They Dictate What You Like, They Dictate What You Crave and They May Even Determine Whether You're Lean or Fat: The Bacteria in the Gut - The Latest Evidence Reviewed

The alien inside - billions of bacteria in your gut interact with your central nervous system and take command over your metabolism and - probably - even about what you want to put into your mouth.

Wouldn't it be great if it was not your lack of willpower and your unhealthy food choices that were to blame for the potbelly you're carrying around? Wouldn't it be awesome if you could blame your misery on someone else? And wouldn't it be best if that someone was a dirty little microbe in your gut? Someone who cannot fight back, when you chose him as a scapegoat? That would be great, right?

Well, in today's SuppVersity Article we're going to take a look at a bunch of studies and hypothesis that may actually allow you to find a new excuse for your inability to lose weight. But beware! While I wouldn't say that researchers who favor the "evolutionary conflict between host and microbes" theory as an alternative explanation for the ever-increasing obesity rates are totally off. What I will say, however, is that this is at best a contributing, maybe even just a corollary factor in the etiology of the obesity epidemic.

You can learn more about the gut & your health at the SuppVersity

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

We know for quite some time that individual members of the microbiota, and consortia of those microbes are highly dependent on the nutrient composition of the diet.

• Prevotella grows best on carbohydrates; dietary fiber provides a competitive advantage to Bifidobacteria (González‐Rodríguez. 2013)
• Bacteroidetes has a substrate preference for certain fats (Wu. 2011)

Scientists have also found some specialist microbes, e.g. mucin degrading bacteria such  as Akkermansia mucinophila. They thrive on secreted carbohydrates provided by host cells. Other butyrate producing microbes, e.g. Roseburiaspp., fare better when they are delivered polysaccharide growth substrates in the diet. Specialist microbes that digest seaweed have been isolated from humans in Japan (Hehemann. 2010). African children raised on sorghum have unique microbes that digest cellulose (De Filippo. 2010). Many other examples exist (Fava. 2012).

We have tons of associations, but little experimental evidence: All this does yet not mean that the specialized gut microbiome will also affect the dietary intake of the host. You could after all argue that you could get rid of Prevotella by simply cutting out all carbs from your diet, but scientists believe that the specialization works both ways.

There is circumstantial evidence for a connection between cravings and the composition of gut microbiota. Individuals who are “chocolate desiring” have different microbial metabolites in their urine than “chocolate indifferent” individuals, despite eating identical diets (Rezzi. 2007).

Figure 1: A study by Rezzi et al. showed that chocolate cravers have a different microbiome than their peers (Rezzi. 2007)

In spite of these intriguing results and a plethora of evidence for mood and central nervous system effects of certain bacteria in rodents, the definite evidence of a causal relationship between gut microbes A, B & C and certain food preferences, let alone "addictions" is still missing.

It's not as if there was no evidence, it's just not really compelling (yet?)

An area where the mechanisms appear to be more evident is the effect of certain bacteria on the expression of certain molecular receptors in the gut. Germ-free mice for example have altered taste receptors for fat on their tongues and in their intestine compared to mice with a normal microbiome (Duca. 2012). Since an increase in fat receptors is associated with an increased preference and intake for fatty foods and energy, an over-expression of these receptors could certainly be involved in the etiology of obesity.

Both, low dose penicillin at weaning (blue) and at birth (red) lead to significant obesity in male pups later in life (Cox. 2014).

Latest research says: Disruption of gut bacteria early in life can lead to obesity in adulthood! Certain microbes found in the gut may protect against obesity and diabetes. A study published by Cell Press August 14th in the journal Cell reveals that these microbes shape their hosts' metabolism very early in life and that disrupting them with short-term exposure to antibiotics during infancy can cause metabolic changes that appear to increase the risk of obesity in adulthood.

These findings in mice are helping researchers identify which gut bacteria are crucial to metabolic health. Such information could be used to help restore levels of those helpful microbes after an infant has received life-saving antibiotics, thereby promoting healthy metabolism in adulthood.

In conjunction with other scientific evidences, such as the increased intestinal expression of cannabinoid and opioid receptors in mouse and rat intestines in response to the oral supplementation of L. acidophilus NCFM in rats and similar effects in human epithelial cell culture (Rousseaux. 2006), the Duca study suggests that the composition of microbes in our guts could in fact actively alter our food preferences by modulating the receptor expression or transduction (Collins. 2012).

Is a "gut dysbiosis" the reason we are fat?

The idea that not having the "right" bacterial make-up could be at the heart of the obesity epidemic has recently received significant scientific attention. Backhed and colleagues showed that mice genetically predisposed to obesity remained lean when they were raised without microbiota (Bäckhed. 2004).

