260 CNO REPORT FOR TESTING

 

260CNO14DEC2018CNO

Report # 260

Release Date: 08 JAN 2019

Draft Report Compiled by

Ralph Turchiano

www.clinicalnews.org

 

 

In this issue:

  1. Essential oils from garlic and other herbs kill ‘persister’ Lyme disease bacteria
  2. Curry spice boosts exercise performance in mice with heart failure
  3. Study links vitamin D-deficient older adults with greater risk of developing depression
  4. New study shows that fish oil does not increase bleeding risk in surgery patients
  5. Vitamin C may reduce harm to infants’ lungs caused by smoking during pregnancy
  6. Hazelnuts improve older adults’ micronutrient levels
  7. Green leafy vegetables may prevent liver steatosis
  8. Using light to stop itch
  9. Study shows magnesium optimizes vitamin D status
  10. Probiotics could help millions of patients suffering from bipolar disorder
  11. Exercise may be as effective as prescribed drugs to lower high blood pressure
  12. How dietary fiber and gut bacteria protect the cardiovascular system
  13. Could this widely used food additive cause celiac disease?
  14. Metabolic syndrome patients need more vitamin C to break cycle of antioxidant depletion
  15. Essential nutrient may help fight Alzheimer’s across generations

 

Public Release: 3-Dec-2018

Essential oils from garlic and other herbs kill ‘persister’ Lyme disease bacteria

Laboratory study hints that plant compounds may be better than current antibiotics at treating persistent Lyme bacteria and associated symptoms

Johns Hopkins University Bloomberg School of Public Health

Oils from garlic and several other common herbs and medicinal plants show strong activity against the bacterium that causes Lyme disease, according to a study by researchers at Johns Hopkins Bloomberg School of Public Health. These oils may be especially useful in alleviating Lyme symptoms that persist despite standard antibiotic treatment, the study also suggests.

The study, published October 16 in the journal Antibiotics, included lab-dish tests of 35 essential oils–oils that are pressed from plants or their fruits and contain the plant’s main fragrance, or “essence.” The Bloomberg School researchers found that 10 of these, including oils from garlic cloves, myrrh trees, thyme leaves, cinnamon bark, allspice berries and cumin seeds, showed strong killing activity against dormant and slow-growing “persister” forms of the Lyme disease bacterium.

“We found that these essential oils were even better at killing the ‘persister’ forms of Lyme bacteria than standard Lyme antibiotics,” says study senior author Ying Zhang, MD, PhD, professor in the Department of Molecular Microbiology and Immunology at the Bloomberg School.

There are an estimated 300,000 new cases of Lyme disease each year in the United States. Standard treatment with doxycycline or an alternative antibiotic for a few weeks usually clears the infection and resolves symptoms. However, about 10 to 20 percent of patients report persistent symptoms including fatigue and joint pain–often termed “persistent Lyme infection” or “post-treatment Lyme disease syndrome” (PTLDS) that in some cases can last for months or years.

The cause of this lingering syndrome isn’t known. But it is known that cultures of Lyme disease bacteria, Borrelia burgdorferi, can enter a so-called stationary phase in which many of the cells divide slowly or not at all. The slow-dividing or dormant cells are “persister” cells, which can form naturally under nutrient starvation or stress conditions, and are more resistant to antibiotics. Some researchers have sought other drugs or medicinal compounds that can kill persister Lyme bacteria in the hope that these compounds can be used to treat people with persistent Lyme symptoms.

Zhang and his laboratory have been at the forefront of these efforts. In 2014, his lab screened FDA-approved drugs for activity against persister Lyme bacteria and found many candidates including daptomycin (used to treat MRSA) that had better activity than the current Lyme antibiotics. In 2015, they reported that a three-antibiotic combination–doxycycline, cefoperazone and daptomycin–reliably killed Lyme persister bacteria in lab dish tests. In a 2017 study they found that essential oils from oregano, cinnamon bark, clove buds, citronella and wintergreen killed stationary phase Lyme bacteria even more potently than daptomycin, the champion among tested pharmaceuticals.

In the new study Zhang and his team extended their lab-dish testing to include 35 other essential oils, and found 10 that show significant killing activity against stationary phase Lyme bacteria cultures at concentrations of just one part per thousand. At this concentration, five of these oils, derived respectively from garlic bulbs, allspice berries, myrrh trees, spiked ginger lily blossoms and may change fruit successfully killed all stationary phase Lyme bacteria in their culture dishes in seven days, so no bacteria grew back in 21 days.

Oils from thyme leaves, cumin seeds and amyris wood also performed well, as did cinnamaldehyde, the fragrant main ingredient of cinnamon bark oil.

Lab-dish tests such as these represent an early stage of research, but Zhang and colleagues hope in the near future to continue their investigations of essential oils with tests in live animals, including tests in mouse models of persistent Lyme infection. If those tests go well and the effective doses seem safe, Zhang expects to organize initial tests in humans.

“At this stage these essential oils look very promising as candidate treatments for persistent Lyme infection, but ultimately we need properly designed clinical trials,” he says.

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“Identification of Essential Oils with Strong Activity against Stationary Phase Borrelia burgdorferi” was written by Jie Feng, Wanliang Shi, Judith Miklossy, Genevieve M. Tauxe, Conor J. McMeniman, and Ying Zhang.

Support for the research came from the Global Lyme Alliance, LivLyme Foundation, NatCapLyme, and the Einstein-Sim Family Charitable Fund.

Media contacts for the Johns Hopkins Bloomberg School of Public Health: Barbara Benham at 410-614-6029 or bbenham1@jhu.edu and Robin Scullin at 410-955-7619 or rsculli1@jhu.edu.

Public Release: 29-Nov-2018

Curry spice boosts exercise performance in mice with heart failure

Curcumin treatment improved muscle function, exercise capacity in mice with heart failure and healthy controls

American Physiological Society

Rockville, Md. (November 29, 2018)–New research suggests that curcumin, a main ingredient in curry, may improve exercise intolerance related to heart failure. The study is published ahead of print in the Journal of Applied Physiology.

Curcumin, a chemical that comes from the turmeric plant, has been used as a traditional Asian medicine for centuries, primarily to treat gastrointestinal ailments and skin wounds. Studies increasingly suggest that the compound may prevent or limit muscle wasting associated with a number of health conditions, including heart failure.

