Supplementation with vitamin B3 reduces nonmelanoma skin cancer recurrence

University of Sydney (Australia), October 23 2015. 

The New England Journal of Medicine published the outcome of a randomized trial which found a protective effect for supplementation with a form of vitamin B3 against the risk of nonmelanoma skin cancer in high-risk patients.

The Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) study included 386 men and women with a history of at least two basal or squamous cell carcinomas within five years prior to enrollment. Participants received a placebo or 500 milligrams of the nicotinamide form of vitamin B3 for twelve months.

At the end of one year, the incidence of new nonmelanoma skin cancers was 23% lower among those who received nicotinamide compared to the placebo. For basal cell carcinomas, the risk was 20% lower and for squamous cell carcinomas, the risk was 30% lower. Nicotinamide supplementation was additionally associated with a reduction in precancerous sun-induced lesions. There was a trend toward greater effectiveness among subjects with higher numbers of cancers over the previous five years, however, the researchers stated that, in light of nicotinamide’s safety and low cost, the difference was insufficient to warrant restricting treatment to a specific subgroup. “Nicotinamide is widely accessible as an inexpensive over-the-counter vitamin supplement and presents a new opportunity for the chemoprevention of nonmelanoma skin cancers that is readily translatable into clinical practice,” they conclude.

“This is the first clear evidence that we can reduce skin cancers using a simple vitamin, together with sensible sun protection,” stated senior author, Diona L. Damian, PhD, who is a professor of dermatology at the University of Sydney and Royal Prince Alfred Hospital. “We hope that these findings can be immediately translated into clinical practice. However, people at high risk of skin cancer still need to practice sun safe behavior, use sunscreens and have regular check-ups with their doctor.”

Polyphenol-rich diets improve leaky gut syndrome in the elderly

University of Barcelona (Spain), October 29, 2021

The increase of intestinal permeability is associated with factors such as ageing, food allergies and intolerances and unhealthy diets. This alteration causes a reduction of the gut integrity barrier that triggers the transit of potentially-toxic substances for the blood, and is related to the development of chronic diseases such as diabetes, cardiovascular diseases and even Alzheimer’s.

A polyphenol-rich diet improves the intestinal permeability in old people, according to an article published in the journal Clinical Nutrition. The study is led by Cristina Andrés-Lacueva, profesor at the Faculty of Pharmacy and Food Sciences and head of the Research Group of Biomarkers and Nutritional Metabolomics of Food of the University of Barcelona and the Biomedical Research Center of Fragility and Healthy Ageing (CIBERFES), also part of the Catalan Food Innovation Network (XIA).

This European study, conducted within the framework of the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL), was carried out in people aged over sixty who underwent a polyphenol-rich diet for eight weeks. The results show that including up to three daily portions of apple, cocoa, dark chocolate, green tea, cranberries, oranges or pomegranate juice, improves intestinal permeability when making specific changes in the intestinal microbiota.

According to the experts Gregorio Perón and Tomás Meroño (UB-INSA and CIBERFES), “we studied the existing relationship between the metabolism of the elements of the diet, microbiota and intestinal permeability, by analysing the changes that are caused by a polyphenol-rich diet in the microbiota of the participants in our study and testing the resulting improvement of their gut barrier”.

The analysis of plasmatic and faecal samples showed an increase of the serum metabolome related to the polyphenol intake. “For instance, theobromine and methylxanthine ─ derived from cocoa and green tea─ are positively correlated with butyrate-producing bacteria (a fatty acid in the intestinal flora), and inversely with zonulin, a protein related to the intestinal permeability”, note the authors.

According to Professor Cristina Andrés-Lacueva, “the study of the relationship between intestinal permeability, microbiota composition and food metabolism has to be the base for establishing customized diets for every life stage, especially for the elderly”.

Changes in food and lifestyle for a healthy ageing 

In short, changes in lifestyle and food are decisive as a prevention strategy for intestinal permeability associated to ageing and chronic diseases. “A higher intake of fruits, vegetables and foods such as those described in this paper provide fiber and polyphenols that could help counterbalance the damaging of permeability due to ageing”, notes Andrés-Lacueva.

