New Studies Validate Age-Delaying Effects of CarnosineDecember 2016
By Cynthia Wylie
In year 2000, Life Extension® became the first organization to introduce the concept of high-dose carnosine supplementation.
Before then, carnosine was available only in low doses (50 mg) that did not provide any benefit because enzymes in the blood rapidly degrade it.
There was compelling evidence 16 years ago to recommend 1,000 mg a day of supplemental carnosine. What’s transpired since then is nothing short of a major scientific advance. New human studies are demonstrating broad-spectrum properties of carnosine that exceed our original expectations.
For cost-conscious consumers, the price of carnosine has come down as more efficient ways have been discovered to produce it.
This article reveals new findings demonstrating the longevity potential when higher carnosine doses are utilized. This is especially important for those with less-than-optimal blood glucose levels, which happens to be most aging humans.
Carnosine Protects Tissues
Even at blood sugar levels considered “normal,” glycation tissue damage occurs throughout the body.1
Glycation creates structure/function changes to blood vessels, skin, nerves, heart muscle and the brain. This leads to premature aging.2-4
It is especially important to protect the body against even temporary glucose elevations such as those following meals. High after-meal glucose levels are strongly correlated with heart disease and other systemic risks.5
Elevated blood glucose leads to reduced levels of carnosine in muscle tissue, especially prominent in those with type II diabetes.6 A human study evaluated the impact of carnosine supplementation on a group of obese adults at risk for developing diabetes and cardiovascular disease.7 Subjects were randomly assigned to receive very high-dose carnosine, 2,000 mg/day, or a placebo, for 12 weeks.
In order to determine the effects of carnosine, researchers used models that quantify insulin resistance and insulin secretion (beta-cell function).8,9
After 12 weeks, both groups saw increases in insulin resistance and insulin secretion, but the increases were smaller in the carnosine group. Insulin resistance in the placebo group increased 3.8-fold more than the carnosine group.
In order to overcome cellular insulin resistance, the pancreas responds by secreting lots of insulin. Numerous studies show excess insulin is highly undesirable, especially as it relates to cancer. In this study, placebo recipients increased insulin secretion by 36%, whereas the increase in carnosine recipients was only 3%.
Importantly, among subjects with impaired glucose tolerance (that is, those with “prediabetes,” or “borderline high” blood sugar), carnosine supplementation decreased blood glucose to nondiabetic levels two hours after a glucose tolerance test, while unsupplemented subjects remained significantly higher, at more than 160 mg/dL.
This study strongly supports the concept that carnosine supplementation can play a major role in preventing the development of type II diabetes and its multiple negative consequences.
These findings would hardly be surprising to scientists who have studied carnosine’s antidiabetic effects for years, and are familiar with its abilities to protect tissues from glycation.
Carnosine Confers Systemic Protection
Animal studies show that carnosine supplementation delays diabetes-induced deterioration of heart, liver, and kidney functions, lowering blood sugar and lipid levels, and reducing lipid oxidation.10 Carnosine also reduces levels of pro-inflammatory cytokines10 and glycation-indicative tissue damage in diabetic animals.11
Laboratory studies show that carnosine, added to kidney cells in culture, can prevent the glucose-induced deposition of extracellular material that slows the kidney’s filtering and cleansing functions. This is a common cause of kidney failure in diabetics.12
In the eye, carnosine supplementation delayed progression of cataracts, the clouding of the lens that can lead to blindness in diabetics, after just four weeks of supplementation.11 Similarly, supplementation with carnosine prevented the blood vessel damage that leads to another cause of glucose-induced blindness, diabetic retinopathy.13
Elevated blood glucose damages cells in the immune system and in those involved in healing tissues, leading to delayed wound healing and even amputation in severe cases. But carnosine supplementation enhanced wound healing in diabetic rats through protection of cells against glucose-induced damage.14
The impact of glycation is felt throughout the body, and is not restricted to just those with diabetes. Carnosine supplementation may protect tissues most vulnerable to glucose-induced damage, including the heart and the brain.
Carnosine Protects the Cardiovascular System
Carnosine has been found to prevent early oxidation of fats in the bloodstream, and reduces the resultant tissue damage and inflammatory responses in animal studies.15 A human study has now validated those findings in living patients.
Basing their work on the high levels of carnosine found in healthy heart muscle and on studies in people showing that carnosine improves exercise performance, researchers studied 50 patients with stable congestive heart failure.16 The goal was to determine if carnosine could improve exercise performance and quality of life in such patients.
Congestive heart failure results when an ailing heart cannot pump sufficient blood to meet the metabolic needs of tissues in the body. It can limit mobility and physical functioning, and severely impairs quality of life for its victims.
In the study, subjects were randomly assigned to receive standard congestive heart failure medical therapy alone, or with added carnosine, 500 mg/day over a 6-month period.16
Compared with the patients not taking carnosine, the supplemented group significantly improved their physical condition in a number of ways. Patients saw improvement in their quality-of-life scores, their 6-minute walking distance, their peak exercise workload, and their ability to deliver oxygen for use in their tissues during exercise.16
Patients with congestive heart failure are among the most challenging to medically manage, and have a uniformly poor prognosis without complicated medication regimens. The finding that naturally-occurring carnosine has these dramatic effects in this population is an important milestone in our understanding of the disorder, and offers great hope for the future.
