Day: 02/07/2024

Solar power decline: Why the industry is struggling right now, and what it needs.

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Solar Power Isn’t Over Yet

The industry is having a somewhat visible freakout. But broadly, it’s doing OK.

A solar panel with an expressionless face.

To take it from recent headlines, it seems as though the global solar-power industry, following half a decade of record growth and governmental investment, flew just a bit too close to the sun. California, a longtime pioneer in solar development, has earned the most attention here: The tiny Golden State companies dedicated to rooftop-solar installation, assembly, and production are slashing thousands of jobs and facing bankruptcies, thanks to a steep drop in demand that, executives claim, is the direct consequence of reduced solar-boosting incentives from the state government. But it’s not just California: Home-security company ADT, based in Florida, recently decided to close its solar-installation arm after just three years. And larger solar firms across the country, like Texas-based Sunnova, are also facing financial headwinds, as Time magazine’s Alana Semuels noted in a report grimly headlined “The Rooftop Solar Industry Could Be on the Verge of Collapse.” About a dozen other states, including Idaho, are also cutting rooftop-solar benefits.

The broader market is facing troubles in solar-happy Europe too. After Germany’s last domestic solar-module producer announced plans to relocate to the United States, a regional solar association warned, “We’re about to lose the whole European [photovoltaic] manufacturing industry.” Other solar factories are either fully shuttering, planning to try their luck in the U.S., or begging European Union lawmakers for additional financial support, citing the challenges of a market suddenly saturated with cheap Chinese imports. This echoes calls from swing-state senators back in the U.S. for the Biden administration to raise its already-high tariffs on imports of key Chinese solar parts, even though many solar manufacturers dependent on those components claim this would harm their businesses. Meanwhile, prices for essential solar-panel elements, like silver, remain high, as do interest rates and disaster-insurance premiums, causing nervousness among potential investors.

It all sounds pretty bad! Is solar doomed?

I am happy to report that the era of harnessing power from the sun is not yet over. On a wider scale, the solar sector is still ballooning and providing record amounts of green energy worldwide. Despite its manufacturing woes, Germany’s nationwide solar installation through 2023 beat expectations. Greece is well on the way to tripling its solar capacity by the end of the decade. China, the undisputed champion of solar, grew its economy last year primarily through rapid renewables development; by the end of this year, the country’s solar and wind output is set to finally outpace the rate of electricity generated from coal, assisted by innovations in ocean-floating panels. (Just one indicator of this success: In 2023 alone, China added more solar panels than the U.S. has ever deployed.) Worldwide renewables capacity grew much more in 2023 than in 2022, despite continuing post-COVID economic shake-ups in supply-chain stability, inflation, and hiked interest rates. North of the U.S. border, Canadian solar has become a hot investment vehicle. And even within the U.S., there are success stories in unexpected places: The most Republican voting district in the country is excited about a solar factory coming to town. Puerto Rico is expanding its rooftop-solar incentives, which have helped the territory to stabilize its grid. The Biden administration is setting aside millions of acres of Western public lands for utility-scale solar. Cooperatively owned solar systems are still taking off in both California and Texas, while the Lone Star State continues to beat records for solar-power production. The Tennessee Valley Authority just inked significant new contracts to expand its arrays of solar panels and batteries, and New Jersey passed a bill to curb limits on expanding community solar.

It’s a confusing mishmash of good and bad news, not unlike all the contradicting forecasts that hit wind energy all of last year, especially offshore. But a finer analysis of all the factors at play here consistently points to the main issue: the folly of leaning primarily on the private sector to shoulder the burden of an existentially necessary energy transition.

The original sin of U.S. solar goes back to the 1980s, when the country that produced the first silicon cells for capturing energy from the sun (that would be America) bucked its initial interest in supporting solar at home. This allowed East Asian countries, which already benefited from ample deposits of necessary minerals and metals, to attract hopeful developers, while established Western fossil-fuel firms like Exxon, which had previously explored alternative-energy sources, scrapped such projects to go all in on oil instead. Then, in its attempt to catch up after decades of neglect, the Obama administration passed legislation that, at most, provided liquid subsidies to private firms willing to pick up the slack. Although those tax credits were and continue to be helpful, they didn’t do much to sustain companies, leaving them vulnerable to U.S.–China tariff wars that made establishing a homegrown sector prohibitively expensive. Speaking of China: Thanks to its decadeslong, government-aided mission to dominate solar (which has also included human rights abuses), the country set up a large-scale operation that could shoot out cheap solar panels and components at scale, all the way to export routes. This simultaneously exploded Chinese renewable-power capacity and undermined international competitors who couldn’t beat such low prices for parts.

There’s a reason America is so far behind. Taking advantage of low global prices afforded by the explosion of cheap Chinese supplies is one thing; coordinating a supply chain, sourcing all needed ingredients, training skilled workers, and withstanding regular price fluctuation are all tougher without more governmental backstops and assistance. (Consider the fact that houses of worship, which don’t pay taxes, could not qualify for Obama-era subsidies if they wanted to go solar—an issue that was fixed thanks only to subsequent adjustments in the Inflation Reduction Act.) Plus, in the early 2010s, batteries for energy storage were nowhere near as prevalent and cost-effective as they are today, which made the infamous “intermittency” issue (the sun doesn’t shine at night, wind is not as plentiful in certain regions, etc.) much more of a concern back then as opposed to now.

That (welcome) boom in battery manufacturing is one reason the solar industry is currently shape-shifting. Before then, rooftop-solar users tended to take advantage of generous “net-metering” policies in certain states, which compensate homeowners for feeding their excess solar energy back into the grid for wider use. For New Mexico and Maine, the thinking behind today’s solar-incentive adjustments is that net-metering has worked almost too well, making it imperative that they raise additional state revenue so that budgeted tax credits don’t run out too quickly. And as Heatmap News’ Matthew Zeitlin has explained, California is now so awash in roof-solar power that it’s instead incentivizing the ownership of solar-and-battery systems that can store energy, rather than promoting energy exchange that may stress the grid.

The problem is, those battery systems are difficult to deal with. Batteries are cheaper than they once were, but they’re still pricey on an individual level, which is why they’ve been adopted far more in commercial applications than residential ones. (State regulators in Connecticut recently increased their incentives for residential battery storage by nearly $10,000.) A lot of the smaller solar companies out West lack the means to expand out into providing dual panel-battery apparatuses, leaving them at a stark disadvantage in the new market. There’s also the fact that several homeowners have panels from companies that went out of business long ago or were swallowed up by private equity vultures—which, as Time’s Semuels has written, have little to no interest in actually maintaining the quality and capacity of pre-installed panels. This has left behind a lot of abandoned panels and frustrated homeowners.

