Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain."

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

Scientists discover strange link between vitamin D and pain 

Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D 

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain.

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

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

Scientists discover strange link between vitamin D and pain | ScienceDaily

Vitamin D Deficiency Linked to Fatigue, Studies Show

In continuation of my update on Vitamin D

Prevalence and Link to Fatigue

Approximately 40% to 75% of the teen and adult population in the United States is deficient in vitamin D, according to Raymond Francis in “The Great American Health Hoax.” ^[1] Low energy and occasional fatigue are commonly reported among individuals with low vitamin D status, according to a report on the silent epidemic of nutrient deficiencies. ^[2] The scale of the problem is vast, with estimates suggesting that nearly half of all adults may have insufficient levels, the report stated.

Vitamin D deficiency is not confined to a single demographic. Factors such as limited sun exposure, darker skin pigmentation, and indoor lifestyles contribute to widespread insufficiency, researchers said. The link between low vitamin D and fatigue has been documented in multiple studies, though many individuals remain unaware of their own deficiency status.

Mechanism: Vitamin D and Cellular Energy

Vitamin D supports mitochondrial function, which is responsible for cellular energy production, according to research cited in an article on fatigue and mitochondria. ^[3] The mitochondria act as the powerhouses of the cell, generating adenosine triphosphate (ATP) from nutrients. A deficiency may disrupt mitochondrial efficiency, contributing to feelings of lethargy, experts said. ^[4]

The role of mitochondria in energy production is central to understanding why vitamin D insufficiency can lead to persistent tiredness. As noted in the book “Dissolving Illusions,” proper mitochondrial metabolism is essential for normal cellular function, and any disruption can manifest as weakness or apathy. ^[5] Although that text focuses on vitamin C, the principle applies broadly to nutrients that support mitochondrial health, including vitamin D.

Supporting Studies

Multiple studies have reported a connection between low vitamin D levels and fatigue. A 2016 study of 200 female nurses in Iran found that low vitamin D levels accounted for 13% to 18% of reported prolonged tiredness, according to a review of nutrient deficiencies. ^[2] A 2019 study published in Nutrients similarly found that older adults with occasional fatigue had a significantly worse vitamin D status than those without fatigue, the review added. ^[2]

Other research has reinforced these findings. In a broader analysis, researchers noted that individuals frequently reporting low energy were more likely to have suboptimal vitamin D levels compared to their peers, according to an article on fatigue and mitochondrial function. ^[4] The consistency of the association across different populations suggests a robust relationship, though causation requires further investigation, scientists said.

Other Health Impacts

Beyond fatigue, vitamin D deficiency has been linked to several other health issues. Vitamin D directly modulates the body’s innate and adaptive immune responses, according to a review of the critical role of vitamin D in immune function. ^[6] Immune cells require adequate vitamin D to respond efficiently to threats, the review stated. Low levels have also been associated with increased susceptibility to infections and longer recovery times.

Vitamin D also influences bone health and cellular aging. Raymond Francis wrote that vitamin D is essential for calcium metabolism, supports bone health, helps control blood sugar, and protects against cancer. ^[1] The nutrient significantly increases the production of telomerase, an enzyme that repairs telomeres and slows aging, according to the same source. ^[1] These wide-ranging effects underscore the importance of maintaining optimal levels.

Solutions: Increasing Vitamin D Levels

Optimal vitamin D levels are considered to be above 50 nanograms per milliliter, and supplementation with 5,000 IU daily is recommended by some nutritionists, according to an interview on health testing and supplementation. ^[7] At-home blood tests can help individuals assess their current levels, the interview stated. ^[7] Testing allows for personalized dosing rather than generic recommendations.

The safety of higher vitamin D doses has been affirmed by recent reassessments. A news report noted that a “schoolboy error” in earlier guidelines led to overly cautious upper limits, and the Academy of Medicine has since acknowledged that higher intakes are not toxic for most people. ^[8] Dietary sources such as fatty fish, egg yolks, and fortified foods can also contribute, though supplementation is often the most reliable way to correct a deficiency, experts said.