Numerous animal and basic science studies offer further insights into how carnosine benefits the heart and blood vessels.
Research has shown that carnosine inhibits formation of advanced glycation end products (AGEs), the sugar-protein complexes that damage tissues and impair function. Carnosine also inhibits formation of advanced lipoxidation end products, while also rapidly neutralizing them when they form.15,17,18 This is important, because advanced lipoxidation end products are oxygen-damaged fat molecules that can trigger inflammation and lay the foundation for the atherosclerotic plaques that damage blood vessels and impede blood flow, eventually resulting in a heart attack or stroke.18,19
Studies show that carnosine inhibits formation of the lipid-filled inflammatory cells called “foam cells” that play a large role in the formation of atherosclerotic plaque.20 Furthermore, in an animal study, carnosine significantly prevented the development of the lipid abnormalities, high blood pressure, and kidney damage associated with cardiovascular diseases, and also preserved kidney function and prevented microscopic kidney damage related to hypertension.17
Remarkably, carnosine not only lowers plasma triglycerides, but it also promotes the removal of damaged fats from atherosclerotic lesions and stabilizes those lesions against catastrophic rupture, which suggests that it might be useful in treating patients with known atherosclerosis.18,21
Carnosine Supplementation Protects Brain Tissue
Brain cells are highly vulnerable to glycation-induced damage and to blood-flow impairments caused by atherosclerosis.
Carnosine helps prevent both of those problems. Scientists have now confirmed that carnosine supplementation has meaningful effects in the brain, especially in prevention of age-related disorders such as cognitive impairment and memory loss.
In a study of 51 adults 65 and older, subjects received a placebo or a carnosine-rich diet for 13 weeks.22 Compared with the placebo group, subjects receiving the carnosine-rich diet performed significantly better by the end of the study on a variety of cognitive function and physical fitness scores. Intriguingly, supplemented subjects also lost weight.
Carnosine supplementation has now shown promising results in a variety of brain disorders. For example, 12 weeks of carnosine supplementation (given as 500 mg, 1,000 mg, and 1,500 mg, increasing at 4 week intervals) lessened cognitive dysfunction in veterans suffering fatigue and pain from Gulf War Illness, a disorder thought to be related to toxic chemicals during that war.23
A preliminary study of schizophrenic patients also showed that carnosine, 2,000 mg/day, could improve executive (decision-making) function, helping subjects perform faster and with improved strategy on tests of executive function.24
A Japanese study of “chicken essence,” a traditional remedy for fatigue, rich in carnosine, found that supplementation, when administered to healthy men, improved cognitive performance following mental fatigue induced by a stressful task.25
These studies clearly demonstrate that carnosine provides direct benefit for the brain. Lab and animal studies suggest how.
Healthy aging brains undergo changes in signaling molecules (neurotransmitters) and their receptors that impede normal thinking and information processing.26,27 Carnosine supplementation can restore normal production and breakdown of the important neurotransmitter serotonin, which may in turn explain its ability to prevent age-induced cognitive decline.26,27
Neurodegenerative diseases such as Alzheimer’s and Parkinson’s can result from protein glycation and oxidative stress that leads to the accumulation of toxic abnormal proteins.28,29 Carnosine treatment prevented the damage to tiny brain vessels induced by a chemical used to model Parkinson’s disease in animals, and restored brain cells’ ability to utilize energy.29
Stroke is another age-related threat to brain function and cognition. While there are few effective therapeutic options for treatment, carnosine may provide protection in the event of a stroke.30
Studies show that carnosine protects brain tissue against the abrupt loss, followed by abrupt restoration, of oxygen-rich blood that occurs during a stroke and can induce widespread brain damage and death.30-32 Similar protection was seen against hemorrhagic stroke, another threat to older adults’ memory and cognitive function.33 Indeed, a collective analysis of multiple animal studies of ischemic stroke concluded that carnosine, either before or after the onset of a stroke, has robust effectiveness.34
Such studies make a strong case for maintaining ample carnosine blood levels in anyone at elevated risk for stroke.
Every adult, diabetic or not, suffers continuous, low-grade tissue damage from chronic exposure to the glucose that is needed to fuel our cells.
As a result, protein and fat in our body becomes damaged, dysfunctional, and, in fact, toxic, leading to increased inflammation. This leads to increased risks for type II diabetes, cardiovascular disease, and brain damage from stroke and neurodegenerative diseases.
That means that protecting against glucose-induced damage requires more than keeping blood sugar levels down.
Carnosine is coming to the forefront as a supplement capable of reducing risk for blood sugar damage and its consequences—renal failure, neuropathy, cardiovascular disease, and loss of brain function.
