223 CNO Report 31 JAN 2016



CNO Report 223

Release Date 31 JAN 2016

Draft Report Compiled by

Ralph Turchiano



In This Issue:

1.       Study suggests that what you eat can influence how you sleep

2.       Higher dietary nitrate and green leafy vegetable intake associated with lower risk of glaucoma

3.       A nutrition supplement is associated with lower death rate in patients, new study shows

4.       New study shows aged garlic extract can reduce dangerous plaque buildup in arteries

5.       Ancient medicinal clay shows promise against today’s worst bacterial infections

6.       Study shows zinc supplement boosted serum zinc levels and immunity in older adults

7.       Asthma and allergies: A protective factor in farm milk

8.       Flavonoids from fruits and vegetables may help with weight maintenance

9.       University of Arizona researchers identify food additive that may prevent skin cancer

10.   Texas A&M research hints at a nutritional strategy for reducing autism risk


Public Release: 14-Jan-2016

Study suggests that what you eat can influence how you sleep

Daily intake of fiber, saturated fat and sugar may impact sleep quality

American Academy of Sleep Medicine


DARIEN, IL – A new study found that eating less fiber, more saturated fat and more sugar is associated with lighter, less restorative, and more disrupted sleep.

Results show that greater fiber intake predicted more time spent in the stage of deep, slow wave sleep. In contrast, a higher percentage of energy from saturated fat predicted less slow wave sleep. Greater sugar intake also was associated with more arousals from sleep.

“Our main finding was that diet quality influenced sleep quality,” said principal investigator Marie-Pierre St-Onge, PhD, assistant professor in the department of medicine and Institute of Human Nutrition at Columbia University Medical Center in New York, N.Y. “It was most surprising that a single day of greater fat intake and lower fiber could influence sleep parameters.”

Study results are published in the January issue of the Journal of Clinical Sleep Medicine.

“This study emphasizes the fact that diet and sleep are interwoven in the fabric of a healthy lifestyle,” said American Academy of Sleep Medicine President Dr. Nathaniel Watson, who was not involved in the study. “For optimal health it is important to make lifestyle choices that promote healthy sleep, such as eating a nutritious diet and exercising regularly.”

The study also found that participants fell asleep faster after eating fixed meals provided by a nutritionist, which were lower in saturated fat and higher in protein than self-selected meals. It took participants an average of 29 minutes to fall asleep after consuming foods and beverages of their choice, but only 17 minutes to fall asleep after eating controlled meals.

“The finding that diet can influence sleep has tremendous health implications, given the increasing recognition of the role of sleep in the development of chronic disorders such as hypertension, diabetes and cardiovascular disease,” said St-Onge.

The randomized, crossover study involved 26 adults – 13 men and 13 women – who had a normal weight and an average age of 35 years. During 5 nights in a sleep lab, participants spent 9 hours in bed from 10 p.m. to 7 a.m., sleeping for 7 hours and 35 minutes on average per night. Objective sleep data were gathered nightly by polysomnograhy. Sleep data were analyzed from night 3, after 3 days of controlled feeding, and night 5, after one day of ad libitum food intake.

According to the authors, the study suggests that diet-based recommendations might be used to improve sleep in those with poor sleep quality. However, future studies are needed to evaluate this relationship.


Public Release: 14-Jan-2016

Higher dietary nitrate and green leafy vegetable intake associated with lower risk of glaucoma

The JAMA Network Journals


Greater intake of dietary nitrate and green leafy vegetables was associated with a 20 percent to 30 percent lower risk of primary open-angle glaucoma, according to a study published online by JAMA Ophthalmology.

Elevated intraocular pressure and impaired autoregulation of optic nerve blood flow are implicated in primary open-angle glaucoma (POAG; optic nerve damage from multiple possible causes that is chronic and progresses over time). Evidence suggests that nitrate or nitrite, precursors for nitric oxide, is beneficial for blood circulation. Jae H. Kang, Sc.D., of Brigham & Women’s Hospital and Harvard Medical School, Boston, and colleagues evaluated the association between dietary nitrate intake, derived mainly from green leafy vegetables, and POAG. The researchers followed up participants biennially in the prospective cohorts of the Nurses’ Health Study (63,893 women; 1984-2012) and the Health Professionals Follow-up Study (41,094 men; 1986-2012). Eligible participants were 40 years or older, were free of POAG, and reported eye examinations. Information on diet was updated with questionnaires.

