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Mitochondrial disease could be treated with antioxidants
March 30 2018. A report published online on February 23, 2018 in Molecular Genetics and Metabolism reveals a benefit for antioxidants in mitochondrial diseases: progressive and potentially severe multisystem energy deficiency disorders caused by genetic mutations. The disease, characterized by malfunctioning mitochondria which are the energy-producing organelles of the cells, can affect both adults and children.
We are pursuing a precision medicine approach that investigates therapeutic candidates in preclinical models--simple laboratory animals and human cells--to discover the best potential leads to bring to patients in clinical trials," commented study leader Marni J. Falk, MD, who is the executive director of the Mitochondrial Medicine Frontier Program at Children's Hospital of Philadelphia (CHOP).
Acting on the knowledge of an increase in oxidative stress in mitochondrial disease, Dr Falk and her colleagues tested the effects of antioxidants in zebrafish and the worm Caenorhabditis elegans, as well as in cultured human skin cells. All three models of the disease had genetically-induced mitochondrial respiratory chain malfunctions.
The team found that the amino acid N-acetylcysteine (NAC) improved survival in the human cells, while vitamin E and NAC prolonged lifespan in the worms and protected against brain damage in zebrafish. "In addition to showing clear benefits in animal survival and cellular viability in these animal models of genetic-based mitochondrial disease, we learned that these compounds effectively relieved oxidative stress that was present throughout the entire cell, not only within the mitochondria," Dr Falk reported. "Both NAC and vitamin E are the lead antioxidant candidates from this work to be evaluated in clinical trials, to determine whether they effectively benefit the survival, function and feeling of mitochondrial disease patients. They may have particular promise to improve the resiliency of the nervous system in patients with malfunctioning mitochondria."
“The means are now at hand to conquer Alzheimer's disease”
March 28 2018. Articles published rel="noopener noreferrer" during March 2018 in the Journal of Alzheimer's Disease suggest that Alzheimer’s disease can be prevented by self-treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, as well as with a Mediterranean diet and antioxidants including quercetin. “The means are now at hand to conquer Alzheimer’s disease,” announce authors Patrick L. McGeer, MD, PhD, and colleagues.
In 2016, Dr McGeer reported the development of a saliva test that measures amyloid beta protein 42. "What we've learned through our research is that people who are at risk of developing Alzheimer's exhibit the same elevated amyloid beta 42 levels as people who already have it; moreover, they exhibit those elevated levels throughout their lifetime so, theoretically, they could get tested anytime," Dr McGeer commented. "Knowing that the prevalence of clinical Alzheimer's Disease commences at age 65, we recommend that people get tested ten years before, at age 55, when the onset of Alzheimer's would typically begin. If they exhibit elevated amyloid beta 42 levels then, that is the time to begin taking daily ibuprofen to ward off the disease.”
"Unfortunately, most clinical trials to date have focused on patients whose cognitive deficits are already mild to severe, and when the therapeutic opportunities in this late stage of the disease are minimal,” he noted. “Consequently, every therapeutic trial has failed to arrest the disease's progression. Our discovery is a game changer. We now have a simple test that can indicate if a person is fated to develop Alzheimer's disease long before it begins to develop. Individuals can prevent that from happening through a simple solution that requires no prescription or visit to a doctor. This is a true breakthrough since it points in a direction where Alzheimer’s disease can eventually be eliminated."
Nutrients can reduce psychotic symptoms
March 26 2018. rel="noopener noreferrer" A review published on March 21, 2018 in Early Intervention in Psychiatry vindicates one of the oft-contested tenets of orthomolecular medicine: that providing the right nutrients to individuals with psychiatric diseases can improve symptoms.
“The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long-term schizophrenia,” write Joseph Firth of Western Sydney University and colleagues. “However, no systematic evaluation of trials in ‘first-episode psychosis’ (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness.”
The researchers selected 11 studies involving a total of 451 patients with first episode psychosis for their review. While the six studies that examined the effects of omega-3 found inconsistent effects on psychiatric symptoms, mechanistic studies revealed improvements in brain glutathione levels and hippocampal neural health in association with the fatty acids. Studies that evaluated the effects of N-acetylcysteine and vitamin C found improved oxidative status, which was associated with a decrease in psychiatric symptoms. In the study that examined the effects of taurine, 4 grams per day of the amino acid lowered symptoms within 12 weeks.