There are still many solar and battery incentives left in the U.S., allowing places like sun-soaked Arizona to push ahead with hybrid facilities and setups. The members of the European Union, on the other hand, have often failed to coordinate sensible, consistent clean-energy rebates and buildouts over time, resulting in an impressive array of solar tech that’s then built and distributed unevenly throughout their continent

It seems pretty apparent, on both sides of the Atlantic, that a strategy of throwing cash at small-scale manufacturers—without providing more top-down insurance and support for less-resourced firms, without establishing wide-scale job-training and just-transition programs, without careful coordination among cooperative, local, national, and international authorities—has helped create the energy transition economy while leaving it fatally susceptible to shocks and changes. America’s rooftop-solar mess demonstrates that, while private enterprise can be a player in greening global energy, it cannot be solely relied upon to complete the task with some government funds in its pocket. To leave a necessary energy transition to the directives of the profit motive, just because China helped to cheapen the price of solar supply and generation, is to abandon smaller solar companies to the weirdness of a still-growing, often-speculative market. It also expects that more-capitalized private firms or utilities will care about producing and maintaining solar systems for altruistic reasons—even though private equity’s rooftop misadventures show this to be a lie. The future of a healthy, stable clean-energy industry should be spurred by publicly stewarded, communitarian projects, with more intensive government support for training, setup, installation, power pricing, maintenance, and recycling (and batteries!). Plus, accountability for those companies that benefit from state incentives only to abandon solar when it’s no longer in their interest.

The U.S. may be taking some heed of all this at last, with the Federal Emergency Management Agency offering to compensate local governments that fuel their recovery from extreme-weather disasters by installing solar panels, heat pumps, and microgrids. In a time when durably installed solar panels have been demonstrably advantageous in helping communities recover from climate change–fueled storms, this is a step toward the right kind of top-down action. The federal government is also accelerating efforts to green its own infrastructure, with rooftop solar coming to the Pentagon and batteries coming for important observatories. Maybe the U.S. government won’t do everything—but at least it can do its part to maintain a sunny forecast for the solar business, whether out in Western lands or on its own buildings. More structure for everyone else’s roofs would be welcome too, though.

To conclude: Despite recent challenges facing the solar industry, global solar capacity is expanding, with notable growth in Germany, Greece, China, and even unexpected places like the most Republican voting district in the U.S. However, the current dependency on the private sector has left the industry vulnerable, highlighting the need for more government support and oversight.

FLASH radiation therapy shows promise in first-in-human trial

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Ultra-high-dose-rate radiation treatment found safe and effective for pain relief in small trial of patients with metastatic cancer

SAN ANTONIO

FLASH radiation treatment – which delivers therapeutic doses of radiation in a fraction of a second – may hold promise as a potential treatment for tough-to-kill tumors, a first-in-human study in a small number of people with bone cancer suggests. The technology, previously tested in animals, was shown to be as safe and appeared to be as effective as conventional radiation without causing unexpected side effects. Findings of the FAST-01 trial (NCT04592887) will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“Our study shows FLASH radiotherapy with protons is a practical modality to reduce pain,” said Emily C. Daugherty, MD, lead author of the study and an assistant professor of clinical radiation oncology at the University of Cincinnati Cancer Center. “It deserves further exploration because of its potential to decrease the side effects associated with conventional radiation treatments.”

FLASH radiotherapy (RT) delivers radiation at dose rates that are more than 300 times higher than those used in conventional radiation treatments. This induces a phenomenon known as the FLASH effect, which reduces the harm that may occur to normal tissue surrounding a tumor during conventional radiation therapy, while still killing the cancer cells at the tumor site.

“Because FLASH radiotherapy is given at ultra-high dose-rates, it appears to cause less normal tissue injury. This offers the possibility of delivering larger doses of radiation – which could result in higher cure rates for patients with resistant tumors – without increasing side effects,” said John Breneman, MD, FASTRO, principal investigator on the trial and a professor of radiation oncology and neurosurgery at the University of Cincinnati Cancer Center.

Most early research on FLASH RT used electron beams to deliver the radiation, but these beams don’t penetrate very deep into tissue, limiting its applicability for this treatment approach. Using proton beams for ultra-high dose-rate radiation allows for penetration sufficient to reach tumor locations in most people. While pre-clinical trials with animals suggested FLASH-RT could safely deliver high doses of radiation with fewer harmful side effects, prior to the FAST-01 trial, the treatment had never been tested under a clinical trial in humans.

In this study, ultra-high-dose-rate radiation was delivered to 10 patients, ages 27-81 years, each with one to three painful bone metastases in their extremities. Treatments were delivered to a cumulative 12 metastatic sites in patients’ arms and legs. Patients were given 8 Gy of radiation in a single fraction, delivered at ≥40 Gy per second via a FLASH-enabled proton therapy system. Pain, use of pain medications and adverse events were measured on the day of treatment, 15 days following treatment, and at one, two and three months following treatment. Researchers continued measuring these results every two months for up to 13 months. The median follow-up was 4.8 months.

Researchers chose patients who would have received conventional radiation therapy at the same dose as they were given with FLASH RT. “We used the exact same regimen, but with FLASH dose-rate radiation. The patient experience is the same as it would have been receiving conventional radiation, only the treatment delivery process is shorter,” said Dr. Daugherty.

Following FLASH RT, seven of the 10 patients experienced complete or partial pain relief. Of the 12 treated sites, pain was relieved completely for six sites and partially for two additional sites. Temporary pain flares occurred in four of the 12 sites treated.

Side effects from treatment were mild. Four patients experienced mild skin hyperpigmentation (darkening skin tone), one experienced skin discoloration, two experienced mild limb edema (swelling or puffiness), two experienced pruritis (itchy skin), one experienced fatigue, one experienced erythema (reddening of the skin) and one experienced extremity pain.

Each FLASH treatment takes about 3/10 of a second, Dr. Daugherty explained. Following treatment, “both pain relief and side effects were in-line with what might have happened with conventional radiation. We did not see any unexpected additional toxicity with the substantially shorter treatment.”

FLASH RT would potentially be most useful in treating hard-to-kill cancers in the brain, lungs or gastrointestinal area, where healthy tissue surrounding tumors is particularly vulnerable to radiation exposure, said Dr. Breneman. However, clinical trials in these sites cannot be authorized until studies show ultra-high dose-rate radiation is safe and effective in other, less-sensitive areas. The FDA limited its approval for this study to adults with bone metastases in their arms and legs, areas at much lower risk should complications arise.

“From a practical standpoint, this is not the type of cancer that FLASH is designed to treat, but we need human data to see if there are any unexpected side effects. Treating arms and legs is not as risky as treating someone’s brain or lungs,” said Dr. Breneman, who he also serves as medical director of the Cincinnati Children’s/UC Medical Center Proton Therapy Center.

Ultimately, FLASH RT could also be useful in treating pediatric cancers, since children are more sensitive to the side effects of radiation therapy, he said. But much more research needs to be done before that can occur.

Researchers don’t fully understand why FLASH RT kills tumors with fewer side effects than conventional radiation and further research is needed to determine the biological mechanisms driving the FLASH effect, said Dr. Daugherty.

Next, the research team will test the safety and efficacy of FLASH RT with patients who have metastases closer to the lungs and heart. The FAST-02 trial (NCT05524064) is currently enrolling adult patients with thoracic bone metastases.

Withdrawal symptoms from antidepressants can last over a year

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We must rethink the “chemical imbalance” theory of mental health.

In her book, “Blue Dreams: The Science and Story of the Drugs That Changed Our Minds,” psychotherapist Lauren Slater discusses psilocybin and MDMA as potential treatments for depression. Sadly, she hasn’t tried either given her longstanding antidepressant usage. As she told me in 2018, psychedelics are contraindicated to Prozac. Yet she sees hope in this class of drugs for a wide range of mental health treatments.

