Carnosine. A Potent Anti-glycation Ally?

For many in the wellness industry, especially those with an interest in ‘anti-aging’, carnosine is relatively new.

But industry leaders Life Extension was one of the first to publish data almost 18 years ago on carnosine supplementation which showed promising anti-aging effects.

In this context, it’s all about preventing the damaging effects of glycation reactions and oxidation which increase the signs and symptoms of many age-related chronic diseases.

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What is carnosine

Carnosine is a dipeptide (a combination of two amino acids) of beta-alanine, and histidine linked together, a.k.a. beta-alanyl-L-histidine (1). It’s found in the brain, kidney, and muscles of fish, birds, and mammals (like you and me) although it’s primarily found in red meat (2).

Carnosine is considered non-essential, as your body can form it from histidine and beta-alanine. You can make enough carnosine to prevent a deficiency, provided you’re getting the other amino acids in your diet, but what’s of interest to researchers is whether or not getting more carnosine can offer additional health benefits.

Food sources of carnosine

The best food sources of carnosine are red meat/beef, fish, chicken and turkey, especially the white meat, and pork, etc. Any skeletal muscle tissue that’s eaten as food will contain carnosine.

To that end, carnosine is only found in animal-based foods. This is of importance because although vegetarians and vegans can get beta-alanine and histidine in their diets, it might not be enough to maintain carnosine levels for optimal, long-term health – the truth, we just don’t know.

Unlike those who include sources of carnosine such as meat, poultry, and fish, vegans and vegetarians have less carnosine in their muscles (3, 4). Vegetarian nutrition tends to focus on nutrients such as vitamin D3, calcium, iron, zinc, the omega-3 fats EPA, DPA, and DHA, etc but there are other more nuanced concerns with carnosine being one of them.

The amount of carnosine in a large-sized serving (200 g or 7 oz) of red meat is about 250 mg. While this maintains muscle carnosine concentrations, along with what your body produces on its own, it’s not enough to provide what studies suggest is a therapeutic amount.

How is carnosine used?

Carnosine is used as a nutritional supplement, eye drops and it’s added to skincare products such as lotions and creams.

Possible carnosine benefits

Carnosine’s claim to fame is its role as an antioxidant (5). Studies continue to examine how it neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), but more importantly, how it prevents glycation (6).

While a promising compound, the research on carnosine is limited and includes some poor-quality studies. It’s still very much in its infancy but there is some compelling data; enough for some anti-aging and longevity enthusiasts to take while more research rolls in. The good news for them is that carnosine is relatively inexpensive, it’s safe, and its benefits are biologically, physiologically and mechanistically plausible.

Below are some of the purported benefits from carnosine supplementation.

Cardiovascular

Some preliminary studies have found a potential role for carnosine in promoting heart health.

In one trial in patients with congestive heart failure (CHF), carnosine was able to improve markers of heart function unique to this patient population as an add-on supplement to standard treatment and care (7). A dosage of 500 mg once a day resulted in beneficial effects on exercise performance and quality of life scores in stable CHF patients.

Other studies suggest that carnosine may improve calcium levels and activity in heart muscles thereby improving heart function. Animal studies suggest that carnosine may have a novel role for carnosine as a modulator of intracellular calcium and contractility in cardiac tissue (8, 9).

Other studies have looked at carnosine’s anti-inflammatory, antioxidant, anti-glycation, anti-ischemic and chelating properties to address many of the markers and drivers of atherosclerosis (10). While promising, more research is needed before confident recommendations can be made (11).

Long-term, carnosine may prove to be effective at preventing harmful modifications of LDL cholesterol molecules by oxidative and glycation reactions. A pivotal first step in the atherosclerotic process is damage to LDL molecules which contribute to the early stages of arterial plaque formation (12, 13, 14).

In addition to offering protection to LDL, carnosine has been shown to prevent the oxidation (rusting) of fats, such as triglycerides, in the bloodstream, a.k.a. “lipids”, and the subsequent tissue damage and inflammation that accompanies oxidized blood lipids and atherosclerosis (15).

Animal studies show that carnosine inhibits the formation of the lipid-filled inflammatory cells called “foam cells” that play a large role in the formation of atherosclerotic plaque (13). When LDL is oxidized and damaged, white blood cells seek them out to envelop and sequester them resulting in the formation of foam cells. Over time, with more and more foam cells building up within the artery walls, arteries thicken leading to a blockage.

Combating the effects of high blood sugar

A consequence of elevated blood sugar is the glycation of various cells and tissues. Glycation occurs when sugar molecules, glucose, galactose, and fructose in your bloodstream, basically glom onto the fats and proteins that make up your cells (and therefore ultimately your tissues and organ) (16).

