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Can Sauna Use Boost Collagen Production?

By Saunas.org - Kat | | Cosmetics & Make-Up, Detoxification, Healthspan, Longevity, Research & Data

Regular sauna use of any kind will improve both the health and appearance of skin. If you are curious if saunas can actually boost collagen production and augment the quality of your skin and other organs that rely on collagen for functionality, you may be surprised to find out that regular sauna use of a specific kind may actually improve collagen production. 

Large numbers of  individuals are concerned about their personal collagen production because this protein combined with elastin are responsible for the bouncy youthful appearance of skin. Many skin  creams purport to contain collagen enhancing agents, but these creams and lotions may not always actually affect collagen production. 

There are certainly ways to improve collagen production within your body that actually have sound scientific evidence to support this truth. 

Saunas may not be the most direct means to enhance collagen production, so you may also want to consider partnering your sauna use with other protocols to improve collagen production. 

Find out what the scientific data is saying about sauna use and collagen production, and what type of sauna you should use if collagen production is high on your list of reasons to use a sauna.

What is the Big Deal With Collagen and Skin

The skin is the outermost layer of the human body and is the first barrier between the inner world of the body and its environment. This means that skin is exposed directly to many different toxins, pollutants, and chemicals. Improving the overall quality and appearance of the skin requires more than just improving collagen production; however, an uptake in collagen production will certainly help to maintain skin health. 

Elastin and collagen are proteins that weave together to create a matrix-like formation throughout the skin organ. These two proteins working in tandem help to keep the skin taught and plump. This is why discussions surrounding collagen are so much in the forefront of media and skin care. (1)

As we age, the presence of collagen in the skin lessens, and eventually fine lines, wrinkles, and sagging skin begins to appear. For those looking to avoid or delay the onset of these portions of aging,  improving collagen production will certainly help with maintaining the appearance of youthful skin. 

Saunas may help with skin health in many more ways beyond collagen production. Increased sweating allows the pores to open up and release pathogens and toxins out through the skin instead of just absorbing environmental toxins. Saunas also help to improve blood flow, reduce inflammation, and improve immunity. 

For the purpose of this article we will primarily focus on how saunas may improve collagen production. 

How Sauna Use May Improve Collagen Production: The Research Behind the Claim

  • Mild Wrinkling
  • Photo-aged Facial Skin Lesions
  • Hyperpigmentation

A study published by the National Institute of Health revealed the impact that far infrared light exposure has on aging skin and its potential to reverse the effects of aged or damaged skin. This study primarily focused on the presence of the proteins elastin and collagen before and after in study participants to determine the efficacy of infrared light on skin health. (2)

The published study “Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation” evaluated the presence of collagen in 20 participants over a six month period. Both before, during (every 4 weeks), and after biopsies were taken of the participants skin to monitor changes in the presence of collagen and elastin. All of the participants reported mild-wrinkling, and hyperpigmentation as well as other signs of early aging skin before the study began. (2)

In both objective measurements as well as subjective measurements the study revealed a 50-75% increase in the overall quality of the participants skin.

“These results suggest that infrared radiation may have beneficial effects on skin texture and wrinkles by increasing collagen and elastin contents from the stimulated fibroblasts. Therefore, skin treatment with infrared radiation may be an effective and safe non-ablative remodeling method, and may also be useful in the treatment of photo-aged skin.” (2)

There may be faster ways to improve collagen production than using a far infrared or full spectrum infrared sauna. However, in just six months participants in this study noticed a remarkable uptake in the appearance of their skin, and those conducting scientific sampling indicated a clinically significant uptake in the presence of collagen in its participants. 

Support Your Collagen Production With Infrared Saunas, and Ingestible Collagen

If your goal in using a sauna is to improve collagen production, it will need to be a far infrared sauna, or a sauna that includes far infrared light. The participants of the study mentioned above were exposed to far infrared light for 20 minutes a day for 5 days a week over the course of six months. 

This may seem like a lot of time to spend in the sauna, but most research suggests that sauna use needs to be implemented 3-4 times a week to effect significant biological change. If you have already committed to using a sauna for other health reasons then following a similar protocol to improve collagen production will not be out of the ordinary. 

In addition to using a far infrared sauna for collagen production, recent studies suggest that ingesting collagen can also dramatically improve its presence in the body. 

