That’s right, despite everything else that’s come along promising to make you younger over the last 18 years, carnosine is still the best proven anti-aging supplement out there. Yes, I’m talking about boring, old, been-there-done-that carnosine.

Unfortunately, somehow, carnosine has seemed to slip yet again from fashion, replaced by sexier, newer options. In fact, this is a repeat of a problem we saw in late 2012. How did this happen again? Well, first, I think you can thank Dr. Oz. And second, I think you can look at our almost genetically encoded belief that newer is better.

When I first started using carnosine in formulations in the mid ‘90s, there were really only two information sources in the United States promoting carnosine benefits: myself and the Life Extension Foundation. Not only was carnosine not well known in the US, but it was also hard to find good (high purity) sources for it to use in any formulations. In fact, we both had to turn to Germany at that time for sourcing our carnosine. For the next 13 years, carnosine benefits were kind of “secret” and sexy as one by one different alternative health gurus and companies began promoting them and using carnosine in formulations–often incorrectly, but that’s a different story. And then in early 2012, almost 15 years after the fact, Dr. Oz “discovered” carnosine and touted it on his show as the miracle pill for anti-aging. And suddenly, carnosine was the “it” supplement of the day. Carnosine benefits were featured in news reports; carnosine was all over the internet; and hack company after hack company started selling their own carnosine formulas that had been quickly thrown together with no understanding of how it worked or what made sense in a formula. This meant, of course, that a lot of the information about carnosine benefits was simply wrong and a lot of those formulas didn’t work. Remember: just because you see something on the internet doesn’t make it true.

Unfortunately, when anything gets that popular and with that many hacks in the game, the detractors move in. Suddenly, there were claims that carnosine might cause carnosinemia, which is utter nonsense because carnosinemia is a genetic disorder. And there were claims that it failed to perform as advertised, which was a bit more justifiable since there were so many badly formulated supplements now on the market, often using low purity, inexpensive sources for their carnosine, and too little carnosine to make any difference. But the biggest problem is that once the market gets oversaturated with your presence, it gets tired of you and moves on to the next hot thing. Speaking of which, has anyone seen Psy lately?¹ http://www.youtube.com/watch?v=CH1XGdu-hzQ

Which leads us to the second problem: as a species, we always seem to be chasing the “new and improved.” Let me give you an example.

In 1985, Robert Palmer and Power Station released an ultrafunk cover of the classic rock song, Bang a Gong, originally written and recorded in 1972 by Marc Bolan and T-Rex. In Boston, where I was living at the time, all of the radio stations started running a faceoff between the two versions, letting listeners vote on which version they liked best. Most chose the Power Station version.² http://www.youtube.com/watch?v=alFlaMC2b3c Personally, I thought the original version was grittier and far superior–a true rock and roll classic³ http://www.youtube.com/watch?v=TVEhDrJzM8E –but hey, each to their own. What really bothered me, though, was the reasons people gave for their votes. Essentially, listener after listener said things like:

• It’s new so it must be better, right?
• Man, it’s new. New is good.
• I like the new version because it’s new.

I kid you not. That was the reason for their vote, which of course had nothing to do with the actual music, and the memory of that has stayed with me strongly for the last 30 years. People didn’t vote for the new version because they liked it better…but simply because it was new. (By the way, I thought Robert Palmer redeemed himself later that year with his release of Addicted to Love, made famous by its iconic video.⁴ http://www.youtube.com/watch?v=XcATvu5f9vE )

So what does this have to do with carnosine benefits? Just that while everyone has been chasing the shiny and new in the world of anti-aging, carnosine hasn’t gone anywhere. In fact, as I mentioned earlier, this is the second time I’ve addressed this exact same issue, with the previous article published in 2012 after the initial Dr. Oz excitement began to fade. Today, we’re going to pick up where that article left off because, unlike the general public, mainstream research has latched onto carnosine with a vengeance. Study after study is now reporting new benefits for this amazing natural supplement–several dozen in the last year alone.

Carnosine Studies 2013-2014

Most of these studies involving carnosine now have no direct connection with anti-aging, which is difficult for researchers to quantify. Instead, now that carnosine is considered “real” by the scientific community, the studies tend to be much more specific–and measurable–with an emphasis on the role carnosine supplementation can play in reversing things like cardiovascular disease, cancer, and dementia. What makes these studies especially interesting is that although they involve measuring benefits in particular areas of the body, those benefits can easily be extrapolated out to the body as a whole, thus serving as confirmation of carnosine’s overall anti-aging benefits. Here’s a sampling.

