AGEs: Where do You Find (>500 Foods), How do You Avoid (a Dozen Tips) Them? And Why Should You Even Care?

100g fried bacon contains record-breaking 91,677 kU of AGEs. If you microwave it instead, you reduce the AGE concentration (and its taste) by ~90%! Learn more about the complex relationship between food, type, processing, AGEs and your health...

"AGEs kill!" That's the message many headlines of mainstream science-news outlets have been sending over the last 2-3 decades - headlines that are usually based on observational studies.

Most of them will then discuss epidemiological data, commonly ignoring that the very same food groups that are most likely to contain significant amounts of advanced glycation end products will also contribute to metabolic disturbances, which, in turn, increase the endogenous production of AGEs...

So, is the answer your usual "just eat healthily"? Don't worry I am going to go beyond that recommendation in today's SuppVersity article, but I would say: eating a minimally processed whole foods diet, should be the basis of everything you do for cardio-metabolic health, anyway.

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Back to the AGEs, though. The first question we have to answer is a very similar one: Do dietary AGEs even matter? If you look at the (earlier) research on AGEs in foods, there have been a number of researchers who acknowledged the ill effects of glycation on the cells of your body (just think of HbA1c, for example). More recently, though, the interaction circulating dietary AGEs with AGE-receptors has gained significant attention, so that the overview of the mechanism of ill health effects of AGEs from the 2016 review "Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention" in the peer-reviewed scientific journal "Nutrition" (Yamagishi 2016) is probably right when it signifies that dietary AGEs matter:

Figure 1: Pathologic role of dietary AGEs in various cardiometabolic disorders and aging (Yamagishi 2016) | Plus: Random selection of the low, medium and high AGE foods from the >500 item list at the bottom of the article.

Apart from their interaction with RAGE (review of RAGE and cancer, RAGE in health & disease, RAGE in aging), AGEs, and their highly reactive intermediates, such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone, bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, and aging. In that, they are yet still only "more or less undebated". 

Figure 2: Absolution for coffee? Not exactly: While it does contain only very low amounts of pentosidine and no detectable fructoselysine or pyrraline, the larger part (75%) of its pentosidine content is free and appears to be absorbed much easier than the higher, but largely bound (<1% free) amounts of this biomarker for AGEs (Förster 2006). 

What is still debated is the general validity of the first arrow in Figure 1, which signifies that dietary AGEs make (physiologically significant) contribution to the AGE concentration in our circulating and tissues, which is, in turn, driving the previously referenced organ damage (especially in the heart and endothelium), metabolic syndrome, cancer (not shown in Figure 1, but unquestionably an issue | Yamagishi 2005 & 2015; Sparvero 2009 | depending on one's microbiome they may also have protective effects, though, Aljahdali 2019) and even seem to accelerate the general aging process (Chaudhuri 2018).

The link between dietary AGEs and the formation of a "sugar-coating" on your cells is not as obvious and self-evident as you'd think.

In fact, studies investigating the contribution of the health effects of dietary AGEs are of rather low(ish) quality. As Nowotny et al. point out in their 2018 review, studies investigating the methodological quality of such studies with the Heyland Methodological Quality Score identified a low methodological quality for 58% of the trials", in general. Puyvelde et al. (2014) who, analyzing observation studies with the STROBE (strengthening the reporting of observational studies in epidemiology) statement and intervention studies with the National Institute for Health and Clinical Excellence (NICE) checklist, report a generally reasonable quality for observational studies. Good? Well, not really. As previously stated, ...

...observational studies cannot tell us whether dietary AGEs are the actual culprit or just come alongside other pro-carcinogenic, pro-diabesity molecules in our favorite cookies and pastries; ...

and if we turn to those studies that could provide the information we're looking for, we have to read that the few actual intervention studies that exist are of generally low quality (van Puyvelde 2014). Even worse, most of the trials were conducted in patients with chronic kidney disease or diabetes, so that the authors of the 2014 systematic review ar right to demand that "additional studies in healthy individuals are needed" (van Puyvelde 2014).

Are dietary AGEs even absorbed? The notion that everything we swallow will also end up in our bodies is overly simplistic. How much of the AGE-content is present in unbound form, for example, has not been appropriately considered in either observational or experimental research - in other words: We don't know if the 103 mg of bound pentosidine in pretzel sticks are worse than the 2 mg of the non-peptide‐bound glycated amino acid in coffee. What we do know from Förster et al. is that the latter was more efficiently absorbed by the N=18 healthy volunteers ... if we go by how much of it was recovered in the urine, that is.

Roasted and BBQ-ed chicken skin doesn't just look like the worst offenders. With a whopping 18,520 kU/100g it is also the worst chicken choice you can make... quite healthy, though compared to fried (w/out oil) bacon which contains the crazy amount of 91,577 kU/100g when it was fried (Uribarri's | data of AGEs in 549 commonly consumed foods. You can find my compilation of all >500 values by clicking on the table in the bottom line.

Hence, a switch from a diet with plenty of grilled or roasted meats, fats, and highly processed foods, which is associated with more than 50% increased AGE-intakes over the certainly suboptimal standard diet of the average New Yorker (Uribarri 2010), to a diet that is rich in virtually AGE-free foods such as legumes, vegetables, fruits, and dairy (all three were among the lowest dAGE items in Uribarri 2010), may promote your health or, at least, reduce your risk of consuming enough AGEs to actually do harm.

Tipp: If you want to minimal-invasively lower your AGE intake 11,905kU/d simply stop eating that slice (13g) of bacon in the AM - that's ~50% of the AGE intake of the average New Yorker.

By the way, the study by Uribarri et al. (2010) has a list of the AGE content of 549 commonly consumed foods ranging from "A" as in almonds (1600-1900 kU/serving, depending on whether the almonds were roasted (higher end of the AGE range) or not (lower end of the AGE range), to "T" as in Tofu (sautéed on the outside 5,289 kU/serving) - check out all the data!

Moreover, the previously cited study by Nowotny et al. reminds us that even meta-analyses can be misleading. How's that? Well in some cases their results are dominated by a single study. As an example the researchers refer to Baye et al. (2017), where the significant effect on blood lipids the scientists detected was driven by a single study that was weighted up to 99% - "this means that this one study (out of 6) mainly influenced the result of the meta-analysis" (Nowotny 2018).

Table 1: While certain foods may be more prone to AGE formation than others, it's eventually what you do to your foods in your (or commercial) kitchens that is the #1 determinant of their AGE content; here, expressed in arbitrary AGE kilounits per 90 g serving for meats and 100 g serving for potatoes (Uribari 2015).

Things are further complicated by the way(s) in which individual differences in food preparation affect the content and type of AGEs in foods; an effect that I've illustrated for a couple of examples in Table 1. In short, proving the "causality of dietary AGEs on health outcomes due to different diets is challenging" (Nowotny 2018) - to say the least:

"Intervention studies examining the effect of dietary AGEs are predominantly based on diets in which the cooking method was changed. To achieve differences in dietary AGE intake, diets are based on raw and steam-cooked foods on one side and on the other side on foods prepared with high cooking techniques such as grilling, roasting or frying. The latter is often associated with the normal diet. Different cooking techniques not only influence levels of dietary AGEs but also other Maillard products such as acrylamide and hydroxy-methylfurfural" (Nowotny 2018).