Conclusion

Individuals experiencing unexplained fatigue may consider testing their vitamin D levels, clinicians advised. ^[7] Supplementation and dietary changes can help restore levels to the optimal range, though consulting a healthcare provider is recommended before starting any regimen, according to the interview. ^[7]

The evidence linking vitamin D deficiency to fatigue is supported by prevalence data, mechanistic studies, and clinical observations. Given the high rates of insufficiency in the general population, testing and appropriate supplementation offer a straightforward strategy for addressing a common but often overlooked contributor to low energy, researchers concluded.

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

Vitamin D Deficiency Linked to Fatigue, Studies Show 

FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that the U.S. Food and Drug Administration (FDA) approved Palsonify (paltusotine) for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Palsonify, a selectively-targeted somatostatin receptor type 2 nonpeptide (SST2) agonist, is now the first once-daily, oral treatment approved for adults with acromegaly.

“With the FDA approval of our lead therapy Palsonify, today marks a new era for those living with acromegaly and also for Crinetics as a company,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. “We are very pleased to be fulfilling our commitment to transforming patient lives. This approval is the first to come from our deep pipeline of first-in-class, small molecule drugs. This would not be possible without the help and partnership of people living with acromegaly, their caretakers, our employees, and the clinical researchers and health care professionals who contributed to Palsonify’s successful development program. Thank you to all involved.”

The approval is based on data from the PATHFNDR-1 and PATHFNDR-2 Phase 3 pivotal trials, which evaluated Palsonify’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, Palsonify consistently demonstrated rapid onset, reliable biochemical control, and sustained efficacy.

Participants also reported significant reductions in signs and symptoms associated with acromegaly as measured by the Acromegaly Symptom Diary (ASD) — an FDA-aligned patient-reported outcome tool developed to capture the symptoms that matter to people living with acromegaly. Symptoms include headaches, joint pain, sweating, fatigue, weakness, swelling, and/or numbness/tingling. Palsonify was generally well-tolerated, with no serious adverse events reported in the randomized controlled portion of the trial.

Long-term results from the open-label extension (OLE) phases of both trials were presented at this year’s Endocrine Society’s annual meeting, ENDO 2025, providing further evidence of Palsonify’s ability to deliver durable IGF-1 control, sustained improvements in patient symptom burden, and a consistent safety profile. Ninety-one percent of patients from PATHFNDR-1 and 97 percent of completers from PATHFNDR-2 enrolled in the OLE.

“The PATHFNDR clinical development program set a new standard for acromegaly treatment by demonstrating the ability of Palsonify to drive both biochemical and symptom control, regardless of the degree of underlying disease severity,” said Dr. Shlomo Melmed, Executive Vice President of Medicine and Health Sciences and Dean of the Medical Faculty at Cedars-Sinai, “The approval of Palsonify is a significant advancement for our patients, as there is an unmet need for an easy-to-administer and safe therapeutic option with a rapid action and durable response that can consistently manage acromegaly.”

“For people living with acromegaly, treatment once meant burdensome injections, breakthrough symptoms, and lifestyle sacrifices just to stay on track,” said Jill Sisco, President of Acromegaly Community. “What matters most to our community – maintaining consistent control so the disease doesn’t control us – led us to partner with the FDA on Externally Led Patient-Focused Drug Development meetings. This new treatment reflects that our voices have been heard in shaping the next generation of acromegaly care.”

Palsonify is expected to be available in the U.S. in early October. Crinetics is ensuring broad access to Palsonify by working closely with payers, healthcare providers, and patient advocacy organizations to support those who may benefit from this treatment.

As part of this commitment, Crinetics has launched CrinetiCARE®, a comprehensive support program designed to assist people living with acromegaly throughout their treatment journey. CrinetiCARE provides disease and product education, benefit verification, financial assistance resources, and access to dedicated nurse educators who can offer support with treatment onboarding and ongoing adherence.

A Marketing Authorization Application (MAA) for paltusotine in acromegaly is currently under review for use in the European Union, and the current timeline for the Committee for Medicinal Products and Human Use (CHMP) opinion is the first half of 2026. Crinetics is in partnership with Sanwa Kagaku Kenkyuso (SKK) to develop and commercialize paltusotine for acromegaly in Japan.

