Beta Alanine

 GENERAL EFFECTS:

• Beta-alanine is the rate-limiting precursor for carnosine synthesis. Carnosine is a dipeptide found in high levels in muscles and brain.

• Carnosine levels decline with age (2015). Supplementing with beta-alanine has been shown to increase carnosine levels.

• Carnosine has antioxidant properties and can protect cells from oxidative damage. Oxidative stress is a major contributor to aging.

• Carnosine can reduce formation of advanced glycation end-products (AGEs). AGE accumulation is associated with aging and age-related diseases.

• Carnosine may help reduce inflammation. Chronic inflammation increases with aging.

• In animal studies, it extended the lifespan of rotifers, fruit flies and laboratory mice. Mechanisms likely involve antioxidant effects, AGE reduction, and improved protein homeostasis.

• Animal studies demonstrate carnosine can bind to and neutralize formaldehyde, a toxic compound. A rat study showed carnosine supplements reduced oxidative damage and improved learning impairments caused by inhaled formaldehyde.

• Human data is limited. Some studies show improved exercise capacity and cognition in the elderly with beta-alanine supplementation.

• Human studies find lower carnosine levels in patients with diseases like Alzheimer's and autism that have been linked to formaldehyde toxicity. However, direct evidence of carnosine's protective effects in humans is still lacking.

• Optimal dosing is not established. Doses of 800-3000 mg beta-alanine per day are commonly used, split into multiple servings.

EFFECTS ON CANCER:

• Some users report life-changing relief from severe itching from polycythemia vera.

• Reduced cancer growth significantly in cell and mice studies across cancers: Breast, renal, cervical, pancreatic etc. 

• Animal and cell studies show carnosine and beta-alanine inhibit growth and proliferation in many cancer cell types through various proposed mechanisms. These include reducing ATP energy production, inhibiting cell signaling pathways like mTOR, decreasing inflammation, and buffering lactic acid.

• Small human studies provide preliminary evidence of anticancer effects, but larger clinical trials are required to verify optimal dosing, safety and efficacy in humans.

EFFECTS ON EXERCISE (REF): 

• Beta-alanine is a popular ingredient in pre-workout stacks.

• Beta-alanine is a non-essential amino acid that combines with histidine to form carnosine in muscles. 

• Carnosine acts as a buffer against acid buildup during high-intensity exercise, reducing fatigue. Secondary to that, at improving time to exhaustion.

• Supplementation enhances muscular endurance. Many people report being able to perform one or two additional reps in the gym. Also improves moderate- to high-intensity cardiovascular exercise performance.

• Acts as an acid buffer in the body. Carnosine is stored in cells and released in response to drops in pH. Increased stores of carnosine can protect against diet-induced drops in pH (which might occur from ketone production in ketosis, for example), as well as offer protection from exercise-induced lactic acid production.

• Beta-alanine may aid older adults by improving muscle endurance and function.

• Typical dosage is 2-5 grams per day, split into smaller doses throughout the day.

• Side effects can include flushing, tingling, and numbness but are usually mild.

• It appears safe overall but long-term studies are limited.

Examine.com

https://examine.com/supplements/beta-alanine/

Can beta-alanine treat cancer?

[Breast Cancer] β-alanine treatment reduces extracellular acidity, a constituent of the invasive microenvironment that promotes progression, we investigated the effect of β-alanine on breast cell viability and migration. β-alanine was shown to reduce both cell migration and proliferation without acting in a cytotoxic fashion. Moreover, β-alanine significantly increased malignant cell sensitivity to doxorubicin, suggesting a potential role as a co-therapeutic agent.

[RCC & Cervical Cancer] Our experimental data suggest that β-alanine may be a potential anti-tumor agent exhibiting several anti-cancer effects in renal and cervical tumor cells. 

[Pancreatic Cancer] βA supplementation reprograms cell metabolism by normalizing energy production and reducing microenvironment acidification, thus enhancing chemo-sensitivity in Gem resistant PDAC cells and xenografts. βA can be potentially used as a co-therapeutic in Pancreatic ductal adenocarcinoma (PDAC).

Does beta-alanine make you gain weight?

Beta alanine does nothing to boost muscle gain or burn fat, rather, it buffers against acid build up which then allows the individual to work out harder and longer. The net result of this is of course greater muscle gain and fat loss.

