Vitamin B3

Form of vitamin B3 may help manage Parkinson’s disease

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Researchers estimate that more than 10 million people around the world have Parkinson’s disease, making it the second most prevalent neurodegenerative disease after Alzheimer’s disease.

There is currently no cure for Parkinson’s disease. Medications, lifestyle changesTrusted Source, and sometimes surgery are used to manage symptoms through the disease’s stages.

Over the past few years, researchers have also looked at nicotinamide adenine dinucleotide (NAD+) — an important molecule that helps the body create energy — as a possible treatment for Parkinson’s disease.

Previous research suggests people with Parkinson’s may have a NAD+ deficiencyTrusted Source, and increasingTrusted Source NAD+ levels may have a positive effect.

Now, a phase 1 clinical trial has found that a high dose supplementation of nicotinamide ribosideTrusted Source (NR) — a source of vitamin B3 and precursor to NAD+ — increased whole blood NAD+ levels and expanded the NAD+ metabolomeTrusted Source in people with Parkinson’s disease, and may be associated with clinical symptomatic improvement for those with the condition.

The research is still in its early stages, and it has not been conclusively proven that NR supplementation can improve the symptoms of Parkinson’s disease.

The study was recently published in the journal Nature CommunicationsTrusted Source.

What are NR and NAD+?

According to Prof. Charalampos Tzoulis, professor of neurology and neurogenetics at the University of Bergen and Haukeland University Hospital, Bergen Norway, and co-lead author of this study, NR is a form of vitamin B3 and a precursor of NAD+.

“NAD+ is an essential coenzyme that plays a vital role in multiple cellular processes, including mitochondrial function — the powerhouses of the cell — and cellular energy metabolism, regulation of gene expression, and DNA repair,” Dr. Tzoulis explained to Medical News Today.

“Research has shown that abnormal energy metabolism, due to dysfunction in the mitochondria, occurs in the Parkinson’s disease brain and is believed to play a role in the initiation and progression of the disease,” he added.

Dr. Daniel Truong, a neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, who was not involved in this study, told MNT that NAD+ levels tend to decline with ageTrusted Source.

“Some potential benefits and uses associated with NR include anti-aging, energy metabolism, mitochondrial function, [and] DNA repair,” Dr. Truong detailed. “Some research suggests that NR might have neuroprotective properties.”

NR supplementation may help in Parkinson’s

This study was part of the ChromaDex External Research Program (CERP™), which donated ChromaDex’s patented NR ingredient, Niagen®, for the advancement of this research.

The phase 1 clinical trial included 20 study participants with idiopathic Parkinson’s disease. Participants received either 3,000 milligrams (mg) of NR in oral supplement form, or a placebo each day for 4 consecutive weeks.

Study participants were then assessed based on clinical and molecular measures, an electrocardiogram, and the severity of Parkinson’s disease symptoms through the MDS-UPDRS rating scale.

Researchers found that NR significantly increased NAD+ levels and modified the NAD+ metabolome in whole blood, compared to those who received the placebo.

Daily supplementation ‘safe’ in the short term

The study also reportedly found the high-dose NR was safe and well-tolerated by study participants, and was associated with a significant improvement of clinical symptoms of Parkinson’s disease, measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), suggesting augmenting NAD+ levels may have a symptomatic anti-Parkinson’s effect.

“The study showed that treatment with high dose NR 3 gr [grams] daily is short-term safe for a month and may, therefore, be explored in larger clinical trials,” Dr. Tzoulis said. “It must be stressed that our study does not establish general safety for this NR dose, or whether it is safe to take for any period longer than 30 days. This remains to be determined in longer studies.”

“In addition, the study showed that NR 3 gr daily leads to a pronounced increase in blood NAD levels and related metabolites, without causing any adverse metabolic effects after 30 days,” he continued.

However, he cautioned that, “[w]hile NR treatment was associated with a small clinical improvement in this study, this cannot be interpreted as a sign of clinical effect, as the study was not designed to detect clinical improvement.”

Would higher doses of NR be safe?

One of the main purposes of the phase 1 study was to determine the short-term safety of 3,000 mg NR daily.

