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To ice or not to ice? Icing promotes muscle regeneration after mild injury

Cumulative research by a multi-institutional Japanese research collaboration reveals that ‘to ice or not to ice’ may depend on the degree of muscle injury.

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Applying ice to a muscle injury is a widespread first-aid treatment, but exactly what effect does this have on the muscle regeneration and does it really help? Cumulative research by a multi-institutional Japanese research collaboration reveals that ‘to ice or not to ice’ may depend on the degree of muscle injury.

In their latest research, the group consisting of Associate Professor ARAKAWA Takamitsu and Master’s student NAGATA Itsuki (from Kobe University’s Graduate School of Health Sciences), and Assistant Professor KAWASHIMA Masato (Kawasaki University of Medical Welfare) et al. have shown that applying ice to muscle damage in a small percentage of muscle fibers in rats promotes muscle regeneration. This is believed to be the first study in the world to show benefits of icing on muscle repair. In conjunction with their previous study on serious muscle injuries (‘Icing muscle injuries may delay recovery’), it is hoped that these results can be used as a basis for more accurate guidelines on whether or not to ice such injuries.

These research findings were first reported in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology on March 6, 2023.

Main Points

  • The experiments showed that applying ice after a mild muscle injury promotes muscle regeneration.
  • This is believed to be the first time in the world that a study has shown a positive effect of icing on muscle regeneration.
  • The researchers showed that the extent of the injury may have a greater impact on the effectiveness of icing than the method or timing employed.
  • The findings of this ongoing research will lead to the spread of more accurate information on the effects of icing throughout hospitals, and in the realms of sports and physical education.

‘RICE treatment’ is a common approach for treating the acute phase of sports injuries. This acronym stands for Rest, Ice, Compression and Elevation and it is also often used in physical education in schools and even clinical settings. There are a variety of subsequent steps that can be taken to treat the injury afterwards, yet opinions vary as to whether or not icing should be applied. However, there is a lack of evidence on the benefits of icing.

The current research team has conducted many experiments to investigate the effectiveness of icing, which led them to publish their previous findings (‘Icing muscle injuries may delay recovery’ ). However, no previous animal experiments have indicated that icing promotes muscle regeneration.

In this study, the researchers focused on altering the severity of the muscle injury in the experiments. The reasoning behind this was that the majority of sports-related muscle injuries are limited; in other words less than 10% of the overall number of muscle fibers (myofibers) are damaged and necrotized. However, all animal experiments up until now had looked at more serious injuries where over 20% of the myofibers were damaged.

Thus, the team devised an animal model for mild muscle injuries, and experimented with applying ice after injury using a similar method as before.

After the animal was anaesthetized, the muscle was exposed and clamped between forceps to induce injury. In their previous experiments, the researchers attached a 500g weight to the forceps, which induced an injury that affected 20% of the total number of fibers in the muscle. In the present study, they tried attaching a 250g weight to the forceps and demonstrated that this could be used to consistently injure 4% of the fibers (Figure 1). This is similar to the degree of injury that often occurs after sports activities such as vigorous exercise or long-distance marathon running.

Icing was carried out by placing polyethylene bags of ice on surface of the skin over three 30-minute sessions per day, with each session being 1.5 hours apart. This was continued until two days after injury for a total of 9 icing sessions (i.e. immediately after injury = 3 sessions, 1 day after injury = 3 sessions, 2 days after injury = 3 sessions). The icing method was the same as in the previously reported study (‘Icing muscle injuries may delay recovery’).

Observations of muscles that were regenerating in the icing group and no-icing group 2 weeks after injury revealed significant differences in the size of regenerating fibers in cross-sections (Figure 2). In other words, this demonstrated the possibility that skeletal muscle regeneration is promoted by icing.