"Certainly, there is early indication that certain nutrients may be beneficial, not to replace standard treatment, but as an 'add-on' treatment for some patients," concluded Dr Firth, who is a Research Fellow at NICM Health Research Institute, Western Sydney University.
"Individual nutrients appear to have moderate effects on mental health, at best,” he noted. "A combined nutrient intervention, explicitly designed from the evidence-base in psychosis, may therefore confer larger and more beneficial effects for young people with this condition. We will be testing this in Sydney, Australia in 2018, to learn more about the potential role of nutrition in mental health for the future."
Fat occurring in olive oil associated with lower mortality risk during 22-year period
March 23 2018. A study reported at the American Heart Association's Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2018 revealed a lower risk of dying from any cause during a 22-year average follow-up period among men and women who consumed greater amounts of plant-sourced monounsaturated fat such as that contained in olive and other vegetable oils, as well as avocados, nuts and seeds. In contrast, having a higher intake of monounsaturated fat from animal sources, including red meat, poultry and full-fat dairy products, was associated with a greater risk of death during follow-up.
The study included 29,966 men enrolled in the Health Professionals Follow-Up Study and 63,412 women from the Nurses' Health Study. Dietary questionnaires administered every four years provided information concerning the intake and source of monounsaturated fat.
Over the 22-year follow-up period, 20,672 deaths occurred, including 4,588 deaths from heart disease. Subjects whose intake of monounsaturated fatty acids from plants was categorized as high had a 16% lower risk of all-cause mortality in comparison with those whose intake was low. However, having a high intake of monounsaturated fat derived from animals was associated with a 21% greater risk of death during follow-up.
Research associate Marta Guasch-Ferré, PhD, of the Harvard T.H. Chan School of Public Health and colleagues suggest that the replacement of saturated fat, refined carbohydrates or trans fats with an equal number of calories from plant-sourced monounsaturated fatty acids might lower the risk of heart disease deaths and death from any cause by 10%-15%.
"Our results emphasize the importance of the source and quantity of monounsaturated fatty acids in the diet - we should eat more monounsaturated fatty acids from plant sources and less monounsaturated fatty acids from animal sources," Dr Guasch-Ferré recommended.
Insufficient vitamin D linked to postmenopausal metabolic syndrome
March 21 2018. The January 2018 issue of Maturitas reported the results of a study conducted at São Paulo State University which found an increased risk of metabolic syndrome among postmenopausal women who had insufficient levels of vitamin D. Metabolic syndrome is characterized by increases in waist circumference, triglycerides, fasting glucose and blood pressure, along with low levels of high density lipoprotein (HDL) cholesterol.
The study included 463 postmenopausal women. Blood samples were analyzed for total cholesterol, HDL, LDL, triglycerides, glucose, insulin and 25-hydroxyvitamin D. Metabolic syndrome was diagnosed in 241 women who had three or more of the syndrome’s characteristics.
Metabolic syndrome was revealed in 57.8% of those with insufficient or deficient vitamin D and in 39.8% of participants with sufficiency. "We measured the participants' blood vitamin D levels and also analyzed parameters indicating metabolic syndrome,” reported lead researcher Eliana Aguiar Petri Nahas, who is a professor at São Paulo State University's Botucatu Medical School’s Department of Gynecology & Obstetrics. “We found that the lower the level of blood vitamin D, the greater the occurrence of metabolic syndrome. The results suggest that supplementing and maintaining adequate levels of vitamin D in postmenopausal women can reduce the risk of disease."
"Exposure to the sun activates a sort of pre-vitamin D in the adipose tissue under the skin," she explained. "Aging leads not just to loss of muscle mass but also to changes in body composition, and this pre-vitamin D is lost. That's why older people produce less vitamin D even if they get plenty of sunlight."
"More studies are required in order to make these important associations in terms of the effects of supplementation on cardiometabolic syndrome, the immune and inflammatory mechanisms of cardiovascular disease in postmenopausal women, and their quality of life," Dr Nahas noted.