Published by the Journal of Cosmetic Dermatology, the study ‘The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo-controlled clinical trials’, elaborates on the effectiveness of ingesting collagen orally.

“The oral supplementation with collagen peptides is efficacious to improve hallmarks of skin aging.” (3)

This same study elaborates on the efficacy of oral collagen supplementation in this statement:

“Oral collagen peptide supplementation significantly increased skin hydration after 8 weeks of intake. The collagen density in the dermis significantly increased and the fragmentation of the dermal collagen network significantly decreased already after 4 weeks of supplementation.” (3)

If improving collagen production is a priority, then it is definitely worth ingesting it orally in addition to your sauna protocol. Sauna use can be wildly helpful in many areas of health and it is also worth considering adding other protocols for a well rounded result.

Below the First Layer: Collagen is Also Radically Important in the Maintenance of Connective Tissues For Joint Health

Beyond improving skin appearance and health, collagen is very important in maintaining the health of connective tissues, particularly as aging occurs. Even if your primary interest in improving collagen production is for the augmentation of your skin’s youthful appearance, then as a secondary benefit, you will also be aiding the health of your tendons and ligaments that are so important for joint health. 

Whether improving collagen production is on your radar for cosmetic reasons or for deeper healing within the joints, then finding ways to uptake collagen in your body is well worthwhile. 

With a combination of far infrared sauna use and collagen ingestion of the right variety you will be sure to improve the overall presence of the magnanimous protein called collagen. 

To find the best type of collagen to ingest please consult with your dermatologist or healthcare professional. As always if you plan to use a sauna regularly please be sure to stay well hydrated as this will also affect your overall health and the appearance of your skin. 

Sources Cited:

  1. https://www.webmd.com/skin-problems-and-treatments/elastin-what-to-know
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687728/
  3. https://onlinelibrary.wiley.com/doi/10.1111/jocd.12174
  4. https://www.hubermanlab.com/episode/how-to-improve-skin-health-appearance

Is it Too Late to Begin Using a Sauna? Find Out How Infrared Sauna Use May Positively Affect Geriatric Syndrome and Frailty

By Saunas.org - Kat | | Cardiovascular Health, Dementia, Elderly, Health Benefits, Healthspan, Heart Health, Longevity

There is a plethora of positive data regarding the impact that sauna bathing may have on longevity and healthspan. If you have already reached your golden years you may be wondering if it is worth beginning a sauna bathing protocol, or if you have simply missed the window of opportunity. 

A recent study examined the impact of infrared sauna use on elderly assisted living community dwelling individuals who were already living with geriatric syndrome or frailty, and the results were overall quite positive. This suggests that even if you are past retirement age, or even if you are already living in an elderly community, it may still be worth taking time to use an infrared sauna a couple of times a week. 

Geriatric syndrome generally encompasses the following symptoms: Cold extremities, leg edema, breathlessness, urinary incontinence, chronic headache, chronic pain, a sense of numbness, anorexia, constipation, insomnia and skin trouble. (1) It appears that many of these symptoms improved in clinically significant ways for individuals already living in spaces with assistance at home when they were able to take an infrared sauna at least twice a week. 

Even if you are feeling as if you missed the opportunity to reap the benefits from infrared sauna use, in fact it may never be too late to start your sauna journey to improve your overall quality and quantity of life.

The Science Behind Geriatric Syndrome and Infrared Sauna Use

In a recent study that examined the effects of infrared sauna use on individuals with geriatric syndrome, as well as pre-geriatric syndrome, it appears that it is certainly worthwhile to use an infrared sauna several times a week at lower temperatures to improve many of the symptoms experienced by the elderly. 

The study entitled: ‘Effectiveness of a far-infrared low-temperature sauna program on geriatric syndrome and frailty in community-dwelling older people’ worked with individuals that were between the ages of 79 to 86 years of age and that were already living in ‘living assisted’ communities. The study aimed to examine the effect of infrared sauna use on these symptoms of geriatric syndrome.