Does beta-alanine give you energy?

Beta-alanine can fuel the athlete in all of us. As the go-to ingredient for sports nutrition formulations, beta-alanine helps build better muscle, faster. It helps us gain focus, energy, and strength. When it comes to enhancing muscle strength, power, growth, and endurance, beta-alanine is the athlete's secret weapon.

β-Alanine intercede metabolic recovery for amelioration of human cervical and renal tumors, 2017 (link)

β-Alanine is a non-essential amino acid and presents as a major component of various sports supplements. It is a non-proteogenic amino acid, formed in vivo by degradation of carnosine, anserine, balenine, and dihydrouracil. The present study was aimed at investigating the anti-tumor effects of β-alanine in renal and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis were used to measure cell viability. Lactate dehydrogenase (LDH) expression was analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine triphosphate (ATP) content was measured using bioluminescence method. Cell migration was determined by the simple standard-scratch method. β-Alanine reduced renal and cervical cell growth significantly. Percentage of inhibition of renal and cervical tumor cells was increased at higher concentration of β-alanine. LDH expression and ATP content were significantly reduced in renal and cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell migration were significantly reduced following 10 and 100 mM of β-alanine treatment. In our study, β-alanine exerts no significant effect on normal MDCK cells except a marginal effect at the highest concentration (100 mM). In summary, our experimental data suggest that β-alanine may be a potential anti-tumor agent exhibiting several anti-cancer effects in renal and cervical tumor cells.

β-alanine suppresses malignant breast epithelial cell aggressiveness through alterations in metabolism and cellular acidity in vitro, 2014

Background: Deregulated energetics is a property of most cancer cells. This phenomenon, known as the Warburg Effect or aerobic glycolysis, is characterized by increased glucose uptake, lactate export and extracellular acidification, even in the presence of oxygen. β-alanine is a non-essential amino acid that has previously been shown to be metabolized into carnosine, which functions as an intracellular buffer. Because of this buffering capacity, we investigated the effects of β-alanine on the metabolic cancerous phenotype.

Methods: Non-malignant MCF-10a and malignant MCF-7 breast epithelial cells were treated with β-alanine at 100 mM for 24 hours. Aerobic glycolysis was quantified by measuring extracellular acidification rate (ECAR) and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR). mRNA of metabolism-related genes was quantified by qRT-PCR with corresponding protein expression quantified by immunoblotting, or by flow cytometry which was verified by confocal microscopy. Mitochondrial content was quantified using a mitochondria-specific dye and measured by flow cytometry.

Results: Cells treated with β-alanine displayed significantly suppressed basal and peak ECAR (aerobic glycolysis), with simultaneous increase in glucose transporter 1 (GLUT1). Additionally, cells treated with β-alanine exhibited significantly reduced basal and peak OCR (oxidative metabolism), which was accompanied by reduction in mitochondrial content with subsequent suppression of genes which promote mitochondrial biosynthesis. Suppression of glycolytic and oxidative metabolism by β-alanine resulted in the reduction of total metabolic rate, although cell viability was not affected. Because β-alanine treatment reduces extracellular acidity, a constituent of the invasive microenvironment that promotes progression, we investigated the effect of β-alanine on breast cell viability and migration. β-alanine was shown to reduce both cell migration and proliferation without acting in a cytotoxic fashion. Moreover, β-alanine significantly increased malignant cell sensitivity to doxorubicin, suggesting a potential role as a co-therapeutic agent.

Conclusion: Taken together, our results suggest that β-alanine may elicit several anti-tumor effects. Our observations support the need for further investigation into the mechanism(s) of action and specificity of β-alanine as a co-therapeutic agent in the treatment of breast tumors.

Metabolic reprogramming with β-alanine to overcome chemotherapy resistance in pancreatic cancer, 2019

Background: Increased aerobic glycolysis (Warburg effect) leading to acidic microenvironment confers chemoresistance to weakly basic Gemcitabine, the standard treatment in Pancreatic ductal adenocarcinoma (PDAC). Metabolomic perturbations in two PDAC cell lines having differential sensitivity to Gemcitabine was investigated by profiling over 40 metabolites using 1H-NMR spectroscopy. Notably, a significant decrease in the concentration of β-alanine (βA) was observed in Gem resistant compared to Gem sensitive cell line, suggesting βA may have a role in chemotherapy response. We aimed to evaluate the role of βA supplementation in improving Gem efficacy in Gem resistant cell lines