Macrophages are immune cells that orchestrate the reparative process of injured muscle. Pro-inflammatory macrophages accumulate in the damaged site soon after injury occurs, however they express an inducible nitric oxide synthase (iNOS), which has a disadvantageous side-effect of expanding the injury’s sizeThe results of this team’s experiments revealed that icing after mild muscle injury reduces the accumulation of iNOS-expressing pro-inflammatory macrophagesBy causing this phenomenon, icing prevents the expansion of muscle injury size.

In other words, icing attenuates the recruitment of pro-inflammatory macrophages in the injury site. This was also reported in their previous study (‘Icing muscle injuries may delay recovery’), demonstrating that this is an effect caused by icing regardless of whether the muscle injury is serious or mild. In the previous study, icing was found to delay the regeneration of muscle after a serious injury that destroyed many fibers because the pro-inflammatory macrophages were unable to sufficiently phagocytose (*5) the injured muscle. In contrast to this, the current study shows that icing has a positive effect when the muscle injury is mild because it prevents the secondary expansion of the muscle injury caused by the pro-inflammatory macrophages. It suggests that this particular effect of icing is connected to the promotion of muscle regeneration.

Icing has been used in the treatment of muscle injuries for a long time, however the positive effects of icing had yet to be elucidated until now. This study has shown that icing can promote muscle regeneration when used to treat commonly-occurring mild muscle injuries.

However, this does not mean that icing is effective for all types or degree of muscle injury. The researchers aim to further elucidate and raise awareness of this. For example, the group’s previous study showed that icing actually inhibited regeneration in cases of serious muscle injury. In addition, the term ‘muscle injury’ also includes extremely minute injuries that have yet to be observed through the team’s animal experiments, so it is still unclear as to what effect icing has on the repair from such microtraumas.

The researchers’ next challenge is to determine the extent of muscle injury up to which icing is appropriate. By building upon their previous investigations, they aim to contribute towards guidelines that will enable people in sports and clinical rehabilitation to make accurate judgements about whether or not to ice an injury.

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NewsMakers

Aerobic exercise can help fight liver diseases

he Mfn-2 protein would regulate the curve of the mitochondrial membrane in promoting the oxidation of fat in a specific population of mitochondria, through its interaction and ability to form specific domains with membrane phospholipids.

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Aerobic exercise could help fight the non-alcoholic fatty liver disease, the most common liver disease worldwide: it affects nearly 24% of the global population and it usually causes a certain stigma among the affected people.

This is according to a study – “Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD” that appeared in the journal Metabolism. The study was led by Professor María Isabel Heràndez-Alvarez, in collaboration with Rodrigo Troncoso, and Víctor Cortés.  

When the liver accumulates large amounts of fat

One of the features of the fatty liver disease or non-alcoholic steatohepatitis (NAFLD) is the large concentration of lipid droplets (LD) that accumulate in the liver cells. “Our findings reveal that aerobic exercise, that is, moderate physical activity over time, helps metabolize the fats because it reduces the size of lipid droplets, and therefore, the severity of the disease”, notes the author. 

“Therefore, the energy demands induced by the exercise determine regulated changes in physical and functional relationships between fat droplets and mitochondria, the cell organelles that provide energy for the metabolism.”

This interaction may take place in a specific population of mitochondria known as peridroplet mitochondria (PDM). “As a result, there is a higher oxidation of lipids in this specific population of mitochondria, a process that helps prevent the progress of the disease”.

Discovering a previously unknown connection

“The interaction between the lipid droplets (LD) and the mitochondria is functionally important for the homeostasis of the fat metabolism. Exercise improves fatty liver disease, but to date, it was unknown whether the disease had a direct impact on the interactions between hepatic LDs and mitochondria,” noted María Isabel Hernàndez-Alvarez, Ramón y Cajal postdoctoral researcher at the UB’s Department of Biochemistry and Molecular Biomedicine.

The study also stresses that mitofusin 2 (Mfn-2) — a protein located in the external membrane of mitochondria — plays a decisive role in this process, since it modifies the communication between lipid droplets and the specific population of mitochondria.

