Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

In continuation of my update on Nicotineamide

Nicotinamide supplementation was associated with a decreased risk for melanoma among patients with a history of other skin cancers, according to a retrospective cohort study of more than 33,000 veterans.

The study, which won a first-prize poster award at the American Academy of Dermatology (AAD) 2026 Annual Meeting, “suggests that nicotinamide could potentially be effective for primary prevention of melanoma among patients who have had a prior nonmelanoma skin cancer,” noted Lee Wheless, MD, PhD, one of the senior authors, an assistant professor of dermatology at Vanderbilt University and a staff physician with the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee.

The effect of nicotinamide, at a dose of 500 mg twice daily, was statistically significant for invasive, but not in situ, melanoma, and it was consistent in both sun-exposed and sun-protected areas, he told Medscape Medical News.

The retrospective cohort study used data from the Veterans Affairs (VA) Corporate Data Warehouse from January 1, 2007, to December 31, 2024. It included a total of 33,581 patients with one or more prior skin cancers of any type. The cohort was predominantly White and men, with comparable mean ages (77.5 years in the exposed group vs 77.1 years in the unexposed group).

The US Department of VA offers nicotinamide, a vitamin B3 derivative, on formulary. Patients exposed to nicotinamide 500 mg twice daily were propensity score matched to unexposed patients based on “numerous skin cancer risk variables to make sure risks at specific timepoints in the patients’ lives matched up,” explained Wheless.

Baseline matching variables included age, sex, race, age at first skin cancer, number and year(s) of prior skin cancers of any type, number of dermatology visits after baseline, chronic lymphocytic leukemia, solid organ transplantation, exposure to acitretin, and field therapy.

More...

https://en.wikipedia.org/wiki/Nicotinamide

Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

Discovery of compound that reverses the fertility clock

                                

Nicotinamide adenine dinucleotide (NAD)     

 Nicotinamide mononucleotide ("NMN", "NAMN", and "β-NMN") 

The reproductive years of a woman are at their peak before the age of 30. Beyond that, fertility starts to decline, and by the age of 40, fertility potential is about half the level it was before 30 years old. Many women experience fertility issues, but now a new study on mice may help reverse the clock on eggs, offering new fertility hope to older women.

A team of scientists at the University of Queensland reports that they have lifted fertility rates in older female mice with the use of a compound, which can reverse the aging process in eggs. The discovery may pave the way for human use in the future, offering hope for some women who are struggling to conceive.

When women reach the age of 40, conceiving is harder and nearly impossible for some women. This loss of fertility is due to poor egg quality, something that becomes a problem in developed countries where women would wait until they're older before they get married and bear children.

Newfound hope

Published in the journal Cell Reports, the study highlights reversing the fertility clock, improving egg quality that's important for pregnancy success. The team found that losing egg quality due to aging was because of the declining levels of a cell molecule that's vital for producing energy.

Taking an oral dose of a precursor compound, which is utilized to create the molecule, can help boost fertility. The molecule called nicotinamide adenine dinucleotide (NAD) and the precursor, nicotinamide mononucleotide (NMN), are key drivers to promote reversal of aging fertility.

To arrive at their findings, the team treated aging female mice with low doses of NMN infused in their drinking water for one month. They found that the mice had restored egg quality and increased live births during a breeding trial.

Assisted reproductive technologies

The new treatment, if applicable to humans, can help maintain and restore egg cell quality during aging. Further, it helps reduce a rate-limiting barrier to pregnancy for older women. With more aging women facing fertility problems, there had been a sharp increase in the demand for assisted reproductive technologies, including In vitro fertilization (IVF).

However, since the study involved mice models, it's essential to conduct further research on humans to determine if the effect of the compound is the same.

"IVF cannot improve egg quality, so the only alternative for older women at present is to use eggs donated by younger women," UQ's Professor Hayden Homer said in a statement.