During follow-up, 1,483 incident cases of POAG were identified. Participants were divided into quintiles (one of five groups) of dietary nitrate intake (quintile 5, approximately 240 mg/d; quintile 1, approximately 80 mg/d). The researchers found that greater intake of dietary nitrate and green leafy vegetables was associated with a 20 percent to 30 percent lower POAG risk; the association was particularly strong (40 percent-50 percent lower risk) for POAG with early paracentral visual field loss (a subtype of POAG linked to dysfunction in blood flow autoregulation).

“These results, if confirmed in observational and intervention studies, could have important public health implications,” the authors write.

(JAMA Ophthalmol. Published online January 14, 2016.doi:10.1001/jamaopthalmol.2015.5601; Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Related Content from JAMA Ophthalmology: Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up


A nutrition supplement is associated with lower death rate in patients, new study shows

Research examined effects of a specialized oral nutrition supplement on hospital readmissions and mortality rates in malnourished adults aged 65 or older1



ABBOTT PARK, Ill. Jan. 18, 2016 -Results from a new clinical trial show that a specialized oral nutrition supplement was associated with a 50 percent lower death rate in older malnourished patients with a heart or lung disease 90 days following hospitalization. The study, published online today in Clinical Nutrition and supported by Abbott, estimated that within this population one life could be saved for every 21 patients who received the specialized nutrition supplement, demonstrating it as a highly effective therapy.

The NOURISH (Nutrition effect On Unplanned ReadmIssions and Survival in Hospitalized patients) study – one of the largest nutrition clinical studies of its kind – was a prospective, randomized, double-blind, placebo-controlled trial. The study was designed to build upon the body of evidence demonstrating that oral nutrition supplements may reduce complications, mortality and hospital readmissions in malnourished patients. Participants in the NOURISH study included 652 malnourished adults, aged 65 or older, who were admitted to the hospital and suffered from heart or lung disease. Researchers compared the effects of a specialized nutrition supplement with high protein (20 grams), HMB* (a muscle-preserving ingredient) and Vitamin D to a placebo supplement on rates of readmissions or death 90-days after leaving the hospital.

Results showed no significant differences between the two groups for the primary composite (i.e. combined) endpoint of hospital readmissions or death. However, the study individual components and additional analyses showed:

·         A significantly lower (50 percent) death rate for those patients who received the specialized nutrition supplement. This lower incidence of death began at 30 days and continued for 90 days after participants left the hospital.

·         Similar rates of hospital readmissions between the two groups.

·         Improvements in other health outcomes including body weight, nutritional status and Vitamin D levels at 30 and 60 days after leaving the hospital, and continued body weight and nutritional status improvements at 90 days for the group taking the specialized nutrition supplement.

“The NOURISH study clearly reinforces the power of nutrition in impacting health outcomes. For the people in this study who were ill and malnourished, nutrition was critical to survival because it helps keep your body, especially your muscles, functioning properly,” said Nicolaas E. Deutz, MD, PhD, Center for Translational Research in Aging & Longevity, Department of Health and Kinesiology, Texas A&M University, and lead study author. “This is more proof that we need to change the standard and include nutrition as an integral part of care, much like flu shots or aspirin, to help older adults who already have or are at risk for malnutrition and chronic illness.”


Up to 1 in 2 older adults are malnourished when they are admitted to the hospital.2-4 Many adults may not even realize they are malnourished – they can be of normal weight, or overweight, but have low levels of muscle or lean body mass. The loss of muscle, strength and energy can intensify in malnourished patients and those with a health issue like a heart attack or pneumonia. Other studies have shown that malnutrition can worsen their health outcomes including higher chances of complications, readmissions and even death.5-7

“Surprisingly, malnutrition in older adults is very common – and it’s a condition that is having a rippling effect on our health and health system,” said Alfonso Cruz-Jentoft, MD, PhD, head of the Geriatrics Department, Hospital Ramón y Cajal, Spain, and past president of the European Union Geriatric Medicine Society. He was not involved in the study. “People underestimate how critical strength and muscle health are to recovery from hospitalization and illness. Proper nourishment is a key component and cannot be left out of the conversation.”