Figure 2: Germ-free mice stayed lean, in spite of the fact that they were genetically predisposed to become obese and irrespective of their increased food intake (Bäckhed. 2004). When they were inoculated with the microbiota from regular obese mice (CONV-D), however, they became just as obese as their conventional peers (CONV-R)

When the mice were "infected" with fecal pellets from a conventionally raised obese mice, they became obese again. That this could happen in humans as well is supported by data from Ridaura et al. (2013) who observed that the inoculation of germfree mice with microbiota from an obese human produced similar results.

Let's put everything together, now!

As you can see in the graphical illustration in Figure 3, the taste receptor interactions are not the only scientifically proven changes. There are also well-known endotoxin induced effects on mood and anxiety (Amaral. 2008; Chiu. 2013) of which Hill et al. have shown (albeit in a different context) that it will affect food cravings (Hill. 1991).

Beware! If the scientists are right, the same probiotics that are good for people on a mixed diet may be bad for those who consume a low carb or ketogenic diet. I would thus be very reluctant to make any form of one-size-fits it all supplement recommendation! If there is one take home message from what we already know, it's that, in the long run, unbalanced diets (low-to-no whatever) will obviously put you at greater risk of developing a highly specialized obesity-promoting gut microbiome.

Figure 3: Like microscopic puppetmasters, microbes may control the eating behavior of hosts through a number of potential mechanisms including microbial manipulation of reward pathways, production of toxins that alter mood (shown in pink, diffusing from a microbe), changes to receptors including taste receptors, and hijacking of neurotransmission via the vagus nerve (gray), which is the main neural axis between the gut and the brain (Alcock. 2014)

Now Alcock et al. who created this illustration speculate that the weight loss and inhibition of weight gain we've seen in trials using probiotic yogurts (Kadooka. 2010; Mozaffarian. 2011) could be mediated, at least in parts, by microbial interactions with the vagus nerve:

If microbial control is mediated through the vagus nerve, then microbial signals should interfere to some extent with the physiological regulation coordinated by the vagus nerve. [...] We predict that people experiencing cravings should have lower vagal tone. Furthermore, it is possible to block or sever the vagus, which we predict would subdue microbial signaling via the vagus nerve, and thereby alter food preferences. This would be consistent with studies showing that blocking the vagus nerve can lead to weight loss." (Alcock. 2014)

In conjunction with the aforementioned effects and the influence of population size and composition on cravings and high fat, high carbohydrate preferences foods Alcock et al. believe to have enough evidence for the existence of what they call an "evolutionary conflict between the host and microbiota" which may lead to cravings and cognitive conflict with regard to food choice.

Will Engineered Super-Bacteria Help Even Gluttons to Stay Lean? Scientists "Produce" Anti-Obesity Bacteria to be Administered in the Water | more

Personally I don't consider the evidence convincing enough to assume that the suppression oo modification of microbial signals from the gut alone will fix what is currently deemed a problem of self-control and bad food choices | What's your take? Comment on Facebook!

I do not doubt though that "acquired tastes" may at least be reinforced by corresponding microbial selection in the gut. Resetting the microbial make-up and/or modifying it via pre- and probiotic foods and supplements is thus unquestionable an interesting, yet still not fully understood strategy to complement lifestyle intervention that focus on diet and exercise.

And let's not forget: Both diet and exercise have been shown to have a major impact on the gut microbiome, as well (Gotthardt. 2014; Hold. 2014)!

References:

• Alcock, Joe, Carlo C. Maley, and C. Aktipis. "Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms." BioEssays (2014).
• Amaral, F. A., et al. "Commensal microbiota is fundamental for the development of inflammatory pain." Proceedings of the National Academy of Sciences 105.6 (2008): 2193-2197.
• Bäckhed, Fredrik, et al. "The gut microbiota as an environmental factor that regulates fat storage." Proceedings of the National Academy of Sciences of the United States of America 101.44 (2004): 15718-15723. 
• Chiu, Isaac M., et al. "Bacteria activate sensory neurons that modulate pain and inflammation." Nature (2013).
• Collins, Stephen M., Michael Surette, and Premysl Bercik. "The interplay between the intestinal microbiota and the brain." Nature Reviews Microbiology 10.11 (2012): 735-742.
• Cox et al. "Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences." Cell 158 (2014):705–721.
• De Filippo, Carlotta, et al. "Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa." Proceedings of the National Academy of Sciences 107.33 (2010): 14691-14696.
• Duca, Frank A., et al. "Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota." PloS one 7.6 (2012): e39748. 
• Fava,Francesca, et al. "The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’population." International Journal of Obesity 37.2 (2012): 216-223.
• González‐Rodríguez, Irene, et al. "Factors involved in the colonization and survival of bifidobacteria in the gastrointestinal tract." FEMS microbiology letters 340.1 (2013): 1-10.
• Gotthardt, J. D., et al. "Exercise Promotes Enhanced Gut Microbial Diversity Compared to Sedentary Counterparts." International Journal of Exercise Science: Conference Proceedings. Vol. 9. No. 2. 2014. 
• Hehemann, Jan-Hendrik, et al. "Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota." Nature 464.7290 (2010): 908-912.
• Hill, Andrew J., Claire FL Weaver, and John E. Blundell. "Food craving, dietary restraint and mood." Appetite 17.3 (1991): 187-197. 
• Hold, Georgina L. "The gut microbiota, dietary extremes and exercise." Gut (2014): gutjnl-2014.
• Kadooka, Y., et al. "Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial." European Journal of Clinical Nutrition 64.6 (2010): 636-643.
• Miras, Alexander D., and Carel W. le Roux. "Mechanisms underlying weight loss after bariatric surgery." Nature Reviews Gastroenterology and Hepatology 10.10 (2013): 575-584.
• Mozaffarian, Dariush, et al. "Changes in diet and lifestyle and long-term weight gain in women and men." New England Journal of Medicine 364.25 (2011): 2392-2404.
• Rezzi, Serge, et al. "Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals." Journal of proteome research 6.11 (2007): 4469-4477.
• Ridaura, Vanessa K., et al. "Gut microbiota from twins discordant for obesity modulate metabolism in mice." Science 341.6150 (2013): 1241214.
• Rousseaux, Christel, et al. "Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors." Nature medicine 13.1 (2006): 35-37. 
• Wu, Gary D., et al. "Linking long-term dietary patterns with gut microbial enterotypes." Science 334.6052 (2011): 105-108.

L-Tryptophan is Reduced While Dieting - Does This Make the Essential Amino Acid a Key to Succesfull Weight Loss?

Trp and it's metabolite 5-HTP may be particularly useful for female sugar cravings and binges.

Can l-tryptophan help you lose body fat? If you look at the results of the latest study from the University for Health Sciences, Medical Informatics and Technology it would seem that the answer to this question may be "Possibly, yes, but..." Before we come to the implications I would yet like to take a closer look at said study which shows that a lack of tryptophan (Trp) during diets does not just affect the biosynthesis of serotonin, but may also be associated with increased susceptibility for mood disturbances and carbohydrate craving. Accordingly, "strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms" (Strasser. 2014).

Honestly, fasting and eating / skipping breakfast may be more promising weight loss tools

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Breakfast & Glucose Metab.

Breaking the Fast, Cardio & the Brain

Does the Break- Fast-Myth Break?

Fasting = Muscle- Loss - Always?

As Strasser et al. point out, both overweight and obesity go hand in hand with significant increases in low-grade inflammation. The latter is not just the reason that obesity increases the risk of cardiovascular disease, though. Recent evidence suggests that it is also associated with errors in the kynurenine (Kyn) pathway, in which tryptophan is broken down to kynurenine which in turn has been associated with increased risk of depressive symptoms, cognitive deficits in schizophrenia, Alzheimer's and, as mentioned before, cardiovascular disease. Weight loss, on the other hand,

"[...] has been shown to improve or prevent many of the aforementioned conditions. Bariatric surgical intervention in patients with adiposity was found not to improve tryptophan breakdown rates and other signs of immune activation and inflammation [4], whereas caloric restriction is known to be a strong activator of protective metabolic pathways, thereby leading to lower blood pressure, improved blood lipids, and reduced inflammatory markers, including CRP [9]. Still, little is known about the effects of an extreme short-term hypocaloric diet on Trp metabolism and changes in inflammatory biomarkers" (Strasser. 2014).

The study Barbara Strasser, Ken Berger and Dietmar Fuchs conducted was thus designed to assess the effect of a 2-week caloric restriction weight loss diet on Trp breakdown, leptin, and inflammatory biomarkers in over weight adults.

Taking tons of BCAAs can deplete your brain Trp and serotonin and leave you tired and depressed.

Beware of your beloved BCAAs,  Trp competes with the other large neutral amino acids (LNAA), namely valine, leucine, isoleucine, Tyr, and Phe for transport across the blood–brain barrier. In fact, scientists use large boluses of BCAAs to practically deplete tryptophan and thus reduce serotonin (Fernstrom. 2005). If you want to learn more about this unwanted side effects of BCAA, I'd suggest you take another look at my article "The Neurotransmitter Depleting Effects of Branched Chain Amino Acids (BCAAs) and Their Potential Ergolytic, Anxiogenic & Depressive Downstream Effects" | read more.