So, if you start paying attention to your AGE intake, your efforts to reduce your intake of the glycated proteins and fats will lead to several changes regarding the diet composition (Pouillart 2008). The latter include, but are not limited to...

• 

  Table 1: The high vs. low AGE diets were rarely as similar as reported by Pouillart et al, and even here the complex effect of their heat-reduced preparation precludes making definite statements about the contribution of AGEs to the final outcomes feasible.

  decreasing kcal-density, as avoiding high-temperature cooking techniques nullifies the decrease in water content of foods so that the caloric intake of food decreases;
• increasing nutrient density, as the corresponding cooking methods such as low heat cooking or steaming preserve micro-nutrients that would be lost during regular high heat treatment; and 
• limiting 'trash fats', i.e. those low quality, often partially oxidized oils and fats that are used during the frying process and thus inflammation and total caloric intake. 

In other words: While we do have evidence that interventions that reduce our intake of dietary AGEs will lead to significant improvements in markers of overall and metabolic health, ...

... we do not know how much of the beneficial effects of low-AGE diets are actually mediated by lowering the intake of AGEs and no collateral effect on food quality and quantity...

which are almost inevitable when you switch from an AGE-laden Western to a low-AGE diet, because the latter happens to be based on exactly those dietary principles of which the current evidence suggests that they have general benefits for your metabolic and cardiovascular health.

And if you feel that things aren't complicated enough, yet, I suggest you revisit Figure 2 and remember the putative role of bioavailability and hence downstream (ill) health effects also seem to depend on the form (protein-bound vs. free) of AGEs in your food.

Figure 3: The dAGE content of milk increases 2.7- and 3.5-fold when it's pasteurized or sterilized (Ahmed 2005).

Are there patterns that emerge when you look at the AGE-content of foods? Yes, you can! Here's how:

[1] fats tend to contain more dietary AGEs (dAGE) per gram of weight, [2] meats will likely contribute more to overall dAGE intake because meats are served in larger portions than are fats.

When items in the meat category prepared by similar methods were compared, the highest dAGE levels were observed in beef and cheeses followed by poultry, pork, fish, and eggs.

Lamb ranked relatively low in dAGEs compared to other meats (see Figure in the bottom line for the complete tabular overview). As Uribarri et al. point out, ...

"[...it] is noteworthy that even lean red meats and poultry contain high levels of dAGEs when cooked under dry heat[, which] is attributable to the fact that among the intracellular components of lean muscle there exist highly reactive amino-lipids, as well as reducing sugars, such as fructose or glucose-6-phosphate, the combination of which in the presence of heat rapidly accelerates new dAGE formation" (Uribarri 2010)

Speaking of heat, [3] low-heat processing is one of the keys to reducing your dAGE exposure. On the other hand, t is interesting to note that [4] even uncooked, animal-derived foods such as cheeses can contain large amounts of dAGEs. This is likely due to pasteurization (see Figure 3) and/or holding times at ambient room temperatures (eg, as in curing or aging processes).

Figure 4: If you want to protect your meat from AGE-formation, vinegar or lemon juice containing marinades may limit the formation of AGEs - 1=raw beef. 2=roasted beef with no vinegar or lemon. 3=roasted beef after marinating with either vinegar or lemon for 1 hour (Uribarri 2015).

Not all means of processing are bad, though: [5] Marinades, for example, can protect your steak (and other meats) from 'AGE-ing'. Uribarri et al. (2010) observed a >50% reduction in AGE formation when beef (25 g) was roasted for 15 minutes at 150°C after pre-marinating in 10 mL vinegar (A) or lemon juice (B) for 1 hour. Moreover, [6] not all processed (fake) food are worse than the original: regular mayonnaise has ~50-fold more AGEs than mayonnaise imitation, for example.

When you're cooking your foods, the [7] oil/fat you choose may easily make a ~50-70% difference, as it has been observed for scrambled eggs prepared with a cooking spray, margarine, or oil versus cooked with butter (details see tabular overview linked in the bottom line).

Lastly, you should remember that their name ("glycation end products") may falsely mislead you to conclude that high carbohydrate foods contain generally more AGEs than your beloved keto-foods - often, the opposite is the case, though: [8] high(er) carbohydrate foods generally contain lower amounts of AGEs. As Uribarri et al. (2010) explain, this may be due to the often higher water- and/or higher antioxidant- & vitamin-content and in these foods, which may diminish new AGE formation, as well as the high prevalence of polysaccharides consisting of non-reducing sugars, which are less likely to give rise to AGEs - needless to say that they lose their protection when they are mixed and processed as potatoes in chips, crackers, cookies, and other popular snacks (e.g. biscuits had more than 10 times the amount of dAGEs found in low-fat breads, rolls, or bagels).

Why don't we have AGE-tables or even an AGE label on the packaging? While there is no "this is why"-answer to this question, there are at least four limits to our ability to produce, verify, and use tables to calculate our personal (dietary) AGE exposure, Nowotny et al. summarize as follows:

Relative contribution of food items to dietary intake of a CML, b HMF, c AP and d acrylamide in the ICARE study on healthy adults. (Tessier 2012).  Bacon is high in AGEs, but the "healthy" breakfast cereals (imho the worst food on the market, 'cause it's AGE-loaden candy in disguise with an incredibly unwarranted health halo) and plain bread contribute much more to your AGE load.

the data analyzed the AGE content in food items with validated instrumental methods is restricted; 

the current data on different AGEs in a great number of foods is limited; ...

similar food items differ often in their nutritional profile so that the comparability with existing database is difficult; and ...

the AGE content in food might depend on small variations of food processing making it difficult to generalize measured AGE levels 

You can find some information about the worst and least offenders, as well as the influence of processing techniques in the red box above. Until corresponding data is included in commonly used calorie counting software, it will yet be difficult to monitor your individual exposure on a daily basis.

AGE content of 549 commonly consumed foods from Uribarri (2010) | color indicates AGE density/100g.

So what should I remember and what can I do to avoid getting sugar-coated? While we do know that the AGEs in our bodies pose a major threat to our cardiometabolic health and may accelerate the aging process (Clarke 2016), it is not clear to which extent these well-established effects are triggered, mediated, promoted or totally unrelated to dietary AGEs.

It seems to be certain, though, that high AGE intakes of several 10,000 kU/d pose a threat to your cardio-metabolic health.

That's also because dietary AGEs seem to be absorbed irrespective of leaky guts and co (Scheijen 2018); and if that's not enough, it may convince you that "the majority of studies indicate that restriction of dietary AGEs improves primary and secondary health outcomes in humans" (Nowotny 2018). Keep in mind, though: Many of these "improved health outcomes" may be mediated by a general decrease in inflammation and oxidative stress. These general benefits, on the other hand, could occur independent of the actual AGE content of the diet and may be attributable to other qualities of the low AGE diets, as well as the removal of unhealthy high-AGE foods that were used in corresponding clinical trials...

... long story short: While we cannot tell for sure how, considering the AGE data from the tabular overview in Uribarri 2015, avoiding (dry) heat processing, using vinegar-/lemon juice-based marinades, frying with cooking spray vs. butter, and all the other strategies you can extrapolate from patterns [1]-[8] in the red box have a huge potential as health-preserving, life-extending dietary and cooking tweaks Comment on Facebook!