Human studies now demonstrate that carnosine can lower blood sugar and insulin levels even in nondiabetic adults, and thereby forestall blood vessel and heart muscle damage, while also preventing cognitive decline.
Rarely can a nutrient produce so many good results, but that’s precisely what carnosine represents. It belongs in any thoughtful approach to a healthier aging process.
People taking 500 mg of carnosine twice a day along with certain B-vitamins are likely to obtain optimal anti-glycation benefits.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc. 2003;78(12):1471-8.
- Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev. 2013;93(4):1803-45.
- Reddy VP, Garrett MR, Perry G, et al. Carnosine: a versatile antioxidant and antiglycating agent. Sci Aging Knowledge Environ. 2005;2005(18):pe12.
- Jakus V. [The role of nonenzymatic glycation and glyco-oxidation in the development of diabetic vascular complications]. Cesk Fysiol. 2003;52(2):51-65.
- Blaak EE, Antoine JM, Benton D, et al. Impact of postprandial glycaemia on health and prevention of disease. Obes Rev. 2012;13(10):923-84.
- Gualano B, Everaert I, Stegen S, et al. Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients. Amino Acids. 2012;43(1):21-4.
- de Courten B, Jakubova M, de Courten MP, et al. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial. Obesity (Silver Spring). 2016;24(5):1027-34.
- Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.
- Wallace TM, Levy JC, Matthews DR. Use and Abuse of HOMA Modeling. Diabetes Care. 2004;27(6):1487-95.
- Lee YT, Hsu CC, Lin MH, et al. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol. 2005;513(1-2):145-50.
- Yan H, Guo Y, Zhang J, et al. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats. Mol Vis. 2008;14:2282-91.
- B, Hohenadel D, Brinkkoetter P, et al. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes. 2005;54(8):2320-7.
- Pfister F, Riedl E, Wang Q, et al. Oral carnosine supplementation prevents vascular damage in experimental diabetic retinopathy. Cell Physiol Biochem. 2011;28(1):125-36.
- Ansurudeen I, Sunkari VG, Grunler J, et al. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes. Amino Acids. 2012;43(1):127-34.
- Stegen S, Stegen B, Aldini G, et al. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. Appl Physiol Nutr Metab. 2015;40(9):868-76.
- Lombardi C, Carubelli V, Lazzarini V, et al. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition. 2015;31(1):72-8.
- Aldini G, Orioli M, Rossoni G, et al. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J Cell Mol Med. 2011;15(6):1339-54.
- Barski OA, Xie Z, Baba SP, et al. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2013;33(6):1162-70.
- Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000;28(12):1708-16.
- Rashid I, van Reyk DM, Davies MJ. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett. 2007;581(5):1067-70.
- Brown BE, Kim CH, Torpy FR, et al. Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis. 2014;232(2):403-9.
- Szczesniak D, Budzen S, Kopec W, et al. Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity. Arch Gerontol Geriatr. 2014;59(2):485-90.
- Baraniuk JN, El-Amin S, Corey R, et al. Carnosine treatment for gulf war illness: a randomized controlled trial. Glob J Health Sci. 2013;5(3):69-81.
- Chengappa KN, Turkin SR, DeSanti S, et al. A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in schizophrenia. Schizophr Res. 2012;142(1-3):145-52.
- Yamano E, Tanaka M, Ishii A, et al. Effects of chicken essence on recovery from mental fatigue in healthy males. Med Sci Monit. 2013;19:540-7.
- Banerjee S, Poddar MK. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine. Neuroscience. 2016;319:79-91.
- Banerjee S, Poddar MK. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity. Neurosci Res. 2015;92:62-70.
- Hipkiss AR. Could carnosine or related structures suppress Alzheimer’s disease? J Alzheimers Dis. 2007;11(2):229-40.
- Zhang L, Yao K, Fan Y, et al. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H(1) and H(2) receptors in vitro. Clin Exp Pharmacol Physiol. 2012;39(12):1019-25.
- Bae ON, Majid A. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage. Brain Res. 2013;1527:246-54.
- Baek SH, Noh AR, Kim KA, et al. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke. 2014;45(8):2438-43.
- Zhang H, Guo S, Zhang L, et al. Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model. Eur J Pharmacol. 2014;727:174-80.
- Zhang ZY, Sun BL, Yang MF, et al. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model. Cell Mol Neurobiol. 2015;35(2):147-57.
- Davis CK, Laud PJ, Bahor Z, et al. Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke. J Cereb Blood Flow Metab. 2016.
- Hipkiss AR, Preston JE, Himsworth DT, et al. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann N Y Acad Sci. 1998;854:37-53.
- Wang AM, Ma C, Xie ZH, et al. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc). 2000;65(7):869-71.
- McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994;212(2):167-75.
- Hipkiss AR, Baye E, de Courten B. Carnosine and the processes of ageing. Maturitas. 2016.
- Shao L, Li QH, Tan Z. L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts. Biochem Biophys Res Commun. 2004;324(2):931-6.
- Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One. 2015;10(9):e0138646.