L-CARNOSINE
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L-Carnosine:
The interest in longevity-boosting compounds has led to the intensive research of L-Carnosine. This compound has shown significant anti-aging qualities that help protect you from certain age-related diseases, as well as providing support to tissues in the heart, brain and eyes. Carnosine is highly concentrated in the brain and muscles, but these levels drop with encroaching age .
Apart from the fact that it is an antioxidant and glycation-fighting nutrient, L-Carnosine also acts as a PH buffer that protects muscle cell membranes from oxidation during muscular exertion. Cells and tissues benefit throughout the body from this compound which would otherwise yield to the adverse effects of aging.
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Carnosine first appeared in the mainstream health community around a decade ago in the form of supplements, eyedrops, and skin creams; mostly from companies who touted Carnosine as an elixir of youth. Fast forward ten years and a ton of research have shown that Carnosine‘s benefits stretch well beyond anti-aging.
Health Benefits of Carnosine
1) Carnosine is Anti-Aging & Promotes Longevity
In rat studies, Carnosine levels have been shown to decline with age (R).
A number of experiments carried out in Australia showed that Carnosine reinvigorates cells as they approach senescence (the stage just before they die when the cell is not functioning). Cells were given Carnosine actually looked and behaved younger than untreated cells (R, R1).
Importantly, Carnosine reversed the signs of aging in these senescent (nearly dead) cells. This means that Carnosine is a great hack for older people who want to look younger, as well as those who want to continue looking young (R, R1).
Signs of cellular aging soon reappeared when Carnosine was taken away from the cells. Therefore, it’s probably necessary to take Carnosine long term to achieve continued benefits (R).
In a Russian study on mice, 44% of the mice given Carnosine had young, healthy looking fur into old age, compared to just 5% of the untreated mice. Similarly, 9% of the untreated mice behaved youthfully in old age, whereas 58% of the mice treated with Carnosine showed youthful vigor (R, R1).
Protein glycation involves the reaction of protein and sugars in the blood stream. This reaction damages the proteins involved and is a major factor in aging. Carnosine has been shown to protect cellular proteins from damage in the following ways:
Carnosine bonds with the carbonyl/aldehyde groups that would otherwise bind with and damage proteins (R).
Carnosine limits the formation of oxidized sugars, commonly known as Advanced Glycosylation End-products (AGEs) by acting as an antioxidant. From an anti-aging perspective, the fewer AGEs created in your body the better (R, R1).
Vegetarians have higher levels of these AGEs than omnivores. This may be because of the absence of Carnosine in vegetarian diets – although high fructose consumption could also play a role (R).
When placed in the connective tissue of rats, Carnosine promoted the production of vimentin. It has been suggested that vimentin plays an important role in the elimination of oxidized proteins (via oxidized protein hydrolase) that contribute to aging (R, R1).
Carnosine prevents lipid, DNA, and protein damage by removing harmful metals via chelation (R).
Carnosine glycates easily and, in doing so, may spare important proteins, such as Hsc-70, from glycation that, if sustained, contributes to aging (R).
Supplementing Carnosine to the food of fruit flies resulted in a 20% increase in the average lifespan of males, but no change in the average life span of females (R).
In one study, Carnosine administered to the brain increased blood cortisone levels, which have been linked to increased lifespan of human fibroblast cells (R).
In agreement with this, human fibroblast cells treated with Carnosine had longer lifespans (413 days versus up to 139 days for the control cells) (R).
Although speculative, some researchers have suggested that there is a relationship between the life-extending properties of anti-convulsants and their ability to increase Carnosine levels (R, R1).
2) Carnosine Helps Fix Mitochondria
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Italian researchers found that mice given Carnosine had a complete reversal of age-related mitochondrial dysfunction. The improvement was so dramatic that the treated mice actually had better mitochondrial function than normal, healthy mice (R).
