Sunday, November 18, 2012

Pigs Would Pick MSG - Glutamate Seals the Gut, Decreases Liver & Muscle Fat & Increases Plasma Amino Acids in Swine

Piglets would buy MSG food ;-)
Mono-sodium glutamate (MSG) and the "Chinese restaurant syndrome", obesity and overeating are often thrown together into a single psedo-scientific crock pot with the result being a brew that's 50% hear-say, 40% fear and 10% science. The study we are going to look at today is unquestionably part of the latter ingredient and its results do stand in line with my previously stated concern "that MSG is one of those substances that is usually found in foods with a whole host of other nutrient-poor ingredients, anti-nutrients and proven obesogenic, pro-inflammatory and otherwise unhealthy substances and food additives" ("MSG, NFALD, Leaky Gut & Brain ...") and could thus rather be corollary to, than causative of the toll the fast, convenient and nutrient deficient foods in the Western diet are taking on our health.

Published ahead of print in the online version of the journal Amino Acids you will find a study by a group of researchers from the Texas A&M University. The study was, according to the authors intended to "fill [the] important gap of knowledge about glutamate nutrition and metabolism in animals" (Rezaei. 2012). Luckily their study subjects were pigs, allegedly young pigs, but still omnivores like us and one of the best models of the human digestive tract we have:
"Both humans and pigs are highly dependent on dietary quality since symbiotic microorganisms within the gut play a relatively minor role in modifying the nutrients that are ingested. Intestinal  transit times and digestive efficiencies are comparable. Postabsorptive metabolism is also similar in many respects, although the wide differences in length of gestation and the numbers of young born introduce a potentially significant divergence in nutrient needs for reproduction. [...] Nevertheless, when minimum nutrient requirements of swine and established recommended daily allow­ ances of humans are expressed per kilogram of dietary dry matter (assuming an intake of 500 to 800 g of dry matter per day by teenagers and adults), these values are highly related. It is only reasonable that one not draw unsupport­able inferences from one species to another, but with the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human." (Miller. 1987)
Against that background it is quite intriguing that Rezaei. et al. did not find any of the suspected negative side effects of MSG up to a dosage of 4% in the diet of their piglets.
Figure 1: Weight development and feed intake and effciacy in pigs on diet containing different amounts of supplemental MSG (data based on Rezaei. 2012)
In fact, instead of eating more, the pigs that received the MSG-supplemented diets consumed slightly, but significantly less food than their peers. Despite these appetite suppressing effects of the diet, the piglets in the high MSG arm of the study still gained the most body weight and thusly had the 'optimal' (for lovers of Chines restaurant probably rather 'most detrimental') gain:feed ratio.

The amino acid modifying effects of MSG

When we are seaching for the underlying reasons of these changes, it may be worth taking a look at the amino acid composition of the plasma of the piglets after 21 days on diets supplemented with different amounts of MSG at 1 and 4 h after feeding. During this prostprandial phase, the scientists observed
  • More about MSG in human health
    significant increases  in aspartate, glutamate, glutamine, histidine, citrulline, arginine, taurine, alanine, methionine, valine, phenylalanine, isoleucine, leucine, proline, cysteine, ornithine, and lysine in plasma at both time points, i.e. one and four hours after feedin,
  • highly significant increases in asparagine, serine, threonine, tryptophan, and tyrosine 1h after feeding and
  • significant increases in alanine, citrulline, glutamate, methionine, ornithine, phenylalanine, proline, and tryptophan in the first hour of the postprandial window
If we also take into account previous rodent studies which have shown that MSG reduces the deposition of fatty acids in white adipose tissue (Kondoh. 2008), it cannot be ruled out though that these increases in weight gain were related to increases in lean- not fat tissue (remember: muscle is heavier than fat); after all we are dealing with growing young pigs, in which you would expect an increase in essential and non essential amino acid availability to help with skeletal muscle metabolism (Mahan. 1998).
Figure 2: Total lipid content in percent of control in response to MSG feeding at different doses (left) and the modulatory effects of sodium intake (NaCl) on the effects of MSG (right; data based on Rezaei. 2012)
As the data in figure 2 goes to show this hypothesis appears to stand in line with the decreased fatty acid deposition in liver and skeletal muscle, which will at the same time prevent negative side effects of intra-hepatic and -skeletal lipid accumulation on liver and muscle glucose uptake.