“We analyzed indices of physical frailty and cognitive depression, exercise tolerance and health-related quality of life as frailty related indices, and the participants completed a questionnaire regarding common geriatric symptoms (cold extremities, leg edema, breathlessness, urinary incontinence, chronic headache, chronic pain, a sense of numbness, anorexia, constipation, insomnia and skin trouble).” (1)

The participants used a far infrared sauna that was set at a low temperature (FILTS) twice a week for three months. The results were incredibly positive in most areas that were studied. The primary areas that most participants had a marked improvement in were walking speed, peak oxygen uptake, geriatric depression, improvements in frailty scores, and  amelioration in the coldness of extremities. (1)

The study concluded that ‘a program of taking a far infrared sauna at a low temperature twice a week ameliorates geriatric syndrome, the severity of frailty and frailty related indices in older people’ (1).

So, if you have been hearing about all of the wonderful health benefits of sauna use and are afraid that it is too late for you or a loved one to begin a sauna program, then perhaps consider the above mentioned study. It is never too late to begin a safe and well organized sauna protocol.

Why an Infrared Sauna Versus Other Forms of Heat Therapy Maybe a Safer Sauna Option For the Elderly?

It is important to sauna safely for everyone always, but particularly for the elderly who may have more health risks. This is why understanding the acronym FILTS is so important. 

FILTS: Far Infrared Low Temperature Sauna

For anyone living with frailty, or other high risk health conditions getting into an extremely hot (190 degrees) traditional sauna may be prohibitive. Traditional steam saunas or steam rooms can be difficult to breathe in for some individuals and present great challenges for moving around safely. Wet floors can be hazardous for anyone, but especially for someone who is already living with geriatric conditions. 

Any amount of moisture on the floor of the sauna can potentially present lethal (2) consequences to anyone in the later years of life, and therefore using a sauna that is mostly dry becomes critical. 

Furthermore, the low heat of an infrared sauna does not mean that benefits are limited as is the case with traditional saunas because the light of an infrared sauna, regardless of its temperature, is deeply beneficial. 

Infrared saunas use radiant heat, and these light waves move invisibly through the cabin structure of the sauna to positively impact the human body, without any of the hazards of high temperatures and humidity. Consider the multifaceted health benefits that infrared light has on human physiology: Cellular regeneration, circulation, muscular health, bone density, heart health, lowered risk of dementia, and  improved immunity. (3)

For many conditions as well as demographics the idea of taking an infrared sauna at a low temperature is gaining in popularity as more individuals understand the function of infrared heat. If the idea of a sauna feels prohibitive, consider an infrared sauna set to a low temperature as taking a dry light bath.

Beginning an Infrared Sauna Protocol in Your Golden Years

Even if you are not in a living assisted home, you can still benefit from beginning an infrared sauna program. It is important for anyone with limited mobility or the risk of frailty to approach sauna use with the utmost care. 

It will be important to set your temperature to a very low degree (105) should suffice in your infrared sauna. You should also have a sauna buddy, or someone who can be available to help in case you need it. You should set the timer for 30 minutes to make sure that you are not staying in the sauna for too long. Start your program with a low temperature and with a low amount of time and slowly work up to a higher temperature, and duration (but it is not necessary to increase time or temperature). 

It may be worth investing in a wheelchair adaptable sauna if you are using a walker, or any other device to assist in walking. (There are wheelchair FDA approved saunas available right here at saunas.org).

As is the case with all sauna use, even if you are not sweating tremendously (if at all), it is still very important to maintain excellent levels of hydration. Your fluids should include electrolyte rich compounds, and some magnesium if possible. 

The good news is that It is never too late to start benefiting from sauna use. If you or a loved one does decide to begin using a sauna to treat geriatric or pre-geriatric syndrome with an infrared sauna then please be sure to consult your medical care professional before beginning your sauna protocol. 

Sources Cited:

  1. https://pubmed.ncbi.nlm.nih.gov/32776407/
  2. https://www.cdc.gov/falls/data-research/index.html
  3. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/infrared-sauna/faq-20057954

July Sauna Sale: $400 Off All Summit Series Saunas

By Saunas.org - Kat | | Sauna Pricing, Sauna Shopping

At saunas.org our goal is to make high quality saunas available year around at the most affordable prices possible. In celebration of summer, for the month of July, we are offering a rare opportunity for additional savings on our full spectrum saunas with Himalayan salt walls. Use the code summer2024 and save $400!