References:

• Ahmed, Naila, et al. "Assay of advanced glycation endproducts in selected beverages and food by liquid chromatography with tandem mass spectrometric detection." Molecular nutrition & food research 49.7 (2005): 691-699.
• Aljahdali, Nesreen, and Franck Carbonero. "Impact of Maillard reaction products on nutrition and health: Current knowledge and need to understand their fate in the human digestive system." Critical reviews in food science and nutrition 59.3 (2019): 474-487.
• Baye, Estifanos, et al. "Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: Meta-analysis of randomized controlled trials." Scientific reports 7.1 (2017): 2266.
• Chaudhuri, Jyotiska, et al. "The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality." Cell metabolism 28.3 (2018): 337-352.
• Clarke, Rachel, et al. "Dietary advanced glycation end products and risk factors for chronic disease: a systematic review of randomised controlled trials." Nutrients 8.3 (2016): 125.
• Fleming, Thomas H., et al. "Reactive metabolites and AGE/RAGE-mediated cellular dysfunction affect the aging process–a mini-review." Gerontology 57.5 (2011): 435-443.
• Förster, Anke, Yvonne Kühne, and Henle, Thomas. "Studies on absorption and elimination of dietary maillard reaction products." Annals of the New York Academy of Sciences 1043.1 (2005): 474-481.
• Nowotny, Kerstin, et al. "Dietary advanced glycation end products and their relevance for human health." Ageing research reviews (2018).
• Palanissami, Gowri, and Solomon FD Paul. "RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer—a Review." Hormones and Cancer 9.5 (2018): 295-325.
• Peyroux, J., and M. Sternberg. "Advanced glycation endproducts (AGEs): pharmacological inhibition in diabetes." Pathologie Biologie 54.7 (2006): 405-419.
• Pouillart, Philippe, et al. "Strategy for the study of the health impact of dietary Maillard products in clinical studies: the example of the ICARE clinical study on healthy adults." Annals of the New York Academy of Sciences 1126.1 (2008): 173-176.
• Prasad, Kailash, and Manish Mishra. "AGE–RAGE Stress, Stressors, and Antistressors in Health and Disease." International Journal of Angiology 27.01 (2018): 001-012.
• Scheijen, Jean LJM, et al. "Dietary intake of advanced glycation endproducts is associated with higher levels of advanced glycation endproducts in plasma and urine: The CODAM study." Clinical Nutrition 37.3 (2018): 919-925.
• Shahab, Uzma, et al. "The receptor for advanced glycation end products: A fuel to pancreatic cancer." Seminars in cancer biology. Vol. 49. Academic Press, 2018.
• Sparvero, Louis J., et al. "RAGE (Receptor for Advanced Glycation Endproducts), RAGE ligands, and their role in cancer and inflammation." Journal of translational medicine 7.1 (2009): 17.
• Uribarri, Jaime, et al. "Advanced glycation end products in foods and a practical guide to their reduction in the diet." Journal of the American Dietetic Association 110.6 (2010): 911-916.
• Uribarri, Jaime, et al. "Dietary advanced glycation end products and their role in health and disease." Advances in nutrition 6.4 (2015): 461-473.
• Tessier, Frédéric J., and Ines Birlouez-Aragon. "Health effects of dietary Maillard reaction products: the results of ICARE and other studies." Amino acids 42.4 (2012): 1119-1131.
• Yamagishi, S., et al. "Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients." Medical hypotheses 64.6 (2005): 1208-1210.
• Yamagishi, Sho-ichi, Takanori Matsui, and Kei Fukami. "Role of receptor for advanced glycation end products (RAGE) and its ligands in cancer risk." Rejuvenation research 18.1 (2015): 48-56.
• Yamagishi, Sho-ichi, and Takanori Matsui. "Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention." Nutrition 32.2 (2016): 157-165.

Platelet-Rich Plasma - Mar-2019 Update: What? How? For Whom? And How Useful? PRP Summarized + Illustrated

This article focuses on the use of PRP for mobility issues, but it's also used for hair growth and cosmetics.

In a point-/counter-point article that was recently published in the Strength and Conditioning Journal Morey J. Kolber, professor at Nova Southeastern University, and Paul A. Salamh, assistant professor at the University of Indianapolis discuss the usefulness of PRP for different joint/ligament issues ranging from the proverbial Achilles heel to the often overused rotator cuff - with additional references and illustrations, their paper consitutes the backbone of this brief research update.

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• Whether PRP works is not a "yes-or-no"-question. As Kolber points out, "additional factors such as the type of injury and outcome of interest (e.g., pain, function, and tissue healing) must be considered" (Kolber & Salamh 2019). To this ends, scientists would have to identify those injuries and athletes, as well as other patient groups who will benefit most/at all from PRP treatments, as well as to evaluate, whether the "published outcomes are comparable with an alternative intervention, consideration of risk and cost may lead to an individualized decision" (Kolber & Salamh 2019).
  
  The experimental evidence we'd need to make definite statements, however, is not yet available. Hence, the information in the next bullet-point must be considered preliminary.

• 

  Figure 1:  The most convincing data of benefits is that on patellar tendons seem, whereas the results in the Achilles tendon do not justify the application of PRP. The efficacy for the treatment of rotator cuffs "are still too limited to provide viable indications" (Filardo 2018), but... in patients with lateral elbow tendinopathy, there were improvements in most of the high-level studies (based on the results of a systematic review by Filardo et a. 2018). *useless independent of whether it's used in conjunction with conservative or surgical treatments.

  For tendon-related disorders (overuse or acute), Filardo et al. found no general, beneficial effect based on their 2018 systematic review of 50 studies. They did, however, do what Kolber demands in the debate, they considered different tendon disorders and found that "the patellar tendon seems to benefit from PRP injections, whereas results in the Achilles tendon do not justify the application of the evaluated platelet concentrates, neither conservatively nor surgically" (Filardo 2018).
  
  Mixed results were observed when the scientists limited the scope of their analysis to rotator cuff and elbow tendinopathies. And, the previously-hinted-at comparison of PRP treatments to conservative and/or surgery-based treatments are rare. Those that exist, such as studies of PRP use for lateral elbow tendinopathy "showed an improvement in most of the high-level studies, but the lack of proven superiority with respect to the more simple whole-blood injections still questions its use in the clinical practice" (Filardo 2018).

Figure 2: It takes some time, but at the12-months follow-up 91.3% of the PRP patients in Vetrano 2013 were satisfied with their treatment, while only 60.8% of those who received extracorporeal shock wave therapy reported satisfactory results.

Best practice: If it works for the patellar tendon, how effective is PRP, exactly, and how often does it have to be applied? When it was combined with surgical intervention, "a better pain control was documented in the initial post-op phases and, at 6-month follow-up [even after a single injection], MRI evaluation showed also a better tissue healing after PRP administration in the harvest site" (Filardo 2018). Used as part of conservative treatment, benefits were observed for PRP often after a single, most consistently, however, in response to 2-3 bi-weekly treatments.

Another question that has been debated back and forth is when to start the PRP treatment - specifically for acute injury recovery. In her editorial from 2010, Kimberley Harmon comes to the conclusion that "PRP should not be administered in the first 24 h after injury" (Harmon 2010). Her rationale, however, i.e. that one would better "limit the ‘secondary injury’ using traditional means of controlling inflammation, namely compression, elevation and ice" leads us back to the still unresolved hormesis"-debate, I will briefly discuss in the context of high vs. low leukocyte preparations in the next section of this research update.