After I described the psychedelic experience, she replied,

“I can imagine them very vividly, but it’s not the same as actually getting to take them. I think if I could actually get to take a psychedelic, a lot of what I fear would go away. And I think I would be a better person because of it. But I do understand I have a sort of intuitive understanding of what they do.”

Slater has been taking antidepressants for decades. While aware of the problems with long-term usage, she is unable to withdraw given the crippling side effects. This is a serious problem for millions of antidepressant users, as detailed in a new review published in the journal Psychotherapy and Psychosomatics.

Written by University of Florence Associate Professor of Clinical Psychology, Fiammetta Cosci, and Maastricht University’s Guy Chouinard, the review points out popular antidepressant and antipsychotic medications, including SSRIs and SNRIs, exhibit more severe withdrawal symptoms than benzodiazepines (such as Valium and Xanax), Z-drugs, and ketamine.

Benzodiazepines were first synthesized in 1955. This class of tranquilizers took the place of Meprobamate (Miltown), which is considered one of the world’s first blockbuster drugs. As Miltown lost favor due to a growing population of addicts, benzos took its place in psychiatry offices. By the late seventies, benzos were the world’s most prescribed medications despite growing evidence of their addictiveness and side effects. By contrast, SSRIs and SNRIs are generally considered less damaging than benzos—an assessment that must now be reconsidered.

With the global antidepressant market expected to reach $28.6 billion this year, pharmaceutical companies go to great lengths to downplay the long-term effects of these drugs. Slater writes that lithium showed clinical efficacy in treating depression but has never been approved by the FDA (except for manic-depressive disorder). The real issue: you can’t patent an element.

In the review, Cosci and Chouinard categorize withdrawal symptoms into three groups. University of West Georgia instructor of psychology, Ayurdhi Dhar, breaks them down:

“New withdrawal symptoms and rebounds are short-lived, temporary, and reversible. However, new withdrawal symptoms are new for the patient (nausea, headaches etc), while rebound symptoms refer to the sudden return of primary symptoms that are often more severe than pre-treatment. Persistent post-withdrawal disorder refers to ‘a set of long-lasting, severe, potentially irreversible symptoms which entitle rebound primary symptoms or primary disorder at a greater intensity and/or new withdrawal symptoms and/or new symptoms or disorders that were not present before treatment.’”

Each class of drugs cited in the review produce some withdrawal symptoms. Benzos and Z-drugs can cause confusion, sweating, rebound anxiety, and psychosis, generally lasting between two to four weeks (though in some cases, impaired cognition can last longer). Ketamine, the first psychedelic approved for clinical use in America, can produce rage, tremors, palpitations, and hallucinations, though the effects are short-lived: three days to two weeks.

The authors find that SSRIs, SNRIs, and antipsychotics have the worst record for withdrawal symptoms. Antidepressants can produce pain, numbness, depression, stroke-like symptoms, and much more. With SSRIs, impaired memory, sexual dysfunctions, panic attacks, and pathological gambling can continue for a year after discontinuation even if the patient tapers off slowly.

In 2014, Professor Peter C. Gøtzsche of The Nordic Cochrane Centre in Copenhagen published an article highlighting the dangers of antidepressants (featured in Robert Whitaker’s “Anatomy of an Epidemic”). Gøtzsche calls for psychiatrists to abandon the longstanding myth of the chemical imbalance theory of the brain. He believes popular pharmacological interventions are the true source of imbalances.

“We have no idea about which interplay of psychosocial conditions, biochemical processes, receptors and neural pathways that lead to mental disorders, and the theories that patients with depression lack serotonin and that patients with schizophrenia have too much dopamine have long been refuted. It is very bad to give patients this message because the truth is just the opposite. There is no chemical imbalance to begin with, but when treating mental illness with drugs, we create a chemical imbalance, an artificial condition that the brain tries to counteract.”

As the #BLM protests are exposing more than ever, systemic issues around inequality and racism create the environmental conditions for mental health problems to manifest. Chemical imbalances are a symptom; writing a script does not treat the cause of depression or anxiety.

While a certain percentage of depressed and anxious patients will benefit from short-term usage of prescription medication, mounting evidence against their long-term use, as detailed in this new review, must force the medical establishment to rethink its approach. The for-profit health care system has failed us too long. We can no longer afford to pay its toll.

“Zepbound,” the newest weightloss drug

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As Zepbound dominates headlines as a new obesity-fighting drug, experts warn that weight loss shouldn’t be the only goal.

A tube with the word Zepbond on it, designed specifically for weight loss.

Zepbound is the newest addition to the weight loss drug arena. In November 2023, it joined the list of obesity-fighting drugs – administered as an injection – to be approved by the U.S. Food and Drug Administration. 

The key to Zepbound’s weight loss potential is its active ingredient, tirzepatide. This is the same active ingredient found in the drug Mounjaro, which is approved to treat Type 2 diabetes. 

The relationship between Zepbound and Mounjaro is similar to two other popular drugs making headlines, Wegovy and Ozempic. Both Wegovy and Ozempic contain the active ingredient semaglutide, with Ozempic approved for the treatment of Type 2 diabetes and Wegovy approved for the treatment of obesity.

Tirzepatide and semaglutide both mimic the digestive hormone GLP-1, which is released by the intestines when we eat to stimulate insulin production and help regulate blood sugar. GLP-1 also suppresses appetite while promoting a sensation of fullness.

Weight loss medications are intended to be used in conjunction with lifestyle changes, such as exercise and a healthy diet. But too often, people view them as a silver bullet for weight loss. And the high price tag and variable insurance coverage for these popular weight loss drugs create a barrier for many people. 

Health risks of obesity

The potential impact of these drugs is staggering, since more than 2 in 5 American adults are obese, according to the National Institutes of Health. 

Obesity is not just an American issue, nor is it going away. The World Obesity Federation estimates that by 2030, 1 in 5 women and 1 in 7 men will be living with obesity worldwide.

Many serious health conditions are associated with obesity, including heart disease, diabetes, high blood pressure, stroke, certain cancers, and osteoarthritis. By treating obesity, a person can reduce or reverse obesity-related disease and improve both their health and quality of life.

However, long-term weight management depends on a number of complex factors. Meal timing and types of foods eaten can affect energy levels, satisfaction and hunger levels. A person’s typical schedule, culture and preferences, activity level and health history must be taken into consideration as well. No single “best strategy” for weight management has been identified, and research indicates that strategies for weight loss and maintenance need to be individualized.

In addition, it is critical to note that research on the long-term effects of these newer weight loss drugs is limited. The available research has focused specifically on weight loss, heart health and metabolism and has found that ongoing use of these new medications is necessary to maintain improvements in weight and related health benefits. 

Common side effects and the emotional toll experienced by those who regain weight once they stop taking the drugs are trade-offs that need to be considered. More research is needed to better understand the long-term impact of both direct and indirect health consequences of taking drugs for weight loss.

It’s not just what you see on the scale

Throughout my years working as a registered dietitian, I have counseled numerous people about their weight loss goals. I often see a hyperfocus on weight loss, with much less attention being placed on the right nutrients to eat.

Societal standards and weight stigma in the health care setting can negatively affect patients’ health and can lead them to obsess about the number on a scale rather than on the health outcome.

Weight loss may be necessary to reduce risks and promote health. But weight loss alone should not be the end goal: Rather, the focus should be on overall health. Tactics to reduce intake and suppress appetite require intention to ensure that the body receives the nutrients it needs to support health.