This forms Advanced Glycation End Products (a.k.a. AGEs), which cause protein fibers to become stiff and malformed. Much of what is known about the ill effects of glycation comes from diabetes research.

The connective-tissue damage and chronic inflammation resulting from diabetics’ sustained high blood sugar can lead to debilitating conditions, such as cataracts, Alzheimer’s, vascular damage, cardiovascular disease, and diseases of the pancreas, kidney, and liver.

To an extent, glycation is a fact of life. It’s happening right now, to all of us whether or not one has diabetes. It can even be measured.

Obviously, those who have metabolic disorders such as pre-diabetes or insulin resistance or full-blown diabetes have glycation happening at an very accelerated rate. But, even those without diabetes will have accelerated glycation if they’re exposed to high amounts of dietary carbohydrate; all those carbs have to be absorbed and are ultimately carried through the bloodstream. As they are, glycation occurs which is why lower-carb diets (eating fewer starches, added and free sugars etc) are associated with less glycation.

Because carnosine has anti-glycation properties, it’s being researched as a way to combat the dangers of elevated blood sugars. This may not only apply to those with pre and established diabetes but to those who want to slow down and reduce the formation of AGEs which contribute to symptoms of aging and age-related tissue damage (6, 17).

While there’s been some research on carnosine’s ability to lower blood sugar, improve the autonomic nervous system and improve insulin sensitivity, the evidence is very preliminary and is too soon to recommend it for those specific reasons.

Where it seems to have better efficacy is in its ability to mitigate any damage from elevated blood sugar (18, 19, 20, 21, 22). Interestingly, carnosine supplementation in animals delays the onset of diabetes and increases the mass of insulin-secreting pancreatic cells thereby maintaining metabolic health and glucose metabolism (23).

Novel anti-cancer properties

The use of carnosine as a chemopreventive is in its infancy, but in terms of benchtop research, (think lab work, etc) encouraging studies are emerging as researchers explore ways to leverage its antioxidant, anti-inflammatory features.

As an antioxidant, carnosine helps block the DNA damage that can lead to cancerous transformation in cultured cells. Damaged DNA is one of the ways that cancers of various types can occur. Preventing DNA is the strategy behind lifestyle interventions such as an anti-inflammatory diet, avoiding excessive sun exposure, alcohol consumption, and smoking. By preventing DNA damage, cancer risk may be reduced (24).

Carnosine also prevents the release of inflammatory cytokines (pro-inflammatory proteins) in intestinal cells, reducing a significant risk for colon cancers (25). Its ability to inhibit new metastases (spreading), and to interfere with cancer cells’ energy metabolism (which may starve them), make it a potential anticancer nutrient of interest in the future (26, 27, 28).

Memory

Some preliminary studies have found a benefit with l-carnosine and memory but large-sized trials are lacking. A small study looking at 31 healthy participants found that 500 mg of carnosine per day might positively impact cognitive function due to network connectivity changes (29).

Similarly, another study involving 39 healthy elderly volunteers demonstrated improved verbal episodic memory when they were given a combination of anserine (a different but similar form of carnosine) along with carnosine (30).

Protecting your brain

Brain cells are highly vulnerable to glycation-induced damage, as well as, blood-flow impairments caused by atherosclerosis.

Fortunately, brain tissue naturally contains high levels of carnosine because there’s lots of specific transport proteins that selectively move carnosine into brain tissue, across the blood-brain barrier. There, carnosine is capable of reducing the oxidative, nitrosative, and glycemic stress to which the brain is especially vulnerable (31, 32, 33).

By preventing glycation-related damage, carnosine may prove to support normal brain function and everything that goes with it. This includes reduced blood vessel and brain cell damage including decreased cross-linking of proteins in brain tissue, improved blood flows, maintaining cognition, and preventing memory loss while minimizing toxicity created by high levels of metals in certain brain regions (34, 35, 36, 37).

Additional research supports carnosine supplementation’s role in preventing age-related disorders such as cognitive impairment and memory loss. A double-blind study of 51 adults, 65 and older with some cognitive decline received a standard or anserine-carnosine-supplemented diet for 13 weeks.

Compared to the standard diet, the carnosine-rich group performed significantly on various cognitive function tests (38).

Another interesting study in Japan that used “chicken essence” (an extraction of chicken meat), a traditional remedy for fatigue which just so happens to be rich in carnosine saw improvement in cognitive performance following mental fatigue induced by a stressful task (39).

The product, BEC, or Brand’s Essence of Chicken, comes in 68 ml bottles but doesn’t list how much carnosine is present. Because this is not a standardized supplement, it’s impossible to verify the dosage of carnosine.

Preventing cataract formation

The lens of the eye is highly sensitive to the glycation of its proteins, which render it opaque.