Methods: PDAC Panc-1 cell line extracts treated with Gem with and without βA supplementation were analysed via 1H-NMR spectroscopy. Aerobic glycolysis was quantified by measuring extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) using the Seahorse XF analyser platform. Global mRNA profiling was done by Next Generation Sequencing. Proliferation, migration and cell cycle analysis was measured by Xcelligence real time cell analysis system and flow cytometry, respectively. PANC-1 and BxPC-3 tumor xenografts treated with Gemcitabine with and without βA for 4 weeks and the tumor volumes and weights were measured.

Results: βA supplementation in Gem resistant cells results in: (1) decreased basal glycolytic rate, proton leak and ATP production; (2) increased pyruvate, decreased lactic acid and NAD+ concentrations with decreased LDH-A transcription; also increased carnosine levels with a more basic pH in the conditioned media; (3) enhanced sensitivity to Gem treatment, with a significant reduction in proliferation, cell migration, and increased apoptosis and relative hENt-1 mRNA levels and (5) xenograft tumor volumes and weights were significantly reduced upon βA supplementation.

Conclusion: βA supplementation reprograms cell metabolism by normalizing energy production and reducing microenvironment acidification, thus enhancing chemo-sensitivity in Gem resistant PDAC cells and xenografts. βA can be potentially used as a co-therapeutic in PDAC.

Can anyone suggest anything to do about severe itching from polycythemia vera. Thank you.

Changed my life: Nutricost Beta Alanine Powder 300 Grams (10.6oz) - 3 Grams Per Serving

Carnosine and beta-alanine from a supplement that increase physical performance to potent anticancer agent, Jose de Felippe Junior

L-carnosine is a dipeptide formed by the amino acids Beta-alanine and L-histidine. It is believed that L-carnosine (beta-alanyl-L histidine) inhibits the senescence of somatic cells and thus exhibits their anticancer activities. It is a naturally occurring substance with a high potential to inhibit the growth of neoplastic cells, socalled “malignant” cells, in vivo. Carnosine mimics rapamycin, a powerful mTOR inhibitor.

Carnosine has an anti-inflammatory effect, neurotransmitter, aldehyde scavenger, works as organic pH buffer and metal chelator. It has therapeutic potential

in Alzheimer’s disease, stroke, diabetes and vision disorders.

Beta-alanine administration increases carnosine tissue concentration through carnosine synthetase. In this way, carnosine-synthetase-rich neoplastic tissues

generate carnosine from Beta-alanine causing a decrease in proliferation, increased apoptosis and increased cell differentiation. It is important to know that

glioblastoma multiform is very rich in the enzyme carnosine synthetase.

The usual dose of L-carnosine is 400mg twice daily. The usual dose of beta-alanine is 800-1000mg 3 times daily in fasting. The smell of carnosine is unbearable

for many people.

The carnosine formula is C9H14N4O3, molecular weight 226.3 g/mol, known as: L-Carnosine, Carnosine, Beta-Alanyl-L-histidine, Ignotine, Karnozin and Karnozzin. It donates 4 electrons and is acceptor of 5: oxidant molecule.

We prefer to use beta-alanine.

Carnosine or Beta-alanine molecular targets on malignant gliomas

1. Decrease cell proliferation in vitro and in vivo.

2. Increases apoptosis or necrosis.

3. Mimetizes caloric restriction.

4. Mimetizes rapamycin and inhibits mTOR.

5. Decreases anaerobic glycolysis.

6. Drastically decreases the ATP production of the glycolytic pathway of T98G malignant glioma and does not interfere in the mitochondrial pathway.

7. Scavenger of reactive oxygen and aldehyde species.

8. Inhibits carbonic anhydrase – CAIX and acidifies the cytoplasm.

9. Decreases ERK pathway activation and decreases mitotic proliferation.

10. Inhibits ERK1/2.

11. Stops the cell cycle in G1/S.

12. Inhibits p38 MAP Kinase.

13. Inhibits Akt phosphorylation.

14. Inhibits the PI3K/Akt proliferative pathway.

15. Inhibits proliferative pathway ras/MAP Kinase.

16. Inhibits initiation of RNA translation via eIF4E.

17. Decreases HIF-1alpha expression.

18. Inhibits EGFR-2 – erbB-2 tyrosine kinase family involved in cell cycle and differentiation.

19. Inhibits erbB-2.

20. Decrease DHL activity and decrease the generation of glycolytic ATP.

21. Carnosine induces inhibition of the proliferation of glioblastoma U-118-MG cells associated with decreased oxidative stress, increased SOD-Mn and

increased expression of cyclin D1 resulting in blocking the cycle in G2.

