LED Therapy: 30% Increase in Max. # of Reps in New Study, Increased Stamina and More Recent LLLT / LEDT Data

The scientists used an LEDT device from Thor on two points on the distal portion of the vastus lateralis, two points on the distal portion of the vastus medialis and two centered points along the rectus femoris (see Figure 1, right).

It may be partly my fault that most of you ask me for supplements to take to increase their performance and do not expect often not even consider the possibility of being told about technological items like a low-level laser diode device to up their gains or boost their fat loss...

When I started this blog a few years ago, I was guilty of believing that supplements would be the most relevant ergogenics for anyone who trains, myself. Today, ~2,300 articles later, this has changed: don't get me wrong - supplements can be useful, but diet, training and - at least in a few cases - even things like using light emitting diode therapy (LEDT) or low-level laser therapy (LLLT), as it is also called, are much higher on the "things that really work"-list.

Read more short news at the SuppVersity to learn more about training & nutrition.

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In that, it is important to point out that a recent study from the Georgia Southern University (Hemmings. 2016) is neither the first study to show significant performance / recovery benefits from LEDT, nor is it the first study I wrote about (read previous articles). The experiment Hemmings et al. conducted is yet the first to evaluate the effects of different dosages of LEDT (30 vs. 60 vs. 120 seconds on each irradiation point, see Figure 1, right) that was applied by the means of a low-level laser (THOR, London, UK) on muscular fatigue of the quadriceps after two sets of three maximal voluntary isometric contractions (MVIC).

Figure 1: Comparison of repetitions and blood lactate concentrations between all four trials; illustration of the irradiation points that were used for LEDT (Hemmings. 2016)

A total of 34 recreationally resistance trained athletes between the ages of 18 and 26 participated in four trials. Each trial included pre/post exercise blood lactate measurements, the previously hinted at MVIC and a single set of eccentric leg extensions (at 120% of the previously determined MVC) to exhaustion that was done three minutes after the initial exercises and used as a yard-stick for the recovery benefits of using 30s, 60s and 120s of LEDT compared to a 45s placebo treatment of which the subjects thought that it was yet another irradiation time that was to be tested.

LLLT therapy has also been shown to almost double the muscle gains in a study with an 8-week eccentric training program | more

LLLT and LEDT - What does the science say?: Here's how the authors explain the difference, between different forms of laser light therapy (LLT) and light emitting diode therapy (LEDT): "The difference between LLT and LEDT is the power output and depth of penetration due to various patterns in wavelengths" (Hemmings. 2016). The potential mechanism, on the other hand is always the same: "[r]esearch suggests that LLLT can prolong the binding of nitric oxide to the cytochrome C oxidase enzyme, which permits the muscle to produce more ATP in the preferred oxidative pathway" (Hemmings. 2016).

A recent meta-analysis (Nampo. 2016) evaluated both, the effects of LLLT and LEDT, on exercise capacity and muscle performance of people undergoing exercise when compared to placebo treatment. Sixteen studies involving 297 participants were included in the meta-analysis that shows a mean improvement of the number of repetitions of 3.51 reps (0.65–6.37; P = 0.02), a 4,01 second delay in time to exhaustion (2.10–5.91; P < 0.0001), and - unlike the study at hand - a sign. reduction in lactate levels (MD = 0.34 mmol/L [0.19–0.48]; P < 0.00001) and increased peak torque (MD = 21.51 Nm [10.01–33.01]; P < 0.00001).

Exercise capacity - Number of reps (left), time to exhaustion (right | Nampo. 2016)

Reason enough for the authors to conclude that their "results suggest that LASERtherapy is effective in improving skeletal muscle exercise capacity" - one thing Nampo et al. rightly add is that "the quality of the current evidence is limited" (Nampo. 2016).

As you would expect it for any effective ergogenic, the scientists observed a "significant increase in the number of repetitions performed between the placebo treatment" (Hemmings. 2016). In that, it is interesting to see that both treatments, i.e. 60 seconds (p= 0.023), as well as the 120 seconds (p=0.004) LEDT treatment triggered a significant increase in the number of reps the subjects completed - without, however, significantly affecting the accumulation of blood lactate levels in the subjects' blood. Another thing the data in Figure 1 tells us that must not be forgotten is the lack of effect of applying LEDT for only 30 seconds per irradiation point (see Figure 1, right).

Lactate is not the enemy - remember? Caffeine and Bicarbonate (NaHCO3), two proven ergogenics increase, not decrease blood lactate accumulation while still boosting subjects' performance during a standardized yo-yo performance test | learn more.

While the last-mentioned lack of effect of a shorter treatment is probably something you'd expect, the lack of effect on the accumulation of lactate may come as a surprise. Eventually, however, the exercise duration was probably simply too short to accumulate exuberant lactate levels. It is imho also questionable why the scientists used lactate, not CK or another potential measure of muscle damage (or a biopsy) to judge the effects of the LEDT treatment on a molecular level. After all, the often-heard hypothesis that the accumulation of lactate would be the reason you fail due to muscular exhaustion is - in view of the existing evidence - at least questionable.

What about gains and does timing matter? No, you don't have to be afraid that LLLT would have the same negative effects on your gains as ice-baths. It has, after all, already been shown to double the gains in a 2015 8-week study in healthy volunteers | read more! And the timing, yeah... Well, yes timing does matter! You have to apply it before the workout to see effects... at least for immediate 1RM strength gains this is the case according to a very recent study by Vanin (2016) - future studies will tell if using it post, as a recovery tool can be effective in the long-term.