Carnosine Benefits and Your Cardiovascular System

As we have discussed in previous newsletters, carnosine has been shown to modulate triglyceride and glycation levels in both cell and animal systems. But a study just published last month took things one step further when it concluded that long term supplementation with carnosine may actually lower triglyceride levels and thus suppress plaque instability in diabetes-associated atherosclerosis.⁵ Brown BE, Kim CH, Torpy FR, Bursill CA,et al. “Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice.” Atherosclerosis. 2014 Feb;232(2):403-9. http://www.ncbi.nlm.nih.gov/pubmed/24468155

And there’s more.

Atherosclerotic lesions are also associated with the accumulation of reactive aldehydes formed from the oxidation of fats in the bloodstream. But carnosine helps here too. A study published last June suggests that carnosine inhibits atherogenesis (the formation of arterial plaque) by facilitating aldehyde removal from atherosclerotic lesions.⁶ Barski OA, Xie Z, Baba SP, Sithu SD, et al. “Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice.” Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1162-70. http://www.ncbi.nlm.nih.gov/pubmed/23559625 This should not be a surprise to readers of this newsletter as we pointed out a number of years ago that one of the primary benefits of carnosine is that it bonds with carbonyl (or aldehyde) groups that if left alone attack and bind with proteins–thus destroying them. According to this study, deep tissue levels of carnosine may be an important determinant of atherosclerotic lesion formation, and treatment with carnosine could be a useful therapy for the prevention or the treatment of atherosclerosis.

Carnosine Benefits and Cancer

Back in 2012, we reported on studies that showed that carnosine protects against genetic structure damage caused by the chemotherapy drug cyclophosphamide. This is significant because cyclophosphamide is one of the most widely used chemotherapy drugs in treating cancers. But there’s another problem with cyclophosphamide beyond its tendency to destroy DNA: it suppresses the ability of the body to create new blood cells. It makes you anemic. Well, new studies published this year have found that carnosine has the potential to promote recovery from the blood building suppression induced by cyclophosphamide, as well as other chemotherapy agents, and that it can substantially improve the overall anti-tumor effects of the standard chemotherapies.⁷ Xu M1, He RR, Zhai YJ, Abe K, Kurihara H. “Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.” Am J Chin Med. 2014;42(1):131-42. http://www.ncbi.nlm.nih.gov/pubmed/24467540

So why is this important to you–assuming you don’t have cancer at the moment?

Because cancer and old age are not dissimilar. They both involve the relentless diminishing of cellular DNA, cellular integrity, and ultimately cellular function. The fact that carnosine can protect against this tri-headed assault when your body is confronted by some of the most toxic drugs known attests to its ability to protect against the same kind of assault presented by simple aging.

Meanwhile a study published last month took a look at just how carnosine might inhibit the growth of tumor cells.⁸ Hipkiss AR1, Gaunitz F. “Inhibition of tumour cell growth by carnosine: some possible mechanisms.” Amino Acids. 2014 Feb;46(2):327-37. http://www.ncbi.nlm.nih.gov/pubmed/24292217 Possibilities include effects on (i) glycolytic enzymes, (ii) metabolic regulatory activities, (iii) redox biology, (iv) protein glycation, (v) glyoxalase activity, (vi) apoptosis, (vii) gene expression and (viii) metastasis. The authors stated that it is possible, by acting at various sites that this “pluripotent dipeptide” [their exact words] might be an example of an internally produced “smart drug” [again, their exact words].

And finally, a study published last November found that carnosine can protect against both the damage and dysfunction caused to cells by exposure to radiation.⁹ Haeri SA1, Rajabi H, Fazelipour S, Hosseinimehr SJ. “Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice.” Andrologia. 2013 Nov 12. http://www.ncbi.nlm.nih.gov/pubmed/24215656 Specifically, the study found that carnosine protects against the cellular dysfunction caused by testicular cell exposure to gamma-irradiation–ultimately even restoring the ability of those same cells to produce sperm. That’s astounding, as are its implications for carnosine’s ability to protect against the cellular dysfunctions associated with simple aging–as well as its ability to restore function where it may have been lost.