The NOURISH study builds upon existing research that shows the role nutrition plays in a patient’s health, ranging from rebuilding muscle mass to helping with recovery from disease and time in the hospital. The nutrients in the specialized nutrition supplement used in the study – protein, HMB and Vitamin D – are all important components in repairing and rebuilding muscle while recovering from hospitalization and illness.

“As medicine has advanced, so has the science of nutrition. We know proper nutrition is foundational for good health, but the medical community and patients don’t always turn to it when recovering from a health issue like pneumonia,” said Refaat Hegazi, MD, PhD, Abbott medical director and study author. “While the prevalence of malnutrition is high, research shows that less than two percent of malnourished patients in the hospital receive an oral nutrition supplement. Nutrition must be one of our critical tools to help adults live longer, better lives.”

The commercially available versions of the specialized nutrition supplement evaluated in the study are Ensure® Plus Advance in Europe, and it will be available this year as Ensure® Enlive® in the United States. The specialized nutrition supplement is also expected to be available in other countries around the world in the next couple of years.


Public Release: 21-Jan-2016

New study shows aged garlic extract can reduce dangerous plaque buildup in arteries

Supplement can help prevent progression of heart disease

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)


LOS ANGELES – The supplement Aged Garlic Extract can reverse the buildup of deadly plaque in arteries and help prevent the progression of heart disease, according to a new study scheduled for publication in the Journal of Nutrition.

The research, conducted at LA BioMed, found a reduction in the amount of low-attenuation plaque, or “soft plaque,” in the arteries of patients with metabolic syndrome who took Aged Garlic Extract. Metabolic syndrome is characterized by obesity, hypertension and other cardiac risk factors.

“This study is another demonstration of the benefits of this supplement in reducing the accumulation of soft plaque and preventing the formation of new plaque in the arteries, which can cause heart disease,” said Matthew J. Budoff, MD, an LA BioMed lead researcher. “We have completed four randomized studies, and they have led us to conclude that Aged Garlic Extract can help slow the progression of atherosclerosis and reverse the early stages of heart disease.”

The study involved 55 patients, aged 40 to 75 years, who had been diagnosed with metabolic syndrome. All the participants underwent screening at the beginning of the study to measure the total coronary plaque volume as well as dense calcium, non-calcified plaque and low-attenuation plaque. The screening was conducted using Cardiac Computed Tomography Angiography (CCTA), a noninvasive imaging technology that accurately measures calcium deposits and plaque buildup in the arteries.

Following evaluation, the participants were given either a placebo or a dose of 2,400 milligrams of Aged Garlic Extract every day. A follow-up screening conducted a year after the initial screening found those who had taken Aged Garlic Extract had slowed total plaque accumulation by 80%, reduced soft plaque and demonstrated regression (less plaque on follow-up) for low-attenuation plaque.


Public Release: 26-Jan-2016

Ancient medicinal clay shows promise against today’s worst bacterial infections

University of British Columbia


Naturally occurring clay from British Columbia, Canada — long used by the region’s Heiltsuk First Nation for its healing potential — exhibits potent antibacterial activity against multidrug-resistant pathogens, according to new research from the University of British Columbia.

The researchers recommend the rare mineral clay be studied as a clinical treatment for serious infections caused by ESKAPE strains of bacteria.

The so-called ESKAPE pathogens — Enterococcus faecium, <i<=””>, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species — cause the majority of U.S. hospital infections and effectively ‘escape’ the effects of antibacterial drugs.</i

“Infections caused by ESKAPE bacteria are essentially untreatable and contribute to increasing mortality in hospitals,” says UBC microbiologist Julian Davies, co-author of the paper published today in the American Society for Microbiology’s mBio journal.

“After 50 years of over-using and misusing antibiotics, ancient medicinals and other natural mineral-based agents may provide new weapons in the battle against multidrug-resistant pathogens.”

The clay deposit is situated on Heiltsuk First Nation’s traditional territory, 400 kilometres (250 miles) north of Vancouver, Canada, in a shallow five-acre granite basin. The 400-million kilogram (400,000 tonne) deposit was formed near the end of the last Ice Age, approximately 10,000 years ago.

Local First Nations people have used the clay for centuries for its therapeutic properties — anecdotal reports cite its effectiveness for ulcerative colitis, duodenal ulcer, arthritis, neuritis, phlebitis, skin irritation, and burns.