Paltusotine is also being evaluated for the treatment of carcinoid syndrome in the pivotal Phase 3 CAREFNDR trial. Global enrollment for CAREFNDR is expected throughout 2025.

Palsonify (paltusotine) INDICATION:

Palsonify is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS:

Cholelithiasis and Its Complications: Cholelithiasis, including related complications such as acute cholecystitis and pancreatitis, have been reported. Monitor patients periodically. Discontinue Palsonify if complications of cholelithiasis occur and treat appropriately.

Hyperglycemia and Hypoglycemia: Hyperglycemia, diabetes mellitus, or hypoglycemia, may occur. Monitor blood glucose levels when Palsonify treatment is initiated or when dosage is altered. Adjust antidiabetic treatment accordingly.

Cardiovascular Abnormalities: Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation, bradycardia, sinus arrest, and atrioventricular block may occur in patients with acromegaly and were reported in Palsonify clinical trials. Dosage adjustments of concomitant drugs that have bradycardic effects may be necessary.

Thyroid Function Abnormalities: Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function is recommended.

Steatorrhea and Malabsorption of Dietary Fats: Somatostatin analog treatment may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new or worsening symptoms are reported with Palsonify, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.

Vitamin B12 Deficiency: Vitamin B12 deficiency may occur. Monitor vitamin B12 levels, if clinically indicated.

ADVERSE REACTIONS:

Most common adverse reactions (>5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.

FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

Daily Multivitamin May Protect Against Cognitive Decline in Older Adults

In continuation of my update on Vitamin and their importance 

A daily multivitamin may provide cognitive benefits for older adults, according to a study published online Sept. 14 in Alzheimer’s & Dementia.

Laura D. Baker, Ph.D., from the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues assessed whether daily use of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in 2,262 older women and men (mean age, 73 years).

The researchers found that cocoa extract had no effect on global cognition. However, compared with placebo, daily MVM supplementation resulted in a statistically significant benefit on global cognition, with a more pronounced effect seen in participants with a history of cardiovascular disease. Benefits of MVM were also seen for memory and executive function. There were no significant interactions observed between cocoa extract and MVM for any of the cognitive composites.

"Our study showed that although cocoa extract did not affect cognition, daily multivitamin-mineral supplementation resulted in statistically significant cognitive improvement. This is the first evidence of cognitive benefit in a large longer-term study of multivitamin supplementation in older adults," Baker said in a statement. "It's too early to recommend daily multivitamin supplementation to prevent cognitive decline. While these preliminary findings are promising, additional research is needed in a larger and more diverse group of people."

Ref : Daily Multivitamin May Protect Against Cognitive Decline in Older Adults 

Is Green Tea a Fad or a Real Health Boost?

In continuation of my updates on Green tea

Green tea is a popular health trend, with many people sipping in hopes of deriving benefits from the brew.

There's nothing wrong with that, dietitians say -- green tea is a healthy drink loaded with antioxidants. But the jury's still out on many of its purported health benefits.

"Clinical trials related to green tea are still in their early stages," said Nancy Farrell Allen, a registered dietitian nutritionist in Fredericksburg, Va. "I say drink it, enjoy it. It's not going to hurt, and it might have worthy benefits to it. But nutrition is a science, and it takes time for our understanding to evolve."

Green tea's potential health benefits derive from catechins, which are powerful antioxidant compounds known as flavonoids, said Chelsey Schneider, clinical nutrition supervisor at Mount Sinai Beth Israel Cancer Center in New York City.

One catechin in particular, known as EGCG, is found at higher levels in green tea than in either white or black tea, she said.

"This compound can be even stronger than vitamin C and E, which are very, very strong antioxidants," Schneider said. Antioxidants help prevent damage to cells.

Green, black and white tea all come from the same plant, said Allen, who is a spokeswoman for the Academy of Dietetics and Nutrition.

Green tea is made from the leaves of the mature plant, while white tea is made of leaves plucked early in development. Black tea is made from green tea leaves that are laid out and covered with a damp cloth, she said.