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3) Carnosine May Heal the Gut
In a cell study, Zinc Carnosine decreased damage to the hair-like structures, called villi, that line the gut (R).
Zinc Carnosine was able to protect against a drug (indomethacin) that would otherwise cause leaky gut (R).
Indomethacin triggers the death of RGM1 cell – a type of cell found in the mucosal membrane of mouse guts. Zinc Carnosine prevented this (R).
When the stomach is exposed to bacteria, Zinc Carnosine decreases the production of inflammatory cytokines – the sort of inflammation that would cause bloating and discomfort (R).
4) Carnosine is Neuroprotective and Prevents Neurodegeneration
Malondialdehyde (MDA) is a toxic end-product of lipid peroxidation. A study on rats showed that Carnosine protects against MDA-induced toxicity, and inhibits protein modification caused by MDA (deleterious formation of cross-links and carbonyl groups) (R).
Taking common anesthetics often results in an increase in serotonin-derived melanoid (SDM). Carnosine protects against the neurotoxic effects of SDM. Therefore, Carnosine may be an important tool for limiting postoperative cognitive dysfunction (R).
Carnosine was shown to protect the mitochondria of cultured brain cells (astroglia) against nitric oxide-induced damage (R).
In mice, Carnosine prevents the swelling, cell death, and free radical stress that occurs when the brain is starved of blood (R).
In mice, treatment with Carnosine significantly improved neurological function after a stroke-like event (R).
Animal studies definitively show that Carnosine can affect brain function & activity (R, R1).
That Carnosine can affect neurological function is no surprise seeing as Carnosine is produced by the brain and that Carnosine-specific transporters are found in parts of the blood–brain barrier (R).
In mice, Carnosine is able to protect against cognitive decline induced by a high fat diet – possibly by neutralizing cytotoxic unsaturated aldehydes caused by a high-fat diet (R).
Because of Carnosine’s affinity for zinc ions, it is likely that it plays some role in controlling the availability of zinc ions in neuronal tissue, especially the olfactory lobe where both Carnosine and zinc are found in high amounts (R). This is important because the olfactory lobe controls smell – a loss of which is the first sign of neurodegeneration (R, R1). (Ghanbari et al., 2004; Kovaks, 2004)
Carnosine increases mental capability in schizophrenics (R).
5) Carnosine Improves Memory
Memory
One study found that after 3 months of Carnosine supplementation at 500mg/day, patients performed better on verbal episodic memory tests (R).
Similarly, another study demonstrated improved verbal episodic memory in elderly people when they were given a combination of Anserine & Carnosine (R).
Carnosine, when combined with other compounds, such as polyphenols from blueberry and green tea and other amino acids, was shown to maintain the health of existing neurons and to promote neurogenesis (R).
6) Carnosine is an Anti-Depressant
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Studies have shown that Carnosine has antidepressant activity in rats (R).
7) Carnosine Regulates the Immune System and is Anti-inflammatory
Carnosine was found to lower excessive immune responses in patients who have overactive immune systems. At the same time, Carnosine increases the immune response in those with under-active immune systems (like the elderly) (R).
This dual, regulatory ability of Carnosine makes it a vital tool for people with delicate immune systems, such as those with allergies and autoimmune conditions (R).
In rats, Carnosine decreases IL-1a and normalizes levels of gamma-glutamyltransferase (R).
In brain tissues, Carnosine reduces inflammation by lowering TNF-a as well as nitric oxide synthesis (R).
Zinc-Carnosine has been shown to down-regulate pro‐inflammatory cytokine expression in gastric epithelial cells that are exposed to Helicobacter pylori (R).
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8) Carnosine May Treat Cancer
Cancer
The anti-tumor properties of Carnosine were recognized more than three decades ago (R)
Carnosine limits DNA damage that can transform healthy cells into cancerous cells (R).
Carnosine inhibits tumor growth and helps prevent the spreading of existing cancers (metastasis) to healthy tissue (R, R1).
