Research Update: Protect Against Formaldehyde ExposureJanuary 2019
By Cynthia Grotton
On a daily basis, we are often surrounded by the toxic chemical formaldehyde.
It is used in carpeting, wood products, automobiles, paper products, and even wrinkle-resistant clothing.1 E-cigarettes deliver a substantial concentration of formaldehyde.2
Scientists are recognizing that long-term, chronic exposure to low levels of formaldehyde poses a serious health threat. This pathology is similar to that posed by another problem: excess blood sugar.
High blood sugar and formaldehyde destroy cell structures by cross-linking the body’s proteins. When this happens as a result of high glucose levels, it is called glycation.
Emerging research shows that formaldehyde may be as destructive as excess glucose.
Formaldehyde may play a role in dementia, diabetes, and possibly depression.3 All three have been proposed to share a common cause, which is formaldehyde-induced crosslinking of the body’s proteins.
Crosslinking of the body’s proteins occurs in the presence of excess blood sugar. This causes formation of advanced glycation end-products that render portions of the body’s tissues non-functional.
Formaldehyde cross-linking and glycation are similar chemical processes. Exposure to formaldehyde may be implicated in accelerated aging.3
These destructive processes have a potential resolution: the supplement called carnosine.
What you need to know
Excess exposure to formaldehyde can increase cross-linking of cells, which results in accelerated aging and disease. In the scientific literature, Carnosine, a peptide molecule well known to have glycemic benefits, is showing it may prevent the damage caused by excess formaldehyde exposure.
Three Disorders of Aging: A Connection with Formaldehyde
Most physicians think of diabetes, dementia, and depression as three separate conditions that grow more common with aging. New research has proposed a fascinating possibility: that the ubiquitous environmental toxin formaldehyde interrupts the vital structure and function of proteins and DNA in our cells.
Not only that, but this same destructive formaldehyde-driven cross-linking speeds aging and raises our risk for age-related disorders,3 in a fashion similar to high blood glucose–driven glycation.
Many studies reveal associations between formaldehyde exposure and age-related problems, including glaucoma, stroke, Alzheimer’s disease, and cognitive decline.3-10 The fact that all these conditions have known links to glycation demonstrates that formaldehyde-caused cross-linking may be just as pernicious.11-14
Compounding the problem, formaldehyde has been shown to interfere with basic mitochondrial function.3,15,16 In preclinical studies, formaldehyde has been shown to contribute to memory decline and impair normal DNA function.3,10, 15-17
Since it is nearly impossible to avoid exposure to this ubiquitous toxin, the question is whether there’s a way to reduce its harmful effects.
The answer is yes, and it is found in carnosine.
Carnosine Combats Formaldehyde Effects
Carnosine (not to be confused with carnitine) has many functions in human biology. The most important function of carnosine is in protecting our proteins and DNA against deformation as a result of cross-linking.
Just as carnosine can protect against sugar-induced crosslinking (glycation), it also is now of interest for its ability to protect against formaldehyde-caused crosslinking.18
Further evidence of carnosine’s anti-crosslinking ability comes from how it neutralizes methylglyoxal,3,19,20 a byproduct of excessive blood sugar that has been associated with many of the complications of type II diabetes, including damage to eyes, brain, kidneys, and other organs.21-23
In cell cultures, carnosine delayed senescence, the cellular manifestation of aging that leads to tissue and organ failure.3,24
In addition to its ability to fight destructive cross-linking caused by formaldehyde and glucose, carnosine can inhibit the enzymes that break down neurotransmitters.25
Carnosine has been shown to react directly with formaldehyde, suppressing its ability to entangle DNA strands,18 while also stimulating mitochondrial activity.26-28
One recent animal study found that carnosine protected rats from the ill effects of acute formaldehyde inhalation.29 Elevated formaldehyde levels were found in the brains of age-accelerated lab animals,30,31 while carnosine supplementation delayed the onset of accelerated aging.31
These findings suggest that carnosine can react with and help neutralize formaldehyde while also suppressing the age-related generation of formaldehyde in the brain. Our bodies produce small amounts of toxic aldehydes as part of so-called normal metabolic process.3,17
Taken together these findings suggest that:
- Dementia, depression, and diabetes (type II) share potential relationships to formaldehyde exposure and toxicity.
- Carnosine directly prevents the formaldehyde- and glycation-induced cross-linking that makes our proteins and DNA dysfunctional.
These combined actions make carnosine an appealing defense against the ubiquitous presence of formaldehyde in our environments.3
Carnosine has long been regarded as a useful dietary supplement for its anti-aging benefits. This includes fighting oxidative stress and glycation.
Evidence now indicates that carnosine can defend our tissues from formaldehyde poisoning and the age-acceleration it brings.
New research suggests that chronic, low-level formaldehyde exposure may be linked to dementia diabetes, and possibly depression. Specifically, formaldehyde can disturb neurotransmitter and mitochondrial function, and by cross-linking with our proteins and DNA, it can alter myriad critical cell functions.
Carnosine fights destructive cross-linking caused by the toxin formaldehyde as well as from glucose-induced glycation.