“We found a decrease in the content related to saturated fatty acids in the hepatic mitochondrial membranes of animals that had done physical activity. This suggests that membrane fluidity increases in the mitochondria,” noted the researcher. “In the case of the mice without the Mfn-2 gene, exposed to physical activity, we did not observe changes in the saturation and the metabolism of fatty acids. These results show that the Mfn-2 protein takes part in the regulation of the composition of fatty acids of the mitochondrial membranes in response to exercise”.

According to the authors, the Mfn-2 protein would regulate the curve of the mitochondrial membrane in promoting the oxidation of fat in a specific population of mitochondria, through its interaction and ability to form specific domains with membrane phospholipids.

The study is a step forward to boosting research on mediators and molecular mechanisms that could promote new strategies to prevent the progression of NAFLD. “Considering the Mfn-2 functions in mitochondrial morphology and in the liver, the therapeutic manipulations of the levels and the activity of Mfn-2 could contribute to the improvement of the NAFLD-related inflammation and the fibrosis”, concluded the researcher.

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Fitness

Treatment options to help overcome knee pain for sports enthusiasts

“Sports-related pain should be evaluated quickly, especially when it’s difficult to put weight on the knee, swelling occurs or there is restricted range of motion,” said Dr. Alexander Meininger, orthopedic surgeon and MACI consultant.

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Millions of people experience chronic pain, with knee pain among the most common. Athletes and active adults know the impact activities like running and skiing can have on their knees, but when chronic knee pain makes it difficult to do those activities, or even day-to-day tasks like walking up the stairs, people may often face challenges.

According to the journal “Cartilage,” unlike other tissues, cartilage does not repair itself and, without proper treatment, can worsen over time and become more difficult to treat. However, options like FDA-approved knee cartilage repair surgery MACI (autologous cultured chondrocytes on porcine collagen membrane) uses a patient’s cells to help repair cartilage defects and may help alleviate knee pain.

“Sports-related pain should be evaluated quickly, especially when it’s difficult to put weight on the knee, swelling occurs or there is restricted range of motion,” said Dr. Alexander Meininger, orthopedic surgeon and MACI consultant.

Justin Keys, a former patient of Meininger and avid skier, knows that the long-term outcomes of knee cartilage surgery can be worth the short-term sacrifices. After several injuries, including an ACL injury, Keys struggled with most activities except walking on flat, paved surfaces. After consulting with Meininger, Keys chose knee cartilage repair to help get back to his active lifestyle.

Keys considered whether to manage the injury as-is or choose MACI and undergo rehabilitation to potentially get back to his favorite activities in the future. He knew he could no longer use short-term relief methods and had to address his pain with a treatment to help provide lasting relief.

For athletes like Keys who want to fix knee pain, it’s important to consider these steps:

Discuss Options with Your Doctor

Patients should talk to their doctors and undergo an MRI to help assess the internal structures of the knee. Meininger recommends patients and their doctors discuss options for long-term knee restoration health, preserving function for future decades and recognizing the short-term sacrifice.

Set Yourself Up for Success

Experts like Meininger suggest patients take steps ahead of surgery to help their recovery.

“The important thing is to be as fit as possible and use the preseason months to undergo surgery and rehab,” Meininger said.

Patients can take steps to prep their home for recovery, which may include:

  • Bringing necessities down from hard-to-reach shelves
  • Moving furniture to ensure clear pathways
  • Installing shower safety handles to minimize potential falls

The Road to Rehab and Recovery

Rehabilitation takes time and everyone’s experience is unique. It can be as much of a mental challenge as it is physical. Committing to a physical therapy regime, staying hydrated and eating well are important aspects to support recovery. Patients should talk to their doctors with questions and before starting any exercises.