22. Carnosine decreases the proliferation of glioblastoma associated with “BCL2-associated athanogene 2” and “von Hippel-Lindau binding protein 1”

which links the action of carnosine to decrease HIF-1alpha signaling.

23. Carnosine inhibits the growth of cells isolated from human glioblastoma multiform. It reduces the activity of dehydrogenases and thus significantly decreases the generation of ATP. It reduces DNA synthesis by 10% to 50% depending on the culture. Inhibits cell proliferation.

24. Carnosine inhibits glycolytic ATP production in malignant glioma, T98G.

25. Decreased circulating carnosine dipeptidase-1 is associated with poor prognosis and cachexia.

26. Aldehyde dehydrogenase increases stem cells proliferation. Carnosine inhibits aldehyde dehydrogenase.

27. Carnosine increases expression of SOD-Mn and cyclin B1 and inhibits proliferation of glioblastoma U-118-MG cells.

28. In normal astrocytes, mitochondrial respiration accounts for 80% of total cellular respiration and 85% of ATP synthesis. Carnosine in normal astrocytes

reduces the cellular ATP concentration by 42%.

29. Carnosine selectively inhibits migration of IDHwild type glioblastoma cells in a co-culture model with fibroblasts (Oppermann-2018).

Carnosine or Beta-alanine. Molecular targets in other neoplasias

1. Carnosine and rapamycin (sirolimus) inhibit glycolytic activity, stimulate proteolysis, and modulate protein synthesis at the translational level, both of

which inhibit the onset of translation via effects on eukaryotic translation initiation factor 4E (eIF4E).

2. Carnosine decreases the proliferation of NIH3T3 fibroblasts expressing HER2/neu (human epidermal growth factor receptor 2) in vivo. Fibroblasts implanted in the mouse.

3. Carnosine reacts strongly with aldehyde groups and keto groups of sugars in the Amadori reaction and thus depletes certain intermediates of glycolysis: one of the anticancer mechanisms.

4. Immune System

a) Suppresses sympathetic activity of the spleen, increases the activity of Natural-Killer cells and decreases the proliferation of colorectal cancer.

b) Non-specific increase in immune system function.

5. Breast cancer

a) Beta-alanine suppresses the aggressiveness of breast cancer epithelial cells through changes in metabolism and cellular acidity in vitro.

b) Beta-alanine suppresses glycolytic and oxidative metabolism and decreases metabolic rate, without altering cell viability, in the MCF-7 line of breast cancer. It reduces extracellular acidity and decreases invasion and metastasis. Increases glucose uptake into cells via increased GLUT-1.

6. Gastric cancer

a) Decrease of circulating carnosine dipeptidase-1 is associated with poor prognosis and cachexia.

b) Carnosine does not induce apoptosis or necrosis in gastric cancer cells, SGC-7901, however, reduces its proliferation through the inhibition of

mitochondrial and glycolytic respiration.

c) Carnosine inhibits the proliferation of gastric carcinoma cells by delaying the Akt/mTOR/ p70S6K signaling pathway. It mimics the rapamycin and thus inhibits mTOR.

7. Hepatoma

a) Inhibits metastasis of hepatocarcinoma by inhibiting the expression of MMP-9 and inducing the anti-metastatic gene nm23-H1 in SK-Hep-1 strain.

b) Anti-carcinogenic effects of L-carnosine on human liver carcinoma cells SNU-423. There is a significant decrease in proliferation in a dose-dependent manner (Ding, 2018).