Heart failure affects more than 6 million people living in the U.S. People with heart failure have a reduced function of the left ventricle–the chamber of the heart that pumps blood out to the rest of the body–called reduced ejection fraction. A decreased ability to exercise (exercise intolerance) is another significant characteristic of heart failure. Previous research has found that higher than normal levels of oxidative stress–an imbalance of two different kinds of molecules that can result in cell damage–contribute to exercise intolerance in people with heart failure. Heart failure is also associated with lower than normal expression of antioxidant enzymes in the muscles, but the reason for this is unclear. Antioxidant enzymes both prevent and repair damage from oxidative stress. Boosting enzyme levels may improve exercise performance in people in heart failure.

Researchers from the University of Nebraska Medical Center theorized that a reduction in the normal signaling of Nrf2, a protein that regulates the expression of antioxidant enzymes, may play a role in the impaired expression of antioxidant enzymes. They examined the effects of curcumin, which is known to promote activation of Nrf2, on a mouse model of heart failure with reduced ejection fraction. One group of mice with heart failure received daily doses of curcumin for 12 weeks, and another group did not receive treatment. The heart failure groups were compared to a control group of healthy mice that received curcumin and an untreated control group.

The research team measured the exercise capacity of all the mice before and after curcumin treatment. The researchers also examined muscle fiber samples to assess enzyme expression levels. They found that expression of Nrf2 increased and levels of antioxidant enzymes improved in the animals with heart failure that were given curcumin. In addition, both groups that received curcumin–even the animals without heart failure–had improved exercise capacity when compared with the untreated groups, suggesting the effects of curcumin on skeletal muscle is not exclusive to heart failure.

“These data suggest that activation of Nrf2 in skeletal muscle may represent a novel therapeutic strategy to improve … quality of life” in people with heart failure with reduced ejection fraction, the researchers wrote.

Public Release: 5-Dec-2018

Study links vitamin D-deficient older adults with greater risk of developing depression

Trinity College Dublin

A new study by researchers from The Irish Longitudinal Study on Ageing (TILDA) at Trinity College Dublin has shown for the first time in Ireland that a deficiency in vitamin D was associated with a substantial increased risk of depression (+75%) over a four-year follow up period. The findings form part of the largest representative study of its kind and have just been published in the prestigious journal, The Journal of Post-Acute and Long-Term Care Medicine (JAMDA).

Later life depression can significantly reduce quality of life and is a potent risk factor for functional decline, admission to residential care and early death. Given the complex nature of depression, including the fact that the majority of older adults are undiagnosed, prevention is a priority and the identification of important risk factors is crucial.

Vitamin D or the ‘sunshine vitamin’ is essential for bone health and deficiency, and has recently been linked with other non-bone health outcomes such as inflammation and diabetes. Small studies have found links between vitamin D and depression but few have followed up with the same affected people over time, while others have not taken into account other factors that can also affect depression. These findings are important as the TILDA team has previously reported that 1 in 8 older Irish adults are deficient in vitamin D.

The current study investigated the links between vitamin D and depression in older Irish adults and then re-examined the participants four years later to see if vitamin D status affected the risk of developing depression.

The authors found that:

  • Vitamin D deficiency was associated with a 75% increase in the risk of developing depression by 4 years
  • This finding remained robust after controlling for a wide range of relevant factors including depressive symptoms, chronic disease burden, physical activity and cardiovascular disease
  • Furthermore, excluding participants taking anti-depressant medication and vitamin D supplementation from the analyses did not alter the findings

The authors suggest that the findings could be due to the potential direct effect of vitamin D on the brain. Given the structural and functional brain changes seen in late life depression, vitamin D may have a protective effect in attenuating these changes. Similarly, other studies have shown that vitamin D status has also been linked with neurodegenerative conditions such as dementia, Parkinson’s disease and Multiple Sclerosis.

These finding are important as vitamin D status is relatively easy and inexpensive to modify through supplementation or fortification. However, In Ireland, fortification of food products with vitamin D is voluntary and few manufacturers do this. This is compounded by the lack of any vitamin D guidelines from Government.

Commenting on the significance of the research, first author of the study and Specialist Registrar in Geriatric Medicine, St James’ Hospital Dublin, Dr Robert Briggs, said: “This is the largest representative and most comprehensive study of depression risk and vitamin D status in older adults ever conducted in Ireland. Our findings will provide useful information to help inform public health policy – particularly regarding the proposition of the usefulness of vitamin D treatment/supplementation for depression.”

Senior author of the study, and Research Fellow with TILDA, Dr Eamon Laird, added: “This study shows that vitamin D is associated with a health condition other than bone health. What is surprising is the large effect on depression even after accounting for other control variables. This is highly relevant for Ireland as our previous research has shown that one in eight older adults are deficient in the summer and one in four during the winter. Moreover, only around 8% of older Irish adults report taking a vitamin D supplement.”

“Given that vitamin D is safe in the recommended intakes and is relatively cheap, this study adds to the growing evidence on the benefits of vitamin D for health. It also helps to continue to impress the need on our public health bodies to develop Irish vitamin D recommendations for the general public. Up to this point, these are severely lacking.”

Principal Investigator of TILDA, Professor Rose Anne Kenny, said: “The new finding that the development of depression could potentially be attenuated by having a higher vitamin D status could have significant policy and practice implications for Government and health services. TILDA has consistently assisted policy makers by providing strong evidence-based data on which to make recommendations but also by assisting with information of most vulnerable people and therefore those who should be targeted.”

“It is our responsibility to now ascertain whether supplementation will influence depression. There are many reasons for vitamin D supplementation in Ireland. Benefits to something as disabling and often ‘silent’ as depression are therefore important for wellbeing as we age.”

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Public Release: 4-Dec-2018

New study shows that fish oil does not increase bleeding risk in surgery patients

Higher omega-3 blood levels were associated with lower risk of bleeding

Wright On Marketing & Communications

A new study published in Circulation showed that fish oil — which contains the omega-3s EPA and DHA — did not increase perioperative bleeding in surgery patients. In fact, higher blood omega-3 levels were associated with lower risk of bleeding.

To explore the question of whether high-dose EPA+DHA supplementation affects the risk for bleeding in surgery patients, researchers conducted a secondary analysis of the Omega-3 fatty acids for the PrEvention of post-opeRative Atrial fibrillation (OPERA) study.

For this study, 1516 patients scheduled for cardiac surgery were randomized to omega-3s or placebo. The dose was 6.5-8 grams of EPA+DHA over 2 to 5 days before surgery, and then 1.7 grams per day beginning on the morning of surgery and continuing until discharge.

The primary outcome of the study was risk for major peri-operative bleeding as defined by the Bleeding Academic Research Consortium (BARC). The number of units of blood needed for transfusion was one of the secondary outcomes.