Additionally, I remind people that long-term results require attention to diet and lifestyle. When a person stops taking a medication, the condition it’s meant to treat can often return. If you stop taking your high blood pressure pills without altering your diet and lifestyle, your blood pressure goes back up. The same effects can happen with medications used to treat cholesterol and obesity.

Nourish your body with nutrients

Despite the prevalence of obesity and the emergence of newer drugs to treat it, 95% of the world’s population doesn’t get enough of at least one nutrient. According to one study, nearly one-third of Americans have been found to be at risk of at least one nutrient deficiency. Additional research indicates that those actively trying to lose weight are more prone to nutrient deficiencies and inadequate intake. 

For instance, a decline in iron intake can lead to iron deficiency anemia, which can cause fatigue as well as an increased risk of many conditions. Adequate intake of calcium and Vitamin D reduce the risk of bone fractures, yet many people get less than the recommended amounts of these nutrients. 

It is true that a healthy body weight is associated with reduced health risks and conditions. But if a person loses weight in a manner that does not provide their body with adequate nourishment, then they may develop new health concerns. For example, when a person follows a diet that severely restricts carbohydrates, such as the ketogenic diet, intake of many vitamins, minerals, phytochemicals – or biologically active compounds found in plants – and fiber are reduced. This can increase risk of nutrient deficiencies and impair the health of bacteria in our gut that are important for nutrient absorption and immune function.

Nutrition recommendations set by the Food and Nutrition Board of the National Academies of Sciences, Engineering, and Medicine and the Dietary Guidelines for Americans provide guidance and resources to help meet nutrient needs to promote health and prevent disease, regardless of the strategy used to lose weight.

Optimizing health

There is no doubt that striving for a healthy body weight can reduce certain health risks and prevent chronic disease. Whether a person strives to maintain a healthy body weight through diet alone or with medications to treat obesity, the following tips can help optimize health while attempting to lose weight.

  1. Adopt an individualized approach to healthy behaviors that promote weight loss while considering personal preferences, environmental challenges, health conditions and nutrient needs.
  2. Focus on nutrient-dense foods to ensure the body is getting required nutrients for disease prevention and optimal function. If medications reduce your appetite, it is crucial to maximize the amount of nutrients in the foods you do consume.
  3. Include exercise in your program. Weight loss as a result of reduced calorie intake can decrease both fat and lean body mass, or muscle. An exercise routine that includes strength training will help improve muscle strength and preserve muscle during weight loss. 
  4. Seek professional help. If you are uncertain about how to adopt an individualized approach while ensuring adequate intake of essential nutrients, talk to a registered dietitian. They can learn about your individual needs based on preferences, health conditions and goals to make dietary recommendations that support health.

New non-opioid pain reliever moves closer to approval

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In clinical trials, it significantly reduced patients’ pain after surgery.

Vertex Pharmaceuticals’ new painkiller significantly reduced moderate-to-severe pain in two phase 3 trials — suggesting it could be the new, non-addictive pain reliever we’ve been waiting for.

The challenge: Pain is the most common reason people seek out medical care, and while there are seemingly infinite causes of pain — from migraines and broken bones to infections and nerve disorders — we have very few options for treating it.

Over-the-counter meds, like ibuprofen and aspirin, are safe and easily accessible, but they are only effective for mild pain. Prescription opioids, like oxycodone and morphine, meanwhile, are highly effective, but they also cause a “high” that can be addictive and lead to misuse.

The new painkiller ​​led to a “clinically meaningful” reduction in pain in the 48 hours after the surgery.

Bocking pain’s pathway: A new painkiller that’s highly effective, but non-addictive is one of the holy grails of medicine, and the search for it has led Vertex Pharmaceuticals to a class of drugs called “sodium channel modulators.”

These medications act on a group of proteins that are involved in pain processing. Vertex is developing a drug, called VX-548, that it hopes will interfere with one of those proteins in a way that relieves pain, without any euphoric or addictive side effects.

What’s new? On January 30, Vertex shared the topline results of two phase 3 trials of its new painkiller as a treatment for moderate-to-severe acute pain (“acute” pain is usually defined as coming on suddenly, like from an injury or surgery, and lasting less than six months, while “chronic” pain develops gradually and lasts longer).

The trials involved a total of about 2,200 participants who were given either VX-548 or a placebo after undergoing abdominoplasty surgery (a “tummy tuck”) or surgery to remove a bunion from their foot. 

According to Vertex, the new painkiller ​​led to a “clinically meaningful” reduction in pain in the 48 hours after the surgery. It did not, however, meet its secondary endpoint: delivering more pain relief than a combination of the opioid drug hydrocodone (Vicodin) and acetaminophen (Tylenol).

Vertex also shared the results of a third phase 3 trial in which 256 people experiencing acute pain for a variety of reasons received VX-548 for up to 14 days. 

The drug was safe and well tolerated in that trial, leading to only mild-to-moderate adverse effects. About 83% of the participants rated the new painkiller as being “good,” “very good,” or “excellent” at treating their pain.

Looking ahead: There’s no word on when Vertex plans to publish the full trial results, but the company has said that it hopes to apply to the FDA by mid-2024 to get the medication approved to treat moderate-to-severe acute pain.

“For years, our goal has been to make a medicine with clinically meaningful pain relief for moderate-to-severe acute pain, with a safety and tolerability profile that’s better than an opioid,” David Altshuler, Vertex’s chief science officer, told BioPharma Drive. “We will file for approval with urgency.”

Vertex isn’t limiting itself to acute pain, though — an estimated one in five adult Americans lives with chronic pain, and a phase 3 trial of the new painkiller for long-lasting pain due to nerve damage from diabetes is ongoing.

FLASH radiotherapy: What, how and why?

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Ultra-high dose rate (FLASH) radiotherapy is a new way of treating tumours caused by cancer. Higher doses of radiotherapy are associated with trauma to the healthy tissue surrounding the tumour, whereas FLASH radiotherapy demonstrates a sparing effect of the healthy tissues without compromising the anti-tumour action. Dr Kristoffer Petersson at the Oxford Institute for Radiation Oncology, University of Oxford, along with collaborators Joseph D. Wilson, Ester M. Hammond and Geoff S. Higgins, review the available data on FLASH radiotherapy and its clinical potential in the treatment of cancer.

One in every two people in the UK born after 1960 is estimated to be diagnosed with some form of cancer during their lifetime. Radiotherapy (a non-invasive radiation treatment which damages and kills tumour cells) forms part of the treatment in 30-50% of these cases. Unfortunately, radiotherapy also damages the healthy tissue surrounding the tumour. Treatment success is dependent on delivering a high enough dose of radiation to destroy the tumour cells without causing severe trauma to the surrounding tissues. FLASH radiotherapy (FLASH-RT) is a new technique, involving treatment of tumours at ultra-high dose rates which actually reduces the trauma to normal tissue around the tumour, whilst equalling the anti-tumour effect of conventional dose rate radiotherapy (CONV-RT). However, very little is known about the mechanisms behind the FLASH effect.

Kristoffer Petersson and his colleagues at the Oxford Institute of Radiation Oncology, aim to better understand these mechanisms in the hope of bringing us closer to a successful implementation of FLASH technology in our radiotherapy clinics.

Ultra-high dose rate (FLASH) radiotherapy is a new way of treating tumours caused by cancer.

