Studies Suggesting(IMO) We Have Been Too Aggressive with LLLT

[OtyMac]

I remember the overmachogrande devices which were excellent in design and power but were simply too powerful to work. The U shaped response curve is there for LLLT dosage(in Joules) too apparently.

Since joules involve time, the number of minutes past a certain amount appears to be detrimental.

Comparative effectiveness of low-level laser therapy for adult androgenic alopecia: a system review and meta-analysis of randomized controlled trials | 10.1007/s10103-019-02723-6_Science Hub

www.tesble.com

The present meta-analysis revealed that LLLT can improve hair
density for Androgenetic Alopecia patients. Both male and female are ideal can-
didates for LLLT treatment. The hair growth efficacy of long
treatment course (> 20 weeks) and short treatment course (16–
20 weeks) are both promising treatment strategies. Both comb-
and helmet-type device can produce a significant increase in
hair density, but the increase in hair density is not significantly
different between these two devices.

Furthermore, low treatment frequency (< 60 min/week) seems to be more effective
than high treatment frequency (> 60 min/week)

____________
As we increase the dose in joules we are moving towards hair removal ground and obviously the wrong direction.

If my skin can only take 12-14 joules...

If my skin can only take 12-14 joules on an alexandrite laser, does this mean that I will never be able to kill all of the hair, or does it mean that it will take many more treatments to do so?

hairtell.com

___________
This is a in vivo mice study treated with testosterone. I realize the short-comings of this that mice are not humans with Androgenetic Alopecia but it IMO is a much better approximation than any in vitro study.


So what happen...the U shaped response curve shows up again:

Low-Level Laser (Light) Therapy (LLLT) for Treatment of Hair Loss - PMC

Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil ...

pmc.ncbi.nlm.nih.gov

Shukla et al. [49] investigated the effect of helium–neon (He–Ne) laser (632 nm, at doses of 1 and 5 J/cm2 at 24-hour intervals for 5 days) on the hair follicle growth cycle of testosterone-treated and un-treated Swiss albino mice skin.

Testosterone treatment led to the inhibition of hair growth which was characterized by a significant increase in catagen follicles [49].

The results showed that exposure of testosterone treated mice to the He–Ne laser at a dose of 1 J/cm2 led to significant increase in the number of hair follicles in anagen phase when compared to the other groups. However, the 5 J/cm2 treated group showed a significant decrease in the number of anagen hair and an increase in telogen hair follicles.

This is consistent with the biphasic effect of LLLT wherein low irradiation doses may cause biostimulation and high irradiation doses may cause inhibition [32,49].

Since hair growth promoting effect of He–Ne laser (1 J/cm2) was much higher for the testosterone-treated mice than the non-testosterone treated mice, it can be suggested that cells growing at slower rate or under stress conditions respond better to the stimulatory effects of LLLT. A

 

[OtyMac]

One question opens up 10 more..which is good I guess.<groan>

Nitric oxide is thought to be the main(?) cause of any regrowth that occurs thru LLLT. But could we be exhausting up cell nitric oxide faster than it can be "refilled"? If so...this is a SERIOUS rate limiting step to be dealt with. Perhaps precursors(citrulline ?) on the rest days to get cell NO back to "full" again. I think in fact that is the case and that's why studies that are under 60 minutes per week do better is to give the cell a chance to replenish NO.


How much NO does the cell have? According to this about 5 minutes at peak..

Low-Level Laser Treatment with Near-Infrared Light Increases Venous Nitric Oxide Levels Acutely | 10.1097/phm.0b013e318269d70a_Science Hub

tesble.com

Conclusions​

LLLT increased NO levels in venous blood draining from the treatment site in healthy subjects. The peak increase in NO occurred 5 mins into the treatment, after which it slowly waned. Further research is necessary to assess NO increases with LLLT in patients with pathologies.

 

[HairOnFire]

Good stuff.

 

[OtyMac]

Here is a listing of available LLLT devices and their recommended treatment times which are too high IMO.
We are shooting for a 1-5 J/cm2 treatment range and just using a 5 mw laser x 30 minutes(1800 seconds) = 9000/1000 =9 joules or too much.