Carnosine lowers ATP levels in cancer cells, thereby depriving them of the energy they need to develop (R).
The inclusion of dietary Carnosine in vitamin E-deficient rats increased the time period from exposure to a carcinogen to the development of a tumor (R).
By modifying MMP-9 gene expression, Carnosine was able to stop the spreading of liver cancer by inhibiting the cell migration and invasion of SK-Hep-1 cells (R).
Carnosine decreases AGEs, in vivo and in-vitro, which are commonly implicated in cancer (R).
Carnosine increases the efficacy of chemotherapeutic drugs, like 5-FU (R).
In neck cancer, Carnosine reduced the number of cancer cells (by binding to caspase 3) (R).
Carnosine, when combined with a protein shell (capsid) of an oncolytic adenovirus, caused cell death in lung cancer cells by enhancing viral replication and affecting the expression of Hsp27r (R).
By reducing mitochondrial oxidative stress, Carnosine slows the aging of cells that leads to ovarian cancer (R).
Cancer cells exposed directly to Carnosine showed less ability to thrive or proliferate and increased frequency of death (R).
Note that when pyruvate or other metabolic intermediates (oxaloacetate and a-ketoglutarate) are present, Carsonine’s anti-cancer properties appear inhibited (R).
9) Carnosine May Prevent & Treat Alzheimer’s Disease
Low blood levels of Carnosine have been associated with Alzheimer’s (R).
Carnosine may prevent Alzheimer’s by counteracting the build up of aldehydes and amyloid plaques, which are widely considered to be the primary causes of Alzheimer’s (R).
The aggregation of beta amyloid into fibrillar structures contributed to Alzheimer’s disease. Carnosine was found to impede the formation of fibrillar structures by altering the hydrogen bond network involved in fibrillogenesis (R).
Research has demonstrated that introducing beta amyloid to cultured rat brain cells causes toxic effects, but that this damage could be significantly lowered by adding Carnosine to the mixture (R).
It has been proposed that Carnosine’s protective activity against the toxicity of beta amyloid is exerted via regulation of glutamate release (R).
By protecting the brain against free radical and advanced glycation end-products (discussed below), Carnosine may provide a useful tool for tackling Alzheimer’s (R, R1, R2).
Carbonic anhydrase (CA) is lower in Alzheimer’s patient brains. CA activators improve learning in animals. Carnosine acts as a CA activator (R).
An imbalance of naturally occurring metals, such as copper, iron, and zinc have all been reported to play an important role in exacerbating Alzheimer’s pathology. Carnosine is able to chelate these metals (R, R1).
As mentioned above, Carnosine supplementation decreases the formation of AGEs. Increased levels of AGEs in the spinal fluid are associated with Alzheimer’s (R).
10) Carnosine May Treat Parkinson’s Disease
Carnosine reduces the formation and promotes the breakdown, of abnormal proteins that are a cause of Parkinson’s (R).
It is thought that mitochondrial dysfunction as a result of oxidative damage plays an important role in Parkinson’s. Carnosine has been shown to suppress the type of oxidative damage linked with Parkinson’s (R).
MPTP is a neurotoxin that induces symptoms akin to Parkinson’s (short term tremor, weight loss, rigidity etc.). One study found that, in animals, Carnosine (100mg/kg for 14 days) decreased the severity of MPTP-induced symptoms. This corresponded with lower levels of protein carbonyls, lipid hydroperoxides, and monoamine oxidase-B activity in their brains (R).
Studies have shown that patients with Parkinson’s often have damaged glyceraldehyde dehydrogenase, an important enzyme found in the frontal cortex of the brain. This damage leads to decreased ATP production and increased production of the highly toxic agent, methylglyoxal. Carnosine protects against damage to the glyceraldehyde dehydrogenase enzyme (R).
Carnosine promotes protein balance by decreasing methylglyoxal, which is often raised in those with Parkinson’s (R).
