Tag: vitamin C

Categories : CancerTags :

A Shot of Vitamin C Gives Dendritic Cells a Potent Cancer-fighting Boost

On By ModernMedia
Vitamin C pills and orange
Photo by Diana Polekhina on Unsplash

New research published in Nucleic Acids Research has shown that vitamin C improves the immunogenic properties of dendritic cells, activating genes involved in the immune response. This discovery could help the development of potent new dendritic cell-based immunotherapies.

Since the onset of anticancer cell therapies, many types of immune cells have been used. The best-known of these cell therapies use lymphocytes, as in the highly successful CAR-T therapies. Recently, researchers have to turned to dendritic cells, known as the ‘master regulators of the immune system‘, for their ability to uptake and present antigens to the T-lymphocytes and induce an antigen-specific potent immune activation. This approach entails loading dendritic cells with specific antigens to create immune memory to make dendritic cell (DC)-vaccines.

To study dendritic cells in the lab, researchers differentiate them from monocytes using a particular set of molecular signalling. This differentiation is accomplished through a complex set of gene activation processes in the nucleus, mostly thanks to the activity of the chromatin remodelling machinery spearheaded by the TET family of demethylases, proteins that act upon the DNA epigenetic marks.

Vitamin C was already known to interact with several TET proteins to enhance its activity, but the specific mechanism was still poorly understood in human cells. In this study, a team lead by Dr Esteban Ballestar hypothesised that treating monocytes in vitro while differentiating into dendritic cells, would help the resulting cells be more mature and active.

The results obtained show that vitamin C treatment triggers an extensive demethylation at NF- kB/p65 binding sites compared with non-treated cells, promoting the activity of genes involved in antigen presentation and immune response activation. Vitamin C was also found to increase the communication of the resulting dendritic cells with other components of the immune system and stimulates the proliferation of antigen-specific T cells.

The researchers proved that vitamin C-stimulated dendritic cells loaded with antigens specific for the SARS-CoV-2 virus were able to activate T cells in vitro more efficiently than non-treated cells.

Overall, these new findings support the hypothesis that treating monocyte-derived dendritic cells with vitamin C may help generate more effective DC-vaccines. After consolidating these results in preclinical models and, hopefully, in clinical trials, a new generation of cell therapies based on dendritic cells may be used in the clinic to fight cancer more efficiently.

Source: Josep Carreras Leukaemia Research Institute

Categories : Ethics and Law Medical Research & TechnologyTags :

Controversial Vitamin C Sepsis Trial Faked?

On By ModernMedia
Patient's hand with IV drip
Photo by Anna Shvets on Pexels

The data underpinning a controversial study of the use as vitamin C as a sepsis treatment may in fact be fraudulent, according to an analysis by an Australian physician and statistician, reports MedPage Today.

PhD student Kyle Sheldrick, MBBS, alleges that the pre- and post- comparison groups involved in the 94-patient study were too similar to be realistic.

In an interview with MedPage Today, Sheldrick said the case is “extreme”, stating that “This is probably the most obviously fake data I have seen. … These groups are more similar than would be probable.”

The paper, led by Paul Marik, MD – who led another COVID protocol study that has since been retracted – has been the subject of much debate in the intensive care community since it was published in 2017. The so-called HAT protocol was a simple regimen of hydrocortisone, ascorbic acid (vitamin C), and thiamine which could have saved many lives easily if it indeed worked. Obviously, there was much excitement worldwide about the significance of the findings – but not all were convinced.

“The effect size seemed just impossible,” said Nick Mark, MD, an ICU physician at Swedish Medical Center. “It seemed too good to be true.”

The trial was followed by larger studies, and so far none have shown shown a similar reduction in mortality, raising suspicions even further, Dr Mark said. With Sheldrick’s analysis, the penny dropped: “This was under our noses for 5 years,” Mark said. “This isn’t just a mistake. We know things can be done unethically, but to actually fake it? That it’s not just flawed, but perhaps actually fraudulent?”

Sheldrick told MedPage Today the key problem with the Marik paper is “probably the most common sign of fraud that we see, which is overly similar groups at baseline.” That is, people tend to fake data which do not vary enough from the average.

Sheldrick said he first looked at the study methods, which noted a pre- and post- comparison design, rather than a randomised or matched case-control design. With such a design, one would expect a more random distribution of baseline characteristics, but that wasn’t the case for the Marik paper, he said.

A further analysis with Fisher’s test showed that most P-values were 1, meaning they were distributed perfectly evenly across two time periods – and only one fell below 0.5. Instead, an even spread should be expected with an overall value of 0.5.

Sheldrick sent his findings to the journal CHEST and to Marik’s former employer Sentara Norfolk General Hospital, but had not heard back from either.

While Sentara Norfolk General Hospital did not respond to comment, and the journal CHEST could not confirm whether an investigation was underway but that it did take ethical concerns very seriously.