"Our findings suggest there is an opportunity to restore egg quality and, in turn, female reproductive function using oral administration of NAD-boosting agents – which would be far less invasive than IVF. It is important to stress, however, that although promising, the potential benefits of these agents remains to be tested in clinical trials," he added.

Infertility by the numbers

Infertility is a growing concern among couples who are having a hard time conceiving. The Centers for Disease Control and Prevention (CDC) defines infertility as the inability to get pregnant after one year of unprotected sex; it may be longer for some. For women who are 35 years old and beyond, doctors may begin treatment if they fail to conceive within six months of regular and unprotected sex.

In the United States, about 6 percent of married women between the age of 15 and 44 are having problems conceiving after one year of trying. Moreover, approximately 12 percent of women of the same age group have issues getting pregnant or carrying a pregnancy to term.

About 12 to 13 of 100 couples have trouble becoming pregnant in the country, while ten in 100 or 6.1 million women have problems getting pregnant. Fertility issues in women cause one-third of all infertility cases.

Worldwide, one in every four couples in developing countries are experiencing infertility, but the exact rates are hard to determine. The latest data were responses from women in Demographic and Health Surveys in 2004. However, in a 2010 study by the WHO, it shows that the rates in 190 countries remained similar to the estimated numbers between 1990 and 2010.

https://www.sciencedirect.com/science/article/pii/S2211124720300838?via%3Dihub

https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide

https://en.wikipedia.org/wiki/Nicotinamide_mononucleotide

Nicotinamide riboside can protect against obesity

A natural ingredient found in milk can protect against obesity even as mice continue to enjoy diets that are high in fat. 

The researchers identified this ingredient, known as nicotinamide riboside (see structure), as they were searching for alternative ways to boost the well-known gene SIRT1, which comes with benefits for both metabolism and longevity. One way to do that is to target SIRT1 directly, as the red wine ingredient resveratrol appears to do, at least at some doses.

Auwerx's team lead by Johan Auwerx, suspected there might be a simpler way to go about it, by boosting levels of one of SIRT1's molecular sidekicks, the cofactor NAD+. 

This milk ingredient does just that in a rather appealing way. Not only is it a natural product, but it also gets trapped within cells, where it can do its magic.

Mice that take nicotinamide riboside in fairly high doses along with their high-fat meals burn more fat and are protected from obesity. They also become better runners thanks to muscles that have greater endurance.

http://www.youtube.com/embed/5YwzyqXzntY

Nicotinamide riboside can protect against obesity

Compound prevents neurological damage, shows cognitive benefits in mouse model of Alzheimer’s disease

The supplement nicotinamide riboside (NR) – a form of vitamin B3 – prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease. The results of the study, conducted by researchers at the National Institute on Aging (NIA) part of the National Institutes of Health, suggest a potential new target for treating Alzheimer’s disease. The findings appear in the Feb. 5, 2018, issue of Proceedings of the National Academy of Sciences.

NR acts on the brain by normalizing levels of nicotinamide adenine dinucleotide (NAD+), a metabolite vital to cellular energy, stem cell self-renewal, resistance to neuronal stress and DNA repair. In Alzheimer’s disease, the brain’s usual DNA repair activity is impaired, leading to mitochondrial dysfunction, lower neuron production, and increased neuronal dysfunction and inflammation.

“The pursuit of interventions to prevent or delay Alzheimer’s and related dementias is an important national priority,” said Richard J. Hodes, M.D., director of the NIA. “We are encouraging the testing of a variety of new approaches, and this study’s positive results suggest one avenue to pursue further.”

The international team of scientists was led by Vilhelm A. Bohr, M.D., Ph.D., senior investigator and chief of the Laboratory of Molecular Gerontology of the NIA’s Intramural Research Program, with Dr. Yujun Hou, a postdoctoral investigator in the laboratory.