Because carnosine has antiglycation properties and it’s been shown to help reverse existing glycation, it seems mechanistically plausible that carnosine may help to prevent, and possibly reduce cataracts (40).

Some animal studies have shown both risk reduction and severity of cataracts using carnosine supplementation (41). Using a diabetic model in rats, carnosine was shown to reduce cataract formation using different delivery systems (42, 43, 44).

The use of 1% carnosine eye drops (containing N-acetyl-carnosine) for up to a year reduced vision deficiencies (measured by lens opacity and visual acuity) that are usually a side effect of cataracts (45, 46). Not surprisingly, more research is needed.

Reduce muscle fatigue and improve performance

As with many other important molecules such as ubiquinone, NAD, creatine, etc, carnosine levels in the body decline with age.

Muscle levels can decrease a whopping 63% between ages 10 to 70, which may account, in part, for the reduction in muscle mass (sarcopenia) and muscle function seen in aging humans (47).

What’s interesting about carnosine is that it not only acts not only as an antioxidant in muscle but also as a pH buffer (48). In this way, it pulls double duty. It protects muscle cell membranes from oxidation and damage but amazingly, carnosine also helps to buffer the excess hydrogen ions generated by lactic acid; a by-product of muscle exertion.

Carnosine is being researched as a performance enhancer via its role in energy production and acid buffering.

One study of 12 healthy, muscle-fatigued men found that 2 g of carnosine and 2 g of beta-alanine (which is converted into carnosine within muscle cells) 4 hours prior to an exercise test increased measures of physical performance (maximal muscle contraction during knee extensions and jump height). But an increase in muscle pain (delayed onset muscle soreness or DOMS) occurred 24 hours later; likely due to the increase in muscle exertion (49).

The results are mixed. A study examing the impact of the equivalent of a single 1.5 g dose of carnosine did not affect power during intense rower sprints – but, to be fair, a single dose wouldn’t effectively improve carnosine status (50).

A few studies have reported that beta-alanine (precursor of carnosine which is converted within the muscle cells) supplementation can increase high-intensity exercise performance, lean muscle gains, VO2 max, and the speed of training adaptations.

The consensus is that this is due to carnosine’s ability to buffer the low pH that increases with exercise/activity duration. The low pH (hydrogen ions) interfere with muscle cells’ ability to contract. If you can prevent this kind of all-out muscle fatigue, it will improve measures of physical training (51).

Anti-aging and longevity

The concept of anti-aging or longevity medicine and lifestyle and nutrition is an intervention that can slow down, and/or reserve, many of the changes associated with the normal part of aging. While not a new concept, the term du jour is ‘hack’ or ‘biohacking’.

Where carnosine is concerned, it’s about the very things reviewed in this post. Reducing inflammation and oxidative damage, preventing the impact of glycation on cells, improving and maintaining cellular energy levels via maintaining optimal mitochondrial function and slowing down premature cell death, a.k.a. senescence.

How this applies to anti-aging nutrition is due to the fact that carnosine levels decline with age. The theory goes that by maintaining, throughout life, or by restoring carnosine levels to what they are in younger aged people may help to mitigate many of the symptoms associated with aging – fingers crossed!

Most of the carnosine research to date has been in cell cultures (think petri dishes), test tubes, with fruit flies, rats and mice, and some limited studies in humans. In cell research, carnosine has been shown to “rejuvenate” cells as they approach the end of their lifecycle but drawing conclusions is difficult (52, 53).

To give an idea of this using animals, one study found that 44% of mice given carnosine had young, healthy-looking fur into old age, compared to just 5% of the untreated mice. Also, only 9% of the untreated mice acted more youthfully in old age, whereas 58% of the mice treated with carnosine showed robust youthfulness (54, 55).

Interestingly vegetarians have been found to have higher levels of AGEs (advanced glycation end-products) than omnivores. Some think this may be because there is very little carnosine in vegetarian and vegan diets, and consequently their cells and tissues. Another possibility is that vegetarian and vegan diets tend to be much higher in sugars and carbohydrates which ultimately are digested and absorbed as glucose, fructose, and galactose (56).

Alzheimer’s and Parkinson’s disease

Carnosine levels are significantly lower in patients with Alzheimer’s and other neurodegenerative disorders, and carnosine levels are linked to these.

One suggestion is that carnosine deficiency contributes to the disease, or, perhaps these disease processes use up carnosine to quell the increased oxidation and inflammation in Alzheimer’s and dementia (57, 58).

