In The News: October 2015

Using supplements donated by the Life Extension Foundation, researchers revealed in Advances in Integrative Medicine that the addition of the nutritional supplement S-adenosylmethionine (SAMe) to selective serotonin reuptake inhibitor (SSRI) therapy improved symptoms in adults who failed to optimally respond to drugs.*

Acting on the positive findings of a previous clinical trial that involved the use of SAMe in depressed serotonin-reuptake inhibitor non-responders, Matthew Bambling of the University of Queensland and colleagues compared the effects of adding 15 weeks of high-dose (1,600 mg) and low-dose (800 mg) SAMe supplementation to the regimens of patients using SSRIs who had less-than-optimal treatment response. Tests administered before and after treatment evaluated depressive symptoms.

After 15 weeks, all patients showed significant improvement in the depressive symptoms. The researchers note that the low dose of 800 mg of SAMe added to SSRI therapy is all that’s necessary to have a positive effect.

Editor’s Note: One-third of patients treated for depression with SSRIs suffer a second depressive episode within one year, report the authors. Patients who have experienced two depressive episodes have a 90% chance of experiencing a third episode of depression within a year, with 40% relapsing in less than three months.

Aspirin has been shown in numerous studies to substantially reduce the risk of many types of cancer.

Life Extension has long advocated that those stricken with cancer ask their oncologist about adding aspirin as an adjuvant therapy, as studies show improved survival in cancer patients who take aspirin.

In the journal Laboratory Investigation, researchers at the Kansas City Veterans Affairs Medical Center report a protective effect for aspirin (acetylsalicylic acid) against the development of breast cancer in cell cultures and in mice that received tumor implants.* The findings also suggest a role for aspirin in preventing breast cancer relapse.

By administering varying doses of aspirin to breast cancer cell cultures, Sushanta K. Banerjee and colleagues found an increase in the rate of cell death and a reduction in growth among surviving cells. In mice that received implanted breast cancer tumors, 15 days of low-dose aspirin therapy resulted in tumors that were 47% smaller on average than those of animals who did not receive the drug. And in another experiment, mice that were pretreated with aspirin for 10 days prior to cancer cell exposure were found to have less cancerous growth in comparison with those that were not pretreated.

Editor’s Note: “We find that acetylsalicylic acid not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells/breast cancer stem cells and delays the formation of a palpable tumor,” Dr. Banerjee and associates report.

A study published in the Journal of Pineal Research of postmenopausal women with osteopenia has shown that long-term treatment with melatonin, which naturally decreases in the body with age, can improve the density of bone at the neck of the femur, in proportion to the level of treatment.*

In the trial, researchers gave 81 healthy postmenopausal women with osteopenia, aged 56 to 73, nightly doses of 1 or 3 mg of melatonin or a placebo, and measured them at the beginning of the trial and after a year. “We were looking at body composition and, at the spine and hip, bone mass density,” said lead researcher Dr. Anne-Kristine Amstrup. Biochemical markers of calcium homeostasis were also measured throughout the trial.

“Compared with the women taking the placebo, those on the 1 mg dose experienced a bone mass density increase of 1.4% at the neck of the femur,” added Dr. Amstrup. “Those on the higher dose experienced an increase of 2.3%. The treatment did not affect bone mass density elsewhere, nor bone turnover.”

Editor’s Note: The study also found that the melatonin treatment helped study participants lose fat (almost 7% over the course of the year) while gaining lean tissue instead.

An excerpt from the June 2015 editorial written by Life Extension^®’s Co-founder, William Faloon, was cited in the International Journal of Pharmaceutical Compounding (IJPC). This Life Extension^® article revealed that lower levels of testosterone and higher levels of estrogen in men are strongly associated with a greater risk of sudden cardiac arrest. IJPC is a scientific and professional journal covering pharmaceutical compounding topics that are relevant in allowing today’s pharmacists to meet the needs of patients.*

The “As We See It” editorial quoted in the IJPC is entitled “Surprising Factor Behind Sudden Cardiac Arrest.” In the article, Mr. Faloon quotes a study that concludes that 50% of cardiovascular deaths are the result of a condition called sudden cardiac arrest—the unexpected acute loss of heart function.