Tissue toxicity
It was first noted in the 1960s that non-cancerous cells exposed to ultra-high dose rates of radiotherapy were more likely to be viable than those exposed to conventional dose rates. This has been more recently supported by studies in mice, one of which demonstrated much less lung damage in the chests of mice treated with FLASH-RT compared to those treated with CONV-RT. In another study, mice exposed to whole brain irradiation at conventional dose rates performed much worse in recognition tests compared to those treated at ultra-high dose rates. Radiation-induced skin reactions can include reddening and breakdown and have been shown to be much reduced in rodents being treated with FLASH-RT compared to CONV-RT. FLASH-RT also compared favourably in one study comparing the skin reaction of a mini-pig to different dose rates of radiotherapy. Another study involving treatment of nasal cancer in cats with FLASH-RT showed complete remission of tumours with minimal trauma to surrounding tissues.

 Researching the FLASH effect is of value to establish how it can be used in a clinical scenario to treat cancer patients. 

Anti-tumour response
Many studies demonstrate that in addition to reducing tissue toxicity, FLASH-RT also produces the same tumour response as CONV-RT. One such study compared mice with breast cancer and head and neck carcinoma grafts which had been exposed to either FLASH-RT or CONV-RT; there was no difference in treatment success between the two methods. In another study, mice were inoculated with cancer cells into their lungs, then later irradiated and CT-scanned to measure tumour size. The tumours of the mice treated with FLASH-RT were smaller than those treated with CONV-RT. There is therefore some evidence that FLASH-RT may even produce a superior anti-tumour response to CONV-RT.

Influencing factors
There are multiple factors that could influence the FLASH effect, including dose rate, total dose, pulse rate, fractionation, and modality of radiation. The dose rate needed for the FLASH effect may also vary depending on the affected tissue and the delivery method. Many studies vary in the total dose of radiation used, or use doses unattainable in clinical scenarios, which complicate the findings. The source of the radiation is also a factor, as the FLASH effect has been mostly observed following the use of electron linear accelerators. More recently, the FLASH effect has also been seen following the use of proton and X-ray radiation. Pulsing the radiation at a high frequency can induce a FLASH effect, at a suitable dose-per-pulse. Further study is needed to confirm the key parameters for inducing the FLASH effect, as there are so many variables at play.

Kristoffer Petersson’s research lab aims to identify the mechanisms behind FLASH radiation, with a view to finding the optimum way of implementing the technique in clinical practice.

Oxygen depletion
Exactly why the FLASH effect occurs is not yet fully understood but has been hypothesised. Hypoxic tissues (tissues that are deprived of oxygen) are more resistant to radiation (and therefore less likely to become damaged) than well-oxygenated tissues. It is therefore thought that the difference in tissue toxicity between FLASH-RT and CONV-RT may be due to the level of hypoxia at ultra-high dose rates and subsequent radioresistance transferred to the irradiated tissue.

Immune modification
Another proposed theory for the FLASH effect is a modified immune response − as it involves a shorter treatment time, less lymphocytes (white blood cells involved in the immune system) are affected by the radiation. One study reported less immune system activation in mice following FLASH-RT compared to CONV-RT. It should be noted that it is unclear if any immune response following FLASH-RT is contributing to the FLASH effect or caused by it. Other biological responses such as DNA damage and inflammation could also be contributing, and more studies are needed for clarification.

Clinical applications
Ultimately, researching the FLASH effect is of value to establish how it can be used in a clinical scenario to treat cancer patients. It could be used in the clinic to allow for an increase of total dose in the treatment of tumours resistant to radiation that are currently associated with worse patient outcomes, as a higher dose could be used without the associated surrounding tissue toxicity of CONV-RT. It could also be used in situations where radiotherapy offers good tumour control but is associated with tissue toxicity as the same dose could be administered but with less toxicity than that of CONV-RT. The clinical viability of FLASH-RT in practice is complicated by inconsistencies, lack of clarity and limitations in the various studies performed. Some also do not have a control group irradiated with CONV-RT for comparison.

FLASH radiotherapy demonstrates a sparing effect of the healthy tissues without compromising on anti-tumour action.

One human patient has been treated with FLASH-RT. He had an aggressive form of lymphoma and had previously been treated with CONV-RT which caused severe reactions to the skin surrounding the cancerous lesions and took months to heal. One lesion was successfully treated with FLASH-RT and had only mild redness and inflammation around the area treated. Although a promising outcome, this study only involved one patient and therefore allowed for limited comparison between the two methods of radiotherapy.

Electron linear accelerators have been the source of the radiation in most studies demonstrating a FLASH effect. Clinical linear accelerators can be modified to deliver FLASH-RT with electrons, which would allow for the translation into clinical trials. A limitation of this is the depth of tissue which can be treated, which is restricted to a few centimetres with these electron beams. A solution would be to use higher energy electron beams, which can have improved depth penetration. Using electromagnets, the beam can theoretically be focused to the volume of tumour, resulting in dose-to-target conformity with a single beam, comparable to that of modern X-ray techniques. A single beam delivery such as this may prove essential in producing the FLASH effect; however, these beams are currently exclusive to research accelerators which are either very great in size or associated with low pulse rate, small beam size, and stability issues.

 The FLASH effect offers superior tissue protection in comparison to CONV-RT without compromising on tumour treatment. 

One recent study demonstrated that X-ray tubes could potentially be used in FLASH-RT studies. These are small, relatively cheap and available in clinical practice. They are also limited by depth penetration to a few millimetres of tissue and only have a small beam size. Synchrotrons are a type of particle accelerator which are another potential source and have similar beam energies as X-ray tubes, as well as the possibility of using spatially fractionated ultra-high dose rate microbeam radiation therapy (MRT). The combination of MRT and the FLASH effect have been shown to achieve superior clinical effects in small animal models compared to conventional X-ray or CONV-RT dose rates in a range of cancers. Synchrotrons are of limited availability due to being very large and expensive.

PHASER (Pluridirectional High-energy Agile Scanning Electronic Radiotherapy) is another concept for using FLASH-RT in the clinic. Part of this is a technique involving image-guidance. Image-guidance techniques are necessary for clinical FLASH-RT treatment of deep tumours, regardless of the delivery mode used. The PHASER concept is still in development and relies on further advances in technology. A clinically available method of treating deep-seated tumours with FLASH-RT is to use proton beams, although they are both costly and sizeable. Clinical proton beams have good depth penetration and can produce accurate dose distributions with single or few beams. These are likely to be used in future clinical trials in FLASH-RT.

The FLASH effect offers superior tissue protection in comparison to CONV-RT without compromising on tumour treatment. It has been studied across various species and now a single human case has been documented. While its mechanism of action is likely to involve oxygen depletion, it is not fully understood and therefore requires further study. The doses required to achieve the FLASH effect make it unsuitable for many clinical cases. Furthermore, the availability of radiation sources capable of producing suitable beams for treatment of both superficial and deep tumours is a limiting factor in clinical trials. If further study yields more understanding of the biological mechanisms of the FLASH effect, it may be possible to achieve it at lower doses, increasing its clinical viability.

What are the next steps in understanding more about the biological mechanisms of FLASH-RT?