The brain’s substantia nigra, the section where dopamine is made, is prone to reaction with methylglyoxal, especially in the presence of high blood sugar. This harmful reaction, which makes ACTIQ, is prevented by Carnosine (R).
Carnosine inhibits malondialdehyde (MDA) toxicity in neuronal cells and limits the formation of protein carbonyls and protein cross-linking associated with Parkinson’s (R).
L-dopa is often used as a way to maintain dopamine levels in Parkinson’s sufferers. Unfortunately, some of the by-products of L-dopa are neurotoxic (e.g. those containing aldehyde groups). Carnosine neutralizes these toxic compounds and, therefore, is probably a fantastic supplement to combine with L-dopa therapy (R).
In fact, one study showed that a combination of L-dopa and Carnosine treatment (1.5 g/day) improved a number of neurological symptoms, such as rigidity of the hands and legs, and increased hand movement and leg agility. This corresponded to a decrease in protein carbonyls in blood plasma (R).
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11) Carnosine Is Beneficial For Diabetics/Pre-Diabetics
Studies show that people who are diabetic or pre-diabetic have low concentrations (63% below normal) of Carnosine in their muscle and brain cells (R).
Obese individuals who were given Carnosine had a decrease in their blood sugar levels (R).
Carnosine strengthens the sympathetic and parasympathetic nerves that communicate with the adrenal glands, liver, kidney, pancreas, stomach, and white and brown fat tissues; all important regulators of blood sugar levels, not to mention blood pressure, appetite, fat cell death, and the burning of fat (R).
As well as stabilizing blood sugars in diabetics, Carnosine also protects against the many complications of diabetes, such as organ failure, hearing loss, osteoporosis, eye problems, heart damage and more (R, R1, R2, R3).
People with diabetes often have peripheral neuropathy – a condition where the nerves in the body’s extremities (hands, feet, and arms) are damaged. Carnosine can prevent pain associated with this condition (R).
Carnosine can prevent the formation of glycated low-density lipoprotein which can stimulate the formation of foam cells that are linked with circulatory disorders commonly seen in diabetics (R).
12) Carnosine Makes Wounds Heal Faster
One study that treated rodents with Carnosine (100mg/kg internally and applied topically) found that Carnosine significantly improved wound healing by increasing the expression of beneficial growth factors and cytokines (R).
A cell study found that Carnosine increased the ability of human dermal fibroblasts (the cells that encourage skin healing) and microvascular endothelial cells (the cells that regenerating blood vessels after an injury) to function optimally in the presence of high glucose. Therefore, Carnosine may be an important tool for encouraging wound healing in groups who typically have high blood sugars (e.g. elderly and diabetics) (R).
13) Carnosine Protects Against Lack of Blood Flow
Rats treated with Carnosine prior to having blood flow restricted to their livers for 2 hours exhibited far less liver damage (e.g. tissue & cell death) than the untreated rats. Therefore, Carnosine might be useful as a preventative treatment to protect tissues against a lack of blood flow and hypoxia (R).
14) Carnosine May Help You Detox Metals
Carnosine is able to chelate metal ions (R).
Carnosine has been shown to form complexes with calcium, copper, and zinc ions (R, R1).
15) Carnosine May Protect the Heart
Studies have shown that Carnosine can improve cardiac function, possibly by regulating cellular calcium levels – as Carnosine has been shown to do in rats (R, R1).
Carnosine provides protection against the hardening of arteries (R).
16) Carnosine May Improve Physical Performance
Several studies have reported that β-alanine (precursor of Carnosine) supplementation can increase high-intensity exercise performance, lean muscle gains, increase VO2 max and speed up training adaptations. The mechanism behind these effects are not fully understood but are at least partly attributable to Carnosine’s ability to increase muscle buffering capacity (R).
17) Carnosine May Treat Epilepsy
A study on rats who were given artificially induced seizures found that administration of Carnosine (at 500mg/kg) decreased the severity and duration of seizures (R).