As a SuppVersity reader you will, for example, remember that proven ergogenics such as bicarbonate and beta alanine increase the accumulation of lactate significantly... ok, you may argue that they simply protect the muscle from the tiring effects of lactate, but eventually there are other more likely candidates to explain the onset of fatigue such as the accumulation of other muscle metabolite, a decrease in free energy of adenosine triphosphate, limited O2 or other substrate availability, increased glycolysis, pH disturbance, increased muscle temperature, reactive oxygen species production, and altered motor unit recruitment patterns (Grassi. 2015; Poole. 2015), which could eventually explain why our muscles fatigue and why the lactate levels increase (reduced ATP, for example, will necessarily increase glycolysis and eventually the lactate accumulation).

This is only one of of several LLLT studies I've discussed in detail in older SV articles. Examples? What about this one from Aug 2015: Phototherapy Doubles Fat Loss (11 vs. 6%) & Improvements in Insulin Sensitivity (40 vs. 22%) and Helps Conserve Lean Mass in Recent 20 Weeks 'Exercise for Weight Loss Trial' | read more

Bottom line: Yeah, the scienists are right to conclude that "light emitting diode therapy had a positive effect on performance when irradiating six points on the superficial quadriceps for 60 seconds and 120 seconds prior to an eccentric leg extension" (Hemmings. 2016).

What can be refuted based on their results, however, is that this effect was a consequence of reduced lactate levels. That's in contrast to another recent study in a particularly vurnerable subgroup of hobby athletes, i.e. the hospitalized patients with heart failure in a pilot study by Bublitz et al. who found a significant decrease in lactate accumulation, albeit in response to a 6-minute walking exercise, during which LLDT was able to reduce the subjective fatigue and the previously discussed lactate concentrations, but not the subjects' performance.

Overall, it seems reasonable to conclude that further research is necessary to (a) elucidate the underlying mechanism behind the (pro-)recovery / performance enhancing effects, as well as LEDT's / LLLT's previously reported beneficial effects on insulin sensitivity and body composition and the most promising areas of application (according to the study at hand this could be resistance training / any sport that requires maximal anaerobic performance) | Comment!

References:

• Bublitz, Caroline, et al. "Acute effects of low-level laser therapy irradiation on blood lactate and muscle fatigue perception in hospitalized patients with heart failure—a pilot study." Lasers in medical science (2016): 1-7.
• Byrne, Christopher, Craig Twist, and Roger Eston. "Neuromuscular function after exercise-induced muscle damage." Sports medicine 34.1 (2004): 49-69.
• Grassi, Bruno, Harry B. Rossiter, and Jerzy A. Zoladz. "Skeletal muscle fatigue and decreased efficiency: two sides of the same coin?." Exercise and sport sciences reviews 43.2 (2015): 75-83.
• Hemmings, Thomas J. "Identifying Dosage Effect of LEDT on Muscular Fatigue in Quadriceps." Journal of Strength and Conditioning Research (2016): Publish Ahead of PrintDOI: 10.1519/JSC.0000000000001523..
• Poole, David C., and Thomas J. Barstow. "The critical power framework provides novel insights into fatigue mechanisms." Exercise and sport sciences reviews 43.2 (2015): 65-66.
• Vanin, Adriane Aver, et al. "What is the best moment to apply phototherapy when associated to a strength training program? A randomized, double-blinded, placebo-controlled trial." Lasers in Medical Science (2016): 1-10.

Phototherapy Doubles Fat Loss (11 vs. 6%) & Improvements in Insulin Sensitivity (40 vs. 22%) and Helps Conserve Lean Mass in Recent 20 Weeks 'Exercise for Weight Loss Trial'

LLLT has also been shown to improve the appearance of cellulite (Jackson. 2013) | Learn more about what really helps against cellulite in this SV Classic

You know that I am not a fan of isolated "exercise / supplement for weight loss trials", but there's one thing I like about them. When the diet is not controlled for and the subjects still lose weight, it is very likely that the intervention is going to work in the real-world, as well. And if the exercise protocol is both manageable and useful, as it was the case in a recent study from the University of Sao Paulo (Sene-Fiorese. 2015), this makes me even more inclined to actually write about the study, even though it may be - from a mere scientific perspective - not provide "bulletproof" evidence of what's the exact cause of the effects, the exercise or supplement, it's effect on energy intake or both.

Learn more about the nuances of dieting and fat loss here, at the SuppVersity

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But let's return to the study at hand: Manageable and useful, in this case, meant three exercise sessions per week with 30 minutes of aerobic training and 30 minutes of resistance training per session.

"During the intervention period, the voluntaries [sic!] followed a combined exercise training therapy. The protocol was performed three times per week and included 30 minutes of aerobic training and 30 minutes of resistance training per session. The aerobic training consisted of running on a motor-driven treadmill (Movement®) between 70 and 85% of maximal heart frequency, which was determined previously by treadmill submaximal test. The resistance exercise training was composed using exercises for the main muscular groups: bench press, leg press, sit-ups, lat pull-down, hamstring curls, calf raises, Straight-Bar Cable Curl (biceps), triceps pushdown, adductor and abductor chairs [see Table 1]. Training loads were successively adjusted, with volume and intensity being inversely modified and the number of repetitions being decreased to between 6 and 20 repetitions for three sets. The training loads were adjusted in each training session and evaluated according to the increase in participants’ strength. Thus, the training was conducted with maximal repetitions (RM)" (Sene-Fiorese. 2015).

For the study, the scientists recruited a total of 64 adult obese women via classic newspapers and magazines as well as electronic media, TV and radio. The inclusion criteria were (i) primary obesity, body mass index (BMI) between 30 and 40 kg/m², (ii) age between 20 and 40 years old. Exclusion criteria were (i) the use of cortisone, anti-epileptic drugs; (ii) history of renal disease; (iii) alcohol intake; (iv) smoking; and (v) secondary obesity due to endocrine disorders. The inclusion and exclusion criteria were assessed by clinical evaluation by physician (endocrinologist).