"They dry and blacken and ferment a little, giving black tea that darker, richer flavor," Allen said. But this process also reduces levels of catechins in black tea.

Weight loss has been associated with green tea, with experts suggesting that its mixture of caffeine and catechins can enhance a person's metabolism and processing of fat, according to the University of California-Davis Department of Nutrition.

But it appears that folks have to drink a lot of green tea to get substantial weight loss benefits and carefully watch the rest of their diet, UC-Davis says.

Green tea also has been tied to heart health.

For example, green tea was shown to reduce "bad" LDL cholesterol in a 2018 study of more than 80,000 Chinese published in the Journal of the American Heart Association.

Evidence suggests catechins in green tea also could lower risk of heart attacks, help blood vessels relax and reduce inflammation, UC-Davis says.

Green tea even has been associated with a lower risk of some cancers.

The American Cancer Society says studies have linked green tea to a reduction in ovarian cancer risk. And UC-Davis said experimental models have shown that green tea might reduce risk of a variety of other cancers.

But a 2016 evidence review by the Cochrane Library concluded that there is "insufficient and conflicting evidence to give any firm recommendations regarding green tea consumption for cancer prevention."

Schneider said the research is limited. "Some small studies say green tea can maybe be preventative for certain cancers, like breast, ovarian, endometrial, pancreatic and oral cancers, but there aren't so many conclusive human trials that support that," she said.

Green tea also might help keep your brain younger. A 2014 study in the journal PLOS One found that Japanese who drank more green tea had significantly less decline in brain function, although researchers couldn't rule out the possibility that these folks might have other healthy habits that helped keep them mentally sharp.

One caveat with all of this research is that it tends to take place in Asian countries, where people drink much more green tea. There might be significant differences for Americans.

And the way you take your green tea could diminish any potential positive effects, Schneider added.

"A lot of people are adding processed white sugar to their green tea, which really makes something beautiful and healthy into something unhealthy," she said.

Adding milk or cream to your tea also might not be a good idea.

"There are some studies that say having milk in green tea can actually block the effects of you absorbing the antioxidant," Schneider said. "If it was me, I'd drink it straight up."

FDA Approves Sorilux for Adolescent Plaque Psoriasis

In continuation of my update on Sorilux(calcipotriene) 

 

Mayne Pharma Group Limited, announced that the US Food and Drug Administration (FDA) has approved Sorilux(calcipotriene) Foam, 0.005% in adolescents.

Sorilux is now approved for treating plaque psoriasis of the scalp and body in patients aged 12 years and older.

The FDA approved Sorilux in 2010 based on evidence from two 8-week placebo controlled clinical trials in patients with mild to moderate plaque psoriasis of the body and one 8-week placebo controlled clinical trial in patients with moderate plaque psoriasis of the scalp. Further data was obtained in a follow-on open label study in patients aged 12 to 17 years of age with psoriasis.

Sorilux Foam contains calcipotriene, a synthetic vitamin D analog that has a similar receptor binding affinity as natural vitamin D. The exact mechanism of action contributing to the clinical efficacy is unknown.

Psoriasis is a chronic disease of the immune system affecting approximately 7.5 million Americans each year[1]. The most common form, plaque psoriasis affects roughly 80 percent of people who have the condition.

Mayne Pharma's CEO, Mr Scott Richards, said "Sorilux is an elegant foam formulation that is marketed by Mayne Pharma's Specialty Brands sales team alongside recently launched LEXETTE™ (halobetasol propionate) Foam, a potent topical corticosteroid also used to treat plaque psoriasis in adult patients. Topical products are the mainstay of treatment for plaque psoriasis patients and the foam delivery platform has a well-established reputation with dermatologists due to ease of application and lack of greasiness and stickiness, especially in hair-bearing areas and under clothing."

Mayne Pharma directly markets more than 60 products in the US including four branded dermatology products FABIOR® (tazarotene) Foam, Sorilux Foam, DORYX® MPC (doxycycline hyclate) delayed-release tablets and LEXETTE Foam. The Company also markets TOLSURA® (SUBA®-itraconazole) capsules used to treat certain fungal infections which was recently approved and launched this year.