There are many studies that still need to be performed for us to better understand the biological mechanisms responsible for the highly beneficial FLASH sparing effect. In Oxford, we aim to perform real time oxygen concentration measurements in cells and in mice during FLASH irradiation, in order to verify (or discard) oxygen depletion as a main explanation of the effect. Most FLASH studies to date have been in vivo studies. For a better understanding of the biological mechanisms of FLASH-RT, several more specific in vitro studies are needed, for example investigating levels of DNA damage and DNA damage response.

Experimental “FLASH” cancer treatment aces first human trial

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There may be a faster, less-painful way to use radiation against cancer.

The first-in-human trial of FLASH radiotherapy found the experimental treatment to be safe and effective — suggesting that there may be a faster, less painful way to use radiation against cancer.

The status quo: Radiation therapy is a common cancer treatment that uses high doses of radiation to kill or slow the growth of cancer cells. Usually, this is done by aiming a beam of radiation directly at a tumor for a few minutes. This part of the process is painless, like getting an X-ray.

Patients typically undergo daily treatments five days a week for several weeks, and including setup time, a treatment usually takes about 15 to 30 minutes.

With traditional radiation therapy, dosages may have to be limited to avoid painful side effects.

The challenge: By shrinking a tumor, radiation therapy can not only fight cancer, but also potentially relieve patients’ pain or other symptoms caused by it. But the beam of radiation can damage healthy tissue near the tumor, too, causing pain and other side effects.

To minimize these adverse effects, doctors have to limit the radiation dosage, which may reduce how effective the treatment is at fighting the cancer.

“[FLASH radiotherapy] offers the possibility of delivering larger doses of radiation, which could result in higher cure rates.”JOHN BRENEMAN

The FLASH effect: FLASH radiotherapy is a promising alternative to traditional radiation therapy.

It delivers a dose of radiation that’s over 300 times higher than traditional radiation therapy in just a fraction of a second. This induces something called the “FLASH effect” — a not-entirely-understood phenomenon in which the radiation still attacks the tumor, but doesn’t harm surrounding tissue.

“This offers the possibility of delivering larger doses of radiation — which could result in higher cure rates for patients with resistant tumors — without increasing side effects,” said John Breneman, principal investigator of the new trial.

In animal studies, FLASH radiotherapy has been shown to be safe and just as effective as traditional radiation therapy without causing unexpected side effects. Now, a University of Cincinnati-led team has shared the results of FAST-01, the first-in-human trial of the treatment.

One FLASH radiotherapy treatment lasts just 0.3 seconds.

The trial: The primary goal of the trial was to prove that FLASH radiotherapy is safe for people and has a feasible workflow. A secondary goal was to determine its efficacy by measuring how much pain relief it provided patients.

The trial included 10 patients with painful cancerous growths in the bones of their arms or legs. Each received one FLASH radiotherapy treatment — lasting just 0.3 seconds — at the site(s) of their cancer.

Their pain, use of pain meds, and adverse effects were measured the day they received the therapy, 15 days later, and one, two, and three months after treatment.

“We did not see any unexpected additional toxicity with the substantially shorter treatment.”EMILY C. DAUGHERTY

The results: Patients’ average time on the table was just 15.8 minutes per treated site — demonstrating that the workflow is feasible — and of the 12 total cancer sites treated, pain was fully relieved in six and partially relieved in two others. 

“[B]oth pain relief and side effects were in-line with what might have happened with conventional radiation,” said lead author Emily C. Daugherty. “We did not see any unexpected additional toxicity with the substantially shorter treatment.”

Looking ahead: Ultimately, the researchers believe FLASH radiotherapy would be most useful for treating cancers in the brain, lungs, or gastrointestinal area, as the tissues around those tumors are particularly vulnerable to damage from traditional radiation therapy.

It could also be useful for treating cancers in children, who are more sensitive to the side effects of radiation therapy. 

Since the limb treatments didn’t produce any unexpected side effects in people, they’ve begun enrolling patients in FAST-02, a trial that will target cancerous growths in the bones of the thorax, which surround the heart and lungs.

A mineral produced by plate tectonics has a global cooling effect, study finds

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An accordion-textured clay called smectite efficiently traps organic carbon and could help buffer global warming over millions of years.

MIT geologists have found that a clay mineral on the seafloor, called smectite, has a surprisingly powerful ability to sequester carbon over millions of years.

Under a microscope, a single grain of the clay resembles the folds of an accordion. These folds are known to be effective traps for organic carbon.

Now, the MIT team has shown that the carbon-trapping clays are a product of plate tectonics: When oceanic crust crushes against a continental plate, it can bring rocks to the surface that, over time, can weather into minerals including smectite. Eventually, the clay sediment settles back in the ocean, where the minerals trap bits of dead organisms in their microscopic folds. This keeps the organic carbon from being consumed by microbes and expelled back into the atmosphere as carbon dioxide.

Over millions of years, smectite can have a global effect, helping to cool the entire planet. Through a series of analyses, the researchers showed that smectite was likely produced after several major tectonic events over the last 500 million years. During each tectonic event, the clays trapped enough carbon to cool the Earth and induce the subsequent ice age.

The findings are the first to show that plate tectonics can trigger ice ages through the production of carbon-trapping smectite.

These clays can be found in certain tectonically active regions today, and the scientists believe that smectite continues to sequester carbon, providing a natural, albeit slow-acting, buffer against humans’ climate-warming activities.

“The influence of these unassuming clay minerals has wide-ranging implications for the habitability of planets,” says Joshua Murray, a graduate student in MIT’s Department of Earth, Atmospheric, and Planetary Sciences. “There may even be a modern application for these clays in offsetting some of the carbon that humanity has placed into the atmosphere.”

Murray and Oliver Jagoutz, professor of geology at MIT, have published their findings in Nature Geoscience.

A clear and present clay

The new study follows up on the team’s previous work, which showed that each of the Earth’s major ice ages was likely triggered by a tectonic event in the tropics. The researchers found that each of these tectonic events exposed ocean rocks called ophiolites to the atmosphere. They put forth the idea that, when a tectonic collision occurs in a tropical region, ophiolites can undergo certain weathering effects, such as exposure to wind, rain, and chemical interactions, that transform the rocks into various minerals, including clays.

“Those clay minerals, depending on the kinds you create, influence the climate in different ways,” Murray explains.

At the time, it was unclear which minerals could come out of this weathering effect, and whether and how these minerals could directly contribute to cooling the planet. So, while it appeared there was a link between plate tectonics and ice ages, the exact mechanism by which one could trigger the other was still in question.

With the new study, the team looked to see whether their proposed tectonic tropical weathering process would produce carbon-trapping minerals, and in quantities that would be sufficient to trigger a global ice age.

The team first looked through the geologic literature and compiled data on the ways in which major magmatic minerals weather over time, and on the types of clay minerals this weathering can produce. They then worked these measurements into a weathering simulation of different rock typesthat are known to be exposed in tectonic collisions.

“Then we look at what happens to these rock types when they break down due to weathering and the influence of a tropical environment, and what minerals form as a result,” Jagoutz says.

Next, they plugged each weathered, “end-product” mineral into a simulation of the Earth’s carbon cycle to see what effect a given mineral might have, either in interacting with organic carbon, such as bits of dead organisms, or with inorganic, in the form of carbon dioxide in the atmosphere.

From these analyses, one mineral had a clear presence and effect: smectite. Not only was the clay a naturally weathered product of tropical tectonics, it was also highly effective at trapping organic carbon. In theory, smectite seemed like a solid connection between tectonics and ice ages.