There was no effect of omega-3 treatment on the primary outcome (post-op atrial fibrillation), but surprisingly there was a significant reduction in the number of units of blood needed for transfusions. In another analysis, the higher the blood EPA+DHA level on the morning of surgery, the lower the risk for bleeding according to the BARC criteria.

“The researchers in this study concluded that these findings support the need to reconsider current recommendations to stop fish oil or delay procedures for people on fish oil before cardiac surgery,” said Dr. Bill Harris, PhD, founder of OmegaQuant, co-inventor of the Omega-3 Index, and one of the authors on this paper. “In other words, bleeding in surgery (and in normal life) is not a safety concern for omega-3 supplements.”

Omega-3s, specifically EPA and DHA, are important for heart, brain, eye and joint health. Unfortunately, most people don’t get enough of these valuable fatty acids, which can increase their risk of several of the most serious health issues.

The Omega-3 index is expressed as a percent of total red blood cell (RBC) fatty acids and is a long-term, stable marker of omega-3 status that accurately reflects tissue levels of EPA and DHA. An Omega-3 Index between 8% and 12% is considered the optimal range. Why? Because at these levels your risk of fatal cardiovascular disease decreases dramatically.

About Dr. Bill Harris, PhD: Dr. Harris is an internationally recognized expert on omega-3 fatty acids and how they can benefit patients with heart disease. He obtained his PhD in Human Nutrition from the University of Minnesota, and did post-doctoral fellowships in Clinical Nutrition and Lipid Metabolism with Dr. Bill Connor at the Oregon Health Sciences Universit

PUBLIC RELEASE: 7-DEC-2018

Vitamin C may reduce harm to infants’ lungs caused by smoking during pregnancy

Helping mothers quit smoking should still be primary goal

AMERICAN THORACIC SOCIETY

Dec. 7, 2018–Vitamin C may reduce the harm done to lungs in infants born to mothers who smoke during their pregnancy, according to a randomized, controlled trial published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

In “Oral Vitamin C (500 mg/day) to Pregnant Smokers Improves Infant Airway Function at 3 Months: A Randomized Trial,” Cindy T. McEvoy, MD, MCR, and her co-authors report that at three months of age, the infants whose mothers took 500 mg of vitamin C in addition to their prenatal vitamin had significantly better forced expiratory flows (FEFs). FEFs measure how fast air can be exhaled from the lung and are an important measure of lung function because they can detect airway obstruction.

The researchers also discovered an association between the infant FEFs and a genetic variant some of the mothers possessed that appeared to amplify the negative impact of nicotine on the babies before they were born. Other studies have linked this genetic factor, specifically for the α5 nicotinic acetylcholine receptor, to increased risk of lung cancer and obstructive lung disease.

“Smoking during pregnancy reflects the highly addictive nature of nicotine that disproportionately affects the most vulnerable populations,” said Dr. McEvoy, lead study author and professor of pediatrics at Oregon Health & Science University. “Finding a way to help infants exposed to smoking and nicotine in utero recognizes the unique dangers posed by a highly advertised, addictive product and the lifetime effects on offspring who did not choose to be exposed.”

In a previous study, the authors had shown that 72 hours after birth, babies of mothers who smoked had better lung function if their mothers were randomized to vitamin C (500 mg/day) during their pregnancies compared to those born to mothers who smoked and were randomized to placebo.

That study used passive methods to measure lung function, and the authors note that FEFs provide a more direct assessment of airway function and are similar to methods used to diagnose lung disease in adults and older children.

In the current study, 251 pregnant women who smoked were randomly assigned at 13 to 23 weeks of gestation to either receive vitamin C (125 women) or a placebo (126 women). Smoking was defined as having had one or more cigarettes in the last week. All participants received smoking cessation counseling throughout the study, and about 10 percent of the women quit smoking during the study.

The researchers wrote that study results support the hypothesis that oxidative stress caused by cigarette smoking reduces the amount of ascorbic acid, a component of vitamin C, available to the body. At the time they enrolled in the study, the women had lower levels of ascorbic acid than have been reported among women who do not smoke.

Those levels rose in study participants who received vitamin C to become comparable to women who do not smoke.

Infants in this study will continue to be followed to track their lung function and respiratory outcomes. The authors believe that future trials of vitamin C supplementation in pregnant smokers should determine whether the benefits are greater if the supplementation starts earlier and continues postnatally in the babies themselves.

Summing up the findings of the current study, Dr. McEvoy said that a relatively low dosage of vitamin C may present “a safe and inexpensive intervention that has the potential to help lung health of millions of infants worldwide.”

However, she added, helping mothers quit smoking should remain the primary goal for health professionals and public health officials. “Although vitamin C supplementation may protect to some extent the lungs of babies born to mothers who smoke during pregnancy, those children will still be at greater risk for obesity, behavioral disorders and other serious health issues,” she said.

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“For mothers who smoke during pregnancy, vitamin C may reduce harm #smoking causes to their babies’ #lungs, finds new study of #vitaminC supplementation. #Nosmokingduringpregnancy.”

PUBLIC RELEASE: 6-DEC-2018

Hazelnuts improve older adults’ micronutrient levels

OREGON STATE UNIVERSITY

CORVALLIS, Ore. – Older adults who added hazelnuts to their diet for a few months significantly improved their levels of two key micronutrients, new research at Oregon State University indicates.

In the study, 32 people age 55 and older ate about 57 grams of hazelnuts – 2 ounces or about one-third cup – daily for 16 weeks.

Results showed increased blood concentrations of magnesium and elevated urinary levels of a breakdown product of alpha tocopherol, commonly known as vitamin E.

The findings, published in the Journal of Nutrition, are important because many Americans do not eat adequate amounts of either micronutrient. Older adults are at particular risk – lower concentrations of the micronutrients are associated with increased risk of age-related health problems including Alzheimer’s disease.

“This is one of the first times a study of this type has focused only on older adults,” said co-author Alex Michels, a researcher at OSU’s Linus Pauling Institute. “We wanted to fill in a piece of the puzzle – can hazelnuts improve the nutritional status of older adults specifically?”

Michels also noted few hazelnut studies have involved Oregon hazelnuts, which account for 99 percent of U.S. production of a nut also known as the filbert.

“Not that we think Oregon hazelnuts are much different than other sources,” he said, “but now the booming crop that we have in this state finally has science behind it. Perhaps other benefits of Oregon hazelnuts are awaiting future study.”

Maret Traber, the study’s corresponding author, notes that she and her collaborators used a novel biomarker – an alpha tocopherol metabolite – to determine hazelnuts had improved the research subjects’ vitamin E levels.