The scientists randomized 27 overweight and 11 obese participants (22 men and 16 women, mean age 52.8 ± 9.1 years) from the health center Lanserhof, Innsbruck–Lans, into two diet groups:

• a very low kcal diet group (VLCD; Ø 600 kcal/ day) and 
• a low kcal diet group (LCD; Ø 1,200 kcal/day). 

Only healthy subjects with BMI [25 kg/m²] between the ages of 35 and 70 years were accepted for the study. A physician performed physical examinations on all subjects before the study. Subjects were excluded if they consume any anti-inflammatory drugs (e.g., ibuprofen or aspirin) or supplements (such as antioxidants or fish-oil capsules). None from either group was involved in regular training programs.

Figure 1: Changes in body composition pre- vs. post (Strasser. 2015).

As the measurements of body composition, which were just like the energy intake and biologic markers conducted in all subjects before and after the 2-week energy restriction intervention period, indicate, both diets lead to significant reductions in body mass - and that almost exclusively in form of body fat.

Table 1: Biologic markers before and after a 2-week very low kcal diet (VLCD) or low kcal die (LCD) in 38 overweight subjects (mean ± SD)

"Data for biologic markers are shown in Table [1]. Fasting blood glucose declined significantly (P < 0.05) in the LCD group with no significant changes in insulin sensitivity in both groups after 2 weeks of caloric restriction. Weight loss diet lowered leptin levels in both groups, although not reaching the level of significance. Inflammatory biomarkers were not significantly altered during the trial, although there was a tendency toward an increase in IL-6 and TNF-a in the LCD group" (Strasser. 2015).

In contrast to what the researchers expected, both the Trp and Kyn concentrations decreased significantly by 21 and 16 % for VLCD and by 15 and 17 % for the LCD group, respectively, with no significant difference between groups. Practically speaking, this means that the ratio of Kyn/Trp concentrations did not change significantly in both groups.

Adding 900mg 5-HTP to the diet of obese women helps them to reduce their energy intake significantly (Cangiano. 1992).

5-HTP the better choice? While it makes sense to keep an eye on the Trp:LNAA ratio in your diet, it is questionable, whether supplementing with Trp on top of a Trp-sufficient diet will have significant beneficial effects. In this respect, 5-hydroxytryptophan aka 5-HTP a direct serotonin precursor appears to be the more promising supplement. Taken in dosages of 400-1,000mg/day it has been shown to (a) reduce food intake (up to 18% more than placebo in a 1989 study w/ obese women | Ceci. 1989), (b) increase weight loss in 12-week study with obese women (Cangiano. 1992) and (c) reduced the food and specifically carbohydrate intake in both male and female type II diabetics (Cangiano. 1998).

A significant reduction in Phe concentrations was only seen after VLCD. Neopterin and Tyr levels remained unchanged during the trial. Which leaves us with only one significant finding:

"Trp concentrations decreased significantly with a caloric restriction weight loss diet, and lowest Trp concentrations were observed in the group of individuals with the lowest calorie intake." (Strasser. 2015)

This reduction in Trp levels may well induce a disturbance in the biosynthesis of neurotransmitter 5-hydroxytryptamine (5-HT | Anderson. 1990), and appears to be associated with an increased susceptibility for depression (Widnet. 2002; Raison. 2009). Strasser et al. highlight:

Figure 2: The consumption of tryptophan-free amino acid supplements leads to highly significant increases in hunger ratings in healthy female subjects (Rieber. 2010).

"Because Trp is precursor in various biochemical pathways, e.g., it is hydroxylated by tryptophan-5-hydroxylase (T5H) into the intermediate product 5-hydroxy-tryptophan, which by decarboxylation is further converted to neurotransmitter 5-HT (serotonin), and because substrate saturation of T5H is only about 50 % (Dantzer. 2011), changes in plasma Trp levels may have an immediate impact on brain serotonin levels" (Strasser. 2014).

Experiments in which Trp was acutely depleted (in many studies by administering BCAAs | see red boy) support this assumption. Young et al. (2013), for example, confirmed that the acute depletion of tryptophan will lead to low serotonin and subsequently lower mood and increased aggression, although results vary somewhat between studies with similar participants.

Figure 3: Correlations between changes in tryp:LNAA ratio and appetite ratings (Gendall. 2000).

For the link to obesity, though, the correlation (r-values in Figure 3) between high Trp:LNAA (BCAAs, tyrosine, phenlylanine) and a reduction carbohydrate cravings, general hunger and binge eating is yet way more important - and that specifically for women, who appear more vulnerable than men both to the diet-induced reductions in Trp and to its consequences for brain serotonin function (Anderson. 1990).

