For anyone following both my blog and Richard over at Free the Animal, you will notice that I have blatantly and shamelessly stolen the title of his latest blog post… but not quite. Richard’s post referred to creatine. This one of mine focuses on carnosine (not to be confused with carnitine). I read Richard’s post and wondered whether there was much around on carnosine and diet, and specifically, carnosine and vegetarian/vegan diets. I entered ‘carnosine’ and ‘vegetarian’ into the Pubmed database to see what would come up.
Short background story of my interest in carnosine. Carnosine (beta-alanyl-L-histidine) is a dipeptide of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues. Beta-alanine is the rate-limiting precursor of carnosine, which is to say carnosine levels are limited by the amount of available beta-alanine. Supplementation with beta-alanine has been shown to increase the concentration of carnosine in muscles, decrease fatigue in athletes and increase total muscular work done.
I used to coach track cyclists – sprinters. And my own natural bias for riding my bike is toward anaerobic power and capacity (rather than aerobic power/capacity). When you are training elite cyclists, you look for every single advantage and edge you can legally get. In about 2006/07 I began to read about the benefits of supplementing beta alanine on sprint-based athletes. We got some, trialled it, and it simply left everything else we had tried for dead. It is a very weird feeling when you have the after-burners on in the legs, and right at the point you would normally expect them to die… they keep going… and going.
Watching my main sprinter on the track that season was amazing. She could initiate her run for the line 50-100m earlier than usual and still maintain confidence she wasn’t going to die before the line. And when she did jump, there was daylight between her and other riders. It was something we had to keep a tight lid on, and fair to say with the lift in performance she got raised a few eyebrows and a few questions were asked.
For a performance return on investment, you just simply cannot go past beta alanine… I get a bit pissed to be honest when I speak to cyclists (not the fat ones – they have other priorities) about what they can do to go faster and they are invariably focused on spending very large amounts of money saving a few grams on a non-rotating piece of bike componentary (my ceramic bottom bracket cost half the price of a top line carbon fibre handlebar but will give me infinitely more of a performance jump with my bike), but when you start talking food and/or supplements, you often get the answer “I can’t really afford that”.
Supplement advertising over… though having not taken beta alanine since ‘going paleo’ (some would suggest going troppo is more like it), I would wonder if it still has such a profound effect. I might have to do a n=1 experiment on that one. It might just be that I am near saturation point with diet alone, compared to where I was a few years back.
Back to carnosine. So – to make carnosine, you need the amino acids histadine and beta alanine, though it is the availability of the latter that determines the rate at which carnosine can be produced. Do read the wikipedia entry for carnosine and, for those who follow some of the various bits and pieces of biochemistry some of us have been throwing out there, a few light bulbs might start going off. Particularly when you read the last statement on the entry in conjunction with my posts title:
Typical vegetarian diets are thought to be lacking in carnosine, but whether this has a detrimental effect on vegetarians is controversial.
But I’m picking you want something a bit more substantial than that. Well try these papers on for size and note what carnosine, not found in a vegetarian/vegan diet, is being linked with.
Glycation, ageing and carnosine: are carnivorous diets beneficial?
Non-enzymic protein glycosylation (glycation) plays important roles in ageing and in diabetes and its secondary complications. Dietary constituents may play important roles in accelerating or suppressing glycation. It is suggested that carnivorous diets contain a potential anti-glycating agent, carnosine (beta-alanyl-histidine), whilst vegetarians may lack intake of the dipeptide. The possible beneficial effects of carnosine and related structures on protein carbonyl stress, AGE formation, secondary diabetic complications and age-related neuropathology are discussed.
Glycation huh? What’s the big deal?
Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose and galactose have approximately ten times the glycation activity of glucose, the primary body fuel.
Glycation is the first step in the evolution of these molecules through a complex series of very slow reactions in the body… all lead to advanced glycation endproducts (AGEs). Some AGEs are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as: cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged), Alzheimer’s disease (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy (the myelin is attacked), and other sensory losses such as deafness (due to demyelination).