IMPORTANT SAFETY INFORMATION

Do not use if you are allergic to antibiotics such as gentamicin or materials from cow or pig; have severe osteoarthritis of the knee, other severe inflammatory conditions, infections or inflammation in the bone joint and other surrounding tissue or blood clotting conditions; had knee surgery in the past 6 months, not including surgery for obtaining a cartilage biopsy or a surgical procedure to prepare your knee for a MACI implant; or cannot follow a rehabilitation program post-surgery.

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Wellness

Whether you exercise regularly or one-to-two days a week, weight loss is possible

Whether you engage in physical activity on a regular basis or one-to-two days a week, both options produce weight loss suggests a new study published in the journal Obesity.

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Whether you engage in physical activity on a regular basis or one-to-two days a week, both options produce weight loss suggests a new study published in the journal Obesity, The Obesity Society’s (TOS) flagship journal. The study is the first of its kind to examine the association between physical activity patterns and objectively-measured fat tissue mass.

Guidelines from the World Health Organization recommend that adults perform at least 150 minutes per week of moderate physical activity, 75 minutes per week of vigorous physical activity or an equivalent combination of both intensities. However, many individuals find it challenging to meet this recommendation due to physical activity being time consuming in a fast-paced society. The new study found that people defined by researchers as “weekend warriors”—individuals who condense their exercise into one-to-two days a week—can also lose weight similar to individuals who exercise on a regular basis as long as they achieved the recommended goals.

“The weekend warrior pattern is worth promoting in individuals who cannot meet the recommended frequency in current guidelines,” said Lihua Zhang, health care scientist, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Zhang is one of the corresponding authors of the study.

Zhang suggested that office workers, bus drivers and other employees who have to sit for many hours during the work day care about the research. “Those people are struggling to catch up in their exercise plan in daily life to offset the hazard of a sedentary lifestyle but have less free time to get to the gym,” she said. “Our study could offer them an alternative choice to keep fit,” said Zhang, who added that there are suitable activities for weekend warriors such as climbing, hiking, cycling or running.

Researchers extracted data from more than 9,600 participants in the National Health and Nutrition Examination Survey from 2011 to 2018. Participants ranged in age from 20- to 59-years-old.

Abdominal and general adiposity were assessed by dual-energy x-ray absorptiometry (DXA)—a non-invasive and easily accessible body composition scan—and anthropometric measures. Physical activity levels were collected from the Global Physical Activity Questionnaire and classified as inactive, weekend warrior and regularly active. Survey linear regression models were used to assess associations between physical activity patterns and adiposity indicators.

Results showed that 772 participants reported the weekend warrior pattern and 3,277 reported the regularly active pattern. Compared to the 5,580 inactive participants, both the weekend warrior and regular active groups had lower DXA-measured abdominal adiposity, waist circumference, whole-body fat mass and body mass index. These two groups were also younger, more likely to be non-Hispanic White, have higher educational backgrounds, and less likely to be unemployed or to have hypertension or diabetes.

“On a high level, this study reaffirms the old adage about physical activity and health: any activity is better than no activity. Notably, the weekend warriors’ workout was of higher intensity and longer duration, and more intensity and longer duration correlated with even lower abdominal fat. The main takeaway, though, is that people should be active in any manner that suits their lifestyle,” said Assistant Professor of Clinical Medicine Beverly Tchang, MD, DABOM, Comprehensive Weight Control Center, Weill Cornell Medicine in New York. Tchang was not associated with the research study.

Steven B. Heymsfield, MD, professor, Pennington Biomedical Research Center, Baton Rouge, La., who was also not associated with the study added, “Findings in a cross-sectional sample such as reported by the study’s researchers need confirmation in prospective longitudinal studies.”

Other authors of the study include Lubi Lei, Jingkuo Li, Wei Wang, Yanwu Yu, Boxuan Pu and Yue Peng, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Another corresponding author, Zhenyan Zhao, is from the Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The authors declared no conflicts of interest.

The study, titled “The Associations of ‘Weekend Warrior’ and Regularly Active Physical Activity with Abdominal and General Adiposity in U.S. Adults,” will be published in the April 2024 issue of Obesity.

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