Carnosine Benefits for Your Brain and Nervous System

Brain damage from reduced blood flow to the brain in infants from about three months before birth to one month after (HIBD) is a major cause of mortality and morbidity in neonates. Currently there is no effective therapy for HIBD. But studies published earlier this year show that indeed carnosine can reduce brain damage in such situations.¹⁰ Zhang H, Guo S, Zhang L, Jia L, et al. “Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.” Eur J Pharmacol. 2014 Jan 23. pii: S0014-2999(14)00024-7. http://www.ncbi.nlm.nih.gov/pubmed/24463179 Coupled with previous studies that have demonstrated the neuroprotective role carnosine can play when it comes to adult brain damage, it’s not hard to see why carnosine supplementation has built a reputation as one of the best things you can do to reduce your chances of succumbing to Alzheimer’s disease and dementia.

In fact, it looks like carnosine offers the same kind of protection to every nerve cell in your body, not just brain cells. A study published in November found that carnosine can protect nerve cells in your eyes, for example, from damage caused by reduced blood flow to cells in the retina.¹¹ Ji YS, Park JW, Heo H, Park JS, Park SW. “The Neuroprotective Effect of Carnosine (ß-Alanyl-l-Histidine) on Retinal Ganglion Cell Following Ischemia-Reperfusion Injury.”Curr Eye Res. 2013 Nov 8. http://www.ncbi.nlm.nih.gov/pubmed/24206188

A study published in PLos One in December found that carnosine’s ability to break up alpha-crystallin amyloid fibrils is most likely associated with carnosine’s ability to inhibit the amyloid induced cytotoxicity of human neuronal cells, thereby reducing cell deaths.¹² Wu JW, Liu KN, How SC, Chen WA, et al. “Carnosine’s Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme.” PLoS One. 2013 Dec 11;8(12):e81982. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859581/ Amyloid diseases, including hemodialysis amyloidosis, type II diabetes, Parkinson’s disease, transmissible spongiform encephalopathies, Huntington’s disease, and Alzheimer’s disease, are all characterized by the formation of insoluble deposits (aka, amyloid fibrils) in certain tissues and organs. The bottom line is that a constant stream of studies now indicates that if you don’t want to take supplemental carnosine to “look” younger and live longer, you will absolutely want to take it to better your odds of avoiding Alzheimer’s and a whole host of other amyloid related diseases.

This echoes another study published last July, also in PLoS One, that suggested that carnosine could play an effective role against the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, which is also a major hallmark of Alzheimer’s disease injury.¹³ Aloisi A1, Barca A, Romano A, Guerrieri S, et al. “Anti-aggregating effect of the naturally occurring dipeptide carnosine on aß1-42 fibril formation.” PLoS One. 2013 Jul 3;8(7):e68159. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700870/

But again, it’s not just dementia. An analytical paper published in December indicated that carnosine could play a role in protecting against a range of age related diseases of the nervous system such as Parkinson’s, as we’ve already mentioned.¹⁴ Hipkiss AR. “Aging risk factors and Parkinson’s disease: contrasting roles of common dietary constituents.” Neurobiol Aging. 2013 Dec 4. pii: S0197-4580(13)00616-7. http://www.ncbi.nlm.nih.gov/pubmed/24388766 Keep in mind that aging is a known risk factor for Parkinson’s disease. Specifically, there is evidence that indicates that excessive carbohydrate (glucose or fructose) catabolism is a factor in causing the mitochondrial dysfunction seem in Parkinson’s. One consequence of this dysfunction is an increased production of methylglyoxal (MG), an advanced glycation end product. But carnosine can not only scavenge MG but can also influence some of the biochemical events (signal transduction, stress protein synthesis, glycation, and toxin generation) associated with Parkinson’s pathology.

Miscellaneous Carnosine Benefits

An article appearing in the Sep-Oct issue of Advances in Clinical and Experimental Medicine concluded that due to its antioxidant, protective, chelating, and anti-glycation activity, carnosine could be used to prevent and treat diseases such as diabetes, neurodegenerative diseases, diseases of the sense organs and even cancers.¹⁵ Budzen S1, Rymaszewska J. “The biological role of carnosine and its possible applications in medicine.” Adv Clin Exp Med. 2013 Sep-Oct;22(5):739-44. http://www.advances.am.wroc.pl/pdf/2013/22/5/739.pdf It may also cure or alleviate many other disorders thanks to its wide spectrum of activity. The authors noted that carnosine is already used by athletes to achieve better results, due to its buffering feature, which contributes to the maintenance of the acid-base balance in the muscles. And they stated that future studies on the influence of carnosine on the human organism may lead to the therapeutic use of this dipeptide for many diseases, in addition to improving both amateur and professional athletes’ results.

