Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity and aging-associated pathologies. A combination of nicotinamide, lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low), was identified to lower glycation by reducing MGO and MGO-derived AGE, MG-H1, in mice. Administration of Gly-Low reduced food consumption, lowered body weight, improved insulin sensitivity, and increased survival in both leptin receptor-deficient (Leprdb) and wild-type C57B6/J mice. Unlike caloric restriction, Gly-Low modulated hypothalamic signaling by upregulating mTOR pathway signaling to inhibit ghrelin-mediated hunger response. Gly-Low also slowed hypothalamic aging and increased survival when administered as a late-life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary caloric restriction and reducing glycation.
Lauren Wimer, Kiyomi R. Kaneshiro, Jessica Ramirez, Neelanjan Bose, Martin Valdearcos Contreras, Muniesh Shanmugam, Dominique Gaffney, Parminder Singh, Jennifer Beck, Durai Sellegounder, Lizbeth Enriquez Najera, Lisa Ellerby, Soo-Jin Cho, John Newman, James Galligan, Suneil Koliwad and Pankaj Kapahi
So they use pyridoxamine in their experiments but sell a supplement Gly-Lo with just pyridoxine (B6)! It is highly unlikely that pyridoxine has the same anti-glycation benefit as pyridoxamine.
Has anyone in USA found a way to order pyridoxamine from Europe ? Perhaps using a reshipper like this one https://mygermany.com/shipping-cost-calculator/ ? The risk is that a commercial re-shipper will have to use a customs declaration that is more likely to be intercepted by US customs than a package sent by a private party. A private party is allowed to just list “Vitamins” , which is usually not inspected by US customs if sender and receiver are both private parties.
“The Effect of Pyridoxamine on Large Artery Stiffening and Brain Oxidative Stress and Inflammation with Age”
As people age, large elastic arteries become stiffer and cerebral arteries become dysfunctional. This research sought to determine whether treatment with pyridoxamine, a form of vitamin B6, prevents age-related arterial stiffening by limiting the increases in advanced glycation end products (AGEs), and thereby ameliorates the downstream consequences in cerebral arteries and cerebral cortex by limiting increases in oxidative stress and inflammation. 20 old mice were treated with pyridoxamine for 4 months and pulse wave velocity (PWV), a measure of aortic stiffness, was performed at baseline and every other month. Tissue samples from old control, young control, and old pyridoxamine treated mice were analyzed for gene expression of pro- and antioxidant enzymes and inflammatory cytokines. Aorta samples from each group were analyzed for AGEs by immunofluorescence and for thickness of the arterial wall by Verhoeff Van Gieson staining. Aortic PWV was greater in old control versus young control arteries (306 ± 12 cm/s vs. 273 ± 16 cm/s, p=0.005) however, aortic PWV in pyridoxamine-treated mice did not increase over time (p>0.05). Pyridoxamine did not change AGEs (0.05 ± 0.02 AU) versus old and young control arteries (0.01 ± 0.003 AU vs 0.1 ± 0.05 AU, p=0.10). There was no change to arterial wall structure between groups. In the cerebral cortex, SOD1 trended toward elevation in old pyridoxamine arteries as compared to old controls. IL-1 was significantly increased in old pyridoxamine versus young control (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03), the same was true in the MCA (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03). These results suggest that pyridoxamine may reduce arterial stiffening. While previous studies have indicated a reduction in AGEs with pyridoxamine treatment, this was not evident in the present study. Pyridoxamine may increase SOD1 expression, while increases in IL-1 is likely a result of the aging process and not modified by pyridoxamine treatment. Further studies are needed to identify the mechanism by which pyridoxamine prevents age-related arterial stiffening.
I currently take those + P5P (100mg 2x/day) + Aminoguanedine (75mg 2-4x/day) : The latter 2 are both weaker than pyridoxamine for anti-glycation, but the best available substitutes for those in USA who cannot get pyridoxamine.
Only the Renosave Forte from India product still includes 75mg Pyridoxamine (along with 300mg NAC) : 3x/day would give the recommended dose of Pyridoxamine, and the 900mg of NAC you get along with it is probably OK : the recommended dose for GLYNAC supplementation for 70kg is 7-9g of NAC/day + 6g Glycine, so anyone doing GLYNAC should have no problem adjusting their dosage of NAC! Even if you are sensitive to high dosages of NAC (I take the more expensive Glutamylcystein, instead of NAC to avoid the side effects of NAC) 900mg/day in 3 divided doses should cause no problems.
All the other products, including the bulk versions, only include Pyridoxine (the generic form of B6), though from the images it looks like some of them (Ageless & Stylecystin EF) once included Pyridoxamine.
N-Acetylcysteine and Pyridoxamine Dihydrochloride
STYLECYSTIN FORTE are two separate medications that are sometimes used in combination to treat certain medical conditions.