This range of diseases is the result of the very basic level at which glycations interfere with molecular and cellular functioning throughout the body and the release of highly-oxidizing side-products such as hydrogen peroxide.
So yeah… it might be important to minimise some of this glycation (glycation gets blamed for the formation of wrinkles too]. And none of us really want to age any quicker than we currently do!
Would carnosine or a carnivorous diet help suppress aging and associated pathologies?
Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues. Carnosine has the potential to suppress many of the biochemical changes (e.g., protein oxidation, glycation, AGE formation, and cross-linking) that accompany aging and associated pathologies. Glycation, generation of advanced glycosylation end-products (AGEs), and formation of protein carbonyl groups play important roles in aging, diabetes, its secondary complications, and neurodegenerative conditions.
Due to carnosine’s antiglycating activity, reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and low toxicity, carnosine and related structures could be effective against age-related protein carbonyl stress. It is suggested that carnivorous diets could be beneficial because of their carnosine content, as the dipeptide has been shown to suppress some diabetic complications in mice. It is also suggested that carnosine’s therapeutic potential should be explored with respect to neurodegeneration. Olfactory tissue is normally enriched in carnosine, but olfactory dysfunction is frequently associated with neurodegeneration. Olfactory administration of carnosine could provide a direct route to compromised tissue, avoiding serum carnosinases.
Does that mean we should start cutting lines of carnosine to stave off the likes of Alzheimer’s?
Carnosine and its possible roles in nutrition and health.
The dipeptide carnosine has been observed to exert antiaging activity at cellular and whole animal levels. This review discusses the possible mechanisms by which carnosine may exert antiaging action and considers whether the dipeptide could be beneficial to humans.
Carnosine’s possible biological activities include scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS), chelator of zinc and copper ions, and antiglycating and anticross-linking activities. Carnosine’s ability to react with deleterious aldehydes such as malondialdehyde, methylglyoxal, hydroxynonenal, and acetaldehyde may also contribute to its protective functions.
Physiologically carnosine may help to suppress some secondary complications of diabetes, and the deleterious consequences of ischemic-reperfusion injury, most likely due to antioxidation and carbonyl-scavenging functions.
Other, and much more speculative, possible functions of carnosine considered include transglutaminase inhibition, stimulation of proteolysis mediated via effects on proteasome activity or induction of protease and stress-protein gene expression, upregulation of corticosteroid synthesis, stimulation of protein repair, and effects on ADP-ribose metabolism associated with sirtuin and poly-ADP-ribose polymerase (PARP) activities. Evidence for carnosine’s possible protective action against secondary diabetic complications, neurodegeneration, cancer, and other age-related pathologies is briefly discussed.
If you are a complete nerd like me, please do click through on the transglutaminase link – I dare ya to not start connecting a few dots up between meat eating and some well known diseases…
On the enigma of carnosine’s anti-ageing actions.
Carnosine (beta-alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine’s enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms responsible remain uncertain.
In addition to carnosine’s well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered.
When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nematodes extend organism lifespan, hence carnosine’s anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically.
Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine’s real in vivo functions. More experimentation is clearly required.
Whoddathunk that little old carnosine could do so much to keep you young and spritely. In summary… carnosine helps keep you young (or at least slows down your rate of death); carnosine comes from meat; vegetarians and vegans don’t eat meat. I’m not going to draw any further links from there as suggesting that vegetarians age more rapidly because they do not ingest meat and therefore carnosine, has similar bad science overtones to the lipid hypothesis. So I’ll just leave that one alone.
Carnosine is very abundant in protein-rich foods. Some common examples of such foods include milks, eggs and cheese. However, the best food sources of carnosine include beef, poultry and pork products. People who want to increase their carnosine consumption should focus on eating more food from these categories.
Extra for experts: Do Vegetarian’s Live Longer?
[From a pro-supplementation site, but ignore the drive to supplement with everything and the rest stacks up well].