“It’s hard to determine changes in α-tocopherol levels in the blood of older adults because they tend toward elevated cholesterol levels which leads to more α-tocopherol being retained in the blood,” said Traber, a professor in the OSU College of Public Health and Human Sciences and the Ava Helen Pauling Professor at the Linus Pauling Institute. “So what we did instead was look at the urine to see how much of a vitamin E catabolite was in it. The catabolite should only increase if the body is getting enough vitamin E.”

The catabolite is alpha carboxyethyl hydroxychromanol, abbreviated to α-CEHC.

“It’s basically a vitamin E molecule where the tail has been chewed up into nothing, part of the natural breakdown process of vitamin E as the body uses it,” Michels said. “We saw urinary α-CEHC levels go up in almost every participant.”

In addition, blood analysis showed decreases in glucose and low-density lipoproteins, also known as “bad” cholesterol, in addition to increases in magnesium.

“All of which says that hazelnuts are good for you,” Traber said. “The findings demonstrate the power of adding hazelnuts to your diet, of just changing one thing. Vitamin E and magnesium are two of the most underconsumed micronutrients in the U.S. population, and there’s much more to hazelnuts than what we analyzed here. They’re also a great source of healthy fats, copper and B6. People don’t like taking multivitamins, but hazelnuts represent a multivitamin in a natural form.”

PUBLIC RELEASE: 17-DEC-2018

Green leafy vegetables may prevent liver steatosis

KAROLINSKA INSTITUTET

A larger portion of green leafy vegetables in the diet may reduce the risk of developing liver steatosis, or fatty liver. In a study published in PNAS researchers from Karolinska Institutet in Sweden show how a larger intake of inorganic nitrate, which occurs naturally in many types of vegetable, reduces accumulation of fat in the liver. There is currently no approved treatment for the disease, which can deteriorate into life-threatening conditions such as cirrhosis and liver cancer.

Liver steatosis, or fatty liver, is a common liver disease that affects approximately 25 per cent of the population. The most important causes are overweight or high alcohol consumption and there is currently no medical treatment for the disease. Researchers at Karolinska Institutet have now shown how a greater intake of inorganic nitrate can prevent the accumulation of fat in the liver.

“When we supplemented with dietary nitrate to mice fed with a high-fat and sugar Western diet, we noticed a significantly lower proportion of fat in the liver,” says Mattias Carlström, Associate Professor at the Department of Physiology and Pharmacology, Karolinska Institutet.

Their results were confirmed by using two different cell culture studies in human liver cells. Apart from a lower risk of steatosis, the researchers also observed reduction of blood pressure and improved insulin/glucose homeostasis in mice with type 2 diabetes.

The research group’s focus is the prevention of cardiovascular diseases and type 2 diabetes through dietary changes and by other means. Previous studies have shown that dietary nitrate from vegetables enhances the efficiency of the mitochondria, the cell’s power-plant, which can improve physical endurance. It has also been shown that a higher intake of fruit and vegetables has a beneficial effect on cardiovascular function and on diabetes.

“We think that these diseases are connected by similar mechanisms, where oxidative stress causes compromised nitric oxide signalling, which has a detrimental impact on cardiometabolic functions,” says Dr Carlström. “We now demonstrate an alternative way to produce nitric oxide, where more nitrate in our diet can be converted to nitric oxide and other bioactive nitrogen species in our body.”

Even though many clinical studies have been done, there is still considerable debate about what properties of vegetable make them healthy.

“No one has yet focused on nitrate, which we think is the key,” continues Dr Carlström. “We now want to conduct clinical studies to investigate the therapeutic value of nitrate supplementation to reduce the risk of liver steatosis. The results could lead to the development of new pharmacological and nutritional approaches.”

While larger clinical studies are needed to confirm the role of nitrate, the researchers can still advise on eating more green leafy vegetables, such as regular lettuce or the more nitrate-rich spinach and rocket.

“And it doesn’t take huge amounts to obtain the protective effects we have observed – only about 200 grams per day,” says Dr Carlström.” Unfortunately, however, many people choose not to eat enough vegetables these days.”

PUBLIC RELEASE: 17-DEC-2018

Using light to stop itch

EMBL Rome researchers find way to stop itch in mice with light

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it’s a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional inflammation and even more itch. EMBL researchers have now found a way to stop itch with light in mice. Nature Biomedical Engineering publishes their results on 17 December 2018.

The specialized nerve cells that sense itch are located in the upper surface of the skin. Linda Nocchi, Paul Heppenstall and colleagues at EMBL Rome developed a light-sensitive chemical that binds only to those cells. By first injecting a mouse’s affected skin area with the chemical and then illuminating it with near-infrared light, the itch-sensing cells withdraw from the skin. This stops the itch and allows the skin to heal.

The effect of the treatment can last several months. Other types of nerve cells in your skin – which make you feel specific sensations like pain, vibration, cold or heat – are not affected by the light treatment: the skin only stops itching.

The method works well in mice with eczema (AD: atopic dermatitis), and a rare genetic skin disease called amyloidosis (FPLCA: familial primary localized cutaneous amyloidosis), for which there’s currently no cure. “For me, the most exciting part of this project was seeing the improvements in the animals’ health”, says Linda Nocchi, first author of the paper and postdoctoral researcher in the Heppenstall group. “Their skin looked much better after treatment and they scratched less.”

“We hope that one day, our method will be able to help humans suffering from a disease like eczema, which causes chronic itching”, says Paul Heppenstall, who led the study. It is already known that mice and humans have the same target molecule for itch therapy: a small protein called Interleukin 31 (IL-31). One of the team’s next steps will be to test the light therapy in human tissues.

Previously, the Heppenstall group published a method to manage chronic pain with light. “We think that the mechanism we’ve discovered might be a general method for controlling sensation through the skin”, says Heppenstall. “Our goal now is to take these therapies further. We want to collaborate with industry partners to develop therapies for humans, but also for veterinary medicine, as itch is a major problem in dogs as well.”

PUBLIC RELEASE: 14-DEC-2018

Study shows magnesium optimizes vitamin D status

VANDERBILT UNIVERSITY MEDICAL CENTER

A randomized trial by Vanderbilt-Ingram Cancer Center researchers indicates that magnesium optimizes vitamin D status, raising it in people with deficient levels and lowering it in people with high levels.

The study reported in the December issue of The American Journal of Clinical Nutrition is important because of controversial findings from ongoing research into the association of vitamin D levels with colorectal cancer and other diseases, including a recent report from the VITAL trial. It gave confirmation to a prior observational study in 2013 by the researchers that linked low magnesium levels with low vitamin D levels.

The trial also revealed something new — that magnesium had a regulating effect in people with high vitamin D levels. The research provides the first evidence that magnesium may play an important role in optimizing vitamin D levels and preventing conditions related to vitamin D levels.