Table 1: The scientists a resistance training protocol that had previously been used in Foschini (2010)

While the treatment consisted of physical exercise intervention and the individual application of phototherapy immediately after the end of the exercise training session for all volunteers. The scientists randomly assigned the subjects to an active ET-PHOTO and a "SHAM" control group ET-SHAM.

This is a placebo controlled study! I think it's worth highlighting the fact that both groups believed they'd received the treatment, because all subjects had to go to the phototherapy sessions, but the device was actually turned on only for those in the ET-PHOTO, not for those in the ET-SHAM group.

In the ET-SHAM group the device which emits light at a wavelength that's too long for the human eye to actually see it was turned off. Thus the subjects in the SHAM = control group received a simulated phototherapy application ... and yes, that's basically the same thing as the "placebo group" in your average supplement study..

Figure 1: Photo of the Device, Illustration of the Area of Application; Device Information, Irradiation and Treatment Parameters (Sene-Fiorese. 2015).

"The phototherapy equipment was developed by Laboratory Technology Support-LAT, Center for Research in Optics and Photonics Institute of Physics in São Carlos city at University of São Paulo-USP. The device is a prototype equipment that was submitted for registration as a new patent. The device is composed of four plates made of rubberized material measuring 20 by 20 centimeters (cm) each. Each two plates are connected to an electronic control box. The emitters of Ga-Al-As diode Lasers are distributed in the plate every 2.5 cm, totaling 16 emitters per plate and 64 emitters in total. The prototype is illustrated and irradiation parameters are [mentioned in Figure 1]" (Sene-Fiorese. 2015).

As I already hinted at in the previous paragraph, 805 nm is a pretty high wavelength. It's classified as near-infrared (near as in "near, but not in the visible spectrum"), which is too "long" to be seen by human beings... what it was not too long for, though, was to augment the beneficial effects the 48 workouts the subjects performed over the whole study period had on the women's body composition and metabolic health.

Figure 1: Overview of the changes in body comp and glucose metabolism in both groups (Sene-Fiorese. 2015).

What is (imho) pretty astonishing is yet not the fact that benefits occurred, but rather that these benefits were not just statistically significant, but also practically relevant. I mean you will certailny agree, that it makes a difference if you lose 11% or 6% body fat and improve your insulin sensitivity by 40% vs. 22% - right?

If we also take into account that the the scientists observed similarly profound differences when they analyzed the subjects adiponectin levels, which decreased by 7% in the SHAM group (bad) and increased by a whopping 20% (good!) in the PHOTO group, it's really hard to argue that the benefits wouldn't be worth the hassle, even though one may question the accuracy of the body fat / lean mass data which was measured with a body impedance, instead of a DEXA device. Since the overall results do support significant additive effects, there's simply no reason to assume that the BIA data would be incorrect. In addition, BIA is actually relatively useful if you measure relative changes in body composition. If you want a correct one-time reading of your body fat, though, I wouldn't rely blindly on what a BIA device says.

Bottom line: As the authors point out, their latest study "demonstrated for the first time that phototherapy enhances the physical exercise effects in obese women undergoing weight loss treatment promoting significant changes in inflexibility metabolic profile" (Sene-Fiorese. 2015). While I would probably have replaced the grammatically questionable and nondescript phrase"inflexibility metabolic profile" with something more tangible like "insulin sensitivity" or "glucose control," Sene-Fiorese's conclusion is generally right.

The same LLLT therapy has also been shown to almost double the muscle gains in a study with an 8-week eccentric training program | more

Furthermore their findings may be somewhat surprising, but they are by no means unrealistic in view of the existing evidence that demonstrates that phototherapy (or low-level-laser-therapy | LLLT) is effective as an adjuvant tool in non-invasive body countering. It has been shown to help w/ the reduction of cellulite, fatigue, pain, blood circulation, wound healing, lipid metabolism and recovery after exercise (Neira. 2002; Ferraresi. 2010; Aquino. 2013; Paolillo. 2013; Houreld. 2014), as well as to increase  the mitochondrial activity in irradiated cells by up-regulating genes involved in the mitochondrial complexes (Masha. 2013).

Unfortunately, our understanding of the underlying mechanisms that make LLLT so effective is still in its infancy. It is yet most likely that they are mediated on a cellular level by increases in PGC-alpha (the mitochondria builder) and sirtuins like SIRT-1. These proteins are all important regulators of mitochondrial function; and as you may remember from previous SuppVersity articles, they are also activated by resveratrol and a bunch of other supplements that have been shown to increase the health of the cells' mitochondria. How exactly the previously reported increases in muscle gains or the profoundly accelerated fat loss in the study at hand are brought about, will have to be elucidated in future studies, though | Comment on Facebook!

References:

• Aquino Jr, Antonio E., et al. "Low-level laser therapy (LLLT) combined with swimming training improved the lipid profile in rats fed with high-fat diet." Lasers in medical science 28.5 (2013): 1271-1280.
• Ferraresi, Cleber, et al. "Effects of low level laser therapy (808 nm) on physical strength training in humans." Lasers in medical science 26.3 (2011): 349-358.
• Foschini, Denis, et al. "Treatment of obese adolescents: the influence of periodization models and ACE genotype." Obesity 18.4 (2010): 766-772. 
• Houreld, Nicolette N. "Shedding light on a new treatment for diabetic wound healing: a review on phototherapy." The Scientific World Journal 2014 (2014).
• Masha, Roland T., Nicolette N. Houreld, and Heidi Abrahamse. "Low-intensity laser irradiation at 660 nm stimulates transcription of genes involved in the electron transport chain." Photomedicine and laser surgery 31.2 (2013): 47-53.
• Neira, Rodrigo, et al. "Fat liquefaction: effect of low-level laser energy on adipose tissue." Plastic and reconstructive surgery 110.3 (2002): 912-922.
• Paolillo, Fernanda Rossi, et al. "Infrared LED irradiation applied during high-intensity treadmill training improves maximal exercise tolerance in postmenopausal women: a 6-month longitudinal study." Lasers in medical science 28.2 (2013): 415-422.
• Sene‐Fiorese, Marcela, et al. "The potential of phototherapy to reduce body fat, insulin resistance and “metabolic inflexibility” related to obesity in women undergoing weight loss treatment." Lasers in Surgery and Medicine (2015).