“We’re fortunate to be able to partner with UBC on this significant research program” says Lawrence Lund, president of Kisameet Glacial Clay, a business formed to market cosmetic and medicinal products derived from the clay. “We hope it will lead to the development of a novel and safe antimicrobial that can be added to the diminished arsenal for the fight against the ESKAPE pathogens and other infection-related health issues plaguing the planet.”

In the in vitro testing conducted by Davies and UBC researcher Shekooh Behroozian, clay suspended in water killed 16 strains of ESKAPE bacteria samples from sources including Vancouver General Hospital, St. Paul’s Hospital, and the University of British Columbia’s wastewater treatment pilot plant.


Public Release: 27-Jan-2016

Study shows zinc supplement boosted serum zinc levels and immunity in older adults

Tufts University, Health Sciences Campus


BOSTON (Jan. 27, 2016)–The immune system weakens as the body ages, making older adults more susceptible to infections. Low levels of zinc impair immunity, particularly in older adults. A research team set out to determine if it was feasible to increase serum zinc concentrations in older adults in nursing homes who were zinc-deficient. Their work appears today in The American Journal of Clinical Nutrition.

“Our previous work showed that 30 percent of nursing home residents have low serum zinc levels and those with low serum zinc levels had a significantly higher incidence of pneumonia and morbidity from it. Our new finding that serum zinc levels can be improved in older adults with zinc supplementation and that this is associated with enhancement of T-cell numbers and function strongly suggests that ensuring adequate zinc consumption by older adults could have a significant impact on reducing the incidence of and morbidity from infection, which is a major public health problem in older adults,” said the study’s lead author, Simin Nikbin Meydani, D.V.M., Ph.D., the director of the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, and senior scientist and director of its Nutritional Immunology Laboratory.

The small double-blind, placebo-controlled trial involved adults age 65 or older from three Boston-area nursing homes. The study participants had baseline serum levels of zinc that ranged from moderately to very zinc-deficient. Participants were given zinc supplements or a placebo for three months. A total of 25 people completed the study, with 13 receiving the placebo (a daily multi-vitamin with only 5 mg of zinc), and 12 receiving a daily multi-vitamin with 30 mg of zinc. A serum-level of 70 micrograms per deciliter was used as the cut-off standard for adequate serum zinc level and measuring improvement from supplementation. The function of the immune response was assessed by determining the immune cell profile and function.

In addition to serum zinc concentrations, the researchers found that zinc supplementation improved the function of T-cells as determined by their ability to proliferate in response to stimuli that mimicked infection. Furthermore, they saw a positive correlation between serum zinc levels and the number and function of T-cells. This effect of zinc was attributed to increasing the number of T-cells rather than enhancing the function of each T-cell. At the end of three months, researchers found that:

·         Zinc supplementation increased serum zinc concentrations in nursing home residents with low zinc levels.

·         Zinc supplementation increased both the number and effectiveness of T-cells in the treatment group at a much higher rate than the control group

·         The increase of serum zinc rose higher in the treatment group, at a rate of 16 percent, compared to those in the control group, which rose at a rate of 0.7 percent.

·         For those in the treatment group who were moderately zinc-sufficient at baseline, their serum zinc levels exceeded the cut-off standard.

·         Participants in the treatment group whose serum levels were measured as substantially zinc-deficient at baseline did not experience an increase to normal levels during the trial.

“Having a positive response to zinc supplementation may take some time in people who have been highly zinc deficient. We need to better understand how much supplementation is needed for certain people, and for how long a period, so that more refined recommendations can be made,” added first author Junaidah B. Barnett, M.C.H. (N), Ph.D., scientist in the Nutritional Immunology Laboratory at the HNRCA.

“It is worth noting that zinc deficiency is not just a problem in nursing home residents; it also exists in non-institutionalized older adults,” Meydani continued. “On average, zinc supplementation measurably improved serum zinc levels in these older adults, with most participants achieving serum zinc levels considered to be adequate.”