Qi Dai, MD, PhD, Ingram Professor of Cancer Research, the study’s lead author, described the ideal level as being in the middle range of a U-shape because vitamin D at this level has been linked to the lowest risk of cardiovascular disease in previous observational studies.

However, vitamin D was not related to cardiovascular disease in the recent VITAL trial. He and Martha Shrubsole, PhD, research professor of Medicine, Division of Epidemiology, are investigating the role that magnesium may play with cancer as part of the Personalized Prevention of Colorectal Cancer Trial.

“There’s a lot of information being debated about the relationship between vitamin D and colorectal cancer risk that is based upon observational studies versus clinical trials,” Shrubsole said. “The information is mixed thus far.”

They became interested in a role for magnesium because people synthesize vitamin D differently with levels of the vitamin in some individuals not rising even after being given high dosage supplements.

“Magnesium deficiency shuts down the vitamin D synthesis and metabolism pathway,” Dai said.

The randomized study involved 250 people considered at risk for developing colorectal cancer because of either risk factors or having a precancerous polyp removed. Doses of magnesium and placebo were customized based on baseline dietary intake.

“Vitamin D insufficiency is something that has been recognized as a potential health problem on a fairly large scale in the U.S.,” Shrubsole said. “A lot of people have received recommendations from their health care providers to take vitamin D supplements to increase their levels based upon their blood tests. In addition to vitamin D, however, magnesium deficiency is an under-recognized issue. Up to 80 percent of people do not consume enough magnesium in a day to meet the recommended dietary allowance (RDA) based on those national estimates.”

Shrubsole stressed that the magnesium levels in the trial were in line with RDA guidelines, and she recommended dietary changes as the best method for increasing intake. Foods with high levels of magnesium include dark leafy greens, beans, whole grains, dark chocolate, fatty fish such as salmon, nuts and avocados.

PUBLIC RELEASE: 13-DEC-2018

Probiotics could help millions of patients suffering from bipolar disorder

Gut-brain

AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY

About 3 million people in the US are diagnosed every year with bipolar disorder, a psychiatric condition characterized by dramatic shifts in mood from depression to mania. Currently, the standard treatment includes a combination of psychotherapy and prescription medications such as mood stabilizers and antipsychotics.

However, an emerging field of research is exploring the use of probiotics–often thought of as “good bacteria”–as a potential new avenue for treatment of bipolar and other psychiatric mood disorders. And a new study from Baltimore’s Sheppard Pratt Health System, conducted by a research team led by Faith Dickerson, finds that a probiotic supplement may reduce inflammation of the gut, which is known to exacerbate bipolar disorder. Probiotic organisms are non-pathogenic bacteria that, when present in the gut flora, are known to improve the overall health of the host.

In recent years, research has demonstrated a strong link between the gastrointestinal tract and the central nervous system. This connection, named the “gut-brain axis” (GBA), allows for crosstalk between the endocrine, immune, and autonomic nervous systems. The GI tract is also home to the intestinal microbiome, a complex population of roughly 100 trillion microorganisms (more than ten times the number of cells that make up the human body) that interacts with the mucosal lining of the GI tract. Studies have shown that the intimate association between the gut microbiome and GI tissue has a significant effect on the GBA.

There is also mounting evidence linking imbalances in the microbial species that make up the gut microbiome to a number of health problems including allergies, autoimmune disorders, and psychiatric mood disorders.

In the case of bipolar disorder and the GBA, previous studies have shown that inflammation, or overstimulation of the body’s immune system, is a contributing factor in the disease. With this in mind, researchers developed a probiotic supplement aimed at reducing inflammation caused by microbial imbalances in the gut.

A group of patients recently hospitalized for mania participated in a 6-month study to track the effects of probiotic treatment on both their mood and the status of their immune system.

The patients were randomly selected to receive either the probiotic supplement or a placebo in addition to their usual medications. The results showed that the group receiving the probiotic supplement, on average, didn’t return to the hospital as quickly and required less in-patient treatment time compared to the placebo group. The beneficial effects were most pronounced in those patients who exhibited abnormally high levels of inflammation at the beginning of the study.

Overall, these results indicate that changes in intestinal inflammation can alter the trajectory of psychiatric mood disorders and that modulating the intestinal microbiota may be a new avenue of treatment for patients suffering from these diseases.

PUBLIC RELEASE: 18-DEC-2018

Exercise may be as effective as prescribed drugs to lower high blood pressure

But no direct head to head comparative trials and relatively small numbers for some studies

BMJ

Exercise may be as effective as prescribed drugs to lower high (140 mm Hg) blood pressure, suggests a pooled analysis of the available data, in what is thought to be the first study of its kind, and published online in the British Journal of Sports Medicine.

But there are no direct head to head comparative trials of exercise and blood pressure lowering drugs, and the numbers of participants in some of the included studies were relatively small, caution the researchers.

While promising, the findings shouldn’t persuade patients to ditch their blood pressure lowering drugs in favour of an exercise regimen just yet, although patients might want to boost their physical activity levels, advises the lead study author in a linked podcast.

Exercise can lower systolic blood pressure–the amount of pressure in the arteries when the heart is beating and expressed as the top number in any blood pressure reading. But what isn’t clear is how exercise compares with blood pressure lowering drugs, of which there are several types, as no direct head to head clinical trials have been carried out.

To get round this, the researchers pooled the data from 194 clinical trials looking at the impact of drugs on lowering systolic blood pressure and 197 trials looking at the impact of structured exercise, and involving a total of 39,742 people.

Structured exercise was categorised as: endurance, to include walking, jogging, running, cycling and swimming, and high intensity interval training; dynamic resistance, to include strength training–for example, with dumbbells or kettle bells; isometric resistance, such as the static push-up (plank); and a combination of endurance and resistance.

Three sets of analyses were done: all types of exercise compared with all classes of blood pressure lowering drugs; different types of exercise compared with different types of drug; and different intensities of exercise compared with different drug doses.

And finally, these analyses were repeated, but in a group of exercise trials that included only participants with high blood pressure, as most of these trials were of young healthy participants with normal blood pressure.

The results showed that blood pressure was lower in people treated with drugs than in those following structured exercise programmes.

But when the analyses were restricted to those with high blood pressure, exercise seemed to be just as effective as most drugs. What’s more, the effectiveness of exercise increased the higher the threshold used to define high blood pressure–that is, anything above 140 mm Hg.

The researchers also found “compelling evidence that combining endurance and dynamic resistance training was effective in reducing [systolic blood pressure].”