Low Level Laser Therapy (LLLT) Almost Doubles Muscle Gains & Ramps Up Concentric & Eccentric Peak Torque Development During 8-Week Eccentric Training Program

No, this is no photo from the study. Obviously the LLLT was applied to the legs, but LLLT is also used for shoulder and general muscle pain.

I am usually very skeptical when it comes to therapies that sound extremely cool on paper, but have hitherto only proven to improve markers of muscle damage and/or growth. Before I saw the latest paper from the Universidade Federal de Ciências da Saúde de Porto Alegre (Baroni. 2015) low level laser therapy aka LLLT fell into this exact category of promising, but not proven post-exercise recovery therapies (Baroni 2010a, b).

Said study involved thirty healthy male subjects without previous training/LLLT experience were randomized into three groups.

Read more short news at the SuppVersity to learn more about training & nutrition.

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The subjects in the control group remained sedentary for the whole 8-week study period. The subjects who had been randomized to the training (TG) and training + LLLT (TLG) groups, on the other hand, were engaged in an 8-week knee extensor isokinetic eccentric training program.

Figure 1: Application points (black circles) used for LLLT (Baroni. 2014)

"Volunteers allocated in TG and TLG were engaged in an 8-week knee extensor eccentric training program. Training sessions were performed twice a week (except for the 1st and 5th weeks), with a minimum interval of 72 h between ses sions. Subjects performed only one training session in the 1st training week to allow for progressive introduction to the training regimen and to avoid having participants undertake an exercise session in the presence of clinical symptoms of exercise-induced muscle damage, such as delayed onset mus cle soreness (Byrne et al. 2004). At the 5th training week, only one training session was performed because the training volume was increased from three to four sets of 10 maximal eccentric contractions.

Each training session was initiated by a 5-min warm-up exercise on a cycle ergometer, followed by eccentric exercises on the isokinetic dynamometer performed according to the protocol of Baroni et al. (2010a). Before each eccentric contraction, the limb was extended passively to 30° of knee flxion and subjects were encouraged to per form a maximal contraction of the knee extensor as soon as the dynamometer arm reached this position. In response to the subject’s extensor torque, the dynamometer drove the seg ment to 90° of knee flxion (range of motion = 60°) at an angular velocity of 60° s−1. A 1-min rest period was respected between sets and verbal encouragement was provided by team throughout the training session" (Baroni. 2014).

Obviously, only the subjects from TLG were treated with LLLT (wavelength = 810 nm; power output = 200 mW; total dosage = 240 J) before each training session, too.

Figure 2: Muscle size and peak torque changes over the course of the 8-week study (Baroni. 2014).

Knee extensor muscle thickness and peak torque were assessed through ultrasonography and isokinetic dynamometry, respectively; and as the data in Figure 2 indicates. Using the low-level laser therapy using a Thor Photomedicine infra-red laser cluster probe consisting of fie GaAlAs laser diodes (810 nm) immediately before each training session with the probe held stationary in skin contact at a 90°
angle with slight pressure had significant effects on the outcome of the 8-week eccentric strength training protocol.

How exactly does this work? On a molecular level LLLT has been shown to increase the body's natural anti-oxidant activity (Avni. 2005), boost the mitochondrial respiratory chain activity (Silveira. 2009) and increase the ATP production (Karu. 1995). In conjunction, these effects are probably the reason for both the performance and hypertrophy enhancing effects of LLLT. Further studies are yet warran- ted to identify how they add up / interact.

I am still a bit concerned that most of the research comes from one research group only. Nevertheless, the evidence that the previously recorded LLLT induced decreases in muscle damage (Baroni. 2010a) and fatigue (Baroni. 2010b) are practically relevant in terms of increased size and strength gains is finally there. Whether this warrants spending the money on an expensive LLLT device does yet remain just as questionable as the usefulness of cheaper copy cat machines you can buy on the Internet.

That being said, I will keep you in the loop as far as future studies are concerned. Studies of which I hope that they will (a) use previously trained athletes and (b) a more realistic leg workout that incorporates leg presses and/or squats, as well. These studies would complement the evidence we have from acute studies which have already proven the efficacy of phototherapy after both resistance training (Ferraresi. 2011) and endurance training sessions (de Brito. 2012). | Comment on Facebook!