Higher omega-3 levels linked to lower risk of premature mortality
March 19 2018. An article appearing in the Journal of Clinical Lipidology revealed a lower risk of mortality during a seven year median in association with having a higher level of omega-3 fatty acids.
William S. Harris and colleagues examined data from 2,500 men and women enrolled in the Framingham Heart Study Offspring cohort. The Omega-3 Index, which quantifies levels of the omega-3 fatty acids EPA and DHA in red blood cell membranes, was determined from blood samples collected when the participants were approximately 66 years of age. The subjects, who were free of cardiovascular disease at the beginning of the study, were followed for up to 11.2 years, during which 350 deaths occurred.
In comparison with subjects whose Omega-3 Index values were among the lowest 20% of participants, those whose values were among the top 20% had a 34% lower risk of death from any cause over follow-up, a 39% lower risk of cardiovascular disease, a 42% lower risk of coronary heart disease and a 55% lower risk of stroke. There was a 47% lower risk of death from causes other than cancer and cardiovascular disease among those whose Omega-3 Index values were among the highest in comparison with those whose values were among the lowest group.
Serum cholesterol levels were not associated with the risk of any outcome. "We all know that the serum cholesterol level is a major risk factor for CHD, and since the latter is a major cause of death in the Western world, it would be reasonable to expect that a high cholesterol level would portend higher risk for premature death," Dr Harris stated. "This did not turn out to be the case here. When baseline serum cholesterol levels were substituted for the Omega-3 Index in the same multi-variable models, the former was not significantly associated with any of the tracked outcomes whereas the latter was related to 4 of the 5 outcomes assessed."
Low fat, calorie restricted diet protects mouse brains from aging effects
March 16 2018. A report published on March 12, 2018 in the journal Frontiers in Molecular Neuroscience revealed the finding of researchers at the University Medical Center Groningen, Netherlands, of a protective effect in aged mice for calorie restriction plus a low fat diet against inflammatory activation of the brain’s microglia. Microglia are the brain’s immune cells that aid in the maintenance of brain tissue function and integrity, whose dysfunction is associated with neurodevelopmental and neurodegenerative conditions. Microglia-driven inflammation in some areas of the brain is associated with aging.
"Obesity and aging are both prevalent and increasing in societies worldwide, but the consequences for the central nervous system are not well understood," noted lead researcher Bart Eggen, of the University Medical Center Groningen’s Department of Neuroscience. "We determined if a high- or low-fat diet, in combination with exercise and food restriction, impacted microglia during aging in mice."
The researchers gave groups of mice high or low-fat diets with or without calorie restriction or access to exercise, beginning at 4, 6 or 12 weeks of age. The hypothalamus glands in the animals’ brains were examined for inflammation and other factors at ages of up to 24 months. "Aging-induced inflammatory activation of microglia could only be prevented when mice were fed a low-fat diet in combination with limited caloric intake," Dr Eggen reported. "A low-fat diet per se was not sufficient to prevent these changes."
“These data do show that, in mice, the fat content of a diet is an important parameter in terms of the detrimental effects of aging on the brain, as well as caloric intake," he remarked. "Only when fat content and caloric intake are limited, can aging-induced changes in microglia be prevented."
Supplementation could prevent heart surgery-associated drop in vitamin D
March 14 2018. At the American College of Cardiology Scientific Session on March 12, 2018, findings from a study conducted at the Intermountain Medical Center Heart Institute were presented that suggest a protective role for vitamin D supplementation prior to open heart surgery.
The ASSESS-D study included 150 patients who elected to have open heart surgery. Half of the participants received 50,000 IU vitamin D3 for three days beginning before and ending after their surgeries, while the remainder received a placebo. Blood samples were analyzed for vitamin D throughout the subjects’ hospital stays and six months following the surgery.
While vitamin D levels declined after open heart surgery in the placebo group, they rose to the normal range among those who received vitamin. "Now that we know that the stress from surgery causes vitamin D levels to drop, we want to continue our research and see if supplementing vitamin D levels will help prevent heart problems in the future, given our understanding that low levels of vitamin D can cause an increased risk for heart problems," commented lead researcher Brent Muhlestein, MD.