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

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

High vitamin D levels may help prevent cancer

In continuation of my update on Vitamin D, 

The study reinforces the existing theory that vitamin D helps defend against certain cancers. Exposure to sunlight stimulates the production of vitamin D by our skin. Vitamin D contributes to calcium level maintenance in our bodies, which in turn helps teeth, muscles and bones remain healthy. Aside from established benefits of vitamin D on bone diseases, evidence continues to emerge that vitamin D could be effective for other cancers and chronic diseases.   

Yet more comprehensive research needs to be conducted, as to date, the majority of studies have been conducted throughout American and European populations, and more studies focusing on Asian populations are necessary.
It is vital to determine whether the effects are the same in non-Caucasian populations, since Vitamin D metabolism and concentrations differ dependant on ethnicity.
The study published by the BMJ was carried out to determine if vitamin D was linked to site specific and total cancer.

Data spanning nine public health centres across Japan was analysed, from 33,736 female and male participants between the ages of 40 and 69 years old.
Participants were required to disclose a comprehensive overview of their lifestyle, diet and medical history and have blood samples taken to assess their vitamin D levels. Factors such as seasons affected vitamin D levels; summer and autumn typically produced higher levels compared to spring or winter. Samples were then assigned to one of four groups, based on levels.

Researchers then monitored the study participants for a mean period of 16 years, during which 3,301 new cancer cases were registered.
Once multiple known cancer risk factors had been accounted for, including weight (BMI), physical activity, age, dietary factors, smoking and alcohol intake, researchers discovered that high levels of vitamin D  reduced the overall risk of cancer by 20% in both women and men.

Higher levels were linked to a 30-50% lower relative risk of liver cancer, and more so in men than women. No cancers exhibited a higher risk connected to high vitamin D levels, and there was no evidence of a link to prostate or lung cancer.
Adjustments were made for dietary and other factors to confirm the strength of the findings, but this did little to affect the results. One limitation of the study was an insufficient number of organ specific cancers. In addition, even with the risk factor adjustments, there is no absolute certainty that the results were skewed by unidentified factors.  For this reason, no concrete conclusions about cause and effect can be asserted.

The large sample size for overall cancer, large number of blood samples tested and the extensive follow up period were vital strengths of the study. The result reinforce the theory that vitamin D has a role in defending against the risk of cancer, but the authors emphasize that vitamin D may carry additional health benefits too, that were not measured in this study.  

Further studies are needed to clarify the optimal concentrations (of vitamin D) for cancer prevention."

Further studies are needed to clarify the optimal concentrations (of vitamin D) for cancer prevention."

Ref : https://www.eurekalert.org/pub_releases/2018-03/b-hvd030618.php

High vitamin D levels may help prevent cancer

Vitamin A Compound Might Aid in Colon Cancer Fight

In continuation of my update on Retinoic acid

Retinoic acid, a compound derived in the body from vitamin A, might have a role in suppressing colon cancer, new animal research suggests.

"Retinoic acid has been known for years to be involved in suppressing inflammation in the intestine," said study senior author Dr. Edgar Engleman, professor of pathology and medicine at Stanford University School of Medicine in Palo Alto, Calif.

Meanwhile, the development of colon cancer has been linked to inflammation. For example, inflammatory bowel disease, such as ulcerative colitis, has been associated with colon cancer, he said in a university news release.

"We wanted to connect the dots and learn whether and how retinoic acid levels directly affect cancer development," Engleman added.

When the researchers looked at mice with colon cancer, they saw lower levels of retinoic acid in the intestines of the mice.

The researchers also found that boosting levels of retinoic acid in the intestines of mice with colon cancer slowed progression of the disease.

In humans, colon cancer patients who had high levels of a protein that degrades retinoic acid in their intestinal tissue tended to have worse outcomes than other patients, the study authors noted.

The findings suggest new ways to prevent or treat colon cancer. However, it's important to note that animal research doesn't always produce the same results in humans.

"The intestine is constantly bombarded by foreign organisms. As a result, its immune system is very complex," Engleman said.

"We found that bacteria, or molecules produced by bacteria, can cause a massive inflammatory reaction in the gut that directly affects retinoic acid metabolism," he said.