References:

• Avni, Dorit, et al. "Protection of skeletal muscles from ischemic injury: low-level laser therapy increases antioxidant activity." Photomedicine and Laser Therapy 23.3 (2005): 273-277.
• Baroni, Bruno Manfredini, et al. "Low level laser therapy before eccentric exercise reduces muscle damage markers in humans." European journal of applied physiology 110.4 (2010a): 789-796.
• Baroni, Bruno Manfredini, et al. "Effect of light-emitting diodes therapy (LEDT) on knee extensor muscle fatigue." Photomedicine and laser surgery 28.5 (2010b): 653-658.
• Baroni, Bruno Manfredini, et al. "Effect of low-level laser therapy on muscle adaptation to knee extensor eccentric training." European journal of applied physiology (2014): 1-9.
• Byrne C, Twist C, Eston R. Neuromuscular function after exercise-induced muscle damage: theoretical and applied implications. Sports Med 34 (2014):49–69.
• de Brito Vieira, Wouber Hérickson, et al. "Effects of low-level laser therapy (808 nm) on isokinetic muscle performance of young women submitted to endurance training: a randomized controlled clinical trial." Lasers in medical science 27.2 (2012): 497-504.
• Ferraresi, Cleber, et al. "Effects of low level laser therapy (808 nm) on physical strength training in humans." Lasers in medical science 26.3 (2011): 349-358.
• Karu, T., L. Pyatibrat, and G. Kalendo. "Irradiation with He Ne laser increases ATP level in cells cultivated in vitro." Journal of Photochemistry and photobiology B: Biology 27.3 (1995): 219-223.
• Silveira, Paulo CL, et al. "Evaluation of mitochondrial respiratory chain activity in muscle healing by low-level laser therapy." Journal of Photochemistry and Photobiology B: Biology 95.2 (2009): 89-92.

SuppVersity Cellulite Special: The Etiology of Cellulite, Genetical and Behavioural Risk Factors? Physical and Supplemental Treatment Strategies & Their Efficacy

This photo of a 37-year old woman some of you may already have seen Facebook testifies to the success of 12 weeks on 333U/cc retinol cream + high intensity laser pulses (Fink. 2006)

I guess, or should I say, I'd hope (?) that some of you have already been waiting eagerly for the write-up of yesterday's Special Installment of the SuppVersity Science Round-Up on the Super Human Network and all the details and obviously the supps, Carl and I could not squeeze into this 1h+ show.

Before you go over this huge (and this is also why it took me so long to post this) serving of the "Seconds", I do yet highly recommend that you download and listen to the podcast, first. You can grap the MP3, right here.  It's free and if you don't like the ads, just skip forward, but please come to terms with the fact that a daily 2h radio has to be financed one way or another!

Let's dig right into this lumpy-bumby skin condition, now!

Despite the fact that they did not identify the underlying reasons for the development of cellulite correctly, Alquier and Paviot (1920), who described cellulite as a non-inflammatory complex cellular dystrophy of the mesenchymal tissue caused by a disorder of water metabolism, which produced saturation of adjacent tissues by interstitial liquids that was brought about by a reaction to traumatic, topical, infectious or glandular stimuli, already had a pretty decent understanding of the structural characteristics of cellulite (cf. Rossi. 2000).

Figure 1: Overview of the four main stages in the development of cellulite. If you take closer look they actually reflect much of what Alquier & Paviot (1920) already suspected: a disorder in water metabolism and a complex tissue dystrophy, which can yet become inflammatory in the late stages

The fact that cellulite is nothing but the highly visible manifestation of the messed up structural grid that holds the skin (epidermis) and the underlying fat layer in place is also important in view of the fact that up to today, way too many people look at cellulite as if it was something like a transient allergic reactions you could get rid of, once you stop eating things high GI carbs or whatever the contemporary dietary villain may be.

Unfortunately, this is not the case so that Nürnber et al. are not totally off, when they write a a 1978 paper about the ..

“[…] the essential normality and inevitability of [cellulite] in women, the supervention of it in hormonally feminized men, and the near futility of treating the non-disease” (Review by Nürnberger. 1978)

It is, and this is something that was completely missing from the previously cited first description of the “disease”, in fact partly Mother Nature who is to blame for the

• abnormal hyperpolymerization of the connective tissue,
• primary alterations in the fatty tissue,
• microcirculatory alterations

with genetic and hormonal factors determining the basic risk profile and inactivity, a messed up diet, obesity, medication etc. being nothing but corroborating factors.

If you will, the X-chromosome and is myriad downstream effects that make a man a men could even be perceived as a genetic factor – a highly protective one that is.

Figure 2: Relative contribution of perpendicular, tilted and parallel septae to the "structural part" of the dermis (left; Querleux. 2002); comparison female vs. male skin (Rosenbaum. 1998), note: the comparison misses the important parallel structures esp. in the male skin, but I guess it still conveys the basic idea

As you can see in figure 2 (right), the mere fact that the upper most parts of the skin, the Epidermis and the Corium is much thicker in men than in women would already conceal major parts of the pumpy structure in a man. In women, on the other hand, the sclerotic macronodules that form during step four in the etiology of cellulite are highly visible through the “thin skin” of a woman.

Female skin with and without cellulite – what are the differences?

Figure 3: Photos of patients with grade II-IV cellulite. Mind the extreme difference between the contracted and uncontrated state in grade II (top vs. bottom; Rossi. 2002)

In addition to the general sex differences, Querleux et al. (2002) observed that women who suffer from cellulite have a 4x higher fat volume in the dermis, than normal women (note: the total amount of fat in men and women is not significantly different).

It goes without saying that this increase in volume would actually require an increase in strength or the number of stabilizing elements in the flexible structure that holds the fat, liquids and other components of the skin in place.In conjunction with the increased interstitial pressure that is a result of the microcirculatory alterations and the defect in collagen synthesis this increase in fat volume is however more than the comparatively unorganized fibrous structure of the female skin can hold.

If you think of the skin as three-dimensional grid that is filled with balls and lacks the structural components that separate the balls in the 1st row from those in the 2nd, 3rd, … etc. row, it should be obvious that any endogenously (interstitial pressure) or exogenously applied pressure (from within = muscle; or from outside = pinching) will push the balls or rather fat cells against the top-layer that's covering the grid (the uppermost parts of the skin) and cause pumps to appear at the surface.

A very similar mechanism is responsible for the appearance of the bumps and the valleys you see through the thin layer that’s covering the underlying fluid and fat-filled part of the dermis in women with cellulite.