Editor’s Note: The editorial states that the FDA is preventing more lives from being saved by continuing to discourage hormone balance in aging men. The FDA also announced in March 2015 that labels of testosterone drugs must carry a warning that testosterone may increase the risk of heart attack and stroke. This inappropriate new warning will curtail the prescribing of testosterone, limit insurance coverage, and drive up consumer costs. Consequences will include more deaths from sudden cardiac arrest.

A trial published in Parkinsonism & Related Disorders evaluating the effects of a reduced form of CoQ10 known as ubiquinol in men and women with Parkinson’s disease found improvement among a group of subjects experiencing “wearing off”—a return of symptoms that occurs when treating the disease with levodopa, which indicates the need for adjustment of dosage or change in medication.*

The trial compared the effects of 300 mg ubiquinol to a placebo among a group of Parkinson’s disease patients who had exhibited wearing off and another group of subjects with early disease not treated with levodopa. Participants in the first group were treated for 48 weeks, while those with early disease received 96 weeks of treatment. Unified Parkinson’s Disease Rating Scale (UPDRS) scores were used to grade the subjects’ symptoms before, during, and after treatment.

By the end of the trial, the change in total UPDRS scores compared to baseline values indicated improved symptoms among the groups receiving ubiquinol.

Editor’s Note: “A recent trial of the oxidized form of CoQ10 for Parkinson’s disease failed to show benefits; however, the reduced form of CoQ10 (ubiquinol-10) has shown better neuroprotective effects in animal models,” writes author Asako Yoritaka of Japan’s Juntendo University and associates. “These findings are in agreement with an observation of a higher plasma concentration of CoQ10 after ingestion of the reduced form versus the oxidized form, indicating that the reduced form is absorbed more efficiently.”

An article in Cell Metabolism reports that periodic fasting could provide some of the same benefits as prolonged fasting. Fasting, an intensive form of dietary restriction, has been associated with numerous health benefits and has prolonged life span in experimental models.*

Following positive findings in yeast, mice were administered diets that included bimonthly cycles of four days of a low-calorie regimen or a control diet that provided the same amount of calories per month beginning in middle age. The researchers, led by Valter Longo of the University of Southern California, observed a decrease in visceral fat, skin lesions, and cancer, accompanied by slowed bone mineral density loss, immune system rejuvenation, and greater longevity in the periodically-fasted group compared with a control group. In older mice, the treatment group also had enhanced hippocampal neurogenesis and better cognitive performance compared to the control animals.

Editor’s Note : In a pilot study involving 19 human participants, three cycles of a similar diet for five days was associated with a reduction in biomarkers for aging, cardiovascular disease, cancer, and diabetes. “It’s about reprogramming the body so it enters a slower aging mode, but also rejuvenating it through stem cell-based regeneration,” Dr. Longo explained. “It’s not a typical diet because it isn’t something you need to stay on.”

A meta-analysis of trials examining the effects of vitamin E supplementation in individuals with nonalcoholic steatohepatitis (NASH) affirmed a benefit for the vitamin in association with several facets of the disease.*

Dr. Renfan Xu and associates selected three articles that met the criteria for their analysis, which included a total of 245 men and women with NASH. Trials involved daily supplementation with a placebo or vitamin E alone or in combination with other compounds.

In the two studies that compared pretreatment to post-treatment histological factors that included steatosis (abnormal cellular retention of lipids), ballooning (a form of programmed cell death), and lobular inflammation, all factors were improved to a greater extent by the end of the trials among those who received vitamin E in comparison with the control groups. In all trials, vitamin E supplementation was associated with improvement in fibrosis compared to controls.

Editor’s Note: “This meta-analysis revealed that vitamin E supplementation resulted in significant improvements in histological parameters in NASH patients,” the authors conclude. “Additional large-scale high-quality studies are needed to investigate the effect of vitamin E supplementation on NASH patients with outcomes (histological parameters, biochemical variables, and adverse events) oriented to obtain more comprehensive information on supplementation for clinical use.”

A case-control study reported in the American Journal of Clinical Nutrition found a protective effect for high plasma levels of carotenoids against the risk of developing breast cancer.*

The study included 2,188 Nurses’ Health Study participants who developed breast cancer over the 20 years following an initial blood sample collection during 1989 to 1990, and an equal number of matched controls who did not develop the disease. Initial and subsequently collected blood samples were analyzed for plasma alpha carotene, beta carotene, beta cryptoxanthin, lutein and zeaxanthin, and lycopene.