But structured exercise trials were fewer and smaller than those for drugs, they caution.

The researchers point out that prescriptions for drugs to lower blood pressure have risen sharply in recent years. In England alone the number of adults prescribed them increased by 50 per cent between 2006 and 2016.

This trend is likely to continue, say the researchers, given that major clinical practice guidelines have recently lowered the threshold for high systolic blood pressure to 130 mm Hg.

But substituting exercise for drugs may be challenging as people with high blood pressure often have several long term conditions, and an estimated 40 per cent of adults in the US and many European countries are physically inactive, they say.

“We don’t think, on the basis of our study, that patients should stop taking their antihypertensive medications,” says lead author Dr Huseyin Naci, Department of Health Policy, London School of Economics and Political Science, in a linked podcast.

“But we hope that our findings will inform evidence based discussions between clinicians and their patients,” he adds.

As to whether doctors should be handing out prescriptions for exercise to patients with high blood pressure, there are some issues to consider, he suggests.

“It’s one thing to recommend that physicians start prescribing exercise to their patients, but we also need to be cognisant of the resource implications and ensure that the patients that have been referred to exercise interventions can adhere to them and so really derive benefit,” he emphasises.

PUBLIC RELEASE: 21-DEC-2018

How dietary fiber and gut bacteria protect the cardiovascular system

MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE IN THE HELMHOLTZ ASSOCIATION

The fatty acid propionate helps defend against the effects of high blood pressure, including atherosclerosis and heart tissue remodeling, a study on mice has found. Gut bacteria produce the substance – which calms the immune cells that drive up blood pressure – from natural dietary fiber.

“You are what you eat,” as the proverb goes. But to a large extent our well-being also depends on what bacterial guests in our digestive tract consume. That’s because gut flora help the human body to utilize food and produce essential micronutrients, including vitamins.

Beneficial gut microbes can produce metabolites from dietary fiber, including a fatty acid called propionate. This substance protects against the harmful consequences of high blood pressure. A Berlin research team from the Experimental and Clinical Research Center (ECRC), a joint institution of the Max Delbrück Center for Molecular Medicine (MDC) and Charité – Universitätsmedizin Berlin, shows why this is the case. Their study has been published in advance online in the journal Circulation.

The researchers fed propionate to mice with elevated blood pressure. Afterwards, the animals had less pronounced damage to the heart or abnormal enlargement of the organ, making them less susceptible to cardiac arrhythmia. Vascular damage, such as atherosclerosis, also decreased in mice. “Propionate works against a range of impairments in cardiovascular function caused by high blood pressure,” says MDC researcher and research group leader Professor Dominik N. Müller. “This may be a promising treatment option, particularly for patients who have too little of this fatty acid.”

Detour via the immune system

“Our study made it clear that the substance takes a detour via the immune system and thus affects the heart and blood vessels,” say Dr. Nicola Wilck and Hendrik Bartolomaeus from the ECRC, who have been working together on the project for nearly five years. In particular, T helper cells, which enhance inflammatory processes and contribute to high blood pressure, were calmed.

This has a direct effect on the functional ability of the heart, for example. The research team triggered heart arrhythmia in 70 percent of the untreated mice through targeted electrical stimuli. However, only one-fifth of the animals treated with the fatty acid were susceptible to an irregular heartbeat. Further investigations with ultrasound, tissue sections, and single-cell analyses showed that propionate also reduced blood pressure-related damage to the animals’ cardiovascular system, significantly increasing their survival rate.

But when researchers deactivated a certain T cell subtype in the mice’s bodies, known as regulatory T cells, the positive effects of propionate disappeared. The immune cells are therefore indispensable for the substance’s beneficial effect. A research group under Johannes Stegbauer, an adjunct professor at Düsseldorf University Hospital, confirmed the team’s findings in a second animal model.

Short-chain fatty acid as a therapeutic option

The results explain why a diet rich in fiber, which has been recommended by nutrition organizations for many years, helps prevent cardiovascular diseases. Whole-grain products and fruits, for example, contain cellulose and inulin fibers, from which gut bacteria produce the beneficial molecules like propionate, a short-chain fatty acid with a backbone of just three carbon atoms.

“Previously, it had not been clear which fatty acid is behind the positive effects and how it works,” says Wilck. The study opens up new avenues in the treatment of cardiovascular diseases. “It might make sense to administer propionate or a chemical precursor directly as a drug” – for example, when the blood of those affected contains too little of the substance.

Propionate still has to prove itself in everyday clinical practice. The research team now hopes to validate their findings by examining the substance’s effects on human subjects. It is already known that propionate is safe for human consumption and can also be produced economically: The substance has been used for centuries as a preservative, for example. It is already approved as a food additive. “With these favorable conditions, hopefully propionate will soon make the leap from the lab to patients who need it,” says Wilck.

PUBLIC RELEASE: 3-JAN-2019

Could this widely used food additive cause celiac disease?

Research suggests that celiac disease could be caused by a bacterial enzyme used to manufacture sausages, cheese, bread and other processed foods.

FRONTIERS

Myths about gluten are hard to bust. Intolerance, allergy, sensitivity, hypersensitivity. What is what?

Celiac disease is none of these things. It is an autoimmune disorder, where gluten triggers the immune system to attack the gut. It is common, lifelong, and can seriously harm health – but nobody knows for sure what causes it. Now a review in Frontiers in Pediatrics says a common food additive could both cause and trigger these autoimmune attacks, and calls for warnings on food labels pending further tests.

Environment causes celiac disease – but only in susceptible individuals

Gluten-free diets have become popular despite little or no evidence of benefit for most people. But for the 1 in 100 with celiac disease, even a mouthful of bread can trigger an immune response that damages the small intestine, impairing nutrient absorption.

Exactly what causes this autoimmune reaction to gluten – a protein found in wheat, rye and barley – is uncertain. Specific mutations in an important immunity-related gene called HLA-DQ seem to be necessary for developing celiac disease, with one of two HLA-DQ variants present in virtually every sufferer – but insufficient, as these variants are also present in about 30% of the general population.

As a result, myriad environmental factors have proposed to interact with genetic risk to cause celiac disease. These span infections, food and toxins; vaccination, drugs and surgery. Most recently, food additives have been suggested to contribute. Among these, microbial transglutaminase – a bacterial enzyme heavily used in industrial processing of meat, dairy, baked and other food products – has emerged as a likely culprit, according to the new review.

How a food binder could be our undoing

“Microbial transglutaminase can glue together proteins, so it’s used to improve food texture, palatability and shelf-life,” says co-author Aaron Lerner, visiting professor at the Aesku.Kipp Institute in Germany. “This enzyme functions like the transglutaminase produced by our body, which is known to be the target of autoimmunity in celiac disease.”

