Which Crosslinking Inhibitors and Breakers Are Right for You?

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Acarbose

AcarboseAcarbose (precose or glucobay) interferes with alpha-glucosidase, an enzyme key in breaking down complex carbohydrates into simple sugars. This reduces blood-sugar levels,  inhibiting crosslinking and AGE formation. It does not, however, interfere with the actual binding of sugars to proteins.

Lowering blood-sugar levels protects organs with many delicate blood vessels such as the retina, kidney, brain, etc. from damage. The problem with acarbose is twofold: The long-term effects of suppressing carbohydrate breakdown are unknown, and it leaves high levels of unabsorbed carbohydrates in the intestines, causing pain, cramps, bloating, and diarrhea. Given the risks and problems, it is unsuitable as an anti-aging compound.

Acetyl-L-Carnitine

ALCAcetyl-L-carnitine protects the eye’s lens from cataracts. (Its numerous antiaging properties will be covered in the future.)
The protective effect comes from the acetyl group potential binding sites; aspirin and n-acetyl-cysteine contain an acetyl group and have a similar effect. While taurine also protects the lens of the eye, the underlying mechanism is different, suggesting benefits from using multiple inhibitors.   No such protection was seen for the unacetylated L-carnitine, since it cannot preempt the binding sites.

Aminoguanidine

AminoguanidineAminoguanidine (pimagidine) targets molecules created in the later stages of AGE formation. This prescription drug is based on the guanidine found in French Lilac (aka Goat’s Rue), a bushy perennial.

Diabetics have used French Lilac since medieval times, but were limited to small amounts because the plant contains the toxic molecule galegine.

Protecting collagen against crosslinking, aminoguanidine shields the skin and connective tissue from stiffening and wrinkling, and muscle, like the heart, from hardening. Typical  dosages do not inhibit the routine collagen crosslinking required for strength.

Preventing crosslinking between proteins and fats, aminoguanidine spares the arteries from clogging. By protecting small arteries feeding the peripheral nervous system, it reduces age- and diabetes-associated nerve damage. It also prevents lipofuscin (age spots), a signature sign of aging and crosslinking.

Aminoguanidine is among the most effective crosslinking inhibitors, with vitamin B-6 comparable. But don’t rush out to get a prescription quite yet!

The drug has numerous side effects, including anemia and autoimmune disorders. While a potent inhibitor of diabetic complications, aminoguanidine is not safe enough to justify its use by nondiabetics.

Aspirin (Acetylsalicylic Acid)

AspirinOriginally isolated in tree bark, salicylic acid has been used for millennia for fever and inflammation; the famed physician Hippocrates praised its benefits.
The addition of an acetyl group – done twice in the 1800s by two different chemists – finally eliminated much of the harsh side effects on the stomach, increasing its popularity and therapeutic potential. Aspirin is now the most commonly prescribed drug.

More recently, aspirin has been discovered to interfere with post-Amadori reaction because the phenol ring provides antioxidant properties and the physical structure chelates iron and copper.

Both of these metal ions have been implicated in crosslinking; the betaamyloid plaques found in Alzheimer’s disease, for example, contain both AGEs and complexes with copper and iron.

Aspirin, like acetyl-L-carnitine and taurine, also protects the lens of the eye from cataracts. Experiments using eye lenses submersed in sugar solutions show a profound reduction in cataract formation when aspirin is added.

Benfotiamine

BenfotiamineBenfotiamine (S-benzoylthiamine-O-monophosphate) is a fat-soluble vitamin B-1 (thiamine) derivative that prevents crosslinking and inhibits AGE formation. The body metabolizes it into thiamine pyrophosphate (TPP), vitamin B-1’s active form.

An allithiamine – it is found in the allium family of vegetables, including garlic, onions, and leeks – benfotiamine is a fairly old compound, having been discovered in 1951. (Alteon Pharmaceutical’s alagebrium is derived from B-1.)

Its original application was in the treatment and prevention of a variety of conditions in both diabetics and nondiabetics: nerve damage, including neuropathy, sciatica, and shingles; cardiovascular damage, including heart, kidneys, and eyes, and high blood pressure; and general aging related disorders.

Diabetes damages blood vessels through four chemical pathways, and benfotiamine completely blocks three of them. It also converts the toxic triosephosphates to the more benign pentosephosphates.

Absorption of B-1 is so poor that supplements often contain far more than is usable. Benfotiamine uptake, however, can exceed one hundred times that for B-1.

Reducing AGE levels – preventing retinopathy, renal damage, etc., even in the healthy – benfotiamine can undo damage, substantially improving nerve function while profoundly reducing pain.