A Systematic Review and Meta-analysis of Randomized Controlled Trials of United States Food and Drug Administration-Approved, Home-use, Low-Level Light/Laser Therapy Devices for Pattern Hair Loss: Device Design and Technology - PMC

Low-level light/laser therapy (LLLT) can potentially stimulate hair growth in pattern hair loss (PHL), with many available home-use LLLT devices of different designs and technology on the market. However, not all devices are cleared by the United ...

pmc.ncbi.nlm.nih.gov

And all along we have been unwittingly discovering what Townsend and Lucky discovered in 1960 that LLLT and like the other 100 or so other compounds they discovered have a mild hormesis effect at low dosages and high dosages an inhibitory effect.

3.1. Dose dependence and dose rate effects—the biphasic curve
A biphasic response has been demonstrated many times in LLLT
research (Lanzafame et al. 2007; Oron et al. 2001a) and the “Arndt-Schulz
Law” is frequently quoted as a suitable model to describe dose dependent
effects of LLLT (Chow et al. 2006; Hawkins and Abrahamse 2006a;
Hawkins and Abrahamse 2006b; Lubart et al. 2006; Sommer et al. 2001).
The concept of the Arndt-Schulz Law dates from the years around the
end of the nineteenth century, when H. Schulz published a series of
papers that examined the activity of various kinds of poisons (iodine,
bromine, mercuric chloride, arsenious acid, etc.) on yeast, showing that
almost all these agents have a slightly stimulatory effect on the yeast
metabolism when given in low doses (Schulz 1877; Schulz 1888). He then
came into contact with the psychiatrist R. Arndt and together they devel-
oped a principle that later became known as the ‘Arndt-Schulz law’, stat-
ing that weak stimuli slightly accelerate vital activity, stronger stimuli raise
it further, but a peak is reached and even stronger stimuli suppress it,
until a negative response is finally achieved (Martius 1923). In 1960
Townsend and Luckey surveyed the field of classic medical pharmacolo-
gy and published a list of 100 substances known to be capable of causing
an inhibition at high concentrations and stimulation at low concentra-
tions and termed the phenomenon “hormoligosis” (Townsend and
Luckey 1960). The modern term “hormesis” was first used by Stebbing in
1982 (Stebbing 1982) and has been thoroughly reviewed by Calabrese
(Calabrese 2001b; Calabrese 2002; Calabrese 2004a; Calabrese 2004b;
Calabrese 2005)


Recognize any of the compounds in the list below? I sure do and this even explains why ethyl alcohol alone as proved in the minoxidil study grows hair. Caffeine at very low doses something like 0.2 % does also. How many people have used waaaaaay more than 0.2% over the years?.
We also see onion and garlic listed too...hahaha.

If hormesis is truly the "universal pathway" to hair growth...then we had better not do it every day. Hormesis should ideally be a small stress as the authors of the paper noted. Hormesis isn't homesis if done enough that the cell just kicks up its threshold.

So ideally, a stacking perhaps of different hormesis compounds at low levels and combined with LOW level laser therapy too since it is also a creator of hormesis. Continually applying 0.2% of caffeine DAY after DAY after DAY will create a point of diminishing returns. Rest days are needed... to get the cell's defenses down again to where the compound is again a stressor.

The biological half-life effect on the cell probably is way longer than the compound concentration half-life in the body. The cell just doesn't instantly revert back to normal the very second the compound is gone.

Can we stack different hormetic compounds and use LLLT together for a synergistic effect? Probably...

HORMOLIGOSIS IN PHARMACOLOGY | 10.1001/jama.1960.73020190007010_Science Hub

www.tesble.com

 

[OtyMac]

The triggering mechanism for all hormesis may just be n-acetyltyrosine. So..we don't need a myriad of compounds perhaps but only just NAT?
More questions...

N-acetyl-l-tyrosine is an intrinsic triggering factor of mitohormesis in stressed animals​

N-acetyl-l-tyrosine is an intrinsic triggering factor of mitohormesis in stressed animals - PubMed

Under stress conditions, mitochondria release low levels of reactive oxygen species (ROS), which triggers a cytoprotective response, called "mitohormesis". It still remains unclear how mitochondria respond to stress-derived stimuli and release a low level of ROS. Here, we show that...

pubmed.ncbi.nlm.nih.gov

N-acetyltyrosine-induced redox signaling in hormesis​

https://www.sciencedirect.com/science/article/pii/S0167488921000446

 

[Jakejr]

Yes.. There are scientific studies on LLLT to stimulate hair follicles/stem cells… I do medical grade laser treatments every other day..