He said that retinoic acid levels are normally regulated very tightly.

"Now that we've shown a role for retinoic acid deficiency in colorectal cancer, we'd like to identify the specific microorganisms that initiate these changes in humans. Ultimately we hope to determine whether our findings could be useful for the prevention or treatment of colorectal cancer," he concluded.

The study was published online Aug. 30 in the journal Immunity.

FDA Approves Rayaldee (calcifediol) to Treat Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

OPKO Health, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Rayaldee (calcifediol) extended release capsules for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee is a patented extended release product containing 30 mcg of a prohormone called calcifediol (25-hydroxyvitamin D3).

 calcifediol

"FDA's approval of Rayaldee represents an important milestone for OPKO," noted Dr. Phillip Frost, CEO and Chairman of OPKO. "Rayaldee is the first product to receive FDA approval for this important indication and is one of OPKO's many pharmaceutical products being developed for significant medical problems which will benefit from new treatment options."

Results from two 26 week placebo controlled, double blind phase 3 trials demonstrated that a larger proportion of stage 3 or 4 CKD patients with SHPT and vitamin D insufficiency achieved ≥30% reductions in plasma intact parathyroid hormone (iPTH) when treated with Rayaldee than with placebo. Vitamin D insufficiency was corrected in more than 80% of the patients receiving Rayaldee compared with less than 7% of subjects receiving placebo. Mean serum calcium and phosphorus levels increased by 0.1 mg/dL during Rayaldee treatment compared to placebo treatment, but these changes were deemed clinically irrelevant. No differences in Rayaldee's efficacy or safety were observed between patients with stage 3 CKD or stage 4 CKD.

"Rayaldee fills a large void in the current treatment options for SHPT in predialysis patients," commented Dr. Charles W. Bishop, CEO of OPKO's Renal Division. "The current standard of care is high dose vitamin D supplementation, an approach for treating SHPT that is neither FDA approved nor demonstrated to be safe and effective in this population. SHPT is a progressive disease that becomes increasingly debilitating and difficult to treat, necessitating timely and effective treatment."

"Rayaldee is an important new option for treating SHPT in patients with stage 3 or 4 CKD and vitamin D insufficiency," stated Kevin J. Martin, Director of Research, Division of Nephrology at Saint Louis University School of Medicine. "The great majority of SHPT cases in this patient population are associated with vitamin D insufficiency, a problem that Rayaldee can correct."

About Rayaldee

Rayaldee (calcifediol) extended release capsules are approved by the U.S. Food and Drug Administration (FDA) for the treatment of SHPT in adult patients with stage 3 or 4 CKD and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee has a patented formulation designed to raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) and to reduce elevated iPTH. OPKO expects to launch Rayaldee in the U.S. through its dedicated renal sales force in the second half of 2016. Rayaldee is not indicated in patients with stage 5 chronic kidney disease or end-stage renal disease on dialysis. The full prescribing information for Rayaldee will be available at www.opkorenal.com.

Potential side effects of Rayaldee include hypercalcemia (elevated serum calcium), which can also lead to digitalis toxicity, and adynamic bone disease with subsequent increased risk of fractures if intact PTH levels are suppressed by Rayaldee to abnormally low levels. Severe hypercalcemia may require emergency attention; symptoms of hypercalcemia may include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss. Digitalis toxicity can be potentiated by hypercalcemia of any cause. Excessive administration of Rayaldee can cause hypercalciuria, hypercalcemia, hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of vitamin D overdosage may include constipation, decreased appetite, dehydration, fatigue, irritability, muscle weakness, or vomiting. Patients concomitantly taking cytochrome P450 inhibitors, thiazides, cholestyramine, phenobarbital or other anticonvulsants may require dose adjustments and more frequent monitoring.

The most common adverse reactions in clinical trials (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.