“To harness the full therapeutic potential of NR, we need to explore higher-dose regimens,” Dr. Tzoulis said. “This study establishes the short-term safety of 3,000 mg NR daily and allows high-dose options to be explored in future therapeutic trials.”

Another study, called the NO-PARK study, is still ongoing.

“As for conclusive proof on the therapeutic potential of NR in Parkinson’s disease, we look forward to the results from our year-long NO-PARK phase 2/3 study on 400 persons with Parkinson’s disease, which is already ongoing at our Center and estimated to conclude by the end of 2024,” he added. “Public information on the NO-PARK study can be viewed at neuro-sysmed.no and at clinicaltrials.gov.”

Larger, long-term studies needed

After reviewing this study, Dr. Rocco DiPaola, movement disorders neurologist at the Hackensack Meridian Neuroscience Institute at Jersey Shore University Medical Center, told MNT his first reaction is that it offers a potential treatment that may help slow the progression of Parkinson’s Disease.

“There [are] currently no treatments that offer neuroprotection and this would be a treatment that may help prevent some of the long-term complications related to advancing disease. The current study was on a small scale and short duration to demonstrate safety. A large-scale trial with [a] longer duration of treatment would be necessary to further demonstrate safety and a neuroprotective benefit.”

– Dr. Rocco DiPaola

Dr. Truong agreed, noting that “[the findings are promising, but this is just one study, and its results need to be replicated and expanded upon in larger and longer-term trials, especially double-blind studies.”

“I am intrigued by the mechanism of action proposed in the study, namely the increase in NAD+ levels and its potential neuroprotective effects,” he said.

Dr. Truong noted that it will be interesting to find out how the new findings “could be integrated into current treatment protocols for Parkinson’s disease, considering the safety profile and patient tolerance.”

“Given the current status of treating Parkinson’s disease, any potential new therapeutic avenue is of interest,” Dr. Truong added. “The idea of a supplement that could improve clinical symptoms and potentially slow disease progression is particularly appealing.”

Too much vitamin B3 may contribute to heart disease, study finds.

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Consuming too much niacin may be bad for the heart.

  • There are several non-modifiable and preventable risk factors for heart disease.
  • Researchers recently found that high levels of a common B vitamin called niacin in the body may contribute to cardiovascular disease.
  • They saw that excess niacin can trigger vascular inflammation, which in turn may lead to atherosclerosis — or plaque buildup on artery walls.

About 20.5 million people around the world died from cardiovascular disease in 2021, making it responsible for a third of all deaths globally.

While there are some unmodifiable risk factors for heart disease, including genderTrusted Source, family historyTrusted Source, and ethnicityTrusted Source, there are several preventable causes for cardiovascular disease, including obesityTrusted Source, high cholesterol levelsTrusted Source, high blood pressureTrusted Source, smokingTrusted Source, eating an unhealthy dietTrusted Source, and not getting enough physical activityTrusted Source.

Now, researchers from the Cleveland Clinic Lerner Research Institute have added to the list of potentially modifiable risk factors with a new study reporting high levels of a common B vitamin called niacin in the body may contribute to cardiovascular disease.

The study was recently published in the journal Nature MedicineTrusted Source.

Searching for new heart disease pathways

Finding a potential link between niacin and heart disease was not the original intention of this study, Dr. Stanley Hazen, The Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis, director of the Center for Cardiovascular Diagnostics & Prevention, and director of the Center for Microbiome & Human Health at the Cleveland Clinic Lerner Research Institute, and lead author of this study told Medical News Today.

“Our initial goal was to identify new pathways that contribute to heart disease. Even when treating cardiovascular disease risk factors to goal (e.g. cholesterol, blood pressure, diabetes, etc.), the majority of events (heart attack, stroke, death) continue to occur, or at best, we reduce the event rate by 50%. This means there are other pathways we are not addressing,” Dr. Hazen explained.

Dr. Hazen said he and his team were looking for compounds in the blood that might contribute to the future development of heart attack, stroke, or death independent of traditional risk factors.

“The compound 4PYTrusted Source was identified that is linked to future CVD events — in a U.S. cohort initially, then replication in a U.S. cohort, and further validation in a European cohort,” he continued.