But were enough of the clays actually present to trigger the previous four ice ages? Ideally, researchers should confirm this by finding smectite in ancient rock layers dating back to each global cooling period.

“Unfortunately, as clays are buried by other sediments, they get cooked a bit, so we can’t measure them directly,” Murray says. “But we can look for their fingerprints.”

A slow build

The team reasoned that, as smectites are a product of ophiolites, these ocean rocks also bear characteristic elements such as nickel and chromium, which would be preserved in ancient sediments. If smectites were present in the past, nickel and chromium should be as well.

To test this idea, the team looked through a database containing thousands of oceanic sedimentary rocks that were deposited over the last 500 million years. Over this time period, the Earth experienced four separate ice ages. Looking at rocks around each of these periods, the researchers observed large spikes of nickel and chromium, and inferred from this that smectite must also have been present.

By their estimates, the clay mineral could have increased the preservation of organic carbon by less than one-tenth of a percent. In absolute terms, this is a miniscule amount. But over millions of years, they calculated that the clay’s accumulated, sequestered carbon was enough to trigger each of the four major ice ages.

“We found that you really don’t need much of this material to have a huge effect on the climate,” Jagoutz says.

“These clays also have probably contributed some of the Earth’s cooling in the last 3 to 5 million years, before humans got involved,” Murray adds. “In the absence of humans, these clays are probably making a difference to the climate. It’s just such a slow process.”

“Jagoutz and Murray’s work is a nice demonstration of how important it is to consider all biotic and physical components of the global carbon cycle,” says Lee Kump, a professor of geosciences at Penn State University, who was not involved with the study. “Feedbacks among all these components control atmospheric greenhouse gas concentrations on all time scales, from the annual rise and fall of atmospheric carbon dioxide levels to the swings from icehouse to greenhouse over millions of years.”

Could smectites be harnessed intentionally to further bring down the world’s carbon emissions? Murray sees some potential, for instance to shore up carbon reservoirs such as regions of permafrost. Warming temperatures are predicted to melt permafrost and expose long-buried organic carbon. If smectites could be applied to these regions, the clays could prevent this exposed carbon from escaping into and further warming the atmosphere.

“If you want to understand how nature works, you have to understand it on the mineral and grain scale,” Jagoutz says. “And this is also the way forward for us to find solutions for this climatic catastrophe. If you study these natural processes, there’s a good chance you will stumble on something that will be actually useful.”

Calcific Tendinitis of the Triceps Tendon

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Calcific tendonitis is a common condition in which the body deposits calcium hydroxyapatite crystals within tendons. The natural course of the condition starts with calcium deposition followed by spontaneous resorption, which is often painful, followed by improvement of clinical symptoms. The condition is slightly more common in women than men and generally occurs in patients between ages 30 and 60. The pathogenesis of calcific tendonitis remains unclear.1,2

Calcific tendonitis can occur at any point of tendon insertion in the body; however, the shoulder and hips are the most common sites. The presentation includes a rapid onset of severe pain in a tendon insertion in the absence of trauma from a precipitating event. In many cases, calcific tendonitis can be found incidentally on radiographs in asymptomatic patients while other patients experience severe pain.1,2

Treatment begins with conservative methods including a period of rest, nonsteroidal anti-inflammatory drugs, and gentle range of motion exercises to preserve joint motion. Symptoms often resolve in 2 to 3 months as the calcium deposit is slowly absorbed.  If conservative treatments fail other treatments such as extracorporeal shockwave lithotripsy, needle aspiration and steroid injection, and surgery are options

Is Cryotherapy Good For You?

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Cryotherapy has both physical and mental benefits, from relieving chemotherapy side effects, cancers, arthritis and pain to improving your metabolic markers, muscles, skin, mood and sleep

Cryotherapies, or cold therapies, include a variety of methods. Common types include cold water immersion (CWI), spa cryotherapy — immersing the whole body in a cryotherapy chamber with freezing or nearly freezing temperatures for three to five minutes — and cryotherapy applications using ice cubes, ice packs, frozen gloves or socks.

Another example is medical cryotherapy, also known as cryoablation or cryosurgery, which uses extreme cold to freeze and remove abnormal tissue to treat skin diseases such as warts and skin tags in addition to prostate, cervical, skin, bone or liver cancers.[i]

Cryotherapy for Cancer-Related Adverse Effects

Chemotherapy treatments for cancer often result in adverse effects such as oral mucositis — red, sore mouth and/or gums and open sores in the mouth[ii] — anorexia, or abnormally low body weight, or peripheral neuropathy — damaged nerves leading to weakness, numbness and pain usually found in the hands and feet.

In 72 patients with esophageal cancer who were treated with chemotherapy of docetaxel, cisplatin and fluorouracil (DCF), 58 patients received cryotherapy — where they sucked on ice cubes or chips during their DCF administration — while 14 received no cryotherapy. The cryotherapy group had significantly lower incidences of mucositis and anorexia compared to the non-cryotherapy group.[iii]

In 50 subjects given chemotherapy for gynecologic cancers, half of the participants were assigned to oral cryotherapy during chemotherapy and the other half were the control group receiving 0.9% normal saline gargles three times before meals. The study revealed that oral cryotherapy was more effective than the usual care regime of saline gargles to reduce oral mucositis, reactive oxygen series and inflammatory cytokines and to improve oral comfort in the cancer subjects.[iv]

From a meta-analysis of 14 trials with 1,577 participants, oral cryotherapy was conclusively associated with a significantly lower risk of developing oral mucositis from cancer chemotherapies and promising but not conclusive evidence for those in a bone marrow transplant setting. More high-quality trials in the future are needed for this setting.[v]

The empirical evidence supports recommendations for oral cryotherapy to prevent oral mucositis in  patients undergoing autologous hematopoietic stem cell transplants either with high-dose melphalan conditioning protocols or bolus 5-fluorouracil chemotherapy in a systematic review of 36 research papers.[vi]

Such transplants are most often indicated in multiple myeloma and lymphoma cancers.[vii] Results of another meta study — examining 15 research trials involving 919 cancer patients — provide a scientific basis for oral cryotherapy as a viable treatment to significantly reduce severe oral mucositis.[viii]

To treat the side effect of chemotherapy-induced peripheral neuropathy, a number of studies have shown the significant effectiveness of wearing frozen gloves and socks including research involving 40 breast cancer patients,[ix] 44 women with breast cancer,[x] 39 breast cancer subjects[xi] and 54 early stage breast cancer participants who were in the cryotherapy group compared to the control group.[xii]

Cryotherapy May Relieve Exercise-Induced Effects

Cryotherapy may relieve sleep and muscle issues caused by exercise-induced muscle damage, muscle atrophy and exercise-induced muscle soreness. The use of a three-minute whole body cryotherapy (WBC) session after exercise training in the evening improved subjective and objective sleep quality in 22 physically active men, which is believed to be related to greater pain relief and improved parasympathetic nervous activity during the slow wave sleep period.[xiii]

In a study of 21 physically active men who strength trained for 12 weeks, two days per week, the men had either cold water immersion (CWI) treatment or active recovery (ACT) with low intensive exercise after high-intensity exercising (the control group). Both groups had strength and muscle mass increases in the short run. 