8. Colorectal cancer

a) Inhibits the proliferation of colorectal cancer: decreases glycolytic ATP, decreases mitochondrial ROS, decreases via ERK1/2 and increases protein p21waf1.

b) Decreases HIF1-alpha and induces apoptosis in HT29 colon cancer cells.

c) Decreases HIF1-alpha and induces apoptosis in HT29 cells of 5-fluoracil resistant colon cancer.

d) Decrease HIF-1 expression in human colon cancer HCT-116 cells.

e) Anti-proliferative effect of L-carnosine correlates with decreased HIF1-alpha expression in colon cancer cells, HCT-116.

f) In the HCT116 line, the activation of the KRAS mutation induces the production of free radicals of oxygen (ERTOS) mitochondrial, which increases neoplastic proliferation. Carnosine inhibits KRAS, decreases the proliferation of HCT116 cells from colon cancer by decreasing ATP and ERTOS, and induces cell cycle arrest in G1. These feats are related to ERK1/2 pathway decrease and p21waf1 protein increase.

g) Carnosine has protective effect against oxidative stress in intestinal epithelial cells.

h) Carnosine activates the CREB pathway and CREB-related pathways by activating Ca++ related pathways in Caco-2 colon cancer cells which regulate genes of the intestinal mucosa.

i) L-carnosine induces apoptosis and cell cycle arrest via suppression of NF-kappaB/STAT1 in HCT116 colorectal cancer cells (Lee, 2018).

9. Cervical cancer

a) Carnosine inhibits cell growth by 23%, ERTOS increase by 30% in HeLa and MDCK cells (Madin-Darby Kidney Cells) and apoptosis occurs in 42 and 14% in normal and neoplastic cells, respectively.

b) Carnosine inhibits carbonic anhydrase IX that causes extracellular acidosis and suppresses growth of the HeLa tumor implanted in the mouse. I believe the following happened: extracellular acidosis caused intracellular acidosis that inhibited glycolysis and provoked tumor growth suppression.

c) Carnosine inhibits the proliferation of cervical carcinoma glandular cells, HeLa and SiHa (squamous cell carcinoma) by inhibiting mitochondrial and glycolytic bioenergetics, which slows the progression of the cell cycle. It reduces the activity of isocitrate dehydrogenase and malate dehydrogenase from the Krebs cycle and reduces the activity of the mitochondrial electron transport chain l, II, III and IV in HeLa cells, but not in SiHa. It induces cell cycle arrest in G1 by inhibiting the G1-S transition in both strains.

d) Carnosine inhibits the proliferation of HeLa human cervical carcinoma cells by inhibiting mitochondrial bioenergetics and glycolysis that delays the progression of the proliferative cell cycle. There is a decrease in mitochondrial and glycolytic ATP generation; reduction of isocitrate dehydrogenase and malate dehydrogenase activity; decrease in mitochondrial electron chain activity I, II, II, and IV and cell cycle arrest in G1 (Bao2018).

10. Ovarian cancer

a) Carnosine is an anticancer drug of real value in the prevention and treatment of intraperitoneal metastases of ovarian cancer.

11. Renal cancer

a) Carnosine activates caspase-3 in human renal carcinoma and inhibits proliferation in 40%.

12. Leukemia and Lymphomas

a) Antigenotoxic and antioxidant in culture of human lymphocytes.

13. Sarcoma

a) In murine sarcoma 180: decreases proliferation, prolongs survival and decreases mortality.

b) Antineoplastic effects of carnosine and beta-alanine on solid sarcoma 180: inhibits tumor growth and increases survival by 132%.

c) Carnosine and gallic acid inhibit MMP-2 and MMP-9 in HT1080 fibrosarcoma cells (Kim2014).

d) Beta-alanine inhibits PTHR1 (parathyroid hormone 1 receptor) and suppresses proliferation, adhesion, invasion, migration and carcinogenesis in human osteosarcoma metastatic U2OS. There is a decrease in mMP-2/9 mRNA expression, reduction of PTHR1 protein and mRNA and increase of tissue inhibitors of MMPs (Li2018).

e) Carnosine and beta-alanine in mice implanted with the solid tumor Sarcoma-180. Occurs tumor growth inhibition, prolongation of survival,

and decreased mortality (Nagai-1986).

f) Beta-2-thienyl-DL-alanine decreases the growth of sarcoma T241 in C57 black mice (Jacquez1953).

14. Renal carcinoma

a) Carnosine inhibited renal cancer cell growth up to 40%, whereas it was 25% in normal cells. Caspase-3 enzyme activity gradually increased in

renal carcinoma cells in a concentration-dependent manner that indicated apoptosis. It is suggested that the carnosine may be a potential antiproliferative agent in renal carcinoma tumor.