There is a direct positive correlation between rising use of industrial enzymes in bakery products and rising incidence of celiac disease in the last four decades, according to Lerner and co-author Dr Matthias Torsten of the Aesku.KIPP Insritute, Germany. But if transglutaminase is produced normally in our tissues – and by our own gut microbes – what difference should a little more in our diet make?

“This is mostly a question of scale,” argues Lerner. “Our own transglutaminase has a different structure to the microbial sort, which allows its activity to be tightly controlled. And while the relatively indiscriminate microbial transglutaminase is produced by some of our normal gut fauna, the amount of the enzyme could be significantly increased when this microbial population is altered by factors like infection, antibiotics or stress – or, indeed, through consumption of industrially processed foods.”

What links gluten, transglutaminase, HLA-DQ genes and autoimmunity?

Gluten is tough to break down completely. This is useful for helping baked goods to rise and keep their shape, but in celiac sufferers presents a problem.

“The gluten protein fragments or ‘peptides’ that remain after digestion are highly susceptible to transglutaminase, which modifies them to make a variety of new peptides” Lerner explains. “These unusual peptides are particularly likely to resist further breakdown, and to be recognized as ‘foreign’ by HLA-DQ immune receptors inside the gut wall – but only in those carrying the HLA-DQ variants associated with celiac disease.”

Compounding this, components of gluten also loosen the connections between cells lining the gut, allowing more gluten-derived proteins – as well as microbial transglutaminase – to breach this barrier and interact with immune cells.

“Microbial transglutaminase itself could also increase intestinal permeability by directly modifying proteins that hold together the intestinal barrier,” adds Lerner.

Human studies implicate microbial transglutaminase

This all begs the question: if it is gluten-derived proteins that stimulate immune cells, why does the immune response target transglutaminase? And are microbial and human transglutaminase recognized interchangeably by the immune system?

“In one of our own studies, we tested antibodies from the blood of celiac patients. We found that more antibodies were active against complexes of transglutaminase bound to gluten fragments, than against either component alone. The anti-complex antibody count was also the best predictor of intestinal damage in these patients. This was true of both microbial and human transglutaminase complexes, for which there were similar antibody counts.”

In other words, microbial transglutaminase (bound to gluten fragments) could in fact be the target of the immune response in celiac disease – and the attack on our own transglutaminase merely a case of mistaken identity. Microbial transglutaminase present in processed foods is therefore a potential environmental cause of celiac disease.

Is microbial transglutaminase safe?

But according to Lerner, the jury is still out.

“Ultimately all we have so far are associations between microbial transglutaminase and celiac disease. To test whether this enzyme causes or triggers immune damage in celiac disease will require experimenting with exposure in animal models, intestinal cell lines or biopsies”.

Nevertheless, with no known cure for celiac disease, treatment depends on preventive measures – namely, adhering to a gluten-free diet.

“Until there is a clearer answer, we recommend transparency and vigilance with regards to labeling of foods processed using microbial transglutaminase.”

In Switzerland for example, such products must be labelled as unsuitable for persons with celiac disease.

PUBLIC RELEASE: 2-JAN-2019

Metabolic syndrome patients need more vitamin C to break cycle of antioxidant depletion

OREGON STATE UNIVERSITY

CORVALLIS, Ore. – A higher intake of vitamin C is crucial for metabolic syndrome patients trying to halt a potentially deadly cycle of antioxidant disruption and health-related problems, an Oregon State University researcher says.

That’s important news for the estimated 35 percent of the U.S. adult population that suffers from the syndrome.

“What these findings are really saying to people as we move out of the rich-food holiday season and into January is eat your fruits and vegetables,” said Maret Traber, a professor in the OSU College of Public Health and Human Sciences and Ava Helen Pauling Professor at Oregon State’s Linus Pauling Institute. “Eat five to 10 servings a day and then you’ll get the fiber, you’ll get the vitamin C, and you’ll really protect your gut with all of those good things.”

A diet high in saturated fat results in chronic low-grade inflammation in the body that in turn leads to the development of metabolic syndrome, a serious condition associated with cognitive dysfunction and dementia as well as being a major risk factor for cardiovascular disease, fatty liver disease and type 2 diabetes.

A patient is considered to have metabolic syndrome if he or she has at least three of the following conditions: abdominal obesity, high blood pressure, high blood sugar, low levels of “good” cholesterol, and high levels of triglycerides.

Findings published in Redox Biology suggest the type of eating that leads to metabolic syndrome can prompt imbalances in the gut microbiome, with impaired gut function contributing to toxins in the bloodstream, resulting in vitamin C depletion, which subsequently impairs the trafficking of vitamin E.

It’s a treadmill of antioxidant disruption that serves to make a bad situation worse; antioxidants such as vitamins C and E offer defense against the oxidative stress brought on by inflammation and the associated free radicals, unstable molecules that can damage the body’s cells.

“Vitamin C actually protects vitamin E, so when you have lipid peroxidation, vitamin E is used up and vitamin C can regenerate it,” Traber said. “If you don’t have the vitamin C, the vitamin E gets lost and then you lose both of those antioxidants and end up in this vicious cycle of depleting your antioxidant protection.”

Lipid peroxidation is the oxidative degradation of polyunsaturated fatty acids that are a major component of living cells; it’s the process by which free radicals try to stabilize themselves by stealing electrons from cell membranes, causing damage to the cell.

“If there’s too much fat in the diet, it causes injury to the gut,” Traber said. “Bacterial cell walls can then leak from the gut and slip into circulation in the body, and they’re chased down by neutrophils.”

Neutrophils are the most abundant type of white blood cells, a key part of the immune system. Neutrophils attack bacteria with hypochlorous acid: bleach.

“The white blood cells are scrubbing with bleach and that destroys vitamin C,” Traber said. “The body is destroying its own protection because it got tricked by the gut dysbiosis into thinking there was a bacterial invasion.”

And without intervention, the process keeps repeating.

“People with metabolic syndrome can eat the same amount of vitamin C as people without metabolic syndrome but have lower plasma concentrations of vitamin C,” Traber said. “We’re suggesting that’s because this slippage of bacterial cell walls causes the whole body to mount that anti-inflammatory response.”

Vitamin C is found in fresh vegetables and fruits; sources of vitamin E include almonds, wheat germ and various seeds and oils.

Federal dietary guidelines call for 65 to 90 milligrams daily of vitamin C, and 15 milligrams of vitamin E.