Ah, and in case you are asking yourself why carbohydrate / sugar binges are a common consequence of low tryptophane:LNAA ratios, it's important to know that increases in glucose and insulin in response to high carbohydrate meals will trigger an increase in brain tryptophan and serotonin synthesis (Benton. 2002). This is why the effects of low tryptophan or high LNAA (BCAA, tyrosine, phenylalanine) levels are more pronounced if you avoid dietary carbohydrates.

There is evidence of direct effects of serotonine on metabolic rate, but there is no evidence that the administration of Trp will induce similar increases in fatty acid oxidation and thermogenesis as serotonin (Le Feuvre. 1991; Cui. 1993). It does therefore remain speculative whether the use of tryptophan supplements will have beneficial effects on the success of your next diet that go beyond an increased ability to stick to your predetermined caloric deficit due to reduced hunger and (CHO) cravings. Furthermore it's not 100% clear whether taking 5-HTP which is significantly closer to serotonin would have different and/or more pronounced beneficial effects compared to its precursor Trp.

This raises the question: Does supplementation help? It's one thing to observe correlations, it's another thing to have scientific evidence from controlled trials which support a causative link between higher tryptophan intakes and/or supplementation and increased adherence to calorically restricted diets and/or reduced cravings and binges.

Let's take the study by Rieber et al. (2010 | Figure 2), for example, in their study a tryptophan-free amino acid supplement like the ones people sell as muscle builders lead to significant increases in hunger scores in healthy young women. Only recently, scientists from the University of Barcelona were able to show that chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women. A result that suggests that chronic vs. acute treatments may have different effects, as well.

Direct evidence that tryptophan will also affect the reduction in energy expenditure, when dieting is yet not available from human trials. As of now, it's thus the reduction in appetite and cravings that is furthermore particularly pronounced in women that may considered among the scientifically warranted benefits of tryptophan supplementation and the avoidance of tryptophan depleting Trp-free amino acid supplements containing BCAAs, phenylalanine and tyrosine | Comment on Facebook!

References:

• Anderson, I. M., et al. "Dieting reduces plasma tryptophan and alters brain 5-HT function in women." Psychological medicine 20.04 (1990): 785-791. 
• Benton, David. "Carbohydrate ingestion, blood glucose and mood." Neuroscience & Biobehavioral Reviews 26.3 (2002): 293-308.
• Cangiano, Carlo, et al. "Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan." The American journal of clinical nutrition 56.5 (1992): 863-867.
• Cangiano, Carlos, et al. "Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 22.7 (1998): 648-654.
• Ceci, F., et al. "The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects." Journal of neural transmission 76.2 (1989): 109-117.
• Cui, Y., T. F. Lee, and L. C. H. Wang. "Thermoregulatory responses following injection of 5-hydroxytryptamine into the septohippocampal complex in rats." Pharmacology Biochemistry and Behavior 45.4 (1993): 935-939.
• Dantzer, Robert, et al. "Inflammation-associated depression: from serotonin to kynurenine." Psychoneuroendocrinology 36.3 (2011): 426-436. 
• Fernstrom, John D. "Branched-chain amino acids and brain function." The Journal of nutrition 135.6 (2005): 1539S-1546S.
• Gendall, Kelly A., and Peter R. Joyce. "Meal-induced changes in tryptophan: LNAA ratio: effects on craving and binge eating." Eating behaviors 1.1 (2000): 53-62. 
• Le Feuvre, R. A., L. Aisenthal, and N. J. Rothwell. "Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds." Brain research 555.2 (1991): 245-250.
• Nieuwenhuizen, Arie G., et al. "Acute effects of breakfasts containing α-lactalbumin, or gelatin with or without added tryptophan, on hunger,‘satiety’hormones and amino acid profiles." British journal of nutrition 101.12 (2009): 1859-1866.
• Raison, Charles L., et al. "CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α: relationship to CNS immune responses and depression." Molecular psychiatry 15.4 (2009): 393-403.
• Rieber, N., et al. "Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects." Neurogastroenterology & Motility 22.7 (2010): 752-e220.
• Strasser, Barbara, Ken Berger, and Dietmar Fuchs. "Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults." European journal of nutrition (2014): 1-7.
• Widner, Bernhard, et al. "Neopterin production, tryptophan degradation, and mental depression—What is the link?." Brain, behavior, and immunity 16.5 (2002): 590-595.
• Young, Simon N. "The effect of raising and lowering tryptophan levels on human mood and social behaviour." Philosophical Transactions of the Royal Society B: Biological Sciences 368.1615 (2013): 20110375.