15. Metabolism

a) Reacts with AGE’s.

b) Slows aging.

c) Delays lactate accumulation during exercise by turning lactate into pyruvate.

d) Carnosine and Beta-alanine stimulate granulation and accelerate the healing of wounds, besides increasing immunocompetence, which accelerates the healing of the traumatized region.

Carnosine: A Longevity Factor, 2012

Carnosine is concentrated in the brain, heart, and muscles. Studies have shown that carnosine slows the aging of human cells and protects against age-inducing processes such as glycation and mitochondrial dysfunction. Carnosine levels in the body plummet as humans age, making supplementation a key component of an age-delaying program.

12. Snell TW, Fields AM, Johnston RK. Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations. Biogerontology. 2012 Jan 24.

Carnosine extends the life span of rotifers, a microscopic aquatic organism now being used as a model of aging in many laboratories.12 In this experiment, scientists tested many different antioxidant compounds, identifying carnosine as one of just four that had significant effects on the organisms’ longevity.

13. Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA. Effect of carnosine on Drosophila melanogaster life span. Bull Exp Biol Med. 2002 Jun;133(6):559-61.

14. Stvolinsky S, Antipin M, Meguro K, Sato T, Abe H, Boldyrev A. Effect of carnosine and its Trolox-modified derivatives on life span of Drosophila melanogaster. Rejuvenation Res. 2010 Aug;13(4):453-7.

Carnosine extends the life span of fruit flies, another organism commonly used to study aging, up to 20% in males.13,14 Normally, male fruit flies die much sooner than do females, but when fed a steady diet including a carnosine supplement, the males attained the same age as the females.

15. Boldyrev AA, Gallant SC, Sukhich GT. Carnosine, the protective, anti-aging peptide. Biosci Rep. 1999 Dec;19(6):581-7.

16. Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc). 2000 Jul;65(7):866-8.

Carnosine extends the life span of laboratory mice, complex, warm-blooded mammals with many of the aging features common to humans.15,16

Effect of Carnosine on Age-Induced Changes in Senescence-Accelerated Mice, 1999

The effect of carnosine on the life span and several brain biochemical characteristics in senescence-accelerated mice—prone 1 (SAMP1) was investigated. A 50% survival rate of animals treated with carnosine increased by 20% as compared to controls. Moreover, the number of animals that lived to an old age significantly increased. The effect of carnosine on life span was accompanied by a decrease in the level of ′-tiobarbituric acid reactive substances (TBARS), monoamine oxidase b (MAO b), and Na/K-ATPase activity. There was also an increase in glutamate binding to N-methyl-D-aspartate receptors. These observations are consistent with the conclusion that carnosine increases life span and quality of life by diminishing production of lipid peroxides and reducing the influence of reactive oxygen species (ROS) on membrane proteins.

Long-term supplementation with EGCG and beta-alanine decreases mortality but does not affect cognitive or muscle function in aged mice, 2017 

We have previously shown that 6weeks of a diet containing epigallocatechin gallate (EGCG) and beta-alanine (B-ALA) was not effective in improving either cognitive or muscle function in aged (18month) mice (Gibbons et al. Behav Brain Res 2014). However, diet reduced oxidative stress in the brain, and previous studies using longer-term interventions have documented beneficial effects in cognitive, but not muscle, function. Therefore, we investigated the effect of 6months of feeding on measures of cognitive and muscle function in mice. Mice (12months, N=15/group) were fed AIN-93M containing 0.15% EGCG and 0.34% B-ALA or standard AIN-93M for 6months, then underwent a battery of tests for cognitive and muscle function at 18months. Interestingly, a higher percentage of mice receiving EGCG and B-ALA (E+B, 80%) survived to study end compared to control (Ctrl, 40%) mice (p=0.02). E+B did not affect arm preference in the Y-maze test (p=0.74, novel arm) and did not alter performance in an active avoidance test (p=0.16, avoidances per 50 trials). E+B increased rotarod performance (p=0.03), did not affect grip strength (p=0.91), and decreased time to exhaustion in a treadmill fatigue test (p=0.02) compared to Ctrl. In conclusion, E+B reduced mortality, had no effect on cognitive function and variable effects on muscle function.

On the enigma of carnosine's anti-ageing actions, 2009

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.