Does salt modify the effects of MSG? And what's the role of the gut in all this?

Against that background it is actually a pitty that we don't have data on the fatty acid content of liver and muscle tissue in response to the different levels of dietary salt in the diets (figure 2, right). I mean, at first sight it appears that more salt could 'ameliorate' the detrimental effects of MSG feeding on the body weight of the rodents, but if the latter was not detrimental, but beneficial, this would certainly entail the question if it's not MSG per se, but rather it's co-appearance with too much, or due to it's ability to boost all taste perception to little sodium in the previously mentioned fast, convenient and nutrient deficient foods, way too many people have gotten addicted to.

You see, just as so many times before things are way more complex than they may seem at first sight and if the interactions of body weight, lean mass, intrahepatic and intramuscular lipids and dietary salt with MSG was not already enough, the data in figure 3 brings another (side?) effect into play the importance of which must not be underestimated - the effect of MSG on the intestinal morphology of the pigs:
Figure 3: Jejunal morphology and jejunal concentrations of DNA, RNA, protein, ATP, and glutathione in 28-day-old pigs weaned at 21 days of age (Rezaei. 2012)
I don't know if you remember the side effect of the chronic ingestion of zinc on the intestinal structure of rodents that caused quite a stir in the zinc-loving bodybuilding community back in June!? In essence, the effects of mono-sodium glutamate on the microvilli, which are responsible for the absorption of nutrients look very similar to the ones that were observed by Taneja et al.in response to Zinc supplementation (SuppVersity: June 13, 2012). As previously mentioned this is per se not a bad thing and could in fact come very hand to people with chronic inflammatory conditions suffering from a "leaky gut" or people who want to protect their gut from the side effects of the chronic use of NSAIDs, where MSG has only recently been implicated as a viable tool to prevent and heal mucosal damage (Amagas. 2012).
Figure 4: Postprandial glucose levels (left) and intestinal morphology (right) of mice on diets with different concentrations of mono-sodium glutamate (Rezaei. 2012)
As figure 4 goes to show this could actually work with MSG without the zinc-induced increases in insulin and blood glucose (see figure 2 in previous article). Whether these effects are directly related to the ingestion of MSG or its glutamin-sparing effects n the gut cannot be said for sure, though:
"Grant alert" Despite the fact that I am pretty sure that the actuall data in this study is accurately reported, I still want to point out that the scientists received "a grant from the International Glutamate Technical Committee". It's explicitly listed in the "acknowledgments" and probably not much of an issue outside of the discussion in which you will obviously miss references to potential negative side effects (which have not been observed in the study, though).
"Thus, dietary supplementation with glutamate may enhance the availability of dietary glutamine in plasma. As a versatile amino acid, glutamate participates in both synthetic and oxidative pathways in the small intestine, resulting in the production of proteins, ornithine, citrulline, proline, arginine, alanine, aspartate, glutathione, CO2, and ATP. Therefore, dietary supplementation with glutamate increased the plasma concentrations of these amino acids  and jejunal concentrations of glutathione in weaned pigs. Compelling evidence shows that dietary glutamate is a major energy substrate for the small intestine, which is an organ with a particularly high met- abolic rate. In support of this notion, we found that dietary MSG supplementation increased jejunal concentrations of ATP in weaned pigs. Additionally, glutamate is an excitatory neurotransmitter, thereby regulating the motility of the gastrointestinal tract. Thus, when a weaning diet is deficient in glutamate, gut atrophy occurs and the efficiency of utilization of dietary protein for growth and other physiological functions is greatly decreased." (Rezaei. 2012)
As evidence from previous studies by Kondoh et al. suggests, the effects of glutamate do not end at the intestinal brush border. Its centrally mediated downstream effects after interacting with l-Glutamate receptors in the intestines are however still not fully understood and could either be beneficial (as the work by Kondoh et al. would suggest; Kondoh. 2008 & 2009), be without physiological consequences or - as the mainstream myth suggests - "be the devil"; with the latter being much more likely in people with genetic or already established metabolic problems which result in a deficiency of glutamate dehydrogenase (Stanley. 2009).