Women Can't Go Without Fat, Men Not Without Glucose!? Plus: Could Fat & Glucose Be Created Equal(ly Important)?

Image 1: Are we missing the cacao (=fat) for the chocolate? Study suggests that women do better without glucose than men (img. stern.de)

Ladies, I know I am neglecting you. Testosterone here, bodybuilding there and rarely something about your issues. In the end, it is not fundamentally different with today's news, but the study we are going to look at today is at least food (all pun intended) for thought for both sexes. In fact, Mallory, one of the few women who has not yet been put off by "half naked bodydbuilding types" (if you don't know what I am hinting at, check out the "Biggest Winner" blogpost) and all the hoopla around the "muscle building effects of testosterone", reminded me that I had stashed away a study on the sex-specific reaction to glucose- and lipid-deprivation by scientists from the University of Cincinatti a few weeks ago for "future reference" - a study with quite remarkable results (Sandoval. 2012).

"Gimme those extra sweet twinkies, honey!"

One of the common diet-related clichés is that while men love their greasy barbecue, women just can't live without their chocolate. If we disregard the actual macronutrient content of these foods and go just by their taste, this cliché tells us that women are "carbo-" and men "protein-o-fat-o-holics" - or put simply: Common wisdom would suggest that men are made for low-carbing, while women are going to have a tough time without their sweet treats. The results of the aforementioned study by Sandoval et al. do yet indicate that, from a merely physiological perspective, the exact opposite should be the case... but let's tackle one thing at a time.

Figure 1: Low carb and low fat extreme. By force-feeding the rodents 2-deoxyglucose (2-DG) or mercaptoacetate (MD), the scientists effectively blocked the use of glucose or fatty acids, respectively.

What the scientists did was take a couple of male and female rats and force-fed (IP dosing) the animals with either 80, 250 or 750 mg/kg of 2-deoxyglucose (Figure 1, left) or 115, 200 and 355µmol/kg mercaptoacetate (Figure 1, right). With the former being a "unusable" form of glucose and the latter being a fatty acid that is not susceptible to mitochondrial oxidation, the treatments hamper the use of glucose or fatty acids as a fuel and result in a dose depend glucose or fatty acid deprivation state. In a way this is like jamming the fuel pipe of a car - no matter how much gasoline you put into your tank the engine is not going to be able to use it... similarly, no matter how much carbohydrates, respectively fats the rodents would eat, their "hunger" for glucose of fatty acids would not be satisfied.

No, what would conventional wisdom tell us, should have happened? Right! The female rats would have gone crazy in the 2-DG trial (without their "sweet" glucose) and the male rodents would have gone on one of the infamous "hunter and gatherer" greasy meat binges... but in fact, the exact opposite was the case.

Figure 2: Relative food intake of male and female rats in the 3h after the IP injection of 80, 250 and 750mg 2-deoxyglucose (data adapted from Sandoval. 2012)

As the data in figure 2 shows, the "binge response", i.e. the overeating in response to the artificially induced glucose deprivation, was more pronounced (+170% food intake) and was triggered at lower doses of 2DG (meaning that there was still more glucose available) in male than in female rats. In the mercaptocetate fat deprivation trial, on the other hand, ...

[...] the males significantly increased food intake over saline only in response to the highest dose of MA used [...] In contrast, compared with saline, females had significantly greater
food intake at 115 and 355 µmol/kg, and a strong trend (P < 0.06) at the 200µmol/kg doses of MA.

These findings are not only of interest, because they may shed some (albeit counter-intuitive) light on why men and women tend to "diet" differently, but also because they strongly suggest that we are not dealing with either lipo- or glucostatic controls of energy intake (and probably metabolism), but with both. 

No-carb or no-fat? In the end neither will work

Image 2: Everyone understands that Micheal Phelps seems to understand that he/she cannot eat as many carbs as Michael Phelps (img. Fox), but more and more people fail to realize that they can, ... and for many even, that they must eat more carbs than a sedentary 200lbs overweight type II diabetic.

Despite the fact that he male rats overate "earlier"* to glucose and the female rats "earlier"* to fat deprivation (*earlier means at an overall higher availability of the respective nutrient), when a given threshold was surpassed, both sexes did react with eating everything in sight. In other words, if these results apply to humans as well (2DG studies by Davis et al. would suggest that they do; cf. Davis. 2000), it does not matter if you starve yourself of fat or the ostensibly dispensable and fattening glucose, you still starve and if there is anything everyone should by now have understood, then this: Nothing stalls healthy weightloss more effectively than starvation.