These results indicate that Carnosine is a powerful anticonvulsant that, in future, could be used as an anti-epileptic drug with few side effects (R, R1).
18) Carnosine Protects Bone Health
Carnosine-zinc complexes (Zinc Carnosine) have been shown to treat and reverse bone loss in animal and human models by stimulating bone growth by osteoblasts (R, R1).
It is speculated that Carnosine may enhance the anabolic (growth) impact of estrogen on bone growth (R).
Carnosine reduces glycation, a process which can cause problems with bone mechanics by causing damage to osteoblast function (R, R1).
When placed in the connective tissue of rats, Carnosine promoted the production of vimentin, a cell protein important for the maintenance of bone integrity (R).
19) Carnosine Lowers Blood Pressure
Carnosine lowers blood pressure through vasodilation (opening blood vessels). One mechanism by which it achieves this is by increasing nitric oxide production (R, R1).
20) Carnosine May Protect Against Chemotherapy
Carnosine protects the bone marrow cells of mice against genetic damage caused by the chemotherapy drug, cyclophosphamide. Carnosine’s antioxidant properties reduced the oxidative stress and genetic toxicity of the drug (R).
21) Carnosine Protects the Liver
In mice, Carnosine protects against alcohol damage: Following 3 weeks of alcohol poisoning, Carnosine treatment lowered liver MDA (raised during liver injury) levels by 40%, increased liver glutathione levels and down-regulated inflammatory cytokine production (R).
Carnosine can prevent and repair chemical alterations and structural damage to the liver caused by excessive alcohol. Therefore Carnosine might be a useful supplement to take next time you drink (R).
Carnosine prevented cell death, swelling, and thickening of the connective tissue in carbon tetrachloride-induced liver injury. These changes corresponded decreased levels of TNF-a, and a normalization of IL-10 levels (R).
In rats with injured livers, Carnosine reduced oxidative stress by balancing the levels of Nrf-2 (R).
22) Carnosine Prevents Deafness
Carnosine was able to protect against the loss of hearing caused by antibiotics and other drugs. The mechanism by which this happens is unclear but it could be a result of Carnosine’s antioxidant properties; reactive oxygen species (ROS) has been repeatedly linked with deafness in both humans and animals (R).
23) Carnosine Increases Rates of Reproduction
Yeast, raised on a glucose medium, reproduced far quicker in the presence of Carnosine (R).
24) Carnosine Helps Regulate the Nervous System and Reduce Glutamate
Carnosine strengthens the sympathetic and parasympathetic nerves that communicate with the adrenal glands (R).
The kidney brush border possesses a Carnosine transport system and Carnosine has been shown to influence sympathetic nervous system activity in the kidney (R, (R1).
Carnosine increases GABA, reduces glutamate and increases nervous system transporters (GLT-1 & EAAC1) (R).
25) Carnosine Promotes Eye Health
Russian studies have verified that Carnosine prevents cataracts, probably via a combination of its antioxidant and anti-glycating properties (R).
The use of Carnosine-containing eye-drops for 2 to 6 months reduced vision deficiencies (measured by lens opacity & visual acuity) that are usually a side effect of cataracts (R, R1).
26) Carnosine Prevents Hangovers
It is thought that acetaldehyde generation is a major source of hangovers experienced after drinking alcohol. Seeing as Carnosine has been proven to react with acetaldehyde and protect cultured human fibroblasts and lymphocytes against its toxicity (R), it is likely that Carnosine supplementation is an effective way to prevent ‘hangovers’ , while also protecting the brain and other important tissues against alcohol-induced glycol-oxidative damage (R).
Cautions
By most accounts, Carnosine is non-toxic and perfectly safe (R).
It is theoretically possible that Carnosine may compromise blood clotting by inhibiting the enzyme, serum transglutaminase. However, at this point, this suggestion is purely speculative and I wouldn’t worry about it (R).
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