During the heat of summer it may not seem appealing to think of getting into a hot sauna, however, this month happens to be among the best times of year to purchase a sauna. Sauna stock is at its highest, so that means that you have the opportunity to choose the right sauna for your individual health and wellness needs. 

Our summit series saunas are among the most healthful saunas on the market today. Find out more about our Summit series saunas and the health benefits associated with their features. 

Remember to use this promo code at checkout: Summer2024

Summit Series Saunas

  • Himalayan Salt Walls
  • Hyper-Allergenic Hemlock Wood
  • Full Spectrum Infrared light

Our summit series saunas are our most popular sauna because they are unique in their healing qualities, and may be considered our most healthful sauna. The summit series ranges in size from 1 person to 6 person, however, regardless of the size of the sauna, each unit contains the same features. 

Himalayan salt walls are associated with two primary health benefits: negative ionizing factors, and pulmonary health. Despite keeping the emf reading in our summit series saunas as low as possible, the salt particles that are released from the salt walls when the sauna heats up are negatively charged, and help to mitigate the experiential effects of the positively charged electrical componentry of the sauna. If you are someone who is particularly sensitive, or concerned with the effects of emfs on your body, then your mind can rest at ease with a sauna that comes with Himalayan salt walls. 

Secondly, Himalayan salt walls are associated with halotherapy (inhalation of salt particles for the benefit of the respiratory tract), and although the presence of salt walls in your sauna will not be as powerful as a salt generator in terms of its dramatic effect on pulmonary health, it will still be beneficial to include in your sauna. Himalayan salt walls in a sauna may not be the most powerful form of halotherapy, but it is certainly a net positive gain for lung health.

Whether you choose a 1 person or a 6 person sauna, our Summit series saunas are all constructed with Hemlock wood. Hemlock wood has a soft blond coloration and is absolutely odorless. Hemlock is odorless and will not irritate allergies. All of the wood used in our saunas has been kiln dried and therefore no toxic glues, or varnishes, are used in or on any of our products.

Finally, the summit series saunas are all full spectrum, which means that they include heaters that emit mid-far infrared light, as well as heaters specifically designed for near infrared light. The added inclusion of near infrared light into your sauna will be important for anyone living with autoimmune disorders or any other serious medical condition as this spectrum of light is known to be associated with mitochondrial health. So, if you are looking to purchase a sauna for the purpose of including it as a portion of your treatment protocol, you will most likely want to include near infrared light. 

Furthermore, near infrared light, when coupled with red light from the ceiling color light therapy, may induce photobiomodulation, which is often associated with pain management because of its effect on cellular health.

If you are looking for a sauna that will truly benefit your overall health, especially if you or a loved one are living with a more serious health condition, then the Summit series will be an excellent option for you. If you own your own clinic and are a practicing physician, physical therapist, massage therapist, or in the wellness field, then you will also want to offer your patients and clients the healthiest possible option.

Until The End of July You Can Receive $400 Off Your Summit Series Sauna

Even though getting into a hot sweaty sauna may be the last thing on your mind, consider taking advantage of this rare opportunity to bring into your home or business the healthiest of saunas: The Summit Series.

Can Sauna Bathing Really Lower the Risk of Dementia?

By Saunas.org - Kat | | Dementia, Health Benefits, Healthspan, Heat Shock Proteins, Hormesis, Neurological Benefits Of Sauna use, Sauna Sleep

If you could prevent the onset of dementia in yourself or a loved one, would you do so? 

For most people the answer to this question is a resounding YES! A multi-author peer reviewed study published in 2020 that investigates the possibility of preventing dementia based on a wide spectrum of the Finnish demographic demonstrates compelling evidence that it is in fact possible to lower the risk of dementia in most people with habitual sauna use. 

There are specific biochemical alterations that occur in both the body and brain during passive sweating (non-exercise induced perspiration) that may prevent the onset of dementia in the later years of life. This study followed individuals from all walks of life, many of the participants were regular users of tobacco products as well as alcohol, the participants were both male and female. When these individuals took a minimum of 9-12 saunas that were relatively evenly distributed throughout the month the risk of dementia was significantly lowered. 

It seems too good to be true that engaging in a relatively pleasant activity such as sauna bathing, without eliminating harmful habits such as smoking, individuals may still be able to significantly lower their risk of dementia. 