Based on their studies in human postmortem brain, they developed a new strain of mice mimicking major features of human Alzheimer’s such as tau pathology, failing synapses, neuronal death and cognitive impairment. Using this animal model, the researchers tested the effects of an NR supplement by adding it to the drinking water of the mice. Over a three-month period, researchers found that mice who received NR showed reduced tau in their brains, but no change in amyloid-beta.

The NR-treated mice also had less DNA damage, higher neuroplasticity (activity and reorganization of brain cells associated with learning or memory), increased production of new neurons from neuronal stem cells, and lower levels of neuronal damage and death. In the hippocampus area of the brain – in which damage and loss of volume is found in people with dementia – NR seemed to either clear existing DNA damage or prevent it from spreading further.

The NR-treated mice also performed better than control mice on multiple behavioral and memory tests, such as water mazes and object recognition. NR mice also showed better muscular and grip strength, higher endurance, and improved gait compared to their control counterparts. The research team believes that these physical and cognitive benefits are due to a rejuvenating effect NR had on stem cells in both muscle and brain tissue.

“We are encouraged by these findings that see an effect in this Alzheimer’s disease model,” said Dr. Bohr. “We are looking forward to further testing of how NR or similar compounds might be pursued for their possible therapeutic benefit for people with dementia.”

Next steps for the research team include further studies on the underlying mechanisms and preparations towards intervention in humans.

The team’s work also included contributions from researchers at the Danish Aging Research Center at the University of Aarhus, and the Center for Healthy Aging at the University of Copenhagen. The Bohr lab has a Cooperative Research and Development Agreement -- which allows NIH investigators to join colleagues from industry and academia to pursue common research goals -- with ChromaDex Corp.

Compound prevents neurological damage, shows cognitive benefits in mouse model of Alzheimer’s disease

Carboranes Increase the Potency of Small Molecule Inhibitors of Nicotinamide Phosphoribosyltranferase - Journal of Medicinal Chemistry (ACS Publications)

We know that,  carborane is a cluster composed of boron and carbon atoms. Like many of the related boranes, these clusters are polyhedra and are similarly classified as closo-, nido-, arachno-, hypho-, etc. based on whether they represent a complete (closo-) polyhedron, or a polyhedron that is missing one (nido-), two (arachno-), or more vertices. Interesting examples of carboranes are the extremely stable icosahedral closo-carboranes.

A prominent example is the charge-neutral C₂B₁₀H₁₂ or o-carborane with the prefix o derived from ortho, which has been explored for use in a wide range of applications from heat-resistant polymers to medical applications.  

Now researchers lead by Dr. Lee of University of Missouri used carboranes to build new drugs designed to shut off a cancer cell's energy production, which is vital for the cell's survival. All cells produce energy through complex, multi-step processes. The key to an effective drug is targeting the process that cancer cells depend on more than healthy cells. By increasing the binding strength of a drug, a smaller dose is required, minimizing side effects and increasing the effectiveness of the therapy. With carboranes, Lee found that the drug is able to bind 10 times more powerfully.

"The reason why these drugs bind stronger to their target is because carboranes exploit a unique and very strong form of hydrogen bonding, the strongest form of interactions for drugs," Lee said.

Lee said that this discovery also will lead to further uses for the drug.

"Too often, after radiation or chemotherapy, cancer cells repair themselves and reinvade the body," Lee said. "This drug not only selectively shuts off the energy production for the cancer cells, but it also inhibits the processes that allow those cancer cells to repair themselves. When we tested our carborane-based drugs, we found that they were unimaginably potent. So far, we have tested this on breast, lung and colon cancer, all with exceptional results."

According to Lee, this is the first study to show systematically how carboranes can improve the activity of a drug. Lee believes this discovery will open additional possibilities of improving drugs that are used to treat other diseases, not just cancer.

"The end result is that these new drugs could be many thousands of times more potent than the drugs that are used in the clinics today," Lee said.

 Carboranes Increase the Potency of Small Molecule Inhibitors of Nicotinamide Phosphoribosyltranferase - Journal of Medicinal Chemistry (ACS Publications)