One-third of osteoporotic women taking oral bisphosphonates have elevated risk for bone fracture

Chemical structure of pyrophosphate (A, above) and bisphosphonates (B, below). P = phosphorus, O = oxygen, H = hydrogen, C = carbon, R = side chain. In bisphosphonates, the central oxygen atom is replaced with a carbon atom. All bisphosphonates share a common phosphorus-carbon-phosphorus motif with two side chains (R1 and R2 in the figure). The R2 side chain determines the chemical properties of the drug, and distinguishes individual types of bisphosphonates. This chemical structure affords a high affinity for calcium hydroxyapatite, allowing for rapid and specific skeletal targeting.

More than 53 million Americans age 50 and older, primarily women, have osteoporosis or are at high risk for the condition due to low bone density. A recent study of oral bisphosphonates, the most commonly prescribed osteoporosis treatment, found that approximately a third of women prescribed these drugs continue to be at elevated risk for bone fracture, an outcome that may have several origins.

Oral bisphosphonates are a pillar of preventive treatment for patients with osteoporosis and have been shown to be effective in reducing the risk of disabling bone fractures. It is known from clinical trials that no medication completely eliminates the risk of fracture. Additionally, medication effectiveness may be different in clinical practice compared to well-controlled research trials.

Research from the Regenstrief Institute-Merck (Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.) collaboration suggests that many women still have indicators consistent with higher risk of fracture while taking these medications. The cross-sectional population health study was based on a retrospective database analysis of 7,435 women age 50 and older taking bisphosphonates for at least two years during the 2000-2012 time period. The analysis was published in the peer-reviewed journal Bone.

"While we found that a substantial proportion of patients who took oral bisphosphonates remain at risk for hip, spine, and other major fractures, this class of drug does improve bone density in the majority of patients and should remain a mainstay of osteoporosis management," said Erik Imel, M.D., the Indiana University School of Medicine endocrinologist and Regenstrief Institute-affiliated scientist who led the study.

"We limited our study to patients who were considered to be compliant with taking their medication, based on drug dispensing days covered, with the presumption being that those who filled prescriptions took the medication properly. We would expect even less benefit if patients fail to take their medication properly. To increase treatment effectiveness, patients and their doctors should be vigilant that the drug is taken reliably and properly. However, osteoporosis drugs are not enough. Physicians and their patients are well advised to discuss additional important modifications to decrease fall risk and fracture risk. These include exercise, smoking cessation, use of assistive devices such as canes or walkers, modifying the home to avoid obstacles that might lead to falls, and taking appropriate amounts of vitamin D and calcium."

Conducted under the auspices of a Regenstrief Institute-Merck collaboration, the retrospective cohort study utilized anonymized data from the Indiana Network for Patient Care, a health information exchange founded by the Regenstrief Institute. The study authors note that the data they used reflects real-life medical practice and patient behavior from a wide range of physicians and patient backgrounds. Adherence to bisphosphonate therapy was determined by prescription fulfillment records. Clinical data included information on bone density and fractures.

"We know that taking bisphosphonates decrease fracture risk compared to those not taking these drugs," Dr. Imel said. "But what about those women who weren't getting the anticipated benefit and are not improving bone density or even are losing bone density? What predicted that? The purpose of this study was to focus attention on those not doing well, in order to begin to decrease the odds of future fractures in this large group of vulnerable patients.

"Not everyone responds the same way to oral bisphosphonates or any drug. Various factors could convey continued risk of fracture in spite of bisphosphonate therapy, including other medical problems and risk factors for falling. Since we know that such a high percentage of women continue to have elevated fracture risk we -- doctors and patients -- need to focus on these factors," Dr. Imel said. "For example, we found that women who had other medical conditions in addition to low bone density--a frequent occurrence in this older population--had higher fracture risk. Taking some medications in combination with bisphosphonates seemed to increase fracture risk. However, having more medical conditions and taking more drugs are most likely markers of heightened risk rather than causative factors."

Neurologic problems, often linked to heightened risk of falls, as well as inflammatory and other chronic joint conditions including arthritis were found to be associated with higher odds of having a fracture among those taking bisphosphonates.

"I always tell my osteoporosis patients, 'Don't fall,'" said Dr. Imel. "They usually chuckle, and then we talk about things they can do to decrease the risk of falling, including proper footwear and assistive devices. Many patients are reluctant to use a cane or a walker. I try to get them to understand the importance of using any tool that decreases the chance of falling."