Overall, a statement from 's paper on "Best Current Clinical Practice" does yet still apply: "The best PRP formulation and treatment regimen cannot be deduced from the present state of the art" (Andia & Mafulli 2015). So, yes, additional research is needed to determine not just the optimal time-point, bus also the optimal leukocyte-content, processing techniques, injection-intervals and -volume,  etc. - but hey, I will keep you in the loop.

• Practitioners are asking themselves rightly: "Do I minimize, maximize or retrain the white blood cells aka leukocytes from an inflamed patient to avoid, maximize or modulate inflammation?" A simple answer to this question would probably be insufficient - after all, a recent study by Mariani et al. 2016 found no effects on markers of inflammation before and after the injection of the allegedly pro-inflammatory high leukocyte PRP in thirty-six OA patients. This result refutes previous "in vitro studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes - whether that's for better (inflammation => healing) or for worse (inflammation => further destruction) is unknown, though, and in view of the fat that the presence leukocyte-rich PRP doesn’t induce a relevant change in pro-inflammatory mediators", as Mariani et al. report in their 2016 paper it could well be completely irrelevant.
  
  

  

  Figure 3: For osteoarthritis of the knee Riboh et al calculated SUCRA values (which quantify the surface under the cumulative ranking, as well as the treatment rankings) favoring leukocyte-poor treatments using the IKDC scale - the difference was, however, everything but earth-shattering and the outcome, the SUCRA is already only an assessment of how likely it is that the treatment is the best of all treatments that went into the analysis | plot based on data from Riboh et al. 2016 who reviewed  6 randomized controlled trials (evidence level 1) and 3 prospective comparative studies
  (evidence level 2) with a total of 1055 patients to compare clinical outcomes and rates of adverse reactions between leukocyte-poor PRP and -rich PRP in the treatment of knee osteoarthritis.

  Hence, it stands to be tested in humans if and to which extent the white blood cells should be reduced, removed, or modula-ted before injecting the PRP - also according to the body part where it's used. In osteo-arthritic knees, for example, there is initial evidence that the low leukocyte variety may (despite identical effects on inflammation) lead to slightly better functional outcomes (Riboh 2016).
  
  As Figure 3 shows, the advantage is small for the IKDC scale, and surprisingly large for WOMAC (McConnell 2001), which ranks placebo #2 with a SUCRA of 41% in front of 'regular' leukocyte-rich PRP.
  
  Leukocytes are yet only one of the putative drivers of the pro-recovery effect of PRP. IGF-1 is another factor to consider. In her previously cited editorial Kimberley Harmon explicitly recommends practitioners use "a product which includes a higher proportion of plasma [as it] may have increased levels of IGF-1 and potentially enhance healing and decrease fibrosis (Harmon 2010)

What is SUCRA? And how reliable is the data? SUCRA values, which quantify the surface under the cumulative ranking, as well as the treatment rankings, themselves, must be taken with a grain of healthy skepticism. While the SUCRA for a given treatment represents the probability that that treatment is ideal (here the SUCRA for WOMAC scores for low vs. high leukocyte PRP is 98% vs. 39.9%). So, low leuko-PRP may be 2.5 times more likely to be the best out of the four treatments the review by Riboh et al. (2016) compared to high leukocyte. What it does not take into consideration, though, are the magnitude or clinical significance of the difference between treatments (using the example above, treatment A might have a success rate of 2% and treatment B a success rate of 1.9%, even with such a large difference in SUCRA).

• When inflammation is involved, SuppVersity readers will ask themselves: Do I want to avoid cooling and NSAIDs when using PRP? Keyword: hormesis. The answer is, as it is the case for the whole "anti-inflammatory substances blunt your gains"-issue, still in the open. As Kolber points out, "NSAIDs may allow individuals to be more comfortable during the initial inflammatory phase and is likely to promote earlier movement after a PRP injection" (Kolber & Salamh 2019). But what about the repair-processes? Well, we don't know that yet - in studies in canines, it seems as if NSAIDs were no problem.
  

  

  Table 1: Summary effects of platelet-rich plasma (Kolber 2018)

  The situation for cryotherapy is similar. Just like NSAIDs, ice-baths and co are often used in the post-injury period and thus the week(s) during which PRP is supposed to do its magic it seems to help deal with acute symptoms without affecting the healing process - "several studies have used some form of cryotherapy after a PRP injection with positive outcomes " (Kolber & Salamh 2019). On the other hand, Kolber rightly cautions that "there is [neither] conclusive evidence to preclude use [nor evidence that would allow us to] state with absolute certainty that ice is responsible for improved outcomes" (Kolber & Salamh 2019)... as usually: more research is necessary.

Table 2: What can you expect from a PRP treatment? Summary of clinical evidence from recent review (Kolber 2018)

So what's the verdict then? As so often, the answer to the question "Are PRP injections worth it?" depends on several confounding factors: injection/injury site, leukocyte-content, number and frequency of treatment, the overall quality of the PRP, etc.

The crux of the matter is - likewise, "as so often" - that these parameters may well interact with each other, with leukocyte-poor PRP offering benefits when used for the 'classic' osteoarthritis of the knee that were not observed for other injection sites.

Overall, there is accumulating evidence in favor of the use of PRP in acute muscle injuries (Harmon 2010; Andia 2011; Hamid 2014)  While generally "promising" (Arshdeep 2014), research on PRP in dermatology and aesthetic medicine (check out my article about hair loss = alopecia; also worth mentioning are applications for skin rejuvenation, avoiding or fixing scars and contour defects, stretch marks, and others) is still in its infancy.

With that being said, the treatment, which is not regulated by WADA, by the way, should always be applied by an accredited physician. In his contribution to the debate, Kolber names the following criteria for choosing a proper practitioner for your PRP treatments: (1) trained physician, (2) specialty in musculoskeletal injury (e.g., board certification in orthopedic or physical medicine or fellowship training in sports medicine), (3) training in the various imaging modalities needed to diagnose musculoskeletal conditions and administer an injection under guidance, (4) familiarity with indications and contraindications, plus postprocedural pain management, and (5) adequate training in the form of continuing medical education, clinical proctoring, and ongoing study.

What should I remember at this point, then? Well, as Kolber points out in what is probably the latest review of the literature (Colber 2018), PRP is an autologous blood product that is processed and injected into the site of injury or pathology: It derives its healing properties from growth factors (GFs), fibroblasts, cytokines, and chemokines in supraphysiological concentrations that harness the body's natural healing process; the latter involves neovascularization and increases blood supply necessary for the proliferation and differentiation of cells that promote tissue regeneration; contemporary clinical evidence identifies PRP as a potentially beneficial intervention for tendinopathy, osteoarthritis (OA), discogenic pain, and acute muscle injuries; PRP has an excellent safety profile and requires little to no downtime from activity; and PRP is typically not a service covered by insurance (Kolber 2018) | Comment on Facebook!