So, don't be a bigoted pighead and acknowledge the value of both, fat and carbohydrates not as mutually exclusive, but as synergistic and with an "optimal" that is in constant flux and will be determined not only by your sex by, but also by your overall, metabolic and endocrine health, by your body composition, by your activity level and the type of activity and many other physiological, psychological, seasonal and environmental parameters that are just as diverse for each of us as our "optimal" macronutrient ratios.

Milk & Exercise a Perfect Match? A Summary of the Latest Scientific Studies on Its Ability to Sustain Muscle Growth, Protect from Muscle Damage, Binges and Dehydration

Is milk the perfect fluid replacement + anti-post-workout binge + muscle protector for gymrats, fitness junkies and professional athletes? 

It stands out of question. Compared to Coke and many of the so-called "sports-" or "energy drinks" that are in fact no much more than over-caffeinated liquid sugar bars, milk is a healthy beverage. Whether it's also a potent ergogenic though, is still intensely debated.

A recent study from the McMaster University in Hamilton, Ontaria, for example, indicates that the initial surge in post-workout protein synthesis cannot be sustained solely by the low amount of protein in regular milk (Volterman. 2015). Its inability to trigger longlasting increases in protein synthesis and thus to promote a positive whole body protein balance does yet not negate the already proven benefits milk and some of its less-known constituent (I am not talking about whey or casein!) may have for athletes and gymrats.

You can learn more about dairy at the SuppVersity

Dairy Has Branched-Chain Fatty Acids!

Is There Sth. Like a Dairy Weight Loss Miracle?

There is Good A2 and Bad A1 Dairy, True or False?

Lactulose For Your Gut & Overall Health

Is There a "Fat Advantage" for Dairy Lovers

Dairy, Diabetes, Estrogen, IGF-1, Cancer & More

You want to know what kind of advantages this may be? Well, here is a brief overview of the latest scientific evidence that is either directly or indirectly related to potential beneficial effects of milk:

• Consumption of 500 ml of milk post-exercise-induced muscle damage can limit decrements in muscle function in females, and limit increases in soreness and serum markers of muscle damage in females and males.
  
  That's not something I say, but something, scientists from the Institute of Technology in Carlow, Ireland, conclude based on their observations in 32 team sport players (male n = 16; female n = 16) who were randomly, but equally divided into four groups: male milk, male carbohydrate, female milk, and female carbohydrate. Immediately following muscle damaging exercise, participants consumed either 500 ml of milk or 500 ml of an energy-matched carbohydrate solution. Skeletal troponin I (sTnI), creatine kinase (CK), peak torque, counter movement jump height, 20 m sprint performance and passive and active soreness were recorded prior to and 24, 48 and 72 h post-exercise-induced muscle damage (EIMD).
  

  

  Figure 1: Brief overview of the most important facts (Rankin. 2015).

  What the scientists found was that the women experienced likely to very likely beneficial effect on attenuating losses in peak torque at 60°/s from baseline to 24, 48 and 72 h, and a likely beneficial effect in minimizing decrements in sprint performance and soreness over 72 h. Furthermore, the milk consumption was unlikely to have a negative effect on serum markers of damage from baseline to 48 and 72 h.
  
  For males, on the other hand, milk had an unclear effect on muscle function variables. Milk had a most likely/likely beneficial effect on limiting muscle soreness from baseline to 72 h, and a possible beneficial effect on attenuating increases in CK. The effect on sTnI was unlikely to be negative from baseline-72 h. In that, the female participants demonstrated smaller increases in sprint time, passive soreness, active soreness (non-dominant leg) and sTnI values and did thus benefit to a greater yet not significantly greater extent from the 500 ml of milk - that's a difference that could be both sex- and/or protein-specific; I mean, for a man, 500 ml of milk yield significantly less protein on a per kg body weight basis than the same 500 ml do for a woman. That's a difference that could well partly explain why women benefit more from milk vs. carbohydrates only compared to men.
• The consumption of skimmed milk following 30 min of moderate-vigorous cycling exercise reduces subsequent energy intake in female recreational exercisers.
  
  Obviously, working out will only help you shed body fat if the increased energy expenditure during the workout is not (over-)compensated by increased food intake after your workouts. Against that background the results from a recent study from the Northumbria University (Rumbold. 2015) are significant, because they indicate that 600 mL of skimmed milk have a significantly more pronounced "anti-binging" effect than 600 mL of an isocaloric orange drink when they are ingested immediately after a workout.
  

  

  Figure 2: Absolute and relative energy intake during the milk vs. orange juice trials (Rumbold. 2015).

  As the data in Figure 2 indicates the 9 female recreational exercisers (19.7 ± 1.3 years) who completed a standardized exercise regimen consisting of an VO2 peak test and 30 min of moderate-vigorous exercise (65% V̇O2peak) consumed 25.2% ± 16.6% less energy on an ad-libitum pasta meal that was served 60 minutes after the workout.
  