Cold, not valsodilated & "lumpy-bumpy"

The presence of the sclerotic perpendicular macronodules in-between the pumps and dentures, only contribute to the nasty appearance and do little to maintain the structural integrity of the tissue that’s actually supposed to be pervaded by numerous small & flexible, randomly but highly crosslinked septae that keep the fat cells in place.

Figure 4: I assume you would not have needed this thermograph to tell me that cellulite ain't exactly hot ;-)

If you look at the thermograph to the right of this paragraph you will also notice that the metabolic activity of the tissue is similarly irregular and (don’t get fooled by the colors) overall much lower in women with cellulite compared to their “healthy” counterparts.

This is both a contributing factor, as well as a results of the decreased micro-circulation in the dermis (see cold green areas) and contributes to the increased water retention in the skin. The latter will increase the pressure and worsen the condition… it is a self-perpetuating viscous cycle, yet one that opens therapeutic doors not to reverse, but at least to halt the progress of the ongoing dystrophic processes.

Estrogen drives cellulite development

And while we are going to deal with the "therapeutic" options in just a minute, let's briefly recapitulate, what I said about the causes / confounding factors during yesterday's show (listen to the podcast for details):

• genes and sex - simply being a women predisposes you to develop cellulite; I know it's not fair, but that's how it is; the same goes for the genes: if your mother and grandmother had it, chances are you will develop it, as well 

• 

  Figure 5: The influence of estrogen on the pathophysiology of cellulite (Rossi. 2002); easy to see, estrogen is the motor of cellulite development

  high estrogen, low progesterone (e.g. puberty, pregnancy, birth control, PMS; partial revision in menopause possible) - estrogen (E2) increases the accumulation of fat, spec. in the areas that are typically affected by cellulite, it renders the fibroblasts more hydrophobic and predisposes to water retention and edema, it increases the permeability and thus the leakage from the cells and promotes the formation of sclerotic tissue (figure 5)
• insulin resistance / diabetes - does not only accelerate fat gain (at least as long as there is still some insulin around), but will also increase the production of glycosaminoglycans which will draw even more water into the tissue (Lotti. 1990)
• obesity (and obesogenic diets) - the faster the fat accumulates and the larger the cells become the greater the demand on the structural components of the dermis and the more likely it will give in and the bumps and start to appear (remember: cellulite is not about having too much body fat, if it is acquired slowly and you are not genetically pre-dispositioned to cellulite you can accumulate quite an amount of fat without developing cellulite)
• hypothyroidism - thyroid hormone increases hyaluronic acid and chondroitin sulphate production, low levels will thus hamper the formation and renewal of the structural parts of the dermis
• stress / corticosteroids - if you are not taking exogenous corticosteroids like prednisone, stress and high corticosteroid levels are actually identical and have similar effects as low thyroid hormone (by the way, stress, even "eu-stress" such as exercise, will also have thyroid hormone levels plummet; learn more)
• lack of exercise - decreased vasodilation, increased weight gain, increased water retention, increased risk of diabetes... I don't have to enumerate all of them, right?
• low potassium, zinc, copper and selenium intake - while the former will help your body regulate the water balance, zinc and copper are important for the formation of the net that keeps the fat in place and have, just as selenium anti-oxidant properties as part of Copper/Zinc Superoxide Dismutase
• smoking and boozing - both will promote the decline in micro-circulation

Now that you know what you cannot change and / or should not do, let's take a look at what you can do as far as physical treatments and supplements / drugs are concerned.

Currently available physical "treatment" options

I highly encourage you to also listen to the podcast, as I am going to keep this short in view of the fact that Carl went through all the items, anyway:

• Iontophoresis: Applies a galvanic current on the surface of the skin to depolarize it and alllow drugs pass through the dermis; it is also used to increase the vasomotor action (vasoconstriction, followed by vasodilation) of which practitioners of this method believe that it may have a positive effect on the compromised metabolism in cellulite skin
• Acoustic wave therapy / ultrasound: Uses high frequency vibrations, which have a thermic and vasodilator effect; is also used as an adjunct to "hammer" drugs into the skin; there is some evidence that it can provoke lipolysis and is thus used during liposculpture procedures. Russe-Wifingseder et al. reported only recently that the use of ultrasaund that acts only on the subcutaneous tissue produced "improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference" (Russe-Wifingseder. 2013) in placebo-controlled trial.
• Thermotherapy: The heat is suppose to increase vasodilation. Experts say that its effectiveness is questionable, as some reports suggest that it did actually aggravated cellulite, maybe in consequent protein denaturation due to the high temperature. 
• Pressotherapy / Massage therapy: Either done by hand or with a pneumatic massager, the intention is to help the skin to release the liquid that's accumulating in the tissue and activate the venous return; it is also used to to treat lymphatic, venous or mixed oedema of the limbs, so that you can expect cosmetic effects of unknown (probably short ;-) duration
• Lymphatic drainage: While it has been used since 1936, the pumping movements using gentle and rhythmic pressures will stimulate the lymphatic flux, but have no proven and above all persistent effect on cellulite
• Laser therapy Low‐level, dual‐beam laser energy, as well as high intensity pulsed laser that are commonly used for "body-contouring" have been reported in several studies to "help" with cellulite. Most of those do yet only report reductions in subcutaneous fat and results like "increased well-being" among the particpants.
• Elecrolipophyresis: Unlike with the #1 on the list the electric current is not applied to the surface of the skin, but rather to several pairs of thin (0.3 mm) long (5–15 cm) needles which are connected to a low frequency current generator. This generates an electromagnetic field which is supposed to modify the interstitial tissue and aid in the circulatory drainage, as well as lipolytic processes. High quality evidence for its usefulness is absent.
• Mesotherapy – This is the well known injections of "solvents" into the adipose tissues. While there are various protocols available most involve phosphatidylcholine. What they all have in common is a highly questionable safety profile and the fact that they yield very ambiguous (mainly negative in peer-reviewed studies) results. Aside from that, dissolving the fat cells within an already corrupted structure is not exactly what I would deem helpful...