"We're gathering more evidence that vitamin D deficiency is strongly associated with heart disease and death," he added. "Our study was a mechanistic approach to try and figure out what exactly is happening with vitamin D, and perhaps give us some information as we press forward with a randomized trial to find out the real answer to the question of the impact of vitamin D on heart disease and related problems."Dr Muhlestein plans to evaluate vitamin D’s effects on patients who have had a heart attack. "We need hard evidence, and we hope the Target-D trial will give us real randomized controlled outcomes data to figure out if it's good to take vitamin D supplements if you're a heart patient who has low vitamin D levels," he remarked.
Large study finds higher vitamin D levels equal lower cancer risk
The current study included 33,736 men and women between the ages of 40 and 69 years who were enrolled in the Japan Public Health Center-based Prospective Study, an ongoing population-based cohort study started in 1990. Questionnaires administered upon enrollment provided information concerning past medical history and lifestyle factors, and food frequency questionnaires provided dietary data. Blood samples collected at the baseline health check-up were analyzed for plasma 25-hydroxyvitamin D. Subjects were followed for an average of 16 years, during which 3,301 cases of cancer were diagnosed.
In comparison with men and women whose vitamin D levels were among the lowest 25% of participants, subjects whose levels were among second, third and fourth 25th percentiles had an adjusted risk of developing cancer that was 19%, 25% and 22% lower, respectively. When site-specific cancers were analyzed, those whose vitamin D levels were highest had a 55% lower risk of liver cancer compared to subjects whose levels were among the lowest 25%. Having higher vitamin D levels failed to be associated with an increased risk of cancer among any types of cancer examined.
“We observed that a higher circulating concentration of vitamin D was associated with a lower risk of subsequent cancer in a large Japanese population,” write Motoki Iwasaki, division chief for the Japan Public Health Center-based Prospective Study Group, and colleagues. “Our findings support the hypothesis that vitamin D may confer protection against the risk of cancer.”
“Future studies are needed to clarify the dose-response pattern and the optimal concentrations for cancer prevention,” they conclude.
Vitamin D could protect heart attack patients from developing heart failure
March 9 2018. A report published on February 3, 2018 in Heart Lung and Circulation suggests a protective role for vitamin D against the prevention of scarring and thickening of the heart muscle after a heart attack, which can lead to heart failure.
"The benefits of vitamin D are becoming increasingly known, but we still don't fully understand how mechanistically it can help with heart disease management,” commented lead researcher James J. H. Chong, of the University of Sydney. “We wanted to know more about how vitamin D protects the heart after a heart attack."
When blood supply to the heart is blocked during a heart attack, cardiac colony-forming unit fibroblasts (cCFU-Fs) replace damaged tissue with collagen-based scar tissue. "This is a problem because scarring of heart tissue can reduce the heart's ability to pump blood effectively, which can lead to heart failure," Dr Chong explained.
Using cCFU-Fs taken from mouse hearts, Dr Chong and his colleagues studied the effects of the administration of 1,25-dihyroxyvitamin D3 on cell proliferation and differentiation. "Our research shows that vitamin D actually blocks the cCFU-Fs from forming scar tissue,” Dr Chong reported. “By blocking cCFU-Fs, vitamin D may play an important role in lowering the risk of heart failure after a heart attack."
"Cardiovascular diseases, including heart attacks and heart failure, are the leading cause of death worldwide," he remarked. "To change this, we need to research heart conditions from every possible angle. This study is the first to demonstrate the role of 1,25D in regulating cardiac progenitor cells, and the findings are encouraging.”
"With further study, vitamin D could prove to be an exciting, low-cost addition to current treatments, and we hope to progress these finding into clinical trials for humans," Dr Chong concluded.
Astaxanthin supplementation associated with improved recovery from fatigue
March 7 2018. A randomized, double-blind crossover study reported on February 28, 2018 in Nutrients found an improvement in the ability to recover from mental fatigue among participants who received the carotenoid astaxanthin plus sesamin, an antioxidant lignin present in sesame seeds.
“Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism,” write authors Ayano Imai and colleagues. “The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin, strong food-derived antioxidants, on fatigue.”