This article will outline the key factors that may help to lower the risk of dementia by using a sauna regularly, and further, how to safely use a sauna to attain these results without harming the body or brain with too high a temperature in your sauna. 

The Anti-Dementia Cocktail: Heat Shock Protein Production, Sufficient Sleep, and Decreased Inflammation

This article aims to bring to life the lengthy and detailed peer reviewed journal: “Does sauna bathing protect against dementia?” This article was authored by 5 different PhDs whose names can be found below at the end of this article, and was originally published by Preventive Medicine Reports, and can also be found in the National Library of Medicine.

The primary takeaways from this study are the following three points:

  • Frequent sauna bathing predicted decreased risk of dementia
  • Results were independent of several dementia risk factors, and were not modified by sex
  • Findings support benefits of sauna and passive body heating to the brain. (1)

So, how does it all work? Is it really plausible that relaxing in a sauna could alter the course of one’s life in such a drastic and positive way as to eliminate or at least drastically lower the possibility of dementia?

The cocktail of positive biochemical reactions seems to comprise at least the following three key factors: Heat Shock Protein (HSP) production, improved sleep quality and quantity, and decrease in overall inflammation. 

Heat Shock Protein Production & The Human Brain

The intentional elevation of the body’s core temperature causes perspiration to occur and this can be attained via exercise or through passive heating of the body as seen in sauna use, hot tub, or other heat related activities to induce the augmented appearance of Heat Shock Proteins HSPs. (2)

The pivotal question then becomes how do HSPs protect against brain degeneration? The journal that is presently being illuminated writes the following:

“Heat shock proteins are important regulators in normal cell functions and have an essential role in guarding and controlling protein formation. Because disturbances of protein construction and folding are central to the development of neurological diseases, heat shock proteins may be important in maintaining protein homeostasis in the brain.” (1)

In addition to the role that HSPs play in immunity there seems to be a clear correlative effect on brain function and health. In order to induce the increased production of HSPs the individual needs to engage in passive heating (ideally) to the point that an artificial fever is induced. This means that internal body temperature rises to at least 101.5 degrees. This process of heat stress is a form of hormesis. Further studies have shown that the heat source is not as important as the maintenance of an internal body temperature that is increased enough for a specific period of time to induce sweating. The individual should move through the gateway of feeling uncomfortably hot before perspiration begins to ensure that adequate heat stress has been experienced. 

If you can sit in a sauna of any variety through the period of discomfort just before perspiration begins, and then stay in the sauna during the sweating portion for 15 minutes,  then you can rest assured that improved HSP production has occurred.

In order for the sauna to be used to reduce the risk factor of developing dementia each individual should take at least 3 saunas per week. Ideally, the objective is to take 3-4 saunas per week with each session lasting 20 minutes. There should be caution taken in the initiation period so as not to overwhelm the body with too much heat. 

Decrease Inflammation in the Brain

Prolonged inflammation of the body and brain has been linked with neurodegenerative diseases; therefore, activities that are able to consistently diminish inflammation may help in the prevention of dementia. (3)

“Inflammatory processes are suggested to be important in neurodegenerative diseases. In cross-sectional and longitudinal studies sauna bathing was associated with lower levels of inflammatory serum markers implicating reduced inflammation among those bathing frequently. It is possible that some of the effects of sauna in the brain are conveyed via reduced inflammation.” (1)

Regular use of a sauna can help to reduce inflammation in all parts of the body including neuroinflammation. It may be possible not only to reduce the risk of dementia by using a sauna frequently, but moreover other neurodegenerative diseases adversely affected by inflammation of the brain including parkinson’s disease, Alzeimer’s disease, and multiple sclerosis.(3)

Getting into the sauna at least three times per week may help to reduce the risk of dementia as well as other brain degenerative diseases in most people by decreasing neuroinflammation.

Improved Sleep

Ongoing sleep disturbances have been linked with the onset of dementia. This does not mean that one sleepless night can lead to dementia, but rather that over the course of several decades of shift work, insomnia, as well as other reasons for lack of quality and quantity of sleep the risk of dementia goes up. 