Before we go on to the supplements, let me briefly mention that a meta-analysis of cosmetic products marketed for cellulite reduction did show an overall effect, with respect to the thigh circumference (-0.46cm, analysis of 21 original papers; cf. Turati. 2013), while there was no consistent improvement in the nasty look of the skin.

Supplements & drugs for cellulite prevention (and reduction!?)

As mentioned on the show, most of the supplements in the following list are going to help mitigate some of the symptoms, reduce the fat load (literally) on the weak structure of improve the micro-circulation. Aside from retinol and maybe silicon, of which esp. the former appears to have a direct effect on what's going on beneath the surface of the skin, most don't hold much promise for getting rid of the underlying problems.

• 

  Suggested read: "Brown Algae Extract Reduces Body Fat Without Dieting or Exercise. Ecklonia Cava Polyphenols Help Shed Weight Even in The Presence of a Slight Caloric Surplus." | read more...

  Supplements to burn the fat - Methylxanthines (theobromine, theophylline, aminophylline, caffeine), which act through phosphodiesterase inhibition, isoproterenol and adrenaline which are beta-adrenergic agonists, and yohimbine, piperoxan, phentolamine and dihydroergotamine which are alpha-antagonists and will "encourage" the fat cells in this "stubborn fat area" to release more of the fat that's stored in them -- just pick the next best fat-burner from your local supplement story invent something that will have it pass through the stratum corneum and you got your "topical fat burner", of which I can only repeat that it will not get rid of the bumps - if anything it will reduce the severity.
  
  In view of the importance of Co-enzyme A in this process, adequate vitamin B5 and cysteine, which are used for its synthesis and maybe even carnitine, which helps to transport and burn the fat that's actually released from the fat traps on your thighs can enhance the effects of the previously mentioned agents. This is important because free fatty acids may saturate the system, leading to negative feedback of lipolysis (Di Salvo. 1995).

• 

  Suggested read: "How Working Out Changes the Morphology of Your Body Fat" | read more...

  Supplements to increase micro-circulation: Ivy and Indian chestnut extracts, ginkgo biloba and rutin, maybe pycegnol and the pharmacological agent Pentoxifylline, which is a drug commonly sold by Aventis under the brand name Trental it improves microcirculatory perfusion through its effect on haemorrheological factors, including erythrocyte shape, platelet aggregation and plasma fibrinogen concentration. While Pentoxifylline has been used to treat chronic venous insufficiency, stasis ulcers in controlled studies, its efficacy wrt to cellulite has not been proven.

• Antioxidant and immune modulatory supplements: Vitis Vinifera, borage oil, fucus. The latter is a common type of brown algae, that will also enhance the metabolism and reduce the oedema and intestinal inflammation.  

• Asiatic centella extract aka guta cola: The main reason this is a standalone is the frequency with which it is mentioned in the literature. Centella has a vegetable origin and consists of asiaticosideo (40%), madecassic acid (30%) and Asiatic acid (30%), triterpenic derivatives which act in vitro on fibroblasts, stimulating collagen and mucopolysaccharide synthesis.
  
  

  

  Chronic overtraining is no solution and the stress could in fact cause your to your cellulite problems. In addition, it is also the cause of chronic injuries, which persist even, when you finally realized that your own ambition is about to ruin your health (learn more).

  It has been used in the past both topically and systemically, and reported benefits of the oral administration route must probably be ascribed to its beneficial effects on the micro-circulation. According to Hausen (1993) it does neither lead to cutaneous hypersensitivity, nor does it have a toxic effect, when it is ingested.
  
  In a histopathological, double-blind study by Hachem & Borgoin from the late seventies it the administration of 60 mg of dry Asiatic centella extract orally once a day for 90 days brought about a significant reduction in the diameter of adipocytes in both the deltaoid and gluteofemoral regions in the patients who received centella compared to those who received placebo. Interestingly, this reduction was more apparent on the gluteofemoral region and went in hand with a decrease in interadipocyte fibrosis. 
  
  If it were not for the missing placebo control in most of the hitherto published studies, this could actually be a supplement worth trying.

• 

  Suggested read: "Evidence From the Metabolic Ward: 1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet" 2x-3x higher than RDA protein intakes work equally well for men and women, to get and stay lean and lose fat and build / maintain muscle - it does not always take supplements, you see (learn more)?

  Sillicium: While you probably never thought about it, sillicium (organic) is present in celery, peppers, carrots, potatoes, unrefined grains and cereals and beets, all sorts of veggies and fruits, basically everything that growth on earth that has silica in it. The maximum daily recommended dose is 10.5 mg Si/day; and being a structural element of the connective tissue, it is actually not surprising that studies (mostly in vitro or rodent, unfortunately) have demonstrated that silanols (groups of hydrogen and sillicium compounds, similar to the hydrocarbides) provoke the formation of bridges between the hydroxylated amino acids of the elastic fibres and collagen fibres protecting them from non-enzymatic glycolysation and decreasing their degradation rate.
  
  Sillicum also acts as a coenzyme during interstitial matrix macromolecule synthesis. As such it helps reorganize structural glycoproteins and proteoglycans by stimulating polar amino acid grouping and normalizing hydrophilic capacity. Both effects which would obviously be highly desirable for someone suffering from a compromised dermal glycoprotein matrix. 
  