The study, conducted in collaboration with the Quadram Institute (United Kingdom) and the University of Milan and University of Perugia (Italy), and funded by the International Joint Programming Initiatives PCIN-2015-238, has also received support from the European Regional Development Fund (ERDF) and the former Spanish Ministry of Economy, Industry and Competitiveness (MINECO) via the Joint Programming Initiative – A Healthy Diet for A Healthy Life.

Walking may reduce postpartum depression symptoms

University of West Ontario, October 29, 2021

The COVID-19 pandemic has meant countless women are looking beyond harder-to-access, traditional postpartum depression (PPD) treatment options—like psychiatry and medication—and finding that physical activity could be key.

A new Western study suggests brisk walking—as little as 15 minutes a day—may be the answer for many women struggling with PPD, though some severe cases may still require traditional medical care.

Different from “baby blues,” PPD can cause severe mood swings, exhaustion, and even a sense of hopelessness. About 23 percent of new mothers in Canada experience some of these symptoms, while recent studies in Europe and Asia indicate this number has increased to nearly 30 percent during the COVID-19 pandemic.

This first-of-its-kind study, published today by Journal of Women’s Health, was led by Western undergraduate student Veronica Pentland and assistant professor Marc Mitchell from the Faculty of Health Sciences.

“PPD can have major effects on a woman’s mental health, but also on the child’s development,” said Pentland. “If you are depressed, it’s harder to care for yourself, and by extension, your child.”

The study, which analyzed data from five research projects involving 242 participants, recommends women walk at a “moderate intensity” 90 to 120 minutes per week to reduce PPD symptoms.

“Walking is fairly accessible and the great thing is, you can do it with your baby,” said Mitchell. “If you can get out three or four times a week for half an hour or even 15 minutes a day with your baby in a stroller, our findings show it could make a really big difference in how you feel.”

Mitchell, Pentland and their collaborators, including Faculty of Health Sciences professor Michelle Mottola, found walking resulted in clinically significant reductions in PPD symptoms and these improvements remained even three months after the mothers stopped their walking programs.

There are many long-standing barriers for accessing treatment, especially for mental health, including social stigma, marginalization and discrimination of racialized communities; and wait times and the ongoing global pandemic has only worsened the situation, said Pentland.

“Walking provides a treatment that circumvents many of these barriers. There could not be a more relevant time for an accessible route to mental health treatment,” she said.

Over 4 million deaths per year caused by obesity

Beth Israel Deaconess Medical Center, October 28, 2021

Novel obesity treatments such as modulation of the gut microbiome and gene therapy are underutilized and could help fight the obesity epidemic, according to a new manuscript published in the Endocrine Society’s journal, Endocrine Reviews.

Nearly half of the adults and 20 percent of children in the United States have obesity, yet doctors are under prescribing effective weight loss medications and many patients are not receiving the treatment they need. The weight stigma that exists in healthcare settings makes people with obesity hesitant to seek care until comorbidities develop and reach a dangerous stage. Lack of insurance coverage and cost issues are another factor that creates barriers to obesity treatment.

“Obesity is the epidemic crisis of our time. The disease leads to serious comorbidities such as diabetes, fatty liver disease and cardiovascular disease and significantly shortens a person’s length and quality of life,” said Christos S. Mantzoros, M.D., Sc.D., of Beth Israel Deaconess Medical Center in Boston, Mass. “Until recently we did not understand the genetic and hormonal causes of obesity and how obesity leads to these comorbidities. We have recently started to understand the causes of obesity in humans, which is a big discovery that has led to designing effective therapies.”

In the article, the researchers map out the molecular and hormonal pathways that lead to obesity and the disease’s related comorbidities. This data gives researchers the insights they need to design, test and implement new obesity therapies.