Zinc is found in a wide variety of foods, including oysters, pork, red meat, poultry, seafood, and fortified breakfast cereals. Zinc is also found in beans, nuts, whole grains, cucumber peel, and dairy products and is common in multi-vitamins. The Office of Dietary Supplements of the National Institutes of Health notes that zinc deficiency is rare in North America, but that some groups of people are more likely to have trouble getting enough zinc, including those with digestive disorders and vegetarians. Too much zinc (the upper limit for adults is 40 mg/day) can be harmful. Some researchers suspect, however, the older adults do not absorb or use zinc as efficiently as others. In addition, while serum zinc levels are a commonly used measure to evaluate zinc deficiency, they might not accurately reflect cellular zinc status. Some cells might exhibit low zinc levels, which impacts their function, even when serum zinc levels are normal.


Public Release: 27-Jan-2016

Asthma and allergies: A protective factor in farm milk

Ludwig-Maximilians-Universität München


Fresh, unprocessed cow’s milk has a higher content of omega-3 fatty acids than does pasteurized, homogenized or low-fat milk. This factor partly explains why children who consume the unprocessed product are less likely to develop asthma.

Children who regularly drink fresh farm milk are less likely to develop asthma than kids who consume the industrially processed product. A number of epidemiological studies have already pointed toward this effect, and it has now been verified by Ludwig-Maximilians-Universitaet (LMU) in Munich researchers in the Pasture birth cohort. Moreover, this latest study shows that the protective effect is partly attributable to the fact that fresh milk contains more omega-3 fatty acids than does processed milk. Nevertheless, the authors of the study refrain from recommending the consumption of untreated milk, since it may contain pathogenic micro-organisms. The new findings appear in the Journal of Allergy and Clinical Immunology.

The long-term research project PASTURE followed over a thousand children living in rural areas, whose mothers kept records of their child’s nutrition and it’s illnesses up until the age of 6. The analysis of these health diaries revealed that the proportion of children who had developed asthma by that age was significantly lower in the cohort who had regularly consumed untreated farm milk. “The effect can be partly explained by the higher overall fat content and the higher levels of omega-3 fatty acids found in farm milk,” says Tabea Brick, a member of the research group led by Erika von Mutius, Professor of Pediatric Allergology at LMU and Head of the Department of Asthma and Allergies at Dr. von Hauner Children’s Hospital in Munich. According to the study, this effect is specific and can be clearly distinguished from the possible impact of other modulatory factors.

Omega-3 fatty acids are essential for human health. However, they cannot be synthesized in the human body and must therefore be obtained from dietary sources. The compounds are thought to have a number of positive physiological effects. “For example, they are known to serve as precursors for the synthesis of anti-inflammatory substances,” Brick explains.

Less processing = more benefit?

In collaboration with a team at Marburg University, the LMU researchers assessed the composition of untreated farm milk, and shop milk that had undergone different degrees of industrial processing (pasteurization, homogenization, fat reduction). The results revealed that the level of omega-3 fatty acids remaining in the finished product was inversely proportional to the intensity of processing. In contrast, the content of omega-6 fatty acids, which mainly act as precursors for the production of pro-inflammatory modulators in the body, was virtually unchanged by any of the treatments used.

The standard industrial treatment process involves pasteurization of the raw milk at a temperature of between 72 and 75°C, and homogenization to avoid creaming of the milk. The authors of the new study argue for the development of milder methods of milk processing that will ensure the retention of beneficial components present in raw milk, while ensuring that potentially dangerous pathogens are effectively eliminated.

Public Release: 27-Jan-2016

Flavonoids from fruits and vegetables may help with weight maintenance



Eating fruit and vegetables that contain high levels of flavonoids, such as apples, pears, and berries, may be associated with less weight gain, suggests findings from a study published in The BMJ today.

Dietary flavonoids are natural compounds found in fruits and vegetables. These have been linked to weight loss, but most studies have looked at a particular flavonoid found in green tea, and have mostly been limited to small samples.

So a team of researchers examined the association between the dietary intake of seven flavonoid subclasses and weight change in a large study of 124,086 men and women based across the US over 24 years.

They tracked participants who were part of three prospective cohort studies: the Health Professionals Follow Up Study, Nurses’ Health Study, and Nurses’ Health Study II.

Participants self-reported their weight, lifestyle habits, and any recently diagnosed diseases via questionnaire every two years, between 1986 and 2011. In addition, they self reported their diet every four years.

Findings revealed that increased consumption of flavonoid subclasses was associated with less weight gain.