The trial included 24 healthy volunteers between the ages of 30 and 60 years who received capsules containing a placebo or 3 milligrams astaxanthin plus 5 milligrams sesamin. Subjects were instructed to consume two capsules daily for 4 weeks, after which they were assigned to tasks that induced mental and physical fatigue. After a month during which no treatments were administered, the treatments were then switched for a subsequent 4-week period.
Better ability to recovery from video display terminal-induced mental fatigue was reported by the astaxanthin and sesamin supplemented group as compared to the placebo. No adverse effects were observed in association with the treatment. Plasma phosphatidylcholine hydroperoxide (PCOOH, a marker of oxidative stress), which was measured before and after mental and physical tasks, rose in both groups after fatigue-inducing tasks; however, the rate of change was significantly lower among those who received astaxanthin plus sesamin.
Dr Imai and associates suggest that the antioxidant activity exhibited by astaxanthin and sesamin could be a mechanism for its anti-fatigue effect. “Our results suggest the novel possibility that supplementation with astaxanthin/sesamin may reduce subjective fatigue in healthy subjects,” they conclude. “The safety of a four-week astaxanthin/sesamin supplementation period was also confirmed.”
Fatty acid supplements may protect preterm children from autism
March 5 2018. The February 2018 issue of the Journal of Nutrition published the finding of researchers from Nationwide Children's Hospital of a potential protective effect for omega fatty acid supplementation against the development of autism spectrum disorder (ASD) symptoms among children born preterm, who are at increased risk of ASD.
"The trial had two goals,” explained lead author Sarah Keim, PhD, of The Research Institute at Nationwide Children's. “First, we wanted to confirm the feasibility of a large study of toddlers born very preterm and exhibiting symptoms often seen with ASD. Second, we wanted to see what the effects of omega fatty acids would be on parent-reported ASD symptoms and related behaviors."
The trial included 31 children aged 18 to 38 months who were born more than 11 weeks early. Fifteen children received a supplement that contained 338 mg eicosapentaenoic acid (EPA), 225 mg docosahexaenoic acid (DHA) and 83 mg gamma-linolenic acid (GLA) while the remainder received a canola oil supplement as a placebo for 90 days. Questionnaires completed by a parent at the beginning of the trial and at the last study visit assessed ASD symptoms.
Children who received EPA, DHA and GLA had a greater reduction in ASD symptoms than those who received the placebo. The researchers suggest decreased inflammation as a potential mechanism for these omega fatty acids.
"Currently, no medications are available to help children born prematurely with the developmental delays and behavior problems they often experience,” Dr Keim observed. “For very young children, the medications that physicians sometimes try tend to have many side effects. And we don't know what effect those medications have on brains that are still developing. If using omega fatty acid supplementation helps, it would have a really huge impact for these kids."
Intake of fish, omega-3 supplements linked with lower MS risk
March 2 2018. A study scheduled for presentation at the American Academy of Neurology's 70th Annual Meeting, to be held in Los Angeles April 21 to 27, found a lower risk of multiple sclerosis (MS) among people who consumed fish once per week or more, or one to three times per month in addition to daily fish oil supplements in comparison with those who consumed less than one serving fish per month and no supplements.
"Consuming fish that contain omega 3 fatty acids has been shown to have a variety of health benefits, so we wanted to see if this simple lifestyle modification, regularly eating fish and taking fish oil supplements, could reduce the risk of MS," stated study author Annette Langer-Gould, MD, PhD, of Kaiser Permanente Southern California in Pasadena, California.
The study included 1,153 subjects with an average age of 36, among whom approximately one-half had been diagnosed with MS or clinically isolated syndrome (an initial MS episode lasting at least 24 hours). Reported intake of fish, such as salmon, shrimp and tuna, was defined as high among those who consumed one serving of fish weekly, or one to three servings per month plus daily fish oil. Low intake was characterized as less than one serving per month and no fish oil supplementation.
One hundred eighty of the subjects with MS had high fish intake compared to 251 controls. In comparison with a low intake, high fish consumption was associated with a 45% lower risk of MS or clinically isolated syndrome. The researchers also determined that 2 of 13 genetic variations in a human gene cluster that regulates fatty acid levels were associated with lower MS risk.
The findings suggest that omega-3 fatty acids may be involved in modifying MS risk.