A lot of research is being done with carnosine to see how it may be preventative and treatment in the pathology that’s seen in Alzheimer’s. This includes counteracting the build-up of aldehydes and amyloid plaques, impeding the organization of beta-amyloid into the problematic fibrillar structures, by activating the enzyme carbonic anhydrase which is inactivated in Alzheimer’s and mitigating the potential toxic of effects of minerals normally found in the brain including iron, zinc, and copper (59, 60, 61, 62, 63, 64, 65).

Similarly with Parkinson’s, research is investigating whether or not carnosine addresses many of the changes seen in this brain disease such as preventing the breakdown of proteins that might lead to Parkinson’s (66). Cell studies are looking at carnosine’s ability to inhibit malondialdehyde (MDA, a marker of oxidation) in brain cells, thereby limiting the formation protein-cross linking and protein carbonyls; pathologies seen in Parkinson’s disease (67).

A pilot study using 1.5 g (1500 mg) of carnosine per day in addition to the standard medication L-dopa, carnosine helped to improve neurological symptoms such as rigidity of the legs and hands, and improvements in hand movement and leg agility (68).

In either case, as more research is done, supplementation with carnosine may prove to be a strategy to reduce risk factors of these diseases, as well as, supportive treatment. Some of the animal and human studies point to this direction (69, 70, 71, 72, 73).

Autism

While there is a lot of chatter online and in autism support groups, at this time there isn’t sufficient evidence to support the use of l-carnosine for autism.

Where some might be getting their information on the role of carnosine and autism is from a small study of 31 children with autism. Researchers gave 800 mg of L-carnosine per day for 8 weeks. While there were improvements in autism severity and symptoms (such as socialization, communication, and vocabulary), it’s premature to draw any meaningful conclusions. One major limitation of the study is that they didn’t include a control group (74).

What about zinc carnosine?

Zinc carnosine is different from l-carnosine. Zinc carnosine is a molecule of zinc (a mineral) bound to the amino acid carnosine. This unique formulation allows the zinc to be released much slower than other zinc formulations. It’s not a reliable source or carnosine but rather is used to treat digestive health disorders and diseases by delivering zinc to the epithelial cells in there gut. There, zinc is used to support gut healing; I’ll be writing a comprehensive post specifically on zinc carnosine soon.

How do you increase carnosine levels?

It’s simple. You have two choices really, well three if you include dietary sources. The first is to use l carnosine supplements which typically comes in 500 mg dosages per dose (capsules etc). Alternatively, you can use an amino acid derivative called beta-alanine.

Beta-alanine benefits your carnosine levels a little differently compared to l carnosine. Beta-alanine is absorbed into your cells where it’s converted to carnosine. The drawback with using beta-alanine is that it temporarily causes a safe, yet annoying, itchy and prickly feeling in your skin.

PRO TIP: studies show that beta-alanine is more effective at raising intra-muscular levels of carnosine than does preformed supplementation carnosine

Does carnosine dosage matter?

Carnosine is an amino acid compound found primarily in meats, especially red meat, fish and the white meat of chicken and turkey.

Carnosine is relatively, quickly broken down by your body by the carnosinase enzyme. What this means is that in order to get any established or theoretical benefit from carnosine, enough of it would have to be consumed to ensure adequate amounts remain in your bloodstream throughout the day.

Using the example of red meat, 7 ounces (200 g) has about 250 mg of carnosine which is broken down over the course of about 5.5 hours (75). Based on studies, this wouldn’t provide enough carnosine to offer any meaningful benefit because it’s broken down too quickly. This is where carnosine supplements come in.

Supplementation with 1,000 mg (500 mg twice a day) of carnosine overwhelms the carnosinase enzyme, thus enabling you to maintain consistent, beneficial blood levels of this critical nutrient.

Carnosine safety

Carnosine supplements are likely safe when used appropriately (76). It is theoretically possible that carnosine may compromise blood clotting by inhibiting the enzyme, serum transglutaminase (62). Pregnant and breastfeeding women should avoid carnosine due to the lack of safety data.

Bottom line

Growing scientific interest in longevity medicine and nutrition has included research on carnosine.

Highly concentrated in the brain, heart, liver, kidneys, and muscles, carnosine is a natural antioxidant and anti-glycation molecule whose levels decline as we age.

Research has focused on carnosine’s role in preventing many of the symptoms and chronic diseases associated with aging such as cardiovascular disease, cataracts, decreased energy levels including muscle fatigue and performance, cognitive decline, the negative impact from failing blood sugar control, Alzheimer’s and Parkinson’s disease, poor memory and may even have some novel anti-cancer properties.

While present in some foods, carnosine supplementation may prove to be a supportive treatment capable of reducing the risk of pre-diabetes and diabetes-related 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 possibly also preventing cognitive decline.

Because carnosine is degraded quickly by your body, supplementation of 1000 mg (500 mg twice a day) per day is needed to get the beneficial effects of this emerging longevity nutrient.