The greatest association was found for anthocyanins, flavonoid polymers, and flavonols: each greater standard deviation of daily intake was associated with 0.16 to 0.23 lbs (equivalent to 0.07- 0.10 kg) less weight gained over four year intervals.

Blueberries and strawberries were the main source of anthocyanins, and flavan-3-ols and their polymers were mainly derived from tea and apples. Orange juice and oranges were the main sources of flavanone and flavones, and tea and onions were the main sources of flavonols.

The study adjusted for a range of dietary and lifestyle factors that may have influenced the results, such as smoking status and physical activity. Results were consistent across men and women, and different ages.

This is the first study to examine the associations between consumption of seven flavonoid subclasses and weight gain in a large sample size.

It is an observational study so no definite conclusions can be made, and several limitations exist due to the design of the study. Nevertheless, the authors say that the findings “may help to refine previous dietary recommendations for the prevention of obesity and its potential consequences.”

In addition, they say that losing or preventing even small amounts of weight can reduce risk of diabetes, cancer, hypertension and cardiovascular disease. They add that the results can provide guidance on which fruits and vegetables to choose for preventing weight gain.

In the US, for example, most people consume less than one cup of fruits, and less than two cups of vegetables daily. The authors suggest that this should be increased to two cups of fruits, and two and a half cups of vegetables.

Furthermore, they add that people may be able to maximize the health benefits of eating fruit and vegetables by choosing those with high levels of flavonoids, such as apples, pears, and berries.

Public Release: 28-Jan-2016

University of Arizona researchers identify food additive that may prevent skin cancer

Unlike sunscreen, the nutritional compound protects skin from the inside out

University of Arizona, College of Pharmacy


TUCSON, Ariz. – Researchers at the University of Arizona College of Pharmacy have discovered that a compound found in the natural food additive annatto prevents the formation of cancer cells and skin damage from UV radiation in mice. In the future the compound, bixin, may be valuable in the prevention and treatment of human skin cancers.

Georg Wondrak, PhD, associate professor, and Donna Zhang, PhD, professor, both members of the University of Arizona Cancer Center, recently published a study in Free Radical Biology and Medicine titled, “System Administration of the Apocarotenoid Bixin Protects Skin against Solar UV-Induced Damage through Activation of Nrf2.”

Bixin is a bright reddish orange compound found in annatto, a natural condiment and food coloring derived from the seeds of the achiote fruit. Annatto, also known as achiote, has been a common ingredient in Latin American cooking since the pre-Columbian era.

Dr. Wondrak’s lab works to find small molecules, often in edible plants, that can prevent skin cancer. Dr. Zhang is a leading expert on the Nrf2 transcription factor, which strengthens cells against exposure to carcinogens. Dr. Wondrak’s investigations occasionally identify a compound that activates the Nrf2 pathway, and he calls on Dr. Zhang to collaborate in determining whether the compound has cancer-preventive properties.

In the recent study, mice injected with bixin and uninjected mice were exposed to UV radiation. The mice with the bixin injection experienced much less severe skin sun damage.

Dr. Wondrak says this discovery is unique because bixin is a nutritional factor, not a sunscreen applied to the skin. It prevents UV skin damage from the inside out by inducing cells to make protective antioxidants and repair factors. The compound does not kill skin cancer cells, but prevents their forming in the first place. Drs. Wondrak and Zhang find this research especially compelling because it involves a commonly consumed food substance.

The next steps for this line of research include finding out whether bixin prevents UV skin damage in humans as it does in mice. Because annatto is approved by the Food and Drug Administration asa safe food additive, its use in future clinical trials is expected to require fewer rounds of testing. With continued research into bixin’s effects, scientists soon may know if foods with annatto can help prevent sun damage, photo-aging and cancer in humans.


Public Release: 28-Jan-2016

Texas A&M research hints at a nutritional strategy for reducing autism risk

Texas A&M University


Folic acid has long been touted as an important supplement for women of childbearing age for its ability to prevent defects in the baby’s developing brain and spinal cord. In fact, folic acid is considered so important that it is added as a supplement to breads, pastas, rice and cereals to help ensure that women are exposed to sufficient amounts of this nutrient even before they know they’re pregnant.