References:

• Andia, Isabel, Mikel Sánchez, and Nicola Maffulli. "Platelet rich plasma therapies for sports muscle injuries: any evidence behind clinical practice?." Expert opinion on biological therapy 11.4 (2011): 509-518.
• Andia, Isabel, and Nicola Maffulli. "Use of platelet-rich plasma for patellar tendon and medial collateral ligament injuries: best current clinical practice." The journal of knee surgery 28.01 (2015): 011-018.
• Arshdeep, Kumaran M. Sendhil. "Platelet-rich plasma in dermatology: Boon or a bane?." Indian Journal of Dermatology, Venereology, and Leprology 80.1 (2014): 5.
• Filardo, Giuseppe, et al. "Platelet-rich plasma in tendon-related disorders: results and indications." Knee Surgery, Sports Traumatology, Arthroscopy 26.7 (2018): 1984-1999.
• Hamid, Mohamad Shariff A., Ashril Yusof, and Mohamed Razif Mohamed Ali. "Platelet-rich plasma (PRP) for acute muscle injury: a systematic review." PloS one 9.2 (2014): e90538.
• Harmon, Kimberly G. "Muscle injuries and PRP: what does the science say?." (2010): 616-617.
• Kolber, Morey J., et al. "Platelet-Rich Plasma: Basic Science and Biological Effects." Strength & Conditioning Journal 40.5 (2018): 77-94.
• Leo, Michael S., et al. "Systematic review of the use of platelet‐rich plasma in aesthetic dermatology." Journal of cosmetic dermatology 14.4 (2015): 315-323.
• Mariani, Erminia, et al. "Leukocyte-rich platelet-rich plasma injections do not up-modulate intra-articular pro-inflammatory cytokines in the osteoarthritic knee." PloS one 11.6 (2016): e0156137.
• McConnell, Sara, Pamela Kolopack, and Aileen M. Davis. "The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties." Arthritis Care & Research: Official Journal of the American College of Rheumatology 45.5 (2001): 453-461.
• Vetrano, Mario, et al. "Platelet-rich plasma versus focused shock waves in the treatment of jumper’s knee in athletes." The American journal of sports medicine 41.4 (2013): 795-803.
• Riboh, Jonathan C., et al. "Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis." The American journal of sports medicine 44.3 (2016): 792-800.
• Salanti, Georgia, A. E. Ades, and John PA Ioannidis. "Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial." Journal of clinical epidemiology 64.2 (2011): 163-171.

Leafy Green Veggies Set Omega-6 on Fire? Plus: Proprietary but Worth Mentioning Milk Protein Contrate for Knee Pain

Not new, but still novel: "Proprietary Milk Protein Concentrate" about to make a come(back) in your joint supplements? And what are the implications of the counter-intuitive effects of leafy greens in a(n unhealthy) diet? Does this mean you have to stay away from collard greens (CG), purslane (PL), or orange flesh sweet potato greens (SPG) and other putative health foods?

If you follow @SuppVersity on Facebook, you will know the peer-reviewed open access journal "Nutrients" - they publish a lot of interesting papers every month and some even make it from the short news on Facebook to an actual full-length article on the SuppVersity - two studies did just that, today: A study by Johnson et al. with the potential to (eventually unwarrantedly) spoil your appetite for leafy greens and an RCT by Ziegenfuss et al. you should know if you want to stay on top of the research on "joint supplements"... joint supplements that seem to work even for people with minor (=non-osteoporotic) ailments.

Learn more about the effects of your diet on your health at the SuppVersity

Only Whey, Not Soy Works for Wheytloss

Taste Matters - Role of the Taste Receptors

Dairy Protein Satiety - Casein vs. Whey

How Much Carbs Before Fat is Unhealthy?

5 Tips to Improve & Maintain Insulin Sensitivity

Carbohydrate Shortage in Paleo Land

• Omega-6/3 ratio and how its ill effect seem to be mitigated by collard greens (CG), purslane (PL) and orange flesh sweet potato greens (SPG) -- Johnson 2019 
  Eating way too much vegetable and seed-oils that are high in omega-6 and low in omega-3? Then, you're like one o the rats in a recent study from the Tuskegee University who were randomly assigned to a 25:1 ω-6:ω-3 diet with 4% (green leafy vegetables =GLVs, dried weight) of either collard greens (CG), purslane (PL), or orange flesh sweet potato greens (SPG) CG, PL or SPG.
  
  Dietary intake, body weight, blood pressure, plasma adiponectin, high sensitivity C-reactive protein (hsCRP), oxygen radical absorbance capacity and lipid profile were determined using standardized procedures. Following a 6-week consumption period, systolic blood pressure, plasma adiponectin, total and low-density lipoprotein (LDL) cholesterol decreased following the consumption of diets containing GLVs. 

While the food intake was hardly different, the rats on all high N6:N3 diets weighed 13-15% more than peers on an unmodified AIN-76A (Johnson 2019).

Warning: Pounding green leafy vegetables won't keep you lean on your Westernized omega-6-super-charged diet... as the data from Johnson's study indicates (see Figure on the left) even if you're a mouse you're gonna gain significantly more weight irrespective of added collard greens (CG), purslane (PL), or orange flesh sweet potato greens.

Remember: We're talking about the stuff you usually throw away - the greens of your superfood).

Moreover, it is no coincidence that those "extra pounds" are - in relative terms - in a similar range as the extra energy intake from the high(er) fat chow (440kcal/100g vs. 370kcal/100g) - in the end, for body weight, calories count... whether and to which extent that depends on the N6:N3 ratio will have to be tested using isocaloric diets in future studies.

• 

  Figure 1: GLVs lowered adiponectin, and - if anything - increased the overall inflammation as measured by hs-CRP (total antioxidant potential was lowered, too | Johnson 2019)

  While hsCRP increased in the rodents receiving the high N6:N3 diets (see Figure 1) - interestingly enough, especially in those who received extra CG and PL... and as if that wasn't bad enough, "the antioxidant capacity was significantly reduced (p < 0.05) with the consumption of diets containing the GLVs", in other words:
  
  Leaving out the green green leafy vegetables was a plus in terms of antioxidant defenses!
  
  Against that background, it is unsurprising that plasma adiponectin levels (the anti-inflammatory were significantly reduced (p < 0.05) among the rodents consuming the PL (29.5 μg/mL) diet versus those consuming the AIN-76A (43.0 μg/mL) and C (38.6 μg/mL) diets, too.
  
  The authors still recommend eating leafy greens! And so do I!
  
  Yet, our rationale differs: Johnson et al. posit that "CG, PL and SPG have the potential to decrease risks for cardiovascular disease (CVD)" (Johnson 2019), as both have been linked not just to inflammation (which clearly didn't improve, here, but also and specifically to blood lipids and blood pressure in mammals.
  
  The claim seems all the more warranted in view of the fact that collard greens, purslane, and sweet potato greens prevented both high blood pressure, and dyslipidemia (i.e., hypercholesterolemia, hypertriglyceridemia) in the spontaneously hypertensive rats in the study at hand. More, specifically...

  "[...a]t week 6, consumption of the CG (173.4 mmHg) diet resulted in a decrease (p < 0.05) in systolic blood pressure compared to the AIN-76A (181.4 mmHg) and control (181.1 mmHg) diets. Among SHRs consuming diets containing GLVs, CG were able to modulate slightly greater non-significant decreases in systolic blood pressure in comparison to PL and SPG" (Johnson 2019).

  Furthermore, the scientists' analysis of the blood lipids showed that ...