A spokesperson for Dr Marik emailed a statement to MedPage Today, claiming that the conclusions had been validated in several meta-analyses, and recommended the source examine “this and other research on the data before making false allegations on social media. Such claims are harmful and do not add to the public discourse.”

This wouldn’t be the first time concerns have been raised about data in a paper that Dr Marik co-authored. In November 2021, the Journal of Intensive Care Medicine (JICM) retracted an article by Marik and others on their MATH+ protocol for COVID. The retraction followed a communication that raised concerns about the accuracy of COVID mortality data from the hospital used in the article.

“It seems a bit improbable for someone to discover two miracle cures in three years,” Dr Mark commented to MedPage Today.

Dr Mark noted that the 2017 paper is widely cited, and even if the intervention was not directly harmful, the resources invested in subsequent large, high-quality trials of vitamin C and sepsis could have been better spent.

“While I’m really glad we did high-quality studies and had brilliant people working on this, it’s kind of a shame,” he said. “Instead of studying vitamin C based on a faulty premise, we could have spent our efforts elsewhere.”

Source: MedPage Today

Categories : Diet and NutritionTags :

WHO Vitamin C Guidelines from World War II Study Challenged

On By ModernMedia
Source: Diana Polekhina on Unsplash

Researchers have re-analysed a landmark study on Vitamin C conducted during World War II, which informed the WHO’s recommended daily amount, finding the amount to be half that actually required.

When food was scarce during World War II, gruelling experiments were conducted in Britain to determine the bare minimums of food and water that were required for health and survival, and how to prioritise the allocation of food.

One of the more robust experiments run on human subjects during this time in Britain, which has had long-lasting public health consequences, was a vitamin C depletion study started in 1944. This medical experiment involved 20 subjects, most of whom were conscientious objectors living in a building in Sorby where many similar experiments were conducted. They were overseen by a future Nobel Prize winner, and detailed data was kept on each participant in the study.

“The vitamin C experiment is a shocking study,” said Philippe Hujoel, lead author of a new analysis of the Sorby vitamin C experiment, a practicing dentist and professor of oral health sciences in the UW School of Dentistry. “They depleted people’s vitamin C levels long-term and created life-threatening emergencies. It would never fly now.”

Despite two participants developing life-threatening heart problems from the vitamin C depletion, Hujoel added, none of the subjects were permanently harmed, and later many indicated they would participate again.

Due to vitamin C shortages, they wanted to be conservative with the supplies, explained Hujoel, who is also an adjunct professor of epidemiology. The goal of the Sorby investigators was not to determine the required vitamin C intake for optimal health; it was to find out the minimum vitamin C requirements for preventing scurvy.

Vitamin C is important for wound healing because scar tissue formation depends on collagen, which needs vitamin C. In addition to knitting skin back together, collagen also maintains the integrity of blood vessel walls, thus protecting against stroke and heart disease.

In the Sorby trial, researchers assigned participants to zero, 10 or 70 milligrams a day for an average of nine months. The depleted subjects were then repleted and saturated with vitamin C. Experimental wounds were made during this depletion and repletion. The scar strength of these experimental wounds was a measure of adequate vitamin C levels since poor wound healing, in addition to such conditions as bleeding gums, is indicative of scurvy.

The Sorby researchers concluded that 10 milligrams a day was enough to ward off signs of scurvy. Partly based on this, the WHO recommends 45 milligrams a day. Hujoel said that the re-analyses of the Sorby data suggest that the WHOrecommendation is too low to prevent weak scar strength.

In a bit of scientific detective work, Hujoel said he tracked down and reviewed the study’s data, and with the aid of Margaux Hujoel, a scientist with Brigham and Women’s Hospital/Harvard Medical School, put the data through modern statistical techniques designed to handle small sample sizes, techniques not available to the original scientists. They published their findings in the American Journal of Clinical Nutrition.

The Hujoels found that the data from this unique study, which formed a cornerstone for dietary recommendations worldwide, needed more than just being assessed with the ‘eyeball method’.

“It is concluded that the failure to reevaluate the data of a landmark trial with novel statistical methods as they became available may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies,” the researchers wrote.

“Robust parametric analyses of the (Sorby) trial data reveal that an average daily vitamin C intake of 95 mg is required to prevent weak scar strength for 97.5% of the population. Such a vitamin C intake is more than double the daily 45 mg vitamin C intake recommended by the WHO but is consistent with the writing panels for the National Academy of Medicine and (other) countries,” they added.

The Hujoels’ study also found that recovery from a vitamin C deficiency is lengthy, requiring higher levels of vitamin C. Even an average daily dose of 90 milligrams a day of vitamin C for six months failed to restore normal scar strength for the depleted study participants.

Source: University of Washington