It’s practically impossible to avoid formaldehyde, but supplementing with carnosine offers a way to help protect against its toxic, age-accelerating effects.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Available at: https://www.ncbi.nlm.nih.gov/books/NBK138711/. Accessed 20 November, 2017.
- Available at: https://www.nytimes.com/2018/04/04/opinion/formaldehyde-diacetyl-e-cigs.html. Accessed September 17, 2018.
- Hipkiss AR. Depression, Diabetes and Dementia: Formaldehyde May Be a Common Causal Agent; Could Carnosine, a Pluripotent Peptide, Be Protective? Aging Dis. 2017 Apr;8(2):128-30.
- Li T, Su T, He Y, et al. Brain Formaldehyde is Related to Water Intake behavior. Aging Dis. 2016 Oct;7(5):561-84.
- Song MS, Baker GB, Dursun SM, et al. The antidepressant phenelzine protects neurons and astrocytes against formaldehyde-induced toxicity. J Neurochem. 2010 Sep 1;114(5):1405-13.
- Li Y, Song Z, Ding Y, et al. Effects of formaldehyde exposure on anxiety-like and depression-like behavior, cognition, central levels of glucocorticoid receptor and tyrosine hydroxylase in mice. Chemosphere. 2016 Feb;144:2004-12.
- Cui Y, Su T, Zhang SD, et al. Elevated urine formaldehyde in elderly patients with primary open angle glaucoma. Int J Ophthalmol. 2016;9(3):411-6
- Tong Z, Wang W, Luo W, et al. Urine Formaldehyde Predicts Cognitive Impairment in Post-Stroke Dementia and Alzheimer’s Disease. J Alzheimers Dis. 2017;55(3):1031-8.
- Tong Z, Han C, Qiang M, et al. Age-related formaldehyde interferes with DNA methyltransferase function, causing memory loss in Alzheimer’s disease. Neurobiol Aging. 2015 Jan;36(1):100-10.
- Mei Y, Jiang C, Wan Y, et al. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline. Aging Cell. 2015 Aug;14(4):659-68.
- Emanuele E, D’Angelo A, Tomaino C, et al. Circulating levels of soluble
receptor for advanced glycation end products in Alzheimer disease and
vascular dementia. Arch Neurol. 2005 Nov;62(11):
- Gasparotto J, Girardi CS, Somensi N, et al. Receptor for advanced glycation
end products mediates sepsis-triggered amyloid-beta accumulation, Tau
phosphorylation, and cognitive impairment.
J Biol Chem. 2018 Jan 5;293(1):226-44.
- Kizer JR, Benkeser D, Arnold AM, et al. Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. Atherosclerosis. 2014 Jul;235(1):116-21.
- Schlotzer-Schrehardt U. [Oxidative stress and pseudoexfoliation glaucoma]. Klin Monbl Augenheilkd. 2010 Feb;227(2):108-13.
- Tulpule K, Dringen R. Formaldehyde in brain: an overlooked player in neurodegeneration? J Neurochem. 2013 Oct;127(1):7-21.
- Tulpule K, Dringen R. Formate generated by cellular oxidation of formaldehyde accelerates the glycolytic flux in cultured astrocytes. Glia. 2012 Apr;60(4):582-93.
- Tulpule K, Hohnholt MC, Dringen R. Formaldehyde metabolism and formaldehyde-induced stimulation of lactate production and glutathione export in cultured neurons. J Neurochem. 2013 Apr;125(2):260-72.
- Hipkiss AR, Preston JE, Himsworth DT, et al. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann N Y Acad Sci. 1998 Nov 20;854:37-53.
- Colzani M, De Maddis D, Casali G, et al. Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study. ChemMedChem. 2016 Aug 19;11(16):1778-89.
- Hipkiss AR, Baye E, de Courten B. Carnosine and the processes of ageing. Maturitas. 2016 Nov;93:28-33.
- Rabbani N, Thornalley PJ. Dicarbonyl proteome and genome damage in metabolic and vascular disease. Biochem Soc Trans. 2014 Apr;42(2):425-32.
- Spoerl E, Boehm AG, Pillunat LE. The influence of various substances on the
biomechanical behavior of lamina cribrosa and peripapillary sclera. Invest
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- Tajes M, Eraso-Pichot A, Rubio-Moscardo F, et al. Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: Implications for Alzheimer’s disease. Neurosci Lett. 2014 Sep 19;580:78-82.
- McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994 Jun;212(2):167-75.
- Banerjee S, Poddar MK. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity. Neurosci Res. 2015 Mar;92:62-70.
- 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 Oct;36(10):1686-94.
- Baek SH, Noh AR, Kim KA, et al. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke. 2014 Aug;45(8):2438-43.
- Macedo LW, Cararo JH, Maravai SG, et al. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats. Mol Neurobiol. 2016 Oct;53(8):5582-90.
- Aydin S, Ogeturk M, Kuloglu T, et al. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation. Peptides. 2015 Feb;64:14-23.
- Qiang M, Xiao R, Su T, et al. A novel mechanism for endogenous formaldehyde elevation in SAMP8 mouse. J Alzheimers Dis. 2014;40(4):1039-53.
- Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc). 2000 Jul;65(7):866-8.