On a different note, it has been proposed that that human blood platelet monoamine oxidase (MAO) activity is a biological marker of vulnerability to a variety of psychiatric diseases. Its activity is significantly inhibited as a result of aging, thus increasing the risk of problems as we age. A study published last July in the Journal of Physiological Sciences found that this age-induced inhibition of platelet MAO-A activity is reversed in as little as 21 days following the application of sufficient dosages of carnosine.¹⁶ Banerjee S1, Poddar MK. “Platelet monoamine oxidase-A activity and aging: effect of carnosine.”J Physiol Sci. 2013 Jul;63(4):279-85. http://www.ncbi.nlm.nih.gov/pubmed/23657886 The study concluded that these results suggest that carnosine withdraws the aging-induced inhibition of mammalian blood platelet MAO-A activity and restores its activity towards that observed in young mammalian blood platelets. It seems that carnosine pushes the clock on aging back anywhere and everywhere we look in the body.

Perhaps the best example to end with is another analytical paper published a year ago February in the Chemistry Central Journal that noted that carnosine has contrasting but beneficial effects on cellular activity.¹⁷ Hipkiss AR, Cartwright SP, Bromley C, Gross SR, Bill RM. “Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?” Chem Cent J. 2013 Feb 25;7(1):38. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602167/ As we discussed years ago, carnosine delays cellular senescence and rejuvenates cultured senescent mammalian cells. The paper then went on to explain that studies have now also confirmed that carnosine inhibits the growth of cultured tumor cells as well. Based on studies in several organisms, the authors speculated that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s influence on cellular ATP concentrations. Carnosine’s ability to reduce the formation of altered proteins after exposure to methylglyoxal (see three paragraphs above) and enhance the breakdown of aberrant polypeptides is indicative of its ability to help maintain protein integrity throughout the body.

What makes this paper so special is the breadth of its conclusions as they cover virtually every disease commonly associated with aging. And I quote:

“Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer’s disease, Parkinson’s disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine’s mode of action on human cells.”

Conclusion

Last year, Kristen and I attended the Renaissance Faire with some friends. While walking around, we heard a cry from one of the tent stalls. “Shiny things! Shiny things! Come see the shiny things.”

We turned to see a peddler inside the tent, gently shaking a rack of silver earrings in the afternoon sunlight. And the silver earrings danced and sparkled in the light. And like genetically programmed moths, a substantial number of the people who heard his cry and saw the sparkling earrings were drawn to the flame. Of course, upon closer inspection, the silver earrings turned out to be more sparkle than substance.

I think that in a sense, we are like moth-people, genetically encoded to respond to the new and shiny. We are easily bored and chase the next sparkly new ingredient or face crème that promises to keep us young forever–and in the process, we abandon the familiar and boring even though it may be remarkably effective. When it comes to carnosine, that would be a mistake. Yes, it’s been around for 18 years, and Dr. Oz gave it its 15 minutes of sparkle in the sun some two years ago, but that’s no reason to abandon it. In truth, carnosine is anything but dull, boring, and old fashioned. While people are hunting for the next “big thing” in anti-aging, the active research on carnosine’s known and potential benefits in terms of slowing down the aging process and protecting against the widest possible range of age related diseases is, as we have seen, absolutely exploding. If anything, the cascade of new studies detailing carnosine’s benefits demonstrates  that, in actuality, carnosine is the next big thing.

Recommendation

The bottom line is that a well-designed L-carnosine formula is still your best bet for slowing down the aging process and–as we’ve seen from just a sampling of all the studies completed in the last year alone–so much more. I’m still partial to a formula that provides upwards of 1500 mg of carnosine a day along with its complements, 1200 mg of Acetyl-L-carnitine and 240 mg of DMAE bitartrate. For now, it’s the closest thing I know of to Ponce De Leon’s Fountain of Youth. I’ve personally been taking my own version of this formula for the last 18 years.

Note: A number of people have been writing in lately asking about using beta alanine to boost carnosine levels to experience carnosine’s benefits. And yes, alanine is one of the two peptides, along with histidine, that combine to make up carnosine. And yes, if you supplement with beta alanine, your body will use it to raise carnosine levels in your body. The problem is that it’s not very efficient.   According to a review of the current literature published in the Jan 2010 issue of Nutrients, you need to supplement with 4.8 to 6.4 grams of beta-alanine a day to significantly increase muscle carnosine levels.¹⁸ Julie Y. Culbertson, Richard B. Kreider, Mike Greenwood, and Matthew Cooke. “Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current Literature.” Nutrients. Jan 2010; 2(1): 75–98. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257613/ Using carnosine supplements is far more efficient.