  "In comparison to the control diet (97.0 mg/dL), triglyceride levels were increased among SHRs consuming the PL (113.0 mg/dL) and SPG (118.4 mg/dL) diets and decreased following the consumption of the CG diet (92.2 mg/dL) [Plus:] Although not significant, total cholesterol and LDL-C + VLDL-C levels were decreased among SHRs consuming the CG, PL and SPG diets in comparison to the AIN-76A and control diets [and] in comparison to the control diet (33.7 mg/dL), levels of HDL-C were increased among SHRs consuming the CG (38.7 mg/dL) and PL (41.3 mg/dL) diets" (Johnson 2019).

  Johnson et al. are also right to point out: "In addition to CVD, risks associated with other diseases such as atherosclerosis, diabetes, cancer and other inflammatory conditions may potentially be reduced as well with the consumption of these vegetables" (Johnson 2019).
  
  And still, I would like to add that the overall research in favor of the detrimental effects of exorbitant N6:N3 ratios and health benefits of all sorts of green leafy vegetables (outside of PUFA protection, btw, which would probably improve more with high vitamin E foods) indicates in my humble opinion that you would be best off if you normalized (N6:N3 < 6, total PUFA intake <20% energy intake) your intake of readily oxidizable polyunsaturated fats and ate a variety of green leafy vegetables on top of that ;-)

• "Proprietary" is not exactly everyone's favorite word when it comes to supplements, but when it's used in the title of a paper that's called "Proprietary Milk Protein Concentrate [MPC] Reduces Joint Discomfort While Improving Exercise Performance in Non-Osteoarthritic Individuals" (Ziegenfuss 2019) that's still intriguing.
  
  Milk? Yeah,... I know dairy is not exactly what you will think about 'natural joint/arthritis prevention/treatment'. That's however, partly due to the fact that you didn't do your homework. As Ziegenfuss et al. point out, special forms of milk, such as skim milk powder from hyperimmunized cows can reduce cholesterol (Golay 1990) and inflammation (Omrod 1991 & 92) - problem: inconvenient, tastes like crap, don't solve well, etc.

In vitro data from the previously cited study by Ormrod & Miller suggests that MPC exerts its by immuno-modulating effects - more precisely, by suppressing the ability of neutrophils to emigrate from the vasculature into cartilage and co (Ormrod 1992).

Glucosamine and Milk Protein Concentrate (#MPC) - alternatives, complements, or synergists? Even though their efficacy is still debated, glucosamine supplements are the go-to supplement for people with knee pain and have at least some scientific back-up for their efficacy (Knapik 2018). Hence, the obvious question is: Should I take one or the other or both?

In this context, it is important to note that MPC does not seem to work by modulating changes in cartilage oligomeric matrix protein (COMP), a marker of cartilage breakdown. COMP, which is found in human chondrocytes and is known to increase after knee injury, early stages of osteoarthritis, and also in response to endurance-training in runners (Neidhart 2000). For glucosamine, Petersen et al. (2010) were able to show that it can alter cartilage turnover in osteoarthritis patients in response to physical training.

In the present study, on the other hand, Ziegenfuss et al. did not observe significant changes in COMP from MPC supplementation, which is not actually a surprise, though - after all, the subjects didn't train or sustain otherwise induced wear-and-tear on the knee joint in form of high volumes of endurance training.

In the absence of other news on the mechanism, we do thus simply have to assume that MPC works due to its high concentration of immune factors and could work both, additively and/or synergistically w/ glucosamine. On the other hand, it seems rather unlikely that one will cancel out the effects of the other and/or offer absolutely zero extra-benefit... note: this benefit may, however, very well be clinically irrelevant :-/

• ... sounds like manageable obstacles, doesn't it? I guess that's what Colker et al. (2002) et al. also thought when "[t]o address these shortcomings", they developed the previously mentioned "proprietary (lactose-free) milk protein concentrate" from milk produced in hyperimmunized cows in (a) way(s) that will retain "much of the valuable high-molecular-weight immunoglobulins and low-molecular-weight bioactives while removing much of the carbohydrate, salt and fat resulting in its ability to be concentrated and encapsulated". To examine its effects, Colker et al. (2002) conducted a randomized, double-blind study, in which 31 adults with physician-diagnosed osteoarthritis in their knees, received either a placebo or said concentrated milk protein (12 oz daily).
  

  

  Figure 2: Relevant outcomes of Coker's 2002 study comparing 12oz/d of the "proprietary (lactose-free) milk protein concentrate" from milk produced in hyperimmunized cows to placebo (Colker 2002).

  As the data in Figure 2 shows, a significant treatment effect was observed in the WOMAC, knee pain score, sports function and quality of life for those participants who consumed the concentrated milk protein while only improvements in sports function and quality of life were found in the placebo group. 

Lighten the load to reduce burden and pain! Not the easiest, but the simplest and most obvious pain to tackle (osteoporotic) knee pain is to lose weight. A 2006 study from Sri Lanka shows that "participants required ≥7.7% (95% confidence interval 5.2, 13.3) body weight loss to achieve a minimal clinically important improvement in function" (Atukorola 2016)... and what's best: more helps more!

• Follow-up studies yielded similarly beneficial results, but all of them were conducted in patients with pre-existing osteoarthritis; and, as Ziegenfuss et al. highlight: "[B]eyond markers of clinical safety, neither study reported on any biomarkers that might help to offer any insight into potential mechanism(s) of action" (Ziegenfuss 2019) - reason enough to conduct another follow-up study to ...

  "examine the impact of ingesting [said] concentrated milk protein derived from the milk produced by hyperimmunized cows on alleviating pain (discomfort) and function with and without an external physical stimulus in non-osteoarthritic participants who reported having mild to moderate functional knee pain during/after physical activity [and to] examine changes in physical performance and a biomarker of cartilage breakdown" (Ziegenfuss 2019).

  For many athletes who fall into the same category of "non-osteoarthritic participants who [report] having mild to moderate functional knee pain", defined as a rating of 30/100 or higher on a 100-mm visual analog scale for knee discomfort, the results of the study are intriguing (see Figure 3).
  

  

  Figure 3: Mean differences in selected WOMAC scores (based on Table 3 in Ziegenfuss 2019)

  Unlike previous studies, Ziegenfuss et al. used capsules to deliver the 4000 milligrams of a proprietary milk protein concentrate from hyperimmunized cows (or a placebo) in a randomized, double-blind fashion. Subjects took one dose (5 capsules totaling 2000 mg) in the morning and one dose (5 capsules totaling 2000 mg) in the evening with 12 fluid ounces of cold tap water. In that, it is remarkable, 'cause unfortunately by no means common practice that the "[s]upplement purity and potency was confirmed by a third party (independent) laboratory" (Ziegenfuss 2019). 
• Overall the data (see Figure 3 & 4) seem to suggest that - assuming that you get a similarly pure/potent product - using the product from Stolle Milk Biologics who also sponsored the study with an external grant, may constitute an alternative for (or adjunct to?) standard supplements such as glucosamine (cf. comparison of MPC w/ glucosamine by Zenk et al. 2002)... and, the only unexpected 'side effect' was an MPC-induced reduction of the subjects' back and neck pain.
  
  However, as the authors readily admit, the results "are specific to a middle-aged population with no resting knee pain, no previous diagnosis of joint disease and only mild to moderate joint pain with physical exertion" and thus not suitable for uncritical extrapolation of the findings to other populations. The study also failed to provide conclusive evidence as to the underlying mechanisms and the effect of long-term supplementation (16-24 weeks).

Remember: Optimal joint health is at best also about taking the right supplements (like C+gelatine).