  In view of the fact that it has also been reported to increase microcirculation by modifying venous capillary and lymphatic permeability and has even been shown to stimulates cAMP synthesis as well as triglyceride hydrolysis and thus promote the release of fatty acids from the stored fat cells, it appears to be the perfect nutrient for any woman suffering from cellulite... in view of this fact it is surprising that I could not find a single reputable study proving its effects (note: I did not find one showing the opposite either) 

Actually, the next and last item on the list would be retinol,  but instead of just adding it to the bottom I want to briefly recapitulate that it was a 12-week treatment with weekly applications of intense pulsed light (the equipment used was a Quadra Q4 IPL) with a wavelength of 585-nm and nightly applications of a compounded retinyl-based cream (330 U/cc) that was applied after the ladies had used some aceton to remove the protecive layer of the skin 5x / week (Fink. 2006).

Some more details on the retinol / retinyl palmitat studies

In that it is interesting to note that the scientists picked retinyl palmitate not just for its better safety profile (compared to all-trans-retinoic acid) but also due to its short half-life, its well-known ability to stimulate type I collagen, and its ability to resist air oxidation.

Figure 6: Increase in blood flow in 20 women with moderate cellulite of the thighs treated twice daily on one side for 6 months with a 0.3% stabilized retinol cream while the opposite side was treated with the vehicle (Kligman. 1999)

In a previous study by Kligman et al. (1999) a similar cream containing 0.3% stabilized retinol did lead to marked increases in the blood flow as well as the synthesis of glycosaminoglycans and collagen in a group of 20 women with moderate cellulite on the thighs. Moreover, ...

"[t]here was also a marked reduction in the density of hypoechogenic areas on the retinol sides, from 53% to 18% of black pixels on image analysis. Blood flow measurements were unchanged on the vehicle sides but increased significantly on the retinol sides. Thickness measurements by ultrasound scan were unchanged on the vehicle sides but increased significantly on the retinol sides, from 1.44 to 1.60 mm." (Kligman. 1999)

In their study, Fink et al. observed responses in both the patients who received the combination treatment with the pulsed laser and retinol, as well as in those who received only the laser therapy; and with 60% (9) of their patients having a ≥ 50% improvement in cellulite at 3 months that lasted for 7 of the women up to the 8-months follow up, the overall results are pretty impressive.

Visible not just measurable improvements most likely due to vitamin A

Before and after pictures of the second, 50 year old patient in the vitamin A + pulsed laser study (Fink. 2006)

As I already mentioned on the show, though, the actual reason I picked this study to anchor the show were the two before and after pictures. The first set of which (see top of the page) is the one I already published on the SuppVersity Facebook Wall as a sneak preview, the other one that was taken from a 50 year-old patient (see image to the right) shows similar improvements. Due to the fact that she started out with a higher grade of cellulite, the end-result is yet not as astonishing as the one of the 37 year-old women you "know" already. Both women were in the combined treatment group and in all honesty, I personally consider the retinol the more promising therapeutic agent of the two.

As I told Carl on the show it cannot be excluded that the combination of tissue breakdown from the laser and the "collagen-anabolic" effects of retinol are perfect synergists. Similarly, it is difficult to say, whether the use of aceton only rendered the 2x/day application that was used in the Kligman study unnecessary or whether it was the removal of the stratum corneum that made the treatment so effective.

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Bottom line: I would hope to see ongoing research in particular with regards to topical based retinol treatments for cellulite. And if respective results are published outside of the bazillion of small scale "studies" that come with the endless (and endlessly hilarious) amount of patents for all sorts of snake oil, I can guarantee that they will be part of the regular SuppVersity news (NO, I am not going to write another special, I am exhausted any you can keep all typos and worse mistakes for yourself ;-)


References:

• Di Salvo RM. Controlling the appearance of cellulite: surveying the cellulite reduction effectiveness of xanthines, silanes, CoA, 1-carnitine and herbal extracts. Cosm Toil 1995; 110: 50–59.
• Fink JS, Mermelstein H, Thomas A, Trow R. Use of intense pulsed light and a retinyl-based cream as a potential treatment for cellulite: a pilot study. J Cosmet Dermatol. 2006 Sep;5(3):254-62.
• Hachem A, Borgoin JY. Étude anatomo – clinique des effets de l’extrait titré de centella asiatica dans la lipodystrophie localisée. La Méd Prat 1979; 12(4): 17–21.
• Hausen BM. Centella asiatica (indian pennywort), an effective therapeutic but a weak Sensitizer. Contact Dermatitis. 1993; 29(4): 175–179. 
• Kligman AM, Pagnoni A, Stoudemayer T. Topical retinol improves cellulite. Journal of Dermatological Treatment. 1999; 10: 119–25
• Lotti T, Ghersetich I, Grappone C, Dini G. Proteoglycans in so-called cellulite. Int J Dermatol. 1990 May;29(4):272-4.
• Querleux B, Cornillon C, Jolivet O, Bittoun J. Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic resonance imaging and spectroscopy: relationships with sex and presence of cellulite. Skin Res Technol. 2002 May;8(2):118-24.
• Rosenbaum M, Prieto V, Hellmer J, Boschmann M, Krueger J, Leibel RL, Ship AG. An exploratory investigation of the morphology and biochemistry of cellulite. Plast Reconstr Surg. 1998 Jun;101(7):1934-9.
• Rossi AB, Vergnanini AL. Cellulite: a review. J Eur Acad Dermatol Venereol. 2000 Jul;14(4):251-62.
• Russe-Wilflingseder K, Russe E, Vester JC, Haller G, Novak P, Krotz A. Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment. J Cosmet Laser Ther. 2013 Jun;15(3):155-62.
• Turati F, Pelucchi C, Marzatico F, Ferraroni M, Decarli A, Gallus S, La Vecchia C, Galeone C. Efficacy of cosmetic products in cellulite reduction: systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2013 Jun 14.