The use of a sauna or hot bath before bedtime has been associated with improved sleep: 

“Problems with sleeping and lack of sleep are often associated with Alzheimer’s disease and dementia. An increased risk of dementia was associated with frequent sleep disturbances in a study of middle-aged men from Finland during a 20-year follow-up. Findings from experiments which used warm water baths for passive body heating suggest that an increase in the body core temperature beneficially affects sleep, depending on the increase in body core temperature and the proximity to sleep. Potentially sauna bathing affects sleeping similarly. In a survey of middle-aged urban dwellers in Finland, sauna bathing was mentioned among the factors that were perceived to promote sleep.” (1)

A major factor in the initial stages of falling asleep is a drop in internal body temperature by about 2.5 degrees Fahrenheit. In fact, if the body does not drop in internal temperature the individual will not fall asleep. By artificially elevating the body’s temperature through a hot bath or sauna the natural process of the drop in temperature that the body experiences will help the individual to fall asleep and stay asleep. If an individual can consistently sleep well for at least 8 hours per night the risk factors over time for developing dementia are much lower. 

If you are choosing a sauna to reduce the risk of developing a brain degenerative disease be sure to time your sauna for later in the day so that it can help you to fall and stay asleep. 

Brain Safety: Contraindications For Sauna Use To Attain Ideal Results

While it is true that heat stress is the key player in the necessary biochemical reactions that take place during and after a sauna to affect positive changes in the brain, it is very important to not overdo the duration of time spent in the sauna or the temperature of the sauna. Heat stress can harm the brain permanently at times if it overloads the body’s system. 

“Although a major part of research on the effects of sauna bathing is in favor of the benefits of the habit, it cannot be excluded that strong passive body heating could have harmful effects in the brain. Severe heat stress may result in a reduction of the cerebral blood flow and may increase blood–brain barrier permeability. It is thus possible that during bathing at very high sauna temperatures, the body core temperature rises high enough to harmfully affect cerebral blood flow. The elderly and other groups with compromised thermoregulatory control are especially vulnerable during severe passive heat stress. Among young people the effects of moderate and high thermal stress on the brain may be counterbalanced by cardiovascular, cerebral and metabolic alterations.” (1)

It is very important that the body has time to slowly adjust to the heat of a sauna over the course of several weeks. Just as you would a new exercise regime, it is important to begin your sauna therapy at low temperatures for a shorter period of time for the first few weeks and slowly build up. 

Ideally individuals will aim to take a sauna 3-4 times a week for around 20 minutes (depending on the heat source, infrared saunas allow for longer sauna sessions because of the lower atmospheric temperature.)

Studies have shown that there is an optimal window of sauna bathing that allows individuals to create a positive impact on their health without hindering it. Please be sure to never use a sauna that is set to a temperature over 190 degrees Fahrenheit as this could possibly damage the brain or body. If you are using a traditional sauna 180 degree Fahrenheit temperature is more than sufficient, and if you are using an infrared sauna anywhere from 120-150 degrees Fahrenheit will help you reach your goal internal temperature of 101.5 degrees. 

It May be Possible to Lower the Risk of Dementia with Regular Sauna Use

Robust scientific studies suggest that when a sauna is used correctly over a period of several years consistently, regardless of your gender or other lifestyle habits, it is possible to lower your risk of developing dementia: 

“The findings of this population-based study, including men and women from Finland, are in line with the hypothesis that sauna bathing provides protection against the development of dementia.” (1)

A sauna protocol is an effective way to improve health, but it also must be respected as a powerful medicinal tool. This means hydration must be maintained with diligence at all times. If you are unsure if it is safe for you to use a sauna consult with a medical professional. Saunas can only provide significant results if the user is committed to taking a sauna at least 3 times per week for 20 minutes and ensuring that the internal temperature is raised to 101.5 degrees Fahrenheit during the sauna session. 

If you are only taking a sauna a few times a year it is doubtful that it will have a long lasting impact on health even if it is enjoyable and fun at the time. Please be sure to follow clinically significant protocol to ascertain the results you are looking for. When in doubt, be sure to talk to your  primary care physician. 

Happy Sauna’ing!

Sources Cited:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560162/
  2. https://pubmed.ncbi.nlm.nih.gov/28944271/
  3. https://pubmed.ncbi.nlm.nih.gov/26935478/
  4. https://pubmed.ncbi.nlm.nih.gov/28890168/