Leafy greens, dairy, and osteoarthritis? Yes, you're right, there's a common link between the former two and the debilitating disease.

So, while it is not yet clear if and to which extent the effects of MPC and glucosamine will add up (see infobox), the latter can be safely assumed for increases in micronutrient-rich leafy green vegetables and (fermented) dairy, and decreased intakes of pro-inflammatory junk foods and -fats, similar to those people who transition from the standard Western to the USDA, DASH, and MED diets undergo.

Hence, diet (and sane physical activity) should constitute the foundation of any anti-joint pain... or, any intervention to prevent that your knee and other joints start to hurt in the first place | Comment on Facebook!

References: 

• Atukorala, Inoshi, et al. "Is there a dose‐response relationship between weight loss and symptom improvement in persons with knee osteoarthritis?." Arthritis care & research 68.8 (2016): 1106-1114.
• Colker, Carlon M., et al. "Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation." Nutrition 18.5 (2002): 388-392.
• Neidhart, M., et al. "Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners." Osteoarthritis and Cartilage 8.3 (2000): 222-229.
• Ormrod, D. J., and T. E. Miller. "The anti-inflammatory activity of a low molecular weight component derived from the milk of hyperimmunized cows." Agents and Actions 32.3-4 (1991): 160-166.
• Ormrod, Douglas J., and Thomas E. Miller. "A low molecular weight component derived from the milk of hyperimmunised cows suppresses inflammation by inhibiting neutrophil emigration." Agents and actions 37.1-2 (1992): 70-79.
• Petersen, Susanne Germann, et al. "Glucosamine but not ibuprofen alters cartilage turnover in osteoarthritis patients in response to physical training." Osteoarthritis and Cartilage 18.1 (2010): 34-40.
• Zenk, John L., Tami R. Helmer, and Michael A. Kuskowski. "The effects of milk protein concentrate on the symptoms of osteoarthritis in adults: an exploratory, randomized, double-blind, placebo-controlled trial." Current Therapeutic Research 63.7 (2002): 430-442.

Revisited: Squatting W/ Weightlifting Shoes and "Elevation Masks" - Results of New Studies Appear Initially Surprising

Weight lifting shoes don't make a difference and "elevation masks" (those things that simply impair your ability to breath) work... they increase your cerebral oxygenation - don't rely on the potentially misleading abstracts, alone... read SuppVersity!

Stronger, faster, leaner, ... and obviously more muscular. If you want to achieve all that, you got to invest the effort it takes to trigger the adaptational processes that will get your skinny-fat Western a** into Instagram-ready pre-Olympic shape. But what about the myriad of training gadgets will they take you there any faster? A cursory look at the latest scientific evidence seems to suggest that weight lifting shoes may not be as beneficial and - more surprisingly - elevation masks not as useless as many people believe... a cursory look, that is ;-)

Hitting a wall? Try one of these exercises, workouts, and programming techniques:

30% More on the Big Three: Squat, DL, BP!

Mix Things Up to Make Gains - no 'M. Confusion'

Linear vs. Undulating Periodization

BFR, Detraining & Kettlebells - Will They Help?

Deadlifting w/ Resistance Bands

Tapering 101 - Learn How It's Done!

• Heel-Raised Foot Posture Does Not Affect Trunk and Lower Extremity Biomechanics During a Barbell Back Squat in Recreational Weight lifters (Lee 2019)
  
  

  

  Re-read my previous in-depth article about weightlifting shoes | more

  You will probably remember my confusingly controversial article about weightlifting shoes from November 2017. Some of you almost seemed to be offended by objective data... data that was albeit not in line with your bias towards the "super stable" and "muscle activation promoting" shoes.
  
  Long story short, I am curious what you will make of Lee's latest study. 
  
  As Lee et al. point out, Adidas, Reebok and other shoe companies claim "that weightlifting shoes with a raised heel may lead to a more upright trunk posture, and thus reduce the risk of back injuries during a barbell back squat" (Lee 2019).
  
  As with almost every marketing promise, "[t]hese proclaimed biomechanical effects have [, however,] not been thoroughly investigated" (Lee 2019) - outside of your N=1 'study', bro ;-) 

Figure 1: Illustration of the kinematic measures from previous studies; here Sato et al. (2012).

What do we know about the heel-effect? A number of published research studies assessed the effects of the heel-raised foot posture on the trunk and lower extremity biomechanics during execution of the barbell back squat. In that, the results of studies like Sato et al. (16) or Legg et al. (11) are probably the most cited investigations; and what shall I say? Both "found less relative displacement between the hip and the bar in the weightlifting shoes condition, indicating a less flexed trunk posture" (Lee 2019). As Lee et al. point out, though, Legg's conclusion that "wearing Olympic weightlifting shoes may aid those with back pain because of the decreased trunk flexion causing less strain on the spine" (Lee 2019)... So far so good, another claim, namely an increase knee extensors and reduction of spinal extensor activity was postulated but not measured by the UK researchers (Legg 2017).

And Lee et al. highlight other "limitations" in the introduction to their latest paper in the Journal of Strength and Conditioning Research: First, the investigators tracked trunk movement as represented by the relative motion between the bar and the hip/pelvis. This type of method does not directly capture the angular displacements of the thoracic and lumbar spine segments. Second, nonstandardized running and athletic shoes were used in previous studies, which are variable by style and may differ in stiffness. [...] Third, the weight the subjects lifted during some of the studies was relatively low (unloaded to 60% of the subjects' 1 repetition maximum (1-RM)), meaning that the results cannot be extrapolated to more challenging efforts commonly used in training for recreational weight lifters" (Lee 2019).

• 

  Figure 2: Photos of foot placement from all three conditions (A-C), photo of the shoes that were used (VS Athletics).

  To get to the bottom of the squat movement, the scientists from Nevada recruited N = 14 "recreational weight lifters (7 men and 7 women" to "compare trunk and lower extremity biomechanics during barbell back squats in three foot postures" (ibid.). The subjects were 18 and 50 years old and performed the barbell back squats in three conditions
  • barefoot on a flat surface,
  • barefoot on a heel-raised platform, and
  • wearing weightlifting shoes (Fig. 2)
  at 80% of their 1 repetition maximum. Surface electromyography was used to assess the activation of the knee extensors and paraspinal muscles at L3 and T12 spinal levels.
  
  A 3D motion capture system and an electrogoniometer recorded the kinematics of the thoracic spine, lumbar spine, and knee during the back squat to a depth where the hip was at least at the same level to the knee; and the effects of the shoes were ... non-significant:
  
  "[...] none of the heel-raised foot postures significantly affected trunk and lower extremity muscle activation (thoracolumbar paraspinal [p = 0.52], lumbar paraspinal [p = 0.179], knee extensor [p = 0.507]) or the trunk angles (thoracolumbar spine [p = 0.348], lumbar spine [p = 0.283]) during the squat" (Lee 2019).
  
  This result obviously implies that "during barbell back squats, heel-raised foot postures do not significantly affect spinal and knee extensor muscle activations, and trunk and knee kinematics"; and yes, that also means that "heel-raised weightlifting shoes are unlikely to provide significant protection against back injuries for recreational weight lifters during the barbell back squat" and hence "recommendations of heel-raised footwear for performing the barbell back squat cannot be made on the basis of back injury prevention" (Lee 2019).
  