The researchers highlight the need for safer and more effective obesity therapies, including new drug delivery systems, vaccines, modulation of the gut microbiome and gene therapy. Novel medications, including combinations of gastrointestinal hormones and other molecules, are being tested and are expected to lead to significant percentages of weight loss with less side effects once available. As our understanding of obesity improves, more effective medications with fewer side effects will be developed.

Recently approved medications such as semaglutide, a modified gastrointestinal hormone administered once a week, can lead to 15% weight loss when combined with lifestyle changes. Bariatric surgery can lead to up to 40% weight loss, but it is invasive and linked to complications.

“Insurance companies need to pay attention to data from studies and the scientific progress we are making and start covering the medications that are and will be approved soon, given that currently only a small minority of patients with obesity have coverage for the medications and medical care they need,” Mantzoros said. “It would be much more cost effective to cover treatments early instead of waiting for comorbidities and their complications to develop.”

Other authors of the study include: Angeliki Angelidi and Matthew Belanger of Harvard Medical School in Boston, Mass., and Alexander Kokkinos and Chrysi Koliaki of Laiko General Hospital in Athens, Greece.  The research received no external funding.

Ashwagandha supplementation associated with improved female sexual function

Trupti Hospital & Santati Center (India), October 30 2021

An article appearing in BioMed Research International reveals the outcome of a pilot study that found improvements in sexual function among women who received a highly concentrated ashwagandha (Withania somnifera) root extract.

The study included 50 women aged 21 to 50 years diagnosed with female sexual dysfunction, which included hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder or combined genital and subjective arousal disorder. Twenty-five women received 300 milligrams ashwagandha twice per day with food and the remainder received a placebo for eight weeks. Sexual function (including desire, arousal, lubrication, orgasm, satisfaction and pain), sexual distress, sexual activity, response to therapy and tolerability of therapy were evaluated before treatment, and at four and eight weeks.

Women who received ashwagandha had improved sexual function scores in the areas of arousal, lubrication, orgasm and satisfaction; improvement in sexual distress, and an increased number of successful sexual encounters by the end of the treatment period compared with the placebo group. Fifteen of the 25 women who received ashwagandha rated their response to treatment as excellent and nine rate their response as good. No adverse effects were observed.

As a possible mechanism, authors Swati Dongre and colleagues note that ashwagandha may reduce the effects of chronic stress (which interferes with sexual response) by lowering serum cortisol. In men, the herb has been shown to increase serum testosterone, which is involved in sexual function in both genders.

“The results suggest that ashwagandha root extract could be useful for the treatment of female sexual function,” the authors conclude. “The lack of adverse effects suggests that the extract is safe to consume.”

For effective weight maintenance, eat breakfast and stop late-night snacking

Vanderbilt University, October 28, 2021

Researchers have confirmed that due to daily circadian rhythms regulating metabolism, when you eat is as important as the how much and what you eat when trying to gain, lose or maintain weight.

Carl Johnson, professor of biological sciences at Vanderbilt University, collaborated with graduate student Kevin P. Kelly to test how the timing of daily meals and snacks throughout the day affects weight maintenance.

With 24-hour access to some food, those eating the biggest meal of the day in the morning gained less weight than those who ate their biggest meal at the end of the day and before sleep. “These differences are mostly due to natural differences in circadian metabolic regulation throughout the day,” Johnson said. “We found that the timing of meals changes the proportion of fat the body is burning while sleeping, regardless of fasting.”

Studies before this one have not isolated the variable of meal time because they have always included mandatory fasting periods. While past studies have demonstrated the importance of timing meals by periods of feeding and fasting, Johnson and Kelly found that even without fasting, the timing of large, high-fat meals still has a significant effect on weight gain.

These results, along with those from a previous study Johnson conducted, suggest that eating a larger, protein-filled breakfast is one of the best ways to maintain a healthy weight. A smaller but still significant change would be to avoid late-night snacking. Optimally, it is best to avoid snacking between supper and bedtime so that when you fall asleep, your stomach is empty, Johnson said.