  If we assume that they women didn't compensate for the "missing" 25% of the energy later during the day and assuming that they did the workout 2x per week, the 169kcal per workout would yield a total fat loss of 1.9kg per 6 months - well, if the 7,000kcal deficit per 1kg of fat equation actually held ;-)
• Milk-based drinks are more effective rehydration options compared with traditional sports drinks. The additional energy, protein, and sodium in a milk-based liquid meal supplement facilitate superior fluid recovery following exercise.
  
  The aim of a recent study from the Griffith University study was to compare the rehydration potential of a carbohydrate-electrolyte beverage with several varieties of milk following exercise-induced fluid losses. Fifteen male participants (age 24.9 ± 5.5 years, height 179.3 ± 4.9 cm, body mass 75.8 ± 6.6 kg (mean ± SD)) lost 2.0% ± 0.2% body mass through intermittent cycling before consuming a different beverage on 4 separate occasions.
  
  The drinks that were tested included cow's milk (286 kJ·100 mL(-1)), soy milk (273 kJ·100 mL(-1)), a milk-based liquid meal supplement (Sustagen Sport (Nestle); 417 kJ·100 mL(-1)), and a sports drink (Powerade (Coca Cola Ltd); 129 kJ·100 mL(-1)). Beverages were consumed over 1 h in volumes equivalent to 150% of body mass loss. Body mass, blood and urine samples, and measures of gastrointestinal tolerance were obtained before and hourly for 4 h after beverage consumption.
  

  

  Figure 3: Overview of the most important study results (Desbrow. 2014).

  The results show that the net body mass at the conclusion of each trial was significantly less with Powerade (-1.37 ± 0.3 kg) than with cow's milk (-0.92 ± 0.48 kg), soy milk (-0.78 ± 0.37 kg), and Sustagen Sport (-0.48 ± 0.39 kg). Net body mass was also significantly greater for Sustagen Sport compared with cow's milk trials, but not soy milk. Upon completion of trials, the percentage of beverage retained was Sustagen Sport 65.1% ± 14.7%, soy milk 46.9% ± 19.9%, cow's milk 40.0% ± 24.9%, and Powerade 16.6% ± 16.5%.
  
  If it were not for the fact that some of the subjects were complaining over increased bloating and fullnessduring all milk trials compared with Powerade, there would thus be no reason to go for the "classic" high carb + electrolyte solutions.

Are the hormonal side effects of dairy and its cancerous consequences even worse than they're painted by the steadily growing anti-dairy lobby? Find the answer to this and related questions in a previous SuppVersity article from January 2014 | read more.

Not all that glitters white like milk is gold, though. Only recently scientists from the Tokyo Metropolitan Institute of Gerontology had to realize that milk fat globule membranes, of which previous studies have shown that they may help avoiding metabolic syndrome (Pfeuffer. 2007), do not boost the already beneficial effects of exercise on the frailty status of elderly men and women (Kim. 2015).

Just like the previously discussed disappointing results of the Volterman (2014) study, the results Kim et al. present in their latest study do not negate the existing beneficial effects on satiety / anti-binging, muscle damage and function in response to muscle damaging exercise and rehydration discussed in this article | Comment on Facebook!

References:

• Desbrow, Ben, et al. "Comparing the rehydration potential of different milk-based drinks to a carbohydrate–electrolyte beverage." Applied Physiology, Nutrition, and Metabolism 39.12 (2014): 1366-1372.
• Kim H, Suzuki T, Kim M, Kojima N, Ota N, Shimotoyodome A, Hase T, Hosoi E, Yoshida H. "Effects of Exercise and Milk Fat Globule Membrane (MFGM) Supplementation on Body Composition, Physical Function, and Hematological Parameters in Community-Dwelling Frail Japanese Women: A Randomized Double Blind, Placebo-Controlled, Follow-Up Trial." PLoS One 6;10.2 (2015):e0116256.
• Pfeuffer, M., and J. Schrezenmeir. "Milk and the metabolic syndrome." Obesity reviews 8.2 (2007): 109-118.
• Rankin P, Stevenson E, Cockburn E. "The effect of milk on the attenuation of exercise-induced muscle damage in males and females. Eur J Appl Physiol. (2015): Feb 12. [Epub ahead of print] 
• Rumbold, Penny, et al. "Milk Consumption Following Exercise Reduces Subsequent Energy Intake in Female Recreational Exercisers." Nutrients 7.1 (2015): 293-305.
• Volterman, Kimberly A., et al. "Effects of postexercise milk consumption on whole body protein balance in youth." Journal of Applied Physiology 117.10 (2014): 1165-1169.