  

  

  "Full Squat for Full Size Gains, Partial Squat for Full Strength" | read more.

  We have to be careful, though, after all, the study doesn't refute another often-cited benefit of squatting w/ heels, i.e. their ability to facilitate ankle mobility to achieve the desired squat depth and increase foot-floor stability in non-recreational weightlifters where the depth of squat is an important criterion - not the least, because previous studies have implicated its role in making optimal gains (see SV Classic "Full Squat for Full Size Gains, Partial Squat for Full Strength Benefits" | read more).
  
  What we really need are studies w/ actually relevant outcomes
  
  These studies, i.e. long-term studies investigating the beneficial and/or negligible effects of weight lifting shoes on actual strength and size gains, as well as the number of injuries real strength athletes sustain with vs. without the 'heeled super shoes' or latest fitness fashion accessory, respectively, have not been conducted yet. Accordingly, I'd suggest you follow your instinct: if squatting with a bar under the heel feels right/better for you and/or you feel unstable squatting without or with minimalist shoes, weight lifting shoes are probably for you. If you don't feel that propping up your heels helps your squat and you're fine without the extra-fixation in the weight lifting shoes, invest your money in a bag of creatine to improve your squat ;-)
• Oxygenation Responses While Wearing the Elevation Training Mask During an Incremental Cycling Test (Romero-Arenas 2018) - Absolutely what everyone would have predicted!
  
  

  

  The masks are no alternative for altitude training - that's quite certain.

  While I have always been open to the use of weight lifting shoes in those who feel they benefit from the increased stability and/or the inclined heel position, I have to admit that I have been significantly less open-minded when it comes to so-called "elevation training masks" - not without reason, as I've discussed in quite some detail in a previous article that discusses actually relevant (=hard) outcomes in terms of improved gains/performance [(re-)read "Elevation Masks are STILL a Useless Torture Tool & Fashion Accessory for Gymrats, But Some Athletes May Benefit" | more]...
  
  "Wait, so the study at hand is not 'actually relevant'?" Why's that?
  
  While it does make sense to probe the "oxygenation responses while wearing the elevation training mask during an incremental cycling test", the results of the study at hand tell us absolutely nothing about the efficacy of regular use of the tested training mask, the "Elevation Training Mask 2.0" (ETM) - and, as you know, te often-claimed benefits "have not been conclusively demonstrated" (Romero-Arenas 2018) by previous research.
  

  

  Figure 3: Brain and muscle oxygenation kinetics during the incremental cycling test during the CTR (open circles) and ETM (black circles) conditions (Romero-Arenas 2018).

  So why discuss the results, then? Well, both the primary (brain oxygenation) as well as the secondary outcomes, which included heart rate (HR) response, perception of effort (rating of perceived exertion [RPE]), arterial oxygen saturation (SaO2), blood lactate (La+), and performance (POpeak), are interesting and worth discussing.

Don't freak out about a potentially increased stroke risk... yet! Unless you have pre-established asaccular cerebral aneurysms, the major risk factor for subarachnoid hemorrhage and strokes, the mask is - just like the Valsaöva Maneuver - likely pretty safe. Speaking of Valsalva, if you want to learn more about that, check out this 2013 article at Starting Strength.

• As the abstract already tells us, the study from the Catholic University of Murcia involved fourteen active males who completed an incremental cycling test to volitional exhaustion in 2 separate and counterbalanced conditions, wearing the mask set at 9,000 feet (i.e., 2743 m) and a control condition (CTR, without ETM). To assess the oxygenation of the blood "during the trial, muscle and cerebral oxygenation were monitored continuously using near-infrared spectroscopy" (Romero-Arenas 2018 | check out Figure 1, too).
  
  As any sane individual would expect, wearing the ETM significantly reduced the POpeak by −6.9 ± 6.6% (p = 0.002) and this was accompanied by lower La+ values (−12.8 ± 21.6%; p = 0.027). Since the oxygen content of the blood (SaO2) was also significantly lower at maximal intensity in comparison with the CTR condition (−1.5 ± 0.3%; p = 0.028), while neither the heart rate or rate of perceived exertion and muscle oxygenation showed statistical differences, you could safely file this study under practically hardly relevant evidence of the uselessness of ETMS. Yes, if it was not for the primary outcome:
  
  "[T]he mask caused an increase in brain oxygenation compared with the CTR condition (p < 0.05)" (Romero-Arenas 2018).
  
  In conclusion, while the most relevant parameters that would suggest that RTMs can increase the efficacy of your training (HI(I)T) sessions were not improved from suffocating yourself, the "increase in O2Hb and tHb in the frontoparietal cortex without any change in the muscle oxygenation" (Romero-Arenas 2018) is both counter-intuitive and unexpected.
  
  Keep in mind, though: The increase in cerebral blood flow (i.e., higher tHb levels) possibly being "related to an increased intracranial pressure, which, in turn, is a major risk condition for cerebral autoregulation" (Romero-Arenas 2018).
  
  Therefore, what may look as a great benefit initially does, after all, constitute yet another potentially "life or death"-argument (see red box) against the use of ETMs  - ah,... and yes, the fact that the study at hand confirms that "ETM does seem to negatively influence cycling performance (i.e., peak power output), which may attenuate training outcomes over time" (Romero-Arenas 2018) doesn't really make this funky gym gimmick more attractive to anyone but elevation mask producers, either.

If you want to use NaHCO3 to improve your performance but cannot stomach it, try to "serial load" it | learn how that works.

Bottom line: It's always good to stay open-minded and listen to both, research & practice (esp. what your own body tells you about using weightlifting shoes ;-). In that, the elevation training mask study clearly shows, though, that, at least, the former needs careful interpretation - I mean, if I had chosen to title "elevation mask increases brain blood oxygenation" that would have been an absolutely evidence-based statement, of which many (if not the majority of people) would have been misled to believe that my previously voiced concerns about the use(less!)ness of respiratory training masks would, at least, have taken a hit; when, in fact, the results Romero-Arenas et al. present in their ahead-of-print article in the Journal of Strength and Conditioning Research provide yet another reason not to bank on "looking like Bane" when you're at the gym --unless, obviously, you're doing it to stick out... as a critically uncritical victim of bro-science ;-) | Comment! 

References:

• Lee, S-P, Gillis, CB, Ibarra, JJ, Oldroyd, DF, and Zane, RS. Heel-raised foot posture does not affect trunk and lower extremity biomechanics during a barbell back squat in recreational weight lifters. J Strength Cond Res 33(3): 606–614, 2019.
• Legg HS, Glaister M, Cleather DJ, Goodwin JE. The effect of weightlifting shoes on the kinetics and kinematics of the back squat. Journal of Sports Sciences 4;35(5):508-15, 2017.
• Molinari, Filippo, et al. "Relationship between oxygen supply and cerebral blood flow assessed by transcranial Doppler and near–infrared spectroscopy in healthy subjects during breath–holding." Journal of neuroengineering and rehabilitation 3.1 (2006): 16.
• Sato, K, Fortenbaugh, D, and Hydock, DS. Kinematic changes using weightlifting shoes on barbell back squat. J Strength Cond Res 26(1): 28–33, 2012
• Romero-Arenas, S, López-Pérez, E, Colomer-Poveda, D, and Márquez, G. Oxygenation responses while wearing the elevation training mask during an incremental cycling test. J Strength Cond Res XX(X): 000–000, 2018—