-life of about two hours in the circulation of humans. The treatment was generally well tolerated; with modest side effects including frequent trips to the bathroom and dry mouth. Rarely, some patients developed high blood pressure that subsided quickly following infusion.

Why is this approach safe? Vitamin C, even at high levels, isn’t toxic to normal cells. The research group at Iowa found, however, that tumor tissue’s abnormally high levels of redox active iron molecules (a by-product of abnormal mitochondrial metabolism) react with vitamin C to form hydrogen peroxide and free radicals derived from hydrogen peroxide. These free radicals are believed to cause DNA damage selectively in cancer cells (versus normal cells) leading to enhanced cancer cell death as well as sensitization to radiation and chemotherapy in cancer cells.

“This is a significant example of how knowing details of potential mechanisms and the basic science of redox active compounds in cancer versus normal cells can be leveraged clinically in cancer therapy,” says co-senior author Douglas Spitz, who focused on the biochemical studies. “Here, we verified convincingly that increased redox active metal ions in cancer cells were responsible for this differential sensitivity of cancer versus normal cells to very high doses of vitamin C.”

The safety study sets the stage for phase II clinical trials looking at whether high dose vitamin C is effective at extending overall lifespan and quality of life for patients undergoing radiation and chemotherapy. The researchers are currently enrolling patients with stage 4 lung cancer and will soon begin enrolling people with glioblastoma multiforme (brain cancer) in these phase II trials. They are hopeful that brain cancer responses to radiation and chemotherapy can be enhanced in these phase II trials. This guarded optimism is based on the phase I trial data showing an increase in overall survival of 4-6 months in 11 glioblastoma multiforme patients (18-22 months) versus the 14-16 months survival typically seen with the standard treatment.

“The majority of cancer patients we work with are excited to participate in clinical trials that could benefit future patient outcomes down the line,” says co-senior author Bryan Allen, who led the clinical side of the study. “Results look promising but we’re not going to know if this approach really improves therapy response until we complete these phase II trials.”

The cost per patient above standard insurance billing for the phase II vitamin C glioblastoma multiforme protocol is approximately $8000 spread over 9 months of test infusions. This cost can be less than a single dose of some immunotherapy and/or chemotherapy drugs.