Benfotiamine is widely regarded as safer than the already-safe vitamin B-1 it is derived from.

Bioflavonoids

A family of more than four thousand compounds with antioxidant properties, bioflavonoids are found in citrus, grape seeds and skins, green tea, cranberries, pine bark, and fruits. Common bioflavonoids are oxerutin, green-tea polyphenols, proanthocyanidin, and quercetin.

Bioflavonoids inhibit oxidation and aldose reductase, reducing conversion of glucose into the more damaging sorbitol. Pairing with taurine and n-acetyl-cysteine reduces crosslinking far more than these compound do alone.

Biotin

BiotinBiotin has a crucial role in the metabolism of sugar, moving glucose into cells, stimulating the release of insulin, and increasing the conversion of glucose into fatty acids burned for energy and glycogen for stored energy.

Diabetics taking 10 -15mg. of biotin daily have significantly lower fasting blood-sugar levels -‘nearly fifty percent lower – and can reduce the size and frequency of their insulin  injections. Lowering levels of sugar in the blood also reduces AGE formation. Results suggest biotin improves or reverses m a n y symptoms of diabetes. It has no known toxicity even in very high dosages.

BHT

BHTWidely used as a food preservative, butylated hydroxytoluene (BHT) is also a potent antioxidant. Like other antioxidants – vitamins C and E, lipoic acid, and rosmarinic acid – it inhibits oxidation of glucose and thus prevents the formation of the Schiff bases, which start the AGE creation cycle.

BHT is technically approved for use only as a food preservative, so supplement sellers market it only for that purpose.

Chromium

The body uses the element chromium (chromium picolinate, glucose tolerance factor, GTF) in combination with insulin to regulate blood-sugar levels. Chromium deficiencies are common, and supplementing reduces blood sugar levels and AGE formation.

Coenzyme Q10 & Idebenone

Ubiquinone

As potent antioxidants and metabolic enhancers, coenzyme Q10 (CoQ10) and idebenone reduce AGE formation and lower blood-sugar levels by stimulating insulin, improving the metabolism and preventing the oxidation of glucose.

CoQ10 and idebenone are regarded as very safe and well tolerated.

L-Arginine & L-Lysine

L-Arginine

L-Arginine

The amino acids L-arginine and L-lysine inhibit glycation and AGE formation by sacrificially reacting with carbonyls, ketones, aldehydes, and metal ions, saving the body’s proteins from attack.

L-Lysine

L-Lysine

In large doses, L-arginine can lower blood pressure and increase viral replication, particularly for the herpes family. L-lysine, however, suppresses L-arginine’s effect on viral replication. Together, the two slow or prevent AGE formation.

L-Carnosine

L-CarnosineMade by the body and found in muscle and nervous system tissue, L-carnosine (beta alanyl-Lhistidine or n-acetyl-L-carnosine) is composed of two amino acids: alanine and histadine and has several important roles.

By binding to free carbonyl groups, it inhibits sugar binding to proteins and DNA, and reduces protein-protein and protein-DNA crosslinking. As an antioxidant, it preserves the body’s primary antioxidant, glutathione. Finally, by breaking the bonds in crosslinked proteins it undoes damage.

Known to reduce levels of AGEs and free radicals in the body, L-carnosine prevents and even removes age-related cataracts. (It may also benefit age-related eye conditions like glaucoma.)

Combining L-carnosine with AGE breakers like benfotiamine may eliminate newly liberated carbonyls before they can bind to other proteins. L-carnosine is regarded as safe in normal amounts. Large dosages – typically more than one gram per day – have been linked to histamine-type allergies.

Lipoic Acid

Alpha Lipoic AcidA potent sulfur-bearing antioxidant, lipoic acid (thioctic acid) inhibits glucose oxidation, Schiff-base formation, lipid peroxidation, and the binding of fats to proteins.

Complexing excess metal ions, lipoic acid reduces AGE formation. It also recycles oxidized vitamin C, preventing it from producing the reactive carbonyls leading to AGEs. Finally, lipoic acid works like insulin, lowering blood-sugar levels without injections. Like other antioxidants lipoic acid is an earlystage inhibitor. It pairs nicely with mid- and late-stage inhibitors like L-carnosine, PABA, vitamin B-6, and benfotiamine.

Metformin

MetforminMetformin (glucophage) is a prescription drug for diabetes. A slightly modified double guanidine, the drug prevents the liver’s breakdown of carbohydrates into glucose – thereby lowering bloodsugar levels – and inhibits the formation of AGEs, particularly those involving collagen in the heart, connective tissue, and skin.