Soon, another prenatal supplement could protect against a certain type of autism, according to research published today in the journal Cell Reports. The supplement is called carnitine, and it is already available in the market.

Carnitine, which the body can manufacture itself or extract from dietary sources, is required for transport of fatty acids into mitochondria — the compartment within the cell that converts these fats into energy. Previous studies have shown that inherited mutations in a gene (called TMLHE) that is required for carnitine biosynthesis are strongly associated with risk for development of autism-spectrum disorders, but the basis for that association has been unclear — until now. The latest findings show that genetic defects in the body’s ability to manufacture carnitine might be associated with an increased risk of autism because carnitine deficiency interferes with the normal processes by which neural stem cells promote and organize embryonic and fetal brain development.

The study’s lead author, Zhigang Xie, Ph.D., assistant research scientist at the Texas A&M Health Science Center College of Medicine, has refined a new technology that allows him to mark, follow and analyze individual neural stem cells in their native environment in a real developing brain. “It’s very difficult to study neural stem cells in their complex natural environment,” Xie said. “But now we have a technology that makes such studies possible.”

“Until now, this technology has not been used in this way,” added Vytas A. Bankaitis, Ph.D., the E.L. Wehner-Welch Foundation Chair in Chemistry at the Texas A&M College of Medicine and Xie’s collaborator. “Our application of this technology is powerful because it allows us to identify specific neural stem cell defects that are invisible in the cell culture systems typically used by brain scientists. With regard to autism spectrum disorders, one has to consider the entire cellular environment, or niche.”

Their work, which was funded by the National Institutes of Health and the Robert A. Welch Foundation, is important because some one percent of Americans are afflicted with autism, and the annual cost of autism management in the United States alone is estimated to be at least $236 billion.

The researchers found that neural stem cells unable to produce carnitine don’t behave properly and are inappropriately depleted from the developing brain, but when genetically at-risk neural stem cells are supplied with carnitine from an outside source, they don’t have the same problems.

Without getting too technical, the autism-associated TMLHE gene encodes an enzyme that the body needs to manufacture carnitine. Autism risk mutations inactivate this gene and, in the absence of their own ability to produce carnitine and without adequate outside supplementation, neural stem cells become less efficient at self-renewal. That is, when they divide, neural stem cells produce two “daughter” cells, one of which should remain a neural stem cell and the other that should differentiate. Neural stem cells confronted with carnitine deficiency too often divide to produce two differentiated cells, thereby failing to resupply the developing brain with a cache of neural stem cells.

“Inborn errors in carnitine production cause significant issues in a cell type one would believe has to contribute to autism risk,” Bankaitis said. As the autism risk gene is located on the X chromosome and males have only one X chromosome (females have two), they are at greater risk.

Some pregnant women might absorb enough carnitine from their diet so as to make normal enzyme function less important in the context of autism risk for their babies. High levels of carnitine can be found in red meat, and one of the best vegetarian sources is whole milk. Women who don’t ingest sufficient carnitine, however, might be placing their unborn child at risk.

Because the TMLHE is a recognized autism risk gene and its location on the chromosome is known, one possible first step for prevention is to test prospective mothers for TMLHE mutations before pregnancy. If a prospective mother is a carrier for the mutated autism risk gene, supplementation of her diet with carnitine before and during pregnancy could help ensure that a sufficient supply of the nutrient is available to the developing embryo and fetus, thus helping to offset the genetic defect.

“In retrospect, this preventative approach seems obvious,” Bankaitis said. “But, metabolic deficiencies are complicated scenarios to interpret, and we believe these complexities obscured what will hopefully prove to be a rather simple path towards prevention.”

It’s important to note that this particular prevention strategy will not apply to all cases of autism. “Even if this strategy works, it will not be a panacea for reducing all autism risk,” Bankaitis said. “While it could work in cases involving carnitine-deficiency, other pathways are also in play because as many as 1000 genes might ultimately be found to relate to autism risk. Still, the potential impact of even such a limited preventive strategy could be significant as mutant TMLHE alleles are surprisingly common in the human population.”

“Here we have indications, at least for some types of autism risk, that a dietary carnitine prevention method might be effective,” Xie said. “For some individuals, this simple nutritional supplement might really help reduce the risk of developing autism spectrum disorder. Any progress on the prevention front would be welcome given the number of people affected.”