A second trial of nine active men who did single-leg exercises followed by CWI or ACT revealed CWI attenuated more acute changes in satellite cell numbers and activity of kinases that regulate muscle hypertrophy, a large growth in muscle or bulking of the muscle. This translates into smaller but long-term training gains in muscle strength and hypertrophy compared to ACT.[xiv]

Oxidative Stress and Metabolic Markers

Ten sessions of WBC performed in a closed cryochamber for three minutes a day followed by kinesiotherapy or movement therapy for 60 minutes significantly improved the lipid profile and decreased oxidative stress in 16 healthy subjects.[xv]

Researchers studied different temperatures and duration of cryotherapy using a mouse model on oxidative stress markers and found that WBC at a temperature below 60 degrees centigrade (C) may be more beneficial than below 90 degrees C for most of the markers. The highest total antioxidant capacity was observed in the below 60 degrees C for five days rather than 10 days.[xvi]

In a study comparing winter swimmers who ice bathed with healthy people who have never been swimming in winter, winter swimmers were found to have more tolerance to environmental stress and an increased ability to adapt to repeated oxidative stress markers.[xvii]

In a systematic review of 104 studies on voluntary cold water immersion, the treatment seems to reduce and/or transform body adipose tissue, as well as reduce insulin resistance and improve insulin sensitivity, which could protect against cardiovascular diseases, obesity and other metabolic diseases while offering prophylactic or disease-prevention health effects.[xviii]

Arthritis

Nearly 1 in 3 U.S. adults with doctor-diagnosed arthritis — which includes rheumatoid arthritis, osteoarthritis, fibromyalgia, lupus, gout or ankylosing spondylitis[xix] — have severe joint pain, fatigue and functional limitations or disabilities.[xx] In a review of six studies with a total of 257 rheumatoid arthritis (RA) patients, chronic cryotherapy resulted in significant decreases in pain and a 28-joint disease activity score.

For molecular pathways, local cryotherapy induced an intra-joint temperature decrease, thought to downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but more molecular studies are needed in RA to verify. Using cryotherapy to treat RA could potentially reduce corticosteroid and nonsteroidal anti-inflammatory drug doses.[xxi]

In a study of 47 patients with various knee inflammation diseases including gout, RA, spondyloarthritis and calcium pyrophosphate dihydrate crystal deposition diseases (CPPD) or pseudogout, local ice cryotherapy significantly reduced pain and inflammation measured by pro-inflammatory cytokines including interleukin six (IL-6), interleukin one beta (IL-1β), vascular endothelial growth factor (VEGF), and impacted signaling mechanism of nuclear factor kappa p65 (NF-kB-p65) and immunity mediation of prostaglandin E2 (PG-E2) synovial levels, especially in the microcrystal-induced arthritis group.

Only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients with the ice therapy.[xxii] In a trial of 60 fibromyalgia (FM) patients, those treated with WBC using the Cryosense TCT cabin had decreased pain and disease severity compared to those who just rested (the control) with cryotherapy recommended as a useful complementary FM therapy. [xxiii]

In supervised therapy of 92 ankylosing spondylitis (AS) patients, subjects were assigned to one of three groups for eight days:

  • WBC below 110 degrees C with exercise therapy
  • WBC below 60 degrees C with exercise therapy
  • Exercise therapy alone

WBC at below 110 degrees C with exercise therapy had the most significant AS disease activity reduction compared with the other two groups.[xxiv]

Multiple Sclerosis

Oxidative stress is an important factor that contributes to disease progression in multiple sclerosis (MS). Treatment of 28 MS patients who underwent 10 WBC exposures of below 120 degrees C for three minutes per day resulted in Increased total antioxidative status level of their MS, meaning decreased oxidative stress and MS progression.[xxv]

Dividing 60 MS patients into three groups,  including cryotherapy, physical exercise training and cryotherapy with physical exercise training, research showed that the combined WBC with physical exercise training had the most statistically significant differences in psychosocial well-being, reduction of depressive symptoms and improved functional status of MS.[xxvi]

Depression, Anxiety and Brain Disorders

In a control and study group of 60 outpatients 18 to 65 years old with depression and anxiety disorders who received standard psychopharmacotherapy, the study group was also treated with 15 daily visits to a cryogenic chamber for two to three minutes from below 160 degrees C to below 110 degrees C. After three weeks, scientists observed a decrease of at least 50% from the baseline depression scores in 34.6% of the study group and 2.9% of the control group.

A decrease of at least 50% from the baseline anxiety scores in 46.2% of the study group and in none of the control group for mood and anxiety was also found.[xxvii]

In a trial of 30 adults diagnosed with depressive episodes, those treated with 10 WBC sessions lasting two minutes with temperatures below 110 degrees C to below 135 degrees C within a two-week period showed significant improvement in reduced total scores in scales assessing depressive symptoms, higher quality of life including physical, psychological and environmental health and a significant increase in self-reported well-being.[xxviii]

In a nine-week study of 84 adults aged 60 or older, those given computerized cognitive training alone or combined with 10 sessions of WBC experienced decreased cognitive decline or dysfunction and improvement in several cognitive domains including verbal fluency, learning ability and memory. However, only in the group with combined interventions did the participants show significantly fewer depressive symptoms compared to the control group of no WBC intervention.[xxix]

Alzheimer’s disease (AD) — the most common form of dementia — is one of the major causes of disability and mortality in aging adults. Mild cognitive impairment is regarded as the first detectable sign of cognitive decline. In their research review, scientists show the mechanisms of cryostimulation and postulate that WBC would be a viable means of preventing AD due to its anti-inflammatory and antioxidative effects.[xxx]

Warts

Common warts are benign growths caused by human papilloma viruses (HPV). One study involved 35 patients with 414 common warts divided into two groups treated either by cryotherapy using liquid nitrogen spray or by 90% trichloroacetic acid (TCA).

The liquid nitrogen cryotherapy group beat the TSA group with significantly better results in the mean percentage of improvement, grade of improvement and complete cure of warts.[xxxi]

Genital warts are a common sexually transmitted disease. Cryotherapy using liquid nitrogen represents the first line of therapy. In a retrospective study, data from 50 women with genital warts who were treated with cryotherapy in a period from 2012 to 2018 were analyzed. Cryotherapy had a high success rate of 78% in healing genital warts, decreased the concentration of HPV virus and removed the trigger that allows the development of cancer.[xxxii]

Two genital warts of 16 male patients each were randomly assigned to receive either cryotherapy using the Wartner mixture of dimethyl ether (75%) and propane (25%) (treatment) or liquid nitrogen cryotherapy (control). The Wartner compound was as effective as the conventional cryotherapy method using liquid nitrogen for treating genital warts.[xxxiii]

Cryotherapy or Not?

Cryotherapy, in its many forms, is considered a safe nontoxic way for many cancer patients undergoing chemotherapy to reduce harmful side effects such as oral mucositis, anorexia and peripheral neuropathy. It may also be helpful to address the negative effects of strenuous exercise and offers support for diseases including certain cancers, arthritis, MS, AD, depression, anxiety and warts.

Cryotherapy is also seen as a preventive strategy to improve metabolic markers and lower oxidative stress, which are highly associated with cardiovascular diseases, diabetes and obesity. On balance, cryotherapy could lift your mood, create better sleep, decrease muscle and joint pain, increase your cognitive abilities and improve your health, so why not try it?