Like L-carnosine, metformin binds to carbonyl groups, interfering with crosslinking. It also ties up binding sites on the fibrin proteins responsible for coagulation and, like aspirin, reduces the risk of heart attack and stroke.

Metformin, unfortunately, has serious side effects: lactic acidosis, liver and kidney damage, and decreased folate and vitamin B-12 levels. Drops in these vitamins are known to raise the homocysteine levels associated with heart and circulatory system damage.

The chemically similar drug phenformin killed a number of patients before being removed from the market. Given the risks, metformin is too risky to use as an antiaging compound.

N-Acetyl-Cysteine

NACN-acetyl-cysteine is a powerful antioxidant with wide antiaging properties. By preventing the oxidation of glucose, it slows down early-stage AGE formation.

Like aspirin and acetyl-L-carnitine, n-acetyl-cysteine acetylates potential binding sites, preventing AGE formation. It pairs nicely with inhibitors like L-carnosine, PABA, vitamin B-6, and benfotiamine.

Penicillamine

PenicillamineA distinct molecule from the antibiotic, penicillamine (dimethyl cysteine) inhibits crosslinking, but not particularly well. Its primary use is in chelation, like EDTA, since it complexes metals and reactive molecules. It also interferes with routine metabolism.

Known side effects include immune system suppression, impaired collagen synthesis, lupus, aplastic anemia, and myasthenia gravis. Given the serious risks, penicillamine is suitable only for life-threatening illnesses on a short-term basis.

PABA (Para-Amino Benzoic Acid)

PABAA vitamin B cofactor, PABA (para-amino benzoic acid) is an antioxidant and crosslinking inhibitor. It is the active ingredient in many sunscreens.

PABA is generally safe and well tolerated, even up to several grams daily. Some users find it disagrees with them, even in small quantities, so some caution is required. The typical side effects of high dosages are nausea and diarrhea, which vanish upon dosage reduction.

Rosmarinic Acid

Rosmarinic AcidA potent antioxidant, rosmarinic acid inhibits the oxidation of glucose, slowing the formation of the Schiff bases created in the early stages of AGE formation. It also is a strong anti-inflammatory, which may prevent autoimmune reactions to AGEs and the tissues containing them.

As an inhibitor of aldose reductase, rosmarinic acid prevents the conversion of glucose into sorbitol. Many cells, like those in the eye, cannot metabolize sorbitol, and suffer damage.
(See taurine for details.)

Selenium

The element selenium (selenomethionine, sodium selenate) is a key ingredient in the antioxidants made by the body that prevent the oxidation of glucose, thereby inhibiting AGE formation.

Taurine

TaurineThe amino acid taurine (2-aminoethane sulfonic acid) is several times better at inhibiting AGE formation than the risky prescription drug aminoguanidine.

Taurine is believed to work by binding to sugar, sparing the proteins in the eye’s lens. This has particular value when it comes to protecting sight.

About the size of a shirt button, the eye’s lens is made of transparent protein that focuses light onto the retina. When crosslinked by the sun’s ultraviolet rays or by sugar, it turns cloudy with cataracts, causing a loss of vision.

The high taurine levels in the eye protect the lens by preferentially bonding to sugars. In addition to taurine, high levels of vitamins C and E are known to halve the risk of cataracts.

Vitamin B-6

Pyridoxamine (PM)

PyridoxaminePyridoxal (PL)

PyridoxalPyridoxine (PN)

PyridoxineVitamin B-6 is crucial for metabolism of proteins, carbohydrates, and fats. It is found in three different forms: pyridoxal (pyridoxal-5-phosphate, P5P, and PL), pyridoxine (PN), and pyridoxamine (PM). The best crosslinking inhibitor is PM.

Trapping carbonyls and acting as an antioxidant, B-6 inhibits AGE formation better than aminoguanidine, but without the risk of injury or death.

Vitamin C

Vitamin CLike other antioxidants, vitamin C inhibits glucose oxidation, reducing chiff-base formation. An early-stage inhibitor, it pairs nicely with mid- and late-stage inhibitors like L-carnosine, PABA, vitamin B-6, and benfotiamine.

Vitamin E

Vitamin E

Vitamin E (tocopherol, tocotrienol) is a family of antioxidants that, among its other benefits, prevents the oxidation of glucose, reducing the formation of Schiff bases. It also slightly inhibitscarbonyl formation. Using a single synthetic supplement like DL-tocopherol will not deliver optimal protection from oxidation and AGEs; evidence suggests synthetics are inferior to natural vitamin E and can cause a variety of problems. Supplementing with a blend of natural tocopherols and tocotrienols is superior to using a single synthetic supplement.

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