 

[feelsbad]

Hmm. Given this, I wonder what would be in theory the most effective devices currently on the market

 

[OtyMac]

I've seen where minoxidil and LLLT are not synergistic which probably means LLLT is working thru NO already.

Interesting that nitric oxide is yet another hormesis inducing compound as probably everything is that grows hair. Hormesis balances the mTOR pathway which dht is pro-mTOR.

Nitric oxide and hormesis

https://www.sciencedirect.com/science/article/abs/pii/S1089860323000137

Mitochondrial Signaling in Mammalian Cells Activated by Red and Near-IR Radiation | 10.1111/j.1751-1097.2008.00394.x_Science Hub

www.tesble.com

Therefore, a window exists(ME:again too much energy > 5 Joules as the above study said is bad) at which a
low level of NO• can regulate mitochondrial ROS generation
without affecting ATP synthesis.

 

[OtyMac]

What wounding is really doing?

Hormesis: Wound healing and keratinocytes​

https://www.sciencedirect.com/science/article/abs/pii/S1043661822003383

 

[Jakejr]

I didn’t fully read your hypothesis… LLLT is scientifically proven to regrow hair … However at this point the studies show users should do LLLT EVERY OTHER DAY for best results. Presumably overstimulation of hair follicles have a diminishing return..Hairmax has done significant clinical trials accepted by FDA.
So this is a starting point for those who want to incorporate LLLT into their regimen. But any hypothesis has to be proven.. because no one has come up with a simple remedy to male pattern baldness we get a hodgepodge of different regimens.. but no universal one. I think this addresses the first part of your observation. The second about the effects & counter effects of people experimenting is probably true.. Dosage is important. Over doing it may defeat the original purpose.. Combining treatments may do the same.. But a person with years of non-results will experiment.
There is a difference between laser & LED light therapy… I learned this..there’s a difference between laser & medical grade laser. There are differences in the light spectrum. Some laser spectrum regrow hair.. others reduce scalp inflammation…Hairmax has products combining the two..

 

[OtyMac]

All successful regimens all impact mTOR thru hormesis is what I'm saying. The hodge podge set of treatments ALL do this including LLLT which just uses nitric oxide as the eustressor upon the mitochondria. Dht drives mTOR hyperactivation which increases aging rate this is the target we are all aiming to interrupt whether we know it or not.

So..the mitochondria becomes highly fissioned and poor at generating ATP and good at generating free radicals. We need to use mitochondria control and remove fissioned mitochondria and increase mito-fusion which hormetic compounds do.

The associated problems of metabolic syndrome that Androgenetic Alopecia sufferers have are because of excessive fission. Anything that grows hair is increasing fusion thru hormesis slowing the mTOR overactivation which dht(and other things) increase.
There is ONLY ONE pathway and that is hormetic type agents acting on the mitochondria which can include LLLT, wounding, vitamin d3, flavonoids(which are nature's insecticide) and many compounds that are eustressors at right dose.

Association of Androgenetic Alopecia with Metabolic Syndrome: A Case–control Study on 100 Patients in a Tertiary Care Hospital in South India - PMC

Androgenetic alopecia (Androgenetic Alopecia) is the most common cause of hair loss. Although it is a medically benign condition, it can have a significant psychosocial impact on patients. “Metabolic syndrome” (MetS) is a collection of clinical signs that focus on ...

pmc.ncbi.nlm.nih.gov

Mitochondrial Fission as a Therapeutic Target for Metabolic Diseases: Insights into Antioxidant Strategies - PMC

Mitochondrial fission is a crucial process in maintaining metabolic homeostasis in normal physiology and under conditions of stress. Its dysregulation has been associated with several metabolic diseases, including, but not limited to, obesity, type ...

pmc.ncbi.nlm.nih.gov

 

[OtyMac]