I suffer from Itchy skin, Aquagenic Pruritus and change in temperature itch. Beta Alanine has been a game changer. I take 1,500 mg 30 mins before showering and have little – to no itch. I also take 750 mg when I get up in the morning and anytime during the day when I feel an itch coming on…and it stops the itch.

β-Alanine intercede metabolic recovery for amelioration of human cervical and renal tumors, 2017

Abstract and Figures

β-Alanine is a non-essential amino acid and presents as a major component of various sports supplements. It is a non-proteogenic amino acid, formed in vivo by degradation of carnosine, anserine, balenine, and dihydrouracil. The present study was aimed at investigating the anti-tumor effects of β-alanine in renal and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis were used to measure cell viability. Lactate dehydrogenase (LDH) expression was analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine triphosphate (ATP) content was measured using bioluminescence method. Cell migration was determined by the simple standard-scratch method. β-Alanine reduced renal and cervical cell growth significantly. Percentage of inhibition of renal and cervical tumor cells was increased at higher concentration of β-alanine. LDH expression and ATP content were significantly reduced in renal and cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell migration were significantly reduced following 10 and 100 mM of β-alanine treatment. In our study, β-alanine exerts no significant effect on normal MDCK cells except a marginal effect at the highest concentration (100 mM). In summary, our experimental data suggest that β-alanine may be a potential anti-tumor agent exhibiting several anti-cancer effects in renal and cervical tumor cells.

Integrated transcriptomic and metabolomic analysis shows that disturbances in metabolism of tumor cells contribute to poor survival of RCC patients

Purpose: Cellular metabolism of renal cell carcinoma (RCC) tumors is disturbed. The clinical significance of these alterations is weakly understood. We aimed to find if changes in metabolic pathways contribute to survival of RCC patients.

Material and methods: 35 RCC tumors and matched controls were used for metabolite profiling using gas chromatography-mass spectrometry and transcriptomic analysis with qPCR-arrays targeting the expression of 93 metabolic genes. The clinical significance of obtained data was validated on independent cohort of 468 RCC patients with median follow-up of 43.22months.

Results: The levels of 31 metabolites were statistically significantly changed in RCC tumors compared with controls. The top altered metabolites included beta-alanine (+4.2-fold), glucose (+3.4-fold), succinate (-11.0-fold), myo-inositol (-4.6-fold), adenine (-4.2-fold), uracil (-3.7-fold), and hypoxanthine (-3.0-fold). These disturbances were associated with altered expression of 53 metabolic genes. ROC curve analysis revealed that the top metabolites discriminating between tumor and control samples included succinate (AUC=0.91), adenine (AUC=0.89), myo-inositol (AUC=0.87), hypoxanthine (AUC=0.85), urea (AUC=0.85), and beta-alanine (AUC=0.85). Poor survival of RCC patients correlated (p<0.0001) with altered expression of genes involved in metabolism of succinate (HR=2.7), purines (HR=2.4), glucose (HR=2.4), beta-alanine (HR=2.5), and myo-inositol (HR=1.9).

Conclusions: We found that changes in metabolism of succinate, beta-alanine, purines, glucose and myo-inositol correlate with poor survival of RCC patients.

Effect of Carnosine or β-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis, 2021

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or β-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. 

Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-β, and HOMA-IR).

The model provides evidence that supplementation decreases 

fasting glucose [humans: mean difference (MD)0.5 = –0.95 mmol/L (90% CrI: –2.1, 0.08); 

HbA1c [humans: MD0.5 = –0.91% (90% CrI: –1.46, –0.39);

HOMA-IR [humans: standardized mean difference (SMD)0.5 = –0.41 (90% CrI: –0.82, –0.07)

fasting insulin [humans: SMD0.5 = –0.41 (90% CrI: –0.77, –0.07)].

Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner (link, link)

New research identifies formaldehyde, a molecule produced by the body's own metabolism, as a source of DNA damage that can accelerate aging and increase cancer risk in blood stem cells. The research found that formaldehyde causes DNA damage that triggers increased levels of the p53 protein, which speeds up aging in mice blood stem cells. This provides evidence that DNA damage drives aging in blood stem cells in a programmed way through p53 activation, rather than just through gradual accumulation of damage. The researchers suggest that if we can find ways to lower formaldehyde levels in cells, we may be able to slow this accelerated aging process and reduce cancer risk. The findings may be relevant not just for blood cancers but possibly other cancer types as well.