For women whose total carotenoid levels were among the top 20% of subjects, there was a 23% lower risk of breast cancer in comparison with those whose levels were among the lowest 20%. Among individual carotenoids, alpha carotene, beta carotene, and lycopene were significantly protective. High levels of carotenoids were more protective against recurrent or lethal breast cancer than non recurrent and nonlethal disease.

Editor’s Note: “These results suggest carotenoids may inhibit tumor initiation, which is compatible with hypothesized mechanisms, including the conversion of provitamin A carotenoids to retinol, which regulates cell growth, differentiation, and apoptosis, and the antioxidant capacity to scavenge reactive oxygen species and prevent DNA damage,” stated authors Heather Eliassen of Harvard University and colleagues.

Findings from a trial reported in the American Journal of Clinical Nutrition reveal improvements in muscle mass and function in adults supplemented with omega-3 polyunsaturated fatty acids (PUFA) in comparison with a placebo group.*

Researchers at Washington University School of Medicine randomized 60 men and women to receive supplements containing a total of 1.86 grams eicosapentaenoic acid (EPA) and 1.5 grams docosahexaenoic acid (DHA), or a placebo daily for six months. Thigh muscle volume, handgrip strength, one-repetition maximum upper and lower body strength, and average isokinetic muscle power were evaluated at the beginning of the study, at three months (with the exception of thigh muscle volume), and at the end of the treatment period.

At six months, handgrip strength, thigh muscle volume, and one-repetition maximum muscle strength were significantly increased in omega-3 fatty acid supplemented participants in comparison with the control group.

Editor’s Note: “Additional studies are needed to determine whether long-term omega-3 PUFA therapy can sufficiently slow the declines in muscle mass and function that normally occur in older adults to significantly delay or even prevent sarcopenia and a loss of physical independence or cure it in already sarcopenic persons,” the authors say.

In an article appearing in Cell Metabolism, scientists from McMaster University describe the role of AMPK, an enzyme that activates autophagy, in maintaining muscle mass.* Previous research by the team revealed that AMPK is activated by exercise as well as the drug metformin.

The current research involved mice that were modified to lack skeletal muscle AMPK.

“We found that the body’s fuel gauge, AMP-activated protein kinase (AMPK), is vital to slow muscle wasting with aging,” reported lead researcher Gregory Steinberg, who is a professor of medicine at McMaster’s Michael G. DeGroote School of Medicine and co-director of the Metabolism and Childhood Obesity Research Program. “Mice lacking AMPK in their muscle developed much greater muscle weakness than we would have expected to see in a middle-aged mouse. Surprisingly, these AMPK-deficient mice, which were the equivalent of being just 50 years old, had muscles like that of an inactive 100-year-old.”

Editor’s Note: “It is known that AMPK activity in muscle is ‘dialed down’ with aging in humans, so this may be an important cause of muscle loss during aging,” Dr. Steinberg added. “We know we can turn on the AMPK pathway with intense exercise and commonly-used type II diabetes medications. By knowing that AMPK is vital for maintaining muscle mass with aging, we can now try to adapt exercise regimes and existing drugs to switch on AMPK in muscle more effectively. The development of new selective activators of the AMPK pathway in muscle may also be effective to prevent muscle loss with aging.”

A new study reported in the journal Oncotarget found that a synthetic version of the common cooking spice curcumin can significantly reduce resistance to cisplatin, a chemotherapy drug used to treat head and neck cancer.*

Researchers at UCLA Jonsson Comprehensive Cancer Center used a brand new technology to deliver the synthetic curcumin to the cancerous cells. Drs. Marilene Wang and Eri Srivatsan used liposomes—a kind of microscopic vehicle that delivers encapsulated synthetic curcumin—to target resistant head and neck squamous cell carcinoma.

“Cisplatin goes through the p16 and p53 pathways, while the curcumin uses an alternate pathway,” said Dr. Wang. “The resistant cell lines don’t respond to the typical pathway that cisplatin would go through; that’s why curcumin is able to kill the resistant cancer cells.”

Researchers hope the results will lead to human clinical trials and the development of new therapies for head and neck cancer patients.

Editor’s Note: Head and neck cancers affect 42,000 people in the US each year. The five-year survival rate for all head and neck cancer patients is 57%; for patients with stage IV oral cancers, the survival rate is 20%.