“If you do an enforced fast, the subjects did gain a little less weight, but not restricting access to food does not cause as much extra weight gain as we originally thought,” Johnson said. “About 80 percent of the benefit of eating larger meals at the beginning of the day is present even if you do not have an enforced fast.”

This novel research shows that timing of meals is important for weight maintenance regardless of fasting. “This is important because as humans, most of us have access to food 24/7,” Johnson said.

Johnson plans to maintain his focus on circadian metabolism by looking into how it may affect those with the neurodevelopmental disorder Angelman syndrome.

The article, “Time-optimized feeding is beneficial without enforced fasting.” was published in the journal Open Biology on Oct. 6. Former Vanderbilt psychology professor Martin Katahn pioneered the rotation diet that has been critical for this research, and researchers at the University of Exeter Medical School and Vanderbilt University Medical Center collaborated on this study.

Johnson has conducted additional research relevant to this topic in recent years. The article entitled “Eating breakfast and avoiding late-evening snacking sustains lipid oxidation” was published in the journal PLoS Biology in February 2020.

In that research, Johnson described the metabolic effects of eating the biggest meal of the day in the morning, compared with snacking before bed. “If you eat a large meal at the end of the day, your metabolism preferentially digests those carbohydrates instead of the fat reserves in your body, which can lead to weight gain,” Johnson said. “Our circadian rhythm wants to burn fat during the night when we are sleeping, but if you give your digestive system carbohydrates to burn by snacking between supper and bedtime, it will burn those easily digestible carbohydrates instead.” The results from this informed some of the questions answered in his most recent work.

Has a treatment for Alzheimer’s been sitting on pharmacy shelves for decades? Scientists have two possible candidates

Rush University Medical College, November 1, 2021

Two drugs approved decades ago not only counteract brain damage caused by Alzheimer’s disease in animal models, the same therapeutic combination may also improve cognition.

Sounds like a slam dunk in terms of a cure—but not yet. Researchers currently are concentrating on animal studies amid implications that remain explosive: If a surprising drug combination continues to destroy a key feature of the disease, then an effective treatment for Alzheimer’s may have been hiding for decades in plain sight.

A promising series of early studies is highlighting two well known medicine cabinet standbys—gemfibrosil, an old-school cholesterol-lowering drug, and retinoic acid, a vitamin A derivative. Gemfibrosil, is sold as Lopid and while it’s still used, it is not widely prescribed. Doctors now prefer to prescribe statins to lower cholesterol. Retinoic acid has been used in various formulations to treat everything from acne to psoriasis to cancer.

The two drugs are being studied for their robust impact on the brain and a potential new role that could one day thrust them into fighting what is now an incurable brain disease. Both medications have an uncanny capability to zero in on the brain’s astrocytes, cells that originally got their name because they look like stars. But astrocytes are intimately involved in a key process that progressively—and insidiously—destroys the brain.

Researchers at Rush University Medical Center in Chicago have found that astrocytes may be responsible for the accumulation of amyloid beta (Aβ), the gooey plaque that damages neurons. As a result, these star-like cells aid in the cascade of deleterious events that rob people of their sense of self, their memories, and ultimately steals their lives.

The team of medical investigators also has discovered that gemfibrozil and retinoic acid, when used in combination, force astrocytes to reverse their destructiveness, and instead reduce amyloid beta in the brain—improving cognitive function. The findings suggest that, perhaps in the not-too-distant future, these drugs can be repurposed to coax astrocytes into a beneficial role, serving as Aβ “clearing machines,” eliminating the accumulation of plaques and preventing Alzheimer’s from unraveling the brain.

“From a therapeutic angle, these results suggest that low-dose [gemfibrozil and retinoic acid]
might be repurposed as a treatment for reducing the plaque burden and improving cognition,” wrote Dr. Sumita Raha, first author of a paper published in Science Translational Medicine.

“Astrocytes are a type of glial cell that are implicated in the buildup of amyloid beta in Alzheimer’s disease,” Raha added about the drug duo. Along with her Rush Medical Center colleagues, the team is proposing that rather than being intricately involved in the promotion of Aβ accumulation “astrocytes could be induced to take up and destroy Aβ fibrils with an orally ingested combination of drugs that are approved for other indications.”