“We then performed preclinical studies (animal model) and cell-based studies — all of which showed this compound contributes to vascular inflammation. 4PY, it turns out, is a breakdown product made from excess niacin,” he told MNT.

What is niacin? 

Niacin — also known as vitamin B-3 — is one of eight different B vitamins.

Niacin helps the body convert foods eaten into energy. It also helps keep the skin healthyTrusted Source and the nervous systemTrusted Source running smoothly.

As the body cannot make niacin, it needs to get it from the foods we eat or via a supplement.

For example, the body convertsTrusted Source the amino acid tryptophanTrusted Source — found in most animal products, including meat and dairy — into niacin.

Niacin can also naturally be found in legumes, whole grains, nuts, and seeds. And there are also some foods, such as cereals and breads, fortified with niacin.

The body does not store niacin — any excess not used is removed from the body via urine.

Higher levels of 4PY associated with adverse cardiac event

For this study, Dr. Hazen and his team studied the fasting plasma from about 1,100 people with stable cardiac health.

Upon analysis, researchers discovered that higher circulating levels of N1-methyl-4-pyridone-3-carboxamide, or 4PY, were strongly associated with the development of a heart attack, stroke, or other unhealthy cardiac events.

“Our studies found high levels of 4PY in the blood predict future cardiac disease. These new studies help identify a new pathway that contributes to heart disease,” Dr. Hazen said.

However, Dr. Hazen said the main takeaway for readers is not that we should cut out our entire intake of niacin — that’s not a realistic or healthy approach.

OTC niacin supplements

“Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the U.S. could be warranted. Patients should consult with their doctors before taking over-the-counter supplements and focus on a diet rich in fruit and vegetables while avoiding excess carbohydrates.”
— Dr. Stanley Hazen

Excess 4PY triggers vascular inflammation

Scientists also found that 4PY directly triggers vascular inflammation, which can damage blood vessels and lead to a buildup of plaque on artery walls, known as atherosclerosis.

“Atherosclerosis is caused by both high cholesterol and inflammation. We know how to treat the high cholesterol side of the equation, but not the inflammation side. This pathway appears to be a major participant in vascular inflammation,” Dr. Hazen said.

“(Our) research uncovered that excess niacin fuels inflammation (and) cardiovascular disease through a newly discovered pathway. (These) findings are significant because they provide a foundation for potential new interventions and therapeutics to reduce or prevent inflammation.”
— Dr. Stanley Hazen

Dr. Hazen said that now with the discovery of this link, there is much more research to do.

“On the one hand, we need to explore what other cardiovascular diseases/phenotypes are linked to 4PY since vascular inflammation is a fundamental contributor to many diseases/phenotypes — e.g. heart failure, stroke, (and) other forms of vascular disease,” he explained.

“Beyond this, we then want to focus on how to disrupt this pathway to leverage the newly gained knowledge to develop a therapeutic,” he added.

Should I stop using niacin supplements?

MNT also spoke with Dr. Cheng-Han Chen, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, about this study.

“This study identifies excess niacin, specifically its breakdown metabolite 4PY, as a risk factor for major adverse cardiovascular events such as heart attack and stroke,” Dr. Chen explained.

“While niacin was previously prescribed as acholesterol-lowering medicationTrusted Source, its use has fallen out of favor as multiple studies did not find as much benefit to cardiovascular health as initially thought. This study will put another nail in the coffin for the use of niacin in heart disease.”
— Dr. Cheng-Han Chen

Dr. Chen said more studies need to be performed to better understand the dose relationship between niacin supplementation and cardiovascular disease.

“For now, I would caution against routine intake of niacin supplements in the average person,” he continued. “It may be more difficult, however, to avoid niacin-fortified foods given its ubiquity in the food chain; niacin fortification may need to be examined at a higher level as a matter of public policy.”

Vitamin B3 might have been made in space, delivered to Earth by meteorites.

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Ancient Earth might have had an extraterrestrial supply of vitamin B3 delivered by carbon-rich meteorites, according to a new analysis by NASA-funded researchers. The result supports a theory that the origin of life may have been assisted by a supply of key molecules created in space and brought to Earth by comet and meteor impacts.