N-Acetylcysteine (NAC) is a medication that is commonly used as a mucolytic agent to thin mucus in the airways, making it easier to cough up. STYLECYSTIN FORTE is also used as an antidote for acetaminophen overdose, as it helps to restore glutathione, a natural antioxidant in the liver that is depleted during acetaminophen toxicity. NAC is also sometimes used as a treatment for certain respiratory conditions such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
Pyridoxamine Dihydrochloride is a form of vitamin B6 that is sometimes used as a dietary supplement. It has antioxidant properties and may help to reduce inflammation in the body. It is sometimes used as a treatment for diabetic nephropathy, a kidney disorder that can occur in people with diabetes.
When used together, STYLECYSTIN FORTE may be beneficial in the treatment of certain medical conditions, particularly those that involve inflammation and oxidative stress. However, the use of these medications in combination should be supervised by a healthcare professional, as there may be potential interactions or side effects.
Looks like there are 2 versions of Stylecystin : Stylecystin Forte comes with Pyridoxamine 75mg + NAC 300mg (same as Renosave Forte), while Stylecystin EF is formulated with 600mg NAC :
Some of the adds on IndiaMart show the picture for Stylecystin Forte, but describe the product as Stylecystin EF and state Pyridxoamine + NAC : the price of Rs 50/strip suggests it is just 600mg NAC, since Stylecystin Forte sells for closer to Rs 200/strip at most other sites, and Pyridoxamine is a much more expensive ingredient than NAC.
Is anyone on this forum taking pyridoxamine? — I did a quick search and didn’t see any mention in their protocol (maybe I didn’t realize it has different brand names). I see some are taking P5P but not sure how to guess the overlap in “dose” and effect. Maybe one of our EU/UK friends? Any longevity researchers?
If one were to take pyridoxamine for reducing glycation (and one wasn’t a mouse) what kind of dosing would you think might be a good end-goal (and daily? Pulsed?).
This interests me because:
I have a daughter who is Type-1 diabetic (although is low carb and dramatically dropped her serum glucose levels in the two months since we found out): do you think it may be appropriate for a 16-year old girl to clean out any advanced glycation end products from the 9-12 months her glucose levels were through-the-roof and no-one diagnosed her? — I’d hate for her to suffer eye and kidney damage long-term because some resident was too busy/tired to look at the urine glucose of >1000 and ketones of 80-100 right on her test results….(grrrr)
I am keto (unpopular here) with higher LDL (172 last measure, before five months of taking 1000mg daily of citrus bergamot) so preventing atherosclerosis would be nice. I am hesitant to add to my “stack” but this seems a good preventative measure for an actual risk (high LDL although lowish triglycerides 64, highish HDL 68, decent pulse and blood pressure, good cardio fitness, good waist/height, low glucose levels 82 last measure, etc). And seems reasonable to prevent longer-term ASCVD regardless of LDL.
3). Also I might be able to grab some in Europe this summer: is it just in the vitamin section of pharmacies/ Carrefour? Or is it prescription?
It has been demonstrated that glycation of LDL particles on the apolipoprotein B (ApoB) and phospholipid components [65], [66] contributes to the exacerbation of atherosclerosis. Higher levels of glycated LDL (AGE-LDL) were found in patients with diabetes and suggested to belong to the features of dyslipidemia related to diabetes mellitus and renal insufficiency [66], [67]. Glycation of ApoB results in impairment of LDL receptor-mediated uptake with subsequently reduced clearance of LDL [68]. In contrast, AGE-LDL uptake by macrophages is greater than that of native LDL by an LDL-receptor-independent mechanism involving a high-capacity, low-affinity scavenger receptor[69]. Glycation thus enhances LDL uptake by human aortic intimal cells [70] and monocyte-derived macrophages [69], thereby stimulating the formation of foam cells and promoting atherosclerosis [64]. Alternatively, glycation of LDL promotes atherosclerosis via the increased susceptibility of AGE-LDL for oxidation, another critical pathway in the development of atherosclerosis [64], [68], [71].
Interesting - pyridoxamine was prohibited as a supplement in the US (someone wanting to sell it as a drug, and got the FDA to go along). But it’s available in Europe (e.g. SuperSmart as mentioned).
A look on Google Scholar showed that 200mg is considered a “high” dose, though one study (on obese patients w/ Type 2) showed no impact on insulin sensitivity:
I asked ChatGPT (sorry!) for food sources, which said it’s found in the foods that typically are high in B vitamins: fatty fish, poultry (I assume dark meat), organ meats especially liver, potatoes and non-citrus fruits like banana and avocado.
I’m dubious about potato and fruits having enough, but do hope to boost liver consumption if my wife will allow it haha.
I hope your daughter improves quickly! As an aside, we have a friend who has lifelong Type 1 diabetes and is never without her monitor and injection kit. She and her partner discovered that medical people (e.g., nurses) tend to be rather dismissive of Type 1 people - even disbelieving she actually has it! Maybe they just assume that Type 1 is a form of Type 2? This became an issue during a recent surgery (I forget, but she was in hospital a few days) and her partner had to yell at the staff to take her seriously. Anyway - heads-up in case your daughter is ever in a similar situation and might need advocacy.