I didn’t fully read your hypothesis… LLLT is scientifically proven to regrow hair … However at this point the studies show users should do LLLT EVERY OTHER DAY for best results. Presumably overstimulation of hair follicles have a diminishing return..Hairmax has done significant clinical trials accepted by FDA.
So this is a starting point for those who want to incorporate LLLT into their regimen. But any hypothesis has to be proven.. because no one has come up with a simple remedy to male pattern baldness we get a hodgepodge of different regimens.. but no universal one. I think this addresses the first part of your observation. The second about the effects & counter effects of people experimenting is probably true.. Dosage is important. Over doing it may defeat the original purpose.. Combining treatments may do the same.. But a person with years of non-results will experiment.
There is a difference between laser & LED light therapy… I learned this..there’s a difference between laser & medical grade laser. There are differences in the light spectrum. Some laser spectrum regrow hair.. others reduce scalp inflammation…Hairmax has products combining the two..

Btw, I saw this YouTube video on some expert talking about methylene blue.He said lllt greatly increases the effectiveness of MB like 1000x. He was not talking about hair growth but for somebody using lllt that would be a must try and low dose MB increases hormesis as does lllt and if the guy is correct they are massively synergistic.

 

[losingbattle88]

I remember the overmachogrande devices which were excellent in design and power but were simply too powerful to work. The U shaped response curve is there for LLLT dosage(in Joules) too apparently.

Since joules involve time, the number of minutes past a certain amount appears to be detrimental.

Comparative effectiveness of low-level laser therapy for adult androgenic alopecia: a system review and meta-analysis of randomized controlled trials | 10.1007/s10103-019-02723-6_Science Hub

www.tesble.com

The present meta-analysis revealed that LLLT can improve hair
density for Androgenetic Alopecia patients. Both male and female are ideal can-
didates for LLLT treatment. The hair growth efficacy of long
treatment course (> 20 weeks) and short treatment course (16–
20 weeks) are both promising treatment strategies. Both comb-
and helmet-type device can produce a significant increase in
hair density, but the increase in hair density is not significantly
different between these two devices.

Furthermore, low treatment frequency (< 60 min/week) seems to be more effective
than high treatment frequency (> 60 min/week)

____________
As we increase the dose in joules we are moving towards hair removal ground and obviously the wrong direction.

If my skin can only take 12-14 joules...

If my skin can only take 12-14 joules on an alexandrite laser, does this mean that I will never be able to kill all of the hair, or does it mean that it will take many more treatments to do so?

hairtell.com

___________
This is a in vivo mice study treated with testosterone. I realize the short-comings of this that mice are not humans with Androgenetic Alopecia but it IMO is a much better approximation than any in vitro study.


So what happen...the U shaped response curve shows up again:

Low-Level Laser (Light) Therapy (LLLT) for Treatment of Hair Loss - PMC

Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil ...

pmc.ncbi.nlm.nih.gov

Shukla et al. [49] investigated the effect of helium–neon (He–Ne) laser (632 nm, at doses of 1 and 5 J/cm2 at 24-hour intervals for 5 days) on the hair follicle growth cycle of testosterone-treated and un-treated Swiss albino mice skin.

Testosterone treatment led to the inhibition of hair growth which was characterized by a significant increase in catagen follicles [49].

The results showed that exposure of testosterone treated mice to the He–Ne laser at a dose of 1 J/cm2 led to significant increase in the number of hair follicles in anagen phase when compared to the other groups. However, the 5 J/cm2 treated group showed a significant decrease in the number of anagen hair and an increase in telogen hair follicles.

This is consistent with the biphasic effect of LLLT wherein low irradiation doses may cause biostimulation and high irradiation doses may cause inhibition [32,49].

Since hair growth promoting effect of He–Ne laser (1 J/cm2) was much higher for the testosterone-treated mice than the non-testosterone treated mice, it can be suggested that cells growing at slower rate or under stress conditions respond better to the stimulatory effects of LLLT. A

U mean my overmachogrande laser helmet is useless? I shouldnt use it??

 

[OtyMac]

U mean my overmachogrande laser helmet is useless? I shouldnt use it??

Depends how long you use it.

5mw x 200 seconds = 1 Joule. Since we are aiming for 1 Joule if we are using the mice study. Mice may or may not be a good experiment but we DO KNOW that they also WILL NOT have a placebo effect.

My guess is the results from LLLT will be better if used less and that is the conclusion from the study above from those that use their LLLT devices less than 60 minutes per week had better results.