“It is always difficult to put a value on the connection between meteorites and the origin of life; for example, earlier work has shown that vitamin B3 could have been produced non-biologically on ancient Earth, but it’s possible that an added source of vitamin B3 could have been helpful,” said Karen Smith of Pennsylvania State University in University Park, Pa. “Vitamin B3, also called nicotinic acid or niacin, is a precursor to NAD (nicotinamide adenine dinucleotide), which is essential to metabolism and likely very ancient in origin.” Smith is lead author of a paper on this research, along with co-authors from NASA’s Goddard Space Flight Center in Greenbelt, Md., now available online in the journal Geochimica et Cosmochimica Acta. 

This is not the first time vitamin B3 has been found in meteorites. In 2001 a team led by Sandra Pizzarello of Arizona State University, in Tempe discovered it along with related  called pyridine carboxylic acids in the Tagish Lake . 

In the new work at Goddard’s Astrobiology Analytical Laboratory, Smith and her team analyzed samples from eight different carbon-rich meteorites, called “CM-2 type carbonaceous chondrites” and found vitamin B3 at levels ranging from about 30 to 600 parts-per-billion. They also found other pyridine carboxylic acids at similar concentrations and, for the first time, found pyridine dicarboxylic acids. 

“We discovered a pattern – less vitamin B3 (and other pyridine carboxylic acids) was found in meteorites that came from asteroids that were more altered by . One possibility may be that these molecules were destroyed during the prolonged contact with liquid water,” said Smith. “We also performed preliminary laboratory experiments simulating conditions in interstellar space and showed that the synthesis of vitamin B3 and other pyridine carboxylic acids might be possible on ice grains.” 

Scientists think the solar system formed when a dense cloud of gas, dust, and ice grains collapsed under its own gravity. Clumps of dust and ice aggregated into comets and asteroids, some of which collided together to form moon-sized objects or planetesimals, and some of those eventually merged to become planets. 

Space is filled with radiation from nearby stars as well as from violent events in deep space like exploding stars and black holes devouring matter. This radiation could have powered chemical reactions in the cloud (nebula) that formed the solar system, and some of those reactions may have produced biologically important molecules like vitamin B3. 

Asteroids and comets are considered more or less pristine remnants from our solar system’s formation, and many meteorites are prized samples from asteroids that happen to be conveniently delivered to Earth. However, some asteroids are less pristine than others. Asteroids can be altered shortly after they form by chemical reactions in liquid water. As they grow, asteroids incorporate radioactive material present in the solar system nebula. If enough radioactive material accumulates in an , the heat produced as it decays will be sufficient to melt ice inside the asteroid. Researchers can determine how much an asteroid was altered by water by examining chemical and mineralogical signatures of water alteration in meteorites from those asteroids. 

When asteroids collide with meteoroids or other asteroids, pieces break off and some of them eventually make their way to Earth as meteorites. Although meteorites are valued samples from asteroids, they are rarely recovered immediately after they fall to Earth. This leaves them vulnerable to contamination from terrestrial chemistry and life. 

The team doubts the vitamin B3 and other molecules found in their meteorites came from terrestrial life for two reasons. First, the vitamin B3 was found along with its structural isomers – related molecules that have the same chemical formula but whose atoms are attached in a different order. These other molecules aren’t used by life. Non-biological chemistry tends to produce a wide variety of molecules—basically everything permitted by the materials and conditions present—but life makes only the molecules it needs. If contamination from terrestrial life was the source of the vitamin B3 in the meteorites, then only the vitamin should have been found, not the other, related molecules. 

Second, the amount of vitamin B3 found was related to how much the parent asteroids had been altered by water. This correlation with conditions on the asteroids would be unlikely if the vitamin came from contamination on Earth. 

The team plans to conduct additional interstellar chemistry experiments under more realistic conditions to better understand how vitamin B3 can form on  in space. “We used pyridine-carbon dioxide ice in the initial experiment,” said Smith. “We want to add water ice (the dominant component of interstellar ices) and start from simpler organic precursors (building-block molecules) of B3 to help verify our result.”