Bottom line: The last mentioned problems certain individuals who have inherited or acquired problems with the enzymatic conversion of glutamate are yet not the only reason why I strongly caution against taking the results of the study at hand as a free ticket for limitless MSG consumption. If it's not the MSG that's going to make you fat, I can assure you that those 'foods' in which it is used will be getting the job done pretty quickly and will thus compensate for any possibly existent improvements in intestinal and whole body amino acid metabolism.

Parmigiano Reggiano aside from seaweed the #1 "real food" offender in terms of MSG and still good for your bones (Pampaloni. 2011) - one of many examples of the fallacy of black-and-white thinking. To heal your gut, glutamine would yet still be your better choice, I suppose ;-)
That said, there are still unresolved issues related to the negative effects of MSG on the immune system and the thymus. The dosages that are required to observe toxic effects may be hilarious if you take into account how much of it you find in an individual food item, and even if you started supplementing with MSG, or lived on fast- and convenient food, only, you will probably be hard pressed to get up to the 50g+ human equivalent of mono-sodium glutamate which was sufficient to significantly decrease thymus cell viability in rats (Pavlovic. 2009). In case you feel you are endangered and belong to the people who rather wear a helmet than stop hammering their head against a wall, you could try to counter that with an additional 6-7g of vitamin C (for the rodents that worked)... but let's be honest, wouldn't your life be much easier, if you simply stuck to whole foods and don't worry about the occasional piece of aged Parmesan cheese with 1680 mg glutamate per 100g. It could not just be good for your gut, but has been shown to be good for your bones (Pampaloni. 2011), probably not because, but at least despite the high MSG content.

References:
  • Amagase K, Ochi A, Kojo A, Mizunoe A, Taue M, Kinoshita N, Nakamura E, Takeuchi K. New therapeutic strategy for amino acid medicine: prophylactic and healing promoting effect of monosodium glutamate against NSAID-induced enteropathy. J Pharmacol Sci. 2012;118(2):131-7.
  • Kondoh T, Torii K (2008) MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats. Physiol Behav 95:135–144.
  • Kondoh T, Mallick HN, Torii K. Activation of the gut-brain axis by dietary glutamate and physiologic significance in energy homeostasis. Am J Clin Nutr. 2009 Sep;90(3):832S-837S.
  • Mahan DC, Shields RG Jr. Essential and nonessential amino acid composition of pigs from birth to 145 kilograms of body weight, and comparison to other studies. J Anim Sci. 1998 Feb;76(2):513-21.
  • Miller ER, Ullrey DE. The pig as a model for human nutrition. Annu Rev Nutr. 1987;7:361-82. 
  • Pampaloni B, Bartolini E, Brandi ML. Parmigiano Reggiano cheese and bone health. Clin Cases Miner Bone Metab. 2011 Sep;8(3):33-6.
  • Pavlovic V, Pavlovic D, Kocic G, Sokolovic D, Sarac M, Jovic Z. Ascorbic acid modulates monosodium glutamate induced cytotoxicity in rat thymus. Bratisl Lek Listy. 2009;110(4):205-9.
  • Stanley CA. Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. Am J Clin Nutr. 2009 Sep;90(3):862S-866S.
  • Rezaei R, Knabe DA, Tekwe CD, Dahanayaka S, Ficken MD, Fielder SE, Eide SJ, Lovering SL, Wu G. Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids. 2012 Nov 2.