PUBLIC RELEASE: 8-JAN-2019

Essential nutrient may help fight Alzheimer’s across generations

ARIZONA STATE UNIVERSITY

 

In a new study, researchers at the Biodesign Institute explore a safe and simple treatment for one of the most devastating and perplexing afflictions: Alzheimer’s disease (AD).

Lead authors Ramon Velazquez and Salvatore Oddo, along with their colleagues in the ASU-Banner Neurodegenerative Disease Research Center (NDRC), investigate the effects of choline, an important nutrient that may hold promise in the war against the memory-stealing disorder.

The study focuses on mice bred to display AD-like symptoms. Results showed that when these mice are given high choline in their diet, their offspring show improvements in spatial memory, compared with those receiving a normal choline regimen in the womb.

Remarkably, the beneficial effects of choline supplementation appear to be transgenerational, not only protecting mice receiving choline supplementation during gestation and lactation, but also the subsequent offspring of these mice.

While this second generation received no direct choline supplementation, they nevertheless reaped the benefits of treatment, likely due to inherited modifications in their genes.

The exploration of such epigenetic alterations may further exciting new avenues of research and suggest ways of treating a broad range of transgenerational afflictions, including fetal alcohol syndrome and obesity.

Supplementing the brain

Choline acts to protect the brain from Alzheimer’s disease in at least two ways, both of which are explored in the new study. First, choline reduces levels of homocysteine, an amino acid that can act as a potent neurotoxin, contributing to the hallmarks of AD: neurodegeneration and the formation of amyloid plaques.

Homocysteine is known to double the risk of developing Alzheimer’s disease and is found in elevated levels in patients with AD. Choline performs a chemical transformation, converting the harmful homocysteine into the helpful chemical methionine.

Secondly, choline supplementation reduces the activation of microglia–cells responsible for clearing away debris in the brain. While their housekeeping functions are essential to brain health, activated microglia can get out of control, as they typically do during AD. Over-activation of microglia causes brain inflammation and can eventually lead to neuronal death. Choline supplementation reduces the activation of microglia, offering further protection from the ravages of AD.

The findings appear in the current issue of the Nature journal Molecular Psychiatry. The NDRC researchers were joined by co-authors from the Translational Genomics Research Institute in Phoenix. (Oddo is also a researcher with ASU’s School of Life Sciences.)

Unremitting devastation

Alzheimer’s disease is now believed to begin its path of destruction in the brain decades before the onset of clinical symptoms. Once diagnosed, the disease is invariably fatal, shutting down one vital system after another. Mental decline is relentless, with patients experiencing a range of symptoms that may include confusion, disorientation, delusions, forgetfulness, aggression, agitation, and progressive loss of motor control.

The disease is poised to afflict 13.5 million people in the U.S. alone by mid-century if nothing is done to address the disease. The staggering costs of Alzheimer’s are projected to exceed $20 trillion in the next 40 years. Developing effective treatments rooted in a more thorough understanding of this complex disease is one of the most daunting challenges facing modern medicine and the global healthcare infrastructure.

Altered states

Research into the origins of Alzheimer’s disease strongly suggests that a great variety of factors are at play. While advancing age remains the greatest risk factor, other hazards that have been implicated in the disease include genetic predisposition and lifestyle.

To this end, studies suggest that diet can have a significant effect in increasing or lowering the risk of cognitive decline, and the risks may be transmitted across generations. A classic case is known as the Dutch Hunger Winter–a severe famine in 1944-45 that affected pregnant women and their offspring.

When a recent study examined the adult health records of those born in the Netherlands during this period, results suggested that the severe dietary deprivation endured by the mothers of these children heightened the occurrence of obesity, above-average LDL cholesterol and, intriguingly, schizophrenia in their offspring. Mortality after 68 years of age increased by 10 percent in this population. It is believed that these adverse health effects occur as a result of the silencing of genes in unborn children. These health-related genes remain silenced throughout life, leading to poor health outcomes.

On a more hopeful note, a healthy diet has been shown to offer protection from diseases, including cancer and Alzheimer’s disease. Patients following a Mediterranean diet for 4.5 years lowered their risk of AD by 54 percent. Another study pointed to the effects of a Mediterranean diet rich in fruits and vegetables, whole grains, legumes and nuts, as well as fish and poultry in reducing the accumulation of Aβ-amyloid, the protein responsible for plaque formation.

Effects of choline

Choline is a vitamin-like essential nutrient that is naturally present in some foods and also available as a dietary supplement. It is a source of methyl groups needed for many steps in metabolism. All plant and animal cells require choline to maintain their structural integrity.

Choline is used by the body to produce acetylcholine, an important neurotransmitter essential for brain and nervous system functions including memory, muscle control and mood. Choline also plays a vital role in regulating gene expression.

It has long been recognized that choline is particularly important in early brain development. Pregnant women are advised to maintain choline levels of 550 mg per day for the health of their developing fetus. “There’s a twofold problem with this,” lead author Velazquez says. “Studies have shown that about 90 percent of women don’t even meet that requirement. Choline deficits are associated with failure in developing fetuses to fully meet expected milestones like walking and babbling. But we show that even if you have the recommended amount, supplementing with more in a mouse model gives even greater benefit.”

Indeed, when the AD study mice received supplemental choline in their diet, their offspring showed significant improvements in spatial memory, which was tested in a water maze. Subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed the epigenetic alterations induced by choline supplementation. Modified genes associated with microglial activation and brain inflammation, and reduced levels of homocysteine resulted in the observed performance improvements in spatial memory tasks.

Due to the epigenetic modifications induced by choline, the improvements carried over to the offspring of mice receiving supplemental choline in the womb. “We found that early choline supplementation decreased homocysteine while increasing methionine, suggesting that high choline levels convert homocysteine to methionine,” Velazquez said. “This conversion happens thanks to an enzyme known as betaine-homocysteine methyltransferase (BMHT). We found that choline supplementation increased the production of BMHT in 2 generations of mice”

The study’s significance is two-fold, establishing beneficial effects from nutrient supplementation in successive generations and proposing epigenetic mechanisms to account for the reduction of AD memory deficit in mice. “No one has ever shown transgenerational benefits of choline supplementation,” Velazquez said. “That’s what is novelabout our work.”

Choline is an attractive candidate for treatment of AD as it is considered a very safe alternative, compared with many pharmaceuticals. The authors note that it takes about 9 times the recommended daily dose of choline to produce harmful side effects.

Future work will explore the effects on AD of choline administered in adult rather than fetal mice. The authors stress however that while results in mice are promising, a controlled clinical trial in humans will ultimately determine the effectiveness of choline as a new weapon in the fight against Alzheimer’s disease.

 

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