Astrocytes studied in cell cultures and in Alzheimer’s mouse models were stimulated by retinoic acid to phagocytose—destroy Aβ—through the activation of the low-density lipoprotein cholesterol receptor and triggered to subsequently degrade Aβ in lysosomes by the cholesterol-lowering drug gemfibrozil.

Earlier research led by Raha’s colleague, Dr. Kalipada Pahan, also of Rush, and an author of the current study, found that a combination of gemfibrozil and retinoic acid accelerated the formation of lysosomes in mouse brain cells. Lysosomes are the organelles that contain digestive enzymes and are involved in the breakdown of excess or worn-out cell parts. The word organelle means “little organ,” a term for the components in cells with specialized functions, such as the Golgi apparatus or mitochondria.

Raha, Pahan, and colleagues discovered that gemfibrosil and retinoic acid also caused mouse astrocytes to take in more amyloid beta from outside of the cell. Their experiments revealed that the drug combination activated a receptor called PPARα, which encouraged astrocytes to destroy the mind-damaging amyloid, the cause of plaques. PPARα stands for peroxisome proliferator-activated receptor-alpha. PPARα is a transcriptional factor that regulates the expression of genes involved in fatty acid oxidation and is also a major regulator of energy homeostasis. PPARα is critical in the elimination of amyloid beta, Aβ.

Gemfibrosil is an old drug, first patented in the 1968 as a cholesterol reducer. Retinoic-acid-based drugs are even older. For example, Tretinoin, a retinoic acid medication, was patented in 1957. If the gemfibrosil/retinoic acid drug combination ultimately works in humans, then the Chicago-based team will have ushered into use a new treatment made up of two very old medications.

Although the team at Rush University Medical Center is well into its pursuit of the two-drug combination, it’s not yet known when the experiments might advance to a full-blown human clinical trial. Yet, along with identifying a potential two-drug approach to Alzheimer’s disease, the Chicago experiments also have added to the scholarship about the biology of astrocytes in the brain.

Astrocytes, or astroglia, as they are also known, are a type of glial cell, and they dramatically outnumber neurons. Some estimates suggest there is a fivefold difference between the two types of brain cells favoring astrocytes. While neurons are the cells of all higher functions, such as learning and memory, astrocytes play a major role regulating increases in intracellular calcium. Upping intracellular calcium is required to maintain astrocyte-to-astrocyte and astrocyte-to-neuron communication, studies have shown.

Yet as the gemfibrosil/retinoic acid combination evolves as a potential Alzheimer’s therapy, the larger story about drugs to treat Alzheimer’s has been a tale marred by setbacks and disappointments for decades. The most recent involves questions that arose following the approval in June of Biogen’s Aduhelm, a medication that carries a breathtakingly high price tag—$56,000 a year in the United States.

Medical experts voiced concern about studies leading to the drug’s approval. Taken as a whole, the research demonstrated mixed results. But the drug, which is administered as an infusion, was fast-tracked through the U.S. Food and Drug Administration’s authorization process.

Worse, Aduhelm is one of slightly more than a half dozen drugs approved in a quarter century to treat Alzheimer’s, a disease that is rapidly becoming one of the largest health crises on the planet, according to the World Health Organization.

Currently, an estimated 55 million people globally have Alzheimer’s disease, and that number could explode to more than 152 million worldwide by 2050 unless a cure is found.

In Chicago, meanwhile, the team at Rush University Medical Center has found a novel way to control Alzheimer’s progression in mouse models using drugs off the shelf. “We found that the same combination of gemfibrosil and retinoic acidenhanced the uptake of Aβ from the extracellular space and its subsequent degradation in astrocytes through a PPARα-dependent pathway,” Raha asserted. “These findings uncover a new function of PPARα in stimulating astroglial uptake and degradation of Aβ and suggest possible repurposing of gemfibrosil-retinoic acidcombination therapy for Alzheimer’s disease.”